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Background Among patients with osseous metastases, breast cancer (BC) patients typically have the best prognosis. In the palliative setting, BC is often considered a single disease, but based on receptor status there are four distinct subtypes: luminal A (LA), luminal B (LB), triple negative (TN), and HER2‐enriched (HER2). We hypothesize that survival and palliative outcomes following palliative RT for osseous metastases correlate with breast cancer subtype (BCS). Methods We identified 3,895 BC patients with known receptor status who received palliative RT for osseous metastases from 2004–2013 in the National Cancer Database. Kaplan–Meier method with log‐rank testing and univariate/multivariate Cox‐regression was used to identify survival factors. Incomplete radiation courses, 30‐day mortality rate, and percentage remaining life spent receiving RT (PRLSRT) were calculated. Results Subtypes were 54% LA, 33% LB, 8% TN, and 5% HER2 with median survival of 34.1, 28.2, 5.3, and 15.7 months, respectively (p, This study demonstrates the impact of breast cancer subtype on survival and palliative outcomes after palliative radiation for osseous metastases. Patients with triple negative and HER2‐enriched subtypes had shorter survival, higher 30 and 90‐day mortality, had more incomplete treatments, spent more of their remaining lives receiving radiation treatments, but received similar radiation regimens compared to Luminal A and Luminal B patients. This correlation should be considered when selecting palliative radiotherapy regimens to avoid unnecessary treatment and improve palliative outcomes for poor‐prognosis patients.

Medical students applying for radiation oncology residency rated “perceived quality of didactics” within the top 5 factors in ranking programs (1). However, according to a 2013 national survey, only 27% of radiation oncology clerkships included didactic components specifically for medical students (2). In 2012, a pilot radiation oncology clerkship curriculum was developed at two institutions using the six-step conceptual framework for medical education curriculum development by Kern et al (3). Eighteen students completed the pilot curriculum. Students rated the curriculum highly and reported improved comfort with their decision to pursue radiation oncology as a specialty (4). Using the cooperative group research model, the curriculum was expanded to 11 selected academic medical centers within the United States in 2013 with the goal of increasing the number of participating students to provide more robust feedback for further curriculum development. Here, we describe the structure of the curriculum with corollary student feedback that can be used by other institutions to design or enhance their medical student curriculum. The curriculum consisted of three 1-hour lectures delivered by a senior resident or faculty member; topics included: (1) an overview of radiation oncology, including a history of the specialty, types of treatments, and basic clinic flow; (2) fundamentals of radiation biology and radiation physics; and (3) practical aspects of radiation treatment simulation and planning and radiation emergencies. Ideally, one session was conducted per week with all students present. The lecture format was open, and students were encouraged to ask questions. In addition, a 1-hour hands-on radiation treatment workshop facilitated by a senior resident, faculty, physicist, or dosimetrist was implemented to teach students the fundamentals of radiation treatment planning (5). While using a radiation treatment planning workstation, each student was provided with a step-by-step guide to delineating a radiation target, selecting appropriately directed radiation beams, and modifying various beam parameters to achieve an optimal plan. Individual institutions were encouraged to adapt the lectures according to institutional treatment or practice patterns, but all institutions retained the core curriculum format (3 lectures, 1 planning session). All participating institutions obtained institutional review board exemption. A total of 94 students participated in the curriculum in the 2013 academic year, allowing both wide dissemination and robust feedback. Upon completion of the clerkship, students were invited to complete an anonymous internet-based survey to rate the curriculum components, which yielded a 73% response rate. Qualitative analysis of the evaluations was undertaken by two authors (P.M. and J.C.Y.). Evaluation-free responses were reviewed independently and divided into positive and negative “consistent” themes (Table 1). These themes reflected the students' subjective overall feeling that the course laid an excellent knowledge foundation for transition to residency and their concern that they might not retain the knowledge during the two years prior to beginning residency. Future directions for curriculum development include expansion to additional institutions while using these constructive comments to enhance the learning experience. For example, one negative theme was that lectures should be scheduled earlier in the rotation to ensure that students have a good knowledge base for the remainder of the clinical rotation. This and other constructive feedback will be considered in the future when implementing the curriculum. Table 1 Consistent positive and negative feedback themes for individual curriculum components and how the curriculum will or will not be useful for transition to residency and for the overall curriculum This successful implementation of a standardized curriculum piloted at multiple institutions provides proof-of-principle that curriculum development can follow the multi-institutional cooperative group model. In the process, we identified areas of positive and negative needs as perceived by the students, who represent the most important stakeholders. Additional data are being collected to assess the impact of this curriculum on the students' decision to apply for radiation oncology residency. In the interim, the current data can help individual departments enhance their ongoing curriculum for rotating medical students.

Cutaneous squamous cell carcinoma (SCC) is a common skin cancer affecting more than 3,000,000 individuals worldwide each year. The risk of SCC is strongly linked with immunosuppressive treatment in organ transplant recipients (OTR). Population-based standard incidence ratios for SCC are increased 65–250-fold and for basal cell carcinomas 10–16-fold in OTR compared with non-transplanted population. Skin cancers in immunocompromised patients tend to be more aggressive and metastasize more frequently. Therefore adjuvant radiotherapy and definitive radiotherapy for surgically incurable cancers plays an important role in the therapeutic options. In this chapter we discuss indications, approaches, planning, efficacy, and side effects of radiation treatment of non-melanoma skin cancer in OTR.

Patients confronted with various treatment options for the treatment of nonmelanomatous skin cancers in visible areas of the face may not be fully informed of the expected outcomes associated with treatment. Radiation therapy may be particularly advantageous in treating lesions in which surgical resection would risk poor cosmetic outcomes. Results from several large series demonstrate local recurrence rates of

Purpose: Radiation therapy (RT) of left sided breast cancers with deep-inspiratory breathhold (DIBH) can reduce the dose to heart. The purpose of this study is to develop and test a new laser-based tool to improve ease of RT delivery using DIBH. Methods: A laser sensor together with breathing monitor device (Anzai Inc., Japan) was used to record the surface breathing motion of phantom/volunteers. The device projects a laser beam to the chestwall and the reflected light creates a focal spot on a light detecting element. The position change of the focal spot correlates with the patient's breathing motion and is measured through the change of current in the light detecting element. The signal is amplified and displayed on a computer screen, which is used to trigger radiation gating. The laser sensor can be easily mounted to the simulation/treatment couch with a fixing plate and a magnet base, and has a sensitivity range of 10 to 40 cm from the patient. The correlation of breathing signals detected by laser sensor and visionRT is also investigated. Results: It is found that the measured breathing signal from the laser sensor is stable and reproducible and has no noticeable delay. It correlates well with the VisionRT surface imaging system. The DIBH reference level does not change with movement of the couch because the laser sensor and couch move together. Conclusion: The Anzai laser sensor provides a cost-effective way to improve beam gating with DIBH for treating left breast cancer. It can be used alone or together with VisionRT to determine the correct DIBH level during the radiation treatment of left breast cancer with DIBH.

Localized, radiation (XRT)-induced sternal bone marrow (BM) aplasia was described in early studies in the radiation oncology literature; however, no pathologic studies have examined in detail this phenomenon in random iliac crest biopsies and its relationship to overall hematopoiesis. We retrospectively reviewed aplastic iliac crest BMs with discrepant peripheral blood (PB) counts after localized pelvic XRT. BM aplasia was defined as 5% or less cellularity in an adequate biopsy and/or hypocellular particles on aspirate smears. Discrepant PB counts were defined as either within or higher than normal limits or mild cytopenias. Eight patients with BM aplasia and discrepant PB counts were identified; each had received localized XRT to the sacrum, lumbar spine, or pelvis. Aplastic BMs showed replacement by mature fat and/or virtually acellular spicules. One case showed focal reticulin fibrosis. Mild cytopenias were seen in 6 cases and normal or increased counts in one case each. Aplastic BMs were observed 5 to 43 months after XRT. A myeloproliferative neoplasm was diagnosed in one case based on PB findings and JAK-2 mutation, despite BM aplasia. In one case, a right-sided aplastic BM, diagnosed 8 months after XRT, was followed 14 months later by a normocellular right aspirate and aplastic left BM biopsy. Prolonged, localized BM sterilization may be seen as a result of XRT to the iliac crest for several years. In the setting of preserved PB counts, this is not likely representative of overall hematopoiesis and serves as a potential diagnostic pitfall. Regeneration of hematopoietic activity at exposed sites may be possible.

Introduction: Inflammatory breast cancer (IBC) is an aggressive and lethal form of locally advanced breast cancer that makes up 1-6% of all breast cancers and has a median overall survival of less than 4 years. Physically, IBC is characterized by erythema, edema, and fine dimpling, so treatment can be delayed due to misdiagnosis as mastitis or dermatitis. Therapy for IBC tends to vary since no treatments are highly effective. Because IBC is such a rare subtype, studies have been challenged to demonstrate patterns of IBC treatment and analyze factors affecting differences in treatment. In this study we examined factors affecting the receipt of guideline-concordant care and survival for IBC patients. Methods: Patients diagnosed with non-metastatic IBC in 2004 were identified from the Breast and Prostate Cancer Data Quality and Patterns of Care Study, containing information from cancer registry reports in seven states supplemented through medical record re-abstraction and physician verification. Variation in guideline-concordant care for IBC, based on 2003 National Comprehensive Cancer Network (NCCN) guidelines, was assessed according to patient, physician, and hospital characteristics. Additionally, survival based on receipt of guideline-concordant care was analyzed using Kaplan-Meier curves and log-rank tests. Results: Of the 107 IBC patients in the study, only 25.8% of them received treatment that was fully concordant with guidelines. The majority of patients received guideline-concordant surgery (90.4%), with percentages lower for chemotherapy (51.9%), radiation (40.7%), and hormone therapy (78.0%). Guideline-concordant care was less common among patients with extreme categories of patient age (under 40 or over 80 years; P = 0.19), non-white race (P = 0.03), lower body mass index (BMI Results suggested that IBC patients experienced longer breast cancer-specific survival if they received guideline-concordant treatment based on 2003 (P = 0.06) and 2013 (P = 0.06) NCCN guidelines. Conclusion: Targeting factors associated with receipt of care that is not guideline-concordant may reduce survival disparities in IBC patients. Further research is needed to identify approaches to ensure that physicians are adhering to NCCN guidelines for IBC cases and to identify reasons for non-adherence to guidelines. Citation Format: Ryan A. Denu, John M. Hampton, Adam Currey, Roger T. Anderson, Rosemary D. Cress, Steven T. Fleming, Joseph Lipscomb, Susan A. Sabatino, Xiao-Cheng Wu, J F. Wilson, Amy Trentham-Dietz. Influence of patient, physician, and hospital characteristics on the receipt of guideline-concordant care for inflammatory breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3727. doi:10.1158/1538-7445.AM2015-3727

Purpose: MRI-guided radiation therapy (RT) delivery would be beneficial for breast irradiation. The electron return effect due to the presence of a transverse magnetic field (TMF) may cause dosimetric issues on dose on skin and at the lung-tissue interface. The purpose of this study is to investigate these issues. Methods: IMRT plans with tangential beams and VMAT plans with 200 degree arcs to cover ipsilateral breast were generated for 10 randomly selected breast cancer cases using a research planning system (Monaco, Elekta) utilizing Monte Carlo dose calculation with or without a TMF of 1.5 T. Plans were optimized to deliver uniform dose to the whole breast with an exclusion of 5 mm tissue under the skin (PTV-EVAL). All four plans for each patient were re-scaled to have the same PTV-EVAL volume to receive the same prescription dose. The skin is defined as the first 5 mm of ipsilateral-breast tissue, plus extensions in the surrounding region. Results: The presence of 1.5 T TMF resulted in (1)increased skin dose, with the mean and maximum skin dose increase of 5% and 9%, respectively; (2) similar dose homogeneity within the PTV-EVAL; (3) the slightly improved (3%) dose homogeneity in the whole breast; (4) Averagesmore » of 9 and 16% increases in V5 and V20, respectively, for ipsilateral lung; and (5) increased the mean heart dose by 34%. VMAT plans don’t improve whole breast dose uniformity as compared that to the tangential plans. Conclusion: The presence of transverse magnetic field in MRI-guided RT delivery for whole breast irradiation can Result in slightly improved dose homogeneity in the whole breast, increased dose to the ipsilateral lung, heart, and skin. Plan optimization with additional specific dose volume constraints may eliminate/reduce these dose increases. This work is partially supported by Elekta Inc.« less

Objective/Purpose While we await outcomes from randomized studies, APBI has seen increasing use as an alternative to whole breast irradiation (WBI) after lumpectomy for early stage breast cancer. Recently, there has been concern generated about excess toxicity associated with brachytherapy APBI. Multi-catheter (MCT) brachytherapy, as the initial APBI method developed, has the longest follow-up and provides a means for looking at late outcomes.

98 Background: Recently, SSO/ASTRO published a consensus statement on margins for stage I and II invasive breast cancer treated with breast conserving surgery (BCS). We examined patients with ductal carcinoma in situ (DCIS) who underwent BCS to determine the effect of clinicopathologic and treatment factors including margin status, on locoregional recurrence (LRR), breast cancer-specific (BCSS) and overall survival (OS). Methods: From 2003-2010, we conducted a retrospective chart review of 253 consecutively diagnosed patients who underwent BCS for DCIS. Clincopathologic and treatment data were extracted. Margin status was defined by pathology reports with a negative margin as ≥ 2mm, close margin < 2mm and positive margin as tumor on ink. Clinicopathologic variables were tested using the Fisher’s exact test, Chi-square test, ANOVA F-test, and Kruskal-Wallis test. A Cox proportional - Hazards model was used to calculate the impact of these factors on LRR, BCSS and OS. Results: The median age of the cohort was 57 (range 21-89) and the majority were white (79%), ER+ (78%) and underwent radiation therapy (67%). Forty six percent took anti-endocrine therapy. Of 252 patients, 29% had close margins, 63% had negative margins and 7% had unknown margins. One patient had a positive margin and was alive without disease at last follow-up. At a median follow-up of 5 years, OS was 96%. Thirteen patients experienced a LRR with a median time to recurrence of 4.9 years (5 with close margins, 7 with negative, 1 unknown). On multivariate analysis, age and PR status were significant predictors of LRR. Patients with age >70 were more likely to recur than those age 50-69 (HR 6.7 95% CI (1.7-25.4) p= 0.005) as were patients with PR negative tumors (HR 5.7 95% CI (1.7-19.5) p= 0.005). Those patients who did not receive radiation therapy had a worse OS than those who did (HR 4.3 95%CI (1.5-12.6) p = 0.007). No variables were significant for BCSS. Conclusions: In this cohort of patients with DCIS treated with BCS, age and PR status were the only predictors of LRR. OS was only impacted by receipt of radiotherapy. Margin status was not predictive of LRR, BCSS or OS. This data suggests that routine re-excision for close margins may not be warranted.

83 Background: A consensus statement was recently published by SSO/ASTRO on margins for stage I and II invasive breast cancer treated with breast conserving surgery (BCS). We examined patients with invasive breast cancer who underwent BCS to determine if margin status and molecular subtype influence outcomes. Methods: We the reviewed charts of 754 Stage I-III breast cancer patients treated with BCS from 2003-2010. Margin status was defined as negative ≥ 2mm, close < 2mm and positive as tumor on ink. Conventional receptor analyses were used as markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal). Clinicopathologic variables were tested using the Fisher’s exact, Chi-square, ANOVA F-test, and Kruskal-Wallis tests. A Cox proportional - Hazards model was used to measure the impact of these variables on locoregional recurrence (LRR), breast cancer-specific (BCSS) and overall survival (OS). Results: The median age of the cohort was 58 (range 27-89 years). Most were white (88%), had T1 tumors (76%), luminal A tumors (66%), invasive ductal histology (80%), and were node negative (76%). Of the 754 patients, 26% had close margins, 2% positive margins, and 9% unknown margins. With a median follow-up of 5.2 years, OS was 92%. Twenty eight patients had a LRR with a median time to recurrence of 5.1 years. On multivariate analysis, molecular subtype, pathologic grade (p=0.01), and use of radiation (p

Purpose: For whole breast irradiation (WBI) followed by sequential boost of the lumpectomy cavity (LC), the LC shape and volume can change significantly after WBI. Consequently, the boost plan, normally generated together with WBI plan before the start of treatment, may not be optimal. Here we propose the use of online adaptive replanning at the time of boost to account for the LC change. Methods: Daily diagnostic‐quality CT sets acquired during IGRT using an in‐room CT (CTVision, Siemens) for 19 breast cancer patients treated with WBI with sequential boost in prone position were used. Contours of LC, treated breast, ipsilateral lung, and heart were generated by deformably registering the planning CT with the fraction CT acquired on the first boost fraction using an auto‐segmentation tool (ABAS, Elekta) with manual editing, if necessary. Three plans were generated based on the daily CT: (1) repositioning plan by applying the original boost plan with the shift, (2) adaptive plan by quickly modifying the original plan using a tool (RealArt, Prowess), and (3) reoptimization plan by a fully‐blown optimization. Results: Significant changes were observed in the LC volume and shape. The LC volume on the first day of boost changes in the range of 30% and 130% from that on planning CT. The plan quality of the adaptive plans and the re‐optimization plans were comparable. Compared to the repositioning plans, the adaptive plans generally lead to improvement in target coverage and normal tissue sparing, with an average increase in LC V95 of 2.3% and decrease in breast tissue V50 of 3.0%. Conclusion: Significant changes in LC shape and volume at the time of boost from the original plan for WBI with sequential boost can be addressed by the online replanning at the first boost fraction.

Purpose: Interfractional anatomy changes (e.g., changes in breast shape and volume) in breast radiotherapy (RT) can be significant and cannot be fully accounted for by the current IGRT repositioning practice. This work aims to quantify dosimetric impact of these changes based on accumulative dose for IMRT and 3DCRT. Methods: Daily CT data acquired using a CT‐on‐Rails (CTVision, Siemens) during IGRT for 5 representative breast cancer patients treated in prone position were analyzed. Each daily CT was registered with corresponding planning CT by aligning the lumpectomy cavity, mimicking the IGRT repositioning. Contours of breast, lumpectomy PTV and critical structures on daily CTs were generated using an auto‐segmentation tool (ABAS, Elekta) based on deformable image registration. For each patient, plans for IMRT and 3DCRT with wedge were developed, and were applied to each registered daily CT set to reconstruct the daily doses with the deformation fields from ABAS which were used to compute the accumulative dose. Results: Daily variations in D95 (dose received by 95% of treated breast volume) and D50 were not significantly different between 3DCRT and IMRT plans (within 0.5–2%). Variation of daily dose maximum for IMRT was statistically significantly higher than that for the 3DCRT plans, with some fractions increased by up to 15–20%. However, the variations of the accumulated doses from the original plans for both 3DCRT and IMRT plans are comparable. Conclusion: Although daily doses from IMRT are more sensitive to the interfractional anatomy changes than those from 3DCRT, the variations of the accumulated doses from the original plans are comparable, as the higher variation in the hot spots for IMRT were “washed out” due to the random interfractional changes.

Purpose: To assess dosimetric planning feasibility for enrolling patients into a new prospective multi‐center protocol (ACOSOG Protocol Z11102) of breast conservation surgery with radiotherapy (RT) of multiple ipsilateral breast cancers (MIBC) including multicentric and/or multifocal breast cancers. Methods: CT data for 9 representative breast patients with two lumpectomy cavities in a breast treated in prone position were retrospectively analyzed. The boost PTV for lumpectomy cavity was delineated based on the seroma and/or surgical clips with 1 to 2 cm non‐uniform 3D expansion, not including chestwall, skin, and bone. A whole breast irradiation (WBI) of 50 Gy in 25 fractions was planned using 3D tangential beams of 6 or 15 MV photons with necessary wedges and/or field‐in‐field techniques to provide uniform dose coverage. No nodal irradiation was planned. The dose was calculated with heterogeneity correction using a treatment planning system (Xio v4.80, Elekta). For each boost PTV, additional 10 Gy in 5 fractions was planned by using one single photon beam, either 6 or 15 MV depending on the depth of the PTV, oriented in the direction with shortest depth to the PTV. All plans were evaluated to check whether all the dose‐volume criteria required by the protocol can be met. Results: All plans generated for patients in our study meet the dose‐volume criteria required by the protocol. For all dose‐volume parameters, the discrepancies between the patient averages and dose‐volume goals were separated by at least 1.4 sigmas (standard deviation). The average for the percentage breast volume receiving 60 Gy, a major concern because of the large boost PTVs, was (29.7±7.3)%, well below the required value of 40%. Conclusion: The dose‐volume criteria required for the new multi‐center protocol of radiotherapy for multiple ipsilateral breast cancers can be met with no major difficulties with the standard planning techniques.

neoadjuvant hormone therapy (NAHT) versus (vs) those treated with neoadjuvant chemotherapy (NACT) followed by surgery with or without radiation (XRT). Materials/Methods: We reviewed the records of 110 consecutive postmenopausal women treated pre-operatively with either NAHT or NACT from 2004 to 2011. We included subjects with non-metastatic, noninflammatory, ER+ breast cancer and excluded those with Her2neu positive tumors. We compared pathologic complete response (pCR) and breast conserving surgery (BCS) rates as well as long-term rates of local control, distant metastasis free survival (DMFS), and overall survival (OS). Results: Median follow-up time for all patients was 45.7 months. Twentyeight subjects received NAHT, while 82 received NACT. The most commonly prescribed NAHT was an aromatase inhibitor (93%) followed by tamoxifen (7%). Median duration of NAHT was 8.0 months. Fifty-six percent of NACT patients received an anthracycline (A) and taxane-based regimen, while 33% of patients received an A-based regimen alone. Patients receiving NAHT were older than patients receiving NACT (Median age 67 vs 58 years, p < 0.01). There were no significant differences in initial T stage, clinical tumor size, progesterone receptor status, tumor grade, or histology between groups. NACT patients, however, had more advanced N stage compared to NAHT patients (p Z .03). All NAHT patients had residual invasive cancer at the time of surgery, while 7.3% of NACT subjects achieved a pCR (p Z 0.1). Indeed, NACT patients were more likely to develop any pathologic response to treatment (median tumor size decrease of 1.7 cm vs 1.0 cm in NAHT patients, p Z .05), but were less likely to undergo BCS than NAHT subjects (30% vs 68%, p < 0.01). Among BCS patients, 96% of the NACT vs 79% of NAHT patients received post-lumpectomy XRT (p Z .09). Among patients treated with mastectomy, NACT patients were more likely to receive XRT (78% vs 43%, p Z .05). Among all patients, only one patient developed a local recurrence following NAHT and mastectomy without XRT. There was no difference in 4-year DMFS or OS between groups. On multivariate analysis, tumor grade and N stage but not NAHT predicted for poorer OS. Conclusions: Our data suggests that although pCR rates following NAHT in post-menopausal patients with ER+ breast cancer are low, outcomes do not appear to be adversely affected by NAHT treatment in our patient population. NAHT appears to be a viable and potentially less toxic option in select post-menopausal women with ER+ breast cancer. Author Disclosure: D.M. Marcus: None. R. Prabhu: None. R. O’Regan: None. A. Zelnak: None. C. Fasola: None. D. Mister: None. M. Torres: None.