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Sunil W Dutta,1 Shayna L Showalter,2 Timothy N Showalter,1 Bruce Libby,1 Daniel M Trifiletti1 1Department of Radiation Oncology, 2Division of Surgical Oncology, Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA Abstract: Accelerated partial breast irradiation (APBI) provides an attractive alternative to whole breast irradiation (WBI) through normal tissue radiation exposure and reduced treatment duration. Intraoperative radiation therapy (IORT) is a form of APBI with the shortest time interval, as it delivers the entirety of a planned radiation course at the time of breast surgery. However, faster is not always better, and IORT has been met with healthy skepticism. Patients treated with IORT have an increased compliance and overall satisfaction when compared to patients treated with WBI. However, early randomized trial results demonstrated an increased rate of recurrence after IORT, slowing its widespread adoption. Despite these controversies, IORT utilization is increasing nationally and several novel developments are aimed at continuing to minimize the risk of recurrence and treatment-related toxicity while maximizing the patient experience. Keywords: IORT, lumpectomy, breast conservation, electron, photon, evidence

Introduction: We compared the rates of long-term adjuvant endocrine therapy (AET) adherence after various radiation therapy (RT) modalities among patients with early stage breast cancer., Materials and Methods: Medical records from patients with stage 0, I, or IIA (tumors ≤3 cm), hormone receptor (HR) positive breast cancer that received adjuvant radiation therapy (RT) from 2013 to 2015 at a single institution were retrospectively reviewed. All patients received breast conserving surgery (BCS) followed by adjuvant RT via one of the following modalities: whole breast radiotherapy (WBI), partial breast irradiation (PBI) with either external beam radiation therapy (EBRT) or fractionated intracavitary high-dose rate (HDR) brachytherapy, or single fraction HDR-brachytherapy intraoperative-radiation therapy (IORT)., Results: One hundred fourteen patients were reviewed. Thirty patients received WBI, 41 PBI, and 43 IORT with a median follow up of 64.2, 72.0, and 58.6 months, respectively. For the entire cohort, AET adherence was approximately 64% at 2 years and 56% at 5 years. Among patients in the IORT clinical trial, adherence to AET was approximately 51% at 2 years and 40% at 5 years. After controlling for additional factors, DCIS histology (vs invasive disease) and IORT (compared to other radiation modalities) were associated with decreased endocrine therapy adherence (P < 0.05)., Conclusion: DCIS histology and receipt of IORT were associated with lower rates of adherence to AET at 5 years. Our findings suggest that examination of the efficacy of RT interventions such as PBI and IORT in patients who do not receive AET is warranted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Patients with brain metastases (BrMs) arising from EGFR and ALK driven non-small cell lung cancer (NSCLC) have favorable prognoses and evolving treatment options. We evaluated multicenter outcomes for stereotactic radiosurgery (SRS) to multiple (≥4) BrMs, where randomized data remain limited., Methods: Data were collected retrospectively from 5 academic centers on EGFR and ALK NSCLC who received SRS to ≥4 BrMs with their first SRS treatment between 2008 and 2018. Analyzed endpoints included overall survival (OS), freedom from CNS progression (FFCNSP), and freedom from whole-brain radiotherapy (FFWBRT)., Results: Eighty-nine patients (50 EGFR, 39 ALK) received a total of 159 SRS treatments to 1,080 BrMs, with a median follow up of 51.3 months. The median number of BrMs treated with SRS treatment-1 was 6 (range 4-26) and median for all treatments was 9 (range 4-47). Sixteen patients (18 %) had received WBRT prior to SRS treatment-1. The median OS was 24.2, 21.2, and 33.2 months for all patients, EGFR, and ALK subsets, respectively. After multivariable adjustment, only receipt of a next-generation tyrosine kinase inhibitor was associated with OS (HR 0.40, p = 0.005). No differences in OS were observed based on number of BrMs treated. The median FFCNSP was 9.4, 11.6, and 7.5 months, for all patients, EGFR, and ALK subsets, respectively. After multivariable adjustment, the number of BrMs (continuous) treated during treatment-1 was the only negative prognostic factor associated with FFCNSP (HR 1.071, p = 0.045). The 5-year FFWBRT was 73.6 %., Conclusions: This multicenter analysis over a >10-year period demonstrated favorable OS, FFCNSP, and FFWBRT, in patients with EGFR and ALK driven NSCLC receiving SRS to ≥4 BrMs. These data support SRS as an option in the upfront and salvage setting for higher burden CNS disease in this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Precision breast intraoperative radiation therapy (PB-IORT) is a novel approach to adjuvant radiation therapy for early-stage breast cancer performed as part of a phase II clinical trial at two institutions. One institution performs the entire procedure in an integrated brachytherapy suite which contains a CT-on-rails imaging unit and full anesthesia capabilities. At the other, breast conserving surgery and radiation therapy take place in two separate locations. Here, we utilize time-driven activity-based costing (TDABC) to compare these two models for the delivery of PB-IORT., Methods: Process maps were created to describe each step required to deliver PB-IORT at each institution, including personnel, equipment, and supplies. Time investment was estimated for each step. The capacity cost rate was determined for each resource, and total costs of care were then calculated by multiplying the capacity cost rates by the time estimate for the process step and adding any additional product costs., Results: PB-IORT costs less to deliver at a distributed facility, as is more commonly available, than an integrated brachytherapy suite ($3,262.22 vs. $3,996.01). The largest source of costs in both settings ($2,400) was consumable supplies, including the brachytherapy balloon applicator. The difference in costs for the two facility types was driven by personnel costs ($1,263.41 vs. $764.89). In the integrated facility, increased time required by radiation oncology nursing and the anesthesia attending translated to the greatest increases in cost. Equipment costs were also slightly higher in the integrated suite setting ($332.60 vs. $97.33)., Conclusions: The overall cost of care is higher when utilizing an integrated brachytherapy suite to deliver PB-IORT. This was primarily driven by additional personnel costs from nursing and anesthesia, although the greatest cost of delivery in both settings was the disposable brachytherapy applicator. These differences in cost must be balanced against the potential impact on patient experience with these approaches., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To reduce the likelihood of errors in organ delineations used for radiotherapy treatment planning, a knowledge-based quality control (KBQC) system, which discriminates between valid and anomalous delineations is developed., Method and Materials: The KBQC is comprised of a group-wise inference system and anomaly detection modules trained using historical priors from 296 locally advanced lung and prostate cancer patient computational tomographies (CTs). The inference system discriminates different organs based on shape, relational, and intensity features. For a given delineated image set, the inference system solves a combinatorial optimization problem that results in an organ group whose relational features follow those of the training set considering the posterior probabilities obtained from support vector machine (SVM), discriminant subspace ensemble (DSE), and artificial neural network (ANN) classifiers. These classifiers are trained on nonrelational features with a 10-fold cross-validation scheme. The anomaly detection module is a bank of ANN autoencoders, each corresponding with an organ, trained on nonrelational features. A heuristic rule detects anomalous organs that exceed predefined organ-specific tolerances for the feature reconstruction error and the classifier's posterior probabilities. Independent data sets with anomalous delineations were used to test the overall performance of the KBQC system. The anomalous delineations were manually manipulated, computer-generated, or propagated based on a transformation obtained by imperfect registrations. Both peer-review-based scoring system and shape similarity coefficient (DSC) were used to label regions of interest (ROIs) as normal or anomalous in two independent test cohorts., Results: The accuracy of the classifiers was ≥ $\ge$ 99.8%, and the minimum per-class F1-scores were 0.99, 0.99, and 0.98 for SVM, DSE, and ANN, respectively. The group-wise inference system reduced the miss-classification likelihood for the test data set with anomalous delineations compared to each individual classifier and a fused classifier that used the average posterior probability of all classifiers. For 15 independent locally advanced lung patients, the system detected > $&gt;$ 79% of the anomalous ROIs. For 1320 auto-segmented abdominopelvic organs, the anomaly detection system identified anomalous delineations, which also had low Dice similarity coefficient values with respect to manually delineated organs in the training data set., Conclusion: The KBQC system detected anomalous delineations with superior accuracy compared to classification methods that judge only based on posterior probabilities., (© 2022 American Association of Physicists in Medicine.)

Background: This analysis evaluates the impacts of biologically effective dose (BED) and histology on local control (LC) of spinal metastases treated with highly conformal radiotherapy to moderately-escalated doses., Materials and Methods: Patients were treated at two institutions from 2010-2020. Treatments with less than 5 Gy per fraction or 8 Gy in 1 fraction were excluded. The dataset was divided into three RPA classes predictive of survival (1). The primary endpoint was LC., Results: 223 patients with 248 treatments met inclusion criteria. Patients had a median Karnofsky Performance Status (KPS ) of 80, and common histologies included breast (29.4%), non-small cell lung cancer (15.7%), and prostate (13.3%). A median 24 Gy was delivered in 3 fractions (BED: 38.4 Gy) to a median planning target volume (PTV) of 37.3 cc. 2-year LC was 75.7%, and 2-year OS was 42.1%. Increased BED was predictive of improved LC for primary prostate cancer (HR = 0.85, 95% CI: 0.74-0.99). Patients with favorable survival (RPA class 1) had improved LC with BED ≥ 40 Gy (p = 0.05), unlike the intermediate and poor survival groups. No grade 3-5 toxicities were reported., Conclusions: Moderately-escalated treatments were efficacious and well-tolerated. BED ≥ 40 Gy may improve LC, particularly for prostate cancer and patients with favorable survival., Competing Interests: Conflicts of interest The wife of R.O.K. is a senior technical product manager at GE Healthcare., (© 2021 Greater Poland Cancer Centre.)

Purpose: Proton beam therapy can significantly reduce cardiopulmonary radiation exposure compared with photon-based techniques in the postmastectomy setting for locally advanced breast cancer. For patients with metallic port tissue expanders, which are commonly placed in patients undergoing a staged breast reconstruction, dose uncertainties introduced by the high-density material pose challenges for proton therapy. In this report, we describe an intensity modulated proton therapy planning technique for port avoidance through a hybrid single-field optimization/multifield optimization approach., Methods and Materials: In this planning technique, 3 beams are utilized. For each beam, no proton spot is placed within or distal to the metal port plus a 5 mm margin. Therefore, precise modeling of the metal port is not required, and various tissue expander manufacturers/models are eligible. The blocked area of 1 beam is dosimetrically covered by 1 or 2 of the remaining beams. Multifield optimization is used in the chest wall target region with blockage of any beam, while single-field optimization is used for remainder of chest wall superior/inferior to the port., Results: Using this technique, clinical plans were created for 6 patients. Satisfactory plans were achieved in the 5 patients with port-to-posterior chest wall separations of 1.5 cm or greater, but not in the sixth patient with a 0.7 cm separation., Conclusions: We described a planning technique and the results suggest that the metallic port-to-chest wall distance may be a key parameter for optimal plan design., (© 2021 The Authors.)

Background: Chordoma is a rare primary bone tumour with a high propensity for local recurrence. Surgical resection is the mainstay of treatment, but complete resection is often morbid due to tumour location. Similarly, the dose of radiotherapy (RT) that surrounding healthy organs can tolerate is frequently below that required to provide effective tumour control. Therefore, clinicians have investigated different radiation delivery techniques, often in combination with surgery, aimed to improve the therapeutic ratio., Objectives: To assess the effects and toxicity of proton and photon adjuvant radiotherapy (RT) in people with biopsy-confirmed chordoma., Search Methods: We searched CENTRAL (2021, Issue 4); MEDLINE Ovid (1946 to April 2021); Embase Ovid (1980 to April 2021) and online registers of clinical trials, and abstracts of scientific meetings up until April 2021., Selection Criteria: We included adults with pathologically confirmed primary chordoma, who were irradiated with curative intent, with protons or photons in the form of fractionated RT, SRS (stereotactic radiosurgery), SBRT (stereotactic body radiotherapy), or IMRT (intensity modulated radiation therapy). We limited analysis to studies that included outcomes of participants treated with both protons and photons., Data Collection and Analysis: The primary outcomes were local control, mortality, recurrence, and treatment-related toxicity. We followed current standard Cochrane methodological procedures for data extraction, management, and analysis. We used the ROBINS-I tool to assess risk of bias, and GRADE to assess the certainty of the evidence., Main Results: We included six observational studies with 187 adult participants. We judged all studies to be at high risk of bias. Four studies were included in meta-analysis. We are uncertain if proton compared to photon therapy worsens or has no effect on local control (hazard ratio (HR) 5.34, 95% confidence interval (CI) 0.66 to 43.43; 2 observational studies, 39 participants; very low-certainty evidence). Median survival time ranged between 45.5 months and 66 months. We are uncertain if proton compared to photon therapy reduces or has no effect on mortality (HR 0.44, 95% CI 0.13 to 1.57; 4 observational studies, 65 participants; very low-certainty evidence). Median recurrence-free survival ranged between 3 and 10 years. We are uncertain whether proton compared to photon therapy reduces or has no effect on recurrence (HR 0.34, 95% CI 0.10 to 1.17; 4 observational studies, 94 participants; very low-certainty evidence). One study assessed treatment-related toxicity and reported that four participants on proton therapy developed radiation-induced necrosis in the temporal bone, radiation-induced damage to the brainstem, and chronic mastoiditis; one participant on photon therapy developed hearing loss, worsening of the seventh cranial nerve paresis, and ulcerative keratitis (risk ratio (RR) 1.28, 95% CI 0.17 to 9.86; 1 observational study, 33 participants; very low-certainty evidence). There is no evidence that protons led to reduced toxicity. There is very low-certainty evidence to show an advantage for proton therapy in comparison to photon therapy with respect to local control, mortality, recurrence, and treatment related toxicity., Authors' Conclusions: There is a lack of published evidence to confirm a clinical difference in effect with either proton or photon therapy for the treatment of chordoma. As radiation techniques evolve, multi-institutional data should be collected prospectively and published, to help identify persons that would most benefit from the available radiation treatment techniques., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The clinical outcomes of multicourse lung stereotactic body radiotherapy (SBRT) have yet to be validated in a prospective study, and there are a lack of data on allowable composite dosimetry., Patients and Methods: Forty-four patients underwent multicourse lung SBRT for recurrent or metachronous NSCLC. The median biologically effective dose (BED 10 ) for the first course and subsequent courses were 132 and 100 Gy, respectively. Patient and treatment characteristics were evaluated to determine the correlation with the development of radiation pneumonitis (RP)., Results: The local control rate was 91%. A total of 13.6% developed a grade 2+ RP, and 4.5% developed a grade 3+ RP, including one grade 5. On univariable analysis, multiple composite dosimetric factors (V 5 [proportion of lung structure receiving at least 5 Gy], V 10 , V 20 , V 40 , and mean lung dose) were correlated with the development of RP. When comprised of the first and second course of SBRT, a composite lung V 5 of < 30% and > 50% was associated with a 0 and 75% incidence of grade 2+ RP, respectively. We identified no significant correlation on multivariable analysis but observed a strong trend between composite lung V 5 and the development of grade 2+ RP (hazard ratio, 1.157; P = .058). Evaluation of multiple clinical factors also identified a significant correlation between the timing of repeat lung SBRT and the development of grade 2+ RP after the second course (P = .0028)., Conclusion: Subsequent courses of lung SBRT, prescribed to a median BED 10 of 100 Gy, can provide a high rate of local control with a 4.5% incidence of grade 3+ toxicity. Composite lung V 5 and the timing of the second course of lung SBRT may be correlated to the development of RP., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To investigate the safety and outcomes of elective para-aortic (PA) nodal irradiation utilizing modern treatment techniques for patients with node positive cervical cancer., Methods: Patients with pelvic lymph node positive cervical cancer who received radiation were included. All patients received radiation therapy (RT) to either a traditional pelvic field or an extended field to electively cover the PA nodes. Factors associated with survival were identified using a Cox proportional hazards model, and toxicities between groups were compared with a chi-square test., Results: 96 patients were identified with a mean follow up of 40 months. The incidence of acute grade ≥ 2 toxicity was 31% in the elective PA nodal RT group and 15% in the pelvic field group (Chi-square p = 0.067. There was no significant difference in rates of grade ≥ 3 acute or late toxicities between the two groups (p>0.05). The KM estimated 5-year OS was not statistically different for those receiving elective PA nodal irradiation compared to a pelvic only field, 54% vs. 73% respectively (log-rank p = 0.11)., Conclusions: Elective PA nodal RT can safely be delivered utilizing modern planning techniques without a significant increase in severe (grade ≥ 3) acute or late toxicities, at the cost of a possible small increase in non-severe (grade 2) acute toxicities. In this series there was no survival benefit observed with the receipt of elective PA nodal RT, however, this benefit may have been obscured by the higher risk features of this population. While prospective randomized trials utilizing a risk adapted approach to elective PA nodal coverage are the only way to fully evaluate the benefit of elective PA nodal coverage, these trials are unlikely to be performed and instead we must rely on interpretation of results of risk adapted approaches like those used in ongoing clinical trials and retrospective data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sanders, Muller, Dutta, Corriher, Ring, Showalter and Romano.)

Purpose: This study aims to develop a local control risk stratification using recursive partitioning analysis (RPA) for patients receiving stereotactic body radiation therapy (SBRT) for metastatic cancer., Methods and Materials: A single institutional database of 397 SBRT treatments to the liver, spine, and lymph nodes was constructed. All treatments required imaging follow-up to assess for local control. Cox proportional hazards analysis was implemented before the decision tree analysis. The data were split into training (70%), validation (10%), and testing (20%) sets for RPA to optimize the training set., Results: In the study, 361 treatments were included in the local control analysis. Two-year local control was 71%. A decision tree analysis was used and the resulting model demonstrated 93.10% fidelity for the validation set and 87.67% for the test set. RPA class 3 was composed of patients with non-small cell lung cancer (NSCLC) primary tumors and treatment targets other than the cervical, thoracic, and lumbar spines. RPA class 2 included patients with primary cancers other than NSCLC or breast and treatments targets of the sacral spine or liver. RPA class 1 consisted of all other patients (including lymph node targets and patients with primary breast cancer). Classes 3, 2, and 1 demonstrated 3-year local controls rates of 29%, 50%, and 83%, respectively. On subgroup analysis using the Kaplan-Meier method, treatments for lymph nodes and primary ovarian disease demonstrated improved local control relative to other treatment targets ( P < .005) and primary disease sites ( P < .005), respectively., Conclusions: A local control risk stratification model for SBRT to sites of metastatic disease was developed. Treatment target and primary tumor were identified as critical factors determining local control. NSCLC primary lesions have increased local failure for targets other than the cervical, thoracic, or lumbar spines, and improved local control was identified for lymph node sites and breast or ovarian primary tumors., (© 2020 The Authors.)

Purpose: Radiation therapy is a well-established treatment for symptomatic bone metastases. Despite continued advances in both planning techniques and treatment delivery, the standard workflow has remained relatively unchanged, often requiring 1 to 3 weeks and resulting in patient inconvenience and delayed palliation. We developed an expedited method wherein computed tomography simulation, treatment planning, quality assurance, and treatment delivery are performed in 1 day. This prospective pilot clinical trial evaluates the safety, efficacy, and patient satisfaction of this rapid workflow., Methods and Materials: Patients with 1 to 3 painful bone metastases were prospectively enrolled and treated with 1 fraction of stereotactic body radiation therapy, using a same-day Scan-Plan-QA-Treat workflow, termed STAT RAD, in a phase 1/2 dose escalation trial from 8 Gy to 15 Gy per fraction. Bone pain, opioid use, patient satisfaction, performance status, and quality of life were evaluated before and at 1, 4, 8, 12, 26, and 52 weeks after treatment. Outcomes and treatment-related toxicity were analyzed., Results: A total of 49 patients were enrolled, and 46 patients with 60 bone metastases were treated per the protocol. Partial or greater pain response occurred in 50% of patients at 1 week, 75% of patients at 8 weeks, 68.7% of patients at 6 months, and 33.3% of patients at 12 months. There were 2 grade-3 toxicities, including 1 spinal fracture associated with disease progression and hyperbilirubinemia. Reirradiation was required in 16.7% of treated lesions at a median time to retreatment of 4.9 months. Most patient responses (78.6%) indicated that patients would choose this workflow again., Conclusions: The results demonstrate that treating bone metastases with palliative stereotactic body radiation therapy via a single-fraction, patient-centric workflow is feasible and safe with doses up to 15 Gy. However, pain response decreased at 12 months and was associated with a 16.7% retreatment rate, which suggests that further dose escalation is warranted., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose/objective(s): Tyrosine kinase inhibitors (TKIs) are commonly employed for patients with brain metastases from lung cancer and specific driver mutations. We sought to identify the correlation between intracranial tumor burden and outcomes in patients with brain metastases treated with TKIs., Materials/methods: We identified and retrospectively reviewed cases of EGFR-mutant or ALK-rearranged lung cancer with brain metastases at any time during their cancer course. Clinical characteristics and treatment information were abstracted from the medical records. Brain metastases were contoured to calculate total volume of disease at diagnosis and after initial therapy. High intracranial burden was defined as either > 10 brain metastases, volume of brain metastases > 15 cc, or largest lesion > 3 cm. Intracranial response was determined according to Response Assessment in Neuro-Oncology (RANO) criteria on the patient level. We determined the correlation between clinical and imaging characteristics and intracranial progression free survival (IC-PFS) and overall survival (OS)., Results: Fifty-seven patients with EGFR (n = 49) and ALK (n = 8) alterations were identified. Median follow-up from initial brain metastasis diagnosis was 17 months. Neurological symptoms were present in 54% at brain metastasis diagnosis. For those receiving TKIs alone or TKIs with radiation, at least a partial intracranial response (≥ 65% volume reduction) at 3 months from starting therapy was achieved in 94% and 58%. Progressive intracranial disease at 3 months occurred in 6.3% and 8.3%. Patients with high intracranial burden (n = 21) had a median 17 brain metastases, 6.5 cc volume, and 1.9 cm maximal tumor diameter. Median IC-PFS and OS for patients with high intracranial burden was 13.9 and 35.4 months. Patients with high intracranial burden and neurological symptoms at diagnosis had similar IC-PFS and OS compared to those with low burden and absence of neurological symptoms (p > 0.05 for each)., Conclusion: Most patients receiving TKIs as part of their initial therapy achieve an early and durable volumetric intracranial response, irrespective of presenting disease burden or neurologic symptoms.

Purpose: The prognosis of lower grade glioma (LGG) patients depends (in large part) on both isocitrate dehydrogenase (IDH) gene mutation and chromosome 1p/19q codeletion status. IDH-mutant LGG without 1p/19q codeletion (IDHmut-Noncodel) often exhibit a unique imaging appearance that includes high apparent diffusion coefficient (ADC) values not observed in other subtypes. The purpose of this study was to develop an ADC analysis-based approach that can automatically identify IDHmut-Noncodel LGG., Methods: Whole-tumor ADC metrics, including fractional tumor volume with ADC > 1.5 × 10 -3 mm 2 /s (V ADC>1.5 ), were used to identify IDHmut-Noncodel LGG in a cohort of N = 134 patients. Optimal threshold values determined in this dataset were then validated using an external dataset containing N = 93 cases collected from The Cancer Imaging Archive. Classifications were also compared with radiologist-identified T2-FLAIR mismatch sign and evaluated concurrently to identify added value from a combined approach., Results: V ADC>1.5 classified IDHmut-Noncodel LGG in the internal cohort with an area under the curve (AUC) of 0.80. An optimal threshold value of 0.35 led to sensitivity/specificity = 0.57/0.93. Classification performance was similar in the validation cohort, with V ADC>1.5  ≥ 0.35 achieving sensitivity/specificity = 0.57/0.91 (AUC = 0.81). Across both groups, 37 cases exhibited positive T2-FLAIR mismatch sign-all of which were IDHmut-Noncodel. Of these, 32/37 (86%) also exhibited V ADC>1.5  ≥ 0.35, as did 23 additional IDHmut-Noncodel cases which were negative for T2-FLAIR mismatch sign., Conclusion: Tumor subregions with high ADC were a robust indicator of IDHmut-Noncodel LGG, with V ADC>1.5 achieving > 90% classification specificity in both internal and validation cohorts. V ADC>1.5 exhibited strong concordance with the T2-FLAIR mismatch sign and the combination of both parameters improved sensitivity in detecting IDHmut-Noncodel LGG.

Purpose: To compare radiation dose to organs at risk in patients with early-stage breast cancer treated with lumpectomy and intraoperative radiation therapy with CT-guided HDR brachytherapy (precision breast IORT; PB-IORT) and those treated with external beam whole breast irradiation (WB-DIBH) or partial breast irradiation (PB-DIBH) with deep inspiratory breath hold., Methods: We retrospectively identified 52 consecutive patients with left-sided breast cancers treated with either PB-IORT (n = 17, 76% outer breast) on a phase I clinical trial, adjuvant PB-DIBH (n = 18, 56% outer breast, 6% cavity boost), or WB-DIBH (n = 17, 76% outer breast, 53% with lumpectomy cavity boost). Conventional (2 Gy/fraction) or moderate hypofractionation (2.66 Gy/fraction) was prescribed for the external beam cohorts and 12.5 Gy in 1 fraction to 1 cm from the balloon surface was prescribed to the HDR brachytherapy cohort. CT-based planning was used for all patients. Organ at risk doses and excess risk ratios (ERR) for secondary lung cancers, contralateral breast cancers, and cardiac toxicity were compared between treatment techniques., Results: Compared to WB-DIBH and PB-DIBH, PB-IORT resulted in lower ipsilateral lung V5, V10, V20, mean, and max dose (P < .05). Mean ipsilateral lung BED 3Gy was as follows: 1.32 Gy for PB-IORT, 4.33 Gy for WB-DIBH, 3.35 Gy for PB-DIBH. The ERR for lung cancer was lowest for PB-IORT (P < .001). There was significantly higher contralateral breast max dose but lower mean BED 3Gy for WB-DIBH compared with PB-IORT (P = .012, P = .011, respectively). Mean contralateral breast BED 3Gy was as follows: 0.10 Gy for PB-IORT, 0.06 Gy for WB-DIBH, and 0.08 Gy for PB-DIBH. The ERR for contralateral breast cancer was low for all breast techniques, but WB-DIBH showed lower ERR compared to PB-IORT (P = .019). Mean heart BED 2Gy was higher with PB-IORT at 1.26 Gy compared to 0.48 Gy and 0.24 Gy for WB-DIBH and PB-DIBH, respectively (P < .001)., Conclusions: Patients with early-stage breast cancer treated with PB-IORT and with tissue-sparing external beam techniques all received low organ at risk doses, but PB-IORT resulted in far lower ipsilateral lung dose compared with external beam techniques. Our data indicate the lowest mean contralateral breast BED in the WB-DIBH group, likely due to the simplicity of the field design in low-risk patients using tangential whole breast radiation. External beam using DIBH results in lowest heart dose, but all techniques were well within recommended heart constraints., (© 2019 Wiley Periodicals, Inc.)

Purpose: For cervical brachytherapy planning, magnetic resonance imaging (MRI) is preferable to computed tomography (CT) for target delineation. However, due to logistical and financial restrictions, in-room MRI is sometimes not routinely available in brachytherapy centers. Our institution has created a workflow that integrates MRI-based target delineation with an in-room CT scanner, with the aim of improving target coverage and conformality. This study reports the initial dosimetric results with using this workflow., Material and Methods: A retrospective review was performed on 46 consecutive patients who received definitive chemoradiation with 5 fraction intracavitary high-dose-rate (HDR) brachytherapy for cervical cancer. Fraction 1 was planned from CT only. Outpatient MRI was obtained after Smit sleeve placement and first insertion to assess concurrent chemoradiotherapy tumor response. This MRI was registered to the CT for planning fractions 2-5. The median prescription dose for the cohort was 25 Gy (range, 25-29 Gy)., Results: The D 90 to the high-risk clinical target volume (HR-CTV) and D 2cc rectal dose were increased from fraction 1 to fraction 2-5 averaged ( p < 0.05). Among the 18 patients with complete volumetric data, there was no significant difference in HR-CTV size, with an average decrease of 1.73 cc ( p > 0.05) with MRI fusion. Eleven out of 18 patients had changes in high-risk target volume greater than 20%, with an absolute average change in volume of 31.5%., Conclusions: The use of asynchronous MRI for target delineation, with co-registration to CT for each fraction of brachytherapy was associated with higher D 90 to the HR-CTV. We observed slightly higher D 2cc rectal doses with MRI, but cumulative rectal doses were within accepted thresholds. High-risk target volumes were not consistently increased or decreased, but MRI fusion was associated with target volume changes greater than 20% in over half of the treated patients., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 Termedia.)

Introduction: Intraoperative radiation therapy is an emerging option for adjuvant therapy for early stage breast cancer, although it is not currently considered standard of care in the United States. We applied time-driven activity-based costing to compare two alternative methods of breast intraoperative radiation therapy, including treatment similar to the techniques employed in the TARGIT-A clinical trial and a novel version with CT-guidance and high-dose-rate (HRD) brachytherapy., Methods and Materials: Process maps were created to describe the steps required to deliver intraoperative radiation therapy for early stage breast cancer at each institution. The components of intraoperative radiation therapy included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource. Based on this, the delivery costs were calculated for each regimen. For comparison across centers, we did not account for indirect facilities costs and interinstitutional differences in personnel salaries., Results: The CT-guided, HRD form of intraoperative radiation therapy costs more to deliver ($4,126.21) than the conventional method studied in the TARGIT-A trial ($1,070.45). The cost of the brachytherapy balloon applicator ($2,750) was the primary driver of the estimated differences in costs. Consumable supplies were the largest contributor to the brachytherapy-based approach, whereas personnel costs were the largest contributor to costs of the standard form of intraoperative radiation therapy., Conclusions: When compared with the more established method of intraoperative radiation therapy using a portable superficial photon unit, the delivery of treatment with CT guidance and HDR brachytherapy is associated with substantially higher costs. The excess costs are driven primarily by the cost of the disposable brachytherapy balloon applicator and, to a lesser extent, additional personnel costs. Future work should include evaluation of a less expensive brachytherapy applicator to increase the anticipated value of brachytherapy-based intraoperative radiation therapy., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Adjuvant vaginal cuff brachytherapy is well tolerated and reduces the risk of local recurrence in endometrial cancer. However, there is provider variation in the number of radiation treatments, which ranges from three to six fractions. Using time-driven activity-based costing, we calculated the cost to deliver three vs six fractions to determine the value of each regimen at our brachytherapy suite with CT-on-rails., Methods and Materials: Process maps were created to represent each step from initial consult to completion of therapy. Components of care included personnel, equipment, and consumable supplies. The capacity cost rate was determined for each resource and calculated for each regimen., Results: The total direct costs to deliver three- and six-fraction treatment courses were $1,415 and $2,227, respectively. Personnel cost accounted for 63% of overall expenditures. Computed tomography simulation and planning, required for the first fraction, cost $232 for both regimens. Duties of the procedural nurse (scheduling, patient setup, and turnover) consumed the most time at 35% of total personnel minutes., Conclusions: Time-driven activity-based cost analysis revealed a 57% relative increase, but modest absolute increase, in delivery costs for six vs three fractions of brachytherapy at our institution. This current analysis may influence considerations of the relative value between the two treatment schedules, but this methodology should not be interpreted as informative for reimbursement policy evaluation., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

We present the case of radiation myonecrosis of the iliopsoas muscle, identified five months after stereotactic body radiation therapy (SBRT, 21 Gy in three fractions) to a metastatic lesion in the right iliac bone of a patient with leiomyosarcoma. The patient had been treated with various chemotherapeutic agents, most notably docetaxel and gemcitabine for five cycles 10 months prior to SBRT. As skeletal muscle is a radio-resistant organ, myonecrosis is rare, but previous case reports suggest that the administration of gemcitabine may increase the likelihood of radiation toxicity, including radiation myonecrosis. Physicians may consider conventional fractionation, rather than a hypofractionated course, in patients who have received or will receive gemcitabine., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors have nothing to disclose., (© 2020 Old City Publishing, Inc.)

Purpose: A multidisciplinary team at our institution developed a novel method of intraoperative breast radiation therapy (precision breast intraoperative radiation therapy [PB-IORT]) that uses high-dose-rate brachytherapy with CT on-rails imaging to deliver high-dose, customized radiotherapy to patients with early-stage breast cancer. This report summarizes our program's experience developing and implementing PB-IORT., Methods and Materials: Literature on PB-IORT was reviewed including published articles and abstracts. To evaluate case volume, all patients with a breast cancer diagnosis who underwent breast surgery or breast radiation (2010-2017) at our academic institution were identified. Patients were stratified into pre-IORT and post-IORT eras with initiation of our PB-IORT program in October 2013. Overall trends in surgical and radiation therapy volume in each era were analyzed by linear regression. Travel distance for all surgical patients was calculated using Google Maps (Alphabet Inc.) and then compared between IORT and non-IORT patients., Results: Data from a PB-IORT Phase 1 trial found that the primary endpoints were met and that PB-IORT is feasible and safe. The direct health system's delivery costs for PB-IORT exceed those of 16-fraction whole-breast irradiation when accounting for consumable supplies (multilumen balloon applicator = $2,750 per patient). There was a significant increase in yearly growth of breast cancer surgical volume with PB-IORT., Conclusions: Accrual rates for the ongoing Phase II trial have been quicker than expected in an area where more research is needed. The rapid accrual indicates patient interest and demand for this treatment and that it is very feasible to get more data from randomized trials., (Copyright © 2019. Published by Elsevier Inc.)

Using modern sentinel lymph node techniques, occult nodal metastases including micrometastases or isolated tumor cells are being increasingly discovered in up to 10% of early-stage breast cancers. Furthermore, the rate of nonsentinel lymph node involvement is approximately 10%. However, the impact of these findings on disease-free survival is low, particularly with regards to axillary recurrences. Current evidence suggests small-volume lymph node involvement in breast cancer patients is only one of several factors that should guide adjuvant therapy options. In otherwise favorable patients, adjuvant radiation and systemic therapy can help mitigate the risk of recurrence when omitting axillary lymph node dissection., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Given the uncertainty with regard to the effectiveness of pelvic nodal irradiation (PNI) for prostate cancer, we aimed to determine whether patients with prostate cancer who are treated with PNI are at a higher risk of developing radiation-related lymphopenia (RRL)., Methods and Materials: The electronic charts of 886 consecutive patients treated with radiation therapy for prostate cancer between 2006 and 2018 at our institution were retrospectively analyzed. Qualifying patients were those with total lymphocyte counts within 1 year before and 3 to 24 months after the start of radiation therapy. Lymphopenia was the primary outcome, and overall survival and biochemical progression-free survival were secondary outcomes., Results: Thirty-six patients with and 95 patients without PNI qualified for inclusion. In the PNI cohort, 61.1% of patients developed RRL (median follow-up total lymphocyte count < 1000 cells/μL) versus 26.3% of non-PNI patients ( P  < .001). On univariate analysis, initial prostate-specific antigen level, baseline lymphopenia, treatment modality, PNI status, increased planned target volume, and androgen deprivation therapy administration were all significant predictors of RRL ( P  < .05). On multivariate analysis, PNI status was a significant predictor of RRL (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.22-9.61; P  < .001), as were initial prostate-specific antigen values (HR, 1.05; 95% CI, 1.00-1.11; P  = .006) and baseline lymphopenia (HR, 8.32; 95% CI, 2.19-31.6; P  = .007). RRL was not predictive for biochemical progression-free survival, distant metastasis, or overall survival on multivariate analysis, but the number of events was likely insufficient for these analyses., Conclusions: The higher risk of RRL among patients with PNI comports with other papers that show that increased treatment volumes are associated with higher rates of RRL. Mounting evidence for the adverse effects of RRL on clinical outcomes supports the significance of our findings and suggests that further studies are needed on RRL as a potential harm of PNI that may affect the interpretation of results from clinical trials of PNI.

Pituitary adenomas represent a common intracranial pathology, usually resulting in the systemic secretion of hormones and compression of local endocrine and optic structures, causing a wide variety of clinical sequelae. While they are typically treated with upfront endocrine and/or surgical decompressive therapy, in patients with residual, recurrent, or refractory disease, decades of data support management with stereotactic radiosurgery. This modality offers favorable local tumor control, endocrine remission rates, and infrequent toxicity. In the future, this alternative to resection will continue to gain popularity among patients and health care providers., (© 2019 S. Karger AG, Basel.)

Introduction: The purpose of this study was to compare the utilization, pathologic response, and overall survival (OS) between long-course neoadjuvant chemoradiation (LC-CRT) and short-course neoadjuvant radiation (SC-RT) in the treatment of non-metastatic rectal cancer., Methods and Materials: Retrospective data was obtained from the National Cancer Database (NCDB) for patients diagnosed with clinical stage II or III (limited to T3, any N or T1-2, N1-2) rectal cancer between 2004 and 2014 (28,193 patients). Univariate and multivariate analyses were performed to investigate factors associated with receipt of SC-RT, pathologic complete response (pCR) rate, and OS. Patients were compared based on the neoadjuvant therapy they received prior to tumor resection. SC-RT was defined as 25 Gy given over 1 week prior to surgery (with or without chemotherapy as part of their treatment course). LC-CRT was defined as 45 to 60 Gy given over 5 to 6 weeks (with chemotherapy) prior to surgery., Results: A total of 27,988 (99%) of patients received LC-CRT, and 205 (1%) patients received SC-RT. Receipt of SC-RT was associated with older age, more comorbidities, and treatment at an academic facility (P < .001 for each). Additional days from radiation completion to surgery was associated with a higher pCR rate (P < .001 for both). LC-CRT did not lead to increased OS compared with SC-RT (P = .517)., Conclusions: In this United States database study, there was no improvement in OS for patients receiving LC-CRT compared with SC-RT; however, a longer interval between radiation therapy and surgery led to a higher pCR rate. Academic facilities were more likely to utilize SC-RT compared with other facilities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Leverage the National Cancer Database (NCDB) to evaluate trends in management of nonmetastatic squamous cell cancer (SCC) of the rectum and their effect on survival for this uncommon tumor., Methods and Materials: Retrospective data was obtained from the NCDB for patients diagnosed with SCC of the rectum between 2004 and 2014, including cT1-4, cN0-2, cM0 tumors (cohort A, n = 2296). A subgroup analysis was performed on locally advanced tumors (cT1-T2, N+ or cT3, N any, subcohort B, n = 883), treated with chemoradiation (n = 706) or trimodality therapy (n = 177) including chemotherapy, radiation, and surgery. Pathological complete response rate following neoadjuvant therapy was obtained. Univariate and multivariate logistic regression analyses were performed to generate hazard ratios (HR) investigating factors associated with overall survival. Kaplan-Meier (K-M) method was used to estimate overall surviving proportion at 5 and 10 years., Results: The K-M estimated 5 and 10 year overall survival for stage I disease was 71.3% and 57.8%, respectively; stage II disease was 57.0% and 38.9%, respectively; stage III disease was 57.8% and 41.5%, respectively. On multivariate analysis, higher cT category (P < 0.001) resulted in worse survival. For locally advanced tumors (subcohort B), there was no significant difference in survival between chemoradiation alone compared to trimodality therapy (P = 0.909 on multivariate analysis)., Conclusions: Most providers manage locally advanced SCC of the rectum similar to anal cancer, which results in equivalent overall survival and spares patients from the additional morbidity associated with surgical resection., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To determine the magnitude and reason for discrepancies between frame- and cone beam computed tomography (CBCT)-determined stereotactic coordinates, we reviewed frame-based Gamma Knife radiosurgery procedures in which CBCT was performed before treatment., Methods and Materials: Clinical and treatment documentation was reviewed for 150 frame placements for which stereotactic coordinates were defined via both frame and fiducials on computed tomography imaging and CBCT. Treatment planning system-reported rotational and translational differences and standard deviations (SDs) between frame-based and CBCT-based stereotactic coordinates were recorded. Potential clinical predictors for increased differences were collected. Multiple linear regressions were performed to evaluate for associations with increased translations and rotations., Results: The absolute mean of the measured pitch, yaw, and roll shifts was 0.14 degrees (range -0.71-0.63 degrees, SD 0.19 degrees), 0.16 degrees (range -0.50 to 0.83 degrees, SD 0.21 degrees), and 0.12 degrees (range 0.37-0.51 degrees, SD 0.15 degrees), respectively. The absolute mean of the measured shifts in the left-right, anteroposterior, and superior-inferior direction was 0.29 mm (range -1.29 to 0.82 mm, SD 0.35 mm), 0.24 mm (range -0.59 to 0.33 mm, SD 0.19 mm), and 0.24 mm (range -0.69 to 0.91 mm, SD 0.27 mm), respectively. Three cases (2.0%) exceeded 1 mm in translational difference, all in the left-right direction (1.05, 1.13, and 1.29 mm). Lower Karnofsky Performance Scale status was associated with greater translational differences (vector magnitude, P = .023) and rotation (pitch, P = .044; yaw, P = .002). Usage of longer total pin length (sum of all 4 fixation pin lengths) was associated with increased rotation but not with translation (P < .001 and P = .56, respectively)., Conclusions: CBCT imaging in this cohort of frame-based cases suggests that the discrepancy in stereotactic coordinates is less than 1 mm or degree in most cases. Low Karnofsky Performance Scale status and longer total pin length correlate with larger differences between frame-defined and CBCT-defined stereotactic coordinates., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Currently no firm consensus exists regarding utilization of stereotactic radiosurgery (SRS) alone versus whole brain radiation (WBRT) ± SRS in patients with multiple brain metastases. The International Gamma Knife Research Foundation conducted a survey to review international practice patterns., Methods: Through 2 international radiosurgery societies, clinicians who are involved in the radiosurgical management of patients with brain metastases were invited to complete a questionnaire. Respondents selected therapeutic options based on brief case vignettes and could select (1) SRS alone, (2) SRS with adjuvant WBRT, (3) WBRT alone, or (4) omission of upfront local radiation., Results: A total of 71 respondents replied to the survey, including 41 radiation oncologists (57%), 24 neurosurgeons (34%), and 6 (8%) other clinicians. For a patient with 7 brain metastases (NSCLC), all under 1 cm, and stable extracranial disease, 77% would perform SRS alone and 17% would recommend WBRT alone. For a patient with 7 or more brain metastases, the majority selected SRS alone, irrespective of tumor histology (p > 0.5). However, neurosurgeons would more often utilize SRS alone or SRS combined with WBRT compared to radiation oncologists (p = 0.002). Key clinical factors in selection were KPS (82% of respondents), total tumor volume (81%), number (80%), and less-so histology (42%)., Conclusion: Regardless of number of metastases, patients with small total volume of brain disease, high KPS, or who are receiving novel therapies are often recommended to undergo SRS. Neurosurgeons more often recommend SRS, emphasizing the importance of additional studies to clarify the role of SRS in these patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: We evaluated the impact of MRI-based target delineation on toxicity and tumour control after implementation of a protocol to incorporate MRI while minimizing impact on overall procedural time., Methods: We retrospectively reviewed outcomes for a cohort of 96 consecutive patients who received intracavitary brachytherapy for cervical cancer at our institution during 2012-2016. Starting in October 2014, an outpatient MRI was obtained for patients after Smit sleeve placement and first insertion to assess concurrent chemoradiotherapy tumour response. Then, for subsequent fractions, the MRI was co-registered by the Smit sleeve to the planning CT for target volume delineation. The primary and secondary outcomes were toxicity and local control, respectively., Results: Median follow-up for the pre- (n = 50) and post-MRI-based (n = 46) planning groups was 24.6 and 14.7 months, respectively. Median treatment duration for patients before and after MRI implementation was 56 and 58 days (P = 0.052), respectively. Cumulative rectal D2 cc was less for those with MRI-based target delineation (P = 0.005). On multivariable analysis, patients with MRI-based target delineation experienced fewer severe late (CTCAE grade ≥ 3) toxicities (P = 0.025, hazard ratio = 0.25). Local control was 86% and 91% of the pre- and post-MRI groups, respectively (P = 0.959)., Conclusions: Preliminary findings using this technique, which is applicable to other institutions without in-room MRI availability, are associated with lower radiation prescription doses, lower rectal doses and favourable toxicity rates while maintaining a rapid workflow. Longer follow-up is required to confirm equivalent local control., (© 2018 The Royal Australian and New Zealand College of Radiologists.)

Purpose: To analyze the national treatment trends of patients diagnosed with benign intracranial meningioma., Methods and Materials: Data was obtained from the National Cancer Database (NCDB) for patients with WHO grade I meningioma tumors between 2004 and 2014 (190,527 patients), diagnosed by either surgical specimen or diagnostic imaging. Univariable and multivariable analyses (binary logistic models) were performed to generate odds ratios (OR) and investigate factors associated with definitive initial treatment compared to initial observation. Initial treatments considered included surgical resection and/or radiation, including either fractionated external beam radiotherapy (EBRT) or stereotactic radiosurgery (SRS)., Results: The rate of observation increased over time, from 37% in 2004 to 55% in 2014 (p < 0.001). Conjointly, the rate of resection decreased from 50% to 37% from 2004 to 2014 (p < 0.001). The utilization of radiotherapy, including SRS, remained generally stable over time at 6% or less. SRS was more frequently utilized, compared to EBRT, as definitive treatment (4.6% versus 1.7%, respectively, p < 0.001). Compared to Community Cancer programs, patients at Academic/Research programs were more likely to receive definitive initial treatment over observation (OR = 2.909, each p < 0.001)., Conclusions: There is a national trend favoring initial observation for radiographically diagnosed WHO grade I meningioma. However, patients presenting to academic facilities are more likely to receive definitive initial treatment. Further research into differing approaches among treatment facilities for this common tumor may help clarify this trend., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: To evaluate the clinical outcomes of patients treated with 3D conformal Hypo-fractionated, deep Inspiratory breath-hold (DIBH), Partial breast radiotherapy, termed "HIP." HIP was implemented to merge the schedule of once-daily breast hypofractionation with partial breast treatment., Methods: We identified 38 breast cancers in 37 patients from 2013 to 2014 treated at our institution with HIP following lumpectomy for early stage breast cancer. Patients received a hypo-fractionated course (≤ 20 fractions) of once daily radiation to the partial breast (lumpectomy cavity + margin) utilizing DIBH regardless of laterality. Clinical and treatment-related characteristics were obtained, including target volume and organ at risk (OAR) dosimetric characteristics. Patients were followed clinically and with at least yearly mammograms for up to 36 months (range 5-36 months). Acute and late toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03., Results: Patients received a median dose of 42.56 Gy in 16 Fractions (Fx) (range 40.05-53.2 Gy; and 15-20 Fx). OAR doses were low, with a mean heart dose of 0.37 Gy, an ipsilateral lung V20 mean of 4%, and a contralateral lung V5 of 1%. Acute toxicity (≤ grade 2) was present in 79% (n = 30) of the cases, with dermatitis being the most common finding (63%). Late grade 1-2 toxicity was present in 42% (n = 16) of the cases, with hyperpigmentation being the most common finding (n = 9). There were no severe acute or late toxicities (≥ grade 3). At a median follow up of 21 months, there were no local, regional, or distant failures., Conclusions: We report limited toxicity in this low risk cohort of patients with early stage breast cancer treated with HIP, a unique and logical combination of 3-D conformal external beam radiotherapy, moderate hypo-fractionation, and DIBH.

Purpose: To investigate clinical characteristics and patterns of care among patients with central neurocytomas in a large cohort of patients., Methods: The National Cancer Database (NCDB) was queried to identify patients with biopsy confirmed neurocytoma from 2004 to 2015. Patterns of care were described and univariable and multivariable models were performed to investigate the impact of prognostic factors on overall survival., Results: Among 223,404 patients with brain tumors in the NCDB, 868 patients were diagnosed with biopsy-proven neurocytoma and analyzed (0.4% or approximately 75 patients annually). Median age at diagnosis was 31 years and median tumor size was 4-5 cm. Diagnosis was similar between male (49.5%) and female (50.5%). Regarding location, 622 (72%) tumors were intraventricular, 168 (19%) were extra-ventricular, and 78 (9%) overlapping or unspecified. Five-year overall survival among all patients was 89%. On multivariable analysis tumor location, extent of resection, and use of radiation, were not predictive for improved survival (each p > 0.05); however, patient age (p < 0.001), WHO grade (p < 0.001), and medical comorbidity scores (p = 0.002) were independently associated with overall survival., Conclusion: Patients with central neurocytoma often present as young adults with sizable tumor burden and are well managed with surgery alone. Considering their favorable survival, efforts to improve tumor control should be carefully weighed against the long-term risks associated with adjuvant therapy like radiation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To compare and describe the time to endocrine remission and new hypopituitarism among patients with growth hormone (GH) and adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas after radiosurgery, controlling for several known prognostic factors., Methods and Materials: An institutional review board-approved, institutional retrospective analysis of patients with GH- and ACTH-secreting pituitary adenomas was performed, with matching for patient sex, age at radiosurgery, interval between the last resection and radiosurgery, use of previous radiation therapy, whole sella treatment, suprasellar extension, cavernous sinus invasion, and margin dose. Endocrine remission was defined as a normal serum insulin-like growth factor-1 (GH secreting) or a normal 24-hour urine-free cortisol (ACTH secreting) level without suppressive medications. Endocrine remission and the incidence of new hypopituitarism after single-fraction radiosurgery were recorded and compared between the 2 groups., Results: The data from 242 patients were evaluated, 121 with GH-secreting tumors and 121 with ACTH-secreting tumors. Of the 242 patients, 75% had cavernous sinus invasion and 10% had suprasellar extension at radiosurgery. The median radiosurgical marginal dose was 25 Gy to the 50% isodose line between each group. After multivariable adjustment, the factors associated with an increased time to endocrine remission included patient age (hazard ratio [HR] 1.016; P = .023), cavernous sinus invasion (HR 1.793; P = .004), and the presence of acromegaly (HR 2.912; P < .001). The incidence of new hypopituitarism developing after stereotactic radiosurgery was 29% and did not appreciably differ by adenoma subtype (P = .180)., Conclusions: After radiosurgery, patients with ACTH-secreting tumors achieved endocrine remission sooner than did those with GH-secreting tumors. These results provide insight into the relative tumor biology and disease course after radiosurgery that will serve to further improve clinical outcomes and patient treatment in the future., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To develop a quality assurance (QA) tool that identifies inaccurate organ at risk (OAR) delineations., Methods: The QA tool computed volumetric features from prior OAR delineation data from 73 thoracic patients to construct a reference database. All volumetric features of the OAR delineation are computed in three-dimensional space. Volumetric features of a new OAR are compared with respect to those in the reference database to discern delineation outliers. A multicriteria outlier detection system warns users of specific delineation outliers based on combinations of deviant features. Fifteen independent experimental sets including automatic, propagated, and clinically approved manual delineation sets were used for verification. The verification OARs included manipulations to mimic common errors. Three experts reviewed the experimental sets to identify and classify errors, first without; and then 1 week after with the QA tool., Results: In the cohort of manual delineations with manual manipulations, the QA tool detected 94% of the mimicked errors. Overall, it detected 37% of the minor and 85% of the major errors. The QA tool improved reviewer error detection sensitivity from 61% to 68% for minor errors (P = 0.17), and from 78% to 87% for major errors (P = 0.02)., Conclusions: The QA tool assists users to detect potential delineation errors. QA tool integration into clinical procedures may reduce the frequency of inaccurate OAR delineation, and potentially improve safety and quality of radiation treatment planning., (© 2018 American Association of Physicists in Medicine.)

Purpose: To evaluate the delivery cost of frequently used radiotherapy options offered to patients with intermediate- to high-risk prostate cancer using time-driven activity-based costing and compare the results with Medicare reimbursement and relative value units (RVUs)., Methods and Materials: Process maps were created to represent each step of prostate radiotherapy treatment at our institution. Salary data, equipment purchase costs, and consumable costs were factored into the cost analysis. The capacity cost rate was determined for each resource and calculated for each treatment option from initial consultation to its completion. Treatment options included low-dose-rate brachytherapy (LDR-BT), combined high-dose-rate brachytherapy single fraction boost with 25-fraction intensity-modulated radiotherapy (HDR-BT-IMRT), moderately hypofractionated 28-fraction IMRT, conventionally fractionated 39-fraction IMRT, and conventionally fractionated (2 Gy/fraction) 23-fraction pelvis irradiation with 16-fraction prostate boost., Results: The total cost to deliver LDR-BT, HDR-BT-IMRT, moderately hypofractionated 28-fraction IMRT, conventionally fractionated 39-fraction IMRT, conventionally fractionated 39-fraction IMRT, and conventionally fractionated (2 Gy/fraction) 23-fraction pelvis irradiation with 16-fraction prostate boost was $2719, $6517, $4173, $5507, and $5663, respectively. Total reimbursement for each course was $3123, $10,156, $7862, $9725, and $10,377, respectively. Radiation oncology attending time was 1.5-2 times higher for treatment courses incorporating BT. Attending radiation oncologist's time consumed per RVU was higher with BT (4.83 and 2.56 minutes per RVU generated for LDR-BT and HDR-BT-IMRT, respectively) compared to without BT (1.41-1.62 minutes per RVU)., Conclusions: Time-driven activity-based costing analysis identified higher delivery costs associated with prostate BT compared with IMRT alone. In light of recent guidelines promoting BT for intermediate- to high-risk disease, re-evaluation of payment policies is warranted to encourage BT delivery., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Early-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is associated with a favorable prognosis. Our aim was to evaluate the patterns of care of radiotherapy utilization in this disease and to define the relationship between treatment modality and survival. The National Cancer Database was queried for patients with stages I-II NLPHL diagnosed from 2004 to 2012. Patients were compared based on primary therapy into four categories: radiotherapy, chemotherapy, both, or neither. Covariate-adjusted and propensity score-weighted (PS) Cox proportional hazards models were used, adjusting for potential factors confounding survival. After exclusions, 1420 patients were evaluated, 571 (40%) received radiotherapy alone, 318 (22%) received chemotherapy alone, 351 (25%) received both, and 180 (13%) received neither. Younger patient age (P = 0.001), female gender (P = 0.019), and chemotherapy use (P < 0.001) were associated with decreased radiotherapy utilization. On PS, radiation alone (HR = 0.298, P < 0.001) and chemoradiotherapy (HR = 0.258, P < 0.001) were associated with improved survival compared to no upfront therapy, but the use of chemotherapy alone did not statistically differ compared to no initial therapy (HR = 0.784, P = 0.078). In this large database analysis, over one-third of patients with early-stage NLPHL did not receive radiotherapy as a component of initial therapy. The omission of upfront radiotherapy was associated with inferior survival., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: There is an established relationship between hormone receptor (HR; estrogen and/or progesterone receptors) status, HER2 status, and locoregional recurrence. The purpose of this study was to analyze how HR and HER2 receptor status have influenced the surgical management trends among patients with early stage breast cancer., Patients and Methods: The National Cancer Database was queried for patients with cT1 to cT3, cN0, and cM0 breast carcinoma from 2004 to 2012. Patients were grouped on the basis of receptor status and surgical management (mastectomy or breast-conserving surgery [BCS]). Multivariable analyses were performed to investigate factors associated with increased odds of receiving mastectomy over BCS. Among a subgroup of patients who underwent ipsilateral mastectomy, analyses were performed to determine any association between contralateral prophylactic mastectomy (CPM) and receptor status., Results: We found 280,241 patients who met inclusion criteria for analyzing mastectomy or BCS surgical decision. Patients with HER2-positive (HER2 + ) tumors (HR + /HER + and HR - /HER2 + ) were the most likely to undergo mastectomy (odds ratio [OR], 1.212 and 1.499 respectively, compared with HR + /HER2 - patients, each P < .001). HR status alone did not affect ipsilateral surgical management as patients with HR + /HER2 - and HR - /HER2 - tumors demonstrated similar mastectomy rates (P = .391). Among the 108,018 who underwent mastectomy, 20% underwent CPM. After adjustment, patients with HR + /HER2 + , HR - /HER2 + , and HR - /HER2 - were all more likely to undergo CPM (OR 1.356, 1.608, and 1.358, respectively compared with HR + /HER2 - patients, each P < .001)., Conclusion: This analysis indicates that patients with early stage breast cancer are more likely to undergo a mastectomy and CPM if they have HER2 + tumors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To identify if facility type and/or facility volume impact overall survival (OS) following diagnosis of glioblastoma (GBM). We also sought to compare early post-surgical outcomes based on these factors., Methods: The National Cancer Database was queried for patients with GBM diagnosed from 2004 to 2013 with known survival. Patients were grouped based on facility type and facility volume. Multivariable analyses were performed to investigate factors associated OS following diagnosis and Chi-square tests were used to compare early post-surgical outcomes., Results: 89,839 patients met inclusion criteria. Factors associated with improved OS on multivariable analysis included younger patient age, female gender, race, lower comorbidity score, higher performance score, smaller tumor size, unifocal tumors, MGMT hypermethylation, fully resected tumors, radiotherapy, and chemotherapy (each p < .001). Also, OS was improved among patients treated at centers averaging at least 30.2 cases per year (HR 0.948, compared to <7.4 cases/year, p < .001), and patients treated at Academic/Research programs had improved survival compared to those treated at Comprehensive Community Cancer programs (HR 1.069, p < .001) and Integrated Network Cancer programs (HR 1.126, p < .001). Similarly, Academic/Research programs and high volume centers demonstrated improved 30- and 90-day morality as well as 30-day readmission rates (p < .001)., Conclusions: This study suggests that patients treated in Academic/Research programs and high patient-volume centers have increased survival and more favorable early-postsurgical outcomes. The extent to which differences in patient populations, socioeconomic factors, and/or provider expertise play into this cause will be areas of future research., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Cone beam CT (CBCT) imaging has been integrated into the most recent version of the Leksell Gamma Knife for the primary purpose to facilitate fractionated therapy., Case Description: This case study presents three patients where the CBCT system of the Gamma Knife Icon discovered potentially clinically significant frame shifts. In each case, patients were imaged with volumetric MR prior to stereotactic frame placement. Immediately following frame placement, diagnostic stereotactic CT imaging was acquired with a stereotactic indicator box attached to the frame. Following treatment planning and immediately before radiosurgery, a CBCT was acquired using the on-board imaging functionality of the Gamma Knife Icon, which provides a registration of the patient's anatomy to stereotactic space independent of that provided by the stereotactic frame/fiducials. Co-registration of the CT and CBCT provides an estimate of the difference between these two estimates of stereotactic coordinates. The vector magnitudes of the differences measured at the center of stereotactic space were 0.93mm, 2.64mm and 2.18 mm for Case 1, Case 2 and Case 3 respectively., Conclusions: Use of the CBCT functionality of the Gamma Knife Icon to verify the consistency of frame placement can prevent clinically significant targeting errors due to frame slippage or frame adapter mounting errors, and allows any required adjustments to be made without interrupting the overall treatment workflow., Competing Interests: Authors’ disclosure of potential conflicts of interest Dr. Schlesinger reports grant from Elekta Instrument, AB, outside the submitted work. Dr. Trifiletti reports other support from Novocure, outside the submitted work. Drs. Dutta, Larner, Peach and Sheehan have nothing to disclose.

Introduction: Patients with intermediate to high risk disease (prostate specific antigen (PSA) ≥ 10, Gleason score ≥ 7, or clinical stage ≥ T2b) suffer from poorer long-term biochemical control (freedom from an increasing prostate specific antigen level) when treated with external beam radiation (EBRT) alone. In order to improve biochemical control while limiting long-term complications, brachytherapy has been incorporated into radiotherapy treatment, either alone or in combination with EBRT., Areas Covered: Current literature regarding the use of high dose-rate (HDR) brachytherapy for localized prostate cancer, including as a boost and monotherapy. The efficacy and toxicities of various approaches are evaluated including comparisons to low dose-rate (LDR) brachytherapy., Expert Commentary: Prostate HDR brachytherapy has higher conformality than EBRT, potentially improving the therapeutic ratio by allowing higher doses per fraction to tumor cells. The improved biochemical control shown in trials have resulted in EBRT plus brachytherapy to be included as a standard treatment option supported by the NCCN and ASCO guidance documents for intermediate to high risk prostate cancer.

Background: To analyze the national trends of patients treated radiotherapy for brain metastases from non-small cell lung cancer (NSCLC) that were found at diagnosis., Methods: The National Cancer Database was queried for patients with NSCLC diagnosed from 2004 to 2013 that received brain irradiation for metastases and patients grouped into having had received fractionated brain radiotherapy (5-15 fractions with or without radiosurgery) or intracranial radiosurgery alone (1-5 fractions). Univariable and multivariable (MVA) analyses were performed to investigate factors associated with the receipt of SRS alone, and temporal/regional trends., Results: 47,746 patients met inclusion criteria, of which 42,148 received fractionated brain irradiation (88%) and 5,598 received radiosurgery (12%). 345 patients received fractioned brain irradiation with a radiosurgical boost (0.8%). The utilization of radiosurgery-alone increased over time owing to increases in each radiosurgery modality. On MVA, several factors were associated with increased odds of receiving intracranial radiosurgery-alone over fractionated brain radiotherapy including more recent year of diagnosis, increased median income, eastern U.S. regions, further distance to the hospital, and the receipt of chemotherapy (each p<0.001). Patients of Asian descent were less likely to receive radiosurgery alone (p=0.044)., Conclusions: In the management of brain metastases from NSCLC, overall utilization of an intracranial radiosurgery alone treatment strategy has increased over the past decade. Despite this, there appear to be significant geographic variations and disparities remain based on patient income level and race. Further study is needed to define the reasons for these disparities and appropriate actions to mitigate them., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the effectiveness of radiation therapy among elderly patients who are deemed medically inoperable., Methods and Materials: We searched PubMed to identify studies from the past 25 years that reported outcomes of medically inoperable endometrial cancer patients treated with radiation alone. The National Cancer Database (NCDB) was queried to identify patients 65 years and older with Stage I-II medically inoperable endometrial cancer. Univariable and multivariable models were performed to investigate the impact of prognostic factors on overall survival., Results: Thirteen papers met inclusion criteria for the systematic review. Overall survival for Stage I tumors at 5 years was 30-95%. Reported pelvic control for the 888 total patients with Stage I tumors was 80-100% and 61-89% for Stage II. Late complications for all patients treated ranged from 0% to 21% across patients. The NCDB analysis demonstrated that any radiotherapy was associated with improved survival over no local therapy. Combination therapy (external beam radiation therapy + brachytherapy) was associated with the most favorable survival with a hazard ratio (HR) of 0.442 (p < 0.001 over no radiotherapy), although benefits were also seen with external beam radiation therapy alone (HR 0.694, p < 0.001) and with brachytherapy alone (HR 0.499, p < 0.001) compared to no radiotherapy., Conclusions: The available evidence suggests high rates of local control after radiation therapy for elderly women with Stage I-II medically inoperable endometrial cancer. Our analysis of the NCDB suggests that radiation therapy improves survival, and combination therapy provides the most favorable outcomes. Given a relatively favorable toxicity profile, definitive radiation therapy should be considered a preferred approach for patients with medically inoperable endometrial cancer., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)