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As new findings in oncology suggest a focus on individualized and targeted therapies, the demand for adequate clinical trial designs rises, whereby the focus is mainly on early development phases (phase I and II). Phase II oncology trials are often planned and analysed by Simon two-stage design, which corresponds to a one-armed trial design with the option to stop early for futility. Whereas a classical phase II study focuses on one tumour type and location, the relatively new basket trial design allows testing the efficacy of a single drug simultaneously in a number of patient subsets, which correspond to different tumour types. Such trials can be analysed in various ways, including separate analyses of all baskets or by pooling across all baskets. The work presented here tries to find an adequate compromise between these two extremes by implying rules for clustering some baskets, which are reasonably homogeneous. By means of Monte-Carlo simulations, we compare the efficiency of our proposed cluster-based basket trial design with a standard approach proposed recently which only allows for complete pooling or separate analyses. The results suggest that our new design offers a considerable advantage in power, sensitivity and specificity as well as in average sample size compared to the standard approach. The proposed clustering design is an attractive option to conduct basket trials in oncology with higher efficiency and better performance.
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Neoplasms , Research Design , Cluster Analysis , Humans , Medical Oncology , Neoplasms/diagnosis , Neoplasms/drug therapy , Sample SizeABSTRACT
PURPOSE: Treatment of patients with primary and secondary liver tumors remains challenging. This study analyzes the efficacy and safety of transarterial radioembolization (TARE) combined with CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT) for the treatment of primary and secondary liver tumors. PATIENTS AND METHODS: A total of 77 patients (30 female) with various liver malignancies were treated. Primary endpoints were median overall survival (OS) and time to untreatable progression (TTUP). Additionally, subgroup analyses were performed in consideration of diagnosis and procedure sequence. Median OS and TTUP prediction were estimated using Kaplan-Meier analysis and hazard ratios (HR) were calculated using a multivariate Cox proportional hazard model. RESULTS: A total of 115 CT-HDRBT and 96 TARE procedures were performed with no significant complications recorded. Median OS and TTUP were 29.8 (95% CI 18.1-41.4) and 23.8 (95% CI 9.6-37.9) months. Median OS for hepatocellular carcinoma (HCC)-, cholangiocarcinoma carcinoma (CCA) and colorectal cancer (CRC) patients was 29.8, 29.6 and 34.4 months. Patients starting with TARE had a median OS of 26.0 (95% CI 14.5-37.5) compared to 33.7 (95% CI 21.6-45.8) months for patients starting with CT-HDRBT. Hazard ratio of 1.094 per month was shown for patients starting with CT-HDRBT. CONCLUSION: Combining TARE and CT-HDRBT is effective and safe for the treatment of advanced stage primary and secondary liver tumors. Our data indicate that early TARE during the disease progression may have a positive effect on survival.
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Background Among patients with breast cancer undergoing neoadjuvant chemotherapy (NACT), the association between pathological complete remission (pCR) in the breast and clinical/pathological parameters is well established, whereas the association between these parameters and residual axillary involvement after NACT remains unclear. Methods Patients with clinically occult nodal metastases (i.e. negative by clinical assessment but positive by SLNB prior to NACT, i.e. Arm B of the SENTINA trial) were included in the presented analysis. All patients received a second sentinel lymph node biopsy (SLNB) and axillary dissection after NACT. Univariate and multivariate analyses were carried out to evaluate the association between clinical/pathological parameters and axillary involvement after NACT. Results Arm B of the SENTINA study contained 360 patients, 318 of which were evaluable for this analysis. After NACT, 71/318 (22.3%) patients had involved SLNs or non-SLNs after NACT. Overall, 71/318 (22.3%) patients achieved a pCR in the breast. Associations of extranodal spread, lack of multifocality and pCR in the breast with residual axillary burden were statistically significant. In a descriptive analysis including all patients with clinically negative axilla before NACT in the SENTINA trial 1.2% of triple negative (TN) patients and 0.5% of HER/2 positive patients had residual axillary disease in case of a breast pCR. Conclusions Patients in the SENTINA trial with clinically negative axilla and involved SLNs still carried a significant risk of nodal metastases after NACT. However, the risk of residual axillary burden was particularly low in TN and HER/2 positive tumors in case of a breast pCR.
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[This corrects the article DOI: 10.1055/a-1298-3453.].
