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Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. (c) 2021 Elsevier Inc. All rights reserved.

Objective To identify pretreatment variables associated with the development of acute vestibular symptoms after Gamma Knife (GK) treatment for Vestibular Schwannoma (VS). Study design Retrospective case series. Setting Tertiary neurotology referral center. Patients Patients treated with GK radiosurgery for VS between March 2007 and March 2017 were considered for this study. Patients with neurofibromatosis type II, previous VS surgery, follow-up less than 6 months, or the lack of T2 magnetic resonance imaging (MRI) sequences from the day of treatment were excluded. Main outcome measures The presence of acute vestibular symptoms arising within 6 months after GK was the main outcome variable. Tumor, patient, and treatment characteristics were gathered from the medical record. Results In total, 98 patients met inclusion criteria. The incidence of acute vestibular symptoms occurring within 6 months after GK treatment was 46.9%. Post-GK vestibular symptoms were reported at a significantly higher frequency among subjects who had reported vestibular symptoms before their treatment (p = 0.001). Tumor size was not associated with a propensity to develop acute vestibular symptoms (p = 0.397). The likelihood of receiving a referral to vestibular rehabilitation services was not significantly different among patients with larger versus smaller tumor size, as defined by 1.6 cm and 1.4 cm thresholds (p = 0.896, p = 0.654). Conclusions Inquiries aimed at revealing a history of vestibular complaints may prove useful in counseling patients on the likelihood of experiencing acute vestibular symptoms after treatment of Vestibular Schwannoma with Gamma Knife therapy.

OBJECTIVE Assess inner ear radiation dose magnitude as it relates to fundal cap length and hearing outcomes in the radiosurgical treatment of vestibular schwannoma. STUDY DESIGN Retrospective case series. SETTING Tertiary neurotology referral center. PATIENTS Patients treated with Gamma Knife radiosurgery for vestibular schwannoma between March 2007 and March 2017 were considered for this study. Exclusion criteria included pretreatment pure-tone average (PTA) >90 dB, neurofibromatosis type II, history of previous surgical resection, and follow-up less than 1 year. MAIN OUTCOME MEASURE (s): Hearing function was assessed by maintenance of class A/B hearing level and maintenance of baseline hearing (≤20 dB change in PTA following Gamma Knife radiosurgery). RESULTS Lower radiation doses delivered to the inner ear were associated with longer fundal cap lengths: mean cochlear dose (r = -0.130; p = 0.184), mean labyrinth dose (r = -0.406; p

Objective To evaluate the relationship between fundal fluid and hearing outcomes after treatment of vestibular schwannoma (VS) with Gamma Knife radiosurgery (GKRS). Study design Retrospective case series. Setting Tertiary neurotology referral center. Patients Patients treated with GKRS for vestibular schwannoma between March 2007 and March 2017 were considered for this study. Exclusion criteria included pretreatment pure-tone average (PTA) >90 dB, neurofibromatosis type II, history of previous surgical resection, and follow-up less than 1 year. Main outcome measure(s) Hearing function was assessed both by preservation of serviceable hearing and by preservation of baseline hearing (≤20 dB change in PTA) after GKRS. Hearing preservation comparisons were made between groups of patients with and without a fundal fluid cap. Results Patients with a fundal cap had significantly higher rates of baseline hearing preservation (≤20 dB change in PTA) according to Kaplan-Meier survival analysis of all 106 patients (p = 0.006). By the 3rd year posttreatment, 70.9% of patients with a fundal cap had maintained a ≤20 dB change in PTA, while only 43.6% of patients without a fundal fluid cap achieved this outcome (p = 0.004). Conclusions Fundal fluid present on pretreatment magnetic resonance imaging is predictive of improved baseline hearing preservation rates in patients undergoing GKRS for vestibular schwannoma when considering all patients with PTA ≤90 dB. Fundal fluid cap presence may serve as a favorable prognostic indicator to help set hearing expectations and guide patient selection efforts.

BackgroundPulsed radiation therapy (PRT) has shown effective tumor control and superior normal-tissue sparing ability compared with standard radiotherapy (SRT) in preclinical models and retrospective clinical series. This is the first prospective trial to investigate PRT in the treatment of patients with newly diagnosed glioblastoma (GBM).MethodsThis is a single-arm, prospective study. Patients with newly diagnosed GBM underwent surgery, followed by 60 Gy of PRT with concurrent temozolomide (TMZ). Each day, a 2-Gy fraction was divided into ten 0.2-Gy pulses, separated by 3-minute intervals. Patients received maintenance TMZ. Neurocognitive function (NCF) and quality of life (QoL) were monitored for 2 years using the Hopkins Verbal Learning Test‒Revised and the European Organisation for Research and Treatment of Cancer QLQ-C30 QoL questionnaire. Change in NCF was evaluated based on a minimal clinically important difference (MCID) threshold of 0.5 standard deviation.ResultsTwenty patients were enrolled with a median follow-up of 21 months. Median age was 60 years. Forty percent underwent subtotal resection, and 60% underwent gross total resection. One patient had an isocitrate dehydrogenase (IDH)–mutated tumor. Median progression-free survival (PFS) and overall survival (OS) were 10.7 and 20.9 months, respectively. In a post-hoc comparison, median OS for the prospective cohort was longer, compared with a matched cohort receiving SRT (20.9 vs 14 mo, P = 0.042). There was no decline in QoL, and changes in NCF scores did not meet the threshold of an MCID.ConclusionsTreatment of newly diagnosed GBM with PRT is feasible and produces promising effectiveness while maintaining neurocognitive function and QoL. Validation of our results in a larger prospective trial warrants consideration.

There is limited retrospective evidence addressing the utility of post-mastectomy radiotherapy (PMRT) in patients with T3N0 breast cancer. We performed a retrospective analysis of the National Cancer Database (NCDB) comparing overall survival (OS) in T3N0 patients treated with mastectomy alone (MTX) or with PMRT.We performed a matched-cohort analysis of NCDB breast cancer patients with pT3N0 disease who did not receive NAC, or cT3N0 patients who received NAC treated between 2006 and 2014. Patients were matched for all available baseline characteristics using propensity scores with inverse probability of treatment weighting (IPTW) with stabilized weights.We identified 13,901 eligible patients. In the pT3N0 cohort, median follow-up was 47 months for the MTX group and 50 months for the PMRT group. In the cT3N0 cohort, median follow-up was 44 months for the MTX group and 46 months for the PMRT group. OS was higher in pT3N0 patients treated with PMRT compared to MTX: 7-year OS of 74% vs. 65% (P 0.001). Doubly robust multivariable analysis showed an association between PMRT and improved OS (HR 0.78, 95% CI 0.68-0.89, P 0.001). There was no benefit to PMRT in patients who received adjuvant chemotherapy (AC). In the NAC cohort, PMRT did not change OS, with 7-year OS of 78% with MTX and 79% with PMRT. There was a trend of improved OS with PMRT in patients with residual disease in the breast and lymph nodes (HR 0.70, 95% CI 0.46-1.07).PMRT improves OS in patients with pT3N0 disease, but the benefit appears limited to those who do not receive AC. PMRT does not improve OS in patients with cT3N0 disease who receive NAC, but there might be a benefit in patients with a poor response to chemotherapy. However, longer follow-up may be needed to make a definitive conclusion about the benefit of PMRT in patients who receive chemotherapy.

Recent retrospective studies suggest improved overall survival (OS) with breast conserving therapy (BCT), including breast conserving surgery and adjuvant whole breast radiotherapy, compared to mastectomy in the modern era. The patient subset most likely to benefit from BCT remains unclear, and the role of Oncotype DX Recurrence Score (RS) in this context is unknown. We compared BCT to mastectomy in early-stage, node-negative breast cancer. We further explored outcomes after stratification by RS and age.We performed a matched-cohort analysis of National Cancer Database (NCDB) patients with pT1-2, pN0, cM0 breast cancer treated between 2006 and 2014 with BCT or mastectomy. Patients were matched for all available baseline characteristics using propensity scores with inverse probability of treatment weighting (IPTW) with stabilized weights.We identified 144,263 eligible patients treated with BCT and 87,379 patients treated with mastectomy. After IPTW-matching, OS was higher with BCT compared to mastectomy: 5-year OS of 94.4% vs. 91.8% (P 0.001) and 7-year OS of 90% vs. 85.2% (P 0.001). Doubly robust multivariable analysis showed an association between BCT and improved OS (HR 0.66, 95% CI, 0.64-0.69, P 0.001). In a subset analysis, BCT was associated with improved OS in patients with RS25, but not patients with RS ≤25. When stratified by age, only patients50 years had improved OS with BCT.BCT is associated with improved OS compared to mastectomy in women with early-stage, node-negative breast cancer. The improvement in OS with BCT appears to be most pronounced in patients with high RS and50 years of age. Prospective validation of these findings is required.

Background The long-term risk of necrosis after radiosurgery for brain metastases is uncertain. We aimed to investigate incidence and predictors of radiation necrosis for individuals with more than 1 year of survival after radiosurgery for brain metastases. Methods Patients who had a diagnosis of brain metastases treated between December 2006 and December 2014, who had at least 1 year of survival after first radiosurgery were retrospectively reviewed. Survival was analyzed using the Kaplan-Meier estimator, and the incidence of radiation necrosis was estimated with death or surgical resection as competing risks. Patient and treatment factors associated with radiation necrosis were also analyzed. Results A total of 198 patients with 732 lesions were analyzed. Thirty-four lesions required salvage radiosurgery and 10 required salvage surgical resection. Median follow-up was 24 months. The estimated median survival for this population was 25.4 months. The estimated per-lesion incidence of radiation necrosis at 4 years was 6.8%. Medical or surgical therapy was required for 60% of necrosis events. Tumor volume and male sex were significant factors associated with radiation necrosis. The per-lesions incidence of necrosis for patients undergoing repeat radiosurgery was 33.3% at 4 years. Conclusions In this large series of patients undergoing radiosurgery for brain metastases, patients continued to be at risk for radiation necrosis throughout their first 4 years of survival. Repeat radiosurgery of recurrent lesions greatly exacerbates the risk of radiation necrosis, whereas treatment of larger target volumes increases the risk modestly.

The appropriateness of substituting sentinel lymph node dissection (SLND) and regional nodal irradiation (RNI) for axillary lymph node dissection (ALND) in patients with residual lymph node (LN) disease following neoadjuvant chemotherapy (NAC) is unknown. We used the National Cancer Database (NCDB) to compare survival following SLND and ALND in breast cancer patients with residual LN disease. We analyzed NCDB patients, treated between 2006 and 2014, with cT1–3, cN1, cM0 breast cancer and residual disease in 1–3 axillary LNs (ypN1) following NAC. Patients were grouped into those who received SLND (defined as removal of ≤ 4 LNs) and RNI, or ALND and RNI. Patients were matched for all patient, tumor, and treatment characteristics. We identified 1313 eligible patients in the ALND group and 304 patients in the SLND group. For the matched cohorts, SLND was associated with significantly lower survival in both univariate and doubly robust multivariable analyses (MVA) (HR 1.7, 95% CI 1.3–2.2, P

Purpose/Objective(s) Though microsurgery remains the most common method for management of acoustic neuromas (ANs), stereotactic radiosurgery continues to be a promising alternative. This study assesses long-term quality of life (QOL) outcomes and changes in hearing acuity in patents who have undergone single fraction Gamma Knife stereotactic radiosurgery (GKSRS) for AN. Materials/Methods Prospective QOL outcomes were collected and analyzed to include Hearing Handicap Inventory (HHI), Dizziness Handicap Inventory (DHI), Tinnitus Handicap Inventory (THI), and 36-Item Short-Form Survey (SF-36) scores. Likewise, audiometric outcomes including speech discrimination (SD) and pure-tone average (PTA) were assessed. These data points were collected prior to and following GKSRS at regular intervals up to 5 years post-treatment. A mixed effects model for repeated measures was employed to assess QOL data for statistical significance. Results A total of 235 patients underwent GKSRS for AN at our institution from January 2007 to January 2017. Of these, 130 patients had available QOL and audiometric follow-up data and were included in this study. Median age was 60 y and median follow-up time was 36 mo. Median tumor size was 1.6 cm (0.1 - 3.6 cm), with median tumor volume of 0.552 cm3 (0.028 - 11.31 cm3), while median cochlear mean dose was 2.4 Gy (0 - 9.7 Gy). Baseline mean (median) HHI, DHI, THI, and SF-36 scores were 31.7 (28), 19.3 (12), 18.2 (12), and 70.0 (73.4) respectively. For each of these QOL metrics, mixed effects analysis indicated no statistically significant decline at any time point out to 5 years post-treatment. Indeed, 87% of patients had baseline SD and PTA scores available; 70% had follow-up SD and PTA available. Of these, 59% had baseline serviceable hearing (Gardner-Robertson score of I or II). Serviceable hearing was preserved in 71% of patients at 1 month, 79% at 6 months, 79% at 12 months, 62% at 18 months, 67% at 24 months, and 68% at 36 months. Conclusion GKSRS provides long-term maintenance of QOL in the treatment of AN. HHI, DHI, THI, and SF-36 scores showed no significant decline up to 5 years post-radiosurgery. Patients with baseline serviceable hearing exhibited adequate hearing preservation. Author Disclosure J.S. Lee: None. K.C. Lee: Royalty; Regents of the University of Michigan. Patent/License Fees/Copyright; Regents of the University of Michigan. D. Bojrab: None. P.Y. Chen: Stock; Greater Michigan Gamma Knife (GMGK). J. Jacob: None. I.S. Grills: Greater Michigan Gamma Knife.

Purpose/Objective(s) Accelerated partial breast irradiation (APBI) can reduce treatment time and spare normal breast tissue. Techniques for APBI include applicator-based, external beam radiotherapy (EBRT), intra-operative radiotherapy (IORT), and interstitial implant-based. Data comparing these various APBI modalities and associated outcomes are lacking in the literature. We conducted a single-institution retrospective analysis of patients treated with APBI to compare treatment techniques and report outcomes. Materials/Methods Patients treated with APBI between 1990 and 2019 were included. Baseline patient characteristics, clinical and pathological features, treatment details, and clinical outcomes were retrospectively reviewed using a single-institution database. Outcomes were updated through August 2020. Statistical methods included Kruskal-Wallis test, Fisher's exact test, chi-square test of independence, and Kaplan-Meier analysis. Results A total of 926 APBI cases were analyzed, a majority of which were invasive ductal carcinoma (50.6%). Comparing applicator-based to EBRT, IORT, and implant-based, there was no difference in overall survival, freedom from local recurrence, or freedom from mastectomy (Table 1). 5-, 10-, and 25-year cumulative incidence of ipsilateral breast tumor recurrence (IBTR) was 1.5% (0.87-2.5%), 3.3% (2.3-4.7%), and 5.2% (3.9-6.7%), with no difference between treatment techniques. The median follow-up time was 121.6 months (66-165.7 months). Cosmesis was good/excellent in 91%, 84%, and 93%, for applicator, EBRT, and interstitial techniques, respectively. Late toxicities assessed included pigmentary changes, telangiectasias, induration/fibrosis, and fat necrosis. The majority of late toxicities were none or Grade 1, with less than 10% of patients experiencing Grade 2 or greater toxicity. Conclusion With our 30-year single-institution APBI experience using various treatment techniques, long term outcomes of both disease control and local morbidity demonstrate that the various APBI techniques are equally effective for suitable early-stage breast cancer patients. As evolving radiotherapy paradigms incorporate more shortened time-course treatments, these results affirm that APBI remains a viable alternative for such favorable patients.

PURPOSE/OBJECTIVE(S) Definitive chemoradiation for HPV-positive oropharyngeal squamous cell carcinoma (HPV+ OPC) is associated with high cure rates, but also with significant patient morbidity. Using previously described techniques to create heterogenous radiotherapy dose level selection, combined with data from patients followed by serial FDG-PET/CT during definitive chemoradiation, we generated hypothetical adaptive radiation plans with the goal of decreasing dose to normal tissues while maintaining equivalent local control. MATERIALS/METHODS Five patients with HPV+ OPC enrolled on a prospective single-institution protocol with serial FDG-PET/CT imaging during the course of definitive chemoradiation were analyzed. Two radiotherapy plans were then generated for each patient: one in which gross disease was prescribed a uniform dose of 60 Gy, and a second using adaptive tumor response to progressively reduce the prescription dose to gross disease in a heterogenous fashion. Voxel-level changes in FDG avidity were combined with a previously described tumor voxel control probability model to guide dose de-escalation in radiosensitive regions of tumor while maintaining equivalent local control. Dose accumulation to nearby organs at risk (OARs), incorporating changes due to progressive de-escalation, were then compared for the two sets of plans using the paired samples Wilcoxon test. RESULTS The de-escalated plans created using voxel-level tumor response resulted in treatment plans with significantly reduced dose to all evaluated OARs. Significant improvements included a decreased spinal cord maximum dose, brainstem maximum dose, parotoid gland mean dose, constrictor muscle mean and maximum dose, and mandible maximum dose (P = 0.03). Projected tumor control probability remained high, despite de-escalation of dose in PET-sensitive areas of gross disease. CONCLUSION Adaptive FDG-PET response can be used to guide de-escalation to reduce dose to nearby OARs. Using a novel technique for dose selection based on voxel-level tumor response, heterogeneous de-escalation can further reduce toxicity while maintaining optimal local control in most patients with HPV+ OPC. This concept will be used to design a non-randomized prospective trial investigating the role of heterogeneous de-escalation in this patient population.

Purpose/Objective(s) Shorter courses of breast radiotherapy are offered as an alternative to 4-6 weeks of whole breast irradiation after lumpectomy, including brachytherapy. A prospective phase II multi-institution clinical trial to study 3-fraction accelerated partial breast irradiation (APBI) delivered by brachytherapy was conducted. Materials/Methods The trial treated selected breast cancers after breast-conserving surgery with brachytherapy applicators that delivered 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 2 cm beyond the surgical cavity. Eligible women were age ≥ 45 years with unicentric invasive or in situ tumors ≤ 3 cm excised with negative margins and with positive estrogen or progesterone receptors and no metastases to axillary nodes. Strict dosimetric parameters were required to be met and follow up information was collected from the participating sites. Results A total of 175 patients who were enrolled were followed for a median of 3.63 years. Three-fraction brachytherapy was associated with low chronic toxicity. There was excellent or good cosmesis in 95% of patients. There were no grade 4 toxicities. Grade 3 fibrosis at the treatment site was present in 1.7% and 32% percent had grades 1 or 2 fibrosis at the treatment site. There was 1 rib fracture. Other late toxicities included 7.4% grade 1 hyperpigmentation, 2% grade 1 telangiectasias, 1.7% symptomatic seromas, 1.7% abscessed cavities, and 1.1% symptomatic fat necrosis. There were 2 (1.1%) ipsilateral local recurrences, 2 (1.1%) nodal recurrences and no distant recurrences. Other incidents included one contralateral breast cancer and 2 second malignancies (lung). Conclusion Ultra-short breast brachytherapy is feasible and with acceptable late toxicity and could be an alternative to standard 5-day, 10 fraction APBI in eligible patients. Patients from this prospective trial will continue to be followed to evaluate long term outcomes.

PURPOSE/OBJECTIVE(S) There is mixed and limited scientific evidence regarding radiotherapy (RT) tolerance in carriers of a pathogenic, germline ATM variant. The ASTRO-ASCO-SSO guidelines on management of hereditary breast cancer suggest offering RT to these patients if clinically indicated. We investigate RT toxicity for carriers of either a pathogenic ATM variant, or variant of unknown significance (VUS), in ATM. MATERIALS/METHODS Patients with a breast cancer history who had hereditary genetic testing and were found to carry either a pathogenic variant or VUS in ATM were identified. For those who received RT at our institution, toxicity metrics were recorded including dermatitis (scored per CTCAE version 4.0), moist desquamation, and cosmetic outcome (scored per Harvard scale). Fisher's exact test for count data was performed to compare toxicity between the two cohorts. Wilcoxon rank-sum testing was performed to assess for differences in cohort patient characteristics. RESULTS Forty-four carriers of a pathogenic ATM variant, and 163 carriers of an ATM VUS, were identified. Fifteen pathogenic and 56 VUS patients, respectively, received RT at our institution and had available toxicity records. The cohorts did not statistically differ in race, medical comorbidities, clinical or pathologic T-stage, hormone receptor status, receipt of chemotherapy, fractionation schedule, or receipt of a boost. No patients had a known collagen vascular disease. 77% of patients (55/71) had breast conservation. 62% received whole breast RT, 7% received chest wall RT, 4.2% received partial breast RT, and 26.8% received whole breast or chest wall RT with regional nodal RT. 58% received conventionally-fractionated RT, and 38% received hypofractionated RT. Median toxicity follow up was 11.6 months. 29% (4/15) of pathogenic carriers and 26.4% (14/56) of VUS carriers developed moist desquamation (P = 0.7). The rates of grade 2+ acute dermatitis were 71% in pathogenic carriers and 57% in VUS carriers (P = 0.4). 100% of pathogenic carriers and 91% of VUS carriers had a good/excellent cosmetic outcome at first follow up (P > 0.9). No patients with a pathogenic variant had a fair or poor cosmetic outcome at last follow up. CONCLUSION RT is well tolerated in carriers of a pathogenic ATM variant, with rates of grade 2+ dermatitis and moist desquamation comparable to a matched VUS cohort. High rates of good or excellent cosmetic outcome were seen following treatment. Further analyses including an ATM wild type cohort and continued detailed toxicity documentation/analysis is on-going to elucidate longer term morbidity.

PURPOSE/OBJECTIVE(S) Post-mastectomy radiotherapy (PMRT) improves survival in appropriately selected patients but is associated with a risk of unplanned surgery (US) and implant loss (IL) due to the impact of radiation on skin integrity, infection risk, contracture, and cosmetic outcome. If reliable dosimetric correlates for these outcomes can be found, optimization during radiation treatment planning may be useful to reduce their occurrence. We hypothesize that near-surface dosimetry predicts for increased US and IL risk. MATERIALS/METHODS Patients who received PMRT at a single institution from 2016-2019 were retrospectively analyzed. Demographic, clinical, and treatment parameters were reviewed. Three structures were retrospectively generated, encompassing the volumes bound by 0-3 mm (SR3), 0-5 mm (SR5), and 5-10 mm (SR10) from the skin surface. Dose volume histograms (DVHs) were exported for analysis. Univariate (UVA) and multivariate analyses (MVA) were used to identify predictors of US and IL among demographic and treatment variables. Dosimetric analysis was performed to determine candidate dose constraints for SR3, SR5, and SR10. Clinical variables included age, smoking history, hypertension, diabetes, body mass index (BMI), menopause status, TNM stages with total and positive lymph nodes as continuous variables, receptor status, margin status, type of lymph node surgery, reconstruction type, mastectomy type, and receipt of chemotherapy, trastuzumab, or hormone therapy. RESULTS Of 126 patients reviewed, 109 were analyzable. Median follow up was 2.3 years. Twenty-five patients (23%) underwent US, 10 (9.2%) of whom experienced IF. Among clinical variables, BMI significantly predicted for US on UVA and MVA. There were no significant predictors of IF per se. Dosimetric analysis in 2 Gy intervals identified V44 Gy < 81% to SR3 (AUC 0.711) or V44 Gy < 83% to SR5 (AUC 0.685) as potentially useful for predicting US. V44 Gy remained a significant predictor of US when included on MVA. There were no significant dosimetric parameters using SR10. CONCLUSION Near-surface dosimetry is useful to predict US following PMRT. V44 Gy < 81% to SR3 should be further explored as a constraint for treatment planning optimization. The absence of significant predictors for IF is likely due to a paucity of events in this cohort.

Objective Needlestick and sharp injuries (NSIs) experienced by physicians have been identified as a major occupational hazard. Blood-borne pathogens resulting from the NSIs experienced by physicians pose severe physical and psychological threats to them, as well as people who are around them. However, there is little research focusing on physicians’ behaviours to prevent NSIs. In the present study, we investigated the roles of safety climate, job demands experienced by physicians, and physicians’ self-efficacy in affecting physicians’ behaviours to prevent NSIs. Methods 401 physicians from four teaching hospitals in Northern Taiwan were recruited to participate in an anonymous survey. Among them, 189 physicians returned the completed survey with a response rate of 47.1%. Results Overall, respondents reported frequently engaging in NSI prevention behaviours. As expected, safety climate in hospitals and physicians’ self-efficacy to prevent NSIs were significantly related to their behaviours to prevent NSIs (r = 0.22 and r = 0.33, respectively). The moderating analysis also revealed that physicians with high self-efficacy tended to engage in NSI prevention behaviours regardless of levels of job demand they experienced. In contrast to our expectation, however, physicians with low self-efficacy engaged in more NSI prevention behaviours when job demands were high than when the demands were low. Conclusions Our findings show the important roles safety climate, job demands and self-efficacy play in shaping physicians’ NSI prevention behaviours. Hospitals may consider improving safety climate via strengthening management commitments to NSIs prevention, reducing job demands by training physicians to proactively redesign their own jobs, and increasing physicians’ self-efficacy via well-designed skill-based training.

BACKGROUND Using a prospectively collected institutional database, we compared rectal toxicity following high dose rate (HDR) brachytherapy as monotherapy relative to dose-escalated external beam radiotherapy (EBRT) for patients with localized prostate cancer. METHODS 2683 patients treated with HDR or EBRT between 1994 and 2017 were included. HDR fractionation was 38 Gy/4 fractions (n = 321), 24 Gy/2 (n = 96), or 27 Gy/2 (n = 128). EBRT patients received a median dose of 75.6 Gy in 1.8 Gy fractions [range 70.2-82.8 Gy], using either 3D conformal or intensity modulated radiotherapy (IMRT). EBRT patients underwent 3D image guidance via an off-line adaptive process. RESULTS Median follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 545 patients (20.3%) received HDR brachytherapy and 2138 (79.7%) EBRT. 69.1% of EBRT patients received IMRT. Compared to EBRT, HDR was associated with decreased rates of acute grade ≥2 diarrhea (0.7% vs. 4.5%, p

Purpose We examined the distribution of pretreatment nodal metastases to the level I axilla (Ax-L1) to assess the appropriateness of current breast atlases and provide guidelines in relationship to easily identifiable anatomic landmarks for accurate delineation of this lymph node (LN) basin. Methods and Materials Patients with newly diagnosed breast cancer and biopsy-proven metastatic Ax-L1 LNs were identified. We related the location of each LN to its most adjacent rib and its distance from the bottom of the humeral head, axillary vessels, and a line connecting the anterior aspects of the pectoralis and latissimus dorsi muscles (P-L line). LNs were mapped onto a representative planning computed tomography scan, and their distribution was used to validate the current Radiation Therapy Oncology Group, European Society for Radiotherapy and Oncology, and Radiotherapy Comparative Effectiveness breast atlases. Furthermore, we examined metastases to a subregion encompassing the superolateral Ax-L1, irradiation of which correlates highly with lymphedema. Results We identified 106 eligible patients with 107 biopsied LNs. All LNs fell between the second and fifth ribs (mean, 3.8 ± 0.56). Mean distance from the inferior aspect of the humeral head was 4.3 ± 1.6 cm (range, 0.3-8.4). Mean distance from the inferior aspect of the axillary vessels was 2.9 ± 1.5 cm (range, –0.6 to 5.4). Mean distance from the P-L line was 0.01 ± 1.9 cm (range, –2.2 to 2.4); negative and positive values denote medial or lateral to the P-L line. A Radiation Therapy Oncology Group–compliant Ax-L1 consensus contour, created from contours by 4 attending breast radiation oncologists, partially or fully missed 45% of mapped LNs. European Society for Radiotherapy and Oncology– and Radiotherapy Comparative Effectiveness–compliant Ax-L1 similarly missed 46% and 34% of mapped LNs, respectively. LNs were most frequently missed in the lateral direction. The superolateral Ax-L1 encompassed 9.3% of the mapped LNs. Conclusions A significant percentage of at-risk Ax-L1 tissue falls outside current contouring atlases. We propose expansion of the recommended Ax-L1 borders, most notably in the lateral direction.

BACKGROUND Atypical teratoid/rhabdoid tumors (AT/RTs) are rare aggressive central nervous system tumors. The use of radiation therapy (RT) remains controversial, especially for patients younger than three years of age. The purpose of the current investigation is to robustly analyze the impact of RT among pediatric AT/RT patients using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS SEER 18 Custom Data registries were queried for AT/RT (ICD-0-3 9508/3). A total of 190 pediatric AT/RT patients were identified, of whom 102 underwent surgery + chemotherapy and 88 underwent trimodality therapy. Univariate and multivariable analyses using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting was performed to account for indication bias. The landmark method was used to account for immortal time bias. RESULTS The majority of patients were

To explore the relationship between baseline information, personal factors, working characteristics and job performance among nurses in emergency department in northern Taiwan. Two-hundred twenty-two nursing staff were interviewed repeated with structured questionnaires for data collection in 3 time points (From August to September, 2008, from February to March, 2009, and from November to December, 2009). The generalized estimating equation (GEE) is used to test the relationship between the domains of independent variables (baseline information, personal factors, working characteristics) and dependent variables (task performance, contextual performance). The mean age of participants is 30.1 ± 5.1 years. 50.0% are junior college or bachelor degrees. From the GEE model, biological protection (β = 0.17, P value = .002) and safety climate (β = 0.24, P value

Although whole breast irradiation (WBI) represents the standard radiotherapy technique in breast conserving therapy, accelerated partial breast irradiation (APBI) has emerged as an option to reduce treatment duration with comparable clinical outcomes. The purpose of this analysis is to present long-term clinical outcomes between WBI and APBI.A total of 3009 patients were treated with breast conserving therapy at a single institution between 1980 and 2012. Among them, 2528 patients received WBI and 481 received APBI (interstitial or balloon based). A matched-pair analysis was performed with patients matched by age (±3 years), stage (T-stage vs. T1 vs. T2), and estrogen receptor status (+/-). All patients had a minimum of 12 months follow-up. A total of 274 matches (ratio 1:1) were made.No differences between groups were noted with respect to clinicopathologic features; WBI patients demonstrated a trend for slightly larger tumors (1.3 vs. 1.1 cm, P=0.06). At 10 years, no differences were noted with respect to rates of ipsilateral breast tumor recurrence (4% vs. 4%, P=0.11), regional recurrence (1% vs. 1%, P=0.20), contralateral breast failure (9% vs. 3%, P=0.06), or distant metastases (3% vs. 6%, P=0.47) for WBI and APBI, respectively. In addition, 10-year disease-free survival (93% vs. 91%, P=0.10) and overall survival (83% vs. 75%, P=0.34) were similar. Long-term cosmesis was good to excellent in 94% of WBI patients versus 95% of APBI patients (P=0.78).At 10 years, no differences in recurrence or survival were found between patients undergoing WBI or brachytherapy-based APBI.

Purpose Recent prospective data have shown that patients with solitary or oligometastatic disease to the brain may be treated with upfront stereotactic radiosurgery (SRS) with deferral of whole-brain radiation therapy (WBRT). This has been extrapolated to the treatment of patients with resected lesions. The aim of this study was to assess the risk of leptomeningeal disease (LMD) in patients treated with SRS to the postsurgical resection cavity for brain metastases compared with patients treated with SRS to intact metastases. Methods and Materials Four hundred sixty-five patients treated with SRS without upfront WBRT at a single institution were identified; 330 of these with at least 3 months' follow-up were included in this analysis. One hundred twelve patients had undergone surgical resection of at least 1 lesion before SRS compared with 218 treated for intact metastases. Time to LMD and overall survival (OS) time were estimated from date of radiosurgery, and LMD was analyzed by the use of cumulative incidence method with death as a competing risk. Univariate and multivariate analyses were performed with competing risk regression to determine whether various clinical factors predicted for LMD. Results With a median follow-up time of 9.0 months, 39 patients (12%) experienced LMD at a median of 6.0 months after SRS. At 1 year, the cumulative incidence of LMD, with death as a competing risk, was 5.2% for the patients without surgical resection versus 16.9% for those treated with surgery (Gray test, P P P =.03) were significant predictors of LMD development. The median OS times for patients undergoing surgery compared with SRS alone were 12.9 and 10.6 months, respectively (log-rank P =.06). Conclusions In patients undergoing SRS with deferral of upfront WBRT for intracranial metastatic disease, prior surgical resection and breast cancer primary are associated with an increased risk for the development of LMD.

Purpose We report the outcomes associated with 3 high-dose-rate (HDR) brachytherapy regimens used as monotherapy for favorable-risk prostate cancer. Methods and Materials Four hundred ninety-four patients with stage ≤T2b prostate cancer, Gleason score ≤7, and prostate-specific antigen levels ≤15 ng/mL underwent HDR brachytherapy as monotherapy. Of those, 319 received 38 Gy in 4 fractions, 79 received 24 Gy in 2 fractions, and 96 received 27 Gy in 2 fractions. Acute and chronic genitourinary (GU) and gastrointestinal (GI) toxicities were defined as side effects occurring ≤6 and >6 months, respectively, after radiation therapy (RT) and were graded according to the Common Terminology Criteria for Adverse Events version 3.0. The time to toxicity was calculated from the date of RT completion. Variables were analyzed with χ2 test. P values Results The median overall follow-up time was 4 years (range, 5.5, 3.5, and 2.5 years for 38 Gy, 24 Gy, and 27 Gy, respectively, P Conclusions The acute and chronic toxicity profiles associated with these 3 HDR brachytherapy schedules were similar and were well tolerated. Acceptable grade 2, minimal grade 3, and no grade 4 or 5 toxicities were seen. This, combined with the fact that the clinical outcomes were similar, leads to the conclusion that all 3 regimens may be acceptable options for the management of low-risk to intermediate-risk prostate cancer.

Purpose Shorter courses of accelerated partial-breast irradiation delivered as single-fraction intraoperative therapy are now offered as an alternative to 4 to 6 weeks of whole-breast irradiation after lumpectomy. However, this approach has potential shortcomings in patient selection and target volume definition and in dosimetric, radiobiological, and logistical issues. We designed a prospective, phase 2, multi-institution clinical trial to study 2- or 3-day accelerated partial breast irradiation delivered with brachytherapy applicators. Methods and Materials This trial treats select breast cancers after breast-conserving surgery with brachytherapy applicators that deliver 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 1.5 cm beyond the surgical cavity. Eligible women were aged ≥45 years with unicentric invasive or in situ tumors ≤3.0 cm with positive estrogen or progesterone receptors and no metastasis to axillary nodes that have been excised with negative margins. Strict dosimetric parameters were required to be met before acceptance into the trial. Results A group of 200 patients was prospectively enrolled and followed for a minimum of 6 months. Two- or 3-day brachytherapy was associated with low acute or subacute toxicity, 97.25% excellent or good cosmetic outcomes, and excellent local control in select breast cancers. Conclusions Ultrashort breast brachytherapy is dosimetrically feasible and can be delivered with excellent short-term tolerance and low toxicity.

// Bryan J. Thibodeau 1 , Vincent Lavergne 2 , Nayana Dekhne 3 , Pamela Benitez 3 , Mitual Amin 4 , Samreen Ahmed 1 , Jean L. Nakamura 2 , Philip R. Davidson 5 , Alice O. Nakamura 5 , Inga S. Grills 6 , Peter Y. Chen 6 , Jessica Wobb 6 and George D. Wilson 1, 6 1 Beaumont BioBank, Beaumont Health, Royal Oak, MI, USA 2 Department of Radiation Oncology, University of California, San Francisco, CA, USA 3 Department of Surgery, Beaumont Health, Royal Oak, MI, USA 4 Department of Pathology, Beaumont Health, Royal Oak, MI, USA 5 Department of Finance and Statistical Analysis, University of Alberta, Edmonton, Alberta, Canada 6 Department of Radiation Oncology, Beaumont Health, Royal Oak, MI, USA Correspondence to: George D. Wilson, email: george.wilson@beaumont.edu Keywords: angiosarcoma; radiation-associated; breast; mutational signature; next generation sequencing Received: September 15, 2017 Accepted: October 13, 2017 Published: January 19, 2018 ABSTRACT Purpose: Radiation-associated breast angiosarcomas are a rare complication of radiation therapy for breast carcinoma. With relatively little is known about the genetic abnormalities present in these secondary tumors, we examined genomic variation in biospecimens from radiation-associated breast angiosarcomas. Experimental Design: Patients were identified that had a previous breast cancer diagnosis, received radiation therapy, and developed angiosarcoma in the ipsilateral breast as the earlier cancer. Tumor regions were isolated from archival blocks using subsequent laser capture microdissection. Next generation sequencing was performed using a targeted panel of 160 cancer-related genes. Genomic variants were identified for mutation and trinucleotide-based mutational signature analysis. Results: 44 variants in 34 genes were found in more than two thirds of the cases; this included 12 variants identified as potentially deleterious. Of particular note, the BRCA1 DNA damage response pathway was highly enriched with genetic variation. In a comparison to local recurrences, 14 variants in 11 genes were present in both the primary and recurrent lesions including variants in genes associated with the DNA damage response machinery. Furthermore, the mutational signature analysis shows that a previously defined IR signature is present in almost all of the current samples characterized by predominantly C→T substitutions. Conclusions: While radiation-associated breast angiosarcomas are relatively uncommon, their prognosis is very poor. These data demonstrate a mutational pattern associated with genes involved in DNA repair. While important in revealing the biology behind these tumors, it may also suggest new treatment strategies that will prove successful.

Purpose Four-dimensional (4D) adaptive radiation therapy (ART) treatment planning is an alternative to the conventional margin-based treatment planning approach. In 4D ART, interfraction patient geometric variations, gathered from computed tomography (CT) or cone beam CT (CBCT) images acquired during the patient treatment course, are directly incorporated into the adaptive plan optimization using a probabilistic treatment planning method. The goal of the present planning study was to evaluate the dosimetric differences between 4D ART and conventional margin-based adaptive planning strategies for head and neck cancers. In addition, we examined whether the dose differences achieved with 4D ART would translate into clinically relevant toxicity reductions using the existing normal tissue complication probability (NTCP) models. Methods and Materials For 18 head and neck cancer patients, the treatment plans were retrospectively generated for 4 different treatment strategies, including a solely image guided radiation therapy (IGRT) strategy (IGRT-only), 2 conventional adaptive treatment planning strategies using 3- and 0-mm planning target volume (PTV) margins, and the 4D ART strategy. In the IGRT-only strategy, a conventional 3-mm PTV margin treatment plan was applied for the entire treatment course. In the 2 conventional adaptive strategies, 2 new treatment plans were generated during the treatment course using diagnostic planning CT scans acquired after the 10th and 22nd fractions. The 4D ART followed the same adaptive schedule, except that the 4D adaptive plan was generated using 5 CBCT images acquired during the 5 most recent treatment fractions. For each strategy, the actual delivered dose for the entire treatment course was constructed by calculating the daily doses on 35 CBCT scans, deforming back to the pretreatment planning CT scan, and accumulating over all 35 fractions. The target coverage was evaluated using the percentage of target volume receiving ≥100% of the prescription dose (V100%) and the minimum dose to 99% of the target volume (D99). It was considered adequate if the V100% was ≥95% and the dose deficit in D99 was ≤2 Gy (with respect to the prescription dose). For each strategy, the dose received by the organs at risk (OARs) was also evaluated, and the corresponding NTCP values were subsequently calculated using 3 NTCP models. Results Adequate target coverage was achieved for the primary clinical target volume (CTV1) and elective nodal CTV (CTV2) with a 3-mm PTV margin, regardless of adaptation. The 3-mm ART plan reduced the OAR mean dose by 1 to 2 Gy compared with the IGRT-only plan. The 0-mm ART plan further reduced the OAR dose by another 2 to 3 Gy at the expense of target coverage: 3 and 1 patient had V100% 2 Gy dose deficit in D99 for the CTV1 and CTV2, respectively. Use of 4D ART improved target coverage and attained OAR sparing similar to that with 0-mm ART. The number of patients with V100% 2 Gy D99 deficit decreased to 0 and 0 for CTV1 and 0 and 2 for CTV2, respectively. The NTCP calculations suggested that 4D ART could benefit a substantial portion of patients compared with IGRT-only because 17 and 12 patients had ≥5% and ≥10% NTCP reductions for parotid toxicity and 18 and 3 patients had ≥5% and ≥10% NTCP reductions for swallowing toxicity, respectively. Conclusions Compared with margin-based adaptive planning strategies, 4D ART provides a better balance between target coverage and OAR sparing. NTCP estimation predicted for theoretical clinical benefits that warrant further clinical validation.

Importance The use of a radiotherapy (RT) boost to the tumor bed after whole-breast RT (WBRT) for ductal carcinoma in situ (DCIS) is largely extrapolated from invasive cancer data, but robust evidence specific to DCIS is lacking. Objective To compare ipsilateral breast tumor recurrence (IBTR) in women with DCIS treated with vs without the RT boost after breast-conserving surgery and WBRT. Design, Setting, and Participants This retrospective analysis pooled deidentified patient-level data from 10 academic institutions in the United States, Canada, and France from January 1, 1980, through December 31, 2010. All patients had newly diagnosed pure DCIS (no microinvasion), underwent breast-conserving surgery, and received WBRT with or without the boost with a minimum of 5 years of follow-up required for inclusion in the analysis. Given the limited events after WBRT, an a priori power analysis was conducted to estimate the DCIS sample size needed to detect the anticipated benefit of the boost. Data were uniformly recoded at the host institution and underwent primary and secondary reviews before analysis. Sample size calculations (ratio of patients who received the boost dose to those who did not, 2:1; α = .05; power = 80%) estimated that 2982 cases were needed to detect a difference of at least 3%. The final analysis included 4131 patients (2661 in the boost group and 1470 in the no-boost group) with a median follow-up of 9 years and media boost dose of 14 Gy. Data were collected from July 2011 through February 2014 and analyzed from March 2014 through August 2015. Interventions Radiotherapy boost vs no boost. Main Outcomes and Measures Ipsilateral breast tumor recurrence. Results The analysis included 4131 patients (median [SD] age, 56.1 [10.9] years; range, 24-88 years). Patients with positive margins, unknown estrogen receptor status, and comedo necrosis were more likely to have received an RT boost. For the entire cohort, the boost was significantly associated with lower IBTR (hazard ratio [HR], 0.73; 95% CI, 0.57-0.94; P = .01) and with IBTR-free survival (boost vs no-boost groups) of 97.1% (95% CI, 0.96-0.98) vs 96.3% (95% CI, 0.95-0.97) at 5 years, 94.1% (95% CI, 0.93-0.95) vs 92.5% (95% CI, 0.91-0.94) at 10 years, and 91.6% (95% CI, 0.90-0.93) vs 88.0% (95% CI, 0.85-0.91) at 15 years. On multivariable analysis accounting for confounding factors, the boost remained significantly associated with reduced IBTR (HR compared with no boost, 0.68; 95% CI, 0.50-0.91; P = .01) independent of age and tamoxifen citrate use. Conclusions and Relevance This patient-level analysis suggests that the RT boost confers a statistically significant benefit in decreasing IBTR across all DCIS age groups, similar to that seen in patients with invasive breast cancer. These findings suggest that a DCIS RT boost to the tumor bed could be considered to provide an added incremental benefit in decreasing IBTR after a shared discussion between the patient and her radiation oncologist.

Human papillomavirus (HPV) has been shown to have a causal role in the development of head and neck squamous cell carcinoma. While HPV-positive head and neck cancer is associated with a better response to treatment in the majority of patients, there is a subset who does not respond favorably to current therapy. Identification of these patients could prevent unnecessary morbidity and indicate the need for alternative therapeutic options. Tissue samples were obtained from 19 patients with HPV-positive head and neck squamous carcinoma treated with chemoradiation therapy. HPV status was confirmed by polymerase chain reaction analysis through detection of HPV16 E7 in both DNA and RNA. RNA was isolated from tissue samples and subjected to microarray gene expression analysis. In addition to identification of potential genetic biomarkers (including LCE3D, KRTDAP, HMOX1, KRT19, MDK, TSPAN1), differentially expressed genes associated with genomic stability, cell cycle, and DNA damage were detected between responders and non-responders. These results were further validated with publicly available gene expression studies. This pilot study suggests prospective biomarkers that predict response to therapy. The importance of genes involved with genomic stability is highlighted in both development and progression of head and neck squamous cell carcinoma but also recurrence. Potential development of an assay may prove beneficial to clinicians, assisting them to provide alternative care sooner thus lowering morbidity.

To report outcomes of patients with medical and/or surgical refractory trigeminal neuralgia (TN) treated with gamma knife stereotactic radiosurgery (GK SRS).One hundred and forty-nine patients with 152 cases of TN treated with GK SRS were analyzed. All patients, except one, received a dose of 40Gy to the 50% isodose volume. The Barrow Neurological Institute (BNI) pain intensity score was used to grade pain. Actuarial rates of pain relief were calculated. Multiple factors were analyzed for association with pain relief.The median follow up was 27 months (4-71 months). Overall 92% of cases achieved a BNI score I-III after GK SRS. Of those who had pain relief after GK SRS, 32% developed pain recurrence defined as a BNI score of IV or V. The actuarial rate of freedom from pain recurrence (BNI scores I-III) of all treated cases at 1, 2 and 3-years was 76%, 69% and 60%, respectively. On univariate analysis age ≥70 was predictive of better pain relief (p=0.046). Type of pain, prior surgery, multiple sclerosis, number of isocenters, treated nerve length, volume and thickness and distance from the root entry zone to the isocenter were not significant for maintaining a BNI score of I-III. Those who achieved a BNI score of I or II were more likely to maintain pain relief compared to those who only achieved a BNI score of III (93% vs 38% at three years, p0.01). The rate of pain relief of twenty-seven patients who underwent repeat GK SRS was 70% and 62% at 1 and 2 years, respectively. Toxicity after first GK SRS was minimal with 25% of cases experiencing only new or worsening post-treatment numbness.GK SRS provides acceptable pain relief with limited morbidity in patients with medical and/or surgical refractory TN.

Background We compared dependence rates, complications, toxicities, and costs associated with prophylactic versus reactive percutaneous endoscopic gastrostomy (PEG) tube placement. Methods One hundred ninety-three patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy were retrospectively reviewed. Results The 1-year and 2-year actuarial PEG tube dependence rate of the entire cohort was 24% and 13%, respectively. There was no difference in the PEG tube dependence rates between those placed prophylactically versus reactively. Patients who received a PEG tube reactively had a significantly higher stricture rate (p = .03) and aspiration rate (p < .001) compared to the prophylactic group. There were significantly fewer hospitalizations in the prophylactic group compared to the reactive group (p = .003). When accounting for both PEG placement and hospitalizations, the prophylactic approach was found to be more cost effective. Conclusion PEG tubes placed prophylactically were associated with lower rates of strictures, aspirations, hospitalizations, and costs compared to those placed reactively. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1155–1161, 2014

Object The aim of this study was to examine tumor volume as a prognostic factor for patients with brain metastases treated with Gamma Knife surgery (GKS). Methods Two hundred fifty patients with 1–14 brain metastases who had initially undergone GKS alone at a single institution were retrospectively reviewed. Patients who received upfront whole brain radiation therapy were excluded. Survival times were estimated using the Kaplan-Meier method. Univariate and multivariate analyses using Cox proportional hazard regression models were used to determine if various prognostic factors could predict overall survival, distant brain failure, and local control. Results Median overall survival was 7.1 months and the 1-year local control rate was 91.5%. Median time to distant brain failure was 8.0 months. On univariate analysis an increasing total tumor volume was significantly associated with worse survival (p = 0.031) whereas the number of brain metastases, analyzed as a continuous variable, was not (p = 0.082). After adjusting for age, Karnofsky Performance Scale score, and extracranial disease on multivariate analysis, total tumor volume was found to be a better predictor of overall survival (p = 0.046) than number of brain metastases analyzed as a continuous variable (p = 0.098). A total tumor volume cutoff value of ≥ 2 cm3 (p = 0.008) was a stronger predictor of overall survival than the number of brain metastases (p = 0.098). Larger tumor volume and extracranial disease, but not the number of brain metastases, were predictive of distant brain failure on multivariate analysis. Local tumor control at 1 year was 97% for lesions < 2 cm3 compared with 75% for lesions ≥ 2 cm3 (p < 0.001). Conclusions After adjusting for other factors, a total brain metastasis volume was a strong and independent predictor for overall survival, distant brain failure, and local control, even when considering the number of metastases.

We reviewed our institution's long-term experience treating patients diagnosed with ductal carcinoma in situ (DCIS) of the breast with breast-conserving therapy (BCT) to determine the impact of patient age on outcome over time. All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics (including age

Limited 5-year data exist on clinical outcomes and toxicities for patients undergoing 3-dimensional conformal radiation therapy (3D-CRT) APBI.Two hundred five patients were treated with 3D-CRT APBI between August, 2000 and December, 2011. Cases with1 year of follow-up were analyzed for cosmesis, chronic toxicities, and clinical outcomes. Outcome by American Society for Radiation Oncology (ASTRO) Consensus Panel (CP) group were also compared. Rates of excellent and good cosmesis for 3D-CRT were evaluated over time for stability.One hundred ninety-two patients were evaluated; median follow-up was 4.8 years (range, 1.0-11.2 years). Seventy-two patients (37.5%) were categorized as ASTRO CP subgroup 'suitable,' 89 (46.4%) 'cautionary,' and 31 (16.1%) 'unsuitable.' At 5 years, the rate of IBTR, regional recurrence, distant metastases, cause-specific survival, and overall survival were 0%, 0%, 2%, 99%, and 92%, respectively. Thirty-seven percent of patients had excellent cosmesis, 44% good cosmesis, 15% fair cosmesis, and 4% poor cosmesis. No statistically significant differences in excellent (37% vs. 37%; P = .99) or good (49% vs. 37%; P = .28) cosmesis were noted between patients with5 years follow-up and those with ≥ 5 years follow-up. The rates of grade III fibrosis and telangiectasia were 7.5% and 7.6%, respectively.In the largest group of patients published to date using 3D-CRT to deliver APBI, no local recurrences were noted at 5 years. More than 80% of patients had excellent or good cosmesis.

Object Hearing loss after Gamma Knife surgery (GKS) in patients with vestibular schwannoma has been associated with radiation dose to the cochlea. The purpose of this study was to evaluate serviceable hearing preservation in patients with VS who were treated with GKS and to determine if serviceable hearing loss can be correlated with the dose to the cochlea. Methods Forty patients with vestibular schwannoma with serviceable hearing were treated using GKS with a median marginal dose of 12.5 Gy (range 12.5–13 Gy) to the 50% isodose volume. Audiometry was performed prospectively before and after GKS at 1, 3, and 6 months, and then every 6 months thereafter. Hearing preservation was based on pure tone average (PTA) and speech discrimination (SD). Serviceable hearing was defined as PTA less than 50 dB and SD greater than 50%. Results The median cochlear maximum and mean doses were 6.9 Gy (range 1.6–16 Gy) and 2.7 Gy (range 0.7–5.0 Gy), respectively. With a median audiological follow-up of 35 months (range 6–58 months), the 1-, 2-, and 3-year actuarial rates of maintaining serviceable hearing were 93%, 77%, and 74%, respectively. No patient who received a mean cochlear dose less than 2 Gy experienced serviceable hearing loss (p = 0.035). Patients who received a mean cochlear dose less than 3 Gy had a 2-year hearing preservation rate of 91% compared with 59% in those who received a mean cochlear dose of 3 Gy or greater (p = 0.029). Those who had more than 25% of their cochlea receiving 3 Gy or greater had a higher rate of hearing loss (p = 0.030). There was no statistically significant correlation between serviceable hearing loss and age, tumor size, pre-GKS PTA, pre-GKS SD, pre-GKS Gardner-Robertson class, maximum cochlear dose, or the percentage of cochlear volume receiving 5 Gy. On multivariate analysis there was a trend toward significance for serviceable hearing loss with a mean cochlear dose of 3 Gy or greater (p = 0.074). Local control was 100% at 24 months. No patient developed facial or trigeminal nerve dysfunction. Conclusions With a median mean cochlear dose of 2.7 Gy, the majority of patients with serviceable hearing retained serviceable hearing 3 years after GKS. A mean cochlear dose less than 3 Gy was associated with higher serviceable hearing preservation.

Objectives To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy in node-positive compared with node-negative patients. Materials and methods From 1992 to 2013, 1351 patients (1369 breast cancers) were treated with breast-conserving surgery and adjuvant APBI using interstitial multicatheter brachytherapy. A total of 907 patients (835 node negative, 59 N1a, and 13 N1mic) had >1 year of data available and nodal status information and are the subject of this analysis. Median age (range) was 59 years old (22 to 90 y). T stage was 90% T1 and ER/PR/Her2 was positive in 87%, 71%, and 7%. Mean number of axillary nodes removed was 12 (SD, 6). Cox multivariate analysis for local/regional control was performed using age, nodal stage, ER/PR/Her2 receptor status, tumor size, grade, margin, and adjuvant chemotherapy/antiestrogen therapy. Results The mean (SD) follow-up was 7.5 years (4.6). The 5-year actuarial local control (95% confidence interval) in node-negative versus node-positive patients was 96.3% (94.5-97.5) versus 95.8% (87.6-98.6) (P=0.62). The 5-year actuarial regional control in node-negative versus node-positive patients was 98.5% (97.3-99.2) versus 96.7% (87.4-99.2) (P=0.33). The 5-year actuarial freedom from distant metastasis and cause-specific survival were significantly lower in node-positive versus node-negative patients at 92.3% (82.4-96.7) versus 97.8% (96.3-98.7) (P=0.006) and 91.3% (80.2-96.3) versus 98.7% (97.3-99.3) (P=0.0001). Overall survival was not significantly different. On multivariate analysis age 50 years and below, Her2 positive, positive margin status, and not receiving chemotherapy or antiestrogen therapy were associated with a higher risk of local/regional recurrence. Conclusions Patients who have had an axillary lymph node dissection and limited node-positive disease may be candidates for treatment with APBI. Further research is ultimately needed to better define specific criteria for APBI in node-positive patients.

Purpose To determine in breast tumor recurrence (IBTR) and regional nodal recurrence (RNR) rates for women treated with multicatheter interstitial accelerated partial breast irradiation. Methods and Materials Data from five institutions were collected for patients treated from 1992 to 2013. We report outcomes of 582 breast cancers with ≥1 year of followup. Molecular subtype approximation was performed using estrogen receptor, progesterone receptor, Her2, and grade. The Kaplan–Meier method was used to calculate overall survival, IBTR, RNR, and distant recurrence rates. Univariate and multivariate Cox proportional hazard models were performed to estimate risks of IBTR and RNR. Results With a median followup time of 5.4 years, the 5-year IBTR rate was 4.7% overall, 3.5% for Luminal A, 4.1% for Luminal B, 5.2% for Luminal Her2, 13.3% for Her2, and 11.3% for triple-negative breast cancer. Positive surgical margins and high grade were associated with increased risk for IBTR, as was Her2 subtype in comparison with Luminal A subtype. Other individual subtypes comparisons did not show a significant difference. Analysis of Luminal A vs. all other subtypes demonstrated lower IBTR risk for Luminal A (5-year IBTR 3.5% vs. 7.3%, p = 0.02). The 5-year RNR rate was 2.1% overall, 0.3% for Luminal A, 4.6% for Luminal B, 2.6% for Luminal Her2, 34.5% for Her2, and 2.3% for triple-negative breast cancer. RNR risk was higher for women with Her2 compared to the other four subtypes and for Luminal B compared to Luminal A subtype. Conclusions Molecular subtype influences IBTR and RNR rates in women treated with multicatheter interstitial accelerated partial breast irradiation.

The purpose of the study was to determine outcomes for patients treated with accelerated partial breast irradiation (APBI) on the basis of breast cancer subtype (BCST).Our single-institution, institutional review board-approved APBI database was queried for patients who had complete testing results for the estrogen (ER), progesterone (PR), and HER2/neu receptors to determine outcomes for each BCST. Women were assigned as luminal A (LA), luminal B (LB), HER2, and basal BCST using their ER, PR, and HER2/neu receptor status. Degree of ER expression supplemented the receptor-based luminal BCST assignment. Two hundred seventy-eight patients had results for all 3 receptors (LA = 164 [59%], LB = 81 [29%], HER2 = 5 [2%], basal = 28 [10%]), which were submitted for analysis (ipsilateral breast tumor recurrence [IBTR], regional nodal failure, distant metastasis [DM], disease-free survival [DFS], cause-specific survival [CSS], and overall survival [OS]).Median follow-up was 5.4 years (range, 0.1-12.4 years). Basal and HER2 subtype patients had higher histologic grades (Grade 3 = 75% vs. 10% LA/LB; P .001), larger tumors (13.0 mm basal vs. 10.7 mm LA/LB; P = .059), and were more likely to receive chemotherapy (68% vs. 15% LA/LB; P .001). Margin and nodal status were similar among BCSTs. At 5 years, IBTR rates were similar (1.8%, 2.9%, 0%, and 4.8%) for LA, LB, HER2, and basal subtypes, respectively (P = .62). DM was only seen in LA (2.9%) and LB (1.3%) (P = .83). DFS (95%-100%), CSS (97%-100%), and OS (80%-100%) were not statistically different (P = .97, .87, .46, respectively).Five-year local control rates after breast-conserving surgery, APBI, and appropriate systemic therapy are excellent for luminal, HER2, and basal phenotypes of early-stage breast cancer; however, further study of receptor subtype effect on risk stratification in early-stage breast cancer is needed.