scholarly journals Microsatellite Status Affects Tumor Response and Survival in Patients Undergoing Neoadjuvant Chemotherapy for Clinical Stage III Gastric Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Zhenghao Cai ◽  
Weiwei Rui ◽  
Shuchun Li ◽  
Abraham Fingerhut ◽  
Jing Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Microsatellite Instability ◽  
Tumor Response ◽  
Tumor Regression ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Hazard Ratio ◽  
Stage Iii ◽  
Histological Response

BackgroundWe assessed the association between microsatellite instability-high (MSI-H) and tumor response to neoadjuvant chemotherapy (NAC) as well as its prognostic relevance in patients with clinical stage III gastric cancer (cStage III GC).Materials and MethodsThe NAC + surgery and the control cohorts consisted of 177 and 513 cStage III GC patients, respectively. The clinical and pathological features were compared between patients with MSI-H [n=57 (8.3%)] and microsatellite stability or microsatellite instability-low (MSS/MSI-L) [n=633 (91.7%)]. Radiological and histological response to NAC were evaluated based on response evaluation criteria in solid tumors (RECIST) and tumor regression grade (TRG) systems, respectively. The log-rank test and Cox analysis were used to determine the survival associated with MSI status as well as tumor regression between the two groups in both NAC + surgery and the control cohorts.ResultsA statistically significant association was found between MSI-H and poor histological response to NAC (p=0.038). Significant survival priority of responders over poor-responders could only be observed in MSS/MSI-L but not in MSI-H tumors. However, patients with MSI-H had statistically significantly better survival compared to patients with MSS/MSI-L in both the NAC + surgery (hazard ratio=0.125, 95% CI, 0.017–0.897, p=0.037 ) and the control cohort (hazard ratio=0.479, 95% CI, 0.268–0.856, p=0.013).ConclusionMSI-H was associated with poorer regression and better survival after NAC for cStage III GC. TRG evaluation had prognostic significance in MSS/MSI-L but not in MSI-H. Further studies are needed to assess the value of NAC for cStage III GC patients with MSI-H phenotype.

Histopathological tumor regression or ypN: Which better predicts survival of patients who received neoadjuvant chemotherapy and surgery for non-type 4 locally advanced gastric cancer?

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 114-114
Author(s):  
Kazumasa Fujitani ◽  
Kenichi Nakamura ◽  
Junki Mizusawa ◽  
Takeshi Kuwata ◽  
Tadakazu Shimoda ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Residual Tumor ◽  
Hazard Ratio ◽  
Cox Proportional Hazards Model ◽  
Phase Ii Trials

114 Background: Histopathological tumor regression with < 10% residual tumor is a globally accepted prognostic factor in gastric cancer patients who received neoadjuvant chemotherapy (NAC) and curative surgery, however, impact of ypN remains unclear. Methods: Previously, Japan Clinical Oncology Group (JCOG) had conducted 3 phase II trials to evaluate NAC with irinotecan/CDDP (JCOG0001) and S-1/CDDP (JCOG0405) for extensive nodal disease, and with S-1/CDDP (JCOG0210) for large type 3 and type 4 (linitis plastica) disease. Prognostic factors, including ypN and histopathological tumor regression with < 10% residual tumor, were analyzed in patients with curative resection excluding type 4 advanced gastric cancer in these trials by univariable and multivariable analyses using the Cox proportional hazards model. Results: Among 85 patients, 5-year OS was 46.0% (95% CI, 35.0-56.4). Median OS was not reached in patients with < 10% residual tumor (n = 26), whereas that was 2.7 years (95% CI, 1.4-4.5) in patients with > 10% residual tumor (n = 59) (p = 0.008). Median OS was not reached in patients with ypN0-1 (n = 25), whereas that was 2.6 years (95% CI, 1.5-4.0) in patients with ypN2-3 (n = 60) (p = 0.003). On multivariable analysis, only ypN2-3 was an independent predictor of OS (hazard ratio, 3.67; 95% CI, 1.55 to 8.69), whereas < 10% residual tumor was not (hazard ratio, 2.24; 95% CI, 0.98 to 5.10). Conclusions: It is suggested that ypN may have greater impact on the survival than histopathological tumor regression in patients who received NAC and surgery for AGC.

Phase II Study of Docetaxel and S-1 (DS) as Neoadjuvant Chemotherapy for Clinical Stage III Resectable Gastric Cancer

2014 ◽  
Vol 21 (7) ◽  
pp. 2340-2346 ◽  
Author(s):  
Eiji Oki ◽  
Yasunori Emi ◽  
Tetsuya Kusumoto ◽  
Yoshihisa Sakaguchi ◽  
Manabu Yamamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Clinical Stage ◽  
Stage Iii ◽  
Resectable Gastric Cancer

Tumor response score with neoadjuvant FLOT versus FOLFOX in gastric cancer patients: Results from a United States-based cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16573-e16573
Author(s):  
James Pereira De Andrade ◽  
Hye Seong Ahn ◽  
Joseph Chao ◽  
Laleh Golkar Melstrom ◽  
Isaac Benjamin Paz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Response ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Locally Advanced Gastric Cancer ◽  
Poorly Differentiated ◽  
Gastric Cancer Patients

e16573 Background: A recent RCT comparing FLOT and ECF regimens for locally advanced gastric cancer found FLOT to be superior in pathologic complete response (PCR) rates: 16% versus 6%. We evaluated patients who underwent resection after FLOT and FOLFOX in a diverse US population. Methods: Patients diagnosed with gastric adenocarcinoma at a single institution who underwent preoperative chemotherapy either with FLOT or FOLFOX between 2017 and 2019 were evaluated for pathologic response. Results: Fifty-nine patients underwent gastrectomy for adenocarcinoma. Of these, 59% underwent neoadjuvant chemotherapy: FLOT 20 patients, FOLFOX 12 patients, ECF 1 patient, other regimen 2 patients. Racial/ethnic background of patients were 20% non-Hispanic white, 23% Hispanic/Latino, 40% Asian, 6% black, and 6% other. Three patients (8.6%) had PCR, two received FLOT and one FOLFOX. Four patients had a near complete response (tumor regression score 1), all of whom received FLOT. In total, 16 of 20 patients who received FLOT had at least a partial response whereas only 5 of 12 patients who received FOLFOX had any tumor response (p = 0.027). Among all patients receiving neoadjuvant chemotherapy, 66% had poorly differentiated tumors. Only 1 of these patients experiencing a complete or near complete response compared to 50% of patients with non-poorly differentiated tumors (p = 0.001). Conclusions: In an ethnically diverse US population, tumor regression rates were improved with FLOT when compared to FOLFOX. For medically appropriate patients, strong consideration should be given for FLOT in the neoadjuvant setting.

Tumor Stage After Neoadjuvant Chemotherapy Determines Survival After Surgery for Adenocarcinoma of the Esophagus and Esophagogastric Junction

2014 ◽  
Vol 32 (27) ◽  
pp. 2983-2990 ◽  
Author(s):  
Andrew R. Davies ◽  
James A. Gossage ◽  
Janine Zylstra ◽  
Fredrik Mattsson ◽  
Jesper Lagergren ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Esophagogastric Junction ◽  
Cox Regression ◽  
Tumor Regression ◽  
Clinical Stage ◽  
Tumor Stage ◽  
Response To Treatment ◽  
Cox Regression Analysis ◽  
Systemic Recurrence

Purpose Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable. Methods We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis. Results Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v 13%, respectively; P = .030) and systemic recurrence (19% v 29%, respectively; P = .027) and improved Mandard tumor regression scores (P < .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation. Conclusion The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.

A phase II study of neoadjuvant chemotherapy with S-1 and cisplatin for stage III gastric cancer: KUGC03

2015 ◽  
Vol 113 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Hiroshi Okabe ◽  
Hiroaki Hata ◽  
Shugo Ueda ◽  
Masazumi Zaima ◽  
Atsuo Tokuka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Stage Iii

The interaction between microsatellite instability high (MSI-high) gastric cancer and chemotherapy on survival.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 244-244
Author(s):  
Elvira Lise Vos ◽  
Steven Brad Maron ◽  
Robert Wallace Krell ◽  
Masaya Nakauchi ◽  
Megan Fiasconaro ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Microsatellite Instability ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Tumor Stage ◽  
High Status ◽  
High Group ◽  
Locally Advanced Gastric Cancer

244 Background: Subgroup analysis of trials data suggested a favorable prognostic role for microsatellite instability high (MSI-high) status in resectable gastric cancer, but a lack of survival benefit from neoadjuvant/adjuvant chemotherapy; questioning current standard of care for MSI-high locally advanced gastric cancer. To help guide treatment decision making, we retrospectively studied the interaction between MSI status and chemotherapy on survival in a single institution. Methods: All clinically advanced (tumor stage 3-4 or positive lymph nodes) gastric cancer patients that underwent gastrectomy between 2000-2018 with MSI status available from immunohistochemistry (IHC, deficient mismatch repair protein expression (dMMR) vs proficient (pMMR)) or DNA next generation sequencing testing (NGS, MSI-high vs low/stable (MSS)) were included. Clinicopathological characteristics and overall survival (OS) was compared between patients with neoadjuvant/adjuvant chemotherapy and without, stratified for MSI status, by Kaplan-Meier and Cox regression analysis. Results: From a total of 1,844 clinically advanced patients with resection, MSI status was available in 559 as determined by IHC in 420, NGS in 88, and both in 51 with a concordance rate of 50/51 (98%). Tumors were dMMR/MSI-high in 84 (15%) and pMMR/MSS in 475 (85%). Patients with dMMR/MSI-high tumors were more often older, female, and had distal tumors with intestinal subtype. Neoadjuvant and/or adjuvant chemotherapy was administered in 53 (63%) in the dMMR/MSI-high group and 367 (77%) in the pMMR/MSS (p = 0.006). Median (interquartile range) time of follow-up was 32 (19-57) months. In the total cohort, OS after 3 years was 82% in the dMMR/MSI-high and 59% in pMMR/MSS (p < 0.001). In the patients with neoadjuvant/adjuvant chemotherapy only, the dMMR/MSI-high had improved OS (3-years OS: 80% vs 60%, p = 0.001), and after adjustment for age and clinical tumor stage in multivariable analysis, dMMR/MSI-high status was associated with improved OS (HR 0.38 95%CI 0.22-0.68). In the dMMR/MSI-high group only, 3-year OS was 80% with chemotherapy vs 86% without (p = 0.374), and chemotherapy was not associated with a difference in OS after multivariable analysis (HR 1.03 95%CI 0.40-2.66). In case of neoadjuvant chemotherapy, grade 1 pathological response ( > 90%) was observed in 1/41 (2.4%) of the dMMR/MSI-high tumors vs 43/278 (16%) of the pMMR/MSS tumors respectively (p = 0.026). Conclusions: The incidence of MSI-high tumors in our cohort of clinically locally advanced, resectable, gastric cancers was 15%. Patients with MSI-high tumors had worse pathological treatment response to neoadjuvant chemotherapy, but better OS, compared to microsatellite stable tumors. However, in patients with MSI-high tumors, OS was not altered by neoadjuvant/adjuvant chemotherapy. We recommend assessing MSI status in locally advanced gastric cancer.

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