Publications by authors named "Libero Ciuffreda"

64 Publications

Quality of life among germ-cell testicular cancer survivors: The effect of time since cancer diagnosis.

PLoS One 2021 6;16(10):e0258257. Epub 2021 Oct 6.

Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO-Piemonte, Torino, Italy.

Introduction: Testicular cancer is one of the most treatable cancers, with a 10-year survival of more than 95%. Many patients will be long-term survivors and this disease strikes men in an important phase of their lives, therefore the quality of life (QoL) among these patients is an area of particular interest. We aimed to study whether QoL in testicular cancer survivors depends on the time since cancer diagnosis.

Methods: Data were collected from the EPSAM (Esposizioni postnatali e salute maschile) study, a case-control study on patients with testicular cancer, diagnosed between 1997 and 2008 in the province of Turin, Northern Italy, and interviewed between 2008 and 2010 (response rate among cases 57%). Patients were contacted through their oncologist at the San Giovanni Batista Hospital in Turin or through their general practitioner (GP) in the rest of the Province of Turin. QoL was assessed cross-sectionally using the short form 12 (SF-12) questionnaire, a generic short-form health survey that produces two summary scores, PCS (physical component score) and MCS (mental component score), to evaluate physical and mental health, respectively.

Results: Out of 234 study patients, 125 cases were seminomas and 109 cases were nonseminomas. The mean age at diagnosis was 34.5 years. After adjusting for age, time since diagnosis was not associated with PCS and MCS scores. Among nonseminomas, the median PCS slightly increased (adjusted OR (odds ratio) for 5+ vs < 2 years since cancer diagnosis: 1.78 (1.17-2.73), p = 0.008) and MCS slightly decreased (adjusted OR per 1-year increase since cancer diagnosis: 0.92, 95% CI: 0.82-1.05, p = 0.23) with time. Similar findings of no association between time since diagnosis and PCS and MCS were found when the analyses were restricted to the subgroup of cancer patients contacted through their oncologist, whose response proportion was 82%.

Conclusion: In a study of testicular cancer patients interviewed cross-sectionally at 1 to more than 10 years since diagnosis, time since cancer diagnosis was not associated with QoL when we considered all germ-cell testicular cancer patients together. When stratified by histology type, we found certain evidence that nonseminoma cases report higher PCS over time since cancer diagnosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258257PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494333PMC
October 2021

Oral vinorelbine and cisplatin as first-line therapy for advanced squamous NSCLC patients: a prospective randomized international phase II study (NAVoTrial 03).

Ther Adv Med Oncol 2021 16;13:17588359211022905. Epub 2021 Jul 16.

Clinical Oncology, ICESP - Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.

Objective: The study investigated the efficacy and safety of oral vinorelbine-cisplatin (OV-CDDP) and gemcitabine-cisplatin (GEM-CDDP) in patients with squamous non-small cell lung cancer (sq-NSCLC).

Patients And Methods: This was an open-label, prospective, multicenter, international phase II study that enrolled untreated patients with advanced sq-NSCLC. Patients were randomized to receive 3-week cycles of either 60-80 mg/m OV days 1 and 8 in combination with 80 mg/m CDDP day 1 (arm A) or 1250 mg/m GEM days 1 and 8 in combination with 75 mg/m CDDP day 1 (arm B). After four cycles, patients without disease progression continued maintenance dose of OV or GEM until progression or unacceptable toxicity. The primary objective was disease control rate (DCR). Secondary objectives included progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), safety, and quality of life (QoL).

Results: A total of 114 patients with sq-NSCLC were randomized, and 113 were treated (57 in arm A and 56 in arm B). DCR was high in both arms: 73.7% (95%CI: 62.4-100.0) in arm A and 75.0% (95%CI: 63.7-100.0) in arm B. Median PFS and TTF were similar in arm A and B 4.2 and 2.8 months, and 4.3 and 3.1 months, respectively. Even though the difference was not significant, the OS was 10.2 for arm A and 8.4 months for arm B. The safety profiles were consistent with the current knowledge of adverse events. QoL results revealed an improvement in patients under OV treatment.

Conclusion: The OV-CDDP combination showed comparable efficacy to GEM-CDDP with acceptable safety profile and enhanced patients' QoL.

Trial Registration: The study was registered under EudraCT number 2012-003531-40.
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http://dx.doi.org/10.1177/17588359211022905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287271PMC
July 2021

Trabectedin for Patients with Advanced Soft Tissue Sarcoma: A Non-Interventional, Retrospective, Multicenter Study of the Italian Sarcoma Group.

Cancers (Basel) 2021 Mar 2;13(5). Epub 2021 Mar 2.

Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, 1 Via Pupilli, 40136 Bologna, Italy.

The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1-40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior ( < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective responses and/or disease stabilization, treated in an early line and treated with reduced dose. Bone marrow toxicity (61.4%) and transaminase increases (21.9%) were the most common grade 3/4 adverse events. The results of this real-life study suggest that trabectedin is an active treatment, which is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic L-sarcoma (clinical trial information: NCT02793050).
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http://dx.doi.org/10.3390/cancers13051053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958606PMC
March 2021

Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in older patients: A subgroup analysis from the TOSCA trial.

Eur J Cancer 2021 05 18;148:190-201. Epub 2021 Mar 18.

Cancer Center ASST Papa Giovanni XXIII, Bergamo, Italy.

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results.

Patients And Methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged <70 years and 693 ≥ 70 years) randomised to receive 3 or 6 months of FOLFOX or CAPOX within the frame of the phase III, TOSCA study.

Results: Older patients compared with younger ones presented more frequently an Eastern Cooperative Oncology Group performance status equal to 1 (10.5% vs 3.3%, p < 0.001), a greater number of right-sided tumours (40.9% vs 26.6%, p < 0.001), and were at higher clinical risk (37.2% vs 33.2%, p = 0.062). The treatments were almost identical in the two cohorts (p = 0.965). We found a greater proportion of dose reductions (46.7% vs 41.4%, p = 0.018), treatment interruptions (26.1% vs 19.3%, p < 0.001) and a higher proportion of recurrences (24.2% vs 20.3%, p = 0.033) in the older patients. The multivariable analysis of the TTR did not indicate a statistically significant effect of age (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 0.98-1.44; p = 0.082). The HR comparing older with younger patients was 1.34 (95% CI: 1.12-1.59; p = 0.001) for DFS, 1.58 (95% CI: 1.26-1.99; p < 0.001) for OS, and 1.28 (95% CI: 0.96-1.70; p = 0.089) for CSS.

Conclusions: Worse prognostic factors and reduced treatment compliance have a negative impact on the efficacy of oxaliplatin-based adjuvant therapy in older patients.
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http://dx.doi.org/10.1016/j.ejca.2021.01.051DOI Listing
May 2021

Ga-DOTATOC PET/CT-Based Radiomic Analysis and PRRT Outcome: A Preliminary Evaluation Based on an Exploratory Radiomic Analysis on Two Patients.

Front Med (Lausanne) 2020 26;7:601853. Epub 2021 Jan 26.

Nuclear Medicine Unit, Department of Medical Sciences, University of Turin, Turin, Italy.

This work aims to evaluate whether the radiomic features extracted by 68Ga-DOTATOC-PET/CT of two patients are associated with the response to peptide receptor radionuclide therapy (PRRT) in patients affected by neuroendocrine tumor (NET). This is a pilot report in two NET patients who experienced a discordant response to PRRT (responder vs. non-responder) according to RECIST1.1. The patients presented with liver metastasis from the rectum and pancreas G3-NET, respectively. Whole-body total-lesion somatostatin receptor-expression (TLSREwb-50) and somatostatin receptor-expressing tumor volume (SRETV wb-50) were obtained in pre- and post-PRRT PET/CT. Radiomic analysis was performed, extracting 38 radiomic features (RFs) from the patients' lesions. The Mann-Whitney test was used to compare RFs in the responder patient vs. the non-responder patient. Pearson correlation and principal component analysis (PCA) were used to evaluate the correlation and independence of the different RFs. TLSREwb-50 and SRETVwb-50 modifications correlate with RECIST1.1 response. A total of 28 RFs extracted on pre-therapy PET/CT showed significant differences between the two patients in the Mann-Whitney test ( < 0.05). A total of seven second-order features, with poor correlation with SUVmax and PET volume, were identified by the Pearson correlation matrix. Finally, the first two PCA principal components explain 83.8% of total variance. TLSREwb-50 and SRETVwb-50 are parameters that might be used to predict and to assess the PET response to PRRT. RFs might have a role in defining inter-patient heterogeneity and in the prediction of therapy response. It is important to implement future studies with larger and more homogeneous patient populations to confirm the efficacy of these biomarkers.
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http://dx.doi.org/10.3389/fmed.2020.601853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870479PMC
January 2021

Assessment of Duration and Effects of 3 vs 6 Months of Adjuvant Chemotherapy in High-Risk Stage II Colorectal Cancer: A Subgroup Analysis of the TOSCA Randomized Clinical Trial.

JAMA Oncol 2020 04;6(4):547-551

Medical Oncology Unit, IRCCS San Martino-IST, Genova, Italy.

Importance: The addition of oxaliplatin to the standard 6-month fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer has been reported to reduce the risk of relapse although it does not increase survival. The Three or Six Colon Adjuvant (TOSCA) trial compared 3 months with 6 months of adjuvant fluoropyrimidine and oxaliplatin-based chemotherapy in patients with stage III colon cancer. The utility remains unknown.

Objective: To assess the noninferiority and toxic effects of 3 vs 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) adjunct chemotherapy among patients with high-risk stage II resected colorectal cancer enrolled in the TOSCA trial.

Design, Setting, And Participants: The TOSCA study was a noninferiority phase 3 randomized clinical trial conducted from June 2007 to March 2013 in 130 Italian centers. Included patients had resected colorectal cancer located 12 cm from the anal verge by endoscopy or above the peritoneal reflection at surgery. In this preplanned study assessing the per-protocol population, 5-year relapse-free survival was evaluated in 1254 patients with high-risk stage II resected colorectal cancer who had received adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin).

Interventions: Patients were originally randomized (1:1) in the TOSCA trial to receive 3 months (experimental group) or 6 months (control) of standard doses of FOLFOX or CAPOX at the discretion of the treating physician.

Main Outcome And Measures: A hazard ratio of at least 1.2 between the 3-month and 6-month chemotherapy groups was set to reject the null hypothesis of noninferiority.

Results: Overall, 1254 patients (mean [SD] age, 62.4 [9.8] years; 565 women [45.1%]) with clinical high-risk stage II resected colorectal cancer were analyzed at a median follow-up of 62 months (interquartile range, 53-71) months. Of them, 301 patients (24.0%) had pT4N0M0 tumors, and the remaining 953 patients (76.0%) had high-risk pT3N0M0 tumors; 776 patients (61.9%) received FOLFOX and 478 (38.1%) received CAPOX. The 5-year relapse-free survival was 82.2% for the 3-month arm and 88.2% for the 6-month arm, with an estimated hazard ratio of 1.41 (95% CI, 1.05-1.89; P = .86 for noninferiority). For CAPOX, the 5-year relapse-free survival was similar in the 2 arms (difference, 0.76% favoring the 6-month arm; 95% CI, -6.28% to 7.80%), whereas for FOLFOX, the difference was pronounced: 8.56% in favor of the longer-duration arm (95% CI, 3.45%-13.67%). Nevertheless, the test for an interaction between duration and regimen was not statistically significant. Neurotoxicity was approximately 5 times lower in the shorter duration arm than in the longer duration arm.

Conclusions And Relevance: In the 3-month arm, the treatment was significantly less toxic than in the 6-month arm. Noninferiority was not shown for 5-year relapse-free survival. However, a possible regimen effect was observed, suggesting that either 3 months of CAPOX or 6 months of FOLFOX therapy can be used whenever an oxaliplatin doublet is indicated for treatment of patients with stage II colorectal cancer.

Trial Registration: ClinicalTrials.gov Identifier: NCT0064660.
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http://dx.doi.org/10.1001/jamaoncol.2019.6486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042800PMC
April 2020

Syndrome of inappropriate anti-diuretic hormone secretion in cancer patients: results of the first multicenter Italian study.

Ther Adv Med Oncol 2019 27;11:1758835919877725. Epub 2019 Sep 27.

Dipartimento di Oncologia-Ematologia, AUSL della Romagna, Ravenna, Italy.

Background: Hyponatremia in cancer patients is often caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The aim of this observational multicenter study was to analyze the medical and economic implications of SIADH in this setting.

Methods: This study included 90 oncological patients from 28 Italian institutions that developed SIADH between January 2010 and September 2015. Data on clinical-pathological characteristics, anticancer therapies, hyponatremia, and related treatments were statistically analyzed.

Results: The majority were lung cancer patients (73%) with metastatic disease at the onset of hyponatremia (83%). A total of 76 patients (84%) were hospitalized because of SIADH and less than half (41%) received tolvaptan for SIADH treatment. The duration of hospitalization was significantly longer in patients who did not receive tolvaptan and in those who do not reach sodium normalization during hospitalization. Patients who experienced a second episode of hyponatremia following tolvaptan dose modification/discontinuation presented a significantly lower serum sodium value at the time of hospitalization and minimum sodium value during hospitalization compared with patients who had not experienced another episode. The severity of hyponatremia, defined as minimum sodium value during hospitalization with a cut-off value of 110 mmol/l, and not obtaining sodium correction during hospitalization significantly correlated with overall survival rate.

Conclusions: Hyponatremia due to SIADH could result in longer hospitalization and in a decreased overall survival when not adequately treated, and tolvaptan represents an effective treatment with a potential effect of both improving overall survival and decreasing duration of hospitalization.
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http://dx.doi.org/10.1177/1758835919877725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767731PMC
September 2019

Liquid Biopsy Testing Can Improve Selection of Advanced Non-Small-Cell Lung Cancer Patients to Rechallenge with Gefitinib.

Cancers (Basel) 2019 Sep 25;11(10). Epub 2019 Sep 25.

Cell Biology and Biotherapy Unit, Istiuto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, 80131 Naples, Italy.

The ICARUS trial is a phase II, open label, multicenter, single arm study conducted to investigate the efficacy, safety, and tolerability of a rechallenge treatment with the first-generation tyrosine kinase inhibitor (TKI) gefitinib in advanced non-small-cell lung cancer (NSCLC) patients carrying activating mutations of the epidermal growth factor receptor (). The ICARUS trial enrolled 61 patients who were rechallenged with gefitinib at progression after second-line chemotherapy. Serum-derived circulating cell-free DNA (cfDNA) collected before the rechallenge from a cohort of 29 patients, was retrospectively analyzed for the exon 19 deletions and for the p.L858R and p.T790M single nucleotide variants (SNV). The analysis of cfDNA detected the same activating mutation reported in the tumor tissue in 20/29 patients, with a sensitivity of 69%. Moreover, a p.T790M variant was found in 14/29 patients (48.3%). The median progression-free survival (PFS) was 2.7 months for p.T790M positive patients (CI 95% 1.4-3.1 months) versus 3.5 months for the p.T790M negative patients (CI 95% 1.6-5.3 months), resulting in a statistically significant difference (Long rank test = 0.0180). These findings confirmed the role of the p.T790M mutation in the resistance to first-generation TKIs. More importantly, our data suggest that TKI rechallenge should be guided by biomarker testing.
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http://dx.doi.org/10.3390/cancers11101431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826724PMC
September 2019

Final results of the SENECA (SEcond line NintEdanib in non-small cell lung CAncer) trial.

Lung Cancer 2019 08 27;134:210-217. Epub 2019 Jun 27.

Department of Oncology, University of Turin, AOU San Luigi, Orbassano, Italy.

Objectives: Despite the scant docetaxel's tolerability, second-line association with nintedanib still represents a standard-of-care for non-squamous non-small cell lung cancer (nsNSCLC), giving to rapidly-progressing patients the greatest survival advantage. The SENECA trial is a phase IIb, open-label, study evaluating whether nintedanib/docetaxel can be equally effective and safe regardless docetaxel schedule.

Materials And Methods: Recurrent nsNSCLC patients were stratified into cohort 1 and 2, according to relapse-time (within or over 3 months) from end of first-line chemotherapy. They were treated with docetaxel (T1: 33 mg/mq on days 1 and 8 in a 21-days cycle; T2: 75 mg/mq q3wks) plus nintedanib, allowing maintenance in case of disease-control. Primary endpoint was progression-free survival (PFS) by investigator's assessment; secondary endpoints: overall survival (OS), safety and quality-of-life.

Results: Between January 2016-April 2018, 212 patients were evaluated: 30 resulted screening-failures, 12 were excluded for lack of compliance. According to investigator's choice, 85 patients received T1 docetaxel and 85 T2; 138 (81.2%) were stratified in C1, 32 (18.8%) in C2, with a median relapse-time of 0.54 and 9.29 months, respectively. Baseline characteristics were balanced between groups. After 35.5 months follow-up, no survival differences appear between cohorts and treatments; toxicity seems to be slightly higher in T2, especially for chemotherapy-related events. Perception of quality-of-life remains stable and docetaxel schedule doesn't modify patients' load.

Conclusion: The SENECA trial confirms efficacy of second-line nintedanib/docetaxel for nsNSCLC, regardless time of recurrence and docetaxel schedule; higher toxicities for q3wks docetaxel, without alterations in quality-of-life, have been described, underling the possibility, adopting the weekly schedule, to maintain efficacy with better tolerability.
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http://dx.doi.org/10.1016/j.lungcan.2019.06.028DOI Listing
August 2019

Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: the ARMANI phase III trial.

BMC Cancer 2019 Mar 29;19(1):283. Epub 2019 Mar 29.

Department of Medical Oncology, Ospedale San Donato, Azienda USL Toscana Sudest Via Pietro Nenni, 20/22, 52100, Arezzo, Italy.

Background: Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4-6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment.

Methods: This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis.

Discussion: The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression.

Trial Registration: ARMANI is registered at ClinicalTrials.gov ( NCT02934464 , October 17, 2016) and EudraCT(2016-001783-12, April 202,016).
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http://dx.doi.org/10.1186/s12885-019-5498-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440108PMC
March 2019

Discontinuation of first-line bevacizumab in metastatic colorectal cancer: the BEAWARE Italian Observational Study.

Tumori 2019 Jun 11;105(3):243-252. Epub 2019 Mar 11.

12 OUC Oncologia, Policlinico Universitario Campus Bio-Medico, Rome, Italy.

Aims: BEAWARE investigated the pattern of first-line bevacizumab early interruption in the Italian real-world setting of metastatic colorectal cancer.

Methods: A total of 386 patients were followed for 15 months after first-line chemotherapy + bevacizumab start. The rate of bevacizumab interruption for progression or adverse drug reactions (ADRs) constituted the primary endpoint.

Results: A total of 78.2% of patients interrupted bevacizumab: 56.6% for progression, 7.3% for ADRs, and 36.1% for other reasons. Median treatment duration was 6.7, 2.5, and 4.6 months, respectively. Median progression-free survival was 10.3 months; however, 35.8% of patients were not progressed and were thus censored at the data cutoff of 15 months, while 21.8% were still receiving bevacizumab. Patients discontinuing for progression/ADRs more frequently had metastases in >1 site ( = .0001), and a shorter median progression-free survival (6.9 vs 13.9 months, < .0001).

Conclusions: In Italy, first-line bevacizumab is interrupted mainly for progression, only 7.3% due to adverse events, and about one third of cases for other reasons. In clinical practice, the attitude to treat until progression as per guidelines might be implemented. ClinicalTrials.gov Identifier: NCT01609075.
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http://dx.doi.org/10.1177/0300891619834126DOI Listing
June 2019

Nivolumab and brain metastases in patients with advanced non-squamous non-small cell lung cancer.

Lung Cancer 2019 03 15;129:35-40. Epub 2019 Jan 15.

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Objectives: Brain metastases are common among patients with non-squamous non-small-cell lung cancer (NSCLC) and result in a poor prognosis. Consequently, such patients are often excluded from clinical trials. In Italy an expanded access program (EAP) was used to evaluate nivolumab efficacy and safety in this subpopulation outside a clinical trial.

Materials And Methods: In this EAP, nivolumab was available for patients with non-squamous NSCLC in progression after at least one systemic treatment for stage IIIB/IV disease. Nivolumab 3 mg/kg was administered intravenously every 2 weeks. Patients with brain metastases could be included if they were asymptomatic, neurologically stable and either off corticosteroids or on a stable or decreasing dose of ≤10 mg/day prednisone.

Results: 409 out of 1588 patients included had asymptomatic or controlled brain metastases. A median of 7 doses (range 1-45) were delivered. Median follow-up was 6.1 months (range 0.1-21.9). The disease control rate was 39%: 4 patients had a complete response, 64 a partial response and 96 showed stable disease. At baseline, 118 patients were on corticosteroids and 74 were undergoing concomitant radiotherapy. The median overall survival in this subpopulation was 8.6 months (95% CI: 6.4-10.8). 337 discontinued treatment for various reasons, 23 (7%) of whom due to adverse events, in line with that observed in the overall population and in previous studies.

Conclusions: Our results confirm that nivolumab is active in non-squamous NSCLC patients with brain metastases, despite their poor prognosis. Its safety profile is also concordant with results in the EAP overall population and in patients with other malignancies.
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http://dx.doi.org/10.1016/j.lungcan.2018.12.025DOI Listing
March 2019

Thymic stromal lymphopoietin in human pancreatic ductal adenocarcinoma: expression and prognostic significance.

Oncotarget 2018 Aug 28;9(67):32795-32809. Epub 2018 Aug 28.

Department of Medical Sciences, University of Turin, 10126 Turin, Italy.

Thymic stromal lymphopoietin (TSLP) has emerged as an important, but contradictory, player conditioning tumor growth. In certain contexts, by driving T helper (h) 2 responses via tumor-associated OX40 Ligand (OX40L) dendritic cells (DCs), TSLP may play a pro-tumorigenic role. The study elucidates the importance of TSPL in pancreatic ductal adenocarcinoma (PDAC), by analyzing: i) TSLP levels in PDAC cell-line supernatants and plasma from patients with locally-advanced/metastatic PDAC, pre- and post-treatment with different chemotherapeutic protocols, in comparison with healthy donors; ii) TSLP and OX40L expression in PDAC and normal pancreatic tissues, by immunohistochemistry; iii) OX40L expression on -generated normal DCs in the presence of tumor-derived TSLP, by flow cytometry; iv) clinical relevance in terms of diagnostic and prognostic value and influence on treatment modality and response. Some PDAC cell lines, such as BxPC-3, expressed both TSLP mRNA and protein. Normal DCs, generated in the presence of TSLP-rich-cell supernatants, displayed increased expression of OX40L, reduced by the addition of a neutralizing anti-TSLP polyclonal antibody. OX40L cells were detected in pancreatic tumor inflammatory infiltrates. Abnormally elevated TSLP levels were detected in situ in tumor cells and, systemically, in locally-advanced/metastatic PDAC patients. Of the chemotherapeutic protocols applied, gemcitabine plus oxaliplatin (GEMOX) significantly increased circulating TSLP levels. Elevated plasma TSLP concentration was associated with shorter overall survival and increased risk of poor outcome. Plasma TSLP measurement successfully discriminated PDAC patients from healthy controls. These data show that TSLP secreted by pancreatic cancer cells may directly impact PDAC biology and patient outcome.
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http://dx.doi.org/10.18632/oncotarget.25997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132354PMC
August 2018

Efficacy and safety data in elderly patients with metastatic renal cell carcinoma included in the nivolumab Expanded Access Program (EAP) in Italy.

PLoS One 2018 6;13(7):e0199642. Epub 2018 Jul 6.

Azienda Ospedaliera Universitaria di Modena, Modena, Italy.

Background: Results from phase III clinical trial CheckMate 025 have established nivolumab as the standard of care for treatment of metastatic renal-cell carcinoma (mRCC) after VEGF inhibitor failure; however, elderly patients are under-represented in the registration trial and little is known about the activity of nivolumab in this subgroup. The purpose of the Expanded Access Program was to provide nivolumab to patients with mRCC who had progressed despite treatment with other agents that were considered standard of care.

Methods: Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months or until progression or unacceptable toxicity. The current analysis included all patients from the EAP Italian cohort who had received ≥1 dose of nivolumab. Adverse events (AEs) were monitored using Common Terminology Criteria for Adverse Events v4.0.

Results: A total of 389 patients with advanced RCC were enrolled in the Italian cohort of the EAP and treated with nivolumab. Of these patients, 125 (32%) were at least 70 years of age and 70 (18%) were at least 75 years of age. Efficacy with nivolumab in the elderly patients was similar to that observed in the overall EAP population and in the CheckMate 025 trial. Safety was comparable between the elderly patients and the overall EAP population, and was consistent with what previously reported.

Conclusion: The final results suggest that elderly patients with pretreated metastatic RCC may benefit from therapy with nivolumab.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199642PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034807PMC
December 2018

FOLFOX or CAPOX in Stage II to III Colon Cancer: Efficacy Results of the Italian Three or Six Colon Adjuvant Trial.

J Clin Oncol 2018 05 5;36(15):1478-1485. Epub 2018 Apr 5.

Alberto Sobrero, IRCCS San Martino-IST, Genova; Sara Lonardi and Vittorina Zagonel, Istituto Oncologico Veneto-IRCCS, Padova; Gerardo Rosati, Ospedale San Carlo, Potenza; Maria Di Bartolomeo, Fondazione Istituto Nazionale Tumori-IRCCS; Monica Ronzoni, Ospedale San Raffaele-IRCCS; Maria Giulia Zampino, Istituto Europeo di Oncologia-IRCCS; Daris Ferrari, Azienda Ospedaliera San Paolo; and Eliana Rulli, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano; Nicoletta Pella, Azienda Ospedaliero Universitaria Santa Maria della Misericordia, Udine; Mario Scartozzi, University Hospital and University of Cagliari, Cagliari; Maria Banzi, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia; Felice Pasini, Ospedale Santa Maria della Misericordia, Rovigo; Paolo Marchetti, Sant'Andrea Hospital, Sapienza University of Roma and IDI-IRCCS, Roma; Maurizio Cantore, Civico Hospital Carrara, Carrara; Alberto Zaniboni, Fondazione Poliambulanza, Brescia; Lorenza Rimassa, Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano; Libero Ciuffreda, Azienda Ospedaliero Universitaria San Giovanni Battista, Molinette, Torino; Evaristo Maiello, Hospital Casa Sollievo della Sofferenza-IRCCS, San Giovanni Rotondo; Sandro Barni, Treviglio-Caravaggio Hospital, Treviglio; and Roberto Labianca, Cancer Center ASST Papa Giovanni XXIII, Bergamo, Italy.

Purpose Given the cumulative neurotoxicity associated with oxaliplatin, a shorter duration of adjuvant therapy, if equally efficacious, would be advantageous for patients and health-care systems. Methods The Three or Six Colon Adjuvant trial is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III colon cancer to receive 3 months or 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin). Primary end-point is relapse-free survival. Results 3,759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX and 36% CAPOX. Two-thirds were stage III. The median time of follow up was 62 months and 772 relapses or deaths have been observed. The hazard ratio (HR) of the 3 months versus 6 months for relapse/death was 1.14 (95% CI, 0.99 to 1.32; P [for noninferiority] = .514) and the CI crossed the noninferiority limit of 1.20. However, the absolute difference in 3-year RFS was 1.9% (95% CI, -0.7% to 4.4%). Counter-intuitively, while the RFS curves were similar for stage III (HR, 1.07; 95% CI, 0.91 to 1.26) and for CAPOX treated patients (HR, 0.98; 95% CI, 0.77 to 1.26), they were not for stage II and for FOLFOX treated patients, with HR of 1.41 (95% CI, 1.05 to 1.89) and 1.23 (95% CI, 1.03 to 1.46), respectively, favoring the 6 months of treatment. Conclusion The Three or Six Colon Adjuvant trial failed to formally show noninferiority of 3 versus 6 months of treatment to the predefined margin of 20% relative increase. The results depended on the adjuvant regimen and risk. For CAPOX, 3 months were as good as 6 months; for FOLFOX, 6 months added extra benefit. Counter-intuitively, the low-risk patients benefitted more than the high-risk population from the 6-month duration. The choice of regimen and duration should depend on patient characteristics and be balanced against the extra toxicity of longer therapy.
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http://dx.doi.org/10.1200/JCO.2017.76.2187DOI Listing
May 2018

Aflibercept Plus FOLFIRI in the Real-life Setting: Safety and Quality of Life Data From the Italian Patient Cohort of the Aflibercept Safety and Quality-of-Life Program Study.

Clin Colorectal Cancer 2018 09 8;17(3):e457-e470. Epub 2018 Mar 8.

Medical Oncology Unit, ARNAS Garibaldi, Catania, Italy.

Background: Aflibercept combined with FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) as second-line treatment of metastatic colorectal cancer (mCRC) significantly improved survival compared with FOLFIRI alone in the pivotal VELOUR (aflibercept vs. placebo in combination with irinotecan and 5-fluorouracil in the treatment of patients with metastatic colorectal cancer after failure of an oxaliplatin-based regimen) trial. No quality-of-life assessment was performed in VELOUR; therefore, the ASQoP (Aflibercept Safety and Quality-of-Life Program) trial was designed to capture the safety and health-related quality of life (HRQL).

Patients And Methods: ASQoP was an international, open-label, single-arm trial evaluating the safety and HRQL of aflibercept combined with FOLFIRI administered in a real-life setting to 781 patients with mCRC, pretreated with an oxaliplatin-based regimen with or without bevacizumab. The Italian subset of ASQoP enrolled 200 patients from 28 institutions. The primary endpoint was safety; HRQL was a secondary endpoint, assessed by validated questionnaires (European quality of life 5-dimension instrument 3-level; European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30, version 3; and EORTC-CR29) at baseline, during treatment, and at the end of treatment.

Results: The median age of the Italian ASQoP population was 63 years; the median number of aflibercept and FOLFIRI cycles was 7. Treatment-emergent adverse events were reported in 97.5% of patients. Hypertension (28.5%), neutropenia (27.5%; from laboratory data), asthenic conditions (20.0%), diarrhea (17.0%), and stomatitis (13.0%) were the most frequent (incidence, ≥ 5%) grade 3/4 toxicities. One toxic death occurred during the study period due to sepsis, without neutropenic complications. No significant worsening of HRQL was shown during treatment.

Conclusion: Aflibercept combined with FOLFIRI was well tolerated when administered as second-line treatment for patients with mCRC in a real-life setting. It did not affect HRQL and showed similar rates of treatment-emergent adverse events as those observed in the VELOUR trial. No new safety signals were identified.
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http://dx.doi.org/10.1016/j.clcc.2018.03.002DOI Listing
September 2018

Quality of life, compliance, safety and effectiveness in fit older metastatic colorectal patients with cancer treated in first-line with chemotherapy plus cetuximab: A restrospective analysis from the ObservEr study.

J Geriatr Oncol 2018 05 9;9(3):243-248. Epub 2018 Feb 9.

Careggi University Hospital, Florence, Italy.

Objectives: The influence of age (<70 years and ≥70 years) was retrospectively studied on the quality of life (QoL), incidence of side effects (including skin reactions) and efficacy of chemotherapy plus cetuximab in patients with KRAS wild type (WT) metastatic colorectal cancer (mCRC).

Methods: 225 patients of the Observed study (PS 0-1) were retrieved based on age (< 70 and ≥70 years) and evaluated through EORTC QLQ-C30 and DLQI questionnaires.

Results: The two patient groups (141 < 70 and 84 ≥ 70 years, respectively) were balanced with no differences in any of the clinical and pathological characteristics considered. Both groups underwent similar type of first-line chemotherapy plus cetuximab, treatment duration and compliance. Cetuximab therapy caused similar incidence of side effects and impact on QoL in older and younger patients. No difference was observed in progression free survival (PFS) and in disease control rates between the two patient populations. Median overall survival (OS) was higher in patients <70 (27 months, 95% CI: 22.7-31.27) than in patients ≥70 (19 months, 95% CI: 14.65-23.35) (p = 0.002), which is likely due to higher proportions of metastatic resection (27.0% vs 8.3%; p = 0.001) and utilization of second-line therapy in younger group (58.9% vs 42.9%; p = 0.028).

Conclusion: The current data suggest that fit older patients with mCRC can be safely treated with a cetuximab-based therapy, as QoL and safety profile do not seem to be affected by age. In addition, age did not impact the choice of chemotherapy to be associated to cetuximab and treatment compliance.
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http://dx.doi.org/10.1016/j.jgo.2018.01.009DOI Listing
May 2018

Postnatal risk factors for testicular cancer: The EPSAM case-control study.

Int J Cancer 2017 11 27;141(9):1803-1810. Epub 2017 Jul 27.

Cancer Epidemiology Unit-CERMS, Department of Medical Sciences, University of Turin and CPO-Piemonte, Torino, Italy.

Testicular cancer is considered to originate from an impaired differentiation of fetal germ cells, but puberty could represent another time window of susceptibility. Our study aimed at investigating the association between environmental exposures acting during puberty/adolescence (13-19 years of age) and the risk of testicular cancer. We used data of the EPSAM study, a case-control study on germ-cell testicular cancer conducted in the province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Histologically confirmed cases (n = 255) and controls (n = 459) completed a postal questionnaire focusing in particular on the pubertal period (namely age 13 years) with questions on physical activity (competitive sports, gardening), lifestyle (alcohol consumption, smoking), occupational history and medical conditions. All analyses were adjusted for the matching variables, cryptorchidism and educational level. Having done at least one competitive sport during puberty (odds ratio [OR]: 0.72, 95% confidence interval: 0.52-1.00), gardening activities during puberty (OR: 0.62, 0.42-0.94) and having a lower weight than peers during puberty (OR: 0.64, 0.42-0.97) were all inversely associated with the risk of testicular cancer. No evidence of association between smoking or alcohol consumption during puberty and the risk of testicular cancer was observed. Regarding agriculture-related occupations, we found an association with the risk of testicular cancer both for occasional jobs during puberty (OR: 2.40, 95% CI: 1.08-5.29) and ever employment in adolescence (OR: 2.59, 95% CI: 0.83-8.10). Our results suggest that postnatal exposures could play a role in testicular cancer aetiology, at least when acting in puberty or adolescence.
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http://dx.doi.org/10.1002/ijc.30884DOI Listing
November 2017

Subfertility and Risk of Testicular Cancer in the EPSAM Case-Control Study.

PLoS One 2016 30;11(12):e0169174. Epub 2016 Dec 30.

Cancer Epidemiology Unit-CeRMS, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.

Background/objectives: It has been suggested that subfertility and testicular cancer share genetic and environmental risk factors. We studied both subfertility and the strongest known testicular cancer susceptibility gene, the c-KIT ligand (KITLG), whose pathway is involved in spermatogenesis.

Methods: The EPSAM case-control study is comprised of testicular cancer patients from the Province of Turin, Italy, diagnosed between 1997 and 2008. The present analysis included 245 cases and 436 controls from EPSAM, who were aged 20 years or older at diagnosis/recruitment. The EPSAM questionnaire collected information on factors such as number of children, age at first attempt to conceive, duration of attempt to conceive, use of assisted reproduction techniques, physician-assigned diagnosis of infertility, number of siblings, and self-reported cryptorchidism. Genotyping of the KITLG single nucleotide polymorphism (SNP) rs995030 was performed on the saliva samples of 202 cases and 329 controls.

Results: Testicular cancer was associated with the number of children fathered 5 years before diagnosis (odds ratio (OR) per additional child: 0.78, 95% confidence interval (CI): 0.58-1.04) and sibship size (OR per additional sibling: 0.76, 95% CI: 0.66-0.88). When considering the reproductive history until 1 year before diagnosis, attempting to conceive for at least 12 months or fathering a child using assisted reproduction techniques was not associated with the risk of testicular cancer, nor was age at first attempt to conceive or physician-assigned diagnosis of infertility. The SNP rs995030 was strongly associated with risk of testicular cancer (per allele OR: 1.83; 95%CI: 1.26-2.64), but it did not modify the association between number of children and the risk of testicular cancer.

Conclusion: This study supports the repeatedly reported inverse association between number of children and risk of testicular cancer, but it does not find evidence of an association for other indicators of subfertility.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169174PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201268PMC
July 2017

Jaw osteonecrosis associated with aflibercept, irinotecan and fluorouracil: attention to oral district.

Tumori 2016 Nov 11;102(Suppl. 2). Epub 2016 Nov 11.

Colorectal Cancer Unit, Division of Medical Oncology 1, San Giovanni Battista Hospital, Città della Salute e della Scienza, Turin - Italy.

Introduction: The antiangiogenic monoclonal antibody aflibercept in association with fluorouracil and irinotecan improves the survival of patients with metastatic colorectal cancer (mCRC) treated previously with oxaliplatin-based therapy. Multiple reports raised the hypothesis that the concomitant use of antiresorptive drugs and antiangiogenic drugs may increase the risk of osteonecrosis of the jaw (ONJ). Some reports have been published regarding cases of ONJ during treatment with bevacizumab for mCRC.

Case Description: Here we describe the first reported case of ONJ occurring in a 64-year-old woman with untreated periodontitis and episodic previous pyorrhea occurring during treatment with aflibercept plus FOLFIRI during the expanded-access program.

Conclusions: This case report warrants further investigation into the potential association between the use of anti-VEGF agents and ONJ. Given the serious nature of ONJ, we recommend that particular attention be paid to the oral district prior to treating patients and during treatment with chemotherapy and targeted agents, especially anti-VEGF agents. Such measures could also be useful in reducing the incidence of stomatitis.
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http://dx.doi.org/10.5301/tj.5000405DOI Listing
November 2016

Observational study on quality of life, safety, and effectiveness of first-line cetuximab plus chemotherapy in KRAS wild-type metastatic colorectal cancer patients: the ObservEr Study.

Cancer Med 2016 11 17;5(11):3272-3281. Epub 2016 Oct 17.

Careggi University Hospital, Florence, Italy.

Cetuximab improves efficacy when added to chemotherapy for metastatic colorectal cancer (mCRC). Effective management of skin reactions from cetuximab improves quality of life (QoL), and treatment compliance in clinical trials. No data are available from real-world settings. The ObservEr observational, multicenter, prospective study evaluated QoL, the incidence of skin reactions, and management of chemotherapy plus cetuximab in first-line for mCRC. The primary endpoint was QoL measured with the Dermatology Life Quality Index (DLQI) and EORTC QLQ-C30. Secondary endpoints were the incidence of skin and serious adverse events, median overall and progression-free survival, tumor response, and resection rates. Between May 2011 and November 2012, 228 patients with KRASwt mCRC were enrolled at 28 Italian centers, 225 evaluable, median age 65 years. QoL did not change during treatment and was not affected by the choice of prophylactic or reactive skin management. The incidence of cetuximab-specific grade ≥3 skin reactions was 14%, with no grade 4/5 events. Skin reactions correlated with survival (P = 0.016), and their incidence was influenced by chemotherapy regimen (oxaliplatin vs. irinotecan-Incidence rate ratio [IRR] 1.72, P < 0.0001) and gender (male vs. female-IRR 1.38, P = 0.0008). Compliance at first postbaseline evaluation was 97.75%. Median overall survival was 23.6 months, median progression-free survival 8.3 months. Cetuximab plus chemotherapy did not compromise QoL in the routine clinical setting when patients receive close monitoring plus prophylactic or reactive management of skin reactions. We observed the same correlation between overall survival (OS) and skin reactions reported in controlled clinical trials, also in this setting.
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http://dx.doi.org/10.1002/cam4.888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119983PMC
November 2016

Current therapeutic strategies for advanced pancreatic cancer: A review for clinicians.

World J Clin Oncol 2016 Feb;7(1):27-43

Rosella Spadi, Federica Brusa, Agostino Ponzetti, Isabella Chiappino, Nadia Birocco, Libero Ciuffreda, Maria Antonietta Satolli, Department of Oncology, Azienda Ospedaliera Città della Salute e della Scienza, 10126 Torino, Italy.

Pancreatic cancer (PC) would become the second leading cause of cancer death in the near future, despite representing only 3% of new cancer diagnosis. Survival improvement will come from a better knowledge of risk factors, earlier diagnosis, better integration of locoregional and systemic therapies, as well as the development of more efficacious drugs rising from a deeper understanding of disease biology. For patients with unresectable, non-metastatic disease, combined strategies encompassing primary chemotherapy and radiation seems to be promising. In fit patients, new polychemotherapy regimens can lead to better outcomes in terms of slight but significant survival improvement associated with a positive impact on quality of life. The upfront use of these regimes can also increase the rate of radical resections in borderline resectable and locally advanced PC. Second line treatments showed to positively affect both overall survival and quality of life in fit patients affected by metastatic disease. At present, oxaliplatin-based regimens are the most extensively studied. Nonetheless, other promising drugs are currently under evaluation. Presently, in addition to surgery and conventional radiation therapy, new locoregional treatment techniques are emerging as alternative options in the multimodal approach to patients or diseases not suitable for radical surgery. As of today, in contrast with other types of cancer, targeted therapies failed to show relevant activity either alone or in combination with chemotherapy and, thus, current clinical practice does not include them. Up to now, despite the fact of extremely promising results in different tumors, also immunotherapy is not in the actual therapeutic armamentarium for PC. In the present paper, we provide a comprehensive review of the current state of the art of clinical practice and research in PC aiming to offer a guide for clinicians on the most relevant topics in the management of this disease.
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http://dx.doi.org/10.5306/wjco.v7.i1.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734936PMC
February 2016

Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study).

Cancer 2016 Feb 5;122(4):574-81. Epub 2015 Nov 5.

Department of Oncology, University of Turin Medical School/Piedmont Foundation for Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy.

Background: Biliary tract cancer (BTC) is a rare and lethal disease with few therapeutic options. Preclinical data suggest that the epidermal growth factor receptor (EGFR) pathway could be involved in its progression.

Methods: This open-label, randomized phase 2 trial recruited chemotherapy-naive patients with advanced BTC displaying a wild-type (WT) KRAS status. Patients were randomized to gemcitabine (1000 mg/m(2) ) and oxaliplatin (100 mg/m(2) ) with (arm A) or without (arm B) panitumumab (6 mg/kg) for up to 12 cycles. The primary endpoint was progression-free survival (PFS) analyzed in an intention-to-treat fashion.

Results: Eighty-nine patients (45 in arm A and 44 in arm B) were enrolled between June 2010 and September 2013. After a median follow-up of 10.1 months, the median PFS was 5.3 months (95% confidence interval, 3.3-7.2 months) in arm A and 4.4 months (95% confidence interval, 2.6-6.2 months) in arm B (P = .27). No survival differences were observed: the median overall survival was 9.9 months in arm A and 10.2 months in arm B (P = .42). In a subgroup analysis, no differences in PFS according to the site of the primary tumor were observed; patients with intrahepatic cholangiocarcinoma treated with panitumumab may have had a survival benefit in comparison with the control group (15.1 vs 11.8 months, P = .13). As for safety, skin toxicity was the main adverse event in arm A (80% of the patients). A higher incidence of diarrhea (55.5% vs 31.8%), mucositis (22.2% vs 13.6%), and constipation (24.4% vs 15.9%) was seen in arm A.

Conclusions: These results confirm the marginal role of anti-EGFR therapy even for WT KRAS-selected BTC.
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http://dx.doi.org/10.1002/cncr.29778DOI Listing
February 2016

Oral chemotherapy and patient perspective in solid tumors: a national survey by the Italian association of medical oncology.

Tumori 2016 Jan-Feb;102(1):108-13. Epub 2015 Jul 2.

Division of Medical Oncology, Hospital of Legnano, Legnano, Milan - Italy.

Aim: To assess patient perception toward oral chemotherapy for solid tumors, the Italian Association of Medical Oncology performed a large multi-institutional national survey.

Methods: A 17-item anonymous questionnaire including 7 general and 10 investigational questions with free-text, single-choice, or multiple-choice answers was administered. Analysis of response distribution according to predefined factors was described by summary measures and conducted by χ2 test and other nonparametric tests.

Results: From January to June 2010, 581 patients completed the questionnaire; data of 404 patients constituted the final study sample. Three groups could be distinguished according to treatment: IV chemotherapy (IV group, n = 313), oral chemotherapy (oral group, n = 48), or combined therapy (combined group, n = 43). Thirty-one (72%) patients in the combined group and 187 (60%) in the IV group expressed preference for oral therapy (p = 0.028). Limitations in family and work commitment were more frequently perceived by patients on IV than oral chemotherapy (147 (47%) vs 14 (29%) patients, p<0.05, and 134 (43%) vs 11 (23%) patients, p<0.05). A total of 134 (43%) patients on IV chemotherapy versus 15 (31%) patients in the oral group did not point out any limitation for number of tablets per day (p = 0.004).

Conclusions: We observed a propensity from the patient perspective in favor of oral chemotherapy that was considered to have a lower impact on family and work commitments than IV chemotherapy. The treatment that patients were taking when the questionnaire was administered likely influenced their perception and related results.
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http://dx.doi.org/10.5301/tj.5000383DOI Listing
July 2016

Safety and efficacy of sunitinib in patients from Italy with metastatic renal cell carcinoma: final results from an expanded-access trial.

Oncology 2015 15;88(5):273-80. Epub 2015 Jan 15.

San Camillo Forlanini Hospital, Rome, Italy.

Objectives: Patients with metastatic renal cell carcinoma (mRCC) received sunitinib in a global expanded-access program (EAP). Here, we report the efficacy and safety results for the EAP subpopulation in Italy.

Methods: Patients ≥18 years old with previously treated or treatment-naïve mRCC received oral sunitinib 50 mg/day on a 4-weeks-on/2-weeks-off schedule. Tumor measurements were scheduled per local practice (using Response Evaluation Criteria in Solid Tumors). Safety was regularly assessed.

Results: A total of 521 patients participated, including 40% aged ≥65 years, 11% with an Eastern Cooperative Oncology Group performance status ≥2, 14% with non-clear cell RCC, and 11% with brain metastases. The median treatment duration and posttreatment follow-up were 7.4 and 12.3 months, respectively. The objective response rate was 12%, and the median progression-free and overall survival was 9.1 and 27.2 months, respectively. 514 patients (99%) discontinued treatment; reasons included death (17%), nonresponse (46%), or adverse events (AEs; 13%). The most common any-grade treatment-related AEs were asthenia (44%, plus 15% reporting fatigue), thrombocytopenia and stomatitis (both 37%), diarrhea (36%), mucosal inflammation (29%), hypertension (26%), and dysgeusia (25%). The most common grade 3/4 treatment-related AEs were thrombocytopenia (10%), asthenia (9%, plus 3% reporting fatigue), neutropenia, stomatitis (both 6%), and hypertension (5%).

Conclusion: In a large population of Italian mRCC patients, sunitinib had a manageable safety profile and encouraging efficacy.
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http://dx.doi.org/10.1159/000369256DOI Listing
July 2015

Oral vinorelbine plus cisplatin as first-line chemotherapy in nonsquamous non-small-cell lung cancer: final results of an International randomized phase II study (NAVotrial 01).

Clin Lung Cancer 2014 Jul 15;15(4):258-65. Epub 2014 May 15.

Department of Medical Oncology, National Cancer Centre, Singapore.

Background: The combination of oral vinorelbine plus cisplatin has been studied in numerous trials as first-line treatment of patients with non-small cell lung cancer (NSCLC) regardless of histologic subtype. NAVoTrial 01 is the first study that explores this combination specifically in nonsquamous (NS) NSCLC by assessing the feasibility of this doublet (ratio 1:2) in an investigational approach. A reference arm with pemetrexed plus cisplatin was included. Maintenance therapy with single-agent therapy after 4 cycles of combination therapy was included in the study schedules because it reflected a trend in first-line treatment of NSCLC.

Patients And Methods: Stage IIIB/IV untreated/relapsed patients with NS NSCLC received a 3-week cycle of pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) on day 1 (arm A) or oral vinorelbine 80 mg/m(2) on days 1 and 8 (first cycle 60 mg/m(2)) and cisplatin 80 mg/m(2) on day 1 (arm B). After 4 cycles, patients without disease progression received single-agent maintenance treatment with pemetrexed or oral vinorelbine.

Results: Overall, 153 patients were randomized (arm A/arm B: 51/102). Disease control rate (%) for arm A was 76.5 (95% confidence interval [CI], 62.5-87.2) and for arm B it was 75.0 (95% CI, 65.3-83.1), Response rates for arm A were 31.4% (95% CI, 19.1-45.9) and for arm B were 24.0% (95% CI, 16.0-33.6). Median progression-free survival for arm A was 4.3 months (95% CI, 3.8-5.6) and for arm B it was 4.2 months (95% CI, 3.6-4.7). Median survival for arm A was 10.8 months (95% CI, 7.0-16.4) and for arm B it was 10.2 months (95% CI, 7.8-11.9). Main grade 3/4 hematologic toxicities were neutropenia 18.3% (arm A) and 44.0% (arm B), whereas febrile neutropenia was reported in 2% of patients in each arm.

Conclusion: Oral vinorelbine and cisplatin had an efficacy in line with that achieved with a standard treatment such as pemetrexed and cisplatin, coupled with an acceptable safety profile.
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http://dx.doi.org/10.1016/j.cllc.2014.04.007DOI Listing
July 2014

Inferior vena cava prosthetic replacement in a patient with horseshoe kidney and metastatic testicular tumor: technical considerations and review of the literature.

BMC Urol 2014 May 22;14:40. Epub 2014 May 22.

Division of Vascular Surgery, Department of Surgical Sciences, Città della Salute e della Scienza- Molinette Hospital, University of Turin, Turin, Italy.

Background: Seminomatous and non-seminomatous Germ Cell Tumors (GCT) of the testis are a rare cancer, with an estimated incidence of 56.3 per million white males and 10 per million black males in the United States.The association between non-seminomatous GCT and horseshoe kidney is a rare event and is seen in about 1.3% of patients requiring retroperitoneal lymph node dissection. To our knowledge, no cases have been reported in which replacement of the IVC was also necessary.

Case Presentation: We report the case of a 22-year-old man with horseshoe kidney and metastatic non-seminomatous germ cell tumor involving the wall of the inferior vena cava.Following post-chemotherapy retroperitonal lymph node dissection, the inferior vena cava was replaced with an expanded polytetrafluoroethylene graft.At 2-years follow-up, the patient was in good health and the graft was patent. No clinical or diagnostic signs of renal impairment or recurrence of neoplastic disease were noted.

Conclusion: Radical surgery is warranted in patients with non-seminomatous germ cell tumor metastasizing to the retroperitoneal lymph nodes. When vena cava replacement is required, and the situation is further complicated by horseshoe kidney, as in this case, surgical technique will rely on multidisciplinary surgical treatment planning by a team composed of urologists, vascular surgeons and oncologists.
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http://dx.doi.org/10.1186/1471-2490-14-40DOI Listing
May 2014

Role of multidimensional assessment of frailty in predicting short-term outcomes in hospitalized cancer patients: results of a prospective cohort study.

Tumori 2014 Jan-Feb;100(1):91-6

Aims And Background: The study analyzed the value of physical and psychosocial frailty assessment in predicting the need for supportive care and the risk of short-term failures after discharge in hospitalized cancer patients.

Methods And Study Design: Frailty was assessed in 350 consecutive patients using a multidimensional tool. Patients were followed for 4 months after discharge to record the occurrence of chemotherapy interruption, urgent hospital readmission or death. The association between patient characteristics and the outcomes were analyzed with either logistic or Cox multivariable models.

Results: About 40% of patients were classified as frail, with a higher prevalence of clinical frailty (alone or together with psychosocial frailty). Psychosocial frailty was positively associated with the need for supportive care at discharge (adjusted OR, 3.46; 95% CI, 1.55-7.76) but did not predict a worse prognosis when other important clinical factors were considered. However, the need for supportive care at discharge, in addition to advanced disease and reduced performance status, was a strong predictor of short-term hospital readmission or death (HR 7.50; 95% CI, 3.12-18.02).

Conclusions: A more comprehensive assessment of frailty in cancer patients can aid in the timely identification of the need for supportive care after hospital discharge and improves the prediction of the short-term risk of hospital readmission or death.
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http://dx.doi.org/10.1700/1430.15822DOI Listing
May 2014

Sorafenib as first- or second-line therapy in patients with metastatic renal cell carcinoma in a community setting.

Future Oncol 2014 Aug 18;10(10):1741-50. Epub 2014 Mar 18.

S.C. Oncologia Medica 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, 20133 Milano, Italy.

Aim: The Italian Retrospective Analysis of Sorafenib as First or Second Target Therapy study assessed the efficacy and safety of sorafenib in metastatic renal cell carcinoma patients treated in the community.

Patients & Methods: Patients receiving first- or second-line single-agent sorafenib between January 2008 and December 2010 were eligible. Retrospective data collection started in 2012 and covers at least 1-year follow-up. The primary end point was overall survival (OS).

Results: Median OS was 17.2 months (95% CI: 15.5-19.6): 19.9 months (95% CI: 15.9-25.3) in patients treated with first-line sorafenib and 16.3 months (95% CI: 13.1-18.2) with second-line sorafenib. Overall median (95% CI) progression-free survival was 5.9 months (95% CI: 4.9-6.7): 6.6 (95% CI: 4.9-9.3) and 5.3 months (95% CI: 4.3-6.0) in first- and second-line patients, respectively.

Conclusion: The efficacy and safety of sorafenib in routine community practice was generally good, especially in relation to OS in patients treated in the second line, where results were similar to those seen in recent prospective clinical trials.
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http://dx.doi.org/10.2217/fon.14.48DOI Listing
August 2014

Lifetime growth and risk of testicular cancer.

Int J Cancer 2014 Aug 10;135(3):695-701. Epub 2014 Jan 10.

Cancer Epidemiology Unit Department of Medical Sciences, University of Turin, Turin, Italy; Centre for Public Health Research, Massey University, Wellington, New Zealand.

Adult height is associated with testicular cancer risk. We studied to what extent this association is explained by parental height, childhood height and age at puberty. We conducted a case-control study on germ-cell testicular cancer patients diagnosed in 1997-2008 and resident in the Province of Turin. Information was collected using mailed questionnaires in 2008-2011. Specifically, we asked for adult height (in cm), height at age 9 and 13 (compared to peers) and age at puberty (compared to peers). We also asked for paternal and maternal height (in cm) as indicators of genetic components of adult height. The analysis included 255 cases and 459 controls. Odds ratios (ORs) of testicular cancer were estimated for the different anthropometric variables. Adult height was associated with testicular cancer risk [OR: 1.16, 95% confidence interval (CI): 1.03-1.31 per 5-cm increase]. The risk of testicular cancer was only slightly increased for being taller vs. shorter than peers at age 9 (OR: 1.55, 95% CI: 0.91-2.64) or age 13 (OR: 1.26, 95% CI: 0.78-2.01), and parental height was not associated with testicular cancer risk. The OR for adult height was 1.32 (95% CI: 1.12-1.56) after adjustment for parental height. Among participants with small average parental height (<167 cm or less), the OR of testicular cancer for tall (>180 cm) vs. short (<174 cm) subjects was 3.47 (95% CI: 1.60-7.51). These results suggest that the association between height and testicular cancer is likely to be explained by environmental factors affecting growth in early life, childhood and adolescence.
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http://dx.doi.org/10.1002/ijc.28688DOI Listing
August 2014
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