Systemic treatments and outcomes in CIC-rearranged Sarcoma: A national multi-centre clinicopathological series and literature review.

CIC-rearranged sarcoma is a recently established, ultra-rare, molecularly defined sarcoma subtype. We aimed to further characterise clinical features of CIC-rearranged sarcomas and explore clinical management including systemic treatments and outcomes. METHODS: A multi-centre retrospective cohort study of patients diagnosed between 2014-2019. RESULTS: Eighteen patients were identified. The median age was 27 years (range 13-56), 10 patients were male (56%), 11 patients (61%) had localised disease and 7 patients had advanced (metastatic or unresectable) disease at diagnosis. Of 11 patients with localised disease at diagnosis, median overall survival (OS) was 40.6 months and the 1-, 2- and 5-year OS estimates were 82%, 64% and 34% respectively. Nine patients (82%) underwent surgery (all had R0 resections), 8 (73%) patients received radiotherapy to the primary site (median dose 57Gy in 28 fractions), and 8 (73%) patients received chemotherapy (predominantly Ewing-based regimens). Metastases developed in 55% with a median time to recurrence of 10.5 months. In patients with advanced disease at diagnosis, median OS was 12.6 months (95% CI 5.1-20.1), 1-year OS was 57%. Median progression-free survival was 5.8 months (95% CI 4.5-7.2). Durable systemic therapy responses occurred infrequently with a median duration of systemic treatment response of 2.1 months. One durable complete response of metastatic disease to VDC/IE chemotherapy was seen. Responses to pazopanib (n = 1) and pembrolizumab (n = 1) were not seen. CONCLUSION: In this series, CIC-rearranged sarcomas affected young adults and had a high incidence of presenting with, or developing, metastatic disease. The prognosis overall was poor. In advanced disease, durable systemic therapy responses were infrequent.

Verification using in vivo optically stimulated luminescent dosimetry of the predicted skin surface dose in patients receiving postmastectomy radiotherapy.

The purpose of this study was to evaluate whether dose to the skin surface underneath bolus, was accurately predicted by a 3D treatment planning system (TPS) in patients receiving 50 Gy/25# postmastectomy radiotherapy (PMRT) using optically stimulated luminescent dosimetry (OSLD) for verification. In vivo dosimetry using OSLDs was performed in 20 consecutive patients receiving PMRT. An array of 9 OSLDs were applied to the chest wall or neobreast in a grid arrangement. Dosimetry data were recorded on 3 separate treatment fractions, averaged, and extrapolated to 25 fractions. On the 3D TPS, the predicted dose was calculated using the departmental planning algorithm at points corresponding to the OSLDs. The mean within patient difference between the planned and measured dose at each of the 9 points was calculated and Bland-Altman limits of agreement used to quantify the extent of agreement. Paired t-tests were used to test for evidence of systematic bias at each point. The coefficient of variation of the 3 OSLD readings per patient at each of the 9 points was low for 8 points (≤4.4%) demonstrating comparable dose received per fraction at these points. The mean ratio between the in vivo measured extrapolated OSLD (IVME OSLD) dose and the planned TPS dose ranged between 0.97 and 0.99 across all points (standard deviation range 0.05 to 0.08). The mean within patient difference between the IVME OSLD and planned TPS was <1 Gy at 7 of the 9 points and the t-test for evidence of systematic bias was significant (p = 0.03) at only 1 of the 9 points. Our commercially available 3D TPS closely predicted PMRT skin surface dose underneath bolus as verified by OSLDs. At all sites, the average ratio of delivered to predicted dose was >0.97 but <1. This practical and feasible OSLD assessment of only 3 of 25 fractions facilitates quality assurance of a TPS in predicting skin surface dose under bolus.