Intensity-modulated proton radiotherapy spares musculoskeletal structures in regional nodal irradiation for breast cancer: a dosimetric comparison.

BACKGROUND AND PURPOSE: Regional nodal irradiation (RNI) for breast cancer delivers radiation in proximity to the shoulder and torso, and radiation exposure may contribute to long-term upper extremity and postural morbidity. To date, no studies have assessed the differential dosimetric impact of proton versus photon radiation on shoulder and torso anatomy. This study examined clinically relevant musculoskeletal (MSK) structures and assessed the dose delivered with each modality. PATIENTS/MATERIAL AND METHODS: Ten MSK structures were contoured on IMPT (intensity-modulated proton therapy) and VMAT (volumetric modulated arc therapy) plans for 30 patients receiving RNI. Relevant dose metrics were compared for each of the structures. Intensity-modulated proton therapy dose was calculated using the relative biological effective value of 1.1. Hypo-fractionated plans were scaled to the equivalent dose in 2 Gy fractions (EQD2) using an alpha/beta ratio of four. Wilcoxon signed rank sum tests compared doses. Select three-dimensional and optimised VMAT plans were also informally compared. RESULTS AND INTERPRETATION: Each of the 10 structures received a statistically significantly lower dose with the use of IMPT compared with VMAT. Differences were greatest for posterior structures, including the trapezius, latissimus dorsi and glenohumeral joint. Mean absolute differences were as great as 23 Gy (supraspinatus D5cc) and up to 30-fold dose reductions were observed (deltoid D50cc). An average 3.7-fold relative dose reduction existed across all structures. Measures of low/intermediate dose (V15Gy and D50cc) showed the largest differences. Intensity-modulated proton therapy results in statistically lower radiation exposure to relevant shoulder and torso anatomy compared to photon radiation for patients requiring RNI. Prospective study is needed to correlate functional outcomes with radiation dose.

The Timing of Acute and Late Complications Following Mastectomy and Implant-based Reconstruction.

BACKGROUND/OBJECTIVE: Implant-based breast reconstruction is a common plastic surgery procedure with well-documented clinical outcomes. Despite this, the natural history and timing of key complication endpoints are not well described. The goal of this study is to determine when patients are most likely to experience specific adverse events after implant-based reconstruction. METHODS: Retrospective consecutive series of patients who received mastectomy and implant-based reconstruction over a 6-year period were included. Complications and unfavorable outcomes including hematoma, seroma, wound infection, skin flap necrosis, capsular contracture, implant rippling, and implant loss were identified. A time-to-event analysis was performed and Cox regression models identified patient and treatment characteristics associated with each outcome. RESULTS: Of 1473 patients and 2434 total reconstructed breasts, 785 complications/unfavorable outcomes were identified. The 12-month cumulative incidence of hematoma was 1.4%, seroma: 4.3%, infection: 3.2%, skin flap necrosis: 3.9%, capsular contracture: 5.7%, implant rippling: 7.1%, and implant loss: 3.9%. In the analysis, 332/785 (42.3%) complications occurred within 60 days of surgery; 94% of hematomas, 85% of skin necrosis events, and 75% of seromas occurred during this period. Half of all infections and implant losses also occurred within 60 days. Of the remaining complications, 94% of capsular contractures and 93% of implant rippling occurred >60 days from surgery. CONCLUSIONS: Complications following mastectomy and implant-based reconstruction exhibit a discrete temporal distribution. These data represent the first comprehensive study of the timing of adverse events following implant-based reconstruction. These findings are immediately useful to guide postoperative care, follow-up, and clinical trial design.

Exploring the Perceived Educational Impact of COVID-19 on Postgraduate Training in Oncology.

This study sought to report the degree to which postgraduate trainees in radiation oncology perceive their education has been impacted by the COVID-19 pandemic. A cross-sectional online survey was administered from June to July 2020 to trainee members of the Canadian Association of Radiation Oncology (CARO) (n = 203). Thirty-four trainees responded with a 17% response rate. Just under half of participants indicated that COVID-19 had a negative/very negative impact on training (n = 15; 46%). The majority agreed/strongly agreed that they feared family/loved ones would contract COVID-19 (n = 29, 88%), felt socially isolated from friends and family because of COVID-19 (n = 23, 70%), and had difficulty concentrating on tasks because of concerns about COVID-19 (n = 17, 52%). Changes that had a negative/very negative impact on learning included limitations to travel and networking (n = 31; 91%) and limited patient contact (n = 19; 58%). Virtual follow-ups (n = 25: 76%) and in-patient care activities (n = 12; 36%) increased. Electives were cancelled in province (n = 10; 30%), out-of-province (n = 16; 49%), and internationally (n = 15; 46%). Teaching from staff was moderately reduced to completely suppressed (n = 23, 70%) and teaching to medical students was moderately reduced to completely suppressed (n = 27, 82%). Significant changes to radiation oncology training were wrought by the pandemic, and roughly half of trainees perceive that these changes had a negative impact on training. Innovations in training delivery are needed to adapt to these new changes.

Radiation Oncology Virtual Education Rotation (ROVER) 2.0 for Residents: Implementation and Outcomes.

The COVID-19 pandemic catalyzed the integration of a virtual education curriculum to support radiation oncologists in training. We report outcomes from Radiation Oncology Virtual Education Rotation (ROVER) 2.0, a supplementary virtual educational curriculum created for radiation oncology residents globally. A prospective cohort of residents completed surveys before and after the live virtual webinar sessions (pre- and post-surveys, respectively). Live sessions were structured as complex gray-zone cases across various core disease sites. Resident demographics and responses were summarized using means, standard deviations, and proportions. Nine ROVER sessions were held from October 2020 to June 2021. A total of 1487 registered residents completed the pre-survey, of which 786 attended the live case discussion and 223 completed post-surveys. A total of 479 unique radiation oncology residents (of which 95, n = 19.8%, were international attendees) from 147 institutions (national, n = 81, 55.1%; international, n = 66, 44.9%) participated in the sessions. There was similar participation across post-graduate year (PGY) 2 through 5 (range n = 86 to n = 105). Of the 122 unique resident post-surveys, nearly all reported learning through the virtual structure as "very easy" or "easy" (97.5%, n = 119). A majority rated the ROVER 2.0 educational sessions to be "valuable or "very valuable" (99.2%, n = 121), and the panelists-attendee interaction as "appropriate" (97.5%, n = 119). Virtual live didactics aimed at radiation oncology residents are feasible. These results suggest that the adoption of the ROVER 2.0 curricula may help improve radiation oncology resident education.

Do you mind if I record?: Perceptions and practice regarding patient requests to record clinic visits in oncology.

BACKGROUND: Audio recordings of oncology clinic discussions can help patients retain and understand information about their disease and treatment decisions. Access to this tool relies on acceptance of recordings by oncologists. This is the first study to evaluate experience and attitudes of oncologists toward patients recording clinic visits. METHODS: Medical, radiation, and surgical oncologists from 5 US cancer centers and community affiliates were surveyed to evaluate clinicians' experience, beliefs, and practices regarding patient-initiated recordings. RESULTS: Among 360 oncologists (69% response rate), virtually all (93%) have experienced patients seeking to record visits. Although 75% are comfortable with recording, 25% are uncomfortable and 56% report concerns ranging from less thorough discussions to legal liability. Most (85%) always agree when patients ask to record, but 15% never or selectively allow recording. Although 51% believe recording is positive for the patient-physician relationship, a sizable minority report that it can lead to less detailed conversations (28%) or avoidance of difficult topics, including prognosis (33%). Views did not vary based on subspecialty, practice setting, or geographic region, but older age and years in practice were associated with more positive views of recording. The majority of clinicians (72%) desire institutional policies to govern guidelines about recordings. CONCLUSIONS: Most oncologists are comfortable with patient requests to record visits, but a sizable minority remain uncomfortable, and access to recording varies solely on physician preference. This difference in care delivery may benefit from institutional policies that promote access while addressing legitimate physician concerns over privacy and appropriate use of recordings.

Radiation Oncology Education Collaborative Study Group Annual Spring Symposium: Initial Impact and Feedback.

The Radiation Oncology Education Collaborative Study Group (ROECSG) is an international collaborative network of radiation oncology (RO) professionals with the goal of improving RO education. This report summarizes the first two ROECSG annual symposia including an overview of presentations and analysis of participant feedback. One-day symposia were held in June 2018 and May 2019. Programs included oral and poster presentations, RO education leadership perspectives, and keynote addresses. Post-symposia surveys were collected. Research presentations were recorded and made available online. The 2018 symposium was had 36 attendees from 25 institutions in three countries. The 2019 symposium had 76 individuals from 41 institutions in five countries. Attendees represented diverse backgrounds including attending physicians (46%), residents (13%), medical students (14%), physicists (2%), nurses (1%), and program coordinators (1%). Fifty-five oral presentations were given with 53 released online. Ninety percent of attendees rated the symposium as improving their knowledge of RO educational scholarship, 98% felt the symposium provided the opportunity to receive feedback on RO education scholarship, and 99% felt that the symposium fostered the development of collaborative RO education projects. ROECSG was rated higher than professional organizations in fostering educational scholarship (p<0.001). All attendees felt that the symposium produced new RO education scholarship ideas and provided unique networking opportunities. The first two ROECSG symposia drew a diverse population of attendees and provided unique opportunities for presentation of RO education scholarship. Future ROECSG symposia will be designed to enhance opportunities to present RO education scholarship and to facilitate networking.

Management and outcomes of men diagnosed with primary breast cancer.

BACKGROUND: Fewer than 1% of all breast cancers occur in men. As a result, a distinct lack of data exists regarding the management and outcomes in this cohort. METHODS: Any male patient with pathologically confirmed breast cancer diagnosed between August 2000 and October 2017 at either Massachusetts General Hospital or Brigham and Women's Hospital/Dana-Farber Cancer Institute and their affiliate satellite locations were included. Primary chart review was used to assess clinical and pathologic characteristics. Patient and treatment variables were reported via descriptive statistics. Local-regional failure (LRF), overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS) were estimated using the Kaplan-Meier method. RESULTS: 100 patients were included in this study. Median follow-up was 112 months (range 1-220 months). Approximately 1/3 of patients experienced at least a 3-month delay to presentation. 83 patients ultimately underwent mastectomy as definitive surgical treatment. 46 patients received adjuvant radiation therapy, and 37 patients received chemotherapy. Of 82 hormone receptor-positive patients with invasive cancer, 94% (n = 77) received endocrine therapy. Of the fifty-eight patients who underwent genetic testing, 15 (26%) tested positive. The 5-year OS, BCSS, DFS, and LRF rates were 91.5%, 96.2%, 86%, and 4.8%, respectively. Delay to presentation was not associated with worse survival. CONCLUSIONS: Male breast cancer remains a rare diagnosis. Despite this, the majority of patients in this study received standard of care therapy and experienced excellent oncologic outcomes. Penetration for genetic testing improved over time.

Target coverage and cardiopulmonary sparing with the updated ESTRO-ACROP contouring guidelines for postmastectomy radiation therapy after breast reconstruction: a treatment planning study using VMAT and proton PBS techniques.

BACKGROUND: The European Society for Therapeutic Radiology and Oncology Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) recently released new contouring guidelines for postmastectomy radiation therapy (PMRT) after implant-based reconstruction (IBR). As compared to prior ESTRO guidelines, the new guidelines primarily redefined the chest wall (CW) target to exclude the breast prosthesis. In this study, we assessed the impact of these changes on treatment planning and dosimetric outcomes using volumetric-modulated arc therapy (VMAT) and proton pencil-beam scanning (PBS) therapy. METHODS: We performed a treatment planning study of 10 women with left-sided breast cancer who underwent PMRT after IBR. All target structures were delineated first using standard (ESTRO) breast contouring guidelines and then separately using the new (ESTRO-ACROP) guidelines. Standard organs-at-risk (OARs) and cardiac substructures were contoured. Four sets of plans were generated: (1) VMAT using standard ESTRO contours, (2) VMAT using new ESTRO-ACROP contours, (3) PBS using standard contours, and (4) PBS using new contours. RESULTS: VMAT plans using the new ESTRO-ACROP guidelines resulted in modest sparing of the left anterior descending coronary artery (LAD) (mean dose: 6.99 Gy standard ESTRO vs. 6.08 Gy new ESTRO-ACROP, p = 0.010) and ipsilateral lung (V20: 21.66% vs 19.45%, p = 0.017), but similar exposure to the heart (mean dose: 4.6 Gy vs. 4.3 Gy, p = 0.513), with a trend toward higher contralateral lung (V5: 31.0% vs 35.3%, p = 0.331) and CW doses (V5: 31.9% vs 35.4%, p = 0.599). PBS plans using the new guidelines resulted in further sparing of the heart (mean dose: 1.05 Gy(RBE) vs. 0.54 Gy(RBE), p < 0.001), nearly all cardiac substructures (LAD mean dose: 2.01 Gy(RBE) vs. 0.66 Gy(RBE), p < 0.001), and ipsilateral lung (V20: 16.22% vs 6.02%, p < 0.001). CONCLUSIONS: PMRT after IBR using the new ESTRO-ACROP contouring guidelines with both VMAT and PBS therapy is associated with significant changes in exposure to several cardiopulmonary structures.

A common Chk1-dependent phenotype of DNA double-strand break suppression in two distinct radioresistant cancer types.

PURPOSE: Triple-negative breast cancers (TNBC) are often resistant to treatment with ionizing radiation (IR). We sought to investigate whether pharmacologic inhibition of Chk1 kinase, which is commonly overexpressed in TNBC, preferentially sensitizes TNBC cells to IR. METHODS: Ten breast cancer cell lines were screened with small molecule inhibitors against Chk1 and other kinases. Chk1 inhibition was also tested in isogenic KRAS mutant or wild-type cancer cells. Cellular radiosensitization was measured by short-term and clonogenic survival assays and by staining for the DNA double-strand break (DSB) marker γ-H2AX. Radiosensitization was also assessed in breast cancer biopsies using an ex vivo assay. Aurora B kinase-dependent mitosis-like chromatin condensation, a marker of radioresistance, was detected using a specific antibody against co-localized phosphorylation of serine 10 and trimethylation of lysine 9 on histone 3 (H3K9me3/S10p). Expression of CHEK1 and associated genes was evaluated in TNBC and lung adenocarcinoma. RESULTS: Inhibition of Chk1 kinase preferentially radiosensitized TNBC cells in vitro and in patient biopsies. Interestingly, TNBC cells displayed lower numbers of IR-induced DSBs than non-TNBC cells, correlating with their observed radioresistance. We found that Chk1 suppressed IR-induced DSBs in these cells, which was dependent on H3K9me3/S10p-a chromatin mark previously found to indicate radioresistance in KRAS mutant cancers. Accordingly, the effects of Chk1 inhibition in TNBC were reproduced in KRAS mutant but not wild-type cells. We also observed co-expression of genes in this Chk1 chromatin pathway in TNBC and KRAS mutant lung cancers. CONCLUSIONS: Chk1 promotes an unexpected, common phenotype of chromatin-dependent DSB suppression in radioresistant TNBC and KRAS mutant cancer cells, providing a direction for future investigations into overcoming the treatment resistance of TNBC.

Tattoo free setup for partial breast irradiation: A feasibility study.

PURPOSE: Patients undergoing external beam accelerated partial breast irradiation (APBI) receive permanent tattoos to aid with daily setup alignment and verification. With the advent of three-dimensional (3D) body surface imaging and two-dimensional (2D) x-ray imaging-based matching to surgical clips, tattoos may not be necessary to ensure setup accuracy. We compared the accuracy of conventional tattoo-based setups to a patient setup without tattoos. MATERIALS/METHODS: Twenty consecutive patients receiving APBI at our institution from July 10, 2017 to February 13, 2018 were identified. All patients received tattoos per standard of care. Ten patients underwent setup using tattoos for initial positioning followed by surface imaging and 2D matching of surgical clips. The other ten patients underwent positioning using surface imaging followed by 2D matching without reference to tattoos. Overall setup time and orthogonal x-ray-based shifts after surface imaging per fraction were recorded. Shift data were used to calculate systematic and random error. RESULTS: Among ten patients in the "no tattoo" group, the average setup time per fraction was 6.83 min vs 8.03 min in the tattoo cohort (P < 0.01). Mean 3D vector shifts for patients in the "no tattoo" group were 4.6 vs 5.9 mm in the "tattoo" cohort (P = NS). Mean systematic errors in the "no tattoo" group were: 1.2 mm (1.5 mm SD) superior/inferior, 0.5 mm (1.6 mm SD) right/left, and 2.3 mm (1.9 mm SD) anterior/posterior directions. Mean systematic errors in the "tattoo" group were: 0.8 mm (2.2 mm SD) superior/inferior, 0.3 mm (2.5 mm SD) right/left, and 1.4 mm (4.4 mm SD) anterior/posterior directions. The random errors in the "no tattoo" group ranged from 0.6 to 0.7 mm vs 1.2 to 1.7 mm in the "tattoo" group. CONCLUSIONS: Using both surface imaging and 2D matching to surgical clips provides excellent accuracy in APBI patient alignment and setup verification with reduced setup time relative to the tattoo cohort. Skin-based tattoos may no longer be warranted for patients receiving external beam APBI.

Cluster Analysis Demonstrates the Need to Individualize Care for Cancer Survivors.

BACKGROUND: In efforts to inform clinical screening and development of survivorship care services, we sought to characterize patterns of health care needs among cancer survivors by (a) identifying and characterizing subgroups based on self-reported health care needs and (b) assessing sociodemographic, clinical, and psychosocial factors associated with these subgroups. METHODS: We conducted a cross-sectional self-administered survey among patients presenting for routine follow-up care for early-stage cancer at our academic medical center. Latent class cluster analysis was used to identify clusters of survivors based on survivorship care needs within seven domains. Multiple logistic regression analyses were used to assess factors associated with these clusters. RESULTS: Among 292 respondents, the highest unmet needs were related to the domains of side effects (53%), self-care (51%), and emotional coping (43%). Our analysis identified four clusters of survivors: (a) low needs (n = 123, 42%), (b) mainly physical needs (n = 46, 16%), (c) mainly psychological needs (n = 57, 20%), and (d) both physical and psychological needs (n = 66, 23%). Compared with cluster 1, those in clusters 2, 3, and 4 were younger (p < .03), those in clusters 3 and 4 had higher levels of psychological distress (p < .05), and those in clusters 2 and 4 reported higher levels of fatigue (p < .05). CONCLUSION: Unmet needs among cancer survivors are prevalent; however, a substantial group of survivors report low or no health care needs. The wide variation in health care needs among cancer survivors suggests a need to screen all patients, followed by tailored interventions in clinical care delivery and research. IMPLICATIONS FOR PRACTICE: The characterization of patients as having few needs, predominantly physical needs, predominantly psychological needs, or substantial needs that are both physical and psychological provides a productive framework for clinical care of cancer survivors and to guide further research in this field. Further research is needed to define the tailored information and services appropriate for each group of patients and to define optimal screening tools to efficiently identify the needs of individuals in oncology practice.

Management and outcomes of women diagnosed with primary breast lymphoma: a multi-institution experience.

PURPOSE: Primary breast lymphoma (PBL) comprises < 1% of breast malignancies, leading to a paucity of data to guide management. We evaluated PBL recurrence patterns across two academic hospitals in the era of modern systemic-therapy and radiotherapy. METHODS: Patients diagnosed with PBL between October 1994 and June 2016 were identified. Demographic/clinical variables were assessed via primary chart review. Local control (LC) was estimated using the cumulative incidence function and overall survival (OS) using the Kaplan-Meier method. RESULTS: Thirty-five patients were identified. Median follow-up 5.8 years (range 0.3-17.8 years). Median age at diagnosis 66 years (range 35-86 years). Indolent versus aggressive lymphoma represented 57% (n = 20) and 43% (n = 15) of the cohort, respectively. All patients with aggressive lymphoma received systemic therapy. Thirty patients (86%) received radiotherapy (RT). Breast-only RT was used in 57% (n = 20); 23% (n = 7) received regional nodal irradiation (RNI), and 6% (n = 2) received limited-field RT. Local recurrences were observed in 3% (n = 1), contralateral breast 9% (n = 3), CNS 6% (n = 2), distant non-CNS 30% (n = 10), both local and distant 3% (n = 1). There were no regional nodal recurrences. The 6-year LC rate was 95% for indolent and 81% for aggressive subtypes. The 6-year OS rate was 87% for indolent and 70% for aggressive subtypes. CONCLUSIONS: The majority of patients in this PBL cohort received breast-only RT with no nodal relapses, suggesting that prophylactic RNI may be unnecessary. Given the prevalence of contralateral breast involvement at diagnosis and at recurrence, vigilant surveillance of bilateral breasts may be warranted. The role of CNS prophylaxis requires further investigation.

Local control after fractionated stereotactic radiation therapy for brain metastases.

Stereotactic radiosurgery (SRS) is frequently used in the management of brain metastases, but concerns over potential toxicity limit applications for larger lesions or those in eloquent areas. Fractionated stereotactic radiation therapy (SRT) is often substituted for SRS in these cases. We retrospectively analyzed the efficacy and toxicity outcomes of patients who received SRT at our institution. Seventy patients with brain metastases treated with SRT from 2006-2012 were analyzed. The rates of local and distant intracranial progression, overall survival, acute toxicity, and radionecrosis were determined. The SRT regimen was 25 Gy in 5 fractions among 87 % of patients. The most common tumor histologies were non-small cell lung cancer (37 %), breast cancer (20 %) and melanoma (20 %), and the median tumor diameter was 1.7 cm (range 0.4-6.4 cm). Median survival after SRT was 10.7 months. Median time to local progression was 17 months, with a local control rate of 68 % at 6 months and 56 % at 1 year. Acute toxicity was seen in 11 patients (16 %), mostly grade 1 or 2 with the most common symptom being mild headache. Symptomatic radiation-induced treatment change was seen on follow-up MRIs in three patients (4.3 %). SRT appears to be a safe and reasonably effective technique to treat brain metastases deemed less suitable for SRS, though dose intensification strategies may further improve local control.

Evolving Role of Proton Radiation Therapy in Clinical Practice.

With the expansion of proton radiation therapy centers across the United States and a gradually expanding body of academic evidence supporting its use, more patients are receiving-and asking about-proton therapy than ever before. Here, we outline, for nonradiation oncologists, the theoretical benefits of proton therapy, the clinical evidence to date, the controversies affecting utilization, and the numerous randomized trials currently in progress. We also discuss the challenges of researching and delivering proton therapy, including the cost of constructing and maintaining centers, barriers with insurance approval, clinical situations in which proton therapy may be approached with caution, and the issue of equitable access for all patients. The purpose of this review is to assist practicing oncologists in understanding the evolving role of proton therapy and to help nonradiation oncologists guide patients regarding this technology.

Association of Sarcopenia With Toxicity-Related Discontinuation of Adjuvant Endocrine Therapy in Women With Early-Stage Hormone Receptor-Positive Breast Cancer.

PURPOSE: Sarcopenia, an age-related decline in muscle mass and physical function, is associated with increased toxicity and worse outcomes in women with breast cancer (BC). Sarcopenia may contribute to toxicity-related early discontinuation of adjuvant endocrine  therapy (aET) in women with hormone receptor-positive (HR+) BC but remains poorly characterized. METHODS AND MATERIALS: This multicenter, retrospective cohort study included consecutive women with stage 0-II HR+ BC who received breast conserving therapy (lumpectomy and radiation therapy) and aET from 2011 to 2017 with a 5-year follow-up. Skeletal muscle index (SMI, cm2/m2) was analyzed using a deep learning model on routine cross-sectional radiation simulation imaging; sarcopenia was dichotomized according to previously validated reports. The primary endpoint was toxicity-related aET discontinuation; logistic regression analysis evaluated associations between SMI/sarcopenia and aET discontinuation. Cox regression analysis evaluated associations with time to aET toxicity, ipsilateral breast tumor recurrence (IBTR), and disease-free survival (DFS). RESULTS: A total of 305 women (median follow-up, 89 months) were included with a median age of 67 years and early-stage BC (12% stage 0, 65% stage I). A total of 60 (20%) women experienced toxicity-related aET discontinuation. Sarcopenia was associated with toxicity-related early discontinuation of aET (odds ratio, 2.18; P = .036) and shorter time to aET toxicity (hazard ratio [HR], 1.62; P = .031). SMI or sarcopenia were not independently associated with IBTR or DFS; toxicity-related aET discontinuation was associated with worse IBTR (HR, 9.47; P = .002) and worse DFS (HR, 4.53; P = .001). CONCLUSIONS: Among women with early-stage HR+ BC who receive adjuvant radiation therapy and hormone therapy, sarcopenia is associated with toxicity-related early discontinuation of aET. Further studies should validate these findings in women who did not receive adjuvant radiation therapy. These high-risk patients may be candidates for aggressive symptom management and/or alternative treatment strategies to improve outcomes.

Axillary Recurrence in Sentinel Lymph Node Negative Mastectomy Patients at 16 Years Median Follow Up: Natural History in the Absence of Radiation.

BACKGROUND: Axillary recurrence following lumpectomy with a negative sentinel lymph node biopsy (SLNB) is rare, possibly due to routine use of whole breast radiation. In this study, we characterized the rate of any axillary recurrence among mastectomy patients with a negative SLNB and no adjuvant radiation therapy. METHODS: We identified women who underwent mastectomy with SLNB for early-stage breast cancer (1999-2005) and included patients with pathologically negative nodes and no axillary dissection or adjuvant radiation. The primary outcome was ipsilateral axillary recurrence. RESULTS: A total of 234 women, median age 50 years, underwent 242 mastectomies. Histology showed 112 (46%) invasive cancers, 16 (7%) ductal carcinoma in-situ (DCIS) with microinvasion, and 114 (47%) pure DCIS. Cancers were predominantly estrogen receptor positive (59%) and moderate (41%) or high grade (32%). A mean of 2 final sentinel nodes were excised (range 1-6) and 21 patients (9%) had isolated tumor cells on SLNB pathology. At 16 years median follow up (range 1-22 years), 3 patients (1.2%) developed an isolated axillary failure, and 1 had concurrent axillary and chest wall recurrences (total axillary recurrence rate 1.7%). Three of four axillary recurrences occurred in patients with moderate or high-grade estrogen receptor-positive DCIS without invasion on mastectomy histology. Median time to axillary recurrence was 70.5 months (range 29-132 months). CONCLUSIONS: Axillary recurrence is rare after a negative SLNB, even in the absence of adjuvant radiation. This supports the safety of forgoing additional surgery or radiation to the axilla in the early-stage breast cancer and a negative SLNB.

Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial.

PURPOSE: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). RESULTS: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. CONCLUSIONS: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.

Metaplastic breast cancer: A review.

Metaplastic breast cancer (MpBC) is an uncommon aggressive malignancy that is associated with a poor prognosis. Due to its rarity, the relationships between the clinical and pathological features of MpBC, treatment approach, and clinical outcomes remain underexplored. In the following review article, we synthesize the existing data on the clinical, pathological and genomic features, management, and outcomes of MpBC. We also identify potential targets for future clinical trials.