Fluorodeoxyglucose positron emission tomography scans in patients with alcohol use disorder.

BACKGROUND: Diminished uptake of fluorodeoxyglucose (FDG) has been observed in patients with alcohol use disorder (AUD) but little statistical contrast of the regional brain deficits has been undertaken. This study examined prefrontal cortex inter-regional Brodmann area differences to delineate patterns associated with behavioral, neurotransmitter, and general toxicity hypotheses of cerebral involvement in AUD. METHODS: We obtained data from FDG positron emission tomography (PET) and anatomical magnetic resonance imaging (MRI) for 87 patients with AUD and 41 age- and sex-matched healthy volunteers. Patients were alcohol dependent and had negative breathalyzer tests at the time of imaging. They were assessed with the Beck Depression Inventory, Alcohol Urge Questionnaire, Obsessive Compulsive Drinking Scale, Spielberger State/Trait Anxiety Scale, Buss-Durkee Hostility Inventory, and the Drinker Inventory of Consequences (DrInC). PET images were co-registered to MRI and both voxel × voxel statistical mapping and stereotaxic regions of interest were obtained. RESULTS: Compared with healthy volunteers, patients with AUD had lower relative metabolic rates in the frontal, temporal, and parietal lobes, localizable most prominently to the dorsolateral and nearly all orbital prefrontal cortex, superior temporal gyrus, and inferior parietal lobule. In contrast, metabolic rates in the medial orbitofrontal and anterior cingulate cortex, and the subcortical structures (thalamus, cerebellum, ventral striatum, and the dorsal raphe nucleus) in patients were significantly greater. The severity of alcohol-related consequences as assessed by the DrInC scale was most highly associated with lower metabolism in the caudate, dorsolateral prefrontal, frontopolar, and anteroposterior cingulate cortex. CONCLUSIONS: Despite widespread metabolic abnormalities, decreases in AUD were most marked in frontal executive areas, consistent with diminished impulse control, and increases were most prominent in the striatum and cingulate areas, consistent with a suppressed reward system.

Association of chemotherapy and radiotherapy sequence with overall survival in locoregionally advanced endometrial cancer.

OBJECTIVE: The optimal adjuvant management of women with FIGO Stage III-IVA endometrial cancer (EC) is unclear. While recent prospective data suggest that treatment with pelvic radiotherapy (RT) prior to chemotherapy (CT) is not associated with a survival benefit compared to CT alone, no prospective randomized trial has included a treatment arm in which CT is given before RT. METHODS: An observational cohort study was performed on women with FIGO Stage III-IVA Type 1 (grade 1-2, endometrioid) EC who underwent hysterectomy and received multi-agent CT and/or RT from 2004 to 2014 at Commission on Cancer-accredited hospitals. Multivariable parametric accelerated failure time models were performed to estimate the association of sequence of adjuvant CT and RT with overall survival (OS) using propensity score-adjusted matched cohorts. RESULTS: Of 5795 women identified, 1260 (21.7%) received RT only, 2465 (42.5%) received CT only, 593 (9.7%) received RT before CT, and 1506 (26.0%) received RT after CT. Women who received RT after CT experienced significantly longer 5-year OS than women who received RT before CT (5-year OS: 80.1% vs 73.3%; time-ratio (TR) = 1.37, 95% CI = 1.18-1.58, P < 0.001), CT only (68.9%; TR = 1.33, 95% CI = 1.19-1.48, P < 0.001), or RT only (64.5%, TR = 1.50, 95% CI = 1.32-1.70, P < 0.001). CONCLUSIONS: For women with advanced EC, treatment with multi-agent CT followed by RT is associated with longer OS compared with treatment with RT followed by CT or either treatment alone. These hypothesis-generating data support inclusion in future prospective trials of regimens in which multi-agent CT starts prior to RT.

Disease Site Specialization in the Academic Radiation Oncology Workforce: Evidence of Gender Differences.

PURPOSE: Because some stakeholders within medicine seek to diversify and attain greater workforce equity, it is critical to understand gender-based divisions within specialization. Radiation oncology (RO) has one of the smallest proportions of women representation of all specialties, and to our knowledge, no prior studies have investigated gender differences in all the disease site specializations within RO. Thus, we analyzed the relationship between gender and disease site(s) treated in academic RO (ARO). METHODS AND MATERIALS: Faculty gender and disease site(s) treated by faculty from ARO departments were collected via publicly available department websites in January 2020. X2 analyses were conducted to assess differences between the proportions of women faculty treating each disease site. RESULTS: Of 1337 ARO faculty, 408 (30.5%) were identified as women. Breast, gynecology, and pediatrics had the largest proportions of women faculty (all >40%; P < .001). A majority (53%; P < .001) of women ARO faculty treated breast. Genitourinary, thoracic, and head and neck had the smallest proportions of women faculty (all <25%; P < .001). Women ARO faculty were twice as likely to treat breast and gynecologic malignancies compared with men faculty (risk ratio [RR] with 95% CI, 2.01 [1.75-2.50]; P < .001 and RR [95% CI], 2.06 [1.72-2.79]; P <.001, respectively). Men ARO faculty were 3 times more likely to treat genitourinary cancer compared with women faculty (RR [95% CI], 0.40 [0.34-0.48]; P < .001). There was no difference in the mean number of disease sites treated between women and men ARO faculty (2.63 vs 2.53; P = .29). CONCLUSIONS: Gender differences in disease site specialization were observed in ARO. Future research into the drivers of disease site selection should be explored.

Automated, Real-Time Integration of Biometric Data From Wearable Devices With Electronic Medical Records: A Feasibility Study.

PURPOSE: A major barrier to the incorporation of biometric data into clinical practice is the lack of device integration with electronic medical records (EMRs). We developed infrastructure to transmit biometric data from an Apple Watch into the EMR for physician review. The study objective was to test feasibility of using this infrastructure for patients undergoing radiotherapy. METHODS: The study included patients with breast or prostate cancer receiving ≥3 weeks of radiotherapy who reported owning an Apple Watch. Daily resting heart rate (HR), HR variability, step count, and exercise minutes were automatically transferred to our EMR using a custom app installed on each patient's iPhone. Biometric data were presented to the treating radiation oncologist for review on a weekly basis during creation of the on-treatment note. Feasibility was defined a priori as physician review of biometric data for at least 90% of patients. Time trends in biometric data were tested using the Jonckheere-Terpstra test. Patient satisfaction was assessed using the System Usability Scale (SUS), with scores above 80 considered above-average user experience. RESULTS: Of the 20 patients enrolled, biometric data were successfully transmitted to the EMR and reviewed by the radiation oncologist for 95% (n = 19) of patients, thus meeting the a priori feasibility threshold. For patients with radiation courses ≥4 weeks, exercise minutes decreased over time (P = .01) and daily mean HR variability increased over time (P = .02). The median SUS was 82.5 (IQR, 70-87.5). CONCLUSION: Our study demonstrates the feasibility of real-time integration of biometric data collected from an Apple Watch into the EMR with subsequent physician review. The high rates of physician review and patient satisfaction provide support for further development of large-scale collection of wearable device data.

ACR-ARS Practice Parameter on Informed Consent Radiation Oncology.

OBJECTIVES: Consent is a communication process between the patient and a health care provider, in which both parties have the opportunity to ask questions and exchange information relevant to the patient's diagnosis and treatment. The process of informed consent is designed to protect a patient's autonomy in their medical decision-making in the context of an asymmetric relationship with the health care system. A proper consent process assures a patient's individual autonomy, reduces the opportunity for abusive conduct or conflicts of interest, and raises trust levels among participants. This document was developed as an educational tool to facilitate these goals. METHODS: This practice parameter was produced according to the process described under the heading "The Process for Developing ACR Practice Parameters and Technical Standards" on the ACR website ( https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. Committee members were charged with reviewing the prior version of the informed consent practice parameter published in 2017 and recommending additions, modifications, or deletions. The committee met through remote access and subsequently through an online exchange to facilitate the development of the revised document. Focus was given on identifying new considerations and challenges with informed consent given the evolution of the practice of radiation oncology in part driven by the COVID-19 pandemic and other external factors. RESULTS: A review of the practice parameter published in 2017 confirmed the ongoing relevance of recommendations made at that time. In addition, the evolution of the practice of radiation oncology since the publication of the prior document resulted in the need for new topics to be addressed. These topics include remote consent either through telehealth or telephone and with the patient or their health care proxy. CONCLUSIONS: Informed consent is an essential process in the care of radiation oncology patients. This practice parameter serves as an educational tool designed to assist practitioners in optimizing this process for the benefit of all involved parties.

Prospective, early longitudinal assessment of lymphedema-related quality of life among patients with locally advanced breast cancer: The foundation for building a patient-centered screening program.

BACKGROUND: We examined how breast cancer-related lymphedema (BCRL) affects health-related quality of life (HRQOL), productivity, and compliance with therapeutic interventions to guide structuring BCRL screening programs. METHODS: We prospectively followed consecutive breast cancer patients who underwent axillary lymph node dissection (ALND) with arm volume screening and measures assessing patient-reported health-related quality of life (HRQOL) and perceptions of BCRL care. Comparisons by BCRL status were made with Mann-Whitney U, Chi-square, Fisher's exact, or t tests. Trends over time from ALND were assessed with linear mixed-effects models. RESULTS: With a median follow-up of 8 months in 247 patients, 46% self-reported ever having BCRL, a proportion that increased over time. About 73% reported fear of BCRL, which was stable over time. Further in time from ALND, patients were more likely to report that BCRL screening reduced fear. Patient-reported BCRL was associated with higher soft tissue sensation intensity, biobehavioral, and resource concerns, absenteeism, and work/activity impairment. Objectively measured BCRL had fewer associations with outcomes. Most patients reported performing prevention exercises, but compliance decreased over time; patient-reported BCRL was not associated with exercise frequency. Fear of BCRL was positively associated with performing prevention exercises and using compressive garments. CONCLUSIONS: Both incidence and fear of BCRL were high after ALND for breast cancer. Fear was associated with improved therapeutic compliance, but compliance decreased over time. Patient-reported BCRL was more strongly associated with worse HRQOL and productivity than was objective BCRL. Screening programs must support patients' psychological needs and aim to sustain long-term compliance with recommended interventions.

Implications of Medical Board Certification Practices on Family Planning and Professional Trajectory for Early Career Female Radiation Oncologists.

PURPOSE: Our purpose was to evaluate the effect of the current structure and schedule of the American Board of Radiology (ABR) radiation oncology initial certification (RO-IC) examinations, with a primary focus on implications for family planning and early professional barriers among female radiation oncologists. METHODS AND MATERIALS: A survey was conducted of crowdsourced ABR candidates and diplomates for radiation oncology between June and July of 2020. The primary study cohort was early career female radiation oncologists of the 2016 through 2021 graduating classes. RESULTS: The survey response rate of early career female radiation oncologists was 37% (126 of an estimated 337). Among this cohort, 58% (73 of 126) reported they delayed or are currently delaying/timing pregnancy or adoption to accommodate the annual schedule of the 4 qualifying and certifying examinations required to achieve board certification in radiation oncology. One in every 3 respondents who had attempted to become pregnant reported experiencing infertility (25 of 79, 32%). Women who reported intentionally delaying pregnancy to accommodate the ABR RO-IC examination schedule were significantly more likely to experience infertility (46% vs 18%, P = .008). Seven women (6%) reported at least a 1-year delay in sitting for a RO-IC examination due to an unavoidable scheduling conflict related to childbirth and/or the peripartum period. A majority reported that full board certification had a significant effect on achieving academic promotion or professional partnership (52%), annual compensation (54%), and nonclinical professional commitments (58%) - these rates mirror those of surveyed early career male counterparts (n = 101). CONCLUSIONS: The current structure and scheduling of the ABR RO-IC examinations imposes noteworthy hurdles for many female radiation oncologists when entering the workforce. The recent transition to virtual examination platforms creates an important opportunity to increase flexibility in the structure and scheduling of the board examination process to improve equitable board certification practices.

The Role of Circulating Tumor Cells in Breast Cancer and Implications for Radiation Treatment Decisions.

Tumor biomarkers are used routinely in oncology to assign risk categorization, screen and assist in diagnosis of malignancy, allow for prognostication and prediction of outcomes and treatment response, and allow for monitoring of patients after treatment completion. Although tissue-based biomarkers have a long history of use, the emergence of liquid-based biomarkers, including circulating tumor cells (CTCs), may soon revolutionize the management of patients with cancer. Here, we review the discovery of CTCs and their role as prognostic and predictive biomarkers, with an emphasis on breast cancer. We discuss the platforms for CTC enumeration and focus on studies using the only US Food and Drug Administration-approved platform for CTC enumeration (CellSearch). In addition, we examine the role of CTCs in women with metastatic, inflammatory, and nonmetastatic breast cancer, as well as the clinical evidence for their use as a surrogate for radiation treatment response as well as surveillance after treatment. Finally, we conclude by investigating ongoing clinical studies assessing CTCs as radiation response predictors and discuss unanswered questions.

Radiation Oncology Initial Certification Qualification Examinations: The Resident Experience in 2019.

PURPOSE: To characterize the resident experience preparing for the 2019 American Board of Radiology initial certification (IC) qualifying examinations in radiation oncology. METHODS AND MATERIALS: The Association of Residents in Radiation Oncology distributed a survey to 360 radiation oncology residents from the 2019 and 2020 graduating classes covering topics pertinent to preparation for the medical physics (MP), radiation and cancer biology (RCB), and clinical radiation oncology (CRO) qualifying examinations. RESULTS: The response rate was 58% (n = 210). In the 12 weeks before the MP and RCB examinations, first-time examinees studied a median of 160 hours (interquartile range, 96 to 270). Residents reported a "moderate" or "significant" negative effect on research productivity (3 [2-4]), mental health (3 [2-4]), clinical development (3 [2-4]), and family life (3 [2-4]). Half of surveyed residents (52%, n = 110) used a protected research or elective block to study while an additional 21% (n = 45) used a median of 5 (3-20) vacation days. Residents overall "agreed" (4 [2-4]) that their program's physics course was "important" for their preparation but were "neutral" (3 [2-4]) regarding the value of their program's radiobiology course. Question-based educational resources were most frequently rated as "important" study resources. Respondents "strongly" endorsed the development of a consensus radiation oncology curriculum (5 [4-5]) and "agreed" (4 [3-4]) that consolidation of the MP, RCB, and CRO qualifying examinations into a single written examination would be preferred. CONCLUSIONS: Radiation oncology residents dedicate substantial time preparing for the IC examinations at the expense of training- and health-related outcomes. Residents report a wide range in quality of internal program didactic courses in physics and radiobiology, endorse development of a consensus radiation oncology curriculum, and prefer consolidation of the three qualifying examinations into a single written IC examination. We caution the high pass rates seen on the 2019 examinations do not obviate the need for ongoing improvement in radiation oncology graduate medical education and the board certification process.

The Geography of Employment Outcomes for Radiation Oncology Graduates in 2019.

PURPOSE: The geographic distribution of practicing radiation oncologists is of concern for multiple stakeholders within the field. Employment outcomes of graduating residents can affect that distribution, and they are of major concern to current residents. Data investigating employment outcomes of recent graduates are sparse. We aimed to analyze the employment outcomes of the radiation oncology residency class of 2019. METHODS AND MATERIALS: Using publicly available information, we identified the employment of 179 of 183 graduating residents in the class of 2019. For each, the place of employment, residency program, and medical school were geocoded using Google Maps. We used the rural-urban continuum code (RUCC) published by the United States Department of Agriculture to determine the rurality of each location and compared employment outcomes by RUCC and program size. RESULTS: Two thirds of graduates (66%) took a position in a county within a metropolitan area with a population greater than 1,000,000 people; only 3.4% took a position in a county outside of a metropolitan area. Graduates of smaller programs (≤6 residents) and those in smaller metropolitan areas were more likely to take positions in smaller metropolitan areas or nonmetropolitan areas. The geographic distance between location of employment and residency program did not significantly vary by program size or size of metropolitan area where a residency program was located. CONCLUSIONS: Among the class of 2019, a small proportion took positions in nonmetropolitan areas. Smaller programs and those in smaller metropolitan areas may be more likely to produce graduates that practice in similar settings, but those graduates might not do so locally. We advocate for a centralized, prospective data collection of employment outcomes for graduating residents to refine these analyses and to reduce employment prospect information asymmetry for trainees.

Mentorship Initiatives in Radiation Oncology: A Scoping Review of the Literature.

PURPOSE: Although mentorship is described extensively in academic medical literature, there are few descriptions of mentorship specific to radiation oncology. The goal of the current study was to investigate the state of mentorship in radiation oncology through a scoping review of the literature. METHODS AND MATERIALS: A search protocol was defined according to Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for scoping reviews (PRISMA-ScR) guidelines. Predefined search terms and medical subject headings were used to search PubMed for English language articles published after January 1, 1990, on mentorship in radiation oncology. Additionally, in-press articles from major radiation oncology and medical education journals were searched. Three reviewers determined article eligibility. Included articles were classified based on predefined evaluation criteria. RESULTS: Fourteen publications from 2008 to 2019 met inclusion criteria. The most commonly described form of mentorship was the dyad (64.3%), followed by team (14.3%) and peer (7.1%); 2 articles did not specify mentorship type (14.3%). The most commonly mentored participants were residents (35.7%), followed by medical students (35.7%) and attendings (21.4%); 1 study included participants of all levels (7.1%). Thirteen studies (92.9%) identified an experimental study design, most of which were cross-sectional (42.9%), followed by cohort studies (28.6%) and before/after (21.4%). Median sample size, reported in 12 of 13 experimental studies, was 132 (coefficient of variation, 1.06). Although outcomes varied widely, the majority described successful implementation of mentorship initiatives with high levels of participant satisfaction. CONCLUSIONS: Although few initiatives are currently reported, the present study suggests that these initiatives are successful in promoting career development and increasing professional satisfaction. The interventions overwhelmingly described mentorship dyads; other forms of mentorship are either less common or understudied. Limitations included interventions not being evaluated in a controlled setting, and many were assessed using surveys with low response rates. This review highlights rich opportunities for future scholarship to develop, evaluate, and disseminate radiation oncology mentorship initiatives.

No Longer a Match: Trends in Radiation Oncology National Resident Matching Program (NRMP) Data from 2010-2020 and Comparison Across Specialties.

PURPOSE: To report trends in the number and types of applicants and matched trainees to radiation oncology in comparison to other specialties participating in the National Resident Matching Program (NRMP) between 2010 and 2020. METHODS AND MATERIALS: Data from the NRMP and Electronic Residency Application System (ERAS) were obtained for 18 medical specialties between 2010 and 2020. We assessed the numbers and types of applicants and matched trainees relative to available positions in the NRMP and Supplemental Offer and Acceptance Program (SOAP). RESULTS: In the 2020 NRMP, 122 US MD senior graduates preferentially ranked radiation oncology, a significant decrease from a median of 187 between 2010 to 2019 (interquartile range [IQR], 170-192; P < .001). Across all 18 specialties, radiation oncology experienced the greatest declines in the 2020 NRMP cycle relative to 2010 to 2019, in both the number of ERAS applicants from the United States and Canada (-31%) and the percentage of positions filled by US MD or DO senior graduates (-28%). Of 189 available positions, 81% (n = 154) filled in the NRMP prior to the SOAP, of which 65% (n = 122) were "matched" by US MD senior graduates who preferentially ranked radiation oncology as their top choice of specialty, representing a significant decrease from a median of 92% between 2010 to 2019 (IQR, 88%-94%; P = .002). The percentages of radiation oncology programs and positions unfilled in the NRMP prior to the SOAP were significantly increased in 2020 compared with 2010 to 2019 (programs: 29% vs 8% [IQR, 5%-8%; P < .001]; positions: 19% vs 4% [IQR, 2%-4%; P <.001]). Despite >99% (n = 127 of 128) of US MD or DO senior applicants preferring radiation oncology successfully matching to a radiation oncology position in the 2020 NRMP, 16 of 35 remaining unfilled positions were filled via the SOAP. Radiation oncology was the top user of the SOAP across all specialties participating in the 2020 NRMP, filling 15% of total positions versus a median of 0.9% (IQR, 0.3%-2.3%; P <.001). CONCLUSIONS: The supply of radiation oncology residency positions now far exceeds demand by graduating US medical students. Efforts to nullify a market correction revealed by medical student behavior via continued reliance on the SOAP to fill historical levels of training positions may not be in the best of interest of trainees, individual programs, or the specialty as a whole.

Quantification of global lung inflammation using volumetric 18F-FDG PET/CT parameters in locally advanced non-small-cell lung cancer patients treated with concurrent chemoradiotherapy: a comparison of photon and proton radiation therapy.

INTRODUCTION: Radiation pneumonitis is a major dose-limiting complication in thoracic radiation therapy (RT) and presents clinically in the first few months after RT. We evaluated the feasibility of quantifying pulmonary parenchymal glycolysis (PG) as a surrogate of global lung inflammation and radiation-induced pulmonary toxicity using a novel semiautomatic lung segmentation technique in non-small-cell lung cancer (NSCLC) patients and compared PG in patients treated with photon or proton RT. PATIENTS AND METHODS: We evaluated 18 consecutive locally advanced NSCLC patients who underwent pretreatment and post-treatment F-FDG PET/CT treated with definitive (median: 66.6 Gy; 1.8 Gy fractions) photon or proton RT between 2010 and 2014. Lung volume segmentation was conducted using 3D Slicer by performing simple thresholding. Pulmonary PG was calculated by summing F-FDG uptake in the whole lung. RESULTS: In nine patients treated with photon RT, significant increases in PG in both ipsilateral (mean difference: 1400±510; P=0.02) and contralateral (mean difference: 1200±450; P=0.03) lungs were noted. In nine patients treated with proton therapy, no increase in pulmonary PG was observed in either the ipsilateral (P=0.30) or contralateral lung (P=0.98). CONCLUSION: We observed a significant increase in global lung inflammation bilaterally as measured by quantification of PG. However, no significant change in global lung inflammation was noted after proton therapy. Future larger studies are needed to determine whether this difference correlates with lower risks of radiation pneumonitis in NSCLC patients treated with proton therapy.

#WomenWhoCurie: Leveraging Social Media to Promote Women in Radiation Oncology.

The proportion of female trainees in radiation oncology has generally declined despite increasing numbers of female medical students; as a result, radiation oncology is among the bottom 5 specialties in terms of the percentage of female applicants. Recently, social media has been harnessed as a tool to bring recognition to underrepresented groups within medicine and other fields. Inspired by the wide-reaching social media campaign of #ILookLikeASurgeon to promote female physicians, members of the Society for Women in Radiation Oncology penned a new hashtag and launched the #WomenWhoCurie social media campaign on Marie Curie's birthday November 7th, as part of their strategy to raise public awareness. From November 6, 2018 until November 10, 2018, the #WomenWhoCurie hashtag delivered 1,135,000 impressions, including 408 photos from all over the world including United States, Spain, Canada, France, Australia, Ireland, the United Kingdom, Mexico, Japan, the Netherlands, India, Ecuador, Panama, Brazil, and Nigeria. Alongside continued gender disparity research, social media should continue to be used as a tool to engage the community and spur conversations to formulate solutions for gender inequity.

FDG-PET study in pathological gamblers. 1. Lithium increases orbitofrontal, dorsolateral and cingulate metabolism.

BACKGROUND: Pathological gambling affects 1-3% of the adult population, and has high comorbidity. Although mood stabilizers and serotonin reuptake inhibitors have shown some efficacy in the treatment of this condition, there is little known about how these pharmacological interventions work. METHODS: Twenty-one patients with pathological gambling, who met lifetime comorbid bipolar spectrum diagnoses, received baseline PET scans. Sixteen of these patients were entered into a randomized double-blind placebo-controlled parallel group design trial of lithium, and received follow-up PET scans at 10 weeks. A comparison group of 32 age- and sex-matched controls was also available. Anatomical MRIs were obtained as a structural template. RESULTS: In patients with pathological gambling, relative glucose metabolic rates (rGMR) in the orbitofrontal cortex and medial frontal cortex were significantly increased at baseline compared to normal controls. Lithium increased rGMR further in the orbitofrontal cortex, heightening normal/patient differences, but it also increased the rGMR of the posterior cingulate and the dorsolateral frontal cortex normalizing the metabolic rate in these regions. CONCLUSION: Cortical areas implicated in impulse control disorders show increased rGMR in pathological gambling at baseline. Lithium treatment, while alleviating the symptoms, further increases rGMR in these areas.

21-Gene Recurrence Score Assay Predicts Benefit of Post-Mastectomy Radiotherapy in T1-2 N1 Breast Cancer.

Purpose: Post-mastectomy radiotherapy (PMRT) yields improvements in both locoregional control and overall survival (OS) for women with T1-2 N1 breast cancer. The value of PMRT in this population has been questioned given advances in systemic therapy. The 21-gene recurrence score (RS) assay was evaluated as a predictor of OS among women with T1-2 N1 breast cancer who received or did not receive PMRT.Experimental Design: An observational cohort study was performed on women with T1-2 N1 estrogen receptor-positive breast cancer from the National Cancer Database (NCDB) and, as a validation cohort, from the surveillance, epidemiology, and end results (SEER) registry who underwent mastectomy and were evaluated for RS. Multivariable parametric accelerated failure time models were used to estimate associations of RS and PMRT with OS using propensity score-adjusted matched cohorts.Results: In both the NCDB (N = 7,332) and SEER (N = 3,087) cohorts, there was a significant interaction of RS and PMRT with OS (P = 0.009 and P = 0.03, respectively). PMRT was associated with longer OS in women with a low RS [NCDB: time ratio (TR) = 1.70; 95% CI (confidence interval), 1.30-2.22; P < 0.001; SEER: TR = 1.85; 95% CI, 1.33-2.57; P < 0.001], but not in women with an intermediate RS (NCDB: TR = 0.89; 95% CI, 0.69-1.14; P = 0.35; SEER: TR = 0.84; 95% CI, 0.62-1.14; P = 0.26), or a high RS (NCDB: TR = 1.10; 95% CI, 0.91-1.34; P = 0.33; SEER: TR = 0.79; 95% CI, 0.50-1.23; P = 0.28).Conclusions: Longer survival associated with PMRT was limited to women with a low RS. PMRT may confer the greatest OS benefit for patients at the lowest risk of distant recurrence. These results caution against omission of PMRT among women with low RS. Clin Cancer Res; 24(16); 3878-87. ©2018 AACR.

Association of Circulating Tumor Cell Status With Benefit of Radiotherapy and Survival in Early-Stage Breast Cancer.

Importance: Circulating tumor cells (CTCs) represent the liquid component of solid tumors and are a surrogate marker for residual cancer burden. Although CTC status is prognostic of recurrence and death in breast cancer, its role in guiding clinical management remains unknown. Objective: To determine whether CTC status is predictive of radiotherapeutic benefit in early-stage breast cancer. Design, Setting, and Participants: The cohort studies in the present analysis included patients with stages pT1 to pT2 and pN0 to pN1 breast cancer and known CTC status from the National Cancer Database (NCDB) and the multicenter phase 3 SUCCESS clinical trial. Multivariable parametric accelerated failure time models were used to evaluate the association of CTC status and radiotherapy (RT) with survival outcomes. Data were collected from January 1, 2004, through December 31, 2014, from the NCDB cohort. The SUCCESS trial collected data from September 1, 2005, through September 30, 2013. The analyses were completed from November 1, 2016, through December 17, 2017. Exposure: Adjuvant RT. Main Outcomes and Measures: Overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). Results: A total of 1697 patients from the NCDB (16 men [0.9%] and 1681 women [99.1%]; median age, 63 years; interquartile range, 53-71 years) and 1516 patients from the SUCCESS clinical trial (median age, 52 years; interquartile range, 45-60 years) were identified. Circulating tumor cells were detected in 399 patients (23.5%) in the NCDB cohort and 294 (19.4%) in the SUCCESS cohort. The association of RT with survival was dependent on CTC status within the NCDB cohort (4-year OS, 94.9% for CTC-positive RT vs 88.0% for CTC-positive non-RT vs 93.9% for CTC-negative RT vs 93.4% for CTC-negative non-RT groups; P < .001) and 5-year DFS within the SUCCESS cohort (88.0% for CTC-positive RT vs 75.2% for CTC-positive non-RT vs 92.3% for CTC-negative RT vs 88.3% for CTC-negative non-RT; P = .04). In the NCDB cohort, RT was associated with longer OS in patients with CTCs (time ratio [TR], 2.04; 95% CI, 1.55-2.67; P < .001), but not in patients without CTCs (TR, 0.80; 95% CI, 0.52-1.25; P = .33). In the SUCCESS cohort, CTC-positive patients treated with RT exhibited longer LRFS (TR, 2.73; 95% CI, 1.62-4.80; P < .001), DFS (TR, 3.03; 95% CI, 2.22-4.13; P < .001), and OS (TR, 1.83; 95% CI, 1.23-2.72; P = .003). Among patients from both cohorts who underwent breast-conserving surgery, RT was associated with longer OS in patients with CTCs (TR, 4.37; 95% CI, 2.71-7.05; P < .001) but not in patients without CTCs (TR, 0.87; 95% CI, 0.47-1.62; P = .77). Radiotherapy was not associated with OS after mastectomy in CTC-positive or CTC-negative patients. Conclusions and Relevance: Treatment with RT was associated with longer LRFS, DFS, and OS in patients with early-stage breast cancer and detectable CTCs. These results are hypothesis generating; a prospective trial evaluating CTC-based management for RT after breast-conserving surgery in women with early-stage breast cancer is warranted.

Photon irradiation using a water bath technique for treatment of confluent carcinoma in situ of the hand, digits, and nail bed: a case report.

BACKGROUND: Confluent squamous cell carcinoma in situ, or Bowen's disease, involving the hand, digit, and nail bed is rare and represents a significant therapeutic challenge. Surgical excision is recommended as first-line treatment but in cases of extensive disease can lead to unacceptable functional morbidity or cosmetic outcomes. Radiation therapy has been shown to be equally efficacious to surgery in the treatment of carcinoma in situ but its use has historically been limited due to concerns regarding toxicity. In this case report we present a novel therapeutic technique that may enable radiotherapy to be employed as a definitive treatment option in these challenging cases. CASE PRESENTATION: A 75-year-old white man with a previous history of carcinoma in situ of his right hand previously treated with 5-fluorouracil presented with recurrent biopsy-proven confluent squamous cell carcinoma in situ of multiple surfaces of his right hand and digits with involvement of nail beds. To avoid extensive resection and possible amputation he was offered definitive external beam radiation therapy utilizing a water bath as a tissue-equivalent bolus material. This protocol enabled improved dose homogeneity to the target volume while minimizing acute toxicity. He experienced complete clinical resolution of the disease with only minimal acute edema and hyperpigmentation. Twenty months following treatment completion he remains disease-free with normal function and excellent cosmesis. CONCLUSIONS: Therapeutic radiation utilizing water as a tissue-equivalent bolus in this complicated case enabled definitive treatment of disease without compromising functional or cosmetic outcomes. Radiotherapy may therefore be an alternative and under-utilized approach to surgical excision in difficult-to-treat cases of carcinoma in situ.