Does Graded Histologic Response After Neoadjuvant Chemotherapy Predict Survival for Completely Resected Gastric Cancer?

Mansour, John C.; Tang, Laura H.; Shah, Manish A.; Bentrem, David J.; Klimstra, David S.; Gönen, Mithat; Kelsen, David P.; Brennan, Murray F.; Coit, Daniel G.

doi:10.1245/s10434-007-9574-6

Cited by 99 publications

(108 citation statements)

References 10 publications

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“…Whether pathological response is an indicator of efficacy for neoadjuvant treatment for GC is controversial [35][36][37]. In this study, pathological response did not correlate with survival, but grade 0 (no evidence of tumor regression) was associated with extremely poor survival.…”

Section: Discussionmentioning

confidence: 58%

A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival

Kim

Ryu

et al. 2015

Gastric Cancer

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Background We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association between CYP2A6 genotype and outcome. Methods Patients with LAGC [clinical stage III-IV (M0) by the Japanese staging system] received three cycles of pre-and postoperative chemotherapy (S-1 40 mg/m 2 twice daily on days 1-14; intravenous docetaxel 35 mg/m 2 on days 1 and 8, every 3 weeks) followed by gastrectomy with D2 dissection. We also performed a pharmacokinetic and CYP2A6 genotyping study (*1, *4, *7, *9, *10) for S-1.Results From October 2006 to June 2008, 44 patients entered the study. 43 eligible patients completed preoperative chemotherapy and 40 completed postoperative chemotherapy. The most common G3/4 toxicities during pre-and postoperative chemotherapy were neutropenia, stomatitis, and abdominal pain. The clinical response rate by RECIST was 74.4 % (95 % CI, 61.4-87.4 %), and the R0 resection rate was 97.7 %. Clinical downstaging in T or N occurred in 41.9 % of patients. The 3-year progressionfree survival (PFS) rate was 62.8 % and 5-year overall survival (OS) rate was 69.6 %. PFS and OS differed significantly according to clinical response, clinical downstaging, and CYP2A6 genotype. Patients with CYP2A6 variant/variant genotypes had a higher tegafur C max and worse survival than those with wild/wild or wild/variant genotypes. Conclusion Perioperative S-1 plus docetaxel is active with a manageable toxicity in patients with LAGC receiving D2 surgery. Clinical tumor response, clinical downstaging, and CYP2A6 genotype may predict efficacy.

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Section: Discussionmentioning

confidence: 58%

A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival

Kim

Ryu

et al. 2015

Gastric Cancer

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“…Since 1999, response to neoadjuvant chemotherapy has been well established to be predictive of survival in patients with resectable gastric cancer 26,27 . Another more recent study conducted at Memorial Sloan-Kettering Cancer Center showed that 3-year disease-specific survival was significantly higher for patients achieving a better than 50% pathologic response to preoperative chemotherapy than for those achieving a lesser histologic response (69% vs. 44%) 28 . Currently, identifying the patients who would best respond to neoadjuvant therapy remains a challenge; no demographic variable or tumour characteristic can, as yet, identify responders a priori.…”

Section: Discussionmentioning

confidence: 97%

Perioperative Chemotherapy for Gastroesophageal Cancer in British Columbia: A Multicentre Experience

2014

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“…However, the therapeutic strategies by which clinicians distinguish between the various treatment options remain a contentious issue. One point of clinical importance is that, although preoperative therapy has the potential to improve the therapeutic outcome for responders (42), it runs the risk of shifting the status of nonresponders from potentially resectable to unresectable, despite that radical resection is the only curative treatment modality, requiring the predictive marker for treatment response. Therefore, information on Reprimo promoter methylation may provide much needed guidance in determining the therapeutic strategies, such as the selection of the most suitable patients for preoperative therapy in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

DNA Damage-Inducible Gene, Reprimo Functions as a Tumor Suppressor and Is Suppressed by Promoter Methylation in Gastric Cancer

Ooki

Yamashita

Yamaguchi

et al. 2013

Molecular Cancer Research

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In several types of human cancer, the gene expression of Reprimo, a highly glycosylated protein, is frequently silenced via methylation of its promoter. The aim of this study was to characterize the epigenetic inactivation of Reprimo and its biologic function and clinical relevance in gastric cancer. The correlation between Reprimo methylation and clinical relevance was assessed in 83 primary human gastric cancer tissues. The effects of Reprimo expression were also examined using in vitro and in vivo assays. Reprimo methylation was cancer specific and frequently observed. In two gastric cancer cell lines without Reprimo methylation, we observed faint or weak Reprimo expression under normal conditions and high expression under DNAdamaging conditions. In four gastric cancer cell lines with Reprimo methylation, however, Reprimo expression remained faint even under DNA-damaging conditions, with expression being restored in combination with agents that induce demethylation. Enforced Reprimo expression robustly inhibited cell proliferation and anchorage-independent colony formation and enhanced DNA damage-induced apoptosis. Inverse effects were observed via siRNA-mediated knockdown of endogenous Reprimo. Reprimo expression inhibited tumorigenesis in vivo. Reprimo methylation was also associated with a poor response in patients with gastric cancer treated with chemotherapy (P

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Does Graded Histologic Response After Neoadjuvant Chemotherapy Predict Survival for Completely Resected Gastric Cancer?

Abstract: Posttreatment nodal status and perineural or vascular invasion at resection, but not graded histologic response, independently predict DSS after neoadjuvant chemotherapy and surgical resection of gastric cancer.

Cited by 99 publications

References 10 publications

A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival

A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival

Perioperative Chemotherapy for Gastroesophageal Cancer in British Columbia: A Multicentre Experience

DNA Damage-Inducible Gene, Reprimo Functions as a Tumor Suppressor and Is Suppressed by Promoter Methylation in Gastric Cancer

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