Skip to main content
SpringerLink
Log in

Proton Beam Therapy in Gastrointestinal Cancers: A Paradigm Shift in Radiotherapy

  • Chapter
  • First Online:
GI Surgery Annual

Part of the book series: GI Surgery Annual ((GISA,volume 26))

  • 219 Accesses

Abstract

Proton beam therapy (PBT) is a newer radiation modality that reduces inadvertent spillage of radiation to normal tissues surrounding a target tumour. Conventional X-ray-based radiation therapy for gastrointestinal (GI) cancers has been associated with not insignificant toxicity to surrounding organs at risk (OAR). Proton therapy has the potential to minimise this. There has been a recent rise in the number of facilities worldwide offering proton therapy as the technology becomes more easily accessible. This article aims to review the current role and future potential that PBT can offer in the context of gastrointestinal malignancies.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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. American Cancer Society. Global cancer facts & figures. 4th ed. Atlanta: American Cancer Society; 2018. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/global-cancer-facts-and-figures/global-cancer-facts-and-figures-4th-edition.pdf. Accessed 18 Feb 2020.

  2. van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.

    Article  PubMed  Google Scholar 

  3. Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–30.

    Article  CAS  PubMed  Google Scholar 

  4. Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33. https://doi.org/10.1200/JCO.2011.40.1836.

    Article  CAS  PubMed  Google Scholar 

  5. Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, et al. Chemoradiotherapy of locally advanced oesophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). JAMA. 1999;281(17):1623–7. https://doi.org/10.1001/jama.281.17.1623.

    Article  CAS  PubMed  Google Scholar 

  6. Hammel P, Huguet F, van Laethem J, 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(17):1844–53. https://doi.org/10.1001/jama.2016.4324.

    Article  CAS  PubMed  Google Scholar 

  7. James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol. 2013;14(6):516–24.

    Article  CAS  PubMed  Google Scholar 

  8. International Atomic Energy Agency, Suntharalingam N, Podgorsak EB, Hendry JH. “Basic radiobiology”, radiation oncology physics: a handbook for teachers and students. Vienna: IAEA; 2005. p. 485–504.

    Google Scholar 

  9. Kole TP, Aghayere O, Kwah J, Yorke ED, Goodman KA. Comparison of heart and coronary artery doses associated with intensity-modulated radiotherapy versus three dimensional conformal radiotherapy for distal oesophageal cancer. Int J Radiat Oncol Biol Phys. 2012;83:1580–6.

    Article  PubMed  Google Scholar 

  10. Lin SH, Wang L, Myles B, Thall PF, Hofstetter WL, Swisher SG, et al. Propensity-score based comparison of long-term outcomes with 3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy for oesophageal cancer. Int J Radiat Oncol Biol Phys. 2012;84(5):1078–85.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Wang J, Wei C, Tucker SL, Myles B, Palmer M, Hofstetter WL, et al. Predictors of postoperative complications after trimodality therapyfor esophageal cancer. Int J Radiat Oncol Biol Phys. 2013;86:885–91.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Liu C, Bhangoo RS, Sio TT, Yu NY, Shan J, Chiang JS, Ding JX, et al. Dosimetric comparison of distal esophageal carcinoma plans for patients treated with small-spot intensity-modulated proton versus volumetric-modulated arc therapies. J Appl Clin Med Phys. 2019;20(7):15–27.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Van Benthuysen L, Hales L, PodgorsakMB. Volumetric modulated arc therapy vs IMRT for the treatment of distal esophageal cancer. Med Dosim. 2011;36(4):404–9.

    Article  PubMed  Google Scholar 

  14. Wang J, Palmer M, Bilton SD, et al. Comparing proton beam to intensity modulated radiation therapy planning in esophageal cancer. Int J Part Ther. 2015;1:866–77. https://doi.org/10.14338/IJPT-14-00018.1.

    Article  Google Scholar 

  15. Lin SH, Komaki R, Liao Z, Wei C, Myles B, Guo X, et al. Proton beam therapy and concurrent chemotherapy for esophageal cancer. Int J Radiat Oncol Biol Phys. 2012;83:e345–51.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lin S, Merrell KW, Shen J, Verma V, Correa M, Wang L, et al. Multi-institutional analysis of radiation modality use and postoperative outcomes of neoadjuvant chemoradiation for esophageal cancer. Radiother Oncol. 2017;123(3) https://doi.org/10.1016/j.radonc.2017.04.013.

  17. Lin SH, Hobbs BP, Verma V, Tidwell RS, Smith GL, Lei X, et al. Randomized phase IIB trial of proton beam therapy versus intensity-modulated radiation therapy of locally advanced esophageal cancer. J Clin Oncol. 2020;38(14):1569–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Garant A, Whitaker TJ, Spears GM, Routman DM, Harmsen WS, Wilhite TJ, et al. A comparison of patient-reported health-related quality of life during proton versus photon chemoradiation therapy for esophageal cancer. Pract Radiat Oncol. 2019;9(6):410–7. https://doi.org/10.1016/j.prro.2019.07.003.

    Article  PubMed  Google Scholar 

  19. ClinicalTrials.gov. Identifier NCT03801876. Phase III randomized trial of proton beam therapy (PBT) versus intensity modulated photon radiotherapy (IMRT) for the treatment of esophageal cancer. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29; 2019 Jan 14; [about 6 screens]. https://clinicaltrials.gov/ct2/show/NCT03801876?term=NCT03801876&draw=2&rank=1. Accessed 4 Apr 2020.

  20. ClinicalTrials.gov. Identifier: NCT02213497. Phase I dose escalation of neoadjuvant proton beam radiotherapy with concurrent chemotherapy in locally advanced esophageal cancer. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29; 2014 Apr; [about 6 screens]. https://clinicaltrials.gov/ct2/show/NCT02213497?term=NCT02213497&draw=2&rank=1. Accessed 4 Apr 2020.

  21. Bujold A, Massey CA, Kim JJ, Brierley J, Cho C, Wong RKS, et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol. 2013;31(13):1631–9. https://doi.org/10.1200/JCO.2012.44.1659.

    Article  PubMed  Google Scholar 

  22. Chiba T, Tokuuye K, Matsuzaki Y, Sugahara S, Chuganji Y, Kagei K, et al. Proton beam therapy for hepatocellular carcinoma: a retrospective review of 162 patients. Clin Cancer Res. 2005;11:3799–805.

    Article  PubMed  Google Scholar 

  23. Kawashima M, Furuse J, Nishio T, Konishi M, Ishii H, Kinoshita T. Phase II study of radiotherapy employing proton beam for hepatocellular carcinoma. J Clin Oncol. 2005;23:1839–46.

    Article  PubMed  Google Scholar 

  24. Sugahara S, Nakayama H, Fukuda K, Mizumoto M, Tokita M, Abei M, et al. Proton beam therapy for hepatocellular carcinoma associated with portal vein tumor thrombosis. Strahlenther Onkol. 2009;185:782–8.

    Article  PubMed  Google Scholar 

  25. Mizumoto M, Oshiro Y, Okumura T, Fukumitsu N, Numajiri H, Ohnishi K, et al. Proton beam therapy for hepatocellular carcinoma: a review of the University of Tsukuba experience. Int J Part Ther. 2016;2(4):570–8. https://doi.org/10.14338/IJPT-15-00035.2.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mizumoto M, Tokuuye K, Sugahara S, Nakayama H, Fukumitsu N, Ohara K, et al. Proton beam therapy for hepatocellular carcinoma adjacent to the porta hepatis. Int J Radiat Oncol Biol Phys. 2008;71:462–7.

    Article  PubMed  Google Scholar 

  27. Komatsu S, Fukumoto T, Demizu Y, Miyawaki D, Terashima K, Sasaki R, et al. Clinical results and risk factors of proton and carbon ion therapy for hepatocellular carcinoma. Cancer. 2011;117:4890–904.

    Article  CAS  PubMed  Google Scholar 

  28. Qi W-X, Shen F, Qing Z, Xiao-Mao G. Charged particle therapy versus photon therapy for patients with hepatocellular carcinoma: a systematic review and meta-analysis. Radiother Oncol. 2015;114:289–95.

    Article  PubMed  Google Scholar 

  29. Sugahara S, Oshiro Y, Nakayama H, Fukuda K, Mizumoto M, Abei M, et al. Proton beam therapy for large hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2010;76(2):460–6.

    Article  PubMed  Google Scholar 

  30. Hata M, Tokuuye K, Sugahara S, Fukumitsu N, Hashimoto T, Ohnishi K, et al. Proton beam therapy for hepatocellular carcinoma with limited treatment options. Cancer. 2006;107:591–8.

    Article  PubMed  Google Scholar 

  31. Kim TH, Park JW, Kim BH, Kim H, Moon SH, Kim SS, et al. Does risk-adapted proton beam therapy have a role as a complementary or alternative therapeutic option for hepatocellular carcinoma? Cancers (Basel). 2019;11(2):230. https://doi.org/10.3390/cancers11020230.

    Article  CAS  Google Scholar 

  32. Hong TS, DeLaney TF, Mamon HJ, Willett CG, Yeap BY, Niemierko A. A prospective feasibility study of respiratory gated proton beam therapy for liver tumors. Pract Radiat Oncol. 2014;4(5):316–22. https://doi.org/10.1016/j.prro.2013.10.002.

    Article  PubMed  Google Scholar 

  33. Hong TS, Wo JY, Yeap BY, Ben-Josef E, McDonnell E, Blaszkowsky LS, et al. Multi-institutional phase II study of high-dose hypofractionated proton beam therapy in patients with localized, unresectable hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2016;34(5):460–8.

    Article  CAS  PubMed  Google Scholar 

  34. Bush DA, Smith JC, Slater JD, Volk ML, Reeves ME, Cheng J, et al. Randomized clinical trial comparing proton beam radiation therapy with transarterial chemoembolization for hepatocellular carcinoma: results of an interim analysis. Int J Radiat Oncol Biol Phys. 2016;95(1):477–82. https://doi.org/10.1016/j.ijrobp.2016.02.027.

    Article  PubMed  Google Scholar 

  35. Kim TH, Koh YH, Kim BH, Kim MJ, Lee JH, Park B, et al. Proton beam radiotherapy vs. radiofrequency ablation for recurrent hepatocellular carcinoma: a randomized phase III trial. J Hepatol. 2021;74(3):603–12. https://doi.org/10.1016/j.jhep.2020.09.026.

    Article  CAS  PubMed  Google Scholar 

  36. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–81.

    Article  CAS  PubMed  Google Scholar 

  37. Chopra S, Mathew AS, Engineer R, Shrivastava SK. Positioning high-dose radiation in multidisciplinary management of unresectable cholangiocarcinomas: review of current evidence. Indian J Gastroenterol. 2014;33(5):401–7. https://doi.org/10.1007/s12664-014-0495-6.

    Article  PubMed  Google Scholar 

  38. Lee J, Yoon WS, Koom WS, Rim CH, et al. Efficacy of stereotactic body radiotherapy for unresectable or recurrent cholangiocarcinoma: a meta-analysis and systematic review. Strahlenther Onkol. 2019;195:93–102. https://doi.org/10.1007/s00066-018-1367-2.

    Article  PubMed  Google Scholar 

  39. Tao R, Krishnan S, Bhosale PS, Javle MM, Aloia TA, Shroff RT, et al. Ablative radiotherapy doses lead to a substantial prolongation of survival in patients with inoperable intrahepatic cholangiocarcinoma: a retrospective dose response analysis. J Clin Oncol. 2016;34:219–26.

    Article  CAS  PubMed  Google Scholar 

  40. Smart AC, Goyal L, Horick N, Petkovska N, Zhu AX, Ferrone CR, et al. Hypofractionated radiation therapy for unresectable/locally recurrent intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2020;27:1122–9.

    Article  PubMed  Google Scholar 

  41. Hong TS, Wo JY, Yeap BY, Ben-Josef E, McDonnell EI, Drapek LC, et al. Multi-institutional phase II study of high dose, hypofractionated proton beam therapy (HF-PBT) for unresectable primary liver cancers: long term outcomes in patients with intrahepatic cholangiocarcinoma. J Clin Oncol. 2016;34(5):460–8.

    Article  CAS  PubMed  Google Scholar 

  42. Ohkawa A, Mizumoto M, Ishikawa H, Abei M, Fukuda K, Hashimoto T, et al. Proton beam therapy for unresectable intrahepatic cholangiocarcinoma. J Gastroenterol Hepatol. 2015;30:957–63.

    Article  PubMed  Google Scholar 

  43. Shimizu S, Okumura T, Oshiro Y, et al. Clinical outcomes of previously untreated patients with unresectable intrahepatic cholangiocarcinoma following proton beam therapy. Radiat Oncol. 2019;14:241.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Makita C, Nakamura T, Takada A, et al. Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma. Radiat Oncol. 2014;9:26.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Versteijne E, Suker M, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, 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(16):1763–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. National Comprehensive Cancer Network. Bone cancer (version 2.2021). http://www.nccn.org/professionals/physician_gls/pdf/pancreatic_blocks.pdf. Accessed 23 Dec 2021.

  47. Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.

    Article  CAS  PubMed  Google Scholar 

  48. Versteijne E, Suker M, Groothuis 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(16):1763–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Palta M, Godfrey D, Goodman KA, Hoffe S, Dawson LA, Dessert D, et al. Radiation therapy for pancreatic cancer: executive summary of an ASTRO clinical practice guideline. Pract Radiat Oncol. 2019;9(5):322–32.

    Article  PubMed  Google Scholar 

  50. Ding X, Dionisi F, Tang S, Ingram M, Hung CY, Prionas E, et al. A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT). Med Dosim. 2014;39:139–45.

    Article  PubMed  Google Scholar 

  51. Thompson RF, Mayekar SU, Zhai H, Both S, Apisarnthanarax S, Metz JM, et al. A dosimetric comparison of proton and photon therapy in unresectable cancers of the head of pancreas. Med Phys. 2014;41:081711.

    Article  PubMed  Google Scholar 

  52. Kozak KR, Kachnic LA, Adams J, Crowley EM, Alexander BM, Mamon HJ, et al. Dosimetric feasibility of hypofractionated proton radiotherapy for neoadjuvant pancreatic cancer treatment. Int J Radiat Oncol Biol Phys. 2007;68:1557–66.

    Article  PubMed  Google Scholar 

  53. Hong TS, Ryan DP, Blaszkowsky LS, Mamon HJ, Kwak EL, Mino-Kenudson M, et al. Phase I study of preoperative short course chemoradiation with proton beam therapy and capecitabine for resectable pancreatic ductal adenocarcinoma of the head. Int J Radiat Oncol Biol Phys. 2011;79:151–7.

    Article  CAS  PubMed  Google Scholar 

  54. Hong TS, Ryan DP, Borger DR, Blaszkowsky LS, Yeap BY, Ancukiewicz M, et al. A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma. Int J Radiat Oncol Biol Phys. 2014;89:830–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Nichols RC Jr, George TJ, Zaiden RA Jr, Awad ZT, Asbun HJ, Huh S, et al. Proton therapy with concomitant capecitabine for pancreatic and ampullary cancers is associated with a low incidence of gastrointestinal toxicity. Acta Oncol. 2013;52:498–505.

    Article  CAS  PubMed  Google Scholar 

  56. Sachsman S, Nichols RC, Morris CG, Zaiden R, Johnson EA, Awad Z. Proton therapy and concomitant capecitabine for non-metastatic unresectable pancreatic adenocarcinoma. Int J Part Ther. 2014;1(3):692–701.

    Article  Google Scholar 

  57. Woodhouse KD, Elrakhawy JA, et al. Acute toxicity of proton versus photon adjuvant chemoradiation in the treatment of pancreatic cancer: a cohort study. Int J Radiat Oncol Biol Phys. 2016;96:E208–9.

    Article  Google Scholar 

  58. Hiroshima Y, Fukumitsu N, Saito T, Numajiri H, Murofushi KN, Ohnishi K, et al. Concurrent chemoradiotherapy using proton beams for unresectable locally advanced pancreatic cancer. Radiother Oncol. 2019;136:37–43.

    Article  PubMed  Google Scholar 

  59. Kim TH, Lee WJ, Woo SM, Kim H, Oh ES, Lee JH, et al. Effectiveness and safety of simultaneous integrated boost-proton beam therapy for localized pancreatic cancer. Technol Cancer Res Treat. 2018;17:1533033818783879.

    PubMed  PubMed Central  Google Scholar 

  60. ClinicalTrials.gov. Identifier: NCT02598349. A phase II trial of escalated dose proton radiotherapy with elective nodal irradiation and concomitant chemotherapy for patients with unresectable, borderline resectable or medically inoperable pancreatic adenocarcinoma. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29; 2016 Apr; [about 8 screens]. https://clinicaltrials.gov/ct2/show/NCT02598349. Accessed 22 Dec 2021.

  61. ClinicalTrials.gov. Identifier: NCT03652428. Phase I study of concurrent nab-paclitaxel + gemcitabine with hypofractionated, ablative proton therapy for locally advanced pancreatic cancer. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29; 2018 Aug; [about 6 screens]. https://clinicaltrials.gov/ct2/show/NCT03652428. Accessed 23 Dec 2021.

  62. Colaco RJ, Nichols RC, Huh S, Getman N, Ho MW, Li Z, Morris CG, et al. Protons offer reduced bone marrow, small bowel, and urinary bladder exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer. J Gastrointest Oncol. 2014;5(1):3–8. https://doi.org/10.3978/j.issn.2078-6891.2013.041.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Wolff HA, Wagner DM, Conradi LC, et al. Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: a planning study with clinical implications. Radiother Oncol. 2012;102(1):30–7.

    Article  PubMed  Google Scholar 

  64. Isacsson U, Montelius A, Jung B, Glimelius B. Comparative treatment planning between proton and X-ray therapy in locally advanced rectal cancer. Radiother Oncol. 1996;41:263–72.

    Article  CAS  PubMed  Google Scholar 

  65. Tatsuzaki H, Urie MM, Willett CG. 3-D comparative study of proton vs. x-ray radiation therapy for rectal cancer. Int J Radiat Oncol Biol Phys. 1992;22:369–74.

    Article  CAS  PubMed  Google Scholar 

  66. Appelt AL, Pløen J, Harling H, Jensen FS, Jensen LH, Jørgensen JCR, et al. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol. 2015;16:919–27.

    Article  PubMed  Google Scholar 

  67. Dionisi F, Batra S, Kirk M, Both S, Vennarini S, McDonough J, et al. Pencil-beam scanning proton therapy in the treatment of rectal cancer. Int J Rad Oncol Biol Phys. 2013;87(2):S341–2.

    Article  Google Scholar 

  68. Chung SY, Koom WS, Keum KC, Chang JS, Shin SJ, Ahn JB, et al. Treatment outcomes of re-irradiation in locoregionally recurrent rectal cancer and clinical significance of proper patient selection. Front Oncol. 2019;9:529.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Mokutani Y, Yamamoto H, Uemura M, Haraguchi N, Takahashi H, Nishimura J, et al. Effect of particle beam radiotherapy on locally recurrent rectal cancer: three case reports. Mol Clin Oncol. 2015;3:765–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ogi Y, Yamaguchi T, Kinugasa Y, Shiomi A, Kagawa H, Yamakawa Y, et al. Effect and safety of proton beam therapy for locally recurrent rectal cancer. J Clin Oncol. 2018;36:743.

    Article  Google Scholar 

  71. Kawamura H, Honda M, Matsunaga R, Todate Y, Nakayama Y, Kobayashi H, et al. Four patients who underwent proton beam therapy after debulking surgery and omental wrapping of the residual tumor as a spacer for unresectable local recurrence of rectal cancer. Gan To Kagaku Ryoho. 2019;46(1):79–82.

    PubMed  Google Scholar 

  72. Combs SE, Kieser M, Habermehl D, Weitz J, Jäger D, Fossati P, et al. Phase I/II trial evaluating carbon ion radiotherapy for the treatment of recurrent rectal cancer: the PANDORA-01 trial. BMC Cancer. 2012;12:137.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Tzeng CW, Aloia TA. Colorectal liver metastases. J Gastrointest Surg. 2013;17(1):195–201.

    Article  PubMed  Google Scholar 

  74. Abbas S, Lam V, Hollands M. Ten-year survival after liver resection for colorectal metastases: systematic review and meta-analysis. ISRN Oncol. 2011;2011:763245.

    PubMed  PubMed Central  Google Scholar 

  75. Comito T, Clerici E, Tozzi A, D'Agostino G. Liver metastases and SBRT: a new paradigm? Rep Pract Oncol Radiother. 2015;20(6):464–71.

    Article  PubMed  Google Scholar 

  76. Ohri N, Tomé WA, Méndez Romero A, Miften M, Ten Haken RK, Dawson LA, et al. Local control after stereotactic body radiation therapy for liver tumors. Int J Radiat Oncol Biol Phys. 2021;110(1):188–95.

    Article  PubMed  Google Scholar 

  77. Mondlane G, Gubanski M, Lind PA, Henry T, Ureba A, Siegbahn A. Dosimetric comparison of plans for photon- or proton-beam based radiosurgery of liver metastases. Int J Part Ther. 2016;3(2):277–84.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Mondlane G, Gubanski M, Lind PA, Ureba A, Siegbahn A. Comparative study of the calculated risk of radiation-induced cancer after photon- and proton-beam based radiosurgery of liver metastases. Phys Med. 2017;42:263–70.

    Article  PubMed  Google Scholar 

  79. Colbert LE, Cloyd JM, Koay EJ, Crane CH, Vauthey JN. Proton beam radiation as salvage therapy for bilateral colorectal liver metastases not amenable to second-stage hepatectomy. Surgery. 2017;161(6):1543–8.

    Article  PubMed  Google Scholar 

  80. Fukumitsu N, Okumura T, Takizawa D, Makishima H, Numajiri H, Murofushi K, et al. Proton beam therapy for metastatic liver tumors. Radiother Oncol. 2015;117(2):322–7.

    Article  PubMed  Google Scholar 

  81. Fukumitsu N, Okumura T, Takizawa D, Numajiri H, Ohnishi K, Mizumoto M, et al. Proton beam therapy for liver metastases from gastric cancer. J Radiat Res. 2017;58(3):357–62.

    Article  PubMed  Google Scholar 

  82. Gohongi T, Tokuuye K, Iida H, Nakai R, Gunji N, Akine Y, et al. Concurrent proton beam radiotherapy and systemic chemotherapy for the metastatic liver tumor of gastric carcinoma: a case report. Jpn J Clin Oncol. 2005;35(1):40–4.

    Article  PubMed  Google Scholar 

  83. Muroi H, Nakajima M, Satomura H, Takahashi M, Domeki Y, Murakami M, et al. Effectiveness of proton beam therapy on liver metastases of esophageal cancer: report of a case. Int Surg. 2015;100(1):180–4.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Miyazaki T, Sohda M, Sakai M, Kumakura Y, Yoshida T, Kuriyama K, et al. Therapy including proton beam therapy for AFP producing esophageal cancer with multiple liver metastases. Intern Med. 2018;57(16):2333–9.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Fukumitsu N, Okumura T, Numajiri H, Takizawa D, Ohnishi K, Mizumoto M, et al. Follow-up study of liver metastasis from breast cancer treated by proton beam therapy. Mol Clin Oncol. 2017;7(1):56–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hong TS, Wo JY, Borger DR, Yeap BY, McDonnell EI, Willers H, et al. Phase II study of proton-based stereotactic body radiation therapy for liver metastases: importance of tumor genotype. J Natl Cancer Inst. 2017;109(9) https://doi.org/10.1093/jnci/djx031.

  87. Kang JI, Sufficool DC, Hsueh CT, Wroe AJ, Patyal B, Reeves ME, et al. A phase I trial of proton stereotactic body radiation therapy for liver metastases. J Gastrointest Oncol. 2019;10(1):112–7.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Kachnic LA, Winter K, Myerson RJ, Goodyear MD, Willins J, Esthappan J, et al. RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2013;86(1):27–33.

    Article  CAS  PubMed  Google Scholar 

  89. Anand A, Bues M, Rule WG, Keole SR, Beltran CJ, Yin J, et al. Scanning proton beam therapy reduces normal tissue exposure in pelvic radiotherapy for anal cancer. Radiother Oncol. 2015;117(3):505–8.

    Article  PubMed  Google Scholar 

  90. Devisetty K, Mell LK, Salama JK, Schomas DA, Miller RC, Jani AB, et al. A multi-institutional acute gastrointestinal toxicity analysis of anal cancer patients treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy. Radiother Oncol. 2009;93(2):298–301.

    Article  PubMed  Google Scholar 

  91. Bazan JG, Luxton G, Kozak MM, Anderson EM, Hancock SL, Kapp DS, et al. Impact of chemotherapy on normal tissue complication probability models of acute hematologic toxicity in patients receiving pelvic intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2013;87(5):983–91.

    Article  CAS  PubMed  Google Scholar 

  92. Kronborg C, Serup-Hansen E, Lefevre A, Wilken EE, Petersen JB, Hansen J, et al. Prospective evaluation of acute toxicity and patient reported outcomes in anal cancer and plan optimization. Radiother Oncol. 2018;128(2):375–9.

    Article  PubMed  Google Scholar 

  93. Meier T, Mascia A, Wolf E, Kharofa J. Dosimetric comparison of intensity-modulated proton therapy and volumetric-modulated arc therapy in anal cancer patients and the ability to spare bone marrow. Int J Part Ther. 2017;4(2):11–7.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Wo JY, Plastaras JP, Metz JM, Jiang W, Yeap BY, Drapek LC, et al. Pencil beam scanning proton beam chemoradiation therapy with 5-fluorouracil and mitomycin-C for definitive treatment of carcinoma of the anal canal: a multi-institutional pilot feasibility study. Int J Radiat Oncol Biol Phys. 2019;105(1):90–5.

    Article  CAS  PubMed  Google Scholar 

  95. Buchberger D, Kreinbrink P, Kharofa J. Proton therapy in the treatment of anal cancer in pelvic kidney transplant recipients: a case series. Int J Part Ther. 2019;6(1):28–34.

    Article  PubMed  PubMed Central  Google Scholar 

  96. ClinicalTrials.gov. Identifier: NCT03690921. Linear energy transfer (LET)-optimized intensity modulated proton therapy (IMPT) as a component of definitive chemoradiation for newly diagnosed squamous cell carcinoma of the anal canal: a feasibility trial. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29; 2018 Oct; [about 6 screens]. http://clinicaltrials.gov/ct/show/NCT00287391?order=1. Accessed 23 Dec 2021.

Download references

Acknowledgements

Dr. Anindita Das for her contributions towards illustrations and Dr. Nagarjuna Burela for technical editing and proofreading.

Editorial Comments

Multimodal therapy has long been shown to improve survival in common gastrointestinal malignancies such as gastro-oesophageal, pancreatic and hepatocellular carcinomas. Both chemotherapy and radiotherapy are used in this. Radiotherapy has been used with or without concomitant chemotherapy (usually for its radiosensitising effect). The problem of radiotherapy in the management of gastrointestinal cancer is high toxicity related to undesirable radiation to surrounding non-tumour-bearing organs such as the lung and heart in case of oesophageal cancers; small bowel, liver, kidneys and heart in gastric cancer; and normal liver surrounding the tumour-bearing area of the liver, stomach, small bowel and kidneys following radiotherapy for hepatocellular carcinomas and stomach (causing ulcer with not too infrequent incidence of severe gastrointestinal bleeding), bile duct (stricture, cholangitis) and duodenum (radiation induced stenosis). All these effects are noted with the use of conventional radiotherapy.

With the advent of proton beam radiotherapy, this has changed. This is related to the nature of proton particles―these concentrate on the target volume on its entering path and diminishing maximally at its exit. The result is obvious tumouricidal to the target sparing maximally the surrounding critical organ(s). Thus, proton beam therapy has given us hope in managing gastrointestinal cancers more efficiently. Researchers are continuously striving to improve, and we are sure we will see even better results in the not too distant future.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Apollo Proton Cancer Centre, Chennai, India

    Ashwathy Susan Mathew & Sapna Nangia

Authors
  1. Ashwathy Susan Mathew
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sapna Nangia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ashwathy Susan Mathew .

Editor information

Editors and Affiliations

  1. Department of Gastrointestinal Surgery and Liver Transplantation, All India Institute of Medical Sciences, New Delhi, India

    Peush Sahni

  2. Department of Gastrointestinal Surgery and Liver Transplantation, All India Institute of Medical Sciences, New Delhi, India

    Sujoy Pal

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Mathew, A.S., Nangia, S. (2022). Proton Beam Therapy in Gastrointestinal Cancers: A Paradigm Shift in Radiotherapy. In: Sahni, P., Pal, S. (eds) GI Surgery Annual. GI Surgery Annual, vol 26. Springer, Singapore. https://doi.org/10.1007/978-981-19-0828-6_9

Download citation

  • DOI: https://doi.org/10.1007/978-981-19-0828-6_9

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-19-0827-9

  • Online ISBN: 978-981-19-0828-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation