Comparisons of Propensity Score Methods for Time to Event Outcomes: Evaluation through Simulations and Oral Squamous Cell Carcinoma Case Study

Introduction & Objective: In observational studies, it is recommended to use propensity score (PS) methods or covariate adjustment for confounding effect adjustment. However, few guidelines are available regarding the choice of PS approaches or covariate adjustment for the best performance in a particular data. In this study, we compared different PS methods and conventional covariate adjustment to investigate the treatment effect for the overall population on time-to-event outcomes. Methods: In the Monte Carlo simulations, we compared the hazard ratio (HR) and precision estimated using covariate adjustment and eight different PS approaches, including matching, stratification, and inverse probability of treatment weighting (IPTW). In the Oral Squamous-Cell Carcinoma Cancer case study, we applied the aforementioned PS approaches to compare the effect of receiving post-operative radiation therapy (PORT) and having engraftable tumors on different time-to-event clinical outcomes. Results: In the simulations, both IPTW and covariate adjustment produced unbiased HR estimates with small uncertainty. In the case study, covariate adjustment showed that patients with engraftable tumors were twice as likely to have local/regional recurrence (HR 1.98 [1.23, 3.18], p-value<0.005) and any recurrence or death (HR 2.02 [1.38, 2.96], p-value<0.001); patients received PORT were twice as likely to develop either local, regional, or distance recurrence (HR 2.12 [1.32, 3.41], p-value<0.005). Results produced by IPTW were consistent with covariate adjustment method (within ± 0.1 differences). Conclusion: Covariate adjustment and the IPTW method performed well across simulations and the case study. In practice, care should be taken to select the most suitable method when estimating the treatment, exposure or intervention effect on time-to-event outcomes

Stereotactic Body Radiotherapy for Extracranial Oligometastatic Disease from Head and Neck Primary Cancers: A Systematic Review and Meta-Analysis

Introduction: Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT. Methods: A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I2 statistic and Cochran Qtest. Forest plots were generated for each endpoint. Results: Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6–81) and 63 lesions (range: 6–126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1–10 fractions (20–70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3–91.9%). LC2 was 77.9% (95% CI: 66.4–86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0–51.4%) and PFS2 of 23.9% (95% CI: 17.8–31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2–85.0%) and OS2 of 60.7% (95% CI: 51.3–69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported. Conclusions: SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted