Modern Radiation Further Improves Survival in Non-Small Cell Lung Cancer: An Analysis of 288,670 Patients.

Background: Radiation therapy plays an increasingly important role in the treatment of patients with non-small-cell lung cancer (NSCLC). The purpose of the present study is to assess the survival outcomes of radiotherapy treatment compared to other treatment modalities and to determine the potential role of advanced technologies in radiotherapy on improving survival. Methods: We used cancer incidence and survival data from the Surveillance, Epidemiology, and End Results database linked to U.S. Census data to compare survival outcomes of 288,670 patients with stage I-IV NSCLC treated between 1999 and 2008. The primary endpoint was overall survival. Results: Among the 288,670 patients diagnosed with stage I-IV NSCLC, 92,374 (32%) patients received radiotherapy-almost double the number receiving surgery (51,961, 18%). Compared to other treatment groups and across all stages of NSCLC, patients treated with radiotherapy showed greater median and overall survival than patients without radiation treatment (p < 0.0001). Radiotherapy had effectively improved overall survival regardless of age, gender, and histological categorization. Radiotherapy treatment received during the recent time period 2004 - 2008 is correlated with enhanced survival compared to the earlier time period 1999 - 2003. Conclusion: Radiation therapy was correlated with increased overall survival for all patients with primary NSCLC across stages. Combined surgery and radiotherapy treatment also correlates with improved survival, signaling the value of bimodal or multimodal treatments. Population-based increases in overall survival were seen in the recent time period, suggesting the potential role of advanced radiotherapeutic technologies in enhancing survival outcomes for lung cancer patients.

Racial Differences in 21-Gene Recurrence Scores Among Patients With Hormone Receptor-Positive, Node-Negative Breast Cancer.

Purpose The 21-gene recurrence score (RS) breast cancer assay is clinically used to quantify risk of 10-year distant recurrence by category (low, < 18; intermediate, 18 to 30; high, ≥ 31) for treatment management among women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative, lymph node-negative breast cancer. Although non-Hispanic black (NHB) women have worse prognosis compared with non-Hispanic white (NHW) women, the equivalency of 21-gene RS across racial groups remains unknown. Patients and Methods Using the Metropolitan Detroit Cancer Surveillance System, we identified women who were diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative, lymph node-negative invasive breast cancer between 2010 and 2014. Multinomial logistic regression was used to quantify racial differences in 21-gene RS category. Results We identified 2,216 women (1,824 NHW and 392 NHB) with invasive breast cancer who met clinical guidelines for and underwent 21-gene RS testing. The mean RS was significantly higher in NHBs compared with NHWs (19.3 v 17.0, respectively; P = .0003), where NHBs were more likely to present with high-risk tumors compared with NHWs (14.8% v 8.3%, respectively; P = .0004). These differences were limited to patients younger than 65 years at diagnosis, among whom NHBs had significantly higher RS compared with NHWs (20 to 49 years: 23.6 v 17.3, respectively; P < .001 and 50 to 64 years: 19.6 v 17.4, respectively; P = .023). NHBs remained more likely to have high-risk tumors compared with NHWs after adjusting for age, clinical stage, tumor grade, and histology (odds ratio [OR], 1.75; 95% CI, 1.18 to 2.59). Conclusion NHBs who met clinical criteria for 21-gene RS testing had tumors with higher estimated risks of distant recurrence compared with NHWs. Further study is needed to elucidate whether differences in recurrence are observed for these women, which would have clinical implications for 21-gene RS calibration and treatment recommendations in NHB patients.

Patterns of Treatment and Outcomes for Definitive Therapy of Early Stage Non-Small Cell Lung Cancer.

BACKGROUND: Definitive surgical and radiation therapy (RT) treatments are evolving rapidly for stage I non-small cell lung cancer (NSCLC). We hypothesized that utilization of definitive therapies increased between 2000 and 2010 and that survival improved for stage I NSCLC patients over the same time period. Secondary objectives were determining trends in patterns of care and predictors of utilization. METHODS: Population-based, observational, comparative effectiveness study used Surveillance, Epidemiology, and End Results-18 data from 2000 to 2010. The main outcome measure was 2-year risk of death for stage I NSCLC. RESULTS: Between 2000 and 2010, 40,589 patients (62%) underwent surgery, 10,048 (15%) received RT, 2,130 (3%) received both surgery and RT, and 11,537 (18%) received neither surgery nor RT. Annually, the odds of receiving either definitive RT or undergoing surgery increased relative to the odds of receiving no treatment (odds ratio [OR] radiation 1.04, 95% confidence interval [CI]: 1.03 to 1.05; OR surgery 1.05, 95% CI: 1.04 to 1.05). Among surgical patients, the proportion of sublobar resections steadily increased from 12.9% to 17.9%. For all patients, the 2-year risk of death decreased by 3.5% each year (hazard ratio [HR] 0.965, 95% CI: 0.962 to 0.969), driven primarily by improved survival for surgical (annualized HR 0.959, 95% CI: 0.954 to 0.964) and RT (annualized HR 0.942, 95% CI: 0.935 to 0.949) patients. CONCLUSIONS: Between 2000 and 2010, stage I NSCLC patients were more likely to receive definitive treatment with either surgery or RT, leading to a decline in the number of untreated patients. Survival also improved substantially for stage I NSCLC patients, with the largest survival improvements observed in patients undergoing definitive RT.

Miscoding of Melanoma Thickness in SEER: Research and Clinical Implications.

Melanoma-related deaths and metastases among patients with thin (≤1 mm) and ultrathin (≤0.25 mm) melanomas have been reported. These observations might reflect adverse biology and/or errors in administrative data. Cumulative melanoma-related death rates for thickness groups of patients with thin melanomas were compared among five cohorts including the Surveillance, Epidemiology, and End Results (SEER) registry. Thickness in one SEER region was reexamined in pathology reports. The 5-year cumulative melanoma-related death rate of patients with ultrathin melanomas was higher in SEER (2.8%) compared with other registries (0.6-0.9%). The rates across the 16 SEER regions were 0.25% to 8.4%. In SEER, 21% of thin melanomas were ultrathin; in other registries, they comprised 5.8-15%. A reexamination of thickness in one SEER site revealed that 114 of 447 ultrathin melanomas had errors; after correction, only 17 of the 114 remained ultrathin. The majority of errors were related to decimal point placement. The 86 thin melanomas reclassified to >1.00 mm included 96% of the original ultrathin-associated deaths and 100% of the original positive lymph nodes. Significant miscoding of thickness that is concentrated in ultrathin lesions is present in SEER and results in mischaracterization of patient outcomes. When using administrative data, validation of results can identify critical data issues.

Risk of brain metastases in patients with nonmetastatic lung cancer: Analysis of the Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) data.

BACKGROUND: Brain metastases (BM) remain an important cause of morbidity and mortality in patients with lung cancer. The current study evaluated population-based incidence and outcomes of BM in patients with nonmetastatic lung cancer. METHODS: Patients diagnosed with nonmetastatic first primary lung cancer between 1973 and 2011 in the Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry were used for the current analysis. Age-adjusted odds ratios of developing BM based on various demographic characteristics and histology were calculated with 95% confidence intervals. Adjusted Cox proportional hazard ratios and log-rank tests of Kaplan-Meier survival curves were calculated to evaluate survival differences for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). RESULTS: The incidence of BM in patients with nonmetastatic NSCLC and SCLC was 9% and 18%, respectively. There was variation in the incidence of BM according to NCSLC histology. The incidence of BM was higher in patients aged <60 years for both NSCLC and SCLC, but there were no differences noted by race for either histological group. Female patients with NSCLC were more likely to have BM than male patients. There was variation in the proportion of BM in both patients with NSCLC and SCLC over the three 13-year periods of diagnosis. The risk of death (hazard ratio) was found to be significantly higher for patients with NSCLC with BM, but was not significantly higher in patients with SCLC with BM. CONCLUSIONS: The incidence of BM in patients with nonmetastatic lung cancer varies according to histology, age, and sex. BM are associated with worse survival for patients with NSCLC but not those with SCLC. Cancer 2016;122:1921-7. © 2016 American Cancer Society.

Reducing prostate cancer racial disparity: evidence for aggressive early prostate cancer PSA testing of African American men.

BACKGROUND: There is continuing controversy about prostate cancer testing and the recent American Urological Association guidelines. We hypothesize that the reduction and elimination of racial survival disparity among African American men (AAM; high-risk group) compared with European American men (EAM; intermediate-risk group) during the PSA testing era compared with the pre-PSA era strongly supports the use of PSA testing in AAM. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) data to investigate relative survival disparities between AAM and EAM. To evaluate pre-PSA testing era, we selected malignant first primary prostate cancer in AAM and EAM, all stages, diagnosed during 1973-1994. To evaluate relative survival disparities in the current PSA testing era, we selected malignant first primary local, regional, and distant stage prostate cancers diagnosed during 1998-2005 to calculate 5-year relative survival rates. RESULTS: Age-adjusted 5-year relative survival of prostate cancer diagnosed during 1973-1994 in the national SEER data revealed significantly shorter survival for AAM compared with EAM (P < 0.0001). The SEER-based survival analysis from 1995 to 2005 indicated no statistical difference in relative survival rates between AAM and EAM by year of diagnosis of local, regional, or distant stage prostate cancer. CONCLUSION: We conclude that the elimination of prostate cancer racial disparity of local, regional, and metastatic prostate cancer relative survival in the current PSA testing era compared with pre-PSA era as an endpoint to test PSA efficacy as a marker for prostate cancer diagnosis is evidence for aggressive testing of AAM. IMPACT: Evidence for screening AAM.

The effect of targeted therapy on overall survival in advanced renal cancer: a study of the national surveillance epidemiology and end results registry database.

INTRODUCTION: With the advent and availability of targeted therapy, the treatment of advanced/metastatic renal cell carcinoma (RCC) underwent a drastic change in 2005. The effect of this change on clinical outcome within the population has not been studied. The aim of this study was to evaluate the overall survival (OS), before, and after availability of targeted therapy, for advanced RCC cases in the population-based Surveillance, Epidemiology, and End Results (SEER) cancer registry. MATERIALS AND METHODS: All advanced (regional and distant stage) RCC cases diagnosed within the 2000 to 2008 time periods were included. Because SEER does not report the exact therapy, and because targeted therapy was initially approved in 2005, we evaluated and compared the OS outcomes of advanced RCC cases diagnosed between the years 2000 and 2003 (before targeted therapy era) with that of those diagnosed between 2005 and 2008 (targeted therapy era). RESULTS: There was a significant improvement in OS for advanced RCC patients treated in the targeted therapy era (n = 12,330) compared with those treated in the era before targeted therapy (n =11,565) (median OS 20 months vs. 15 months, P = .0006). Multivariate analysis revealed that in the time period before targeted therapy, age older than 65 years, black race, and lack of nephrectomy were predictors of a shorter OS. CONCLUSION: In univariate and multivariate analysis, targeted therapy demonstrated improvement in OS. Increasing access to targeted therapies is likely to improve outcomes in advanced RCC.

The epidemiology and pathogenesis of neoplasia in the small intestine.

PURPOSE: The mucosa of the small intestine encompasses about 90% of the luminal surface area of the digestive system, but only 2% of the total annual gastrointestinal cancer incidence in the United States. METHODS: The remarkable contrast in age-standardized cancer incidence between the small and large intestine has been reviewed with respect to the cell type patterns, demographic features, and molecular characteristics of neoplasms. RESULTS: Particularly noteworthy is the predominance of adenocarcinoma in the colon, which exceeds 98% of the total incidence by cell type, in contrast to that of 30% to 40% in the small intestine, resulting in an age-standardized ratio of rates exceeding 50-fold. The prevalence of adenomas and carcinomas is most prominent in the duodenum and proximal jejunum. The positive correlation in global incidence rates of small and large intestinal neoplasms and the reciprocal increases in risk of second primary adenocarcinomas suggest that there are common environmental risk factors. The pathophysiology of Crohn inflammatory bowel disease and the elevated risk of adenocarcinoma demonstrate the significance of the impaired integrity of the mucosal barrier and of aberrant immune responses to luminal indigenous and potentially pathogenic microorganisms. CONCLUSION: In advancing a putative mechanism for the contrasting mucosal susceptibilities of the small and large intestine, substantial differences are underscored in the diverse taxonomy, concentration and metabolic activity of anaerobic organisms, rate of intestinal transit, changing pH, and the enterohepatic recycling and metabolism of bile acids. Experimental and epidemiologic studies are cited that suggest that the changing microecology, particularly in the colon, is associated with enhanced metabolic activation of ingested and endogenously formed procarcinogenic substrates.

Risk of other cancers in individuals with a family history of pancreas cancer.

BACKGROUND: Inherited predisposition to pancreas cancer accounts for approximately 10% of cases. Familial aggregation may be influenced by shared environmental factors and shared genes. We evaluate whether a family history of pancreas cancer is a risk factor for ten specified cancers in first-degree relatives: bladder, breast, colon, head and neck, lung, lymphoma, melanoma, ovary, pancreas, and prostate. METHODS: Risk factor data and cancer family history were obtained for 1,816 first-degree relatives of pancreas cancer case probands (n = 247) and 3,157 first-degree relatives of control probands (n = 420). Unconditional logistic regression models using generalized estimating equations were used to estimate odds ratios (ORs), and 95% confidence intervals of having a first-degree relative a specified cancer. RESULTS: A family history of pancreas cancer was associated with a doubled risk of lymphoma (OR = 2.83, 95% CI = 1.02-7.86) and ovarian cancer (OR = 2.25, 95% CI = 0.77-6.60) among relatives after adjustment. Relatives with a family history of early-onset pancreas cancer in a proband had a sevenfold increased risk of lymphoma (OR = 7.31, 95% CI = 1.45 to 36.7). Relatives who ever smoked and had a family history of pancreas cancer had a fivefold increased risk of ovarian cancer (OR = 4.89, 95% CI = 1.16-20.6). CONCLUSION: Family history assessment of cancer risk should include all cancers. Assessment of other known and suspected risk factors in relatives will improve risk evaluation. As screening and surveillance methods are developed, identifying those at highest risk is crucial for a successful screening program.

Racial differences in breast cancer survival in the Detroit Metropolitan area.

African American (AA) women have poorer breast cancer survival compared to Caucasian American (CA) women. The purpose of this analysis was to determine whether socioeconomic status (SES) and treatment differences influence racial differences in breast cancer survival. The study population included 9,321 women (82% CA, 18% AA) diagnosed with local (63%) or regional (37%) stage disease between 1988 and 1992, identified through the Metropolitan Detroit SEER registry. Data on SES were obtained through linkage with the 1990 Census of Population and Housing Summary Tape and cases were geocoded to census block groups. Pathology, treatment and survival data were obtained through SEER. Cox proportional hazards models were used to compare survival for AA versus CA women after adjusting for age, SES, tumor size, number of involved lymph nodes, and treatment. AA women were more likely to live in a geographic area classified as working poor than were CA women (p<0.001). AA women were less likely to have lumpectomy and radiation and more likely to have mastectomy with radiation (p<0.001). After multivariable adjusted analysis, there were no significant racial differences in survival among women with local stage disease, although AA women with regional stage disease had persistent but attenuated poorer survival compared to CA women. After adjusting for known clinical and SES predictors of survival, AA and CA women who are diagnosed with local disease demonstrate similar overall and breast cancer-specific survival, while race continues to have an independent effect among women presenting at a later stage of disease.

Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System.

PURPOSE: Population-based estimates of the incidence of brain metastases are not generally available. The purpose of this study was to calculate population-based incidence proportions (IPs) of brain metastases from single primary lung, melanoma, breast, renal, or colorectal cancer. PATIENTS AND METHODS: Patients diagnosed with single primary lung, melanoma, breast, renal, or colorectal cancer (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System (MDCSS) were used for analysis. IP of brain metastases by primary site and variable of interest (race, sex, age at diagnosis of primary cancer, and Surveillance, Epidemiology, and End Results [SEER] stage of primary cancer) was calculated with 95% CIs. RESULTS: Total IP percentage (IP%) of brain metastases was 9.6% for all primary sites combined, and highest for lung (19.9%), followed by melanoma (6.9%), renal (6.5%), breast (5.1%), and colorectal (1.8%) cancers. Racial differences were seen with African Americans demonstrating higher IP% of brain metastases compared with other racial groups for most primary sites. IP% was significantly higher for female patients with lung cancer, and significantly higher for male patients with melanoma. The highest IP% of brain metastases occurred at different ages at diagnoses: age 40 to 49 years for primary lung cancer; age 50 to 59 years for primary melanoma, renal, or colorectal cancers; and age 20 to 39 for primary breast cancer. IP% significantly increased as SEER stage of primary cancer advanced for all primary sites. CONCLUSION: Total IP% of brain metastases was lower than previously reported, and it varied by primary site, race, sex, age at diagnosis of primary cancer, and SEER stage of primary cancer.

Race, socioeconomic status and stage at diagnosis for five common malignancies.

BACKGROUND: African-Americans are more likely than Caucasians to be diagnosed at an advanced stage of colorectal, lung, breast, cervical, and prostate cancers. This study explores if racial differences in stage at diagnosis can be explained by socioeconomic status (SES) differences. Previous studies investigating this association have used aggregate SES indicators from census tract of residence; we used census block-group data, representing a smaller, potentially more homogenous group. METHODS: We included all African-American and Caucasian invasive cancers of the colon and rectum, lung and bronchus, female breast, cervix uteri, and prostate that were diagnosed between January 1, 1988 and December 31, 1992 in the Detroit area. Stage of disease at diagnosis was grouped as local or non-local. An SES value was calculated for each case using aggregate 1990 US Census data for education, poverty status, and occupation specific to each case's census block-group. Logistic regression analysis was used to model the probability of non-local stage using SES, race, age group, and sex as covariates. RESULTS: SES was an independent predictor of stage at diagnosis for each cancer site, with cases from the highest SES block-group more likely to present with local stage disease than those from the lowest SES group. Race independently predicted stage only for breast and prostate cancers; African-Americans presented with more advanced stage than Caucasians. CONCLUSIONS: Based on census block-group aggregate data, SES is an important predictor of stage at diagnosis, most likely accounting for much of the disparity in stage between African-Americans and Caucasians for colorectal, lung, and cervical cancers. Biological factors may play a role in racial disparities for breast and prostate cancer stage at diagnosis.