Faculty Bibliography

PURPOSE/OBJECTIVE:Randomized data support accelerated partial breast irradiation (APBI) for early-stage breast cancer with variable techniques and cosmesis outcomes. We have treated patients with 5-fraction prone external beam APBI for over a decade and herein report acute and late outcomes. METHODS AND MATERIALS/METHODS:Patients receiving APBI 600 cGy × 5 between 2010 and 2019 were included. APBI was primarily delivered prone, with opposed tangents targeting the tumor bed expanded by 1.5 cm (cropped 6 mm from skin). Ipsilateral breast was constrained to V50% < 60% and V100% < 35%. Survival was estimated with Kaplan-Meier. Late toxicities and clinician- and patient-rated cosmesis were evaluated for patients with >6 months follow-up (FU). RESULTS:Of 345 patients meeting criteria, 14 were excluded due to APBI given for ipsilateral breast tumor recurrence (IBTR; n = 3), palliation (n = 9), and incomplete radiation therapy course (n = 2). Of the 331 remaining, median age was 70, 7.2% had ductal carcinoma in situ, and 94.3% were treated prone, with 32% treated every other day and 68% on consecutive days. Mean heart dose was 23.8 cGy for left-sided and 12.7 cGy for right-sided cancers. Ipsilateral lung V30% was 0.4%. At 5-year median FU, there were 7 (2.1%) IBTR, 9 (2.7%) contralateral recurrences, and 1 (0.3%) distant metastasis. Five-year local recurrence-free, disease-free, and overall survival was 99.5%, 96.7%, and 98.1%, respectively. When comparing patients with IBTR versus without, a higher proportion did not receive hormone therapy (71.4% vs. 26.2%, P = .018). Rates of acute grade 1 to 2 dermatitis, fatigue, and pain were 35.4%, 21.8%, and 9.4%, respectively, with no grade 3 toxicity. The rate of good-excellent physician- and patient-rated cosmesis (n = 199, median FU 2.8 years) was 92.5% and 89.4%, respectively. Patients experienced low rates of telangiectasia, fibrosis, and retraction/atrophy. CONCLUSIONS:We report excellent dosimetric, oncologic, cosmetic, and late toxicity outcomes for patients treated with 5-fraction APBI. To our knowledge this is the largest series of women treated with prone APBI.

PURPOSE/OBJECTIVE(S): The supraclavicular (SCV), medial axillary and internal mammary nodes (IMNs) are not typically resected in breast cancer patients (pts). The optimal local therapy of pts with nodal disease in these regions is not well-studied. We aim to evaluate outcomes of breast cancer patients with unresected nodal disease. MATERIALS/METHODS: We identified 79 pts at our institution from 2016- 2021 with unresected nodal disease in the axilla, SCV and/or IMNs defined as grossly enlarged nodes on CT, MRI or PET scan +/- biopsy confirmation. Pts were treated with breast/chest wall and regional nodal irradiation with an additional boost to the unresected nodal region. Distant failure (DF) and local-regional failure (LRF) were assessed. Kaplan-Meier was used to calculate disease-free survival (DFS), overall survival (OS) and local recurrence-free survival (LRFS). Logistic regression was used to identify variables associated with worse DFS. Acute and late toxicity of RT were evaluated.
RESULT(S): 33% of pts were treated with breast-conserving surgery, 65% with mastectomy and all had axillary surgery (81% ALND, 19% SLNB). 47% of pts received IMN boost (IMN), 40% axillary/SCV boost (axSCV) and 15% both IMN and axSCV boost (IMN/axSCV). Most had cT2-3 (72%), hormone receptor positive (75%), and HER-2 negative disease (84%). 57% of axSCV had cN3A disease; 84% of IMN and 83% of IMN/axSCV had cN3b disease. 7% of axSCV and 17% of IMN/axSCV had cN3c disease. Most pts received chemotherapy (97%). Median nodal boost dose was 10 Gy (range 10-20 Gy), with 17% axSCV, 22% IMN, and 17% IMN/axSCV receiving 14-20 Gy. Rates of acute and late grade 3 toxicity did not differ by boost location (acute: IMN: 20%, axSCV: 11% and IMN/axSCV 20%, P=0.559; late: IMN: 40%, axSCV: 25%, IMN/axSCV: 40%, P=0.630) nor by boost dose (10 Gy vs 14-20 Gy). There were no grade 4+ toxicities. With a median follow up of 30 months, the 3-year LRR, DFS, and OS was 94.5%, 86.3% and 93.8% respectively. Crude rates of failure for the entire group were 13.9% (10.1% DF; 3.8% DF+LRF). Rates of failure by boost group were axSCV: 13.3% (10% DF; 3.3% DF+LRF), IMN: 5.4% (2.7% DF, 2.7% DF+LRF), IMN/axSCV 41.7% (33.3% DF, 8.3% DF+LRF). There were no LRFs without DFs. Median time to failure was 23 months (IQR 18-34). On univariate analysis clinical tumor size (cT) and IMN/axSCV vs. IMN or axSCV alone was associated with worse DFS (HR: 9.78 95% CI 2.07-46.2, P=0.004 and HR: 9.49 95% CI 2.67-33.7, P=0.001). On multivariate analysis, cT approached significance (HR 6.15; 95% CI 0.95-39.8, P=0.05). IMN/axSCV vs. IMN or axSCV alone retained significance (HR 4.80; 95% CI 1.27-18.13, P=0.02). The difference between the axSCV vs. IMN group was not significant.
CONCLUSION(S): In this population of pts with unresected nodal disease, boost RT to radiographically positive LN regions can be safely delivered with low rates of grade 3+ toxicity. The majority of failures were distant with no isolated LRFs. Failures were highest in the IMN/axSCV group (~40%). Further treatment escalation is necessary for these pts.
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PURPOSE/OBJECTIVE(S): Healthcare data often exist in silos and in unstructured formats that limit interoperability and require tedious manual extraction. Our institution has adopted a flexible and scalable big data platform built on Hadoop that integrates data from Epic/Clarity as well as Aria and allows users to leverage modern data science tools to facilitate access. We hypothesize that a data analytics and visualization dashboard can be built using open-source tools that will (1) allow non-technical users to explore de-identified clinical data within our institutional big data platform and (2) connect with repositories of molecular data to demonstrate potential methods of integrating clinical and basic science data. MATERIALS/METHODS: De-identified patient-level radiation oncology data from the institutional big data platform (Hadoop) were extracted with the python packages pyodbc and pandas. For the purposes of this dashboard, radiation oncology specific clinical data elements were queried including the date of first radiation treatment, treatment location, treatment modality (SBRT, external beam, SRS, TBI, LDR/HDR brachytherapy), ICD10 codes, anatomic treatment site, number of fractions, treatment prescription, and dose per fraction. A python client connection with the publicly accessible instance of cBioPortal for Cancer Genomics was established using the Bravado library. Data transformation and cleaning was performed in python using panda's data frames. A web-based dashboard to facilitate user-defined visualizations was implemented using the Dash python library and interactive visualizations of subsets of extracted data were generated in real-time using the plotly plotting library.
RESULT(S): We developed a web-based dashboard that gives users without extensive programming expertise the ability to explore de-identified clinical data extracted from Hadoop. As proof of principle, the dashboard was used to visualize the clinical impact of the COVID-19 pandemic on radiation oncology patient volumes, revealing a significant decline in new radiation treatments in April and May of 2020 (-54% and -36% compared to 2019) during the initial COVID-19 surge. Furthermore, the dashboard allows users to interact with the cBioPortal for Cancer Genomics repository, which currently houses clinical and molecular data from 301 publicly available studies spanning 869 different cancer types. This interface with cBioPortal illustrates the potential for future integration of clinically meaningful sequencing results with clinical outcomes data.
CONCLUSION(S): We built an interactive web-based dashboard to enable general users' easy access to de-identified clinical data stored within the institutional big data platform. Additional data sources, including external molecular data can be connected to the dashboard allowing for future integration.
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PURPOSE/OBJECTIVE(S): TBI is a backbone of many conditioning regimens for hematopoietic stem cell transplants but can lead to both acute and late toxicity including radiation-induced interstitial pneumonitis. The incidence of idiopathic pneumonia syndrome (IPS) after TBI-based myeloablative conditioning regimens ranges from 7% to 35%. The purpose of this study is to implement image guided volumetrically modulated technique (VMAT) for TBI with the goal of lung sparing and improved target coverage. MATERIALS/METHODS: Nine patients have been treated using image-guided VMAT based TBI at our institution as part of a single-arm phase 2 clinical trial for patients undergoing myeloablative conditioning regimens. The trial was approved by our internal review board (IRB) in September 2020 and aims to accrue 15 patients within one year. All patients enrolled in the trial have signed informed consent. The primary endpoints of the study are the following dosimetric constraints: V100% >= 90%, D98% >= 85% of Rx dose for the planning target volume (PTV), and a mean lung dose < 9 Gy. PTV is defined as the body contour cropped 5 mm from the surface and excluding lungs and kidneys but extended 3 mm into these organs. Additional secondary dosimetric endpoints include mean dose to each individual kidney < 11 Gy, and maximum dose to 2cc of the entire body < 130% of Rx dose. Clinical endpoints include the occurrence of IPS in the first 100 days after transplant, occurrence of acute graft versus host disease (GVHD), transplant related mortality or mortality in the first 100 days following transplant.
RESULT(S): Patients were treated to 12 Gy in 8 BID fractions (n=6) or 13.2 Gy in 8 BID fractions (n=3) over four consecutive days. All patients were able to complete treatment to the prescribed dose as planned. All patient plans met dosimetric constraints of the study. The median PTV V100% was 93.2% of Rx dose (Max: 95.6%, Min: 92.1%), the median PTV D98% was 90.2% of Rx dose (Max: 94.3%, Min: 88.3%), and the median lung dose mean was 7.63 Gy (Max: 7.94 Gy, Min: 7.29 Gy). In addition, individual kidney mean doses were < 11 Gy, and body maximum dose (D2cc) was < 130% of Rx dose for all patients. At this time, only one patient (12 Gy treatment) has reached the 100 day post-transplant follow-up with the following findings: no relapse on bone marrow biopsy, no pneumonitis, resolved acute GVHD overall grade 1 (skin: 1, GI: 0, Liver: 0), resolved dermatitis (grade 1), resolved vomiting (grade 2), ongoing diarrhea and nausea (grade 1, previously grade 2).
CONCLUSION(S): Our initial results indicate that primary and secondary dosimetric endpoints were achievable for all protocol patients treated thus far. As the trial progresses, secondary clinical endpoints at 100 day follow-up will be analyzed to evaluate occurrence of IPS, survival, and treatment related toxicities.
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PURPOSE/OBJECTIVE(S): Use of local therapy such as stereotactic body radiation therapy (SBRT) to treat oligometastatic malignancy is a well-established paradigm, but whether benefit extends to the oligoprogressive setting remains unclear. We present our institutional series of patients with oligometastatic or oligoprogressive malignancy treated with SBRT. MATERIALS/METHODS: We performed a retrospective study of patients with oligometastatic and oligoprogressive malignancy treated with SBRT between 2014 and 2019. Oligometastatic patients were defined as those with five or fewer metastatic lesions in total. Oligoprogressive patients were defined as those with more than five and up to twenty metastatic lesions in total, of which five or fewer metastases were progressing on current systemic therapy. Patients lacking complete treatment records or follow-up imaging were excluded. The study was approved by the NYU Institutional Review Board.
RESULT(S): A total of 114 patients were treated with 123 courses of SBRT, of which 96 treated oligometastasis and 27 treated oligoprogression. Primary sites of disease included lung (38%), prostate (20%), and GI (12%), as well as gynecologic, abdominal, and cutaneous malignancies. Median follow-up was 21 months. No grade 3 or higher radiation-related adverse events were reported. Patients with oligometastatic malignancy had longer 2-year overall survival (79% vs 59%; P=0.003), local control (73% vs 55%; P=0.01), and progression-free survival (26% vs 8%; P < 0.001), but similar freedom from new systemic therapy (36% vs 31%; P=0.8). This result held true in subgroup analysis regardless of lung vs non-lung primary site, and regardless of the presence or absence of a targetable mutation.
CONCLUSION(S): In this hypothesis-generating retrospective cohort study, patients with oligoprogressive malignancy treated with SBRT have similar freedom from new systemic therapy to patients with oligometastatic malignancy, strengthening the rationale for treating oligoprogressive malignancy with SBRT.
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PURPOSE/OBJECTIVE:Stereotactic radiosurgery (SRS) has become an important modality in the treatment of brain metastases. The purpose of this study is to investigate the potential of radiomic features from planning magnetic resonance (MR) images and dose maps to predict local failure after SRS for brain metastases. MATERIALS/METHODS/METHODS:Twenty-eight patients who received Gamma Knife (GK) radiosurgery for brain metastases were retrospectively reviewed in this IRB-approved study. 179 irradiated tumors included 42 that locally failed within one-year follow-up. Using SRS tumor volumes, radiomic features were calculated on T1-weighted contrast-enhanced MR images acquired for treatment planning and planned dose maps. 125 radiomic features regarding tumor shape, dose distribution, MR intensities and textures were extracted for each tumor. Logistic regression with automatic feature selection was built to predict tumor progression from local control after SRS. Feature selection and model evaluation using receiver operating characteristic (ROC) curves were performed in a nested cross validation (CV) scheme. The associations between selected radiomic features and treatment outcomes were statistically assessed by univariate analysis. RESULTS:The logistic model with feature selection achieved ROC AUC of 0.82 ± 0.09 on 5-fold CV, providing 83% sensitivity and 70% specificity for predicting local failure. A total of 10 radiomic features including 1 shape feature, 6 MR images and 3 dose distribution features were selected. These features were significantly associated with treatment outcomes (p < 0.05). The model was validated on independent holdout data with an AUC of 0.78. CONCLUSIONS:Radiomic features from planning MR images and dose maps provided prognostic information in SRS for brain metastases. A model built on the radiomic features shows promise for early prediction of tumor local failure after treatment, potentially aiding in personalized care for brain metastases.

Purpose: This study investigated the accuracy of two dose calculation algorithms (AAA version 15.6.05 and AcurosXB (AXB) version 15.6.05) in lung, fat, and bone regions of a lung phantom using 2D Gamma analysis.
Method(s): A commercial thorax phantom (CIRS) was marked and CT simulated with 1.5 mm slice thickness then planned in Eclipse v15.6 (Varian) using an oblique 3x3 cm field traversing soft tissue, lung, and spine regions. Dose was calculated using AAA and AXB algorithms at 1.0 mm resolution for four different beam energies with the same number of monitor units: 6X, 6X-FFF, 10X and 10X-FFF. Each field was separately delivered to the phantom with Gafchromic EBT3 film placed in the axial plane through the beam isocenter. Film alignment was performed using built-in phantom pins as registration marks. Gamma analysis was performed in SNC Patient 8.2 (Sun Nuclear Corp.) software using distanceto- agreement (DTA) to compare AAA and AXB calculated doses against one another and against measured dose.
Result(s): Considerable dosimetric differences occurred between AAA and AXB especially at tissue interfaces and in the beam penumbra within the lung. About 10% and 30% of analyzed points had dose differences larger than 3% for 6X and 10X, respectively. The differences were a few percentages smaller for non-flattened beams. In comparison of calculation with measurement, the 3%/2mm-DTA passing rate for AAA was 3.7% higher than AXB for the 6X beam (3.9% for 6X-FFF), but -15.9% lower for 10X (- 24.9% for 10X-FFF).
Conclusion(s): Dose calculation algorithm accuracy was assessed in a heterogeneous thorax phantom using 2D gamma analysis and Gafchromic film. Large differences in the passing rate, especially at 10X(FFF), suggest to verify that clinical plan evaluation metrics such as coverage and dose constrains are not compromised by the choice of dose calculation algorithm

Purpose: To investigate the effect of patient positioning in Volumetric Modulated Arc Therapy (VMAT) for Total Body Irradiation (TBI) given the use of multiple isocenters, by simulating offsets in patient positioning and evaluating changes to planned dose distributions.
Method(s): VMAT treatment plans for seven TBI patients treated as part of a prospective stage II clinical trial were evaluated. Plan uncertainties were calculated by introducing 5mm and 10mm translational shifts to the plans' isocenters in the lateral (x), vertical (y), and longitudinal (z) directions. Dose distributions were then re-calculated in the treatment planning system (Eclipse), in order to evaluate dosimetric robustness to one global imaging shift at treatment. Differences in target volume (PTV) coverage and doses to organs at risk were evaluated based on four parameters: lung mean dose, PTV-V100%, PTV-D98%, and kidney mean doses.
Result(s): Lung mean dose increased an average of 8.2cGy, 4.4cGy, and 3.3cGy when shifted 5mm in the x, y, z directions (respectively) across seven patients; 33.2CGy, 18.5cGy, 18.3cGy for 10mm shifts in x, y, z. Target coverage V100% decreased an average of 0.3%, 0.03%, 0.1% for 5mm shifts, and 1.1%, 0.8%, 0.4% for 10mm shifts in x, y, z. D98% decreased 0.9%, 0.3%, 0.3% when shifted 5mm; 3.5%, 2.1%, 1.0% when shifted 10mm in x, y, z. Mean dose to the left kidney increased 6.6cGy, 9.7cGy, 2.8cGy for 5mm, and 28.1cGy, 32.7cGy, 18.0cGy for 10mm shifts in x, y, z. Right kidney mean dose increased 11.9cGy, 8.9cGy, 3.1cGy for 5mm, and 36.5, 30.5, 19.8cGy for 10mm.
Conclusion(s): Though small in relation to total dose, the largest increase in mean lung dose and decrease in coverage was seen with lateral shifts as compared to vertical or longitudinal shifts. These results support the use of an approach with preferential alignment to the chest region (lung-sparing), as long as residual imaging alignment outside the chest is kept below 10mm. Jose Teruel has received honorarium from Varian Medical Systems

Purpose: Multi-isocentric treatment delivery for CSI and TBI poses specific challenges for treatment delivery. We have developed a software tool to streamline all aspects of delivery for therapists and physicists at the machine, as well as to inform attending physicians of setup variability and image residuals at different locations.
Method(s): Our institution delivers VMAT-based CSI and TBI with up to 3 and 7 isocenters, respectively. A software tool was developed to assist with treatment delivery including initial patient setup, patient imaging, automatic calculation of the optimal global shift based on each isocenter's ideal shift, and automatic calculation of each isocenter's couch coordinates. Initial treatment couch coordinates are queried via the Eclipse scripting API. The global shift was calculated prioritizing the head isocenter for CSI treatments and the chest isocenter for TBI treatments by first maximizing residual tolerance at any other location prior to accepting any residual deviation at these locations. Maximum residuals tolerance was determined based on target margins, plan uncertainty and as per physician instructions. Delivery parameters are reported to a document uploaded to ARIA via API.
Result(s): The developed tool was employed for 11 cases. The software tool replaced the need for plan shift comments or instructions for therapists. In particular, its use eliminated the need to provide isocenter shifts to therapists by directly providing final couch parameters for treatment, greatly reducing the risk of delivery errors. The software effectively informed the therapists if any expected tolerance was surpassed, triggering a patient setup evaluation.
Conclusion(s): The described software tool is a core component to our multi-isocenter treatment programs and has streamlined delivery of these complex techniques that would otherwise require complicated instructions, including multiple shifts and on-the-fly calculations of optimal image alignment based on multiple imaging locations. This has substantially reduced the possibility of delivery errors