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Table of Contents
Year : 2022  |  Volume : 5  |  Issue : 1  |  Page : 167-169

Does the radiation dose in neoadjuvant chemoradiation in resectable esophageal carcinoma matter in the Indian scenario?

Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India

Date of Submission28-Jan-2022
Date of Decision14-Feb-2022
Date of Acceptance17-Feb-2022
Date of Web Publication31-Mar-2022

Correspondence Address:
Subramanyeshwar Rao Thammineedi
Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Road number 10, Banjara hills, Hyderabad, Telangana - 500 034
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/crst.crst_58_22

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How to cite this article:
Thammineedi SR, Patnaik SC, Nusrath S. Does the radiation dose in neoadjuvant chemoradiation in resectable esophageal carcinoma matter in the Indian scenario?. Cancer Res Stat Treat 2022;5:167-9

How to cite this URL:
Thammineedi SR, Patnaik SC, Nusrath S. Does the radiation dose in neoadjuvant chemoradiation in resectable esophageal carcinoma matter in the Indian scenario?. Cancer Res Stat Treat [serial online] 2022 [cited 2022 May 28];5:167-9. Available from: https://www.crstonline.com/text.asp?2022/5/1/167/342404

We read with interest the article by Dora et al. titled, “Neoadjuvant chemoradiotherapy (NACRT) followed by surgery for operable carcinoma esophagus: Ground reality in a tertiary care center of rural India,”[1] and the accompanying editorial by Rajappa.[2] The authors have highlighted the challenges in implementing NACRT followed by surgery for resectable esophageal cancer in a center where esophageal cancer surgery could be performed. The authors noted a trend toward better disease-free survival (DFS) for patients who received NACRT alone and did not undergo surgery compared to those who underwent NACRT followed by surgery. However, the overall survival (OS) was similar between the two groups.

For locally advanced carcinoma esophagus, NACRT followed by surgery remains the current standard of care.[3],[4] NACRT followed by surgery leads to a higher rate of radical (R0) resections and better DFS and OS compared to surgery alone.[3],[4] Though there are no head-to-head comparison trials or prospective studies, the available literature shows the superiority of NACRT and surgery over definitive chemoradiotherapy in resectable esophageal cancer.[5]

We wish to highlight certain essential points pertinent to this study, especially in the Indian context. Firstly, as this was a small study, it is likely that it was underpowered to detect any significant difference between the two arms, that is, NACRT followed by surgery versus NACRT alone. The poorer oncological outcomes with NACRT could be due to the relatively shorter follow-up duration, loss to follow-up (19% in NACRT with surgery and 70% with NACRT alone), and high perioperative mortality (19%). Out of 55 patients who received NACRT for resectable carcinoma of the esophagus (predominantly squamous cell histology) over a period of 2.5 years, 23 did not undergo surgery because they refused surgery (35%), had locally advanced or metastatic disease (35%), were medically unfit for surgery (22%), or had radiation mortality (4%).

To start with, all 55 patients had stage II/III cancers, and after NACRT, 8 patients were found to have locally advanced disease, precluding curative resection (14.5%). A good-quality pre-therapy positron emission tomography with computed tomography of the chest could have reduced this number. It is rare for tumors with squamous histology to progress on NACRT. In the NEOCRTEC5010 trial, a multicentric randomized study comparing NACRT and surgery to surgery alone in stage II/III eophageal squamous cell carcinomas, only 2 (0.9%) out of 224 patients in the NACRT arm had disease progression.[4] Similarly, 7 (4%) out of 178 in the NACRT arm in the CROSS trial (three fourths with adenocarcinoma and one fourth with squamous histology) could not undergo resection due to tumor progression.[3] We believe that many patients in this cohort may have had advanced disease initially and were erroneously assigned to a lower stage. With proper initial imaging and staging, patients with advanced and unresectable disease could directly proceed to definitive chemoradiation.

The issue of unwillingness to undergo surgery in patients receiving NACRT cannot be neglected. With proper pre-therapy counseling, this issue can be addressed. However, in the Indian setting, patients with squamous histology tumors come from lower economic backgrounds, most being daily wage workers, aiming to return to work early for their livelihood after improvement of symptoms. The majority of the patients interpret the amelioration of symptoms as synonymous with disease cure. In this context, we feel it is better to deliver a radiation dose of 50.4 Gy instead of 41.4 Gy in the neoadjuvant setting, which is also the dose for definitive chemoradiation. If the patient defaults for surgery, the chances of disease cure are higher.

We are surprised by the postoperative mortality of 18% reported in this study, which is very high by any standard. This stresses on the need to restrategize the treatment in favor of planned definitive chemoradiation or develop a strong thoracic service to complement the efforts of the other teams.

Lastly, we would like to comment on the attrition rate during the follow-up period. Loss to follow-up usually occurs when patients are ill, unable to communicate, missing, dead, or symptom-free and visit the hospital only with the resurgence of symptoms. We believe that cancer outcomes and follow-up will be better if patients undergo complete treatment at a single cancer center.

Based on the results of the landmark INT0123 trial, 50.4 Gy has become the accepted standard radiation dose.[6] Therefore, considering the high attrition rates in the Indian scenario, at least 50.4 Gy should be delivered in the neoadjuvant setting.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Dora TK, Aeron T, Chatterjee A, Deshmukh J, Goel A, Bose S, et al. Neoadjuvant chemoradiotherapy followed by surgery for operable carcinoma esophagus: Ground reality in a tertiary care center of rural India-A retrospective audit. Cancer Res Stat Treat 2021;4:647-55.  Back to cited text no. 1
  [Full text]  
Rajappa SJ. At crossroads with CROSS: Implementing the CROSS protocol in a resource-limited setting. Cancer Res Stat Treat 2021;4:734-6.  Back to cited text no. 2
  [Full text]  
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.  Back to cited text no. 3
Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, et al. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010): A phase III multicenter, randomized, open-label clinical trial. J Clin Oncol 2018;36:2796-803.  Back to cited text no. 4
Barbetta A, Hsu M, Tan KS, Stefanova D, Herman K, Adusumilli PS et al. Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by surgery for stage II to III esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg 2018;155:2710-21.  Back to cited text no. 5
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.  Back to cited text no. 6


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