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

e23093 Background: Despite vaccination, COVID-19 could still cause severe disease in immunocompromised patients (pts). While subsequent vaccine doses increase immune response in the general population, few data concerning cancer pts under systemic treatment are reported. Methods: This study will be conducted on blood samples from 1000 pts admitted to Reggio Emilia AUSL-IRCCS Cancer Center and undergoing systemic therapies who received ≥ 2 vaccine doses. The samples will be analyzed at Clinical Microbiology and Chemistry Laboratories of Reggio Emilia AUSL-IRCCS. We will perform antibody IgM-IgG serology by means of COVID-19 VIRCLIA® Monotest and anti-spike antibodies evaluation using LIAISON® SARS CoV-2 Trimerics IgG. We will also investigate cell immune response (B and T lymphocyte counts) and analyze specific lymphocyte subsets on the first 200 pts treated with chemo- (CT) or immunotherapy (IO). Then, we will evaluate the T-cell response on the first 50 pts and those with an inadequate anti-spike serologic response through the T-SPOT.COVID test. Statistical analyses will be conducted by the Clinical Studies and Statistical Unit Staff. Results: Here, we report preliminary data on the first 240 pts enrolled and treated with CT (55.4%), IO (26.3%), or other therapies (18.3%). Most of the pts were male (58%), had metastatic cancer (82%), and no previous COVID-19 infection (60%). 84% of pts were affected by gastrointestinal, lung, urogenital and breast cancer. We stratified pts in three groups according to the time from the last vaccine dose (0-6/6-12/ > 12 months). We showed no significant decrease in cellular and humoral immune response over time from the last vaccine dose, independent of the specific treatment received, also if CT (Table 1). Furthermore, clinical characteristics as gender, treatment, and primary tumor site appear not to influence immune response, even if a trend to a higher response in pts previously affected by COVID-19 has been observed. The T-SPOT.COVID test performed on the first 27 pts showed that 19% had no T-cell activation, even with good IgG response. Conclusions: This feasible and cost-effective study has a potential impact on public health. Although these are preliminary data, the immune response to COVID-19 vaccines remains good after 12 months from the last dose administered in cancer pts. The enrollment is ongoing, and we could provide relevant information on the influence of clinical factors on the immune response and identify specific subgroups that could benefit from different vaccine approaches. [Table: see text]

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]

BACKGROUND:There is evidence that early integration of palliative care improves quality of life, lowers spending and helps clarify preferences and goals for advanced cancer patients. Little is known about the feasibility and acceptability of early integration.AIM:Assessing feasibility of early integration of palliative care, and exploring concerns perceived and problems encountered by patients, relatives and oncologists.DESIGN:A phase 2 mixed-methods study ( ClinicalTrials.Gov :NCT02078700).METHODS:Oncologists of two outpatient clinics offered a specialised palliative care intervention integrated with standard oncological care to all consecutive newly diagnosed metastatic respiratory/gastrointestinal cancer patients. We interviewed samples of patients, relatives and oncologists to explore strengths and weaknesses of the intervention.RESULTS:The intervention was proposed to 44/54 eligible patients (81.5%), 40 (90.1%) accepted, 38 (95.0%) attended the first palliative care visit. The intervention was completed for 32 patients (80.0%). It did not start for three (7.5%) and was interrupted for three patients who refused (7.5%). The Palliative Care Unit performed 274 visits in 38 patients (median per patient 4.5), and 24 family meetings with relatives of 16 patients. All patients and most relatives referred to the usefulness of the intervention, specifically for symptoms management, information and support to strategies for coping. Oncologists highlighted their difficulties in informing patients on palliative intervention, sharing information and coordinating patient's care with the palliative care team.CONCLUSION:Early integration of palliative care in oncological setting seems feasible and well accepted by patients, relatives and, to a lesser extent, oncologists. Some difficulties emerged concerning patient information and inter-professional communication.

e15656 Background: Neuroendocrine tumors (NETs) are considered rare tumors and can produce a variety of hormones. In this study, we examined the epidemiology and prognostic factors for NETs, in Italy. Methods: The Italian Association of Cancer Registries (AIRTUM) were researched to identify NETs: 38/39 cancer registries participated for the period 1976-2010. Malignant infiltrating tumors were included with the following morphology codes: 8150-8157, 8240-8246 and 8249. Results: We identified 9,707 patients with NETs: 55% males; 61% in the age 50-74 years, 17.5% under 50 years and 21.5 % in the 75+. We observed a significant increase in the reported annual age-adjusted incidence from 1976 (0.7/100,000) to 2010 (5.3/100,000). The highest rate was recorded in northern Italy (Milan 5.8/100,000), the lowest in southern Italy (Ragusa 0,81/100,000). The distribution of the tumor site was: lung 32.8%, small intestine 14.4%, colon 10.7%, stomach 8.8%, rectum 4.7%, breast 1.4%, other sites 20.3% and in 6.9% the primary site was unknown. Overall we found 2033 second tumors: 29 NETs and 2004 other sites: these were divided into before (1,360, 68%), and after (644, 22%) diagnosis of NETs. Among after diagnosis, we separate the synchronous within two months of diagnosis (78 cases, mainly lung 19% and colon 14%) by metachronous if diagnosed after two months of diagnosis (566 cases, mainly skin 18%, prostate12,5%, colon 8,5%, lung and bladder). Conclusions: We observed a increased reported incidence of NETs over time, suggesting that NETs are more prevalent than previously reported. Clinicians need to be become familiar with the natural history and patterns of disease progression, which are characteristics of these tumors. The association with second cancers should better direct the follow- up of patients with NETs .

e15242 Background: FOLFIRINOX and nab-paclitaxel (nab-p) plus gemcitabine are approved regimens for metastatic pancreatic cancer (mPC).NabucCO study was a phase I/II trial designed in two steps.The first one defines dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of Nab-FOLFIRI and Nab-FOLFOX, obtained by the substitution of oxaliplatin or irinotecan with nab-p in FOLFIRINOX classical schedule. In the second step (phase II) we will evaluate the activity of these new regimens.Now we report final results of dose-finding (DLTs/ MTD) for Nab-FOLFIRI. Methods: Study started on February 2014 and patients (pts) with mPC without prior treatment for metastatic disease and PS ECOG 0-1 received irinotecan 180 mg/m2iv, leucovorin 400 mg/m2iv, 5FU bolus 400 mg/m2iv and 5-FU 48h ci 2400 mg/m2iv plus nab-p iv through 6 levels of escalation (level 1:90 mg/m2,level 2:100 mg/m2,level 3:110 mg/m2,level 4:120 mg/m2,level 5:130 mg/m2,level 6:140 mg/m2) every 2 weeks for up to12 cycles.The design was the standard 3+3 phase I dose escalation. The MTD was established by DLTs according with Common Toxicity Criteria for Adverse Events (CTCAE) v. 4.03 during the first cycle of therapy. Results: A total of27 pts were treated with Nab FOLFIRI. The median age was 62 yr (38-75).We treated 3 pts at level 1, 3 pts at level 2, 6 pts at level 3, 6 pts at level 4, 6 pts at level 5, 3 pts at level 6. At level 6, one pt experimented neutropenia gr4, thrombocytopenia gr3, and we also registered one serious adverse event for another pt (hospitalization for fever, asthenia gr3 and anorexia gr2). We planned another 3 pts at level 5 and unexpectedly we observed DLTs in 2 pts: neutropenia gr4, leucopenia gr3, thrombocytopenia gr3. So we defined the MTD at level 4 through a cohort expansion of 3 pts without toxicities. At this time,14 pts completed Nab-FOLFIRI and are evaluable for overall safety and secondary end-points.In the Nab-FOLFOX arm12 pts have been enrolled and no DLTs are detected at level 4. Conclusions: The MTD of nab-p with FOLFIRI is 120mg/m2. Dose finding for Nab-FOLFOX could be completed in May 2015 (Clinicaltrials.gov NCT02109341). Clinical trial information: NCT02109341.

e15242 Background: FOLFIRINOX and nab-paclitaxel (nab-p) plus gemcitabine are approved regimens for metastatic pancreatic cancer (mPC).NabucCO study was a phase I/II trial designed in two steps.The first one defines dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of Nab-FOLFIRI and Nab-FOLFOX, obtained by the substitution of oxaliplatin or irinotecan with nab-p in FOLFIRINOX classical schedule. In the second step (phase II) we will evaluate the activity of these new regimens.Now we report final results of dose-finding (DLTs/ MTD) for Nab-FOLFIRI. Methods: Study started on February 2014 and patients (pts) with mPC without prior treatment for metastatic disease and PS ECOG 0-1 received irinotecan 180 mg/m2iv, leucovorin 400 mg/m2iv, 5FU bolus 400 mg/m2iv and 5-FU 48h ci 2400 mg/m2iv plus nab-p iv through 6 levels of escalation (level 1:90 mg/m2,level 2:100 mg/m2,level 3 …

Although lactate dehydrogenase (LDH) serum levels, indirect markers of angiogenesis, are associated with a worse outcome in several tumours, their prognostic value is not defined in pancreatic cancer. Moreover, high levels are associated even with a lack of efficacy of tyrosine kinase inhibitors, contributing to explain negative results in clinical trials. We assessed the role of LDH in advanced pancreatic cancer receiving sorafenib. Seventy-one of 114 patients included in the randomised phase II trial MAPS (chemotherapy plus or not sorafenib) and with available serum LDH levels, were included in this analysis. Patients were categorized according to serum LDH levels (LDH ≤ vs.> upper normal rate). A significant difference was found in progression free survival (PFS) and in overall survival (OS) between patients with LDH values under or above the cut-off (PFS: 5.2 vs. 2.7 months, p = 0.0287; OS: 10.7 vs. 5.9 months, p = 0.0021). After stratification according to LDH serum levels and sorafenib treatment, patients with low LDH serum levels treated with sorafenib showed an advantage in PFS (p = 0.05) and OS (p = 0.0012). LDH appears to be a reliable parameter to assess the prognosis of advanced pancreatic cancer patients, and it may be a predictive parameter to select patients candidate to receive sorafenib.

The study aimed to evaluate the tissue expression of molecules involved in intracellular signalling pathways as predictors of response to sorafenib in advanced hepatocellular carcinoma (HCC).

AIM:To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC).MATERIALS & METHODS:Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone.RESULTS:Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone.CONCLUSION:A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized.

BACKGROUND:Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma (HCC). The viability of continuing sorafenib at a higher dosage in patients who experienced radiologic disease progression was investigated.METHODS:Patients who experienced disease progression while on sorafenib 400 mg twice daily were randomized to sorafenib 600 mg twice daily (n = 49) or best supportive care (n = 52). The primary end point was progression-free survival (PFS). Time to progression, overall survival, and safety were also evaluated.RESULTS:The study did not meet its primary end point. The difference in PFS between the sorafenib arm (3.91 months) and the best supportive care arm (2.69 months) did not reach statistical significance (p = 0.086). Adverse events were mainly grade 1-2 and similar across both groups. In the sorafenib arm, the most frequent events were diarrhea (80%), weight loss (75%), fatigue (67%), hand-foot-skin reaction (49%), abdominal pain (37%), and stomatitis (26%).CONCLUSIONS:Escalated-dose sorafenib in patients with advanced HCC who progressed while on sorafenib, failed to provide any clinical benefit. Second-line treatment still remains an open issue to be explored in appropriate clinical trials.

PURPOSE:Aim of this phase I study was to identify the maximum tolerated dose and dose limiting toxicity of continuous infusion of Irinotecan through a port-a-cath placed in the hepatic artery in patients with hepatocellular carcinoma and cirrhosis to explore new strategies in advanced hepatocellular carcinoma. Response rate and time-to-progression were analysed.METHODS:Irinotecan was delivered as a five-day continuous infusion every 21 days, with increases of 2.5mg/m(2)/day every three patients, starting from 7.5mg/m(2)/day. Dose limiting toxicity corresponded to one patient in each triplet developing G4 haematological or G3 non-haematological toxicity, confirmed in two triplets. Twenty-eight patients (17 Child-Pugh A, 11 B) received treatment and tumour response was assessed after three courses completed by 22 patients.RESULTS:Dose limiting toxicity was G3 diarrhoea in two patients, reached at 27.5mg/m(2)/day and the recommended dose was set at 25mg/m(2)/day. Nineteen of 30 patients experienced adverse events related to porth-a-cath placement and one died from liver ischemia and sepsis. Median time-to-progression was 11.3 months.CONCLUSION:Intrarterial infusion of Irinotecan is feasible in patients with hepatocellular carcinoma on cirrhosis at a recommended dose of 25mg/m(2)/day, with no major adverse drug-related events, but with some concerns about the insertion and management of the intra-arterial device.