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Introduzione: La soddisfazione lavorativa o job satisfaction è intesa come l’atteggiamento positivo di una persona nei confronti del lavoro che svolge e che può influenzare le performance degli infermieri, sia la qualità delle cure. Un ambiente di lavoro che favorisca un buon reciproco supporto professionale, opportunità di sviluppo e crescita, può aumentare la soddisfazione lavorativa. Obiettivo: Descrivere il grado di job satisfaction degli infermieri di due Aziende Ospedaliere di Roma. Materiali e Metodi: È stato condotto uno studio trasversale in due ospedali metropolitani romani, in diverse aree cliniche, tra Ottobre e Novembre 2017. È stato usata la versione italiana dell’Index of Work Satisfaction di Stamps. L’ANOVA è stata utilizzata per valutare le differenze tra più di due gruppi. Risultati: Dei 504 questionari distribuiti solo 264 sono stati compilati interamente, con un tasso di risposta pari al 52%. Delle 7 aree indagate, l’autonomia ha ottenuto il punteggio medio più alto (Media = 42.4; DS = 7.7) seguita da status professionale (Media = 33.3; DS = 7.2), interazioni con i colleghi (Media = 25.4; DS = 5.6), politiche organizzative (Media = 20.5; DS = 5.7), mansioni richieste dal ruolo (Media = 19.6; DS = 5.9), interazioni con i medici (Media = 18.9; DS = 5.5) e la retribuzione (Media = 14.2; DS = 6.5). Risultano essere associate ad un aumento della soddisfazione lavorativa il turnover (P=0,002) e la tipologia di contratto (P=0.004). Conclusione: La ricerca mostra che l’autonomia, lo status professionale e la retribuzione sono le aree che impattano positivamente sulla soddisfazione lavorativa.

Abstract Background Data on efficacy of bevacizumab (B) beyond first-line taxane -including regimen (BT) as first-line treatment are lacking. Although preclinical results that anti-angiogenic agents combined with hormonal therapy (HT) could be active, no clinical data exist about combination of maintenance Bevacizumab (mBev) with HT. Methods Thirty-five patients who experienced a response after first-line BT, were given mBev at the dose of 15 mg/kg every 3 weeks. Among 30 pts with hormonal receptor-positive metastatic breast cancer (MBC), 20 (66.6%) received HT with mBev (mHTBev). Objective of the study was the outcome and safety of mBev and in two groups of patients receiving HT or not. Results Complete response and partial response was achieved/maintained in 4 (11.4%) and 13 (37.1%) patients, respectively (overall response rate: 48.5%). Clinical benefit was obtained on 23 patients (65.7%). Median of mBev PFS and clinical benefit were 6.8 months (95% CI: 0.8-12.7) and 17.1 months (95% CI :12.2-21.9), respectively. Median PFS of patients who received mHTBev was longer than mBev without HT (13 months and 4.1 months, respectively, p = 0.05). The most common severe toxicities were proteinuria (11.4%) and hypertension (8.5%). No additional toxicity was observed with HTBev. Conclusion Maintenance bevacizumab with or without anti-hormonal therapy in patients with hormone receptor positive breast cancer is tolerable and associated with long-term clinical outcome; these results encourage the strategy of prolonging bevacizumab until progression in combination with anti-hormonal agents.

Abstract Background Ipilimumab and vemurafenib have both been shown to improve survival in phase III trials of patients with metastatic melanoma. Although vemurafenib is associated with a rapid onset of activity, responses are often of limited duration. Conversely, responses to ipilimumab take time to develop, but can be durable. Currently, limited data exist on the sequencing of these agents in patients with the BRAFV600 mutation. The aim of this analysis was to identify factors that could potentially be used to optimise the order in which ipilimumab and BRAF inhibitors are administered in this patient population. Methods This was a retrospective, single-institution, analysis of patients treated with vemurafenib 960 mg or dabrafenib 150 mg twice-daily and ipilimumab 3 mg/kg every 3 weeks for 4 doses as part of a clinical trial or expanded access program. Eligible patients tested positive for the BRAFV600 mutation and had sequentially received treatment with vemurafenib or dabrafenib followed by ipilimumab, or vice versa. Results In total, 34 BRAF-mutation positive patients were eligible, comprising six patients who received ipilimumab followed by a BRAF inhibitor, and 28 patients treated with a BRAF inhibitor who subsequently received ipilimumab. Of these 28 patients, 12 (43 %) had rapid disease progression resulting in death and were unable to complete ipilimumab treatment as per protocol. These patients were classified as having rapid disease progression. Median overall survival for rapid progressors was 5.7 months (95 % CI: 5.0–6.3), compared with 18.6 months (95 % CI: 3.2–41.3; p < 0.0001) for those patients who were able to complete ipilimumab treatment. Baseline factors associated with rapid progression were elevated lactate dehydrogenase, a performance status of 1 and the presence of brain metastases. Patients were more likely to have rapid disease progression if they had at least two of these risk factors at baseline. Conclusions Our analysis suggests it may be possible to identify those patients at high risk of rapid disease progression upon relapse with a BRAF inhibitor who might not have time to subsequently complete ipilimumab treatment. We hypothesise that these BRAF-mutation positive patients may benefit from being treated with ipilimumab first.

Abstract Background Immunoglobulin D multiple myeloma (MM) is rare and has a poorer prognosis than other MM isotypes. Design and methods Seventeen patients (pts) diagnosed from 1993 to 2009 with IgD MM were selected from six institutions of Multiple Myeloma Latium-Region GIMEMA Working Group. Results Median age was 55 years, 14 patients had bone lesions, eight had renal impairment with estimated glomerular filtration rate (eGFR) < 50 ml/min, one serum calcium ≥ 12 mg/dl, 11 had lambda light chains, five stage III of ISS, six with chromosomal abnormalities. Six pts received conventional chemotherapy (CT): five melphalan + steroids based regimens. Eleven underwent high-doses of chemotherapy with autologous stem cell transplantation (HDT/ASCT), five single and six tandem ASCT: six received bortezomib and/or thalidomide as induction therapy and five VAD. Thalidomide maintenance was used in two pts: one in HDT/ASCT and one in CT group; bortezomib was used in one patient after HDT/ASCT. At a median follow up of 38 (range 19-60) and 50 months (range 17-148) for pts treated with CT and HDT/ASCT, respectively, the overall response rate (ORR) was 83% and 90%. In the group of patients treated with CT, median overall survival (OS) was 34 months (95% CI 15- 54 months), median progression free survival (PFS) was 18 months (95% CI 3-33 months) and median duration of response (DOR) was 7 months (95% CI 5-9 months). Median OS, PFS and DOR were not reached at the time of this analysis in the HDT/ASCT group of patients. Death was observed in 27.3% of pts treated with HDT/ASCT and in 66.7% undergone CT. Conclusions Despite the retrospective analysis and the small number of pts our study showed that the use of HDT/ASCT seems to improve also the prognosis of IgD MM patients. Treatment options including new drugs, before and after stem cell transplantation, may further improve the outcomes of these patients.

Abstract Background Although the addition of bevacizumab significantly improves the efficacy of chemotherapy for advanced breast cancer, regulatory concerns still exist with regard to the magnitude of the benefits and the overall safety profile. Methods A literature-based meta-analysis to quantify the magnitude of benefit and safety of adding bevacizumab to chemotherapy for advanced breast cancer patients was conducted. Meta-regression and sensitivity analyses were also performed to identify additional predictors of outcome and to assess the influence of trial design. Results Five trials (3,841 patients) were gathered. A significant interaction according to treatment line was found for progression-free survival (PFS, p = 0.027); PFS was significantly improved for 1st line (Hazard Ratio, HR 0.68, p < 0.0001), with a 1-yr absolute difference (AD) of 8.4% (number needed to treat, NNT 12). A non-significant trend was found in overall survival (OS), and in PFS for 2nd line. Responses were improved with the addition of bevacizumab, without interaction between 1st line (Relative Risk, RR 1.46, p < 0.0001) and 2nd line (RR 1.58, p = 0.05). The most important toxicity was hypertension, accounting for a significant AD of 4.5% against bevacizumab (number needed to harm, NNH 22). Other significant, although less clinically meaningful, adverse events were proteinuria, neurotoxicity, febrile neutropenia, and bleeding. At the meta-regression analysis for 1st-line, more than 3 metastatic sites (p = 0.032), no adjuvant chemotherapy (p = 0.00013), negative hormonal receptor status (p = 0.009), and prior anthracyclines-exposure (p = 0.019), did significantly affect PFS. Conclusions Although with heterogeneity, the addition of bevacizumab to 1st-line chemotherapy significantly improves PFS, and overall activity. Hypertension should be weighted with the overall benefit on the individual basis.

Abstract Background To evaluate activity and tolerability of two anthracycline-containing regimens as first-line treatment for anthracycline-naïve relapsed breast cancer patients. Methods Patients with relapsed breast cancer not previously treated with adjuvant anthracyclines were randomly assigned to epirubicin/vinorelbine (arm A: EPI/VNB, EPI 90 mg/m2 on day 1, VNB 25 mg/m2 on days 1,5 plus G-CSF subcutaneously on days 7-12, with cycles repeated every 21 days), or to pegylated liposomal doxorubicin/VNB (arm B: PLD/VNB, PLD 40 mg/m2 on day 1, VNB 30 mg/m2 on days 1, 15, with cycles repeated every 4 weeks). Primary objective was to evaluate the efficacy of the two regimens in terms of response rate, secondarily toxicity, progression free survival and overall survival. Results One hundred and four patients have been enrolled (arm A 54, arm B 50): characteristics were well balanced between the 2 arms. Responses were as follows: arm A, 3 (5.6%) CR, 20 (37%) PR, (ORR 42.6%, 95%CI 29.3%-55.9%); arm B, 8 (16%) CR, 18 (36%) PR, (ORR 52%, 95%CI 38.2%-65.8%). Median progression free survival was 10.7 months in arm A (95% CI, 8.7-12.6), and 8.8 months in arm B (95% CI, 7.1-10.5). Median overall survival was 34.6 months in arm A (95%CI, 19.5-49.8) and 24.8 months in arm B (95%CI, 15.7-33.9). As toxicity concerns, both treatment regimens were well tolerated; myelosuppression was the dose-limiting toxicity, with G3-4 neutropenia occurring in 18.5% and 22% of the patients of arm A and B, respectively. No relevant differences in main toxic effects have been observed between the two arms, except for alopecia, more common in arm A, and cutaneous toxicity, observed only in arm B. No clinical congestive heart failures have been observed, one case of tachyarrhythmia was reported after the last EPI/VNB cycle, and two reversible ≥ 20% LVEF decreases have been observed in arm A. Conclusions Both anthracycline- containing regimens evaluated in the present study seem to be active and with a satisfactory tolerability in anthracycline-naïve relapsed breast cancer patients.

Abstract Background Hormone therapy plus radiotherapy significantly decreases recurrences and mortality of patients affected by locally advanced prostate cancer. In order to determine if difference exists according to the hormonal treatment duration, a literature-based meta-analysis was performed. Methods Relative risks (RR) were derived through a random-effect model. Differences in primary (biochemical failure, BF; cancer-specific survival, CSS), and secondary outcomes (overall survival, OS; local or distant recurrence, LR/DM) were explored. Absolute differences (AD) and the number needed to treat (NNT) were calculated. Heterogeneity, a meta-regression for clinic-pathological predictors and a correlation test for surrogates were conducted. Results Five trials (3,424 patients) were included. Patient population ranged from 267 to 1,521 patients. The longer hormonal treatment significantly improves BF (with significant heterogeneity) with an absolute benefit of 10.1%, and a non significant trend in CSS. With regard to secondary end-points, the longer hormonal treatment significantly decrease both the LR and the DM with an absolute difference of 11.7% and 11.5%. Any significant difference in OS was observed. None of the three identified clinico-pathological predictors (median PSA, range 9.5-20.35, Gleason score 7-10, 27-55% patients/trial, and T3-4, 13-77% patients/trial), did significantly affect outcomes. At the meta-regression analysis a significant correlation between the overall treatment benefit in BF, CSS, OS, LR and DM, and the length of the treatment was found (p≤0.03). Conclusions Although with significant heterogeneity (reflecting different patient' risk stratifications), a longer hormonal treatment duration significantly decreases biochemical, local and distant recurrences, with a trend for longer cancer specific survival.

Abstract Background Although the addition of bevacizumab to 1st line chemotherapy provides a significant survival benefit for advanced colorectal cancer, the magnitudes of both advantages and toxicities have not been extensively investigated. Methods A literature-based meta-analysis was conducted; Hazard Ratios were extracted from randomized trials for primary end-points (Progression Free Survival, PFS, Overall Survival OS). The log of event-based risk ratio were derived for secondary endpoints (objective/partial response rate, ORR/PR; severe hypertension, bleeding and proteinuria). Absolute differences and the number needed to treat/harm (NNT/NNH) were calculated. A meta-regression analysis with clinical predictors and a sensitivity analysis according to the trial phase-design were conducted as well. Results Five trials (2,728 pts) were selected. The addition of bevacizumab to 1st line chemotherapy significantly increased both PFS (although with significant heterogeneity) and OS over exclusive chemotherapy by 17.1% and 8.6% (NNT 6 and 12), regardless of the study setting (non significant interaction between phase II and III). The chance to improve PR was significantly increased by 6.5% (NNT 15), with a trend for ORR. The risk of hypertension was significantly increased by 6.2% (NNH 16). According to the meta-regression analysis, female gender and rectal primary site were significant predictors for PFS benefit. Conclusions Notwithstanding all the concerns related to costs and the significant HTN risk, the significant outcome improvement provided by bevacizumab in first-line treatment for unselected advanced colorectal cancer patients, should be considered when choosing the appropriate up-front therapy.

Abstract Background Adequate surgery still remains the only curative treatment of chordoma. Interesting clinical data on advanced disease with molecularly targeted therapies were reported. Methods We described the clinical outcome of a series of chordoma patients followed at Regina Elena National Cancer Centre of Rome from 2004 to 2008. Results Twenty-five consecutive patients with sacral (11 patients), spine (13 patients), and skull base (1 patient) chordoma went to our observation. Six patients (24%) had primary disease, 14(56%) a recurrent disease, and 5(20%) a metastatic spreading. Surgery was the primary option for treatment in 22 out of 25 patients. Surgical margins were wide in 5 (23%) and intralesional in 17(77%) patients; 3 out of 4 in-house treated patients obtained wide margins. After first surgery, radiotherapy (protons or high-energy photons) were delivered to 3 patients. One out of the 5 patients with wide margins is still without evidence of disease at 20 months from surgery; 2 patients died without evidence of disease after 3 and 36 months from surgery. Sixteen out of 17 (94%) patients with intralesional margins underwent local progression at a median time of 18 months with a 2-year local progression-free survival of 47%. The 5-year metastasis-free survival rate was 78.3%. Seventeen patients with locally advanced and/or metastatic disease expressing platelet-derived growth factor receptor (PDGFR) β were treated with imatinib mesylate. A RECIST stabilization of the disease was the best response observed in all treated cases. Pain relief with reduction in analgesics use was obtained in 6 out of 11 (54%) symptomatic patients. The 5- and 10-year survival rates of the entire series of patients were 76.7 and 59.7%, respectively. Conclusions Despite progress of surgical techniques and the results obtained with targeted therapy, more effort is needed for better disease control. Specific experience of the multidisciplinar therapeutic team is, however, essential to succeed in improving patients' outcome.

Abstract Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources.

Abstract Background This phase II study was designed to evaluate the activity and safety of a combination of epirubicin, oxaliplatin and docetaxel in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Methods Forty patients with measurable distant metastases received epirubicin 50 mg/m2, docetaxel 60 mg/m2 followed by oxaliplatin 100 mg/m2 on day 1 of each 21-day cycle. Primary end point was response rates (RR). Results All patients were evaluable. The overall RR was 47.5% (95% confidence interval (CI) 32–63). The disease control was 80%. Median time for response was 6 weeks. Median time to progression was 6.3 months (95% CI 5.4–7.2) and the median overall survival time was 12.1 months (95% CI 10.7–13.5). Grade 3/4 neutropenia occurred in 50% of patients with two episodes of febrile neutropenia (5%). Other non-hematological grade 3 toxicities included sensory neuropathy in two patiens (5%), vomiting and mucositis in two patients (5%) and diarrhea in one patient (2.5%). Conclusion The combination of epirubicin, oxaliplatin and docetaxel was found to be effective and well tolerated in patiens with metastatic gastric or GEJ adenocarcinoma and maybe an appropriate regimen to be used in the neoadjuvant setting and with molecularly targeted agents.

Abstract Background Serum levels of IGF-I in patients affected with multiple myeloma (MM) have been scarcely studied. The present study is aimed to explore this point comparing 55 healthy subjects, 71 monoclonal gammopaties of uncertain significance (MGUS) and 77 overt MM patients. In the same subjects, basic FGF and VEGF, have been detected. All three mediators were analyzed in function of K-ras mutation and melphalan response. Concerning IGF-I, two representative monitoring examples have also been added. Methods Cytokine determinations were performed by commercially available ELISA kits, while K12-ras mutation was investigated on genomic DNA isolated from bone marrow cell specimens by RFLP-PCR assay. Results Significant reductions of IGF-I levels were observed in MGUS and MM as compared with healthy controls. In addition, MM subjects showed significantly decreased serum IGF-I levels than MGUS. Conversely, increasing levels were observed for bFGF and VEGF, molecules significantly correlated. A multivariate analysis corrected for age and gender confirmed the significant difference only for IGF-I values (P = 0.01). K12-ras mutation was significantly associated with malignancy, response to therapy and with significantly increased serum bFGF levels. Conclusion IGF-I reduction in the transition: Controls→MGUS→MM and changes observed over time suggest that IGF-I should be furtherly studied in future clinical trials as a possible monitoring marker for MM.

Abstract Background Patients with hereditary non-poliposys colorectal cancer (HNPCC) have better prognosis than sporadic colorectal cancer (CRC). Aim of our retrospective study was to compare the overall survival between sporadic CRC and HNPCC patients. Methods We analyzed a cohort of 40 (25 males and 15 females) HNPCC cases with a hospital consecutive series of 573 (312 males and 261 females) sporadic CRC observed during the period 1970–1993. In 15 HNPCC patients we performed mutational analysis for microsatellite instability. Survival rates were calculated by Kaplan-Meier method and compared with log rank test. Results The median age at diagnosis of the primary CRC was 46.8 years in the HNPCC series versus 61 years in sporadic CRC group. In HNPCC group 85% had a right cancer location, vs. 57% in the sporadic cancer group. In the sporadic cancer group 61.6% were early-stages cancer (Dukes' A and B) vs. 70% in the HNPCC group (p = ns). The crude 5-years cumulative survival after the primary CRC was 94.2% in HNPCC patients vs. 75.3% in sporadic cancer patients (p < 0.0001). Conclusion Our results show that overall survival of colorectal cancer in patients with HNPCC is better than sporadic CRC patients. The different outcome probably relates to the specific tumorigenesis involving DNA mismatch repair dysfunction.