Feasibility, Safety, and Factors Predicting Completion of CROSS Protocol–Based Neoadjuvant Chemoradiotherapy for Esophageal Squamous Carcinoma: Experience from an Indian Tertiary Care Cancer Center

Abstract

Background

Neoadjuvant chemoradiotherapy (NACRT) using the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) protocol has improved esophageal cancer outcomes. This study reports the real-world experience of the CROSS regimen for esophageal squamous cell carcinoma (ESCC) regarding its feasibility, safety, and predictors of treatment completion from an Indian tertiary center.

Methodology

A retrospective review was conducted for patients with ESCC receiving CROSS (radiation dose: 41.4 Gy) or a modified CROSS (mCROSS; radiation dose: 45 Gy) protocol NACRT between 2015 and 2022. We studied the treatment tolerability, factors predicting NACRT completion, and the effect of completion of its chemotherapy component on the pathological outcomes.

Results

Of the109 patients (68.8% males; mean age, 56 ± 9 years; Charlson's comorbidity index [CCI] >2, 19.3%; stage III–IVA, 58%; mean tumor length, 5.5 ± 2.1cm; CROSS, 70.6%; mCROSS, 29.4%), all except 4 completed radiotherapy but only 58 (53.2%) patients completed ≥4 cycles of chemotherapy. Forty-nine patients belonged to the “extended” CROSS trial inclusion criteria. Among the 60 patients who fulfilled the CROSS inclusion criteria, only 51.7% were able to complete ≥4 chemotherapy cycles. The commonest reason for noncompletion of chemotherapy was the occurrence of neutropenia (60.8%). Pretreatment hemoglobin (≥12 vs. <12 g%; odds ratio [OR]: 2.76; 95% confidence interval [CI]: 1.10–6.96; p = 0.031), a low CCI (≤2 vs. >2; OR: 2.98; 95% CI: 1.02–8.73; p = 0.047), and radiation therapy techniques (conformal vs. conventional; OR: 3.29; 95% CI: 1.14–9.50; p = 0.028) were associated with completion of chemotherapy (≥4 cycles). Although there was a trend toward improved R0 resection (95.7 vs. 91.4%), reduced node positivity (17.0 vs. 31.4%), and a high pCR (57.4 vs. 48.6%) in patients completing chemotherapy (≥4 cycles) compared with those not completing chemotherapy (<4 cycles), these differences were statistically nonsignificant.

Conclusion

In this study, ESCC patients receiving the CROSS protocol NACRT could complete their radiotherapy component, but a significant proportion exhibited poor chemotherapy tolerance. Neutropenia was a major factor limiting chemotherapy delivery, but anemia, high CCI, and conventional radiation techniques were also associated with noncompletion of chemotherapy. The omission of a few chemotherapy cycles had no significant effect on the pathological response; however, its impact on cancer survival requires further evaluation.

Keywords

CROSS - esophageal squamous carcinoma - feasibility - neoadjuvant chemoradiotherapy - pathological outcomes - treatment completion

Data Availability

Data are unavailable for public access.

Ethical Approval

Ethical approval was obtained from the institutional review board (IRB Min. No.12998/2020).

Consent to Participate

Waiver was obtained from the Ethics Committee considering the retrospective nature of the study.

Consent for Publication

All the authors gave consent to the publication of the manuscript in the South Asian Journal of Cancer should the article be accepted by the editor-in-chief upon completion of the refereeing process.

Author Contributions

Conception and design were done by S.S., G.M., R.I., and I.S. Acquisition of data was done by S.S. and G.M. Data analysis and interpretation were done by all the authors. Drafting of the manuscript was done by S.S., G.M., and T.M. Critical appraisal and revision were done by S.S., M.M., R.I., N.P., M.Y., B.K.S., S.P., S.C., V.A., S.J., and I.S. Overall guarantors of the work are B.K.S. and I.S. All the author approved the final version of manuscript to be published.

Authors Note

G.M. was affiliated with the Department of General Surgery, Christian Medical College Hospital, Vellore-632004, India, at the time of data collection, analysis, and preliminary write-up of the manuscript and is currently affiliated with the Department of Surgical Oncology, TATA Memorial Hospital, Mumbai, Maharashtra, India. V.A. was affiliated with the Department of General and Upper GI Surgery, Christian Medical College Hospital, Vellore-632004, India at the time of data collection, analysis, and preliminary write-up of the manuscript and is currently affiliated with the Department of Upper GI Surgery, The Queen Elizabeth Hospital, Woodville South, Australia and T.M. was affiliated with the Department of Biostatistics, Christian Medical College Hospital, Vellore-632004, India at the time of data collection, analysis, and preliminary write-up of the manuscript and is currently affiliated as a Postdoctoral Research Fellow, Population Health Research Institute, McMaster University, Hamilton, Canada

Publication History

Received: 23 May 2024

Accepted: 29 July 2024

Article published online:
20 September 2024

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