Use of Radiotherapy in the Management of Vulvar Cancers - Identification and Management of Acute and Late Toxicities.

Radiotherapy plays a critical role in the management of locally advanced vulvar cancers, but can lead to a unique spectrum of side effects, with > 25% of patients experiencing high-grade toxicities. The treatment phase requires meticulous perineal skincare, and may require pharmacologic management of dysuria and cystitis, diarrhea, nausea, and dermatitis/mucositis. The addition of chemotherapy warrants close laboratory monitoring for hematologic and metabolic derangements.

Financial Improvements From Short Course Adjuvant Vaginal Cuff Brachytherapy in Early Endometrial Cancer Compared With Standard of Care, "SAVE" Trial.

PURPOSE: Early-stage endometrial cancer is often treated with hysterectomy followed by adjuvant vaginal cuff brachytherapy (VCB). Financial toxicity from cancer treatment can impact treatment completion. The Short Course Adjuvant Vaginal Cuff Brachytherapy in Early Endometrial Cancer Compared to Standard of Care trial is a multicenter, prospective randomized trial of standard of care (SoC) VCB doses delivered in 3 to 5 fractions per the physician's discretion compared with a 2-fraction course. We report on secondary cost endpoints, quantifying the financial impacts of shorter treatment courses on institutions and participating patients. METHODS AND MATERIALS: Technical (TechCs), professional, and total charges (TotCs) were collected prospectively and are reported as raw and Medicare-adjusted charges per patient. Distance to the treatment center and the median income for each patient's zip code were estimated. The Mann-Whitney U statistic, t test, and X2 test were used to compare characteristics between the 2 groups. RESULTS: One hundred eight patients were analyzed. SoC VCB was delivered in 3, 4, and 5 fractions for 27 of 54 patients (50%), 11 of 54 (20%), and 16 of 54 (30%), respectively. The median total distance traveled per patient for SoC versus experimental arms was 213 versus 137 miles (p = .12), and the median cost of commute for patients was $36.3 versus $18.0 (p = .11). Compared with 2-fraction treatment, 5-fraction treatment resulted in longer travel distances (median, 462 vs 137 miles; p < .01) and increased travel costs (median, $59.3 vs $18.0; p ≤ .01). Unadjusted raw professional charges in USD per patient did not differ between SoC versus experimental arms ($9159 vs $7532; p = .19). TechCs were significantly higher in the SoC arm ($35,734 vs $24,696; p ≤ .01), as were TotCs ($44,892 vs $32,228; p < .01;). Medicare-adjusted TechCs and TotCs were higher for the SoC arm. CONCLUSIONS: Two-fraction VCB resulted in fewer treatments per patient, reduced cost of travel compared with longer courses, and an adjusted reduction in health care expenditures compared with SoC.

Vulvar Cancer: Histopathologic Considerations and Nuances to Management: Vulvar cancer considerations and nuances.

Vulvar cancer, though rare, poses significant challenges in diagnosis and treatment due to its histopathological complexities and nuances. This paper reviews key aspects of the management of vulvar cancer, focusing on histopathological diagnosis, margin status interpretation, lymph node involvement assessment, and ongoing clinical trials.

International Federation of Gynecology and Obstetrics Endometrial 2023 Is Better For Radiation Oncology Patients.

The International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system for endometrial cancer has marked changes from the previous staging system instituted 14 years prior in 2009. The new staging system includes nonanatomic factors for the first time (lymphovascular space invasion and histology) and molecular classification, which impacts the stage in early-stage disease (IAmPOLEmut and IICmp53abn). The purpose of these changes was to provide (1) high accuracy in the predictive prognosis for patients and (2) identification of distinct treatment-relevant subgroups. Our understanding of the biology and natural history of endometrial cancer has undergone a radical transformation since the Cancer Genome Atlas results in 2013. The 2023 FIGO staging system harmonizes and integrates old and new knowledge on anatomic, histopathologic, and molecular features. Moreover, FIGO 2023 has distinct substages that improve adjuvant treatment decision making. Although the practicality of the new staging system has been debated, we postulate that FIGO 2023 is more useful for radiation oncologists aiming to provide personalized care recommendations. FIGO 2023 requires a change in our perception of a staging system, from a traditional anatomic borders-based system to a staging system integrating anatomy and tumor biology as pivotal prognostic factors for patients while providing important information for treatment decision making.

D-TERMINED, a phase 1 trial in newly diagnosed high-grade glioma with temozolomide, radiation, and minocycline followed by adjuvant minocycline/temozolomide.

Background: Standard treatment for newly diagnosed high-grade gliomas remains suboptimal. Preclinical data indicate that mesenchymal transition and radiation resistance in glioblastoma are driven by NF-κB and microglia activation, which can be inhibited by minocycline. We assessed the safety and efficacy of minocycline combined with standard radiation and temozolomide in newly diagnosed high-grade gliomas. Methods: Adults with newly diagnosed high-grade glioma were eligible. Minocycline was given with concurrent and adjuvant temozolomide. Minocycline doses were escalated using a 3 + 3 design and expanded to identify the maximum tolerated dose (MTD) and adverse event profile. Individual progression-free survival (PFS) was compared to predicted PFS based on RTOG RPA class using a binomial test. The relationships between mesenchymal and microglial biomarkers were analyzed with immunohistochemistry. Results: The MTD of minocycline was 150 mg twice per day (N = 20); 1 patient (5%) experienced CTCAE grade 3 + nausea and dizziness, and 2 patients (10%) demonstrated thrombocytopenia requiring temozolomide interruptions. Twelve patients exceeded their predicted PFS (60%), which did not meet the predefined efficacy endpoint of 70%. Symptoms increased during post-radiation treatment but remained mild. No significant correlation was seen between biomarkers and PFS. Expression levels of P-p65, a marker of NF-κB activation, were correlated with the microglia marker IBA-1. Conclusions: Minocycline at 150 mg twice per day is well tolerated with standard chemoradiation in patients with newly diagnosed high-grade gliomas. PFS was not significantly increased with the addition of minocycline when compared to historical controls. NF-κB activation correlates with microglia levels in high-grade glioma.

Clonal hematopoiesis in patients with HIV and cancer.

BACKGROUND: Cancer-related deaths for people living with HIV (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH. METHODS: We conducted a retrospective study to compare the prevalence and clinical outcomes of CH in PWH and people without HIV (PWoH) and cancer. Included in the study were PWH and similar PWoH based on tumor site, age, tumor sequence, and cancer treatment status. Biological aging was also measured using epigenetic methylation clocks. RESULTS: In 136 patients with cancer, PWH had twice the prevalence of CH compared to similar PWoH (23% vs 11%, p=0.07). After adjusting for patient characteristics, PWH were four-times more likely to have CH than PWoH (OR 4.1, 95% CI 1.3-13.9, p=0.02). The effect of CH on survival was most pronounced in PWH, who had a 5-year survival rate of 38% if they had CH (vs 59% if no CH), compared to PWoH who had a 5-year survival rate of 75% if they had CH (vs 83% if no CH). CONCLUSION: This study provides the first evidence that PWH may have a higher prevalence of CH than PWoH with the same cancers. CH may be an independent biological aging risk factor contributing to inferior survival for PWH and cancer.

Cancer Treatment Disparities in People With HIV in the United States, 2001-2019.

PURPOSE: People with HIV (PWH) have worse cancer outcomes, partially because of inequities in cancer treatment. We evaluated cancer treatment disparities among PWH, including an assessment of changes in disparities over time. METHODS: We used data from the HIV/AIDS Cancer Match Study, a population-based HIV and cancer registry linkage to examine diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), and cancers of the cervix, lung, anus, prostate, colon, and female breast. Outcomes included receipt of (1) any cancer treatment and (2) standard therapy among patients with local-stage cancer. We assessed associations between HIV and each outcome by estimating adjusted prevalence odds ratios (aORs) with 95% CI and trends over time. We identified predictors of nonreceipt of cancer treatment in PWH. RESULTS: From 2001 to 2019, compared with people with cancer without HIV (n = 2,880,955), PWH (n = 16,334) were more likely to not receive cancer treatment for cervical cancer (aOR, 2.03 [95% CI, 1.52 to 2.70]), DLBCL (aOR, 1.53 [95% CI, 1.38 to 1.70]), HL (aOR, 1.39 [95% CI, 1.19 to 1.63]), lung cancer (aOR, 1.79 [95% CI, 1.65 to 1.93]), prostate cancer (aOR, 1.32 [95% CI, 1.21 to 1.44]), colon cancer (aOR, 1.73 [95% CI, 1.43 to 2.08]), and breast cancer (aOR, 1.38 [95% CI, 1.07 to 1.77]). Similar associations were observed in PWH with local-stage cancers although no difference was observed for anal cancers. The association between HIV and nonreceipt of cancer treatment significantly decreased over time for breast, colon, and prostate cancers (all P trend <.0001), but PWH remained less likely to receive treatment in 2014-2019 for DLBCL, cervix, and lung cancers. Among PWH, Black individuals, people who inject drugs, and those 65 years and older were less likely to receive cancer treatment. CONCLUSION: Disparities in receipt of cancer treatment persist for PWH in the United States in contemporary time periods. Solutions to address inequitable receipt of cancer treatment among PWH are urgently needed.

Differentiation of survival outcomes by anatomic involvement and histology with the revised 2023 International Federation of Gynecology and Obstetrics staging system for endometrial cancer.

OBJECTIVES: The International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer underwent revision in 2023, incorporating histology, lymphovascular space invasion, and molecular classification. Herein, we compare overall survival (OS) outcomes by anatomic and histologic involvement for patients staged by the 2009 system versus 2023 system. METHODS: The National Cancer Database (NCDB) was queried for patients with newly-diagnosed uterine adenocarcinoma from 2004 to 2015, with follow-up data extending through 2020. Stage was determined by both the 2009 and 2023 FIGO staging systems. Kaplan-Meier estimators and Cox proportional hazards models were used for survival analysis. RESULTS: A total of 134,677 patients were analyzed. Per 2023 classification, patients with stage I disease decreased from 96,161 to 70,101 (-27.1%, p < 0.01), while stage II disease increased from 9295 to 36,294 (+390.5%, p < 0.01). Greatest OS change was observed for 2023 stage IA3 patients (low-risk, synchronous endometrial and ovarian tumors with a clonal relationship), whose 10-year OS was 73.4%, compared to 52.6% for 2009 stage IIIA disease. Ten-year OS for 2023 stage IIIB2 (pelvic peritoneal involvement), previously 2009 stage IVB, was 49.4%, compared to 18.7% for 2009 stage IVB patients. Akaike information criterion, Bayesian information criterion, and Harrel's concordance index were used to evaluate OS prognostication of each staging system across all stages, with likelihood ratio favoring the 2023 system (p = 0.020). CONCLUSIONS: With FIGO's 2023 endometrial cancer anatomic and histologic staging system, stage migration is greatest in early-stage disease. New staging groups may offer more precise prognostication. These changes may affect future management.

The impact of a positive COVID-19 test on timeliness of radiation in patients receiving brachytherapy.

BACKGROUND: Delays in initiating and completing brachytherapy may have adverse oncologic outcomes for patients with cervical, uterine, and prostate cancer. The impact of the COVID-19 pandemic on brachytherapy in the United States has not been well-characterized. OBJECTIVES: We aim to evaluate how a positive COVID-19 test affected timeliness of treatment for patients undergoing brachytherapy for cervical, uterine, and prostate cancer. METHODS: We queried the National Cancer Database to identify patients diagnosed with cervical, uterine, and prostate cancer in 2019 and 2020 who received brachytherapy in their treatment. Patients who tested positive for COVID-19 between cancer diagnosis and start of radiation were compared to those who did not test positive for COVID-19. Time in days from cancer diagnosis to initiation of radiation was compared using two-sample t-tests with p < 0.05 signifying significant differences. RESULTS: We identified 38,341 patients with cervical (n = 6,925), uterine (n = 18,587), and prostate cancer (n = 12,829). Rates of COVID-19 positivity were cervical cancer (n = 135; 2%), uterine cancer (n = 236; 1.3%), and prostate cancer (n = 141; 1%). Of those, 35% of cervical, 49% of uterine, and 43% of prostate cancer patients tested positive between their cancer diagnosis and initiation of radiation. Median days to radiation was significantly longer in these patients: 78 versus 51 for cervical cancer (p < 0.01), 150 versus 104 for uterine cancer (p < 0.01), and 154 versus 124 for prostate cancer (p < 0.01). CONCLUSIONS: For patients with cervical, uterine, and prostate cancer diagnosed between 2019-2020, testing positive for COVID-19 after their cancer diagnosis was associated with a delay to initiation of radiation by 4-7 weeks.

Reducing the Environmental Impact of Health Care Conferences: A Study of Emissions and Practical Solutions.

PURPOSE: We aimed to examine the impact of different conference formats (in-person, virtual, and hybrid) of the ASCO conference on greenhouse gas (GHG) emissions and to recommend sustainable options for future conferences. MATERIALS AND METHODS: This study used data on the number of attendees, their departure locations, and the type of attendance (in-person v virtual) provided by ASCO between 2019 and 2022. The GHG emissions resulting from air and ground travel, remote connectivity, conference space utilization, hotel stays, distributed conference materials, and electricity use were estimated for each year. Emissions were stratified by attendee country of origin, type of attendance, and year. Simulations were conducted to evaluate how changes in conference size, location, and format impact emissions, as well as estimate the resulting mitigations from adopting the proposed changes. RESULTS: The highest estimated GHG emissions, calculated in carbon dioxide equivalents (CO2e), were associated with the 2019 in-person conference (37,251 metric tons of CO2e). Although international attendees had the largest contribution to emissions in all years (>50%), location optimization models, which selected conference locations that most minimized GHG emissions, yielded only minimal reductions (approximately 3%). Simulations examining changes to the conference format, location, and attendance percentage suggested that hub-and-spoke, where multiple conference locations are selected by global region, or hybrid models, with both in-person and virtual components, are likely to cause the largest drops in emissions (up to 86%). CONCLUSION: Using historical conference data, this study identifies key aspects that can be modified to reduce emissions and consequently promote more sustainable and equitable conference attendance. Hybrid conferences may be the best solution to maintain the networking opportunities provided by conferences while balancing out their environmental footprint.

State of the science and future directions for research on HIV and cancer: Summary of a joint workshop sponsored by IARC and NCI.

An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death. Furthermore, the types of cancers occurring among PLWH are shifting over time and vary in their relative burden in different parts of the world. In this context, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) convened a meeting in September 2022 of multinational and multidisciplinary experts to focus on cancer in PLWH. This report summarizes the proceedings, including a review of the state of the science of cancer descriptive epidemiology, etiology, molecular tumor characterization, primary and secondary prevention, treatment disparities and survival in PLWH around the world. A consensus of key research priorities and recommendations in these domains is also presented.

Image-guided preplanning workflow for high-dose-rate interstitial brachytherapy for gynecological malignancies.

PURPOSE: To demonstrate image-guided preplan workflows for high-dose-rate (HDR) brachytherapy for advanced gynecological malignancies. METHODS AND MATERIALS: Two different preplanning scenarios are presented: (1) CT- or MRI-based preplan with partial applicator in place; (2) Preplans generated from prior fractions. The first scenario can be applied to Syed-Neblett template-based implants or hybrid brachytherapy applicators, while the second scenario applies to hybrid applicators. Both scenarios use MRI or CT images acquired with the applicator in place to demonstrate tumor and applicator relative locations and therefore, provide the ability to show optimized suggested needle positions including the implant depths before the actual insertion. RESULTS: The preplanning techniques have demonstrated feasibility and shown five areas of potential improvement: (1) shorter procedure time, (2) decreased number of total needles inserted, (3) shorter physician tumor contour time, (4) shorter planning time, and (5) evaluation of appropriateness for brachytherapy. CONCLUSIONS: The use of image-guided brachytherapy preplanning improves clinical efficiency and is recommended for consideration for adaptation into clinical workflows for HDR interstitial and hybrid brachytherapy.

Culturally-informed adaptation and psychometric properties of the Cataldo Cancer Stigma Scale in Northern Tanzania.

BACKGROUND: Cancer-related stigma impacts patients' emotional health, care engagement, and cancer outcomes, but few measures of cancer stigma exist. We culturally adapted and assessed psychometric properties of the Cataldo Cancer Stigma Scale (CCSS) in Tanzania. METHODS: We administered the CCSS short version (21 items), plus 12 locally-derived items, to 146 adult cancer patients. We conducted exploratory factor analysis, examined internal consistency/reliability, and assessed convergent validity with relevant measures. RESULTS: We identified a 17-item cancer stigma scale with strong psychometric properties and four subscales: enacted stigma, shame and blame, internalized stigma, and disclosure concerns. Stigma was rare except for disclosure concerns. Stigma was positively associated with depression and anxiety and negatively associated with social support, quality of life, and illness acceptance. CONCLUSIONS: The scale provides valid, culturally-informed measurement of cancer stigma in Tanzania. Future studies should assess associations with care engagement, which will inform interventions to reduce stigma and improve outcomes.

Cancer Treatment Decision-Making for People Living With HIV: Physician-Reported Barriers, Facilitators, and Recommendations.

BACKGROUND: Compared with the general cancer population, people living with HIV (PLWH) and cancer are less likely to receive treatment and have significantly elevated cancer-specific mortality for many common cancer types. Physician recommendations drive the cancer therapy that patients receive, yet there is limited information assessing how cancer treatment decisions are made for people living with HIV and cancer. We sought to understand oncologist decision-making in PLWH and cancer by eliciting barriers, facilitators, and recommendations for enhancing care delivery. SETTING: Participants were recruited between May 2019 and May 2021 from one academic medical center in the western United States (n = 13), another in the southeastern United States (n = 7), and community practices nationwide (n = 5). METHODS: Using an inductive qualitative approach, we conducted in-depth interviews with 25 oncologists from two academic medical centers and community practices. RESULTS: Facilitators of cancer care delivery included readily available information regarding HIV status and stage, interdepartmental communication, and antiviral therapy adherence. Barriers included a lack of formal education on HIV malignancies, perceptions of decreased life expectancy, fear of inadvertent disclosure, and drug-drug interactions. Recommendations included improved provider communication, patient social and mental health resources, and continuing education opportunities. CONCLUSION: The study revealed drivers of cancer treatment decision-making, highlighting physician-reported barriers and facilitators, and recommendations to support treatment decision-making. This is the first known study examining oncologists' perceptions of caring for PLWH. Given that cancer is a leading cause of death among PLWH, there is an urgent need to improve care and outcomes.

Multi-Institutional Analysis of Cancer Patient Exposure, Perceptions, and Trust in Information Sources Regarding Complementary and Alternative Medicine.

PURPOSE: Complementary and alternative medicine (CAM) use during cancer treatment is controversial. We aim to evaluate contemporary CAM use, patient perceptions and attitudes, and trust in various sources of information regarding CAM. METHODS: A multi-institutional questionnaire was distributed to patients receiving cancer treatment. Collected information included respondents' clinical and demographic characteristics, rates of CAM exposure/use, information sources regarding CAM, and trust in each information source. Comparisons between CAM users and nonusers were performed with chi-squared tests and one-way analysis of variance. Multivariable logistic regression models for trust in physician and nonphysician sources of information regarding CAM were evaluated. RESULTS: Among 749 respondents, the most common goals of CAM use were management of symptoms (42.2%) and treatment of cancer (30.4%). Most CAM users learned of CAM from nonphysician sources. Of CAM users, 27% reported not discussing CAM with their treating oncologists. Overall trust in physicians was high in both CAM users and nonusers. The only predictor of trust in physician sources of information was income >$100,000 in US dollars per year. Likelihood of trust in nonphysician sources of information was higher in females and lower in those with graduate degrees. CONCLUSION: A large proportion of patients with cancer are using CAM, some with the goal of treating their cancer. Although patients are primarily exposed to CAM through nonphysician sources of information, trust in physicians remains high. More research is needed to improve patient-clinician communication regarding CAM use.

Cancer treatment delays among cancer patients living with HIV during the COVID-19 pandemic in the United States.

BACKGROUND: The COVID-19 pandemic led to care disruptions across the cancer continuum. It is unknown if immunosuppressed patients with cancer, who may be at higher risk for complications of SARS-CoV-2 infection, are disproportionately impacted. Thus, we aimed to compare delays in cancer treatment initiation between people living with HIV (PLWH) and cancer, the general cancer population (GCP), and patients with cancer and a history of solid organ transplant (SOT). Comparisons were made across the period 2 years preceding the pandemic versus the first year of the pandemic. METHODS: We used data from a real-world electronic health record-derived de-identified database (2018-2021) comprised of US patients with cancer from 800 sites of care across the country. We included patients with 19 different cancer types. We calculated time to cancer treatment initiation (TTI) as the difference between the date of cancer diagnosis and the earliest date that cancer treatment was recorded. RESULTS: The sample included 181 PLWH, 65,073 GCP patients, and 195 patients with a SOT. Difference-in-difference regression models adjusted for age, sex, and presence of metastatic disease at cancer diagnosis revealed a significant increase in delayed TTI among PLWH compared to the GCP during COVID-19 versus prior to COVID-19, with delays increasing by approximately 1 month during the pandemic (DID: 32.6 days [8.9-56.3]; p = 0.007). The increase in TTI for PLWH was observed across treatment modalities, including surgery (DID: 55.1 [28.8-81.3], p < 0.001) and systemic therapy (DID: 30.4 [4.6-56.3], p = 0.021). CONCLUSIONS/RELEVANCE: PLWH experienced significant delays in cancer treatment initiation after diagnosis during the first year of COVID-19, delays that may negatively impact cancer outcomes. These data warrant patient and provider attention as the pandemic continues to impact the US healthcare system.