Clinical Impact of Delayed Initiation of Adjuvant Chemotherapy Among Patients With Stage II/III Gastric Cancer: Can We Do Better?
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ABSTRACT:
SUBMITTER: Chen QY
PROVIDER: S-EPMC7412732 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceThe current staging system of gastric cancer is not adequate for defining a prognosis and predicting the patients most likely to benefit from chemotherapy.ObjectiveTo construct a survival prediction model based on specific tumor and patient characteristics that enables individualized predictions of the net survival benefit of adjuvant chemotherapy for patients with stage II or stage III gastric cancer.Design, setting, and participantsIn this multicenter retrospective analysis, a survival prediction model was constructed using data from a training cohort of 746 patients with stage II or stage III gastric cancer who satisfied the study's inclusion criteria and underwent surgery between January 1, 2004, and December 31, 2012, at Nanfang Hospital in Guangzhou, China. Patient and tumor characteristics were included as covariates, and their association with overall survival and disease-free survival with and without adjuvant chemotherapy was assessed. The model was internally validated for discrimination and calibration using bootstrap resampling. To externally validate the model, data were included from a validation cohort of 973 patients with stage II or stage III gastric cancer who met the inclusion criteria and underwent surgery at First Affiliated Hospital in Guangzhou, China, and at West China Hospital of Sichuan Hospital in Chendu, China, between January 1, 2000, and June 30, 2009. Data were analyzed from July 10, 2016, to September 1, 2016.Main outcomes and measuresConcordance index and decision curve analysis for each measure associated with postoperative overall survival and disease-free survival.ResultsOf the 1719 patients analyzed, 1183 (68.8%) were men and 536 (31.2%) were women and the median (interquartile range) age was 57 (49-66) years. Age, location, differentiation, carcinoembryonic antigen, cancer antigen 19-9, depth of invasion, lymph node metastasis, and adjuvant chemotherapy were significantly associated with overall survival and disease-free survival, with P < .05. The survival prediction model demonstrated good calibration and discrimination, with relatively high bootstrap-corrected concordance indexes in the training and validation cohorts. In the validation cohort, the concordance index for overall survival was 0.693 (95% CI, 0.671-0.715) and for disease-free survival was 0.704 (95% CI, 0.681-0.728). Two nomograms and a calculating tool were built on the basis of specific input variables to estimate an individual's net survival gain attributable to adjuvant chemotherapy.Conclusions and relevanceThe survival prediction model can be used to make individualized predictions of the expected survival benefit from the addition of adjuvant chemotherapy for patients with stage II or stage III gastric cancer.
| S-EPMC5831463 | biostudies-literature
Project description:BackgroundAdjuvant chemotherapy is recommended as the standard treatment for patients with stage II/III resected gastric cancer. However, it is unclear whether older patients also benefit from an adjuvant chemotherapy strategy. This study aimed to investigate the clinical impact of adjuvant chemotherapy in older patients with stage II/III gastric cancer.MethodsThis retrospective, real-world study analyzed 404 patients with stage II/III gastric cancer visited at our institute between January 2009 and December 2019. The clinical characteristics and outcomes of patients aged 70 years or older who received adjuvant chemotherapy were compared with those who did not receive this type of treatment. Propensity score analysis was performed to mitigate selection bias.ResultsOf the 404 patients analyzed, 179 were aged 70 years or older. Fewer older patients received adjuvant chemotherapy than did younger patients (60.9% vs. 94.7%, respectively; P < 0.001). Among patients aged 70 years or older, those who received adjuvant chemotherapy had improved disease-free survival (DFS) (5-year DFS rate, 53.1% vs. 30.4%; P < 0.001) and overall survival (OS) (5-year OS rate, 68.7% vs. 52.1%; P = 0.002) compared to those who did not receive adjuvant chemotherapy. A similar survival benefit was observed in the propensity-matched cohort. Multivariate analysis showed that more advanced stage was associated with poorer OS. Receipt of adjuvant chemotherapy was independently associated with a decreased hazard of death (hazard ratio (HR), 0.37; 95% confidence intervals (CI), 0.20-0.68; P = 0.002).ConclusionsAdjuvant chemotherapy may benefit older stage II/III gastric cancer patients aged ≥ 70 years. Further prospective studies are needed to confirm these findings.
| S-EPMC10436551 | biostudies-literature
Project description:Predictors of survival in patients with stage II/III gastric cancer (GC) who received tegafur/gimeracil/oteracil (S-1) adjuvant chemotherapy (ACT) subsequent to gastrectomy were examined. Additionally, the association between dose intensity of S-1 and survival rate was investigated. A total of 62 patients with stage II/III gastric cancer were retrospectively evaluated, each of whom had received a curative D2 gastrectomy and S-1 ACT. The relative performance (RP; administered/planned S-1 doses ×100%), body mass index (BMI), prognostic nutritional index (PNI) and body weight (BW) were calculated, and the association of survival with these factors and other clinicopathological parameters was examined. The 1-year treatment continuation rate for S-1 was 94.2%, excluding patients who experienced cancer recurrences during their ACT year. The initial S-1 reduction rate was 38.7%. Patients with stage II/IIIA disease exhibited significantly improved 5-year overall survival rates compared with patients with stage IIIB GC, 81.6/73.7 vs. 33.8% (P<0.01). No association between RP and survival was observed. BMI, BW and PNI were significantly decreased following surgery compared with preoperative states. In the univariate analysis, postoperative BW loss (BMI loss), pathological stage and >7 lymph node metastases were significantly associated with outcome (P<0.05); in the multivariate analysis, postoperative BW loss >10.6% and pathological stages were independent prognostic factors for survival. Continuing S-1 ACT for the full year exhibited a greater effect on survival compared with dosage. Early postoperative nutritional deterioration may decrease the survival rates in these patients.
| S-EPMC5529945 | biostudies-other
Project description:BackgroundWith the aging of the population, the burden of elderly gastric cancer (EGC) increases worldwide. However, there is no consensus on the definition of EGC and the efficacy of adjuvant chemotherapy in patients with stage II EGC. Here, we investigated the effectiveness of adjuvant chemotherapy in defined EGC patients.MethodsWe enrolled 5762 gastric cancer patients of three independent cohorts from the Sixth Affiliated Hospital of Sun Yat-sen University (local), the Surveillance, Epidemiology, and End Results (SEER), and the Asian Cancer Research Group (ACRG). The optimal age cutoff for EGC was determined using the K-adaptive partitioning algorithm. The defined EGC group and the efficacy of adjuvant chemotherapy for them were confirmed by Cox regression and Kaplan-Meier survival analyses. Furthermore, gene set variation analyses (GSVA) were performed to reveal pathway enrichment between groups.ResultsThe optimal age partition value for EGC patients was 75. In the local, SEER, and ACRG cohorts, the EGC group exhibited significantly worse overall survival and cancer-specific survival than the non-EGC group (P < 0.05) and was an independent risk factor. Stratified analyses based on chemotherapy showed that EGC patients derived little benefit from adjuvant chemotherapy. Furthermore, GSVA analysis revealed the activation of DNA repair-related pathways and downregulation of the p53 pathway, which may partially contribute to the observed findings.ConclusionIn this retrospective, international multi-center study, 75 years old was identified as the optimal age cutoff for EGC definition, and adjuvant chemotherapy proved to be unbeneficial for stage II EGC patients.
| S-EPMC10566074 | biostudies-literature
Project description:ImportanceAdjuvant chemotherapy improves outcomes of patients with breast cancer. However, the optimal timing of chemotherapy initiation is unknown. Delayed administration can decrease the benefit of cytotoxic systemic therapies.ObjectiveTo identify the determinants in delayed chemotherapy initiation and to determine the relationship between time to chemotherapy (TTC) and outcome according to breast cancer subtype. We hypothesized that prolonged TTC would be associated with adverse outcomes.Design, setting, and participantsIn an observational, population-based investigation using data from the California Cancer Registry, we studied a total of 24 843 patients with stage I to III invasive breast cancer diagnosed between January 1, 2005, and December 31, 2010, and treated with adjuvant chemotherapy. Data analysis was performed between August 2014 and August 2015.Main outcomes and measuresTime to chemotherapy was defined as the number of days between surgery and the first dose of chemotherapy, and delayed TTC was defined as 91 or more days from surgery to the first dose of adjuvant chemotherapy. We evaluated overall survival and breast cancer-specific survival. Logistic regression and Cox proportional hazard models were used.ResultsIn all, 24 843 patients were included. Median age at diagnosis was 53 years, and median was TTC was 46 days. Factors associated with delays in TTC included low socioeconomic status, breast reconstruction, nonprivate insurance, and Hispanic ethnicity or non-Hispanic black race. Compared with patients receiving chemotherapy within 31 days from surgery, there was no evidence of adverse outcomes among those with TTC of 31 to 60 or 60 to 90 days. Patients treated 91 or more days from surgery experienced worse overall survival (hazard ratio [HR], 1.34; 95% CI, 1.15-1.57) and worse breast cancer-specific survival (HR, 1.27; 95% CI, 1.05-1.53). In a subgroup analysis according to subtype, longer TTC caused patients with triple-negative breast cancer to have worse overall survival (HR, 1.53; 95% CI, 1.17-2.00) and worse breast cancer-specific survival (HR, 1.53; 95% CI 1.17-2.07).Conclusions and relevanceFor patients with breast cancer, adverse outcomes are associated with delaying initiation of adjuvant chemotherapy 91 or more days. Delayed TTC was particularly detrimental among patients with triple-negative breast cancer. The determinants of delays in chemotherapy initiation appeared to be sociodemographic, and clinicians should provide timelier care to all patients.
| S-EPMC5920529 | biostudies-literature
Project description:BackgroundAdjuvant chemotherapy benefits early-stage breast cancer (BC) patients. Older women receive guideline-adherent treatment less frequently and experience treatment delays more frequently. We evaluated factors associated with delaying adjuvant chemotherapy and the delays' survival impact in a large population-based cohort of elderly BC patients.MethodsPatients age >66 years diagnosed 2001-2015 with localized or regional BC were identified in the SEER-Medicare and Texas Cancer Registry-Medicare databases. Time from surgery to chemotherapy (TTC) was categorized into four groups: 0-30, 31-60, 61-90, and >90 days. We identified predictors of delays, estimated overall (OS) and BC-specific (BCSS) survival, and determined the association between TTC and outcome adjusting for other variables.ResultsAmong 28,968 women (median age 71 years), median TTC was 43 days. 10.7% of patients experienced TTC >90 days. Older age, Black or Hispanic race/ethnicity, unmarried status, more comorbidities, hormone receptor-positivity, mastectomy, Oncotype DX testing, and full state buy-in were associated with increased risk of delay. Five-year OS estimates by TTC group were 0.82, 0.81, 0.80, and 0.74, respectively (p<.001). BCSS demonstrated a similar trend (p<.001). Chemotherapy delay was associated with worse OS (HR=1.33, 95%CI 1.25-1.40) and BCSS (HR=1.39, 95%CI 1.27-1.53). In subgroup analysis, delayed chemotherapy was associated with worse OS and BCSS among patients with hormone receptor-positive (HR=1.56, 95%CI 0.97-2.51), HER2-positive (HR=1.99, 95%CI 1.04-3.79), and triple-negative (HR=2.15, 95%CI 1.38-3.36) tumors.ConclusionChemotherapy delays are associated with worse survival in older BC patients. Providers should avoid delays and initiate chemotherapy ≤90 days after surgery regardless of patients' BC subtype or age.
| S-EPMC7541132 | biostudies-literature
Project description:Overall survival remains unsatisfactory in stage II/III gastric cancer, even after curative surgery and adjuvant chemotherapy. Platelet-derived growth factor receptor-β (PDGFR-β) is associated with the proliferation of cancer cells. The present study therefore investigated the association of PDGFR-β gene expression with patient outcome in 134 stage II/III gastric cancer patients who received adjuvant chemotherapy with S-1. Relative PDGFR-β gene expression was measured in surgical cancer tissue and adjacent normal mucosa specimens by reverse transcription-quantitative polymerase chain reaction. The PDGFR-β gene expression levels were found to be significantly higher in the cancer tissues compared with the adjacent normal mucosa. A high level of PDGFR-β gene expression was associated with a significantly poorer 5-year overall survival rate compared with a low level of PDGFR-β expression. Upon multivariate analysis, PDGFR-β gene expression was found to be an independent predictor of survival. Overall, the study indicates that PDGFR-β overexpression in gastric cancer tissues is a useful independent predictor of outcome in patients with stage II/III gastric cancer who receive adjuvant chemotherapy with S-1.
| S-EPMC5351282 | biostudies-literature
Project description:BackgroundColon cancer incidence is rising in low- and middle-income countries (LMICs), where resource limitations and cost often dictate treatment decisions. In this study, we evaluate the cost-effectiveness of adjuvant chemotherapy for high-risk stage II and stage III colon cancer treatment in South Africa (ZA) and illustrate how such analyses can inform cancer treatment recommendations in a LMIC.MethodsWe created a decision-analytic Markov model to compare lifetime costs and outcomes for patients with high-risk stage II and stage III colon cancer treated with three adjuvant chemotherapy regimens in a public hospital in ZA: capecitabine and oxaliplatin (CAPOX) for 3 and 6 months, and capecitabine for 6 months, compared to no adjuvant treatment. The primary outcome was the incremental cost-effectiveness ratio (ICER) in international dollars (I$) per disability-adjusted life-year (DALY) averted, at a willingness-to-pay (WTP) threshold equal to the 2021 ZA gross domestic product per capita (I$13,764/DALY averted).ResultsCAPOX for 3 months was cost-effective for both patients with high-risk stage II and patients with stage III colon cancer (ICER = I$250/DALY averted and I$1042/DALY averted, respectively), compared to no adjuvant chemotherapy. In subgroup analyses of patients by tumor stage and number of positive lymph nodes, for patients with high-risk stage II colon cancer and T4 tumors, and patients with stage III colon cancer with T4 or N2 disease. CAPOX for 6 months was cost-effective and the optimal strategy. The optimal strategy in other settings will vary by local WTP thresholds. Decision analytic tools can be used to identify cost-effective cancer treatment strategies in resource-constrained settings.ConclusionColon cancer incidence is increasing in low- and middle-income countries, including South Africa, where resource constraints can impact treatment decisions. This cost-effectiveness study evaluates three systemic adjuvant chemotherapy options, compared to surgery alone, for patients in South African public hospitals after surgical resection for high-risk stage II and stage III colon cancer. Doublet adjuvant chemotherapy (capecitabine and oxaliplatin) for 3 months is the cost-effective strategy and should be recommended in South Africa.
| S-EPMC10417185 | biostudies-literature
Project description:BackgroundThere is no consistent evidence about the appropriate treatment strategies for gastric signet ring cell carcinoma (GSRC) to improve prognosis. We conducted a population-based study to examine the effects of combined modality therapies on survival outcomes using the Surveillance, Epidemiology, and End Results (SEER) data.MethodsAnalyses included stage II-III primary GSRC patients who were diagnosed between 2006 and 2016. Therapies were categorized as gastrectomy group, adjuvant chemotherapy (CT) group, neoadjuvant radiotherapy (RT) group, and adjuvant chemoradiotherapy (CRT) group. Survival analyses were conducted by Kaplan-Meier method and Cox proportional hazards models and subgrouped by gender, tumor site, stage at diagnosis, and number of lymph nodes removed.ResultsOf the 1717 cases of stage II-III primary GSRC, the mean (SD) age was 59.6 (13.3) years, and over a half were male (52.8%). A total of 39.9% patients received adjuvant CRT and the 5-year overall survival (OS) rate was 34.6%. The median OS of patients treated with adjuvant CRT was significantly longer than that of the gastrectomy group (33 months vs 24 months, aHR = 0.71, 95% CI: 0.59, 0.84). Although the crude model showed a significant association between adjuvant CT and total survival (cHR = 0.81, 95% CI: 0.68, 0.96), the effect measure turned null in the multivariable and sub-group analysis. We did not find the significant effect of neoadjuvant RT.ConclusionsIn this study, GSRC patients with stage II-III experienced improved overall survival after receiving adjuvant CRT, which provides several treatment implications. More clinical trials will be needed to verify the conclusion derived from this study.
| S-EPMC7520351 | biostudies-literature
Project description:BackgroundSince 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures.MethodsWe performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12.ResultsAfter 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority).ConclusionsAmong patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.).
| S-EPMC6426127 | biostudies-literature