Massimo Usel

Lymph Node Ratio as an Alternative to pN Staging in Node-Positive Breast Cancer

PURPOSE In the current pTNM classification system, nodal status of breast cancer is based on the number of involved lymph nodes and does not account for the total number of lymph nodes removed. In this study, we assessed the prognostic value of the lymph node ratio (LNR; ie, ratio of positive over excised lymph nodes) as compared with pN staging and determined its optimal cutoff points. PATIENTS AND METHODS From the Geneva Cancer Registry, we identified all women diagnosed with node-positive breast cancer between 1980 and 2004 (n = 1,829). The prognostic value of LNRs was calculated for values ranging from 0.05 to 0.95 by Cox regression analysis and validated by bootstrapping. Based on maximum likelihood, we identified cutoff points classifying women into low-, intermediate-, and high-risk LNR groups. RESULTS Optimal cutoff points classified patients into low- (< or = 0.20), intermediate- (> 0.20 and < or = 0.65), and high-risk (> 0.65) LNR groups, corresponding to 10-year disease-specific survival rates of 75%, 63%, and 40%, and adjusted mortality risks of 1 (reference), 1.78 (95% CI, 1.46 to 2.18), and 3.21 (95% CI, 2.54 to 4.06), respectively. In contrast to LNR risk categories, survival curves of pN2 and pN3 crossed after 15 years, and their adjusted mortality risks showed overlapping CIs: 2.07 (95% CI, 1.69 to 2.53) and 2.84 (95% CI, 2.23 to 3.61), respectively. CONCLUSION LNR predicts survival after breast cancer more accurately than pN classification and should be considered as an alternative to pN staging.

Sex differences in presentation, management, and prognosis of patients with non–small cell lung carcinoma

OBJECTIVE AND METHODS To characterize gender differences in lung cancer, we conducted a retrospective analysis including all patients undergoing surgery for non-small cell lung carcinoma in a single institution over a 20-year period. RESULTS Compared with men (n = 839), women (n = 198) were more likely to be asymptomatic (32% vs 20%, P =.006), nonsmokers (27% vs 2%, P <.001), or light smokers (31 pack-years vs 52 pack-years; P <.001). Squamous cell carcinoma predominated in men (65%), and adenocarcinoma predominated in women (54%). Preoperative bronchoscopy contributed more frequently to a histologic diagnosis in men (69% vs 49% in women, P <.001), and fewer pneumonectomies were performed in women (22% vs 32% in men, P =.01). After multivariate Cox regression analysis, women survived longer than men (hazard ratio, 0.72; 95% confidence interval, 0.56-0. 92; P =.009) independently of age, presence of symptoms, smoking habits, type of operation, histologic characteristics, and stage of disease. The protective effect linked to female sex was present in early-stage carcinoma (stage I and II) and absent in more advanced-stage carcinoma (stage III and IV). CONCLUSIONS This study emphasizes strong sex differences in presentation, management, and prognosis of patients with non-small cell lung cancer.

Young patients with endometrial cancer: How many could be eligible for fertility-sparing treatment?

OBJECTIVES To assess the characteristics of young women with endometrial carcinoma, and evaluate those potentially eligible for conservative therapy. METHODS We identified women diagnosed with endometrial cancer between 1970 and 2005 at the population-based Geneva Cancer Registry (n=1365). We classified patients into two age groups (< or =45 and >45 years old). Differences in demographic, tumor, diagnostic and treatment characteristics were tested with chi square. Kaplan-Meier analysis was used to calculate survival from endometrial cancer and the log-rank test to analyze differences in survival between the two groups. RESULTS The young group comprised 44 (3.2%) women and the old group 1321 (96.8%) women. Synchronous ovarian malignancies were found in six patients (14%) in the young group, compared with 23 (2%) in the old group (P<0.001). Tumor stage was also different between the two groups, principally because of more stage II among the young (P=0.012). Histological tumor type, grade and specific endometrial cancer 5-year survival did not significantly differ between the two groups. According to final histopathologic evaluation, eight patients from the young group had FIGO stage IA, grade I disease, i.e. may have been eligible for fertility-sparing treatment, corresponding to an incidence rate of 0.3/100,000. CONCLUSION No significant difference regarding tumor characteristics and survival between young and older patients was observed, except stage of disease and rate of synchronous ovarian malignancy. Conservative approach is a meaningful quality of life goal for patients with cancer, but only suitable for a limited number of patients.

Impact of peritoneal cytology on survival of endometrial cancer patients treated with surgery and radiotherapy.

Stage IIIA endometrial cancer includes patients with serosal or adnexal invasion and patients with positive peritoneal cytology only. In this study, we assessed the impact of peritoneal cytology on endometrial cancer survival. All endometrial cancer patients receiving surgery and radiotherapy at the Geneva University Hospitals between 1980 and 1993 were included. Stage lllA cancers were categorised into ‘cytological’ stage lllA (only positive peritoneal cytology) and ‘histological’ stage lllA (serosal or adnexal infiltration). Survival rates were analysed by Kaplan–Meier method and compared using log-rank test. The prognostic importance of peritoneal cytology was analysed by multivariate regression analysis. This study included 170 endometrial cancers (112 stage I, 17 cytological stage IIIA, 18 histological stage IIIA, 9 stage lllB+). Disease-specific survival of cytological stage IIIA was not different from stage I (94 vs 88% respectively, P=0.5) but better than histological stage IIIA (94 vs 51% respectively, P<0.01). Histological stage IIIA patients were at increased risk to die from cancer compared to stage I patients (HR 2.7, 95% CI 1.0–7.7), while cytological stage IIIA patients were not (HR 0.3, 95% CI 0.3–2.0). Cytological stage lllA endometrial cancer has similar prognosis as stage l and better prognosis than histological stage IIIA. Additional research, definitively separating stage and cytology is warranted.

Excess of cardiovascular mortality among node-negative breast cancer patients irradiated for inner-quadrant tumors

BACKGROUND Radiotherapy of the left breast is associated with higher cardiovascular mortality linked to cardiotoxic effect of irradiation. Radiotherapy of inner quadrants can be associated with greater heart irradiation, but no study has evaluated the effect of inner-quadrant irradiation on cardiovascular mortality. PATIENTS AND METHODS We identified 1245 women, the majority with breast-conserving surgery, irradiated for primary node-negative breast cancer from 1980 to 2004 registered at the Geneva Cancer Registry. We compared breast cancer-specific and cardiovascular mortality between inner-quadrant (n = 393) versus outer-quadrant tumors (n = 852) by multivariate Cox regression analysis. RESULTS After a mean follow-up of 7.7 years, 28 women died of cardiovascular disease and 91 of breast cancer. Patients with inner-quadrant tumors had a more than doubled risk of cardiovascular mortality compared with patients with outer-quadrant tumors (adjusted hazard ratio 2.5; 95% confidence interval 1.1-5.4). Risk was particularly increased in the period with higher boost irradiation. Patients with left-sided breast cancer had no excess of cardiovascular mortality compared with patients with right-sided tumors. CONCLUSIONS Radiotherapy of inner-quadrant breast cancer is associated with an important increase of cardiovascular mortality, a possible result of higher irradiation of the heart. For patients with inner-quadrant tumors, the heart should be radioprotected.

Planning for the future: cancer incidence projections in Switzerland up to 2019

BackgroundProjections of the national burden of cancer play a key role in planning cancer control programmes and investments. We present projections of cancer incidence rates and cases for the period up to 2015-2019 in Switzerland.MethodsProjections were based on cancer incidence data estimated from cancer registries for the 1989-2009 periods and demographic projections of the Federal Statistical Office. Age-specific incidence rates were modelled as a function of age, period-birth cohort using NORDPRED.ResultsUp to 2019 the incidence of all cancers combined is expected to decrease slightly for both sexes. Nevertheless, the overall number of cases is predicted to increase. The number of male cancer cases will increase by 30%, from 20005 in 2005-2009 to 25910/year in 2015-2019. For females the number will increase by 20%, from 16913 to 20359/year in 2015-2019. Changes in the population size and structure will be responsible for most of the increase. Among men, the largest increase is observed for melanoma (+54%), thyroid (+45%), non-Hodgkin lymphoma (+43%), and prostate (+37%). Prostate cancer will contribute with 8083 cases, colorectal cancer with 2908 and lung cancer with 2791. For women, cases of lung and oral cavity cancers will increase by +48% and +38%, respectively; those of thyroid by +45% and non-Hodgkin lymphoma by +36%. The sites with the most cancer predicted are breast (5870), colorectal and lung (over 2000 each), melanoma (1341) and corpus uteri (1040). The overall annual cancer burden predicted for 2015-19 is of 46269 new cases in Switzerland.ConclusionsSubstantial investments appear to be needed in Switzerland cancer services to meet and fill absolute increased demand driven by aging population.

Risk, Characteristics, and Prognosis of Breast Cancer after Hodgkin's Lymphoma

PURPOSE To assess breast cancer (BC) risk after Hodgkins lymphoma (HL) and compare characteristics, risk of second BC, and prognosis of patients with these BCs with patients with first primary BC. PATIENTS AND METHODS We considered all 9,620 women with HL recorded in the Surveillance, Epidemiology and End Results dataset in 1973-2007. We calculated age-period standardized incidence ratios of BC. We compared patient, tumor, and treatment characteristics, risk of second BC, and prognosis between patients with BC after HL (n = 316) and patients with other BCs occurring during the same period (n = 450,413) using logistic regression and Cox models adjusted for confounders. RESULTS HL patients had a 2.4-fold higher risk for developing BC (95% confidence interval [CI], 2.2-2.7) than the general population. Age at HL diagnosis and radiation therapy influenced this risk. Compared with first primary BCs, BCs after HL were diagnosed at a younger age, at an earlier stage, were less frequently hormone receptor positive, were located more frequently in external quadrants, and were less frequently treated using radiotherapy. These patients had a higher risk (adjusted hazard ratio [HR], 2.85; 95% CI, 1.79-4.53) for developing a second BC and had a higher BC mortality risk (adjusted HR, 1.36; 95% CI, 1.05-1.76). The higher mortality risk was only partly explained by the higher occurrence rate of a second BC. CONCLUSION HL survivors have a higher risk for developing BC, their BCs are more aggressive, they have a higher risk for a second BC occurrence, and they have a poorer prognosis. Guidelines of care should be adapted to decrease the impact of BC in these high-risk patients.

Breast cancer prognosis is inherited independently of patient, tumor and treatment characteristics

Population‐based studies have shown a concordance of breast cancer survival among first‐degree relatives (FDRs), suggesting a heritable component. Reasons for such heritability remain to be elucidated. We aimed to determine whether association of breast cancer survival among FDRs is linked to shared patient and tumor characteristics or type of treatment. At the population‐based Geneva Breast Cancer Registry, we identified 162 FDR pairs diagnosed with breast cancer. We categorized FDRs into poor, medium and good familial survival risk groups according to breast cancer–specific survival of their proband (mother or sister). We compared patient, tumor and treatment characteristics between categories and calculated standardized mortality ratios (SMRs) and adjusted disease‐specific mortality for each group. Breast cancer patients in the poor familial survival risk group were more likely to be diagnosed at later stages than those in the good familial survival risk group. Similarly, they had higher SMRs than those in the medium and good survival risk groups (18.7, 95% confidence interval [CI]: 9.4–33.5 vs. 16.5, 95% CI: 7.5–31.3 and 9.4, 95% CI: 3.4–20.4, respectively). After adjustment for patient and tumor characteristics and type of treatment, women in the poor familial survival risk group were almost five times more likely to die of breast cancer than those in the good familial survival risk group (adjusted hazard ratio 4.8, 95% CI: 1.4–16.4). Our study shows that breast cancer prognosis clusters within families and suggests that the hereditary component is independent of patient and tumor characteristics and type of treatment.

Tumor incidence in related hematopoietic stem cell donors

Late malignancies have been discussed as a potential risk for growth factor mobilized donors of hematopoietic stem cells. Little is known about the incidence and potential risk factors. This single center retrospective cohort study evaluated all HLA-identical sibling pairs with hematopoietic stem cell transplantation (HSCT) for a hematological malignancy, treated from 1974 to 2001 at the University Hospital of Basel. Three hundred eighteen pairs were identified, 291 donors (92%) could be contacted. Median observation time was 13.8 years (range 5–32 years). Sixteen (5%) donors had developed a total of 18 tumors, 17 recipients a secondary tumor. According to the age- and sex-adapted cancer incidence, 3.3 tumors in male and 6.8 in female donors were expected, 3 (relative risk (RR): 0.91, 95% confidence interval: 0.19–2.66) and 4 (RR: 0.58, 95% confidence interval: 0.16–1.48), respectively, were found in donors between 0 and 49 years. Between 50 and 69 years, 4.5 tumors in males and 4.8 in females were expected, 5 (RR: 1.11, 95% confidence interval: 0.36–2.59) and 6 (RR: 1.23, 95% confidence interval: 0.45–2.67), respectively, were observed. Tumors do occur in donors of hematopoietic stem cells at least at the rate as expected in a normal population; whether incidence exceeds expected rates needs to be determined in larger international cohorts.

Increased risk of second cancer among patients with ovarian borderline tumors

OBJECTIVES Several studies have demonstrated a higher risk of colorectal and breast cancers subsequent to invasive ovarian cancer. Such risk has not been investigated for ovarian borderline tumors. We aim to evaluate the risk of subsequent cancer occurrence among patients with borderline ovarian tumors in a population-based setting. METHODS We identified 171 patients with a diagnosis of borderline ovarian tumors recorded at the Geneva Cancer Registry, Switzerland. We calculated age and period standardized incidence ratios (SIR) of second tumor occurrence by dividing the number of observed cases by the number of expected cases in the cohort, using cancer incidence rates of the general female population. RESULTS The risk of developing second cancer was 1.85-fold (95% Confidence Interval [CI]: 1.10-2.92, n=16) higher among women with borderline ovarian tumors compared to that expected in the general population. The excess of risk primarily concerned colorectal cancer (SIR: 3.97, CI: 1.38-12.95, n=5) and breast cancer (SIR: 2.09, CI: 0.84-4.31, n=7), but the latter result was not statistically significant (p=0.09). The increased risk of developing second cancer was mainly observed among patients diagnosed with ovarian borderline tumors occurring before the age of 50. These results were not explained by surveillance bias or by metastasis from one site to another. CONCLUSION Women with ovarian borderline tumors have an increased risk of developing secondary cancer, particularly colorectal cancer. These results point to potential common risk factors for these tumors and ask for close surveillance of patients with borderline ovarian tumors.