Updated analysis of SWOG-directed intergroup study 0116: A phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection

Stephen R. Smalley, Jacqueline K. Benedetti, Daniel G. Haller, Scott A Hundahl, Norman C. Estes, Jaffer A. Ajani, Leonard L. Gunderson, Bryan Goldman, James A. Martenson, J. Milburn Jessup, Grant N. Stemmermann, Charles D. Blanke, John S. Macdonald

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Abstract

Purpose: Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses. Patients and Methods: In all, 559 patients with primaries ≥ T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy. Results: Overall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect. Conclusion: Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.

Original languageEnglish (US)
Pages (from-to)2327-2333
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number19
DOIs
StatePublished - Jul 1 2012

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Adjuvant Chemoradiotherapy
Stomach Neoplasms
Observation
Survival
Recurrence
Second Primary Neoplasms
Chemoradiotherapy
Radiotherapy
Leucovorin
Fluorouracil
Histology
Therapeutics
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Updated analysis of SWOG-directed intergroup study 0116 : A phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. / Smalley, Stephen R.; Benedetti, Jacqueline K.; Haller, Daniel G.; Hundahl, Scott A; Estes, Norman C.; Ajani, Jaffer A.; Gunderson, Leonard L.; Goldman, Bryan; Martenson, James A.; Jessup, J. Milburn; Stemmermann, Grant N.; Blanke, Charles D.; Macdonald, John S.

In: Journal of Clinical Oncology, Vol. 30, No. 19, 01.07.2012, p. 2327-2333.

Research output: Contribution to journalArticle

Smalley, SR, Benedetti, JK, Haller, DG, Hundahl, SA, Estes, NC, Ajani, JA, Gunderson, LL, Goldman, B, Martenson, JA, Jessup, JM, Stemmermann, GN, Blanke, CD & Macdonald, JS 2012, 'Updated analysis of SWOG-directed intergroup study 0116: A phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection', Journal of Clinical Oncology, vol. 30, no. 19, pp. 2327-2333. https://doi.org/10.1200/JCO.2011.36.7136
Smalley, Stephen R. ; Benedetti, Jacqueline K. ; Haller, Daniel G. ; Hundahl, Scott A ; Estes, Norman C. ; Ajani, Jaffer A. ; Gunderson, Leonard L. ; Goldman, Bryan ; Martenson, James A. ; Jessup, J. Milburn ; Stemmermann, Grant N. ; Blanke, Charles D. ; Macdonald, John S. / Updated analysis of SWOG-directed intergroup study 0116 : A phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 19. pp. 2327-2333.
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T1 - Updated analysis of SWOG-directed intergroup study 0116

T2 - A phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection

AU - Smalley, Stephen R.

AU - Benedetti, Jacqueline K.

AU - Haller, Daniel G.

AU - Hundahl, Scott A

AU - Estes, Norman C.

AU - Ajani, Jaffer A.

AU - Gunderson, Leonard L.

AU - Goldman, Bryan

AU - Martenson, James A.

AU - Jessup, J. Milburn

AU - Stemmermann, Grant N.

AU - Blanke, Charles D.

AU - Macdonald, John S.

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N2 - Purpose: Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses. Patients and Methods: In all, 559 patients with primaries ≥ T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy. Results: Overall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect. Conclusion: Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.

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