Andrea Bordoni

Changing patterns of cancer incidence in the early-and late-HAART periods: The Swiss HIV Cohort Study

Background:The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposis sarcoma (KS) and non-Hodgkins lymphoma (NHL), but not of other cancers, among people with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy.Methods:We conducted a record-linkage study between the Swiss HIV Cohort Study and nine Swiss cantonal cancer registries. In total, 9429 PWHA provided 20u2009615, 17u2009690, and 15u2009410 person-years in the pre-, early-, and late-HAART periods, respectively. Standardised incidence ratios in PWHA vs the general population, as well as age-standardised, and age-specific incidence rates were computed for different periods.Results:Incidence of KS and NHL decreased by several fold between the pre- and early-HAART periods, and additionally declined from the early- to the late-HAART period. Incidence of cancers of the anus, liver, non-melanomatous skin, and Hodgkins lymphoma increased in the early- compared with the pre-HAART period, but not during the late-HAART period. The incidence of all non-AIDS-defining cancers (NADCs) combined was similar in all periods, and approximately double that in the general population.Conclusions:Increases in the incidence of selected NADCs after the introduction of HAART were largely accounted for by the ageing of PWHA.

Breast cancer classification according to immunohistochemical markers: clinicopathologic features and short-term survival analysis in a population-based study from the South of Switzerland

BACKGROUNDnBreast cancer may be classified into distinct molecular subtypes based on gene expression profiling and/or immunophenotypic characteristics. Aim of the study was to investigate prevalence, clinicopathologic features and overall survival (OS) of molecular subtypes, in a large European population-based study.nnnPATIENTS AND METHODSnAll invasive breast cancers from 2003 to 2007 were selected from the files of Ticino Cancer Registry. Molecular subtypes were defined by immunohistochemical markers. Clinicopathological characteristics and short-term OS were analyzed.nnnRESULTSnOf 1214 invasive breast cancers, 73.2% were luminal A subtype, 13.8% luminal B, 7.4% basal like and 5.6% Her2/neu. Basal like presented largely in premenopausal women and displayed aggressive features, such as large tumor size, poorly differentiated cancers, high Ki-67 proliferation index and the worst 24-month OS. Luminal A included the highest percentage of patients >70, the highest proportion of stage I tumors and well/moderately differentiated lesions. Her2/neu was more frequent in postmenopausal women and showed the highest percentage of positive lymph nodes and stage IV cases.nnnCONCLUSIONnThis is a comprehensive European population-based study on breast cancer molecular subtypes. We provide strong evidence that the molecular classification is useful for clinical management and superior to World Health Organization classification in terms of short-term prognostic value.

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

Between 1984 and 2006, 12u2009959 people with HIV/AIDS (PWHA) in the Swiss HIV Cohort Study contributed a total of 73u2009412 person-years (py) of follow-up, 35u2009551 of which derived from PWHA treated with highly active antiretroviral therapy (HAART). Five hundred and ninety-seven incident Kaposi sarcoma (KS) cases were identified of whom 52 were among HAART users. Cox regression was used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI). Kaposi sarcoma incidence fell abruptly in 1996–1998 to reach a plateau at 1.4 per 1000u2009py afterwards. Men having sex with men and birth in Africa or the Middle East were associated with KS in both non-users and users of HAART but the risk pattern by CD4 cell count differed. Only very low CD4 cell count (<50 cellsu2009μl−1) at enrolment or at HAART initiation were significantly associated with KS among HAART users. The HR for KS declined steeply in the first months after HAART initiation and continued to be low 7–10 years afterwards (HR, 0.06; 95% CI, 0.02–0.17). Thirty-three out of 52 (63.5%) KS cases among HAART users arose among PWHA who had stopped treatment or used HAART for less than 6 months.

Hodgkin lymphoma in the Swiss HIV Cohort Study

Hodgkin lymphoma (HL) risk is elevated among persons infected with HIV (PHIV) and has been suggested to have increased in the era of combined antiretroviral therapy (cART). Among 14,606 PHIV followed more than 20 years in the Swiss HIV Cohort Study (SHCS), determinants of HL were investigated using 2 different approaches, namely, a cohort and nested case-control study, estimating hazard ratios (HRs) and matched odds ratios, respectively. Forty-seven incident HL cases occurred during 84,611 person-years of SHCS follow-up. HL risk was significantly higher among men having sex with men (HR vs intravenous drug users = 2.44, 95% confidence interval [CI], 1.13-5.24) but did not vary by calendar period (HR for 2002-2007 vs 1995 or earlier = 0.65, 95% CI, 0.29-1.44) or cART use (HR vs nonusers = 1.02, 95% CI, 0.53-1.94). HL risk tended to increase with declining CD4(+) cell counts, but these differences were not significant. A lower CD4(+)/CD8(+) ratio at SHCS enrollment or 1 to 2 years before HL diagnosis, however, was significantly associated with increased HL risk. In conclusion, HL risk does not appear to be increasing in recent years or among PHIV using cART in Switzerland, and there was no evidence that HL risk should be increased in the setting of improved immunity.

Treatment of breast cancer in the elderly: A prospective, population-based Swiss study

OBJECTIVESnThe primary objective of this population-based study is to describe the patterns of care of elderly patients with breast cancer (BC), and evaluate potential causative factors for the decrease in BC-specific survival (BCSS) in the elderly.nnnPATIENTS AND METHODSnWe included all or representative samples of patients with newly diagnosed BC from seven Swiss cancer registries between 2003 and 2005 (n=4820). Surgical and non-surgical BC treatment was analyzed over 5 age groups (<65, 65 to <70, 70 to <75, 75 to <80 and ≥80years), and the predictive impact of patient age on specific treatments was calculated using multivariate logistic regression analysis.nnnRESULTSnThe proportion of locally advanced, metastatic and incompletely staged BC increased with age. The odds ratio for performing breast-conserving surgery (BCS) in stages I-II BC (0.37), sentinel lymph node dissection (SLND) in patients with no palpable adenopathy (0.58), post-BCS radiotherapy (0.04) and adjuvant endocrine treatment (0.23) were all in disfavor of patients ≥80years of age compared to their younger peers. Only 36% of patients ≥80years of age with no palpable adenopathy underwent SLND. In the adjusted model, higher age was a significant risk factor for omitting post-BCS radiotherapy, SLND and adjuvant endocrine treatment.nnnCONCLUSIONSnThis study found an increase in incomplete diagnostic assessment, and a substantial underuse of BCS, post-BCS radiotherapy, SLND and adjuvant endocrine treatment in elderly patients with BC. There is a need for improved management of early BC in the elderly even in a system with universal access to health care services.

Assessment of breast cancer opportunistic screening by clinical–pathological indicators: a population-based study

Background:Although some clinical–pathological features of breast cancers, such as the incidence of ductal cancer in situ (DCIS) and the diameter of invasive tumours, are sensitive indicators of early detection, comprehensive population-based studies of opportunistic screening are needed.Methods:Cases of DCIS or invasive breast cancer diagnosed in 1996–2007 were identified from the Ticino Cancer Registry (south of Switzerland). Time trends of age-adjusted incidence and mortality, as well as main clinical–pathological features, such as tumour diameter, AJCC stage and histological grade, were analysed.Results:A total of 3047 incident cases of female breast cancer were identified. The proportion of DCIS with respect to invasive cases increased from 5.8% in the period 1996–2001 to 6.4% in the period 2002–2007. The median tumour size of invasive cancers decreased from 20u2009mm in 1996–2001 to 18u2009mm in 2002–2007 (P<0.0001). An increase in well/moderately differentiated invasive tumours, from 67% in the period 1996–2001 to 73% in 2002–2007 (P<0.001), was detected and resulted in an Annual Percentage Change of incidence of 2.8 (95% confidence interval: 1.3; 4.3).Conclusion:An opportunistic screening strategy can lead to an improvement of prognostic features at diagnosis, but these features are still less favourable than those achieved by organised screening programmes.

Evaluation of completeness of case ascertainment in Swiss cancer registration

This is the first comprehensive evaluation of completeness of case ascertainment in Swiss cancer registration. There is currently no method available that is considered to be the gold standard. Apart from simple measures such as the proportion of cases where registration was initiated by a death certificate and the proportion of diagnoses on the basis of histology or cytology/haematology, we applied two dedicated approaches: (i) the semiquantitative method of comparing the mortality to incidence rate ratio with relative survival (MI-Surv method) and (ii) the Flow method, which provides a quantitative estimate for the completeness depending on time since diagnosis. All 10 Swiss cancer registries in operation since at least 2006 and providing the required parameters were included. Simple and dedicated methods showed high completeness across all cancer registries and for most cancer types tested, with the notable exception of lymphoid leukaemia.

Opportunistic screening strategy for cutaneous melanoma does not change the incidence of nodular and thick lesions nor reduce mortality: a population-based descriptive study in the European region with the highest incidence.

The aim of the present population-based descriptive study was to evaluate the incidence and mortality trends for melanoma to gain insights on the effectiveness of opportunistic secondary prevention strategies. Data on all invasive cutaneous melanoma cases occurring between 1996 and 2011 were retrieved from the Ticino Cancer Registry, southern Switzerland. The European age-standardized incidence rates were computed by the period of diagnosis, Breslow thickness and histological types. Trends in incidence and mortality rates were measured as the annual per cent change (APC). A total of 1230 patients had a diagnosis of invasive cutaneous melanoma. Cases were categorized as follows: superficial spreading melanoma (55.7%), nodular melanoma (10.0%), lentigo maligna melanoma (5.5%), melanoma not otherwise specified (25.2%) and other types (3.6%). The incidence rate of invasive melanoma rose from 17.4 per 100 000 inhabitants in 1996–2003 to 20.6 in 2004–2011, with an overall APC of +2.1% [95% confidence interval (CI): −0.8%, +5.1%]. An increase in incidence was observed for superficial spreading melanoma (APC=+2.9%; 95% CI: −1.1%, +7.0%) and thin melanomas (i.e. ⩽1.00 mm) (APC=+3.4%; 95% CI: +0.2%, +6.7%), whereas we detected a descriptive growing incidence of thick melanomas (APC=+2.1%; 95% CI: −1.4%, +5.8%). Mortality trend analysis revealed constant rates throughout the study period (APC=−1.0%; 95% CI: −5.5%, +3.7%). This population-based study confirms that in a country with the highest incidence of cutaneous melanomas, that is, Switzerland, the opportunistic screening strategy does not change the incidence of thick melanomas nor the overall mortality. This study suggests there is still a need for public health efforts in primary and secondary prevention.

Quality indicators of clinical cancer care (QC3) in colorectal cancer

Objectives Assessing the quality of cancer care (QoCC) has become increasingly important to providers, regulators and purchasers of care worldwide. The aim of this study was to develop evidence-based quality indicators (QIs) for colorectal cancer (CRC) to be applied in a population-based setting. Design A comprehensive evidence-based literature search was performed to identify the initial list of QIs, which were then selected and developed using a two-step-modified Delphi process involving two multidisciplinary expert panels with expertise in CRC care, quality of care and epidemiology. Setting The QIs of the clinical cancer care (QC3) population-based project, which involves all the public and private hospitals and clinics present on the territory of Canton Ticino (South Switzerland). Participants Ticino Cancer Registry, The Colorectal Cancer Working Group (CRC-WG) and the external academic Advisory Board (AB). Main outcome measures Set of QIs which encompass the whole diagnostic-treatment process of CRC. Results Of the 149 QIs that emerged from 181 sources of literature, 104 were selected during the in-person meeting of CRC-WG. During the Delphi process, CRC-WG shortened the list to 89 QI. AB finally validated 27 QIs according to the phase of care: diagnosis (N=6), pathology (N=3), treatment (N=16) and outcome (N=2). Conclusions Using the validated Delphi methodology, including a literature review of the evidence and integration of expert opinions from local clinicians and international experts, we were able to develop a list of QIs to assess QoCC for CRC. This will hopefully guarantee feasibility of data retrieval, as well as acceptance and translation of QIs into the daily clinical practice to improve QoCC. Moreover, evidence-based selected QIs allow one to assess immediate changes and improvements in the diagnostic-therapeutic process that could be translated into a short-term benefit for patients with a possible gain both in overall and disease-free survival.

Socioeconomic and demographic disparities in breast cancer stage at presentation and survival: A Swiss population‐based study

We explored socioeconomic and demographic disparities in breast cancer (BC) stage at presentation and survival in a Swiss population‐based sample of female BC patients linked to the census‐based Swiss National Cohort. Tumor stage was classified according to Surveillance, Epidemiology and End Results Program summary stage (in situ/localized/regional/distant). We used highest education level attained to estimate SEP (low/middle/high). Further demographic characteristics of interest were age at presentation (30–49/50–69/70–84 years), living in a canton with organized screening (yes/no), urbanity of residence (urban/peri‐urban/rural), civil status (single/married/widowed/divorced) and nationality (Swiss/non‐Swiss). We used ordered logistic regression models to analyze factors associated with BC stage at presentation and competing risk regression models for factors associated with survival. Odds of later‐stage BC were significantly increased for low SEP women (odds ratio 1.19, 95%CI 1.06–1.34) compared to women of high SEP. Further, women living in a canton without organized screening program, women diagnosed outside the targeted screening age and single/widowed/divorced women were more often diagnosed at later stages. Women of low SEP experienced an increased risk of dying from BC (sub‐hazard ratio 1.22, 95%CI 1.05–1.43) compared to women of high SEP. Notably, these survival inequalities could not be explained by socioeconomic differences in stage at presentation and/or other sociodemographic factors. It is concerning that these social gradients have been observed in a country with universal health insurance coverage, high health expenditures and one of the highest life expectancies in the world.