5645 - Evaluating Lung CT Density Changes Among Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) Treated with Thoracic Radiotherapy (TRT) alone or TRT Followed by Combined Ipilimumab (IPI) and Nivolumab (NIVO).

Background

Radiation induced CT changes may be apparent following completion of TRT. We sought to quantify differences in radiation-associated densities on serial CT scans of patients with ES-SCLC treated with TRT alone versus TRT followed by combined IPI and NIVO.

Methods

Between 2016 and 2018, patients at a single institution with ES-SCLC who achieved stable disease or better following initial treatment with platinum doublet chemotherapy were offered TRT and prescribed a total dose of 30Gy in 10 fractions targeting initially involved thoracic tumor sites. Combined IPI 3mg/kg and NIVO 1mg/kg was administered every 3 weeks for up to 4 doses. We evaluated an irradiated region of interest (ROI) within the lungs and a volume of lung (outside the Planning Target Volume) receiving > 20 Gy. Within the ROI, we calculated the Hounsfield unit (HU) mean for each patient prior to therapy and at subsequent follow-up CT thorax at least 60 days and closest to 120 days after commencing TRT. To quantify CT density change, we measured the difference in HU mean within the irradiated ROI before and after treatment.

Results

Seventeen patients enrolled on NCT03043599 received TRT followed by combined IPI/NIVO. Two additional patients received the same treatment off protocol. Eleven patients received TRT alone (no IPI/NIVO). The average increase in HU mean within 20Gy irradiated ROI before and after treatment was 9% (max 59%, min -19%) across the study cohort (n = 30). CTCAE grade 3 or higher pulmonary toxicity (N = 8 of 30) was significantly associated with increased CT density change within the ROI (mean 28% vs 2%, p = 0.001). Treatment with TRT and IPI/NIVO (N = 19 of 30) demonstrated a trend towards increased mean CT density change within the ROI compared to patients treated with TRT alone (mean 13% vs. 0%, p = 0.1).

Conclusions

Quantifying CT density change within irradiated lung parenchyma may offer a novel approach to predict radiation associated pulmonary toxicities. Measuring density changes across patient cohorts receiving TRT with novel systemic therapies may help to identify combined treatment strategies likely to be associated with diminished risk of toxicity.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Bristol-Myers Squibb.

Disclosure

S. Kim: Research grant / Funding (institution): Bristol-Myers Squibb. S.A. Rosenberg: Advisory / Consultancy: Novocure. J.E. Gray: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Triptych Health Partners. S.J. Antonia: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Merck; Advisory / Consultancy: CBMG; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: AstraZeneca/MedImmune; Advisory / Consultancy: Memgen; Advisory / Consultancy: FLX Bio; Advisory / Consultancy: Nektar; Advisory / Consultancy: Venn. B. Perez: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.