High dose chemoradiotherapy followed by esophagectomy for adenocarcinoma of the esophagus and gastroesophageal junction: Results of a phase II study of the eastern cooperative oncology group

Steven M. Keller*, Louise M. Ryan, Lawrence R. Coia, Phuong Dang, David J. Vaught, Charles Diggs, Louis M. Weiner, Al B Benson III

*Corresponding author for this work

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

BACKGROUND. To assess the toxicity, local response, and survival associated with multimodality therapy in a cooperative group setting, patients with biopsy-proven clinical Stage I or II adenocarcinoma of the esophagus (staged according to 1983 American Joint Committee on Cancer criteria) or gastroesophageal junction were treated with concomitant radiation and chemotherapy followed by esophagectomy. METHODS. Radiotherapy was administered in daily 2-gray (Gy) fractions 5 days a week until a total of 60 Gy was reached. 5-fluorouracil (5-FU) was infused continuously at a dose of 1000 mg/m2/day for 96 hours on Days 2-5 and 28-31. On Day 2, a 10 mg/m2 bolus of mitomycin was injected intravenously. Esophagectomy was performed 4-8 weeks following completion of the radiotherapy. RESULTS. During the 18-month study period (August 1991 through January 1993), 46 eligible patients were accrued from 21 institutions. Eight patients were Stage I and 38 Stage II. Eighty-seven percent of patients (40 of 46) received 6000 centigray (cGy), and all received >5000 cGy. Seventy-eight percent of patients (36 of 46) received >90% of the planned 5-FU dose. Follow-up ranged from 11 to 36 months (median, 22 months). There were eight treatment-related deaths; two were preoperative (from adult respiratory distress syndrome) and six were postoperative. Complete or partial response prior to esophagectomy was observed in 63% of cases, stable disease in 15%, and progression in 20%. Thirty-three patients underwent esophagectomy (transhiatal, n = 14; Ivor Lewis, n = 16; other, n = 3). No tumor was found in the specimens resected from 8 of these 33 patients; this represented a pathologic complete response rate of 17% overall and 24% for those who underwent esophagectomy. Overall median survival was 16.6 months, 1-year survival 57%, and 2-year survival 27%. Survival was significantly worse for patients with circumferential cancers (median, 18.1 months vs. 8.3 months; P < 0.05). CONCLUSIONS. High dose radiation therapy with concurrent 5-FU and mitomycin may be administered to patients with esophageal adenocarcinoma with acceptable morbidity. However, in a cooperative group setting, esophagogastrectomy following intensive chemoradiotherapy is associated with excessive morbidity and mortality. Circumferential tumor growth is a significant adverse prognostic factor.

Original languageEnglish (US)
Pages (from-to)1908-1916
Number of pages9
JournalCancer
Volume83
Issue number9
DOIs
StatePublished - Nov 1 1998

Fingerprint

Esophagogastric Junction
Esophagectomy
Chemoradiotherapy
Survival
Fluorouracil
Radiotherapy
Mitomycin
Neoplasms
Morbidity
Adenocarcinoma Of Esophagus
Adult Respiratory Distress Syndrome
Disease Progression
Adenocarcinoma
Radiation
Biopsy
Drug Therapy
Mortality

Keywords

  • Adenocarcinoma
  • Esophageal neoplasm
  • Medical ontology
  • Radiotherapy
  • Surgery

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Keller, Steven M. ; Ryan, Louise M. ; Coia, Lawrence R. ; Dang, Phuong ; Vaught, David J. ; Diggs, Charles ; Weiner, Louis M. ; Benson III, Al B. / High dose chemoradiotherapy followed by esophagectomy for adenocarcinoma of the esophagus and gastroesophageal junction : Results of a phase II study of the eastern cooperative oncology group. In: Cancer. 1998 ; Vol. 83, No. 9. pp. 1908-1916.
@article{397176cf5aec4bd9b5439cc6995a1cc6,
title = "High dose chemoradiotherapy followed by esophagectomy for adenocarcinoma of the esophagus and gastroesophageal junction: Results of a phase II study of the eastern cooperative oncology group",
abstract = "BACKGROUND. To assess the toxicity, local response, and survival associated with multimodality therapy in a cooperative group setting, patients with biopsy-proven clinical Stage I or II adenocarcinoma of the esophagus (staged according to 1983 American Joint Committee on Cancer criteria) or gastroesophageal junction were treated with concomitant radiation and chemotherapy followed by esophagectomy. METHODS. Radiotherapy was administered in daily 2-gray (Gy) fractions 5 days a week until a total of 60 Gy was reached. 5-fluorouracil (5-FU) was infused continuously at a dose of 1000 mg/m2/day for 96 hours on Days 2-5 and 28-31. On Day 2, a 10 mg/m2 bolus of mitomycin was injected intravenously. Esophagectomy was performed 4-8 weeks following completion of the radiotherapy. RESULTS. During the 18-month study period (August 1991 through January 1993), 46 eligible patients were accrued from 21 institutions. Eight patients were Stage I and 38 Stage II. Eighty-seven percent of patients (40 of 46) received 6000 centigray (cGy), and all received >5000 cGy. Seventy-eight percent of patients (36 of 46) received >90{\%} of the planned 5-FU dose. Follow-up ranged from 11 to 36 months (median, 22 months). There were eight treatment-related deaths; two were preoperative (from adult respiratory distress syndrome) and six were postoperative. Complete or partial response prior to esophagectomy was observed in 63{\%} of cases, stable disease in 15{\%}, and progression in 20{\%}. Thirty-three patients underwent esophagectomy (transhiatal, n = 14; Ivor Lewis, n = 16; other, n = 3). No tumor was found in the specimens resected from 8 of these 33 patients; this represented a pathologic complete response rate of 17{\%} overall and 24{\%} for those who underwent esophagectomy. Overall median survival was 16.6 months, 1-year survival 57{\%}, and 2-year survival 27{\%}. Survival was significantly worse for patients with circumferential cancers (median, 18.1 months vs. 8.3 months; P < 0.05). CONCLUSIONS. High dose radiation therapy with concurrent 5-FU and mitomycin may be administered to patients with esophageal adenocarcinoma with acceptable morbidity. However, in a cooperative group setting, esophagogastrectomy following intensive chemoradiotherapy is associated with excessive morbidity and mortality. Circumferential tumor growth is a significant adverse prognostic factor.",
keywords = "Adenocarcinoma, Esophageal neoplasm, Medical ontology, Radiotherapy, Surgery",
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High dose chemoradiotherapy followed by esophagectomy for adenocarcinoma of the esophagus and gastroesophageal junction : Results of a phase II study of the eastern cooperative oncology group. / Keller, Steven M.; Ryan, Louise M.; Coia, Lawrence R.; Dang, Phuong; Vaught, David J.; Diggs, Charles; Weiner, Louis M.; Benson III, Al B.

In: Cancer, Vol. 83, No. 9, 01.11.1998, p. 1908-1916.

Research output: Contribution to journalArticle

TY - JOUR

T1 - High dose chemoradiotherapy followed by esophagectomy for adenocarcinoma of the esophagus and gastroesophageal junction

T2 - Results of a phase II study of the eastern cooperative oncology group

AU - Keller, Steven M.

AU - Ryan, Louise M.

AU - Coia, Lawrence R.

AU - Dang, Phuong

AU - Vaught, David J.

AU - Diggs, Charles

AU - Weiner, Louis M.

AU - Benson III, Al B

PY - 1998/11/1

Y1 - 1998/11/1

N2 - BACKGROUND. To assess the toxicity, local response, and survival associated with multimodality therapy in a cooperative group setting, patients with biopsy-proven clinical Stage I or II adenocarcinoma of the esophagus (staged according to 1983 American Joint Committee on Cancer criteria) or gastroesophageal junction were treated with concomitant radiation and chemotherapy followed by esophagectomy. METHODS. Radiotherapy was administered in daily 2-gray (Gy) fractions 5 days a week until a total of 60 Gy was reached. 5-fluorouracil (5-FU) was infused continuously at a dose of 1000 mg/m2/day for 96 hours on Days 2-5 and 28-31. On Day 2, a 10 mg/m2 bolus of mitomycin was injected intravenously. Esophagectomy was performed 4-8 weeks following completion of the radiotherapy. RESULTS. During the 18-month study period (August 1991 through January 1993), 46 eligible patients were accrued from 21 institutions. Eight patients were Stage I and 38 Stage II. Eighty-seven percent of patients (40 of 46) received 6000 centigray (cGy), and all received >5000 cGy. Seventy-eight percent of patients (36 of 46) received >90% of the planned 5-FU dose. Follow-up ranged from 11 to 36 months (median, 22 months). There were eight treatment-related deaths; two were preoperative (from adult respiratory distress syndrome) and six were postoperative. Complete or partial response prior to esophagectomy was observed in 63% of cases, stable disease in 15%, and progression in 20%. Thirty-three patients underwent esophagectomy (transhiatal, n = 14; Ivor Lewis, n = 16; other, n = 3). No tumor was found in the specimens resected from 8 of these 33 patients; this represented a pathologic complete response rate of 17% overall and 24% for those who underwent esophagectomy. Overall median survival was 16.6 months, 1-year survival 57%, and 2-year survival 27%. Survival was significantly worse for patients with circumferential cancers (median, 18.1 months vs. 8.3 months; P < 0.05). CONCLUSIONS. High dose radiation therapy with concurrent 5-FU and mitomycin may be administered to patients with esophageal adenocarcinoma with acceptable morbidity. However, in a cooperative group setting, esophagogastrectomy following intensive chemoradiotherapy is associated with excessive morbidity and mortality. Circumferential tumor growth is a significant adverse prognostic factor.

AB - BACKGROUND. To assess the toxicity, local response, and survival associated with multimodality therapy in a cooperative group setting, patients with biopsy-proven clinical Stage I or II adenocarcinoma of the esophagus (staged according to 1983 American Joint Committee on Cancer criteria) or gastroesophageal junction were treated with concomitant radiation and chemotherapy followed by esophagectomy. METHODS. Radiotherapy was administered in daily 2-gray (Gy) fractions 5 days a week until a total of 60 Gy was reached. 5-fluorouracil (5-FU) was infused continuously at a dose of 1000 mg/m2/day for 96 hours on Days 2-5 and 28-31. On Day 2, a 10 mg/m2 bolus of mitomycin was injected intravenously. Esophagectomy was performed 4-8 weeks following completion of the radiotherapy. RESULTS. During the 18-month study period (August 1991 through January 1993), 46 eligible patients were accrued from 21 institutions. Eight patients were Stage I and 38 Stage II. Eighty-seven percent of patients (40 of 46) received 6000 centigray (cGy), and all received >5000 cGy. Seventy-eight percent of patients (36 of 46) received >90% of the planned 5-FU dose. Follow-up ranged from 11 to 36 months (median, 22 months). There were eight treatment-related deaths; two were preoperative (from adult respiratory distress syndrome) and six were postoperative. Complete or partial response prior to esophagectomy was observed in 63% of cases, stable disease in 15%, and progression in 20%. Thirty-three patients underwent esophagectomy (transhiatal, n = 14; Ivor Lewis, n = 16; other, n = 3). No tumor was found in the specimens resected from 8 of these 33 patients; this represented a pathologic complete response rate of 17% overall and 24% for those who underwent esophagectomy. Overall median survival was 16.6 months, 1-year survival 57%, and 2-year survival 27%. Survival was significantly worse for patients with circumferential cancers (median, 18.1 months vs. 8.3 months; P < 0.05). CONCLUSIONS. High dose radiation therapy with concurrent 5-FU and mitomycin may be administered to patients with esophageal adenocarcinoma with acceptable morbidity. However, in a cooperative group setting, esophagogastrectomy following intensive chemoradiotherapy is associated with excessive morbidity and mortality. Circumferential tumor growth is a significant adverse prognostic factor.

KW - Adenocarcinoma

KW - Esophageal neoplasm

KW - Medical ontology

KW - Radiotherapy

KW - Surgery

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