Introduction: The prognosis of patients with advanced biliary tract cancer (BTC) is still poor, and new strategies improving patients' outcome are needed. In our trial we investigated safety and activity of nab-paclitaxel in combination with gemcitabine and oxaliplatin as first-line systemic treatment for patients with advanced BTC. Methods: In this investigator-initiated, multicenter, dose-escalation, single-arm phase I/II trial, patients were accrued into cohorts of 3 patients and dose escalation was performed following the standard 3 + 3 rule. Primary endpoint was the proportion of patients free from progression at 6 months. Secondary endpoints included safety and tolerability of the combination; progression-free survival (PFS); overall survival (OS); objective response rate (ORR); duration of response. Results: Between July 2017 and December 2020, 67 patients were treated. Among the 10 patients in the phase I, no dose-limiting toxicity was observed, and dose level 2 was defined as recommended phase II dose for the phase II part. At data cutoff, the 6-month PFS rate was 49.1 % (95 % CI 40.8-57.5 %) with 28 patients out of 57 free from progression or death at 6 months. Median PFS was 6.3 months (95 % CI 3.6-10.1) and median OS was 12.4 months (95 % CI 8-23). ORR was 20.89 %. Most common grade 3 and grade 1-2 drug-related adverse events were neutropenia and peripheral neuropathy, respectively. Conclusion: Triple chemotherapy demonstrated a favorable safety profile. However, the study did not meet its primary endpoint. Future studies will clarify the benefit of chemotherapy combinations in different settings. This trial is registered with ClinicalTrials.gov, NCT03943043.

Background and aimBoth tyrosine-kinase inhibitors (TKI) and Atezolizumab/Bevacizumab (A+B) are used as systemic treatment for hepatocellular carcinoma (HCC). Hypertension and proteinuria are among most common side effects caused by these drugs and can lead to treatment discontinuation. Since Angiotensin-Converting Enzyme (ACE) inhibitors are known to reduce proteinuria, we aimed to verify if they had a protective role on proteinuria developmentMethodWe retrospectively included consecutive patients receiving systemic therapy as standard of care for non-resectable HCC from 3 different Italian centers and verified prevalence of proteinuria within 3 months from the start of treatment.Differences between basal characteristics of the group were analyzed using a Mann-Whitney test or X2. A regression analysis was performed to find potential predictors of proteinuria.ResultsA total of 151 patients were analyzed (54 receiving A+B, 97 receiving TKI). Significant proteinuria developed in 29 (19.2%) of the patients without differences between treatment regimen, history of hypertension or anti-hypertensive drug between the two groups. Only serum creatinine, systolic and diastolic blood pressure at the beginning of the treatment were significantly different (p = 0.023, p = 0.014, respectively).Only a basal creatinine serum level and elevated systolic blood pressure (OR 1.14, p = 0.048) among who developed proteinuria were independently associated to the outcome.ConclusionPrevious use of ACE inhibitors does not prevent proteinuria, however a scarce control of blood pressure at the beginning of systemic treatment is independently associated with its occurrence. An aggressive initial approach to lower systemic blood pressure seems justifiable.

BackgroundThe standard treatment of advanced HCC is immune checkpoint inhibitor (ICI) therapy. Metabolic dysfunction-associated steatotic liver disease (MASLD) appears to adversely affect the efficacy of ICI. Recently, the antidiabetic drug metformin has garnered attention for its possible antitumor and immunomodulatory properties, such as reduction of proinflammatory cytokines and CD8+ T cells activation during immunotherapy. The aim of our study was to investigate the role of metformin in patients treated with atezolizumab/bevacizumab (A+B).Patients and Methods159 HCC patients (82% males, mean age 64.5) treated with A+B were enrolled from ARTE dataset. Clinical and radiological factors associated with patients’ response to therapy were used to stratify objective response rate (ORR), overall survival (OS) and progression free survival (PFS) by Kaplan- Meier methodology, followed by Log-rank test in multivariate analysis.Results53.3% patients had MASLD, with 31.9% being diabetic. No differences in OS, PFS and ORR were documented among the different etiologies. Considering 31 ORR patients, no differences between the two groups were underlined regarding sex, age, liver disease etiology. In the multistep multivariate model, diabetes was the only condition remained independently associate to ORR (OR 3.0, 95%CI 1.0-8.3; p=0.030). When diabetic patients were stratified based on antidiabetic treatments, those on metformin had a 12 months survival of 62% [44%-88%, 95% CI] vs insulin treatment with 21% [6%-72%, 95% CI], p<0.05.ConclusionDespite any clear difference in terms of ORR, OS and PFS between different etiologies, diabetic patients treated with metformin exhibited a better ORR and PFS, suggesting a potential immunological combination role of metformin with A+B treatment.

3511 Background: Preop CTRT is considered the standard of care in the management of LARC. RT can induce antigen release from a low neoantigen-burden tumor (such as a mismatch repair proficient colorectal cancer) and activate dendritic cells leading to a CD8+ T lymphocyte-mediated anticancer immune response. In LARC patients, neoadjuvant CTRT increases PD-L1 expression in tumor cells, strongly suggesting a neoadjuvant combinatory strategy with RT and PD-1/PD-L1 pathway blockade. Based on such considerations, we have designed the AVANA study to investigate the role of Ave in combination with preop CTRT in LARC. Methods: This is an Italian multi-center, phase II study. Pts with resectable LARC, defined by the presence of at least one of the following features: cN+, cT4, high risk cT3, received standard preop CTRT (capecitabine 825 mg/sqm/bid 5 days/week+ 50.4 Gy in 28 fractions over 5.5 weeks) plus 6 cycles of Ave 10 mg/Kg every 2 weeks. Surgery with total mesorectal excision was performed at 8-10 weeks after the end of CTRT. The primary end-point was the pCR rate, defined as complete histological regression with no available tumor cells ypT0N0. Secondary end-points were R0 resection rate, tumor downstaging, local recurrence, sphincter preservation rate, progression-free survival, overall survival, safety profile, and the evaluation of exploratory predictive and/or prognostic biomarkers. Assuming as null hypothesis p0 a pCR rate of 15%, a significance level of 5% (one-side), and a power of 80%, a sample size of 101 pts was needed to detect an absolute increment of 10% in pCR rate (from 15% to 25%). The experimental regimen is considered for further studies if, in at least 22 pts, we observe a pCR. Results: From April 2019 to November 2020, a total of 101 resectable LARC pts were enrolled in 10 Italian Centers. The median age was 63 years (23-82), 62 (61.4%) pts were male, 93 (92%) had ECOG PS 0. At baseline, 94 (93%) and 16 (16%) pts had cN+ and cT4 LARC, respectively. All pts completed the induction phase. Out of 96 pts evaluable for pathological response, 22 (23%) pts achieved a pCR and 59 (61.5%) pts a major pathological response (a central review is ongoing). At this time, microsatellite status is available only in 39 pts, of which only one was instable. The rate of grade 3-4 non-immune and immune-related adverse events was 8% and 4%, respectively. Avelumab was early interrupted in 9 pts out 101, mainly due to toxicity. Conclusions: The combination of preop CTRT plus Ave showed a promising activity and a feasible safety profile. According to our statistical considerations, the experimental regimen will be considered for further studies. Updated results will be presented during the Congress. Sponsored by GONO and partially supported by Merck. EUDRACT 2017-003582-10. Clinical trial information: NCT03854799.

Background: In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann-la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment. Patients and methods: In 14-day cycles, patients received FTD/TPI 35 mg/m(2) (twice daily, days 1-5) plus oxaliplatin 85 mg/m(2) (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B). Patients in Cohort B had confirmed MSS status. Results: In total, 54 patients were enrolled: 37 in cohort A and 17 in cohort B. Recruitment in cohort B was stopped early due to the low response rate (RR) observed at interim analyses of efficacy. The most common adverse events (AEs) in cohort A were neutropenia/decreased neutrophils (75.7%), nausea (59.5%), vomiting (40.5%), diarrhoea (37.8%), peripheral sensory neuropathy (37.8%), fatigue (35.1%) and decreased appetite (35.1%). In cohort B, the most common AEs were neutropenia/decreased neutrophils (70.6%), diarrhoea (58.8%), nausea (47.1%), vomiting (47.1%), fatigue (47.1%), asthenia (41.2%), paraesthesia (41.2%), thrombocytopenia/decreased platelets (35.3%) and decreased appetite (35.3%). Confirmed objective RR was 17.1% in cohort A and 7.1% in cohort B; the corresponding values for median progression-free survival in the two cohorts were 6.3 and 6.0 months. Conclusion: FTD/TPI plus oxaliplatin and bevacizumab or nivolumab had an acceptable safety profile and demonstrated antitumour activity in previously treated patients with mCRC.

On February 23rd the first case of SARS-CoV-2 infection was diagnosed at the University Hospital Trust of Verona, Italy. On March 13th, the Oncology Section was converted into a 22 inpatient beds COVID unit and we had to reshape our organization and personnel to face the SARS-CoV-2 epidemic, while maintaining our oncological activity. We tracked down oncological activity from January 1st to March 31st, 2020, in relationship to the organizational changes implemented and in comparison to the same period of 2019. We also recorded cases of SARS-CoV-2 infections observed in oncology health professionals and hospital admissions of active oncology patients for SARS-CoV-2 infection. Progressive restrictions in patients', visitors', and caregivers' access to the inpatient and outpatient facilities of the Oncology section and organizational changes were adopted early on during the epidemic peak. Since March 13th, segregated personnel teams were created, one dedicated to the COVID unit and a "clean" one dedicated to oncological patients, resulting in an overall 40% and 43% reduction in oncology-dedicated medical and nursing/auxiliary staff, respectively. As compared with the same trimester in 2019, the overall reduction in total numbers of inpatient admissions, chemotherapy administrations, and specialty visits in the period January-March 2020 was 8%, 6%, and 3%, respectively; based on the weekly average of daily accesses, reduction in some of the oncological activities became statistically significant from week 11. Patient's acceptance of adopted measures was very high (see abstract by Tregnago D). Overall, 8/85 (9%) health professionals tested positive for SARS-CoV-2 (no hospital admissions and no treatment required) and 7/525 (1.3%) active oncology patients were admitted for SARS-CoV-2 infection (of whom, 2 died of infection-related complications). A minimal (<10%) reduction in Oncology activity was registered during the peak of SARS-CoV-2 epidemic in Verona, Italy. Organizational and protective measures adopted appear to have contributed to keep infections in both health professionals and oncological patients to a minimum.

Loss of pancreatic parenchyma and/or the obstruction of the main duct may cause pancreatic exocrine insufficiency (PEI), resulting in maldigestion and malabsorption of nutrients. Despite the importance of treating PEI and malnutrition, evidence suggests that their early detection and management are usually overlooked in clinical routine. The current analysis aims to investigate the use of PERT and its effects on survival in patients (pts) affected by advanced PDAC undergoing chemotherapy. A retrospective analysis was conducted on non-consecutive pts with advanced pathologically confirmed PDAC. All pts were treated with Gemcitabine plus Nab Paclitaxel-based first-line chemotherapy at two academic medical institutions from March 2015 to October 2018. Descriptive statistics was adopted. Data were correlated with overall survival (OS) using a Cox regression model. Kaplan-Meier curves were compared with Log-Rank test. Data from 110 pts (57 males [51.8%], 53 females [48.2%]) were gathered (median age 65 years [range 37-81], with a median follow-up of 12 months (range 2-55). More than 65% had symptoms that could be related to malabsorption, like abdominal discomfort, bloating and steatorrhea. PERT was administered in 55 pts (50%), with no significant differences in baseline characteristics (age, gender, surgery, stage, weight loss, Performance Status) with those who did not receive PERT. Median OS for the entire group was 12 months (95%CI 9-15). At multivariate analysis, surgery of the primary (HR 3.12, 95% CI 1.51-6.44, p = 0.02) and PERT (HR 2.08, 95% CI 1.26-3.45, p = 0.004) were independent significant predictors of OS. Particularly, pts who received PERT had significantly longer 1-year OS (61.8% vs 32.5%, p = 0.0001). Our analysis suggests that previous surgery and PERT are independently associated with survival outcomes in pts with advanced PDAC receiving first-line chemotherapy. However, patterns of PEI assessment and PERT prescription are inconsistent and specific algorithms should be implemented, in light of the potential impact on survival and QoL.

To evaluate the association between body composition (BC) and systemic inflammatory response (SIR) following neoadjuvant treatment (NAD), and to explore their impact on long-term outcome in pancreatic ductal adenocarcinoma (PDAC) pts. Non-consecutive PDAC pts undergoing surgical exploration after NAD with available CT-scans (both at diagnosis and preoperatively) at two academic medical institutions from 2013 to 2015 were evaluated. BC was assessed by analyzing L3 CT-scan images before and after NAD. Neutrophil-lymphocyte ratio (NLR) was as a marker for SIR. Data were correlated with OS using Cox model. Kaplan-Meier curves were compared with Log-Rank test. The study population consisted of 108 pts (males: 56.5%), with a median follow-up of 16 months. 91 pts (89.8%) received FOLFIRINOX. BC changed significantly during NAD: total and visceral adipose tissue decreased (p<0.001), whereas the lean mass was increased (p<0.001). Sarcopenia was found in 45 pts (41.7%). Moreover, an NLR ≥ 3 was common (58.3%) and significantly related to total adipose and muscle tissue (p=0.032, p=0.002, respectively). Univariate analyses showed that age (HR 1.02, p=0.016), resection (HR 3.77, p=0.001), baseline skeletal mass normalized for height (TAMA) (HR 1.02, p=0.004) and increase in TAMA during NAD (HR 0.98, p=0.035) significantly affected OS. At MVA, age (HR 2.52, p=0.12) and baseline TAMA (HR 4.36, p=0.001) were significant independent predictors for OS. Our data provide evidence that BC impacts on long-term outcome in PDAC pts submitted to NAD. In addition, our results suggest a strict correlation between host SIR and changes in BC during and after NAD.

To explore the prognostic significance of nutritional status in patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC). Clinical data of non-consecutive patients submitted to surgery for PDAC from 2015 to 2018 at Pancreas Institute of Verona were prospectively collected. Nutritional Risk Screening 2002 (NRS) was performed to assess nutritional risk. Body composition was detected by Bioelectrical Impedance Analysis (BIA) the day before the scheduled surgery. Data were correlated to disease-free/overall survival (DFS/OS) using a Cox and logistic regression model. Kaplan-Meier curves were compared with Log-Rank. The final cohort consisted of 73 patients (median follow-up 11 months). The majority were at risk of malnutrition (NRS≥3). At multivariate analysis, stage (HR 4.30, p=0.045), NRS (HR 6.51, p=0.017), fat-free mass (FFM) (HR 1.08, p=0.013) were significant independent predictors for OS. Particularly, patients with preoperative NRS≤3 had significantly longer 2-year OS than those with NRS>3 (94% vs 75%, p=0.02). Contrariwise, BMI did not affect OS. Twenty-four patients (32.9%) were treated with neoadjuvant therapy. NRS was significantly higher in this subset of patients (p=0.026), with a significant difference according to chemotherapy regimens (Folfirinox vs Gemcitabine/Nab-paclitaxel) (p=0.035). In patients treated with adjuvant chemotherapy (45.2%), FFM correlated with worse DSF and OS (p=0.039 and p=0.039, respectively). Our analysis suggests that preoperative malnutrition has a detrimental impact on OS in resected PDAC. Preoperative nutritional screening and, possibly, targeted nutritional intervention may improve outcomes in resectable PDAC patients, particularly in those who are candidate to neoadjuvant therapy.

Background Nutritional derangements are common hallmarks of PDAC. Their early detection and management are usually overlooked in routine practice. The aim of this study was to explore the prognostic value of nutritional status in patients (pts) undergoing surgery for PDAC. Methods We prospectively studied 73 non-consecutive pts submitted to surgery for PDAC from November 2015 to January 2018 at General and Pancreatic Surgery Unit, Pancreas Institute, University Hospital of Verona. Nutritional Risk Screening (NRS) 2002 was used to evaluate the nutritional risk. Body composition was assessed using Bioelectrical Impedance Vector Analysis (BIVA) the day before the scheduled surgery. Clinical, pathological and nutritional data were correlated to disease-free/overall survival (DFS/OS) using a Cox and logistic regression model. Kaplan-Meier curves were compared with Log-Rank. Results The median age was 65 years [range 37-81], 41 pts were male (56.2%) and 32 were female (43.8%). Median follow-up was 11 months [range 1-40]. The majority (80.8%) were at risk of malnutrition (NRS-2002≥3), despite median BMI was 23.9 kg/m2. At multivariate analysis, stage (HR 4.30, 95% CI 1.03-17.92, p = 0.045), NRS-2002 (HR 6.51, 95% CI 1.39-30.38, p = 0.017), fat-free mass (FFM) (HR 1.08, 95% CI 1.02-1.14, p = 0.013) were significant independent predictors for OS. Particularly, pts with preoperative NRS-2002 ≤3 had significantly longer 2-year OS than those with NRS-2002 >3 (94% vs 75%, p = 0.02). Twenty-four pts (32.9%) were treated with neoadjuvant therapy. NRS-2002 was significantly higher in this subset of pts (p = 0.026), with a significant difference according to chemotherapy regimens (Folfirinox vs. Gemcitabine/Nab-paclitaxel) (p = 0.035). In pts treated with adjuvant chemotherapy (n = 33, 45.2%) FFM correlated with worse DSF and OS (p = 0.039 and p = 0.039, respectively). Conclusions Our analysis suggests that preoperative malnutrition has a detrimental impact on OS in PDAC. Therefore, preoperative nutritional screening and, possibly, targeted nutritional intervention may improve outcomes in resectable PDAC pts, particularly in those who are candidate to neoadjuvant therapy. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure M. Milella: Honoraria (self): Pfizer, EUSA Pharma, AstraZeneca. All other authors have declared no conflicts of interest.

Background Preop CTRT is the standard of treatment of LARC and it results in significant tumor downstaging and local control with a complete pathological response (pCR) rate of about 15%. Immunotherapy can lead up to a 50% of response in metastatic colorectal cancer (mCRC) with deficient mismatch repair (MMR) status, but its activity is extremely low in MMR proficient mCRC. In this context, the role of RT in revert the tolerance to a low neoantigen-burden by the induction of antigen release from the tumour and activation of dendritic cells leading to a CD8+ T lymphocyte-mediated anticancer immune response has been widely elucidated. Furthermore, in LARC pts, preop CTRT increases PD-L1 expression in tumor cells, strongly suggesting a neoadjuvant combinatory strategy with RT and PD-1/PD-L1 pathway blockade. On the basis of such premises we are conducting the AVANA study to explore the role of Ave in combination with preop CTRT in LARC. Trial design This is an Italian multi-center, phase II study. Pts with resectable LARC, defined by the presence of at least one of the following features, cN+, cT4, high risk cT3, receive standard preop CTRT (external-beam RT 50.4 Gray in 28 fractions over 5.5 weeks + capecitabine 825 mg/sqm/bid 5 days/week) plus 6 cycles of Ave 10 mg/Kg every 2 weeks. Surgery with total mesorectal excision is performed at week 8-10 after the end of CTRT. Postop CT is recommended according to pathologic response. The primary end-point is pCR rate. Secondary end-points are R0 resection rate, tumor downstaging, local recurrence, sphincter preservation rate, progression-free survival, overall survival, safety profile and the evaluation of exploratory predictive and/or prognostic biomarkers. Assuming as null hypothesis p0 a pCR rate of 15%, a significance level of 5% (one-sided) and a power of 80%, a sample size of 101 pts is needed to detect an absolute increment of 10% in pCR rate (from 15% to 25%). The experimental regimen will be considered for further studies if in at least 22 pts we observe a pCR. The enrollment is ongoing. Sponsored by GONO and partially supported by Merck. Clinical trial identification 2017-003582-10. Legal entity responsible for the study GONO. Funding Merck KGaA. Disclosure All authors have declared no conflicts of interest.

tail (38.1%, 47.3%, 18.8%) respectively.It shows us that the precursor lesions are also frequent in the remaining pancreas after standard Whipple (43.4% of PanIN3).IPMN lesion was found in the body and tail in one surgical specimen.This case also presented PanIN2 lesions.Discussion: In body and tail of the pancreas we found at least one of the precursor lesions of ductal adenocarcinoma and in many of them there are more than one of this lesions.The standard Whipple surgical procedure due to pancreatic head neoplasia may be insufficient to improve the prognosis of patients with PDA.Conclusions: Precursor lesions of adenocarcinoma in pancreatic body and tail are frequent and could have a roll in overall survival.Total pancreatectomy could be useful in this patients.

Background PC remains one of the most lethal solid tumors, mainly because of its intrinsic chemoresistance. We recently identified TAK1 as a central hub integrating the most relevant signals sustaining PC chemoresistance. nal-IRI is a novel standard of care for metastatic PC patients who had beenpreviously treated with a gemcitabine-based therapy.We endeavoured to identify circulating markers for TAK1 activation predicting chemoresistance in this clinical setting. Methods In vivo activity of nal-IRI was validated in an orthotopic nude mouse model of PC cells expressing TAK1- specific shRNA or a scramble sequence as control. Using multiplex xMAP/Luminex technology,the samples from 77 metastatic PC patients progressing after gemcitabine and prospectively enrolled to receive nal-IRI + 5FU/LV were analysed for the plasma concentration of 20 different TH1and TH2cytokines.The optimal cut-off thresholds able to significantly predict patient outcome were obtained based on the maximization of the Youden index. Results A significant tumour volume reduction in mice bearing shTAK1 PCtreated with nal-IRIwas detected, whereas controls were resistant to this agent. Differential gene expression profiling revealed CXCL8 as the most significantly downregulated gene coding for secreted proteins in[Office1] shTAK1PC cell lines. After a 27 month median follow-up, in the overall population the median progression-free survival (PFS) was 3.3 months (95% CI=3.039-3.561) and the median overall survival (OS) was 7.3 months (95% CI=5.487-9.113). Cox proportional hazard regression multivariate analysis confirmed CXCL8 as the circulating factor most significantly correlated with survival outcomes. Patients with CXCL8 higher than 16.68pg/mL cut-off value had a PFS of 2.8 vs 3.4 months (HR=2.61, 95% CI=1.42-4.79, p=0.0014), and an OS of 5.3 vs 8.9 months (HR=3.7, 95% CI=1.93-7.11, p=2.6e-05), respectively. Conclusions We identified CXCL8 as the most significant circulating marker of TAK1 activation. Our study candidates CXCL8 as a potential predictive biomarker of resistance to nal-IRI in gemcitabine-refractory PC patients. Legal entity responsible for the study The authors. Funding Associazione Italiana per la Ricerca sul Cancro (AIRC). Disclosure D. Melisi: Advisory / Consultancy, Research grant / Funding (institution): Shire. All other authors have declared no conflicts of interest.

Background: Patients affected by PC frequently present nutritional disorders that may influence their quality of life and prognosis. In addition to the disease, the systemic treatment may contribute to the malnutrition status of these pts. Few studies investigated the role of nutritional support during treatment of PC pts. Therefore, the aim of this analysis was to assess the nutritional status and the prognostic value of nutritional intervention in pts affected by advanced PC undergone chemotherapy. Materials and methods: Pts affected by locally advanced or metastatic PC, undergone chemotherapy, receiving nutritional counseling at the AOUI of Verona between July 2013 and October 2016 were included. Nutritional status was assessed by Malnutrition Universal Screening Tool (MUST), Body Mass Index (BMI), weight loss in the past 6 months (WL), presence of symptoms that may affect food intake and energy intake. Descriptive statistics was adopted. Clinical, pathological and nutritional data were prospectively correlated to Overall Survival (OS) using a Cox model. Results: Data from 109 pts (47 males [43.1%] and 62 females [56.9%]) were gathered (median age 63 years, median follow-up 8 months). At baseline, in seventy pts (64.2%) the MUST was ³2, significantly correlated with the PS (ECOG) (p < 0.0001), the median WL was 11.5% (range 0–35.4) and most patients suffered from early satiety (78%), loss of appetite (83.5%), dysgeusia (87.2%), dyspepsia (66.1%) and diarrhea or constipation (69.7%). The oncologist initially prescribed the nutrition counseling in only 33% of cases. At multivariate analysis, the time between the diagnosis of PC and the nutritional counseling (HR 2.22, p = 0.017), the Performance Status (HR 1.38, p = 0.075), the surgery of the primary (HR 5.89, p = 0.005) and the response to the first line (HR 5.9, p = 0.03) were significant predictor for OS. Furthermore, a weight gain more than 2% (cut-off defined by the Maximally selected Log-Rank statistics analysis) from the baseline weight was correlated with the time between the diagnosis and the nutritional intervention (p = 0.021): in pts receiving nutritional support within 3 months from diagnosis, a 2% weight gain was associated with a 2-year OS benefit (50.3% vs 33.0%, p = 0.04). Conclusions: These data suggest that the nutritional support may impact on prognosis of pts affected by advanced PC undergone chemotherapy. External validation is ongoing.

Background: According to recent findings from large randomized trials, PTL is suggested to have a role as both prognostic and predictive factor for mCRC. In this regard, the purpose of such analysis was to verify the clinical outcomes and the relationships between upfront treatment with Cet or Bev and PTL in consecutive KRAS-wild-type (wt) mCRC patients (pts) in the context of a 'real-world' setting. Material and methods: A retrospective database including pts with pathologically confirmed wt mCRC undergone upfront Cet or Bev-based chemotherapy from January 2009 to December 2014 at two Oncology Units of Verona was developed. With regard to PTL, left-sided tumors were defined as tumors originating from the splenic flexure to the rectum. Kaplan-Meier analysis and Cox univariate and multivariate model were performed. Log-rank test was adopted to compare survival curves. Results: Data from 141 consecutive wt mCRC pts were gathered; median OS and PFS were 31.1 months (CI 95% 19.6–49.4) and 11.8 (CI 95% 9.1-17.9), respectively. Pts' characteristics: median age 63 (range 36-80); PTL left/right: 101/40 (71.6%/28.4%); liver only metastases: 50 (35.5%); single-site: 80 (56.7%); PS-ECOG (0-1/ ≥ 2): 132/9 (93.6%/6.4%); Cet/Bev: 64/81 (45.4%/54.6%); surgery for metastases: 61 (43.3%). Resection of metastases and PTL resulted to be both independent predictors of OS and PFS. With regard to PTL, median OS was 29.7 versus 20.4 months for left-sided versus right-sided mCRC, respectively (p = 0.013). For patients receiving Cet, median OS was 39.7 months for left-sided tumors and 20.1 months for right-sided (p = 0.022); median OS did not differ according to PTL in pts receiving Bev (25.6 versus 20.4 months, respectively, p = 0.08). Conclusions: Despite the biases in the retrospective nature of this analysis, these data support the hypothesis that a differential effect of Cet or Bev as upfront treatment for wt mCRC pts in a 'real-world' scenario according to PTL might exist. A validation in a larger cohort is mandatory.

Advanced biliary tract adenocarcinoma (BTA) is a rare tumor with a poor prognosis. Since no standard salvage chemotherapy regimen exists, we explored the activity of capecitabine alone or combined with mitomycin C.