Background NRG Oncology NSABP B-39/RTOG 0413 compared whole-breast irradiation (WBI) to accelerated partial-breast irradiation (APBI). APBI was not equivalent to WBI in local tumor control. Secondary outcome was quality of life (QOL).Methods The QOL sub-study used validated self-report questionnaires, including the Breast Cancer Treatment Outcome Scale (BCTOS) and the 36-Item Short Form Health Survey (SF-36) vitality scale. Assessments occurred before random assignment, at treatment completion (chemotherapy or radiotherapy), 4 weeks later, at 6, 12, 24, and 36 months. Primary aims: cosmesis change equivalency (baseline to 3 years; a priori margin of equivalence 0.4 standard deviations) and fatigue change superiority (baseline to end of treatment [EOT]) for APBI vs WBI, by patient groups treated with or without chemotherapy when appropriate.Results From March 21, 2005 to May 25, 2009, 975 patients enrolled in this sub-study; 950 had follow-up data. APBI had 3-year cosmesis equivalent to WBI (95% CI = -0.0001 to -0.16; equivalence margin -0.22 to -0.22) in all patients. The APBI group without chemotherapy had less EOT fatigue (P = .011; mean score APBI 63 vs WBI 59); the APBI group receiving chemotherapy had worse EOT fatigue (P = .011; APBI 43 vs WBI 49). The APBI group reported less pain (BCTOS) at EOT (WBI 2.29 vs APBI 1.97) but worse pain at 3 years (WBI 1.62 vs APBI 1.71). APBI patients reported greater convenience of care than with WBI and reported less symptom severity at EOT and 4 weeks later.Conclusion Cosmetic outcomes were similar for the APBI and WBI groups, with small statistically significant differences in other outcomes that varied over time. Differences in fatigue and other symptoms appeared to resolve by >= 6 months. APBI may be preferred by some patients, for whom extended treatment is burdensome.ClinicalTrials.gov NCT00103181.

PURPOSE Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.

Introduction: VT is often refractory to medical therapy and on rare but critical cases, even EP ablation. Despite investigation into endocardial, mesocardial and occasionally even epicardial ablation for these recalcitrant and deadly arrhythmias, there remains an inability to more effectively, non-invasively, treat VT. Hypothesis: We propose that, paralleling a Gamma Knife ® approach, the use of a novel MRI linear accelerator (MR Linac), the Unity ® (Elekta AB, Stockholm, Sweden), a proof of concept could be applied to highly selected pts with obstinate VT. Methods: A multi-center team with EP, Radiation Oncology and CMR (GE 1.5T) in joint development with Pittsburgh, PA and Utrecht, The Netherlands, developed a completely EP-CMR-guided method for non-invasive VT ablation utilizing S tereo T actic A rrhythmia R adioablation (STAR) with 25 Gy in a single fraction via MR Linac. Results: To evaluate deliverability and applicability of MR Linac plans, four IMRT per clinical scan were developed with varying delivery parameters (7A: 7-beams: 52 o in 70 segments (seg), 7B: 7-beams: 52 o in 100 seg, 15A: 15-beams: 24 o in 70 seg, and 15B: 15-beams: 24 o in 100 seg). We used a 0.2 cm dose grid and a 1% uncertainty via Monte Carlo ® dose calculation. Pt specific QA/QC used ArcCHECK ® (Sun Nuclear, FL) to evaluate individual IMRT plans. 3D CMR with LGE scar fusion for lesion integration guided non-invasive MR LinAc ablation. Accordingly, all IMRT plans were clinically acceptable (>97% of 7-beams and ≥98.0% of 15-beams in 3%/3mm gamma) for MR LinAc VT-ablation successfully with pt target effective arrhythmogenic myocardial ROI volume as ascertained via CMR of 63-99cm 3 . All 4 pts tolerated the 25±5min procedure without esophageal, pericardial or pro-arrhythmic complications and were alive at 30d FU with marked attenuation of VT burden. At 30d FU, no SAE's occurred to include pro-arrhythmias, pericardial effusions or esophageal fistulas. Conclusions: Refractory, complex and anatomically endocardially-remote VT has the potential to be curative, incorporating an analogous Gamma Knife ® approach via MR Linac radioablation heralding a migration to the Unity ® platform. This nearly first-in-man p r oof of concept approach may shepherd a new methodologic era into heretofore intractable VT.

508 Background: Preclinical studies report that T can boost RT effectiveness. The primary aim of this trial assessed the efficacy of concurrent T + RT vs RT alone in preventing recurrence of ipsilateral breast cancer, ipsilateral skin cancer, or ipsilateral DCIS (IBTR) in women with DCIS. Methods: Eligibility: Women ≥18 yrs, ECOG performance status 0 or 1, DCIS resected by lumpectomy, and clear margins. Whole-breast RT after randomization was with 25+ fractions or accelerated with 16-17 fractions. RT boost was allowed. Centralized HER2 testing and ER and/or PR were required before entry. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. T was given at 8 mg/kg IV within 1 wk before and 5 days after RT began (Dose 1) and at 6 mg/kg IV 3 wks after Dose 1 (Dose 2). Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events were recorded or when all accrued pts were on study for ≥5 yrs. Results: 2014 pts were randomized (11/9/08 to 12/8/14);1998 (99.2%) had follow-up information. Median follow-up time on 12/31/19 was 79.2 mos. 2001 pts had RT information, 1965 (98.2%) completed RT: 988 (98.3%) in the RT arm and 977 (98.1%) in the RT+T arm. 996 pts had T compliance information in the RT+T arm, 939 (94.3%) completed two doses of T, 25 (2.5%) had one dose of T, and 32 (3.2%) did not receive T. At primary definitive analysis, 114 IBTR events occurred: 63 in the RT arm and 51 in the RT+T arm (HR = 0.81 [95% CI: 0.56-1.17], p-value = 0.26). 38 were invasive: 18 in the RT arm and 20 in the RT+T arm (HR = 1.11 [95% CI: 0.59-2.10], p-value = 0.74). 76 were DCIS: 45 in the RT arm and 31 in the RT+T arm (HR = 0.68 [95% CI: 0.43-1.08], p-value = 0.10). Annual IBTR event rates were 0.99%/yr in the RT group and 0.80%/yr in the RT+T group. There were 288 events of any kind [iDFS-DCIS] (DFS): 155 in the RT arm and 133 in the RT+T arm (HR = 0.84 [95% CI: 0.66-1.05], p-value = 0.13) and 48 deaths: 26 in the RT arm and 22 in the RT+T arm (OS HR = 0.85 [95% CI: 0.48-1.51], p = 0.59). The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all pts having been on study for ≥5 years. Conclusions: The addition of T to RT did not achieve the protocol objective of 36% reduction in the IBTR rate but did achieve a modest, statistically non-significant reduction of 19%. Support: U10-180868, -180822, UG1-189867; Genentech. The authors thank Elaina Harper and Marlon Jones for data management. Clinical trial information: NCT00769379 .

Background Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation. Methods We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size <= 3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38.5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intentionto-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0.667 and 1.5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181. Findings Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the wholebreast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10.2 years (IQR 7.5-11.5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1.22, 90% CI 0.94-1.58). The 10-year cumulative incidence of IBTR was 4.6% (95% CI 3.7-5.7) in the APBI group versus 3.9% (3.1-5.0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group. Interpretation APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support wholebreast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women.

BackgroundConventionally fractionated and stereotactic body radiation therapy (SBRT) for thoracoabdominal tumors may utilize breath-hold techniques. However, there are concerns that differential amounts of inspired airflow may result in unplanned tumor dislocation and underdosing. Thus, we investigated tumor localization accuracy associated with lung volume variations during breath-hold treatment via an automated-gating interface.MethodsTwelve patients received breath-hold treatment with the active breathing coordinator (ABC) through an automated-gating interface. All breath-hold volumes were recorded at CT simulation, setup imaging, and during treatment, and analyzed as a function of airflow rate into the ABC. The variation of breath-hold volumes was calculated for each fraction over entire course. Intrafraction target motion related to the breathing variation was investigated based on daily imaging acquired before the breath-hold treatment. Correlation between target location and breath-hold variation was statistically analyzed.ResultsThe air volume held by the ABC increased as the airflow rate increased on inhalation and decreased on exhalation. The mean range of airflow rate was 0.77 L/s and 0.29 L/s in the conventionally fractionated and SBRT patients, respectively. The maximum air volume difference with respect to the reference volume at the CT simulation was 1.0 L for conventional fractionation and 0.16 L for SBRT. The target dislocation caused by 0.25 L of air volume difference was 6 mm for SBRT. Three patients showed significant correlation between the target location and breath-hold variations.ConclusionsThis investigation shows that because variations in the breath-hold volume may cause target dislocation, patient-specific breath-hold setting is required to improve tumor localization accuracy.

508 Background: PBI is an alternative to WBI, with potentially greater therapy (tx) compliance, and better integration with chemotherapy (CTX). NSABP B-39/RTOG 0413 clinical outcome results from 2018 did not show equivalence of PBI to WBI in local tumor control; PBI was statistically inferior, but with clinically small differences. PBI may be an acceptable alternative to WBI for some women. Understanding cosmesis and quality of life (QOL) treatment outcomes is important. Methods: B-39/0413 included a prospective QOL substudy with PRO evaluation of breast cancer treatment outcomes (cosmesis, function, pain) and fatigue using BCTOS and SF-36 vitality scales. Secondary QOL parameters included treatment related symptoms, perceived convenience of care, and the BPI pain scale. The study sample was stratified by CTX or not, as CTX is given before WBI but after PBI. PRO assessments occurred before randomization, the last day of adjuvant tx [CTX or radiation], 4 wks later, and 6, 12, 24, and 36 mo later. Primary aims included comparisons of change in fatigue from baseline to end of tx and equivalency of change in cosmesis from baseline to 36 mo for PBI v WBI. Separate analyses were done for CTX and non-CTX pts, controlling for axillary dissection. Each comparison used α=0.0125. Planned sample size was 964. Results: From 3-23-05 to 5-27-09, 975 pts were enrolled in the PRO study; 950 had follow-up data. 504 did not receive CTX and 446 received CTX. In non-CTX pts, PBI had less fatigue (p=0.011) and did not meet criteria for cosmesis equivalence (97.5% CI, -0.02 to 0.22; ∆=0.20). In CTX pts, PBI had worse fatigue (p=0.011) and equivalent cosmesis to WBI (97.5% CI, -0.09 to 0.21; ∆=0.24). In both groups, PBI pts reported less pain at end of tx. In non-CTX pts, PBI had more pain at 36 mo but in CTX pts, there was no difference. Convenience of care and treatment related symptom outcomes will be presented. Conclusions: In non-CTX pts, PBI is more convenient with less fatigue and slightly poorer cosmesis at 36 mo. Cosmesis was equivalent at 36 mo in CTX pts. Support: U10CA180868, -180822, UG1CA189867. Clinical trial information: NCT00103181.

e18563 Background: Oncology care represents the largest driver of medical cost in the US, projected to exceed $ 173 billion per year by 2020. Previous work has identified physician behavior as a variable that results in cost differences for similar patients. Here we test this hypothesis by examining claims data from 30 physicians at Allegheny Health Network (AHN), a large group practice enrolled in the OCM. Methods: We examined reimbursement data from 5 quarterly feedback reports from 4/1/16 – 6/30/17. 592 Medicare beneficiaries with a cancer diagnosis (per ICD10) and E&M code diagnosis requiring chemotherapy were included for 5 cancers: multiple myeloma, breast, lung, prostate and colorectal. Patient metrics such as diagnosis, total cost, admission costs and counts, ED visits, home health and hospice use, HCC (Hierarchical Condition Category) risk score and death were assessed with claim derived metrics such as chemotherapy price and attributed oncologist. Per Member Per Month (PMPM) rates were calculated for costs and admissions. Results: Hospital admissions and chemotherapy contributed 40.3% and 23.7% to total costs respectively. High costs and admission rates were seen in deceased patients ($ 11655 in deceased vs $ 3833 in living patients, p < 0.001; 0.44 vs 0.06 admissions per month in deceased versus living patients, p < 0.001). Home health (HH) and hospice (H) use in deceased patients were associated with lower total costs and admission rates compared to those who died without these services ($ 11331 with HH vs $ 12008 with no HH; $ 9692 with H vs $ 15109 with no H, p: 0.01). Admission costs ($ 3727 with H vs $ 9008 with no H, p 0.002) and ER visits (0.37 with H vs 0.82 with no H, p: 0.002) fell with hospice use. 36.44% and 47.83% of deceased patients did not receive hospice and home health services respectively. Weak correlation was found between HCC risk scores and total costs (r2= 0.41), chemotherapy costs (r2= 0.174) and ER visits (r2= 0.306). Conclusions: Admissions and chemotherapy are major cost drivers subject to variance in physician practice. Hospice and home health care services are underutilized in advanced disease. Weak correlations between HCC risk score and patient metrics suggest that factors besides disease type and severity drive cost and outcomes.

e18929 Background: There exists significant variation in lung cancer treatment depending on physician, payer and stage of disease without significant difference in survival or QoL (Quality of Life). We present a retrospective observational study of advanced stage non-small cell lung cancer (NSCLC) patients across Allegheny Health Network (AHN) to evaluate cost variation from a payer perspective. Methods: All stage III & IV NSCLC patients enrolled between Dec 2008-2012 with commercial or Medicare Advantage coverage, an AHN oncologist and claims data on or after the diagnosis date were reviewed. Patients were divided equally into four quartiles depending on PMPM (per member per month) cost. Total costs (inpatient, outpatient, labs, procedures, chemotherapy, radiation, imaging, etc.) per patient were calculated from diagnosis until disenrollment. Results: 166 patients were analyzed, 50 (30%) insured with commercial and 116 (70%) with Medicare Advantage. 102 patients were stage IV (61%), 24 were stage III B (14.4%) and 41 were stage IIIA (24.6%). Considerable variation in total per member (PM) cost was found between insurance products ($ 68,646 for commercial vs $ 47, 062 for Medicare Advantage) and among oncologists; spikes were seen near the end of life in all quartiles. The mean cost PM ranged from $ 3908 (Quartile 1) to $ 33,399 (Q 4). Each quartile consisted of patients in different stages with a majority of stage IV (31/102, 30%) in Q4 and stage IIIA in Q2 (15/ 41, 36.6%). Patients in Q4 had an average survival of 8 months whereas Q2 had 16 months. The majority of patients dying in the hospital were in Q4 (21/42, 50%) followed by Q3 (11/ 42, 26%). Non-trauma hospital admissions (34 % of total cost) and chemotherapy (39.7 % of total cost) were primary drivers of cost in both populations. Conclusions: Hospital admissions and chemotherapy were the major drivers of cost and are largely attributed to variation in provider practice patterns and insurance product. Our study provides a useful preliminary data for future investigation on the cost of care and budget impact in advanced stage NSCLC.

Purpose: The goal of this ongoing project is to develop and integrate a comprehensive electronic health record (EHR) throughout a multi-facility radiation oncology network to facilitate more efficient workflow and improve overall patient care and safety. Methodology: We required that the EHR provide pre-defined record and verify capability for radiation treatment while still providing a robust clinical health record. In 1996, we began to integrate the Local Area Network Treatment Information System (LANTIS®) across the West Penn Allegheny Radiation Oncology Network (currently including 9 sites). By 2001, we began modifying and expanding the assessment components and creating user-defined templates and have developed a comprehensive electronic health record across our network. Results: In addition to access to the technical record and verify information and imaging obtained for image-guided therapy, we designed and customized 6 modules according to our networks needs to facilitate information acquisition, tracking, and analysis as follows: 1) Demographics/scheduling; 2) Charge codes; 3) Transcription/clinical documents; 4) Clinical/technical assessments; 5) Physician orders 6) Quality assurance pathways. Each module was developed to acquire specific technical/clinical data prospectively in an efficient manner by various staff within the department in a format that facilitates data queries for outcomes/statistical analyses and promotes standardized quality guidelines resulting in a more efficient workflow and improved patient safety and care. Conclusions: Development of a comprehensive EHR across a radiation oncology network is feasible and can be customized to promote clinical/technical standards, facilitate outcomes studies, and improve communication and peer review. The EHR has improved patient care and network integration across a multi-facility radiation oncology system and has markedly reduced the flow and storage of paper across the network.

360 Background: We report on the outcome and toxicity of liver SBRT alone or in combination with surgery for inoperable primary and metastatic liver tumors. Methods: Patients with up to four isolated hepatic metastases (sum of tumor diameters ≤ 8cm) and individual tumor diameter ≤ 9 cm received SBRT at 46.8Gy ± 3.7 in 4-6 fractions. In patients with hepatic cirrhosis, liver dose constraints were imposed exclusively on residual functional liver volume defined on SPECT during SBRT treatment planning. The primary end point was local control with at least 6 months of radiographic followup, and secondary end points were toxicity and survival. Results: Between 2007-2014, 120 lesions in 91 patients with either unresectable primary (n = 43) or metastatic liver cancer (n = 48) completed liver SBRT to 36-60 Gy delivered in 4 to 6 treatment fractions, with a mean BED of 197 Gy3 (range 108 – 300 Gy3). Median followup was 20.3 months (range 1.9 - 64.1). Fourteen patients underwent liver transplant with SBRT as a bridging therapy or for tumor downsizing. Eight patients completed hepatic resections in combination with planned SBRT for unresectable tumors. Two-year local control was 96% for hepatoma and 93.8% for metastases; it was 100% for lesions ≤ 4cm. Ten of 14 transplanted patients developed complete pathological response with median time to transplant of 5.7 months (range 1.7 – 23.3). No incidence of grade > 2 treatment toxicity was observed. There was no accelerated Child-Pugh class migration from A to B or from B to C. There were no operative or perioperative complications in patients who received SBRT prior to liver transplant or in combination with planned hepatectomy. Two-year overall survival was 82.3% (hepatoma) and 64.3% (metastases). Conclusions: In this retrospective analysis we demonstrate that liver SBRT alone or in combination with surgery is safe and effective for the treatment of isolated inoperable hepatic malignancies and provides excellent local control rates with minimal toxicity.

639 Background: Systemic therapy combined with surgery may prolong survival of patients with isolated hepatic metastases from CRC, however, only 10-25% are resectable. We applied a Markov model to estimate and compare cost effectiveness for the two competing treatments of SBRT and RFA in management of unresectable isolated hepatic metastases. Methods: We developed a multistate Markov decision model with probabilistic sensitivity analysis to simulate a randomized controlled trial for SBRT and RFA and compare respective cost effectiveness (in dollars per quality adjusted life years, or QALY). Model assumptions were based on extensive literature search of utilities and recurrence risks, including published data from our institution. Costs were taken from the 2013 Medicare reimbursement tables. In order to reflect reported patient selection variability across literature, two mortality rates due to hepatic metastases were considered for both treatment modalities: 50% probability of death in 1.5 years and 60% in 5 years. Sensitivity analysis was performed to model uncertainty in these parameters. Results: For patients with 5-year life expectancy, Markov cohort analysis demonstrated QALY-adjusted survival advantage of SBRT over RFA with QALY 4.35 vs. 3.89 respectively. This difference was marginal for patients with 1.5-year life expectancy. Physician-hour involvement was less in SBRT group. The incremental cost adjusted effectiveness (Cost/QALY) for SBRT over RFA was $2,379 in the 5-year life expectancy cohort, and $2,216 for SBRT over RFA in the 1.5-year cohort. Sensitivity analysis demonstated robustness of these results across a range of utility values, costs, recurrence rates, and procedure-related morbidity. Conclusions: In comparison to RFA, SBRT was more cost-effective modality for unresectable or potentially resectable hepatic metastases over a wide range of treatment and disease assumptions, including recurrence rates, and procedure-related morbidity. Additionally, SBRT is a relatively fast outpatient procedure requiring less physician-hour involvement.

Purpose The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. Patients and Methods Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m 2 , 5 days per week), with or without intravenous oxaliplatin (50 mg/m 2 once per week for 5 weeks) or oral capecitabine (825 mg/m 2 twice per day, 5 days per week), with or without oxaliplatin (50 mg/m 2 once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). Results From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). Conclusion Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred.

Objectives: To retrospectively compare radiation toxicity in patients treated with concurrent anastrozole and whole breast irradiation versus women treated sequentially with whole breast irradiation followed by hormonal suppression. Methods: The records of 249 consecutive estrogen or progesterone receptor positive breast cancer patients treated with breast-conserving surgery and postoperative whole breast irradiation were reviewed. Of total, 57 patients (the concurrent anastrozole group) received concurrent anastrozole prior to and during radiotherapy. In 126 patients (the sequential group), adjuvant hormone suppression therapy (anastrozole, other aromatase inhibitors, or tamoxifen) was administered after the completion of breast irradiation. In 66, women either concurrent tamoxifen was given with radiation or the sequence of hormonal therapy was not known. These women were excluded from the analysis. Results: The frequency of acute grade 2 radiation dermatitis (24.6% in the concurrent anastrozole group vs. 20.6% in the sequential group; P = 0.55), grade 3 radiation dermatitis (8.8% vs. 7.1%; P = 0.77) and treatment interruptions due to skin reactions (14.0% vs. 11.2%; P = 0.69) did not differ between groups. The rates of clinically detectable breast fibrosis were not different (24.2% vs. 24.7%; P = 0.97). With a median follow-up of 28 months and 30.8 months, respectively, 1 local failure occurred in the concurrent anastrozole group and 5 in the sequential group. Conclusions: Anastrozole, administered concurrently with whole breast irradiation, did not increase acute or late morbidity when compared with sequential administration of radiation and hormonal suppression therapy.

Merkel's cell carcinoma is a rare cutaneous tumor that can affect a wide variety of sites throughout the body. Commonly, it affects the skin alone and the management of limited disease can be confusing since the natural history of the disease involves distant metastasis. Traditional management has required wide local excision with negative margins of resection. We describe a case treated with local therapy alone and review the literature to suggest that complete microscopic excision may not be required if adjuvant radiotherapy is used.

PURPOSE: To compare brachytherapy and three-dimensional (3-D) conformal external beam radiotherapy for breast cancer presenting in the previously irradiated breast.METHODS AND MATERIALS: Thirty-six patients with TIS-T2 breast carcinomas received brachytherapy or 3-D conformal radiotherapy (3-D CRT) after lumpectomy in a previously irradiated breast as an alternative to salvage mastectomy. Brachytherapy consisted of low-dose-rate (LDR) interstitial technique in 21 patients, whereas 11 patients were treated using high-dose-rate (HDR) balloon technique. Four patients received 3-D CRT. Cosmesis was graded according to the Harvard criteria and the Allegheny General Modification of the Harvard criteria. Acute sequelae were graded according to the Common Terminology Criteria for Adverse Events (version 3.0).RESULTS: Thirty-five of 36 patients remained free of local failure, with a mean followup of 37 months. Five patients treated with LDR developed Grade IT and two developed Grade 111 acute side effects. No patient treated with balloon brachytherapy or 3-D CRT developed a Grade II or higher acute effect. Cosmetically, 12 LDR interstitial patients were scored as Grade 1, six as Grade II, and three as Grade III. Nine of the HDR patients were scored as Grade 1, one as Grade II, and one as Grade III. Two 3-D CRT patients were scored as Grade II and two as Grade III. The Allegheny Modification of the Harvard criteria more accurately reflected the cosmetic effects of re-treatment.CONCLUSION: Brachytherapy is feasible for patients who desire breast preservation in a previously irradiated breast. All techniques demonstrated similar local control rates. Acute side effects were less, and cosmesis was superior in HDR balloon brachytherapy. (C) 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Purpose: Electron or photon boost immediately following whole-breast irradiation performed after conservation surgery for early-stage breast cancer is the accepted standard of care. This regimen frequently results in Grade HI dermatitis, causing discomfort or treatment interruption. Herein, we compare patients treated with whole-breast irradiation followed by boost compared with a cohort with a planned intercurrent radiation boost.Methods and Materials: The records of 650 consecutive breast cancer patients treated at Allegheny General Hospital (AGH) between 2000 and 2008 were reviewed. Selected for this study were 327 patients with T1 or T2 tumors treated with external beam radiotherapy postlumpectomy. One hundred and sixty-nine patients were treated by whole-breast radiotherapy (WBRT) followed by boost at completion. One hundred fifty-eight were treated with a planned intercurrent boost (delivered following 3,600 cGy WBRT). The mean whole breast radiation dose in the conventionally treated group was 5,032 cGy (range, 4500-5400 cGy), and the mean whole breast dose was 5,097 cGy (range, 4860-5040 cGy) in the group treated with a planned intercurrent boost.Results: The occurrence of Grade HI dermatitis was significantly reduced in the WBRT/intercurrent boost group compared with the WBRT/boost group (0.6% vs. 8.9%), as was the incidence of treatment interruption (1.9% vs. 14.2%). With a median follow-up of 32 months and 27 months, respectively, no significant difference in local control was identified.Conclusions: Patients treated with intercurrent boost developed less Grade III dermatitis and unplanned treatment interruptions with similar local control. (C) 2010 Elsevier Inc.