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Particle Radiation Therapy for Gastrointestinal Cancers

  • Gastrointestinal Cancers (J Meyer, Section Editor)
  • Published:
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Abstract

Particle irradiation of cancerous disease has gained great traction in recent years. The ability for particle therapy centers to deliver radiation with a highly conformal dose distribution while maintaining minimal exit or excess dose delivered to normal tissue, coupled with various biological advantages particularly found with heavy-ion beams, enables treatment of diseases inapproachable with conventional radiotherapy. Here, we present a review of the current status of particle therapy with regard to cancers of the gastrointestinal tract, including esophagus, liver, pancreas, and recurrent rectal cancer.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Castro JR, Quivey JM. Clinical experience and expectation with helium and heavy ion irradiation. Int. J. Radiat Oncolo. Biol. Phys. 1997;3:127–31.

  2. Tsujii H, Kamada T, Shirai T, Noda K, Tsuji H, Karasawa K. Carbon-Ion Radiotherapy 3-10: Springer Tokyo. 2014. doi:10.1007/978-4-431-54457-9. This is the textbook for recent heavy-ion radiotherapy.

  3. Ohno T. Particle radiotherapy with carbon ion beams. The EPMA Journal. 2013;4(1):9. http://doi.org/ 10.1186/1878-5085-4-9 .

    Article  PubMed  PubMed Central  Google Scholar 

  4. Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) Phase III Trial of combined modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002;20:1167–74.

  5. Morota M, Gomi K, Kozuka T, Chin K, Matsuura M, Oguchi M, et al. Late toxicity after definitive concurrent chemoradiotherapy for thoracic esophageal carcinoma. Int J Radiat Oncol Biol Phys. 2009;75:122–8.

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

  7. 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 esophageal cancer. Int J Radiat Oncol Biol Phys. 2012;84:1078–85.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhang X, Zhao KI, Guerrero TM, Macguire SE, Yaremko B, Komaki R, et al. Four-dimmensional computed tomography-based treatment planning for intensity-modulated radiation therapy and proton therapy for distal oesophageal cancer. Int J Radiat Oncol Biol Phys. 2008;72:278–87.

  9. Palmer M, Bilton SD, Vu KN, Greeg S, Frame R, Liao Z, et al. Comparing Proton Beam to Intensity Modulated Radiation Therapy Planning in Esophageal Cancer. Int J Particle Ther. 2015;1(4):866–877.. This paper demonstrates PBT is superior to IMRT for lowering both mean heart and lung doses in esophageal cancer.

  10. Makishima H, Ishikawa H, Terunuma T, Hashimoto T, Yamanashi K, Sekiguchi T, et al. Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose-volume histogram analysis. J Radiat Res. 2015;56:568–76.

  11. Sugahara S, Tokuuye K, Okumura T, Nakahara A, Saida Y, Kagei K, et al. Clinical Results of Proton Beam Therapy for Cancer of the Esophagus. Int J Radiat Oncol Biol Phys. 2005;61:76–84.

  12. Mitsumoto M, Sugahara S, Okumura T, Hashimoto T, Oshiro Y, Fukumitsu N, et al. Hyperfractionated Concomitant Boost Proton Beam Therapy for Esophageal Carcinoma. Int J Radiat Oncol Biol Phys. 2011;81:e601–6.

  13. Akutsu Y, Yasuda S, Nagata M, Izumi Y, Okazumi S, Shimada H, et al. A phase I/II clinical trial of preoperative short-course carbon-ion radiotherapy for patients with squamous cell carcinoma of the esophagus. J Surg Oncol. 2012;105:750–5.

  14. Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

  15. Dionisi F, Widesott L, Lorentini S, Amichetti M. Is there a role for proton therapy in the treatment of hepatocellular carcinoma? A systematic review. Radiother Oncol. 2014;111:1–10.

    Article  PubMed  Google Scholar 

  16. Trevisani F, Cantarini MC, Wands JR, Bernardi M. Recent advances in the natural history of hepatocellular carcinoma. Carcinogenesis. 2008;29:1299–305.

    Article  CAS  PubMed  Google Scholar 

  17. Llovet JM, Bustamante J, Castells A, Vilana R, Del Carmen Ayuso M, Sala M, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology. 1999;29:62–7.

  18. Hansen E, Roach M. III. Handbook of Evidence-Based Radiation Oncology. (Springer Science & Business Media, 2010). doi:10.1007/978-0-387-92988-0

  19. Huo YR, Eslick GD. Transcatheter arterial chemoembolization plus radiotherapy compared with chemoembolization alone for hepatocellular carcinoma: a systematic review and meta-analysis. JAMA Oncol. 2015. doi:10.1001/jamaoncol.2015.2189

  20. Hennequin C, Quero L, Rivera S. Radiosensitivity of hepatocellular carcinoma. Cancer Radiotherapie. 2011;15:39–42.

    Article  CAS  PubMed  Google Scholar 

  21. Cheng SH, Lin YM, Chuang V, Yang PS, Cheng JCH, Huang AT, et al. A pilot study of three-dimensional conformal radiotherapy in unresectable hepatocellular carcinoma. J Gastroenterol Hepatol. 1999;14:1025–33.

  22. Lawrence TS, Ten Haken RK, Kessler ML, Robertson JM, Lyman JT, Lavigne ML, et al. The use of 3-D dose volume analysis to predict radiation hepatitis. Radiation Oncology Biology. 1992;23:781–8.

  23. Zurlo A, Lomax A, Hoess A, Bortfeld T, Russo M, Goitein G, et al. The role of proton therapy in the treatment of large irradiation volumes: a comparative planning study of pancreatic and biliary tumors. Radiation Oncology Biology. 2000;48:277–88.

  24. Krishnan S, Dawson LA, Seong J, Akine Y, Beddar S, Briere TM, et al. Radiotherapy for hepatocellular carcinoma: an overview. Ann Surg Oncol. 2008;15:1015–24.

  25. Skinner HD, Hong TS, Krishnan S. Charged-Particle Therapy for Hepatocellular Carcinoma. Semin Radiat Oncol. 2011;21:278–86.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Qi W-X, Fu S, Zhang Q, Guo X-M. Charged particle therapy versus photon therapy for patients with hepatocellular carcinoma: a systematic review and meta-analysis. Radiother. Oncol. 2015;114:289–95. This paper is a major review of charged particle therapy vs. photon therapy in HCC, reviewing over 70 papers and their outcomes.

  27. 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.

  28. Nakayama H, Sugahara S, Tokita M, Fukuda K, Mizumoto M, Abei M, et al. Proton beam therapy for hepatocellular carcinoma: the University of Tsukuba experience. Cancer. 2009;115:5499–506.

  29. 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.

  30. Kawashima M, Kohno R, Nakachi K, Nishio T, Mitsunaga S, Ikeda M, et al. Dose-volume histogram analysis of the safety of proton beam therapy for unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2011;79:1479–86.

  31. Bush DA, Kayali Z, Grove R, Slater JD. The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. Cancer. 2011;117:3053–9.

    Article  PubMed  Google Scholar 

  32. Kato H, Tsujii H, Miyamoto T, Mizoe J, Kamada T, Tsuji H, et al. Results of the first prospective study of carbon ion radiotherapy for hepatocellular carcinoma with liver cirrhosis. Radiat Oncol Biol. 2004;59:1468–76.

  33. Imada H, Kato H, Yasuda S, Yamada S, Yanagi T, Kishimoto R, et al. Comparison of efficacy and toxicity of short-course carbon ion radiotherapy for hepatocellular carcinoma depending on their proximity to the porta hepatis. Radiother Oncol. 2010;96:231–5.

  34. Yamashita H, Onishi H, Murakami N, Matsumoto Y, Matuso Y, Nomiya T, et al. Survival outcomes after stereotactic body radiotherapy for 79 Japanese patients with hepatocellular carcinoma. J Radiat Res. 2015;56:561–7.

  35. Cárdenes HR, Price TR, Perkins SM, Maluccio M, Kwo P, Breen TE, et al. Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma. Clin Transl Oncol. 2010;12:218–25.

  36. 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;31:1631–+.

  37. Guo WJ, Yu EX. Evaluation of combined therapy with chemoembolization and irradiation for large hepatocellular carcinoma. Br J Radiol. 2000;73:1091–7.

    Article  CAS  PubMed  Google Scholar 

  38. Yasuda S, Ito H, Yoshikawa M, Shinozaki M, Goto N, Fujimoto H, et al. Radiotherapy for large hepatocellular carcinoma combined with transcatheter arterial embolization and percutaneous ethanol injection therapy. Int J Oncol. 1999;15:467–73.

  39. Seong J, Park HC, Han KH, Chon CY, Chu SS, Kim GE, et al. Clinical results of 3-dimensional conformal radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma in the cirrhotic patients. Hepatol Res. 2003;27:30–5.

  40. Wu D-H, Liu L, Chen L-H. Therapeutic effects and prognostic factors in three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma. World J Gastroenterol. 2004;10:2184–9.

    PubMed  PubMed Central  Google Scholar 

  41. Esposito I, Kleeff J, Bergmann F, Reiser C, Herpel E, Friess H, et al. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15:1651–60.

  42. Allen AM, Pawlicki T, Dong L, Fourkal E, Buyyounouski M, Cengel K, et al. An evidence based review of proton beam therapy: the report of ASTRO’s emerging technology committee. Radiother Oncol. 2012;103:8–11.

  43. 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.

  44. Mizumoto M, Okumura T, Hashimoto T, Fukuda, K Oshiro Y, Fukumitsu N, et al. Proton beam therapy for hepatocellular carcinoma: a comparison of three treatment protocols. Radiat Oncol Biol. 2011;81:1039–45.

  45. Hong TS, Vagal AS, McKenzie JT, McPherson CM, Warnick RE, Batra V, et al. A prospective feasibility study of respiratory-gated proton beam therapy for liver tumors. Pract Radiat Oncol. 2014;4:316–22.

  46. Habermehl D, Debus J, Ganten T, Ganten MK, Bauer J, Brecht IC, et al. Hypofractionated carbon ion therapy delivered with scanned ion beams for patients with hepatocellular carcinoma - feasibility and clinical response. Radiat Onco. 2013;8:59. A trial on an important future direction of particle therapy, highlighting experience with the pencil-scanning method for dose delivery to the liver.

  47. Mori S, Zenklusen S, Inaniwa T, Furukawa T, Imada H, Shirai T, et al. Conformity and robustness of gated rescanned carbon ion pencil beam scanning of liver tumors at NIRS. Radiother Oncol. 2014;111:431–6. Initial work on combining the scanning method with respiration gating for more accurate treatment of respiration-mobile tumors.

  48. Kleeff J, Reiser C, Hinz U, Bachmann J, Debus J, Jaeger D, et al. Surgery for recurrent pancreatic ductal adenocarcinoma. Ann Surg. 2007;245:566–72.

  49. 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.

  50. Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.

  51. Breslin TM, Hess KR, Harbison DB, Jean ME, Cleary KR, Dackiw AP, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol. 2001;8:123–32.

  52. Hoffman JP, Lipsitz S, Pisansky T, Weese JL, Solin L, Benson AB. Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. J Clin Oncol. 1998;16:317–23.

  53. 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.

  54. Shinoto M, Yamada S, Yasuda S, Imada H, Shioyama Y, Honda H, et al. Phase 1 trial of preoperative, short-course carbon-ion radiotherapy for patients with resectable pancreatic cancer. Cancer. 2013;119:45–51.

  55. Takahashi H, Ohigashi H, Gotoh K, Marubashi S, Yamada T, Murata M, et al. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg. 2013;258:1040–50.

  56. Moertel CG, Frytak S, Hahn RG, O’Connell MJ, Reitemeier RJ, Rubin J, et al. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer. 1981;48:1705–10.

  57. Klaassen DJ, MacIntyre JM, Catton GE, Engstrom PF, Moertel CG.  Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil--an Eastern Cooperative Oncology Group study. J Clin Oncol. 1985;3:373–8.

  58. Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouche O, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol. 2008;19:1592–9.

  59. Loehrer Sr PJ, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, 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.

  60. Terashima K, Demizu Y, Hashimoto N, Jin D, Mima M, Fujii O, 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.

  61. Sachsman S, Nichols Jr RC, Morris CG, Zaiden Jr RA, Johnson EA, Awad ZT, et al. Proton therapy and concomitant capecitabine for non-metastatic unresectable pancreatic adenocarcinoma. Int J Particle Ther. 2014;1:692–701.

  62. Shinoto M, Yamada S, Terashima K, Yasuda S, Shioyama Y, Honda H, et al. Carbon-ion radiotherapy with concurrent gemcitabine for patients with locally advanced pancreatic cancer. Int J Radiat Oncol. 2016; in press. This is the latest result on a trial of carbon-ion radiotherapy for locally advanced pancreatic cancer.

  63. Ikeda M, Ioka T, Ito Y, Yonemoto N, Nagase M, Yamao K, et al. A multicenter phase II trial of S-1 with concurrent radiation therapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2013;85:163–9.

  64. Schellenberg D, Kim J, Christman-Skieller C, Chun CL, Columbo LA, Ford JM, et al. Single-fraction stereotactic body radiation therapy and sequential gemcitabine for the treatment of locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2011;81:181–8.

  65. Ben-Josef E, Schipper M, Francis IR, Hadley S, Ten-Haken R, Lawrence T, et al. A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2012;84:1166–71.

  66. Knol HP, Hanssens PE, Rutten HJ, Wiggers T. Effect of radiation therapy alone or in combination with surgery and/or chemotherapy on tumor and symptom control of recurrent rectal cancer. Strahlenther Onkol. 1997;173(1):43–9.

  67. Murata T, Fujii I, Yoshino M. Radiation therapy with or without chemotherapy and hyperthermia for recurrent rectal cancer. J Jpn Soc Ther Radiol Oncol. 1997;9:63–71.

    Google Scholar 

  68. Wanebo HJ, Antoniuk P, Koness JR, James R, Audrey A, Michael V, et al. Pelvic resection of recurrent rectal cancer: technical considerations and outcomes. Dis Colon Rectum. 1999;42:1438–48.

  69. Saito N, Koda K, Takiguchi N, Oda K, Ono M, Sugito M, et al. Curative surgery for local pelvic recurrence of rectal cancer. Dig Surg. 2003;20:192–200.

  70. Mohiuddin M, Marks G, Marks J. Long-term results of reirradiation for patients with recurrent rectal carcinoma. Cancer. 2002;95:1144–50.

    Article  PubMed  Google Scholar 

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Correspondence to Shigeru Yamada.

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Makoto Shinoto, Daniel K. Ebner, and Shigeru Yamada declare that they have no conflict of interest.

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Shinoto, M., Ebner, D.K. & Yamada, S. Particle Radiation Therapy for Gastrointestinal Cancers. Curr Oncol Rep 18, 17 (2016). https://doi.org/10.1007/s11912-016-0499-8

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