Postoperative chemoradiation for resected gastric cancer - is the Macdonald Regimen Tolerable? a retrospective multi-institutional study

Abstract

BackgroundPostoperative chemoradiation as per Intergroup-0116 trial ("Macdonald regimen") is considered standard for completely resected high risk gastric cancer. However, many concerns remain with regards to the toxicity of this regimen. To evaluate the safety and tolerability of this regimen in a routine clinical practice setting, we analyzed our experience with its use. As we did not expect a different toxic profile in patients (pts) with positive margins (R1 resection), these were studied together with pts after complete resection (R0).Patients and MethodsPostoperative chemoradiation therapy was given according to the original Intergroup-0116 regimen. Overall survival (OS) and disease free survival (DFS) rates were calculated using the Kaplan-Meier method. Comparison of OS and DFS between R0 and R1 pts was done using the log-rank test.ResultsBetween 6/2000 and 12/2007, 166 pts after R0 (129 pts) or R1 (37 pts) resection of locally advanced gastric adenocarcinoma received postoperative chemoradiation; 61% were male and the median age was 63 years (range, 23-86); 78% had T ≥ 3 tumors and 81% had N+ disease; 87% of the pts completed radiotherapy and 54% completed the entire chemoradiation plan; 46.4% had grade ≥ 3 toxicity and 32% were hospitalized at least once for toxicity. Three pts (1.8%) died of toxicity: diarrhea (1), neutropenic sepsis (1) and neutropenic sepsis complicated by small bowel gangrene (1). The most common hematological toxicity was neutropenia, grade ≥ 3 in 30% of pts and complicated by fever in 15%. The most common non-hematological toxicities were nausea, vomiting and diarrhea. With a median follow-up of 51 months (range, 2-100), 62% of the R0 patients remain alive and 61% are free of disease. Median DFS and OS for R0 were not reached. R0 pts had a significantly higher 3-year DFS (60% vs. 29%, p = 0.001) and OS (61% vs. 33%, p = 0.01) compared with R1 pts.ConclusionsIn our experience, postoperative chemoradiation as per Intergroup-0116 seems to be substantially toxic, with a mortality rate which seems higher than reported in that trial. Efficacy data appears comparable to the original report. Following postoperative chemoradiation, involvement of surgical margins still has a detrimental impact on patient outcome.

Adjuvant Chemoradiation for Localized Gastric Adenocarcinoma: An Institutional Experience

“…These results are comparable to literature. retrospectives series more than 75% of patients was T3T4 [8,[16][17][18]. In our study, 85% of patients had lymph nodes involvement as like in INT-0116 [11], similar results were cited in literature [8,12,[16][17][18].…”

“…Locoregional recurrences on the tumor bed, on the anastomosis or in lymph nodes occur in 40% to 65% of the patients after resection with curative intent [6,7]. The frequency of this relapse makes regional radiotherapy an attractive possibility for adjuvant therapy [8].…”

“…Locoregional recurrences on the tumor bed, on the anastomosis or in lymph nodes occur in 40% to 65% of the patients after resection with curative intent [6,7]. The frequency of this relapse makes regional radiotherapy an attractive possibility for adjuvant therapy [8].Various chemotherapy regimens used to prevent relapse and improve the poor survival rates provide small but statistically significant clinical benefit [9,10]. Finally, the intergroup of gastrointestinal cancers was the first to demonstrate in a phase III trial that concomitant radio-chemotherapy after complete gastric resection improves median relapse-free survival (30 vs 19 months, p<0.0001) and overall survival (36 vs 27 months, p<0.01) [11].…”

Current Status of the Multidisciplinary Treatment of Gastric Adenocarcinoma

“…Also, this chemoradiotherapy study group when compared to a similar group of patients operated on with D2 lymphadenectomy in Japan, the 5-year survival rate shown in the Japanese study was significantly higher 23 suggesting that a well-performed lymphadenectomy can produce the same results as the adjuvant treatment. Another disadvantage of this treatment method is the non-negligible toxicity of the chemotherapy and radiotherapy association in the postoperative gastrectomy period 13 . Thirty-six percent of patients in the treated group were unable to complete the protocol treatment due to toxicity.…”

The role of different adjuvant therapies in locally advanced gastric adenocarcinoma

“…In a retrospective study of Kundel et al . [ 18 ] higher toxicity rates were registered: 46.4% of patients presented severe adverse events, 32% were hospitalized and 1.8% died.…”