Feng Miao

Survival disparities in non-small cell lung cancer by race, ethnicity, and socioeconomic status.

PurposeNon–small cell lung cancer (NSCLC) is among the leading causes of cancer death in the United States. Previous studies found mixed results regarding disparities in survival by race, ethnicity, and socioeconomic status (SES). However, race comparisons were usually limited, with comparisons made between black and white patients only or by merging race and ethnicity together as non-Hispanic black, non-Hispanic white, and Hispanic patients. Even fewer studies included race, ethnicity, and SES together while controlling for extensive confounding variables. Thus, because we have access to a large and unique population-based database that includes tumor characteristics and patient comorbidities, the purpose of this study was to explore disparities in NSCLC survival. MethodsWe linked data from the 1996 to 2007 Florida Cancer Data System registry to the Florida’s Agency for Health Care Administration and the US Census (n = 98,541). Survival time was from date of diagnosis to death or last contact. Race was white, black, Native American, Asian, Pacific Islander, Asian Indian/Pakistani, or other. Ethnicity was non-Hispanic or Hispanic. Socioeconomic status was measured as percentage of the participant’s census tract living below the federal poverty line. Median survival and survival rates were calculated by Kaplan-Meier method. Cox proportional hazards regression models produced unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). ResultsThe majority of patients were white (91.9%) and non-Hispanic (94.1%). Blacks had the lowest median survival (8.4 months). At 5 years after diagnosis, survival rate was highest in whites (16.3%) and lowest for Pacific Islanders (6.4%). In the adjusted model, Asians had significantly improved survival compared with whites (HR, 0.85; 95% CI, 0.76–0.95). Patients in middle-low (HR, 0.96; 95% CI, 0.94–0.99), middle-high (HR, 0.92; 95% CI, 0.89–0.94), and highest (HR, 0.87; 95% CI, 0.84–0.91) SES areas had significantly improved survival compared with those in lowest areas. Significantly worse survival was found for patients with complicated diabetes (HR, 1.05; 95% CI, 1.01–1.08), weight loss (HR, 1.08; 95% CI, 1.06–1.11), fluid and electrolyte disorders (HR, 1.08; 95% CI, 1.06–1.11), and alcohol abuse (HR, 1.11; 95% CI, 1.07–1.14). DiscussionWe found strong evidence for racial and socioeconomic disparities in Floridian NSCLC survival. Asians had improved survival compared with whites, a novel finding. Our findings confirmed that patients living in lower socioeconomic neighborhoods have worse outcomes than their wealthier neighborhood counterparts. Finally, we found an association between some modifiable factors/comorbidities and worse survival. Clinicians may be able to use this information to improve patients’ likelihood of better outcomes.

Breast cancers from black women exhibit higher numbers of immunosuppressive macrophages with proliferative activity and of crown-like structures associated with lower survival compared to non-black Latinas and Caucasians

Abstract Racial disparities in breast cancer incidence and outcome are a major health care challenge. Patients in the black race group more likely present with an early onset and more aggressive disease. The occurrence of high numbers of macrophages is associated with tumor progression and poor prognosis in solid malignancies. Macrophages are observed in adipose tissues surrounding dead adipocytes in “crown-like structures” (CLS). Here we investigated whether the numbers of CD163+ tumor-associated macrophages (TAMs) and/or CD163+ CLS are associated with patient survival and whether there are significant differences across blacks, non-black Latinas, and Caucasians. Our findings confirm that race is statistically significantly associated with the numbers of TAMs and CLS in breast cancer, and demonstrate that the highest numbers of CD163+ TAM/CLS are found in black breast cancer patients. Our results reveal that the density of CD206 (M2) macrophages is a significant predictor of progression-free survival univariately and is also significant after adjusting for race and for HER2, respectively. We examined whether the high numbers of TAMs detected in tumors from black women were associated with macrophage proliferation, using the Ki-67 nuclear proliferation marker. Our results reveal that TAMs actively divide when in contact with tumor cells. There is a higher ratio of proliferating macrophages in tumors from black patients. These findings suggest that interventions based on targeting TAMs may not only benefit breast cancer patients in general but also serve as an approach to remedy racial disparity resulting in better prognosis patients from minority racial groups.

Factors associated with contralateral preventive mastectomy

Introduction Contralateral prophylactic mastectomy (CPM) is an option for women who wish to reduce their risk of breast cancer or its local recurrence. There is limited data on demographic differences among patients who choose to undergo this procedure. Methods The population-based Florida cancer registry, Florida’s Agency for Health Care Administration data, and US census data were linked and queried for patients diagnosed with invasive breast cancer from 1996 to 2009. The main outcome variable was the rate of CPM. Primary predictors were race, ethnicity, socioeconomic status (SES), marital status and insurance status. Results Our population was 91.1% White and 7.5% Black; 89.1% non-Hispanic and 10.9% Hispanic. Out of 21,608 patients with a single unilateral invasive breast cancer lesion, 837 (3.9%) underwent CPM. Significantly more White than Black (3.9% vs 2.8%; P<0.001) and more Hispanic than non-Hispanic (4.5% vs 3.8%; P=0.0909) underwent CPM. Those in the highest SES category had higher rates of CPM compared to the lowest SES category (5.3% vs 2.9%; P<0.001). In multivariate analyses, Blacks compared to Whites (OR =0.59, 95% CI =0.42–0.83, P=0.002) and uninsured patients compared to privately insured (OR =0.60, 95% CI =0.36–0.98, P=0.043) had significantly less CPM. Conclusion CPM rates were significantly different among patients of different race, socio-economic class, and insurance coverage. This observation is not accounted for by population distribution, incidence or disease stage. More in-depth study of the causes of these disparities in health care choice and delivery is critically needed.

The Modern Role of Radiation Therapy in Treating Advanced-Stage Retinoblastoma: Long-Term Outcomes and Racial Differences

PURPOSE/OBJECTIVE(S) To evaluate the effects of various patient characteristics and radiation therapy treatment variables on outcomes in advanced-stage retinoblastoma. METHODS AND MATERIALS This was a retrospective review of 41 eyes of 30 patients treated with external beam radiation therapy between June 1, 1992, and March 31, 2012, with a median follow-up time of 133 months (11 years). Outcome measures included overall survival, progression-free survival, local control, eye preservation rate, and toxicity. RESULTS Over 90% of the eyes were stage V. Definitive external beam radiation therapy (EBRT) was delivered in 43.9% of eyes, adjuvant EBRT in 22% of eyes, and second-line/salvage EBRT in 34.1% of eyes. A relative lens sparing (RLS) technique was used in 68.3% of eyes and modified lens sparing (MLS) in 24.4% of eyes. Three eyes were treated with other techniques. Doses ≥45 Gy were used in 68.3% of eyes. Chemotherapy was a component of treatment in 53.7% of eyes. The 10-year overall survival was 87.7%, progression-free survival was 80.5%, and local control was 87.8%. White patients had significantly better overall survival than did African-American patients in univariate analysis (hazard ratio 0.09; 95% confidence interval 0.01-0.84; P=.035). Toxicity was seen in 68.3% of eyes, including 24.3% with isolated acute dermatitis. CONCLUSIONS External beam radiation therapy continues to be an effective treatment modality for advanced retinoblastoma, achieving excellent long-term local control and survival with low rates of treatment-related toxicity and secondary malignancy.

Phase II study of (90)Y Ibritumomab tiuxetan (Zevalin) in patients with previously untreated marginal zone lymphoma.

Abstract The best upfront therapy for patients with non-gastric extranodal marginal zone lymphomas (MZLs) is not defined. We assessed the safety and efficacy of radioimmunotherapy with 90yttrium (90Y) ibritumomab tiuxetan as upfront therapy in MZL (NCT00453102). A total of 16 patients were enrolled, 81% with advanced-stage disease and 44% with bulky disease. The overall response rate (ORR) at 12 weeks post-therapy was 87.5% (90% confidence interval [CI]: 65.6–97.7%), including a complete response in eight (50%), complete response unconfirmed in one (6%) and partial response in five (31%) patients. With a median follow-up of 65.6 months (range 4.0–96.5), the median progression-free survival (PFS) was 47.6 months (range 4.0–93.3) and median overall survival (OS) was not reached. The 5-year PFS was 40% (90% CI: 19.9–59.5%) and 5-year OS was 71.8% (90% CI: 46.8–86.5%). Overall, 90Y ibritumomab tiuxetan was well tolerated and led to long-term responses and PFS rates.

Macrophages as independent prognostic factors in small T1 breast cancers

Breast cancer is the second leading cause of death by cancer in women in the United States. The occurrence of high numbers of macrophages in the tumor stroma has been associated with tumor progression and poor prognosis in breast and other solid malignancies. However, macrophage numbers in tumors have not been validated as a prognostic factor in clinical practice. The present analysis was designed as a pilot study aimed at determining whether the presence of CD68+ macrophages is an independent prognostic factor in small T1 estrogen receptor (ER)+ breast cancers across three different ethnic groups, i.e. African-American, Latina and Caucasian women. A retrospective pilot analysis of 30 T1 breast cancer cases encompassing these three ethnic groups was carried out. African-American and Latina women present with less incidence but more aggressive breast cancer disease and, therefore, proportionally higher death rates. Using immuno-histochemistry, we sought to identify whether there was any association between the presence and density of CD68+ macrophages and standard prognostic markers with overall survival in these groups. Our data revealed that overall survival did not differ significantly for the occurrence or density of CD68+ macrophages in T1 ER+ tumors. There were also no significant differences in overall survival for the occurrence of CD68+ macrophages across ethnicities, although macrophage numbers were significantly higher in tumors from African-American and Latina than in Caucasian patients. Importantly, but not surprisingly, the absence of the progesterone receptor was associated very strongly with decreased overall survival. This pilot project shows that CD68+ macrophages are not pivotal in determining tumor prognosis in early T1 breast cancers. New studies are presently being conducted to assess the value of different macrophage markers and macrophage activation profiles as prognostic factors in breast cancers of different clinical stages, using a larger number of patients among these three different ethnicities.

Cancer-testis antigen expression is shared between epithelial ovarian cancer tumors

OBJECTIVES Cancer-testis (CT) antigens have been proposed as potential targets for cancer immunotherapy. Our objective was to evaluate the expression of a panel of CT antigens in epithelial ovarian cancer (EOC) tumor specimens, and to determine if antigen sharing occurs between tumors. METHODS RNA was isolated from EOC tumor specimens, EOC cell lines and benign ovarian tissue specimens. Real time-PCR analysis was performed to determine the expression level of 20 CT antigens. RESULTS A total of 62 EOC specimens, 8 ovarian cancer cell lines and 3 benign ovarian tissues were evaluated for CT antigen expression. The majority of the specimens were: high grade (62%), serous (68%) and advanced stage (74%). 58 (95%) of the EOC tumors analyzed expressed at least one of the CT antigens evaluated. The mean number of CT antigen expressed was 4.5 (0-17). The most frequently expressed CT antigen was MAGE A4 (65%). Antigen sharing analysis showed the following: 9 tumors shared only one antigen with 62% of the evaluated specimens, while 37 tumors shared 4 or more antigens with 82%. 5 tumors expressed over 10 CT antigens, which were shared with 90% of the tumor panel. CONCLUSION CT antigens are expressed in 95% of EOC tumor specimens. However, not a single antigen was universally expressed across all samples. The degree of antigen sharing between tumors increased with the total number of antigens expressed. These data suggest a multi-epitope approach for development of immunotherapy for ovarian cancer treatment.

Marital status and its effect on lung cancer survival

PurposeThe purpose of this study was to determine if marital status, including specific types of single status categories, is associated with length of survival in lung cancer patients.MethodsData from the 1996–2007 Florida Cancer Data System were linked with Agency for Health Care Administration data and U.S. Census data. Patients with both small cell and non-small cell lung cancer were identified (n = 161,228). Marital status was characterized by married, widowed, separated/divorced, and never married. We compared median survival time and 1, 3, and 5-year post diagnosis survival rates.ResultsOverall, 54.6% were married, 19.1% were widowed, 13.5% were separated/divorced, and 12.7% had never married. Median survival in months was longest for married (9.9) and widowed (7.7) patients, and shortest for never married (4.9) and separated/divorced (4.1) patients. Five-year survival rates were 14.2% for married, 10.7% for widowed, 8.9% for separated/divorced, and 8.4% for never married. In univariate Cox regression, marital status was a significant predictor of better survival for married (HR = 0.70; p < 0.001) and widowed (HR = 0.81; p < 0.001) patients compared with never married patients, but worse for separated/divorced patients (HR = 1.03; p = 0.003). Multivariate models demonstrated sustained survival benefits for married (HR = 0.86; p < 0.001) and widowed (HR = 0.88; p < 0.001) patients, and detriments for separated/divorced patients (HR = 1.05; p < 0.001) after adjusting for extensive confounders including demographics; tumor stage, grade, and morphology; comorbidities; treatment; and smoking status.ConclusionsOur study demonstrated that married or widowed lung cancer patients have better survival compared to patients who were never married or separated/divorced. Research to understand the mechanism of this effect, and how the beneficial effect can be extended to those who have never married or have had the marital relationship severed through divorce or separation is needed.

Trends in Utilization of Robotic and Open Partial Nephrectomy for Management of cT1 Renal Masses

BACKGROUND Partial nephrectomy is widely used for surgical management of small renal masses. Use of robotic (RPN) versus open partial nephrectomy (OPN) among various populations is not well characterized. OBJECTIVE To analyze trends in utilization of RPN and disparities that may be associated with this procedure for management of cT1 renal masses in the USA. DESIGN, SETTING, AND PARTICIPANTS Patients who underwent RPN or OPN for clinical stage T1N0M0 renal masses in the USA from 2010 to 2013 were identified in the National Cancer Data Base. A total of 23 154 patients fulfilled the inclusion criteria. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariable and multivariable logistic regression analyses were performed to evaluate differences in receiving RPN or OPN across various patient groups. RESULTS AND LIMITATIONS Utilization of RPN increased from 41% in 2010 to 63% in 2013. Black patients (adjusted odds ratio [aOR] 0.91, 95% confidence interval [CI] 0.84-0.98) and Hispanic patients (aOR 0.85, 95% CI 0.77-0.95) were less likely to undergo RPN. RPN was less likely to be performed in rural counties (aOR 0.80, 95% CI 0.66-0.98) and in patients with no insurance (aOR 0.52, 95% CI 0.44-0.61) or patients covered by Medicaid (aOR 0.81, 95% CI 0.73-0.90). There was no significant difference in RPN utilization between academic and non-academic facilities. Patients with higher clinical stage (aOR 0.58, 95% CI 0.55-0.62) and comorbidities (aOR 0.79, 95% CI 0.71-0.88) were also less likely to undergo RPN. CONCLUSIONS Utilization of RPN has continued to increase over time; however, there are significant disparities in its utilization according to race and socioeconomic status. Black and Hispanic patients and patients in rural communities and with limited insurance were more likely to be treated with OPN instead of RPN. PATIENT SUMMARY The use of robotic surgery in partial nephrectomy for management of small renal masses has increased over time. We found a significant disparity across different racial and socioeconomic groups in use of robotic partial nephrectomy compared to open surgery. Patients living in rural areas, with limited insurance, and multiple medical comorbidities were more likely to undergo open than robotic partial nephrectomy.

Predictors of Surgery Types after Neoadjuvant Therapy for Advanced Stage Breast Cancer: Analysis from Florida Population-Based Cancer Registry (1996-2009).

Purpose Despite the established guidelines for breast cancer treatment, there is still variability in surgical treatment after neoadjuvant therapy (NT) for women with large breast tumors. Our objective was to identify predictors of the type of surgical treatment: mastectomy versus breast-conserving surgery (BCS) in women with T3/T4 breast cancer who received NT. Methods Population-based Florida Cancer Data System Registry, Floridas Agency for Health Care Administration, and US census from 1996 to 2009 were linked for women diagnosed with T3/T4 breast cancer and received NT followed by either BCS or mastectomy. Analysis of multiple variables, such as sociodemographic characteristics (race, ethnicity, socioeconomic status, age, marital status, and urban/rural residency), tumors characteristics (estrogen/progesterone receptor status, histology, grade, SEER stage, and regional nodes positivity), treatment facilities (hospital volume and teaching status), patients’ comorbidities, and type of NT, was performed. Results Of 1,056 patients treated with NT for T3/T4 breast cancer, 107 (10%) had BCS and 949 (90%) had mastectomy. After adjusting with extensive covariables, Hispanic patients (adjusted odds ratio (aOR) = [3.50], 95% confidence interval (CI): 1.38–8.84, P = 0.008) were more likely to have mastectomy than BCS. Compared to localized SEER stage, regional stage with direct extension (aOR = [3.24], 95% CI: 1.60–6.54, P = 0.001), regional stage with direct extension and nodes (aOR = [4.35], 95% CI: 1.72–11.03, P = 0.002), and distant stage (aOR = [4.44], 95% CI: 1.81–10.88, P = 0.001) were significantly more likely to have mastectomy than BCS. Compared to patients who received both chemotherapy and hormonal therapy, patients who received hormonal NT only (aOR = [0.29], 95% CI: 0.12–0.68, P = 0.004) were less likely to receive mastectomy. Conclusion Our study suggests that Hispanic ethnicity, advanced SEER stage, and type of NT are significant predictors of receiving mastectomy after NT.