Clinical outcomes and safety of immune checkpoint inhibitors in patients with solid tumors and paraneoplastic syndromes.

BACKGROUND: Patients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns. Moreover, real-world data on efficacy and safety is scarce. METHODS: In this retrospective study, data were collected on patients with PNS and solid tumors receiving ICI between 2015 and 2022 at nine institutions. Patients were classified into: Cohort 1 (pre-existing PNS before ICI initiation), cohort 2 (PNS during ICI treatment), and cohort 3 (PNS after ICI discontinuation). Patients with metastatic non-small cell lung cancer (NSCLC) (mNSCLC) from cohort 1 were matched to patients who were PNS-free at each institution up to a 1:3 ratio for age, sex, type of ICI, use of concurrent chemotherapy, and number of lines of systemic therapy prior to ICI initiation. Kaplan-Meier method was used to assess overall survival (OS) and time-to-next treatment (TTNT). RESULTS: Among 109 patients with PNS treated with ICIs, median age at ICI initiation was 67 years (IQR: 58-74). The most represented cancer type was NSCLC (n=39, 36%). In cohort 1 (n=55), PNS exacerbations occurred in 16 (29%) patients with median time to exacerbation after ICI of 1.1 months (IQR: 0.7-3.3). Exacerbation or de novo PNS prompted temporary/permanent interruption of ICIs in 14 (13%) patients. For cohort 2 (n=16), median time between ICI initiation and de novo PNS was 1.2 months (IQR: 0.4-3.5). Treatment-related adverse events (trAEs) occurred in 43 (39%) patients. Grade ≥3 trAEs occurred in 18 (17%) patients. PNS-directed immunosuppressive therapy was required in 55 (50%) patients. We matched 18 patients with mNSCLC and PNS (cohort 1) to 40 without PNS, treated with ICIs. There was no significant difference in OS or TTNT between patients with mNSCLC with and without PNS, although a trend was seen towards worse outcomes in patients with PNS. TrAEs occurred in 6/18 (33%) and 14/40 (35%), respectively. Grade ≥3 trAEs occurred in 4 (22%) patients with PNS and 7 (18%) patients without PNS. CONCLUSIONS: Exacerbations of pre-existing PNS occurred in 29% of patients treated with ICIs and both exacerbations and de novo PNS occur early in the ICI course. TrAE from ICIs were similar between patients with and without PNS. Our data suggest that pre-existing PNS should not preclude consideration of ICI therapy although patients may not derive the same clinical benefit compared with patients without PNS.

The role of 18F-FDG PET in minimizing variability in gross tumor volume delineation of soft tissue sarcomas.

BACKGROUND: Accurate gross tumor volume (GTV) delineation is a critical step in radiation therapy treatment planning. However, it is reader dependent and thus susceptible to intra- and inter-reader variability. GTV delineation of soft tissue sarcoma (STS) often relies on CT and MR images. PURPOSE: This study investigates the potential role of 18F-FDG PET in reducing intra- and inter-reader variability thereby improving reproducibility of GTV delineation in STS, without incurring additional costs or radiation exposure. MATERIALS AND METHODS: Three readers performed independent GTV delineation of 61 patients with STS using first CT and MR followed by CT, MR, and 18F-FDG PET images. Each reader performed a total of six delineation trials, three trials per imaging modality group. Dice Similarity Coefficient (DSC) score and Hausdorff distance (HD) were used to assess both intra- and inter-reader variability using generated simultaneous truth and performance level estimation (STAPLE) GTVs as ground truth. Statistical analysis was performed using a Wilcoxon signed-ranked test. RESULTS: There was a statistically significant decrease in both intra- and inter-reader variability in GTV delineation using CT, MR 18F-FDG PET images vs. CT and MR images. This was translated by an increase in the DSC score and a decrease in the HD for GTVs drawn from CT, MR and 18F-FDG PET images vs. GTVs drawn from CT and MR for all readers and across all three trials. CONCLUSION: Incorporation of 18F-FDG PET into CT and MR images decreased intra- and inter-reader variability and subsequently increased reproducibility of GTV delineation in STS.