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Liu W, Chen Y, Xie T, Zhang Z, Wang Y, Xie X, Chen L, Zhou Z. Dual-energy CT extracellular volume fraction predicts tumor collagen ratio and possibly survival for inoperable pancreatic cancer patients. Eur Radiol 2025; 35:1451-1463. [PMID: 39922972 DOI: 10.1007/s00330-024-11330-1] [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: 07/30/2024] [Revised: 10/22/2024] [Accepted: 11/28/2024] [Indexed: 02/10/2025]
Abstract
OBJECTIVES Tumor collagen is vital in chemotherapy resistance of pancreatic cancer (PC), but its non-invasive evaluation remains challenging. This study aims to investigate the association of variables derived from dual-energy CT with the collagen ratio (CR) of PC and to determine the prognostic value of CR in unresectable diseases. MATERIALS AND METHODS A total of 83 patients with resected PC and 71 patients with unresectable PC were enrolled. In the resected group, the correlation between the tumor CR and variables of dual-energy CT was analyzed. In the unresectable group, Cox regression analyses were conducted to investigate the prognostic value of dual-energy CT-predicted CR and other clinicoradiological indicators. RESULTS The patients with resected PC were divided into low and high-CR sets with a threshold of 55%. In the resected group, the extracellular volume fraction calculated by the iodine concentration (ECV_IC) was the only predictor of tumor CR according to univariate and multivariate analysis (hazard ratio [HR] (95% confidence interval [CI]):1.19 [1.03-1.37]). The correlation coefficient r was 0.26 (p = 0.02) between ECV_IC and specific CR values. In the training set of unresectable PC group, ECV_IC (HR (95% CI): 0.94 (0.89-0.99), p = 0.03) and contrast-enhanced pattern (CEP) (HR (95% CI): 3.20 (1.41-7.27), p = 0.01) were independent prognostic factors for overall survival. The nomogram model was constructed and showed a good performance. CONCLUSION The ECV_IC is a non-invasive indicator of tumor CR in PC. The ECV_IC and CEP have the potential to predict the prognosis of unresectable PC. KEY POINTS Question Non-invasive evaluation of tumor collagen, a vital determinant of chemotherapy resistance of pancreatic cancer, remains challenging. Findings Tumor collagen ratio can be noninvasively predicted by extracellular volume fraction based on iodine concentration. Clinical relevance The nomogram model composed of extracellular volume fraction and contrast-enhanced pattern can serve as an effective and convenient tool for stratifying the prognosis of patients with unresectable pancreatic cancer.
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Affiliation(s)
- Wei Liu
- Department of Radiology, Fudan University Shanghai Cancer Center & Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yi Chen
- Department of Radiology, Fudan University Shanghai Cancer Center & Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Tiansong Xie
- Department of Radiology, Fudan University Shanghai Cancer Center & Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Zehua Zhang
- Department of Radiology, Minhang Branch, Fudan University Shanghai Cancer Center, Shanghai, 201100, China
| | - Yu Wang
- Clinical and Technical Support, Philips Healthcare, Shanghai, China
| | - Xuebin Xie
- Department of Radiology, Kiang Wu Hospital, Macao, 999078, China
| | - Lei Chen
- Department of Radiology, Minhang Branch, Fudan University Shanghai Cancer Center, Shanghai, 201100, China.
| | - Zhengrong Zhou
- Department of Radiology, Fudan University Shanghai Cancer Center & Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Department of Radiology, Minhang Branch, Fudan University Shanghai Cancer Center, Shanghai, 201100, China.
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Stoop TF, Theijse RT, Seelen LWF, Groot Koerkamp B, van Eijck CHJ, Wolfgang CL, van Tienhoven G, van Santvoort HC, Molenaar IQ, Wilmink JW, Del Chiaro M, Katz MHG, Hackert T, Besselink MG. Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer. Nat Rev Gastroenterol Hepatol 2024; 21:101-124. [PMID: 38036745 DOI: 10.1038/s41575-023-00856-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/05/2023] [Indexed: 12/02/2023]
Abstract
Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda.
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Affiliation(s)
- Thomas F Stoop
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Rutger T Theijse
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands
- Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Leonard W F Seelen
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands
| | - Casper H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands
| | - Christopher L Wolfgang
- Division of Surgical Oncology, Department of Surgery, New York University Medical Center, New York City, NY, USA
| | - Geertjan van Tienhoven
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Radiation Oncology, Amsterdam, Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - Johanna W Wilmink
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, Netherlands
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Marc G Besselink
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands.
- Cancer Center Amsterdam, Amsterdam, Netherlands.
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Cao BY, Wang QQ, Zhang LT, Wu CC, Tong F, Yang W, Wang J. Survival benefits and disparities in radiation therapy for elderly patients with pancreatic ductal adenocarcinoma. World J Gastrointest Oncol 2023; 15:155-170. [PMID: 36684051 PMCID: PMC9850762 DOI: 10.4251/wjgo.v15.i1.155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 11/27/2022] [Accepted: 12/21/2022] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Older patients represent a unique subgroup of the cancer patient population, for which the role of cancer therapy requires special consideration. However, the outcomes of radiation therapy (RT) in elderly patients with pancreatic ductal adenocarcinoma (PDAC) are not well-defined in the literature.
AIM To explore the use and effectiveness of RT in the treatment of elderly patients with PDAC in clinical practice.
METHODS Data from patients with PDAC aged ≥ 65 years between 2004 and 2018 were collected from the Surveillance, Epidemiology, and End Results database. Multivariate logistic regression analysis was performed to determine factors associated with RT administration. Overall survival (OS) and cancer-specific survival (CSS) were evaluated using the Kaplan–Meier method with the log-rank test. Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors for OS. Propensity score matching (PSM) was applied to balance the baseline characteristics between the RT and non-RT groups. Subgroup analyses were performed based on clinical characteristics.
RESULTS A total of 12245 patients met the inclusion criteria, of whom 2551 (20.8%) were treated with RT and 9694 (79.2%) were not. The odds of receiving RT increased with younger age, diagnosis in an earlier period, primary site in the head, localized disease, greater tumor size, and receiving chemotherapy (all P < 0.05). Before PSM, the RT group had better outcomes than did the non-RT group [median OS, 14.0 vs 6.0 mo; hazard ratio (HR) for OS: 0.862, 95% confidence interval (CI): 0.819–0.908, P < 0.001; and HR for CSS: 0.867, 95%CI: 0.823–0.914, P < 0.001]. After PSM, the survival benefit associated with RT remained comparable (median OS: 14.0 vs 11.0 mo; HR for OS: 0.818, 95%CI: 0.768–0.872, P < 0.001; and HR for CSS: 0.816, 95%CI: 0.765–0.871, P < 0.001). Subgroup analysis revealed that the survival benefits (OS and CSS) of RT were more significant in patients aged 65 to 80 years, in regional and distant stages, with no surgery, and receiving chemotherapy.
CONCLUSION RT improved the outcome of elderly patients with PDAC, particularly those aged 65 to 80 years, in regional and distant stages, with no surgery, and who received chemotherapy. Further prospective studies are warranted to validate our results.
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Affiliation(s)
- Bi-Yang Cao
- Department of Radiation Oncology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- Medical School of Chinese PLA, Beijing 100853, China
| | - Qian-Qian Wang
- Department of Radiation Oncology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Le-Tian Zhang
- Department of Radiation Oncology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- Medical School of Chinese PLA, Beijing 100853, China
| | - Chen-Chen Wu
- Department of Radiation Oncology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- Medical School of Chinese PLA, Beijing 100853, China
| | - Fang Tong
- Department of Radiation Oncology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Wei Yang
- Department of Radiation Oncology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Jing Wang
- Department of Radiation Oncology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
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González-Borja I, Viúdez A, Alors-Pérez E, Goñi S, Amat I, Ghanem I, Pazo-Cid R, Feliu J, Alonso L, López C, Arrazubi V, Gallego J, Pérez-Sanz J, Hernández-García I, Vera R, Castaño JP, Fernández-Irigoyen J. Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma. Cancers (Basel) 2022; 14:5993. [PMID: 36497475 PMCID: PMC9739487 DOI: 10.3390/cancers14235993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 11/28/2022] [Accepted: 11/29/2022] [Indexed: 12/09/2022] Open
Abstract
Despite its relative low incidence, PDAC is one of the most aggressive and lethal types of cancer, being currently the seventh leading cause of cancer death worldwide, with a 5-year survival rate of 10.8%. Taking into consideration the necessity to improve the prognosis of these patients, this research has been focused on the discovery of new biomarkers. For this purpose, patients with BL and resectable disease were recruited. Serum cytokines and growth factors were monitored at different time points using protein arrays. Immune cell populations were determined by flow cytometry in peripheral blood as well as by immunohistochemistry (IHC) in tumor tissues. Several cytokines were found to be differentially expressed between the study subgroups. In the BL disease setting, two different scores were proven to be independent prognostic factors for progression-free survival (PFS) (based on IL-10, MDC, MIF, and eotaxin-3) and OS (based on eotaxin-3, NT-3, FGF-9, and IP10). In the same context, CA19-9 was found to play a role as independent prognostic factor for OS. Eotaxin-3 and MDC cytokines for PFS, and eotaxin-3, NT-3, and CKβ8-1 for OS, were shown to be predictive biomarkers for nab-paclitaxel and gemcitabine regimen. Similarly, oncostatin, BDNF, and IP10 cytokines were proven to act as predictive biomarkers regarding PFS, for FOLFIRINOX regimen. In the resectable cohort, RANTES, TIMP-1, FGF-4, and IL-10 individually differentiated patients according to their cancer-associated survival. Regarding immune cell populations, baseline high levels of circulating B lymphocytes were related to a significantly longer OS, while these levels significantly decreased as progression occurred. Similarly, baseline high levels of helper lymphocytes (CD4+), low levels of cytotoxic lymphocytes (CD8+), and a high CD4/CD8 ratio, were related to a significantly longer PFS. Finally, high levels of CD4+ and CD8+ intratumoural infiltration was associated with significantly longer PFS. In conclusion, in this study we were able to identify several prognostic and predictive biomarker candidates in patients diagnosed of resectable or BL PDAC.
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Affiliation(s)
- Iranzu González-Borja
- OncobionaTras Lab, Navarrabiomed, Navarra University Hospital, Universidad Pública de Navarra (UPNA), 31006 Pamplona, Spain
| | - Antonio Viúdez
- OncobionaTras Lab, Navarrabiomed, Navarra University Hospital, Universidad Pública de Navarra (UPNA), 31006 Pamplona, Spain
- Medical Oncology Department, Navarra University Hospital, 31008 Pamplona, Spain
| | - Emilia Alors-Pérez
- Maimonides Biomedical Research Institute of Córdoba, 14004 Córdoba, Spain
- Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14071 Córdoba, Spain
- Reina Sofía University Hospital, 14004 Córdoba, Spain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), 14004 Córdoba, Spain
| | - Saioa Goñi
- OncobionaTras Lab, Navarrabiomed, Navarra University Hospital, Universidad Pública de Navarra (UPNA), 31006 Pamplona, Spain
| | - Irene Amat
- Pathology Department, Navarra University Hospital, 31008 Pamplona, Spain
| | - Ismael Ghanem
- Medical Oncology Department, La Paz University Hospital, 28046 Madrid, Spain
| | - Roberto Pazo-Cid
- Medical Oncology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain
| | - Jaime Feliu
- Medical Oncology Department, La Paz University Hospital, 28046 Madrid, Spain
| | - Laura Alonso
- Pathology Department, Navarra University Hospital, 31008 Pamplona, Spain
| | - Carlos López
- Medical Oncology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain
| | - Virginia Arrazubi
- Medical Oncology Department, Navarra University Hospital, 31008 Pamplona, Spain
| | - Javier Gallego
- Medical Oncology Department, Hospital General Universitario de Elche, 03203 Elche, Spain
| | - Jairo Pérez-Sanz
- OncobionaTras Lab, Navarrabiomed, Navarra University Hospital, Universidad Pública de Navarra (UPNA), 31006 Pamplona, Spain
| | | | - Ruth Vera
- Medical Oncology Department, Navarra University Hospital, 31008 Pamplona, Spain
| | - Justo P Castaño
- Maimonides Biomedical Research Institute of Córdoba, 14004 Córdoba, Spain
- Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14071 Córdoba, Spain
- Reina Sofía University Hospital, 14004 Córdoba, Spain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), 14004 Córdoba, Spain
| | - Joaquín Fernández-Irigoyen
- Clinical Neuroproteomics Unit, Navarrabiomed, Proteored-ISCIII, Proteomics Unit, Navarrabiomed, Navarra University Hospital, Universidad Pública de Navarra (UPNA), Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
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Kim SS, Lee S, Lee HS, Bang S, Han K, Park MS. Retrospective Evaluation of Treatment Response in Patients with Nonmetastatic Pancreatic Cancer Using CT and CA 19-9. Radiology 2022; 303:548-556. [PMID: 35258374 DOI: 10.1148/radiol.212236] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Background Imaging studies have limitations in evaluating pancreatic ductal adenocarcinoma (PDAC) treatment response. Purpose To investigate the effectiveness of combined CT and carbohydrate antigen 19-9 (CA 19-9) evaluation at 8 weeks after first-line treatment to predict overall survival (OS) of patients with nonmetastatic PDAC. Materials and Methods Patients with nonmetastatic PDAC who received first-line treatment with either chemotherapy or concurrent chemoradiation in a single-center PDAC cohort registry were retrospectively enrolled in the study between January 2013 and December 2016. Follow-up CT images obtained 8 weeks after treatment were evaluated according to Response Evaluation Criteria in Solid Tumors. Patients with partial response (PR) or stable disease (SD) were defined as CT responders, and those with progressive disease (PD) were defined as CT nonresponders. Patients with a normalized CA 19-9 level at 8-week follow-up were defined as CA 19-9 responders, and those with a nonnormalized or nonelevated CA 19-9 level were defined as CA 19-9 nonresponders. OS was compared using the Kaplan-Meier method with Breslow analysis. Results A total of 197 patients (mean age ± standard deviation, 65 years ± 10; 107 men) were evaluated. Patients with PD (n = 17) showed shorter OS than those with SD (n = 147; P < .001) or PR (n = 33; P = .003). OS did not differ between the patients with PR and those with SD (P = .60). When the CT and CA 19-9 responses were integrated, OS was longest in CT and CA 19-9 responders (group 1, n = 27; median OS, 26.6 months [95% CI: 9.0, 44.1]), followed by CT responders but CA 19-9 nonresponders (group 2, n = 153; median OS, 15.9 months [95% CI: 13.3, 18.5]; P = .007 vs group 1) and CT and CA 19-9 nonresponders (group 3, n = 17; median OS, 6.5 months [95% CI: 0.8, 12.2]; P < .001 vs group 2). Conclusion Integrated evaluation with CT and carbohydrate antigen 19-9 response allowed more accurate stratification of survival in patients with pancreatic ductal adenocarcinoma in the early treatment period than did evaluation according to Response Evaluation Criteria in Solid Tumors. © RSNA, 2022 Online supplemental material is available for this article.
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Affiliation(s)
- Seung-Seob Kim
- From the Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea (S.S.K., S.L., M.S.P.); Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea (H.S.L., S.B.); and Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science (CCIDS), Yonsei University College of Medicine, Seoul, Republic of Korea (K.H.)
| | - Sunyoung Lee
- From the Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea (S.S.K., S.L., M.S.P.); Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea (H.S.L., S.B.); and Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science (CCIDS), Yonsei University College of Medicine, Seoul, Republic of Korea (K.H.)
| | - Hee Seung Lee
- From the Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea (S.S.K., S.L., M.S.P.); Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea (H.S.L., S.B.); and Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science (CCIDS), Yonsei University College of Medicine, Seoul, Republic of Korea (K.H.)
| | - Seungmin Bang
- From the Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea (S.S.K., S.L., M.S.P.); Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea (H.S.L., S.B.); and Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science (CCIDS), Yonsei University College of Medicine, Seoul, Republic of Korea (K.H.)
| | - Kyunghwa Han
- From the Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea (S.S.K., S.L., M.S.P.); Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea (H.S.L., S.B.); and Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science (CCIDS), Yonsei University College of Medicine, Seoul, Republic of Korea (K.H.)
| | - Mi-Suk Park
- From the Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea (S.S.K., S.L., M.S.P.); Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea (H.S.L., S.B.); and Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science (CCIDS), Yonsei University College of Medicine, Seoul, Republic of Korea (K.H.)
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Passardi A, Rapposelli IG, Scarpi E, Sullo FG, Bartolini G, Neri E, Ghigi G, Tontini L, Ercolani G, Monti M, Ruscelli S, Matteucci L, Valgiusti M, Frassineti GL, Romeo A. Multimodal Treatment with GEMOX Plus Helical Tomotherapy in Unresectable Locally Advanced Pancreatic Cancer: A Pooled Analysis of Two Phase 2 Studies. Biomolecules 2021; 11:1200. [PMID: 34439866 PMCID: PMC8393939 DOI: 10.3390/biom11081200] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/29/2021] [Accepted: 08/09/2021] [Indexed: 12/29/2022] Open
Abstract
In locally advanced pancreatic cancer (LAPC), the combination of chemotherapy and radiotherapy is a widely used treatment option. We performed a pooled analysis, including an exploratory analysis for prognostic and predictive factors, of two phase 2 trials including 73 patients with LAPC, treated with gemcitabine and oxaliplatin (GEMOX) and hypofractionated tomotherapy. With a median follow-up of 36 months (range 1-65), median progression-free (PFS) and overall survival (OS) were 10.2 (95% confidence interval [CI] 7.8-13.2) and 14.3 (95% CI 12.0-18.1) months, respectively. The overall resectability rate was 23.3% (95% CI 13.6-33.0), and the R0 resection rate was 13.7% (95% CI 5.8-21.6). In the multivariate analysis, ECOG performance status (PS) 0 and low levels of CA 19-9 were associated with improved OS and PFS. Concerning OS, log(CA19-9) resulted in a hazard ratio (HR) of 1.20 (95% CI 1.02-1.42), p = 0.027. For ECOG PS 0, HR was 1.00; for PS 1, HR was 2.69 (95% CI 1.46-4.96); for PS 2, HR was 4.18 (95% CI 0.90-19.46); p = 0.003. Low CA19-9 levels were also predictive for resection, with an odds ratio of 0.71 (95% CI 0.52-0.97), p = 0.034. In conclusion, GEMOX and hypofractionated radiotherapy is a treatment option in LAPC. Further studies are needed to identify differences in tumor biology, which may help to predict resectability and prognosis.
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Affiliation(s)
- Alessandro Passardi
- Department of Medical Oncology, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (A.P.); (F.G.S.); (G.B.); (M.M.); (S.R.); (L.M.); (M.V.); (G.L.F.)
| | - Ilario Giovanni Rapposelli
- Department of Medical Oncology, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (A.P.); (F.G.S.); (G.B.); (M.M.); (S.R.); (L.M.); (M.V.); (G.L.F.)
| | - Emanuela Scarpi
- Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy;
| | - Francesco Giulio Sullo
- Department of Medical Oncology, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (A.P.); (F.G.S.); (G.B.); (M.M.); (S.R.); (L.M.); (M.V.); (G.L.F.)
| | - Giulia Bartolini
- Department of Medical Oncology, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (A.P.); (F.G.S.); (G.B.); (M.M.); (S.R.); (L.M.); (M.V.); (G.L.F.)
| | - Elisa Neri
- Radiotherapy Unit, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (E.N.); (G.G.); (L.T.); (A.R.)
| | - Giulia Ghigi
- Radiotherapy Unit, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (E.N.); (G.G.); (L.T.); (A.R.)
| | - Luca Tontini
- Radiotherapy Unit, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (E.N.); (G.G.); (L.T.); (A.R.)
| | - Giorgio Ercolani
- General and Oncologic Surgery Unit, Morgagni-Pierantoni Hospital, AUSL Romagna, 47121 Forlì, Italy;
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Manlio Monti
- Department of Medical Oncology, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (A.P.); (F.G.S.); (G.B.); (M.M.); (S.R.); (L.M.); (M.V.); (G.L.F.)
| | - Silvia Ruscelli
- Department of Medical Oncology, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (A.P.); (F.G.S.); (G.B.); (M.M.); (S.R.); (L.M.); (M.V.); (G.L.F.)
| | - Laura Matteucci
- Department of Medical Oncology, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (A.P.); (F.G.S.); (G.B.); (M.M.); (S.R.); (L.M.); (M.V.); (G.L.F.)
| | - Martina Valgiusti
- Department of Medical Oncology, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (A.P.); (F.G.S.); (G.B.); (M.M.); (S.R.); (L.M.); (M.V.); (G.L.F.)
| | - Giovanni Luca Frassineti
- Department of Medical Oncology, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (A.P.); (F.G.S.); (G.B.); (M.M.); (S.R.); (L.M.); (M.V.); (G.L.F.)
| | - Antonino Romeo
- Radiotherapy Unit, IRCCS Istituto Romagnolo Per lo Studio dei Tumori “Dino Amadori”—IRST, 47014 Meldola, Italy; (E.N.); (G.G.); (L.T.); (A.R.)
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