Development of Radiomic-Based Model to Predict Clinical Outcomes in Non-Small Cell Lung Cancer Patients Treated with Immunotherapy.

Purpose: We aimed to assess the ability of radiomics features extracted from baseline (PET/CT0) and follow-up PET/CT scans, as well as their evolution (delta-radiomics), to predict clinical outcome (durable clinical benefit (DCB), progression, response to therapy, OS and PFS) in non-small cell lung cancer (NSCLC) patients treated with immunotherapy. Methods: 83 NSCLC patients treated with immunotherapy who underwent a baseline PET/CT were retrospectively included. Response was assessed at 6−8 weeks (PET/CT1) using PERCIST criteria and at 3 months with iPERCIST (PET/CT2) or RECIST 1.1 criteria using CT. The predictive performance of clinical parameters (CP), standard PET metrics (SUV, Metabolic Tumor volume, Total Lesion Glycolysis), delta-radiomics and PET and CT radiomics features extracted at baseline and during follow-up were studied. Seven multivariate models with different combinations of CP and radiomics were trained on a subset of patients (75%) using least absolute shrinkage, selection operator (LASSO) and random forest classification with 10-fold cross-validation to predict outcome. Model validation was performed on the remaining patients (25%). Overall and progression-free survival was also performed by Kaplan−Meier survival analysis. Results: Numerous radiomics and delta-radiomics parameters had a high individual predictive value of patient outcome with areas under receiver operating characteristics curves (AUCs) >0.80. Their performance was superior to that of CP and standard PET metrics. Several multivariate models were also promising, especially for the prediction of progression (AUCs of 1 and 0.96 for the training and testing subsets with the PET-CT model (PET/CT0)) or DCB (AUCs of 0.85 and 0.83 with the PET-CT-CP model (PET/CT0)). Conclusions: Delta-radiomics and radiomics features extracted from baseline and follow-up PET/CT images could predict outcome in NSCLC patients treated with immunotherapy and identify patients who would benefit from this new standard. These data reinforce the rationale for the use of advanced image analysis of PET/CT scans to further improve personalized treatment management in advanced NSCLC.

Targeted RNA-sequencing assays: a step forward compared to FISH and IHC techniques?

INTRODUCTION: ALK and ROS1 rearrangements are molecular targets of several tyrosine kinase inhibitors. RNA-sequencing approaches are regarded as the new standard for fusion gene detection, representing an alternative to standard immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) techniques. PATIENTS AND METHODS: We aimed to compare two recent amplicon-based RNA-sequencing techniques: FusionPlex® Alk Ret Ros1 v2 Kit (Archer® ) with FHS-003Z-12-Human Lung Cancer Panel (Qiagen® ) and assessed the accuracy of the data for therapy management. Thirty-seven formalin-fixed paraffin-embedded non-small cell carcinoma (NSCC) lesions initially explored by IHC and FISH were selected for RNA-sequencing analysis. RESULTS: Qiagen® and Archer® kits produced similar results and correctly identified 85.1% (23/27) and 81.5% (22/27) of IHC/FISH ALK- and ROS1-positive samples, respectively, and 100% (6/6) of the negative samples. With regard to the ambiguous IHC-positive/FISH-negative cases, RNA-sequencing confirmed 75% (3/4) of the FISH conclusion. Although not statistically significant, patients with common EML4-ALK variants presented shorter overall survival and progression-free survival compared with patients harboring rare variants. CONCLUSION: Our findings assessed the implementation of RNA-sequencing approaches to explore ALK and ROS1 rearrangements from formalin-fixed paraffin-embedded samples. We highlighted the similarities between Qiagen® and Archer® kits in terms of handling time, cost, and outcomes. We confirmed the feasibility of molecular testing in routine organization and its possible use not only as an alternative for standard IHC and FISH techniques, but as a supplementary technique helping to classify discrepant cases.

Anti-tumour effect of low molecular weight heparin in localised lung cancer: a phase III clinical trial.

The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated.Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg-1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival.In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±sd age was 61.6±8.9 years, 190 (34.6%) patients had stage II-III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92-1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68-1.30; p=0.70).Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I-IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.

Real-life effectiveness of erlotinib as second-line treatment of stage IIIB/IV squamous non-small cell lung cancer: Results of the PEPiTA observational study.

OBJECTIVES: Erlotinib, an inhibitor of tyrosine kinase activity of the epidermal growth factor receptor, is effective in non-small cell lung cancer (NSCLC). Data on erlotinib use in squamous NSCLC are limited. This observational study aimed at evaluating the efficacy and safety of second-line erlotinib in patients with stage IIIB/IV squamous NSCLC in a real-life setting. MATERIAL AND METHODS: Patients with predominantly squamous stage IIIB/IV NSCLC, who failed first-line platinum-based therapy, were recruited and followed-up for 12 months. Patients underwent visits each trimester. Data were derived from case report forms, and functional assessment of cancer therapy-lung (FACT-L) questionnaires. RESULTS: A total of 152 patients were enrolled; the majority were males (90%) and mean age was 67.7 years. All patients had squamous (97%) or predominantly squamous (3%) NSCLC, of stage IIIB (21%) or IV (79%). Median progression free survival (PFS) and overall survival were 3 and 5.8 months, respectively. Disease progression was observed in the majority of the patients, mostly due to progression of primary tumour and/or metastatic sites, and led to death in 91/107 of patients. Of the 107 deaths reported, none were due to erlotinib. FACT-L questionnaires were interpretable up to the first visit and were in line with PFS data, showing a relatively good quality of life up to Month 3 (mean total score=78.8). No new or unexpected safety issues were reported. CONCLUSIONS: The results of this real-life cohort study like those of previous phase III/IV subgroups study analyses indicate that erlotinib is a valuable option for second-line treatment of stage IIIB/IV squamous NSCLC.

Visual versus quantitative assessment of intratumor 18F-FDG PET uptake heterogeneity: prognostic value in non-small cell lung cancer.

UNLABELLED: The goal of this study was to compare visual assessment of intratumor (18)F-FDG PET uptake distribution with a textural-features (TF) automated quantification and to establish their respective prognostic value in non-small cell lung cancer (NSCLC). METHODS: The study retrospectively included 102 consecutive patients. Only primary tumors were considered. Intratumor heterogeneity was visually scored (3-level scale [Hvisu]) by 2 nuclear medicine physicians. Tumor volumes were automatically delineated, and heterogeneity was quantified with TF. Mean and maximum standardized uptake value were also included. Visual interobserver agreement and correlations with quantitative assessment were evaluated using the κ test and Spearman rank (ρ) coefficient, respectively. Association with overall survival and recurrence-free survival was investigated using the Kaplan-Meier method and Cox regression models. RESULTS: Moderate correlations (0.4 < ρ < 0.6) between TF parameters and Hvisu were observed. Interobserver agreement for Hvisu was moderate (κ = 0.64, discrepancies in 27% of the cases). High standardized uptake value, large metabolic volumes, and high heterogeneity according to TF were associated with poorer overall survival and recurrence-free survival and remained an independent prognostic factor of overall survival with respect to clinical variables. CONCLUSION: Quantification of (18)F-FDG uptake heterogeneity in NSCLC through TF was correlated with visual assessment by experts. However, TF also constitutes an objective heterogeneity quantification, with reduced interobserver variability, and independent prognostic value potentially useful for patient stratification and management.