A regional population-based hereditary breast cancer screening tool in Italy: First 5-year results.

BACKGROUND: Up to 10% of individuals with breast cancer (BC) belong to families with hereditary syndromes. The aim of this study was to develop an instrument to identify individuals/families at high-hereditary risk for BC and offer dedicated surveillance programs according to different risks. METHODS: The instrument consisted of a primary questionnaire collecting history of BC and ovarian cancer (OC). This questionnaire was applied to women enrolled in the Emilia-Romagna Breast Cancer Screening Program. General practitioners (GPs) and specialists could propose the same questionnaire too. Women with a score of ≥ 2, were invited to complete an oncogenetic counseling. According to the Tyrer-Cuzick evaluation, women considered at high risk were invited to involve the most representative alive individual of the family affected with BC/OC for BRCA1/2 genetic testing. RESULTS: Since January 2012 and December 2016, 660 040 women were evaluated by the regional screening program, of which 22 289 (3.5%) were invited to the Spoke evaluation, but only 5615 accepted (25.2%). Totally, also considering women sent by GPs and specialists, 11 667 were assessed and 5554 were sent to the Hub evaluation. Finally, 2342 (42.8%) women fulfilled the criteria for genetic testing, and 544 (23.2%) resulted BRCA1/2 mutation carriers. CONCLUSIONS: To our knowledge, this is the first regional population-based multistep model that is aimed to identify individuals with BRCA1/2 mutations and to offer an intensive surveillance program for hereditary-high risk women. This tool is feasible and effective, even if more efforts must be performed to increase the acceptance of multiple assessments by the study population.

Variation in hospital utilization at the end of life for patients with cancer in the Emilia-Romagna region of Italy.

INTRODUCTION: Despite the preference of many patients to die at home, high proportions of patients with advanced cancer undergo major procedures, receive intensive care, and die in the hospital. The goal of this study is to examine variation in hospital utilization and site of death for patients dying with poor-prognosis cancer in the Regione Emilia-Romagna (RER), Italy. METHODS: We conducted a retrospective, population-level study using administrative data. Patients were included if they died in 2012 and had at least one hospital admission for metastatic or poor-prognosis cancer within 180 days of death. Variations in the use of the hospital, intensive care, and procedures performed were evaluated. RESULTS: 11,470 patients died with metastatic or poor-prognosis cancer in 2012. Seventy-eight percent of patients were hospitalized in the last month of life while 50.7% of patients died in the hospital. Results varied by local health authority from 38.3% to 69.3%. Of patients who had an ICU stay, 55.1% in the community hospitals and 59.8% in the teaching hospitals were admitted to the ICU on the day of death or the day before death. 7.5% of patients underwent a major procedure in the last 30 days of life. CONCLUSIONS: The overall high rate, and substantial variation, in hospital care at the end of life offers the RER the opportunity to evaluate if increasing availability of palliative care, along with provider and patient education, could reduce utilization of high-cost hospital care and increase patient and family satisfaction.

Appropriate use of tumour biomarkers for treatment with innovative drugs: A retrospective study.

Performing randomised clinical trials to address the clinical usefulness of predictive and prognostic tumour markers is a complex process for several reasons, and observational experiences may thus play an important role. The present study performed an observational retrospective analysis in Area Vasta Romagna, Italy, collecting information on tumour marker determination in 760 consecutive patients who started a new line of anticancer therapy between January and June 2010. The determination of well-known biomarkers was requested for all gastrointestinal stromal tumour (GIST) patients (n=13) and for almost all breast cancer patients (n=369), and targeted therapies were consequently prescribed. Conversely, Kirsten rat sarcoma viral oncogene homolog (KRAS) determination in colon cancer patients (n=177) was requested in ~50% of advanced cases, while epidermal growth factor receptor (EGFR) determination was required in slightly more than 30% of the same patients. EGFR and KRAS determinations were requested in only 15% and 7.5% of non-small cell lung cancer (NSCLC) patients (n=201), respectively. There would appear to be greater appropriateness of tumour marker determination for breast cancer and GISTs than for colon cancer and NSCLC. Resources can be further optimised by standardising tumour marker determinations in terms of the timing of requests and the consequent use of the results for tailored treatment planning.

Variation among local health units in follow-up care of breast cancer patients in Emilia-Romagna, Italy.

AIMS AND BACKGROUND: This study examines the patterns of follow-up care for breast cancer survivors in one region in Italy. METHODS AND STUDY DESIGN: This retrospective analysis included 10,024 surgically treated women, with incident cases of breast cancer in the years 2002-2005 who were alive 18 months after their incidence date. Rates of use of follow-up mammograms, abdominal echogram, bone scans and chest x-rays were estimated from administrative data and compared by Local Health Unit (LHU) of residence. Logistic regression analyses were performed to assess possible "overuse", accounting for patient age, cancer stage, type of surgery and LHU of residence. RESULTS: A total of 7168 (72.1%) women received a mammogram within 18 months of their incidence date, while 6432 (64.2%) had an abdominal echogram, 3852 (38.4%) had a bone scan and 5231 (52.2%) had a chest x-ray. The rates of use of abdominal echograms, bone scans and chest x-rays were substantially higher in the population of breast cancer survivors than in the general female population. Taking account of patient age, cancer stage at diagnosis and type of surgery, multivariate analyses demonstrated significant variation in the use of these tests by LHU of residence. CONCLUSIONS: The observed variation in the use of abdominal echograms, bone scans and chest x-rays supports the conclusion that there is substantial misuse of these tests in the population of postsurgical breast cancer patients in the Emilia-Romagna region in Italy. In the absence of a documented survival benefit, overtesting has both a human and financial cost. We recommend additional review of the methods of follow-up care in breast cancer patients in the LHUs of Emilia-Romagna, with the aim of developing, disseminating and evaluating the implementation of specific guidelines targeting primary care physicians and oncologists providing care to breast cancer survivors. Patient education materials may also help to reduce unnecessary testing.

Clinical governance network for clinical audit to improve quality in epithelial ovarian cancer management.

BACKGROUND: Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Several hospitals throughout the region provide primary treatment for these patients and it is well know that treatment quality is correlated to the hospital that delivers. The aim of this study was to investigate the management and treatment of EOC in a Region of the North Italy (Emilia-Romagna, Italy). METHODS: A multidisciplinary group made up of 11 physicians and 3 biostatisticians was formed in 2009 to perform clinical audits in order to identify quality indicators and to develop Region-wide workup in accordance with the principles of evidence-based medicine (EBM). The rationale was that, by setting up an oncogynecology network so as to achieve the best clinical practice, critical points would decrease or even be eliminated. Analysis of cases was based on the review of the medical records. RESULTS: 614 EOC patients treated between 2007 and 2008 were identified. We found only 2 high-volume hospitals (≥ 21 patients/year), 3 medium-volume hospitals (11-20 operated patients/year), and 7 low-volume hospitals (≤ 10 operated patients /year). Only 222 patients (76.3%) had a histological diagnosis, FIGO surgical staging was reported only in 206 patients (70.9%) but not all standard surgical procedures were always performed, residual disease were not reported in all patients. No standard number of neoadjuvant chemotherapy cycles was observed. CONCLUSIONS: The differences in terms of treatments provided led the multidisciplinary group to identify reference centers, to promote centralization, to ensure uniform and adequate treatment to patients treated in regional centers and to promote a new audit involving all regional hospitals to a complete review of the all the EOC patients.

Gemcitabine and paclitaxel combination as second-line chemotherapy in patients with small-cell lung cancer: a phase II study.

BACKGROUND: Although small-cell lung cancer is a chemosensitive malignancy, most patients rapidly relapse. Results of second-line treatment are generally poor. We conducted a phase II study to evaluate the activity and toxicity of a combination of gemcitabine and paclitaxel as second-line chemotherapy. PATIENTS AND METHODS: Eligible patients were refractory or relapsed small-cell lung cancer, with an Eastern Cooperative Oncology Group performance status of 0-2 and measurable disease. Paclitaxel was administered at 135 mg/m(2) days 1 and 8 immediately followed by gemcitabine at 1000 mg/m(2) every 3 weeks up to 6 courses. Restaging of disease was scheduled every 3 courses. RESULTS: Forty-one patients were enrolled. The median age was 65 years. Nineteen patients were considered refractory (progressive disease during or within 90 days from completion of first-line treatment), whereas 22 patients were chemotherapy sensitive. A total of 135 courses was administered (range, 1-6; median, 3). Nine patients achieved a partial remission (partial response, 22%), and 10 patients had stable disease (24%), with a disease control rate (partial response + stable disease) of 46%: in 12 (55%) of 22 patients who were sensitive and in 7 (37%) of 19 patients with refractory disease, respectively. All partial responses but one were observed in the sensitive group. The median duration of response was 5 months. The most-frequent severe toxicities were neutropenia grade 3-4 and neurologic grade 3 in 24% and 7% of delivered courses, respectively. CONCLUSIONS: The combination of gemcitabine and paclitaxel investigated in our study achieved a high disease control rate, but the schedule we adopted appeared to be quite toxic.

Using administrative data to identify and stage breast cancer cases: implications for assessing quality of care.

AIMS AND BACKGROUND: The study evaluated the use of Italian hospital discharge data (SDO, scheda di dimissione ospedaliera) for identifying women with incident breast cancer, determining stage at diagnosis and assessing quality of care. STUDY DESIGN: Women aged 20+ years residing in the Regione Emilia-Romagna, Italy, between 2002 and 2005 were studied. Case identification using algorithms based on ICD-9-CM codes on hospital discharge data were compared with AIRTUM-accredited cancer registry data. Sensitivity, specificity and positive predictive value were computed overall, by age and cancer stage. Compliance with guidelines for radiation therapy using registry and hospital data were compared. RESULTS: A total of 11,615 women was identified by AIRTUM-accredited cancer registries as incident cases, whereas 10,876 women were identified by the SDO algorithm. Sensitivity was 84.8%, specificity was 99.9%, and the positive predictive value was 90.6%. Of the 1,022 who were false positives, 363 (35.5%) were women identified in registry data as having an incident case prior to 2002 and therefore were not included in the analysis. There were 1,761 false negatives; nearly 50% were over 70 years of age or did not undergo a surgical procedure and therefore were not included in our SDO-based case finding. Sensitivity declined as the patient population became older. However, we observed relatively good positive predictive value for all age groups. Algorithms using the SDO data did not clearly identify specific cancer stages. However, the algorithm may have utility where stages are grouped together for use in quality measures. CONCLUSIONS: Cases were identified with good sensitivity, specificity and positive predictive value with SDO data, with better rates than similar previously published algorithms based on Italian data. These hospital claims-based algorithms facilitate quality of care analyses for large populations when registry data are not available by identifying individual women and their subsequent use of health care services.

Receipt of adjuvant systemic therapy among patients with high-risk breast cancer detected by mammography screening.

BACKGROUND: Few studies have compared screen-detected (SD) breast cancer patients with symptomatic patients for the frequency and determinants of receipt of adjuvant systemic therapy according to accepted guidelines. METHODS: Depending on the date of diagnosis, adjuvant therapy guidelines from the 5th, 6th, and 7th St. Gallen International Conferences were used as standards to audit the treatment of 598 node-negative high-risk patients (59% SD) and 430 node-positive patients (40% SD) aged 50-69 years from an Italian cancer registry (1997-2001). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using backward stepwise logistic regression models. RESULTS: Among node-negative high-risk patients, SD cancers were smaller (P = 0.000) and of lower grade (P = 0.003). Downgrading was generally from grade 3 to grade 2, with an increased proportion of patients placed in the high-risk category due to grade 2 alone. The total rates of adjuvant systemic therapy were similar (58 vs. 60%) whereas SD patients were less often treated according to the guidelines (34 vs. 45%; OR = 0.61; 95% CI, 0.44-0.86). After adjustment for tumour size and other weaker confounders, the OR was 0.99 (95% CI, 0.67-1.46). Among node-positive patients, the OR of receiving the standard adjuvant systemic therapy did not differ between SD and symptomatic cancers. CONCLUSIONS: SD cancers amplified the prognostic heterogeneity of node-negative high-risk patients. Their lower likelihood of being treated according to the guidelines was largely explained by their lower risk profile. No evidence was found to suggest that physicians held a priori assumptions about the relative biological indolence of SD cancers.

Developing clinical recommendations for breast, colorectal, and lung cancer adjuvant treatments using the GRADE system: a study from the Programma Ricerca e Innovazione Emilia Romagna Oncology Research Group.

PURPOSE: In the area of anticancer drugs, the legitimate search for effective interventions can be jeopardized by the strong pressure for accelerated approval, which may hinder the full assessment of their benefit-risk profile. We aimed to produce drug-specific recommendations using an explicit approach that separates the judgments on quality of evidence from the judgment about strength of recommendations. MATERIALS AND METHODS: We used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system to develop recommendations for the use of specific anticancer drugs/regimens; 12 clinical questions relevant to adjuvant treatment of breast (three), colorectal (four) and lung (five) cancer have been assessed by multidisciplinary panels supported by a group of methodologists. RESULTS: For nine of 12 questions, recommendations were produced (one strong and six weak in favor and one weak and one strong against the index treatment); for the remaining three questions no specific course of action could be recommended. The perceived benefits to risk balance of the treatment was the most important and statistically significant (P < .01) predictor of panels' recommendations and of their strength, whereas panelists' personal (age, sex) and professional (specialty) characteristics were not statistically associated. CONCLUSION: Because the GRADE system sets out an explicit process going from evaluation of the quality of evidence and benefit-risk profile to the judgment of the strength of recommendations, in this experience, it proved very useful to combine methodologic rigor with the interdisciplinary participation that is important in the definition of evidence based clinical policies.

[Estimating standard performance measures of opportunistic screening for prostate cancer]. / Stima di misure di processo standard dell'attività spontanea di screening per il cancro prostatico.

OBJECTIVE: to estimate the standard performance measures of prostate-specific antigen (PSA) screening as implemented in the existing health care system and to compare the observed results with those fom the European Randomized Screening for Prostate Cancer (ERSPC) trial. DESIGN: in a consecutive series of men living in two Italian health districts, aged > or = 30 years, with at least one total PSA test between 2000 and 2003, those subjects putatively tested for screening purposes were identified using record linkage with multiple local health databases. This was also used to determine the outcomes of follow-up of subjects with positive test result (PSA > or = 4 ng/ml) at 12 and 24 months of observation. SETTING: clinical chemistry laboratories, outpatient urology clinics, pathology departments, and mortality registries of the health districts of Ravenna and Forlì, and the Romagna Cancer Registry. PARTICIPANTS: 52,513 total subjects, 42,398 of whom putatively tested for screening purposes. MAIN OUTCOME MEASURES: the most common performance measures of cancer screening. RESULTS: the 2-year screening rate increased until 80 years of age. In the age range 55-69 years, i.e. the target age of the ERSPC trial, the screening rate was 38.1%, and the rate of positive test results (9.1%) was within the expected range. The PSA level, but not the subjects age, was strongly associated with follow-up procedures. After 24 months of observation, 24.4% PSA-positive patients received no further evaluation, 54.8% underwent repeat testing as the initial follow-up action, and 44.0% were referred for urologic assessment. The biopsy rate was 25.3%, the positive predictive value of PSA testing 10.1%, the detection rate of prostate cancer 9.4 per thousand, and the detected/expected ratio 8.4. CONCLUSION: compared with methods and results of the ERSPC trial, the management of PSA-positive subjects was much more conservative, and the yield of disease much smaller.

Temozolomide and interferon-alpha in metastatic melanoma: a phase II study of the Italian Melanoma Intergroup.

Temozolomide (TMZ) is a new oral alkylating agent which has proven to be as active as dacarbazine (DTIC) in the treatment of melanoma, but with a lower toxicity. A multicentric phase II trial was conducted in an out-patient setting to determine the therapeutic activity and safety of TMZ in combination with interferon-alpha (IFN-alpha). From June 2000 to July 2001, 41 patients were recruited to receive TMZ 200 mg/m orally on days 1-5 every 28 days and with 5 MU IFN-alpha subcutaneously three times a week, continuously for eight cycles or until disease progression occurred. Of the 40 treated patients, two complete responses (5%) and three partial responses (7.5%) were observed, with a median duration of 4 months (range, 1.5-13.5 months). Thirteen patients (32.5%) had stable disease for a median of 2.5 months. Time to progression was 2.6 months and the median overall survival was 11.8 months. Nine patients (22.5%) developed brain metastases. The grade 4 toxicity observed in seven patients was of a transient haematological nature. This combination therapy is well tolerated but does not appear to increase the response rate or overall survival with respect to TMZ alone or to chemotherapeutic regimens. Further and more complex associations of these two drugs could be investigated in specific subsets of patients, in particular to evaluate its real efficacy in preventing brain metastases.