Enhanced Fat Graft Viability and Remodeling Using a Helium-based Radiofrequency Device to Prepare the Recipient Site.

BACKGROUND: Improvements to autologous fat grafting for soft tissue augmentation are needed to overcome the unpredictable volume retention. Approaches such as fat harvesting and processing, injection technique, preparation of the recipient site, and supplemental biologics are topics of ongoing research. Here, an energy-based device was investigated as a stimulatory tool for recipient site preparation for improving fat graft retention. OBJECTIVE: The objective was to measure the stimulatory responses in fat grafts after 4 weeks when using a helium-based radiofrequency device to pretreat the recipient tissue. METHODS: Using an autologous fat grafting mouse model, the inguinal fat pad was grafted in a small cranial pocket after either a saline injection alone (control) or a saline injection followed by pretreatment (treated). The fat pad was resected after 4 weeks, sectioned and stained with immunofluorescence markers to investigate tissue remodeling. RESULTS: Pretreatment resulted in higher viability of adipocytes, a higher concentration of viable ASCs in areas of adipose tissue regeneration, and localized macrophages in the areas of regeneration when compared to the control. There was no observable difference in vascularity or angiogenesis. The staining for ASCs was higher in the pretreated group in comparison with the control group (5.0% vs. 3.3%, p=0.36) when using a pixel classifier in QuPath in the viable adipose tissue regions. CONCLUSIONS: The use of a helium-based radiofrequency device as a pretreatment tool appears to increase the viability of the adipose tissue likely due to higher concentration of ASCs. The apparent increase in viable ASCs may be due to enhanced proliferation or paracrine recruitment of these cells in response to the helium-based radiofrequency treatment. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Bullet List of Important Points: Pretreatment of the fat graft recipient site increases the viability of the adipose tissue after 4 weeks in comparison with the control grafts. The increased viability is likely due to the observed increase in adipose-derived stem cells in the pretreated group. Pretreatment enhanced the adipose tissue remodeling as colocalization of adipose-derived stem cells and macrophages showed an active remodeling, whereas the control group exhibited more necrotic and fibrotic tissue.

Multimorbidity and overall survival among women with breast cancer: results from the South African Breast Cancer and HIV Outcomes Study.

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.

The Impact of HIV Infection on Neoadjuvant and Adjuvant Chemotherapy Relative Dose Intensity in South African Patients with Breast Cancer.

INTRODUCTION: In the South African Breast Cancer and HIV Outcomes (SABCHO) study, we previously found that breast cancer patients living with HIV and treated with neoadjuvant chemotherapy achieve lower rates of complete pathologic response than patients without HIV. We now assess the impact of comorbid HIV on receipt of timely and complete neoadjuvant and adjuvant chemotherapy. MATERIALS AND METHODS: Since June 2015, the SABCHO study has collected data on women diagnosed with breast cancer at 6 South African hospitals. We selected a sample of participants with stages I-III cancer who received ≥2 doses of neoadjuvant or adjuvant chemotherapy. Data on chemotherapies prescribed and received, filgrastim receipt, and laboratory values measured during treatment were captured from patients' medical records. We calculated the mean relative dose intensity (RDI) for all prescribed chemotherapies. We tested for association between full regimen RDI and HIV status, using linear regression to control for demographic and clinical covariates, and for association of HIV with laboratory abnormalities. RESULTS: The 166 participants living with HIV and 159 without HIV did not differ in median chemotherapy RDI: 0.89 (interquartile range (IQR) 0.77-0.95) among those living with HIV and 0.87 (IQR 0.77-0.94) among women without HIV. Patients living with HIV experienced more grade 3+ anemia and leukopenia than those without HIV (anemia: 10.8% vs. 1.9%, P = .001; leukopenia: 8.4% vs. 1.9%, P = .008) and were more likely to receive filgrastim (24.7% vs. 10.7%, P = .001). CONCLUSIONS: HIV status did not impact neoadjuvant or adjuvant chemotherapy RDI, although patients with breast cancer living with HIV experienced more myelotoxicity during treatment.

Discordance between PAM50 intrinsic subtyping and immunohistochemistry in South African women with breast cancer.

PURPOSE: Breast cancer is a heterogeneous disease with different gene expression profiles, treatment options and outcomes. In South Africa, tumors are classified using immunohistochemistry. In high-income countries multiparameter genomic assays are being utilized with implications for tumor classification and treatment. METHODS: In a cohort of 378 breast cancer patients from the SABCHO study, we investigated the concordance between tumor samples classified by IHC and the PAM50 gene assay. RESULTS: IHC classified patients as ER-positive (77.5%), PR-positive (70.6%), and HER2-positive (32.3%). These results, together with Ki67, were used as surrogates for intrinsic subtyping, and showed 6.9% IHC-A-clinical, 72.7% IHC-B-clinical, 5.3% IHC-HER2-clinical and 15.1% triple negative cancer (TNC). Typing using the PAM50 gave 19.3% luminal-A, 32.5% luminal-B, 23.5% HER2-enriched and 24.6% basal-like. The basal-like and TNC had the highest concordance, while the luminal-A and IHC-A group had the lowest concordance. By altering the cutoff for Ki67, and realigning the HER2/ER/PR-positive patients to IHC-HER2, we improved concordance with the intrinsic subtypes. CONCLUSION: We suggest that the Ki67 be changed to a cutoff of 20-25% in our population to better reflect the luminal subtype classifications. This change would inform treatment options for breast cancer patients in settings where genomic assays are unaffordable.

PAM50 intrinsic subtypes, risk of recurrence score and breast cancer survival in HIV-positive and HIV-negative patients-a South African cohort study.

PURPOSE: Treatment decision making for patients with breast cancer increasingly depends on analysis of markers or systems for estimating risk of breast cancer recurrence. Breast cancer intrinsic subtypes and risk of recurrence (ROR) scores have been found to be valuable in predicting survival and determining optimal treatment for individual patients. We studied the association of breast cancer survival with the PAM50 gene expression assay in HIV-positive and HIV-negative patients. METHOD: RNA was extracted from formalin-fixed paraffin-embedded specimens of histologically confirmed invasive carcinoma and was purified using the AllPrep® DNA/RNA FFPE kit, Qiagen (Hilden, Germany). The NanoString RUO PAM50 algorithm was used to determine the molecular subtype and the risk of recurrence score of each sample. The overall and disease-free survival were determined with comparison made among HIV-positive and -negative patients. We then generated Kaplan-Meier survival curves, calculated p-values and estimated hazard ratios and their 95% confidence intervals using Cox regression models. RESULTS: Of the 384 RNA samples analysed, 98.4% met the required RNA quality standard and the specified QC threshold for the test. Luminal B was the most common PAM50 intrinsic subtype and 82.1% of patients were at high risk for disease recurrence based on ROR score. HIV infection, PAM50-based HER2-enriched and basal-like intrinsic subtypes, and high ROR were associated with poor overall and disease-free survival. HIV-positive patients with luminal A & B subtypes had significantly worse survival outcomes than HIV-negative luminal patents. CONCLUSION: Aggressive tumour biology was common in our cohort. HIV infection, PAM50 HER2-enriched,basal-like intrinsic subtypes and high ROR score were associated with poor overall and disease-free survival. HIV infection impacted survival in patients with luminal subtypes only.

The impact of HIV on non-adherence for tamoxifen among women with breast cancer in South Africa.

PURPOSE: Women living with HIV (WLWH) and breast cancer (BC) have worse overall survival than HIV-negative women with BC, and poor adherence to prescribed tamoxifen is known to contribute to poor survival. We therefore investigated the association of HIV infection with adherence to adjuvant tamoxifen among women with localized hormone receptor (HR)-positive breast cancer in South Africa. METHODS: Among 4,097 women diagnosed with breast cancer at six hospitals in the prospective South African Breast Cancer and HIV Outcomes (SABCHO) cohort study between July 2015 and December 2020, we focused on black women with stages I-III HR-positive breast cancer who were prescribed 20 mg of adjuvant tamoxifen daily. We collected venous blood once from each participant during a routine clinic visit, and analyzed concentrations of tamoxifen and its metabolites using a triple quadruple mass spectrometer. We defined non-adherence as a tamoxifen level < 60 ng/mL after 3 months of daily tamoxifen use. We compared tamoxifen-related side effects, and concurrent medication use among women with and without HIV and developed multivariable logistic regression models of tamoxifen non-adherence. RESULTS: Among 369 subjects, 78 (21.1%) were WLWH and 291 (78.9%) were HIV-negative. After a median (interquartile range) time of 13.0 (6.2-25.2) months since tamoxifen initiation, the tamoxifen serum concentration ranged between 1.54 and 943.0 ng/mL and 208 (56.4%) women were non-adherent to tamoxifen. Women < 40 years of age were more likely to be non-adherent than women > 60 years (73.4% vs 52.6%, odds ratio (OR) = 2.49, 95% confidence interval (CI) = 1.26-4.94); likewise, WLWH (70.5% vs 52.6%, OR = 2.16, 95% CI = 1.26-3.70) than HIV-negative women. In an adjusted model WLWH had twice the odds of non-adherence to tamoxifen, compared to HIV-negative women (OR = 2.40, 95% CI = 1.11-5.20). CONCLUSION: High rates of non-adherence to adjuvant tamoxifen may limit the overall survival of black South African women with HR-positive breast cancer, especially among WLWH.

Safety and Efficacy of Renuvion Helium Plasma to Improve the Appearance of Loose Skin in the Neck and Submental Region.

BACKGROUND: Minimally invasive procedures that deliver thermal energy to subcutaneous tissue offer a solution when deciding between excisional and noninvasive options to address face and neck aging-related changes. A minimally invasive helium plasma device, Renuvion, was first utilized for subdermal tissue heating to reduce skin laxity under an FDA general clearance for cutting, coagulation, and ablation of soft tissue. OBJECTIVES: The purpose of this study was to demonstrate the safety and effectiveness of the helium plasma device for improving the appearance of loose skin in the neck and submental region. METHODS: Patients undergoing the procedure with the helium plasma device in the neck and submentum were studied. They were seen for 6 months following the procedure. The primary effectiveness endpoint for improvement in lax skin in the treatment area was determined by 2 of 3 blinded photographic reviewers. The primary safety endpoint was the level of pain after treatment. RESULTS: The primary effectiveness endpoint was met; 82.5% demonstrated improvement at Day 180. The primary safety endpoint was met; 96.9% of patients experienced no pain to moderate pain to Day 7. There were no serious adverse events reported related to the study device or procedure. CONCLUSIONS: The data demonstrate benefit to patients by improvement of the appearance of lax skin in the neck and submental region. Outcomes resulted in US Food and Drug Administration 510(k) clearance in July 2022, expanding indications for the device to include subcutaneous dermatological and aesthetic procedures to improve the appearance of loose skin in the neck and submental region.

Impact of HIV infection on survival among women with stage I-III breast cancer: Results from the South African breast cancer and HIV outcomes study.

In some countries of sub-Saharan Africa, the prevalence of HIV exceeds 20%; in South Africa, 20.4% of people are living with HIV. We examined the impact of HIV infection on the overall survival (OS) of women with nonmetastatic breast cancer (BC) enrolled in the South African Breast Cancer and HIV Outcomes (SABCHO) study. We recruited women with newly diagnosed BC at six public hospitals from 1 July 2015 to 30 June 2019. Among women with stages I-III BC, we compared those with and without HIV infection on sociodemographic, clinical, and treatment factors. We analyzed the impact of HIV on OS using multivariable Cox proportional hazard models. Of 2367 women with stages I-III BC, 499 (21.1%) had HIV and 1868 (78.9%) did not. With a median follow-up of 29 months, 2-year OS was poorer among women living with HIV (WLWH) than among HIV-uninfected women (72.4% vs 80.1%, P < .001; adjusted hazard ratio (aHR) 1.49, 95% confidence interval (CI) = 1.22-1.83). This finding was consistent across age groups ≥45 years and <45 years, stage I-II BC and stage III BC, and ER/PR status (all P < .03). Both WLWH with <50 viral load copies/mL and WLWH with ≥50 viral load copies/mL had poorer survival than HIV-uninfected BC patients [aHR: 1.35 (1.09-1.66) and 1.54 (1.20-2.00), respectively], as did WLWH who had ≥200 CD4+ cells/mL at diagnosis [aHR: 1.39 (1.15-1.67)]. Because receipt of antiretroviral therapy has become widespread, WLWH is surviving long enough to develop BC; more research is needed on the causes of their poor survival.

The Impact of Breast Cancer Treatment Delays on Survival Among South African Women.

BACKGROUND: In high-income settings, delays from breast cancer (BC) diagnosis to initial treatment worsen overall survival (OS). We examined how time to BC treatment initiation (TTI) impacts OS in South Africa (SA). METHODS: We evaluated women enrolled in the South African BC and HIV Outcomes study between July 1, 2015 and June 30, 2019, selecting women with stages I-III BC who received surgery and chemotherapy. We constructed a linear regression model estimating the impact of sociodemographic and clinical factors on TTI and separate multivariable Cox proportional hazard models by first treatment (surgery and neoadjuvant chemotherapy (NAC)) assessing the effect of TTI (in 30-day increments) on OS. RESULTS: Of 1260 women, 45.6% had upfront surgery, 54.4% had NAC, and 19.5% initiated treatment >90 days after BC diagnosis. Compared to the surgery group, more women in the NAC group had stage III BC (34.8% vs 81.5%). Living further away from a hospital and having hormone receptor positive (vs negative) BC was associated with longer TTI (8 additional days per 100 km, P = .003 and 8 additional days, P = .01, respectively), while Ki67 proliferation index >20 and upfront surgery (vs NAC) was associated with shorter TTI (12 and 9 days earlier; P = .0001 and.007, respectively). Treatment initiation also differed among treating hospitals (P < .0001). Additional 30-day treatment delays were associated with worse survival in the surgery group (HR 1.11 [95%CI 1.003-1.22]), but not in the NAC group. CONCLUSIONS: Delays in BC treatment initiation are common in SA public hospitals and are associated with worse survival among women treated with upfront surgery.

Health Technology Assessment in Support of National Health Insurance in South Africa.

South Africa has embarked on major health policy reform to deliver universal health coverage through the establishment of National Health Insurance (NHI). The aim is to improve access, remove financial barriers to care, and enhance care quality. Health technology assessment (HTA) is explicitly identified in the proposed NHI legislation and will have a prominent role in informing decisions about adoption and access to health interventions and technologies. The specific arrangements and approach to HTA in support of this legislation are yet to be determined. Although there is currently no formal national HTA institution in South Africa, there are several processes in both the public and private healthcare sectors that use elements of HTA to varying extents to inform access and resource allocation decisions. Institutions performing HTAs or related activities in South Africa include the National and Provincial Departments of Health, National Treasury, National Health Laboratory Service, Council for Medical Schemes, medical scheme administrators, managed care organizations, academic or research institutions, clinical societies and associations, pharmaceutical and devices companies, private consultancies, and private sector hospital groups. Existing fragmented HTA processes should coordinate and conform to a standardized, fit-for-purpose process and structure that can usefully inform priority setting under NHI and for other decision makers. This transformation will require comprehensive and inclusive planning with dedicated funding and regulation, and provision of strong oversight mechanisms and leadership.

Impact of HIV infection on overall survival among women with stage IV breast cancer in South Africa.

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 < 5% in the United States (US); 20% of new BC diagnoses in SA are in WLWH. We evaluated the impact of HIV on overall survival (OS) among women with stage IV BC. METHODS: We conducted a prospective cohort study of women diagnosed with stage IV BC between February 2, 2015 and September 18, 2019 at six public hospitals in SA. Multivariate Cox regression models were used to estimate the association between HIV status and OS. RESULTS: Among 550 eligible women, 147 (26.7%) were WLWH. Compared to HIV-negative BC patients, WLWH were younger (median age 45 vs. 60 years, p < 0.001), predominantly black (95.9% vs. 77.9%, p < 0.001), and more likely to have hormone receptor-negative (hormone-negative) BC (32.7% vs. 22.6%, p = 0.016). Most women received systemic cancer-directed therapy (80.1%). HIV status was not associated with treatment or OS (Hazard Ratio (HR) 1.13 [95%CI 0.89-1.44]). On exploratory subgroup analysis, WLWH and hormone-negative BC had shorter OS compared to HIV-uninfected women (1-year OS: 27.1% vs. 48.8%, p = 0.003; HR 1.94 [95%CI 1.27-2.94]; p = 0.002), which was not observed for hormone receptor-positive BC. CONCLUSION: HIV status was not associated with worse OS in women with stage IV BC in SA and cannot account for the poor survival in this cohort. Subgroup analysis revealed that WLWH with hormone-negative BC had worse OS, which warrants further investigation.

The multimorbidity profile of South African women newly diagnosed with breast cancer.

Multimorbidity in women with breast cancer may delay presentation, affect treatment decisions and outcomes. We described the multimorbidity profile of women with breast cancer, its determinants, associations with stage at diagnosis and treatments received. We collected self-reported data on five chronic conditions (hypertension, diabetes, cerebrovascular diseases, asthma/chronic obstructive pulmonary disease, tuberculosis), determined obesity using body mass index (BMI) and tested HIV status, in women newly diagnosed with breast cancer between January 2016 and April 2018 in five public hospitals in South Africa. We identified determinants of ≥2 of the seven above-mentioned conditions (defined as multimorbidity), multimorbidity itself with stage at diagnosis (advanced [III-IV] vs. early [0-II]) and multimorbidity with treatment modalities received. Among 2,281 women, 1,001 (44%) presented with multimorbidity. Obesity (52.8%), hypertension (41.3%), HIV (22.0%) and diabetes (13.7%) were the chronic conditions that occurred most frequently. Multimorbidity was more common with older age (OR = 1.02; 95% CI 1.01-1.03) and higher household socioeconomic status (HSES) (OR = 1.06; 95% CI 1.00-1.13). Multimorbidity was not associated with advanced-stage breast cancer at diagnosis, but for self-reported hypertension there was less likelihood of being diagnosed with advanced-stage disease in the adjusted model (OR 0.80; 95% CI 0.64-0.98). Multimorbidity was associated with first treatment received in those with early-stage disease, p = 0.003. The prevalence of multimorbidity is high among patients with breast cancer. Our findings suggest that multimorbidity had a significant impact on treatment received in those with early-stage disease. There is need to understand the impact of multimorbidity on breast cancer outcomes.

A comparison of complete pathologic response rates following neoadjuvant chemotherapy among South African breast cancer patients with and without concurrent HIV infection.

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 and tumor 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.

Primary results from CECILIA, a global single-arm phase II study evaluating bevacizumab, carboplatin and paclitaxel for advanced cervical cancer.

OBJECTIVE: Adding bevacizumab to cisplatin-paclitaxel for advanced cervical cancer significantly improves overall and progression-free survival. We evaluated bevacizumab with a widely used carboplatin-paclitaxel backbone. METHODS: Patients with metastatic/recurrent/persistent cervical cancer not amenable to curative surgery and/or radiotherapy received 3-weekly bevacizumab 15 mg/kg, paclitaxel 175 mg/m2, and carboplatin AUC 5 until progression or unacceptable toxicity. Maintenance bevacizumab was allowed. Patients with ongoing bladder/rectal involvement, prior cobalt radiotherapy, a history of fistula/gastrointestinal perforation, or recent bowel resection/chemoradiation were excluded. The primary objective was to determine incidences of gastrointestinal perforation/fistula, gastrointestinal-vaginal fistula, and genitourinary fistula. RESULTS: Among 150 treated patients, disease at study entry was persistent in 21%, recurrent in 56%, and newly diagnosed metastatic in 23%. After 27.8 months' median follow-up, median bevacizumab duration was 6.7 months; 57% received maintenance bevacizumab. Seventeen patients (11.3%; 95% CI: 6.7-17.5%) experienced ≥1 perforation/fistula event: gastrointestinal perforation/fistula in 4.7% (1.9-9.4%), gastrointestinal-vaginal fistula in 4.0% (1.5-8.5%), and genitourinary fistula in 4.7% (1.9-9.4%). Of these, 16 were previously irradiated, several with ongoing radiation effects. The most common grade 3/4 adverse events were neutropenia (25%), anemia (19%), and hypertension (14%). Five patients (3%) had fatal adverse events. Objective response rate was 61% (95% CI: 52-69%), median progression-free survival was 10.9 (10.1-13.7) months, and median overall survival was 25.0 (20.9-30.4) months. CONCLUSIONS: Bevacizumab can be combined with carboplatin-paclitaxel in the CECILIA study population. The fistula/gastrointestinal perforation incidence is in line with GOG-0240; efficacy results are encouraging. TRIAL REGISTRATION NUMBER: NCT02467907 (ClinicalTrials.gov).

Hepatitis B virus-associated hepatocellular carcinoma in South Africa in the era of HIV.

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).

Colorectal Cancer (CRC) treatment and associated costs in the public sector compared to the private sector in Johannesburg, South Africa.

BACKGROUND: South Africa's divided healthcare system is believed to be inequitable as the population serviced by each sector and the treatment received differs while annual healthcare expenditure is similar. The appropriateness of treatment received and in particular the cost of the same treatment between the sectors remains debatable and raises concerns around equitable healthcare. Colorectal cancer places considerable pressure on the funders, yet treatment utilization data and the associated costs of non-communicable diseases, in particular colorectal cancer, are limited for South Africa. Resources need to be appropriately managed while ensuring equitable healthcare is provided regardless of where the patient is able to receive their treatment. Therefore the aim of this study was to determine the cost of colorectal cancer treatment in a privately insured patient population in order to compare the costs and utilization to a previously published public sector patient cohort. METHODS: Private sector costs were determined using de-identified claim-based data for all newly diagnosed CRC patients between 2012 and 2014. The costs obtained from this patient cohort were compared to previously published public sector data for the same period. The costs compared were costs incurred by the relevant sector funder and didn't include out-of-pocket costs. RESULTS: The comparison shows private sector patients gain access to more of the approved regimens (12 vs. 4) but the same regimens are more costly, for example CAPOX costs approximately €150 more per cycle. The cost difference between 5FU and capecitabine monotherapy is less than €30 per cycle however, irinotecan is cheaper in comparison to oxaliplatin in the private sector (FOLFOX approx. €500 vs. FOLFIRI aprox. €460). Administrative costs account for up to 45% of total costs compared to the previously published data of these costs totaling < 15% of the full treatment cost in South Africa's public healthcare system. CONCLUSION: This comparison highlights the disparities between sectors while illustrating the need for further research to improve resource management to attain equitable healthcare.

Neoadjuvant Chemotherapy Use for Nonmetastatic Breast Cancer at Five Public South African Hospitals and Impact on Time to Initial Cancer Therapy.

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.

Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours.

BACKGROUND: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. METHODS: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs). RESULTS: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77%) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95% confidence interval [CI]) was 13.2 months (10.9-16.7): 13.2 (7.4-16.8) and 13.0 (9.2-20.4) in treatment-naive and previously treated patients, respectively. ORR (95% CI) per RECIST was 24.5% (16.7-33.8) in the total population: 21.3% (11.9-33.7) in treatment-naive and 28.9% (16.4-44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95% CI, 33.0-not estimable). The most common treatment-related AEs were neutropenia (53.8%), diarrhoea (46.2%), and leukopenia (43.4%). CONCLUSIONS: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib.