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Samuel T, Rapic S, Lindsay PE, DaCosta RS. Investigating the effects of stereotactic body radiation therapy on pancreatic tumor hypoxia and microvasculature in an orthotopic mouse model using intravital fluorescence microscopy. Sci Rep 2024; 14:31348. [PMID: 39733027 PMCID: PMC11682216 DOI: 10.1038/s41598-024-82757-1] [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: 09/11/2023] [Accepted: 12/09/2024] [Indexed: 12/30/2024] Open
Abstract
Despite decades of improvements in cytotoxic therapy, the current standard of care for locally advanced pancreatic cancer (LAPC) provides, on average, only a few months of survival benefit. Stereotactic Body Radiation Therapy (SBRT), a technique that accurately delivers high doses of radiation to tumors in fewer fractions, has emerged as a promising therapy to improve local control of LAPC; however, its effects on the tumor microenvironment and hypoxia remain poorly understood. To explore how SBRT affects pancreatic tumors, we combined an orthotopic mouse model of pancreatic cancer with an intravital microscopy platform to visualize changes to the in vivo tumor microenvironment in real-time. Mice received SBRT (5 × 8 Gy) or were left untreated, and were imaged before and 1, 4, 7, and 14 days after treatment (n = 7/group). A fluorescent human pancreatic cancer cell line (BxPC3-DsRed) engineered to express GFP under hypoxic conditions (driven by hypoxia-inducible factor, HIF) was used to monitor tumor hypoxia. Immunohistochemical staining was also performed on tissues to validate in vivo data. Our findings demonstrate a persistent decrease in pancreatic tumor hypoxia as early as one day after SBRT. This coincided with a decrease in both tumor cell proliferation and cell density in the SBRT group. Reduced demand for oxygen after SBRT (due to cell death and growth arrest from treatment) significantly contributed to reoxygenation of the pancreatic TME. Understanding how this reoxygenation phenomenon occurs in a dose-dependent manner will help improve dosing and fractionation schemes for clinical SBRT.
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Affiliation(s)
- Timothy Samuel
- Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Canada
| | - Sara Rapic
- Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
| | - Patricia E Lindsay
- Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Ralph S DaCosta
- Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
- Department of Medical Biophysics, University of Toronto, Toronto, Canada.
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van Goor IWJM, Andel PCM, Buijs FS, Besselink MG, Bonsing BA, Bosscha K, Busch OR, Cirkel GA, van Dam RM, Festen S, Koerkamp BG, van der Harst E, de Hingh IHJT, Kazemier G, Liem MSL, Meijer G, de Meijer VE, Nieuwenhuijs VB, Roos D, Schreinemakers JMJ, Stommel MWJ, Wit F, Verdonk RC, van Santvoort HC, Molenaar IQ, Intven MPW, Daamen LA. Prediction of Isolated Local Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Nationwide Study. Ann Surg Oncol 2024; 31:8264-8275. [PMID: 38937412 PMCID: PMC11467030 DOI: 10.1245/s10434-024-15664-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 06/10/2024] [Indexed: 06/29/2024]
Abstract
BACKGROUND Distinguishing postoperative fibrosis from isolated local recurrence (ILR) after resection of pancreatic ductal adenocarcinoma (PDAC) is challenging. A prognostic model that helps to identify patients at risk of ILR can assist clinicians when evaluating patients' postoperative imaging. This nationwide study aimed to develop a clinically applicable prognostic model for ILR after PDAC resection. PATIENTS AND METHODS An observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014-2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike's Information Criterion, and bootstrapped discrimination and calibration indices were assessed. RESULTS Among 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03-1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68-1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00-2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41-2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01-2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01-1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25-2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved. CONCLUSIONS This nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com , can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication.
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Affiliation(s)
- I W J M van Goor
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands.
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands.
| | - P C M Andel
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - F S Buijs
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - M G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - B A Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - K Bosscha
- Department of Surgery, Jeroen Bosch Hospital, Den Bosch, The Netherlands
| | - O R Busch
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - G A Cirkel
- Department of Medical Oncology, University Medical Center Utrecht Cancer Center & Meander Medical Center Amersfoort, Regional Academic Cancer Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - R M van Dam
- Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - S Festen
- Department of Surgery, OLVG, Amsterdam, The Netherlands
| | - B Groot Koerkamp
- Department of Surgery, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands
| | - E van der Harst
- Department of Surgery, Maasstad Hospital, Rotterdam, The Netherlands
| | - I H J T de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - G Kazemier
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, The Netherlands
| | - M S L Liem
- Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands
| | - G Meijer
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - V E de Meijer
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | | | - D Roos
- Department of Surgery, Renier de Graaf Gasthuis, Delft, The Netherlands
| | | | - M W J Stommel
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - F Wit
- Department of Surgery, Tjongerschans Hospital, Heerenveen, The Netherlands
| | - R C Verdonk
- Department of Gastroenterology, Regional Academic Cancer Center Utrecht, Utrecht, The Netherlands
| | - H C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - I Q Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - M P W Intven
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - L A Daamen
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands.
- Imaging Division, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
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Waheed A, Murland S, Yip E, Heikal A, Ghosh S, Abraham A, Paulson K, Tankel K, Usmani N, Severin D, Wong C, Joseph K. Sharing Mono-Institutional Experience of Treating Pancreatic Cancer with Stereotactic Body Radiation Therapy (SBRT). Curr Oncol 2024; 31:5974-5986. [PMID: 39451750 PMCID: PMC11506591 DOI: 10.3390/curroncol31100446] [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: 07/16/2024] [Revised: 09/14/2024] [Accepted: 09/16/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND Stereotactic body radiotherapy (SBRT) is an evolving treatment for the local management of pancreatic cancer (PC). The main purpose of this study is to report our initial experience in terms of local control (LC) and toxicity for PC patients treated with SBRT. METHODS We conducted a retrospective review of patients treated with SBRT using abdominal compression (AC) or an end-expiratory breath-holding (EEBH) technique. The median prescribed dose was 35 Gy, delivered in five fractions. Toxicities were recorded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and survival was estimated using the Kaplan-Meier method. RESULTS From 2017 to 2023, 17 PC patients were offered SBRT. Their median age was 69 years. The median follow-up from the date of diagnosis was 22.37 months. The overall survival (OS) was 94% at 1 year and 60.9% at 2 years. The progression-free survival (PFS) was 63.1% at 6 months and 56.1% at 9 months. The median OS was 26.3 months, and the median PFS was 20.6 months. The 6-month and 1-year LC rates were 71% and 50.8%, respectively. CONCLUSION We are successful in implementing the SBRT program at our centre. SBRT appears to be a promising treatment option for achieving LC with limited acute toxicities.
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Affiliation(s)
- Asmara Waheed
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada (A.A.); (K.P.); (K.T.); (N.U.); (D.S.)
| | - Shannah Murland
- Department of Radiation Therapy, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada;
| | - Eugene Yip
- Division of Medical Physics, Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada; (E.Y.); (A.H.)
| | - Amr Heikal
- Division of Medical Physics, Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada; (E.Y.); (A.H.)
| | - Sunita Ghosh
- Division of Medical Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada;
| | - Aswin Abraham
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada (A.A.); (K.P.); (K.T.); (N.U.); (D.S.)
| | - Kim Paulson
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada (A.A.); (K.P.); (K.T.); (N.U.); (D.S.)
| | - Keith Tankel
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada (A.A.); (K.P.); (K.T.); (N.U.); (D.S.)
| | - Nawaid Usmani
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada (A.A.); (K.P.); (K.T.); (N.U.); (D.S.)
| | - Diane Severin
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada (A.A.); (K.P.); (K.T.); (N.U.); (D.S.)
| | - Clarence Wong
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T6G 1Z2, Canada;
| | - Kurian Joseph
- Division of Radiation Oncology, Department of Oncology, University of Alberta & Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada (A.A.); (K.P.); (K.T.); (N.U.); (D.S.)
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van Goor IW, Raymakers L, Andel DS, Brosens LA, Kranenburg O, Leusen JH, Meijer GJ, Molenaar IQ, van Santvoort HC, de Vries JW, Wopereis AJ, Intven MP, Daamen LA. Radiation response assessment of organoids derived from patients with pancreatic cancer. Clin Transl Radiat Oncol 2024; 48:100829. [PMID: 39192878 PMCID: PMC11347840 DOI: 10.1016/j.ctro.2024.100829] [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: 06/19/2023] [Revised: 04/26/2024] [Accepted: 07/27/2024] [Indexed: 08/29/2024] Open
Abstract
Background The effectiveness of radiotherapy for pancreatic cancer is debated. Patient-derived organoids (PDOs) already mimicked clinical radiation response in other cancer types, which could be valuable in pancreatic cancer as well. This study aimed to investigate whether PDOs can be used to model RT response in pancreatic cancer and to explore the presence of a dose-response correlation. Methods PDOs derived from two pancreatic cancer patients (HUB-08-B2-022A and HUB-08-B2-026B) were irradiated with doses ranging from 0 to 40 Gray. Viability assessments were conducted after seven and 10 days by measuring ATP-levels. Results were normalized, defining the viability at 0 Gray as 100 % and an absolute viability of 0 as 0 %. The relative area under the curve (rAUC) was calculated (0 = total sensitivity, 1 = total resistance). Results With a readout time of seven days, both HUB-08-B2-022A and HUB-08-B2-026B exhibited viability above 50 % at the highest dose of 12 Gy (rAUC of 0.79 and 0.69, respectively). With a readout time of 10 days, both PDOs showed a dose-response relation although HUB-08-B2-022A was more sensitive than HUB-08-B2-026B (rAUC of 0.37 and 0.51, respectively). Increasing the radiation dose to 40 Gy did not further affect viability, but the dose-response relation remained present (rAUC of 0.13 and 0.26, respectively). In the final experiment with a readout time of 10 days and a maximum dose of 14 Gy, the dose-response correlation was paramount in both PDOs (rAUC 0.28 and 0.45, respectively), with HUB-08-B2-022A being most sensitive. Conclusions In this setup, both pancreatic cancer PDOs showed an irradiation dose-response correlation. These preliminary findings suggest that pancreatic cancer PDOs are suitable for assessing radiation response in vitro. Further experiments are needed to eventually simulate treatment responses to personalized treatment strategies.
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Affiliation(s)
- Iris W.J.M. van Goor
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands
| | - Leon Raymakers
- Center for Translational Immunology, UMC Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Daan S.H. Andel
- Department of Surgical Oncology, Lab of Translational Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Lodewijk A.A. Brosens
- Department of Pathology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands
| | - Onno Kranenburg
- Department of Surgical Oncology, Lab of Translational Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Jeanette H.W. Leusen
- Center for Translational Immunology, UMC Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Gert J. Meijer
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands
| | - I. Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands
| | - Hjalmar C. van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands
| | - J.H. Wilfred de Vries
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands
| | - Andre J.M. Wopereis
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands
| | - Martijn P.W. Intven
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands
| | - Lois A. Daamen
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, the Netherlands
- Imaging Division, University Medical Center Utrecht Cancer Center, Utrecht University, Utrecht, the Netherlands
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de la Pinta C. Stereotactic body radiotherapy in pancreatic adenocarcinoma. Hepatobiliary Pancreat Dis Int 2024; 23:14-19. [PMID: 36990839 DOI: 10.1016/j.hbpd.2023.03.002] [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: 04/14/2022] [Accepted: 02/28/2023] [Indexed: 03/31/2023]
Abstract
BACKGROUND Stereotactic body radiotherapy (SBRT) in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue. This review aimed at the SBRT application in the treatment of pancreatic cancer. DATA SOURCES We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022. Keywords used in the search included: "pancreatic adenocarcinoma" OR "pancreatic cancer" AND "stereotactic ablative radiotherapy (SABR)" OR "stereotactic body radiotherapy (SBRT)" OR "chemoradiotherapy (CRT)". English language articles with information on technical characteristics, doses and fractionation, indications, recurrence patterns, local control and toxicities of SBRT in pancreatic tumors were included. All articles were assessed for validity and relevant content. RESULTS Optimal doses and fractionation have not yet been defined. However, SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT. Furthermore, the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma. CONCLUSIONS SBRT is an effective modality for patients with pancreatic cancer, supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control. SBRT opens a possibility of improving outcomes for these patients, both in neoadjuvant treatment and with radical intent.
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Affiliation(s)
- Carolina de la Pinta
- Radiation Oncology Department, Ramón y Cajal University Hospital, IRYCIS, Alcalá University, 28034 Madrid, Spain.
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Han Z, Sudhyadhom A, Hsu SH, Hu YH, Mak RH, Huynh MA, van Dams RR, Tanguturi S, Venkatachalam V, Mancias JD, Mamon HJ, Martin NE, Lam MB, Leeman JE. Comparison of MR-soft tissue based versus biliary stent based alignment for image guidance in pancreatic SBRT. J Appl Clin Med Phys 2023:e13965. [PMID: 36924220 DOI: 10.1002/acm2.13965] [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: 12/05/2022] [Revised: 01/27/2023] [Accepted: 03/03/2023] [Indexed: 03/18/2023] Open
Abstract
PURPOSE The role of biliary stents in image-guided localization for pancreatic cancer has been inconclusive. To date, stent accuracy has been largely evaluated against implanted fiducials on cone beam computed tomography. We aim to use magnetic resonance (MR) soft tissue as a direct reference to examine the geometric and dosimetric impacts of stent-based localization on the newly available MR linear accelerator. METHODS Thirty pancreatic cancer patients (132 fractions) treated on our MR linear accelerator were identified to have a biliary stent. In our standard adaptive workflow, patients were set up to the target using soft tissue for image registration and structures were re-contoured on daily MR images. The original plan was then projected on treatment anatomy and dose predicted, followed by plan re-optimization and treatment delivery. These online predicted plans were soft tissue-based and served as reference plans. Retrospective image registration to the stent was performed offline to simulate stent-based localization and the magnitude of shifts was taken as the geometric accuracy of stent localization. New predicted plans were generated based on stent-alignment for dosimetric comparison. RESULTS Shifts were within 3 mm for 90% of the cases (mean = 1.5 mm); however, larger shifts up to 7.2 mm were observed. Average PTV coverage dropped by 1.1% with a maximum drop of 26.8%. The mean increase in V35Gy was 0.15, 0.05, 0.02, and 0.02 cc for duodenum, stomach, small bowel and large bowel, respectively. Stent alignment was significantly worse for all metrics except for small bowel (p = 0.07). CONCLUSIONS Overall discrepancy between stent- and soft tissue-alignment was modest; however, large discrepancies were observed for select cases. While PTV coverage loss may be compensated for by using a larger margin, the increase in dose to gastrointestinal organs at risk may limit the role of biliary stents in image-guided localization.
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Affiliation(s)
- Zhaohui Han
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Atchar Sudhyadhom
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Shu-Hui Hsu
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Yue-Houng Hu
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Raymond H Mak
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Mai Anh Huynh
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Ritchell R van Dams
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Shyam Tanguturi
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Veena Venkatachalam
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Joseph D Mancias
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Harvey J Mamon
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Neil E Martin
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Miranda B Lam
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Jonathan E Leeman
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
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7
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van Goor IWJM, Daamen LA, Besselink MG, Bruynzeel AME, Busch OR, Cirkel GA, Groot Koerkamp B, Haj Mohammed N, Heerkens HD, van Laarhoven HWM, Meijer GJ, Nuyttens J, van Santvoort HC, van Tienhoven G, Verkooijen HM, Wilmink JW, Molenaar IQ, Intven MPW. A nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy (ARCADE). Trials 2022; 23:913. [PMID: 36307892 PMCID: PMC9617359 DOI: 10.1186/s13063-022-06829-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 10/06/2022] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Disease recurrence is the main cause of mortality after resection of pancreatic ductal adenocarcinoma (PDAC). In 20-30% of resected patients, isolated local PDAC recurrence occurs. Retrospective studies have suggested that stereotactic body radiation therapy (SBRT) might lead to improved local control in these patients, potentially having a beneficial effect on both survival and quality of life. The "nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy" (ARCADE) will investigate the value of SBRT in addition to standard of care in patients with isolated local PDAC recurrence compared to standard of care alone, regarding both survival and quality of life outcomes. METHODS The ARCADE trial is nested within a prospective cohort (Dutch Pancreatic Cancer Project; PACAP) according to the 'Trials within Cohorts' design. All PACAP participants with isolated local PDAC recurrence after primary resection who provided informed consent for being randomized in future studies are eligible. Patients will be randomized for local therapy (5 fractions of 8 Gy SBRT) in addition to standard of care or standard of care alone. In total, 174 patients will be included. The main study endpoint is survival after recurrence. The most important secondary endpoint is quality of life. DISCUSSION It is hypothesized that additional SBRT, compared to standard of care alone, improves survival and quality of life in patients with isolated local recurrence after PDAC resection. TRIAL REGISTRATION ClinicalTrials.gov registration NCT04881487 . Registered on May 11, 2021.
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Affiliation(s)
- I W J M van Goor
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands.
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands.
| | - L A Daamen
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
- Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - M G Besselink
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - A M E Bruynzeel
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Radiation Oncology, Amsterdam University Medical Center, location Vrije Universiteit, Amsterdam, the Netherlands
| | - O R Busch
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - G A Cirkel
- Department of Medical Oncology, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
| | - B Groot Koerkamp
- Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands
| | - N Haj Mohammed
- Department of Medical Oncology, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
| | - H D Heerkens
- Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - H W M van Laarhoven
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, the Netherlands
| | - G J Meijer
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
| | - J Nuyttens
- Department of Radiation Oncology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - H C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
| | - G van Tienhoven
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Radiation Oncology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - H M Verkooijen
- Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - J W Wilmink
- Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, the Netherlands
| | - I Q Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands
| | - M P W Intven
- Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht, the Netherlands.
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8
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Burkoň P, Trna J, Slávik M, Němeček R, Kazda T, Pospíšil P, Dastych M, Eid M, Novotný I, Procházka T, Vrzal M. Stereotactic Body Radiotherapy (SBRT) of Pancreatic Cancer-A Critical Review and Practical Consideration. Biomedicines 2022; 10:biomedicines10102480. [PMID: 36289742 PMCID: PMC9599229 DOI: 10.3390/biomedicines10102480] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 09/18/2022] [Accepted: 09/30/2022] [Indexed: 11/23/2022] Open
Abstract
Pancreatic cancer is the third leading cause of cancer death in the developed world and is predicted to become the second by 2030. A cure may be achieved only with surgical resection of an early diagnosed disease. Surgery for more advanced disease is challenging and can be contraindicated for many reasons. Neoadjuvant therapy may improve the probability of achieving R0 resection. It consists of systemic treatment followed by radiation therapy applied concurrently or sequentially with cytostatics. A novel approach to irradiation, stereotactic body radiotherapy (SBRT), has the potential to improve treatment results. SBRT can deliver higher doses of radiation to the tumor in only a few treatment fractions. It has attracted significant interest for pancreatic cancer patients, as it is completed quickly, requires less time away from full-dose chemotherapy, and is well-tolerated than conventional radiotherapy. In this review, we aim to provide the reader with a basic overview of current evidence for SBRT indications in the treatment of pancreatic tumors. In the second part of the review, we focus on practical information with respect to SBRT treatment plan preparation the performance of such therapy. Finally, we discuss future directions related to the use of magnetic resonance linear accelerators.
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Affiliation(s)
- Petr Burkoň
- Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 57 Brno, Czech Republic
- Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
| | - Jan Trna
- Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
- Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 53 Brno, Czech Republic
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 53 Brno, Czech Republic
- Correspondence: (J.T.); (M.S.)
| | - Marek Slávik
- Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 57 Brno, Czech Republic
- Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
- Correspondence: (J.T.); (M.S.)
| | - Radim Němeček
- Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 53 Brno, Czech Republic
| | - Tomáš Kazda
- Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 57 Brno, Czech Republic
- Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
| | - Petr Pospíšil
- Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 57 Brno, Czech Republic
- Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
| | - Milan Dastych
- Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
- Department of Gastroenterology, University Hospital Brno, Jihlavska 340/20, 625 00 Brno, Czech Republic
| | - Michal Eid
- Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
- Department of Hematology, Oncology and Internal Medicine, University Hospital Brno, Jihlavska 340/20, 625 00 Brno, Czech Republic
| | - Ivo Novotný
- Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 53 Brno, Czech Republic
| | - Tomáš Procházka
- Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 57 Brno, Czech Republic
- Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
| | - Miroslav Vrzal
- Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 57 Brno, Czech Republic
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9
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de la Pinta C. Radiomics in pancreatic cancer for oncologist: Present and future. Hepatobiliary Pancreat Dis Int 2022; 21:356-361. [PMID: 34961674 DOI: 10.1016/j.hbpd.2021.12.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 12/07/2021] [Indexed: 02/05/2023]
Abstract
Radiomics is changing the world of medicine and more specifically the world of oncology. Early diagnosis and treatment improve the prognosis of patients with cancer. After treatment, the evaluation of the response will determine future treatments. In oncology, every change in treatment means a loss of therapeutic options and this is key in pancreatic cancer. Radiomics has been developed in oncology in the early diagnosis and differential diagnosis of benign and malignant lesions, in the evaluation of response, in the prediction of possible side effects, marking the risk of recurrence, survival and prognosis of the disease. Some studies have validated its use to differentiate normal tissues from tumor tissues with high sensitivity and specificity, and to differentiate cystic lesions and pancreatic neuroendocrine tumor grades with texture parameters. In addition, these parameters have been related to survival in patients with pancreatic cancer and to response to radiotherapy and chemotherapy. This review aimed to establish the current status of the use of radiomics in pancreatic cancer and future perspectives.
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Affiliation(s)
- Carolina de la Pinta
- Radiation Oncology Department, Ramón y Cajal University Hospital, IRYCIS, Alcalá University, 28034 Madrid, Spain.
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10
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Lambin T, Lafon C, Drainville RA, Pioche M, Prat F. Locoregional therapies and their effects on the tumoral microenvironment of pancreatic ductal adenocarcinoma. World J Gastroenterol 2022; 28:1288-1303. [PMID: 35645539 PMCID: PMC9099187 DOI: 10.3748/wjg.v28.i13.1288] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/10/2022] [Accepted: 02/27/2022] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of death from cancer by 2030. Despite intensive research in the field of therapeutics, the 5-year overall survival is approximately 8%, with only 20% of patients eligible for surgery at the time of diagnosis. The tumoral microenvironment (TME) of the PDAC is one of the main causes for resistance to antitumoral treatments due to the presence of tumor vasculature, stroma, and a modified immune response. The TME of PDAC is characterized by high stiffness due to fibrosis, with hypo microvascular perfusion, along with an immunosuppressive environment that constitutes a barrier to effective antitumoral treatment. While systemic therapies often produce severe side effects that can alter patients' quality of life, locoregional therapies have gained attention since their action is localized to the pancreas and can thus alleviate some of the barriers to effective antitumoral treatment due to their physical effects. Local hyperthermia using radiofrequency ablation and radiation therapy - most commonly using a local high single dose - are the two main modalities holding promise for clinical efficacy. Recently, irreversible electroporation and focused ultrasound-derived cavitation have gained increasing attention. To date, most of the data are limited to preclinical studies, but ongoing clinical trials may help better define the role of these locoregional therapies in the management of PDAC patients.
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Affiliation(s)
- Thomas Lambin
- LabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Univ Lyon, Lyon 69003, France
- Department of Gastroenterology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon 69008, France
| | - Cyril Lafon
- LabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Univ Lyon, Lyon 69003, France
| | | | - Mathieu Pioche
- Department of Gastroenterology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon 69008, France
| | - Frédéric Prat
- Service d’Endoscopie Digestive, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy 92110, France
- INSERM U1016, Institut Cochin, Université de Paris, Paris 75014, France
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11
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Erickson BG, Ackerson BG, Kelsey CR, Yin FF, Adamson J, Cui Y. The effect of various dose normalization strategies when implementing linear Boltzmann transport equation dose calculation for lung SBRT planning. Pract Radiat Oncol 2022; 12:446-456. [DOI: 10.1016/j.prro.2022.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/19/2022] [Accepted: 02/07/2022] [Indexed: 11/16/2022]
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12
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Daamen LA, de Mol van Otterloo SR, van Goor IWJM, Eijkelenkamp H, Erickson BA, Hall WA, Heerkens HD, Meijer GJ, Molenaar IQ, van Santvoort HC, Verkooijen HM, Intven MPW. Online adaptive MR-guided stereotactic radiotherapy for unresectable malignancies in the upper abdomen using a 1.5T MR-linac. Acta Oncol 2022; 61:111-115. [PMID: 34879792 DOI: 10.1080/0284186x.2021.2012593] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Introduction of online adaptive MR-guided radiotherapy enables stereotactic body radiation therapy (SBRT) of upper abdominal tumors. This study aimed to evaluate the feasibility of MR-guided SBRT on a 1.5 T MR-linac in patients with unresectable upper abdominal malignancies. MATERIAL AND METHODS Patients treated at the UMC Utrecht (April 2019 to December 2020) were identified in the prospective 'Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac' (MOMENTUM) study. Feasibility of treatment was arbitrarily defined as an on-table time interval of ≤60 min for >75% of delivered fractions and completion of >95% of fractions as scheduled, reflecting patient tolerability. Acute treatment-related toxicity was assessed at 3 months of follow-up and graded according to the National Cancer Institute Common Terminology Criteria of Adverse Events version 5.0. RESULTS Twenty-five consecutive patients with a median follow-up time of 8 (range 4-23) months were treated with 35 Gray (n = 4) and 40 Gray (n = 21) in five fractions over 2 weeks. For all fractions, contours were adapted based on the daily anatomy and delivered within 47 min/fraction (range 30-74). In 98/117 fractions (84%), adapted treatment was completed within 1 h. All patients received the scheduled irradiation dose as planned. No acute grade 3 toxicity or higher was reported. Treatment resulted in pain alleviation in 11/13 patients. DISCUSSION Online adaptive MR-guided SBRT on a 1.5 T MR-linac is feasible and well-tolerated in patients with unresectable upper abdominal malignancies. Dose escalation studies, followed by comparative studies, are needed to determine the optimal radiation dose for irradiation of upper abdominal malignancies.
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Affiliation(s)
- Lois A. Daamen
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands
- Department of Radiation Oncology, UMC Utrecht Cancer Center, Utrecht University, Utrecht, The Netherlands
| | | | - Iris W. J. M. van Goor
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands
- Department of Radiation Oncology, UMC Utrecht Cancer Center, Utrecht University, Utrecht, The Netherlands
| | - Hidde Eijkelenkamp
- Department of Radiation Oncology, UMC Utrecht Cancer Center, Utrecht University, Utrecht, The Netherlands
| | - Beth A. Erickson
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - William A. Hall
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Hanne D. Heerkens
- Department of Radiation Oncology, UMC Utrecht Cancer Center, Utrecht University, Utrecht, The Netherlands
| | - Gert J. Meijer
- Department of Radiation Oncology, UMC Utrecht Cancer Center, Utrecht University, Utrecht, The Netherlands
| | - I. Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands
| | - Hjalmar C. van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands
| | - Helena M. Verkooijen
- Division of Imaging, UMC Utrecht Cancer Center, Utrecht University, Utrecht, The Netherlands
| | - Martijn P. W. Intven
- Department of Radiation Oncology, UMC Utrecht Cancer Center, Utrecht University, Utrecht, The Netherlands
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13
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Hue JJ, Dorth J, Sugumar K, Hardacre JM, Ammori JB, Rothermel LD, Saltzman J, Mohamed A, Selfridge JE, Bajor D, Winter JM, Ocuin LM. Neoadjuvant Radiotherapy is Associated With Improved Pathologic Outcomes and Survival in Resected Stage II-III Pancreatic Adenocarcinoma Treated With Multiagent Neoadjuvant Chemotherapy in the Modern Era. Am Surg 2021; 87:1386-1395. [PMID: 34382877 DOI: 10.1177/00031348211038581] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Neoadjuvant chemotherapy (CT) is being utilized more frequently in patients diagnosed with localized pancreatic cancer. The role of additional neoadjuvant radiotherapy (RT) remains undefined. We explored outcomes associated with neoadjuvant RT in the modern era. METHODS The National Cancer Database (2010-2017) was queried for patients with clinical stage II-III pancreatic adenocarcinoma who received neoadjuvant multiagent systemic CT +/- RT. Demographics, pathologic outcomes, postoperative outcomes, and overall survival were compared. RESULTS A total of 5245 patients were included, of whom 3123 received CT and 1941 received CT + RT. Use of RT decreased over the 8-year study period. On multivariable analysis, treatment at academic facilities (odds ratio (OR) = 1.52, P < .001) and clinical T4 tumors (OR = 1.68, P < .001) were independently associated with receipt of RT. Patients treated with CT + RT had a higher frequency of ypT0-T2 tumors (35.8% vs. 22.7%) and a lower rate of ypT3-T4 tumors (57.3% vs. 72.8%; P < .001), lower rate of node-positive disease (36.6% vs. 59.8%, P < .001), and margin-positive resections (13.8% vs. 20.2%, P < .001), but slightly higher 90-day postoperative mortality (4.9% vs. 3.6%, P = .04). Neoadjuvant chemotherapy+ RT was associated with longer overall survival (32.7 vs. 29.8 months, P = .008), and remained independently associated with survival on multivariable analysis (HR = .85, P < .001). DISCUSSION In patients with stage II-III pancreatic adenocarcinoma, the addition of neoadjuvant RT to multiagent neoadjuvant CT may be associated with increased rates of node-negative and margin-negative resection, as well as improved overall survival.
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Affiliation(s)
- Jonathan J Hue
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jennifer Dorth
- Department of Radiology, Division of Radiation Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Kavin Sugumar
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jeffrey M Hardacre
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - John B Ammori
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Luke D Rothermel
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Joel Saltzman
- Department of Medicine, Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Amr Mohamed
- Department of Medicine, Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jennifer E Selfridge
- Department of Medicine, Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - David Bajor
- Department of Medicine, Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jordan M Winter
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Lee M Ocuin
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
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14
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Janssen QP, van Dam JL, Kivits IG, Besselink MG, van Eijck CHJ, Homs MYV, Nuyttens JJME, Qi H, van Santvoort HJ, Wei AC, de Wilde RF, Wilmink JW, van Tienhoven G, Groot Koerkamp B. Added Value of Radiotherapy Following Neoadjuvant FOLFIRINOX for Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis. Ann Surg Oncol 2021; 28:8297-8308. [PMID: 34142290 PMCID: PMC8591030 DOI: 10.1245/s10434-021-10276-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 05/09/2021] [Indexed: 12/30/2022]
Abstract
Background The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy. Methods A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes. Results We included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4–34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0–37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable. Conclusions In this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-021-10276-8.
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Affiliation(s)
- Quisette P Janssen
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Jacob L van Dam
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Isabelle G Kivits
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
| | | | - Marjolein Y V Homs
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Joost J M E Nuyttens
- Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Hongchao Qi
- Department of Biostatistics, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Hjalmar J van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital and University Medical Center Utrecht, Nieuwegein, The Netherlands
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Roeland F de Wilde
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Johanna W Wilmink
- Department of Medical Oncology, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
| | - Geertjan van Tienhoven
- Department of Radiation Oncology, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
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15
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Ghaly M, Gogineni E, Herman J, Saif MW. New Potential Options for SBRT in Pancreatic Cancer. CANCER MEDICINE JOURNAL 2021; 4:41-50. [PMID: 34355218 PMCID: PMC8336074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Stereotactic body radiotherapy (SBRT) is an emerging treatment option for patients with pancreatic cancer, as it can provide a therapeutic benefit with significant advantages for patients' quality of life over standard conventional chemoradiation (CRT). The objective of this review is to present alternative clinical settings in which SBRT may benefit patients with pancreatic cancer. These include palliation of pain, elderly patients who are not surgical candidates, local therapy in oligometastatic cases and salvaging local failures after surgery or external beam radiation. We will review these individually and provide supporting literature for each.
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Affiliation(s)
- Maged Ghaly
- Northwell Health Cancer Institute, Lake Success, NY 11042, USA
| | - Emile Gogineni
- Northwell Health Cancer Institute, Lake Success, NY 11042, USA
| | - Joseph Herman
- Northwell Health Cancer Institute, Lake Success, NY 11042, USA
| | - Muhammad W Saif
- Northwell Health Cancer Institute, Lake Success, NY 11042, USA
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16
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Li CG, Zhou ZP, Jia YZ, Tan XL, Song YY. Radioactive 125I seed implantation for pancreatic cancer with unexpected liver metastasis: A preliminary experience with 26 patients. World J Clin Cases 2021; 9:792-800. [PMID: 33585625 PMCID: PMC7852643 DOI: 10.12998/wjcc.v9.i4.792] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/03/2020] [Accepted: 12/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Preoperative diagnosis rate of pancreatic cancer has increased year by year. The prognosis of pancreatic cancer patients with unexpected liver metastasis found by intraoperative exploration is very poor, and there is no effective and unified treatment strategy.
AIM To evaluate the therapeutic effect of radioactive 125I seed implantation for pancreatic cancer patients with unexpected liver metastasis.
METHODS The demographics and perioperative outcomes of patients who underwent 125I seed implantation to treat pancreatic cancer with unexpected liver metastasis between January 1, 2017 and June 1, 2019 were retrospectively analyzed. During the operation, 125I seeds were implanted into the pancreatic tumor under the guidance of intraoperative ultrasound, with a spacing of 1.5 cm and a row spacing of 1.5 cm. For patients with obstructive jaundice and digestive tract obstruction, choledochojejunostomy and gastroenterostomy were performed simultaneously. After operation, the patients were divided into a non-chemotherapy group and a chemotherapy group that received gemcitabine combined with albumin-bound paclitaxel treatment.
RESULTS Preoperative imaging evaluation of all patients in this study showed that the tumor was resectable without liver metastasis. There were 26 patients in this study, including 18 males and 8 females, aged 60.5 ± 9.7 years. The most common tumor site was the pancreatic head (17, 65.4%), followed by the pancreatic neck and body (6, 23.2%) and pancreatic tail (3, 11.4%). Fourteen patients (53.8%) underwent palliative surgery and postoperative pain relief occurred in 22 patients (84.6%). The estimated blood loss in operation was 148.3 ± 282.1 mL and one patient received blood transfusion. The postoperative hospital stay was 7.6 ± 2.8 d. One patient had biliary fistula, one had pancreatic fistula, and all recovered after conservative treatment. After operation, 7 patients received chemotherapy and 19 did not. The 1-year survival rate was significantly higher in patients who received chemotherapy than in those who did not (68.6% vs 15.8%, P = 0.012). The mean overall survival of patients in the chemotherapy group and non-chemotherapy group was 16.3 mo and 10 mo, respectively (χ2 = 7.083, P = 0.008).
CONCLUSION Radioactive 125I seed implantation combined with postoperative chemotherapy can prolong the survival time and relieve pain of pancreatic cancer patients with unexpected liver metastasis.
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Affiliation(s)
- Cheng-Gang Li
- Second Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhi-Peng Zhou
- Second Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Yu-Ze Jia
- Second Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiang-Long Tan
- Second Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Yu-Yao Song
- Second Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
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17
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Li CG, Zhou ZP, Jia YZ, Tan XL, Song YY. Radioactive 125I seed implantation for locally advanced pancreatic cancer: A retrospective analysis of 50 cases. World J Clin Cases 2020; 8:3743-3750. [PMID: 32953850 PMCID: PMC7479562 DOI: 10.12998/wjcc.v8.i17.3743] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 05/25/2020] [Accepted: 08/12/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Pancreatic cancer is one of the common malignant tumors of the digestive system, and radical resection is the first choice of treatment for pancreatic cancer. If patients with locally advanced pancreatic cancer cannot be treated in time and effectively, their disease often develops rapidly and their survival period is very short.
AIM To evaluate the therapeutic effect of 125I seed implantation in patients with locally advanced pancreatic cancer.
METHODS The demographics and perioperative outcomes of a consecutive series of patients who underwent 125I seed implantation to treat locally advanced pancreatic cancer between January 1, 2017 and June 30, 2019 were retrospectively analyzed. According to the results of preoperative computed tomography or magnetic resonance imaging, the treatment planning system was used to determine the area and number of 125I seeds implanted. During the operation, 125I seeds were implanted into the tumor under the guidance of intraoperative ultrasound, with a spacing of 1.5 cm and a row spacing of 1.5 cm. For patients with obstructive jaundice and digestive tract obstruction, choledochojejunostomy and gastroenterostomy were performed simultaneously. After operation, the patients were divided into a non-chemotherapy group and a chemotherapy group that received gemcitabine combined with albumin-bound paclitaxel treatment.
RESULTS Among the 50 patients, there were 29 males and 21 females, with a mean age of 56.9 ± 9.8 years. The main reason for the failure of radical resection was superior mesenteric artery invasion (37, 74%), followed by superior mesenteric vein invasion (33, 66%). Twenty-one (62%) patients underwent palliative surgery and postoperative pain relief occurred in 40 (80%) patients. The estimated blood loss in operation was 107.4 ± 115.3 mL and none of the patient received blood transfusion. The postoperative hospital stay was 7.5 ± 4.2 d; one patient had biliary fistula and three had pancreatic fistula, all of whom recovered after conservative treatment. After operation, 26 patients received chemotherapy and 24 did not. The 1-year survival rate was significantly higher in patients who received chemotherapy than in those who did not (60.7% vs 35.9%, P = 0.034). The mean overall survival of patients of the chemotherapy group and non-chemotherapy group was 14 and 11 mo, respectively (χ2 = 3.970, P = 0.046).
CONCLUSION Radioactive 125I seed implantation combined with postoperative chemotherapy can prolong the survival time, relieve pain, and improve the quality of life of patients with locally advanced pancreatic cancer.
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Affiliation(s)
- Cheng-Gang Li
- Second Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhi-Peng Zhou
- Second Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Yu-Ze Jia
- Second Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiang-Long Tan
- Second Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Yu-Yao Song
- Second Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
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Saif MW. Outstanding Outcome of Pancreatic Cancer: What Lessons Do We Learn. PANCREAS (FAIRFAX, VA.) 2020; 4:e012. [PMID: 32685869 PMCID: PMC7367552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Muhammad W. Saif
- Corresponding author: Muhammad W. Saif, MD, Professor, Deputy Physician-in-Chief, Northwell Health Cancer Institute and Donald and Barbara Zucker School of Medicine, Hofstra/Northwell, NY, USA; Tel. (516) 321-2238;
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