A randomized phase II clinical trial of stereotactic body radiation therapy (SBRT) and systemic pembrolizumab with or without intratumoral avelumab/ipilimumab plus CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells in solid tumors.

BACKGROUND: Radiotherapy (RT) synergizes with immune checkpoint blockade (ICB). CD1c(BDCA-1)+/CD141(BDCA-3)+ myeloid dendritic cells (myDC) in the tumor microenvironment are indispensable at initiating effector T-cell responses and response to ICB. METHODS: In this phase II clinical trial, anti-PD-1 ICB pretreated oligometastatic patients (tumor agnostic) underwent a leukapheresis followed by isolation of CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC. Following hypofractionated stereotactic body RT (3 × 8 Gy), patients were randomized (3:1). Respectively, in arm A (immediate treatment), intratumoral (IT) ipilimumab (10 mg) and avelumab (40 mg) combined with intravenous (IV) pembrolizumab (200 mg) were administered followed by IT injection of myDC; subsequently, IV pembrolizumab and IT ipilimumab/avelumab were continued (q3W). In arm B (contemporary control arm), patients received IV pembrolizumab, with possibility to cross-over at progression. Primary endpoint was 1-year progression-free survival rate (PFS). Secondary endpoints were safety, feasibility, objective response rate, PFS, and overall survival (OS). RESULTS: Thirteen patients (10 in arm A, eight non-small cell lung cancer, and five melanoma) were enrolled. Two patients crossed over. One-year PFS rate was 10% in arm A and 0% in arm B. Two patients in arm A obtained a partial response, and one patient obtained a stable disease as best response. In arm B, one patient obtained a SD. Median PFS and OS were 21.8 weeks (arm A) versus 24.9 (arm B), and 62.7 versus 57.9 weeks, respectively. An iatrogenic pneumothorax was the only grade 3 treatment-related adverse event. CONCLUSION: SBRT and pembrolizumab with or without IT avelumab/ipilimumab and IT myDC in oligometastatic patients are safe and feasible with a clinically meaningful tumor response rate. However, the study failed to reach its primary endpoint. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT04571632 (09 AUG 2020). EUDRACT: 2019-003668-32. Date of registration: 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022.

Features of post-obstructive pneumonia in advanced lung cancer patients, a large retrospective cohort.

BACKGROUND: Post-obstructive pneumonia refers to an infection of the lung parenchyma distal to a bronchial obstruction. Previous experience-based studies reported a high prevalence of this infection among patients with a medical history of advanced lung neoplasia, up to 40-55%. OBJECTIVES: The current study was designed to investigate the features of post-obstructive pneumonia in lung cancer, including its predictors and the discriminants for 30-day mortality. METHOD: Data from medical records at the tertiary University centre, UZ Brussel, were collected retrospectively between January 2016 and January 2021. Patients affected by lung cancer stages III and IV were included. A multidisciplinary team, composed of a pulmonologist, an infectious disease specialist and a chest radiologist, identified patients affected by post-obstructive pneumonia. RESULTS: A total of 408 patients were included, of which 46 (11%) were diagnosed with post-obstructive pneumonia. Multivariable logistic regression for predictors of disease onset found significant differences for squamous cell carcinoma (OR:2.46 p-value: .014) and hilar location of the tumour (OR:2.72 p-value: .021). However, no significant differences were identified with regards to age or comorbidities. Furthermore, 30-day mortality among post-obstructive pneumonia patients was 30%. Multivariable logistic regression for prediction of 30-day mortality found significant differences in CURB-65 score (OR:73.20 p-value: .001) and smoking status (OR:0.009 p-value: .015). CONCLUSIONS: Within this cohort, the prevalence of post-obstructive pneumonia in advanced lung cancer patients was lower than previously reported. Squamous cell carcinoma and a hilar tumour location were two variables associated with disease development, independent of age and comorbidities. Furthermore, a higher CURB-65 score at post-obstructive pneumonia diagnosis was correlated with mortality.

A woman and her breathtaking jewelry.

We present the case of a 45-year-old woman, working as a silver polisher since 11 years, complaining of dyspnea on exertion and dry cough. Intensive diagnostic workup, including high-resolution CT scan of the chest and lung biopsy by VATS led to the diagnosis of pulmonary siderosis. Pulmonary siderosis is a benign, non-fibrotic type of pneumoconiosis caused by inhalation of iron oxide, which is generally asymptomatic (except in concurrent smoking or concurrent silicosis). Combination of relevant exposure and the typical findings on CT-imaging (centrilobular nodules without cranio-caudal gradient) usually strongly suggest the diagnosis, but this should always be discussed at a multidisciplinary consultation. This includes discussing whether to perform a lung biopsy for histological confirmation. Cessation of the causative exposure is the only-treatment one can take and then radiological features can improve and even disappear of time. Unfortunately, this treatment has an enormous impact on patient's life because it implies changing profession. Preventive measures can be taken by employers (respiratory equipment and ventilation). This case illustrates that physicians should stay vigilant about occupational exposures in clinical practice as well as the need for multidisciplinary consult in patients suspected of having interstitial lung disease.

The Value of 18F-FDG PET/CT in Predicting the Response to PD-1 Blocking Immunotherapy in Advanced NSCLC Patients with High-Level PD-L1 Expression.

BACKGROUND: The objective of this study was to evaluate if 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-derived parameters are useful in predicting response and survival after programmed cell death protein 1 (PD-1) blocking immunotherapy in patients with advanced NSCLC characterized by a high programmed death-ligand 1 (PD-L1) expression (≥50%) on immunohistochemistry. PATIENTS AND METHODS: In 30 patients with advanced stage IV non-small-cell lung cancer (NSCLC) and high PD-L1 expression, 18F-FDG PET/CT parameters before start of treatment with PD-1 blocking immunotherapy were evaluated retrospectively. In 24 out of the 30 patients, 18F-FDG PET/CT was available 8 to 9 weeks after start of the treatment. Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and metabolic responses assessed on 18F-FDG PET/CT were compared. RESULTS: Median follow-up was 20 months (range, 4.2-37.6). Median PD-L1 expression was 80%. The objective response rate with RECIST 1.1 was 53.3%. Median progression-free survival (PFS) was 12.4 months (95% confidence interval [CI], 1.0-37.8), and median overall survival (OS) was 14.9 months (95% CI, 2.4-38.2). Baseline 18F-FDG PET/CT parameters did not differ between responders and non-responders (all P > .05). The maximum standardized uptake value (SUVmax) was the only 18F-FDG PET/CT parameter associated with PFS (P = .04), with a trend for OS (P = .06). At first evaluation, response according to total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) were associated with PFS and OS (both P < .0001). This was not the case for RECIST 1.1 (P = .29 for PFS and P = .38 for OS). CONCLUSION: Clinical response and survival were independent from metabolic tumor volume at baseline. Reduction of metabolic tumor volume after 8 to 9 weeks of treatment was a better predictor for prolonged survival than RECIST 1.1.