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Javed AA, Habib A, Mahmud O, Fatimi AS, Grewal M, Mughal N, He J, Wolfgang CL, Daamen L, Besselink MG. Prognostic factors in localized pancreatic ductal adenocarcinoma after neoadjuvant therapy and resection: a systematic review and meta-analysis. J Natl Cancer Inst 2025; 117:840-867. [PMID: 39563429 DOI: 10.1093/jnci/djae294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 10/29/2024] [Accepted: 11/06/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND Prognostic markers for overall survival in resected pancreatic ductal adenocarcinoma are well established but remain unclear following neoadjuvant therapy. This systematic review and meta-analysis aimed to determine factors associated with overall survival following neoadjuvant therapy in resected pancreatic ductal adenocarcinoma. METHODS The PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL databases were systematically searched from January 2010 until May 2024. Studies that reported univariable and multivariable hazard ratios were included if patients underwent neoadjuvant therapy and resection for localized pancreatic ductal adenocarcinoma. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was performed using generic inverse-variance random-effects models. RESULTS Among 2208 unique articles identified by the search, 92 were included in the meta-analysis. Of these, 85 were of "good" and 7 of "poor" quality. The neoadjuvant therapy regimen was described in 84 studies of which 62 included patients treated with FOLFIRINOX. Margin status, nodal disease, American Joint Committee on Cancer (AJCC) T-stage, and normalization of cancer antigen 19-9 (CA19-9) after neoadjuvant therapy were prognostic for overall survival, whereas age, sex, perineural invasion, baseline tumor size, and baseline CA19-9 were not. The test for subgroup differences between ypN substages was not statistically significant in the multivariable model. Neoadjuvant FOLFIRINOX was associated with better survival than other regimens. CONCLUSIONS This meta-analysis identified margin status, nodal disease, AJCC T-stage, and normalization of CA19-9 after neoadjuvant therapy as prognostic factors for overall survival in patients with resected localized pancreatic ductal adenocarcinoma following neoadjuvant therapy.
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Affiliation(s)
- Ammar A Javed
- New York University Langone Health, New York University Grossman School of Medicine, New York City, NY 10016, United States
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam 1007 MB, the Netherlands
- Cancer Center Amsterdam, Amsterdam 1007 MB, the Netherlands
| | - Alyssar Habib
- New York University Langone Health, New York University Grossman School of Medicine, New York City, NY 10016, United States
| | - Omar Mahmud
- New York University Langone Health, New York University Grossman School of Medicine, New York City, NY 10016, United States
- Medical College, Aga Khan University, Karachi 74800, Pakistan
| | - Asad Saulat Fatimi
- New York University Langone Health, New York University Grossman School of Medicine, New York City, NY 10016, United States
- Medical College, Aga Khan University, Karachi 74800, Pakistan
| | - Mahip Grewal
- New York University Langone Health, New York University Grossman School of Medicine, New York City, NY 10016, United States
| | - Nabiha Mughal
- New York University Langone Health, New York University Grossman School of Medicine, New York City, NY 10016, United States
| | - Jin He
- Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD 21205, United States
| | - Christopher L Wolfgang
- New York University Langone Health, New York University Grossman School of Medicine, New York City, NY 10016, United States
| | - Lois Daamen
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht 3508 GA, the Netherlands
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam 1007 MB, the Netherlands
- Cancer Center Amsterdam, Amsterdam 1007 MB, the Netherlands
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Sekiguchi N, Takahashi H, Kobayashi S, Sasaki K, Hasegawa S, Iwagami Y, Yamada D, Tomimaru Y, Akita H, Asaoka T, Noda T, Shimizu J, Doki Y, Eguchi H. Surgical outcomes of histopathological stage I pancreatic cancer with special reference to oncological differences between pStage I and ypStage I cases. Surg Oncol 2025; 60:102225. [PMID: 40252582 DOI: 10.1016/j.suronc.2025.102225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 03/21/2025] [Accepted: 04/03/2025] [Indexed: 04/21/2025]
Abstract
OBJECTIVES Histopathological stage I pancreatic cancer (PC) consists of four entities according to the Union for International Cancer Control (UICC) 8th staging system: pStage IA (cases underwent up-front surgery, pT1 [tumor size ≤20 mm] pN0), pStage IB (cases underwent up-front surgery, pT2 [20 mm < tumor size ≤40 mm] pN0), ypStage IA and IB (i.e., underwent neoadjuvant treatment [NAT]). This study aimed to evaluate surgical outcomes in patients with histopathological stage I PC ((y)pStage I). METHODS Patients with PC who underwent resection and were diagnosed with (y)pStage I were included in this study (n = 121). We evaluated and compared recurrence-free survival (RFS) and overall survival (OS) among these four categories: pStage I vs. ypStage I, (y)pStage IA vs. IB, ypStage IA vs. IB, and pStage IA vs. IB. RESULTS There was no difference in the prognosis between pStage I and ypStage I cases, even though ypStage I included more advanced cases at NAT initiation. For pStage I (n = 25), no differences in prognosis were noted between pStage IA and IB (median RFS, 24 vs. 21 months, p = 0.871; median OS, 49.5 vs. 35.5 months, p = 0.213). However, in the ypStage I cohort (n = 96), there was significantly better RFS in ypStage IA (median RFS, 42 vs. 14 months, p = 0.0114; median OS, 52 vs. 36 months, p = 0.250). CONCLUSIONS Survival was comparable between pStage I and ypStage I cohorts, although the subcategories within each cohort (IA vs. IB) had different clinicopathological characteristics and outcomes.
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Affiliation(s)
- Naoko Sekiguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan.
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Shinichiro Hasegawa
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Junzo Shimizu
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2 E2, Suita, Osaka, 565-0871, Japan
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Basree MM, Witt JS, Uboha NV, Lubner M, Minter R, Weber S, Ronnekleiv-Kelly S, Abbott D, Kratz J, Patel M, Zafar SN, LoConte N, Lubner SJ, Deming D, Ritter MA, Mohindra P, Bassetti MF. Neoadjuvant SBRT plus Elective Nodal Irradiation with Concurrent Capecitabine for Patients with Resectable Pancreatic Cancer: Survival Analysis of a Prospective Phase 1 Trial. Pract Radiat Oncol 2025:S1879-8500(25)00011-6. [PMID: 39924052 DOI: 10.1016/j.prro.2025.01.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 12/22/2024] [Accepted: 01/08/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND AND PURPOSE Elective nodal irradiation (ENI) in resectable pancreatic cancer remains undefined, though occult nodal disease is common. This study investigated the use of neoadjuvant stereotactic body radiation therapy (SBRT) to primary disease with ENI, with concurrent capecitabine. Safety data for this protocol were previously reported. In this report, we provide an updated survival analysis. MATERIALS AND METHODS This is a prospective, single institution, phase IA/B dose-escalation trial that enrolled patients with biopsy-proven, resectable, pancreatic adenocarcinoma between 2014 - 2019 (NCT1918644). Patients were enrolled into one of the 3 cohorts with escalating dose levels. Neoadjuvant SBRT to the primary tumor was delivered in 5 fractions of 5, 6, or 7 Gy with concomitant capecitabine (1650 mg/m2). All patients received ENI 5 Gy x 5 fractions. Our initial report found no dose-limiting toxicities. Clinicopathologic features were summarized using descriptive statistics. Kaplan-Meier (KM) curves were employed for survival analysis. RESULTS Of 17 enrolled patients, 16 were evaluable (94.1%). Thirteen (76.5%) proceeded to surgery. Median follow up was 28.0 months (1.7 - 71.9). Four patients (25.0%) received neoadjuvant chemotherapy and six (37.5%) received adjuvant chemotherapy. Pathologic nodal involvement (69.2%) was associated with a higher risk of any relapse (p<0.01) and distant metastasis (p=0.02). Local failure occurred in 4 (25%) patients with 2/4 of those failures occurring partially within the 25 Gy elective nodal field and 1/4 occurred in the 25 Gy elective nodal field and partially within the 35 Gy tumor field. The median overall survival (OS) and disease-free survival (DFS) were 31.1 months (range, 2.3 - 73.6) and 12.0 months (range, 0.4 - 71.9), respectively. Three-year OS and DFS were 50% and 31.3% overall, and 61.5% and 38.5% for the surgical cohort. Patients with pN+ had worse median OS (23.9 vs 69.3 months; p=0.002) and DFS (9.9 vs 58.9 months; p=0.002). No further radiation related toxicities were noted since the prior report. CONCLUSION Neoadjuvant SBRT to the primary tumor with ENI and radiosensitizing chemotherapy is a feasible approach that may improve outcomes in patients with resectable and borderline pancreatic cancer, despite high rates of pathological nodal involvement. Further investigation of this strategy is warranted in a larger cohort.
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Affiliation(s)
- Mustafa M Basree
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
| | - Jacob S Witt
- Cancer Care Specialists of Illinois/Cancer Care Center of O'Fallon, O'Fallon, IL, USA
| | - Nataliya V Uboha
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Meghan Lubner
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Rebecca Minter
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Sharon Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Sean Ronnekleiv-Kelly
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Daniel Abbott
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Jeremy Kratz
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI
| | - Monica Patel
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Syed Nabeel Zafar
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Noelle LoConte
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Sam J Lubner
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Dustin Deming
- Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Mark A Ritter
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Pranshu Mohindra
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, USA
| | - Michael F Bassetti
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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Ueda H, Takahashi H, Kobayashi S, Tomimaru Y, Kubo M, Sasaki K, Iwagami Y, Yamada D, Asaoka T, Noda T, Shimizu J, Doki Y, Eguchi H. ASO Author Reflections: Potential of Peripheral Plasma Exosomal miRNA: miR-6855-5p Could Predict Radiosensitivity in Patients with Pancreatic Cancer, and Enhances Radioresistance. Ann Surg Oncol 2025; 32:529-530. [PMID: 39299990 DOI: 10.1245/s10434-024-16235-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 09/01/2024] [Indexed: 09/22/2024]
Abstract
The efficacy of preoperative treatment for pancreatic cancer (PC) has been reported in randomized controlled trials, but the optimal regimen and the appropriateness of combining radiotherapy remain controversial. Therefore, predicting the efficacy of preoperative treatment using biomarkers and determining whether to combine chemotherapy or radiotherapy based on the biology of individual tumors could help personalize treatment and maximize therapeutic outcomes. In this study, a microRNA (miRNA) microarray analysis was performed using peripheral blood plasma exosomes from 10 PC patients who underwent neoadjuvant chemoradiotherapy, leading to the identification of miR-6855-5p as a candidate miRNA. miR-6855-5p was found to induce radioresistance in PC cells. In another cohort of 28 patients, it was observed that those with higher expression levels of miR-6855-5p in peripheral blood plasma exosomes tended to have increased radioresistance (r = - 0.5964). In future, measuring plasma exosomal miR-6855-5p before treatment could potentially lead to precision medicine by personalizing the decision of whether to include radiotherapy in the treatment plan.
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Affiliation(s)
- Hiroki Ueda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Masahiko Kubo
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Junzo Shimizu
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
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Ueda H, Takahashi H, Sakaniwa R, Kitamura T, Kobayashi S, Tomimaru Y, Kubo M, Sasaki K, Iwagami Y, Yamada D, Asaoka T, Noda T, Shimizu J, Doki Y, Eguchi H. Preoperative treatment response prediction for pancreatic cancer by multiple microRNAs in plasma exosomes: Optimization using machine learning and network analysis. Pancreatology 2024; 24:1097-1106. [PMID: 39278808 DOI: 10.1016/j.pan.2024.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 08/28/2024] [Accepted: 09/10/2024] [Indexed: 09/18/2024]
Abstract
BACKGROUND/OBJECTIVES MicroRNAs (miRNAs) are involved in chemosensitivity through their biological activities in various malignancies, including pancreatic cancer (PC). However, single-miRNA models offer limited predictability of treatment response. We investigated whether a multiple-miRNA prediction model optimized via machine learning could improve treatment response prediction. METHODS A total of 20 and 66 patients who underwent curative resection for PC after gemcitabine-based preoperative treatment were included in the discovery and validation cohorts, respectively. Patients were classified according to their response to preoperative treatment. In the discovery cohort, miRNA microarray and machine learning were used to identify candidate miRNAs (in peripheral plasma exosomes obtained before treatment) associated with treatment response. In the validation cohort, miRNA expression was analyzed using quantitative reverse transcription polymerase chain reaction to validate its ability to predict treatment response. RESULTS In the discovery cohort, six and three miRNAs were associated with good and poor responders, respectively. The combination of these miRNAs significantly improved predictive accuracy compared with using each single miRNA, with area under the curve (AUC) values increasing from 0.485 to 0.672 to 0.909 for good responders and from 0.475 to 0.606 to 0.788 for poor responders. In the validation cohort, improved predictive performance of the miRNA combination over single-miRNA prediction models was confirmed, with AUC values increasing from 0.461 to 0.669 to 0.777 for good responders and from 0.501 to 0.556 to 0.685 for poor responders. CONCLUSIONS Peripheral blood miRNA profiles using an optimized combination of miRNAs may provide a more advanced prediction model for preoperative treatment response in PC.
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Affiliation(s)
- Hiroki Ueda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
| | - Ryoto Sakaniwa
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Suita, Osaka, Japan
| | - Tetsuhisa Kitamura
- Environment Medicine, Department of Social Medicine, Division of Environment Medicine and Population Sciences, Osaka University Graduate School of Medicine, Osaka, Suita, Osaka, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Masahiko Kubo
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Junzo Shimizu
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
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Akita H, Mukai Y, Kubo M, Takahashi H, Hasegawa S, Kitakaze M, Matsuura N, Masuike Y, Sugase T, Shinno N, Kanemura T, Hara H, Sueda T, Nishimura J, Yasui M, Omori T, Miyata H, Ohue M, Wada H. A striking elevation of CA19-9 after preoperative therapy negates prognostic benefit from radical surgery in resectable and borderline resectable pancreatic cancer. Surgery 2024; 176:1215-1221. [PMID: 39079828 DOI: 10.1016/j.surg.2024.06.049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 05/28/2024] [Accepted: 06/23/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND Identifying patients who can be spared nonbeneficial surgery is crucial, as pancreatic cancer surgery is highly invasive, with substantial negative effects on quality of life. The study objective was to investigate a useful indicator of patients who do not gain prognostic benefit from radical surgery after neoadjuvant therapy for resectable and borderline resectable pancreatic cancer. METHOD We compared factors among 609 patients with resectable or borderline resectable pancreatic cancer receiving neoadjuvant therapy during 2005-2019. Patients were divided into a poor-prognosis group (no surgery or postresection recurrence within a year) and a good-prognosis group (no recurrence or recurrence >1 year after resection). RESULTS Patients who experience a recurrence within a year of resection (poor-prognosis group) did no better than patients who received neoadjuvant therapy and progressed but never made it to surgery. The value of carbohydrate antigen 19-9 after neoadjuvant therapy was the most significant indicator to predict the poor prognosis group and the elevation of carbohydrate antigen 19-9 (>200 U/mL) identified only poor prognosis group with high specificity of 96.6%. The overall survival of patients with more than 200 of carbohydrate antigen 19-9 after neoadjuvant therapy was significantly very poor and their 2-year survival rate was only 41.4%. CONCLUSION A striking elevation of carbohydrate antigen 19-9 after neoadjuvant therapy for resectable or borderline resectable pancreatic cancer is a good indicator of poor prognosis. Patients with carbohydrate antigen 19-9 >200 U/mL after neoadjuvant therapy should not undergo radical surgery.
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Affiliation(s)
- Hirofumi Akita
- Department of Surgery, Osaka International Cancer Institute, Japan.
| | - Yosuke Mukai
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masahiko Kubo
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | | | | | | | - Yasunori Masuike
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takahito Sugase
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Naoki Shinno
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takashi Kanemura
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hisashi Hara
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Toshinori Sueda
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | - Masayoshi Yasui
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takeshi Omori
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Miyata
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masayuki Ohue
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Wada
- Department of Surgery, Osaka International Cancer Institute, Japan
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Keltner S, Nelson B, Kharofa J. Indications for Radiation in Pancreatic Adenocarcinoma: A Review. Surg Clin North Am 2024; 104:1007-1016. [PMID: 39237160 DOI: 10.1016/j.suc.2024.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/07/2024]
Abstract
Pancreatic adenocarcinoma remains a deadly disease with 5 year overall survival of 10% among all stages. Standard of care for resectable disease remains surgical resection and adjuvant systemic therapy, but paradigms for borderline resectable and unresectable cases remain more nuanced. Radiation has been explored in the neoadjuvant, adjuvant, and definitive settings in a variety of randomized and non-randomized trials with mixed results. There is strong evidence to support the use of neoadjuvant radiation for borderline resectable pancreatic cancer. Utilization of radiation in the adjuvant setting remains unclear while the results of radiation therapy oncology group (RTOG) 0848 are pending.
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Affiliation(s)
- Samuel Keltner
- Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Bailey Nelson
- Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Jordan Kharofa
- Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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Ueda H, Takahashi H, Kobayashi S, Kubo M, Sasaki K, Iwagami Y, Yamada D, Tomimaru Y, Asaoka T, Noda T, Shimizu J, Doki Y, Eguchi H. miR-6855-5p Enhances Radioresistance and Promotes Migration of Pancreatic Cancer by Inducing Epithelial-Mesenchymal Transition via Suppressing FOXA1: Potential of Plasma Exosomal miR-6855-5p as an Indicator of Radiosensitivity in Patients with Pancreatic Cancer. Ann Surg Oncol 2024:10.1245/s10434-024-16115-w. [PMID: 39269634 DOI: 10.1245/s10434-024-16115-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 08/16/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND Whether radiation should be added to neoadjuvant treatment remains controversial, and liquid biopsy has not been reported to predict radioresistance in pancreatic cancer (PC). We aimed to identify microRNAs (miRNAs) governing radioresistance in PC by utilizing peripheral plasma exosome samples and to verify their usefulness as biomarkers. METHODS miRNA microarray analysis was conducted using pretreatment peripheral plasma exosomes from 10 patients with PC receiving neoadjuvant chemoradiotherapy (NACRT) in the discovery cohort. Patients were categorized into two groups (good and poor responders) based on treatment responses, and candidate miRNAs exhibiting differential expression between the two groups were identified. The radiosensitivity of PC cells was examined after miR-6855-5p overexpression. Next-generation sequencing (NGS) and TargetScan were used to explore the mechanisms of radioresistance. We investigated the correlation between miR-6855-5p expression levels in the pretreatment peripheral plasma exosomes of 28 patients in the validation cohort and the response to NACRT. RESULTS miR-6855-5p expression was higher in poor responders than in good responders. miR-6855-5p induces radioresistance in PC cells. NGS showed that epithelial-mesenchymal transition (EMT) was involved in miR-6855-5p-related radioresistance. Forkhead box protein A1 (FOXA1) was identified as a direct target of miR-6855-5p using NGS and TargetScan. Clinical examination of samples from the validation cohort revealed a tendency for patients with higher expression of miR-6855-5p in peripheral plasma exosomes to exhibit increased radioresistance (r = -0.5964). CONCLUSIONS miR-6855-5p regulates the radioresistance of PC by inducing EMT via suppressing FOXA1, and miR-6855-5p in peripheral plasma exosomes may be a biomarker for radioresistance of PC.
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Affiliation(s)
- Hiroki Ueda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Masahiko Kubo
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Junzo Shimizu
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
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9
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Ueda H, Takahashi H, Akita H, Tomimaru Y, Kobayashi S, Kubo M, Mukai Y, Toshiyama R, Sasaki K, Hasegawa S, Iwagami Y, Sakai K, Yamada D, Noda T, Asaoka T, Wada H, Gotoh K, Doki Y, Eguchi H. Prognostic impact of aberrant right hepatic artery involvement in patients with pancreatic cancer: A multicenter retrospective cohort study. J Surg Oncol 2024; 130:504-515. [PMID: 39099198 DOI: 10.1002/jso.27792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 05/13/2024] [Accepted: 07/20/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND AND OBJECTIVES This study aimed to evaluate the prognostic value of aberrant right hepatic artery (A-RHA) involvement in patients with pancreatic cancer (PC). METHODS This study enrolled 474 patients who underwent upfront pancreatectomy or neoadjuvant treatment for resectable (R) or borderline resectable (BR) PC from four institutions. The patients were divided into three groups: A-RHA involvement group (n = 12), patients who had sole A-RHA involvement without major arterial involvement; BR-A group (n = 104), patients who had major arterial involvement; R/BR-PV group (n = 358), others. RESULTS All patients in the A-RHA involvement group underwent margin-negative resection. The median overall survival of the entire cohort in the A-RHA involvement, R/BR-PV, and BR-A groups was 41.2, 33.5, and 25.2 months, respectively. Although survival in the R/BR-PV group was significantly more favorable than that in the BR-A group (p = 0.0003), no significant difference was observed between the A-RHA involvement group and the R/BR-PV (p = 0.7332) and BR-A (p = 0.1485) groups. CONCLUSIONS The prognosis of patients with PC and sole A-RHA involvement was comparable to that of patients with R/BR-PV.
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Affiliation(s)
- Hiroki Ueda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Masahiko Kubo
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Yousuke Mukai
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Reishi Toshiyama
- Department of Surgery, NHO Osaka National Hospital, Osaka, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Shinichiro Hasegawa
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Kenji Sakai
- Department of Surgery, NHO Osaka National Hospital, Osaka, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Osaka Police Hospital, Osaka, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kunihito Gotoh
- Department of Surgery, NHO Osaka National Hospital, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
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10
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Miyahara S, Takahashi H, Tomimaru Y, Kobayashi S, Sasaki K, Iwagami Y, Yamada D, Akita H, Noda T, Doki Y, Eguchi H. Organ-specific variations in tumor marker dynamics in postoperative pancreatic cancer recurrence: Trends in lung and liver recurrence highlighting biological heterogeneity. Surg Oncol 2024; 55:102103. [PMID: 38986312 DOI: 10.1016/j.suronc.2024.102103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 06/12/2024] [Accepted: 07/03/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND/OBJECTIVES Although tumor recurrence after surgical resection in pancreatic cancer (PC) is generally considered incurable, it is well-accepted that clinical presentations and outcomes vary according to the recurrent sites (e.g., liver vs. lung recurrence), suggesting a possible biological inhomogeneity of PC recurrence. Understanding the behavior of biological factors, specifically tumor markers (TMs), at different recurrence sites may contribute to individualized treatment strategies. Therefore, this study aimed to compare the dynamics of pre-recurrence TMs at liver and lung recurrence sites. METHODS Patients with isolated postoperative liver or lung recurrence as their first recurrence were enrolled. Starting from the recurrence date confirmed by imaging examinations, the values of TMs (carbohydrate antigen 19-9: CA19-9; carcinoembryonic antigen: CEA) were retrospectively evaluated 6 and 3 months before recurrence and at the time of recurrence. RESULTS Patients with liver recurrence displayed a significant increase in CA19-9 and CEA levels from as early as 6 months before recurrence. Contrastingly, patients with lung recurrence demonstrated a significant elevation of CA19-9 levels starting from 3 months before recurrence, with no increase in CEA levels, even at the time of recurrence. The relative change in CA19-9 and CEA levels during each period were significantly lower in patients with lung recurrence. CONCLUSIONS Both TMs exhibited organ-specific variations in patients with postoperative PC recurrence. This disparity may reflect the biological heterogeneity of PC between recurrence patterns, thereby highlighting the importance of conducting postoperative follow-up with consideration of this fact.
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Affiliation(s)
- Satoru Miyahara
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan
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11
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Tanemura M, Furukawa K, Mikamori M, Asaoka T, Yasuoka H, Marukawa D, Urata Y, Yamada D, Kobayashi S, Eguchi H. Clinical impact of high-quality testing for peritoneal lavage cytology in pancreatic cancer. Sci Rep 2024; 14:10199. [PMID: 38702437 PMCID: PMC11068862 DOI: 10.1038/s41598-024-60936-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 04/29/2024] [Indexed: 05/06/2024] Open
Abstract
In pancreatic ductal adenocarcinoma (PDAC) patients, the importance of peritoneal lavage cytology, which indicates unresectability, remains controversial. This study sought to determine whether positive peritoneal lavage cytology (CY+) precludes pancreatectomy. Furthermore, we propose a novel liquid biopsy using peritoneal lavage fluid to detect viable peritoneal tumor cells (v-PTCs) with TelomeScan F35, a telomerase-specific replication-selective adenovirus engineered to express green fluorescent protein. Resectable cytologically or histologically proven PDAC patients (n = 53) were enrolled. CY was conducted immediately following laparotomy. The resulting fluid was examined by conventional cytology (conv-CY; Papanicolaou staining and MOC-31 immunostaining) and by the novel technique (Telo-CY; using TelomeScan F35). Of them, 5 and 12 were conv-CY+ and Telo-CY+, respectively. All underwent pancreatectomy. The two double-CY+ (conv-CY+ and Telo-CY+) patients showed early peritoneal recurrence (P-rec) postoperatively, despite adjuvant chemotherapy. None of the three conv-CY+ Telo-CY- patients exhibited P-rec. Six of the 10 Telo-CY+ conv-CY- patients (60%) relapsed with P-rec. Of the remaining 38 double-CY- [conv-CY-, Telo-CY-, conv-CY± (Class III)] patients, 3 (8.3%) exhibited P-rec. Although conv-CY+ status predicted poor prognosis and a higher risk of P-rec, Telo-CY was more sensitive for detecting v-PTC. Staging laparoscopy and performing conv-CY and Telo-CY are needed to confirm the indication for pancreatectomy.
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Affiliation(s)
- Masahiro Tanemura
- Department of Surgery, Rinku General Medical Center, 2-23 Rinku Orai-kita, Izumisano, Osaka, 598-8577, Japan.
| | - Kenta Furukawa
- Department of Surgery, Osaka Police Hospital, 10-31 Kitayamachyo, Tennouji-ku, Osaka, 543-0035, Japan
| | - Manabu Mikamori
- Department of Surgery, Osaka Police Hospital, 10-31 Kitayamachyo, Tennouji-ku, Osaka, 543-0035, Japan
| | - Tadafumi Asaoka
- Department of Surgery, Osaka Police Hospital, 10-31 Kitayamachyo, Tennouji-ku, Osaka, 543-0035, Japan
| | - Hironao Yasuoka
- Department of Pathology, Osaka Police Hospital, 10-31 Kitayamachyo, Tennouji-ku, Osaka, 543-0035, Japan
| | - Daiki Marukawa
- Department of Surgery, Rinku General Medical Center, 2-23 Rinku Orai-kita, Izumisano, Osaka, 598-8577, Japan
| | - Yasuo Urata
- Oncolys BioPharma Inc., Toranomon Towers 10F, 4-1-28 Toranomon, Minato-ku, Tokyo, 105-0001, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine and Faculty of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine and Faculty of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine and Faculty of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
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12
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Miyahara S, Takahashi H, Akita H, Sasaki K, Mukai Y, Iwagami Y, Hasegawa S, Yamada D, Tomimaru Y, Noda T, Wada H, Kobayashi S, Doki Y, Eguchi H. Prognostic Significance of Biologic Factors in Patients with a Modest Radiologic Response to Neoadjuvant Treatment for Resectable and Borderline Resectable Pancreatic Cancers: Impact of the Combination Index of Sialyl-Lewis Antigen-Related Tumor Markers. Ann Surg Oncol 2024; 31:2932-2942. [PMID: 38368291 DOI: 10.1245/s10434-024-14945-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 01/04/2024] [Indexed: 02/19/2024]
Abstract
BACKGROUND Appropriate re-evaluation after neoadjuvant treatment (NAT) is important for optimal treatment selection. Nonetheless, determining the operative eligibility of patients with a modest radiologic response remains controversial. This study aimed to assess the prognostic significance of biologic factors for patients showing a modest radiologic response to NAT and investigate the tumor markers (TMs), CA19-9 alone, DUPAN-II alone, and their combination, to create an index that combines these sialyl-Lewis antigen-related TMs associated with treatment outcomes. METHODS This study enrolled patients deemed to have a "stable disease" by RECIST classification with slight progression (tumor size increase rate, ≤20%) as their radiologic response after NAT. A sialyl-Lewis-related index (sLe index), calculated by adding one fourth of the serum DUPAN-II value to the CA19-9 value, was created. The prognostic significances of CA19-9, DUPAN-II, and the sLe index were assessed in relation to postoperative outcomes. RESULTS An sLe index lower than the cutoff value (45.25) was significantly associated with favorable disease-free survival. Moreover, the post-NAT sLe index had a higher area under the curve value for recurrence within 24 months than the post-NAT levels of CA19-9 or DUPAN-II alone. Multivariable analysis showed that a post-NAT sLe index higher than 45.25 was the single independent predictive factor for recurrence within 24 months. CONCLUSIONS Additional evaluation of biologic factors can potentially enhance patient selection, particularly for patients showing a limited radiologic response to NAT. The authors' index is a simple indicator for the biologic evaluation of multiple combined sialyl-Lewis antigen-related TMs and may offer a better predictive significance.
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Affiliation(s)
- Satoru Miyahara
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka City, Osaka, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka City, Osaka, Japan.
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka City, Osaka, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yosuke Mukai
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka City, Osaka, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Shinichiro Hasegawa
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka City, Osaka, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka City, Osaka, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
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13
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Jethwa KR, Kim E, Berlin J, Anker CJ, Tchelebi L, Abood G, Hallemeier CL, Jabbour S, Kennedy T, Kumar R, Lee P, Sharma N, Small W, Williams V, Russo S. Executive Summary of the American Radium Society Appropriate Use Criteria for Neoadjuvant Therapy for Nonmetastatic Pancreatic Adenocarcinoma: Systematic Review and Guidelines. Am J Clin Oncol 2024; 47:185-199. [PMID: 38131628 DOI: 10.1097/coc.0000000000001076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
For patients with locoregionally confined pancreatic ductal adenocarcinoma (PDAC), margin-negative surgical resection is the only known curative treatment; however, the majority of patients are not operable candidates at initial diagnosis. Among patients with resectable disease who undergo surgery alone, the 5-year survival remains poor. Adjuvant therapies, including systemic therapy or chemoradiation, are utilized as they improve locoregional control and overall survival. There has been increasing interest in the use of neoadjuvant therapy to obtain early control of occult metastatic disease, allow local tumor response to facilitate margin-negative resection, and provide a test of time and biology to assist with the selection of candidates most likely to benefit from radical surgical resection. However, limited guidance exists regarding the relative effectiveness of treatment options. In this systematic review, the American Radium Society multidisciplinary gastrointestinal expert panel convened to develop Appropriate Use Criteria evaluating the evidence regarding neoadjuvant treatment for patients with PDAC, including surgery, systemic therapy, and radiotherapy, in terms of oncologic outcomes and quality of life. The evidence was assessed using the Population, Intervention, Comparator, Outcome, and Study (PICOS) design framework and "Preferred Reporting Items for Systematic Reviews and Meta-analyses" 2020 methodology. Eligible studies included phases 2 to 3 trials, meta-analyses, and retrospective analyses published between January 1, 2012 and December 30, 2022 in the Ovid Medline database. A summary of recommendations based on the available literature is outlined to guide practitioners in the management of patients with PDAC.
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Affiliation(s)
- Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, MN
| | - Ed Kim
- Department of Radiation Oncology, University of Washington, Seattle, WA
| | - Jordan Berlin
- Department of Medicine, Division of Hematology-Oncology, Vanderbilt-Ingram Cancer Center, Nashville, TN
| | - Christopher J Anker
- Department of Radiation Oncology, University of Vermont Larner College of Medicine, Burlington, VT
| | - Leila Tchelebi
- Department of Radiation Oncology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead
| | | | | | | | - Timothy Kennedy
- Department of Surgery, Rutgers Cancer Institute, New Brunswick, NJ
| | - Rachit Kumar
- Department of Radiation Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Sibley Memorial Hospital, Washington DC
| | - Percy Lee
- Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, CA
| | - Navesh Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, York, PA
| | - William Small
- Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, IL
| | - Vonetta Williams
- Department of Radiation Oncology, Memorial Sloan Kettering, New York, NY
| | - Suzanne Russo
- Department of Radiation Oncology, University Hospitals Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH
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14
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Leonhardt CS, Hank T, Pils D, Gustorff C, Sahora K, Schindl M, Verbeke CS, Strobel O, Klaiber U. Prognostic impact of resection margin status on survival after neoadjuvant treatment for pancreatic cancer: systematic review and meta-analysis. Int J Surg 2024; 110:453-463. [PMID: 38315795 PMCID: PMC10793837 DOI: 10.1097/js9.0000000000000792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 09/10/2023] [Indexed: 02/07/2024]
Abstract
BACKGROUND A greater than 1 mm tumour-free resection margin (R0 >1 mm) is a prognostic factor in upfront-resected pancreatic ductal adenocarcinoma. After neoadjuvant treatment (NAT); however, the prognostic impact of resection margin (R) status remains controversial. METHODS Randomised and non-randomised studies assessing the association of R status and survival in resected pancreatic ductal adenocarcinoma after NAT were sought by systematic searches of MEDLINE, Web of Science and CENTRAL. Hazard ratios (HR) and their corresponding 95% CI were collected to generate log HR using the inverse-variance method. Random-effects meta-analyses were performed and the results presented as weighted HR. Sensitivity and meta-regression analyses were conducted to account for different surgical procedures and varying length of follow-up, respectively. RESULTS Twenty-two studies with a total of 4929 patients were included. Based on univariable data, R0 greater than 1 mm was significantly associated with prolonged overall survival (OS) (HR 1.76, 95% CI 1.57-1.97; P<0.00001) and disease-free survival (DFS) (HR 1.66, 95% CI 1.39-1.97; P<0.00001). Using adjusted data, R0 greater than 1 mm was significantly associated with prolonged OS (HR 1.65, 95% CI 1.39-1.97; P<0.00001) and DFS (HR 1.76, 95% CI 1.30-2.39; P=0.0003). Results for R1 direct were comparable in the entire cohort; however, no prognostic impact was detected in sensitivity analysis including only partial pancreatoduodenectomies. CONCLUSION After NAT, a tumour-free margin greater than 1 mm is independently associated with improved OS as well as DFS in patients undergoing surgical resection for pancreatic cancer.
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Affiliation(s)
- Carl-Stephan Leonhardt
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Thomas Hank
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Dietmar Pils
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Charlotte Gustorff
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Klaus Sahora
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Martin Schindl
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Caroline S. Verbeke
- Department of Pathology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Oliver Strobel
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Ulla Klaiber
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
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15
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Takahashi H, Akita H, Wada H, Miyata H, Eguchi H, Ohigashi H, Sakon M, Ishikawa O. Pathological Nodal and Vascular Involvement Significantly Impacts the Recurrence Risk in Different Time Frames in Patients With Resectable and Borderline Resectable Pancreatic Cancer: Long-term Conditional Recurrence-free Survival Analysis in the Setting of a Neoadjuvant Treatment Strategy. Ann Surg 2023; 278:e1216-e1223. [PMID: 37057622 DOI: 10.1097/sla.0000000000005879] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/15/2023]
Abstract
OBJECTIVE To investigate the long-term dynamics of recurrence risk and the significance of prognostic variables using conditional recurrence-free survival (C-RFS) analysis in neoadjuvant treatment (NAT) for resectable (R) and borderline resectable (BR) pancreatic cancer (PC). BACKGROUND C-RFS analysis assesses the probability of achieving additional RFS according to the RFS already accrued. METHODS Patients with NAT and subsequent resection for R/BRPC were enrolled. In the C-RFS analysis, the actual 5-year RFS (5yRFS) rate was calculated separately in the subgroup that had already gained a given amount of RFS. The significance levels of prognostic variables associated with 5yRFS were assessed regarding their time-dependent dynamics in a conditional fashion. RESULTS Among the total 397 patients, 160 survived for more than 5 years without recurrence after surgery (actual 5yRFS rate: 45%). The probability of 5yRFS incrementally increased based on the RFS already accrued. Pathological nodal and vascular involvement were significant influencers of 5yRFS. The patients with nodal involvement consistently remained at significantly higher risk of recurrence than those without, even after 5yRFS, whereas positivity of vascular involvement was significantly associated with the risk of recurrence only during the early postoperative period and lost its significance after 3yRFS accrued. CONCLUSIONS In NAT for R/BRPC, the probability of gaining additional RFS increases as a function of RFS already accrued, and the significance of prognostic variables time-dependently evolves in their own patterns during the long-term postoperative period.
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Affiliation(s)
- Hidenori Takahashi
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hiroshi Miyata
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hiroaki Ohigashi
- Department of Surgery, Social Welfare Organization, Saiseikai Imperial Gift Foundation Senri-Hospital, Suita, Japan
| | - Masato Sakon
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Osamu Ishikawa
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
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16
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Ohira S, Ikawa T, Kanayama N, Minamitani M, Kihara S, Inui S, Ueda Y, Miyazaki M, Yamashita H, Nishio T, Koizumi M, Nakagawa K, Konishi K. Dual-energy computed tomography-based iodine concentration as a predictor of histopathological response to preoperative chemoradiotherapy for pancreatic cancer. JOURNAL OF RADIATION RESEARCH 2023; 64:940-947. [PMID: 37839063 PMCID: PMC10665298 DOI: 10.1093/jrr/rrad076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 09/08/2023] [Indexed: 10/17/2023]
Abstract
To explore predictors of the histopathological response to preoperative chemoradiotherapy (CRT) in patients with pancreatic cancer (PC) using dual-energy computed tomography-reconstructed images. This retrospective study divided 40 patients who had undergone preoperative CRT (50-60 Gy in 25 fractions) followed by surgical resection into two groups: the response group (Grades II, III and IV, evaluated from surgical specimens) and the nonresponse group (Grades Ia and Ib). The computed tomography number [in Hounsfield units (HUs)] and iodine concentration (IC) were measured at the locations of the aorta, PC and pancreatic parenchyma (PP) in the contrast-enhanced 4D dual-energy computed tomography images. Logistic regression analysis was performed to identify predictors of histopathological response. Univariate analysis did not reveal a significant relation between any parameter and patient characteristics or dosimetric parameters of the treatment plan. The HU and IC values in PP and the differences in HU and IC between the PP and PC (ΔHU and ΔIC, respectively) were significant predictors for distinguishing the response (n = 24) and nonresponse (n = 16) groups (P < 0.05). The IC in PP and ΔIC had a higher area under curve values [0.797 (95% confidence interval, 0.659-0.935) and 0.789 (0.650-0.928), respectively] than HU in PP and ΔHU [0.734 (0.580-0.889) and 0.721 (0.562-0.881), respectively]. The IC value could potentially be used for predicting the histopathological response in patients who have undergone preoperative CRT.
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Affiliation(s)
- Shingo Ohira
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
- Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Comprehensive Radiation Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Toshiki Ikawa
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Naoyuki Kanayama
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Masanari Minamitani
- Department of Comprehensive Radiation Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Sayaka Kihara
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Shoki Inui
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Yoshihiro Ueda
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Masayoshi Miyazaki
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Hideomi Yamashita
- Department of Radiology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Teiji Nishio
- Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Masahiko Koizumi
- Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Keiichi Nakagawa
- Department of Comprehensive Radiation Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Koji Konishi
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
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Ueda H, Takahashi H, Kobayashi S, Sasaki K, Iwagami Y, Yamada D, Tomimaru Y, Asaoka T, Noda T, Tanemura M, Doki Y, Eguchi H. Pancreatic cancer near the splenic hilum has a higher likelihood of splenic vessel invasion and unfavorable survival. Langenbecks Arch Surg 2023; 408:353. [PMID: 37695403 DOI: 10.1007/s00423-023-03089-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 08/29/2023] [Indexed: 09/12/2023]
Abstract
PURPOSE This study aimed to investigate whether clinical outcomes varied based on the tumor location within the pancreatic body and tail in patients with pancreatic cancer (PC). METHODS Ninety-five patients who had undergone a distal pancreatectomy for resectable (R) or borderline resectable (BR) PC within the pancreatic body or tail region were retrospectively investigated and divided into four groups (three subgroups of R-PC according to tumor location, and BR-PC): R-PC in the pancreatic body region (group A, n = 24), R-PC on the right side of the pancreatic tail region (group B, n = 17), R-PC on the left side of the pancreatic tail region (group C, n = 29), and BR-PC located in any region within the pancreatic body and tail (group BR, n = 25). RESULTS Group C patients showed a higher incidence of pretreatment splenic artery and vein involvement than group A and B patients (splenic artery: 8.3/11.8/41.4%, p < 0.010; splenic vein: 25.0/23.5/79.3%, p < 0.010, in groups A/B/C, respectively). The overall survival of group C patients was significantly unfavorable compared to that of group A and B patients (median: 3.9/4.2/2.3 years in groups A/B/C, p = 0.029, respectively). Pretreatment clinical factors were comparable between group C and group BR. Median survival rates were comparable between group C and BR patients (2.3 and 2.0 years, respectively) (p = 0.93). CONCLUSIONS Differences in anatomical location within the pancreatic body and tail characterize the unfavorable outcomes of PC near the splenic hilum.
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Affiliation(s)
- Hiroki Ueda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshihumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Surgery, Osaka Police Hospital, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Masahiro Tanemura
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Surgery, Rinku General Medical Center, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-15, Yamadaoka, Suita, Osaka, 565-0871, Japan
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18
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Falco M, Masojć B, Sulikowski T. Radiotherapy in Pancreatic Cancer: To Whom, When, and How? Cancers (Basel) 2023; 15:3382. [PMID: 37444492 DOI: 10.3390/cancers15133382] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 06/17/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
The diagnosis rate of pancreatic cancer is steadily increasing. The average age of onset is close to 70 years. In most cases, the disease is diagnosed at an advanced stage. The indications for and techniques of radiotherapy are changing over time. The aim of this thesis is to present the role and possibilities of radiotherapy from the perspective of radiation oncologist. The most common cause of treatment failure in pancreatic cancer remains generalisation. The implementation of new systemic treatment regimens contributes to improved treatment outcomes regardless of the stage of the disease. With improved treatment outcomes in terms of the incidence of distant metastases, the impact of local curability on the length and quality of life of patients increases. Modern radiotherapy offers the opportunity to achieve high local cure rates. Postoperative radiotherapy in combination with chemotherapy seems justified in the group of postoperative pancreatic cancer patients with pT3 and pN+ features. In the group of patients with borderline resectable pancreatic cancer, the impact of radiotherapy in combination with the latest chemotherapy regimens is difficult to define clearly. In the setting of a diagnosis of advanced pancreatic cancer, radiotherapy, especially stereotactic radiotherapy, in combination with chemotherapy, contributes to improved local curability and allows to achieve a significantly reduced level of pain.
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Affiliation(s)
- Michał Falco
- Radiation Oncology Department, West Pomeranian Oncology Center, Strzałowska 22, 71-730 Szczecin, Poland
- Hospicjum Św. Jana Ewnagelisty, Pokoju 77, 71-740 Szczecin, Poland
| | - Bartłomiej Masojć
- Radiation Oncology Department, West Pomeranian Oncology Center, Strzałowska 22, 71-730 Szczecin, Poland
| | - Tadeusz Sulikowski
- Department of General, Minimally Invasive, and Gastroenterological Surgery, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland
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Hasegawa S, Takahashi H, Akita H, Mukai Y, Mikamori M, Asukai K, Yamada D, Wada H, Fujii Y, Sugase T, Yamamoto M, Takeoka T, Shinno N, Hara H, Kanemura T, Haraguchi N, Nishimura J, Matsuda C, Yasui M, Omori T, Miyata H, Ohue M, Ishikawa O, Sakon M. DUPAN-II normalisation as a biological indicator during preoperative chemoradiation therapy for resectable and borderline resectable pancreatic cancer. BMC Cancer 2023; 23:63. [PMID: 36653747 PMCID: PMC9850710 DOI: 10.1186/s12885-023-10512-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 01/04/2023] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Duke pancreatic mono-clonal antigen type 2 (DUPAN-II) is a famous tumour maker for pancreatic cancer (PC) as well as carbohydrate antigen 19-9 (CA19-9). We evaluated the clinical implications of DUPAN-II levels as a biological indicator for PC during preoperative chemoradiation therapy (CRT). METHODS This retrospective analysis included data from 221 consecutive patients with resectable and borderline resectable PC at diagnosis who underwent preoperative CRT between 2008 and 2017. We focused on 73 patients with elevated pre-CRT DUPAN-II levels (> 230 U/mL; more than 1.5 times the cut-off value for the normal range). Pre- and post-CRT DUPAN-II levels and the changes in DUPAN-II ratio were measured. RESULTS Univariate analysis identified normalisation of DUPAN-II levels after CRT as a significant prognostic factor (hazard ratio [HR] = 2.06, confidence interval [CI] = 1.03-4.24, p = 0.042). Total normalisation ratio was 49% (n = 36). Overall survival (OS) in patients with normalised DUPAN-II levels was significantly longer than that in 73 patients with elevated levels (5-year survival, 55% vs. 21%, p = 0.032) and in 60 patients who underwent tumour resection (5-year survival, 59% vs. 26%, p = 0.039). CONCLUSION Normalisation of DUPAN-II levels during preoperative CRT was a significant prognostic factor and could be an indicator to monitor treatment efficacy and predict patient prognosis.
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Affiliation(s)
- Shinichiro Hasegawa
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Hidenori Takahashi
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan ,grid.136593.b0000 0004 0373 3971Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871 Japan
| | - Hirofumi Akita
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Yosuke Mukai
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Manabu Mikamori
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Kei Asukai
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Daisaku Yamada
- grid.136593.b0000 0004 0373 3971Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871 Japan
| | - Hiroshi Wada
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Yoshiaki Fujii
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Takahito Sugase
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Masaaki Yamamoto
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Tomohira Takeoka
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Naoki Shinno
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Hisashi Hara
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Takashi Kanemura
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Naotsugu Haraguchi
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Junichi Nishimura
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Chu Matsuda
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Masayoshi Yasui
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Takeshi Omori
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Hiroshi Miyata
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Masayuki Ohue
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Osamu Ishikawa
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
| | - Masato Sakon
- grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-Ku, Osaka, 541-8567 Japan
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Sardar M, Recio-Boiles A, Mody K, Karime C, Chandana SR, Mahadevan D, Starr J, Jones J, Borad M, Babiker H. Pharmacotherapeutic options for pancreatic ductal adenocarcinoma. Expert Opin Pharmacother 2022; 23:2079-2089. [PMID: 36394449 DOI: 10.1080/14656566.2022.2149322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy projected to be the 2nd leading cause of cancer related death in the USA by 2030. This manuscript discusses current and evolving treatment approaches in patients with pancreatic cancer. AREAS COVERED PDAC is classified as: a) resectable, b) borderline resectable, c) unresectable (locally advanced and metastatic). The standard of care for patients who present with resectable pancreatic adenocarcinoma is six months of adjuvant modified (m) FOLFIRINOX, gemcitabine plus capecitabine, or single agent gemcitabine. For many reasons, there has been a paradigm shift to employing neoadjuvant chemotherapy. For resectable and borderline resectable patients, we generally start with systemic therapy and reevaluate resectability with subsequent scans specifically when the tumor is located in the head or body of the pancreas. Combined chemoradiation therapy can be employed in select patients. The standard of care for metastatic PDAC is FOLFIRINOX or gemcitabine and nab-paclitaxel. Germline and somatic genomic profiling should be obtained in all patients. Patients with a germline BRCA mutation can receive upfront gemcitabine and cisplatin. EXPERT OPINION Thorough understanding of molecular pathogenesis in PDAC has opened various therapeutic avenues. We remain optimistic that future treatment modalities such as targeted therapies, cellular therapies and immunotherapy will further improve survival in PDAC.
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Affiliation(s)
- Muhammad Sardar
- Division of Hematology-Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, Az, USA
| | - Alejandro Recio-Boiles
- Division of Hematology-Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, Az, USA
| | - Kabir Mody
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
| | | | | | - Daruka Mahadevan
- Division of Hematology and Oncology, Department of Medicine, University of Texas, San Antonio, Texas, USA
| | - Jason Starr
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
| | - Jeremy Jones
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
| | - Mitesh Borad
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Phoenix, AZ, USA
| | - Hani Babiker
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
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21
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Katz MHG, Shi Q, Meyers J, Herman JM, Chuong M, Wolpin BM, Ahmad S, Marsh R, Schwartz L, Behr S, Frankel WL, Collisson E, Leenstra J, Williams TM, Vaccaro G, Venook A, Meyerhardt JA, O’Reilly EM. Efficacy of Preoperative mFOLFIRINOX vs mFOLFIRINOX Plus Hypofractionated Radiotherapy for Borderline Resectable Adenocarcinoma of the Pancreas: The A021501 Phase 2 Randomized Clinical Trial. JAMA Oncol 2022; 8:1263-1270. [PMID: 35834226 PMCID: PMC9284408 DOI: 10.1001/jamaoncol.2022.2319] [Citation(s) in RCA: 164] [Impact Index Per Article: 54.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 04/27/2022] [Indexed: 01/10/2023]
Abstract
Importance National guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDAC), but the optimal strategy remains unclear. Objective To compare treatment with neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) with or without hypofractionated radiation therapy with historical data and establish standards for therapy in borderline resectable PDAC. Design, Setting, and Participants This prospective, multicenter, randomized phase 2 clinical trial conducted from February 2017 to January 2019 among member institutions of National Clinical Trials Network cooperative groups used standardized quality control measures and included 126 patients, of whom 70 (55.6%) were registered to arm 1 (systemic therapy; 54 randomized, 16 following closure of arm 2 at interim analysis) and 56 (44.4%) to arm 2 (systemic therapy and sequential hypofractionated radiotherapy; all randomized before closure). Data were analyzed by the Alliance Statistics and Data Management Center during September 2021. Interventions Arm 1: 8 treatment cycles of mFOLFIRINOX (oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2) over 46 hours, administered every 2 weeks. Arm 2: 7 treatment cycles of mFOLFIRINOX followed by stereotactic body radiotherapy (33-40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions). Patients without disease progression underwent pancreatectomy, which was followed by 4 cycles of treatment with postoperative FOLFOX6 (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; bolus fluorouracil, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2 over 46 hours). Main Outcomes and Measures Each treatment arm's 18-month overall survival (OS) rate was compared with a historical control rate of 50%. A planned interim analysis mandated closure of either arm for which 11 or fewer of the first 30 accrued patients underwent margin-negative (R0) resection. Results Of 126 patients, 62 (49%) were women, and the median (range) age was 64 (37-83) years. Among the first 30 evaluable patients enrolled to each arm, 17 patients in arm 1 (57%) and 10 patients in arm 2 (33%) had undergone R0 resection, leading to closure of arm 2 but continuation to full enrollment in arm 1. The 18-month OS rate of evaluable patients was 66.7% (95% CI, 56.1%-79.4%) in arm 1 and 47.3% (95% CI 35.8%-62.5%) in arm 2. The median OS of evaluable patients in arm 1 and arm 2 was 29.8 (95% CI, 21.1-36.6) months and 17.1 (95% CI, 12.8-24.4) months, respectively. Conclusions and Relevance This randomized clinical trial found that treatment with neoadjuvant mFOLFIRINOX alone was associated with favorable OS in patients with borderline resectable PDAC compared with mFOLFIRINOX treatment plus hypofractionated radiotherapy; thus, mFOLFIRINOX represents a reference regimen in this setting. Trial Registration ClinicalTrials.gov Identifier: NCT02839343.
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Affiliation(s)
| | - Qian Shi
- Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, Minnesota
| | - Jeff Meyers
- Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, Minnesota
| | - Joseph M. Herman
- Northwell Cancer Institute, National Cancer Institute Community Oncology Research Program, Manhasset, New York
| | | | | | - Syed Ahmad
- University of Cincinnati, Cincinnati, Ohio
| | - Robert Marsh
- NorthShore University Health System, Evanston, Illinois
| | | | | | - Wendy L. Frankel
- The Ohio State University Arthur G James Cancer Hospital, Columbus
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22
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An C, Li D, Li S, Li W, Tong T, Liu L, Jiang D, Jiang L, Ruan G, Hai N, Fu Y, Wang K, Zhuo S, Tian J. Deep learning radiomics of dual-energy computed tomography for predicting lymph node metastases of pancreatic ductal adenocarcinoma. Eur J Nucl Med Mol Imaging 2022; 49:1187-1199. [PMID: 34651229 DOI: 10.1007/s00259-021-05573-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 09/22/2021] [Indexed: 12/13/2022]
Abstract
PURPOSE Diagnosis of lymph node metastasis (LNM) is critical for patients with pancreatic ductal adenocarcinoma (PDAC). We aimed to build deep learning radiomics (DLR) models of dual-energy computed tomography (DECT) to classify LNM status of PDAC and to stratify the overall survival before treatment. METHODS From August 2016 to October 2020, 148 PDAC patients underwent regional lymph node dissection and scanned preoperatively DECT were enrolled. The virtual monoenergetic image at 40 keV was reconstructed from 100 and 150 keV of DECT. By setting January 1, 2021, as the cut-off date, 113 patients were assigned into the primary set, and 35 were in the test set. DLR models using VMI 40 keV, 100 keV, 150 keV, and 100 + 150 keV images were developed and compared. The best model was integrated with key clinical features selected by multivariate Cox regression analysis to achieve the most accurate prediction. RESULTS DLR based on 100 + 150 keV DECT yields the best performance in predicting LNM status with the AUC of 0.87 (95% confidence interval [CI]: 0.85-0.89) in the test cohort. After integrating key clinical features (CT-reported T stage, LN status, glutamyl transpeptadase, and glucose), the AUC was improved to 0.92 (95% CI: 0.91-0.94). Patients at high risk of LNM portended significantly worse overall survival than those at low risk after surgery (P = 0.012). CONCLUSIONS The DLR model showed outstanding performance for predicting LNM in PADC and hold promise of improving clinical decision-making.
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Affiliation(s)
- Chao An
- Department of Minimal Invasive Intervention, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China
| | - Dongyang Li
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Sheng Li
- Department of Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Wangzhong Li
- Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Tong Tong
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
- School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Lizhi Liu
- Department of Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Dongping Jiang
- Department of Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Linling Jiang
- Department of Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Guangying Ruan
- Department of Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Ning Hai
- Department of Ultrasound, Beijing Chao Yang Hospital, Capital Medical University, Beijing, 100010, China
| | - Yan Fu
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Kun Wang
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
- School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China.
| | - Shuiqing Zhuo
- Department of Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
| | - Jie Tian
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China.
- CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
- School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China.
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Long-Term Outcome of Patients with Postoperative Refractory Diarrhea After Tailored Nerve Plexus Dissection Around the Major Visceral Arteries During Pancreatoduodenectomy for Pancreatic Cancer. World J Surg 2022; 46:1172-1182. [PMID: 35119513 DOI: 10.1007/s00268-022-06457-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND For pancreatic ductal adenocarcinoma (PDAC) surgery, extended dissection of the nerve plexus (pl) around the superior mesenteric artery (SMA) or celiac artery (CA) is sometimes necessary. This consequently results in postoperative refractory diarrhea. This study aimed to evaluate the clinical impact of extended nerve plexus dissection around major arteries on postoperative diarrhea. METHODS Patients who underwent pancreatoduodenectomy (PD) for PDAC between January 2013 and December 2016 were included. The frequency of diarrhea (defined as a condition requiring opioid antidiarrheal drug for at least 6 months after surgery) and its short- and long-term outcomes were reviewed. RESULTS Of 200 consecutive patients who underwent PD, 78 (39.0%) developed postoperative refractory diarrhea (diarrhea group), and 73 of them (93.6%) underwent hemi-circumferential or more nerve dissection for SMA or CA; both plSMA and plCA dissection were associated with diarrhea. Borderline resectable artery (BR-A) PDAC was included more in the diarrhea group (32.0% vs. 13.1%, P = 0.001); however, the local recurrence rate in the diarrhea group was significantly lower than that in the non-diarrhea group (14.1% vs. 26.2%, P = 0.036). The completion of adjuvant chemotherapy and overall survival were comparable between the two groups. The pre-albumin level improved in 2 years, and 61.3% of patients with diarrhea could stop opioid antidiarrheal drugs within 3 years of surgery. CONCLUSIONS Although the frequency of diarrhea increased following nerve plexus dissection around arteries, diarrhea was controllable and resulted in a reduced local recurrence rate. Aggressive dissection of the nerve plexus may be justified for local disease control in BR-A PDAC.
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24
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Ikezawa K, Ekawa T, Hasegawa S, Kai Y, Takada R, Yamai T, Fukutake N, Ogawa H, Akazawa T, Mizote Y, Tatsumi K, Nagata S, Asukai K, Takahashi H, Ohkawa K, Tahara H. Establishment of organoids using residual samples from saline flushes during endoscopic ultrasound-guided fine-needle aspiration in patients with pancreatic cancer. Endosc Int Open 2022; 10:E82-E87. [PMID: 35036290 PMCID: PMC8752201 DOI: 10.1055/a-1713-3404] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 10/07/2021] [Indexed: 11/04/2022] Open
Abstract
Background and study aims In patients with pancreatic cancer (PC), patient-derived organoid cultures can be useful tools for personalized drug selection and preclinical evaluation of novel therapies. To establish a less invasive method of creating organoids from a patient's tumor, we examined whether PC organoids can be established using residual samples from saline flushes (RSSFs) during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Methods Five patients with PC who underwent EUS-FNA were enrolled in a prospective study conducted at our institution. RSSFs obtained during EUS-FNA procedures were collected. An organoid culture was considered as established when ≥ 5 passages were successful. Organoid-derived xenografts were created using established organoids. Results EUS-FNA was performed using a 22- or 25-gauge lancet needle without complications. Patient-derived organoids were successfully established in four patients (80.0 %) with the complete medium and medium for the selection of KRAS mutants. Organoid-derived xenografts were successfully created and histologically similar to EUS-FNA samples. Conclusions Patient-derived PC organoids were successfully established using EUS-FNA RSSFs, which are produced as a byproduct of standard manipulations, but are usually not used for diagnosis. This method can be applied to all patients with PC, without additional invasive procedures, and can contribute to the development of personalized medicine and molecular research.
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Affiliation(s)
- Kenji Ikezawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Tomoya Ekawa
- Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute, Osaka, Japan
| | | | - Yugo Kai
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Ryoji Takada
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Takuo Yamai
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Nobuyasu Fukutake
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Hisataka Ogawa
- Nitto Joint Research Department for Nucleic Acid Medicine, Research Center, Osaka International Cancer Institute, Osaka, Japan
| | - Takashi Akazawa
- Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute, Osaka, Japan
| | - Yu Mizote
- Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute, Osaka, Japan
| | - Kumiko Tatsumi
- Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute, Osaka, Japan
| | - Shigenori Nagata
- Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan
| | - Kei Asukai
- Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hidenori Takahashi
- Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuyoshi Ohkawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Hideaki Tahara
- Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute, Osaka, Japan,Project Division of Cancer Biomolecular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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25
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Comment on "Usefulness of artificial intelligence for predicting recurrence following surgery for pancreatic cancer: Retrospective cohort study". Int J Surg 2021; 94:106117. [PMID: 34537395 DOI: 10.1016/j.ijsu.2021.106117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 09/11/2021] [Indexed: 11/23/2022]
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26
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Yamada D, Kobayashi S, Takahashi H, Akita H, Yamada T, Asaoka T, Shimizu J, Takeda Y, Yokoyama S, Tsujie M, Tomokuni A, Tanemura M, Morimoto O, Murakami M, Kim Y, Nakahira S, Hama N, Sugimoto K, Hashimoto K, Doki Y, Eguchi H. Randomized phase II study of gemcitabine and S-1 combination therapy versus gemcitabine and nanoparticle albumin-bound paclitaxel combination therapy as neoadjuvant chemotherapy for resectable/borderline resectable pancreatic ductal adenocarcinoma (PDAC-GS/GA-rP2, CSGO-HBP-015). Trials 2021; 22:568. [PMID: 34446057 PMCID: PMC8394677 DOI: 10.1186/s13063-021-05541-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 08/13/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, and multimodal strategies, such as surgery plus neoadjuvant chemotherapy (NAC)/adjuvant chemotherapy, have been attempted to improve survival in patients with localized PDAC. To date, there is one prospective study providing evidence for the superiority of a neoadjuvant strategy over upfront surgery for localized PDAC. However, which NAC regimen is optimal remains unclear. METHODS A randomized, exploratory trial is performed to examine the clinical benefits of two chemotherapy regimens, gemcitabine plus S-1 (GS) and gemcitabine plus nab-paclitaxel (GA), as NAC for patients with planned PDAC resection. Patients are enrolled after the diagnosis of resectable or borderline resectable PDAC. They are randomly assigned to either NAC regimen. Adjuvant chemotherapy after curative resection is highly recommended for 6 months in both arms. The primary endpoint is tumor progression-free survival time, and secondary endpoints include the rate of curative resection, the completion rate of protocol therapy, the recurrence type, the overall survival time, and safety. The target sample size is set as at least 100. DISCUSSION This study is the first randomized phase II study comparing GS combination therapy with GA combination therapy as NAC for localized pancreatic cancer. TRIAL REGISTRATION UMIN Clinical Trials Registry UMIN000021484 . This trial began in April 2016.
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Affiliation(s)
- Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
| | - Terumasa Yamada
- Department of Surgery, Higashiosaka City Medical Center, Higashiōsaka, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Osaka Police Hospital, Osaka, Japan
| | - Junzo Shimizu
- Department of Gastroenterological Surgery, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Yutaka Takeda
- Department of Gastroenterological Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | - Shigekazu Yokoyama
- Department of Gastroenterological Surgery, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan
| | - Masanori Tsujie
- Department of Gastroenterological Surgery, Osaka Rosai Hospital, Sakai, Japan
| | - Akira Tomokuni
- Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka, Japan
| | - Masahiro Tanemura
- Department of Gastroenterological Surgery, Rinku General Medical Center, Izumisano, Japan
| | - Osakuni Morimoto
- Department of Surgery, Japan Community Health Care Organization Osaka Hospital, Osaka, Japan
| | - Masahiro Murakami
- Department of Gastroenterological Surgery, Itami City Hospital, Itami, Japan
| | - Yongkook Kim
- Department of Surgery, Kaizuka City Hospital, Kaizuka, Japan
| | - Shin Nakahira
- Department of Surgery, Sakai City Medical Center, Sakai, Japan
| | - Naoki Hama
- Department of Surgery, Ikeda City Hospital, Ikeda, Japan
| | | | | | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan.
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Gantois D, Guilbaud T, Scemama U, Girard E, Picaud O, Lefevre M, Elgani M, Hamidou Z, Moutardier V, Balandraud P, Chirica M, Barbier L, Fuks D, Birnbaum DJ. Prognostic impact of splenic vessel involvement and tumor size in distal pancreatectomy for adenocarcinoma: a retrospective multicentric cohort study. Langenbecks Arch Surg 2021; 407:153-165. [PMID: 34373941 DOI: 10.1007/s00423-021-02291-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 07/28/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE Splenic vessel involvement occurs frequently in pancreatic ductal adenocarcinoma (PDAC) of the body and the tail (B/T) but the impact on survival is unknown. We assessed the influence of radiological and pathologic involvement of splenic artery (p-SA +) and vein (p-SV +) on patient outcomes after distal pancreatectomy (DP) for PDAC. METHODS From 2013 to 2019, all DP for PDAC in five centers were included. Factors associated with overall (OS) and disease-free (DFS) survival were identified. RESULTS Among the 76 patients included, 5 (6.6%) had p-SA + only, 11 (14.5%) had p-SV + only, and 24 (31.6%) had both p-SA + and p-SV + . The preoperative CT-scan accuracy to predict p-SV + and p-SA + was high (sensitivity: 91.4% and 82.8%, respectively; negative predictive value: 89.7% and 88.3%, respectively). The 5-year OS and DFS rates were 3.9% and 8.3%, respectively. Multivariate analysis identified splenic vessel involvement (i.e., p-SA + or p-SV + , or both p-SA + and p-SV +) as the only independent factor influencing DFS (HR 4.04; 95% CI [1.22-13.44], p = 0.023). Tumor size ≥ 30 mm was the only independent factor influencing OS (HR 4.04; 95% CI [1.26-12.95], p = 0.019) and was associated with a high risk of p-SA + (p = 0.001) and p-SV + (p < 0.001). CONCLUSION Tumor size ≥ 30 mm and splenic vessel involvement occurred in more than half of the patients who underwent DP for PDAC and had negative impact on long-term survival. Preoperative CT-scan was reliable to identify splenic vessel involvement in B/T PDAC. Large tumor size and radiological splenic vessel involvement could be taken into account to propose a neoadjuvant treatment.
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Affiliation(s)
- Dominique Gantois
- Department of Digestive Surgery, Hôpital Nord, Aix-Marseille University, Marseille, France
| | - Théophile Guilbaud
- Department of Digestive Surgery, Hôpital Nord, Aix-Marseille University, Marseille, France
| | - Ugo Scemama
- Department of Radiology, Hôpital Nord, Aix-Marseille University, Marseille, France
| | - Edouard Girard
- Department of Digestive Surgery and Liver Transplantation, Hôpital Michalon, Grenoble University, Grenoble, France
| | - Olivier Picaud
- Department of Digestive Surgery, Hôpital Nord, Aix-Marseille University, Marseille, France
| | - Marine Lefevre
- Department of Anatomopathology, Institut Mutualiste Montsouris, Paris, France
| | - Myriam Elgani
- Department of Anatomopathology, Hôpital Trousseau, Tours, France
| | - Zeinab Hamidou
- Self Perceived Health Assessment Research Unit and Department of Public Health, Aix-Marseille University, Chemin des Bourrely, 13915, Marseille cedex 20, France
| | - Vincent Moutardier
- Department of Digestive Surgery, Hôpital Nord, Aix-Marseille University, Marseille, France
| | - Paul Balandraud
- Department of Digestive and Oncologic Surgery, Hôpital D'Instruction des Armées St-Anne, Toulon, France
| | - Mircea Chirica
- Department of Digestive Surgery and Liver Transplantation, Hôpital Michalon, Grenoble University, Grenoble, France
| | - Louise Barbier
- Department of Digestive, Oncologic, Metabolic Surgery and Liver Transplantation, Hôpital Trousseau, Tours, France
| | - David Fuks
- Department of Digestive, Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Paris, France
| | - David Jérémie Birnbaum
- Department of Digestive Surgery, Hôpital Nord, Aix-Marseille University, Marseille, France.
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28
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Ryckman JM, Reames BN, Klute KA, Hall WA, Baine MJ, Abdel-Wahab M, Lin C. The timing and design of stereotactic radiotherapy approaches as a part of neoadjuvant therapy in pancreatic cancer: Is it time for change? Clin Transl Radiat Oncol 2021; 28:124-128. [PMID: 33981865 PMCID: PMC8085778 DOI: 10.1016/j.ctro.2021.04.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/06/2021] [Accepted: 04/07/2021] [Indexed: 12/12/2022] Open
Abstract
Stereotactic Radiotherapy (SRT) over 5-15 days can be interdigitated without delaying chemotherapy. Bridging chemotherapy may allow for extended intervals to surgery, potentially improving sterilization of surgical margins and overall survival. SRT for pancreatic adenocarcinoma should not be limited to the tumor, and should consider hypofractionated approaches to regional nodes.
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Affiliation(s)
- Jeffrey M. Ryckman
- Department of Radiation Oncology, West Virginia University Cancer Institute, Parkersburg, WV, USA
| | - Bradley N. Reames
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Kelsey A. Klute
- Department of Medical Oncology, University of Nebraska Medical Center, Omaha, NE, USA
| | - William A. Hall
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Michael J. Baine
- Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, USA
| | - May Abdel-Wahab
- Division of Human Health, International Atomic Energy Agency, Vienna, Austria
| | - Chi Lin
- Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, USA
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29
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Ohira S, Koike Y, Akino Y, Kanayama N, Wada K, Ueda Y, Masaoka A, Washio H, Miyazaki M, Koizumi M, Ogawa K, Teshima T. Improvement of image quality for pancreatic cancer using deep learning-generated virtual monochromatic images: Comparison with single-energy computed tomography. Phys Med 2021; 85:8-14. [PMID: 33940528 DOI: 10.1016/j.ejmp.2021.03.035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 02/25/2021] [Accepted: 03/30/2021] [Indexed: 01/15/2023] Open
Abstract
PURPOSE To construct a deep convolutional neural network that generates virtual monochromatic images (VMIs) from single-energy computed tomography (SECT) images for improved pancreatic cancer imaging quality. MATERIALS AND METHODS Fifty patients with pancreatic cancer underwent a dual-energy CT simulation and VMIs at 77 and 60 keV were reconstructed. A 2D deep densely connected convolutional neural network was modeled to learn the relationship between the VMIs at 77 (input) and 60 keV (ground-truth). Subsequently, VMIs were generated for 20 patients from SECT images using the trained deep learning model. RESULTS The contrast-to-noise ratio was significantly improved (p < 0.001) in the generated VMIs (4.1 ± 1.8) compared to the SECT images (2.8 ± 1.1). The mean overall image quality (4.1 ± 0.6) and tumor enhancement (3.6 ± 0.6) in the generated VMIs assessed on a five-point scale were significantly higher (p < 0.001) than that in the SECT images (3.2 ± 0.4 and 2.8 ± 0.4 for overall image quality and tumor enhancement, respectively). CONCLUSIONS The quality of the SECT image was significantly improved both objectively and subjectively using the proposed deep learning model for pancreatic tumors in radiotherapy.
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Affiliation(s)
- Shingo Ohira
- Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan; Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Suita, Japan.
| | - Yuhei Koike
- Department of Radiology, Kansai Medical University, Osaka, Japan
| | - Yuichi Akino
- Division of Medical Physics, Oncology Center, Osaka University Hospital, Suita, Japan
| | - Naoyuki Kanayama
- Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Kentaro Wada
- Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Yoshihiro Ueda
- Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Akira Masaoka
- Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Hayate Washio
- Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Masayoshi Miyazaki
- Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Masahiko Koizumi
- Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kazuhiko Ogawa
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Teruki Teshima
- Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
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30
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Nara S, Esaki M, Ban D, Takamoto T, Shimada K, Ioka T, Okusaka T, Ishii H, Furuse J. Adjuvant and neoadjuvant therapy for biliary tract cancer: a review of clinical trials. Jpn J Clin Oncol 2021; 50:1353-1363. [PMID: 33037430 DOI: 10.1093/jjco/hyaa170] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Accepted: 08/21/2020] [Indexed: 12/14/2022] Open
Abstract
Cancer originating in the biliary tract can be classified as bile duct cancer (cholangiocarcinoma), gallbladder cancer, or ampullary cancer. Bile duct cancer is further divided to intrahepatic, perihilar and distal bile duct subtypes according to the anatomical location of the tumor. The biological characteristics of each tumor are heterogeneous. However, because of the rarity of each disease, the efficacy of new drugs has been tested in groups of patients with different biliary tract cancers. In patients with metastatic or recurrent biliary tract cancer, recent randomized clinical trials revealed the non-inferiority of gemcitabine + S-1 and the superiority of gemcitabine + cisplatin + S-1 compared with gemcitabine + cisplatin in terms of overall survival, thereby establishing a new standard treatment. In the field of adjuvant therapy for biliary tract cancer, the British BILCAP (capecitabine compared with observation in resected biliary tract cancer) study revealed longer median overall survival in the capecitabine group than in the observation group in the per-protocol analysis (but not in the intention-to-treat analysis), bringing a shift toward postoperative management. Several other studies of adjuvant therapy are ongoing, and they may lead to reforms in treatment strategy for resectable biliary tract cancer in the future. The use of neoadjuvant therapy for biliary tract cancer is in its infancy, but it is expected to overcome the limitations of adjuvant therapy for this malignancy. In this review, we summarized the evidence available from clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer and described ongoing clinical trials.
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Affiliation(s)
- Satoshi Nara
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Tatsuya Ioka
- Oncology Center, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi Ube-shi, Yamaguchi, 755-8505, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Hiroshi Ishii
- Division of Gastroenterology, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba, 260-8717, Japan
| | - Junji Furuse
- Department of Medical Oncology, Kyorin University Faculty of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
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31
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Boros LG, Somlyai I, Kovács BZ, Puskás LG, Nagy LI, Dux L, Farkas G, Somlyai G. Deuterium Depletion Inhibits Cell Proliferation, RNA and Nuclear Membrane Turnover to Enhance Survival in Pancreatic Cancer. Cancer Control 2021; 28:1073274821999655. [PMID: 33760674 PMCID: PMC8204545 DOI: 10.1177/1073274821999655] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 12/18/2020] [Accepted: 01/28/2021] [Indexed: 01/05/2023] Open
Abstract
The effects of deuterium-depleted water (DDW) containing deuterium (D) at a concentration of 25 parts per million (ppm), 50 ppm, 105 ppm and the control at 150 ppm were monitored in MIA-PaCa-2 pancreatic cancer cells by the real-time cell impedance detection xCELLigence method. The data revealed that lower deuterium concentrations corresponded to lower MiA PaCa-2 growth rate. Nuclear membrane turnover and nucleic acid synthesis rate at different D-concentrations were determined by targeted [1,2-13C2]-D-glucose fate associations. The data showed severely decreased oxidative pentose cycling, RNA ribose 13C labeling from [1,2-13C2]-D-glucose and nuclear membrane lignoceric (C24:0) acid turnover. Here, we treated advanced pancreatic cancer patients with DDW as an extra-mitochondrial deuterium-depleting strategy and evaluated overall patient survival. Eighty-six (36 male and 50 female) pancreatic adenocarcinoma patients were treated with conventional chemotherapy and natural water (control, 30 patients) or 85 ppm DDW (56 patients), which was gradually decreased to preparations with 65 ppm and 45 ppm deuterium content for each 1 to 3 months treatment period. Patient survival curves were calculated by the Kaplan-Meier method and Pearson correlation was taken between medial survival time (MST) and DDW treatment in pancreatic cancer patients. The MST for patients consuming DDW treatment (n = 56) was 19.6 months in comparison with the 6.36 months' MST achieved with chemotherapy alone (n = 30). There was a strong, statistically significant Pearson correlation (r = 0.504, p < 0.001) between survival time and length and frequency of DDW treatment.
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Affiliation(s)
- László G. Boros
- Department of Pediatrics, Harbor-UCLA Medical Center and The Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
- SIDMAP, LLC, Los Angeles, CA, USA
| | - Ildikó Somlyai
- HYD LLC for Cancer Research and Drug Development, Budapest, Hungary
| | - Beáta Zs. Kovács
- HYD LLC for Cancer Research and Drug Development, Budapest, Hungary
| | | | | | - László Dux
- Department of Biochemistry, Albert Szent-Györgyi Medical University, University of Szeged, Szeged, Hungary
| | - Gyula Farkas
- Department of Surgery, Albert Szent-Györgyi Medical University, University of Szeged, Szeged, Hungary
| | - Gábor Somlyai
- HYD LLC for Cancer Research and Drug Development, Budapest, Hungary
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Wu Z, Chen W, Chen J, Cao L. WITHDRAWN: Research and application of laparoscopic precision pancreatic cancer surgery based on three-dimensional reconstruction. LAPAROSCOPIC, ENDOSCOPIC AND ROBOTIC SURGERY 2020. [DOI: 10.1016/j.lers.2020.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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Yamada D, Takahashi H, Hama N, Toshiyama R, Asukai K, Hasegawa S, Wada H, Sakon M, Ishikawa O. The clinical impact of splenic artery ligation on the occurrence of digestive varices after pancreaticoduodenectomy with combined portal vein resection: a retrospective study in two institutes. Langenbecks Arch Surg 2020; 406:1469-1479. [PMID: 33063227 DOI: 10.1007/s00423-020-02010-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 10/07/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE Pancreaticoduodenectomy (PD) concomitant with portal vein resection (PVR) often develops into digestive varices with an occurrence rate of 30-50%, and the variceal bleeding is sometimes untreatable and results in fatality. Against this issue, splenic artery (SpA) ligation during PD-PVR is emerging as an easy and effective prophylactic surgical option. The aim of this study was to investigate the significance of SpA ligation in the development of digestive varices in patients undergoing PD-PVR. METHOD We retrospectively investigated 97 patients with PDAC who received PD-PVR in two hospitals. Vascular reconstruction of the splenic vein (SpV) was not performed in either hospital. We assessed the occurrence rate of digestive varices in these patients in association with the performance of SpA ligation. RESULTS The occurrence rate of digestive varices was 23%. SpA ligation was the only significant decreasing factor for the development of digestive varices (odds ratio 0.3, p = 0.035). Although SpV resection was not a significant risk factor for the development of digestive varices in all patients, SpV resection was a significant risk factor for the development of digestive varices in patients without SpA ligation, as demonstrated in previous reports. SpA ligation did not increase surgical complications or impair pancreatic function. CONCLUSION PD-PVR surgery was accompanied by a 23% incidence of digestive varices, and SpA ligation significantly decreased the development of digestive varices without causing clinically significant complications. TRIAL REGISTRATION No. 18196 (Osaka International Cancer Institute) and no. 19006 (National Hospital Organization Osaka National Hospital).
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Affiliation(s)
- Daisaku Yamada
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan.
| | - Naoki Hama
- Department of Surgery, National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan
| | - Reishi Toshiyama
- Department of Surgery, National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan
| | - Kei Asukai
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Shinichiro Hasegawa
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Masato Sakon
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Osamu Ishikawa
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
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Ren L, Mota Reyes C, Friess H, Demir IE. Neoadjuvant therapy in pancreatic cancer: what is the true oncological benefit? Langenbecks Arch Surg 2020; 405:879-887. [PMID: 32776259 PMCID: PMC7541356 DOI: 10.1007/s00423-020-01946-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 07/22/2020] [Indexed: 01/02/2023]
Abstract
BACKGROUND Neoadjuvant therapies (neoTx) have revolutionized the treatment of borderline resectable (BR) and locally advanced (LA) pancreatic cancer (PCa) by significantly increasing the rate of R0 resections, which remains the only curative strategy for these patients. However, there is still room for improvement of neoTx in PCa. PURPOSE Here, we aimed to critically analyze the benefits of neoTx in LA and BR PCa and its potential use on patients with resectable PCa. We also explored the feasibility of arterial resection (AR) to increase surgical radicality and the incorporation of immunotherapy to optimize neoadjuvant approaches in PCa. CONCLUSION For early stage, i.e., resectable, PCa, there is not enough scientific evidence for routinely recommending neoTx. For LA and BR PCa, optimization of neoadjuvant therapy necessitates more sophisticated complex surgical resections, machine learning and radiomic approaches, integration of immunotherapy due to the high antigen load, standardized histopathological assessment, and improved multidisciplinary communication.
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Affiliation(s)
- Lei Ren
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, D-81675, Munich, Germany
- Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Carmen Mota Reyes
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, D-81675, Munich, Germany
| | - Helmut Friess
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, D-81675, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
- CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany
| | - Ihsan Ekin Demir
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, D-81675, Munich, Germany.
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.
- CRC 1321 Modelling and Targeting Pancreatic Cancer, Munich, Germany.
- Department of General Surgery, HPB Unit, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.
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Ashida R, Fukutake N, Takada R, Ioka T, Ohkawa K, Katayama K, Akita H, Takahashi H, Ohira S, Teshima T. Endoscopic ultrasound-guided fiducial marker placement for neoadjuvant chemoradiation therapy for resectable pancreatic cancer. World J Gastrointest Oncol 2020; 12:768-781. [PMID: 32864044 PMCID: PMC7428794 DOI: 10.4251/wjgo.v12.i7.768] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 04/09/2020] [Accepted: 05/12/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Preoperative neoadjuvant chemoradiation therapy (NACRT) is applied for resectable pancreatic cancer (RPC). To maximize the efficacy of NACRT, it is essential to ensure the accurate placement of fiducial markers for image-guided radiation. However, no standard method for delivering fiducial markers has been established to date, and the nature of RPC during NACRT remains unclear.
AIM To determine the feasibility, safety and benefits of endoscopic ultrasound-guided (EUS) fiducial marker placement in patients with RPC.
METHODS This was a prospective case series of 29 patients (mean age, 67.5 years; 62.1% male) with RPC referred to our facility for NACRT. Under EUS guidance, a single gold marker was placed into the tumor using either a 19- or 22-gauge fine-needle aspiration needle. The differences in daily marker positioning were measured by comparing simulation computed tomography and treatment computed tomography.
RESULTS In all 29 patients (100%) who underwent EUS fiducial marker placement, fiducials were placed successfully with only minor, self-limiting bleeding during puncture observed in 2 patients (6.9%). NACRT was subsequently administered to all patients and completed in 28/29 (96.6%) cases, with one patient experiencing repeat cholangitis. Spontaneous migration of gold markers was observed in 1 patient. Twenty-four patients (82.8%) had surgery with 91.7% (22/24) R0 resection, and two patients experienced complete remission. No inflammatory changes around the marker were observed in the surgical specimen. The daily position of gold markers showed large positional changes, particularly in the superior-inferior direction. Moreover, tumor location was affected by food and fluid intake as well as bowel gas, which changes daily.
CONCLUSION EUS fiducial marker placement following NACRT for RPC is feasible and safe. The RPC is mobile and is affected by not only aspiration, but also food and fluid intake and bowel condition.
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Affiliation(s)
- Reiko Ashida
- Department of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Nobuyasu Fukutake
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Ryoji Takada
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Tatsuya Ioka
- Department of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Kazuyoshi Ohkawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Kazuhiro Katayama
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
| | - Hidenori Takahashi
- Department of Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Shingo Ohira
- Department of Radiation Oncology, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Teruki Teshima
- Department of Radiation Oncology, Osaka International Cancer Institute, Osaka 541-8567, Japan
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Takahashi H, Yamada D, Asukai K, Wada H, Hasegawa S, Hara H, Shinno N, Ushigome H, Haraguchi N, Sugimura K, Yamamoto K, Nishimura J, Yasui M, Omori T, Miyata H, Ohue M, Yano M, Sakon M, Ishikawa O. Clinical implications of the serum CA19-9 level in "biological borderline resectability" and "biological downstaging" in the setting of preoperative chemoradiation therapy for pancreatic cancer. Pancreatology 2020; 20:919-928. [PMID: 32563596 DOI: 10.1016/j.pan.2020.05.020] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 05/18/2020] [Accepted: 05/27/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Biological factors are emphasized in borderline resectable pancreatic cancer (BRPC), and CA19-9 is an important factor for biological borderline resectability (b-BR). The aim of this study was to investigate the cut-off value of CA19-9 for biological borderline resectability and "biological downstaging" in chemoradiation therapy (CRT) for pancreatic cancer (PC). METHODS A total of 407 patients with anatomically resectable PC (a-R) and BRPC (a-BR) received preoperative gemcitabine-based CRT. The b-BR was determined, according to the CA19-9 value prior to preoperative CRT (pre-CA19-9), as the subgroup of a-R cases in which the survival was comparable with that in a-BR cases. "Biological downstaging" was determined based on prognostic analyses regarding the CA19-9 value after preoperative CRT (post-CA19-9) in association with the survival of R cases (a-R cases without the b-BR factor). RESULTS The 5-year survival of a-R patients with pre-CA19-9 > 120 U/mL was comparable with that of a-BR patients (44% vs 34%, p = 0.082). The survival of b-BR patients with post-CRT CA19-9 ≤ 37 U/mL (normalized) was comparably favorable with that of R patients (56% vs 65%, p = 0.369). The incidence of distant recurrence was higher in b-BR patients without post-CA19-9 normalization than in those with post-CA19-9 normalization (70% vs 50%, p = 0.003), while the incidence of local recurrence was comparable between these two groups (12% vs 13%, p = 0.986). CONCLUSIONS Biological BRPC was determined to be an anatomically resectable disease with pre-CA19-9 > 120 U/mL, and post-CA19-9 normalization indicated "biological downstaging" in b-BR in the preoperative CRT strategy.
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Affiliation(s)
| | - Daisaku Yamada
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Kei Asukai
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Wada
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | - Hisashi Hara
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Naoki Shinno
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hajime Ushigome
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | - Keijiro Sugimura
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | | | - Masayoshi Yasui
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takeshi Omori
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Miyata
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masayuki Ohue
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masahiko Yano
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masato Sakon
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Osamu Ishikawa
- Department of Surgery, Osaka International Cancer Institute, Japan
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A contemporary evidence basis for neoadjuvant chemotherapy in upfront resectable pancreatic adenocarcinoma: a systematic review of the literature. JOURNAL OF PANCREATOLOGY 2020. [DOI: 10.1097/jp9.0000000000000037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Tomimaru Y, Eguchi H, Iwagami Y, Akita H, Noda T, Gotoh K, Kobayashi S, Nagano H, Mori M, Doki Y. Preoperative chemoradiotherapy using gemcitabine for pancreatic ductal adenocarcinoma in patients with impaired renal function. Cancer Chemother Pharmacol 2020; 85:537-545. [PMID: 31834436 DOI: 10.1007/s00280-019-04005-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 12/04/2019] [Indexed: 10/25/2022]
Abstract
PURPOSE Preoperative chemoradiotherapy (CRT) can be a promising treatment for pancreatic ductal adenocarcinoma (PDAC). However, its administration for patients with impaired renal function has not been well investigated, let alone its clinical effect. We previously reported preliminary feasibility of CRT in PDAC patients with renal impairment. Herein, we aimed to investigate the clinical effects of preoperative CRT including safety and long-term prognosis in more PDAC patients with renal impairment as an extension to our previous work. METHODS This study enrolled twenty patients harboring resectable PDAC with creatinine clearance level less than 60 ml/min. Patients underwent preoperative CRT with gemcitabine, followed by surgery. The clinical effects of the therapy were evaluated in terms of safety and long-term prognosis. RESULTS Preoperative CRT was completed in all 20 patients. Grade 4 leukopenia/neutropenia was identified as an observed toxicity in four cases (20.0%). Renal function was not worsened after CRT. After CRT, 17 cases were judged resectable and underwent laparotomy. Pancreatic resection was performed in 15 of the 17 patients; it was not performed in two patients because of peritoneal dissemination. The 1-/3-/5-year cumulative survival rate from the initiation of CRT for the 20 patients was 88.8%/45.5%/22.8%. In the 15 patients, renal function was not worsened after surgery. CONCLUSION Our findings suggest that the clinical effects of preoperative CRT would be favorable in PDAC patients with renal impairment.
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Affiliation(s)
- Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan
| | - Kunihito Gotoh
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan
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De Jesus-Acosta A, Narang A, Mauro L, Herman J, Jaffee EM, Laheru DA. Carcinoma of the Pancreas. ABELOFF'S CLINICAL ONCOLOGY 2020:1342-1360.e7. [DOI: 10.1016/b978-0-323-47674-4.00078-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Raturi VP, Tochinai T, Hojo H, Rachi T, Hotta K, Nakamura N, Zenda S, Motegi A, Ariji T, Hirano Y, Baba H, Ohyoshi H, Nakamura M, Okumura M, Bei Y, Akimoto T. Dose-Volume and Radiobiological Model-Based Comparative Evaluation of the Gastrointestinal Toxicity Risk of Photon and Proton Irradiation Plans in Localized Pancreatic Cancer Without Distant Metastasis. Front Oncol 2020; 10:517061. [PMID: 33194580 PMCID: PMC7645056 DOI: 10.3389/fonc.2020.517061] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 09/01/2020] [Indexed: 12/25/2022] Open
Abstract
Background: Radiobiological model-based studies of photon-modulated radiotherapy for pancreatic cancer have reported reduced gastrointestinal (GI) toxicity, although the risk is still high. The purpose of this study was to investigate the potential of 3D-passive scattering proton beam therapy (3D-PSPBT) in limiting GI organ at risk (OAR) toxicity in localized pancreatic cancer based on dosimetric data and the normal tissue complication probability (NTCP) model. Methods: The data of 24 pancreatic cancer patients were retrospectively analyzed, and these patients were planned with intensity-modulated radiotherapy (IMRT), volume-modulated arc therapy (VMAT), and 3D-PSPBT. The tumor was targeted without elective nodal coverage. All generated plans consisted of a 50.4-GyE (Gray equivalent) dose in 28 fractions with equivalent OAR constraints, and they were normalized to cover 50% of the planning treatment volume (PTV) with 100% of the prescription dose. Physical dose distributions were evaluated. GI-OAR toxicity risk for different endpoints was estimated by using published NTCP Lyman-Kutcher-Burman (LKB) models. Analysis of variance (ANOVA) was performed to compare the dosimetric data, and ΔNTCPIMRT-PSPBT and ΔNTCPVMAT-PSPBT were also computed. Results: Similar homogeneity and conformity for the clinical target volume (CTV) and PTV were exhibited by all three planning techniques (P > 0.05). 3D-PSPBT resulted in a significant dose reduction for GI-OARs in both the low-intermediate dose range (below 30 GyE) and the highest dose region (D max and V 50 GyE) in comparison with IMRT and VMAT (P < 0.05). Based on the NTCP evaluation, the NTCP reduction for GI-OARs by 3D-PSPBT was minimal in comparison with IMRT and VMAT. Conclusion: 3D-PSPBT results in minimal NTCP reduction and has less potential to substantially reduce the toxicity risk of upper GI bleeding, ulceration, obstruction, and perforation endpoints compared to IMRT and VMAT. 3D-PSPBT may have the potential to reduce acute dose-limiting toxicity in the form of nausea, vomiting, and diarrhea by reducing the GI-OAR treated volume in the low-to-intermediate dose range. However, this result needs to be further evaluated in future clinical studies.
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Affiliation(s)
- Vijay P. Raturi
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
- Course of Advanced Clinical Research of Cancer, Graduate School of Medicine, Juntendo University, Tokyo, Japan
- *Correspondence: Vijay P. Raturi
| | - Taku Tochinai
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Hidehiro Hojo
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Toshiya Rachi
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Kenji Hotta
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Naoki Nakamura
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Sadamoto Zenda
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Atsushi Motegi
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Takaki Ariji
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Yasuhiro Hirano
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Hiromi Baba
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Hajime Ohyoshi
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Masaki Nakamura
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Masayuki Okumura
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Yanping Bei
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
| | - Tetsuo Akimoto
- Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital, Chiba, Japan
- Course of Advanced Clinical Research of Cancer, Graduate School of Medicine, Juntendo University, Tokyo, Japan
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Yamada D, Takahashi H, Asukai K, Hasegawa S, Tomokuni A, Wada H, Akita H, Yasui M, Miyata H, Ishikawa O. Pathological complete response (pCR) with or without the residual intraductal carcinoma component following preoperative treatment for pancreatic cancer: Revisiting the definition of "pCR" from the prognostic standpoint. Ann Gastroenterol Surg 2019; 3:676-685. [PMID: 31788656 PMCID: PMC6875936 DOI: 10.1002/ags3.12288] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 08/15/2019] [Accepted: 09/04/2019] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND AND AIM There are no previous reports describing the prognostic significance of the residual intraductal carcinoma component (carcinoma in situ [CIS]) following preoperative treatment for pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to investigate the prognostic significance of a minimal residual CIS in cases with complete absence of an invasive component after preoperative treatment for PDAC. METHODS Eighty-one of 594 PDAC patients with preoperative treatment and subsequent surgery in our institute showed remarkable remission in the invasive component, which included 48 patients with the minimal residual invasive component (Min-inv group) and 33 with absence of an invasive component (No-inv group). We assessed the survival of these patients in association with the presence or absence of an invasive component and intraductal CIS. RESULTS Five-year overall survival in the No-inv group patients was significantly better than that of the Min-inv group patients (82%/66%, P = .041). Among the 33 patients in the No-inv group, residual CIS was observed in 16 patients (CIS-positive group), and the remaining 17 patients had no residual CIS (CIS-negative group). There was no significant difference in survival between patients in the CIS-positive and CIS-negative groups (92%/78%, P = .31). CONCLUSIONS Residual CIS in the absence of an invasive component after preoperative treatment does not yield a prognostic impact after receiving perioperative treatment for PDAC. It might be reasonable to define pathological complete response (pCR) from the prognostic standpoint as follows: pCR is the complete absence of an invasive carcinoma component regardless of residual CIS.
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Affiliation(s)
- Daisaku Yamada
- Department of Gastroenterological surgeryOsaka International Cancer InstituteOsakaJapan
| | - Hidenori Takahashi
- Department of Gastroenterological surgeryOsaka International Cancer InstituteOsakaJapan
| | - Kei Asukai
- Department of Gastroenterological surgeryOsaka International Cancer InstituteOsakaJapan
| | - Shinichiro Hasegawa
- Department of Gastroenterological surgeryOsaka International Cancer InstituteOsakaJapan
| | - Akira Tomokuni
- Department of Gastroenterological surgeryOsaka International Cancer InstituteOsakaJapan
| | - Hiroshi Wada
- Department of Gastroenterological surgeryOsaka International Cancer InstituteOsakaJapan
| | - Hirofumi Akita
- Department of Gastroenterological surgeryOsaka International Cancer InstituteOsakaJapan
| | - Masayohi Yasui
- Department of Gastroenterological surgeryOsaka International Cancer InstituteOsakaJapan
| | - Hiroshi Miyata
- Department of Gastroenterological surgeryOsaka International Cancer InstituteOsakaJapan
| | - Osamu Ishikawa
- Department of Gastroenterological surgeryOsaka International Cancer InstituteOsakaJapan
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Ushigome H, Nishimura J, Takahashi Y, Yasui M, Ohue M, Yamada D, Yamamoto K, Wada H, Takahashi H, Omori T, Miyata H, Takiguchi S. Colorectal surgery in patients with prior pancreaticoduodenectomy. JOURNAL OF THE ANUS RECTUM AND COLON 2019; 3:121-127. [PMID: 31583327 PMCID: PMC6774738 DOI: 10.23922/jarc.2019-005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 05/16/2019] [Indexed: 01/05/2023]
Abstract
Objectives: Colorectal cancer (CRC) surgery after pancreaticoduodenectomy (PD) is difficult to perform, because PD involves dissection and complex reconstruction of the digestive tract. We evaluated the clinical outcomes of CRC surgery in patients with prior PD. Methods: Between January 2008 and March 2018, a total of 1727 patients received CRC surgery at our institution. Of these, 10 had previously undergone PD (PD group). As a control group, 280 patients were collected who had undergone resection without any history of previous abdominal surgery. The PD and control groups were further subdivided into four groups by right or left side. Outcomes of colorectal surgery were investigated in the PD and control groups. Results: The number of harvested lymph nodes was significantly lower in the PD group. In the right colectomy group, distance from the surgical margin was significantly shorter in the PD group. The rate of postoperative complications was higher in the PD group. Peritoneal dissemination originating from pancreatic cancer was found during CRC surgery for one patient, and one patient developed refractory ascites. Three patients died of pancreatic cancer, rectal cancer, and other disease. Seven patients were alive without recurrence. Conclusions: CRC surgery for patients with prior PD can involve difficulty in dissecting lymph nodes and higher postoperative morbidity rates but can provide sufficiently curative resection for CRC.
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Affiliation(s)
- Hajime Ushigome
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Junichi Nishimura
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Yusuke Takahashi
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Masayoshi Yasui
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Masayuki Ohue
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuyoshi Yamamoto
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Takeshi Omori
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Hiroshi Miyata
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Shuji Takiguchi
- Department of Gastroenterological Surgery, Nagoya City University, Aichi, Japan
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Maggino L, Malleo G, Marchegiani G, Viviani E, Nessi C, Ciprani D, Esposito A, Landoni L, Casetti L, Tuveri M, Paiella S, Casciani F, Sereni E, Binco A, Bonamini D, Secchettin E, Auriemma A, Merz V, Simionato F, Zecchetto C, D’Onofrio M, Melisi D, Bassi C, Salvia R. Outcomes of Primary Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma. JAMA Surg 2019; 154:932-942. [PMID: 31339530 PMCID: PMC6659151 DOI: 10.1001/jamasurg.2019.2277] [Citation(s) in RCA: 89] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Accepted: 05/17/2019] [Indexed: 12/21/2022]
Abstract
IMPORTANCE Chemotherapy is the recommended induction strategy in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. However, the associated results on an intention-to-treat basis are poorly understood. OBJECTIVE To investigate pragmatically the treatment compliance, conversion to surgery, and survival outcomes of patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma undergoing primary chemotherapy. DESIGN, SETTING, AND PARTICIPANTS This prospective study took place in a national referral center for pancreatic diseases in Italy. Consecutive patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma were enrolled at the time of diagnosis (January 2013 through December 2015) and followed up to June 2018. EXPOSURES The chemotherapy regimen, assigned based on multidisciplinary evaluation, was delivered either at a hub center or at spoke centers. By convention, primary chemotherapy was considered completed after 6 months. After restaging, surgical candidates were selected based on radiologic and biochemical response. All surgeries were carried out at the hub center. MAIN OUTCOMES AND MEASURES Rates of receipt and completion of chemotherapy, rates of conversion to surgery, and disease-specific survival. RESULTS Of 680 patients, 267 (39.3%) had borderline resectable and 413 (60.7%) had locally advanced pancreatic ductal adenocarcinoma. Overall, 66 patients (9.7%) were lost to follow-up. The rate of chemotherapy receipt was 92.9% (n = 570). The chemotherapeutic regimens most commonly used included FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) (260 [45.6%]) and gemcitabine plus nanoparticle albumin-bound-paclitaxel (123 [21.6%]). Nineteen patients (3.3%) receiving chemotherapy died within 6 months, mainly for disease progression. The treatment completion rate was 71.6% (408 of 570). The overall rate of resection was 15.1% (93 of 614) (borderline resectable, 60 of 249 [24.1%]; locally advanced, 33 of 365 [9%]; resection:exploration ratio, 63.3%). Independent predictors of resection were age, borderline resectable disease, chemotherapy completion, radiologic response, and biochemical response. The median survival for the whole cohort was 12.8 (95% CI, 11.7-13.9) months. Factors independently associated with survival were completion of chemotherapy, receipt of complementary radiation therapy, and resection. In patients who underwent resection, the median survival was 35.4 (95% CI, 27.0-43.7) months for initially borderline resectable and 41.8 (95% CI, 27.5-56.1) months for initially locally advanced disease. No pretreatment and posttreatment factors were associated with survival after pancreatectomy. CONCLUSIONS AND RELEVANCE This pragmatic observational cohort study with an intention-to-treat design provides real-world evidence of outcomes associated with the most current primary chemotherapy regimens used for borderline resectable and locally advanced pancreatic ductal adenocarcinoma.
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Affiliation(s)
- Laura Maggino
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Giuseppe Malleo
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Giovanni Marchegiani
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Elena Viviani
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Chiara Nessi
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Debora Ciprani
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Alessandro Esposito
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Luca Landoni
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Luca Casetti
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Massimiliano Tuveri
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Salvatore Paiella
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Fabio Casciani
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Elisabetta Sereni
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Alessandra Binco
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Deborah Bonamini
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Erica Secchettin
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Alessandra Auriemma
- Unit of Medical Oncology, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Valeria Merz
- Unit of Medical Oncology, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Francesca Simionato
- Unit of Medical Oncology, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Camilla Zecchetto
- Unit of Medical Oncology, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Mirko D’Onofrio
- Unit of Radiology, Department of Pathology and Diagnostics, University of Verona Hospital Trust, Verona, Italy
| | - Davide Melisi
- Unit of Medical Oncology, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
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Abstract
The aim of this study was to evaluate outcomes of patients with resectable pancreatic adenocarcinoma (PDAC) who underwent neoadjuvant chemotherapy. The MEDLINE and PubMed databases were searched to identify relevant original articles investigating neoadjuvant therapy in resectable PDAC. Qualitative analyses were performed to investigate patient selection, disease stage, impact on perioperative outcomes, and cost-effectiveness. Forty-three studies met inclusion criteria for this review. Neoadjuvant chemotherapy for upfront resectable PDAC is cost-effective, safe, may result in lower stage disease and has potential survival advantages. With proper patient selection, neoadjuvant chemotherapy is an appropriate approach for upfront resectable PDAC. Nevertheless, the risk for disease progression and losing a curative surgical window highlights the need for appropriate patient identification, further discovery of superior biomarkers or molecular profiles representative of positive treatment response, and additional prospective comparative study.
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Shridhar R, Takahashi C, Huston J, Meredith KL. Neoadjuvant therapy and pancreatic cancer: a national cancer database analysis. J Gastrointest Oncol 2019; 10:663-673. [PMID: 31392047 DOI: 10.21037/jgo.2019.02.09] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background We sought to examine the impact of neoadjuvant chemotherapy (NCT), single agent or multiagent chemotherapy, and neoadjuvant chemoradiation (NCRT) on survival in pancreatic cancer. Methods Utilizing the National Cancer Database, we identified patients who underwent pancreatic resection for adenocarcinoma (2006 to 2013). Overall survival (OS) analysis was performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) and propensity score matching (PSM) were developed to identify predictors of survival. For upfront surgery (UFS), OS was limited to receipt of adjuvant treatment. Results We identified 26,563 patients who underwent pancreatic resection: UFS =23,877, NCRT =1,482, and NCT =1,204. Multiagent chemotherapy was utilized in 77% of NCT and 42% of NCRT. There was improved R0 resections associated with neoadjuvant therapy compared to UFS, however, there was no difference between NCT and NCRT. In addition, the was improved R0 with MA-NCT (P<0.001) but not for single agent NCT (P=0.26). After PSM, the median OS for UFS, SA-NCT, MA-NCT, SA-NCRT, and MA-NCRT was 21.9, 21.5, 29.8, 25.3, and 25.8 months in all patients (P=0.001), and 23.6, 23.9, 31.6, 25.9, and 26.6 months in R0 patients (P=0.03), respectively. There was no difference in OS in patients with R1/2 resection. MVA after PSM demonstrated that only MA-NCT was associated with decreased mortality while increasing age, higher Charlson-Deyo index, N1, higher grade, tumor size, and positive margins were associated with higher mortality. Conclusions There was improved OS associated with MA-NCT in pancreatic cancer patients compared to UFS with adjuvant therapy.
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Affiliation(s)
- Ravi Shridhar
- Department of Radiation Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA
| | | | - Jamie Huston
- Department of Surgical Oncology, Sarasota Memorial Hospital, Sarasota, FL, USA
| | - Kenneth L Meredith
- Department of Surgical Oncology, Sarasota Memorial Hospital, Sarasota, FL, USA
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Phase 2 Study of Neoadjuvant Treatment of Sequential S-1-Based Concurrent Chemoradiation Therapy Followed by Systemic Chemotherapy with Gemcitabine for Borderline Resectable Pancreatic Adenocarcinoma (HOPS-BR 01). Int J Radiat Oncol Biol Phys 2019; 105:606-617. [PMID: 31306735 DOI: 10.1016/j.ijrobp.2019.07.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2018] [Revised: 06/21/2019] [Accepted: 07/04/2019] [Indexed: 01/24/2023]
Abstract
PURPOSE Preoperative treatment is recommended for borderline resectable pancreatic ductal adenocarcinoma. However, the standard treatment has not yet been determined. We conducted a multicenter phase 2 study to investigate the efficacy of neoadjuvant treatment of sequential chemoradiation followed by chemotherapy. METHODS AND MATERIALS All enrolled patients were treated by preoperative chemoradiation (a total dose of 50.4 Gy in 28 fractions and orally administered S-1 at 80 mg/m2 on the day of irradiation) followed by chemotherapy (administration of gemcitabine at 1000 mg/m2/dose on days 1, 8, and 15 in 3 cycles of 4 weeks) and attempted curative resection. The primary outcome was an R0 resection rate among patients who completed preoperative treatment and pancreatectomy. The threshold of the R0 resection rate was defined as 74% based on a previous study of up-front surgery. RESULTS Forty-five patients were included. Twenty-one patients could not undergo pancreatectomy because of progressive diseases (n = 14), adverse events (n = 5), or consent withdrawal (n = 2), and 4 patients underwent additional resection after dropping out. The resection rates were 53.3% and 62.2% in the per-protocol set (PPS) and full analysis set (FAS) populations, respectively. The R0 resection rates were 95.8% (95% confidence interval, 78.9%-99.9%) and 96.4% (81.7%-99.9%) in the PPS and FAS populations, respectively. The median overall survival and progression-free survival of all the included patients were 17.3 and 10.5 months, respectively. The median survival time of the patients with pancreatectomy was significantly longer than that of the patients without pancreatectomy in the PPS (27.9 vs 12.3 months; P = .001) and FAS populations (32.2 vs 11.8 months; P < .001). CONCLUSIONS This study revealed that a long duration of preoperative treatment of sequential chemoradiation followed by systemic chemotherapy provides a high rate of R0 resection and sufficient survival time in patients undergoing pancreatectomy.
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Akita H, Takahashi H, Asukai K, Tomokuni A, Wada H, Marukawa S, Yamasaki T, Yanagimoto Y, Takahashi Y, Sugimura K, Yamamoto K, Nishimura J, Yasui M, Omori T, Miyata H, Ochi A, Kagawa A, Soh Y, Taniguchi Y, Ohue M, Yano M, Sakon M. The utility of nutritional supportive care with an eicosapentaenoic acid (EPA)-enriched nutrition agent during pre-operative chemoradiotherapy for pancreatic cancer: Prospective randomized control study. Clin Nutr ESPEN 2019; 33:148-153. [PMID: 31451252 DOI: 10.1016/j.clnesp.2019.06.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 03/10/2019] [Accepted: 06/03/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer (PC) is potentially associated with various toxicities, which can lead to impaired nutritional status. Eicosapentaenoic acid (EPA) can reduce proinflammatory cytokines and positively influence cancer cachexia syndrome. The aim of this study is to clarify the utility of EPA enriched nutrition support during NACRT for PC. METHODS We randomly assigned 62 patients with PC that received NACRT to either a nutrition intervention (NI) or a normal diet (ND). Patients in the NI group received 2 bottles/day (550 kcal/day) of an EPA-enriched nutrition supplement during NACRT. The primary endpoints were the before-to-after NACRT ratios (post/pre ratios) of skeletal muscle mass and psoas major muscle area (PMA). The secondary endpoints were the post/pre ratios of other nutritional parameters and treatment-related toxicities. RESULTS Only 14 patients (45.2%) in the NI group consumed more than 50% of the EPA-enriched supplement provided. The post/pre ratio of skeletal muscle mass in the NI group (0.99 ± 0.060) was not significantly different from that of the ND group (0.96 ± 0.079, p = 0.102). However, patients that consumed ≥50% of the EPA-enriched supplement (the good intake group) had significantly higher skeletal muscle mass ratios than patients in the ND group (p = 0.042). The PMA ratio was significantly higher in the NI group (0.96 ± 0.081) than in the ND group (0.89 ± 0.072, p = 0.001). The NI and ND groups were not significantly different in other nutritional parameters or in NACRT-related toxicity. CONCLUSIONS We found that EPA-enriched intake could potentially improve the nutritional status of patients with PC that received NACRT, but it was difficult for many patients to drink, due to its disagreeable taste. University Hospital Medical Information Network (http://www.umin.ac.jp), registration number UMIN000033589, https://upload.umin.ac.jp/cgi-bin/ctr_e/ctr_view.cgi?recptno=R000038300.
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Affiliation(s)
- Hirofumi Akita
- Department of Surgery, Osaka International Cancer Institute, Japan; Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan.
| | | | - Kei Asukai
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Akira Tomokuni
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Wada
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Satoko Marukawa
- Department of Endocrinology and Metabolism, Osaka International Cancer Institute, Japan
| | - Tomoyuki Yamasaki
- Department of Endocrinology and Metabolism, Osaka International Cancer Institute, Japan
| | | | - Yusuke Takahashi
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Keijiro Sugimura
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | | | - Masayoshi Yasui
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takeshi Omori
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Miyata
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Ayami Ochi
- Department of Nursing, Osaka International Cancer Institute, Japan
| | - Ayano Kagawa
- Department of Nursing, Osaka International Cancer Institute, Japan
| | - Yuko Soh
- Department of Nutrition, Osaka International Cancer Institute, Japan
| | - Yuko Taniguchi
- Department of Nutrition, Osaka International Cancer Institute, Japan
| | - Masayuki Ohue
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masahiko Yano
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masato Sakon
- Department of Surgery, Osaka International Cancer Institute, Japan
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Lewis S, Sastri SC, Arya S, Mehta S, Patil P, Shrivastava S, Phurailatpam R, Shrikhande SV, Engineer R. Dose escalated concurrent chemo-radiation in borderline resectable and locally advanced pancreatic cancers with tomotherapy based intensity modulated radiotherapy: a phase II study. J Gastrointest Oncol 2019; 10:474-482. [PMID: 31183197 DOI: 10.21037/jgo.2019.01.25] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Background We report the response and outcomes of borderline resectable and locally advanced pancreatic cancer (BRPC & LAPC) patients treated with dose escalated neoadjuvant intensity modulated radiotherapy (IMRT). Methods Thirty newly diagnosed patients with BRPC (n=18) and LAPC (n=12) (NCCN criteria V 2.2.12) were accrued in this prospective study from 2008-2011. All patients received neoadjuvant chemoradiation (NACRT) using Helical Tomotherapy (dose of 57 Gy over 25 fractions to the gross tumor volume (GTV) and 45 Gy over 25 fractions to suspected microscopic extension) along with weekly gemcitabine. Results Fifteen patients (50%) had a partial response. A complete metabolic response (CMR) on PET was seen in 9 patients (30%). Among BRPC, 9 patients (50%) were surgically explored and 7 underwent R0 resection (39%). The median follow up of surviving patients was 85 [interquartile range (IQR): 64.5-85.8] months. The median progression free survival (PFS) was 13 months for BRPC and 8.8 months for LAPC. The median overall survival (OS) was 17.3 months for BRPC and 11.8 months for LAPC. Among patients undergoing R0 resection, the median PFS and OS was 27 and 35.5 months respectively. Conclusions Dose escalated radiotherapy with concurrent chemotherapy is feasible and can downsize some tumors resulting in surgery in about 39% of the BRPC.
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Affiliation(s)
- Shirley Lewis
- Department of Radiotherapy and Oncology, Kasturba Medical College, MAHE, Manipal, India
| | | | - Supreeta Arya
- Department of Radiology, Tata Memorial Centre, Mumbai, India
| | - Shaesta Mehta
- Department of Gastroenterology, Tata Memorial Centre, Mumbai, India
| | - Prachi Patil
- Department of Gastroenterology, Tata Memorial Centre, Mumbai, India
| | | | | | | | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India
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Aoki S, Motoi F, Murakami Y, Sho M, Satoi S, Honda G, Uemura K, Okada KI, Matsumoto I, Nagai M, Yanagimoto H, Kurata M, Fukumoto T, Mizuma M, Yamaue H, Unno M. Decreased serum carbohydrate antigen 19-9 levels after neoadjuvant therapy predict a better prognosis for patients with pancreatic adenocarcinoma: a multicenter case-control study of 240 patients. BMC Cancer 2019; 19:252. [PMID: 30898101 PMCID: PMC6427838 DOI: 10.1186/s12885-019-5460-4] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 03/12/2019] [Indexed: 12/15/2022] Open
Abstract
Background Carbohydrate antigen (CA) 19–9 levels after resection are considered to predict prognosis; however, the significance of decreased CA19–9 levels after neoadjuvant therapy has not been clarified. This study aimed to define the prognostic significance of decreased CA19–9 levels after neoadjuvant therapy in patients with pancreatic adenocarcinoma. Methods Between 2001 and 2012, 240 consecutive patients received neoadjuvant therapy and subsequent resection at seven high-volume institutions in Japan. These patients were divided into three groups: Normal group (no elevation [≤37 U/ml] before and after neoadjuvant therapy), Responder group (elevated levels [> 37 U/ml] before neoadjuvant therapy but decreased levels [≤37 U/ml] afterwards), and Non-responder group (elevated levels [> 37 U/ml] after neoadjuvant therapy). Analyses of overall survival and recurrence patterns were performed. Uni- and multivariate analyses were performed to clarify the clinicopathological factors influencing overall survival. The initial metastasis sites were also evaluated in these groups. Results The Responder group received a better prognosis than the Non-responder group (3-year overall survival: 50.6 and 41.6%, respectively, P = 0.026), but the prognosis was comparable to the Normal group (3-year overall survival: 54.2%, P = 0.934). According to the analysis of the receiver operating characteristic curve, the CA19–9 cut-off level defined as no elevation after neoadjuvant therapy was ≤103 U/ml. The multivariate analysis revealed that a CA19–9 level ≤ 103 U/ml, (P = 0.010, hazard ratio: 1.711; 95% confidence interval: 1.133–2.639), tumor size ≤27 mm (P = 0.040, 1.517; (1.018–2.278)), a lack of lymph node metastasis (P = 0.002, 1.905; (1.276–2.875)), and R0 status (P = 0.045, 1.659; 1.012–2.627) were significant predictors of overall survival. Moreover, the Responder group showed a lower risk of hepatic recurrence (18%) compared to the Non-responder group (31%), though no significant difference in loco-regional, peritoneal or other distant recurrence were observed between groups (P = 0.058, P = 0.700 and P = 0.350, respectively). Conclusions Decreased CA19–9 levels after neoadjuvant therapy predicts a better prognosis, with low incidence of hepatic recurrence after surgery. Electronic supplementary material The online version of this article (10.1186/s12885-019-5460-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Shuichi Aoki
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Fuyuhiko Motoi
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan.
| | - Yoshiaki Murakami
- Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan
| | - Masayuki Sho
- Department of Surgery, Nara Medical University, Nara, 634-8521, Japan
| | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Osaka, 573-1010, Japan
| | - Goro Honda
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, 113-8677, Japan
| | - Kenichiro Uemura
- Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan
| | - Ken-Ichi Okada
- Second Department of Surgery, Wakayama Medical University, Wakayama, 641-8510, Japan
| | - Ippei Matsumoto
- Department of Surgery, Kindai University Faculty of Medicine, Osaka, 577-8502, Japan
| | - Minako Nagai
- Department of Surgery, Nara Medical University, Nara, 634-8521, Japan
| | - Hiroaki Yanagimoto
- Department of Surgery, Kansai Medical University, Osaka, 573-1010, Japan
| | - Masanao Kurata
- Department of Gastointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan
| | - Takumi Fukumoto
- Department of Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan
| | - Masamichi Mizuma
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University, Wakayama, 641-8510, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan
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Wolfe AR, Jain R, Pawlik TM, Walker J, Williams TM. Radiation-Induced Colitis in a Pancreatic Cancer Patient With a Germline BRCA2 Mutation: A Case Report. Adv Radiat Oncol 2019; 4:10-14. [PMID: 30706003 PMCID: PMC6349605 DOI: 10.1016/j.adro.2018.08.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 08/31/2018] [Accepted: 08/31/2018] [Indexed: 01/07/2023] Open
Affiliation(s)
- Adam R Wolfe
- Department of Radiation Oncology, Ohio State University James Comprehensive Cancer Center, Columbus, Ohio
| | - Rishi Jain
- Department of Medical Oncology, Ohio State University James Comprehensive Cancer Center, Columbus, Ohio
| | - Timothy M Pawlik
- Department of Surgical Oncology, Ohio State University James Comprehensive Cancer Center, Columbus, Ohio
| | - Jon Walker
- Department of Gastroenterology, Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Terence M Williams
- Department of Radiation Oncology, Ohio State University James Comprehensive Cancer Center, Columbus, Ohio
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