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Adjuvant fluoropyrimidine chemo does not improve RFS in diffuse gastric cancer

Tristan Manalac
27 Sep 2017

The Lauren classification can predict the differential benefits of fluoropyrimidine-based chemotherapeutics in intestinal (IGC) and diffuse (DGC) gastric cancer, a new study has shown. Specifically, adjuvant chemotherapy appears to not improve relapse-free survival (RFS) in DGC patients, opposite to its observed effects in IGC patients.

“Survival from gastric cancer in Western populations remains poor, and while awaiting molecular markers to guide individualised patient treatment, investigation and treatment of diffuse and intestinal gastric cancer as separate entities will improve our ability to tailor treatments to individual patients,” said researchers.

In the study cohort of 164 gastric cancer patients who received curative surgical resection, 33.5 percent (n=55) had DGC and 42.7 percent (n=70) had IGC. The remaining 39 patients either had mixed gastric cancer (12.8 percent; n=21) or adenocarcinoma not otherwise specified (11.0 percent; n=18).

Over a median follow-up of 27.8 months, IGC patients showed the best RFS, with only 41.4 percent (n=29) experiencing relapse compared to 76.4 percent (n=42) in DGC patients, 90.5 percent (n=19) in mixed gastric cancer patients and 72.2 percent (n=13) in adenocarcinoma patients. The difference among groups reached statistical significance (p<0.0001). [PLoS One 2017;doi:10.1371/journal.pone.0183891]

In patients who received adjuvant chemotherapy, the median RFS was calculated to be 25.9 months, while in those who did not receive therapy, RFS reached a median of 24.0 months.

The median RFS for IGC patients who did not undergo adjuvant chemotherapy was 49.2 months. Those who underwent chemotherapy did not reach median RFS.

Interestingly, DGC patients who received adjuvant chemotherapy showed a notably lower median RFS of 13.7 months compared to 34.2 months in those who did not receive adjuvant chemotherapy. Despite the apparent trends, none reached statistical significance.

Kaplan-Meier curves showed that in IGC patients, adjuvant chemotherapy confers some survival benefit (hazard ratio [HR], 0.56; 95 percent CI, 0.27 to 1.17; p=0.12), while in DGC patients, the treatment resulted in no apparent increase in the proportion of relapsing patients (HR, 1.26; 0.70 to 2.38; p=0.47).

“In DGC, the Kaplan-Meier curves are reversed, with the curve for patients receiving adjuvant chemotherapy sitting below patients receiving no adjuvant chemotherapy, and a HR of greater than 1,” explained researchers.

While the differential responses of the different types of gastric cancer have been established in quite a number of previous studies, the exact mechanism that governs this phenomenon is still largely unelucidated.

Investigations of the cancer’s genetics “suggest unique molecular backgrounds for DGC and IGC which likely contribute to variability in survival, response to currently used treatments and response to investigational agents in clinical trials,” researchers said.

Regardless, the current study shows that the Lauren classification is indeed useful in assessing the potential effects of adjuvant chemotherapeutic interventions on patients with different gastric cancer types.

“Treating diffuse and intestinal gastric cancer as separate entities, with identification of efficacious treatments for diffuse gastric cancer will help in improving outcomes from gastric cancer,” they concluded.

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