Immune checkpoint blockers in solid organ transplant recipients and cancer: the INNOVATED cohort.

BACKGROUND: Patients with solid organ transplant (SOT) and solid tumors are usually excluded from clinical trials testing immune checkpoint blockers (ICB). As transplant rates are increasing, we aimed to evaluate ICB outcomes in this population, with a special focus on lung cancer. METHODS: We conducted a multicenter retrospective cohort study collecting real data of ICB use in patients with SOT and solid tumors. Clinical data and treatment outcomes were assessed by using retrospective medical chart reviews in every participating center. Study endpoints were: overall response rate (ORR), 6-month progression-free survival (PFS), and grade ≥3 immune-related adverse events. RESULTS: From August 2016 to October 2022, 31 patients with SOT (98% kidney) and solid tumors were identified (36.0% lung cancer, 19.4% melanoma, 13.0% genitourinary cancer, 6.5% gastrointestinal cancer). Programmed death-ligand 1 expression was positive in 29% of tumors. Median age was 61 years, 69% were males, and 71% received ICB as first-line treatment. In the whole cohort the ORR was 45.2%, with a 6-month PFS of 56.8%. In the lung cancer cohort, the ORR was 45.5%, with a 6-month PFS of 32.7%, and median overall survival of 4.6 months. The grade 3 immune-related adverse events rate leading to ICB discontinuation was 12.9%. Allograft rejection rate was 25.8%, and risk of rejection was similar regardless of the type of ICB strategy (monotherapy or combination, 28% versus 33%, P = 1.0) or response to ICB treatment. CONCLUSIONS: ICB could be considered a feasible option for SOT recipients with some advanced solid malignancies and no alternative therapeutic options. Due to the risk of allograft rejection, multidisciplinary teams should be involved before ICB therapy.

Assessing the impact of structured reporting on learning how to report lung cancer staging CT: A triple cohort study on inexperienced readers.

PURPOSE: To assess the clinical utility of chest computed tomography (CT) reports for non-small-cell lung cancer (NSCLC) staging generated by inexperienced readers using structured reporting (SR) templates from the Royal College of Radiologists (RCR-SR) and the Italian Society of Medical and Interventional Radiology (SIRM-SR), compared to traditional non-systematic reports (NSR). METHODS: In a cohort of 30 NSCLC patients, six third-year radiology residents reported CT examinations in two 2-month-apart separate sessions using NSR in the first and NSR, RCR-SR, or SIRM-SR in the second. Couples of expert radiologists and thoracic oncologists in consensus evaluated completeness, accuracy, and clarity. All the quality indicators were expressed on a 100-point scale. The Wilcoxon signed ranks, and Wilcoxon-Mann Whitney tests were used for statistical analyses. RESULTS: Results showed significantly higher completeness for RCR-SR (90 %) and SIRM-SR (100 %) compared to NSR (70 %) in the second session (all p < 0.001). SIRM-SR demonstrated superior accuracy (70 % vs. 55 %, p < 0.001) over NSR, while RCR-SR and NSR accuracy did not significantly differ (60 % vs. 62.5 %, p = 0.06). In the second session, RCR-SR and SIRM-SR surpassed NSR in completeness, accuracy, and clarity (all p < 0.001, except p = 0.04 for accuracy between RCR-SR and NSR). SIRM-SR outperformed RCR-SR in completeness (100 % vs. 90 %, p < 0.001) and accuracy (70 % vs. 62.5 %, p = 0.002), with equivalent clarity (90 % for both, p = 0.27). CONCLUSIONS: Inexperienced readers using RCR-SR and SIRM-SR demonstrated high-quality reporting, indicating their potential in radiology residency programs to enhance reporting skills for NSCLC staging and effective interaction with all the physicians involved in managing NSCLC patients.

Immunotherapy in unresectable stage III non-small-cell lung cancer: state of the art and novel therapeutic approaches.

The standard of care for patients with stage III non-small-cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT) followed by 1 year of adjuvant durvalumab. Despite the survival benefit granted by immunotherapy in this setting, only 1/3 of patients are alive and disease free at 5 years. Novel treatment strategies are under development to improve patient outcomes in this setting: different anti-programmed cell death protein 1/programmed death-ligand 1 [anti-PD-(L)1] antibodies after CCRT, consolidation immunotherapy after sequential chemoradiotherapy, induction immunotherapy before CCRT and immunotherapy concurrent with CCRT and/or sequential chemoradiotherapy. Cross-trial comparison is particularly challenging in this setting due to the different timing of immunotherapy delivery and different patients' inclusion and exclusion criteria. In this review, we present the results of clinical trials investigating immune therapy in unresectable stage III NSCLC and discuss in-depth their biological rationale, their pitfalls and potential benefits. Particular emphasis is placed on the potential mechanisms of synergism between chemotherapy, radiation therapy and different monoclonal antibodies, and how this affects the tumor immune microenvironment. The designs and questions tackled by ongoing clinical trials are also discussed. Last, we address open questions and unmet clinical needs, such as the necessity for predictive biomarkers (e.g. radiomics and circulating tumor DNA). Identifying distinct subsets of patients to tailor anticancer treatment is a priority, especially in a heterogeneous disease such as stage III NSCLC.