Purpose To prospectively compare survival between human immunodeficiency virus (HIV)-infected versus HIV-uninfected cervical cancer patients who initiated curative chemoradiation therapy (CRT) in a limited-resource setting. Methods and Materials Women with locally advanced cervical cancer with or without HIV infection initiating radical CRT in Botswana were enrolled in a prospective, observational, cohort study from July 2013 through January 2015. Results Of 182 women treated for cervical cancer during the study period, 143 women initiating curative CRT were included in the study. Eighty-five percent of the participants (122 of 143) had stage II/III cervical cancer, and 67% (96 of 143) were HIV-infected. All HIV-infected patients were receiving antiretroviral therapy (ART) at the time of curative cervical cancer treatment initiation. We found no difference in toxicities between HIV-infected and HIV-uninfected women. The 2-year overall survival (OS) rates were 65% for HIV-infected women (95% confidence interval [CI] 54%-74%) and 66% for HIV-uninfected women (95% CI 49%-79%) (P = .70). Factors associated with better 2-year OS on multivariate analyses included baseline hemoglobin >10 g/dL (hazard ratio [HR] 0.37, 95% CI 0.19-0.72, P = .003), total radiation dose ≥75 Gy (HR 0.52, 95% CI 0.27-0.97, P = .04), and age <40 years versus 40-59 years (HR 2.17, 95% CI 1.05-4.47, P = .03). Conclusions Human immunodeficiency virus status had no effect on 2-year OS or on acute toxicities in women with well-managed HIV infection who initiated curative CRT in Botswana. In our cohort, we found that baseline hemoglobin levels, total radiation dose, and age were associated with survival, regardless of HIV status.

IntroductionThe number and lifespan of individuals living with HIV have increased significantly with the scale-up of antiretroviral therapy. Furthermore, the incidence of breast cancer in women with HIV is growing, especially in sub-Saharan Africa (SSA). However, the association between HIV infection and breast cancer is not well understood.MethodsA literature search was performed to identify articles published in journals pertaining to breast cancer and HIV, with an emphasis on SSA. Selected US-based studies were also identified for comparison.ResultsAmong the 56 studies reviewed, the largest study examined 314 patients with breast cancer and HIV in the United States. There is no consensus on whether HIV infection acts as a pro-oncogenic or antioncogenic factor in breast cancer, and it may have no relation to breast cancer. A higher incidence of breast cancer is reported in high-income countries than in SSA, although breast cancer in SSA presents at a younger age and at a more advanced stage. Some studies show that patients with breast cancer and HIV experience worse chemotherapy toxicity than do patients without HIV. Data on treatment outcomes are limited. The largest study showed worse treatment outcomes in patients with HIV, compared with their counterparts without HIV.ConclusionHIV infection has not been associated with different clinical presentation of breast cancer. However, some evidence suggests that concurrent diagnosis of HIV with breast cancer is associated with increased therapy-related toxicity and worse outcomes. Systematic prospective studies are needed to establish whether there is a specific association between breast cancer and HIV.

Gynecologic carcinomas, including cervical cancer, present a significant burden on low- and middle-income countries (LMICs). Brachytherapy plays an integral role in the treatment of gynecologic carcinomas, as it is essential for both curative and palliative treatment. However, there are numerous geographic and economic barriers to providing brachytherapy to cancer patients in LMICs. This article examines the role and delivery of brachytherapy in gynecological cancer treatment; brachytherapy capacity in LMICs, including infrastructure, equipment, and human resources considerations; commissioning, training, and clinical implementation of brachytherapy in LMICs; other challenges, and strategies for improvement in brachytherapy delivery in LMICs, including innovation and current and upcoming international initiatives.

PurposeCervical cancer is a major cause of mortality in low- and middle-income countries (LMICs) and the most common cancer diagnosed in women in Botswana. Most women present with locally advanced disease, requiring chemotherapy and radiation. Care co-ordination requires input from a multidisciplinary team (MDT) to deliver appropriate, timely treatment. However, there are limited published examples of MDT implementation in LMICs.MethodsIn May 2015, a weekly MDT clinic for gynecologic cancer care was initiated at Botswana’s national referral facility. The MDT clinic served as a forum for discussion and coordination of patients with gynecologic cancer and consisted of a gynecologist, pathologist, medical oncologist, radiation oncologist, palliative care specialist, and nurse coordinator.ResultsBetween May 2015 and December 2015, 135 patients were seen in the MDT clinic. The mean age of the patients was 49 years. Most (60%) of the patients were HIV positive. The most common diagnosis was cervical cancer (60%), followed by high-grade cervical intraepithelial neoplastic lesions (12%) and vulvar cancer (11%). Only data up to September 2015 were assessed for treatment delays. It was found that only 38% of patients needed more than one visit for care coordination before treatment initiation. Among patients with cervical cancer, the median delay from date of biopsy to start of radiation treatment was 39 days (interquartile range, 34 to 57 days) for patients treated after MDT initiation, compared with 108 days (interquartile range, 71 to 147 days) for patients treated before MDT initiation (P < .001).ConclusionImplementation of MDT clinics in LMICs is feasible and can help reduce delays in treatment initiation, as demonstrated by a gynecologic MDT clinic in Botswana. Streamlining care through MDT clinics can enhance care coordination and improve clinical outcomes. This model can apply to cancer care in other LMICs.

This study aims to present a full spectrum of individual patient presentations of pancreatic fistula risk, and to define the utility of mitigation strategies amongst some of the most prevalent, and vulnerable scenarios surgeons encounter. Background: The FRS has been utilized to identify technical strategies associated with reduced CR-POPF incidence across various risk strata. However, risk-stratification using the FRS has never been investigated with greater granularity. By deriving all possible combinations of FRS elements, individualized risk assessment could be utilized for precision medicine purposes. Methods: FRS profiles and outcomes of 5533 PDs were accrued from 17 international institutions (2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019). The FRS was used to derive 80 unique combinations of patient ''scenarios.'' Risk-matched analyses were conducted using a Bonferroni adjustment to identify scenarios with increased vulnerability for CR-POPF occurrence. Subsequently, these scenarios were analyzed using multivariable regression to explore optimal mitigation approaches.Results: The overall CR-POPF rate was 13.6%. All 80 possible scenarios were encountered, with the most frequent being scenario #1 (8.1%) -the only negligible-risk scenario (CR-POPF rate ¼ 0.7%). The moderate-risk zone had the most scenarios (50), patients (N ¼ 3246), CR-POPFs (65.2%), and greatest non-zero discrepancy in CR-POPF rates between scenarios (18-fold). In the risk-matched analysis, 2 scenarios (#59 and 60) displayed increased vulnerability for CR-POPF relative to the moderate-risk zone (both P < 0.001). Multivariable analysis revealed factors associated with CR-POPF in these scenarios: pancreaticogastrostomy reconstruction [odds ratio (OR) 4.67], omission of drain placement (OR 5.51), and prophylactic octreotide (OR 3.09). When comparing the utilization of best practice strategies to patients who did not have these conjointly utilized, there was a significant decrease in CR-POPF (10.7% vs 35.5%, P < 0.001; OR 0.20, 95% confidence interval 0.12-0.33). Conclusion: Through this data, a comprehensive fistula risk catalog has been created and the most clinically-impactful scenarios have been discerned. Focusing on individual scenarios provides a practical way to approach precision medicine, allowing for more directed and efficient management of CR-POPF.

BACKGROUND: Earlier detection of transformed cells using target-specific imaging techniques holds great promise. We have developed TAB 004, a monoclonal antibody highly specific to a protein sequence accessible in the tumor form of MUC1 (tMUC1). We present data assessing both the specificity and sensitivity of TAB 004 in vitro and in genetically engineered mice in vivo. METHODS: Polyoma Middle T Antigen mice were crossed to the human MUC1.Tg mice to generate MMT mice. In MMT mice, mammary gland hyperplasia is observed between 6 and 10 weeks of age that progresses to ductal carcinoma in situ by 12 to 14 weeks and adenocarcinoma by 18 to 24 weeks. Approximately 40% of these mice develop metastasis to the lung and other organs with a tumor evolution that closely mimics human breast cancer progression. Tumor progression was monitored in MMT mice (from ages 8 to 22 weeks) by in vivo imaging following retro-orbital injections of the TAB 004 conjugated to indocyanine green (TAB-ICG). At euthanasia, mammary gland tumors and normal epithelial tissues were collected for further analyses. RESULTS: In vivo imaging following TAB-ICG injection permitted significantly earlier detection of tumors compared with physical examination. Furthermore, TAB-ICG administration in MMT mice enabled the detection of lung metastases while sparing recognition of normal epithelia. CONCLUSIONS: The data highlight the specificity and the sensitivity of the TAB 004 antibody in differentiating normal versus tumor form of MUC1 and its utility as a targeted imaging agent for early detection, tumor monitoring response, as well as potential clinical use for targeted drug delivery.

Background: Pancreatoduodenectomies at high risk for clinically relevant pancreatic fistula are uncommon, yet intimidating, situations. In such scenarios, the impact of individual surgeon experience on outcomes is poorly understood. Methods: The fistula risk score was applied to identify high-risk patients (fistula risk score 7e10) from 7,706 pancreatoduodenectomies performed at 18 international institutions (2003e2020). For each case, surgeon pancreatoduodenectomy career volume and years of practice were linked to intraoperative fistula mitigation strategy adoption and outcomes. Consequently, best operative approaches for clinically relevant pancreatic fistula prevention and best performer profiles were identified through multivariable analysis models. Results: Eight hundred and thirty high-risk pancreatoduodenectomies, performed by 64 surgeons, displayed an overall clinically relevant pancreatic fistula rate of 33.7%. Clinically relevant pancreatic fistula Author Contributions: Conception/design (F Casciani, MT Trudeau, CM Vollmer); data acquisition (all authors); data interpretation (all authors) critical revisions (all authors); final approval (all authors).All individuals claiming authorship meet all of the following 3 conditions: (1) Authors made substantial contributions to conception and design, and/or acquisition of data, and/or analysis and interpretation of data; (2) Authors participated in drafting the article or revising it critically for important intellectual content; and (3) Authors gave final approval of the version to be published.

All node positive vulvar cancer patients should benefit from and thus should receive adjuvant radiation, including those with one positive node.