Neoadjuvant twice daily chemoradiotherapy for esophageal cancer

Treatment-related mortality and long-term outcomes

Stuart E. Samuels, Matthew H. Stenmark, Jae Y. Lee, Jonathan B. McHugh, James A. Hayman, Mark B. Orringer, Susan G. Urba, Libin Sun, Congying Xie, Feng Ming Kong, Kyle C. Cuneo

Research output: Contribution to journalArticle

Abstract

Objective Because of the short potential doubling time of esophageal cancer, there is a theoretical benefit to using an accelerated radiation treatment schedule. This study evaluates outcomes and treatment-related mortality and morbidity of patients treated with neoadjuvant hyperfractionated accelerated chemoradiation for resectable esophageal cancer. Methods and materials Outcomes from 250 consecutive patients with resectable esophageal cancer treated with preoperative hyperfractionated accelerated chemoradiotherapy (45 Gy in 30 twice-daily fractions over 3 weeks) followed by planned transhiatal esophagectomy were analyzed. Grade 3 or greater treatment related toxicity, surgical complications, and treatment-related mortality were determined. Additionally, available surgical specimens were graded for pathological response to chemoradiation. Overall survival (OS) and locoregional control were calculated using the Kaplan-Meier method. The log rank test was used to determine statistical significance. Results Median follow-up was 59 months for surviving patients; 87% of patients had adenocarcinoma and 13% had squamous cell carcinoma. Eleven percent of patients did not have surgery because of the development of metastases, declining performance status, or refusal. Twenty-seven patients were found to have unresectable and/or metastatic disease at the time of surgery. Overall, 10 of 223 operated patients died within 3 months, resulting in a perioperative mortality rate of 4%. Median OS was 28.4 months (95% confidence interval, 22.3-35.6 months) for all patients and 35.1 months (95% confidence interval, 27.4-47 months) for patients who underwent esophagectomy. There were 32 isolated locoregional failures with a 3-year locoregional control rate of 83%. Of 129 patients who had independent pathology review, 29% had complete response to treatment. This group had a median OS of 98.9 months and 3-year OS of 74%. Conclusion Neoadjuvant twice-daily chemoradiation for esophageal cancer is a safe and effective alternative to daily fractionation with low treatment-related mortality and long-term outcomes similar to standard fractionation courses.

Original languageEnglish (US)
Pages (from-to)308-315
Number of pages8
JournalAdvances in Radiation Oncology
Volume2
Issue number3
DOIs
StatePublished - Jul 1 2017

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Chemoradiotherapy
Esophageal Neoplasms
Mortality
Therapeutics
Esophagectomy
Survival
Confidence Intervals
Squamous Cell Carcinoma
Appointments and Schedules
Adenocarcinoma
Outcome Assessment (Health Care)
Radiation
Pathology
Neoplasm Metastasis
Morbidity

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Samuels, S. E., Stenmark, M. H., Lee, J. Y., McHugh, J. B., Hayman, J. A., Orringer, M. B., ... Cuneo, K. C. (2017). Neoadjuvant twice daily chemoradiotherapy for esophageal cancer: Treatment-related mortality and long-term outcomes. Advances in Radiation Oncology, 2(3), 308-315. https://doi.org/10.1016/j.adro.2017.05.003

Neoadjuvant twice daily chemoradiotherapy for esophageal cancer : Treatment-related mortality and long-term outcomes. / Samuels, Stuart E.; Stenmark, Matthew H.; Lee, Jae Y.; McHugh, Jonathan B.; Hayman, James A.; Orringer, Mark B.; Urba, Susan G.; Sun, Libin; Xie, Congying; Kong, Feng Ming; Cuneo, Kyle C.

In: Advances in Radiation Oncology, Vol. 2, No. 3, 01.07.2017, p. 308-315.

Research output: Contribution to journalArticle

Samuels, SE, Stenmark, MH, Lee, JY, McHugh, JB, Hayman, JA, Orringer, MB, Urba, SG, Sun, L, Xie, C, Kong, FM & Cuneo, KC 2017, 'Neoadjuvant twice daily chemoradiotherapy for esophageal cancer: Treatment-related mortality and long-term outcomes', Advances in Radiation Oncology, vol. 2, no. 3, pp. 308-315. https://doi.org/10.1016/j.adro.2017.05.003
Samuels, Stuart E. ; Stenmark, Matthew H. ; Lee, Jae Y. ; McHugh, Jonathan B. ; Hayman, James A. ; Orringer, Mark B. ; Urba, Susan G. ; Sun, Libin ; Xie, Congying ; Kong, Feng Ming ; Cuneo, Kyle C. / Neoadjuvant twice daily chemoradiotherapy for esophageal cancer : Treatment-related mortality and long-term outcomes. In: Advances in Radiation Oncology. 2017 ; Vol. 2, No. 3. pp. 308-315.
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abstract = "Objective Because of the short potential doubling time of esophageal cancer, there is a theoretical benefit to using an accelerated radiation treatment schedule. This study evaluates outcomes and treatment-related mortality and morbidity of patients treated with neoadjuvant hyperfractionated accelerated chemoradiation for resectable esophageal cancer. Methods and materials Outcomes from 250 consecutive patients with resectable esophageal cancer treated with preoperative hyperfractionated accelerated chemoradiotherapy (45 Gy in 30 twice-daily fractions over 3 weeks) followed by planned transhiatal esophagectomy were analyzed. Grade 3 or greater treatment related toxicity, surgical complications, and treatment-related mortality were determined. Additionally, available surgical specimens were graded for pathological response to chemoradiation. Overall survival (OS) and locoregional control were calculated using the Kaplan-Meier method. The log rank test was used to determine statistical significance. Results Median follow-up was 59 months for surviving patients; 87{\%} of patients had adenocarcinoma and 13{\%} had squamous cell carcinoma. Eleven percent of patients did not have surgery because of the development of metastases, declining performance status, or refusal. Twenty-seven patients were found to have unresectable and/or metastatic disease at the time of surgery. Overall, 10 of 223 operated patients died within 3 months, resulting in a perioperative mortality rate of 4{\%}. Median OS was 28.4 months (95{\%} confidence interval, 22.3-35.6 months) for all patients and 35.1 months (95{\%} confidence interval, 27.4-47 months) for patients who underwent esophagectomy. There were 32 isolated locoregional failures with a 3-year locoregional control rate of 83{\%}. Of 129 patients who had independent pathology review, 29{\%} had complete response to treatment. This group had a median OS of 98.9 months and 3-year OS of 74{\%}. Conclusion Neoadjuvant twice-daily chemoradiation for esophageal cancer is a safe and effective alternative to daily fractionation with low treatment-related mortality and long-term outcomes similar to standard fractionation courses.",
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AU - Stenmark, Matthew H.

AU - Lee, Jae Y.

AU - McHugh, Jonathan B.

AU - Hayman, James A.

AU - Orringer, Mark B.

AU - Urba, Susan G.

AU - Sun, Libin

AU - Xie, Congying

AU - Kong, Feng Ming

AU - Cuneo, Kyle C.

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N2 - Objective Because of the short potential doubling time of esophageal cancer, there is a theoretical benefit to using an accelerated radiation treatment schedule. This study evaluates outcomes and treatment-related mortality and morbidity of patients treated with neoadjuvant hyperfractionated accelerated chemoradiation for resectable esophageal cancer. Methods and materials Outcomes from 250 consecutive patients with resectable esophageal cancer treated with preoperative hyperfractionated accelerated chemoradiotherapy (45 Gy in 30 twice-daily fractions over 3 weeks) followed by planned transhiatal esophagectomy were analyzed. Grade 3 or greater treatment related toxicity, surgical complications, and treatment-related mortality were determined. Additionally, available surgical specimens were graded for pathological response to chemoradiation. Overall survival (OS) and locoregional control were calculated using the Kaplan-Meier method. The log rank test was used to determine statistical significance. Results Median follow-up was 59 months for surviving patients; 87% of patients had adenocarcinoma and 13% had squamous cell carcinoma. Eleven percent of patients did not have surgery because of the development of metastases, declining performance status, or refusal. Twenty-seven patients were found to have unresectable and/or metastatic disease at the time of surgery. Overall, 10 of 223 operated patients died within 3 months, resulting in a perioperative mortality rate of 4%. Median OS was 28.4 months (95% confidence interval, 22.3-35.6 months) for all patients and 35.1 months (95% confidence interval, 27.4-47 months) for patients who underwent esophagectomy. There were 32 isolated locoregional failures with a 3-year locoregional control rate of 83%. Of 129 patients who had independent pathology review, 29% had complete response to treatment. This group had a median OS of 98.9 months and 3-year OS of 74%. Conclusion Neoadjuvant twice-daily chemoradiation for esophageal cancer is a safe and effective alternative to daily fractionation with low treatment-related mortality and long-term outcomes similar to standard fractionation courses.

AB - Objective Because of the short potential doubling time of esophageal cancer, there is a theoretical benefit to using an accelerated radiation treatment schedule. This study evaluates outcomes and treatment-related mortality and morbidity of patients treated with neoadjuvant hyperfractionated accelerated chemoradiation for resectable esophageal cancer. Methods and materials Outcomes from 250 consecutive patients with resectable esophageal cancer treated with preoperative hyperfractionated accelerated chemoradiotherapy (45 Gy in 30 twice-daily fractions over 3 weeks) followed by planned transhiatal esophagectomy were analyzed. Grade 3 or greater treatment related toxicity, surgical complications, and treatment-related mortality were determined. Additionally, available surgical specimens were graded for pathological response to chemoradiation. Overall survival (OS) and locoregional control were calculated using the Kaplan-Meier method. The log rank test was used to determine statistical significance. Results Median follow-up was 59 months for surviving patients; 87% of patients had adenocarcinoma and 13% had squamous cell carcinoma. Eleven percent of patients did not have surgery because of the development of metastases, declining performance status, or refusal. Twenty-seven patients were found to have unresectable and/or metastatic disease at the time of surgery. Overall, 10 of 223 operated patients died within 3 months, resulting in a perioperative mortality rate of 4%. Median OS was 28.4 months (95% confidence interval, 22.3-35.6 months) for all patients and 35.1 months (95% confidence interval, 27.4-47 months) for patients who underwent esophagectomy. There were 32 isolated locoregional failures with a 3-year locoregional control rate of 83%. Of 129 patients who had independent pathology review, 29% had complete response to treatment. This group had a median OS of 98.9 months and 3-year OS of 74%. Conclusion Neoadjuvant twice-daily chemoradiation for esophageal cancer is a safe and effective alternative to daily fractionation with low treatment-related mortality and long-term outcomes similar to standard fractionation courses.

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