An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BackgroundFatigue is one of the most distressing symptoms of cancer patients. Its characteristics and impact on quality of life have not been fully explored and treatment of cancer-related fatigue in Italian oncological centers has not been codified.MethodsA cross-sectional study was carried out on all patients attending for any reason the 24 participating centers in two non-consecutive days. Patients with fatigue filled out the Brief Fatigue Inventory (BFI) questionnaire and reported any pharmacological or non-pharmacological treatment for fatigue.ResultsFrom October 2014 to May 2015, 1394 cancer patients agreed to participate in the study. Fatigue was referred by 866 (62.1%) of patients; its duration was >4months in 441 patients (50.9%). In the investigators' opinion, the most important (probable or almost sure) determinants of fatigue were reduced physical activity (271 patients), anxiety (149), pain (131), insomnia (125), anemia (123), and depression (123). Fatigue of moderate/severe intensity was reported by 43%/29.2% of patients, while usual fatigue in the last 24h by 45%/33.1%, and the worst fatigue in the last 24h by 33%/54.8%, respectively. Concerning the impact on quality of life, fatigue interfered moderately/severely with general activity in 30.8%/38.6% of patients, with mood in 26.1%/32.8%, with the ability to work in 27.9%/35.6%, with normal work in 26.7%/38.9%, with relationships with others in 21%/23.4% and with the ability to amuse themselves in 22.2%/33.1%. Only 117/866 patients (13.5%) received a pharmacological treatment represented by a corticosteroid in 101 patients (86.3%) while 188 patients (21.7%) received a non-pharmacological treatment such as physical exercise (120 patients, 63.8%) and various alimentary supplements (52 patients, 27.6%).ConclusionsCancer-related fatigue is frequently reported by oncological patients; its intensity and impact on quality of life is relevant.

We sought to develop criteria for ERBB2-positivity (HER2) in colorectal cancer to ensure accurate identification of ERBB2-amplified metastatic colorectal cancer patients suitable for enrolment in a phase II trial of ERBB2-targeted therapy (HERACLES trial). A two-step approach was used. In step 1, a consensus panel of pathologists adapted existing protocols for use in colorectal cancer to test ERBB2 expression and amplification. Collegial revision of an archival test cohort of colorectal cancer samples led to specific recommendations for adapting current breast and gastric cancer criteria for scoring ERBB2 in colorectal cancer. In step 2, from September 2012 to January 2015, colorectal-specific ERBB2 testing protocols and ERBB2 scoring criteria were used to centrally screen for ERBB2-positive KRAS wild-type colorectal cancer patients to be enrolled in the HERACLES trial (clinical validation cohort). In both archival test (N=256) and clinical validation (N=830) cohorts, a clinically sizeable 5% fraction of KRAS wild-type colorectal cancer patients was found to be ERBB2-positive according to the colorectal cancer-specific ERBB2 scoring criteria. ERBB2-positive tumors showed ERBB2 immunostaining consisting of intense membranous ERBB2 protein expression, corresponding to homogenous ERBB2 amplification, in >50% of cells. None of the immunohistochemistry 0 or 1+ cases was amplified. Concordance between SISH and FISH was 100%. In conclusion, we propose specific criteria for defining ERBB2-positivity in colorectal cancer (HERACLES Diagnostic Criteria). In a phase II trial of trastuzumab and lapatinib in a cetuximab-resistant population, HERACLES Diagnostic Criteria shaped the selection of patients and defined ERBB2 as a predictive marker for response to ERBB2-targeted therapy in metastatic colorectal cancer.

Besides promoting the cultural and organizational change to multidisciplinarity, PerSTEP supported by the Italian Society for Urologic Oncology (SIUrO) and the Board of Medical Oncology Directors (CIPOMO) wanted to make a picture of the multidisciplinary activities performed by the 23 participating centers and start a discussion on the efficacy of the interdisciplinary collaboration in the management of prostate cancer (PC) patients. The centers were invited to collect the data of 3 months' activity. Nineteen joined the call and gathered information on:-patients with genito-urinary cancers managed with a multidisciplinary approach-patients to whom the Multidisciplinary Team changed the stage-patients to whom the Multidisciplinary Team changed the therapeutic and observational options-patients who had received partial or incorrect information in previous consultations-patients who required psychological support The patients with genito-urinary cancers managed with a multidisciplinary approach were 1420. PC patients were 920. Fourteen centers reported the multidisciplinary evaluation to be effective in better definning the stage (80 cases, 8.7%). Fifteen centers reported that the multidisciplinary approach led to changing the therapeutic and observational options that patients had received before (153 cases, 12.5%). Sixteen centers reported that patients had received partial or incorrect information in previous consultations (197 cases, 21.4%). Ten centers reported that patients asked for psychological support (86 cases, 0.9%). Despite the limitations of this data collection, PerSTEP centers wanted to see if the interaction of urologists, radiation oncologists and medical oncologists, supported by other specialists such as pathologists, psychologists and imaging specialists, could prove effective in the management of PC patients and confirm the theoretical assumption of the advantages of multidisciplinary working. Further data on the way the centers work are needed to make a more detailed picture and to support these preliminary interesting results. Further effort will be necessary to promote the cultural and organizational change towards a multidisciplinary management of PC patients and overcome the barriers towards multiprofessional team working effective for health professionals and patients. A special thank to SANOFI for supporting the communication plan of PerSTEP

The multidisciplinary management is acknowledged as the best approach to cancer patients. The multiprofessional interaction enables to offer prostate cancer (PC) patients objective information, reduce the number of consultations and favour individualized proposals. PerSTEP is an educational project which promotes the cultural and organizational change to multidisciplinarity supported by the Italian Society for Urologic Oncology (SIUrO) and the Board of Medical Oncology Directors (CIPOMO). PerSTEP Activities:1.collection of information on 23 participating centers2.meetings of the centers3.communication (newsletters, press releases). The information enabled to have a picture of the working models. Some centers were organized according to formalized multidisciplinary models, others enjoyed good collaboration among specialists, others worked in monodisciplinary setting and requested specialistic consultations occasionally. Some centers organized multidisciplinarily improved their organizational models and centers working in a monodisciplinary setting started the reorganizational process. The centers shared information, discussed experiences in the literature and identified minimal requirements favouring the organizational change: 1.support from Admins and Directors of the specialties2.creation of a multidisciplinary team and identification of a leader3.adoption of evidence-based guidelines and paths of care4.decision on multidisciplinary activities (i.e. clinics, case discussions)5.activation of regular case discussions The meetings were the occasion to discuss on problems:1.resistance towards working multidisciplinarily2.not univocal interpretation of guidelines3.no formalized collaboration to overcome the unavailability of a specialty4.unavailability of contractual time to attend multidisciplinary activities The communication plan favoured sensibilization actions on the importance of the multidisciplinary approach. Last updated March 2015, PerSTEP produced marvelous results such as: 1.good interaction among centers2.formalization and update of 6 PC Units3.constitution of 7 new multidisciplinary teams4.activation of 10 tumor boards Further effort is needed to support the change towards the multidisciplinary management of PC patients. Thanks to SANOFI for supporting the communication plan

Leptomeningeal metastasis (LM) is a severe complication in the natural history of malignancies that occurs in 4–15 % of patients (pts) with solid tumors. Clinical presentation, cerebrospinal fluid cytology (CSF), and gadolinium magnetic resonance imaging (gdMRI) of the brain and spine are the methods routinely used to diagnose LM. Treatment encompasses involved-field radiotherapy of bulky or symptomatic disease sites and chemotherapy; however, no standard therapy has been established yet. We collected and reviewed retrospectively the clinical, pathological, radiological findings as well as the outcomes of 50 consecutive patients with LM from solid tumors to determine whether the diagnostic modalities and therapeutic procedures affected the outcomes. The results of this study confirm the role of gdMRI in the diagnosis of LM in clinical practice and suggest that an aggressive treatment may improve survival in patients with this debilitating and increasingly frequent neurological complication.

e22113 Background: The aim of this study is to validate impact of tumor architecture defined according to the novel IASLC/ATS/ERS classification on patient overall survival (OS) in resected pN0 invasive pulmonary adenocarcinomas. Methods: We identified patients who underwent resection of pN0 adenocarcinoma from 1998 to 2008 in our institution. Two pathologists, blinded to patient outcome, independently performed histopathologic subtyping according to IASLC/ATS/ERS classification. Histomorphologic data were correlated with patient outcome. Kaplan-Meier curves were used to calculate 5-year survival. Univariate and multivariate analysis were undertaken to control prognostic factors. The following variables were included in the univariate analysis: Sica grade and patterns, pathological 7th edition TNM stage, pleural invasion, lymphatic invasion, vascular invasion, peritumoral lymphocytic infiltrate, -cell type and tumor diameter. Multivariate analysis was used for variables that were found to be significant in the univariate analysis. Results: Sixty-six patients were studied; median age 65 ys (48-84), 71% male. 29 patients (43%) were staged as I, 25 (37%) as II and 12 (18%) as IIIA. Median follow up was 53 months (range: 3-146). Five mutually exclusive tumor histology pattern groups were identified: solid (30,3%), papillary (18,18%), lepidic (3,03%), acinar (43,9%) and mucinous (4,55%). Solid pattern tumors were associated with a lower OS (median: 21 months) than nonsolid pattern tumors(median: 66 months). At univariate analysis, UICC stage (p < 0.001), T (p<0.001), Sica score (p=0.042), Sica primary pattern (0.030) and lymphocytic infiltrate (p=0.001) were related to shorter OS. The predominant growth pattern (p= 0.051), the cell type (p= 0.134) and the other variables were not associated with OS. Multivariate analysis confirmed Sica patterns as an independent prognostic marker of shorter OS (p = 0.044), together with stage and T. Conclusions: Our data confirm the role of known prognostic factors, such as UICC stage and T, as predictor of survival in pN0 patients and suggest the relevance of architectural pattern according to Sica as an efficient new prognostic factor.

e13009 Background: Epidermal growth factor (EGF) plays an important role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production and contribute to the risk of glioma. However, published data are contradictory. EGF +61G/A polymorphism may contribute to the risk of glioma in different ethnic group. Patients with glioma and GG genotype have been reported to have a risk of poorer otucome than patients with AA genotype. Purpose of this study is to investigate the potential role of this polymorphism in cancer progression and its role as predictive marker of outcome in glioma caucasian patients. Methods: EGF 61A/G polymorphism (rs4444903) was analyzed in glioma patients and was determined by means of Polymerase Chain Reaction and Direct Sequencing method (GenBank reference sequence-accession no. AC005509) from blood samples. Association of this genetic polymorphism with clinical and pathological data of patients was evaluated. Results: We investigated EGF +61G/A polymorphism in 24 glioma patients . EGF +61G allele has been found in 67% of glioma patients (25% G/G genotype and 42% A/G genotype). In astrocytomas, EGF +61G allele represents a 83% frequency; in glioblastomas and in oligodendrogliomas, EGF +61G allele frequency represents respectively 71% and 50%. In WHO IV gliomas, the EGF +61G allele represents a 63% frequency, (27% G/G and 36% A/G ), in WHO III gliomas a 77% frequency (33% G/G and 44% A/G ) and in WHO II gliomas a 50% frequency (100% A/G ). Median PFS of glioblastoma patients was 9 months. 83% of glioblastoma patients with a relapsing disease showed the G/G and A/G genotype. No difference was detected in the others histotypes. Conclusions: Our data conferm previous studies which reported G allele as a risk factor for glioma in Caucasian. G/A and G/G genotypes seem to be more rappresentative in high grade gliomas . Despite limited number of patients, our study supports the predictive role of EGF 61 A/G polymorphism in GBM. Additional large studies are warranted to confirm the role of EGF polymorphism as indipendent prognostic factor in glioma.

Aims and background In recent years, the number of oral anticancer drugs used in clinical practice has rapidly increased. The Italian Society of Medical Oncology (AIOM) conducted a survey to describe the impact of the use of oral anticancer drugs on the daily activity of Italian oncology practices. Methods and study design A survey questionnaire was distributed to the coordinators of the regional sections of AIOM. A 6-month period was considered, from January 1, 2010 to June 30, 2010. The survey addressed (1) quantitative aspects of the use of oral anticancer drugs; (2) practical aspects in the management of patients treated with these drugs; (3) issues related to treatment costs and reimbursement procedures. Results Thirty-six questionnaires were received from institutions distributed throughout the Italian territory. Oral anticancer drugs (both chemotherapy and molecularly targeted agents) accounted for a significant proportion (17%) of prescribed treatments. Among the responding institutions, there were different dispensation procedures of oral drugs to patients: drugs were dispensed by the pharmacist (57%) or directly by the medical oncologist (23%) or nurse (20%). The medical oncologist played a major role in the communication with patients (73% alone and a further 24% in cooperation with other professional figures) and was the point of reference in the event of side effects in 97% of cases. In most cases, the reimbursement of drug costs was separated (“File F” procedure) from the flat fare received by the hospital for outpatient visits or day-hospital access. Conclusions Optimal organization of oral anticancer treatment warrants the cooperation and integration of multiple professional figures. At least three figures are involved in patient management in the hospital: the medical oncologist, the nurse, and the hospital pharmacist. Oral anticancer treatments are associated with specific reimbursement issues: in the majority of cases, the cost of the drug is reimbursed separately from the cost of patient access.

BACKGROUND:The prognosis of pT1a-pT1b breast cancer (BC) used to be considered very good, with a 10-y RFS of 90%. However, some retrospective studies reported a 10-y RFS of 81%-86% and suggested benefit from adjuvant systemic therapy.METHODS:To evaluate the variables that determined the choice of adjuvant chemotherapy and the type of chemotherapy delivered in pT1a-pT1b BC, we analysed the small tumours enrolled in the NEMESI study.RESULTS:Out of 1,894 patients with pathological stage I-II BC enrolled in NEMESI, 402 (21.2%) were pT1a-pT1b. Adjuvant chemotherapy was delivered in 127/402 (31.59%). Younger age, grading G3, high proliferative index, ER-negative and HER2-positive status were significantly associated with the decision to administer adjuvant chemotherapy. An anthracycline without taxane regimen was administered in 59.1% of patients, anthracycline with taxane in 24.4%, a CMF-like regimen in 14.2% and taxane in 2.4%. Adjuvant chemotherapy was administered in 88.4% triple-negative and 73.46% HER2-positive pT1a-pT1b BC. Adjuvant trastuzumab was delivered in 30/49 HER2-positive BC (61.2%).CONCLUSIONS:Adjuvant chemotherapy was delivered in 31.59% T1a-pT1b BC treated at 63 Italian oncological centres from January 2008 to June 2008. The choice to deliver chemotherapy was based on biological prognostic factors. Anthracycline-based chemotherapy was administered in 83.5% patients.

AIMS AND BACKGROUND:In 2009, the Italian Society of Medical Oncology (AIOM) conducted a survey to describe the impact of regional pharmaceutical formularies on the disparity of access to eight new drugs among cancer patients treated in Italian regions. The survey documented some regional restrictions for some anti-cancer drugs. In the study, we analyzed the "time to patient access" to new anti-cancer drugs in Italian regions.METHODS:In March 2010, we analyzed the availability of 17 new anti-cancer drugs at a regional level, specifically the coherence of regional authorizations compared with national authorizations approved by the Italian Medicines Agency (AIFA). In the regions with pharmaceutical formularies, we analyzed the characteristics of technical-scientific committees for the evaluation of inclusion of hospital drugs in these formularies. We also analyzed the time from EMA (CMPH) authorization to AIFA marketing authorization, the time from AIFA marketing authorization to patient availability, and the total time from EMA (CMPH) authorization to patient availability of the drugs in all Italian regions, for 11 of these drugs.RESULTS:Some drugs were included in all the regional pharmaceutical formularies, without restrictions, whereas other drugs were not included in one and others were not included in more than one formulary. Median time from EMA to AIFA was 11.2 months (range, 2.9-17.1). Median time from AIFA to patient availability was 1.4 months (range, 0.0-50.5) in regions with drug formularies versus 0.0 months in regions without drugs formularies. Median total time from EMA to patient availability was longer in regions with formularies (13.3 months; range, 2.9-65.3) than in regions without formularies (11.2 months; range, 2.9-24.0), where drugs are immediately available after AIFA marketing authorization. Moreover, the interval was very long (range, 2.9-65.3) for some drugs in regions with formularies.CONCLUSIONS:The analysis confirmed that the presence of multiple hierarchical levels of drug evaluation can create disparity in drug availability for Italian citizens.

Aims and background. Italy is divided into 20 regions. As a consequence of local autonomy, following marketing authorization by the Italian Medicines Agency, each drug for hospital use is not immediately available, because its approval needs to undergo further steps that can be different among regions. The Italian Society of Medical Oncology conducted the present study to describe the impact of the existence of sub-national pharmaceutical formularies on the disparity of access to new anti-cancer drugs among patients treated in different Italian regions.Methods. The availability of 8 new anti-cancer drugs at a regional level and the coherence of regional authorizations compared with national authorizations approved by the Italian Medicines Agency were analyzed as of April 2009.Results. Fourteen regions and autonomous province of Trento have a regional pharmaceutical formulary. In most cases, the regional pharmaceutical formularies include the eight analyzed drugs, with therapeutic indications coherent with national marketing authorization indications. Five drugs (bevacizumab, trastuzumab, rituximab, erlotinib, sunitinib) were included in all the existing regional pharmaceutical formularies, without restrictions, whereas three drugs (cetuximab, sorafenib, pemetrexed) were found to have restrictions in some regions.Conclusions. The presence of multiple hierarchical levels of drug evaluation creates a potential element of disparity in the access to pharmacological therapies for Italian citizens. Free full text available at www.tumorionlineit

Aims and background. Advanced chemorefractory epithelial thymic tumors are still a challenge in clinical oncology A therapeutic approach targeting a key molecular pathway could be the ideal solution in a neoplasm that can overexpress epidermal growth factor receptor (EGFR) in the epithelial component.Methods. A patient with metastatic heavily pretreated thymic carcinoma was evaluated for EGFR expression in the primary tumor.Results. Strong EGFR expression was revealed by immunohistochemistry. The patient received erlotinib therapy but had obtained no response after four months of treatment.Conclusion. This preliminary experience suggests that erlotinib may not be a useful therapeutic choice in advanced pretreated thymic carcinomas.

Salivary gland carcinomas are rare cancers, comprising 1-5% of head and neck cancers. They represent a morphologically and clinically diverse group of tumors. The most commonly histopathologic types are mucoepidermoid cancer, adenoid cystic cancer and adenocarcinomas. Malignant salivary gland tumors generally present as painless, slow-growing tumors that are indistinguishable from benign tumors. Surgery is the principal treatment and is curative in early stage. Radiation therapy should be considered in most patients after surgical resection. Chemotherapy is reserved for palliative treatment of metastatic disease but results are disappointing. Recent studies have investigated the role of targeted therapies in a palliative setting. Multicentre cooperative group clinical trials are required to assess novel therapies to maximize patient resources in this uncommon tumor.

We describe the case of a 39-year-old man with disseminated testicular seminoma that was refractory to salvage chemotherapy, and who had complete remission after imatinib administration. In September, 1999, the patient underwent a right orchifunicolectomy for a classical seminomatous tumour. A CT scan of the chest and abdomen showed retroperitoneal bulky disease (massive enlargement of right periaortic, paracaval, and interaortocaval lymph nodes of at least 4·3 cm in diameter). Baseline alpha-fetoprotein and human chorionic gonadotropin were within the normal ranges of 0·5–9·0 ng/ml and 0–2 mUI/ml, respectively, whereas lactate dehydrogenase concentration was increased at 722 UI/L (normal range 200–479 UI/L). The tumour was staged as pT1 N2. A classic chemotherapy regimen of cisplatin, etoposide, and bleomicin was given for three cycles, after which the patient's concentrations of lactate dehydrogenase normalised and he had a complete response. The patient had standard follow-up according to the European Society for Medical Oncology recommendations.

Taxanes are widely used chemotherapeutic agents with the potential to induce pulmonary injury through a variety of mechanisms. Patients receiving these agents are at risk of acute or subacute pulmonary damage. The case is presented of a 72-year-old man with hormone-refractory prostate cancer and weekly administration of 30 mg/m(2) docetaxel who developed subacute interstitial pneumonitis-related pulmonary fibrosis after seven doses and died despite mechanical ventilation and high-dose corticosteroid treatment. Even though only a few cases of this adverse event have been reported in the literature, severe docetaxel-induced pulmonary toxicity needs to be considered in the differential diagnosis when such patients present with respiratory symptoms.