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The combination of immune-checkpoint inhibitors (ICI) and platinum-pemetrexed chemotherapy (CT) in first-line setting improved survival outcomes of advanced non-small cell lung cancer (NSCLC) patients. Among the various adverse events, renal toxicity can be a relevant safety issue.We conducted a single-center, observational retrospective study including consecutive patients treated with upfront CT-ICI for advanced nonsquamous NSCLC to investigate incidence and clinical characteristics of acute kidney injury (AKI) using 'Acute Kidney Injury Working Group of Kidney Disease: Improving Global Outcomes' (KDIGO) definition.A total of 89 patients received a first-line CT/ICI. The median age was 69 years. 60.7 % were male, and 87.6 % had an ECOG PS of 0-1. 92.1 % had a baseline glomerular filtration rate of at least 60 ml/min. According to KDIGO criteria, 25 (28 %) patients developed AKI. Considering risk factors for AKI onset, patients receiving10 cycles of CT/ICI were more likely to experience AKI (p 0.001). No other associations were found with other variables, including concomitant medications. Any component of the treatment was discontinued (pemetrexed pembrolizumab or both) in 10 (40 %) patients, and 9 patients (36 %) were addressed to nephrological consultation. These patients had higher mean creatinine variation from baseline (1 vs 0.6 mg/dl, p = 0.025) and creatine level (1.8 vs 1.4 mg/dl, p = 0.015), but lower eGFR (35.7 vs 54.2 ml/min, p = 0.011) in comparison to patients not addressed. No patients had microscopic hematuria or pyuria, but mild proteinuria (0.8 g/24 h) was found in 4 patients. A renal biopsy was performed on 3 patients, revealing acute tubule interstitial nephritis (ATIN), karyomegalic interstitial nephritis, and acute tubular necrosis (ATN).Renal toxicity represents a challenging adverse event that could negatively impact outcomes of metastatic nonsquamous NSCLC patients receiving CT/ICI demanding a multidisciplinary approach.

Background Many patients with non-small cell lung cancer (NSCLC) derive poor benefit from immunotherapy (IO). For some of them, adding chemotherapy (CT) can improve the outcomes, but the reliability of programmed death–ligand 1 (PD-L1) expression as the only biomarker to distinguish these patients is unsatisfactory. We sought to detect clinicopathological and molecular predictive factors of survival that might be added to PD-L1 expression in the selection of patients who should receive IO alone or chemoimmunotherapy (CIT). Methods We conducted a systematic search of randomized controlled clinical trials investigating IO, alone or with CT, vs CT alone in treatment-naïve advanced NSCLC patients. Meta-analyses and meta-regression analyses were performed to investigate IO alone vs CT, CIT vs CT, and IO alone vs CIT. Results A total of 14 367 patients with advanced NSCLC across 25 randomized controlled clinical trials were included. Squamous histology, male sex, current and former smoker status, PD-L1 expression of 50% or more, and high tumor mutational burden (TMB) correlated with improved survival with IO alone compared with CT. Conversely, female sex, no smoking history, negative PD-L1 expression, and low TMB correlated with unsatisfactory outcomes with IO alone vs CT but not with CIT vs CT. CIT improved survival vs IO alone in female patients, never smokers, those having a PD-L1 expression of 1% or more (but not with a PD-L1 of ≥ 50%) or a low TMB and in patients with central nervous system metastasis. Conclusions These findings suggest some clinicopathological and molecular features that, added to PD-L1 expression, could help in the selection of the most appropriate first-line IO-based treatment for advanced NSCLC patients.

Metastatic uveal melanoma (MUM) is the most common form of noncutaneous melanoma. It is different from its cutaneous counterpart and is characterized by a very poor prognosis. Despite groundbreaking improvements in the treatment of cutaneous melanoma, there have been few advances in the treatment of MUM, and standard treatments for MUM have not been defined. We performed a systematic review focusing our attention on all interventional studies, ongoing or already published, concerning the treatment of MUM. We present results from studies of chemotherapy, targeted therapy, immunotherapy and liver-directed therapies. Although the results in this setting have been disappointing until now, trials investigating novel immunotherapeutic strategies alone and in combination with targeted agents and liver-directed therapies are ongoing.

The widespread use of more sensitive detection tools, such as next-generation sequencing, has increased the identification of a variety of BRAF mutations other than V600E/K in melanoma patients. However, there is a lack of established data regarding the efficacy of BRAF/MEK inhibitors and immune-checkpoint immune inhibitors (ICI) for these patients. We performed a retrospective study, including all the patients diagnosed with stage III or IV melanoma that were referred to the University Hospital of Bologna from 2011 to 2021, carrying a non-V600E or V600K mutation of BRAF and who were started on systemic treatment. We found 14 patients with stage III or IV melanoma harboring the following BRAF mutations: V600R, V600_K601delinsE, K601E, p.T599_V600insT, L597V, G466R, S467L, and A598T. Of note, G466R and A598T BRAF mutations have never been previously reported in melanoma. Four patients received combined BRAF/MEK inhibitors, two patients BRAF inhibitor monotherapy, and six patients were treated with ICI for advanced melanoma; four patients received adjuvant treatment with nivolumab. Given the few cases and the absence of randomized clinical trials, it is important to report clinical experiences, which can guide physicians in the treatment of melanomas harboring rare BRAF mutations.

In non-small cell lung cancer (NSCLC), BRAF class 1 alterations are effectively targeted by BRAF inhibitors. Conversely, targeted therapies have very low or absent activity in patients carrying class 2 and 3 alterations. The spectrum of BRAF alterations in NSCLC patients, and their accompanying clinical features, genomic landscape and treatment outcomes have been poorly reported.We identified BRAF alterations of defined functional class across different tumors through a systematic review. Then, we selected NSCLC patients carrying BRAF alterations, according to the systematic review, in the cBioPortal (cBioPortal cohort) to collect and analyze clinical, biomolecular and survival data. Finally, we identified NSCLC patients carrying BRAF non-V600 mutations enrolled in POPLAR and OAK trials (POPLAR/OAK cohort), extracting clinical and survival data for survival analyses.100 different BRAF non-V600 alterations were identified through the systematic review. In the cBioPortal cohort (Different classes of BRAF alterations confer distinctive clinical features, biomolecular signature and disease behavior to NSCLC patients. Non-V600 alterations are characterized by poor prognosis, but key gene co-alterations involved in cancer cell survival and immune pathways may suggest their potential sensitivity to tailored treatments.

Melanoma in giant congenital nevus (M-GCN) is a rare and potentially lethal neoplasm. In children, M-GCN appears as a dermal/deep-seated melanoma (DDM-GCN) with histopathologic features difficult to distinguish from proliferative nodules (PNs-GCN). DDM-GCN in adults is an anecdotal entity and only 8 cases have been described and genetically characterized. We report the first case of DDM-GCN in a 34-year-old man characterized with a large-panel next-generation sequence (NGS) highlighting a TP53 mutation with a UV-signature (C>T substitution) in DDM but not in PNs-GCN and GCN. Curiously, DDM showed an aberrant p16 overexpression without detection of CDKN2A mutation at NGS. In line with previous studies, it supports a different pathway in children and adults: UV-induced mutations may be involved in the latter not only by CDKN2A but also by TP53 mutations, with a potentially confusing overexpression of p16 protein. While these data need to be confirmed in larger cases series, our results show that NGS could be an additional genetic diagnostic tool in DDM-GCN.

Simple Summary The introduction of immune checkpoint inhibitors and targeted therapy for the treatment of unresectable advanced or metastatic melanoma has changed the prognosis of melanoma patients. Five-year overall survival rates for metastatic melanoma have increased from less than 10% up to 40–50%. Despite this revolution in advanced melanoma treatment, many patients do not benefit from currently available therapies or do not achieve durable responses. The introduction of new agents and new strategies of treatment is necessary to improve outcomes. Abstract The prognosis of patients with advanced cutaneous melanoma has radically changed in the past decade. Nevertheless, primary or acquired resistance to systemic treatment occurs in many cases, highlighting the need for novel treatment strategies. This review has the purpose of summarizing the current area of interest for the treatment of metastatic or unresectable advanced cutaneous melanoma, including data from recently completed or ongoing clinical trials. The main fields of investigation include the identification of new immune checkpoint inhibitors (anti-LAG3, GITR agonist and anti-TIGIT), adoptive cell therapy, vaccines, engineered TCR therapy, IL-2 agonists, novel targets for targeted therapy (new MEK or RAF inhibitors, HDAC, IDO, ERK, Axl, ATR and PARP inhibitors), or combination strategies (antiangiogenetic agents plus immune checkpoint inhibitors, intra-tumoral immunotherapy in combination with systemic therapy). In many cases, only preliminary efficacy data from early phase trials are available, which require confirmation in larger patient cohorts. A more in-depth knowledge of the biological effects of the molecules and identifying predictive biomarkers remain crucial for selecting patient populations most likely to benefit from novel emerging treatment strategies.

No abstract available

Background: An acceptable risk-benefit ratio may encourage the prescription of immune checkpoint inhibitors (ICI) near the late stage of life. The lung immune prognostic index (LIPI) was validated in advanced non-small cell lung cancer (NSCLC) patients treated with ICIs. The palliative prognostic (PaP) score without clinical prediction of survival (PaPwCPS) predicts early mortality probability in terminal cancer patients. Methods: We performed a retrospective study including 182 deceased advanced NSCLC patients, treated with single-agent ICI at our Institution. Two prognostic categories of high and low mortality risk were identified through ROC curve analysis for PaPwCPS and LIPI scores. Results: Most were >65 years of age (68.3%) and received second-line ICI (61.2%). A total of 29 (15.9%) and 131 (72.0%) patients died within 30 and 90 days from treatment start, respectively. A total of 81 patients (44.5%) received ICI during the last month of life. Baseline PaPwCPS and LIPI scores were assessable for 78 patients. The AUC of ROC curves was significantly increased for PaPwCPS as compared with LIPI score for both 30-day and 90-day mortality. A high PaPwCPS score was associated in multivariate analysis with increased 30-day (HR 2.69, p = 0.037) and 90-day (HR 4.01, p < 0.001) mortality risk. A high LIPI score was associated with increased 90-day mortality risk (p < 0.001). Conclusion: We found a tendency towards ICI prescription near the late stage of life. The PaPwCPS score was a reliable predictor of 30- and 90-day mortality.

Background: To compare quality of life (QoL) of patients receiving early palliative care (EPC) vs . standard oncologic care (SOC). Methods: Pragmatic, multicenter, randomized trial at five University and Community Hospital Cancer Centers in Northern Italy. Advanced non-small cell lung, gastric, pancreatic and biliary tract cancer patients diagnosed within the previous 8 weeks. In the EPC arm, visits were performed systematically by a dedicated physician/nurse palliative care (PC) team, who assessed physical and psychosocial symptoms, and enacted the necessary services. In the SOC arm, PC visits were only carried out if requested. The primary outcome was the difference in the change of QoL [Functional Assessment of Cancer Therapy-General measure (FACT-G)] from baseline to 12 weeks in the two groups. Results: From November 2014 to March 2016, 281 patients were enrolled (142 EPC, 139 SOC); 218 completed FACT-G at 12 weeks. Baseline demographic and clinical characteristics were similar for the two groups. Values of FACT-G at baseline and 12 weeks were 72.3 (SD 12.6) and 70.1 (SD 15.5) for patients enrolled in the EPC arm, vs . 71.7 (SD 14.7) and 69.6 (SD 15.5) for the SOC arm, but the change scores did not differ significantly between groups. In the multivariable analysis, adjusting for QoL at baseline, two potential prospective prognostic factors were statistically significant: lung cancer (P=0.03) and interaction of living without a partner and intervention arm (P=0.01). Dying within 6 months (P Conclusions: In this study, EPC did not improve QoL in advanced cancer patients, but our findings highlight aspects which may guide future research on EPC.

No abstract available

Background: BRAF (v-raf murine sarcoma viral oncogene homolog B1) and MEK (mitogen activated protein kinase) inhibitors, as well as immunotherapy against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1), have shown good results in improving the disease-free survival of patients with metastatic melanoma (MM). The aim of this review is to summarize the main oral adverse events (oAEs) occurring in patients undergoing target or immunotherapy. We proposed two separate sections: oAEs during the treatment with (1) target therapies with BRAF and MEK inhibitors and tyrosine kinase inhibitors (gingival hyperplasia, pigmentation disorders, squamo-proliferative lesions) and (2) immunotherapies with CTLA-4 or PD1 inhibitors (lichenoid reactions, immuno-bullous reactions, xerostomia and other reactions). Adverse events frequently include oAEs, although these are often misdiagnosed and under-reported. Indeed, the oral cavity is not routinely evaluated during clinical practice. The symptomatology related to oAEs is significant since it may represent the first manifestation of a severe systemic reaction, possibly leading to difficulties in nutrition with a consequent impact on patients’ quality of life. A careful examination of the oral cavity is recommended during the evaluation of oncologic patients in order to promptly detect the onset of new manifestations.

Aims: To assess prognostic value of pre-therapy carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) blood levels in non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors (ICIs) and their early change as predictor of benefit. Materials and methods: This is a retrospective cohort study including patients with stage IIIB–IV NSCLC who received anti PD-1/PD-L1 in first or advanced lines of therapy in two institutions. A control cohort of patients treated only with chemotherapy has been enrolled as well. Results: A total of 133 patients treated with nivolumab or atezolizumab were included in the test set, 74 treated with pembrolizumab first line in the validation set and 89 in the chemotherapy only cohort. CYFRA 21-1 >8 ng/mL was correlated with overall survival (OS) in the test set, validation set and in univariate and multivariate analysis (pooled cohort hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.24–2.93, p 0.003). Early 20% reduction after the third cycle was correlated with OS for CEA (HR 0.12; 95% CI 0.04–0.33; p Conclusions: CYFRA 21-1 pre-therapy assessment provides clinicians with relevant prognostic information about patients treated with ICI. CEA and CYFRA 21-1 repeated measures could be useful as an early marker of benefit.

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.

Despite of the emerging new systemic and local oncologic treatments (immunotherapy and checkpoint inhibitors, oncolytic viral treatments and injected immunostimulants) the management of skin melanoma metastasis can be still challenging. The main aim of this review was to assess the efficacy and the role of imiquimod in local metastatic melanoma disease. An extensive literature review was performed from September 2000 to March 2020 using PubMed, MEDLINE, Embase, and Cochrane Library databases. Selected articles regarded topical imiquimod, its mode of action as an antitumoral agent and its applications in melanoma metastases treatment. We analyzed a total of 18 published article of clinical cases and small case series and five studies: two retrospective large case series, two Phase I and II clinical trials and one cohort non randomized study. Generally, the treatment is safe and well tolerated. Imiquimod lead to an unstable locoregional control. The use of topical imiquimod for the treatment of MM cutaneous metastases should be considered in selected cases and in palliative settings.

Melanoma in giant congenital nevus (M-GCN) is a rare and potentially lethal neoplasm. In children, M-GCN appears as a dermal/deep-seated melanoma (DDM-GCN) with histopathologic features difficult to distinguish from proliferative nodules (PNs-GCN). DDM-GCN in adults is an anecdotal entity and only 8 cases have been described and genetically characterized. We report the first case of DDM-GCN in a 34-year-old man characterized with a large-panel next-generation sequence (NGS) highlighting a TP53 mutation with a UV-signature (C>T substitution) in DDM but not in PNs-GCN and GCN. Curiously, DDM showed an aberrant p16 overexpression without detection of CDKN2A mutation at NGS. In line with previous studies, it supports a different pathway in children and adults: UV-induced mutations may be involved in the latter not only by CDKN2A but also by TP53 mutations, with a potentially confusing overexpression of p16 protein. While these data need to be confirmed in larger cases series, our results show that NGS could be an additional genetic diagnostic tool in DDM-GCN.

Objectives The incidence of any and of severe-grade immune-related adverse events (irAEs) with second-line nivolumab monotherapy is 31–65 % and 2–5 % respectively. While potentially serious and even fatal, in the absence of an appropriate therapy, such events might be indicators of the activation of the immune system and, potentially, of efficacy. Materials and Methods We collected the records of 1959 non-small-cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access program, and we registered the appearance of any and of severe grade irAEs. We retrospectively searched for correlations between toxicity and efficacy parameters by using Cox's regression analysis. Results Overall, 342 (17.8%) patients developed an irAE of any grade. We observed that patients developing irAE of any grade achieved a significantly higher response rate (RR 27.2% vs 15.2%; p Conclusions This report, performed in Caucasian NSCLC patients, showed that the appearance of irAEs correlated with outcome.

Malignant pleural mesothelioma (MPM) is a rare neoplasm that typically arises from mesothelial surfaces of the pleural cavity. Despite treatment improvements, it carries a dismal prognosis. The majority of patients either have unresectable disease or are not candidates for surgery due to medical comorbidities or old age. For such patients, chemotherapy (CT) represents the gold-standard treatment. To date, combination CT with cisplatin plus pemetrexed represents the most widely used regimen in first-line setting for patients with unresectable MPM. Other first-line options are currently available, including the use of raltitrexed instead of pemetrexed combined with platinum. In this review, we discuss the role of CT in MPM mainly focusing on the results of the trials conducted in first-line setting.

Aim: During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases. Materials and methods: We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma). Results: Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). Conclusion: Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

none 10 no Oral pigmentations (OPs) are often neglected, although a meticulous examination of the oral cavity is important not only in the diagnosis of oral melanoma, but also for the detection of important clinical findings that may indicate the presence of a systemic disease. OPs may be classified into two major groups on the basis of their clinical appearance: focal and diffuse pigmentations, even though this distinction may not appear so limpid in some cases. The former include amalgam tattoo, melanocytic nevi, melanoacanthoma and melanosis, while the latter include physiological/racial pigmentations, smoker's melanosis, drug-induced hyperpigmentations, postinflammatory hyperpigmentations and OPs associated with systemic diseases. We will discuss the most frequent OPs and the differential diagnosis with oral mucosal melanoma (OMM), underlining the most frequent lesions that need to undergo a bioptic examination and lesions that could be proposed for a sequential follow-up. none Lambertini, M; Patrizi, A; Fanti, P A; Melotti, B; Caliceti, U; Magnoni, C; Misciali, C; Baraldi, C; Ravaioli, G M; Dika, E Lambertini, M; Patrizi, A; Fanti, P A; Melotti, B; Caliceti, U; Magnoni, C; Misciali, C; Baraldi, C; Ravaioli, G M; Dika, E

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.

Small cell lung cancer (SCLC) was defined as a “recalcitrant cancer” because of its dismal prognosis and lack of outcome improvements in the last 30 years. Immunotherapy with checkpoint inhibitors revolutionized treatment in many cancer types and results from the IMpower133 study, a double-blind placebo-controlled phase III trial, showed overall survival benefit for atezolizumab when added to standard platinum-etoposide chemotherapy in first-line SCLC setting for the first time since years. Trials with other checkpoint inhibitors, e.g. pembrolizumab, durvalumab, nivolumab and ipilimumab, are ongoing in various settings, but, to date, there are no defined factors to identify patients who are more likely to benefit from such treatments. This review summarizes results of immunotherapy trials in SCLC for first-line, maintenance and further-line therapies for single-agents and combinations with checkpoint inhibitors. Predictive factors from these trials are reviewed in order to identify their clinical value, with particular emphasis on PD-L1 expression on both tumor cells and in stroma, especially in pembrolizumab-treated patients, and tumor mutational burden, for patients treated with the ipilimumab and nivolumab combination.

In the last 5 years, several cases of the drug-induced variant have been reported during treatment of metastatic disease with immunotherapy and targeted therapy.The pathogenesis of targeted therapy-associated Sweet syndrome and its significance as a putative marker of therapeutic response remain to be ascertained. Our patient’s skin eruption was temporally related to the beginning of targeted therapy treatment and meets allthe criteria for the drug-induced form.The molecular mechanisms leading to Sweet syndrome during melanoma could differ depending on the types of treatment.

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Antibodies directed against programmed death receptor 1 emerged as beneficial immune-checkpoint inhibitor therapy in many different types of cancer. However, programmed death receptor 1 is critical in promoting self-tolerance and the most common toxicities of checkpoint inhibitors are immune-related adverse events. We present a 48-year-old woman affected by metastatic uveal melanoma treated with nivolumab (3 mg/kg every 2 weeks). The patient had no previous history of autoimmune disease or dermatologic conditions. At the fourth month of treatment, on cutaneous examination, she presented multiple whitish vitiligo-like patches on the trunk, axillae, hands and face. Diagnosis of melanoma-associated leukoderma vitiliginous reaction was made. Over the following months, the melanoma-associated leukoderma lesions slowly progressed with cigarette paper-like appearance and indurated texture. A skin biopsy leaded the diagnosis of extragenital lichen sclerosus. To the best of our knowledge, this is the first reported case of extragenital lichen sclerosus on previous melanoma-associated leukoderma lesions related to nivolumab monotherapy. The increase in clinical experience with anti programmed death receptor 1 enhances the knowledge about adverse effects associated with these immunotherapies and allows to compare therapeutic strategies.

e21078 Background: In advanced EGFR-mutated non-small cell lung cancer (NSCLC) population, osimertinib represents the standard of care both for EGFR tyrosine kinase (TK) inhibitor-naive patients and for those with EGFR-mutated NSCLC harboring the T790M mutation and progressed following prior EGFR-TK inhibitor. No clear data supports the relationship between body mass index (BMI) and osimertinib's efficacy. Methods: We conducted a single-center, retrospective study including advanced EGFR-mutated NSCLC patients treated with Osimertinib as second or subsequent lines from February 2016 to December 2020. We examined survival outcomes according to BMI among a BMI-low group ( < 25 Kg/mq2) and BMI-high group (≥25 Kg/mq2). Results: A total of 37 consecutive patients received osimertinib as second- or subsequent line at our Institution. The mean age was 63.5 years (range 34-83 years), 24 (65%) patients were female, 16 (59%) were former or never smokers, and 25 (67%) had three or more metastatic sites at the start of therapy. The BMI-low group includes 25 (67%) patients and the BMI-high group 12 (33%), respectively. Globally, the median overall survival (mOS) was 29.9 mo. (95% CI, 18.2 – NR) and median progression-free survival (mPFS) was 17.5 mo. (95% CI, 15.7-33.3). The median follow-up was 32.5 mo. (IQR, 13.35-42.06). The mPFS was 21.0 mo. (95 CI, 16.8 – NR) within the BMI-low group and 16.8 mo. (95 CI, 4.4 – NR) within the BMI-high group, respectively (p = 0.03). Analogously, the mOS within the BMI-low group was 29.9 mo. (95 CI, 20.8 – NR) versus 18.2 mo. (95 CI, 11.7- NR) for the BMI-high group (p = 0.01). A BMI ≥25 Kg/mq2 constituted an independent risk factor for mortality [HR 3.99, (95 CI, 1.2 – 13.2), p 0.02] at multivariate analysis, including also age and number of metastatic sites. The BMI-high group showed a non-significant tendency to progression [HR 2.76, (95 CI, 0.9 - 8.3), p 0.06] at the same multivariate analysis. Conclusions: In our experience, a BMI ≥25 Kg/mq2 negatively influenced survival outcomes of 2nd-line osimertinib' treated NSCLC patients. More comprehensive studies are warranted to confirm these findings.

Background: In the field of oncological assistance, nowadays we have to deal with a complex scenario where patients got used to obtain a huge amount of information through internet or social media and to apply them in performing their health-related decisions. This landscape requires that clinicians become able to handle therapeutical approaches and adequate skills in communication tools to satisfy the current needs. Our project aimed to build a communication model based on clinical oncologists’ real experiences in order to find a simple way to share with patients all the innovative therapeutical opportunities today available in lung cancer. The final goal is to design a flexible and personalized model adaptable to clinician’s personal characteristics and to the specific patient he is facing. We applied both traditional educational tools and innovative techniques in order to make the results effective and applicable to support peer learning. Methods: The first step consisted in a Board synthesized the definition of the diagnostic process, the identification of treatment strategies and any potential communication barrier clinicians may face dealing with patients. The second step consisted in teamwork including a theoretical part and a training part. In the third step we produce five training videos and video interviews regarding communication praxis and a “Small communication manual”. The last step consisted in the publication of the produced material on website and its diffusion through the social media. Results: In medicine, the universal application of a single model of communication does not represent the optimal solution. By contrary, the availability of simple and practical suggestions to improve the communicative style could allow clinicians to abandon stereotyped formulas identically repurposed to all patients. The “from bottom to top” training, starting from real-life to take advantage of the clinician’s experience, give the clinicians the possibility to meditate about their own communicative style and to train in the context of a protected environment. Applying these rules, we design an effective communication model, based on healthcare humanization, which could represent a fundamental support for the patient in order to be gently driven by the clinician to the most appropriate therapeutical choice, balancing efficacy and quality of life. The relational training may improve the quality of clinician-patient communication and could be widespread to other clinicians through the media. Conclusions: Considering the innovative therapeutical options available, particularly for lung cancer patients, and the increasing access of health-related information through internet or social media the clinician-patient communication has become crucial to support the achievement of the most appropriate therapeutical choice for the patient, facing the intricate illness experience. Building a shareable and easy-to-apply communication model represents a challenge aimed to help clinicians and including technology not as a threat, but as a positive tool.

This analysis evaluated the efficacy and safety of nivolumab, an immune checkpoint inhibitor, in elderly patients with stage IIIB or IV squamous non-small-cell lung cancer (NSCLC) enrolled in the expanded access programme (EAP) in Italy.Nivolumab was available on physician request. Safety data included adverse events (AEs). Efficacy data included investigator-assessed tumour response, progression date and survival information. Results were analysed for patients aged65, 65-75 and ≥75 years and for the overall population.A total of 371 patients with squamous NSCLC were enrolled at 96 centres between April 2015 and September 2015; 34% (n = 126), 47% (n = 175) and 19% (n = 70) were aged65, 65-75 and ≥75 years, respectively. Efficacy was similar among patients aged65, 65-75 and ≥75 years and the overall population (objective response rates: 18%, 18%, 19% and 18%, respectively; disease control rates: 49%, 47%, 43% and 47%, respectively). Median overall survival was reduced in patients aged ≥75 years (5.8 months) versus patients aged65; years (8.6 months), patients aged 65-75 years (8.0 months) and the overall population (7.9 months). The incidence of grade 3-4 treatment-related AEs was low in patients aged 65, 65-75 and ≥75 years and the overall population (3%, 9%, 3%, 6%, respectively). Discontinuation rates due to treatment-related AEs were low irrespective of age (4-5%).These EAP results suggest that elderly patients with advanced squamous NSCLC benefit from nivolumab, with tolerability similar to that in the overall population.

Pembrolizumab is an immune checkpoint inhibitor approved for the treatment of patients with unresectable or metastatic melanoma. Appearance of bone metastases, either osteolytic or osteoblastic, during treatment qualifies as disease progression. We report the case of a 64-year-old White woman with a metastatic melanoma undergoing second-line treatment with pembrolizumab. At first evaluation, after 3 months of therapy, computed tomography scans showed the onset of osteosclerotic lesions and a significant reduction in all the previously identified metastases; on the contrary, a fluorine-18-fluorodeoxyglucose PET showed the normalization of fluorine-18-fluorodeoxyglucose uptake in all the baseline lesions, including bone metastases. Osteoblastic response, consisting of occurrence of new osteoblastic lesions on computed tomography imaging, as a consequence of an osteoblastic reaction of previously undetectable bone metastases, has been reported in some cancers that receive treatments such as chemotherapy, hormonal or targeted therapy. However, it had never been reported in patients with melanoma treated with immunotherapy. An apparent worsening of bone imaging on standard computed tomography scan in patients under checkpoint inhibitor should not lead to modification of treatment strategy, because misinterpretation as disease progression may lead to the premature cessation of a beneficial treatment and finally have a negative effect on patients' clinical outcome.

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Distinguishing between immune-related pneumonitis and disease progression in advanced Non Small Cell Lung Cancer treated with PD-1 inhibitors: Can serum tumour markers have a role?

Immune checkpoint inhibitors (ICPIs) are considered one of the most important breakthroughs in cancer treatment of the past decade; notably, different studies of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have reported impressive clinical activity and durable responses in patients with advanced non-small cell lung cancer (NSCLC). These findings have led to the changing of the current therapeutic algorithm of advanced NSCLC, adding a new standard first-line treatment option for patients with PD-L1-positive tumors. Pembrolizumab, a highly selective anti-PD-1 humanized monoclonal antibody, was approved by the United States Food and Drug Administration (US FDA) in October 2016 for previously untreated metastatic NSCLC patients whose tumors have high PD-L1 expression, tumor proportion score (TPS) ⩾ 50%, as well as for metastatic NSCLC patients whose tumors express PD-L1 with TPS ⩾ 1% progressing on or after platinum-based chemotherapy. However, many issues remain outstanding, mainly regarding the identification of an optimal biomarker which can help selecting patients more likely to respond to ICPIs. In this review, we discuss the clinical results obtained so far with the anti-PD-1 pembrolizumab in advanced NSCLC, commenting on the role of PD-L1 as a predictive factor and providing an update of the future perspectives.

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.

Background Chemotherapy (CT) in patients with advanced cancer (ACP) near the end of life is an increasing practice of oncology units. A closer integration with palliative care (PC) services could reduce the use of potentially harmful CT. This prospective study is aimed at assessing whether a more integrated care model could reduce CT use near the end of life and increase local PC service utilisation. Methods The study enrolled sequentially two cohorts of ACP with an estimated life expectancy of ≤6 months. In the first cohort, the usual oncologist’s practice to prescribe CT and to activate local PC services were recorded. In cohort 2, the oncologist’s decision was taken after an in-hospital consultation with the local PC teams. After patient death, a follow-back survey was carried out. Results The two cohorts included 109 and 125 evaluable patients, respectively. The oncologist’s decision to prescribe CT occurred in 51.4% and 60%, respectively: the percentages of patients receiving the final CT administration in the last 30 days of life did not differ in the two cohorts (33.9% and 29.3%, respectively,p=0.83). Conversely, an increase in home PC service utilisation (from 56.9% to 82.4%, p=0.00), at home deaths (from 40.4% to 56.8%, p=0.01) and in-hospice deaths (from 8.3% to 19.2%, p=0.00) occurred in cohort 2. Conclusion The implementation of an initial in-hospital consultation of oncologists and experienced home PC teams has not reduced the use of CT near the end of life but increased PC service utilisation and reduced in-hospital deaths.