Skip to main content

Radiation Therapy for Pancreatic Cancer: Current and Evolving Paradigms

  • Chapter
  • First Online:
Pancreatic Cancer

Abstract

Pancreatic cancer is commonly treated with radiation therapy. While treatment paradigms vary by disease stage and are continuing to evolve, radiation therapy may play a role in the treatment of pancreatic cancer at any stage. Many radiation-based strategies have demonstrated success in the treatment of pancreatic adenocarcinoma and continue to actively be utilized, while ongoing efforts are expanding the frontiers of radiation modalities and indications across diverse clinical settings. In this chapter, we present an overview of the role of radiation therapy in treating patients with pancreatic cancer, examining stage- and modality-based indications for radiation therapy, as well as active areas of investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and radiation therapy: current advances and future directions. Int J Med Sci. 2012;9:193–9.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Coveler AL, Herman JM, Simeone DM, Chiorean EG. Localized pancreatic cancer: multidisciplinary management. Am Soc Clin Oncol Educ Book. 2016;35:217–26.

    Article  Google Scholar 

  3. Iacobuzio-Donahue CA, Fu B, Yachida S, 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  PubMed  PubMed Central  Google Scholar 

  4. Berman AT, Plastaras JP, Vapiwala N. Radiation oncology: a primer for medical students. J Cancer Educ. 2013;28:547–53.

    Article  PubMed  Google Scholar 

  5. Prasad S, Cambridge L, Huguet F, et al. Intensity modulated radiation therapy reduces gastrointestinal toxicity in locally advanced pancreas cancer. Pract Radiat Oncol. 2016;6:78–85.

    Article  PubMed  Google Scholar 

  6. Taylor A, Powell ME. Intensity-modulated radiotherapy–what is it? Cancer Imaging. 2004;4:68–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Intensity Modulated Radiation Therapy Collaborative Working G. Intensity-modulated radiotherapy: current status and issues of interest. Int J Radiat Oncol Biol Phys. 2001;51:880–914.

    Article  Google Scholar 

  8. Manzar GS, Lester SC, Routman DM, et al. Comparative analysis of acute toxicities and patient reported outcomes between intensity-modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) for the treatment of oropharyngeal cancer. Radiother Oncol. 2020;147:64–74.

    Article  CAS  PubMed  Google Scholar 

  9. Jin L, Wang R, Jiang S, et al. Dosimetric and clinical toxicity comparison of critical organ preservation with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and RapidArc for the treatment of locally advanced cancer of the pancreatic head. Curr Oncol. 2016;23:41–8.

    Article  Google Scholar 

  10. Abi Jaoude J, Kouzy R, Nguyen ND, et al. Radiation therapy for patients with locally advanced pancreatic cancer: evolving techniques and treatment strategies. Curr Probl Cancer. 2020;44:100607.

    Article  PubMed  Google Scholar 

  11. Paganetti H. Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer. Phys Med Biol. 2014;59:419–72.

    Article  Google Scholar 

  12. Perri G, Prakash LR, Katz MHG. Response to preoperative therapy in localized pancreatic cancer. Front Oncol. 2020;10:516.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Toesca DAS, Koong AJ, Poultsides GA, et al. Management of borderline resectable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2018;100:1155–74.

    Article  PubMed  Google Scholar 

  14. Takagi C, Kikuchi Y, Shirakawa H, et al. Predictive factors for elevated postoperative carbohydrate antigen 19-9 levels in patients with resected pancreatic cancer. Anticancer Res. 2019;39:3177–83.

    Article  CAS  PubMed  Google Scholar 

  15. Arrington AK, Hsu CH, Schaefer KL, O'Grady CL, Khreiss M, Riall TS. Survival after margin-positive resection in the era of modern chemotherapy for pancreatic cancer: do patients still benefit? J Am Coll Surg. 2021;233:100–9.

    Article  PubMed  Google Scholar 

  16. Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358:1576–85.

    Article  CAS  PubMed  Google Scholar 

  17. Winter JM, Cameron JL, Campbell KA, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg. 2006;10:1199–210. discussion 210-1

    Article  PubMed  Google Scholar 

  18. Spitz FR, Abbruzzese JL, Lee JE, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 1997;15:928–37.

    Article  CAS  PubMed  Google Scholar 

  19. Pisters PW, Abbruzzese JL, Janjan NA, et al. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol. 1998;16:3843–50.

    Article  CAS  PubMed  Google Scholar 

  20. Versteijne E, Suker M, Groothuis K, 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  PubMed  PubMed Central  Google Scholar 

  21. Jang JY, Han Y, Lee H, 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  PubMed  Google Scholar 

  22. Katz MHG, Ou FS, Herman JM, 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  PubMed  PubMed Central  Google Scholar 

  23. Katz MHG, Shi Q, Meyers JP, et al. Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX plus hypofractionated radiation therapy (RT) for borderline resectable (BR) adenocarcinoma of the pancreas. J Clin Oncol. 2021;39:377.

    Article  Google Scholar 

  24. Sultana A, Cox T, Ghaneh P, Neoptolemos JP. Adjuvant therapy for pancreatic cancer. Recent Results Cancer Res. 2012;196:65–88.

    Article  PubMed  Google Scholar 

  25. Loehrer PJ Sr, Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011;29:4105–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  27. Klinkenbijl JH, Jeekel J, Sahmoud T, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg. 1999;230:776–82; discussion 82–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gemcitabine hydrochloride with or without erlotinib hydrochloride followed by the same chemotherapy regimen with or without radiation therapy and capecitabine or fluorouracil in treating patients with pancreatic cancer that has been removed by surgery. https://ClinicalTrials.gov/show/NCT01013649.

  29. Regine WF, Winter KW, Abrams R, et al. RTOG 9704 a phase III study of adjuvant pre and post chemoradiation (CRT) 5-FU vs. gemcitabine (G) for resected pancreatic adenocarcinoma. J Clin Oncol. 2006;24:(Suppl 18):4007.

    Google Scholar 

  30. Goodman KA, Hajj C. Role of radiation therapy in the management of pancreatic cancer. J Surg Oncol. 2013;107:86–96.

    Article  PubMed  Google Scholar 

  31. Palta M, Godfrey D, Goodman KA, et al. Radiation therapy for pancreatic cancer: executive summary of an ASTRO clinical practice guideline. Pract Radiat Oncol. 2019;9:322–32.

    Article  PubMed  Google Scholar 

  32. Cloyd JM, Crane CH, Koay EJ, et al. Impact of hypofractionated and standard fractionated chemoradiation before pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Cancer. 2016;122:2671–9.

    Article  CAS  PubMed  Google Scholar 

  33. Krishnan S, Rana V, Janjan NA, et al. Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer. 2007;110:47–55.

    Article  PubMed  Google Scholar 

  34. Huguet F, Andre T, Hammel P, et al. Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol. 2007;25:326–31.

    Article  CAS  PubMed  Google Scholar 

  35. Hammel P, Huguet F, van Laethem JL, 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  PubMed  Google Scholar 

  36. Krishnan S, Chadha AS, Suh Y, 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  PubMed  Google Scholar 

  37. Reyngold M, O’Reilly EM, Varghese AM, et al. Association of ablative radiation therapy with survival among patients with inoperable pancreatic cancer. JAMA Oncol. 2021;7:735–8.

    Article  PubMed  Google Scholar 

  38. Colbert LE, Rebueno N, Moningi S, et al. Dose escalation for locally advanced pancreatic cancer: how high can we go? Adv Radiat Oncol. 2018;3:693–700.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Moser EC, Hoffe SE, Frakes J, et al. Adaptive dose optimization trial of stereotactic body radiation therapy (SBRT) with or without GC4419 (avasopasem manganese) in pancreatic cancer. J Clin Oncol. 2020;38:4670.

    Article  Google Scholar 

  40. Yang F, Jin C, Fu D. Celiac axis compression syndrome and pancreatic head cancer. Pancreatology. 2014;14:310–1.

    Article  PubMed  Google Scholar 

  41. Wolny-Rokicka E, Sutkowski K, Grzadziel A, et al. Tolerance and efficacy of palliative radiotherapy for advanced pancreatic cancer: a retrospective analysis of single-institutional experiences. Mol Clin Oncol. 2016;4:1088–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tian Q, Zhang F, Wang Y. Clinical assessment of palliative radiotherapy for pancreatic cancer. Cancer Radiother. 2018;22:778–83.

    Article  CAS  PubMed  Google Scholar 

  43. Hammer L, Hausner D, Ben-Ayun M, et al. Single-fraction celiac plexus radiosurgery: a preliminary proof-of-concept phase 2 clinical trial. Int J Radiat Oncol Biol Phys. 2022;113:588–93.

    Article  PubMed  Google Scholar 

  44. Takatori K, Terashima K, Yoshida R, et al. Upper gastrointestinal complications associated with gemcitabine-concurrent proton radiotherapy for inoperable pancreatic cancer. J Gastroenterol. 2014;49:1074–80.

    Article  CAS  PubMed  Google Scholar 

  45. Terashima K, Demizu Y, Hashimoto N, et al. A phase I/II study of gemcitabine-concurrent proton radiotherapy for locally advanced pancreatic cancer without distant metastasis. Radiother Oncol. 2012;103:25–31.

    Article  PubMed  Google Scholar 

  46. Durante M, Loeffler JS. Charged particles in radiation oncology. Nat Rev Clin Oncol. 2010;7:37–43.

    Article  PubMed  Google Scholar 

  47. Loeffler JS, Durante M. Charged particle therapy–optimization, challenges and future directions. Nat Rev Clin Oncol. 2013;10:411–24.

    Article  PubMed  Google Scholar 

  48. Trial of carbon ion versus photon radiotherapy for locally advanced, unresectable pancreatic cancer. 2019. https://ClinicalTrials.gov/show/NCT03536182.

  49. Wilson JD, Hammond EM, Higgins GS, Petersson K. Ultra-high dose rate (FLASH) radiotherapy: silver bullet or fool’s gold? Front Oncol. 2019;9:1563.

    Article  PubMed  Google Scholar 

  50. Favaudon V, Caplier L, Monceau V, et al. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice. Sci Transl Med. 2014;6:245ra93.

    Article  PubMed  Google Scholar 

  51. Schuler E, Acharya M, Montay-Gruel P, Loo BW Jr, Vozenin MC, Maxim PG. Ultra-high dose rate electron beams and the FLASH effect: from preclinical evidence to a new radiotherapy paradigm. Med Phys. 2022;49:2082–95.

    Article  PubMed  Google Scholar 

  52. Okoro CM, Schuler E, Taniguchi CM. The therapeutic potential of FLASH-RT for pancreatic cancer. Cancer. 2022;14(5):1167.

    Article  CAS  Google Scholar 

  53. Moeckli R, Goncalves Jorge P, Grilj V, et al. Commissioning of an ultra-high dose rate pulsed electron beam medical LINAC for FLASH RT preclinical animal experiments and future clinical human protocols. Med Phys. 2021;48:3134–42.

    Article  CAS  PubMed  Google Scholar 

  54. Manoharan D, Chang LC, Wang LC, et al. Synchronization of Nanoparticle Sensitization and Radiosensitizing Chemotherapy through Cell Cycle Arrest Achieving Ultralow X-ray Dose Delivery to Pancreatic Tumors. ACS Nano. 2021;15:9084–100.

    Article  CAS  PubMed  Google Scholar 

  55. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393:2051–8.

    Article  PubMed  Google Scholar 

  56. Systemic therapy with or without local consolidative therapy in treating patients with oligometastatic solid tumor. https://ClinicalTrials.gov/show/NCT03599765.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ethan B. Ludmir .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Manzar, G.S., Jaoude, J.A., Taniguchi, C.M., Koong, A.C., Koay, E.J., Ludmir, E.B. (2023). Radiation Therapy for Pancreatic Cancer: Current and Evolving Paradigms. In: Pant, S. (eds) Pancreatic Cancer. Springer, Cham. https://doi.org/10.1007/978-3-031-38623-7_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-38623-7_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-38622-0

  • Online ISBN: 978-3-031-38623-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics