11133 Background: The ability to estimate survival is a cornerstone of care for patients (pts) with advanced cancer, influencing therapeutic strategies, access to clinical trials, and timing of palliative care referral. Existing evidence on clinical prediction of survival (CPS) largely derives from end-of-life pts. The Pre-Sur study addresses this gap by evaluating oncologists’ prognostic accuracy in pts with metastatic solid tumors starting first-line therapy and investigating discordance-related factors. Methods: Pre-Sur is a prospective, observational, monocentric study enrolling pts with advanced tumors prior to first-line therapy (hormonal therapy was excluded). During the baseline consultation, clinicians provided an estimated survival timeframe using categorical intervals (0-4 to >36 months). The primary endpoint was concordance between CPS and overall survival (OS). Survival estimates and outcomes were analyzed descriptively and through cross-tabulation. Secondary analyses explored factors potentially influencing accuracy, including ECOG-PS, age, comorbidities, and clinician characteristics, using Chi-square tests and multivariable models. Results: From October 2022 to December 2025, 183 pts were enrolled; 135 completed the required follow-up. 58% of pts were male and 49% were ≥75 years. Gastrointestinal (45%) and thoracic (35%) cancers were the most prevalent. Median CPS (mCPS) was 18.0 months (95%CI: 15.9–20.0), median OS (mOS) of 8.0 months (95%CI: 5.9–10.0). Prognostic estimates were accurate in 17% of cases, optimistic in two-thirds, and underestimated in less than one-quarter. No significant associations emerged for sex, tumor site, PS or target therapy use. mCPS were often more consistent with the mOS reported in randomized clinical trials (RCT); the observed real-world OS were inferior to that expected from RCT (Table 1). Conclusions: This study highlights the difficulty of predicting OS in pts with metastatic solid tumors. CPS may be influenced by expectations derived from RCT outcomes, which may not fully capture the complexity of real-world pts. Prognostic evaluation in clinical practice should integrate features such as age, PS, comorbidities, and disease burden, to improve prognostic accuracy and support informed decision-making. Overall survival and clinical prediction of survival by disease sites. Site Patients, n (%) mOS, months (CI 95%) mCPS, months (CI 95%) mOS trend in registrative RCTs, months Lung 44 (32.2) 7 (2-12) 12 (11-13) 12-26 Colorectal 24 (17.8) 9 (5-13) 18 (13-23) 25-30 Pancreas 15 (11.1) 8 (2-14) 24 (21-27) 11 Gastric 11 (8.1) 5 (2-8) 12 (7-17) 14 Head and neck 6 (4.4) 6 (0-13) 30 (NA-NA) 15 Kidney 6 (4.4) 6 (4-8) 18 (5-30) 45 Biliary ducts 5 (3.7) 2 (1-3) 18 (13-23) 12 Pleural 4 (3.0) 2 (NA-NA) 8 (NA-NA) 12 Skin 4 (3.0) 22 (NA-NA) 12 (NA-NA) 33 Bladder 3 (2.2) 11 (0-27) 18 (8-28) 21

e14572 Background: EPSCC is a rare and highly aggressive malignancy with a poor prognosis. The low incidence has limited prospective evidence for first-line (1L) treatment. Given histological similarities with small cell lung cancer, where immunotherapy plus chemotherapy (CT) is the standard of care, an agnostic strategy was adopted. The DURVASCC trial aims to evaluate the clinical activity and safety of durvalumab plus platinum–etoposide as 1L treatment in ES-EPSCC. Methods: DURVASCC is an Italian, multicenter, phase II, single-arm study. Patients received durvalumab 1500 mg with carboplatin AUC5-6 or cisplatin 75-80 mg/m 2 on day1 plus etoposide 80-100 mg/m 2 day1-3 Q2W for 4-6 cycles, followed by durvalumab 1500 mg Q4W in patients achieving disease control until progression or unacceptable toxicity, for a max of 24 months. Safety assessment was pre-specified using a continuous toxicity monitoring design based on a Pocock-type group sequential approach, with planned evaluations every 10 patients up to 30 enrolled, each with a minimum follow-up of one month. Early stopping rules were based on the cumulative number of clinically relevant adverse events (AEs). At the second assessment, trial discontinuation would have been triggered if ≥6 relevant AEs (defined as events leading to treatment interruption or withdrawal) had been observed. Safety data and stopping rules were periodically reviewed by an independent data and safety monitoring board. Results: As of November 2025, 20 patients were evaluable for safety. Fifteen patients (75%) experienced at least one AE considered possibly related to durvalumab, with or without concomitant attribution to CT. Seven Grade 4 AEs occurred in five patients; three were serious, and one (thrombocytopenia) led to temporary treatment interruption. Eight Grade 3 AEs occurred in four patients: one (pan-uveitis) was unresolved and resulted in permanent treatment discontinuation.According to the primary safety definition, two AEs were classified as relevant, corresponding to a rate of 10% (95% confidence interval [CI]: 1.2%–31.7%).In a sensitivity analysis including additional Grade 3–4 events more likely attributable to concomitant CT, three patients experienced relevant AEs (two neutropenia—one unresolved and one leading to treatment delay—and one serious febrile neutropenia), corresponding to a rate of 25% (95% CI: 8.7%–49.1%). In both analyses, the pre-specified early stopping threshold of six relevant AEs was not exceeded. Conclusions: Based on the second safety assessment, durvalumab plus platinum–etoposide showed a manageable safety profile, supporting continuation of the DURVASCC trial. Clinical trial information: NCT06464068 .

Immunotherapy achieved remarkable results in patients with deficient mismatch repair (dMMR)/microsatellite instable (MSI) metastatic colorectal carcinoma (mCRC). However, its efficacy in proficient MMR (pMMR)/microsatellite stable (MSS) mCRC remains limited. In the phase II NIVACOR trial, we evaluated the activity and safety of FOLFOXIRI/bevacizumab plus nivolumab as first-line therapy in patients with RAS/BRAF-mutated mCRC (NCT04072198). The primary endpoint of the trial was the Objective Response Rate (ORR) whereas secondary endpoints were safety profile, overall survival (OS), progression free survival (PFS), duration of response (DoR) and quality of life. The primary endpoint was met. Among the 73 enrolled patients, 76.7% achieved an objective response (95% CI, 65.4 to 85.8%), while the disease control rate was 97.3% (95% CI, 90.5 to 99.7%). The median progression-free survival (mPFS) was 10.1 months (95% CI, 9.0 to 14.3 months), and the median overall survival (mOS) was not reached. Treatment-related adverse events of grade 3 or higher occurred in 48 patients out 73 enrolled patients (65.8%). Comprehensive genomic profiling and RNA sequencing analysis revealed genomic and transcriptomic profiles associated with treatment response in pMMR/MSS patients. Alterations in pathways such as PI3K/AKT, chemokine signaling and DNA repair showed correlation with treatment activity. These findings highlight the potential synergy between immune checkpoint inhibitors and cytotoxic chemotherapy in selected patients with pMMR/MSS mCRC.

Abstract Objective This scoping review explores the potential role of cancer-staging chest CT scans in assessing cardiovascular (CV) risk in cancer patients. It aims to evaluate: (1) the correlation between non-gated chest CT and the conventional Agatston score from cardiac CT; (2) the association between coronary calcium scores from non-gated chest CT and CV risk in non-oncological patients; (3) the link between coronary calcium assessed by non-gated chest CT and CV events or endothelial damage in cancer patients. Methods Three different searches were performed on PubMed, according to the three steps described above. Both original articles and systematic reviews were included. Results Many studies in the literature have found a strong correlation between coronary calcium scores from non-gated chest CTs and the conventional Agatston scores from gated cardiac CTs. Various methodologies, including Agatston scoring, ordinal scoring, and the “extent” and “length” methods, have been successfully adapted for use with non-gated chest CTs. Studies show that non-gated scans, even those using iodinated contrast, can accurately assess coronary calcification and predict CV risk, with correlations as high as r = 0.94 when compared to cardiac CTs. In oncological settings, studies demonstrated a significant link between coronary calcium levels on non-gated chest CTs and higher CV risk, including MACE and overall mortality. Conclusions Radiological assessment of coronary calcium on non-gated CT scans shows potential for improving CV risk prediction. Critical relevance statement Non-gated chest CT scans can detect endothelial damage in cancer patients, highlighting the need for standardized radiological practices to assess CV risks during routine oncological follow-up, thereby enhancing radiology’s role in comprehensive cancer care. Key Points Cancer therapies improve outcomes but increase cardiovascular risk, requiring balanced management. Coronary calcification on non-gated CT correlates with Agatston scores, predicting cardiovascular risk. Routinely performed CTs predict cardiovascular risk, optimizing the management of cancer patients. Graphical Abstract

The first part of this review highlighted the evolving landscape of atherosclerosis, noting emerging cardiometabolic risk factors, the growing impact of exposomes, and social determinants of health. The prominent role of atherosclerosis in the bidirectional relationship between cardiovascular disease and cancer was also discussed. In this second part, we examine the complex interplay between multimorbid cardio-oncologic patients, cardiometabolic risk factors, and the harmful environments that lend a “syndemic” nature to these chronic diseases. We summarize management strategies targeting disordered cardiometabolic factors to mitigate cardiovascular disease and explore molecular mechanisms enabling more tailored therapies. Importantly, we emphasize the early interception of atherosclerosis through multifactorial interventions that detect subclinical signs (via biomarkers and imaging) to treat modifiable risk factors and prevent clinical events. A concerted preventive effort—referred to by some as a “preventome”—is essential to reduce the burden of atherosclerosis-driven chronic diseases, shifting from mere chronic disease management to the proactive promotion of “chronic health.”

Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. In recent years, mortality rates have declined due to antismoking policies, earlier detection, and the advent of targeted therapies and immunotherapy, particularly for non-small cell lung cancer (NSCLC), which accounts for 85% of all cases. With improved survival, however, LC patients are increasingly exposed to competing causes of mortality, among which cardiovascular disease (CVD) is highly prevalent, affecting 30–50% of patients and contributing to nearly 30% of deaths. This burden reflects both shared risk factors and the cardiotoxic potential of radiotherapy, chemotherapy, and immunotherapy. Beyond acute adverse cardiovascular events during treatment, real-world data indicate that immune checkpoint inhibitors (ICIs) may also exert chronic cardiovascular effects, significantly accelerating the atherosclerotic process in multimorbid patients. These findings underscore the importance of accurate baseline assessment and aggressive management of cardiovascular risk factors in LC patients—particularly in the adjuvant and neoadjuvant settings, where longer survival is anticipated. Moreover, long-term monitoring should be implemented through a tailored, multiparametric strategy that integrates novel biomarkers and advanced artificial intelligence–assisted imaging techniques. Achieving this ambitious goal requires the close collaboration of a multidisciplinary team, with cardiologists playing a pivotal role. This review will address the complexity of LC patients, focusing on the interplay of cardio-immuno-metabolic factors, summarizing the cardiovascular impact of immunotherapy across metastatic, locally advanced, and perioperative settings, and outlining practical strategies for the management of these vulnerable patients.

The presence of metastatic cancer represents a high-risk condition for the treatment of heart disease requiring surgical or percutaneous procedures. We present the case of a 58-year-old man with pulmonary adenocarcinoma and renal metastases surviving more than 3 years after chemotherapy and immunotherapy suffering dyspnea and chest pain on minimal exertion due to 99% anterior coronary artery stenosis associated with severe aortic stenosis of a bicuspid valve. We treated the cardiac lesions in two steps by coronary angioplasty with drug-eluting stent implantation followed by percutaneous prosthetic aortic valve replacement. The procedures were successful with resolution of the symptoms and recovery of the usual ECOG-PS 0-1 functional capacity which persists 24 months after cardiac procedures. This case demonstrates that the multidisciplinary collaboration between oncologists and cardiologists with a personalized patient-centered approach allows to treat complex clinical situations successfully in the emerging category of patients surviving with metastatic cancer.

The presence of metastatic cancer represents a high-risk condition for the treatment of heart disease requiring surgical or percutaneous procedures. We present the case of a 58-year-old man with pulmonary adenocarcinoma and renal metastases surviving more than 3 years after chemotherapy and immunotherapy suffering dyspnea and chest pain on minimal exertion due to 99% anterior coronary artery stenosis associated with severe aortic stenosis of a bicuspid valve. We treated the cardiac lesions in two steps by coronary angioplasty with drug-eluting stent implantation followed by percutaneous prosthetic aortic valve replacement. The procedures were successful with resolution of the symptoms and recovery of the usual ECOG-PS 0-1 functional capacity which persists 24 months after cardiac procedures. This case demonstrates that the multidisciplinary collaboration between oncologists and cardiologists with a personalized patient-centered approach allows to treat complex clinical situations successfully in the emerging category of patients surviving with metastatic cancer.

Abstract Introduction Growing evidence highlight cancer and cardiovascular diseases (CVD) share common risk factors, including genetic ones, and underlying pathogenesis. Such paradigm has significant implications for cancer survivors, an exponential growing cohort of patients (Pts), due to notable improvements in survival achieved with new oncological treatments. However, many new agents of targeted– and immuno–therapy can cause cardiac damage, mainly for vascular involvement, a pathophysiological mechanism different from classic chemotherapeutic agents. We present the case of left ventricular systolic dysfunction (LVSD) in a man with metastatic papillary renal cell carcinoma (PRCC) previously exposed to anthracyclines for former peripheral T–cell lymphoma (PTCL). He came to our attention for cardiological assessment before starting immunotherapy (Nivolumab), due to the failure of Tyrosine kinase inhibitor (TKIs) (Pazopanib) treatment. Clinical case A 74–year–old Pt with hypertension, severe renal dysfunction, dyslipidemia, and exertional dyspnea (NYHA II) presented at transthoracic echocardiogram (TTE) a normal size chambers with mild concentric hypertrophy and a clinically stable moderate LVSD (LVEF 35–40%) at periodic evaluation. Pt was also performing his radiological follow–up for the estimation of metastases with CT, twice a year since 2016. A retrospective review of these non–contrast and non–ECG–gated CT highlighted an extensive increase in coronary artery calcifications during the last four years, started with the beginning of TKIs therapy. In 2018 only mild LAD calcification was detectable (Figure 1), while in 2022 a severe three–vessel coronary atherosclerosis was present (Figure 3). After multi–disciplinary discussion, an aggressive correction of multiple cardiovascular risk factors (starting Rosuvastatin and adjusting Bisoprolol) was performed and immunotherapy started without any adverse event. Conclusions Non–ECG–gated CT routinely performed for monitoring the state of the oncological disease is a useful tool for the evaluation of coronary artery calcific burden and accelerated atherosclerosis. It provides additional information beyond the traditional evaluation of CV risk and must be integrated with clinical and laboratory data.

e15590 Background: mCRC patients (pts) have a median survival of 13-24 months with a 5-year survival rate of about 1%. LTSs are defined as pts with survival greater than or equal to 36 months after diagnosis of mCRC. Mutational status, new treatments, and surgery resection advances led to improved survival outcomes. Methods: This is a single-center retrospective analysis of 106 consecutive CRC pts with synchronous or metachronous metastases diagnosed from the AUSL-IRCCS of Reggio Emilia Comprehensive Cancer Center between January 1 st , 2017, and November 30, 2019. Clinical and pathological characteristics of pts were obtained from clinical records. Long-term survivors were defined as pts with survival > 36 months. Results: Out of 106 mCRC, 33 (31.1%) were LTSs with a median survival of 53 months (range, 36-129 months). At the data cut-off of November 30, 2022, 24 (72.7%) were still alive. Among all, 18 (54.5%) were men, the median age was 65 years (47-83), and 14 (42.4%) had a right tumor primary site. Synchronous metastases were found in 20 (60.6%), while 13 (39.4%) developed metachronous metastases; the most frequent site of metastases was the liver (63.6%), peritoneum and lymph nodes (21.2%), respectively. Surgical resections and systemic treatment regimens based on fluorouracil, oxaliplatin, and/or irinotecan, cetuximab, bevacizumab, TAS-102, regorafenib, and others are listed in Table 1. Regarding biological status, 28 (84.8%) had an MSS, 18 (54.5%) RAS wild type, and 3 (9.1%) BRAF V600E mutated of which 2 (66.7%) underwent surgical resection of primary tumor and metastases, receiving up to 2 lines of systemic treatments. Conclusions: This study confirms that long-term survivors of mCRC pts are the results of intrinsic tumor biology, appropriate treatment timing including surgery, and the available pharmacological opportunities beyond chemotherapy. Further analysis including the role of liquid biopsy is under investigation to identify prognostic and predictive biomarkers in order to improve survival outcomes. [Table: see text]

with their own set of complications leading to decreased quality of life.Thus, to do prophylactic stoma or not is a matter of constant dilemma that most surgeons face.Ghost Stoma is a technique where in unnecessary prophylactic stoma can be avoided while ensuring that a diversion stoma can be created if need arises without the need of general anaesthesia.Methods: Surgical Technique: Ghost Stoma techniques done by pulling a loop of intestine up to parietal peritoneal layer of anterior abdominal wall with the help of silicone/ plastic tube at the time of anterior resection.If an anastomotic leak is detected in postoperative period, same loop of bowel can be pulled out and fashioned into stoma under local anaesthesia.Study Design: A retrospective analysis of all the cases who underwent this procedure between January 2015 to December 2019 was done.Results: Total 68 patients underwent AR with ghost stoma at our institute during specified time period.Total 7 patients required creation of functional stoma postoperatively for suspected or confirmed leak and was done under local anesthesia in all patients.One patient had congestion of stoma due to rotation of mesentery and required refashioning of stoma under regional anesthesia.Rest of the patients had the plastic tube removed at around 2 weeks.However, none of the patients required re-laparotomy or peritoneal wash under general anaesthesia.None of the patients had any complication due to plastic tube like bowel rotation, obstruction, strangulation, adhesion, stricture or tube migration.Conclusions: Ghost Stoma is a very simple & safe procedure which can decrease the need of prophylactic diversion stoma in most cases of AR.It is technically easy, oncologically safe, decreases intraoperative time & also prevents patient from morbidity as well as psychological and financial burden of stoma.Using this technique unnecessary stoma could be avoided in >80 % patients of AR in this series.

The NIVACOR trial is a phase II study assessing the efficacy and safety of nivolumab in combination with FOLFOXIRI/bevacizumab in first-line setting in patients affected by metastatic colorectal cancer (mCRC) RAS/BRAF mutated. We report safety run-in results in the first 10 patients enrolled. Patients received triplet chemotherapy with FOLFOXIRI scheme plus bevacizumab, in association with nivolumab every 2 weeks for 8 cycles (induction phase) followed by bevacizumab plus nivolumab every 2 weeks (maintenance phase), until progression of disease or unacceptable toxicities. The first ten patients were evaluated: 7 experienced at least one adverse event (AE) related to FOLFOXIRI/bevacizumab and 2 related to nivolumab. The most frequent grade 1–2 AEs related to FOLFOXIRI/bevacizumab were diarrhea and fatigue (71%), nausea and vomiting (57%); 3 (43%) had grade 3–4 neutropenia, and 2 (20%) patients developed grade 1–2 AEs nivolumab related: skin rash and salivary gland infection. Two patients delayed the dose because of serious AEs, proteinuria and salivary gland infection; one patient discontinued experimental treatment due to the ileo-urethral fistula and concurrent Clostridium infection diarrhea. No treatment- related death occurred. The safety run-in analysis of NIVACOR trial reassured using co-administration of FOLFOXIRI/bevacizumab and nivolumab was well tolerated with an acceptable toxicity profile. Clinical Trial Registration https://clinicaltrials.gov/ , (NCT04072198).

The present research describes 25 years of cardiovascular mortality in a cohort of patients in Northern Italy. The study included patients with malignant cancer enrolled in the period of 1996–2019, and describes cardiovascular and cancer mortality in relation to sex, age, year of diagnosis, months of survivorship, tumor site, and standardized mortality ratio (SMR). Out of 67,173 patients, 38,272 deaths (57.7%) were recorded: 4466 from cardiovascular disease (CVD) (6.6%), and 28,579 (42.6%) from cancer. The proportion of CVD death increased from 4.5% in the first two years after diagnosis, to 7.3% after more than 10 years, while the proportion of deaths from cancer decreased from 70.5% to 9.4%. The CVD SMR comparing cancer patients with the general population was 0.87 (95% CI: 0.82–0.92) in 1996–1999, rising to 0.95 (95% CI: 0.84–1.08) in 2015–2019, without differences in terms of sex or age. The risk of dying from CVD was higher compared with the general population (SMR 1.31; 95% CI: 1.24–1.39) only in the first two years after diagnosis. The trend over time underscored that CVD deaths increased in patients with breast, bladder, prostate, and colorectal cancers, and, in the more recent period, for kidney cancer and melanoma patients. Our data confirmed that cardiovascular mortality is an important issue in the modern management of cancer patients, suggesting the need for an extensive interdisciplinary approach.

Pembrolizumab is a programmed death receptor-1 (PD-1) inhibitor that has been approved for treatment of a wide variety of malignancies including non-small-cell lung cancer (NSCLC). Immune-mediated colitis is a known adverse effect of pembrolizumab which can lead to the treatment interruption, although not compromising the control of the oncological disease. Herein, we report the case of a 59-year-old woman on pembrolizumab for advanced NSCLC which developed a severe and persistent colitis treated with infliximab for several months following anti-PD-1 antibody discontinuation. This strategy resulted in an improvement but not complete recovery of the gastrointestinal toxicity despite revealed sustained response and control of the oncological disease with prolonged survival over 24 months.

37 Background: NIVACOR trial is an open-label, multicentric Italian phase II trial of FOLFOXIRI/bevacizumab in association with an anti-PD1 antibody, nivolumab, in patients (pts) with metastatic colorectal cancer (mCRC). We report preliminary safety analysis by an Independent Monitoring Committee. Methods: Pts with mCRC RAS or BRAF mutated, regardless microsatellite status and eligible to receive a first line treatment will be enrolled. FOLFOXIRI/bevacizumab (BEV) in association with nivolumab (NIV) was administered every 2 weeks for 8 cycles (induction) followed by BEV plus NIV every 2 weeks (maintenance) until PD or unacceptable toxicities. BEV was administered intravenously at dose of 5 mg/kg and NIV intravenously as a flat dose of 240 mg every 2 weeks. The primary endpoint was the ORR. The safety is assessed after the inclusion of the 10 th patient, receiving ≥1 dose. Results: As of September 20, 2020, 25/70 pts are enrolled. The first 10 pts were evaluated for preliminary safety analysis. Median age was 58 years (32-66), 60% of pts were male, median cycles of treatment was 5.5 (1-9). 100% were KRAS G12D mut and BRAF wild type, respectively, and 2% MSI-H/dMMR. 7/10 pts experienced at least one AE related to FOLFOXIRI/BEV and 2/10 related to NIV. The most frequent grade 1-2 AEs related to FOLFOXIRI/BEV were nausea and vomiting 4(57%), fatigue 5(71%), and diarrhea 5(71%); 3(43%) pts had grade 3-4 neutropenia, and 1(14%) febrile neutropenia. Only 2 pts developed grade 1-2 AEs related to NIV represented by rash (50%) and salivary gland infection (50%); no grade 3-4 was reported. One of pts with dose delay because of serious AES (proteinuria) BEV related, and one patient discontinued due to serious AEs (ileo-urethral fistula) not related to NIV. Conclusions: Combination of FOLFOXIRI/BEV and NIV was generally well tolerated and showed an acceptable toxicity profile. The final analysis will be scheduled at the end of enrollment. Clinical trial information: NCT04072198.

MPM is an uncommon cancer with limited therapeutic options and poor clinical outcomes. The relative rarity of these tumor has limited the identification of MPM-driver molecular as well as the development of specific drugs RAMES study evaluated the second-line efficacy of gemcitabine/ramucirumab treatment vs. gemcitabine/placebo. From December 2016 to July 2018 (end of enrolment), 164 patients (pts) were admitted to this study. We evaluated by NGS the mutational profile of a panel of 34 genes (ACTB, ACTG1, ACTG2, ACTR1A, BAP1,CDH8, CDK4, CDKN2A, CDKN2B, COL3A1, COL5A2, CUL1, DHFR, GOT1, KDR, KIT, MXRA5, NF2, NFRKB, NKX6,-2, NOD2, PCBD2, PDZK1IP1, PIK3CA, PIK3CB, PSMD13, RAPGEF6, RDX, SETDB1, TAOK1, TP53,TXNRD1, UQCRC1, XRCC6). We reported the results of the first 87 pts (54%): hystotype was epithelioid in 70 pts (80%), biphasic in 14 pts (16%) and sarcomatoid in 3 pts (4%). Median age was 63 years (range 45-81). 70 pts were male (80%) and 17 pts were female (20%). In the present analysis, we included 55 pts in stage III (63%), 26 pts in stage IV (30%) and 6 pts whose stage was unknown. Median first-line PFS platinum/pemetrexed therapy was for 5.75 months (I.C. 95% 4.75-6.76). PFS was ≤6 months for 40 pts (49%), and 6 months for 41 pts (51%). 187 functional somatic mutations were identified. Genomic alterations/patient were 1 gene in 29 pts (33%), 3 genes in 18 pts (21%) and ≥5 genes in 2 pts (2%). The most frequent somatic mutations were RDX in 35 pts (40%), MXRA5 in 20 pts (23%), BAP1 in 13 pts (15%) and ACTG 1 in 9 pts (11%). When patients were collated by stage, the most frequent mutations were: MXRA5 in 16 pts in stage III (29%), BAP1 in 5 pts in stage IV (19%) and RDX in 16 pts in stage IV (62%). The percentage of somatic mutations in patients with PFS as first-line chemotherapy for ≤6 and >6 months was 2.2 and 1.6 (p=0.032), respectively. The most frequent mutations/patient for ≤6 and >6 months PFS were: RDX in 14 pts (35%) with PFS ≤ 6, RDX in 19 pts (46%) with PFS >6 and MXRA5 in 11 pts (27%) with PFS >6. This preliminary data suggests a possible role that a genetic signature may play in distinguishing MPM with different clinical-pathological features. The results are expected to be clarified further in the second step of the study, which is ongoing.

Background: MPM is a highly aggressive pleural tumor associated with asbestos exposure. The ability to analyze entire genomes opens the door to identification of new treatments. Methods: RAMES is a ongoing phase II study to evaluate the efficacy and the safety of the addition of ramucirumab to gemcitabine as the second-line treatment in 160 pts with MPM. We designed a custom panel covering 1040 amplicons spanning 33 genes frequently altered in MPM. To establish the genetic asset of MPMs we used an amplicon-based next generation sequencing approach. Results: To date, 40 FFPE mesothelioma cancer tissues were successfully sequenced A total of 2930 variants passing quality filters were detected. Focusing on potentially functional alterations, polymorphisms and non-coding variants were excluded, leaving 143 alterations in 23 of the analyzed genes. Of these, 59.4% (85/143) were missense mutations, 22.4% (32/143) lead to frameshift alteration of the gene sequence, 13.3% (19/143) were splice variants, while the remaining 4.9% (7/143) were start loss, stop gain alterations and deletion. 97.5% of patients (39/40) displayed at least one mutation, while the average number of mutations per sample was 3.6 (range 0-8), confirming the high mutational load of these tumors. The most frequently altered genes identified were PIK3CA (62.5%), RDX (40%), MXRA5 (20%), BAP1 (15%), NF2 (15%). Molecular analyses have been correlated with Histology and Stage (thoracic vs extrathoracic MPM). We found the following NF2, PIK3CA, RDX altered genes in 9 biphasic tumor and MXRA5, NF2, PIK3CA, RDX, CUL1, BAP1, NF2, TAOK1 altered genes in 31 ephitelioid tumor. We observed a significant correlation between mutations in RDX gene (23.1%) and extrathoracic MPM. CUL1 and RDX genes were found in pts with progression free survival ≥6 months from prior treatment. Conclusions: This preliminary data supports the generation of a genetic signature based on tumor mutational status useful to discriminate MPM with different clinico-pathological features and possible correlation with treatment choice. Legal entity responsible for the study: AUSL-IRCCS Reggio Emilia. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.