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The Effect of Positive SWOG Treatment Trials on Survival of Patients With Cancer in the US Population.

ABSTRACT: Importance:Recently, tremendous prominence has been given to the investigation of the effect of different research processes as part of the Cancer Moonshot. More than half a century ago, the National Cancer Institute (NCI) established a network of publicly funded cancer cooperative research groups to systematically evaluate new treatments for efficacy and safety. Objective:To examine the extent to which positive NCI-sponsored cancer treatment trials have benefited patients with cancer in the US population. Design, Setting, and Participants:This investigation used study data from SWOG, an NCI-sponsored network cooperative research group. All treatment trials during SWOG's 60-year history (1956-2016) were identified for which the new, experimental therapy provided a statistically significant improvement in overall survival. It was assumed that the new, proven treatments from these trials established new standards for cancer care in the treatment community. Twenty-three positive SWOG treatment trials were identified from a variety of different disease settings. Main Outcomes and Measures:This study estimated population life-years gained from the 23 treatment trials through 2015 by mapping the effect of the new treatments onto the US cancer population using an area under the Kaplan-Meier survival curve approach that combined trial-specific hazard function and hazard ratio results, along with Surveillance, Epidemiology, and End Results program and life table data. Calculations were age adjusted. The US dollar return on investment was estimated as the ratio of the total investment by the NCI in the treatment trial program divided by the estimate of life-years gained. Results:In total, 12?361 patients were enrolled to the 23 positive trials from 1965 to 2012. The study estimated that 3.34 million (95% confidence limit, 2.39-4.15 million) life-years were gained from these 23 trials through 2015. Estimates were greater than 2 million life-years gained under most model simulations. The US dollar return on investment was $125 per life-year gained. Conclusions and Relevance:SWOG treatment trials have had a substantial impact on population survival for patients with cancer over 60 years. The NCI's investment in its cancer cooperative group research program has provided exceptional value and benefit to the American public through its research programs generating positive cancer treatment trials. Trial Registration:clinicaltrials.gov Identifiers: NCT00004001, NCT00075764, and NCT00644228.

SUBMITTER: Unger JM

PROVIDER: S-EPMC5710507 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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The Effect of Positive SWOG Treatment Trials on Survival of Patients With Cancer in the US Population.

Unger Joseph M JM LeBlanc Michael M Blanke Charles D CD

JAMA oncology 20171001 10

<h4>Importance</h4>Recently, tremendous prominence has been given to the investigation of the effect of different research processes as part of the Cancer Moonshot. More than half a century ago, the National Cancer Institute (NCI) established a network of publicly funded cancer cooperative research groups to systematically evaluate new treatments for efficacy and safety.<h4>Objective</h4>To examine the extent to which positive NCI-sponsored cancer treatment trials have benefited patients with ca ...[more]

PMID: 28586789

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Project description:BACKGROUND:Racial disparities in cancer outcomes have been described. To the authors' knowledge, it remains unclear whether patients of Hispanic ethnicity have better or worse survival outcomes. In the current study, the authors evaluated whether Hispanic participants in SWOG clinical trials had different survival outcomes compared with non-Hispanics. METHODS:Adult patients registered in SWOG phase 2/3 clinical trials between 1986 and 2012 were analyzed. Studies of similar histology and stage of disease were combined. Within each analysis, Kaplan-Meier survival curves were generated to examine differences in outcome by ethnicity. Multivariate Cox regression was used to estimate the association between ethnicity and survival outcomes, controlling for major disease-specific prognostic factors and demographic variables plus area-level income and education to account for socioeconomic status. RESULTS:A total of 29,338 patients registered to 38 trials were included; 5% of these patients were Hispanic. Hispanic patients were more likely to be younger and from areas of lower income and education (all P<.05). No differences in survival were observed across tumor types except in the patients with advanced stage prostate cancer, in whom the authors observed an association between Hispanic ethnicity and worse overall survival (hazard ratio [HR], 1.40; P = .006), progression-free survival (HR, 1.36; P = .007), and cancer-specific survival (HR, 1.42; P = .013). After adjusting for multiple comparisons, no differences in outcomes were noted. CONCLUSIONS:Hispanic patients participating in SWOG trials who received uniform treatment and follow-up were found to have similar survival outcomes compared with non-Hispanic patients, with the single exception of those patients with advanced stage prostate cancer. The results of the current study demonstrate that Hispanic patients receiving uniform treatment and follow-up have similar outcomes compared with non-Hispanics. Cancer 2018;124:1760-9. © 2018 American Cancer Society.

Project description:BACKGROUND:Aberrant DNA methylation is known to occur in patients with acute myeloid leukemia (AML), whereas methylation signatures and prognostic markers have been proposed. The objective of the current study was to evaluate all CpG sites of the genome and identify prognostic methylation markers for overall survival in patients with AML with normal karyotype (AML-NK). METHODS:AML-NK samples from 7 SWOG trials were analyzed using a novel genome-wide approach called "CHARMcox" (comprehensive high-throughput array-based relative methylation analysis combined with the Cox proportional hazards model) controlling for known clinical covariates. CHARMcox was applied to a phase 1 discovery cohort (72 patients) to identify survival-associated methylation regions (SAMRs). Subsequently, using bisulfite pyrosequencing, SAMRs were studied in phase 2 model-building (65 patients) and phase 3 validation (65 patients) cohorts. An independent external cohort from The Cancer Genome Atlas (TCGA) AML study (LAML) was used for further validation (93 patients). RESULTS:Two SAMRs, located at the CpG island shores of leucine zipper tumor suppressor 2 (LZTS2) and nuclear receptor subfamily 6 group a member 1 (NR6A1), respectively, were identified. Multivariable analyses demonstrated that hypomethylation of either LZTS2 or NR6A1 was associated with worse overall survival in the SWOG cohort (P<.001). The prognosis was validated in patients with AML-NK from the TCGA-LAML cohort. Methylation values below the median at both markers predicted worse overall survival (SWOG: hazard ratio, 1.89 [P<.001]; and TCGA-LAML: hazard ratio, 2.08 [P=.006]). The C-statistic was 0.71 for both cohorts, and the impact was independent of the Fms-related tyrosine kinase 3 internal tandem duplication (FLT3-ITD) status. CONCLUSIONS:The 2 methylation markers, measurable by clinically applicable assays such as bisulfite pyrosequencing, are promising for risk stratification among patients with AML-NK. Cancer 2017;123:2472-81. © 2017 American Cancer Society.

Project description:ImportancePatients with cancer are at risk for unplanned hospitalizations during treatment which can increase the cost of care.ObjectivesTo determine demographic and clinical factors associated with healthcare utilization and costs among clinical trial participants.Design, setting, and patientsWe conducted a retrospective analysis among breast cancer patients over the age of 65 treated on SWOG clinical trials from 1999 to 2011 with trial data linked to Medicare claims.Main outcomes and measuresThe outcomes were healthcare utilization (emergency room visits (ER), hospitalizations) and costs from Medicare Claims. Demographic, clinical, and prognostic factors were captured from clinical trial records. We identified cardiovascular comorbidities/risk factors (CVD-RFs) of diabetes, hypertension, hypercholesterolemia, and coronary artery disease (CAD) from Medicare claims. Multivariable logistic and linear regression were used to assess the association between CVD-RFs and outcomes.ResultsAmong the 708 patients included in the analysis, 160 (22.6%) experienced 234 separate hospitalizations, and 193 (27.3%) experienced 311 separate ER visits. Black race was associated with an increase in hospitalizations (OR [95% CI], 2.52 [1.10-5.79], p = 0.03), but not emergency room visits compared to white race. Diabetes, hypertension, hypercholesterolemia, and CAD were all independently associated with increased risk of both hospitalizations and ER visit. Hypertension had the strongest association, with more than a threefold risk of hospitalization for those with hypertension compared to those without (OR [95% CI], 3.16 [1.85-5.40], p < 0.001). For those with ≥ 3 RFs, the risk of hospitalization was nearly 3 times greater compared to 0 or 1 CVD-RFs (OR [95% CI], 2.74 [1.71-4.38], p < 0.001). Similar results were seen for ER visits. In the first 12 months after trial registration, patients with diabetes ($38,324 vs $30,923, 23.9% increase, p = 0.05), hypercholesterolemia ($34,168 vs $30,661, 11.4% increase, p = 0.02), and CAD ($37,781 vs $31,698, 19.2% increase, p = 0.04) had statistically significantly higher total healthcare costs. Additionally, those with ≥ 2 significant CVD-RFs ($35,353 vs. $28,899, 22.3% increase, p = 0.005) had statistically significantly higher total healthcare costs.ConclusionsAmong participants treated on clinical trials, black race and presence of multiple cardiovascular comorbidities was associated with a substantial increase in ER visits, hospitalizations and healthcare costs. Efforts to reduce unplanned hospitalizations should focus on this high-risk group.

Project description:BackgroundER+HER2+ breast cancer requires most types of systemic therapies perioperatively. However, treatment resistance is often experienced. The current study investigated the predictive and prognostic value of intratumoral heterogeneity and conventional clinicopathological factors in patients with ER+HER2+ breast cancer.MethodsThis research included two patient cohorts with ER+HER2+ breast cancer. Cohort A included patients who underwent surgery without neoadjuvant chemotherapy (NAC). Cohort B comprised patients who received NAC followed by surgery. Intratumoral heterogeneity was assessed via ER and HER2 double staining, and the number of cells stained with different patterns of ER and HER2 was counted.ResultsIn total, 11 of 92 tumors in cohort A and four of 45 tumors in cohort B consisted exclusively of double-positive (ER+ and HER2+) cells (homogeneous). The rest had different combinations of cells (heterogeneous). The pathological complete response (pCR) rates differed based on tumoral cell components but not intratumoral heterogeneity. The pCR rate of tumors with ER-HER2+ cells but without HER2- cells was higher than that of others (45.5% vs 4.3%; p = 0.0013). Low ER and PgR Allred scores indicated better pCR rates than high scores (p = 0.0005 and 0.024, respectively). Multivariate analysis showed that the ER Allred score and cell component of ER-HER2+ cells without HER2- cells were independent predictors of pCR (p = 0.0055 and 0.0081, respectively). In cohort B, posttreatment Ki67, but not pCR, was a prognostic factor of DFS and OS (p = 0.028 and 0.017, respectively). The prognostic value of combined posttreatment Ki67 and pCR was superior to that of either alone. Combined pCR and posttreatment Ki67 had an independent prognostic value for DFS and OS (p = 0.0068 and 0.0101, respectively).ConclusionsIn ER+HER2+ breast cancer, the presence of ER-HER2+ cells without HER2- cells was independently associated with pCR. Combined posttreatment Ki67 and pCR can be more precise in predicting prognosis than pCR alone.

Dataset Information

The Effect of Positive SWOG Treatment Trials on Survival of Patients With Cancer in the US Population.

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The Effect of Positive SWOG Treatment Trials on Survival of Patients With Cancer in the US Population.

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