Theory and practice of involved-field radiotherapy for esophageal squamous cell carcinoma
Luo Yijun,Wang Xiaoli,Yu Jinming,Li Minghuan
College of Medicine and Life Science, Shandong Academy of Medical Sciences,Ji’nan 250022,China (Luo YJ,Wang XL); Department of Radiation Oncology,Shandong Tumor Hospital Affiliated to Shandong University,Ji’nan 250117,China (Luo YJ,Wang XL,Yu JM,Li MH)
Abstract： Chemoradiotherapy is a major treatment for inoperable esophageal carcinoma (EC). However, there is still controversy over the target volume for radiation, particularly nodal target volume. EC is characterized by a high rate of lymph node metastasis, and its metastatic pattern is not always predictable. Elective nodal irradiation (ENI) will increase the radiation field, which may increase the incidence of adverse events. Some investigators used involved-field irradiation (IFI) to reduce treatment-related toxicities without compromising survival. Studies have demonstrated that regional and distant micrometastases can be controlled, to some extent, by chemotherapy, incidental irradiation, and the abscopal effects of radiation. With either ENI or IFI, EC recurrence is usually found in the primary tumor and at distant sites, without survival difference. These data suggest that IFI is feasible in EC patients.
Luo Yijun,Wang Xiaoli,Yu Jinming et al. Theory and practice of involved-field radiotherapy for esophageal squamous cell carcinoma[J]. Chinese Journal of Radiation Oncology, 2017, 26(8): 965-969.
[1] Ajani JA.Gastroesophageal cancers:progress and problems[J].J Natl Compr Canc Netw,2008,6(9):813-814.DOI:10.6004/jnccn.2008.0061. [2] Kumagai K,Rouvelas I,Tsai JA,et al. Meta-analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal and gastro-oesophageal junctional cancers[J].Br J Surg,2014,101(4):321-338.DOI:10.1002/bjs.9418. [3] Minsky BD,Pajak TF,Ginsberg RJ,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].J Clin Oncol,2002,20(5):1167-1174.DOI:10.1200/JCO.2002.20.5.1167. [4] Button MR,Morgan CA,Croydon ES,et al. Study to determine adequate margins in radiotherapy planning for esophageal carcinoma by detailing patterns of recurrence after definitive chemoradiotherapy[J].Int J Radiat Oncol Biol Phys,2009,73(3):818-823.DOI:10.1016/j.ijrobp.2008.04.062. [5] Zhao KL,Ma JB,Liu G,et al. Three-dimensional conformal radiation therapy for esophageal squamous cell carcinoma:is elective nodal irradiation necessary?[J].Int J Radiat Oncol Biol Phys,2010,76(2):446-451.DOI:10.1016/j.ijrobp.2009.02.078. [6] Zhang XL,Li MH,Meng X,et al. Involved-field irradiation in definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma[J].Radiat Oncol,2014,9(1):64.DOI:10.1186/1748-717X-9-64. [7] Kawaguchi Y,Nishiyama K,Miyagi K,et al. Patterns of failure associated with involved field radiotherapy in patients with clinical stage Ⅰ thoracic esophageal cancer[J].Jpn J Clin Oncol,2011,41(8):1007-1012.DOI:10.1093/jjco/hyr069. [8] Yamashita H,Omori M,Takenaka R,et al. Involved-field irradiation concurrently combined with nedaplatin/5-fluorouracil for inoperable esophageal cancer on basis of 18FDG-PET scans:a phase Ⅱ study[J].Radiother Oncol,2014,113(2):182-187.DOI:10.1016/j.radonc.2014.11.004. [9] Nishihira T,Sayama J,Ueda H,et al. Lymph flow and lymph node metastasis in esophageal cancer[J].Surg Today,1995,25(4):307-317.DOI:10.1007/BF00311252. [10] Motoyama S,Maruyama K,Sato Y,et al. Status of involved lymph nodes and direction of metastatic lymphatic flow between submucosal and t2-4 thoracic squamous cell esophageal cancers[J].World J Surg,2009,33(3):512-517.DOI:10.1007/s00268-008-9781-8. [11] Mizutani M,Murakami G,Nawata SI,et al. Anatomy of right recurrent nerve node:why does early metastasis of esophageal cancer occur in it?[J].Surg Radiol Anat,2006,28(4):333-338.DOI:10.1007/s00276-006-0115-y. [12] Herskovic A,Martz K,Al-Sarraf M,et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus[J].N Engl J Med,1992,326(24):1593-1598.DOI:10.1056/NEJM199206113262403. [13] Ding X,Zhang J,Li B,et al. A meta-analysis of lymph node metastasis rate for patients with thoracic oesophageal cancer and its implication in delineation of clinical target volume for radiation therapy[J].Br J Radiol,2012,85(1019):e1110-1119.DOI:10.1259/bjr/12500248. [14] Rice TW,Zuccaro GJr,Adelstein DJ,et al. Esophageal carcinoma:depth of tumor invasion is predictive of regional lymph node status[J].Ann Thorac Surg,1998,65(3):787-792.DOI:10.1016/S0003-4975(97)01387-8. [15] Shimada H,Nabeya Y,Matsubara H,et al. Prediction of lymph node status in patients with superficial esophageal carcinoma:analysis of 160 surgically resected cancers[J].Am J Surg,2006,191(2):250-254.DOI:10.1016/j.amjsurg.2005.07.035. [16] 王洲,刘相燕,刘凡英,等.N0期食管癌术后早期复发与淋巴结微转移的相关性研究[J].中华外科杂志,2004,42(2):68-71.DOI:10.3760/j:issn:0529-5815.2004.02.002. Wang Z,Liu XY,Liu FY,et al. A study of correlation between early postoperative relapse with lymph node micrometastasis in patients with N0 esophageal cancer[J].Chin J Surg,2004,42(2):68-71.DOI:10.3760/j:issn:0529-5815.2004.02.002. [17] Prenzel KL,Knig A,Schneider PM,et al. Reduced incidence of nodal micrometastasis after major response to neoadjuvant chemoradiation in locally advanced esophageal cancer[J].Ann Surg Oncol,2007,14(2):954-959.DOI:10.1245/s10434-006-9141-6. [18] Matsuyama J,Doki Y,Yasuda T,et al. The effect of neoadjuvant chemotherapy on lymph node micrometastases in squamous cell carcinomas of the thoracic esophagus[J].Surgery,2007,141(5):570-580.DOI:10.1016/j.surg.2006.11.007. [19] Formenti SC,Demaria S.Systemic effects of local radiotherapy[J].Lancet Oncol,2009,10(7):718-726.DOI:10.1016/S1470-2045(09)70082-8. [20] Ahmed MM,Guha C,Hodge JW,et al. Immunobiology of radiotherapy:new paradigms[J].Radiat Res,2014,182(2):123-125.DOI:10.1667/RR13849.1. [21] Ji K,Zhao LJ,Yang CW,et al. Three-dimensional conformal radiation for esophageal squamous cell carcinoma with involved-field irradiation may deliver considerable doses of incidental nodal irradiation[J].Radiat Oncol,2012,7(1):200.DOI:10.1186/1748-717X-7-200. [22] Cooper JS,Guo MD,Herskovic A,et al. Chemoradiotherapy of locally advanced esophageal cancer:long-term follow-up of a prospective randomized trial (RTOG 85-01).Radiation Therapy Oncology Group[J].JAMA,1999,281(17):1623-1627.DOI:10.1001/jama.281.17.1623. [23] Kato H,Sato A,Fukuda H,et al. A phase Ⅱ trial of chemoradiotherapy for stage Ⅰ esophageal squamous cell carcinoma:Japan clinical oncology group study (JCOG9708)[J].Jpn J Clin Oncol,2009,39(10):638-643.DOI:10.1093/jjco/hyp069. [24] Michel P,Adenis A,Di Fiore F,et al. Induction cisplatin-irinotecan followed by concurrent cisplatin-irinotecan and radiotherapy without surgery in oesophageal cancer:multicenter phase Ⅱ FFCD trial[J].Br J Cancer,2006,95(6):705-709.DOI:10.1038/sj.bjc.6603328. [25] Kato K,Nakajima TE,Ito Y,et al. Phase Ⅱ study of concurrent chemoradiotherapy at the dose of 50.4 Gy with elective nodal irradiation for Stage Ⅱ-Ⅲ esophageal carcinoma[J].Jpn J Clin Oncol,2013,43(6):608-615.DOI:10.1093/jjco/hyt048. [26] van Hagen P,Hulshof MCCM,van Lanschot JJB,et al. Preoperative chemoradiotherapy for esophageal or junctional cancer[J].N Engl J Med,2012,366(22):2074-2084.DOI:10.1056/NEJMoa1112088. [27] Lin SH,Wang JY,Allen PK,et al. A nomogram that predicts pathologic complete response to neoadjuvant chemoradiation also predicts survival outcomes after definitive chemoradiation for esophageal cancer[J].J Gastrointest Oncol,2015,6(1):45-52.DOI:10.3978/j.issn.2078-6891.2014.054. [28] Ishikawa H,Sakurai H,Tamaki Y,et al. Radiation therapy alone for stage Ⅰ (UICC T1N0M0) squamous cell carcinoma of the esophagus:indications for surgery or combined chemoradiotherapy[J].J Gastroenterol Hepatol,2006,21(8):1290-1296.DOI:10.1111/j.1440-1746.2006.04089.x. [29] Zhong Z,Gu X,Zhang Z,et al. Recombinant human endostatin combined with definitive chemoradiotherapy as primary treatment for patients with unresectable but without systemic metastatic squamous cell carcinoma of the oesophagus[J].Br J Radiol,2012,85(1019):e1104-1109.DOI:10.1259/bjr/15321801. [30] Piessen G,Briez N,Triboulet JP,et al. Patients with locally advanced esophageal carcinoma nonresponder to radiochemotherapy:who will benefit from surgery?[J].Ann Surg Oncol,2007,14(7):2036-2044.DOI:10.1245/s10434-007-9405-9. [31] Welsh J,Settle SH,Amini A,et al. Failure patterns in patients with esophageal cancer treated with definitive chemoradiation[J].Cancer,2012,118(10):2632-2640.DOI:10.1002/cncr.26586. [32] Di Fiore F,Lecleire S,Rigal O,et al. Predictive factors of survival in patients treated with definitive chemoradiotherapy for squamous cell esophageal carcinoma[J].World J Gastroenterol,2006,12(26):4185-4190.DOI:10.3748/wjg.v12.i26.4185. [33] Yamashita H,Okuma K,Wakui R,et al. Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma—a retrospective analysis[J].Radiother Oncol,2011,98(2):255-260.DOI:10.1016/j.radonc.2010.10.021. [34] Onozawa M,Nihei K,Ishikura S,et al. Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus[J].Radiother Oncol,2009,92(2):266-269.DOI:10.1016/j.radonc.2008.09.025. [35] Uno T,Isobe K,Kawakami H,et al. Efficacy and toxicities of concurrent chemoradiation for elderly patients with esophageal cancer[J].Anticancer Res,2004,24(4):2483-2486. [36] Ma JB,Song YP,Yu JM,et al. Feasibility of involved-field conformal radiotherapy for cervical and upper-thoracic esophageal cancer[J].Onkologie,2011,34(11):599-604.DOI:10.1159/000334194. [37] Jing W,Zhu H,Guo HB,et al. Correction:feasibility of elective nodal irradiation (ENI) and involved field irradiation (IFI) in radiotherapy for the elderly patients (Aged≥70 Years) with esophageal squamous cell cancer:a retrospective analysis from a single institute. PLoS One,2016,11(1):e0147453.DOI:10.1371/journal.pone.0147453. [38] Yamashita H,Takenaka R,Omori M,et al. Involved-field radiotherapy (IFRT) versus elective nodal irradiation (ENI) in combination with concurrent chemotherapy for 239 esophageal cancers:a single institutional retrospective study[J].Radiat Oncol,2015,10:171.DOI:10.1186/s13014-015-0482-9. [39] 李曼,乔学英,周志国,等.胸段食管癌三维适形放疗临床靶体积前瞻性随机临床研究[J].中国肿瘤临床,2012,39(17):1294-1298.DOI:10.3969/j.issn.1000-8179.2012.17.008. Li M,Qiao XY,Zhou ZG,et al. A prospectively randomized study of clinical target volume margins for three-dimensional conformal radiotherapy in patients with thoracic esophageal squamous cell carcinoma[J].Chin J Clin Oncol,2012,39(17):1294-1298.DOI:10.3969/j.issn.1000-8179.2012.17.008.
2017, Vol. 26 
