The Proportion of Signet Ring Cell Component in Patients with Localized Gastric Adenocarcinoma Correlates with the Degree of Response to Pre-Operative Chemoradiation

Abstract

Background: Patients with localized gastric adenocarcinoma (LGAC), who get pre-operative therapy, have heterogeneous/unpredictable outcomes. Predictive clinical variables/biomarkers are not established. Methods: We analyzed 107 LGAC patients who had chemoradiation and surgery. LGACs were grouped for (1) presence/absence of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC was assessed (0, 1-10, 11-49, and 50-100%) and correlated with pathologic complete response (pathCR) or <pathCR in the resected specimens. Results: Most patients were men (60%), had stage cIII LGAC (50%), and received chemotherapy before chemoradiation (93%). Most had G3 tumors (78%) and SRC (58%). Presence of SRC was associated with a lower rate of pathCR (11 vs. 36%, p = 0.004), and the association remained significant even with a low percentage of SRC (1-10%; p = 0.014). The higher the fraction of SRC, the lower was the probability of pathCR (p = 0.03). G3 and SRC led to a shorter overall survival (OS) (p = 0.046 and p = 0.038, respectively). yp stage independently prognosticated OS and recurrence-free survival (p < 0.001). Conclusion: Our novel findings suggest that LGACs with SRC are relatively chemoradiation resistant compared to LGACs without SRC. A higher fraction of SRC is associated with higher resistance. Upon validation/biomarker(s) evaluation, reporting of the fraction of SRC may be warranted.

Pathological complete response in patients with esophageal cancer after the trimodality approach: The association with baseline variables and survival—The University of Texas MD Anderson Cancer Center experience

“…With respect to SRCs, few studies have evaluated its predictive role for pathCR and survival in patients with esophageal AC, whereas more data are available for the predictive role of SRCs in gastric cancer . Similarly to gastric cancer, in a study reported by our group, tumors from patients with esophageal AC and SRCs had a lower pathCR rate (9% vs 26%) and more frequently had positive margins (24% vs 10%) in comparison with tumors without SRCs.…”

Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

“…Retrospective case series suggest that this gastric cancer subtype may be less sensitive to chemotherapy and CRT [IV] [96,97]. However, evidence is insufficient to support not adopting standard chemotherapy or surgical approaches for these patients.…”

Reproducibility of the peritoneal regression grading score for assessment of response to therapy in peritoneal metastasis

“…compared the concordance indices of four different TRGs (Mandard (three‐ and five‐category), Dworak/Rödel (three‐ and five‐category), Memorial Sloan Kettering Cancer Center (three‐category) and American Joint Committee on Cancer and College of American Pathologists (AJCC/CAP) (four‐category)) in a cohort of 563 patients with locally advanced rectal cancer, and concluded that the four‐category AJCC/CAP TRG was the most accurate and should be adopted as the standard . Six different TRG systems have been proposed so far for gastric cancer, including the results of a recent Delphi survey . Recently, a six‐tiered and a condensed three‐tiered chemotherapy response score (CRS) for tubo‐ovarian high‐grade serous carcinoma after neoadjuvant chemotherapy and interval debulking surgery has been proposed, and showed high reproducibility with a Kappa coefficient of 0.76 when using the condensed three‐tiered system …”