食管癌质子放疗研究进展

doi:10.3760/cma.j.cn371439-20240805-00007

摘要/Abstract

摘要：

食管癌是世界范围内肿瘤死亡的主要原因之一，放疗在食管癌的治疗中发挥重要作用，质子放疗由于其独特的生物物理学特性使其较光子放疗在剂量学上可降低危及器官的受量，可能是治疗食管癌的一种理想的放疗方式。在食管癌根治性放疗、新辅助放疗以及再程放疗中，质子放疗均发挥出重要的作用，疗效与光子放疗相当或更优，安全性更有优势。质子放疗与免疫治疗的联合、放疗剂量的提升、基于调强质子放疗技术的大型随机对照研究等将是后续研究的热点。

关键词: 食管肿瘤, 放射疗法, 质子疗法

Abstract:

Esophageal cancer is one of the leading causes of death from cancer worldwide. Radiotherapy plays an important role in the treatment of esophageal cancer. Compared with photon radiotherapy， proton radiotherapy significantly reduces normal organ dose due to its unique biophysical properties， which makes this modality potential ideal for esophageal cancer treatment. Proton radiotherapy plays an important role in radical radiotherapy， neoadjuvant radiotherapy and re-radiotherapy for esophageal cancer. The efficacy is equivalent to or better than that of photon radiotherapy， and proton radiotherapy is superior than photon radiotherapy in security. The combination of proton radiotherapy and immunotherapy， the increase of radiotherapy dose， and large-scale randomized controlled studies based on intensity-modulated proton radiotherapy technology will be hot topics for further research.

Key words: Esophageal neoplasms, Radiotherapy, Proton therapy

付成瑞, 李宝生, 黄伟. 食管癌质子放疗研究进展[J]. 国际肿瘤学杂志, 2025, 52(1): 48-52.

Fu Chengrui, Li Baosheng, Huang Wei. Research progress of proton therapy for esophageal cancer[J]. Journal of International Oncology, 2025, 52(1): 48-52.

参考文献 36

[1]	中国医师协会放射肿瘤治疗医师分会, 中华医学会放射肿瘤治疗学分会, 中国抗癌协会肿瘤放射治疗专业委员会. 中国食管癌放射治疗指南(2023年版)[J]. 国际肿瘤学杂志, 2024, 51(1): 1-20. DOI: 10.3760/cma.j.cn371439-20231221-00001.
[2]	于新生, 任磊, 卢晓光. 现代质子放疗和光子放疗的争论与思考[J]. 国际肿瘤学杂志, 2024, 51(7): 411-416. DOI: 10.3760/cma.j.cn371439-20240619-00068.
[3]	Liu C, Bhangoo RS, Sio TT, et al. Dosimetric comparison of distal esophageal carcinoma plans for patients treated with small-spot intensity-modulated proton versus volumetric-modulated arc therapies[J]. J Appl Clin Med Phys, 2019, 20(7): 15-27. DOI: 10.1002/acm2.12623. pmid: 31112371
[4]	Shiraishi Y, Xu C, Yang J, et al. Dosimetric comparison to the heart and cardiac substructure in a large cohort of esophageal cancer patients treated with proton beam therapy or intensity-modulated radiation therapy[J]. Radiother Oncol, 2017, 125(1): 48-54. DOI: 10.1016/j.radonc.2017.07.034. pmid: 28917586
[5]	Visser S, O Ribeiro C, Dieters M, et al. Robustness assessment of clinical adaptive proton and photon radiotherapy for oesophageal cancer in the model-based approach[J]. Radiother Oncol, 2022, 177: 197-204. DOI: 10.1016/j.radonc.2022.11.001. pmid: 36368472
[6]	Lin SH, Hobbs BP, Verma V, et al. Randomized phase ⅡB trial of proton beam therapy versus intensity-modulated radiation therapy for locally advanced esophageal cancer[J]. J Clin Oncol, 2020, 38(14): 1569-1579. DOI: 10.1200/JCO.19.02503.
[7]	Macomber MW, Bowen SR, Gopan O, et al. Heart dose and outcomes in radiation treatment for esophageal cancer[J]. Cureus, 2018, 10(3): e2378. DOI: 10.7759/cureus.2378.
[8]	Wang X, Palaskas NL, Yusuf SW, et al. Incidence and onset of severe cardiac events after radiotherapy for esophageal cancer[J]. J Thorac Oncol, 2020, 15(10): 1682-1690. DOI: 10.1016/j.jtho.2020.06.014. pmid: 32599073
[9]	Zhang A, Deek MP, Kim S, et al. Vertebral body irradiation during chemoradiation therapy for esophageal cancer contributes to acute bone marrow toxicity[J]. J Gastrointest Oncol, 2019, 10(3): 513-522. DOI: 10.21037/jgo.2019.01.20. pmid: 31183202
[10]	Warren S, Hurt CN, Crosby T, et al. Potential of proton therapy to reduce acute hematologic toxicity in concurrent chemoradiation therapy for esophageal cancer[J]. Int J Radiat Oncol Biol Phys, 2017, 99(3): 729-737. DOI: 10.1016/j.ijrobp.2017.07.025.
[11]	Davuluri R, Jiang W, Fang P, et al. Lymphocyte nadir and esophageal cancer survival outcomes after chemoradiation therapy[J]. Int J Radiat Oncol Biol Phys, 2017, 99(1): 128-135. DOI: 10.1016/j.ijrobp.2017.05.037.
[12]	Celik E, Baus W, Baues C, et al. Volumetric modulated arc therapy versus intensity-modulated proton therapy in neoadjuvant irradiation of locally advanced oesophageal cancer[J]. Radiat Oncol, 2020, 15(1): 120. DOI: 10.1186/s13014-020-01570-y. pmid: 32448296
[13]	Feng H, Sio TT, Rule WG, et al. Beam angle comparison for distal esophageal carcinoma patients treated with intensity-modulated proton therapy[J]. J Appl Clin Med Phys, 2020, 21(11): 141-152. DOI: 10.1002/acm2.13049. pmid: 33058523
[14]	Zhang Y, Jabbour SK, Zhang A, et al. Proton beam therapy can achieve lower vertebral bone marrow dose than photon beam therapy during chemoradiation therapy of esophageal cancer[J]. Med Dosim, 2021, 46(3): 229-235. DOI: 10.1016/j.meddos.2020.12.003. pmid: 33454170
[15]	Hobbs BP, Thall PF, Lin SH. Bayesian group sequential clinical trial design using total toxicity burden and progression-free survival[J]. J R Stat Soc Ser C Appl Stat, 2016, 65(2): 273-297. DOI: 10.1111/rssc.12117.
[16]	Sato D, Motegi A, Kadota T, et al. Therapeutic results of proton beam therapy with concurrent chemotherapy for cT₁ esophageal cancer and salvage endoscopic therapy for local recurrence[J]. Esophagus, 2020, 17(3): 305-311. DOI: 10.1007/s10388-020-00715-y.
[17]	Ono T, Wada H, Ishikawa H, et al. Clinical results of proton beam therapy for esophageal cancer: multicenter retrospective study in Japan[J]. Cancers (Basel), 2019, 11(7): 993. DOI: 10.3390/cancers11070993.
[18]	Xi M, Xu C, Liao Z, et al. Comparative outcomes after definitive chemoradiotherapy using proton beam therapy versus intensity modulated radiation therapy for esophageal cancer: a retrospective, single-institutional analysis[J]. Int J Radiat Oncol Biol Phys, 2017, 99(3): 667-676. DOI: 10.1016/j.ijrobp.2017.06.2450.
[19]	Chang CL, Lin KC, Chen WM, et al. Comparative effectiveness of intensity-modulated proton therapy versus intensity-modulated radiotherapy for patients with inoperable esophageal squamous cell carcinoma undergoing curative-intent concurrent chemoradiotherapy[J]. J Thorac Oncol, 2024, 19(5): 818-828. DOI: 10.1016/j.jtho.2023.12.021.
[20]	Abana CO, Damen PJ, van Rossum PS, et al. Esophageal cancer outcomes after definitive chemotherapy with intensity modulated proton therapy[J]. Int J Part Ther, 2024, 11: 100009. DOI: 10.1016/j.ijpt.2024.100009.
[21]	Nonaka T, Kawashiro S, Ishikawa H, et al. Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review[J]. Esophagus, 2023, 20(4): 605-616. DOI: 10.1007/s10388-023-01015-x. pmid: 37328706
[22]	Lin SH, Komaki R, Liao Z, et al. Proton beam therapy and concurrent chemotherapy for esophageal cancer[J]. Int J Radiat Oncol Biol Phys, 2012, 83(3): e345-e351. DOI: 10.1016/j.ijrobp.2012.01.003.
[23]	Crellin A. The road map for National Health Service proton beam therapy[J]. Clin Oncol (R Coll Radiol), 2018, 30(5): 277-279. DOI: 10.1016/j.clon.2018.02.032. pmid: 29530438
[24]	Lin SH, Merrell KW, Shen J, et al. Multi-institutional analysis of radiation modality use and postoperative outcomes of neoadjuvant chemoradiation for esophageal cancer[J]. Radiother Oncol, 2017, 123(3): 376-381. DOI: 10.1016/j.radonc.2017.04.013. pmid: 28455153
[25]	Shiraishi Y, Fang P, Xu C, et al. Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: a propensity matched analysis of the relative risk of proton versus photon-based radiation therapy[J]. Radiother Oncol, 2018, 128(1): 154-160. DOI: 10.1016/j.radonc.2017.11.028. pmid: 29248170
[26]	Bhangoo RS, DeWees TA, Yu NY, et al. Acute toxicities and short-term patient outcomes after intensity-modulated proton beam radiation therapy or intensity-modulated photon radiation therapy for esophageal carcinoma: a Mayo clinic experience[J]. Adv Radiat Oncol, 2020, 5(5): 871-879. DOI: 10.1016/j.adro.2020.04.026. pmid: 33083649
[27]	Simone CB 2nd. First randomized trial supporting the use of proton over photon chemoradiotherapy in esophageal cancer[J]. J Clin Oncol, 2020, 38(26): 2952-2955. DOI: 10.1200/JCO.20.01405. pmid: 32706638
[28]	朱欣欣, 李丹杨, 山周琦玥, 等. 质子放疗与光子放疗治疗食管癌疗效和安全性的meta分析[J]. 现代医药卫生, 2022, 38(6): 964-969. DOI: 10.3969/j.issn.1009-5519.2022.06.014.
[29]	ClinicalTrials. gov. Comparing proton therapy to photon radiation therapy for esophageal cancer[EB/OL]. (2019-01-14)[2024-06-11]. https://clinicaltrials.gov/study/NCT03801876#study-plan.
[30]	PROTECTtrial. Protocol[EB/OL]. (2023-03-30)[2024-06-11]. https://protecttrial.eu/clinical-trial/protocol.
[31]	DeCesaris CM, McCarroll R, Mishra MV, et al. Assessing outcomes of patients treated with re-irradiation utilizing proton pencil-beam scanning for primary or recurrent malignancies of the esophagus and gastroesophageal junction[J]. J Thorac Oncol, 2020, 15(6): 1054-1064. DOI: 10.1016/j.jtho.2020.01.024. pmid: 32145427
[32]	Patel SA, Edgington SK, Adams J, et al. Novel use of proton beam therapy for neoadjuvant treatment of radiation-associated squamous cell carcinoma of the esophagus[J]. J Gastrointest Oncol, 2019, 10(1): 155-160. DOI: 10.21037/jgo.2018.09.06. pmid: 30788171
[33]	Mazal A, Vera Sanchez JA, Sanchez-Parcerisa D, et al. Biological and mechanical synergies to deal with proton therapy pitfalls: minibeams, FLASH, Arcs, and gantryless rooms[J]. Front Oncol, 2020, 10: 613669. DOI: 10.3389/fonc.2020.613669.
[34]	Jethwa KR, Haddock MG, Tryggestad EJ, et al. The emerging role of proton therapy for esophagus cancer[J]. J Gastrointest Oncol, 2020, 11(1): 144-156. DOI: 10.21037/jgo.2019.11.04. pmid: 32175118
[35]	Tryggestad EJ, Liu W, Pepin MD, et al. Managing treatment-related uncertainties in proton beam radiotherapy for gastrointestinal cancers[J]. J Gastrointest Oncol, 2020, 11(1): 212-224. DOI: 10.21037/jgo.2019.11.07. pmid: 32175124
[36]	Hulshof MCCM, Geijsen ED, Rozema T, et al. Randomized study on dose escalation in definitive chemoradiation for patients with locally advanced esophageal cancer (ARTDECO study)[J]. J Clin Oncol, 2021, 39(25): 2816-2824. DOI: 10.1200/JCO.20.03697.