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Context The aim of the study was to determine risk factors of recurrence in resected pancreatic cancer. Methods We retrospectively analyzed 43 patients who underwent pancreatic resection for ductal adenocarcinoma, from January 2006 to December 2009. Demographic (age, sex), surgical (type of resection), pathological data (grading, TNM stage, lymph node ratio, R status, perineural and vascular invasion) and type of therapy (surgery alone versus surgery plus different adjuvant treatment) were evaluated. Adjuvant chemotherapy was performed in 24 patients with R0 status: 19 received gemcitabine alone (GEM) (1,000 mg/m2 days 1, 8, 15 every 28) and 5 GEM plus cisplatin (CDDP) (75 mg/m2 day 1 every 28). Radiotherapy was performed in 9 patients with R1 status: 6 associated with GEM alone and 3 with GEM plus CDDP. Results Overall survival (OS) and disease free survival (DFS) were (mean±SD) 23.3±3.8 and 12.8±1.2 months, respectively. Recurrence of disease occurred in 31 out of 43 patients (72.1%) with local relapse in 11 (35.5%) and distant metastases in 20 patients (65.5%). Among the prognostic factors evaluated, lymph node ratio and grading were significantly related to recurrence (lymph node ratio P=0.010; G1 vs. G2-G3, P=0.012). Regarding to postoperative treatment there were no significant differences between surgery alone versus surgery plus adjuvant therapy (median DFS: 16.8 versus 11 months; P=0.103). Risk of recurrence was increased in patients treated with chemo-radiotherapy compared those who received chemotherapy or surgery alone (P=0.042 and P=0.09, respectively). Conclusions The risk of recurrence was higher in patients treated with surgery plus chemoradiotherapy if compared to the others, probably because the combination treatment with additional radiotherapy was performed in R1 status patients.

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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Atherosclerosis is considered an irreversible process, with crucial contribution of inflammation and immune cells. Impact of cancer immunotherapy on a partly immune-driven disease, such as atherosclerosis, is poorly understood, but preclinical models suggest its worsening on programmed death/ligand-1 (PD-1/PD-L1) inhibitors. In a previously reported cohort of 11 patients with non-small cell lung cancer (NSCLC) treated with nivolumab and pre-existing complicated atheromatous plaques, 3 patients had a dramatic radiologic reduction of aortic plaques while on nivolumab; of these 3, 2 died receiving no further treatment. The remaining patient was an 83-year-old woman with history of arterial hypertension and hypothyroidism who was diagnosed with locally advanced squamous NSCLC. At relapse, complicated aortic atheromatous plaques were demonstrated on scans. The patient was then treated with nivolumab obtaining stable disease at radiological assessment, which also demonstrated almost complete vanishing of aortic plaques. After relapse and interval treatment with chemotherapy, she experienced new development of aortic atheromatous plaques. At further relapse she received atezolizumab, which yielded disease response and new reduction in aortic plaques, until nearly complete resolution. The observation of a repeated improvement of atheromatous plaques on treatment with PD-1/PD-L1 inhibitors favors the protective role of T cells on atheromatous plaques that is impaired by PD-L1 expression by plaque-associated macrophages. Validation by independent and prospective observation is needed.

Background Despite sensitivity to first-line chemotherapy, most small-cell lung cancer (SCLC) patients relapse. In this setting, topotecan demonstrated modest activity with significant toxicity. Paclitaxel was also active. This study was designed to evaluate activity and safety of nab-paclitaxel in relapsed SCLC. Methods In this multicentre prospective Phase 2 trial, patients with refractory or sensitive SCLC progressed to first-line platinum-based chemotherapy received nab-paclitaxel 100 mg/smq on days 1, 8, 15 every 4 weeks up to six cycles, progressive disease or intolerable toxicity. Primary endpoint was investigator-assessed objective tumour response. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results Of the 68 patients treated, partial response was 8% in the refractory cohort and 14% in the sensitive cohort. Most common toxicities of any grade were fatigue (54%), anaemia (38%), neutropenia (29%), leukopenia (26%) and diarrhoea (21%). Median PFS was similar in both refractory (1.8 months) and sensitive cohorts (1.9 months), while median OS was longer in sensitive one (6.6 versus 3.6 months). Conclusions Although nab-paclitaxel has shown some modest anti-tumour activity in relapsed SCLC, associated with a favourable toxicity profile, the primary end-point of the study was not met. Clinical Trial registration Clinical Trial registration number is ClinicalTrials.gov Identifier: NCT03219762.

Clinical Practice Points •Immune checkpoint inhibitors (ICI) have changed the treatment landscape of advanced non–small-cell lung cancer, as they have shown their superiority to chemotherapy in the first-line setting in tumors having programmed death ligand 1 (PD-L1) expression ≥ 50% and in patients with pretreated disease, regardless of PD-L1 expression. • The efficacy and safety of ICI rechallenge in those patients whose disease failed to respond to a prior treatment with these agents remain unclear. • We report the case of a 79-year-old woman, a smoker, with locally advanced, TP53-mutated squamous non–small-cell lung cancer, whose disease responded to an anti–PD-L1 agent despite having experienced disease progression during a prior anti–programmed cell death 1 treatment that followed first-line chemoradiotherapy. The anti–PD-L1 therapy was still ongoing after 9 months. • Our case suggests that ICI rechallenge could be safe and effective, even in a subpopulation of patients with disease that did not respond to prior ICI therapy.

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.

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.

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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.

3067Background: Nivolumab is the first checkpoint inhibitor approved for the treatment of squamous non small cell lung cancer (Sq-NSCLC) to show a survival benefit in a randomised phase III trial. ...