Salvage chemoradiation therapy for recurrence after radical surgery or palliative surgery in esophageal cancer patients: a prospective, multicenter clinical trial protocol

Xiao Chang, Lei Deng, Wenjie Ni, Chen Li, Weiming Han, Lin-Rui Gao, Shijia Wang, Zongmei Zhou, Dongfu Chen, Qinfu Feng, Jun Liang, Nan Bi, Jima Lv, Shugeng Gao, Yousheng Mao, Qi Xue, Zefen Xiao, Xiao Chang, Lei Deng, Wenjie Ni, Chen Li, Weiming Han, Lin-Rui Gao, Shijia Wang, Zongmei Zhou, Dongfu Chen, Qinfu Feng, Jun Liang, Nan Bi, Jima Lv, Shugeng Gao, Yousheng Mao, Qi Xue, Zefen Xiao

Abstract

Background: Currently, adjuvant therapy is not recommended for patients with thoracic esophageal squamous cell cancer (TESCC) after radical surgery, and a proportion of these patients go on to develop locoregional recurrence (LRR) within 2 years. Besides, there is no evidence for salvage chemoradiation therapy (CRT) in patients with residual tumor after esophagectomy (R1/R2 resection). In addition, factors like different failure patterns and relationship with normal organs influence the decision for salvage strategy. Here, we aimed to design a modularized salvage CRT strategy for patients without a chance of salvage surgery according to different failure patterns (including R1/R2 resection), and further evaluated its efficacy and safety.

Methods: Our study was designed as a one arm, multicenter, prospective clinical trial. All enrolled patients were stratified in a stepwise manner based on the nature of surgery (R0 or R1/2), recurrent lesion diameter, involved regions, and time-to-recurrence, and were further assigned to undergo either elective nodal irradiation or involved field irradiation. Then, radiation technique and dose prescription were modified according to the distance from the recurrent lesion to the thoracic stomach or intestine. Ultimately, four treatment plans were established.

Discussion: This prospective study provided high-level evidence for clinical salvage management in patients with TESCC who developed LRR after radical surgery or those who underwent R1/R2 resection.

Trial registration: Prospectively Registered. ClinicalTrials.gov NCT03731442 , Registered November 6, 2018.

Keywords: Chemoradiation therapy; Esophageal neoplasm; Locoregional recurrence; Palliative management; R1/R2 resection.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of the trial
Fig. 2
Fig. 2
Illustration depicting reclassified regions
Fig. 3
Fig. 3
Examples of target volumes delineated in elective nodal irradiation (ENI) pattern are shown based on the planning computed tomography (CT) scans. a Lesions far from the thoracic stomach recurred in right supraclavicular space. The ENI field includes bilateral supraclavicular space, 1R/L, 2R/L, 4R/L, partial 7, and 8 U/M. b Lesions adjacent to the thoracic stomach recurred in Station 8 U, ENI field includes bilateral supraclavicular space, 1R/L, 2R/L, 4R/L, partial 7, and 8 U/M. Pink outlines GTV-N, Red outlines GTV-T, blue outlines CTV, sky blue outlines PGTV, and green outlines PTV
Fig. 4
Fig. 4
Examples of target volumes delineated in involved field irradiation (IFI) pattern are shown based on the planning computed tomography (CT) scans. a Lesions which were > 5 cm and far from the thoracic stomach recurred in Station 7, 8 M/L and 15–17. The IFI field includes Station partial 4R/L, 7, 8 U/M, and 15–17. b Lesions adjacent to the thoracic stomach recurred in Station 2R and palliative CRT was performed because of its time-to-recurrence > 16 months. The IFI field only includes peritumor regions. Pink outlines GTV-N, Red outlines GTV-T, blue outlines CTV, and green outlines PTV

References

    1. National Comprehensive Cancer Network . NCCN clinical practice guidelines in oncology: esophageal and Esophagogastric junction cancers, Version 2. 2018.
    1. Hsu PK, Wang BY, Huang CS, Wu YC, Hsu WH. Prognostic factors for post-recurrence survival in esophageal squamous cell carcinoma patients with recurrence after resection. J Gastrointest Surg. 2011;15(4):558–565. doi: 10.1007/s11605-011-1458-1.
    1. Miyata H, Yamasaki M, Kurokawa Y, et al. Survival factors in patients with recurrence after curative resection of esophageal squamous cell carcinomas. Ann Surg Oncol. 2011;18(12):3353–3361. doi: 10.1245/s10434-011-1747-7.
    1. Lu J, Tao H, Song D, Chen C. 549-555 recurrence risk model for esophageal cancer after radical surgery. Chin J Cancer Res. 2013;25(5):549–555.
    1. Oppedijk V, Van Der Gaast A, Van Lanschot JJB, et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol. 2014;32(5):385–391. doi: 10.1200/JCO.2013.51.2186.
    1. Liu Q, Cai XW, Wu B, Zhu ZF, Chen HQ, Fu XL. Patterns of failure after radical surgery among patients with thoracic esophageal squamous cell carcinoma: implications for the clinical target volume design of postoperative radiotherapy. PLoS One. 2014;9(5):e97225. doi: 10.1371/journal.pone.0097225.
    1. Bhansali MS, Fujita H, Kakegawa T, et al. Pattern of recurrence after extended radical esophagectomy with three- field lymph node dissection for squamous cell carcinoma in the thoracic esophagus. World J Surg. 1997;21(3):275–281. doi: 10.1007/s002689900228.
    1. Nakagawa S, Kanda T, Kosugi SI, Ohashi M, Suzuki T, Hatakeyama K. Recurrence pattern of squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with three-field lymphadenectomy. J Am Coll Surg. 2004;198(2):205–211. doi: 10.1016/j.jamcollsurg.2003.10.005.
    1. Baba M, Aikou T, Yoshinaka H, et al. Long-term results of subtotal esophagectomy with three-field lymphadenectomy for carcinoma of the thoracic esophagus. Ann Surg. 1994;219(3):310–316. doi: 10.1097/00000658-199403000-00012.
    1. Kyriazanos ID, Tachibana M, Shibakita M, et al. Pattern of recurrence after extended esophagectomy for squamous cell carcinoma of the esophagus. Hepatogastroenterology. 2003;50(49):115–120.
    1. Ni W, Yang J, Deng W, et al. Patterns of recurrence after surgery and efficacy of salvage therapy after recurrence in patients with thoracic esophageal squamous cell carcinoma. BMC Cancer. 2020;20(1):144. doi: 10.1186/s12885-020-6622-0.
    1. Raoul JL, Le Prise E, Meunier B, et al. Combined radiochemotherapy for postoperative recurrence of oesophageal cancer. Gut. 1995;37(2):174–176. doi: 10.1136/gut.37.2.174.
    1. Su X-D, Zhang D-K, Zhang X, Lin P, Long H, Rong T-H. Prognostic factors in patients with recurrence after complete resection of esophageal squamous cell carcinoma. J Thorac Dis. 2014;6(7):949–957.
    1. Lu J-C, Kong C, Tao H. Radiotherapy with or without concurrent chemotherapy for lymph node recurrence after radical surgery of thoracic esophageal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2010;78(3):710–714. doi: 10.1016/j.ijrobp.2009.08.065.
    1. Zhang W-W, Zhu Y-J, Yang H, et al. Concurrent radiotherapy and weekly chemotherapy of 5-fluorouracil and platinum agents for postoperative locoregional recurrence of oesophageal squamous cell carcinoma. Sci Rep. 2015;5:8071. doi: 10.1038/srep08071.
    1. Rice TW, Ishwaran H, Ferguson MK, Blackstone EH, Goldstraw P. Cancer of the esophagus and Esophagogastric junction: an eighth edition staging primer. J Thorac Oncol. 2017;12(1):36–42. doi: 10.1016/j.jtho.2016.10.016.
    1. Nemoto K, Ariga H, Kakuto Y, et al. Radiation therapy for loco-regionally recurrent esophageal cancer after surgery. Radiother Oncol. 2001;61(2):165–168. doi: 10.1016/S0167-8140(01)00392-9.
    1. Zhang J, Peng F, Li N, et al. Salvage concurrent radio-chemotherapy for post-operative local recurrence of squamous-cell esophageal cancer. Radiat Oncol. 2012;7:93. doi: 10.1186/1748-717X-7-93.
    1. Shioyama Y, Nakamura K, Ohga S, et al. Radiation therapy for recurrent esophageal cancer after surgery: clinical results and prognostic factors. Jpn J Clin Oncol. 2007;37(12):918–923. doi: 10.1093/jjco/hym138.
    1. Zhang W, Liu X, Xiao Z, et al. Postoperative intensity-modulated radiotherapy improved survival in lymph node-positive or stage III thoracic esophageal squamous cell carcinoma. Oncol Res Treat. 2015;38(3):97–102. doi: 10.1159/000375391.
    1. Sher DJ, Koshy M, Liptay MJ, Fidler MJ. Influence of conformal radiotherapy technique on survival after chemoradiotherapy for patients with stage III non-small cell lung cancer in the National Cancer Data Base. Cancer. 2014;120(13):2060–2068. doi: 10.1002/cncr.28677.
    1. Lai S-Z, Li W-F, Chen L, et al. How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys. 2011;80(3):661–668. doi: 10.1016/j.ijrobp.2010.03.024.
    1. Welsh JW, Riley B, Palmer MB, et al. Intensity Modulated Proton Therapy Allows Dose Escalation and Normal-Tissue Sparing in Locally Advanced Distal Esophageal Tumors. Int J Radiat Oncol. 2010;78(3, Supplement):S808. doi: 10.1016/j.ijrobp.2010.07.1872.
    1. Zhang W-Z, Chen J-Z, Li D-R, et al. Simultaneous modulated accelerated radiation therapy for esophageal cancer: a feasibility study. World J Gastroenterol. 2014;20(38):13973–13980. doi: 10.3748/wjg.v20.i38.13973.
    1. Li C, Deng W, Wang X, et al. A Phase 1/2 Radiation Dose Escalation Trial Using SIB-IMRT Technique With Concurrent Chemotherapy in Unresectable Esophageal Carcinoma. Int J Radiat Oncol. 2017;99(2, Supplement):E166.
    1. Herskovic A, Martz K, al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with Cancer of the esophagus. N Engl J Med. 1992;326(24):1593–1598. doi: 10.1056/NEJM199206113262403.
    1. 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. JAMA. 1999;281(17):1623–1627. doi: 10.1001/jama.281.17.1623.
    1. Chen Y, Guo L, Cheng X, et al. With or without consolidation chemotherapy using cisplatin/5-FU after concurrent chemoradiotherapy in stage II-III squamous cell carcinoma of the esophagus: a propensity score-matched analysis. Radiother Oncol. 2018;129(1):154–160. doi: 10.1016/j.radonc.2017.10.031.
    1. 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. Radiat Oncol. 2015;10(1):1–10. doi: 10.1186/s13014-015-0482-9.
    1. Onozawa M, Nihei K, Ishikura S, et al. Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus. Radiother Oncol. 2009;92(2):266–269. doi: 10.1016/j.radonc.2008.09.025.
    1. Li M, Zhang Y, Zhu H, et al. 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. 2015;10(12):e0143007. doi: 10.1371/journal.pone.0143007.
    1. Ji K, Zhao L, Yang C, Meng M, Wang P. Three-dimensional conformal radiation for esophageal squamous cell carcinoma with involved-field irradiation may deliver considerable doses of incidental nodal irradiation. Radiat Oncol. 2012;7(1):1–8. doi: 10.1186/1748-717X-7-200.
    1. Huang W, Huang Y, Sun J, et al. Atlas of the thoracic lymph nodal delineation and recommendations for lymph nodal CTV of esophageal squamous cell cancer in radiation therapy from China. Radiother Oncol. 2015;116(1):100–106. doi: 10.1016/j.radonc.2015.06.024.
    1. Yamashita H, Okuma K, Wakui R, Kobayashi-Shibata S, Ohtomo K, Nakagawa K. 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. Radiother Oncol. 2011;98(2):255–260. doi: 10.1016/j.radonc.2010.10.021.

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