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Radiotherapy for Resectable and Borderline Resectable Pancreas Cancer: When and Why?

  • Review Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

The role of (chemo) radiation in the perioperative management of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma is controversial. Herein, we review and interpret existing data relating to the ability of (chemo) radiation to “downstage” pancreatic tumors, delay recurrence, and prolong patients’ survival. In sum, the evidence suggests that while neoadjuvant (chemo) radiation may impact pathologic metrics favorably, it rarely converts anatomically unresectable tumors to resectable ones. And while data do support the ability of (chemo)radiation to delay cancer progression, its ability to prolong longevity has not been confirmed. It is possible that (chemo)radiation is effective in prolonging the survival of select patients, but to date, this cohort remains undefined due to heterogeneity in both the populations studied and the regimens used to treat them. Based on our interpretation of existing data, we currently administer neoadjuvant and adjuvant (chemo)radiation selectively to patients with localized pancreatic cancer who we consider at highest risk for local progression. We may also use it as an alternative to pancreatectomy in patients who are poor candidates for surgery. Ultimately, the role of (chemo)radiation in these settings is evolving. Better studies of patients most likely to benefit from its local effects are necessary to clearly define its place within the perioperative treatment algorithms used for patients with localized pancreatic cancer.

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References

  1. Katz MH, Wang H, Balachandran A, Bhosale P, Crane CH, Wang X, et al. Effect of neoadjuvant chemoradiation and surgical technique on recurrence of localized pancreatic cancer. J Gastrointest Surg 2012;16:68-78; discussion -9

    Article  Google Scholar 

  2. Haeno H, Gonen M, Davis MB, Herman JM, Iacobuzio-Donahue CA, Michor F. Computational modeling of pancreatic cancer reveals kinetics of metastasis suggesting optimum treatment strategies. Cell 2012;148:362-75

    Article  CAS  Google Scholar 

  3. Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009;27:1806-13

    Article  CAS  Google Scholar 

  4. Swanson RS, Pezzi CM, Mallin K, Loomis AM, Winchester DP. The 90-day mortality after pancreatectomy for cancer is double the 30-day mortality: more than 20,000 resections from the national cancer data base. Ann Surg Oncol 2014;21:4059-67

    Article  Google Scholar 

  5. Hartwig W, Strobel O, Hinz U, Fritz S, Hackert T, Roth C, et al. CA19-9 in potentially resectable pancreatic cancer: perspective to adjust surgical and perioperative therapy. Ann Surg Oncol 2013;20:2188-96

    Article  Google Scholar 

  6. Khorana AA, McKernin SE, Berlin J, Hong TS, Maitra A, Moravek C, et al. Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update. J Clin Oncol 2019;37(no. 23):2082-8

  7. Khorana AA, Mangu PB, Berlin J, Engebretson A, Hong TS, Maitra A, et al. Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2016;34:2541-56

    Article  Google Scholar 

  8. Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 1985;120:899-903

    Article  CAS  Google Scholar 

  9. Smeenk HG, van Eijck CH, Hop WC, Erdmann J, Tran KC, Debois M, et al. Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891. Ann Surg 2007;246:734-40

    Article  Google Scholar 

  10. Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004;350:1200-10

    Article  CAS  Google Scholar 

  11. Abrams RA, Winter KA, Safran H, Goodman KA, Regine WF, Berger AC, et al. Results of the NRG Oncology/RTOG 0848 Adjuvant Chemotherapy Question-Erlotinib+Gemcitabine for Resected Cancer of the Pancreatic Head: A Phase II Randomized Clinical Trial. Am J Clin Oncol 2020;43:173-9

    Article  Google Scholar 

  12. Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, et al. Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial. JAMA 2016;315:1844-53

    Article  CAS  Google Scholar 

  13. Khorana AA, McKernin SE, Berlin J, Hong TS, Maitra A, Moravek C, et al. Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update. J Clin Oncol 2019;37:2082-8

    Article  CAS  Google Scholar 

  14. Golcher H, Brunner TB, Witzigmann H, Marti L, Bechstein WO, Bruns C, et al. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial. Strahlenther Onkol 2015;191:7-16

    Article  Google Scholar 

  15. Versteijne E, Suker M, Groothius K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: results of the Dutch randomized phase III PREOPANC trial. J Clin Oncol 2020;38:1763-73

    Article  CAS  Google Scholar 

  16. Jang JY, Han Y, Lee H, Kim SW, Kwon W, Lee KH, et al. Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial. Ann Surg 2018;268:215-22

    Article  Google Scholar 

  17. Motoi F, Kosuge T, Ueno H, Yamaue H, Satoi S, Sho M, et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). Jpn J Clin Oncol 2019;49:190-4

    Article  Google Scholar 

  18. Ahmad SA, Duong M, Sohal DPS, Gandhi NS, Beg MS, Wang-Gillam A, et al. Surgical Outcome Results From SWOG S1505: A Randomized Clinical Trial of mFOLFIRINOX Versus Gemcitabine/Nab-paclitaxel for Perioperative Treatment of Resectable Pancreatic Ductal Adenocarcinoma. Ann Surg 2020

  19. Katz MHG, Ou FS, Herman JM, Ahmad SA, Wolpin B, Marsh R, et al. Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas. BMC Cancer 2017;17:505

    Article  Google Scholar 

  20. Cloyd JM, Crane CH, Koay EJ, Das P, Krishnan S, Prakash L, et al. Impact of hypofractionated and standard fractionated chemoradiation before pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Cancer 2016;122:2671-9

    Article  CAS  Google Scholar 

  21. Katz MH, Fleming JB, Bhosale P, Varadhachary G, Lee JE, Wolff R, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 2012;118:5749-56

    Article  Google Scholar 

  22. Gillen S, Schuster T, Meyer Zum Büschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 2010;7:e1000267

    Article  Google Scholar 

  23. Katz MH, Marsh R, Herman JM, Shi Q, Collison E, Venook AP, et al. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol 2013;20:2787-95

    Article  Google Scholar 

  24. Perri G, Prakash L, Malleo G, Caravati A, Varadhachary GR, Fogelman D, et al. The Sequential Radiographic Effects of Preoperative Chemotherapy and (Chemo)Radiation on Tumor Anatomy in Patients with Localized Pancreatic Cancer. Ann Surg Oncol 2020;27:3939-47

    Article  Google Scholar 

  25. Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg 2015;261:12-7

    Article  Google Scholar 

  26. Landau E, Kalnicki S. The Evolving Role of Radiation in Pancreatic Cancer. Surg Clin North Am 2018;98:113-25

    Article  Google Scholar 

  27. Herman JM, Chang DT, Goodman KA, Dholakia AS, Raman SP, Hacker-Prietz A, et al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer 2015;121:1128-37

    Article  CAS  Google Scholar 

  28. Tchelebi LT, Lehrer EJ, Trifiletti DM, Sharma NK, Gusani NJ, Crane CH, et al. Conventionally fractionated radiation therapy versus stereotactic body radiation therapy for locally advanced pancreatic cancer (CRiSP): An international systematic review and meta-analysis. Cancer 2020;126:2120-31

    Article  CAS  Google Scholar 

  29. Zhu X, Ju X, Cao Y, Shen Y, Cao F, Qing S, et al. Patterns of Local Failure After Stereotactic Body Radiation Therapy and Sequential Chemotherapy as Initial Treatment for Pancreatic Cancer: Implications of Target Volume Design. Int J Radiat Oncol Biol Phys 2019;104:101-10

    Article  Google Scholar 

  30. Kharofa J, Mierzwa M, Olowokure O, Sussman J, Latif T, Gupta A, et al. Pattern of Marginal Local Failure in a Phase II Trial of Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy for Resectable and Borderline Resectable Pancreas Cancer. Am J Clin Oncol 2019;42:247-52

    Article  CAS  Google Scholar 

  31. Keane FK, Wo JY, Ferrone CR, Clark JW, Blaszkowsky LS, Allen JN, et al. Intraoperative Radiotherapy in the Era of Intensive Neoadjuvant Chemotherapy and Chemoradiotherapy for Pancreatic Adenocarcinoma. Am J Clin Oncol 2018;41:607-12

    Article  Google Scholar 

  32. Crane CH, Beddar AS, Evans DB. The role of intraoperative radiotherapy in pancreatic cancer. Surg Oncol Clin N Am 2003;12:965-77

    Article  Google Scholar 

  33. Pisters PW, Wolff RA, Janjan NA, Cleary KR, Charnsangavej C, Crane CN, et al. Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J Clin Oncol 2002;20:2537-44

    Article  CAS  Google Scholar 

  34. Doi R, Imamura M, Hosotani R, Imaizumi T, Hatori T, Takasaki K, et al. Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial. Surg Today 2008;38:1021-8

    Article  Google Scholar 

  35. Krishnan S, Chadha AS, Suh Y, Chen HC, Rao A, Das P, et al. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation. Int J Radiat Oncol Biol Phys 2016;94:755-65

    Article  Google Scholar 

  36. Ryan JF, Rosati LM, Groot VP, Le DT, Zheng L, Laheru DA, et al. Stereotactic body radiation therapy for palliative management of pancreatic adenocarcinoma in elderly and medically inoperable patients. Oncotarget 2018;9:16427-36

    Article  Google Scholar 

  37. Perri G, Prakash L, Qiao W, Varadhachary GR, Wolff R, Fogelman D, et al. Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. JAMA Surg. 155:839 2020

    Article  Google Scholar 

  38. Perri G, Prakash L, Wang H, Bhosale P, Varadhachary GR, Wolff R, et al. Radiographic and Serologic Predictors of Pathologic Major Response to Preoperative Therapy for Pancreatic Cancer. Ann Surg 2019

  39. Koay EJ, Katz MHG, Wang H, Wang X, Prakash L, Javle M, et al. Computed Tomography-Based Biomarker Outcomes in a Prospective Trial of Preoperative FOLFIRINOX and Chemoradiation for Borderline Resectable Pancreatic Cancer. JCO Precis Oncol 2019;3

  40. Ryan JF, Groot VP, Rosati LM, Hacker-Prietz A, Narang AK, McNutt TR, et al. Stereotactic Body Radiation Therapy for Isolated Local Recurrence After Surgical Resection of Pancreatic Ductal Adenocarcinoma Appears to be Safe and Effective. Ann Surg Oncol 2018;25:280-9

    Article  Google Scholar 

  41. Gajiwala S, Torgeson A, Garrido-Laguna I, Kinsey C, Lloyd S. Combination immunotherapy and radiation therapy strategies for pancreatic cancer-targeting multiple steps in the cancer immunity cycle. J Gastrointest Oncol 2018;9:1014-26

    Article  Google Scholar 

  42. Katz M, Bauer T, Varadhachary G, Acquavella N, Petroni G, Bullock T, et al. A randomized multicenter Phase Ib/II study to assess the immunological effect of chemoradiation therapy (CRT) in combination with pembrolizumab compared to CRT alone in resectable or borderline resectable pancreatic cancer. J Immunother Cancer 2015

  43. Koay EJ, Lee Y, Cristini V, Lowengrub JS, Kang Y, Lucas FAS, et al. A Visually Apparent and Quantifiable CT Imaging Feature Identifies Biophysical Subtypes of Pancreatic Ductal Adenocarcinoma. Clin Cancer Res 2018;24:5883-94

    Article  Google Scholar 

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Correspondence to Matthew H. G. Katz.

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Maxwell, J.E., Katz, M.H.G. Radiotherapy for Resectable and Borderline Resectable Pancreas Cancer: When and Why?. J Gastrointest Surg 25, 843–848 (2021). https://doi.org/10.1007/s11605-020-04838-6

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  • DOI: https://doi.org/10.1007/s11605-020-04838-6

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