Background Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. Methods In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. Results In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P = 0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P = 0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P = 0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. Conclusions The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)

/pdf/sipuleucel-t-immunotherapy-for-castration-resistant-prostate-31dll2jbjc.pdf

Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

BACKGROUND. The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information regarding cancer occurrence and trends in the United States. This year's report includes trends in colorectal cancer (CRC) incidence and death rates and highlights the use of microsimulation modeling as a tool for interpreting past trends and projecting future trends to assist in cancer control planning and policy decisions. METHODS. Information regarding invasive cancers was obtained from the NCI, CDC, and NAACCR; and information on deaths was obtained from the CDC's National Center for Health Statistics. Annual percentage changes in the age-standardized incidence and death rates (based on the year 2000 US population standard) for all cancers combined and for the top 15 cancers were estimated by joinpoint analysis of long-term trends (1975-2006) and for short-term fixed-interval trends (1997-2006). All statistical tests were 2-sided. RESULTS. Both incidence and death rates from all cancers combined significantly declined (P < .05) in the most recent time period for men and women overall and for most racial and ethnic populations. These decreases were driven largely by declines in both incidence and death rates for the 3 most common cancers in men (ie, lung and prostate cancers and CRC) and for 2 of the 3 leading cancers in women (ie, breast cancer and CRC). The long-term trends for lung cancer mortality in women had smaller and smaller increases until 2003, when there was a change to a nonsignificant decline. Microsimulation modeling demonstrates that declines in CRC death rates are consistent with a relatively large contribution from screening and with a smaller but demonstrable impact of risk factor reductions and improved treatments. These declines are projected to continue if risk factor modification, screening, and treatment remain at current rates, but they could be accelerated further with favorable trends in risk factors and higher utilization of screening and optimal treatment. CONCLUSIONS. Although the decrease in overall cancer incidence and death rates is encouraging, rising incidence and mortality for some cancers are of concern.

/pdf/annual-report-to-the-nation-on-the-status-of-cancer-1975-8rsp6cac3s.pdf

Annual Report to the Nation on the Status of Cancer, 1975-2006, Featuring Colorectal Cancer Trends and Impact of Interventions (Risk Factors, Screening, and Treatment) to Reduce Future Rates

ObjectiveThis update of a 2004 guideline codeveloped by the American Academy of Otolaryngology—Head and Neck Surgery Foundation, the American Academy of Pediatrics, and the American Academy of Family Physicians, provides evidence-based recommendations to manage otitis media with effusion (OME), defined as the presence of fluid in the middle ear without signs or symptoms of acute ear infection. Changes from the prior guideline include consumer advocates added to the update group, evidence from 4 new clinical practice guidelines, 20 new systematic reviews, and 49 randomized control trials, enhanced emphasis on patient education and shared decision making, a new algorithm to clarify action statement relationships, and new and expanded recommendations for the diagnosis and management of OME.PurposeThe purpose of this multidisciplinary guideline is to identify quality improvement opportunities in managing OME and to create explicit and actionable recommendations to implement these opportunities in clinical pra...

https://journals.sagepub.com/doi/pdf/10.1177/0194599815623467

Clinical Practice Guideline Otitis Media with Effusion (Update)

Background. The Surveillance, Epidemiology and End Results (SEER)-Medicare–linked database combines clinical information from population-based cancer registries with claims information from the Medicare program. The use of this database to study cancer screening, treatment, outcomes, and costs has g

Overview of the SEER-Medicare data: content, research applications, and generalizability to the United States elderly population.

https://www.pure.ed.ac.uk/ws/files/8378925/The_benefits_and_harms_of_breast_cancer_screening.pdf

The benefits and harms of breast cancer screening: an independent review

In the United States in 2002, approximately 42% of women with breast cancer received adjuvant radiation therapy after surgery (1). Adjuvant radiation after breast-conserving surgery decreases the risk of local recurrence by two-thirds and results in survival equivalent to that achieved by patients treated with mastectomy (2,3). Radiation is also recommended for selected patients after mastectomy to lower the risk of recurrence and possibly improve survival (4–8). However, two population-based studies (9,10) have demonstrated underuse of adjuvant radiation therapy, possibly because of concerns about radiation-induced toxicity (9,10). In particular, women treated with radiation have an increased risk of mortality from ischemic heart disease (3,11–15).

In a meta-analysis of eight randomized trials that included almost 8000 women, Cuzick et al. (15) found a 62% increase in cardiac deaths in women who received radiation. Similarly, the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis of approximately 20 000 women who were enrolled in 40 randomized trials of radiotherapy found a 30% increase in vascular mortality, although the analysis also documented a statistically significant reduction in breast cancer mortality (3). Because all the trials included in the meta-analysis reported by Cuzick et al. (15) were initiated before 1975 and the trials included in the EBCTCG meta-analysis were also heavily weighted towards trials with patients treated in the 1960s and 1970s, it is unclear whether these data can be applied to women currently undergoing radiotherapy with modern techniques.

Techniques of adjuvant radiation therapy have changed substantially since the 1960s (15–19). Older radiation techniques that resulted in higher doses of cardiac radiation, such as deep tangents and direct internal mammary fields matched to shallow tangents, have been largely abandoned (15–18). In addition, the development of computed tomography-based technology to guide radiation treatment field design has improved the ability to individualize treatment plans. Thus, by accounting for anatomical differences between patients, radiation doses to the heart may be minimized (19). Whether these advances in adjuvant radiotherapy techniques are associated with reduced cardiac mortality has not, however, been rigorously studied.

One approach to study radiation-associated cardiac mortality is to compare outcomes between patients with left-sided breast cancers and those with right-sided breast cancers. Patients with left-sided breast cancer who are treated with radiation have a higher risk of cardiac radiation exposure (13) and higher rates of cardiovascular mortality (11,12,14,20) than patients with right-sided breast cancers. The differential dose of cardiac radiation received by patients with left-sided and right-sided breast cancers allows investigators to use observational data to estimate the risk of cardiac mortality from radiation. No known selection biases exist to otherwise differentiate patients by tumor laterality, and an equal distribution of risks would be expected between patients with left- and right-sided tumors. In this study, we compared cardiac mortality rates for patients with left-sided tumors with cardiac mortality rates for those with right-sided tumors to determine whether the risk of death from ischemic heart disease resulting from breast irradiation decreased over time.

Risk of Cardiac Death After Adjuvant Radiotherapy for Breast Cancer

Background Medicare claims include codes for chemotherapy administration and specific drugs given, and researchers are increasingly using these data to measure the use of chemotherapy. However, the validity and completeness of these data as a source of information has not been established. Objectives This analysis is intended to assess the utility of the Medicare claims to capture chemotherapy use. Methods Persons with breast, colorectal, and ovarian cancer were identified from the linked SEER-Medicare data. Their Medicare claims were reviewed to determine if there were any bills for chemotherapy, and if so, if there were claims for specific agents. This information was compared with data on the first course of treatment obtained from hospitals and treating physicians by the SEER registries through an NCI-supported Patterns of Care Studies (POC). Agreement was measured using kappa statistics. The sensitivity of the Medicare claims to capture chemotherapy, as reported from the POC data, was also measured. An additional comparison assessed the agreement between the two data sources concerning which specific drugs had been given. Results For all of the cancers, there was a high level of agreement between the Medicare claims and the POC data regarding whether or not the patient had received chemotherapy (kappa >or=0.73). The sensitivity of the Medicare data to determine if a person had received chemotherapy was high (>or=88%). In cases where the Medicare claim included a code for a specific drug, there high agreement between Medicare and POC about the specific drug given in breast and colorectal cancers, although the agreement was lower for ovarian cancers. The sensitivity of the Medicare claims to identify specific agents varies by cancer type. Conclusions The Medicare claims can be used to identify which persons are receiving chemotherapy. The utility of Medicare data to measure treatment with specific agents varies by cancer type and specific agent. For some cancers, it is possible to use these claims to assess use of specific drugs, while for other drugs the data are limited.

Utility of the SEER-Medicare data to identify chemotherapy use.

BACKGROUND

The role of androgen deprivation therapy in prostate carcinoma is controversial in earlier stages of disease. The authors examined the time trends and patterns of use for androgen deprivation in the form of gonadotropin-releasing hormone (GnRH) agonists or orchiectomy, in population-based tumor registries.



METHODS

Data were obtained from the linked Surveillance, Epidemiology and End Results-Medicare database. A total of 100,274 men with prostate carcinoma diagnosed from 1991 through 1999 were selected. The main outcome was the proportion of men who received ≥ 1 dose of a GnRH agonist in the first 6 months of diagnosis. This was plotted by year and stratified for age, grade, stage as well as primary versus adjuvant usage. Multiple logistic regression was used to examine predictors of GnRH agonist use in the subset of patients with localized cancer.



RESULTS

There was a consistent increase in GnRH agonist use by year for all ages, stages, and grades. Even in men ≥ 80 years with localized stage and low to moderate grade tumors, primary GnRH agonist use increased over the study period, from 3.7% in 1991 to 30.9% in 1999 (P < 0.001). The multivariable analysis showed that significant variability in GnRH agonist use existed among SEER geographic regions.



CONCLUSIONS

The use of GnRH agonists for prostate carcinoma increased dramatically during the 1990s. This increase occurred across all stages and histologic grades of prostate carcinoma, and was greatest in patients ≥ 80 years. Cancer 2005. © 2005 American Cancer Society.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.20955

Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma

Background. Numerous studies have used the SEER or Medicare data to assess the use of radiation therapy. However, the completeness of these data has not been evaluated.Methods. Using linked SEER-Medicare data, a cohort was created that included incident cases of breast, endometrial, lung, prostate,

Studying Radiation Therapy Using SEER-Medicare-Linked Data

BACKGROUND. The accuracy and completeness of the SEER-Medicare data for measuring cancer-related therapy have not been extensively evaluated. OBJECTIVES. To investigate the best method for measuring cancer-related surgery among patients in the SEER-Medicare database. SUBJECTS. A total of 149,970 incident cases of breast, colorectal, endometrial, lung, pancreatic, and prostate cancer diagnosed between 1991 and 1993. MEASURES. The most invasive surgical procedure identified through Medicare's inpatient, physician, and hospital outpatient claims was compared with corresponding data from the SEER files.

Jean L. Freeman

Papers

Risk of Cardiac Death After Adjuvant Radiotherapy for Breast Cancer

Utility of the SEER-Medicare data to identify chemotherapy use.

Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma

Studying Radiation Therapy Using SEER-Medicare-Linked Data

Use of SEER-Medicare data for measuring cancer surgery.