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Second- or third-line treatment options for metastatic renal cell carcinoma (mRCC) have dramatically changed in the last few years. There are no criteria for the choice between nivolumab and cabozantinib, which both demonstrated overall survival (OS) gain in pivotal trials.We conducted an analysis of oncological outcomes in patients treated in the Veneto Region (Italy), studying different sequences of TKI-nivolumab-cabozantinib or TKI-cabozantinib-nivolumab in a publicly funded healthcare system.We conducted a retrospective, real-world analysis of all consecutive patients with mRCC treated with nivolumab or cabozantinib in 2017-2018 at 19 Oncology Units in the Veneto Region.We identified 170 patients, 73 % males, median age 68.4 years. All patients started second-line treatment, 59 % received a third-line therapy. Patients with NLR3 had a shorter OS (p0.0001). In the second-line treatment, nivolumab was administered to 108 patients (63 %), cabozantinib to 29 (17 %); in the third-line treatment nivolumab was administered to 42 patients (25 %), cabozantinib to 49 (29 %). Median OS and PFS in second line treatment were 28.4 and 6.6 months for nivolumab, 16.8 and 6.6 months for cabozantinib. Median OS and PFS in third-line treatment were 27 and 5.2 months for nivolumab, 16.6 and 7.5 months for cabozantinib. Median OS for nivolumabcabozantinib sequence versus cabozantinibnivolumab was 28.8 versus 19.9 months (p = 0.2); median PFS for both the sequences were similar at 5.7 months. A cost effectiveness per month of survival of the two sequences analysis was performed: the cost per month for the nivolumabcabozantinib sequence was 1738.60whereas the cost for the other one was €1624.80.In our real-world cohort, most patients received nivolumab as second-line treatment. Outcomes of single drugs are superimposable with those in the published literature. Both the sequences of nivolumab and cabozantinib appear to be viable, effective strategies from an OS and cost-effective perspective.

Background Post-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH. Methods Serum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed. Results Median percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P P P P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P P Conclusions Treatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes.

International audience; BACKGROUND: Tivantinib (ARQ 197), a selective, oral MET inhibitor, improved overall survival and progression-free survival compared with placebo in a randomised phase 2 study in patients with high MET expression (MET-high) hepatocellular carcinoma previously treated with sorafenib. The aim of this phase 3 study was to confirm the results of the phase 2 trial. METHODS: We did a phase 3, randomised, double-blind, placebo-controlled study in 90 centres in Australia, the Americas, Europe, and New Zealand. Eligible patients were 18 years or older and had unresectable, histologically confirmed, hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0-1, high MET expression (MET-high; staining intensity score >=2 in >=50% of tumour cells), Child-Pugh A cirrhosis, and radiographically-confirmed disease progression after receiving sorafenib-containing systemic therapy. We randomly assigned patients (2:1) in block sizes of three using a computer-generated randomisation sequence to receive oral tivantinib (120 mg twice daily) or placebo (twice daily); patients were stratified by vascular invasion, extrahepatic spread, and α-fetoprotein concentrations (

6511 Background: Since the beginning of the COVID-19 outbreak, the Veneto Oncology Network ROV licensed dedicated guidelines for cancer patients care during the pandemic, and developed a regional registry (ROVID) aimed at describing epidemiology and clinical course of SARS-CoV-2 infection in cancer patients. Preliminary data on 170 patients mainly diagnosed during the first pandemic wave have been published (Guarneri V, Eur J Cancer 2021). Here we report the data of additional 270 patients, comparing clinical data and outcomes between first (W1) and second (W2) pandemic waves. Methods: All patients with cancer diagnosis and documented SARS-CoV-2 infection are eligible. Data on diagnosis, comorbidities, anticancer treatments, details on SARS-CoV-infection including source of contagion, clinical presentation, hospitalization, treatments and fate of the infection are recorded. Results: 440 patients have been enrolled, 196 diagnosed during W1 (until September 2020) and 244 during W2. The most common cancer type was breast cancer (n = 116). Significant differences in clinical characteristics between W1 and W2 were the followings: ECOG PS 0 (34% vs 58%), presence of cardiac comorbidities (30% vs 13%), presence of any co-morbidities (81% vs 62%), smoking habits (23% vs 13%). Patients diagnosed in W1 were less likely on active anticancer therapy (54% vs 73%) at the time of SARS-CoV-2 infection. Distribution per stage, presence of lung metastases, disease setting (curative vs palliative), active treatment discontinuation due to infection were similar between W1 and W2. Patients diagnosed in W1 were more likely symptomatic for SARS-CoV-2 infection (80% vs 67%), and reported more frequently an in-hospital contact as potential source of infection (44% vs 9%). Significantly more patients diagnosed in W1 were hospitalized (76% vs 25%). All-cause mortality rates were 30.6% for patients diagnosed in W1 vs 12% for patients diagnosed in W2 (p < 0.001). However, deaths due to SARS-CoV-2 infection were more frequent in patients diagnosed in W2 (86% vs 54%, odds ratio 3.22; 95% CI 1.97-5.279). Conclusions: Differences in clinical characteristics between W1 and W2 reflect different pattern of virus circulation. The dramatic reduction of in-hospital contact as a source of infection reflects the efforts put in place to protect this vulnerable population from in-hospital exposure. The lower all-cause mortality rate observed in W2 is in line with the observed less frail population. However, the higher relative risk of death due to SARS-CoV-2 infection observed in W2 reinforces the need to adopt protective measures including vaccination in cancer patients, irrespectively of age, stage, and comorbidities.

290 Background: Second (2L) or third-line (3L) treatment options for mRCC have dramatically changed in the last years. The standard of care as per Italian Regulatory Agencies approvals is N or C. To date, there are no criteria for the choice between N and C, which both demonstrated OS gain in the pivotal trials. Methods: We planned a retrospective, real world analysis of the use of N and C as 2L and 3L treatment in 17 Oncology Units of Veneto Region. All consecutive patients (pts) with mRCC treated in advanced setting in 2017-2018 were included. Results: We identified 170 pts, 73% males, median age 68.4 years. All pts started a 2L treatment while only 59% received a 3L treatment. In our cohort, patients with NLR > 3 at treatment start had a shorter OS (43 vs 90 months (mos), p < 0.0001); IMDC classification maintained its prognostic role. In 2L, N was administrated in 108 pts (63%), C in 29 pts (17%); in 3L N was administrated in 42 pts (25%), C in 49 pts (29%). Reported oncologists’ reasons for 2L choice were: change of mechanism of action compared to first line (28%), response to previous TKI (21.2%), intolerance to TKI (17.6%), previous toxicity (12.9%), tumor burden (11.2%), age of the patient (4.1%). Median OS and PFS in 2L were 28.4 and 6.6 mos for N, 16.8 and 6.6 mos for 2L C. Median OS and PFS in 3L were 27 and 5.2 mos for N, 16.6 and 7.5 mos for C. 46 pts received the sequence of drugs N > C, 12 the opposite sequence C > N. Median OS for N > C vs C > N were 96.6 vs 36 mos (p > 0.0001); median PFS for both the sequences were similar at 5.7 mos (p = ns). The cost per patient of the sequence N > C is 51.606 € while for the sequence C > N is 31.480,00 €. Between the two sequences a cost effectiveness per month of survival analysis was performed: the cost per month of OS for the sequence N > C was 534,18 € while for the sequence C > N was 874,46 €, heavily higher. Conclusions: In our real-world setting cohort, most of the pts received N as 2L treatment and a minority received C. Outcome of single drug are superimposable to published literature. With the limits of the retrospective nature of the study, with a cost per month of OS lower a much longer OS, the sequence N > C appear to be a better treatment strategy.

Pancreatic cancer (PC) is one of the leading cause of cancer death. Neoadjuvant therapy has been progressively used in the context of locally advanced/unresectable disease improve patients’ outcome. New drugs combination are associated with increased response rate but at the expense of higher toxicities. We presented a case of a patient with locally advanced disease treated who could undergo surgery after 14 cycles of therapy with gemcitabine and curcumin conjugated with phospholipids (Meriva®). Treatment was well tolerated without severe toxicities or impairment of quality of life. The patient is disease free at 9 month from surgery and 28 months from initial diagnosis and he still is in good clinical conditions. The combination of gemcitabine and Meriva® was effective in allowing radical surgery in a patient with locally advanced PC. Moreover, this results was obtained with minimally toxic regimen.

Background Recent data suggest a potential activity and a good tolerability of capecitabine in advanced hepatocellular carcinoma (HCC). Aims To evaluate capecitabine activity and safety in a wide cohort of advanced HCC patients. Methods Retrospective analysis of 143 capecitabine-treated patients (January 2010 to December 2017) in three centers of the Veneto Oncology Network. Results Capecitabine was administered in second and third line, but also in first line instead of sorafenib in Child-Pugh B patients (70%), compromised clinical conditions (14%) or contraindications to antiangiogenetics (16%). Median overall survival (OS) and time to progression (TTP) were 6.9 and 2.8 months, respectively. There were no differences in OS and TTP between the 32 patients treated with non-metronomic scheme (2000 mg/day for 14 days) and the 111 patients treated with metronomic scheme (1000 mg/day) after correction for prognostic factors at baseline with a propensity score analysis. Capecitabine was more active in patients intolerant to sorafenib than in those progressing during treatment (p = 0.024). At least one adverse event (mainly hematological) was experienced by 73% of patients but discontinuation was necessary only in 11 (8%). Conclusions Capecitabine can be considered an active and safe option in advanced HCC, especially for patients unfit for other treatments.

1. Abstract 1.1. Background: Complementary and Alternative medicine (CAM) is commonly used by cancer patients (pts). Recent randomised controlled trials showed that acupuncture is safe, effective and feasible for the management of cancer-related fatigue and other adverse events of anti-neoplastic therapies. 1.2. Materials and Methods: Since November 2012 we have been offering a supportive care program of 20 minutes’ weekly session of acupuncture for the management of chemotherapy-induced nausea/vomiting, hot flashes, cancer-related fatigue, xerostomia. A brochure regarding indications and techniques was offered to all cancer patients who received a systemic anticlastic therapy (Chemotherapy, Target Therapy, Endocrine Treatment) and/or radiation therapy. 1.3. Results: More than 500 pts affected by solid tumours or lymphoma were treated in our Operative Unit during the period of the project. None of them preferred to receive acupuncture in addition to the specific pharmacological treatment. 1.4. Conclusion: Cancer pts of the district of Belluno, Italy did not demonstrate any interest in acupuncture for the management of side effects of anti-neoplastic treatments.

Resume Introduction Les cancers du pancreas et de la region peri-ampullaire chez les patients âges de plus de 80 ans posent encore des problemes aux chirurgiens a cause du risque de la chirurgie sur ce terrain. Nous avons revu notre experience et celle rapportee dans la litterature des pancreatectomies chez les patients octogenaires, afin d’evaluer les resultats precoces et la survie a long terme en cas de cancer. Methode Trois cent quatre-vingt-cinq patients ayant eu une pancreatectomie pour tumeur entre 1998 et 2011 etaient inclus dans l’etude et ont ete divises en deux groupes : le groupe 1 forme de patients âges de moins de 80 ans ; et le groupe 2 de patients âges de 80 ans et plus. La morbidite, la mortalite perioperatoires, la survie sans recidive et la survie a long terme etaient analysees. Une recherche bibliographique etait faite sur les resultats des resections pancreatiques chez les patients octogenaires. Resultats Parmi les 385 patients : 362 etaient dans le groupe 1 et 23 dans le groupe 2. Il n’y avait pas de differences significatives pour le sexe et les caracteristiques tumorales entre les deux groupes. Le taux de complications (40 vs 43 %) et de mortalite (4 vs 0 %) et la survie globale mediane pour les cas de cancer du pancreas (21 vs 19 mois) n’etaient pas significativement differentes entre le groupe 1 et le groupe 2. La revue de la litterature a retrouve 14 etudes dont la plupart des etudes (surtout celles provenant de centre a gros volume) montraient des resultats similaires entre les patients octogenaires et les patients plus jeunes. Conclusion La pancreatectomie est une option acceptable chez les patients âges. L’âge seul ne peut etre considere comme une contre-indication a la resection pancreatique, mais une evaluation rigoureuse avant l’intervention et une prise en charge perioperatoire optimale sont essentielles.

Summary Introduction Pancreatic and perampullary neoplasms in patients aged 80 or older trouble the surgeons because of the risk of surgical treatment. We have reviewed our experience and literature's reports of pancreaticoduodenectomy in octogenarians, evaluating early results and long-term survival in pancreatic cancer group. Methods Three hundred eighty-five patients who underwent pancreaticoduodenectomy for neoplasms from 1998 to 2011 were included in the study, and were divided in two groups: group 1, patients younger than 80 years of age, and group 2, patients 80 years of age and older. Operative morbidity, mortality, disease-free and long-term survival were analysed. English literature was systematically searched for pancreatic resection's outcome in octogenarians. Results There were 385 pancreaticoduodenectomies: 362 patients were in group 1 and 23 patients in group 2. There was no significant difference regarding gender, and pathologic findings between the two groups. Complications’ rate (40 vs. 43%), mortality rate (4% vs. 0%), and overall median survival for pancreatic cancer patients were not statistically different in the two groups (median 21 vs. 19 months). Literature's review showed 14 reports of pancreatic resection in octogenarians. Most of the studies (particularly in centres with high-volume pancreatic surgery) showed that outcome after pancreatectomy was not different in octogenarians or in younger patients. Conclusion Pancreaticoduodenectomy is an acceptable option for elderly patients. Age alone should not be considered a contraindication to major pancreatic resection, but a careful preoperative evaluation and an accurate postoperative management are mandatory.

The most common cause of hyperinsulinaemic hypoglycaemia in adult is insulinoma. Although nesidioblastosis is a rare but well-recognized disorder of persistent hypoglycaemia in infants, it is extremely rare in adults.We present a case of a 59-year-old woman with small neuroendocrine tumour of the tail of the pancreas, diagnosed by CT scans and MRI, and hypoglycaemic syndrome. Laparoscopic distal pancreatectomy was performed, and pathologic examination showed a well-differentiated, non-functioning endocrine tumour of the pancreas and diffuse nesidioblastosis in the remnant gland. In the early postoperative period, recurrent hypoglycaemia occurred in spite of oral diazoxide therapy. Plasma proinsulin levels were extremely high. 18F-DOPA positron emission tomography showed a pathologic uptake of tracer in the head and the uncinate process of the pancreas. Subtotal pancreatectomy was suggested but the patient refused operation: she is taking diazoxide 100 mg three times daily. Coexistence of nesidioblastosis with a neuroendocrine tumour makes preoperative diagnosis and management of severe hypoglycaemia more difficult. Nesidioblastosis should be considered in differential diagnosis of hypoglycaemic syndrome, but histological examination is necessary for a definitive tissue diagnosis.

To confirm the efficacy and safety of bevacizumab/XELOX combination for the treatment of locally advanced or metastatic colorectal cancer (CRC) in Italy.This multicentric, prospective, open-label study included patients with CRC previously untreated with chemotherapy. Patients were administered bevacizumab in combination with XELOX. The primary efficacy end-point was progression-free survival (PFS). Secondary end-points included time to overall response (TOR), duration of response (DOR), time to treatment failure (TTF) and overall survival (OS). The incidence and type of adverse events AEs and severe AEs were evaluated. Also, the mutational status of BRAF and KRAS was assessed by high resolution melting and direct sequencing, and quality of life (QoL) was measured by the EuroQoL EQ-5D questionnaire at baseline and at the last visit.The intention-to-treat population included 197 patients (mean age: 62.3 ± 9.9 years, 56.4% males). At baseline, 16/34 evaluable subjects (47.1%) harbored a KRAS and/or a BRAF mutation; the mean QoL index was 80.2 ± 14.3. First-line therapy was given for 223.7 ± 175.9 d, and after a mean follow-up of 387.7 ± 238.8 d all patients discontinued from the study mainly for disease progression (PD, 45.4%) and AEs (25.4%). Median PFS was 9.7 mo (95%CI: 8.4-10.5) and the median values for secondary end-points were: TOR = 3.9 mo (95%CI: 2.6-4.7), DOR = 8.5 mo (95%CI: 7.3-10.3), TTF = 6.7 mo (95%CI: 6.0-7.7) and OS = 23.2 mo (95%CI: 20.1-27.2). Patients carrying at least one lesion had a lower overall response rate (66.7% vs 88.9%) and a lower probability of achieving complete or partial response than those without mutations, but the difference in relative risk was not statistically significant (P = 0.2). Mean EQ-5D-3L raw index score significantly decreased to 74.9 ± 19.1 at the last visit (signed-rank test, P = 0.0076), but in general the evaluation on QoL perceived by patients was good.The efficacy of bevacizumab in combination with XELOX in terms of PFS in patients with aCRC or mCRC in Italy was confirmed, with acceptable toxicity.

A large body of biomedical evidence indicates that activation of Nrf2 by curcumin increases the nucleophilic tone and damps inflammation cumulatively supporting the malignant phenotype. Conversely, genetic analyses suggest a possible oncogenic nature of constitutive Nrf2 activation since an increased nucleophilic tone is alleged increasing chemoresistance of cancer cells. Aiming to contribute to solve this paradox, this study addressed the issue of safety and efficacy of curcumin as complementary therapy of gemcitabine on pancreatic cancer. This was a single centre, single arm prospective phase II trial. Patients received gemcitabine and Meriva®, a patented preparation of curcumin complexed with phospholipids. Primary endpoint was response rate, secondary endpoints were progression free survival, overall survival, tolerability and quality of life. Analysis of inflammatory biomarkers was also carried out. Fifty-two consecutive patients were enrolled. Forty-four (13 locally advanced and 31 metastatic) were suitable for primary endpoint evaluation. Median age was 66 years (range 42–87); 42 patients had Eastern Cooperative Oncology Group performance status 0–1. The median number of treatment cycle was 4.5 (range 2–14). We observed 27.3% of response rate and 34.1% of cases with stable disease, totalizing a disease control rate of 61.4%. The median progression free survival and overall survival were 8.4 and 10.2 months, respectively. Higher IL-6 and sCD40L levels before treatment were associated to a worse overall survival (p

Aim: We investigated the behavior of circulating endothelial cells (CEC) in patients with hepatocellular carcinoma (HCC) receiving sorafenib, and whether CEC levels were associated with time to progression (TTP). Materials & methods: CECs in advanced HCC patients receiving sorafenib were counted at baseline and every 4 weeks. Results: Twenty four HCC patients were enrolled in the study. Median TTP was 3.2 months (1–6). Median baseline CEC levels were 67 cells/ml, with an increase of 169.8% after 4 weeks of treatment. Any time CEC levels in patients with a TTP lower than 4 months were higher, but not statistically significant, compared with those in patients with TTP more than 4 months. Conclusion: Treatment with sorafenib changed CEC levels in HCC patients.

Purpose To report patient-focused outcomes as measured by quality of life (QoL) and performance status (PS) in REACH, a phase III placebo-controlled randomised study, assessing ramucirumab in advanced hepatocellular carcinoma (HCC) patients who received prior sorafenib. Methods Eligible patients had advanced HCC, Child-Pugh A, PS 0 or 1 and prior sorafenib. Patients received ramucirumab (8 mg/kg) or placebo (1:1) on day 1 of a 2-week cycle. QoL was assessed by FACT Hepatobiliary Symptom Index (FHSI)-8 and EuroQoL (EQ-5D) at baseline; cycles 4, 10, and 16; and end of treatment. PS was assessed at baseline, each cycle, and end of treatment. Deterioration in FHSI-8 was defined as a ≥3-point decrease from baseline and PS deterioration was defined as a change of ≥2. Both intention-to-treat and pre-specified subgroup of patients with baseline serum alpha-fetoprotein (AFP) ≥400 ng/mL were assessed. Results There were 565 patients randomised to ramucirumab and placebo. Compliance with FHSI and EQ-5D was high and similar between groups. In the ITT population, deterioration in FHSI-8, EQ-5D, and PS was similar between ramucirumab and placebo. In patients with baseline AFP ≥400 ng/mL, ramucirumab significantly reduced deterioration in FHSI-8 at the end of treatment compared with placebo (P = 0.0381), and there was a trend towards a delay in the deterioration of symptoms in FHSI-8 (HR 0.690; P = 0.054) and PS (HR 0.642; P = 0.057) in favour of ramucirumab. Conclusions We report one of the most comprehensive data sets of QoL and symptom burden in patients undergoing systemic therapy for advanced HCC. Ramucirumab was associated with no worsening of QoL. In patients with baseline AFP ≥400 ng/mL, the significant survival benefit observed in patients treated with ramucirumab was coupled with a trend in patient-focused outcome benefits. Clinical trial registration NCT01140347 .

Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3–4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3–4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs.

Data from a large European prospective observational study were analysed to describe the antiemetic prescribing pattern for chemotherapy-induced nausea and vomiting (CINV) in Italian clinical practice.Post hoc analysis of the Pan European Emesis Registry in chemo-naïve adults initiating single-day highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer.A total of 211 eligible patients were enrolled in the Italian centres, 180 were included in the analyses for cycle 1; 50·6% received MEC. The use of guideline-consistent CINV prophylaxis (GCCP) varied substantially between acute and delayed phases (54·4% during the acute phase vs. 29·4% in the overall 120-hour study period, acute plus delayed phases). Neurokinin-1 receptor antagonist was added to the prophylaxis with dexamethasone+5-hydroxytryptamine type 3 receptor antagonists in only 11·1% of patients (vs. 57·2% of the entire European study population). In the GCCP group, the complete response rate was significantly higher than that recorded in the guideline-inconsistent CINV prophylaxis (GICP) group (75·5 vs. 53·5%, P = 0·006).The proportion of guideline-consistent antiemetic therapy was quite low in the Italian population as it was in the overall European population. The implementation of specific guidelines' recommendations for chemotherapeutic regimens administered according to standard protocols could be considered as a means to reduce the burden of CINV.

Tumor biopsies may help to reliably distinguish hepatocellular carcinoma (HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments, in order to improve the success rate of experimental therapies. Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies. Recently, clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients. Due to their frail status and sometimes fast-progressing disease, the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly, preventing their enrollment in clinical trials. However, the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients, and solid networks between research centers and referring institutions. An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials. Ultimately, institution of multidisciplinary teams can optimize treatment choice, biopsy timing, and quick enrollment of patients in clinical trials, before their performance status deteriorates.

10070 Background: Convergent findings indicate the need of broadening the vision of cancer beyond known prognostic factors, as many variables of different nature equally affect the course of disease. Loneliness has been found to be associated with various health outcomes, but its relationship with cancer remains unclear. Here we aimed to investigate the specific effect of loneliness and other demographic, psychological, and clinical variables on cancer mortality and to validate the Italian UCLA Loneliness Scale in cancer patients. Methods: This descriptive and correlational study was conducted at the Veneto Institute of Oncology in Padua. 400 patients undergoing chemotherapy from 01/2014 to 06/2015 were enrolled. The sample was stratified by sex and age (4 groups, 40-80 y). We collected demographic, clinical (site and stage of cancer, type of chemotherapy, death date), and psychosocial [self-esteem (RSE), perceived social support (MSPSS), social interaction anxiety (SIAS), personality (EPQR), and depression (BDI)] data. Results: GLM analyses: loneliness was higher in women than men (F(1,398) = 7.5, p = .006) and it linearly increased with age (F(1,398) = 10.9, p = .001). Loneliness was also influenced by marital status (F(3,396) = 2.9, p = .037), cohabitant offspring (F(1,398) = 7, p = .008), and educational level (F(3,396) = 4.7, p = .003), but not by clinical variables (all ps > .05). Correlation analyses: loneliness was inversely related to RSE (r = -.51), MSPSS (r = -.52), and extroversion (r = -.32), and directly related to SIAS (r = .46), neuroticism (r = .43), and BDI (r = .44). More importantly, a hierarchical binomial logistic regression revealed that patients’ mortality was reliably predicted by gender, stage of cancer at diagnosis, time from diagnosis to UCLA collection, BDI, and UCLA (HL χ2(8) = 3.53, p = .90). In particular, high BDI predicted higher mortality (Wald = 11.6, p < .001); surprisingly, after controlling for BDI and other effects, high loneliness predicted lower mortality (Wald = 7, p = .008). Conclusions: Our results replicate prior research and reveal a surprising association between loneliness and mortality risk after partialling out the impact of, especially, depression. This suggests the role of loneliness on cancer course as an important health concern.

Bone metastases affect the majority of patients with castration-resistant prostate cancer (CRPC), resulting in significant morbidity and mortality. This review describes the current therapies available for the management of CRPC patients with bone metastases. Areas covered: Studies on the use of currently available therapeutic approaches for palliating pain, delaying skeletal-related events (SREs) and prolonging survival in CRPC patients with bone metastases have been examined. PubMed database was searched in May 2016 starting with the following keywords: ('castration-resistant prostate cancer' OR 'CRPC') AND 'bone metastases', and approximately 270 results were retrieved. More specific searches were then performed on the epidemiology and molecular pathogenesis (in particular, 'vicious cycle' was used as a keyword), the management of pain, SREs and survival. The following keywords were also used individually: abiraterone, cabazitaxel, denosumab, docetaxel, enzalutamide, radium-223, sipuleucel-T, samarium-153, strontium-89, zoledronate. Randomized-controlled trials, observational studies, reviews, systematic reviews and meta-analyses were selected and articles were excluded if not in English. Expert commentary: Currently, clear recommendations on the optimal use of the agents available to treat mCRPC are lacking. Therefore, to ensure patients the best treatment, both their clinical characteristics and the features of each product have to be considered.

In the last 5 years inhibitors of the VEGF/VEGFR and mTOR pathways have dramatically changed the therapeutic approach to metastatic renal cancer. Randomized controlled trials have shown that six targeted agents – sorafenib, sunitinib, temsirolimus, bevacizumab, everolimus and pazopanib – are able to improve patient outcome. Even if the choice of drug for first-line therapy is quite well defined, to date it is not easy to characterize and evaluate the efficacy of new therapies in second-line treatment. It is not clear whether, after first-line therapy with a VEGF/VEGFR inhibitor, use of mTOR or a second TKI inhibitor should be recommended. In this review we report on current evidence supporting the use of targeted agents in second-line therapy. Therefore we try to combine current clinical results with a practical clinical approach, with the goal of evaluating the best clinical decision for different clinical situations.

Introduction Cost-effectiveness analysis provides a ratio that indicates the value created per unit of money by a given therapy but says nothing about the total expected costs or net health and social impact of this therapy in a particular population of interest. Objective The main objective of this study is to define a methodology to calculate the effects of interventions from a local perspective. This will help determine parameters that provide information about resource planning and management to local decision makers. Methods The described methodology calculates four indicators using local demographic and epidemiological data and a Markovian decision tree approach. Results The method was applied to evaluate the economic, health and social impact of introducing a new cancer drug, Trastuzumab, for the early treatment of breast cancer in the Veneto Region of Italy. Discussion The indicators described in this study allow public policy makers to clearly understand the benefits and costs of a particular health intervention in a local population and to compare it with other strategies.

Chemotherapy induced cardio-toxicity is a well known side effect of anticancer treatments, moreover the 70% of all tumors involve patients over 65 years-old, frequently with cardiac co- morbidity. We evaluated the feasibility of the application during chemotherapy administration of some of the most recent diagnostic techniques as 12-diagnostic leads telemetry, 7 days EKG monitoring device (R-Test Evolution 3R), blood level dosage of Brain Natriuretic Peptide (BNP) and Ischemia Modified Albumin (IMA). Some sub-clinical changes in the investigated parameters were found in patients undergoing chemotherapy, mostly containing fluorouracil, as shown in the following paper. Far from suggesting a widespread use of these methods during chemotherapy administration, we think that some more tools are needed to prevent cardiac toxicity in high-risk patients and some of what we studied may deserve further valuation in chemotherapy clinical trials.

The role of bridging therapies for patients with hepatocellular carcinoma (HCC) on the waiting list for liver transplantation (LT) remains controversial. There is strong evidence to support the effectiveness of sorafenib in extending the time to progression of HCC. Using a Markov model, we compared two strategies: one using sorafenib as neoadjuvant therapy before LT (Strategy A), and the other using no bridging therapy in the first 6 months (Strategy B). Reference case: T2 HCC patient with compensated cirrhosis. The benefit of sorafenib in delaying time to HCC progression was expressed as the hazard ratio (HR) and taken from recently published randomized trials. The endpoints considered were: survival benefit measured in quality-adjusted life days (QALDs), transplant probability, costs (C) in €, willingness to pay (WTP), and net health benefit (NHB), where NHB = survival benefit − C/WTP. The calculated WTP of sorafenib in Italy was 346 € per QALD. Probabilistic sensitivity analysis showed a median survival benefit of 94 QALDs (10% percentile = 38, 90% percentile = 210). In the base-case scenario (HR = 0.47, monthly dropout probability = 5%, median time to LT = 3 months), the gain in LT probability due to sorafenib was 5% and it increased proportionally with increasing median times to LT and decreasing HR. In the cost-benefit analysis, the incremental NHB of Strategy A versus Strategy B was 37 QALDs; it increased as sorafenib HR decreased and when median times to LT were shorter than 6 months, whereas for longer times it gradually dropped, particularly when Strategy B included effective locoregional treatments. Conclusion: Sorafenib neoadjuvant therapy is cost-effective by comparison with no therapy for T2-HCC patients waiting for LT, particularly for median times to LT under 6 months. (HEPATOLOGY 2009.)

Cetuximab is a monoclonal antibody that competitively inhibits the epidermal growth factor receptor (EGFR). It is used for the treatment of metastatic colorectal cancer after first-line therapy. We report the first case of a pustular psoriasiform drug eruption induced by cetuximab in a patient with colorectal cancer. This paradoxical side effect could be the result of an imbalance in downstream molecular pathways due to the EGFR signal blockade that could, in selected patients, induce alternative signalling pathways related to keratinocyte proliferation.

Background There are scarce data on the use of sorafenib for the treatment of recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). Patients and Methods Ten patients were treated with sorafenib after OLT following the Italian Drug Agency guidelines: they had well-compensated liver function (Child-Pugh class A in the case of cirrhosis), intermediate-or advanced-stage HCC, good general condition (performance status 0), and not suitable for loco-regional therapies. Patients with HCC recurrence after OLT were treated with sorafenib (400 mg twice daily). Adverse events (AEs) were assessed using National Cancer Institute Common Toxicity Criteria of Adverse Events (NCI-CTCAE) v3.0 with tumor responses evaluated acording to modified Response Evaluation Criteria in Select Tumors) criteria. Results Median duration of treatment was 10 months (range, 2–18). Seven patients (70%) received an additionally targeted therapy with mTOR inhibitors as part of their immunosuppressive regimen. Most common grade 3 AEs included diarrhea (50%), hand-foot skin reaction (30%), and fatigue (20%). Sorafenib had to be discontinued in 3 patients (30%) due to AEs and 4 additional patients (40%) required a dose adjustment. No deterioration of liver graft function occurred. Three patients (30%) stopped treatment due to radiological progression of HCC, whereas 3 are still using the drug. Median time to progression was 8 months (range, 2–16). Median survival from start of therapy was 18 months (range, 4– 36). Conclusion Our preliminary results suggest that sorafenib is a safe effective therapy for recurrent HCC after OLT.

The most common cause of hyperinsulinaemic hypoglycaemia in adult is insulinoma. Although nesidioblastosis is a rare but well-recognized disorder of persistent hypoglycaemia in infants, it is extremely rare in adults.We present a case of a 59-year-old woman with small neuroendocrine tumour of the tail of the pancreas, diagnosed by CT scans and MRI, and hypoglycaemic syndrome. Laparoscopic distal pancreatectomy was performed, and pathologic examination showed a well-differentiated, non-functioning endocrine tumour of the pancreas and diffuse nesidioblastosis in the remnant gland. In the early postoperative period, recurrent hypoglycaemia occurred in spite of oral diazoxide therapy. Plasma proinsulin levels were extremely high. 18F-DOPA positron emission tomography showed a pathologic uptake of tracer in the head and the uncinate process of the pancreas. Subtotal pancreatectomy was suggested but the patient refused operation: she is taking diazoxide 100 mg three times daily. Coexistence of nesidioblastosis with a neuroendocrine tumour makes preoperative diagnosis and management of severe hypoglycaemia more difficult. Nesidioblastosis should be considered in differential diagnosis of hypoglycaemic syndrome, but histological examination is necessary for a definitive tissue diagnosis.

The aim of the present study was to determine the outcome of patients undergoing pancreatic resection with (VR+) or without (VR−) mesenteric-portal vein resection for pancreatic carcinoma. Between January 1998 and December 2012, 241 patients with pancreatic cancer underwent pancreatic resection: in 64 patients, surgery included venous resection for macroscopic invasion of mesenteric-portal vein axis. Morbidity and mortality did not differ between the two groups (VR+: 29% and 3%; VR−: 30% and 4.0%, resp.). Radical resection was achieved in 55/64 (78%) in the VR+ group and in 126/177 (71%) in the VR− group. Vascular invasion was histologically proven in 44 (69%) of the VR+ group. Survival curves were not statistically different between the two groups. Mean and median survival time were 26 and 15 months, respectively, in VR− versus 20 and 14 months, respectively, in VR+ groupp=0.52. In the VR+ group, only histologically proven vascular invasion significantly impacted survivalp=0.02, while, in the VR− group, R0 resectionp=0.001and tumor’s gradingp=0.01significantly influenced long-term survival. Vascular resection during pancreatectomy can be performed safely, with acceptable morbidity and mortality. Long-term survival was the same, with or without venous resection. Survival was worse for patients with histologically confirmed vascular infiltration.

Sorafenib is the only validated pharmacological treatment option for patients with advanced hepatocellular carcinoma (HCC) in the context of Child-Pugh class A liver function. Effective and safe systemic treatments for advanced disease with severe underlying cirrhosis (Child-Pugh class B and C) are not yet available. A few reports have described capecitabine as an option after failure of sorafenib or for patients who were not eligible for clinical trials. Here, we present a case of good response to low dose capecitabine in a patient with advanced HCC.

The incidence of chemotherapy-induced nausea and vomiting (CINV) has been decreasing through improvements of antiemetic drugs and refinements of antiemetic guidelines. However,CINV still occurs in approximately half of patients receiving cancer chemotherapy .

Bone is a common site for tumor spread in patients with solid tumors. So far bisphosphonates have been the main pharmacological treatment option for patients with bone metastases. We present a case of bone metastatic gastric cancer treated with zoledronic acid at first and later with denosumab. After 1 year of denosumab treatment, the 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography scan reassessment documented a metabolic complete response, even in the absence of specific antiblastic treatment. Whether denosumab can be used directly after pretreatment with bisphosphonates has yet to be addressed.

Objective Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, shows activity in multiple tumor types, including those refractory to previous antiangiogenic therapy. This randomized, multicenter, parallel-group, open-label phase II trial compared axitinib with bevacizumab each in combination with 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) or 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) for second-line treatment of metastatic colorectal cancer. Methods Patients were randomized 1:1 to axitinib 5 mg twice daily or bevacizumab 5 mg/kg every 2 weeks plus modified FOLFOX-6 (if previously treated with irinotecan) or FOLFIRI (if previously treated with oxaliplatin) and were stratified by performance status and prior bevacizumab therapy. Primary endpoint was progression-free survival. Results In 171 patients, progression-free survival was 7.6 months with axitinib/FOLFOX vs. 6.4 months with bevacizumab/FOLFOX (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.55-1.96; 1-sided P = .55) and 5.7 months with axitinib/FOLFIRI vs. 6.9 months with bevacizumab/FOLFIRI (HR, 1.27; 95% CI, 0.77-2.11; 1-sided P = .83). Overall survival was 17.1 vs. 14.1 months with axitinib/FOLFOX and bevacizumab/FOLFOX (HR, 0.69; 95% CI, 0.37-1.27; 1-sided P = .12) and 12.9 vs. 15.7 months with axitinib/FOLFIRI and bevacizumab/FOLFIRI (HR, 1.36; 95% CI, 0.82-2.24; 1-sided P = .88). More grade ≥ 3 adverse events (eg, diarrhea, fatigue, decreased appetite) and treatment discontinuations due to adverse events occurred with axitinib. Conclusions Compared with bevacizumab, axitinib did not improve outcomes when added to second-line chemotherapy for metastatic colorectal cancer. With current dosing regimens, axitinib plus FOLFOX or FOLFIRI seems to be less well tolerated than bevacizumab-based regimens.

e15696Background: GEM still represents one of the mostly adopted treatments for PC. Combination treatments provided some improvement in response rate (RR) and progression free survival (PFS), although almost invariably associated to increased toxicity. Aiming to find a complementary therapy to GEM in advanced PC, we tested a preparation of curcumin complexed with phospholipids (Meriva) to increase bioavailability. Curcumin has antinflammatory, antioxidant and potential antitumor properties, seemingly, descending from the activation of nuclear factor Nrf2 and inhibition of NFkB. From this pattern of nutraceutical effects of Curcumin, Meriva emerges as a good candidate for complementary therapy, while also improving quality of life (QoL). Methods: This was a single centre, single arm prospective phase II trial. Inclusion criteria were: previously untreated patients with histologically confirmed metastatic or locally advanced PC, ECOG performance status (PS) of 0-2, adequate organ function and written inform...

An improved understanding of the biological pathways deregulated in renal cell carcinoma has led to the development of various targeted agents, changing dramatically the therapeutic options for this disease. However, despite numerous opinions and guidelines, the optimal treatment still remains uncertain. In this review, we analyze the most recent published reports regarding the agents sunitinib, bevacizumab, sorafenib, temsirolimus, and everolimus. Moreover, we assess the novel targeted drugs pazopanib and axitinib. In addition, given the likely lack of cross-resistance between these targeting agents, we discuss sequential and combination targeted therapy in metastatic renal cell carcinoma, analyzing the most recent data.

Von Hippel-Lindau disease is a rare autosomal dominant inherited disorder that predisposes the occurrence of cysts and various types of cancers such as hemangioblastoma, pheochromocytoma, renal cell carcinoma and more rarely pancreatic tumors. In this review, we analyze the characteristics and management of pancreatic lesions, in particular cysts and neuroendocrine tumors, in Von Hippel-Lindau disease.

Despite recent improvements in surgical techniques and chemotherapy treatments, locally advanced/metastatic gastroesophageal junction (GEJ) and gastric cancer (GC) are still associated with poor clinical outcome. However, increased understanding of molecular mechanisms underlying carcinogenesis and its implementation in the treatment of breast, colon, lung, and other cancers in recent years have spurred focus on the development and incorporation of targeted agents in current therapeutic options for this difficult-to-treat disease. Such agents have the ability to target a variety of cancer relevant targets, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) and its receptor. In this review, we describe the current status of targeted therapies in the treatment of advanced GC and GEJ cancer, focusing on pre-clinical and clinical data available on monoclonal antibodies and tyrosine kinase inhibitors acting in these pathways, including completed and ongoing phase III studies.

Prognostic factors such as surgery and pathology in vulvar squamous cell carcinoma are studied.47 patients with vulva squamous cell carcinoma treated at the Gynecology Department of the University of Padua, have been retrospectively studied.At the univariate relapse-free survival analysis, a significant association was found for histological grade, stage of disease and type of surgery. All patients presented vulvar squamous cell carcinoma: G(1) in 25 (53%), G(2) in 14 (30%), and G(3) in 8 (17%) patients. The distribution of stages was as following: stage 1 in 6 (13%), stage 2 in 20 (43%), stage 3 in 11 (23%), and stage 4 in 10 patients (21%). Radiotherapy was performed in 13 patients. Among the 47 patients evaluable: 26 (55.3%) developed local recurrence, 12 of these patients developed a second local relapse, 3 of these also had distant metastases (lung in 1 patient, lomboaortic and mediastinic lymph nodes in the other 2 patients). Stromal invasions wereor=9 mm in 14 patients with 6 relapses and9 mm in 30 patients with 27 relapses (univariated analysis p=0 0066). Five episodes (10,6%) of thrombosis were observed.After multivariate analysis, surgery, stage and stromal invasion over 9 mm (hazard ratio=3.1; 95% confidence interval: 1.3-7.7) proved to be the most dominant predictor for relapse-free survival. Histological grades 1 and 2 were predictive of better disease-free survival (p=0.0012).

This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer.Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery.Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response.The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.

In recent years with the development of targeted agents such as bevacizumab, sunitinib, sorafenib, temsirolimus, and everolimus, the treatment of metastatic renal cell carcinoma has changed dramatically. In clinical practice, sunitinib and bevacizumab are reserved for first-line treatment, but despite various guidelines, optimal treatment is still uncertain. We present, for the first time, a case of a good response to second-line bevacizumab and interferon-alpha in a patient who failed classical sunitinib treatment.

Malignant pleural effusion is a frequent complication in many types of tumors, and its presence indicates short expected survival. This review updates the current knowledge about diagnosis and management of malignant pleural effusion. In recent years, progress has been made in diagnosis through the use of new pathologic and radiologic approaches, such as the introduction of positron emission tomography-computed tomography, immunohistochemical marker combinations, and genetic studies to identify malignant cells. Treatment is always palliative. New promising drugs have been tested, but, awaiting randomized studies, talc pleurodesis is still the treatment of choice, although doubts remain about its safety. A long-term indwelling pleural catheter could be a valid alternative to talc pleurodesis in selected patients with trapped lung syndrome (a lung that fails to reexpand after drainage of pleural effusion) and short life expectancy. However, the correct treatment depends on several factors such as performance status, expected survival, presence of lung reexpansion following pleural drainage and comorbidities.

There is pre-clinical evidence of synergism between cisplatin and temozolomide due to higher inhibition of O(6)-alkyl-guanine-alkyltransferase (AGAT), an enzyme involved in the mismatch repair system and in the mechanisms of drug resistance to alkylating agents.Heavily pre-treated patients with temozolomide-refractory high-grade malignant glioma received cisplatin at a dose of 75 mg/m(2) on day 1 and temozolomide at a dose of 150 mg/m(2) on days 1 to 5 every 21 days until progression or major toxicity.Twenty-four patients were enrolled and a total of 96 cycles were delivered (median for each patient=4). Toxicity was manageable and mostly grade 1-2: haematological, gastroenterological (nausea and vomiting) and fatigue. In patients with glioblastoma, an overall response rate of 29.4% was achieved, with no complete response, and with a disease control rate (responses plus stabilizations) of 64.7%. The median time to progression was 3.8 months (95% confidence interval 2.4-6.8), progression-free survival at 6 months was 28% and overall survival was 7.0 months (95% confidence interval 4.8-11.0).The combination of temozolomide and cisplatin is safe and moderately effective in the treatment of heavily pre-treated patients with relapsed high-grade glioma refractory to single-agent temozolomide.

Advanced renal cancer remains a challenge for oncologists since no treatment other than surgery has demonstrated a clear survival advantage.Gemcitabine was given to suitable patients at a fixed infusion rate of 10 mg/m2/min. Eighteen patients received concomitant immunotherapy, mostly low doses of interleukin 2 (IL2).Thirty patients were enrolled. The overall response rate was 14% (22% in the subset of patients treated with both chemotherapy and immunotherapy) with a median progression-free survival time of 4.1 + months. Toxicity was not mild, mostly fatigue, nausea and anaemia, even though not life threatening.Gemcitabine at the fixed infusion rate of 10 mg/m2/min with concomitant low doses of IL2 could be useful in the palliative treatment of symptomatic patients with renal carcinoma progressing after tyrosine kinases inhibitor.