Maria Michiara

Long-term survival, prevalence, and cure of cancer: A population-based estimation for 818,902 Italian patients and 26 cancer types

Original, population-based estimates of indicators of long-term survival and cure in cancer patients are provided. More than a quarter of cancer patients in Italy have reached death rates similar to those of the general population. Nearly three quarters of them will not die as a result of cancer. These estimates are potentially helpful to health-care planners, clinicians, and patients.

The changing distribution and survival of colorectal carcinoma: an epidemiological study in an area of northern Italy.

Objective This study analyses the inter-relations of anatomical tumour location, gender, age and incidence rates for colorectal cancer from 1978 to 1999 in an area of northern Italy: the Parma district. Methods Data were obtained from the Parma Cancer Registry. Age-adjusted incidence rates were analysed by gender, age and colorectal cancer subsites. In addition, 5 year observed survival rates were determined. Results In the Parma area, the incidence of colorectal cancer is rising. We have observed a true increase in the rate of the age standardized incidence of right colon cancer, linked to an increased incidence of left colon cancer, while the incidence of rectal cancer has remained constant. The frequency of right-sided colon cancer was higher in aged patients, and in women. Age-standardized relative survival of patients after diagnosis of colorectal cancer between 1992 and 1996 was found to be significantly higher than age-standardized relative survival after diagnosis between 1978 and 1982. Conclusions In the Parma area there has been an increased incidence of right colon cancer, linked to an increased incidence of left colon cancer, while the incidence of rectal cancer has remained constant. We feel that this shift, whatever the reason for it, has important implications for the choice of screening techniques.

Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI – Mel.A.) [ISRCTN75125874]

BackgroundHigh-dose interferon alfa-2b (IFNalfa-2b), according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma patients by the FDA and EMEA. However, the risk/benefit profile has been questioned limiting its world-wide use. In the late nineties, the Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT) to verify if a more intense, but shorter than the ECOG 1684 regimen, could improve survival without increasing the toxicity profile. The safety analysis in the first 169 patients who completed the treatment is here described.MethodsStage III melanoma patients were randomized to receive IFNalfa-2b 20 MU/m2/d intravenously (IV) 5 days/week × 4 weeks, repeated for three times on weeks 9 to 12, 17 to 20, 25 to 28 (Dose-Dense/Dose-Intense, DD/DI, arm), or IFNalfa-2b 20 MU/m2/d IV 5 days/week × 4 weeks followed by 10 MU/m2 subcutaneously (SC) three times per week × 48 weeks (High Dose Interferon, HDI, arm). Toxicity was recorded and graded, according to the WHO criteria, as the worst grade that occurred during each cycle.ResultsThe most common toxicities in both arms were flu-like and gastrointestinal symptoms, leukopenia, liver and neuro-psichiatric morbidities; with regard to severe toxicity, only leukopenia was statistically more frequent in DD/DI arm than in HDI arm (24% vs 9%) (p = 0.0074), yet, this did not cause an increase in the infection risk. Discontinuation of treatment, due to toxicity, was observed in 13 and 17% of the patients in the DD/DI and HDI arm, respectively. The median actual dose intensity delivered in the DD/DI arm (36.4 MU/m2/week) was statistically higher than that delivered in the HDI arm (30.7 MU/m2/week) (p = 0.003).ConclusionFour cycles of intravenous high-dose IFNalfa-2b can be safely delivered with an increase in the median dose intensity. Efficacy results from this trial are eagerly awaited.

Human Epidermal Growth Factor Receptor 2 Status and Interval Breast Cancer in a Population-Based Cancer Registry Study

PURPOSE To determine whether human epidermal growth factor receptor 2 (HER2) -positive status is associated with risk of breast cancer diagnosis in the interval between mammographic screening, we estimated the distribution of features of aggressive tumor behavior in a general population with newly diagnosed breast cancer and known screening status. PATIENTS AND METHODS We evaluated all invasive breast cancers (N = 641) that were systematically collected by the Parma Province Cancer Registry and diagnosed in women age 50 to 69 years from 2004 to 2007. From this population, 292 screen-detected cancers and 48 interval cases with negative screening mammograms on expert rereading (true interval cancers) were selected for study purposes. Unconditional logistic regression adjusted for age and tumor size was used to determine whether interval cancers were associated with selected clinicobiologic characteristics. RESULTS Tumors with a high histologic grade (odds ratio [OR], 1.8; 95% CI, 1.2 to 3.8), high proliferative rate (OR, 2.4; 95% CI, 1.2 to 4.5), negative estrogen receptor status (OR, 1.6; 95% CI, 1.1 to 3.1), or HER2-positive status (OR, 3.4; 95% CI, 1.7 to 7.1) were more likely to be diagnosed in the interval between screening. Women age less than 60 years with HER2-positive breast cancer were four times more likely to be diagnosed in the interval between screening compared with only a two-fold increased risk for older women. CONCLUSION This population-based cancer registry study demonstrated that HER2-positive tumors account for a substantial proportion of mammographic screening failure. The distribution of biologic characteristics in screen-detected cancers differs from that observed in interval cancers and may account in part for the more aggressive behavior of interval-detected cases.

Cancer prevalence in United States, Nordic Countries, Italy, Australia, and France: an analysis of geographic variability.

Background:The objectives of this study were to quantitatively assess the geographic heterogeneity of cancer prevalence in selected Western Countries and to explore the associations between its determinants.Methods:For 20 cancer sites, 5-year cancer prevalence, incidence, and survival were observed and age standardised for the mid 2000s in the United States, Nordic European Countries, Italy, Australia, and France.Results:In Italy, 5-year crude prevalence for all cancers was 1.9% in men and 1.7% in women, while it was ∼1.5% in all other countries and sexes. After adjustment for the different age distribution of the populations, cancer prevalence in the United States was higher (20% in men and 10% in women) than elsewhere. For all cancers combined, the geographic heterogeneities were limited, though relevant for specific cancers (e.g., prostate, showing >30% higher prevalence in the United States, or lung, showing >50% higher prevalence in USA women than in other countries). For all countries, the correlations between differences of prevalence and differences of incidence were >0.9, while prevalence and survival were less consistently correlated.Conclusion:Geographic differences and magnitude of crude cancer prevalence were more strongly associated with incidence rates, influenced by population ageing, than with survival rates. These estimates will be helpful in allocating appropriate resources.

Survival after cancer in Italian persons with AIDS, 1986-2005: a population-based estimation.

Background:Cancer survival in persons with AIDS (PWA) after introduction of antiretroviral therapies remains poorly characterized. The aim is to provide population-based estimates of cancer survival, overall and for the most important cancer types in PWA, and a comparison with persons without AIDS (non-PWA) affected by the same cancer. Methods:PWA with cancer at AIDS diagnosis or thereafter were individually matched with non-PWA by type of cancer, sex, age, year of diagnosis, area of living, and, for lymphomas, histological subtype. Five-year observed survival and hazard ratios (HRs) of death in PWA versus non-PWA with 95% confidence intervals (CIs) were estimated. Results:We included 2262 Italian PWA and 4602 non-PWA with cancer diagnosed during 1986–2005. Between 1986 and 1995, and 1996 and 2005, 5-year survival for all cancers in PWA improved from 12% to 41% and the corresponding HR versus non-PWA decreased from 5.1 (95% CI: 4.3 to 6.1) to 2.9 (95% CI: 2.6 to 3.3). During 1996–2005, HRs were 2.0 (95% CI: 1.4 to 2.9) for Kaposi sarcoma, 3.4 (95% CI: 2.9 to 4.1) for non-Hodgkin lymphoma, and 2.4 (95% CI: 1.4 to 4.0) for cervical cancer. HRs were 2.5 (95% CI: 2.1 to 3.1) for all non–AIDS-defining cancers, 5.9 (95% CI: 3.1 to 11.2) for Hodgkin lymphoma, and 7.3 (95% CI: 2.8 to 19.2) for nonmelanoma skin cancer. A ⩽3-fold survival difference was found for cancers of the stomach, liver, anus, lung, brain, and the most aggressive lymphoma subtypes. Conclusions:The persisting, although narrowing, gap in cancer survival between PWA and non-PWA indicates the necessity of enhancing therapeutic approaches, so that PWA can be provided the same chances of survival observed in the general population, and improving cancer prevention and screening.

Changes in cervical cancer incidence following the introduction of organized screening in Italy.

OBJECTIVE To quantify the impact of organized cervical screening programs (OCSPs) on the incidence of invasive cervical cancer (ICC), comparing rates before and after activation of OCSPs. METHODS This population-based investigation, using individual data from cancer registries and OCSPs, included 3557 women diagnosed with ICC at age 25-74years in 1995-2008. The year of full-activation of each OCSP was defined as the year when at least 40% of target women had been invited. Incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) were calculated as the ratios between age-standardized incidence rates observed in periods after full-activation of OCSPs vs those observed in the preceding quinquennium. RESULTS ICC incidence rates diminished with time since OCSPs full-activation: after 6-8years, the IRR was 0.75 (95% CI: 0.67-0.85). The reduction was higher for stages IB-IV (IRR=0.68, 95% CI: 0.58-0.80), squamous cell ICCs (IRR=0.74, 95% CI: 0.64-0.84), and particularly evident among women aged 45-74years. Conversely, incidence rates of micro-invasive (stage IA) ICCs increased, though not significantly, among women aged 25-44years (IRR=1.34, 95% CI: 0.91-1.96). Following full-activation of OCSPs, micro-invasive ICCs were mainly and increasingly diagnosed within OCSPs (up to 72%). CONCLUSION(S) Within few years from activation, organized screening positively impacted the already low ICC incidence in Italy and favored down-staging.

Multicentre, open, noncomparative Phase II trial to evaluate the efficacy and tolerability of fotemustine, cisplatin, alpha-interferon and interleukin-2 in advanced melanoma patients.

The efficacy and tolerability of fotemustine, cisplatin, &agr;-interferon and interleukin-2 biochemotherapy were evaluated in advanced melanoma patients. The schedule consisted of fotemustine (100 mg/m2) and cisplatin (75 mg/m2) intravenous on day 1, followed by subcutaneous interleukin-2 at a dose of 4.5 MIU on days 3–5 and 8–12 and &agr;-interferon at a dose of 3 MU three times/week, every 3 weeks for six cycles. Sixty patients were evaluated for tumour response, 12 of whom had brain metastases (BM). One patient (1.7%) with BM achieved a complete response and partial responses were observed in 10 patients (16.7%), including one BM patient. Overall response rate was 18.4 and 16.6% in BM patients (median response duration 8.2 months). Disease control, defined as overall response and stable disease, was 58.4% in all patients and 75% in patients with BM. Median time to progression was 3.2 months (4.2 months in BM patients). Median overall survival was 8.9 months (7.6 months in BM patients). Toxic events were mild to moderate. This combination was well tolerated and showed acceptable clinical activity, especially in BM patients.

Lomustine (chloroethylnitrosourea [CCNU]), ifosfamide, bleomycin, vincristine, and cisplatin (CIBO-P) is an effective regimen for patients with poor prognostic refractory or multiple disease recurrent aggressive non-Hodgkin lymphoma

The current study was designed to assess the activity and safety of a novel combination therapy for patients with recurrent or refractory aggressive non‐Hodgkin lymphoma (NHL).

Prognostic risk factors for treatment decision in pT1a,b N0M0 HER2-positive breast cancers

Although outcomes for women with breast cancers may vary by biologic subtype, patients with T1a,b N0M0 tumors have an excellent prognosis across all subgroups. HER2 overexpression occurs in 15-20% of primary breast tumors, and is associated with diminished disease-free and overall survival. The anti-HER2 monoclonal antibody trastuzumab in combination with chemotherapy is an effective treatment for all stages of HER2 positive breast cancer (bc). However, the absolute benefit decreases as the risk of recurrence lessens and no available randomized adjuvant trial has evaluated the role of trastuzumab in women with pT1a,b N0M0, HER2-positive breast tumors. These findings may explain the debate about the appropriate indication for adjuvant chemotherapy plus trastuzumab in this setting of patients. The aim of this review was to describe known and novel prognostic risk factors to be used for tailored treatment decision in pT1a,b N0M0 HER2-positive tumors. Whether patients with small HER2-positive bc may be suitable for (chemo)therapy reduction strategies, the current available data cannot exclude the need for a more aggressive treatment in a small subset of these subjects. Novel clinical prognostic factors such as interval cancer (IC) detection may help to address this clinically important controversy. A multicenter population-based cancer registry study is currently evaluating whether IC detection may identify patients with pT1a N0M0 HER2-positive tumors in whom the rate of recurrence justifies consideration for use of conventional, trastuzumab-based chemotherapy regimens.