Background and purpose: This study aimed to summarize the clinical outcomes of patients with metastatic melanoma who received high‐dose radiation prior to or during systemic therapy at a single academic institution.Methods: We identified patients with metastatic melanoma who underwent high‐dose radiation therapy (HDRT) for extracranial metastases prior to or during systemic therapy from 2010 to 2018. Treatment indications included oligometastases, oligoprogression, and local control. Using the Kaplan‐Meier method, we plotted overall survival (OS), progression‐free survival‐1 (PFS1), and PFS2. Competing risk analysis determined the cumulative incidence of local failure (LF) and the time to start or change systemic therapy (SCST). Univariate and multivariable analyses were used to identify predictive factors.Results: We analyzed 34 patients with 79 lesions, with a median follow‐up of 17.4 months. Sixty‐eight percent of patients received systemic therapy after the first HDRT. The median OS was 22 months, with brain metastases before HDRT being a significant predictor in multivariable analysis. The median PFS1 for first‐line HDRT was 4.1 months, and the median PFS2 was 3.9 months. Rates of LF were 10.3% at 12 months and 11.7% at 24 months. The incidence of SCST following HDRT was 59.8% at 12 months and 76.1% at 24 months, with radiation targeted at the lung associated with a lower incidence of SCST.Conclusion: HDRT for treating metastatic lesions in melanoma demonstrated excellent local control and may play a role in delaying SCST. Additional courses of HDRT may provide cumulative benefits.

(1) Background: Exon 20 insertion mutations (ex20ins) in EGFR and HER2 are uncommon driver mutations in non-small-cell lung cancer (NSCLC), with a poor prognosis and few targeted therapy options, and there are limited real-world data. Here, we report the clinicopathologic features and outcomes for patients with ex20ins NSCLC across British Columbia, Canada. (2) Methods: NSCLC patients with ex20ins in EGFR or HER2 were identified via tumour testing between 1 January 2016 and 31 December 2021 (n = 7233). Data were collected by chart review. Survival analyses were performed using the Kaplan–Meier method using the log-rank test. (3) Results: A total of 131 patients were identified. The median age was 66. Thirty-three percent of patients had brain metastases. For the EGFR cohort, the median OS was 18.6 months for patients who received any systemic therapy (ST) vs. 2.6 months for patients who did not (p < 0.001). Median OS was similar for patients treated with ex20ins-specific tyrosine kinase inhibitors (TKIs) vs. other STs (18.6 vs. 15.9 months; p = 0.463). The median first-line PFS was 4.1 vs. 7.4 months for patients treated with a TKI vs. other ST (p = 0.744). For the HER2 cohort, the median OS was 9.0 months for patients who received any ST vs. 4.9 months for patients who did not (p = 0.015). The median OS was 23.0 months for patients treated with an ex20ins TKI vs. 5.6 months for patients who were not (p = 0.019). The median first-line PFS was 5.4 vs. 2.1 months for patients treated with a TKI vs. other ST (p = 0.343). (4) Conclusions: Overall survival was significantly longer among ex20ins patients who received any systemic therapy vs. those who did not. Overall survival was significantly better among HER2 ex20ins patients who received ex20ins-specific TKIs.