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Background: We examined the impact of race/ethnicity and age on survival in a publicly insured cohort of children and adolescent/young adults (AYA; 15–39 years) with Hodgkin lymphoma, adjusting for...

PURPOSE: African men are disproportionately affected by prostate cancer (PCa). Given the increasing prevalence of obesity in Africa, and its association with aggressive PCa in other populations, we examined the relationship of overall and central obesity with risks of total and aggressive PCa among African men. METHODS: Between 2016 and 2020, we recruited 2,200 PCa cases and 1,985 age-matched controls into a multicenter, hospital-based case-control study in Senegal, Ghana, Nigeria, and South Africa. Participants completed an epidemiologic questionnaire, and anthropometric factors were measured at clinic visit. Multivariable logistic regression was used to examine associations of overall and central obesity with PCa risk, measured by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), respectively. RESULTS: Among controls 16.4% were obese (BMI≥30 kg/m(2)), 26% and 90% had WC>97 cm and WHR>0.9, respectively. Cases with aggressive PCa had lower BMI/obesity in comparison to both controls and cases with less aggressive disease, suggesting weight loss related to cancer. Overall obesity (odds ratio: OR=1.38, 95%CI 0.99–1.93), and central obesity (WC>97cm: OR=1.60, 95%CI 1.10-2.33; and WHtR >0.59: OR=1.68, 95%CI 1.24-2.29) were positively associated with D’Amico intermediate-risk PCa, but not with risks of total or high-risk PCa. Associations were more pronounced in West versus South Africa, but these differences were not statistically significant. DISCUSSION: The high prevalence of overall and central obesity in African men and their association with intermediate-risk PCa represent an emerging public health concern in Africa. Large cohort studies are needed to better clarify the role of obesity and PCa in various African populations.

Purpose Breast cancer outcomes in sub-Saharan Africa is reported to be poor, with an estimated five-year survival of 50% when compared to almost 90% in high-income countries. Although several studies have looked at the effect of HIV in breast cancer survival, the effect of ARTs has not been well elucidated. Methods All females newly diagnosed with invasive breast cancer from May 2015–September 2017 at Charlotte Maxeke Johannesburg Academic and Chris Hani Baragwanath Academic Hospital were enrolled. We analysed overall survival and disease-free survival, comparing HIV positive and negative patients. Kaplan-Meier survival curves were generated with p-values calculated using a log-rank test of equality while hazard ratios and their 95% confidence intervals (CIs) were estimated using Cox regression models. Results Of 1019 patients enrolled, 22% were HIV positive. The overall survival (95% CI) was 53.5% (50.1–56.7%) with a disease-free survival of 55.8% (52.1–59.3) after 4 years of follow up. HIV infection was associated with worse overall survival (HR (95% CI): 1.50 (1.22–1.85), p, Highlights • 22% of participants were HIV positive. • The 4 years overall survival was 53.5%. • The 4 years disease-free survival was 55.8%. • HIV infection was associated with poor overall and disease-free survival. • ART use was associated with better overall and disease-free survival.

PURPOSE: Advanced breast cancer (BC) at diagnosis is common in sub-Saharan Africa (SSA), including among women living with HIV (WLWH). In public hospitals across South Africa (SA), 10–15% of women present with stage IV BC, compared to

We evaluated the prognostic ability of immunohistochemistry (IHC)-based vs. PAM50-based subtypes for breast cancer mortality in a population-based study of breast cancer. We included a total of 463 breast cancer cases from the population-based Long Island Breast Cancer Study Project (LIBCSP). IHC-based markers were abstracted from the medical records, while the PAM50-based intrinsic subtypes were assessed from tumor tissues using NanoString nCounter® Analysis System. Cox proportional hazards models were used to estimate hazards ratios (HRs) for breast cancer-specific mortality associated with subtypes. For IHC-based hormone receptor-positive (HR+) tumors (n = 361), 68.7% were classified as luminal subtypes by PAM50; for HR− tumors (n = 102), 95.1% were classified as non-luminal subtypes. Compared to HR+/HER2− subtype, HR− patients had significantly higher breast cancer mortality (HR−/HER2+: HR = 2.84, 95% CI = 1.58–5.11; triple-negative breast cancer: HR = 2.42, 95% CI = 1.44–4.06). Compared to luminal A, a higher mortality rate was observed for all other PAM50-based subtypes: luminal B (HR = 4.03, 95% CI = 1.97–8.22), HER2-enriched (HR = 6.82, 95% CI = 3.29–14.14) and basal-like (HR = 4.71, 95% CI = 2.24–9.93). Additional subtyping of HR+ patients by PAM50 provided future risk stratification where luminal B patients in this group had significant higher mortality than luminal A patients (HR = 3.93, 95% CI = 1.92–8.03). Similar results were also observed among 291 HR+/HER2− patients, but not among the HR− patients. Our study suggests that for HR+ patients, especially HR+/HER2− patients, additional PAM50-based subtyping would provide better prognostic stratification and improve disease management.

Recent trends in cancer epidemiology in low- and middle-income countries show the need for urgent action. This article focuses on sub-Saharan Africa, where populations are showing an increased risk for diseases associated with the Western lifestyle, including cancer.

PURPOSE: Among patients diagnosed with breast cancer (BC), women also living with HIV (WLWH) have worse survival than women without HIV. Chronic HIV infection may interfere with the effectiveness of BC treatment, contributing to this disparity. We attempted to determine the impact of HIV infection on response to neoadjuvant chemotherapy (NACT) among South African women with BC. METHODS: We evaluated women from the South African Breast Cancer and HIV Outcomes cohort study who had stage I-III disease, initiated NACT, underwent definitive breast surgery, and had available surgical pathology reports. We compared pathologic complete response (pCR) rates among women with and without HIV infection, using multivariable logistic regression to control for differences in tumor characteristics. We also evaluated the impact of HIV-infection on pCR within subgroups based on patient, tumor and treatment factors. RESULTS: Of 715 women, the 173 (24.2%) WLWH were less likely to achieve pCR than women without HIV (8.7% vs 16.4%, (odds ratio (OR) 0.48, 95% confidence interval (95%CI) 0.27–0.86). WLWH continued to have lower likelihood of achieving pCR on multivariable analysis (OR 0.52, 95%CI 0.28–0.98). A similar pattern was seen within subgroups, although HIV infection appeared to affect pCR more in ER/PR positive BC (OR 0.24, 95%CI 0.08–0.71) than in ER/PR negative BC (OR 0.94, 95%CI 0.39–2.29). CONCLUSION: WLWH were less like to achieve pCR following NACT for BC than women without HIV. This reduced response to systemic therapy may contribute to the poorer BC outcomes seen in WLWH.

Previous studies have observed a reduced mortality risk associated with menopausal hormone therapy (MHT) use among breast cancer survivors. We sought to clarify whether such association could be explained by tumor heterogeneity, specific causes of death, confounding from comorbidities or health behaviors, and a comparison group of women without breast cancer. We interviewed 1508 women newly diagnosed with first primary breast cancer in 1996 to 1997 (~3 months after diagnosis), and 1556 age-matched women without breast cancer, about MHT use history. The National Death Index was used to ascertain vital status after a median of 17.6 years of follow-up (N = 597 deaths for breast cancer subjects). Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality, and cause-specific HR (cHR) for breast cancer and cardiovascular disease (CVD). The Fine-Gray model was used to account for competing causes of death. Among women with breast cancer, ever vs never MHT use was inversely associated with all-cause (HR = 0.77, 95%CI = 0.62-0.95), breast cancer-specific (cHR = 0.69, 95%CI = 0.48-0.98), and CVD-specific mortality (cHR = 0.57, 95%CI = 0.38-0.85). Difference of the association was observed in breast cancer-specific mortality according to hormone receptor status (negative tumors: cHR = 0.44, 95%CI = 0.19-1.01; positive tumors: cHR = 0.96, 95%CI = 0.60-1.53). Among the comparison group, we observed similar, but more modest inverse associations for all-cause and CVD-specific mortality. MHT use was inversely associated with mortality after breast cancer, even after accounting for competing causes of death and multiple confounders, and was evident among women without breast cancer. Potential heterogeneity by hormone receptor status requires more study.

Background: Non-adherence to aromatase inhibitors (AIs) for breast cancer is common and increases risk of recurrence. Few prospective studies have systematically evaluated reasons for adherence failure. S1105 randomized women to receive text message reminders or usual care, and no effect of the intervention was observed on the rates of adherence failure. We analyzed baseline characteristics to evaluate factors associated with non-adherence prospectively over 3-years.Methods: Patients enrolled in SWOG S1105 were required to have been on an AI for ≥30 days at enrollment. Patients were assessed for non-adherence of AIs every 3 months for 36 months, with non-adherence defined as urine AI metabolite assay results satisfying any of the following: median) vs low ( Citation Format: Dawn L Hershman, Joeseph M Unger, Anna Moseley, Grace C Hillyer, Kathryn B. Arnold, Julie R Gralow, N. Lynn Henry, Scott D Ramsey, Alfred I Neugut. Baseline patient reported outcomes predict aromatase inhibitor adherence failure among women in enrolled in a randomized trial of text-messaging [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-08.

Purpose: To investigate how a healthy lifestyle index (HLI) is associated with breast cancer risk and survival in a population-based breast cancer study.Methods: The study included 1,319 breast cancer cases and 1,310 controls from the population-based Long Island Breast Cancer Study Project, and its follow-up study of mortality. We determined vital status using the National Death Index (521 deaths, 210 from breast cancer; median follow-up 214.5 months). A healthy lifestyle index (HLI) score, was generated from information on body fatness, physical activity, intake of plant and animal foods, alcohol consumption, breastfeeding and smoking, with higher values representing engagement in healthier behaviors. Multivariable logistic and Cox regression were used to estimate breast cancer odds ratios (ORs) mortality hazards ratios (HRs), respectively.Results: Compared to women in the low HLI tertile, women in the intermediate (OR=0.78, 95%CI=0.65-0.94) and high (OR=0.68, 95%CI=0.56-0.83) tertiles had a decreased odds of breast cancer, and a one-point increase in HLI score was associated a reduction in breast cancer risk (OR=0.85, 95%CI=0.79–0.92). Women in the intermediate (HR=0.75, 95%CI=0.61-0.91) and high (HR=0.74, 95%CI=0.60-0.92) tertiles had a decreased rate of all-cause mortality, and a one-point increase in HLI score was associated with a reduction in all-cause mortality (HR=0.83, 95%CI =0.76-0.91). These associations were significant among postmenopausal.Conclusion: A healthy lifestyle may be beneficial in reducing breast cancer risk and improving overall survival after breast cancer diagnosis, especially among postmenopausal women.

PURPOSE The quality of breast cancer care in sub-Saharan Africa contributes to the region’s dismal breast cancer mortality. ASCO has issued quality measures focusing on delivery of adjuvant chemotherapy, radiotherapy, and endocrine therapy. We applied these measures in five South African public hospitals and analyzed factors associated with care concordance. MATERIALS AND METHODS Among 1,736 women with breast cancer who were enrolled in the South African Breast Cancer and HIV Outcomes study over 24 months, we evaluated care using ASCO’s three measures. We also evaluated adjuvant chemotherapy receipt in 957 women with an indication. We used logistic regression to estimate associations between measure-concordant care and patient factors. RESULTS Of 235 women with hormone receptor–negative cancer, 173 (74%) began adjuvant chemotherapy within 120 days from diagnosis. Of 194 patients who received breast-conserving surgery, 73 (37%) began radiotherapy within 365 days from diagnosis. Of 999 women with hormone receptor–positive cancer, 719 (72%) initiated endocrine therapy within 365 days from diagnosis. Chemotherapy and radiotherapy measure-concordant care were more common among women residing < 20 km from the hospital (odds ratio [OR], 1.79; 95% CI, 1.32 to 2.44 and OR, 3.17; 95% CI, 1.57 to 6.42). Endocrine therapy measure-concordant care was more common among English-speaking women (OR, 2.12; 95% CI, 1.12 to 4.02). Participating hospitals varied in care concordance. HIV infection did not affect care quality. CONCLUSION More timely delivery of chemotherapy, radiotherapy, and endocrine therapy is needed in South Africa, particularly for women living > 20 km from the hospital or not speaking English. Focused quality improvement efforts could support that goal.

Better adherence to supportive care guidelines is needed, especially for common challenges such as chemotherapy-induced nausea and vomiting. This commentary remarks on recently published data on adherence to guidelines, considering treatment options and new strategies to reduce chemotherapy complications.

A breast cancer early detection program in Eswatini using clinical breast exam improved nurses' evaluation skills., PURPOSE Breast cancer (BC) is detected at late stages in sub-Saharan Africa. We piloted a BC early-detection program in Eswatini aimed at increasing breast health knowledge and clinical skills. We also aimed to determine the proportion of patients with breast abnormalities who completed referral to breast specialty clinics. METHODS Nurses and counselors from five human immunodeficiency virus and/or antiretroviral therapy clinics underwent training in BC and clinical breast examination (CBE). We compared knowledge and skill examinations completed before, immediately after, and 90 days after training. Nurses then screened female clinic patients ≥ 18 years for breast symptoms, examined those with symptoms, and referred women with CBE abnormalities to a surgeon or the national breast clinic. Consenting women were contacted at 30 and 60 days after screening to determine if they had completed referral. RESULTS In 2019, 44 nurses underwent training. Median scores (interquartile range) on pretraining, immediate post-training, and 90-day post-training knowledge examinations were 17.5 (16-19), 20 (19-21), and 20 (19-21), respectively. Median scores (interquartile range) on pretraining, immediate post-training, and 90-day post-training skills examinations were 10 (7-11), 23 (21.5-25), and 23 (22-24), respectively. Compared with pretraining scores, post-training scores were significantly improved (P < .0001 for all comparisons). From June 2019 to April 2020, a total of 9,502 clinic patients were screened for breast symptoms: 150 (2%) underwent CBE, 93 (62%) were referred for further evaluation, and 88 (97%) were included in the study. Of those, 54 (61%) completed referral. Referral completion was not associated with age, employment, relationship status, or prior experiences related to BC. CONCLUSION The program's training curriculum improved breast health knowledge and clinical skills. Efforts are needed to improve patients' receipt of recommended evaluation for breast abnormalities.

INTRODUCTION AND OBJECTIVE:Men of African descent have the highest burden of aggressive prostate cancer (PCa). However, the clinical features of PCa within sub-Saharan Africa (SSA) are understudied...

Background Cancer is the leading cause of morbidity and mortality among people living with HIV (PLWH). Although gastrointestinal (GI) cancers are not associated with HIV, their incidence is rising among PLWH, and yet little is known about how HIV affects their presentation, treatment and outcomes. Methods We searched PubMed using "HIV" and "cancer", "esophageal cancer", "gastric cancer", "stomach cancer", "gastroesophageal cancer", "colorectal cancer", "colon cancer", or "rectal cancer". We included studies comparing an HIV-positive group (n ≥ 4) to an HIV-negative group, with respect to clinical presentation, treatment, or mortality of GI cancers. Results Of 18 articles that met inclusion criteria, 17 were retrospective, and 13 described patients in the United States. At diagnosis with colorectal, but not pancreatic, gastric, or esophageal cancer, PLWH were younger than patients who were HIV-negative. PLWH did not present with more advanced stage GI cancers than patients who were HIV-negative. Compared to HIV-negative controls, PLWH with colorectal cancer had a higher proportion of right-sided versus left-sided colon cancers and a higher proportion of rectal versus colon cancers. Among patients diagnosed with colorectal or pancreatic cancer, PLWH were less likely to receive cancer treatment than other patients; no studies examined the association of HIV status with treatment for esophageal or gastric cancer. PLWH with GI malignancies had higher all-cause mortality compared to patients who were HIV-negative, but evidence for cancer-specific mortality was limited and mixed. Conclusion PLWH with GI malignancies were less likely to receive cancer treatment and had higher all-cause mortality than patients who were HIV-negative. Most of the studies focused on colorectal cancer; more studies are needed in pancreatic, gastric and esophageal cancer. Future studies should investigate the effects of HIV on cancer-specific mortality, especially among patients in low- and middle-income countries, including those with high HIV prevalence.

Background: Phthalates and phenols from the environment have been inconsistently associated with breast cancer risk or mortality. Studies on the potential modifying role of leukocyte telomere length (LTL), a biomarker of biological aging, on these associations are lacking. Methods: We included 1,268 women from the Long Island Breast Cancer Study Project with available data on phthalate and phenol analytes and LTL measurements. Twenty-two phthalate and phenol analytes were measured in spot urines and LTL was measured in blood. The modifying effect of LTL on the associations of individual analyte with breast cancer risk as well as mortalities was estimated using interaction terms between LTL and urinary concentrations of analyte in logistic regression and Cox regression models, respectively. ORs, HRs, and corresponding 95% confidence intervals for a one-unit (ln μg/g creatinine) increase of urinary phthalate/phenol level were estimated at 10th, 50th, and 90th percentiles of LTL. Results: LTL significantly (P < 0.05) modified associations between 11 of 22 of urinary phthalate/phenols analytes and breast cancer risk. An inverse association between phthalate/phenols analytes and breast cancer risk at shorter LTL and a positive association at longer LTL was generally suggested. No modifying effect was found for LTL on the association between these phthalate/phenols analytes and breast cancer mortalities. Conclusions: LTL may modify the associations between phthalate and phenol exposures and breast cancer risk. Impact: This study is the first study that determined the modifying effect of biological aging in the association between environmental chemical exposure and breast cancer risk.

The decision to use adjuvant chemotherapy (ACT) after surgical resection for stage II colon cancer remains an area of clinical uncertainty. Many patients diagnosed with stage II colon cancer receive ACT, despite inconclusive evidence of long-term clinical benefit. This study investigates patient experiences and perceptions of treatment decision-making and shared decision making (SDM) for ACT among patients diagnosed with stage II colon cancer. Stage II colon cancer patients engaged in treatment or follow-up care aged >18 years were recruited from two large NYC health systems. Patients participated in 30–60-min semi-structured interviews. All interviews were transcribed, translated, coded, and analyzed using a thematic analysis approach. We interviewed 31 patients, of which 42% received ACT. Overall, patient perspectives indicate provider inconsistency in communicating ACT harms, benefits, and uncertainties, and poor elicitation of patient preferences and values. Patients reported varying perceptions and understanding of personal risk and clinical benefits of ACT. For many patients, receiving a clear treatment recommendation from the provider limited their participation in the decision-making process, whether it aligned with their decisional support preferences or not. Findings advance understanding of perceived roles and preferences of patients in SDM processes for cancer treatment under heightened clinical uncertainty, and indicate a notable gap in understanding for decisions made using SDM models in the context of clinical uncertainty. Educational and communication strategies and training are needed to support providers in communicating uncertainty, risk, treatment options, and implementing clinical guidelines to support patient awareness and informed decisions.

While women with stage III endometrial cancer are often treated with chemotherapy and external beam radiation, the optimal sequence of these modalities is unknown. We examined the association between the sequence of chemotherapy (CT) and external beam radiation therapy (RT) on survival for women with stage IIIC endometrial carcinoma.The National Cancer Database was used to identify women with stage IIIC endometrial carcinoma treated with adjuvant CT and RT from 2004 to 2015. Patients were stratified based on the sequence of therapy: RT before CT, CT before RT, or concurrent therapy. The association between treatment sequence and mortality was examined through a weighted propensity score analysis.A total of 6981 patients were identified, including 5116 (73.3%) who received CT before RT, 696 (10.0%) who received RT before CT, and 1169 (16.7%) who received concurrent therapy. The use of CT-RT increased from 39.9% in 2004 to 75.5% in 2015, while use of RT-CT decreased from 34.0% to 4.4% and concurrent therapy decreased from 26.1% to 20.2% over the same period (P 0.001). Compared to CT-RT, there was no difference in risk of mortality with RT before CT (HR = 1.01; 95% CI, 0.86-1.19) while concurrent therapy was associated with a 47% increased risk of mortality (HR = 1.47; 95% CI, 1.31-1.66). In a sensitivity analysis combining the groups that received RT first (RT before CT or concurrent RT-CT), mortality was 25% higher (HR = 1.25; 95% CI, 1.13-1.39) compared to a strategy of CT followed by RT.Among women with stage IIIC endometrial carcinoma treated with combination chemotherapy and external beam radiation, a strategy employing chemotherapy first is associated with improved survival compared to concurrent therapy.

Background Reproductive characteristics are well-established risk factors for breast cancer, but the underlying mechanisms are not fully resolved. We hypothesized that altered DNA methylation, measured in tumor tissue, could act in concert with reproductive factors to impact breast carcinogenesis. Methods Among a population-based sample of women newly diagnosed with first primary breast cancer, reproductive history was assessed using a life-course calendar approach in an interviewer-administered questionnaire. Methylation-specific polymerase chain reaction and Methyl Light assays were used to assess gene promotor methylation status (methylated vs. unmethylated) for 13 breast cancer-related genes in archived breast tumor tissue. We used case-case unconditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations with age at menarche and parity (among 855 women), and age at first birth and lactation (among a subset of 736 parous women) in association with methylation status. Results Age at first birth > 27 years, compared with CDH1 (OR = 0.44, 95% CI = 0.20–0.99) and TWIST1 (OR = 0.48, 95% CI = 0.28–0.82), and higher odds of methylation of BRCA1 (OR = 1.63, 95% CI = 1.14–2.35). Any vs. no lactation was associated with higher odds of methylation of the PGR gene promoter (OR = 1.59, 95% CI = 1.01–2.49). No associations were noted for parity and methylation in any of the genes assayed. Conclusions Our findings indicate that age at first birth, lactation and, perhaps age at menarche, are associated with gene promoter methylation in breast cancer, and should be confirmed in larger studies with robust gene coverage.

Background Bevacizumab is used for the treatment of metastatic colon cancer in conjunction with first-line chemotherapy. In this study, we examined receipt of first-line bevacizumab and predictors of its use among older patients with stage IV colon cancer. Materials and Methods We used data from the Surveillance, Epidemiology, and End Results-Medicare dataset to identify patients with stage IV colon cancer diagnosed from 2005 to 2013 who received FOLFOX (5-fluorouracil/leucovorin/oxaliplatin) or FOLFIRI (5-fluorouracil/leucovorin/irinotecan) as first-line therapy. We used multivariable regression analysis to determine demographic and clinical factors associated with use of concomitant bevacizumab. Results We identified 3785 patients with stage IV colon cancer who met our eligibility criteria. Of these, 2352 (62.1%) received bevacizumab. Bevacizumab use has decreased over time from 68.2% in 2005 to 57.6% in 2013 (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.91-0.97). Patients were less likely to receive bevacizumab if they were older (compared with 65-69 years, ≥ 80 years: OR, 0.64; 95% CI, 0.52-0.80), or had multiple comorbidities (compared with comorbidity score of 0, score of 1: OR, 0.73; 95% CI, 0.60-0.89). Conclusion Over one-half of elderly patients received bevacizumab as part of their first-line therapy for stage IV colon cancer. Bevacizumab use has been slowly decreasing since 2005. Newer anti-epidermal growth factor receptor treatments have not been supplanting bevacizumab, as first-line biologic use in general has also decreased during this time period.

IntroductionPositron emission tomography-computed tomography (PET-CT) imaging is commonly used to identify nodal involvement in locally advanced cervical carcinoma, but its appropriateness for that purpose among HIV-positive patients has rarely been studied. We analyzed PET-CT findings and subsequent treatment prescribed in patients with locally advanced cervical carcinoma in Cape Town, South Africa.MethodsWe identified a cohort of consecutive cervical carcinoma patients International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIB at our cancer center who underwent a planning 18-fluorodeoxyglucose (18FDG) PET-CT scan from January 2015 through December 2018. Demographics, PET-CT findings, and subsequent treatment prescribed were recorded. Patients were selected for PET-CT only if they had no signs of distant disease on staging chest X-ray or abdominal ultrasound; were deemed suitable for radical chemoradiation by the multi-disciplinary team; and had normal renal function. HIV-positive patients ideally had to have been established on continuous antiviral therapy for more than 3 months and to have a CD4 cell count above 150 cells/μL. Small cell and neuroendocrine carcinoma cases were excluded from the study. Differences in demographic and clinical measures between HIV-positive and HIV-negative patients were evaluated by means of t-tests for continuous variables and χ2 tests for categorical variables.ResultsOver a 4 year period, 278 patients—192 HIV-negative (69.1%) and 86 HIV-positive (30.9%)—met the inclusion criteria. HIV-positive patients had a median CD4 count of 475 cells/µL (IQR 307–612 cells/µL). More than 80% of patients had pelvic nodal involvement, and more than 40% had uptake in common iliac and/or para-aortic nodes. Nodal involvement was not associated with HIV status. Fifty-four patients (19.4%) had at least one site of distant metastatic disease. Overall, 235 patients (84.5%) were upstaged following PET-CT staging scan. Upstaging was not associated with HIV status (HIV-negative 83.9% vs HIV-positive 87.2%; p=0.47). Ten patients who did not return for radiotherapy were excluded from the analysis. Following their PET-CT scan, treatment intent changed for 124 patients (46.3%): 53.6% of HIV-positive patients and 42.9% of HIV-negative patients (p=0.11).ConclusionWe found no differences between HIV-positive or HIV-negative patients in nodal involvement or occult metastases, and PET-CT imaging did not lead to, or justify, treatment differences between the two groups. Future studies will evaluate survival and correlation of upstaging with outcome.

National guidelines recommend maximal safe resection of low-grade and high-grade oligodendrogliomas. However, there is no level 1 evidence to support these guidelines, and recent retrospective studies on the topic have yielded mixed results. To assess the association between extent of resection (EOR) and survival for oligodendrogliomas in the general U.S. population. Cases diagnosed between 2004 and 2013 were selected from the Surveillance, Epidemiology, and End-Results (SEER) Program and retrospectively analyzed for treatment, prognostic factors, and survival times. Cases that did not undergo tumor de-bulking surgery (e.g. no surgery or biopsy alone) were compared to subtotal resection (resection) and gross-total resection (GTR). The primary end-points were overall survival (OS) and cause-specific survival (CSS). An external validation cohort with 1p/19q-codeleted tumors was creating using the TCGA and GSE16011 datasets. 3135 Cases were included in the final analysis. The 75% survival time (75ST) and 5-year survival rates were 47 months and 70.8%, respectively. Subtotal resection (STR, 75ST = 50 months) and GTR (75ST = 61 months) were associated with improved survival times compared to cases that did not undergo surgical debulking (75ST = 20 months, P

Background The authors hypothesized that epigenetic changes may help to clarify the underlying biologic mechanism linking aspirin use to breast cancer prognosis. To the authors' knowledge, this is the first epidemiologic study to examine whether global methylation and/or tumor promoter methylation of breast cancer-related genes interact with aspirin use to impact mortality after breast cancer. Methods Prediagnosis aspirin use was assessed through in-person interviews within a population-based cohort of 1508 women diagnosed with a first primary breast cancer in 1996 and 1997. Global methylation in peripheral blood was assessed by long interspersed elements-1 (LINE-1) and the luminometric methylation assay. Promoter methylation of 13 breast cancer-related genes was measured in tumor by methylation-specific polymerase chain reaction and the MethyLight assay. Vital status was determined by the National Death Index through December 31, 2014 (N = 202/476 breast cancer-specific/all-cause deaths identified among 1266 women with any methylation assessment and complete aspirin data). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs, and the likelihood ratio test was used to evaluate multiplicative interactions. Results All-cause mortality was elevated among aspirin users who had methylated promotor of BRCA1 (HR, 1.67; 95% CI, 1.26-2.22), but not among those with unmethylated promoter of BRCA1 (HR, 0.99; 95% CI, 0.67-1.45; P for interaction ≤.05). Decreased breast cancer-specific mortality was observed among aspirin users who had unmethylated promotor of BRCA1 and PR and global hypermethylation of LINE-1 (HR, 0.60, 0.78, and 0.63, respectively; P for interaction ≤.05), although the 95% CIs included the null. Conclusions The current study suggests that the LINE-1 global methylation and promoter methylation of BRCA1 and PR in tumor may interact with aspirin use to influence mortality after breast cancer.

Long-term outcomes for women with ovarian cancer are improved when they are treated at high volume hospitals by high volume surgeons. We examined changes over time in surgeon and hospital procedural volume for ovarian cancer and explored the association between volume and perioperative outcomes.The New York Statewide Planning and Research Cooperative System (SPARCS) database was used to examine women with ovarian cancer who underwent surgery from 2000 to 2014. Annualized surgeon and hospital procedural volume were estimated and each grouped into quartiles. Changes over time in the annual number of surgeons and hospitals rendering care were estimated. The association between surgeon and hospital volume and perioperative morbidity and mortality were analyzed.We identified 25,044 patients treated by 2728 surgeons at 213 hospitals. The number of surgeons decreased from 598 surgeons with 1737 patients (mean cases = 3) in 2000, to 278 surgeons who operated on 1503 patients (mean cases = 5) (P 0.001) in 2014, while the mean hospital volume rose from 10 cases to 15 cases over the same time period (P 0.001). There was no difference in morbidity based on surgeon volume (RR = 0.99 for high vs .low volume; 95% CI, 0.91-1.07) while perioperative mortality rates decreased with increasing surgeon volume quartile from 2.6% to 1.9%, 1.3% and 1.3%, respectively (P 0.001). Similarly, there was no association between hospital volume and morbidity (RR = 1.00; 95% CI, 0.88-1.15). In contrast, the mortality rate declined with volume quartile from 2.5% in the lowest volume quartile to 0.9% in the highest volume quartile (P 0.001).The surgical care of women with ovarian cancer has been concentrated to a smaller number of surgeons and hospitals over time. There was a modest association between increased surgeon and hospital volume and decreased perioperative mortality.

Background: Little is known about how immigration status influences preference for life-extending care (LEC) at the end of life (EoL). Objective: The purpose was to determine how preference for LEC at the EoL for advanced cancer patients varied by Latino ethnicity and immigrant status, and over time between two large cohorts. Methods: Data were derived from two sequential multi-institutional, longitudinal cohort studies of advanced cancer patients, recruited from 2002 to 2008 (coping with cancer I [CwC-1]) and 2010 to 2015 (coping with cancer II [CwC-2]). Self-reported U.S.-born whites (whites) (N = 253), U.S.-born Latinos (US-L) (N = 34), and Latino immigrants (LI) (N = 65) with a poor-prognosis cancer were included. The primary independent variables were immigrant status, Latino ethnicity, and CwC cohort. The primary dependent variable was preference for LEC. Results: Within CwC-2, LI were 9.4 times more likely to prefer LEC over comfort care versus US-L (adjusted odds ratio [AOR] = 9.4; 95% confidence interval [CI]: 1.2–72.4), and US-L were 0.3 times less likely to prefer LEC versus whites (AOR = 0.3; 95% CI: 0.1–1.0). LI from CwC-2 were 11.4 times more likely to prefer LEC versus LI from CwC-1 (AOR = 11.4; 95% CI: 2.7–48.4). Within CwC-1, there was no difference in LEC preference between LI and US-L, nor between US-L and whites. Conclusions: Immigrant status had a strong effect on preference for LEC at the EoL among the more recent cohort of Latino cancer patients. Preference for LEC appears to have increased significantly over time for LI but remained unchanged for US-L. LI may increasingly want LEC near death.

Objective To compare the outcomes of women with stage III uterine cancer treated with chemotherapy alone, external beam radiation alone, and combination chemotherapy and radiation. Methods The National Cancer Database was used to identify women with stage III endometrioid, serous, and clear cell uterine cancer treated with either chemotherapy (with or without vaginal brachytherapy) alone, external beam radiation (with or without brachytherapy), or combination chemotherapy and external beam radiation (with or without vaginal brachytherapy) from 2004 to 2015. Survival was estimated using Cox proportional hazards models and adjusted survival curves after propensity score analysis using inverse probability of treatment weighting to balance the clinical and demographic characteristics between the cohorts. Results Of the 20,873 patients identified, 9,456 (45.3%) received chemotherapy alone, 2,417 (11.6%) were treated with radiation alone, and 9,000 (43.1%) received chemotherapy in combination with external beam radiation. Use of combination therapy was 33.0% in 2004, and then rose to 50.5% in 2015. The mortality of the cohort was 33.1% and median survival was 115 months. Within the cohort, combination therapy was associated with a 23% reduction in mortality (hazard ratio [HR]=0.77; 95% CI 0.73-0.80) compared with chemotherapy alone. Similar findings of decreased mortality were noted in subgroup analyses for both stage IIIA (HR=0.81; 95% CI 0.68-0.98) and stage IIIC (HR=0.79; 95% CI 0.75-0.84) tumors. Similarly, when compared with radiation alone, combination therapy was accompanied by a 19% decrease in mortality (HR=0.81; 95% CI 0.73-0.89). Combination chemoradiation was associated with decreased mortality across all of the histologic subtypes. Conclusion Among women with stage III uterine cancer, combination chemotherapy and external beam radiation is associated with decreased mortality compared with chemotherapy or radiation alone.

Background Shortly after the year 2000, randomized trials demonstrated that patients with metastatic colon cancer treated with infusional 5-fluorouracil (5-FU)/leucovorin with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) had a comparable progression-free survival benefit, superior to patients who received 5-FU/leucovorin alone. Factors associated with the initial receipt of the FOLFOX or FOLFIRI regimen are unknown. Our goal was to investigate the patterns and predictors of use for first-line FOLFOX and FOLFIRI. Patients and Methods We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data set to identify patients with newly diagnosed stage IV colon cancer between the years 2005 and 2013 who received either first-line FOLFOX or FOLFIRI. We used logistic regression to assess demographic and clinical predictors for FOLFOX versus FOLFIRI. Survival was compared by Kaplan-Meier models. Results Overall, 3000 patients (79.3%) received FOLFOX and 785 (20.7%) FOLFIRI. FOLFOX was associated with later year of diagnosis (odds ratio [OR] = 0.66, 95% confidence interval [CI], 0.54 to 0.82 for 2011-2013 vs. 2005-2007), being female (OR = 0.82; 95% CI 0.69 to 0.98), and living in the southern region of the United States. FOLFIRI was associated with having a higher comorbidity index (OR = 1.33; 95% CI, 1.07 to 1.67 for >1 comorbidity score vs. 0). There was no survival difference observed between the two treatments. Conclusion The majority of SEER-Medicare patients received FOLFOX and not FOLFIRI as a first-line treatment for stage IV colon cancer. Several demographic and clinical factors were associated with the use of each specific regimen. No survival difference was detected for the 2 groups.

OBJECTIVEThe purpose of this meta-analysis was to evaluate the impact of perioperative antiepileptic drug (AED) prophylaxis on short- and long-term seizure incidence among patients undergoing brain tumor surgery. It is the first meta-analysis to focus exclusively on perioperative AED prophylaxis among patients undergoing brain tumor surgery.METHODSThe authors searched PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials, clinicaltrials.gov, and the System for Information on Gray Literature in Europe for records related to perioperative AED prophylaxis for patients with brain tumors. Risk of bias in the included studies was assessed using the Cochrane risk of bias tool. Incidence rates for early seizures (within the first postoperative week) and total seizures were estimated based on data from randomized controlled trials. A Mantel-Haenszel random-effects model was used to analyze pooled relative risk (RR) of early seizures (within the first postoperative week) and total seizures associated with perioperative AED prophylaxis versus control.RESULTSFour RCTs involving 352 patients met the criteria of inclusion. The results demonstrated that perioperative AED prophylaxis for patients undergoing brain tumor surgery provides a statistically significant reduction in risk of early postoperative seizures compared with control (RR = 0.352, 95% confidence interval 0.130–0.949, p = 0.039). AED prophylaxis had no statistically significant effect on the total (combined short- and long-term) incidence of seizures.CONCLUSIONSThis meta-analysis demonstrates for the first time that perioperative AED prophylaxis for brain tumor surgery provides a statistically significant reduction in early postoperative seizure risk.

PURPOSE: Breast cancer is the most common cancer in women and a leading cause of cancer-related mortality worldwide. South Africa has the largest global burden of HIV infection and the largest anti-retroviral treatment (ART) program. This study aimed to analyse the association of HIV and ART use with breast cancer clinico-pathological characteristics. METHODS: Study participants were females, newly diagnosed from May 2015 through September 2017 with invasive breast cancer at two academic Surgical Breast Units in Johannesburg, South Africa at the Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath Academic Hospital. We compared HIV-positive and HIV negative patients’ demographic and clinical-pathological characteristics at the time of breast cancer diagnosis. RESULTS: Of 1050 patients enrolled, 1016 (96.8%) had known HIV status, with 226 (22.2%) being HIV positive. HIV positive patients were younger (median (IQR) age 45 (40–52) years), than HIV-negative patients (median (IQR) age 57 (46–67)) (p

In sub‐Saharan Africa, clinical decisions can be affected by resource constraints. This article analyzes the clinical and sociodemographic factors associated with receiving neoadjuvant chemotherapy among patients from a previously existing cohort: women enrolled in the prospective South African Breast Cancer and HIV Outcomes study., Background. In the U.S., neoadjuvant chemotherapy (NAC) for nonmetastatic breast cancer (BC) is used with extensive disease and aggressive molecular subtypes. Little is known about the influence of demographic characteristics, clinical factors, and resource constraints on NAC use in Africa. Materials and Methods. We studied NAC use in a cohort of women with stage I–III BC enrolled in the South African Breast Cancer and HIV Outcomes study at five hospitals. We analyzed associations between NAC receipt and sociodemographic and clinical factors, and we developed Cox regression models for predictors of time to first treatment with NAC versus surgery. Results. Of 810 patients, 505 (62.3%) received NAC. Multivariate analysis found associations between NAC use and black race (odds ratio [OR] 0.49; 95% confidence limit [CI], 0.25–0.96), younger age (OR 0.95; 95% CI, 0.92–0.97 for each year), T‐stage (T4 versus T1: OR 136.29; 95% CI, 41.80–444.44), N‐stage (N2 versus N0: OR 35.64; 95% CI, 16.56–76.73), and subtype (triple‐negative versus luminal A: OR 5.16; 95% CI, 1.88–14.12). Sites differed in NAC use (Site D versus Site A: OR 5.73; 95% CI, 2.72–12.08; Site B versus Site A: OR 0.37; 95% CI, 0.16–0.86) and time to first treatment: Site A, 50 days to NAC versus 30 days to primary surgery (hazard ratio [HR] 1.84; 95% CI, 1.25–2.71); Site D, 101 days to NAC versus 126 days to primary surgery (HR 0.49; 95% CI, 0.27–0.89). Conclusion. NAC use for BC at these South African hospitals was associated with both tumor characteristics and heterogenous resource constraints. Implications for Practice. Using data from a large breast cancer cohort treated in South Africa's public healthcare system, the authors looked at determinants of neoadjuvant chemotherapy use and time to initiate treatment. It was found that neoadjuvant chemotherapy was associated with increasing tumor burden and aggressive molecular subtypes, demonstrating clinically appropriate care in a lower resource setting. Results of this study also showed that time to treatment differences between chemotherapy and surgery varied by hospital, suggesting that differences in resource limitations were influencing clinical decision making. Practice guidelines and care quality metrics designed for low‐ and middle‐income countries should accommodate heterogeneity of available resources.

To model the effect of implementing minimum-volume standards for women who underwent hysterectomy on patient outcomes and surgeon practice patterns.We conducted a retrospective cohort study using the New York Statewide Planning and Research Cooperative System to capture data for all women who underwent hysterectomy from 2010 to 2014. We estimated the number of hysterectomies performed by each patient's physician during the prior year. Multivariable models were used to estimate the ratio of observed to expected complications based on each surgeon's volume during the prior year. The mean observed/expected ratio of surgeons was then plotted by volume. The number of patients and surgeons who would be eliminated and the reduction in complications if minimum-volume standards (lowest fifth and 10th percentiles) were implemented were analyzed. Separate analyses were performed for each route of hysterectomy.We identified a total of 127,202 patients. For abdominal hysterectomy, increasing surgeon volume was associated with a decreasing rate of complications (P.001). Overall, 17.5% of surgeons (n=1,260) had a prior year volume of one abdominal hysterectomy. The mean observed/expected ratio of surgeons with a prior year abdominal hysterectomy volume of one was 1.47 (SD 2.71). Within this group of surgeons, 31.4% had an observed/expected ratio of 1 or greater, indicating a higher than expected complication rate, and 68.7% of the surgeons had a observed/expected ratio of less than 1, suggesting a lower complication rate than expected based on case mix. Selection of a prior year volume standard of one would restrict 12.5% of surgeons performing robotic-assisted, 16.8% of those performing laparoscopic, and 27.6% of surgeons performing vaginal hysterectomy.Implementing minimum-volume standards for hysterectomy, for even the lowest volume physicians, would restrict a significant number of gynecologic surgeons, including many with outcomes that are better than predicted.

Objectives In South Africa, where HIV prevalence among adults is 18.9%, cervical carcinoma is the second most common malignancy in women. However, oncology services are considerably more accessible in South Africa than in many neighbouring countries. This study reports five-year overall survival in a cohort of HIV-positive and -negative cervix carcinoma patients undergoing primary radiotherapy at a single institution in South Africa. Methods Prospective cohort study of all locally advanced cervix carcinoma patients referred for radiotherapy (EBRT) from July 2007 to November 2011. Overall survival (OS) was the primary end-point. Results A total of 492 patients commenced treatment with radical intent, including 71 HIV-positive patients (14.4%) and 421 HIV-negative patients (85.6%). Of the 433 who were prescribed standard fractionation EBRT, 384 were prescribed concurrent platinum-based chemotherapy (88.7%). Fewer HIV-positive than HIV-negative patients (58.5% vs. 76.1%; p = 0.007) completed ≥4 cycles. The OS of HIV-negative patients was 49.5% (95%CI; 44.6%–54.4%) at 5 years. The OS of HIV-positive patients was significantly lower, 35.9% (95% CI; 23.9%–48.0%) at 5 years (p = 0.002). In our Cox models, factors affecting outcome were HIV infection, stage IIIB disease, presence of hydronephrosis, and delivery of concurrent chemotherapy. Conclusion In our large cohort, HIV-positive patients had poorer survival than HIV-negative patients, however nearly 40% survived 5 years, justifying provision of the best standard of care to HIV-positive patients with cervical carcinoma.

BackgroundCancer patients’ treatment is often dispersed across multiple physician communities that may not exchange information. We measured the association between this type of discoordinated care and healthcare utilization, cost, and mortality in stage IV non-small cell lung cancer (NSCLC).MethodsStage IV NSCLC patients ≥65 years were identified from the Surveillance, Epidemiology, and End Results database attached to Medicare claims. A discoordinated care subgroup was selected using a novel index that approximated how many physician communities each patient encountered. Communities were defined by (1) using claims data to create a nationwide social network of healthcare providers and then (2) dividing that network into communities using cluster label propagation. Associations between discoordinated care and overall survival (OS), cancer-specific survival (CSS), hospitalizations, the burden of diagnostic imaging, and cost were assessed.ResultsOf the 11,417 patients in our cohort, 5,855 received discoordinated care. Discoordination was associated with younger age, higher socioeconomic status, higher physician density, and lack of a home health aide. Discoordinated care was associated with improved OS and CSS (HR = 0.92, 95% CI 0.88 - 0.95 for OS). However, discoordinated patients also received 32% more MRIs (p = 0.007) and paid $494.02 more for imaging (p = 0.004). There was no association with other kinds of imaging, rates of hospitalization, or other healthcare costs, including total cost.ConclusionsDiscoordinated care was associated with additional MRIs, but also improved survival. The reason is unclear, but discoordinated patients may be seeking the best care at the expense of continuity.Key PointsQuestionHow does dispersing healthcare across multiple physician communities impact healthcare utilization and survival in patients with advanced stage non-small cell lung cancer?FindingsIn this retrospective cohort study, we found that discoordinated care was associated with increased utilization of MRIs and total cost of imaging. Surprisingly, it was also associated with improved survival.MeaningCancer patients with dispersed healthcare may be seeking care through a tertiary care center or clinical trial. This may lead to increased healthcare utilization but also improved survival.

Background High-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC). Methods We selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods. Results Of the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86–1.09), ETFS (HR 1.05; 95% CI 0.93–1.18), CSS (HR 0.94; 95% CI 0.84–1.04), or OS (HR 0.95; 95% CI 0.87–1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively. Conclusion hfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost. hfIGRT deserves further scrutiny through a randomized controlled trial.

Background Nonadherence to aromatase inhibitors (AIs) is common and increases risk of breast cancer (BC) recurrence. We analyzed factors associated with nonadherence among patients enrolled in S1105, a randomized trial of text messaging. Methods At enrollment, patients were required to have been on an adjuvant AI for at least 30 days and were asked about financial, medication, and demographic factors. They completed patient-reported outcomes (PROs) representing pain (Brief Pain Inventory), endocrine symptoms (Functional Assessment of Cancer Therapy–Endocrine Symptoms), and beliefs about medications (Treatment Satisfaction Questionnaire for Medicine; Brief Medication Questionnaire). Our primary endpoint was AI nonadherence at 36 months, defined as urine AI metabolite assay of less than 10 ng/mL or no submitted specimen. We evaluated the association between individual baseline characteristics and nonadherence with logistic regression. A composite risk score reflecting the number of statistically significant baseline characteristics was examined. Results We analyzed data from 702 patients; median age was 60.9 years. Overall, 35.9% patients were nonadherent at 36 months. Younger patients (younger than age 65 years) were more nonadherent (38.8% vs 28.6%, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.05 to 2.16; P = .02). Fourteen baseline PRO scales were each statistically significantly associated with nonadherence. In a composite risk model categorized into quartile levels, each increase in risk level was associated with a 46.5% increase in the odds of nonadherence (OR = 1.47, 95% CI =1.26 to 1.70; P Conclusions The presence of multiple baseline PRO-specified risk factors was statistically significantly associated with AI nonadherence. The use of these assessments can help identify patients for targeted interventions to improve adherence.

OBJECTIVE To compare perioperative use and persistent postoperative opioid use among Medicaid-insured women and commercially insured women who underwent gynecologic surgery for benign indications. METHODS The Truven Health MarketScan database, a nationwide data source collecting commercial insurance claims across all states and Medicaid insurance claims from 12 states, was used to identify opioid-naive women without cancer aged 18-64 years who underwent common gynecologic surgeries from 2012 to 2016 and filled a prescription for an opioid perioperatively. Persistent opioid use was defined as filling an opioid prescription 90-180 days after the surgery. Opioid use disorder (OUD) was defined as hospitalizations or emergency department visits for opioid dependence, misuse, or overdose. Multivariable models were developed to examine the insurance-associated disparity in persistent opioid use and OUD. RESULTS A total of 31,155 Medicaid-insured women and 270,716 commercially insured women were identified. Medicaid-insured women received greater quantities of opioids and for longer durations than did commercially insured women. Persistent postoperative opioid use was identified in 14.1% of Medicaid-insured women and 5.8% of commercially insured women (P

Background Women with newly diagnosed cervical cancer are often treated with extensive, multimodal therapies that may include a combination of surgery, radiation, and chemotherapy. Little is known about the cost of treatment or how these costs are passed on to the patients. Objective The objectives of this study were to examine the cost of care during the first year after a diagnosis of cervical cancer, to estimate the sources of the costs, and to explore the out-of-pocket costs. Study Design We performed a study of women with commercial insurance who received a new diagnosis of cervical cancer, and whose cases were recorded in the MarketScan database from 2008 to 2016. Patients were categorized based on the primary treatment received being either surgery (hysterectomy with or without adjuvant radiation or chemotherapy) or radiation. The inflation-adjusted medical expenditures for a 12-month period beginning on the date of the first treatment were estimated. The payments were divided into the expenditures of inpatient care, outpatient care (including chemotherapy), and outpatient pharmacy costs. The out-of-pocket costs incurred by the patients in the form of copayments, coinsurance, and deductibles were estimated. Results A total of 4495 patients, including 3014 (67%) who underwent surgery and 1481 (33%) who primarily underwent radiotherapy, were identified. The median total expenditure per patient during the first year after the diagnosis was $56,250 (interquartile range, $25,767–$107,532). The median total expenditure for patients with surgery as the primary treatment was $37,222 (interquartile range, $20,957–$75,555). The median total expenditure for patients treated primarily with radiotherapy was $101,266 (interquartile range, $63,155–$160,760). For patients treated primarily with surgery, inpatient services accounted for $15,145 (interquartile range, $0–$26,898), outpatient services accounted for $18,430 (interquartile range, $5354–$48,047), and outpatient pharmacy costs accounted for $628 (interquartile range, $141–$1847). The median cost for those women who did not require adjuvant therapy was $26,164 compared with $89,760 for women treated with adjuvant radiation. The median out-of-pocket costs for the cohort was $2253 (interquartile range, $1137–$3990) or 3.9% of the total costs. Conclusion The cost of care for women with newly diagnosed cervical cancer is substantial. Overall, patients are responsible for approximately 3.9% of the costs in the form of out-of-pocket expenditures.

Among men in South Africa, the prevalence of tobacco smoking is as high as 33%. Although smoking is responsible for most lung cancer in South Africa, occupational and environmental exposures contribute greatly to risk. We conducted a tobacco and lung cancer screening needs assessment and administered surveys to adults who smoked >100 cigarettes in their lifetime in Johannesburg (urban) and Kimberley (rural). We compared tobacco use, risk exposure, attitudes toward and knowledge of, and receptivity to cessation and screening, by site. Of 324 smokers, nearly 85% of current smokers had a

Background: Recent data suggest that subcutaneous adiposity represents an independent prognostic marker in cancer. We aimed to determine whether subcutaneous adiposity estimated by the subcutaneous adiposity tissue index (SATI) was associated with mortality in esophageal cancer. Methods: We conducted a retrospective analysis of a prospectively enrolled cohort from 2009 to 2015 with esophageal cancer at two major cancer centers. CT scans for initial staging were used to quantify adiposity and skeletal muscle areas. Subjects were categorized as above or below median SATI using sex-specific values. Sarcopenia was defined using previously established skeletal muscle area cutoffs. Cox proportional hazards modeling was performed to determine associations between SATI and all-cause mortality. Results: Of the original 167 patients, 78 met inclusion criteria and had CT images available. Mean age was 67 years, 81.8% had adenocarcinoma, and 58.9% had stage 3 or 4 disease. Median follow-up time was 29.5 months. Overall 5-year survival was 38.9% [95% confidence interval (CI), 26.8–50.7]. Lower body mass index, higher Charlson comorbidity score, and more advanced stage were independently associated with low SATI. Patients with low SATI had increased mortality (unadjusted HR 2.23; 95% CI, 1.20–4.12), even when adjusted for sarcopenia or for percent weight loss. In a multivariable model including age, histology, stage, and receipt of curative surgery, the association between low SATI and mortality was attenuated (adjusted HR 1.64; 95% CI, 0.81–3.34). Conclusions: Low subcutaneous adiposity as estimated by SATI may be associated with increased mortality in esophageal cancer. Impact: Interventions to reduce loss of subcutaneous fat may improve survival in esophageal cancer.

Author(s): Major-Pedersen, Atheline; McCullen, Mary Kate; Sabol, Mary Elizabeth; Adetunji, Omolara; Massaro, Joseph; Neugut, Alfred I; Sosa, Julie Ann; Hollenberg, Anthony N | Abstract: PurposeTo share better practice in establishing data monitoring committees (DMCs) for observational, retrospective safety studies with joint-industry sponsorship.MethodsA DMC model was created to monitor data from an observational, retrospective, post-authorization safety study investigating risk of medullary thyroid cancer in patients treated with long-acting glucagon-like peptide-1 receptor agonists (LA GLP-1RAs) (NCT01511393). Sponsors reviewed regulatory guidelines, best practice and sponsors' standard operation procedures on DMCs. Discussions were held within the four-member consortium, assessing applicability to observational, retrospective, real-world studies. A DMC charter was drafted based on a sponsor-proposed, adapted DMC model. Thereafter, a kick-off meeting between sponsors and DMC members was held to receive DMC input and finalize the charter.ResultsDue to this study's observational, retrospective nature, assuring participant safety - central for traditional explanatory clinical trial models - was not applicable to our DMC model. The overall strategy and key indication for our real-world model included preserving study integrity and credibility. Therefore, DMC member independence and their contribution of expert knowledge were essential. To ensure between-sponsor data confidentiality, all study committees/corporations and sponsors, besides the DMC, received blinded data only (adapted to refer to data blinding that revealed the specific marketed LA GLP-1RA/sponsor). Communication and blinding/unblinding of these data were facilitated by the contract research organization, which also provided crucial operational oversight.ConclusionsTo our knowledge, we have established the first DMC model for joint industry-sponsored, observational, retrospective safety studies. This model could serve as a precedent for others performing similar post-marketing, joint industry-sponsored pharmacovigilance activities.

PURPOSE Nonadherence to aromatase inhibitors (AIs) for breast cancer is common and increases the risk of recurrence. Text messaging increases adherence to medications for chronic conditions. METHODS We conducted a randomized clinical trial of text messaging (TM) versus no text messaging (No-TM) at 40 sites in the United States. Eligible patients were postmenopausal women with early-stage breast cancer taking an AI for > 30 days with a planned duration of ≥ 36 months. Test messages were sent twice a week over 36 months. Content themes focused on overcoming barriers to medication adherence and included cues to action, statements related to medication efficacy, and reinforcements of the recommendation to take AIs. Both groups were assessed every 3 months. The primary outcome was time to adherence failure (AF), where AF was defined as urine AI metabolite assay results satisfying one of the following: < 10 ng/mL, undetectable, or no submitted specimen. A stratified log-rank test was conducted. Multiple sensitivity analyses were performed. RESULTS In total, 724 patients were registered between May 2012 and September 2013, among whom,702 patients (348 in the text-messaging arm and 354 in the no–text-messaging arm) were eligible at baseline. Observed adherence at 36 months was 55.5% for TM and 55.4% for No-TM. The primary analysis showed no difference in time to AF by arm (3-year AF: 81.9% TM v 85.6% No-TM; HR, 0.89 [95% CI, 0.76 to 1.05]; P = .18). Multiple time to AF sensitivity analyses showed similar nonsignificant results. Three-year self-reported time to AF (10.4% v 10.3%; HR, 1.16 [95% CI, 0.69 to 1.98]; P = .57) and site-reported time to AF (21.9% v 18.9%; HR, 1.31 [95% CI, 0.86 to 2.01]; P = .21) also did not differ by arm. CONCLUSION To our knowledge, this was the first large, long-term, randomized trial of an intervention directed at improving AI adherence. We found high rates of AI AF. Twice-weekly text reminders did not improve adherence to AIs. Improving long-term adherence will likely require personalized and sustained behavioral interventions.

To examine patterns of patient travel among women with ovarian cancer and to explore the association between travel distance and short and long-term outcomes.Women with stage II-IV epithelial ovarian cancer diagnosed from 2004 to 2016 who underwent primary surgery were identified in the National Cancer Database. Mixed-effect log-linear models and proportional hazards models were developed to evaluate the association between travel distance and short and long-term outcomes after propensity score weighting. A further analysis was performed to compare patients who traveled a short distance to a low volume center (Local) to patients who traveled farther to a high volume hospital (Travel).We identified 56,834 patients treated in 1201 hospitals. Hispanic women were 58% and black women 64% less likely than white women to travel to a center in the greatest distance quartile for care. Similarly, Medicaid recipients (vs. commercially insured) were less likely to travel to a quartile four hospital (compared to Q1 of distance traveled). Of all patients, 90-day mortality was significantly lower in patients who traveled farther (Q4 vs. Q1; P 0.0001). Compared to women in the Local group, patients in the Travel group had a decreased 30-day readmission rate. There was no difference in 30-day, 90-day, or 5-year mortality when comparing the Local to the Travel group.Travel distance for ovarian cancer surgery has increased over time. While there may be some short-term benefits in traveling to a regional center for care, there was little difference in long term outcomes based on travel distance.

Background Estrogen metabolite concentrations of 2-hydroxyestrone (2-OHE1) and 16-hydroxyestrone (16-OHE1) may be associated with breast carcinogenesis. However, no study has investigated their possible impact on mortality after breast cancer. Methods This population-based study was initiated in 1996–1997 with spot urine samples obtained shortly after diagnosis (mean = 96 days) from 683 women newly diagnosed with first primary breast cancer and 434 age-matched women without breast cancer. We measured urinary concentrations of 2-OHE1 and 16-OHE1 using an enzyme-linked immunoassay. Vital status was determined via the National Death Index (n = 244 deaths after a median of 17.7 years of follow-up). We used multivariable-adjusted Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the estrogen metabolites-mortality association. We evaluated effect modification using likelihood ratio tests. All statistical tests were two-sided. Results Urinary concentrations of the 2-OHE1 to 16-OHE1 ratio (>median of 1.8 vs ≤median) were inversely associated with all-cause mortality (HR = 0.74, 95% CI = 0.56 to 0.98) among women with breast cancer. Reduced hazard was also observed for breast cancer mortality (HR = 0.73, 95% CI = 0.45 to 1.17) and cardiovascular diseases mortality (HR = 0.76, 95% CI = 0.47 to 1.23), although the 95% confidence intervals included the null. Similar findings were also observed for women without breast cancer. The association with all-cause mortality was more pronounced among breast cancer participants who began chemotherapy before urine collection (n = 118, HR = 0.42, 95% CI = 0.22 to 0.81) than among those who had not (n = 559, HR = 0.98, 95% CI = 0.72 to 1.34; Pinteraction = .008). Conclusions The urinary 2-OHE1 to 16-OHE1 ratio may be inversely associated with long-term all-cause mortality, which may depend on cancer treatment status at the time of urine collection.

Objective: Recent studies of primary central nervous system lymphoma (PCNSL) have found a positive association between cytoreductive surgery and survival, challenging the traditional notion that surgery is not beneficial and potentially harmful. However, no studies have examined the potential added benefits of adjuvant treatment in the post-operative setting. Here, we investigate survival in PCNSL patients treated with surgery plus radiation therapy (RT). Methods: The Surveillance, Epidemiology, and End-Results Program was used to identify patients with PCNSL from 1995–2013. We retrospectively analyzed the relationship between treatment, prognostic factors, and survival using case-control design. Treatment categories were compared to biopsy alone. Results: We identified 5417 cases. Median survival times for biopsy alone (n = 1824, 34%), biopsy + RT (n = 1460, 27%), surgery alone (n = 1222, 27%), and surgery + RT (n = 911, 17%) were 7, 8, 20, and 27 months, respectively. On multivariable analysis, surgery + RT was associated with improved survival over surgery alone (hazard ratio [HR] = 0.58 [95% confidence interval = 0.53–0.64] vs. HR = 0.71 [0.65–0.77]). Adjuvant RT was associated with improved survival, regardless of the extent of resection. HR’s for subtotal resection, gross-total resection, subtotal resection + RT, and gross-total resection + RT were 0.77 (0.66–0.89), 0.66 (0.57–0.76), 0.62 (0.52–0.72), and 0.54 (0.46–0.63), respectively. Survival improved after adjuvant RT in patients under and over 60 years old. All findings were confirmed by multivariable analysis of cause-specific survival. Conclusion: Adjuvant RT was associated with improved survival in PCNSL patients who underwent surgery. Although these data are hypothesis-generating, additional information on neurotoxicity, dosing, and concurrent chemotherapy will be necessary to validate these findings. Cytoreductive surgery for PCNSL is common in the general population, and more studies are needed to assess optimal treatment in the post-operative setting.

Objective To examine the risk of nodal metastases in a contemporary cohort of women based on pathologic risk factors including histology, depth of invasion, tumor grade, and lymphovascular space invasion. Methods Women with endometrial cancer who underwent hysterectomy from 2004 to 2016 who were registered in the National Cancer Database were analyzed. Patients were stratified by T stage: T1A ( 50% myometrial invasion) and T2 (cervical involvement). Lymph node metastases were assessed in relation to tumor T stage and grade, and further stratified by lymphovascular space invasion. Results We identified 161,960 patients. The rate of nodal metastases within the endometrioid histology cohort was 2.2% for T1A cancers, 12.8% for T1B cancers and 19.9% for T2 cancers. For stage TIA cancers, the percent of patients with positive nodes increased from 1.1% for grade 1 cancers, to 2.9% for grade 2 cancers to 4.8% for grade 3 cancers. The corresponding rates of nodal metastases for stage T1B cancers were 8.6%, 13.7%, and 16.9%, respectively. For T1A cancers without lymphovascular space invasion, nodal metastases ranged from 0.6% in those with grade 1 cancers to 3.0% for grade 3 cancers. The corresponding risk of nodal disease ranged from 11.8% to 13.9% for T1A cancers with lymphovascular space invasion. Conclusions There was a sequential increase in the risk of lymph node metastases based on depth of uterine invasion, tumor grade, and the presence of lymphovascular space invasion. The overall rate of nodal metastasis is lower than reported in the original GOG 33.

Background. The 5-year survival rate of patients with metastatic gastric cancer (GC) is only 5%. However, trials have demonstrated promising antitumor activity for targeted therapies/immunotherapies among chemorefractory metastatic GC patients. Pembrolizumab has shown particular efficacy among patients with programmed death ligand-1 (PD-L1) expression and high microsatellite instability (MSI-H). The aim of this study was to assess the effectiveness and cost-effectiveness of biomarker-guided second-line GC treatment. Methods. We constructed a Markov decision-analytic model using clinical trial data. Our model compared pembrolizumab monotherapy and ramucirumab/paclitaxel combination therapy for all patients and pembrolizumab for patients based on MSI status or PD-L1 expression. Paclitaxel monotherapy and best supportive care for all patients were additional comparators. Costs of drugs, treatment administration, follow-up, and management of adverse events were estimated from a US payer perspective. The primary outcomes were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100,000/QALY over 60 months. Secondary outcomes were unadjusted life years (survival) and costs. Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. Results. The most effective strategy was pembrolizumab for MSI-H patients and ramucirumab/paclitaxel for all other patients, adding 3.8 months or 2.0 quality-adjusted months compared to paclitaxel. However, this strategy resulted in a prohibitively high ICER of $1,074,620/QALY. The only cost-effective strategy was paclitaxel monotherapy for all patients, with an ICER of $53,705/QALY. Conclusion. Biomarker-based treatments with targeted therapies/immunotherapies for second-line metastatic GC patients substantially improve unadjusted and quality-adjusted survival but are not cost-effective at current drug prices.

Purpose Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA. Methods We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array. Results We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories. Conclusion We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.

Background Racial/ethnic differences in mortality have not been well studied for either non‐cardia gastric cancer (NCGC) or cardia gastric cancer (CGC). The aim of this study was to examine the US mortality rates for these cancer subtypes, as well as esophageal adenocarcinoma (EAC) as a comparator. Methods We identified 14 164 individuals who died from NCGC, 5235 from CGC, and 13 982 from EAC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Age‐adjusted incidence‐based mortality rates and corresponding annual percent changes (APCs) were calculated. Analyses were stratified by race/ethnicity, age, and stage of disease at diagnosis. Results The mortality rate in NCGC was two‐ to threefold higher in blacks, Hispanics, and Asians/Pacific Islanders (PI) than non‐Hispanic whites, and was significant across all age groups and stages of disease (P, This study examined the US incidence‐based mortality rates for cardia and non‐cardia gastric cancer, as well as esophageal adenocarcinoma as a comparator, and found distinct trends. Mortality was higher in blacks, Hispanics, and Asians/Pacific Islanders compared to non‐Hispanic whites in non‐cardia gastric cancer, but higher in non‐Hispanic whites in cardia gastric cancer and esophageal adenocarcinoma. Further studies are needed to refine prevention strategies for high‐risk individuals dying from these specific cancer subtypes.

Context When religious and spiritual (R/S) care needs of patients with advanced disease are met, their quality of life (QoL) improves. We studied the association between R/S support and QoL of patients with cancer at the end of life in Soweto, South Africa. Objectives To identify R/S needs among patients with advanced cancer receiving palliative care services and to assess associations of receipt of R/S care with patient QoL and place of death. Methods A prospective cohort study conducted from May 1, 2016 to April 30, 2018 at a tertiary hospital in Soweto, South Africa. Nurses enrolled patients with advanced cancer and referred them to the palliative care multidisciplinary team. Spiritual counselors assessed and provided spiritual care to patients. We compared sociodemographic, clinical, and R/S factors and QoL of R/S care recipients and others. Results Of 233 deceased participants, 92 (39.5%) had received R/S care. Patients who received R/S care reported less pain (2.82 ± 1.23 vs. 1.93 ± 1.69), used less morphine, and were more likely to die at home than patients who did not (57.5% compared with 33.7%). On multivariate logistic regression analysis, adjusting for significant confounding influences and baseline African Palliative Care Association Palliative care Outcome Scale scores, receipt of spiritual care was associated with reduced pain and family worry (odds ratio 0.33; 95% CI 0.11–0.95 and odds ratio 3.43; 95% CI 1.10–10.70, respectively). Conclusion Patients with cancer have R/S needs. R/S care among our patients appeared to improve their end-of-life experience. More research is needed to determine the mechanisms by which R/S care may have improved the observed patient outcomes.