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Abstract Background Colon cancer incidence is rising in low‐ and middle‐income countries (LMICs), where resource limitations and cost often dictate treatment decisions. In this study, we evaluate the cost‐effectiveness of adjuvant chemotherapy for high‐risk stage II and stage III colon cancer treatment in South Africa (ZA) and illustrate how such analyses can inform cancer treatment recommendations in a LMIC. Methods We created a decision‐analytic Markov model to compare lifetime costs and outcomes for patients with high‐risk stage II and stage III colon cancer treated with three adjuvant chemotherapy regimens in a public hospital in ZA: capecitabine and oxaliplatin (CAPOX) for 3 and 6 months, and capecitabine for 6 months, compared to no adjuvant treatment. The primary outcome was the incremental cost‐effectiveness ratio (ICER) in international dollars (I$) per disability‐adjusted life‐year (DALY) averted, at a willingness‐to‐pay (WTP) threshold equal to the 2021 ZA gross domestic product per capita (I$13,764/DALY averted). Results CAPOX for 3 months was cost‐effective for both patients with high‐risk stage II and patients with stage III colon cancer (ICER = I$250/DALY averted and I$1042/DALY averted, respectively), compared to no adjuvant chemotherapy. In subgroup analyses of patients by tumor stage and number of positive lymph nodes, for patients with high‐risk stage II colon cancer and T4 tumors, and patients with stage III colon cancer with T4 or N2 disease. CAPOX for 6 months was cost‐effective and the optimal strategy. The optimal strategy in other settings will vary by local WTP thresholds. Decision analytic tools can be used to identify cost‐effective cancer treatment strategies in resource‐constrained settings. Conclusion Colon cancer incidence is increasing in low‐ and middle‐income countries, including South Africa, where resource constraints can impact treatment decisions. This cost‐effectiveness study evaluates three systemic adjuvant chemotherapy options, compared to surgery alone, for patients in South African public hospitals after surgical resection for high‐risk stage II and stage III colon cancer. Doublet adjuvant chemotherapy (capecitabine and oxaliplatin) for 3 months is the cost‐effective strategy and should be recommended in South Africa.

Abstract Background Men of African descent are disproportionately affected by prostate cancer (PCa), and many have metastatic disease at presentation. In South Africa (SA), androgen deprivation therapy (ADT) is the first‐line treatment for stage IV PCa. Objective To identify predictors of overall survival (OS) in Black South African men with stage IV PCa treated with ADT. Design, Setting, and Participants Men diagnosed with prostate cancer (3/22/2016–10/30/2020) at Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, were recruited for the Men of African Descent with Cancer of the Prostate study. We included men with newly diagnosed stage IV PCa treated with ADT who had a prostate‐specific antigen (PSA) level drawn prior to initiation of ADT and had ≥1 PSA drawn ≥12 weeks after ADT start. Outcomes Measures and Statistical Analysis We used Kaplan–Meier statistics to estimate OS and Cox regression models to identify predictors of OS. Results and Limitations Of the 1097 men diagnosed with prostate cancer, we included 153 men with stage IV PCa who received ADT and met PSA requirements. The median age was 68.0 years (interquartile range 64–73 years). Median OS from time of ADT initiation was 3.39 years (95% confidence interval (CI): 3.14%–noncalculable), while biochemical progression‐free survival was 2.36 years (95% CI: 2.03%–3.73%). Biochemical progression (HR 3.52, 95% CI: 1.85%–6.70%), PSA nadir level >4 ng/mL (HR 3.77, 95% CI: 1.86%–7.62%), alkaline phosphatase level at diagnosis >150 IU/dL (HR 3.09, 95% CI: 1.64%–5.83%), and hemoglobin at diagnosis

KRAS G12C mutations are critical in the pathogenesis of multiple cancer types, including non-small cell lung (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and colorectal (CRC) cancers. As such, they have increasingly become a target of novel therapies in the management of these malignancies. However, the therapeutic success of KRAS G12C inhibitors to date has been far more limited in CRC and PDAC than NSCLC. In this review, we briefly summarize the biochemistry of KRAS targeting and treatment resistance, highlight differences in the epidemiology of various G12C-mutated cancers, and provide an overview of the published data on KRAS G12C inhibitors for various indications. We conclude with a summary of ongoing clinical trials in G12C-mutant CRC and a discussion of future directions in the management of this disease. KRAS G12C mutation, targeted therapies, colorectal cancer, non-small cell lung cancer, pancreatic cancer, drug development.

Purpose: The global rise in cancer incidence has been accompanied by disproportionately high morbidity and mortality rates in low- and middle-income countries. Many patients who are offered potentially curative treatment for cervical cancer in low- and middle-income countries never return to start treatment for reasons that are poorly documented and little understood. We investigated the interplay of sociodemographic, financial, and geographic factors as barriers to care among such patients in Botswana and Zimbabwe. Methods and Materials: Patients seen in consultation between 2019 and 2021 who were >3 months late for an appointment to initiate definitive treatment were contacted via telephone and invited to complete a survey. Afterward, an intervention connected patients with resources and counseling to return for treatment. Follow-up data were collected 3 months later to ascertain the outcomes of the intervention. Fisher exact tests analyzed the relationship between the putative number and types of barriers and demographics. Results: We recruited 40 women who initially presented for oncology care but did not return for treatment at [Princess Marina Hospital] in Botswana (n = 20) and [Parirenyatwa General Hospital] in Zimbabwe (n = 20) to complete the survey. Overall, married women experienced more barriers than unmarried women (P < .001), and unemployed women were 10 times more likely to report a financial barrier than employed women (P = .02). In Zimbabwe, financial barriers and belief-associated barriers (eg, fear of treatment) were reported. In Botswana, many patients noted scheduling obstacles associated with administrative delays and COVID-19. At follow-up, 16 Botswana patients and 4 Zimbabwe patients had returned for treatment. Conclusions: Financial and belief barriers identified in Zimbabwe showcase the importance of targeting cost and health literacy to reduce apprehensions. In Botswana, administrative challenges could be addressed with patient navigation. Improving our understanding of the specific barriers to cancer care could enable us to help patients who might otherwise default.

Abstract Background Breast cancer survival in South Africa is low, but when diagnosed with breast cancer, many women in South Africa also have other chronic conditions. We investigated the impact of multimorbidity (≥ 2 other chronic conditions) on overall survival among women with breast cancer in South Africa. Methods Between 1 July 2015 and 31 December 2019, we enrolled women newly diagnosed with breast cancer at six public hospitals participating in the South African Breast Cancer and HIV Outcomes (SABCHO) Study. We examined seven chronic conditions (obesity, hypertension, diabetes, HIV, cerebrovascular diseases (CVD), asthma/chronic obstructive pulmonary disease, and tuberculosis), and we compared socio-demographic, clinical, and treatment factors between patients with and without each condition, and with and without multimorbidity. We investigated the association of multimorbidity with overall survival using multivariable Cox proportional hazard models. Results Of 3,261 women included in the analysis, 45% had multimorbidity; obesity (53%), hypertension (41%), HIV (22%), and diabetes (13%) were the most common individual conditions. Women with multimorbidity had poorer overall survival at 3 years than women without multimorbidity in both the full cohort (60.8% vs. 64.3%, p = 0.036) and stage groups: stages I–II, 80.7% vs. 86.3% (p = 0.005), and stage III, 53.0% vs. 59.4% (p = 0.024). In an adjusted model, women with diabetes (hazard ratio (HR) = 1.20, 95% confidence interval (CI) = 1.03–1.41), CVD (HR = 1.43, 95% CI = 1.17–1.76), HIV (HR = 1.21, 95% CI = 1.06–1.38), obesity + HIV (HR = 1.24 95% CI = 1.04–1.48), and multimorbidity (HR = 1.26, 95% CI = 1.13–1.40) had poorer overall survival than women without these conditions. Conclusions Irrespective of the stage, multimorbidity at breast cancer diagnosis was an important prognostic factor for survival in our SABCHO cohort. The high prevalence of multimorbidity in our cohort calls for more comprehensive care to improve outcomes for South African women with breast cancer.

Abstract Background Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. Results Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608–0.707, OR 2.37–5.71) than for African individuals (AUC 0.502–0.585, OR 0.95–2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. Conclusions Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

Background. To explore preferred and actual involvement in chemotherapy decision making among stage II and III colon cancer (CC) patients by sociodemographic, interpersonal, and intrapersonal communication factors. Methods. Cross-sectional exploratory study collecting self-reported survey data from stage II and III CC patients from 2 cancer centers located in northern Manhattan. Results. Of 88 patients approached, 56 completed the survey. Only 19.3% reported shared involvement in their chemotherapy decisions. We observed significant differences in preferred involvement by gender, with women preferring more physician-controlled decisions. CC patients with higher levels of decisional self-efficacy significantly preferred shared decisions ( F = 4.4 [2], P = 0.02). Actual involvement in decisions differed by race (physician controlled 33% for White v. 67% for Other, P < 0.01), age (shared control 18% for ≤55 y, 55% for 55–64 y, and 27% for 65+ y, P = 0.04), and perception of choice (shared control 73% “yes” v. 27% “no,” P = 0.02). Actual or preferred involvement did not differ by stage. Significantly higher levels of medical mistrust (discrimination t = 2.8 [50], P = 0 .01; lack of support t = 3.6 [49], P < 0.01), and lower levels of decisional self-efficacy ( t = 2.5 [49], P = 0 .01) were reported among women. Discussion. Reports of shared involvement around chemotherapy decisions is limited among CC patients. Factors influencing preferred versus actual chemotherapy decision making are complex and may differ; hence, more research is needed to understand and address factors contributing to discordance between preferred and actual involvement in chemotherapy decision making for CC patients. Highlights Shared involvement around chemotherapy decisions remains limited for patients diagnosed with colon cancer. Sociodemographic (age, race, gender), interpersonal (medical mistrust), and intrapersonal (decisional self-efficacy, perception of choice) factors that influence preferred involvement in chemotherapy decision making may differ from those influencing actual involvement in chemotherapy decision making. Shared involvement in chemotherapy decisions may look different than currently conceptualized, notably when uncertainty around the benefits exists.

Post-colonoscopy consults empower patients to make informed decisions around their subsequent treatment, and non-compliance with these consults ("no-shows") hinders disease management. There is a paucity in the literature regarding self-adherence to post-colonoscopy consults in resource-limited settings such as South Africa. An understanding of self-adherence to post-colonoscopy consults in this setting is required to establish whether improved interventions are needed, and what specific elements of self-adherence should be addressed with these interventions. The objective of this hypothesis-generating, cross-sectional, quantitative survey was to conduct a baseline assessment of cognitive, motivational, social, and behavioural variables related to self-adherence to post-colonoscopy consults in patients who underwent diagnostic colonoscopy at a South African quaternary hospital. The Adherence Determinants Questionnaire (ADQ) was administered in 47 patients to establish a baseline assessment of elements related to self-adherence to post-colonoscopy consults, including interpersonal aspects of care, perceived utility, severity, susceptibility, subjective norms, intentions, and supports/barriers. ADQ scores were transformed to a percentage of the maximum score for each element (100.0%). The overall mean transformed ADQ score was 57.8%. The mean transformed scores for specific ADQ components were as follows: subjective norms (40.8%), perceived severity (55.4%), perceived utility (56.6%), intentions (59.4%), supports/barriers (59.9%), interpersonal aspects (62.2%), and perceived susceptibility (65.9%). There were no statistically significant differences in overall mean transformed ADQ scores and individual ADQ elements across categories of participant age (p-values ranging between 0.180 and 0.949 when compared between participants ≤40 years and >40 years old), gender (p-values ranging between 0.071 and 0.946 when compared between males and females), and race (p-values ranging between 0.119 and 0.774 when compared between Black Africans and non-Black Africans). Our findings suggest a general need for appropriate interventions to improve self-adherence to post-colonoscopy consults in our setting.

The South African Breast Cancer and HIV Outcomes prospective cohort (SABCHO) study was established to investigate survival determinants among HIV-positive and HIV-negative SA women with breast cancer. This paper describes common and unique characteristics of the cancer centres and their participants, examining disparities in pathways to diagnosis, treatment resources and approaches adopted to mitigate resource constraints. The Johannesburg (Jhb), Soweto (Sow), and Durban (Dbn) sites treat mainly urban, relatively better educated and more socioeconomically advantaged patients whereas the Pietermaritzburg (Pmb) and Empangeni (Emp) sites treat predominantly rural, less educated and more impoverished communities The Sow, Jhb, and Emp sites had relatively younger patients (mean ages 54 ±14.5, 55±13.7 and 54±14.3 respectively), whereas patients at the Dbn and Pmb sites, with greater representation of Asian Indian women, were relatively older (mean age 57 ±13.9 and 58 ±14.6 respectively). HIV prevalence among the cohort was high, ranging from 15%-42%, (Cohort obesity (BMI ≥ 30 kg/m2) at 60%, self-reported hypertension (41%) and diabetes (13%). Direct referral of patients from primary care clinics to cancer centre occurred only at the Sow site which uniquely ran an open clinic and where early stage (I and II) proportions were highest at 48.5%. The other sites relied on indirect patient referral from regional hospitals where significant delays in diagnostics occurred and early-stage proportions were a low (15%- 37.3%). The Emp site referred patients for all treatments to the Dbn site located 200km away; the Sow site provided surgery and endocrine treatment services but referred patients to the Jhb site 30 Km away for chemo- and radiation therapy. The Jhb, Dbn and Pmb sites all provided complete oncology treatment services. All treatment centres followed international guidelines for their treatment approaches. Findings may inform policy interventions to address national and regional disparities in breast cancer care.

Objective In low- and middle-income countries (LMICs), advanced-stage diagnosis of breast cancer (BC) is common, and this contributes to poor survival. Understanding the determinants of the stage at diagnosis will aid in designing interventions to downstage disease and improve survival from BC in LMICs. Methods Within the South African Breast Cancers and HIV Outcomes (SABCHO) cohort, we examined factors affecting the stage at diagnosis of histologically confirmed invasive breast cancer at five tertiary hospitals in South Africa (SA). The stage was assessed clinically. To examine the associations of the modifiable health system, socio-economic/household and non-modifiable individual factors, hierarchical multivariable logistic regression with odds of late-stage at diagnosis (stage III-IV), was used. Results The majority (59%) of the included 3497 women were diagnosed with late-stage BC disease. The effect of health system-level factors on late-stage BC diagnosis was consistent and significant even when adjusted for both socio-economic- and individual-level factors. Women diagnosed in a tertiary hospital that predominantly serves a rural population were 3 times (OR = 2.89 (95% CI: 1.40–5.97) as likely to be associated with late-stage BC diagnosis when compared to those diagnosed at a hospital that predominantly serves an urban population. Taking more than 3 months from identifying the BC problem to the first health system entry (OR = 1.66 (95% CI: 1.38–2.00)), and having luminal B (OR = 1.49 (95% CI: 1.19–1.87)) or HER2-enriched (OR = 1.64 (95% CI: 1.16–2.32)) molecular subtype as compared to luminal A, were associated with a late-stage diagnosis. Whilst having a higher socio-economic level (a wealth index of 5) reduced the probability of late-stage BC at diagnosis, (OR = 0.64 (95% CI: 0.47–0.85)). Conclusion Advanced-stage diagnosis of BC among women in SA who access health services through the public health system was associated with both modifiable health system-level factors and non-modifiable individual-level factors. These may be considered as elements in interventions to reduce the time to diagnosis of breast cancer in women.

PURPOSEBreast 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.METHODSNurses 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.RESULTSIn 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.CONCLUSIONThe program's training curriculum improved breast health knowledge and clinical skills. Efforts are needed to improve patients' receipt of recommended evaluation for breast abnormalities.

PURPOSECancer incidence is rising in low- and middle-income countries, where resource constraints often complicate therapeutic decisions. Here, we perform a cost-effectiveness analysis to identify the optimal adjuvant chemotherapy strategy for patients with stage III colon cancer treated in South African (ZA) public hospitals.METHODSA decision-analytic Markov model was developed to compare lifetime costs and outcomes for patients with stage III colon cancer treated with six adjuvant chemotherapy regimens in ZA public hospitals: fluorouracil, leucovorin, and oxaliplatin for 3 and 6 months; capecitabine and oxaliplatin (CAPOX) for 3 and 6 months; capecitabine for 6 months; and fluorouracil/leucovorin for 6 months. Transition probabilities were derived from clinical trials to estimate risks of toxicity, disease recurrence, and survival. Societal costs and utilities were obtained from literature. The primary outcome was the incremental cost-effectiveness ratio in international dollars (I$) per disability-adjusted life-year (DALY) averted, compared with no therapy, at a willingness-to-pay (WTP) threshold of I$13,006.56.RESULTSCAPOX for 3 months was cost-effective (I$5,381.17 and 5.74 DALYs averted) compared with no adjuvant chemotherapy. Fluorouracil, leucovorin, and oxaliplatin for 6 months was on the efficiency frontier with 5.91 DALYs averted but, with an incremental cost-effectiveness ratio of I$99,021.36/DALY averted, exceeded the WTP threshold.CONCLUSIONIn ZA public hospitals, CAPOX for 3 months is the cost-effective adjuvant treatment for stage III colon cancer. The optimal strategy in other settings may change according to local WTP thresholds. Decision analytic tools can play a vital role in selecting cost-effective cancer therapeutics in resource-constrained settings.

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

Abstract 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

Abstract Background Patients co-infected with hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are at risk of developing hepatocellular carcinoma (HCC). In sub-Saharan Africa, the overlap between high HIV and HBV prevalence may increase the incidence of HCC. This study investigated the impact of HBV/HIV co-infection on age at presentation and survival of HCC. Methods Ethical approval was obtained to recruit, following informed written consent, patients diagnosed with HCC at oncology units at four South African hospitals. Between December 2012 and August 2015, patients newly diagnosed with HCC were recruited and provided demographic and clinical data and blood specimens. Patients were tested for HBV, hepatitis C virus (HCV) and HIV. Survival data was available for a subset of patients. Results Of 107 HCC cases, 83 (78%) were male. Median age was 46 years (range 18 to 90 years), 68/106 (64%) were HBsAg-positive, and 22/100 (22%) were HIV infected. Among HBV surface antigen (HBsAg)-positive HCC cases, 18/66 (27%) were HIV-infected compared to 3/34 (9%) among those that were HBsAg-negative (p = 0.04). A greater proportion of HBV/HIV co-infected cases were female than HBV mono-infected (6/18, 33% vs 6/47, 13%; p = 0.005). In addition, HBV/HIV co-infected females presented at a younger mean age (36.8 years) than HBV mono-infected women (50.5 years) (p = 0.09). Median survival was 82 days among the HIV-infected HCC patients compared to 181 days among those without HIV (p = 0.15). Conclusions HCC is an important complication in the HIV/HBV infected patient. HIV-positive patients presented with HCC at a younger age than HIV-negative patients, this effect appears to be greater in women. These data provide more evidence supporting the call to address. HCC as a cause of morbidity and mortality in the HBV/HIV co-infected patient population. (281 words).

Objective With increases in chronic disease, men with prostate cancer are likely to have at least one other chronic health condition. The burden and complexity of each additional chronic disease may complicate prostate cancer treatment and reduce survival. In this paper, we describe the frequency of multimorbid chronic diseases, HIV and depression among men in Soweto, South Africa (SA) with and without prostate cancer and determine whether the presence of multimorbid diseases is associated with metastatic and high-risk, non-metastatic prostate cancer. Methods A population-based case-control study on prostate cancer was conducted among black men in Soweto. All participants completed a baseline survey on sociodemographics, lifestyle, and comorbid medical conditions. All participants completed a depression screening survey and HIV testing at enrolment. Blood pressure measurements and blood testing for fasting glucose, total cholesterol, and high-density lipoprotein were performed on a subset of randomly selected cases and controls. For men with prostate cancer, clinical T staging was assessed with the digital rectal examination, the diagnosis was confirmed with a biopsy and PSA levels were assessed at presentation. The metastatic staging was assessed by bone scans, and this was confirmed with PSMA PET scans, CT scans and X-rays, standard for our resource-constrained setting. Normal PSA scores were used as an inclusion criterion for controls. Results Of the 2136 men (1095 with prostate cancer and 1041 controls) included in the analysis, 43.0% reported at least one chronic metabolic disease; 24.1% reported two metabolic diseases; 5.3% reported three metabolic diseases; and 0.3% reported four metabolic diseases. Men with prostate cancer were more likely to report a multimorbid chronic metabolic disease compared to controls (p20ng/ml; 233 (21.7%) had confirmed metastatic prostate cancer at diagnosis. Older age was associated with metastatic prostate cancer (OR = 1.043 95% CI:1.02–1.07) and NCCN defined high-risk non-metastatic prostate cancer (OR = 1.03 95% CI:1.01–1.05), whilst being hypertensive was protective (OR = 0.63 95% CI:0.47–0.84 and OR = 0.55 95% CI:0.37–0.83) respectively for metastatic and high-risk, non-metastatic prostate cancer. Conclusion The high prevalence of multimorbid metabolic diseases and HIV among men with prostate cancer represents a public health concern in South Africa. There is a need to effectively address multiple chronic diseases among men with prostate cancer by incorporating coordinated care models.

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.

Abstract 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

BackgroundHigh-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).MethodsWe 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.ResultsOf 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.ConclusionhfIGRT 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.

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.

Purpose: The understanding of patients with cancer of their condition and their wishes regarding care as they approach end of life (EoL) have been studied more in high-income countries than in low- and middle-income countries (LMICs). Patients and Methods: Data were analyzed from a cohort study (N = 221) of patients with advanced cancer who were recruited from a palliative care center in Soweto, South Africa (LMIC), between May 2016 and June 2017. Patients were asked about their understanding of their illness, estimated life expectancy, EoL care communication, and EoL care preferences. Results: Only 13 patients (5.9%) acknowledged that they were terminally ill; nine patients (4.1%) estimated accurately that they had months, not years, left to live. A total of 216 patients (97.7%) reported that they had not had an EoL care discussion with their physician, and 170 patients (76.9%) did not want to know their prognosis even if the doctor knew it. Most patients preferred comfort care (72.9%; n = 161) to life-extending care (14.0%; n = 31), and did not want to be kept alive using extreme measures (80.5%; n = 178) or have their doctors do everything possible to extend their lives (78.3%; n = 173). Finally, 127 patients (57.5%) preferred to die at home, and 51 (23.1%) preferred to die in the hospital. Most patients (81.0%; n = 179) had funeral plans. Conclusion: South African patients demonstrated less awareness of the fact that they were terminally ill, were less likely to have discussed their prognosis with their doctor, and more strongly preferred comfort care to life-extending EoL care than US and other LMIC patients in prior research. These differences highlight the need for culturally appropriate, patient-centered EoL care for South African patients with advanced cancer as well as to determine individual preferences and needs in all EoL settings.

Purpose: The goal of this study was to describe the pathologic findings and early follow-up experience of patients who underwent a sentinel lymph node biopsy (SLNB) at Aga Khan University Hospital (AKUH) between 2008 and 2017. Patients and Methods: We performed a retrospective analysis of women with breast cancer who underwent an SLNB at AKUH between 2008 and 2017. The SLNB was performed on patients with stage I and stage II breast cancer, and identification of the sentinel lymph node was made by radioactive tracer, blue dye, or both, per availability and surgeon preference. Demographic, surgical, and pathologic data, including immunohistochemistry of the surgical sample for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, were abstracted from the patient records. Follow-up data were available for a subset of patients. Results: Between 2008 and 2017, six surgeons performed SLNBs on 138 women, 129 of whom had complete records and were included in the study. Thirty-one of 129 (24%) had a positive SLNB, including 10 of 73 (14%) with stage I and 21 of 56 (38%) with stage II disease. Seventy-eight patients (60%) received systemic adjuvant chemotherapy and 79 (62%) received radiation therapy, and of the 102 patients who were estrogen receptor positive, 86 (85%) received endocrine therapy. Seventy-nine patients were observed for > 2 years, and, of these, four (5.1%) had a regional recurrence. Conclusion: The SLNB positivity rates were similar to those of high-income country (HIC) cohorts. However, preliminary data suggest that recurrence rates are elevated at AKUH as compared with those of HIC cohorts, perhaps because of a lower use of radiotherapy and chemotherapy at AKUH compared with HIC cohorts or because of differences in the characteristics of the primary tumor in patients at AKUH as compared with those in HICs.

Purpose: In low- and middle-income, HIV-endemic regions of sub-Saharan Africa, morbidity and mortality from the common epithelial cancers of the developed world are rising. Even among HIV-infected individuals, access to antiretroviral therapy has enhanced life expectancy, shifting the distribution of cancer diagnoses toward non–AIDS-defining malignancies, including breast cancer. Building on our prior research, we recently initiated the South African Breast Cancer and HIV Outcomes study. Methods: We will recruit a cohort of 3,000 women newly diagnosed with breast cancer at hospitals in high (average, 20%) HIV prevalence areas, in Johannesburg, Durban, Pietermaritzburg, and Empangeni. At baseline, we will collect information on demographic, behavioral, clinical, and other factors related to access to health care. Every 3 months in year 1 and every 6 months thereafter, we will collect interview and chart data on treatment, symptoms, cancer progression, comorbidities, and other factors. We will compare survival rates of HIV-infected and uninfected women with newly diagnosed breast cancer and their likelihood of receiving suboptimal anticancer therapy. We will identify determinants of suboptimal therapy and context-specific modifiable factors that future interventions can target to improve outcomes. We will explore molecular mechanisms underlying potentially aggressive breast cancer in both HIV-infected and uninfected patients, as well as the roles of pathogens, states of immune activation, and inflammation in disease progression. Conclusion: Our goals are to contribute to development of evidence-based guidelines for the management of breast cancer in HIV-positive women and to improve outcomes for all patients with breast cancer in resource-constrained settings.

Background: Environmental phenols, compounds used widely in personal care and consumer products, are known endocrine disruptors. Few epidemiologic studies have examined the association of phenol biomarkers with breast cancer incidence and, to our knowledge, none have considered associations with mortality following breast cancer. We examined seven urinary phenol biomarkers in association with breast cancer incidence and subsequent mortality, and examined effect measure modification by body mass index (BMI). Methods: Participants included 711 women with breast cancer and 598 women without breast cancer who were interviewed for the population-based Long Island Breast Cancer Study Project. Among women with breast cancer, phenol biomarkers were quantified in spot urine samples collected on average within three months of a first diagnosis of primary in situ or invasive breast cancer in 1996–1997. Women with breast cancer were monitored for vital status using the National Death Index. After a median follow-up of 17.6 years, we identified 271 deaths, including 98 deaths from breast cancer. We examined creatinine-corrected phenol concentrations and the sum of parabens (Σparabens) in association with breast cancer incidence using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), and with mortality using Cox regression to estimate hazard ratios (HRs) and 95% CIs. We evaluated multiplicative effect measure modification using cross-product terms in nested models. Results: The highest (vs lowest) quintiles of urinary methylparaben, propylparaben, and Σparabens were associated with risk of breast cancer with ORs ranging from 1.31 to 1.50. Methylparaben, propylparaben, and Σparabens were also associated with all-cause mortality HRs ranging from 0.68 to 0.77. Associations for breast cancer incidence were more pronounced among women with BMI

DNA methylation has been implicated in breast cancer aetiology, but little is known about whether reproductive history and DNA methylation interact to influence carcinogenesis. This study examined modification of the association between global DNA methylation and breast cancer risk by reproductive characteristics. A population-based case-control study assessed reproductive history in an interviewer-administered questionnaire. Global DNA methylation was measured from white blood cell DNA using luminometric methylation assay (LUMA) and pyrosequencing assay (long interspersed elements-1 (LINE-1). We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) among 1 070 breast cancer cases and 1 110 population-based controls. Effect modification was assessed on additive and multiplicative scales. LUMA methylation was associated with elevated breast cancer risk across all strata (comparing the highest to the lowest quartile), but estimates were higher among women with age at menarche ≤12 years (OR = 2.87, 95%CI = 1.96-4.21) compared to >12 years (OR = 1.66, 95%CI = 1.20-2.29). We observed a 2-fold increase in the LUMA methylation-breast cancer association among women with age at first birth >23 years (OR = 2.62, 95%CI = 1.90-3.62) versus ≤23 years (OR = 1.32, 95% CI = 0.84-2.05). No modification was evident for parity or lactation. Age at menarche and age at first birth may be modifiers of the association between global DNA methylation and breast cancer risk.