PURPOSE:To evaluate hydrogel visualization as a marker on CT and MR imaging and consider any potential dosimetric effects incurred by placement of the marker on brachytherapy for the treatment of gynecologic malignancies. METHODS:This prospective cohort study enrolled 25 patients with gynecologic cancers who underwent brachytherapy at Johns Hopkins Hospital. MR and CT imaging were used to compare TraceITTM hydrogel visualization immediately after placement with the brachytherapy applicator in place. Rectal dosimetric data of a 2 cm3 volume (D2cc) and equi-effective doses of 2 Gy fractions (EQD2) were obtained. For patients with data collected before and after spacer placement, a comparative analysis was conducted to assess the impact of the marker on rectal dose. RESULTS:Hydrogel was safely injected into the space between the rectum and vagina in 25 patients, with no side effects related to gel placement. When comparing the agreement in gel visualization by 2 interpreters, inter-rater reliability (kappa statistic) was calculated and showed 58.3% (moderate) agreement (p = 0.0007). In patients who received a brachytherapy fraction both before and after TraceITTM placement, the average rectal displacement was 1.33 cm. The change in EQD2 D2cc rectum was significantly lower, with an average pre-TraceITTM dose of 5.02 Gy and a post-TraceITTM average of 4.60 Gy (p = 0.002). CONCLUSIONS:Hydrogel placement is feasible during brachytherapy procedures for the treatment of gynecologic malignancies. Using TraceITTM as a marker resulted in better visualization on MR than on CT. Displacement significantly reduced the D2cc to the rectum. Further research is needed to determine the optimal amount of hydrogel for spacing in gynecologic cancer patients.

PURPOSEAlthough the majority of cervical cancer cases are in sub-Saharan Africa, little is known regarding how the COVID-19 pandemic affected cancer care in this context. Drawing from robust longitudinal data, this study aimed to assess cervical cancer treatment patterns in Botswana before and during the pandemic.METHODSLongitudinal clinical and patient-reported data from a cohort of over 1,000 patients seen at a gynecologic oncology multidisciplinary team clinic in Botswana were used to evaluate treatment initiation patterns before (April 2018-December 2019) and during (April 2020-December 2021) the pandemic. The primary outcome was timeliness of treatment, defined as the number of days between the patient's first clinic visit and treatment initiation date, and categorized as timely (≤30 days), delayed (>30 days), or no treatment. The primary exposure was time of visit (pre–COVID-19 v COVID-19), defined by the month of the clinic visit.RESULTSOf the 559 patients with cervical cancer diagnosed during the study period, 336 were seen pre–COVID-19, and 223 were seen during the COVID-19 period. During the pandemic, a higher proportion of patients experienced treatment delays (66.4%) or received no treatment (24.2%), compared with the pre–COVID-19 period (35.7% and 9.8%, respectively; P < .001). Multivariable regression models indicated that patients seen during the pandemic were 10 times more likely to experience treatment delays (adjusted odds ratio [aOR], 10.01 [95% CI, 5.69 to 17.62]) and 14 times more likely to receive no treatment (aOR, 14.16 [95% CI, 7.14 to 28.10]).CONCLUSIONThe pandemic exacerbated treatment delays for patients with cervical cancer in Botswana. There is a need for evidence-based strategies to address these treatment delays, considering the disproportionate burden of disease and persistent disparities in access to care in Botswana and other low- and middle-income countries.

BACKGROUND:Cervical cancer is a leading morbidity/mortality cause, frequently co-occurring with human immunodeficiency virus (HIV) positivity, in Botswana. We examined long-term outcomes for Ipabalele study participants receiving curative chemoradiation for locally advanced cervical cancer (2015-2019) by HIV status. METHODS:Clinical and outcome data were collected at baseline, treatment completion, and 3 months thereafter. Patients were followed for up to 5 years. Overall survival (OS) was evaluated using Kaplan-Meier curves and Cox regression. RESULTS:The cohort comprised 295 patients (73.8% with HIV, younger at diagnosis [P < .001]) followed for a median of 44.2 months. Complete response was seen in 217/278 (76.1%) patients. Two- and 5-year OS rates were 73.4% and 59.9%, respectively, with no difference by HIV status. OS was associated negatively with advanced disease stage (III: hazard ratio [HR] 13.23, P < .001; IV: HR 7.8, P = .008) and positively with increased radiation (HR 0.977, P = .0005) and chemotherapy (HR 0.85, P = .005). Clinical response was associated negatively with advanced disease (IV: HR 0.113, P = .002) and positively with increased radiation (P = .009). Toxicity did not differ by HIV status. The most common grade-≥-2 non-hematological and hematological toxicities were radiation dermatitis (39.8%) and reduced white blood cell count (66.05%), respectively. CONCLUSIONS:In this cervical cancer cohort with good HIV status control, treatment outcomes and OS were associated with disease and treatment factors, not the HIV status. Early screening and education regarding treatment protocols are crucial to improve cervical cancer outcomes in Botswana.

Background Cervical cancer is a leading morbidity/mortality cause, frequently co-occurring with human immunodeficiency virus (HIV) positivity, in Botswana. We examined long-term outcomes for Ipabalele study participants receiving curative chemoradiation for locally advanced cervical cancer (2015–2019) by HIV status. Methods Clinical and outcome data were collected at baseline, treatment completion, and 3 months thereafter. Patients were followed for up to 5 years. Overall survival (OS) was evaluated using Kaplan–Meier curves and Cox regression. Results The cohort comprised 295 patients [73.8% with HIV, younger at diagnosis (p < .001)] followed for a median of 44.2 months. Complete response was seen in 217/278 (76.1%) patients. Two- and 5-year OS rates were 73.4% and 59.9%, respectively, with no difference by HIV status. OS was associated negatively with advanced disease stage [III: hazard ratio (HR) 13.23, p < .001; IV: HR 7.8, p = .008] and positively with increased radiation (HR 0.977, p = .0005) and chemotherapy (HR 0.85, p = .005). Clinical response was associated negatively with advanced disease (IV: HR 0.113, p = .002) and positively with increased radiation (p = .009). Toxicity did not differ by HIV status. The most common grade-≥-2 non-hematological and hematological toxicities were radiation dermatitis (39.8%) and reduced white blood cell count (66.05%), respectively. Conclusions In this cervical cancer cohort with good HIV status control, treatment outcomes and OS were associated with disease and treatment factors, not the HIV status. Early screening and education regarding treatment protocols are crucial to improve cervical cancer outcomes in Botswana.

Accurate contouring of the high-risk clinical target volume (HR-CTV) is vital for effective radiation therapy of cervical cancer, particularly in brachytherapy, where precise dose delivery is crucial for successful treatment. Several deep neural network models have been recently developed and demonstrated promising performance in HR-CTV segmentation, but the model performance depends on the quality of the image and contour data used for training, which often significantly varies. Existing models lack mechanisms for estimating the uncertainty level of their inference, thus leading to potential overconfidence in the generated segmentations. This study proposes an uncertainty-aware segmentation method based on evidential deep learning approach which estimates confidence of its inference at the same time of computing HR-CTV segmentation from MRI. We employed a dual convolution-transformer U-Net as a backbone to compute the probability for segmentation for each voxel, and incorporated an uncertainty block to the final output of the network for uncertainty estimation. A total of 250 T2-weighted MRIs obtained from 138 cervical cancer patients were used to train, validate, and test the model. For 27 test cases, four sets of manual segmentations were obtained from three radiation oncologists to assess the segmentation and uncertainty estimation performance. In comparison to the consensus of manual contours, the proposed model achieved dice similarity coefficient (DSC) and Hausdorff distance (HD95) of 0.713 +/- 0.106 and 9.309 +/- 4.474, respectively. We observed significant inter/intra-rater variability (DSC: 0.656-0.709; HD95: 9.665-12.364), and the proposed model showed comparable performance to the experts' manual segmentations. Furthermore, the estimated uncertainty represented well the variability in multi-rater segmentations, demonstrating its effectiveness in capturing difficult to segment regions. The experimental results demonstrate that including uncertainty estimates in HR-CTV segmentation leads to a more comprehensive understanding of model prediction, and potentially aids clinicians in making more informed decisions and improving treatment outcome.

Background:Generative artificial intelligence (gAI) models, such as DALL-E 2, are promising tools that can generate novel images or artwork based on text input. However, caution is warranted, as these tools generate information based on historical data and are thus at risk of propagating past learned inequities. Women in medicine have routinely been underrepresented in academic and clinical medicine and the stereotype of a male physician persists. Objective:The primary objective is to evaluate implicit bias among gAI across medical specialties. Methods:To evaluate for potential implicit bias, 100 photographs for each medical specialty were generated using the gAI platform DALL-E2. For each specialty, DALL-E2 was queried with "An American [specialty name]." Our primary endpoint was to compare the gender distribution of gAI photos to the current distribution in the United States. Our secondary endpoint included evaluating the racial distribution. gAI photos were classified according to perceived gender and race based on a unanimous consensus among a diverse group of medical residents. The proportion of gAI women subjects was compared for each medical specialty to the most recent Association of American Medical Colleges report for physician workforce and active residents using χ2 analysis. Results:A total of 1900 photos across 19 medical specialties were generated. Compared to physician workforce data, AI significantly overrepresented women in 7/19 specialties and underrepresented women in 6/19 specialties. Women were significantly underrepresented compared to the physician workforce by 18%, 18%, and 27% in internal medicine, family medicine, and pediatrics, respectively. Compared to current residents, AI significantly underrepresented women in 12/19 specialties, ranging from 10% to 36%. Additionally, women represented <50% of the demographic for 17/19 specialties by gAI. Conclusions:gAI created a sample population of physicians that underrepresented women when compared to both the resident and active physician workforce. Steps must be taken to train datasets in order to represent the diversity of the incoming physician workforce.

Purpose: This systematic review aimed to identify and compare tools used to evaluate quality of life (QoL) after pelvic radiation for cervical cancer and to describe variations in results within commonly used instruments. This review hypothesized regional preferences in the selection of these tools and an absence of uniformity in their application globally. Methods and Materials: A comprehensive search of 6 databases was conducted between the inception of each included database and June 14, 2023, focusing on studies evaluating the QoL of patients with cervical cancer during and after radiation. Excluded were studies involving cancers originating outside the cervix, those not exclusively undergoing radiation or chemoradiation therapy, such as patients who have undergone surgery, and non-English studies. Results: Ultimately, 229 studies covering 25,693 patients and 51 countries were identified. Most studies were conducted in Asia (35.6%) and Europe (32.9%). Ninety-nine QoL instruments were identified, not including those that were specific to a single study. The European Organisation for Research and Treatment of Cancer QoL Questionnaire Core 30 (20.5%) and the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaire cervical cancer module (16.0%) were the most commonly used; however, US-based studies primarily used the Functional Assessment of Cancer Therapy-General surveys. Furthermore, there was significant variability in the timelines of survey usage in relation to when treatment was completed, further limiting the comparisons that can be made. Of the 127 studies that reported data on the time points after completion of treatment at which QoL was measured, 72.4% measured QoL within 1 year of treatment completion, and 48.8% measured QoL >1 year after treatment completion, with some studies using multiple time points for their research. Conclusions: This study revealed a fragmented landscape with significant variability in QoL survey use, limiting the generalizability and usefulness of these results to drive meaningful change. There is a need for a global standardized method to evaluate QoL after treatment of cervical cancer with radiation therapy for comparison across regions. Simplified tools may assist with the broader collection of data, which may lead to advancements for improvement of the QoL of these patients.

PURPOSE:Accurate target delineation is essential when using intensity modulated radiation therapy for intact cervical cancer. In 2011, the Radiation Therapy Oncology Group published a consensus guideline using magnetic resonance imaging (MRI). The current project expands on the previous atlas by including computed tomography (CT)-based contours, contours with MRI and positron emission tomography (PET) registrations, the addition of common and complex scenarios, and incorporating information on simulation and treatment planning techniques. METHODS AND MATERIALS:Twenty-eight experts in gynecologic radiation oncology contoured 3 cases, first on a noncontrast CT simulation scan and then with registered diagnostic scans. The cases included (1) International Federation of Gynecology and Obstetrics (FIGO) IIIC1 with a bulky tumor and vaginal metastasis, (2) FIGO IIB with calcified uterine fibromas, and (3) FIGO IIIC2 with large lymph nodes. The contours on all 6 data sets (3 CT simulations without diagnostic images and 3 with registered images) were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement. The contours were reviewed, discussed, and edited in a group meeting prior to finalizing. RESULTS:Contours showed considerable agreement among experts in each of the cases, with kappa statistics from 0.67 to 0.72. For each case, diagnostic PET ± MRI was associated with an increase in volume. The largest increase was the clinical target volume (CTV) primary for case 2, with a 20% increase in volume and a 54% increase in simultaneous truth and performance level estimation volume, which may be due to variance in registration priorities. For the third case, 92.9% increased their CTVs based on the addition of the diagnostic PET scan. The main areas of variance were in determining the superior extent of CTV coverage, coverage of the mesorectum, and simulation and planning protocols. CONCLUSIONS:This study shows the value and the challenges of using coregistered diagnostic imaging, with an average increase in volumes when incorporating MRI and PET.

BACKGROUND AND OBJECTIVES: In patients treated with stereotactic radiosurgery (SRS) for brain metastases, follow-up imaging demonstrating progression may result from treatment effect/radionecrosis (RN) or tumor progression. We report long-term outcomes for a cohort of patients who demonstrated radiological progression on serial imaging after initial radiation and who underwent resection, at which point histology informed further management. METHODS: A retrospective chart review identified 76 patients with an associated 82 brain lesions between 2009 and 2022, that were initially treated with SRS, and then demonstrated suspicious imaging developing through at least 2 scan time points with either pathologic confirmation of tumor or RN. RESULTS: Of the 82 lesions, 55 lesions (67.1%) were found to be tumor and were treated with repeat radiation and 27 (32.9%) were found to have pathologically confirmed RN and conservatively managed. 14/27 lesions ultimately found to be radionecrotic required steroids preoperatively due to neurological symptoms. None of these lesions required further intervention with median postsurgery follow-up of 24.4 months (range 1-104 months). There were 55 instances (in 51 patients) of confirmed recurrent/progressive tumor who we treated with repeat aggressive radiation with either Cs-131 brachytherapy (12 [21.8%]) or SRS (43 [78.2%]). Among patients treated with reirradiation, the median follow-up to local failure was 15.2 months (95% CI 7.3-26.6 months). The 2-year local control rate was 79.5% (95% CI 68.3%-92.5%). CONCLUSION: These results support resection of radiosurgery-treated lesions with progression continuing through serial imaging, and this pathology-informed management results in excellent control of both RN and tumor progression after radiosurgery.

Purpose : To describe early tumor volume change in patients with rhabdomyosarcoma (RMS) and investigate its association with overall survival (OS) and local failure. Methods : This retrospective study included patients diagnosed with Group III/IV RMS with available CT and/or MRI scans at two-time points: 1) pre-therapy and 2) early therapy (acquired during weeks 8 – 12 of chemotherapy). Relative volumetric change (RVC) was calculated as the percentage of: (early therapy – pre-therapy volume)/ (pre-therapy volume). Cox regression was used to identify variables associated with overall survival (OS). The Fine-Gray model was used to estimate local failure. Results: Eligible patients (n=55) had the following characteristics: median age at diagnosis : 9.6 years and median follow-up: 30.4 months. Most tumors were alveolar (61.8%) followed by embryonal (34.6%) and spindle cell/sclerosing (4%). The median RVC was -86.4% with larger decreases observed in alveolar vs. non-alveolar RMS (-89.4 vs. -69.8%, p=0.043). For embryonal and spindle cell/sclerosing RMS, all of which were FOXO1 fusion negative, RVC was independently associated with OS (Hazard Ratio for every 50% reduction in RVC [HRRVC]: 0.5, 95% Confidence Interval [CI]: 0.26 – 0.96, p=0.037) and local failure (HRRVC: 0.57, 95% CI: 0.33 – 0.99, p=0.049). The predominant pattern of failure in embryonal and spindle cell/sclerosing RMS was local and most were Group III. Conclusion : There was a greater reduction in tumor volume in alveolar vs. non-alveolar RMS. Early tumor volume reduction was associated with OS and local failure in embryonal or spindle cell/sclerosing RMS, all of which were confirmed FOXO1 fusion negative and had higher incidence of local compared to distant failures.

In a pilot experiment, we utilized AI to generate 100 photographs of physicians in 19 medical subspecialties and compared these photographs to the existing and incoming medical specialty workforce. Our work demonstrates that generative AI has a tendency to under represent women in common specialties, and thus the utilization of this tool in the future must be viewed with caution and a lens of known historical bias.

Objective. MRI is the standard imaging modality for high-dose-rate brachytherapy of cervical cancer. Precise contouring of organs at risk (OARs) and high-risk clinical target volume (HR-CTV) from MRI is a crucial step for radiotherapy planning and treatment. However, conventional manual contouring has limitations in terms of accuracy as well as procedural time. To overcome these, we propose a deep learning approach to automatically segment OARs (bladder, rectum, and sigmoid colon) and HR-CTV from female pelvic MRI.Approach. In the proposed pipeline, a coarse multi-organ segmentation model first segments all structures, from which a region of interest is computed for each structure. Then, each organ is segmented using an organ-specific fine segmentation model separately trained for each organ. To account for variable sizes of HR-CTV, a size-adaptive multi-model approach was employed. For coarse and fine segmentations, we designed a dual convolution-transformer UNet (DCT-UNet) which uses dual-path encoder consisting of convolution and transformer blocks. To evaluate our model, OAR segmentations were compared to the clinical contours drawn by the attending radiation oncologist. For HR-CTV, four sets of contours (clinical + three additional sets) were obtained to produce a consensus ground truth as well as for inter/intra-observer variability analysis.Main results. DCT-UNet achieved dice similarity coefficient (mean ± SD) of 0.932 ± 0.032 (bladder), 0.786 ± 0.090 (rectum), 0.663 ± 0.180 (sigmoid colon), and 0.741 ± 0.076 (HR-CTV), outperforming other state-of-the-art models. Notably, the size-adaptive multi-model significantly improved HR-CTV segmentation compared to a single-model. Furthermore, significant inter/intra-observer variability was observed, and our model showed comparable performance to all observers. Computation time for the entire pipeline per subject was 12.59 ± 0.79 s, which is significantly shorter than the typical manual contouring time of >15 min.Significance. These experimental results demonstrate that our model has great utility in cervical cancer brachytherapy by enabling fast and accurate automatic segmentation, and has potential in improving consistency in contouring. DCT-UNet source code is available athttps://github.com/JHU-MICA/DCT-UNet.

Purpose Cervical cancer is the most common cancer treated at Gaborone Private Hospital (GPH), the only facility offering radiotherapy services in Botswana. For curative intent, patients receive concurrent chemoradiation followed by brachytherapy boost. Brachytherapy services commenced in Botswana in 2012, and treatment began by using traditional A points for planning. A successful brachytherapy project was established with mentorship by clinicians from Massachusetts General Hospital and the University of Pennsylvania. In 2021, GPH acquired a new HDR brachytherapy unit with interstitial ability. The Oncologist was sent on a brachytherapy training course (ESTRO, September 2022). We now use adaptive image guided brachytherapy with CT based planning. Initial challenges included: fear of beginning such a project, inadequate skill in whole team, inadequate time to conduct interstitial techniques and planning, lack of pre-brachytherapy imaging, and no access to general anesthesia. We report our experience in initiating adaptive HDR-brachytherapy in a resource-limited setting to assist in spreading knowledge and avert fears on performance of HDR-brachytherapy in similar settings. Materials and Methods We retrospectively reviewed the records of ten patients treated with interstitial brachytherapy in January, 2023. January was selected for analysis as it represents the highest number of interstitial applications (10/29 patients - 35%). Medical records were reviewed to evaluate clinical and demographic information of the patients, treatment methods, and EQD2. Simple proportions and doismetric data are reported. Results (Table 1) Among ten patients treated with interstitial brachytherapy, 60% were stage 3, 70% were women living with HIV. Five (50%) were treated during the last week of EBRT and 50% were treated after completion of EBRT. Only three patients had pre-brachytherapy imaging, which was CT scan. Of the remaining seven patients, brachytherapy applicator choices were made based on clinical examination. Applicators were inserted under conscious sedation, prescribed by the Oncologist. All patients had an IV line inserted and were premeditated with Paracetamol 1g IV, Oxynorm 10 mg orally, Voltaren suppository and Bromazepam 3mg orally. Applicators were inserted under sterile conditions with a free draining urinary catheter. Tandem and ovoids were generally inserted blindly, and individual wires were pushed in under CT guidance. There was no ultrasound guidance. The highest number of wires inserted was 7. Treatment was well tolerated with no significant acute toxicities. All patients attained acceptable doses to HRCTV (D90> 85Gy EQD2). OARs were within tolerance. Note prolonged treatment time to completion was attributed to Linac downtime. Conclusions In a limited resource setting without access to general anesthesia and routine CT imaging, we present a case series of interstitial brachytherapy patients with successful target dose coverage outcomes. We intent to conduct a prospective study to evaluate pain control during the procedures. Further evaluation of long term survival of these patients is warranted; however, this data is encouraging to help increase access to brachytherapy services for clinics and locations with limited access to specialty services. Training and mentorship are essential components of a successful project and it is hoped that brachytherapy training programs could be availed in Africa. Cervical cancer is the most common cancer treated at Gaborone Private Hospital (GPH), the only facility offering radiotherapy services in Botswana. For curative intent, patients receive concurrent chemoradiation followed by brachytherapy boost. Brachytherapy services commenced in Botswana in 2012, and treatment began by using traditional A points for planning. A successful brachytherapy project was established with mentorship by clinicians from Massachusetts General Hospital and the University of Pennsylvania. In 2021, GPH acquired a new HDR brachytherapy unit with interstitial ability. The Oncologist was sent on a brachytherapy training course (ESTRO, September 2022). We now use adaptive image guided brachytherapy with CT based planning. Initial challenges included: fear of beginning such a project, inadequate skill in whole team, inadequate time to conduct interstitial techniques and planning, lack of pre-brachytherapy imaging, and no access to general anesthesia. We report our experience in initiating adaptive HDR-brachytherapy in a resource-limited setting to assist in spreading knowledge and avert fears on performance of HDR-brachytherapy in similar settings. We retrospectively reviewed the records of ten patients treated with interstitial brachytherapy in January, 2023. January was selected for analysis as it represents the highest number of interstitial applications (10/29 patients - 35%). Medical records were reviewed to evaluate clinical and demographic information of the patients, treatment methods, and EQD2. Simple proportions and doismetric data are reported. (Table 1) Among ten patients treated with interstitial brachytherapy, 60% were stage 3, 70% were women living with HIV. Five (50%) were treated during the last week of EBRT and 50% were treated after completion of EBRT. Only three patients had pre-brachytherapy imaging, which was CT scan. Of the remaining seven patients, brachytherapy applicator choices were made based on clinical examination. Applicators were inserted under conscious sedation, prescribed by the Oncologist. All patients had an IV line inserted and were premeditated with Paracetamol 1g IV, Oxynorm 10 mg orally, Voltaren suppository and Bromazepam 3mg orally. Applicators were inserted under sterile conditions with a free draining urinary catheter. Tandem and ovoids were generally inserted blindly, and individual wires were pushed in under CT guidance. There was no ultrasound guidance. The highest number of wires inserted was 7. Treatment was well tolerated with no significant acute toxicities. All patients attained acceptable doses to HRCTV (D90> 85Gy EQD2). OARs were within tolerance. Note prolonged treatment time to completion was attributed to Linac downtime. In a limited resource setting without access to general anesthesia and routine CT imaging, we present a case series of interstitial brachytherapy patients with successful target dose coverage outcomes. We intent to conduct a prospective study to evaluate pain control during the procedures. Further evaluation of long term survival of these patients is warranted; however, this data is encouraging to help increase access to brachytherapy services for clinics and locations with limited access to specialty services. Training and mentorship are essential components of a successful project and it is hoped that brachytherapy training programs could be availed in Africa.

Human papillomavirus (HPV) plays a significant role in the development of cervical cancers in the setting of co-infection with HIV. Botswana has a high prevalence of HIV and cervical cancer. In this study, we investigated the distribution of HPV subtypes in cervical cancer biopsy samples from patients in Botswana using a highly sensitive pan-pathogen microarray technology, PathoChip, to detect both high- (HR-HPV) and low-risk HPV (LR-HPV) subtypes in women living with HIV (WLWH) and women living without HIV. We analyzed samples from 168 patients, of which 73% (n = 123) were WLWH with a median CD4 count of 479.5 cells/μL. Five HR-HPV subtypes were detected in the cohort: HPV 16, 18, 26, 34, and 53. The most prevalent subtypes were HPV 26 (96%) and HPV 34 (92%); 86% of WLWH (n = 106) had co-infection with four or more HR-HPV subtypes compared to 67% (n = 30) of women without HIV (p < 0.01). We detected 66 LR-HPV subtypes among all cervical cancer patients, with HPV 6b and 48 being most prevalent. Notably, signatures for LR-HPV subtypes 10, 41, 90, and 129 were only detected in WLWH. Signal intensity for HPV 18 was significantly weaker in WLWH with CD4 levels ≤200 cells/μL as compared to patients with >200 cells/μL and HIV-negative patients. Although the majority of cervical cancer specimens in this cohort were determined to have multiple HPV infections, the most prevalent HR-HPV subtypes (HPV 26 and HPV34) found in these cervical cancer samples are not covered in the current HPV vaccines. Though no conclusions can be made on the direct carcinogenicity of these subtypes the results do underlie the need for continued screening for prevention of cervical cancer.

Women living with HIV (WLWH) are at an increased risk of developing HPV-related high grade cervical dysplasia and cervical cancer. Prior World Health Organization (WHO) screening guidelines recommended starting screening at age 30. We assessed characteristics of women diagnosed with cervical cancer to further inform and refine screening guidelines. We prospectively enrolled women diagnosed with cervical cancer from January 2015 to March 2020 at two tertiary hospitals in Gaborone, Botswana. We performed chi-square and ANOVA analyses to evaluate the association between age upon diagnosis and HIV status, CD4 count, viral load, and other sociodemographic and clinical factors. Data were available for 1130 women who were diagnosed with cervical cancer and 69.3% were WLWH. The median age overall was 47.9 (IQR 41.2–59.1), 44.6 IQR: 39.8 – 50.9) among WLWH, and 61.2 (IQR 48.6–69.3) among women living without HIV. There were 1.3% of women aged <30 years old, 19.1% were 30–39 and 37.2% were 40–49. Overall, 20.4% (n = 231) of cancers were in women <40 years. Age of cervical cancer diagnosis is younger in countries with higher HIV prevalence, like Botswana. Approximately 20% of the patients presented with cancer at <40 years of age and would have likely benefited from screening 10 years prior to cancer diagnosis to provide an opportunity for detection and treatment of pre-invasive disease.

PURPOSE:To determine the association between consolidative radiation (RT) and survival in children, adolescents, and young adults with metastatic sarcoma. METHODS AND MATERIALS:Eligibility criteria included patients aged ≤39 years with newly diagnosed metastatic bone or soft tissue sarcoma who completed local control of the primary tumor without disease progression. Consolidative RT was defined as RT to all known sites of metastatic disease. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). The least absolute shrinkage and selection operator Cox provided adjusted estimates. To account for immortal time bias, consolidative RT was used as a time-varying covariate in a time dependent Cox model. Distant failure was estimated using the Fine-Gray model. RESULTS:Patients (n = 85) had a median age at diagnosis of 14.8 years. Most common histology was Ewing Sarcoma (45.9%) followed by rhabdomyosarcoma (40.0%). Receipt of consolidative RT was associated with Ewing Sarcoma (P < .001) and local control modality as those who underwent local control with surgery and RT compared with surgery alone were more likely to be treated with consolidative RT (P = .034). Consolidative RT was independently associated with improved OS (hazard ratio [HR], 0.41; 95% CI, 0.17-0.98; P = .045) and improved PFS (HR, 0.37; 95% CI, 0.16-0.88; P = .024) after adjusting for confounding variables and immortal time bias. Patients treated with consolidative RT also experienced a lower risk of distant failure (HR, 0.33; 95% CI, 0.17-0.64; P = .001). In an independent data set of patients with metachronous progression (n = 36), consolidative RT remained independently associated with improved OS. CONCLUSIONS:Consolidative RT was independently associated with improved OS and PFS and decreased risk of distant failure in child, adolescent, and young adult patients with metastatic sarcoma. Future work should evaluate biomarkers to optimize patient selection, timing, and dose for consolidative RT.