Silvia Ess

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 20 615, 17 690, and 15 410 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.

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

Between 1984 and 2006, 12 959 people with HIV/AIDS (PWHA) in the Swiss HIV Cohort Study contributed a total of 73 412 person-years (py) of follow-up, 35 551 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 1000 py 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 cells μl−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.

Risk Factors for Anal Cancer in Persons Infected With HIV: A Nested Case-Control Study in the Swiss HIV Cohort Study

Although persons infected with human immunodeficiency virus (HIV), particularly men who have sex with men, are at excess risk for anal cancer, it has been difficult to disentangle the influences of anal exposure to human papillomavirus (HPV) infection, immunodeficiency, and combined antiretroviral therapy. A case-control study that included 59 anal cancer cases and 295 individually matched controls was nested in the Swiss HIV Cohort Study (1988-2011). In a subset of 41 cases and 114 controls, HPV antibodies were tested. A majority of anal cancer cases (73%) were men who have sex with men. Current smoking was significantly associated with anal cancer (odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.25, 5.34), as were antibodies against L1 (OR = 4.52, 95% CI: 2.00, 10.20) and E6 (OR = ∞, 95% CI: 4.64, ∞) of HPV16, as well as low CD4+ cell counts, whether measured at nadir (OR per 100-cell/μL decrease = 1.53, 95% CI: 1.18, 2.00) or at cancer diagnosis (OR per 100-cell/μL decrease = 1.24, 95% CI: 1.08, 1.42). However, the influence of CD4+ cell counts appeared to be strongest 6-7 years prior to anal cancer diagnosis (OR for <200 vs. ≥500 cells/μL = 14.0, 95% CI: 3.85, 50.9). Smoking cessation and avoidance of even moderate levels of immunosuppression appear to be important in reducing long-term anal cancer risks.

Lung cancer in the Swiss HIV Cohort Study: role of smoking, immunodeficiency and pulmonary infection.

Background:Immunodeficiency and AIDS-related pulmonary infections have been suggested as independent causes of lung cancer among HIV-infected persons, in addition to smoking.Methods:A total of 68 lung cancers were identified in the Swiss HIV Cohort Study (SHCS) or through linkage with Swiss Cancer Registries (1985–2010), and were individually matched to 337 controls by centre, gender, HIV-transmission category, age and calendar period. Odds ratios (ORs) were estimated by conditional logistic regression.Results:Overall, 96.2% of lung cancers and 72.9% of controls were ever smokers, confirming the high prevalence of smoking and its strong association with lung cancer (OR for current vs never=14.4, 95% confidence interval (95% CI): 3.36–62.1). No significant associations were observed between CD4+ cell count and lung cancer, neither when measured within 1 year (OR for <200 vs ⩾500=1.21, 95% CI: 0.49–2.96) nor further back in time, before lung cancer diagnosis. Combined antiretroviral therapy was not significantly associated with lung cancer (OR for ever vs never=0.67, 95% CI: 0.29–1.52), and nor was a history of AIDS with (OR=0.49, 95% CI: 0.19–1.28) or without (OR=0.53, 95% CI: 0.24–1.18) pulmonary involvement.Conclusion:Lung cancer in the SHCS does not seem to be clearly associated with immunodeficiency or AIDS-related pulmonary disease, but seems to be attributable to heavy smoking.

Surgical treatment of early stage breast cancer in elderly: an international comparison

Over 40% of breast cancer patients are diagnosed above the age of 65. Treatment of these elderly patients will probably vary over countries. The aim of this study was to make an international comparison (several European countries and the US) of surgical and radiation treatment for elderly women with early stage breast cancer. Survival comparisons were also made. Data were obtained from national or regional population-based registries in the Netherlands, Switzerland, Ireland, Belgium, Germany, and Portugal. For the US patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Early stage breast cancer patients aged ≥65 diagnosed between 1995 and 2005 were included. An international comparison was made for breast and axillary surgery, radiotherapy after breast conserving surgery (BCS), and relative or cause-specific survival. Overall, 204.885 patients were included. The proportion of patients not receiving any surgery increased with age in many countries; however, differences between countries were large. In most countries more than half of all elderly patients received breast conserving surgery (BCS), with the highest percentage in Switzerland. The proportion of elderly patients that received radiotherapy after BCS decreased with age in all countries. Moreover, in all countries the proportion of patients who do not receive axillary surgery increased with age. No large differences in survival between countries were recorded. International comparisons of surgical treatment for elderly women with early stage breast cancer are scarce. This study showed large international differences in treatment of elderly early stage breast cancer patients, with the most striking result the large proportion of elderly who did not undergo surgery at all. Despite large treatment differences, survival does not seem to be affected in a major way.

Geographic variation in breast cancer care in Switzerland

PURPOSE Regional disparities in breast cancer outcomes have been reported in Switzerland. The purpose of this study is to investigate geographic variation in early diagnosis and management of breast cancer. METHODS We used data from a representative sample of 4820 women diagnosed with invasive breast cancer between January 1, 2003 and December 31, 2005 identified by seven Swiss population based cancer registries. We collected retrospectively detailed information on mode of detection, tumor characteristics and treatments. Differences across geographic regions were tested for statistical significance using chi-square tests and uni- and multivariate logistic regression. RESULTS Considerable disparities in early detection and management of early breast cancer were found across regions. In particular, the proportion of early detected cancer varied from 43% in Valais to 27% in St. Gallen-Appenzell. Mastectomy rates varied from 24% in Geneva to 38% in St. Gallen-Appenzell and Grisons-Glarus. Higher reconstruction rates were observed in regions with lower rates of mastectomy. The use of sentinel node procedure in patients with nodal negative disease was high in Geneva and low in Eastern Switzerland. Differences in compliance with recommendations on the use of endocrine therapy and chemotherapy were less pronounced but statistically significant. CONCLUSIONS This analysis shows considerable geographic variation in breast cancer care in a health system characterized by high expenditures, universal access to services and high decentralization. Further study into the causes and effects of this variation on short- and long term patient outcomes is needed.

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

OBJECTIVES The 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. PATIENTS AND METHODS We 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. RESULTS The 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. CONCLUSIONS This 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.

Extrapulmonary small cell carcinoma: An indication for prophylactic cranial irradiation? A single center experience.

BackgroundInformation about extrapulmonary small cell carcinoma (EPSCC) is limited and the role of prophylactic cranial irradiation (PCI) is unknown.Patients and MethodsDisease presentation and outcome of all EPSCC at our hospital between 1990 and 2009 were retrospectively analyzed.ResultsOf 30 EPSCC, the male:female ratio was 58%:42%; 83% had a performance status of 0–2. Median age was 71 years (32–80). Seventeen (57%) had limited stage (LS), 13 (43%) extensive stage (ES). The location of the primary tumor was gastrointestinal (n = 8), unknown (6), gynecological (6), urogenital (5), and ear nose throat (5). Four (13%) developed brain metastases (2 ES, 2 LS). In ES, first line chemotherapy (CT) was given in 85%, mostly platinum–etoposide (64%). Response rate was 90%. In LS, CT and radiotherapy (RT) ± resection resulted in persistent remissions in 67% of patients. Median survival was 16 months (1–107 months), 18 months (1–107 months), and 9 months (0.4–25 months) for LS + ES, LS, and ES, respectively. Weight loss ≥5 % and ECOG performance status 3 + 4 were associated with poorer survival (p < 0.001 and p < 0.01, respectively).ConclusionThe incidence of brain metastases was relatively low (13%). More studies are necessary, before routinely offering PCI to patients with EPSCC. Best survival outcomes in LS were achieved with multimodality treatment including CT and RT. Prognosis was poor in patients with ES.ZusammenfassungHintergrundUnser Wissen über das extrapulmonale kleinzellige Karzinom (EKK) ist beschränkt, und der Stellenwert der pro-phylaktischen Ganzhirnbestrahlung ist unklarPatienten und MethodenAlle an unserem Krankenhaus zwischen 1990 und 2009 behandelten Patienten mit EKK wurden bezüglich Krankheitspräsentation und Verlauf retrospektiv analysiert.ResultateBei den insgesamt 30 EKK war das Mann/Frau Verhältnis 58%/42%. 83% hatten einen Performance-Status von 0–2. Das mittlere Alter betrug 71 Jahre (32–80). 17 Patienten (57%) präsentierten sich im lokalisierten Stadium (LS), 13 (43%) in metastasiertem Stadium (MS). Lokalisation des Primärtumors: gastrointestinal (8), unbekannt (6), gynäkologisch (6), urogenital (5) und Hals-Nasen-Ohren-Region (5). 4 Patienten (13%) entwickelten Hirnmetastasen (2 MS, 2 LS). Bei MS wurde in 85% eine Erstlinien-chemotherapie (CT) verabreicht, meistens Platin/Etoposid (64%). Die Ansprechrate betrug 90%. Im LS führten CT und Radiotherapie (RT) ± Operation in 67% zu andauernden Remissionen. Das mediane Überleben betrug 16 Monate (1–107 Monate) für alle Patienten, 18 Monate (1–107 Monate) für Patienten mit LS und 9 Monate (0,4–25 Monate) für Patienten mit MS. Gewichtsverlust von ≥5 % und Performance-Status von 3 oder 4 waren mit schlechterem Gesamtüberleben assoziiert (p < 0,001 und p < 0,01).SchlussfolgerungDie Inzidenz von Hirnmetastasen war relativ niedrig (13%). Bevor Patienten mit EKK routinemäßig eine prophylaktische Ganzhirnbestrahlung empfohlen werden sollte, sind weitere Studien notwendig. Im LS wurden mit multi-modalen Therapiekonzepten, welche RT und CT beinhalteten, die längsten Überlebensraten beobachtet. Die Prognose von Patienten im MS war schlecht.

Premature deaths in Switzerland from 1995-2006: causes and trends

PURPOSE Mortality expressed as potential years of life lost (PYLL) underscores premature and preventable mortality. We analysed causes of and trends in premature death in Switzerland to highlight the areas which provide the greatest potential outcome for preventive measures. METHODS Premature mortality rates and trends from 1995-2006 were examined by reviewing potential years of life lost between age 1 and 70, as the upper age limit, considering 4 main categories: circulatory diseases, cancer, external causes of mortality and other causes, and 19 specific causes of death. Trends were assessed using join point analysis with PYLL expressed as age-standardised rate. The analysis was based on the official death certification files provided by the Swiss Federal Statistical Office. RESULTS Age adjusted PYLL rates decreased for all categories of causes, but the decline in cancers was modest compared to circulatory diseases and external causes. The strongest downward trends were observed for AIDS, traffic accidents and ischaemic heart disease. In women breast cancer contributed most to the decline of premature mortality but remains the first cause of early death. Lung cancer in women is the only cause of premature mortality with rising trends. CONCLUSIONS Past efforts in prevention, early detection and treatment, but also a healthier lifestyle and other factors, have very probably contributed to the considerable reduction in the rate of potential years of life lost, but the rising rate of premature mortality caused by lung cancer in women is of concern. Persistent efforts in prevention and early detection are required to further reduce premature death and its burden on society.