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Background: The kinetics of circulating tumor DNA (ctDNA) release following commencement of radiotherapy or chemoradiotherapy may reflect early tumour cell killing. We hypothesised that an increase in ctDNA may be observed after the first fraction of radiotherapy and that this could have clinical significance. Materials and methods: ctDNA analysis was performed as part of a prospective, observational clinical biomarker study of non-small cell lung cancer (NSCLC) patients, treated with curative-intent radiotherapy or chemoradiotherapy. Blood was collected at predefined intervals before, during (including 24 h after fraction 1 of radiotherapy) and after radiotherapy/chemoradiotherapy. Mutation-specific droplet digital PCR assays used to track ctDNA levels during and after treatment. Results: Sequential ctDNA results are available for 14 patients with known tumor-based mutations, including in EGFR, KRAS and TP53, with a median follow-up of 723 days (range 152 to 1110). Treatments delivered were fractionated radiotherapy/chemoradiotherapy, in 2–2.75 Gy fractions (n = 12), or stereotactic ablative body radiotherapy (SABR, n = 2). An increase in ctDNA was observed after fraction 1 in 3/12 patients treated with fractionated radiotherapy with a complete set of results, including in 2 cases where ctDNA was initially undetectable. Neither SABR patient had detectable ctDNA immediately before or after radiotherapy, but one of these later relapsed systemically with a high detected ctDNA concentration. Conclusions: A rapid increase in ctDNA levels was observed after one fraction of fractionated radiotherapy in three cases. Further molecular characterization will be required to understand if a “spike” in ctDNA levels could represent rapid initial tumor cell destruction and could have clinical value as a surrogate for early treatment response and/or as a means of enriching ctDNA for mutational profiling.

There is increasing evidence that epigenetic mechanisms contribute to therapeutic resistance in cancer. Here the authors study AML patient samples and a mouse model of non-genetic resistance and find that transcriptional plasticity drives stable epigenetic resistance, and identify regulators of enhancer function as important modulators of resistance.

Over the past decade, increasing attention has been paid to intervening in individuals' health in the "preconception" period as an approach to optimizing pregnancy outcomes. Increasing attention to the structural and social determinants of health and to the need to prioritize reproductive autonomy has underscored the need to evolve the preconception health framework to center race equity and to engage with the historical and social context in which reproduction and reproductive health care occur. In this commentary, we describe the results of a meeting with a multidisciplinary group of maternal and child health experts, reproductive health researchers and practitioners, and Reproductive Justice leaders to define a new approach for clinical and public health systems to engage with the health of nonpregnant people. We describe a novel "Reproductive and Sexual Health Equity" framework, defined as an approach to comprehensively meet people's reproductive and sexual health needs, with explicit attention to structural influences on health and health care and grounded in a desire to achieve the highest level of health for all people and address inequities in health outcomes. Principles of the framework include centering the needs of and redistributing power to communities, having clinical and public health systems acknowledge historical and ongoing harms related to reproductive and sexual health, and addressing root causes of inequities. We conclude with a call to action for a multisectoral effort centered in equity to advance reproductive and sexual health across the reproductive life course., Competing Interests: Financial Disclosure UCSF hosted the expert panel that this work summarizes. All non-UCSF authors had travel, hotel and per diem expenses covered by UCSF, and were provided with an honorarium of $1,500. Aletha Y. Akers received funds from Merck, Inc. for serving on the HPV Advisory Panel, from the Association of Reproductive Health Professionals for serving on the HPV advisory group, and from Bayer Healthcare for an investigator-initiated grant. Barbara Levy disclosed receiving payments from AbbVie, Elidah Health, Dorsata, Acessa Health, Alydia Health, FLO Health, and Zebra Medical. Laura Jimenez disclosed that on occasion, her organization acts in an advisory capacity to various research entities that are under the UCSF umbrella. The other authors did not report any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: Metastatic breast cancer (mBC) is a heterogenous disease with increasing availability of targeted therapies as well as emerging genomic markers of therapeutic resistance, necessitating timely and accurate molecular characterization of disease. As a minimally invasive test, analysis of circulating tumour DNA (ctDNA) is well positioned for real-time genomic profiling to guide treatment decisions. Here, we report the results of a prospective testing program established to assess the feasibility of ctDNA analysis to guide clinical management of mBC patients., Methods and Findings: Two hundred thirty-four mBC patients (median age 54 years) were enrolled between June 2015 and October 2018 at the Peter MacCallum Cancer Centre, Melbourne, Australia. Median follow-up was 15 months (range 1-46). All patient samples at the time of enrolment were analysed in real time for the presence of somatic mutations. Longitudinal plasma testing during the course of patient management was also undertaken in a subset of patients (n = 67, 28.6%), according to clinician preference, for repeated molecular profiling or disease monitoring. Detection of somatic mutations from patient plasma was performed using a multiplexed droplet digital PCR (ddPCR) approach to identify hotspot mutations in PIK3CA, ESR1, ERBB2, and AKT1. In parallel, subsets of samples were also analysed via next-generation sequencing (targeted panel sequencing and low-coverage whole-genome sequencing [LC-WGS]). The sensitivity of ddPCR and targeted panel sequencing to identify actionable mutations was compared. Results were discussed at a multidisciplinary breast cancer meeting prior to treatment decisions. ddPCR and targeted panel sequencing identified at least 1 actionable mutation at baseline in 80/234 (34.2%) and 62/159 (39.0%) of patients tested, respectively. Combined, both methods detected an actionable alteration in 104/234 patients (44.4%) through baseline or serial ctDNA testing. LC-WGS was performed on 27 patients from the cohort, uncovering several recurrently amplified regions including 11q13.3 encompassing CCND1. Increasing ctDNA levels were associated with inferior overall survival, whether assessed by ddPCR, targeted sequencing, or LC-WGS. Overall, the ctDNA results changed clinical management in 40 patients including the direct recruitment of 20 patients to clinical trials. Limitations of the study were that it was conducted at a single site and that 31.3% of participants were lost to follow-up., Conclusion: In this study, we found prospective ctDNA testing to be a practical and feasible approach that can guide clinical trial enrolment and patient management in mBC., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: M.A.D. has been a member of advisory boards for CTX CRC, Storm Therapeutics, Celgene, Cambridge Epigenetix, and GSK. S. L. receives research funding to her institution from Novartis, Bristol Meyers Squibb, Merk, Roche-Genentech, Puma Biotechnology, Pfizer, and Eli Lilly. She has acted as a consultant (not compensated) to Seattle Genetics, Pfizer, Novartis, BMS, Merck, AstraZeneca, and Roche-Genentech. She has acted as a consultant (paid to her institution) to Aduro Biotech. S.Q.W. has received travel support from BioRad. S-J. D. has received research funding to her institution from Roche-Genentech and CTX CRC. She has been a member of advisory boards for AstraZeneca.

Background: There is increasing support among stakeholders in the United States to make oral contraceptives (OCs) available over the counter (OTC). Previous research on the topic has focused on representative samples of U.S. women, Latina women, low-income women, and abortion clients. However, little is known about the perspectives of African American women, Asian American women, and young women., Methods: We conducted 14 focus group discussions with 138 women. Twenty-three percent of participants were ages 18 or younger, 61% were African American, and 26% were Asian American/Pacific Islander. Community organizations recruited participants through convenience sampling and hosted the discussions. Focus groups were transcribed and coded thematically., Findings: Women reported potential benefits of OTC access, including convenience and privacy. Many believed OTC availability of OCs would help to reduce unintended pregnancy and help to destigmatize birth control. Participants also expressed concerns about OTC access, such as worry that first-time users and young adolescents would not have enough information to use the pill safely and effectively, as well as concerns about whether women would still obtain preventive screenings. Women were also worried that the cost of OTC OCs would be higher if insurance no longer covered them., Conclusions: Overall, women were interested in the option of obtaining the pill OTC. Future research and advocacy efforts should explore women's concerns, including whether adolescents can effectively use OTC pills and ensuring insurance coverage for OTC contraception., (Copyright © 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)

Purpose: Low rates of human papillomavirus (HPV) vaccination among young Asian American and Pacific Islander (AAPI) women need to be addressed, particularly given the high incidence of cervical cancer in this population. The current study aims to investigate predictors of HPV vaccination in young AAPI and non-Latina white (NLW) women., Methods: A secondary data analysis was conducted of a health survey administered to college-aged women (N = 2,270) at a large public university in the Midwest. Andersen's behavioral model of health services utilization guided the study theoretically, and hierarchical logistic regression analysis was conducted to investigate research aim., Results: NLW women had a significantly higher rate of vaccine completion than AAPI women (NLW = 60.7%; AAPI = 38.6%). NLW women also scored higher on all 5 measures of HPV vaccine literacy than AAPI women. Both groups of undergraduate women reported that increasing age, knowledge about HPV, greater use of gynecological services, and knowing someone who had cancer were significant factors related to HPV vaccination completion. In the NLW group, father's income was also found to be a predictor of HPV vaccination completion., Conclusions: Rate and predictors of HPV vaccination completion vary between NLW and AAPI women. Greater promotion of HPV literacy and gynecological service use should be made to young AAPI women to increase their HPV uptake. Further research should examine sociocultural factors that could hinder or promote HPV vaccination in young AAPI women.