Indirect Comparison Showed Survival Benefit from Adjuvant Chemoradiotherapy in Completely Resected Gastric Cancer with D2 Lymphadenectomy

Background. Little data on directly comparing chemoradiotherapy with observation has yet been published in the setting of adjuvant therapy for resected gastric cancer who underwent D2 lymphadenectomy. The present indirect comparison aims to provide more evidence on comparing the two approaches.Methods. We conducted a systematic review of randomized controlled trials, extracted time-to-event data using Tierney methods (when not reported), and performed indirect comparison to obtain the relative hazards of adjuvant chemoradiotherapy to observation on overall and disease-free survival.Results. seven randomized controlled trials were identified. Three trials compared adjuvant chemoradiotherapy with adjuvant chemotherapy, and 4 trials compared adjuvant chemotherapy with observation. Using indirect comparison, the relative hazards of adjuvant chemoradiotherapy to observation were 0.43 (95% CI: 0.33–0.55) in disease-free survival and 0.52 (95% CI: 0.38–0.71) in overall survival for completely resected gastric cancer with D2 lymphadenectomy.Conclusions. Postoperative chemoradiotherapy can prolong survival and decrease recurrence in patients with resected gastric cancer who underwent D2 gastrectomy. Molecular biomarker might be a promising direction in the prediction of clinical outcome to postoperative chemoradiotherapy, which warranted further study.

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A prospective, randomized, controlled, multicenter study of apatinib combined with S-1 plus docetaxel as adjuvant therapy for locally advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16019 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16019-e16019

Author(s):

Zhili Shan ◽

Feng Guo ◽

Hong Chen ◽

Dapeng Li ◽

Zhongqi Mao ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Locally Advanced ◽

Disease Free Survival ◽

Free Survival ◽

Randomized Controlled ◽

Locally Advanced Gastric Cancer ◽

Group A ◽

Group B ◽

Disease Free

e16019 Background: Postoperative adjuvant chemotherapy is commonly given after the curative resection of gastric cancer (GC) in both Eastern and Western countries. Several studies have investigated the feasibility and safety of S-1 plus docetaxel or S-1 plus cisplatin. However, the best choice of adjuvant treatment for patients with gastric cancer is still debated. Apatinib, an oral small molecular of VEGFR-2 TKI, has been confirmed to improve OS and PFS with acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. In this study, we aimed to evaluate the efficacy and safety of apatinib combined with S-1/docetaxel for locally advanced gastric cancer (T3-4aN+M0). Methods: This is a prospective, randomized, controlled, multicenter clinical study. Patients with locally advanced gastric cancer, pathological stage T3-4aN+M0 who underwent D2 lymphadenectomy without prior anti-cancer therapy were included. All these patients were assigned to group A or B. Patients in group A received 6 cycles (21 days a cycle) of adjuvant therapy using S-1 (80-120mg/d, d1-14), and docetaxel (40mg/m2, d1). Group B received the same regimen with the addition of apatinib (250mg, qd.). The primary endpoint was disease-free survival (DFS). The final analysis cutoff date was 30 November, 2020. Results: A total of 45 patients were enrolled from January 2019 to November, 2010 and assigned to group A (21) or group B (24). The DFS was not reached in both of the groups. The 1-year disease-free survival rate was 60% in group A and 90% in the group B, while the difference was not significant. The main AEs in group A were anemia (55%), nausea (50%) and neutropenia (40%); The most common AEs in group B were anemia (45%) neutropenia (40%) and diarrhea (25%). There were no treatment-related deaths. The longest administered time of apatinib with no progression was 457 days. And the median time to receive apatinib was 329 days. Conclusions: Combination of apatinib with S-1/docexal chemotherapy shows clinical benefits in locally advanced gastric cancer (T3-4aN+M0), with tolerable toxicity. The study is still ongoing to reach our final endpoint, DFS. Clinical trial information: ChiCTR2000038900.

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Phase III trial of adjuvant capecitabine/cisplatin (XP) versus capecitabine/cisplatin/RT (XPRT) in resected gastric cancer with D2 nodal dissection (ARTIST trial): Safety analysis

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4537 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4537-4537 ◽

Cited By ~ 1

Author(s):

J. Lee ◽

W. Kang ◽

D. Lim ◽

J. Park ◽

Y. Park ◽

...

Keyword(s):

Gastric Cancer ◽

Disease Free Survival ◽

Standard Of Care ◽

Chemoradiation Therapy ◽

Phase Iii ◽

Eligibility Criteria ◽

Phase Iii Trial ◽

Free Survival ◽

Resected Gastric Cancer ◽

Disease Free

4537 Background: Although the adjuvant chemoradiation therapy has gained popularity and has become the standard of care in patients with resected gastric cancer in U.S., the role of chemoradiation therapy after extended D2 dissection has been questioned. We conducted a phase III trial to compare capecitabine/cisplatin (XP) vs XP + radiotherapy (RT) in curatively D2 resected gastric cancer patients in terms of disease free survival and overall survival. Methods: Eligibility criteria were as follows: stage Ib (T1N1, T2bN0) - IV (M1 excluded), curatively ≥ D2 resected gastric adenocarcinoma. XP only: X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 repeated every 3 weeks, 6 cycles; XP + RT: X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 x 2 cycles ⋄ RT 45 Gy (25 fractions) + X 1,650 mg/m2/d during RT ⋄ X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 x 2 cycles. The primary endpoint is 3-year disease-free survival. Results: From October 2004 to April 2008, 458 patients (XP arm: 228 patients; XP/RT arm: 230 patients) were enrolled. In XP arm, 172 (75%) of 228 enrolled patients completed 6 cycles of chemotherapy. In XP + RT arm, 188 (82%) of 230 patients completed the full course of XP 2 cycles - X + RT - XP 2 cycles. Conclusions: Safety and feasibility analysis of the two arms will be reported at the meeting. No significant financial relationships to disclose.

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Disease-free survival as a surrogate endpoint for overall survival in adjuvant trials of pancreatic cancer: a meta-analysis of 20 randomized controlled trials

BMC Cancer ◽

10.1186/s12885-020-06910-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Run-Cong Nie ◽

Xue-Bin Zou ◽

Shu-Qiang Yuan ◽

Ying-Bo Chen ◽

Shi Chen ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Disease Free Survival ◽

Surrogate Endpoint ◽

Controlled Trials ◽

Free Survival ◽

Randomized Controlled ◽

Disease Free

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Tumor Microenvironment Status Predicts the Efficacy of Postoperative Chemotherapy or Radiochemotherapy in Resected Gastric Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2020.609337 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ran Duan ◽

Xiaoqin Li ◽

Dongqiang Zeng ◽

Xiaofeng Chen ◽

Bo Shen ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Microenvironment ◽

Nk Cell ◽

Disease Free Survival ◽

Predictive Biomarkers ◽

Free Survival ◽

Stage Ib ◽

T Cell Infiltration ◽

Resected Gastric Cancer ◽

Disease Free

PurposeChemotherapy (CT) and radiochemotherapy (RCT) are currently the standard postoperative treatments for resected gastric cancer (GC). However, owing to a lack of predictive biomarkers, their efficacy is currently suboptimal. As tumor microenvironment (TME) has the potential to determine treatment response, we investigated the association of TME status with the efficacy of fluoropyrimidine (FU)-based postoperative CT/RCT in resected GC.MethodsPatients with transcriptome data were screened and selected in three independent cohorts. Favorable (fTME) and poor TME (pTME) were defined by a transcriptome-based TME qualification method. Immune infiltration and hypoxia were assessed.ResultsA total of 535 patients were eligible. fTME, indicating the presence of immune activation, was characterized by NK cell rather than CD8+ T cell infiltration. However, postoperative CT/RCT improved overall survival and disease-free survival time more evidently in patients with pTME GC than those with fTME GC. Stratified by stage in fTME GC, stage III patients benefited from postoperative CT/RCT while stage Ib/II patients did not. In comparison, patients with pTME GC benefited from postoperative CT/RCT, regardless of stage. Furthermore, fTME was more hypoxic than pTME, accompanied by a stronger expression of thymidylate synthase (TS)—the target of FU. Stage Ib/II fTME GC was the most hypoxic and had the strongest TS expression across all the subgroups stratified by TME status and stage.ConclusionsWe found that fTME, with the enrichment of NK cells, may predict the lack of postoperative CT/RCT efficacy in stage Ib/II GC, which may be associated with hypoxia and TS expression. Further validations and mechanism researches are needed.

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Adjuvant chemoradiotherapy versus chemotherapy for resectable gastric cancer: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4066 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4066-4066

Author(s):

Yu Yang Soon ◽

Cheng Nang Leong ◽

Jeremy Chee Seong Tey ◽

Ivan Weng Keong Tham ◽

Jiade Jay Lu

Keyword(s):

Gastric Cancer ◽

Systematic Review ◽

Fixed Effects ◽

Meta Analysis ◽

Disease Free Survival ◽

Adjuvant Chemoradiotherapy ◽

Free Survival ◽

Platinum Based Chemotherapy ◽

Resectable Gastric Cancer ◽

Disease Free

4066 Background: The benefits of adjuvant chemo-radiotherapy (ChRT) over chemotherapy (Ch) for resectable gastric cancer are currently unclear. We performed a systematic review and meta-analysis (direct and indirect) of published randomized controlled trials (RCT) to compare the effects of adjuvant chemo-radiotherapy with chemotherapy on overall and disease-free survival for patients with resectable gastric cancer. Methods: We searched MEDLINE and CENTRAL from the date of inception and annual meeting proceedings of ASCO and ASTRO from 1999 to November 2012 for RCTs comparing adjuvant ChRT with Ch, adjuvant ChRT with surgery alone and adjuvant Ch with surgery alone. The primary outcome was overall survival (OS); secondary outcomes included disease-free survival (DFS) and toxicity. Hazard ratios (HR), confidence intervals (CI) and p values (p) were estimated with fixed effects models using Revman 5.1. Results: We found five trials comparing adjuvant ChRT with Ch (n = 1110), three trials comparing adjuvant ChRT with surgery alone (n = 651) and 31 trials comparing adjuvant Ch with surgery alone (n = 8273). Meta-analysis of direct comparison trials showed that adjuvant ChRT significantly improved both OS (HR 0.79, 95% CI 0.64-0.98, p = 0.03) and DFS (HR 0.76, 95% CI 0.64-0.92, p = 0.004) when compared with Ch. Subgroup analyses showed that the effects on OS and DFS were similar regardless of use of D2 nodal dissection, intensity modulated radiotherapy techniques, fluorouracil or platinum-based chemotherapy. There were no significant differences in toxicity between the two groups. The results for the direct and indirect comparisons were statistically consistent. Conclusions: There was a significant survival benefit of adjuvant chemo-radiotherapy over chemotherapy, with no increase in toxicity for patients with resected gastric cancer. Future efforts should also focus on predictive markers, and toxicity or quality-of-life assessments, to individualize adjuvant therapy and optimize the therapeutic ratio.

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