CT versus FDG-PET/CT response evaluation in patients with metastatic colorectal cancer treated with irinotecan and cetuximab

We compared morphologic computed tomography (CT)-based to metabolic fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/CT-based response evaluation in patients with metastatic colorectal cancer and correlated the findings with survival and KRAS status. From 2006 to 2009, patients were included in a phase II trial and treated with cetuximab and irinotecan every second week. They underwent FDG-PET/CT examination at baseline and after every fourth treatment cycle. Response evaluation was performed prospectively according to Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and retrospectively according to Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Best overall responses were registered. Sixty-one patients were eligible for response evaluation. Partial response (PR) rate was 18%, stable disease (SD) rate 64%, and progressive disease (PD) rate 18%. Partial metabolic response (PMR) rate was 56%, stable metabolic disease rate 33%, and progressive metabolic disease (PMD) rate 11%. Response agreement was poor, κ-coefficient 0.19. Hazard ratio for overall survival for responders (PR/PMR) versus nonresponders (PD/PMD) was higher for CT- than for FDG-PET/CT evaluation. Within patients with KRAS mutations, none had PR but 44% had PMR. In conclusion, morphologic and metabolic response agreement was poor primarily because a large part of the patients shifted from SD with CT evaluation to PMR when evaluated with FDG-PET/CT. Furthermore, a larger fraction of the patients with KRAS mutations had a metabolic treatment response

A retrospective study on immune-related pneumonitis in patients with non-small-cell lung cancer undergoing treatment with PD-1/PD-L1 inhibitors

ABSTRACTBackground Lung cancer patients undergoing treatment with immune checkpoint inhibitors (ICIs) are at risk of developing immune-related (ir-)pneumonitis. Since lung cancer patients have competing reasons for respiratory symptoms, this poses a diagnostic challenge. This study aimed to explore diagnosis and management of ir-pneumonitis in this patient group.Materials and Methods Retrospective database retrieved analysis of patients with non-small cell lung cancer undergoing treatment with PD-1/PD-L1 inhibitors at Department of Oncology, Copenhagen University Hospital, Herlev. Patients being suspected of ir-pneumonitis during the period 01.07.2016 – 15.06-2020 were selected.Results Out of 377 eligible patients, 83 were suspected of ir-pneumonitis. A thoracic computed tomography (CT) was made in 93% of the patients, and 34% had a sputum sample made. A specialist in pulmonology was consulted in seven patient cases. Ir-pneumonitis was radiologically confirmed in 34 patients, however, in 12 patients symptoms could not be confined to ir-pneumonitis and only 22 patients were included in the analysis of the course of treatment. Solely corticosteroids were used as systemic treatment, and the median duration of treatment was 16 weeks (4-34). In seven patients pneumonitis was consistent with recall radiation pneumonitis (RRP).Conclusion Suspected ir-pneumonitis was frequent in this group of patients. The cohort was characterized by high heterogeneity and lack of unequivocal diagnostic conclusions. Treatment of ir-pneumonitis was longer than recommended and involvement of pulmonologist was very infrequent. The result of this study reflects the difficulties in a daily clinical setting to diagnose and manage patients with lung cancer presenting with pulmonary symptoms

Impact of ABCB1 variants on neutrophil depression: A pharmacogenomic study of paclitaxel in 92 women with ovarian cancer

The standard treatment for ovarian cancer in advanced stages is post-surgery treatment with taxane-platin chemotherapy. Despite an initial high response rate, most patients eventually relapse. The dose-limiting toxicities of paclitaxel are neutropenia and neuropathy, but the inter-individual variability is large. The aim of this prospective study was to investigate the impact of genetic variants in key drug metabolizing/transporter genes on toxicity and compliance. CYP2C8*3 and three ABCB1 polymorphisms were chosen for primary analysis, and a host of other candidate genes was explored in 92 prospectively recruited Scandinavian Caucasian women with primary ovarian cancer who were treated with paclitaxel and carboplatin. A single investigator assessed the clinical toxicity in 97% of the patients. Patients carrying variant alleles of ABCB1 C3435T experienced more pronounced neutrophil decrease (63%, 72% and 80% for 3435CC, CT and TT, respectively; p-value 0.03). A similar association was found for G2677T/A, p-value 0.02. For C1236T, there was a trend with p-value 0.06. No statistically significant correlations were found for paclitaxel compliance and sensory neuropathy in the primary analysis. Variants in the drug transporter ABCB1 gene are possibly associated with the neutrophil suppressing effect of paclitaxel in patients with ovarian cancer. This finding has implications for the understanding of bone marrow suppression and future tailored chemotherapy