Maria J. Schymura

Annual Report to the Nation on the Status of Cancer, 1975–2009, Featuring the Burden and Trends in Human Papillomavirus (HPV)–Associated Cancers and HPV Vaccination Coverage Levels

Background The American Cancer Society (ACS), 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 updates on cancer incidence and death rates and trends in these outcomes for the United States. This year’s report includes incidence trends for human papillomavirus (HPV)–associated cancers and HPV vaccination (recommended for adolescents aged 11–12 years). Methods Data on cancer incidence were obtained from the CDC, NCI, and NAACCR, and data on mortality were obtained from the CDC. Long- (1975/1992–2009) and short-term (2000–2009) trends in age-standardized incidence and death rates for all cancers combined and for the leading cancers among men and among women were examined by joinpoint analysis. Prevalence of HPV vaccination coverage during 2008 and 2010 and of Papanicolaou (Pap) testing during 2010 were obtained from national surveys. Results Death rates continued to decline for all cancers combined for men and women of all major racial and ethnic groups and for most major cancer sites; rates for both sexes combined decreased by 1.5% per year from 2000 to 2009. Overall incidence rates decreased in men but stabilized in women. Incidence rates increased for two HPV-associated cancers (oropharynx, anus) and some cancers not associated with HPV (eg, liver, kidney, thyroid). Nationally, 32.0% (95% confidence interval [CI] = 30.3% to 33.6%) of girls aged 13 to 17 years in 2010 had received three doses of the HPV vaccine, and coverage was statistically significantly lower among the uninsured (14.1%, 95% CI = 9.4% to 20.6%) and in some Southern states (eg, 20.0% in Alabama [95% CI = 13.9% to 27.9%] and Mississippi [95% CI = 13.8% to 28.2%]), where cervical cancer rates were highest and recent Pap testing prevalence was the lowest. Conclusions The overall trends in declining cancer death rates continue. However, increases in incidence rates for some HPV-associated cancers and low vaccination coverage among adolescents underscore the need for additional prevention efforts for HPV-associated cancers, including efforts to increase vaccination coverage.

Annual Report to the Nation on the Status of Cancer, 1975–2007, Featuring Tumors of the Brain and Other Nervous System

Background The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute, and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year’s report highlights brain and other nervous system (ONS) tumors, including nonmalignant brain tumors, which became reportable on a national level in 2004. Methods Cancer incidence data were obtained from the National Cancer Institute, CDC, and NAACCR, and information on deaths was obtained from the CDC’s National Center for Health Statistics. The annual percentage changes in age-standardized incidence and death rates (2000 US population standard) for all cancers combined and for the top 15 cancers for men and for women were estimated by joinpoint analysis of long-term (1992–2007 for incidence; 1975–2007 for mortality) trends and short-term fixed interval (1998–2007) trends. Analyses of malignant neuroepithelial brain and ONS tumors were based on data from 1980–2007; data on nonmalignant tumors were available for 2004–2007. All statistical tests were two-sided. Results Overall cancer incidence rates decreased by approximately 1% per year; the decrease was statistically significant (P < .05) in women, but not in men, because of a recent increase in prostate cancer incidence. The death rates continued to decrease for both sexes. Childhood cancer incidence rates continued to increase, whereas death rates continued to decrease. Lung cancer death rates decreased in women for the first time during 2003–2007, more than a decade after decreasing in men. During 2004–2007, more than 213 500 primary brain and ONS tumors were diagnosed, and 35.8% were malignant. From 1987–2007, the incidence of neuroepithelial malignant brain and ONS tumors decreased by 0.4% per year in men and women combined. Conclusions The decrease in cancer incidence and mortality reflects progress in cancer prevention, early detection, and treatment. However, major challenges remain, including increasing incidence rates and continued low survival for some cancers. Malignant and nonmalignant brain tumors demonstrate differing patterns of occurrence by sex, age, and race, and exhibit considerable biologic diversity. Inclusion of nonmalignant brain tumors in cancer registries provides a fuller assessment of disease burden and medical resource needs associated with these unique tumors.

Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993–2002

BackgroundAn inverse relationship between solar ultraviolet-B (UV-B) exposure and non-skin cancer mortality has long been reported. Vitamin D, acquired primarily through exposure to the sun via the skin, is believed to inhibit tumor development and growth and reduce mortality for certain cancers.MethodsWe extend the analysis of this relationship to include cancer incidence as well as mortality, using higher quality and higher resolution data sets than have typically been available. Over three million incident cancer cases between 1998 and 2002 and three million cancer deaths between 1993 and 2002 in the continental United States were regressed against daily satellite-measured solar UV-B levels, adjusting for numerous confounders. Relative risks of reduced solar UV-B exposure were calculated for thirty-two different cancer sites.ResultsFor non-Hispanic whites, an inverse relationship between solar UV-B exposure and cancer incidence and mortality was observed for ten sites: bladder, colon, Hodgkin lymphoma, myeloma, other biliary, prostate, rectum, stomach, uterus, and vulva. Weaker evidence of an inverse relationship was observed for six sites: breast, kidney, leukemia, non-Hodgkin lymphoma, pancreas, and small intestine. For three sites, inverse relationships were seen that varied markedly by sex: esophagus (stronger in males than females), gallbladder (stronger in females than males), and thyroid (only seen in females). No association was found for bone and joint, brain, larynx, liver, nasal cavity, ovary, soft tissue, male thyroid, and miscellaneous cancers. A positive association between solar UV-B exposure and cancer mortality and incidence was found for anus, cervix, oral cavity, melanoma, and other non-epithelial skin cancer.ConclusionThis paper adds to the mounting evidence for the influential role of solar UV-B exposure on cancer, particularly for some of the less-well studied digestive cancers. The relative risks for cancer incidence are similar to those for cancer mortality for most sites. For several sites (breast, colon, rectum, esophagus, other biliary, vulva), the relative risks of mortality are higher, possibly suggesting that the maintenance of adequate vitamin D levels is more critical for limiting tumor progression than for preventing tumor onset. Our findings are generally consistent with the published literature, and include three cancer sites not previously linked with solar UV-B exposure, to our knowledge: leukemia, small intestine, and vulva.

The Impact of Socioeconomic Status on Survival After Cancer in the United States : Findings From the National Program of Cancer Registries Patterns of Care Study

Understanding the ways in which socioeconomic status (SES) affects mortality is important for defining strategies to eliminate the unequal burden of cancer by race and ethnicity in the United States.

Effect of Adjuvant Chemotherapy on Survival of Patients With Stage III Colon Cancer Diagnosed After Age 75 Years

PURPOSE Few patients 75 years of age and older participate in clinical trials, thus whether adjuvant chemotherapy for stage III colon cancer (CC) benefits this group is unknown. METHODS A total of 5,489 patients ≥ 75 years of age with resected stage III CC, diagnosed between 2004 and 2007, were selected from four data sets containing demographic, stage, treatment, and survival information. These data sets included SEER-Medicare, a linkage between the New York State Cancer Registry (NYSCR) and its Medicare programs, and prospective cohort studies Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) and the National Comprehensive Cancer Network. Data sets were analyzed in parallel using covariate adjusted and propensity score (PS) matched proportional hazards models to evaluate the effect of treatment on survival. PS trimming was used to mitigate the effects of selection bias. RESULTS Use of adjuvant therapy declined with age and comorbidity. Chemotherapy receipt was associated with a survival benefit of comparable magnitude to clinical trials results (SEER-Medicare PS-matched mortality, hazard ratio [HR], 0.60; 95% CI, 0.53 to 0.68). The incremental benefit of oxaliplatin over non-oxaliplatin-containing regimens was also of similar magnitude to clinical trial results (SEER-Medicare, HR, 0.84; 95% CI, 0.69 to 1.04; NYSCR-Medicare, HR, 0.82, 95% CI, 0.51 to 1.33) in two of three examined data sources. However, statistical significance was inconsistent. The beneficial effect of chemotherapy and oxaliplatin did not seem solely attributable to confounding. CONCLUSION The noninvestigational experience suggests patients with stage III CC ≥ 75 years of age may anticipate a survival benefit from adjuvant chemotherapy. Oxaliplatin offers no more than a small incremental benefit. Use of adjuvant chemotherapy after the age of 75 years merits consideration in discussions that weigh individual risks and preferences.

Survival after cancer diagnosis in persons with AIDS

The survival of persons with AIDS (PWA) has recently improved because of better antiretroviral therapies. Similarly, the prognosis of cancer has also improved. To determine if survival in PWA with cancer has also improved, we compared cancer survival in adults with and without AIDS using data from New York City from 1980 through 2000. Analyses were made for AIDS-related cancers (Kaposi sarcoma, non-Hodgkin lymphoma [NHL], and cervical cancer) and for 8 non-AIDS-related cancers (lung, larynx, colorectum, anus, Hodgkin lymphoma, breast, prostate, and testis). Death hazard ratios compared survival in PWA with cancer with that in cancer patients without AIDS, adjusted for age, sex, race, and calendar-time of cancer occurrence. The 24-month survival rate of PWA with cancer (9015 AIDS cancers and 929 non-AIDS-related cancers of 8 types) improved significantly for most cancer types. By 1996 through 2000, the 24-month survival rate in PWA was 58% for Kaposi sarcoma, 41% for peripheral NHL, 29% for central nervous system NHL, and 64% for cervical cancer. For non-AIDS-related cancers, survival of PWA was lowest for lung cancer (10%) but was >50% for most other cancer types. In 1996 through 2000, significant differences in survival between cancer patients with and without AIDS still remained for Hodgkin lymphoma and lung, larynx, and prostate cancers. We conclude that recent improvements in AIDS and cancer care have greatly narrowed the gap in survival between cancer patients with and without AIDS. Clinicians should be encouraged by the improving prognosis and be diligent about detecting and treating cancer in PWA.

Comparative Effectiveness of Oxaliplatin vs Non–Oxaliplatin-containing Adjuvant Chemotherapy for Stage III Colon Cancer

BACKGROUND The addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain. SUBJECTS AND METHODS Patients younger than 75 years with stage III colon cancer who received chemotherapy within 120 days of surgical resection were identified from five observational data sources-the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER-Medicare), the New York State Cancer Registry (NYSCR) linked to Medicaid and Medicare claims, the National Comprehensive Cancer Network (NCCN) Outcomes Database, and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS). Overall survival (OS) was compared among patients treated with oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy. Overall survival for 4060 patients diagnosed during 2004-2009 was compared with pooled data from five RCTs (the Adjuvant Colon Cancer ENdpoinTs [ACCENT] group, n = 8292). Datasets were juxtaposed but not combined using Kaplan-Meier curves. Covariate and propensity score adjusted proportional hazards models were used to calculate adjusted survival hazard ratios (HR). Stratified analyses examined effect modifiers. All statistical tests were two-sided. RESULTS The survival advantage associated with the addition of oxaliplatin to adjuvant 5-FU was evident across diverse practice settings (3-year OS: RCTs, 86% [n = 1273]; SEER-Medicare, 80% [n = 1152]; CanCORS, 88% [n = 129]; NYSCR-Medicaid, 82% [n = 54]; NYSCR-Medicare, 79% [n = 180]; and NCCN, 86% [n = 438]). A statistically significant improvement in 3-year overall survival was seen in the largest cohort, SEER-Medicare, and in the NYSCR-Medicare cohort (non-oxaliplatin-containing vs oxaliplatin-containing adjuvant therapy, adjusted HR of death: pooled RCTs: HR = 0.80, 95% CI = 0.70 to 0.92, P = .002; SEER-Medicare: HR = 0.70, 95% CI = 0.60 to 0.82, P < .001; NYSCR-Medicare patients aged ≥65 years: HR = 0.58, 95% CI = 0.38 to 0.90, P = .02). The association between oxaliplatin treatment and better survival was maintained in older and minority group patients, as well as those with higher comorbidity. CONCLUSION The addition of oxaliplatin to 5-FU appears to be associated with better survival among patients receiving adjuvant colon cancer treatment in the community.

Visualization of the spatial scan statistic using nested circles

We propose a technique for the display of results of Kulldorffs spatial scan statistic and related cluster detection methods that provides a greater degree of informational content. By simultaneously considering likelihood ratio and relative risk, it is possible to identify focused sub-clusters of higher (or lower) relative risk among broader regional excesses or deficits. The result is a map with a nested or contoured appearance. Here the technique is applied to prostate cancer mortality data in counties within the contiguous United States during the period 1970-1994. The resulting map shows both broad and localized patterns of excess and deficit, which complements a choropleth map of the same data.

Factors associated with initial treatment and survival for clinically localized prostate cancer: results from the CDC-NPCR Patterns of Care Study (PoC1)

BackgroundDespite the large number of men diagnosed with localized prostate cancer, there is as yet no consensus concerning appropriate treatment. The purpose of this study was to describe the initial treatment patterns for localized prostate cancer in a population-based sample and to determine the clinical and patient characteristics associated with initial treatment and overall survival.MethodsThe analysis included 3,300 patients from seven states, diagnosed with clinically localized prostate cancer in 1997. We examined the association of sociodemographic and clinical characteristics with four treatment options: radical prostatectomy, radiation therapy, hormone therapy, and watchful waiting. Diagnostic and treatment information was abstracted from medical records. Socioeconomic measures were derived from the 2000 Census based on the patients residence at time of diagnosis. Vital status through December 31, 2002, was obtained from medical records and linkages to state vital statistics files and the National Death Index. Multiple logistic regression analysis and Cox proportional hazards models identified factors associated with initial treatment and overall survival, respectively.ResultsPatients with clinically localized prostate cancer received the following treatments: radical prostatectomy (39.7%), radiation therapy (31.4%), hormone therapy (10.3%), or watchful waiting (18.6%). After multivariable adjustment, the following variables were associated with conservative treatment (hormone therapy or watchful waiting): older age, black race, being unmarried, having public insurance, having non-screen detected cancer, having normal digital rectal exam results, PSA values above 20, low Gleason score (2-4), comorbidity, and state of residence. Among patients receiving definitive treatment (radical prostatectomy or radiation therapy), older age, being unmarried, PSA values above 10, unknown Gleason score, state of residence, as well as black race in patients under 60 years of age, were associated with receipt of radiation therapy. Overall survival was related to younger age, being married, Gleason score under 8, radical prostatectomy, and state of residence. Comorbidity was only associated with risk of death within the first three years of diagnosis.ConclusionsIn the absence of clear-cut evidence favoring one treatment modality over another, it is important to understand the factors that inform treatment selection. Since state of residence was a significant predictor of both treatment as well as overall survival, true regional differences probably exist in how physicians and patients select treatment options. Factors affecting treatment choice and treatment effectiveness need to be further explored in future population-based studies.

Breast cancer survival in the US and Europe: A CONCORD high-resolution study.

Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age‐standardized survival. The aim of this study is to explain these survival differences. Population‐based data on stage at diagnosis, diagnostic procedures, treatment and follow‐up were collected for about 20,000 women diagnosed with breast cancer aged 15–99 years during 1996–98 in 7 US states and 12 European countries. Age‐standardized net survival and the excess hazard of death up to 5 years after diagnosis were estimated by jurisdiction (registry, country, European region), age and stage with flexible parametric models. Breast cancers were generally less advanced in the US than in Europe. Stage also varied less between US states than between European jurisdictions. Early, node‐negative tumors were more frequent in the US (39%) than in Europe (32%), while locally advanced tumors were twice as frequent in Europe (8%), and metastatic tumors of similar frequency (5–6%). Net survival in Northern, Western and Southern Europe (81–84%) was similar to that in the US (84%), but lower in Eastern Europe (69%). For the first 3 years after diagnosis the mean excess hazard was higher in Eastern Europe than elsewhere: the difference was most marked for women aged 70–99 years, and mainly confined to women with locally advanced or metastatic tumors. Differences in breast cancer survival between Europe and the US in the late 1990s were mainly explained by lower survival in Eastern Europe, where low healthcare expenditure may have constrained the quality of treatment.