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Background: Circulating tumor cells (CTCs) are a promising source of biological information in cancer. Data correlating PD-L1 expression in CTCs with patients’ response to immune checkpoint inhibitors (ICIs) in non–small-cell lung cancer (NSCLC) are still lacking. Methods: This is a prospective single-center cohort study enrolling patients with advanced NSCLC. CTCs were identified and counted with the CellSearch system. PD-L1 expression on CTCs was assessed with phycoerythrin-conjugated anti-human PD-L1 antibody, clone MIH3 (BioLegend, USA). Primary endpoint was the correlation between the CTCs PD-L1 expression and overall survival (OS). Among secondary objectives, we evaluated the correlation between PD-L1 expression on CTCs and matched tumor tissue and the correlation of CTC number and baseline tumor size (BTS). Results: Thirty-nine patients treated with anti-PD-1/PD-L1 agents as second- or third-line therapy were enrolled. Patients were divided into 3 groups: no CTC detectable (CTCnull, n = 15), PD-L1 positive CTC (CTCpos, n = 13), and PD-L1 negative CTC (CTCneg, n = 11). Median OS in patients with CTCneg was 2.2 months, 95% confidence interval (CI), 0.8-3.6 (reference) versus 3.7 months, 95% CI, 0.1-7.5 (hazard ratio [HR] 0.33; 95% CI, 0.13-0.83; P = .019) in patients with CTCpos versus 16.0 months, 95% CI, 2.2-29.8 (HR 0.17; 95% CI, 0.06-0.45; P< .001) in patients with CTCnull. No correlation was found between PD-L1 expression on CTCs and on tumor tissue. CTC number was correlated with BTS. Conclusion: PD-L1 expression on CTCs is a promising biomarker in patients with NSCLC treated with ICIs. Further validation as predictive biomarker is needed.

We report the case of a young woman who developed metastatic melanoma in the inguinal nodal region, which acquired chondrosarcomatous differentiation and preserved the BRAF mutation found in the primary tumor. The patient was treated with a BRAF/MEK inhibitor combination therapy (dabrafenib/trametinib), which was demonstrated to be effective and well‐tolerated., BRAF‐mutated melanoma with chondrosarcomatoid differentiation and response to targeted therapy.

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Objectives Patients harboring rearrangements of the ROS1 gene are eligible for first-line therapy with Crizotinib, which represents the best available treatment option. Diagnostic criteria, based on break-apart fluorescence in situ hybridization, were mirrored from ALK by analogy and include tumors with 5' deletions. However, the probability of response to Crizotinib in patients with 5' deletion in ROS1 is unknown given the rarity of this condition. Materials and methods We hereby describe clinical outcome of 8 NSCLC patients harboring a 5' deletion at FISH treated with Crizotinib Results Three out of 4 cases whose 5' deletion was confirmed by NGS as a ROS1/EZR fusion displayed an objective response to Crizotinib while a case with ROS1/SDC4 fusion did not. By contrast, among the 4 cases where NGS did not detect ROS1 gene fusions only 2 patients responded to crizotinib therapy with one also harboring a concomitant EML4-ALK rearrangement. Conclusion 5' ROS1 deletions detected by FISH are associated with a high chance of response to Crizotinib in NSCLC, similarly to canonical ROS1 split-apart FISH rearrangements. However, the confirmation of the ROS1 gene fusion with at least another method, such as NGS, seems beneficial in order to define the ROS1 fusion partner and to avoid possible false positive results.

none 9 no Atherosclerosis is considered to be a T-cell-driven disease since the interaction between resident cells, immune cells and their products has been recognized to promote the development of atheromatous plaques in the arterial walls [1]. The process of atherosclerosis evolves from a prelesional phase, which is potentially reversible, to complicated lesions characterized by the formation of a fibrous cap and vulnerable plaques, followed by possible rupture and atherothrombosis. none Gelsomino, F.; Fiorentino, M.*; Zompatori, M.; Poerio, A.; Melotti, B.; Sperandi, F.; Gargiulo, M.; Borghi, C.; Ardizzoni, A. Gelsomino, F.; Fiorentino, M.*; Zompatori, M.; Poerio, A.; Melotti, B.; Sperandi, F.; Gargiulo, M.; Borghi, C.; Ardizzoni, A.

Non-small cell lung cancer (NSCLC) can be associated with pulmonary cystic airspaces (pCAs). pCAs are radiologically classified into four types based on whether the nodule or mass extrudes the wall of the pCAs. In most cases, response evaluation of these lesions by Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 is challenging. Based on the observation of a case of morphological evolution of pCAs associated with NSCLC in a patient receiving immune checkpoint inhibitor (ICI), we reviewed retrospectively imaging scans of 92 consecutive advanced patients with NSCLC treated at our institution. Overall, three cases of pCAs associated with NSCLC obtained a remarkable change following ICI. Of note, these changes were not always seen in the context of a clear radiological objective response. The morphological changes observed may reflect a novel pattern of response to immunotherapy agents that clinicians should be aware of. This pattern of response, not reported before, warrants further investigation and, if confirmed, we believe that it should be considered in future version of immune RECIST.

BACKGROUND: Targeted therapies in melanoma have shown clinical benefit in incrementing the overall survival of metastatic patients. However, cutaneous adverse events have been frequently associated with these drugs. METHODS: We report our experience in the management of patients treated with dabrafenib for metastatic melanoma, focusing on the monitoring of pigmented lesions. Dermatologic evaluation was performed during the first visit, at the start of each treatment and subsequently after every four weeks. Global nevi count, videodermoscopy of suspected lesions, and surgical excisions when necessary were performed at the beginning of the treatment and every fourth week. All other cutaneous adverse events (cAEs) were noted and documented. Eleven patients were included. RESULTS: The most important cAEs included palmo-plantar hyperkeratosis, diffuse xerosis and pigmented lesion changes. Regarding the latter, in 6 patients, especially in the first months of treatment, we observed hyperpigmentation and hyperkeratosis of the nevi, of the pigmented mucosae and, in one patient, hyperkeratotic changes on a cutaneous metastasis. Histopathology of the excised lesions showed one ex novo melanoma occurrence and benign changes to pre-existing nevi. CONCLUSIONS: The awareness of the importance of sequential monitoring of pigmented lesions, with particular attention to the lesions of new onset, is crucial for the best management of these complex patients.

This study compares two cytotoxic regimens comprising the same dose and schedule of cisplatin (CP) plus vinorelbine (VNR) or gemcitabine (GEM) administered under the same schedule to patients with advanced non-small cell lung cancers (NSCLC). From April 1998 to February 2003, 285 patients were randomised to receive either VNR 25 mg/m 2 on days 1 and 8 as an intravenous (i.v.) bolus plus CP 75 mg/m 2 on day 1 (regimen A) or GEM 1200 mg/m 2 on days 1 and 8 as an i.v. 30-min infusion plus CP 75 mg/m 2 on day 1 (regimen B). Both treatments were recycled every 21 days. If no progression had occurred after six cycles, the patients continued to receive VNR or GEM monochemotherapy weekly. Cross-over of the two single agents was considered if disease progression occurred. Objective response (OR), time to progression (TTP) and overall survival (OS) were analysed according to the intention-to-treat principle. 272 patients were ultimately eligible (137 on A and 135 on B). Their main characteristics were: male/female ratio 214/58; median age 63 (range 32-77) years; median Karnofsky Performance Status (PS) 80 (range 70-100); stage IIIB 34%, stage IV 61%, recurrent disease 5%; histology - epidermoid 29%, adenocarcinoma 53%, other NSCLC 18%. The characteristics of the patients in the two arms were well matched. The following response rates were observed in regimens A and B, respectively: complete response (CR) 0.7% and 3.7%, partial response (PR) 31.9% and 22.2% (P = 0.321). Median CR + PR duration was 8 months in both arms. Clinical benefit represented by an improvement in symptoms was evident in 25.7% and 28.1%, respectively. Median TTP was 5 months in both arms and median OS 11 months in both arms. Grade III-IV neutropenia occurred in 30.7% and 17.7% of the patients in arms A and B, respectively (P = 0.017); thrombocytopenia occurred in 0% and 9.3% (P = 0.004), respectively. No difference in the incidence of anaemia was observed. Non-haematological toxicity was generally mild: a higher incidence of grade 1-2 peripheral neurotoxicity and grade 1-2 local toxicity with regimen A and grade 1-2 liver toxicity with regimen B was reported. A pharmaco-economic comparison showed a difference between the two doublets, principally due to the different costs of VNR and GEM. Under the study conditions the combination of VNR or GEM with the same dose and schedule of CP produced similar OR, clinical benefits, TTP and OS in advanced NSCLC, and only mild toxicological differences were observed. Pharmaco-economic evaluation favoured the CP + VNR doublet. © 2004 Elsevier Ltd. All rights reserved.