De-escalation of surgery for occult breast cancer with axillary metastasis.

Occult breast cancer presenting as axillary metastasis is rare and remains a diagnostic and therapeutic challenge. Evidence to guide clinical management is limited, and locoregional treatment remains nonstandardized and highly varied nationally. Historically, occult breast cancer was managed with modified radical mastectomy ± radiotherapy; however, equivalent local control and survival are observed with breast preservation and adjuvant whole breast radiotherapy. Axillary lymph node dissection remains the standard surgical approach to the axilla for occult breast cancer patients. De-escalating axillary surgery in a subset of occult breast cancer patients treated with neoadjuvant chemotherapy with good response to treatment may be appropriate, similar to the management of clinically node-positive patients in a known primary setting. As in other clinically node-positive breast cancer cases, thoughtful integration and tailoring of axillary surgery and regional nodal radiotherapy (for the varying extent of nodal burden) is an area of continued controversy and active investigation.

Established and new horizons in radiotherapy for breast cancer.

Modern advances in diagnostics, surgery, systemic therapies, and radiotherapy (RT) have drastically revolutionized treatment strategies for breast cancer. This review outlines current and evolving treatment paradigms for RT in the breast-conserving therapy and post-mastectomy setting. In early-stage breast cancer, there is active investigation in expanding eligibility for omission of RT in women with more biologically favorable tumors and growing options to effectively irradiate less breast tissue and shorten RT treatment courses. For locally advanced breast cancer, we discuss several patient cohorts in which the necessity of post-mastectomy RT (PMRT) is commonly debated. Ongoing efforts to better refine indications for PMRT and evaluate the feasibility of hypofractionated PMRT are being studied. Metastasis-directed therapy with ablative RT is an emerging topic of interest in many cancers, including its role and impact in oligometastatic breast cancer. In this review, we will discuss the rationale for current standard of care and address in greater detail the aforementioned concepts.

Developing a Mobile Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events Administration System to Capture Postradiation Toxicity in Oncology: Usability and Feasibility Study.

BACKGROUND: Accurate self-reported symptomatic toxicity documentation via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is essential throughout cancer treatment to ensure safety and understand therapeutic efficacy. However, the capture of accurate toxicities from patients undergoing radiation therapy is challenging because this is generally provided only at the time of scheduled visits. OBJECTIVE: This study seeks to establish the usability and feasibility of a mobile PRO-CTCAE Administration System (mPROS) to capture toxicities related to radiation therapy. METHODS: English-speaking adult patients who were undergoing radiation therapy for cancer were enrolled and given a brief demonstration of the Say All Your Symptoms (SAYS) and Symptom Tracking Entry Program (STEP) interfaces of the mPROS app, followed by a patient-use phase where patient actions were observed as they navigated mPROS to enter toxicities. Patient feedback was captured via a semistructured interview and brief questionnaire. RESULTS: We enrolled 25 patients (age: mean 60.7 years; females: n=13, 52%; White patients: n=13; 52%; non-Hispanic patients: n=19, 76%; college graduates: n=17, 68%). Patients almost equally preferred the SAYS (n=14, 56%) or STEP (n=11, 44%) interfaces, with 21 patients (84%) agreeing that they would use mPROS to report their symptoms to their health care team and 19 patients (76%) agreeing that they would recommend mPROS to others. CONCLUSIONS: The mPROS app is usable and feasible for facilitating the patient reporting of radiation therapy-related symptomatic toxicities. A revised version of mPROS that incorporates patient input and includes electronic health record integration is being developed and validated as part of a multicenter trial.

Germline biomarkers predict toxicity to anti-PD1/PDL1 checkpoint therapy.

BACKGROUND: There is great interest in finding ways to identify patients who will develop toxicity to cancer therapies. This has become especially pressing in the era of immune therapy, where toxicity can be long-lasting and life-altering, and primarily comes in the form of immune-related adverse effects (irAEs). Treatment with the first drugs in this class, anti-programmed death 1 (anti-PD1)/programmed death-ligand 1 (PDL1) checkpoint therapies, results in grade 2 or higher irAEs in up to 25%-30% of patients, which occur most commonly within the first 6 months of treatment and can include arthralgias, rash, pruritus, pneumonitis, diarrhea and/or colitis, hepatitis, and endocrinopathies. We tested the hypothesis that germline microRNA pathway functional variants, known to predict altered systemic stress responses to cancer therapies, would predict irAEs in patients across cancer types. METHODS: MicroRNA pathway variants were evaluated for an association with grade 2 or higher toxicity using four classifiers on 62 patients with melanoma, and then the panel's performance was validated on 99 patients with other cancer types. Trained classifiers included classification trees, LASSO-regularized logistic regression, boosted trees, and random forests. Final performance measures were reported on the training set using leave-one-out cross validation and validated on held-out samples. The predicted probability of toxicity was evaluated for its association, if any, with response categories to anti-PD1/PDL1 therapy in the melanoma cohort. RESULTS: A biomarker panel was identified that predicts toxicity with 80% accuracy (F1=0.76, area under the curve (AUC)=0.82) in the melanoma training cohort and 77.6% accuracy (F1=0.621, AUC=0.778) in the pan-cancer validation cohort. In the melanoma cohort, the predictive probability of toxicity was not associated with response categories to anti-PD1/PDL1 therapy (p=0.70). In the same cohort, the most significant biomarker of toxicity in RAC1, predicting a greater than ninefold increased risk of toxicity (p<0.001), was also not associated with response to anti-PD1/PDL1 therapy (p=0.151). CONCLUSIONS: A germline microRNA-based biomarker signature predicts grade 2 and higher irAEs to anti-PD1/PDL1 therapy, regardless of tumor type, in a pan-cancer manner. These findings represent an important step toward personalizing checkpoint therapy, the use of which is growing rapidly.

Development and Pilot Implementation of a Remote Monitoring System for Acute Toxicity Using Electronic Patient-Reported Outcomes for Patients Undergoing Radiation Therapy for Breast Cancer.

PURPOSE: We aimed to develop and study the implementation of a remote system for toxicity assessment and management of acute side effects of breast radiation using electronic patient-reported outcomes (ePROs). METHODS AND MATERIALS: A response-adapted Patient-Reported Outcomes Common Terminology Criteria for Adverse Events-based assessment for breast radiation toxicity was administered weekly during and for 8 weeks after radiation from June 2019 to July 2020. The care team received alerts when "severe" symptoms were reported by patients, who were then contacted. Treatment, clinic, and sociodemographic characteristics were abstracted from patient records. A subsample of patients and care team members was qualitatively interviewed at follow-up. RESULTS: Overall, 5787 assessments were sent to 678 patients, of whom 489 (72%) completed 2607 assessments (45%). Moderate or greater toxicity was reported by 419 responders (86%; 95% CI, 82%-89%). Clinician alerts for severe toxicity were generated for 264 assessments among 139 unique patients, of which 83% occurred posttreatment. The proportion of surveys that prompted an alert was significantly higher after treatment (219 [13%]) than during treatment (45 [5%]) (P < .001). Survey completion rates in the posttreatment period were higher among patients undergoing partial breast irradiation than postmastectomy radiation (incidence rate ratio, 0.70; 95% CI, 0.60-0.81) (P < .001) despite these patients experiencing less severe toxicity. Interviews (15) found that patients had a positive experience with ePROs, although many thought the primary purpose was for research rather than symptom management. CONCLUSIONS: With the majority of toxicity occurring after breast radiation has ended, remote symptom monitoring with ePROs appears to fill a gap in clinical practice, particularly for patients undergoing shorter courses of radiation. It is important to properly onboard patients and explain that the purpose of ePROs is to aid clinical care. Further research is needed to determine whether the costs associated with ePROs can be offset by reducing routine clinic visits and whether this approach is acceptable and appropriate.

A Practical Guide for Navigating the Design, Build, and Clinical Integration of Electronic Patient-Reported Outcomes in the Radiation Oncology Department.

The development and integration of electronic patient-reported outcomes (ePROs) into the radiation oncology clinic workflow provide novel opportunities, accompanied by unique design considerations and implementation challenges. The processes required for implementation of ePROs are entirely distinct from standard paper-based surveys, with the majority of time devoted to conception and design before initiating questionnaire build, detailed workflow process mapping including development of new workflows, comprehensive communication of the vision between providers and the information technology team, and quality assurance. Based on our experience with implementation of ePROs in our radiation oncology department, we developed a stepwise framework for approaching ePRO conceptual design, build, workflow integration, and the electronic health record interface. Here, we provide a guide for the numerous considerations, decision points, and solutions associated with the implementation of ePROs in the radiation oncology department setting. Although various ePRO tools and electronic health record capabilities impose different requirements, opportunities, and limitations, the conceptual processes and many of the electronic build considerations are broadly applicable.

The Declining Residency Applicant Pool: A Multi-Institutional Medical Student Survey to Identify Precipitating Factors.

PURPOSE: The purpose of our study was to better understand and identify concerns that may be responsible for the declining radiation oncology (RO) residency applicant pool. METHODS AND MATERIALS: All RO residency programs affiliated with a US medical school were asked to participate in the study survey. An optional and anonymous survey consisting of 12 questions was emailed to all graduating medical students in 2020 at the 12 allopathic medical schools that agreed to survey administration. Survey responses were collected from March to May 2020. RESULTS: The study consisted of 265 survey responses out of 1766 distributed to eligible medical students, resulting in a response rate of 15.0%. The majority of students reported no exposure to RO (60.8%) and never considered it as a career option (63.8%). Neutral perceptions of the field were more common (54.3%) than positive (39.6%) and negative (6.0%). The top factors attracting medical students to RO were perceptions of high salary, favorable lifestyle and workload, and technological focus. The top negative factors were the field's interplay with physics, competitive United States Medical Licensing Examination board scores for matched applicants, and the focus placed on research during medical school. In the subgroup of students who were interested in RO but ultimately applied to another specialty, the job market was the most salient concern. CONCLUSIONS: Finding a place for RO in medical school curricula remains a challenge, with most surveyed students reporting no exposure during their education. Concern over the job market was the primary deterrent for medical students interested in pursuing RO. For disinterested students who had not considered RO as a career option, the required physics knowledge was the main deterrent.

Influence of the breast prosthesis volume in dose distribution in radiotherapy planning

Introduction: The challenge of modern radiotherapy (RT) in breast cancer is to maintain its satisfactory oncological results, adapting to oncoplastic surgery and avoiding possible cosmetic damage. Considering that the breast prosthesis is not a target volume in RT planning, this study sought to analyze the effect of this volume on the coverage of the clinical target volume (CTV) of the breast. Methods: We performed a retrospective analysis of plans in 48 patients who submitted to RT in the first half of 2014. Two volumes were measured, such as breast CTV (breast tissue with the prosthesis) and real CTV (breast tissue excluding the prosthesis). The D95% values (dose that covers 95% of the volume) for each of them were verified and related to the volume of each one as well as the volume of breast prosthesis. Results: The analysis of the CTVs showed a significant difference between the mean volumes for the real CTV and breast CTV. While performing the CTV coverage, including the prosthesis, there is a perception that the dose covered 95% of the volume. Nevertheless, the analysis of the same plan after prosthesis volume exclusion revealed a difficulty in covering 95% of the breast tissue volume, indicating the interference of the prosthesis in therapy planning. Considering the dosimetric aspects, there were patients with real CTV values below the ideal dose of 47.5 Gy, after exclusion of implant volume. Conclusions: Our data reflected the volume of the prosthesis as an important variable that should be considered when planning adjuvant RT.

Nationwide Survey of Patients' Perspectives Regarding Their Radiation and Multidisciplinary Cancer Treatment Experiences.

PURPOSE: The perspectives of patients with cancer about their treatment can inform interventions to improve the approaches of treating oncologists and experiences of future patients. We sought to identify areas where current toxicity management, informed consent processes, and physician-patient communication merit improvement. METHODS: In a Web-based survey administered from March to May 2018 using quota-based sampling to draw a nationwide sample of US patients with cancer treated with radiotherapy within the past 5 years, we evaluated patient perceptions of adequacy of information about adverse effects, severity of actual adverse effects experienced, and experiences divergent from expectations. RESULTS: Among 403 respondents, 18% felt inadequately informed about what adverse effects to expect from radiotherapy, and 37% experienced radiation adverse effects that they wished they had known more about. Similar proportions of patients treated with chemotherapy (36%) and surgery (34%) experienced toxicities related to those treatments that they wished they had known more about. Patients who noted their adverse effects to be minimal versus severe were significantly more likely to feel informed about radiotherapy adverse effects (odds ratio, 13.05; 95% CI, 5.6 to 30.38; P < .001). Across all evaluated measures, a majority of patients indicated that they did not experience the potentially anticipated radiotherapy adverse effect or that it was the same as or better than expected. CONCLUSION: This study suggests that experiences with radiation adverse effects generally are congruent with expectations. Nevertheless, improvement of pretreatment counseling across all cancer therapy modalities seems warranted to improve informed decision making and treatment experiences.

Serum erythropoietin levels, breast cancer and breast cancer-initiating cells.

BACKGROUND: Cancer is frequently associated with tumor-related anemia, and many chemotherapeutic agents impair hematopoiesis, leading to impaired quality of life for affected patients. The use of erythropoiesis-stimulating agents has come under scrutiny after prospective clinical trials using recombinant erythropoietin to correct anemia reported increased incidence of thromboembolic events and cancer-related deaths. Furthermore, previous preclinical reports indicated expansion of the pool of breast cancer-initiating cells when erythropoietin was combined with ionizing radiation. METHODS: Using four established breast cancer cell lines, we test the effects of recombinant human erythropoietin and the number of breast cancer-initiating cells in vitro and in vivo and study if recombinant human erythropoietin promotes the phenotype conversion of non-tumorigenic breast cancer cells into breast cancer-initiating cells. In a prospective study, we evaluate whether elevated endogenous serum erythropoietin levels correlate with increased numbers of tumor-initiating cells in a cohort of breast cancer patients who were scheduled to undergo radiation treatment. RESULTS: Our results indicate that recombinant erythropoietin increased the number of tumor-initiating cells in established breast cancer lines in vitro. Irradiation of breast cancer xenografts caused a phenotype conversion of non-stem breast cancer cells into induced breast cancer-initiating cells. This effect coincided with re-expression of the pluripotency factors c-Myc, Sox2, and Oct4 and was enhanced by recombinant erythropoietin. Hemoglobin levels were inversely correlated with serum erythropoietin levels, and the latter were correlated with disease stage. However, tumor sections revealed a negative correlation between serum erythropoietin levels and the number of ALDH1A3-positive cells, a marker for breast cancer-initiating cells. CONCLUSIONS: We conclude that physiologically slow-rising serum erythropoietin levels in response to tumor-related or chemotherapy-induced anemia, as opposed to large doses of recombinant erythropoietin, do not increase the pool of breast cancer-initiating cells.

Impact of Open Access to Physician Notes on Radiation Oncology Patients: Results from an Exploratory Survey.

PURPOSE: There is an increasing effort to allow patients open access to their physician notes through electronic medical record portals. However, limited data exist on the impact of such access on oncology patients, and concerns remain regarding potential harms. Therefore, we determined the baseline perceptions and impact of open access to oncology notes on radiation oncology patients. METHODS AND MATERIALS: Patients receiving radiation therapy were provided instructional materials on accessing oncology notes at the time of their initial evaluation. Patients were prospectively surveyed to evaluate baseline interest and expectations before access and to determine the actual usage and impact at the end of their radiation treatment course. RESULTS: A total of 220 patients were surveyed; 136 (62%) completed the baseline survey, of which 88 (40%) completed the final survey. The majority of participants were age >60 years (n = 83; 61%), and 70 were male (51%). Before accessing the notes, the majority of patients agreed that open access to oncology notes would improve understanding of diagnosis (99%), understanding of treatment side effects (98%), reassurance about treatment goals (96%), and communication with family (99%). All patients who accessed the notes found them to be useful. After accessing the notes, approximately 96%, 94%, and 96% of patients reported an improved understanding of their diagnosis, an improved understanding of treatment side effects, and feeling more reassured about their treatment, respectively. Approximately 11%, 6%, and 4% of patients noted increased worry, increased confusion, and finding information they now regret reading, respectively. Patient age, sex, and specific cancer diagnoses were not predictive of experiencing negative effects from accessing the notes. CONCLUSIONS: Radiation oncology patients have a strong interest in open access to their physician notes, and the majority of patients expect and actually report meaningful benefits. These data support strategies to allow more patients with cancer access to their physicians' notes.

Content Validity of Anatomic Site-Specific Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item Sets for Assessment of Acute Symptomatic Toxicities in Radiation Oncology.

PURPOSE: To improve assessment of symptomatic toxicity in cancer clinical trials and complement clinician-based toxicity reporting, the US National Cancer Institute developed a measurement system called the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The objective of this study was to examine the content validity of PRO-CTCAE in patients undergoing radiation therapy and to establish anatomic site-specific item sets for implementation in cancer research. METHODS AND MATERIALS: Patients receiving radiation to the brain, head and neck, breast, thorax, abdomen, or pelvis were recruited during the final week of radiation. Participants described side effects qualitatively and completed anatomic site-specific checklists indicating the presence or absence of symptomatic toxicities drawn from the PRO-CTCAE library. Items endorsed by ≥20% of participants were selected for inclusion. Symptomatic toxicities described qualitatively were content analyzed and summarized. Symptomatic toxicities not reflected in the PRO-CTCAE item library were tabulated. RESULTS: We conducted 389 interviews of patients receiving radiation to the brain (n = 46), head and neck (n = 69), breast (n = 134), thorax (n = 30), abdomen (n = 27), female pelvis (n = 36), or male pelvis (n = 47). Median age was 62 years; 62% were female. The 53 solicited PRO-CTCAE symptoms reflected all reported radiation-induced toxicities with the exception of phlegm/mucus production and mouth/throat pain with swallowing in patients receiving head and neck radiation, eye dryness/irritation in patients undergoing brain radiation, and obstructive urinary symptoms in men receiving pelvic radiation. The PRO-CTCAE items "skin burns" and "pain" require greater specificity to adequately reflect toxicities experienced during radiation. CONCLUSIONS: PRO-CTCAE demonstrates strong content validity as a measure of symptomatic toxicities in patients receiving radiation. These results provide empirical support for the definition of site-specific PRO-CTCAE item sets to assess the symptomatic toxicities of radiation therapy. The site-specific PRO-CTCAE item sets developed herein are currently being deployed in our department via an electronic platform to capture treatment-related toxicity.

The patient's perspective on breast radiotherapy: Initial fears and expectations versus reality.

BACKGROUND: Although the efficacy and toxicity of breast radiotherapy (RT) has been studied extensively, to the authors' knowledge little is known regarding the patient's perspective on the modern breast RT experience. To better inform future patients and providers, the authors explored patient perceptions of their RT experience. METHODS: Consecutive patients who were free of disease recurrence and who had been treated between 2012 and 2016 were surveyed regarding their original fears, how short-term and long-term toxicities compared with initial expectations, and how pretreatment beliefs concerning RT compared with the actual experience. RESULTS: A total of 502 patients were surveyed, with a response rate of 65% (327 patients). The median patient age and posttreatment follow-up was 59 years and 31 months, respectively. Approximately 83% of patients (269 patients) underwent breast conservation therapy. Although approximately 68% of patients (221 patients) endorsed that they initially had little to no knowledge regarding RT, approximately 47% (152 patients) reported that they had heard frightening stories. Approximately 2% of patients (6 patients) agreed that the negative stories they previously heard about RT were actually true. Approximately 92% of patients treated with breast conservation (247 patients) and 81% of patients who underwent mastectomy (47 patients) agreed with the statement "If future patients knew the real truth about RT, they would be less scared about treatment." Approximately 83% (272 patients) and 84% (274 patients), respectively, of all patients reported the overall severity of short-term and long-term side effects to be better than or as expected. CONCLUSIONS: Breast RT is associated with misconceptions and fears. Patients' experiences with modern breast RT appear to be superior to expectations, and the majority of patients in the current study agreed that their initial negative impressions were unfounded. Cancer 2018;124:1673-81. © 2018 American Cancer Society.

Impact of the Primary Information Source Used for Decision Making on Treatment Perceptions and Regret in Prostate Cancer.

OBJECTIVE: To assess the impact of the primary source of information used by prostate cancer patients to select a radiation treatment on their overall treatment experience and on treatment regret. METHODS: Patients with low to favorable intermediate-risk prostate cancer treated with stereotactic body radiation therapy, intensity-modulated radiation therapy, or high-dose rate brachytherapy were surveyed. The questionnaire explored the decision-making experience, treatment experience, and treatment regret. RESULTS: In total, 322 consecutive patients were surveyed with an 86% (n=276) response rate. In total, 48% (n=132) selected their radiation oncologist as the primary information source, 23% (n=62) selected their urologist, 16% (n=44) selected the Internet, 6% (n=17) selected other patients, and 8% (n=21) selected other. In total, 39% of patients who selected the Internet as their primary information source reported their actual treatment experience to be worse than expected versus 13% of respondents who selected their urologist, 12% who selected other patients, and 2% who selected their radiation oncologist (P<0.01). Similarly, 43% who selected the Internet as their primary information source endorsed treatment regret versus 10% who selected their urologist, and 7% who selected their radiation oncologist (P<0.01). On multivariate regression, only patients who selected the Internet as their primary information source were more likely to endorse treatment regret (odds ratio, 46.47; P<0.001) and a worse treatment perception (odds ratio, 83.33; P<0.001). CONCLUSIONS: Patients who used the Internet as their primary information source were significantly more likely to endorse treatment regret and a worse than expected overall treatment experience. These data highlight the potential dangers of Internet-based resources and the importance for physicians to proactively counsel patients.

Assessing the Effect of Lifetime Contralateral Breast Cancer Risk on the Selection of Contralateral Prophylactic Mastectomy for Unilateral Breast Cancer.

INTRODUCTION: Contralateral prophylactic mastectomy (CPM) rates are rising, with fear implicated as a contributing factor. This study used a contralateral breast cancer (CBC) risk stratification tool to assess whether the selection of CPM is reflective of future CBC risk. PATIENTS AND METHODS: This retrospective study evaluated 404 women with unilateral breast cancer treated with breast conservation, unilateral mastectomy, or bilateral mastectomy within a single multidisciplinary clinic. Women were evaluated by the Manchester risk tool to calculate lifetime CBC risk. Logistic regression analysis was used to evaluate whether CBC risk was associated with CPM, and the clinical rationale for prophylactic mastectomy justification was recorded. RESULTS: Sixty-two percent underwent breast conservation, 18% unilateral mastectomy, and 20% bilateral mastectomy. In the CPM cohort, 36% had > 20% calculated lifetime CBC risk. In the invasive cohort, younger age (odds ratio 2.65, P < .0001) and genetic mutation positivity (odds ratio 35.39, P = .019) independently predicted CPM. Other contributing factors included benign contralateral breast findings (29%) and recommendations against breast conservation due to disease burden (28%). Six percent selected CPM as a result of an unsubstantiated fear regarding breast cancer. CONCLUSION: The majority of women (63%) who selected CPM had < 20% CBC risk. In these lower-risk women selecting CPM, factors increasing reasonable fear dominated surgical choice (81% of this subset).

Radioresistance of the breast tumor is highly correlated to its level of cancer stem cell and its clinical implication for breast irradiation.

BACKGROUND AND PURPOSE: Growing evidence suggested the coexistence of cancer stem cells (CSCs) within solid tumors. We aimed to study radiosensitivity parameters for the CSCs and differentiated tumor cells (TCs) and the correlation of the fractions of CSCs to the overall tumor radioresistance. MATERIAL AND METHODS: Surviving fractions of breast cancer cell lines were analyzed using a dual-compartment Linear-quadratic model with independent fitting parameters: radiosensitive αTC, ßTC, αCSC, ßCSC, and fraction of CSCs f. The overall tumor radio-resistance, the biological effective doses and tumor control probability were estimated as a function of CSC fraction for different fractionation regimens. The pooled clinical outcome data were fitted to the single- and dual-compartment linear-quadric models. RESULTS: CSCs were more radioresistant characterized by smaller α compared to TCs: αTC=0.1±0.2, αCSC=0.04±0.07 for MCF-7 (f=0.1%), αTC=0.08±0.25, αCSC=0.04±0.18 for SUM159PT (f=2.46%). Higher f values were correlated with increasing radioresistance in cell lines. Analysis of clinical outcome data is in accordance of a dual-compartment CSC model prediction. Higher percentage of BCSCs resulted in more overall tumor radioresistance and less biological effectiveness. CONCLUSIONS: Percentage of CSCs strongly correlated to overall tumor radioresistance. This observation suggested potential individualized radiotherapy to account for heterogeneous population of CSCs and their distinct radiosensitivity for breast cancer.

Predictors associated with MRI surveillance screening in women with a personal history of unilateral breast cancer but without a genetic predisposition for future contralateral breast cancer.

PURPOSE: For women with a personal history of breast cancer (PHBC), no validated mechanisms exist to calculate future contralateral breast cancer (CBC) risk. The Manchester risk stratification guidelines were developed to evaluate CBC risk in women with a PHBC, primarily for surgical decision making. This tool may be informative for the use of MRI screening, as CBC risk is an assumed consideration for high-risk surveillance. METHODS: Three hundred twenty-two women with a PHBC were treated with unilateral surgery within our multidisciplinary breast clinic. We calculated lifetime CBC risk using the Manchester tool, which incorporates age at diagnosis, family history, genetic mutation status, estrogen receptor positivity, and endocrine therapy use. Univariate and multivariate logistic regression analyses (UVA/MVA) were performed, evaluating whether CBC risk predicted MRI surveillance. RESULTS: For women with invasive disease undergoing MRI surveillance, 66% had low, 23% above-average, and 11% moderate/high risk for CBC. On MVA, previous mammography-occult breast cancer [odds ratio (OR) 18.95, p < 0.0001], endocrine therapy use (OR 3.89, p = 0.009), dense breast tissue (OR 3.69, p = 0.0007), mastectomy versus lumpectomy (OR 3.12, p = 0.0041), and CBC risk (OR 3.17 for every 10% increase, p = 0.0002) were associated with MRI surveillance. No pathologic factors increasing ipsilateral breast cancer recurrence were significant on MVA. CONCLUSIONS: Although CBC risk predicted MRI surveillance, 89% with invasive disease undergoing MRI had <20% calculated CBC risk. Concerns related to future breast cancer detectability (dense breasts and/or previous mammography-occult disease) predominate decision making. Pathologic factors important for determining ipsilateral recurrence risk, aside from age, were not associated with MRI surveillance.

Considerations for Quality Improvement in Radiation Oncology Therapy for Patients with Uncomplicated Painful Bone Metastases.

Background: There is an increasing need for evidence-based efficiency in providing a growing amount of cancer care. One example of a quality gap is the use of multiple-fraction palliative radiation for patients with advanced cancer who have uncomplicated bone metastases; evidence suggests similar pain outcomes for treatment regimens with a lower burden of treatments. Methods: During the first phase of quality improvement work, we used RAND/UCLA appropriateness methodology to understand how radiation oncologists at one academic medical center rate the appropriateness of different treatment regimens for painful uncomplicated bone metastases. We compared radiation oncologist appropriateness ratings for radiation treatments with radiation therapy provided by these oncologists to patients with painful bone metastases between July 2012 and June 2013. Results: Appropriateness ratings showed that single-fraction (8 Gy) treatment (a low burden treatment) was consistently considered an appropriate option to treat a variety of uncomplicated bone metastases. The use of >10 fractions was consistently rated as inappropriate regardless of other factors. Eighty-one patients receiving radiation therapy for painful bone metastases during the study period had an available medical record for chart abstraction. Almost one-third of metastases were considered complicated because of a concern of spinal cord compression, a history of prior irradiation, or an associated pathological fracture. Among uncomplicated bone metastases, 25% were treated with stereotactic body radiation treatment (SBRT). Among the 54 uncomplicated bone metastases treated with conformal radiation, only one was treated with single-fraction treatment and 32% were treated with greater than 10 fractions. Conclusions: Treatment at the study site demonstrates room for improvement in providing low-burden radiation oncology treatments for patients with painful bone metastases. Choosing a radiation treatment schedule for patients with advanced cancer and painful bone metastases requires consideration of many medical and patient-centered factors. Our experience suggests that it will take more than the existence of guidelines to change practice in this area.

Exploring Value From the Patient's Perspective Between Modern Radiation Therapy Modalities for Localized Prostate Cancer.

PURPOSE: Patients' perspectives on their treatment experiences have not been compared between modern radiation modalities for localized prostate cancer. We evaluated treatment regret and patients' perceptions of their treatment experiences to better inform our understanding of a treatment's value. METHODS AND MATERIALS: Patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT), intensity modulated radiation therapy (IMRT), or high-dose-rate (HDR) brachytherapy between 2008 and 2014 with at least 1 year of follow-up were surveyed. The questionnaire explored the decision-making experience, expectations of toxicities versus the reality, and treatment regret by means of a validated tool. RESULTS: Three hundred twenty-nine consecutive patients were surveyed, with an 86% response rate (IMRT, n=74; SBRT, n=108; HDR, n=94). The median patient age and posttreatment follow-up time were 68 years and 47 months, respectively. Eighty-two percent of patients had T1c disease with either Gleason 6 (42%) or Gleason 7 (58%) pathologic features and a median initial prostate-specific antigen of 5.8 ng/mL. Thirteen percent expressed regret with their treatment. Among patients with regret, 71% now wish they had elected for active surveillance. The incidence of regret was significantly different between treatment modalities: 5% of patients treated with SBRT expressed regret versus 18% with HDR and 19% with IMRT (P<.01). On multivariable logistic regression, patients treated with HDR versus SBRT were 7.42 times more likely to have regret, and patients treated with IMRT versus SBRT were 11.11 times more likely to have regret (P<.01 and P<.01, respectively). Significantly more patients treated with SBRT selected that their actual long-term toxicities were significantly less than originally expected, compared with IMRT and HDR patients (SBRT 43% vs IMRT 20% vs HDR 10%, P<.01). CONCLUSIONS: We found significant differences in patients' experiences between SBRT, IMRT, and HDR, with significantly less treatment regret and less toxicity than expected among SBRT patients. The majority of patients with regret would now opt for active surveillance; therefore, pretreatment counseling is essential.