Comparative study between sequential chemoradiotherapy with concurrent chemoradiotherapy for unresectable locally advanced esophageal cancer

Muhammad Adnan Arifeen; A. Z. M. Sumsuzoha; M. Ershadul Haque; Ahammad Al Mamun Sweet; M. Ruhul Amin Bhuiyan; Khandakar MD Rezwan Bayzid; Nayan Bhowmik; Barun Kumar Das

doi:10.18203/2320-6012.ijrms20252386

Authors

Muhammad Adnan Arifeen Department of Oncology, TMSS Medical College & Rafatullah Community Hospital, Bogura, Bangladesh
A. Z. M. Sumsuzoha Department of Oncology, TMSS Medical College & Rafatullah Community Hospital, Bogura, Bangladesh
M. Ershadul Haque Department of Radiotherapy, Rangpur Medical College Hospital, Rangpur, Bangladesh
Ahammad Al Mamun Sweet Clinical & Radiation Oncology, Lab Aid Cancer Hospital and Super Speciality Centre, Dhaka, Bangladesh
M. Ruhul Amin Bhuiyan Department of Oncology, North East Medical College Hospital, Sylhet, Bangladesh
Khandakar MD Rezwan Bayzid Clinical & Radiation Oncology, Lab Aid Cancer Hospital and Super Speciality Centre, Dhaka, Bangladesh
Nayan Bhowmik CMOSH Cancer Institute and Research Centre, Chittagong, Bangladesh
Barun Kumar Das Department of Oncology, Khwaja Yunus Ali Medical College Hospital, Sirajganj, Bangladesh

DOI:

https://doi.org/10.18203/2320-6012.ijrms20252386

Keywords:

Cancer, Chemoradiotherapy, Survival, Therapy

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy in South Asia with a high burden of unresectable cases at presentation. Chemoradiotherapy remains the mainstay of treatment, with concurrent chemoradiotherapy (CCRT) offering improved tumor control but at the cost of higher toxicity. The study aimed to compare the clinical efficacy and treatment-related toxicities of sequential chemoradiotherapy (SCRT) versus concurrent chemoradiotherapy (CCRT) in patients with unresectable locally advanced ESCC.

Methods: This quasi-experimental study was conducted at Khwaja Yunus Ali Medical College and Hospital, Sirajganj, from January 2020 to June 2021. A total of 62 patients with histologically confirmed unresectable ESCC were randomly assigned to two groups: Arm A (CCRT) and Arm B (SCRT), with 31 patients in each group.

Results: The baseline characteristics were comparable between the two arms. At 24 weeks, complete response rates were slightly higher in Arm A (51.61%) than in Arm B (41.93%), though not statistically significant (p>0.05). Toxicity analysis revealed a significantly higher incidence of Grade III esophagitis in the CCRT group (22.58% vs 3.23%; p=0.001). Hematologic and late radiation-related toxicities were also more frequent in Arm A. Weight loss and need for nutritional support (e.g., NG tube) were more common in the CCRT group, although not statistically significant.

Conclusions: While both treatment strategies showed similar tumor response rates, SCRT was associated with a more favorable toxicity profile. Thus, SCRT may serve as an effective and safer alternative for patients with unresectable locally advanced ESCC, especially in resource-constrained settings or among patients with borderline performance status.

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References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49. DOI: https://doi.org/10.3322/caac.21660

Rustgi AK, El-Serag HB. Esophageal carcinoma. N Engl J Med. 2014;371(26):2499–509. DOI: https://doi.org/10.1056/NEJMra1314530

Islami F, Marlow EC, Thomson B, McCullough ML, Rumgay H, Gapstur SM, et al. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States, 2019. CA Cancer J Clin. 2024;74(5):405–32. DOI: https://doi.org/10.3322/caac.21858

Siddiqi K, Husain S, Vidyasagaran A, Readshaw A, Mishu MP, Sheikh A. Global burden of disease due to smokeless tobacco consumption in adults: an updated analysis of data from 127 countries. BMC Med. 2020;18(1):222. DOI: https://doi.org/10.1186/s12916-020-01677-9

Sultana S, Sweety RA, Zhumur M, Islam MA, Jahra FT, Dewan RK. Premalignant and Malignant Esophageal Lesions in Bangladeshi Patients-A Study in a Tertiary Care Hospital. Cent Med Coll J. 2023;7(1):20–5. DOI: https://doi.org/10.3329/cemecj.v7i1.70937

Huang FL, Yu SJ. Esophageal cancer: Risk factors, genetic association and treatment. Asian J Surg. 2018;41(3):210–5. DOI: https://doi.org/10.1016/j.asjsur.2016.10.005

Zhang Z, Leng Z, Fang K, Sun M, Li Z, Kang L, et al. Global research trend of esophageal squamous cell carcinoma from 2012 to 2022: a bibliometric analysis. Front Oncol. 2022;12:76. DOI: https://doi.org/10.3389/fonc.2022.977935

Borggreve AS, Kingma BF, Domrachev SA, Koshkin MA, Ruurda JP, van Hillegersberg R, et al. Surgical treatment of esophageal cancer in the era of multimodality management. Ann NY Acad Sci. 2018;1434(1):192–209. DOI: https://doi.org/10.1111/nyas.13677

Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA, Al-Sarraf M, 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):1623–7. DOI: https://doi.org/10.1001/jama.281.17.1623

Herskovic A, Martz K, Sarraf M, Leichman L, Brindle J, Vaitkevicius V, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992;326(24):1593–8. DOI: https://doi.org/10.1056/NEJM199206113262403

Wang Z, Wan J, Liu C, Li L, Dong X, Geng H. Sequential Versus Concurrent Thoracic Radiotherapy in Combination With Cisplatin and Etoposide for N3 Limited-Stage Small-Cell Lung Cancer. Cancer Control J Moffitt Cancer Cent. 2020;21;27(1):1073. DOI: https://doi.org/10.1177/1073274820956619

Verma V, Simone CB, Werner-Wasik M. Acute and late toxicities of concurrent chemoradiotherapy for locally-advanced non-small cell lung cancer. Cancers. 2017;9(9):120. DOI: https://doi.org/10.3390/cancers9090120

Xu J, Ji Q, Deng J, Yu F. Concurrent vs. sequential chemoradiotherapy: a survival boost for lung cancer patients. Biomed Eng OnLine. 2025;24(1):60. DOI: https://doi.org/10.1186/s12938-025-01390-9

Li LQ, Fu QG, Zhao WD, Wang YD, Meng WW, Su TS. Chemoradiotherapy versus chemotherapy alone for advanced esophageal squamous cell carcinoma: the role of definitive radiotherapy for primary tumor in the metastatic setting. Front Oncol. 2022;12:453. DOI: https://doi.org/10.3389/fonc.2022.824206

Kato K, Muro K, Minashi K, Ohtsu A, Ishikura S, Boku N, et al. Phase II Study of Chemoradiotherapy With 5-Fluorouracil and Cisplatin for Stage II–III Esophageal Squamous Cell Carcinoma: JCOG Trial (JCOG 9906). Int J Radiat Oncol. 2011;81(3):684–90. DOI: https://doi.org/10.1016/j.ijrobp.2010.06.033

Hirota S, Tsujino K, Hishikawa Y, Watanabe H, Kono K, Soejima T, et al. Endoscopic findings of radiation esophagitis in concurrent chemoradiotherapy for intrathoracic malignancies. Radiother Oncol J Eur Soc Ther Radiol Oncol. 2001;58(3):273–8. DOI: https://doi.org/10.1016/S0167-8140(00)00274-7

Luo H, Jiang W, Ma L, Chen P, Fang M, Ding L, et al. Icotinib With Concurrent Radiotherapy vs Radiotherapy Alone in Older Adults With Unresectable Esophageal Squamous Cell Carcinoma: A Phase II Randomized Clinical Trial. JAMA Netw Open. 2020;3(10):2019440. DOI: https://doi.org/10.1001/jamanetworkopen.2020.19440

Wang SA, Li F, Zhu J, Chen X, Ren W, Gao B. Multidisciplinary nutritional management improves nutritional and hospitalized outcomes of patients with esophageal cancer undergoing chemoradiotherapy: A randomized control trial. Medicine (Baltimore). 2023;102(12):33335. DOI: https://doi.org/10.1097/MD.0000000000033335

Xia WX, Lv X, Liang H, Liu GY, Sun R, Zeng Q, et al. A Randomized Controlled Trial Comparing Two Different Schedules for Cisplatin Treatment in Patients with Locoregionally Advanced Nasopharyngeal Cancer. Clin Cancer Res. 2021;27(15):4186–94. DOI: https://doi.org/10.1158/1078-0432.CCR-20-4532

Vellayappan BA, Soon YY, Ku GY, Leong CN, Lu JJ, Tey JC. Chemoradiotherapy versus chemoradiotherapy plus surgery for esophageal cancer. Available at: https://www.cochranelibrary.com. Accessed on 21 December 2024.

Zhao J, Zhang S, Guo X, li C, Yang B, Qu X, et al. PD-1 inhibitors combined with paclitaxel and cisplatin in first-line treatment of esophageal squamous cell carcinoma (ESCC): a network meta-analysis. BMC Cancer. 2023;23(1):1221. DOI: https://doi.org/10.1186/s12885-023-11715-3

Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021;398(10302):759–71. DOI: https://doi.org/10.1016/S0140-6736(21)01234-4