Bronislava M. Sigal

EFFECTS OF MAMMOGRAPHY SCREENING UNDER DIFFERENT SCREENING SCHEDULES: MODEL ESTIMATES OF POTENTIAL BENEFITS AND HARMS

To inform the USPSTF recommendations about breast cancer screening, Mandelblatt and colleagues developed 6 models of breast cancer incidence and mortality in the United States and estimated benefit...

Survival Analysis of Cancer Risk Reduction Strategies for BRCA1/2 Mutation Carriers

PURPOSE Women with BRCA1/2 mutations inherit high risks of breast and ovarian cancer; options to reduce cancer mortality include prophylactic surgery or breast screening, but their efficacy has never been empirically compared. We used decision analysis to simulate risk-reducing strategies in BRCA1/2 mutation carriers and to compare resulting survival probability and causes of death. METHODS We developed a Monte Carlo model of breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years, prophylactic mastectomy (PM) at various ages, and/or prophylactic oophorectomy (PO) at ages 40 or 50 years in 25-year-old BRCA1/2 mutation carriers. RESULTS With no intervention, survival probability by age 70 is 53% for BRCA1 and 71% for BRCA2 mutation carriers. The most effective single intervention for BRCA1 mutation carriers is PO at age 40, yielding a 15% absolute survival gain; for BRCA2 mutation carriers, the most effective single intervention is PM, yielding a 7% survival gain if performed at age 40 years. The combination of PM and PO at age 40 improves survival more than any single intervention, yielding 24% survival gain for BRCA1 and 11% for BRCA2 mutation carriers. PM at age 25 instead of age 40 offers minimal incremental benefit (1% to 2%); substituting screening for PM yields a similarly minimal decrement in survival (2% to 3%). CONCLUSION Although PM at age 25 plus PO at age 40 years maximizes survival probability, substituting mammography plus MRI screening for PM seems to offer comparable survival. These results may guide women with BRCA1/2 mutations in their choices between prophylactic surgery and breast screening.

PROSTATE CANCER IS HIGHLY PREDICTABLE: A PROGNOSTIC EQUATION BASED ON ALL MORPHOLOGICAL VARIABLES IN RADICAL PROSTATECTOMY SPECIMENS

PURPOSE We determine whether biochemical prostate specific antigen (PSA) failure can be accurately predicted from preoperative serum PSA combined with 6 morphological variables from radical retropubic prostatectomy specimens in men with peripheral zone cancers. The unexpected limitation imposed by preoperative serum PSA on biochemical failure led us to compare peripheral zone to transition zone cancers. MATERIALS AND METHODS A total of 326 peripheral zone and 46 transition zone cancers treated only with radical retropubic prostatectomy were followed for a minimum of 3 years (mean and median greater than 5). All prostates were sectioned at 3 mm. intervals and morphological variables were quantitated using the Stanford technique. Biochemical failure was defined as serum PSA 0.07 ng./ml. or greater and increasing. Multivariate logistic regression was used to identify variables with the most independent influence on biochemical failure and derive a clinical equation to predict failure in peripheral zone cancers. The validity of the predictive equation was assessed by out of sample validation and cross validation techniques. The 46 transition zone cancers were compared to the 326 peripheral zone cancers by Students t and Wilcoxon tests. RESULTS Of the peripheral zone failures 60% occurred in the first year after radical retropubic prostatectomy and 95% had occurred by the end of year 4. The highest preoperative serum PSA was 23 ng./ml. among the 181 men biochemically free of disease. Only 15.8% of 57 men with PSA greater than 15 ng./ml. were biochemically disease-free. For the 48 transition zone cancers cure rates were independent of serum PSA with 6 men having PSA greater than 50 ng./ml. Biochemical disease-free status was noted in 80% of transition zone compared to 56% of peripheral zone cancers (p = 0.0009). The most important variables predicting biochemical disease-free status for peripheral zone cancers were percent Gleason grade 4/5, cancer volume, serum PSA and prostate weight. Foci of vascular invasion, intraductal cancer and lymph nodes were less significant variables, and capsular penetration, positive surgical margins and seminal vesical invasion were insignificant. The multivariate logistic equation for predicting failure in peripheral zone cancers was highly accurate and requires only 2 to 3 minutes with a simple calculator. CONCLUSIONS Failure of radical retropubic prostatectomy to cure peripheral zone prostate cancer is highly predictable based on 6 morphological variables from the prostatectomy specimen and serum PSA. The level of serum PSA profoundly limits biochemical cure rates in peripheral zone cancers. Transition zone cancers have a high cure rate, despite high serum PSA and adverse morphological variables. Men with serum PSA greater than 15 and perhaps even greater than 10 ng./ml. have such a low cure rate for peripheral zone cancer that re-biopsy attempts appear indicated to prove a transition zone location or else therapy other than radical retropubic prostatectomy should be sought. Pathologists should indicate whether the primary (largest) cancer is in the peripheral or transition zone to prevent overoptimistic reports of cure with radical prostatectomy procedures, as 85% of all tumors are in the peripheral zone.

Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience

Recent studies report an improvement in overall survival (OS) of patients with follicular lymphoma (FL). Previously untreated patients with grade 1 to 2 FL treated at Stanford University from 1960-2003 were identified. Four eras were considered: era 1, pre-anthracycline (1960-1975, n = 180); era 2, anthracycline (1976-1986, n = 426); era 3, aggressive chemotherapy/purine analogs (1987-1996, n = 471); and era 4, rituximab (1997-2003, n = 257). Clinical characteristics, patterns of care, and survival were assessed. Observed OS was compared with the expected OS calculated from Berkeley Mortality Database life tables derived from population matched by gender and age at the time of diagnosis. The median OS was 13.6 years. Age, gender, and stage did not differ across the eras. Although primary treatment varied, event-free survival after the first treatment did not differ between eras (P = .17). Median OS improved from 11 years in eras 1 and 2 to 18.4 years in era 3 and has not yet been reached for era 4 (P < .001), with no suggestion of a plateau in any era. These improvements in OS exceeded improvements in survival in the general population during the same period. Several factors, including better supportive care and effective therapies for relapsed disease, are likely responsible for this improvement.

Incidental Extracardiac Findings at Coronary CT: Clinical and Economic Impact

OBJECTIVE The purpose of this study was to evaluate the prevalence of incidental extracardiac findings on coronary CT, to determine the associated downstream resource utilization, and to estimate additional costs per patient related to the associated diagnostic workup. MATERIALS AND METHODS This retrospective study examined incidental extracardiac findings in 151 consecutive adults (69.5% men and 30.5% women; mean age, 54 years) undergoing coronary CT during a 7-year period. Incidental findings were recorded, and medical records were reviewed for downstream diagnostic examinations for a follow-up period of 1 year (minimum) to 7 years (maximum). Costs of further workup were estimated using 2009 Medicare average reimbursement figures. RESULTS There were 102 incidental extracardiac findings in 43% (65/151) of patients. Fifty-two percent (53/102) of findings were potentially clinically significant, and 81% (43/53) of these findings were newly discovered. The radiology reports made specific follow-up recommendations for 36% (19/53) of new significant findings. Only 4% (6/151) of patients actually underwent follow-up imaging or intervention for incidental findings. One patient was found to have a malignancy that was subsequently treated. The average direct costs of additional diagnostic workup were

A Simulation Model to Predict the Impact of Prophylactic Surgery and Screening on the Life Expectancy of BRCA1 and BRCA2 Mutation Carriers

17.42 per patient screened (95% CI,

A Simulation Model Investigating the Impact of Tumor Volume Doubling Time and Mammographic Tumor Detectability on Screening Outcomes in Women Aged 40–49 Years

2.84-

Ductal Lavage of Fluid-Yielding and Non–Fluid-Yielding Ducts in BRCA1 and BRCA2 Mutation Carriers and Other Women at High Inherited Breast Cancer Risk

32.00) and

Ductal lavage of non-fluid yielding ducts in BRCA1 and BRCA2 mutation carriers and other women at high genetic risk for breast cancer

438.39 per patient with imaging follow-up (95% CI,

Biological Determinants of Cancer Progression in Men With Prostate Cancer

301.47-