Publications by authors named "Jaroslaw T Hepel"

51 Publications

Quantifying risk using FMEA: An alternate approach to AAPM TG-100 for scoring failures and evaluating clinical workflow.

Brachytherapy 2021 Apr 8. Epub 2021 Apr 8.

Department of Radiation Oncology, The Warren Alpert Medical School of Brown University, Providence, RI. Electronic address:

Purpose: Renovation of the brachytherapy program at a leading cancer center utilized methods of the AAPM TG-100 report to objectively evaluate current clinical brachytherapy workflows and develop techniques for minimizing the risk of failures, increasing efficiency, and consequently providing opportunities for improved treatment quality. The TG-100 report guides evaluation of clinical workflows with recommendations for identifying potential failure modes (FM) and scoring them from the perspective of their occurrence frequency O, failure severity S, and inability to detect them D. The current study assessed the impact of differing methods to determine the risk priority number (RPN) beyond simple multiplication.

Methods And Materials: The clinical workflow for a complex brachytherapy procedure was evaluated by a team of 15 staff members, who identified discrete FM using alternate scoring scales than those presented in the TG-100 report. These scales were expanded over all clinically relevant possibilities with care to emphasize mitigation of natural bias for scoring near the median range as well as to enhance the overall scoring-system sensitivity. Based on staff member perceptions, a more realistic measure of risk was determined using weighted functions of their scores.

Results: This new method expanded the range of RPN possibilities by a factor of 86, improving evaluation and recognition of safe and efficient clinical workflows. Mean RPN values for each FM decreased by 44% when changing from the old to the new clinical workflow, as evaluated using the TG-100 method. This decreased by 66% when evaluated with the new method. As a measure of the total risk associated with an entire clinical workflow, the integral of RPN values increased by 15% and decreased by 31% with the TG-100 and new methods, respectively.

Conclusions: This appears to be the first application of an alternate approach to the TG-100 method for evaluating the risk of clinical workflows. It exemplifies the risk analysis techniques necessary to rapidly evaluate simple clinical workflows appropriately.
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http://dx.doi.org/10.1016/j.brachy.2021.02.005DOI Listing
April 2021

Multi-institutional registry study evaluating the feasibility and toxicity of accelerated partial breast irradiation using noninvasive image-guided breast brachytherapy.

Brachytherapy 2021 Feb 25. Epub 2021 Feb 25.

Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, RI; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, MA.

Purpose: The noninvasive image-guided breast brachytherapy (NIBB) technique is a novel noninvasive yet targeted method for accelerated partial breast irradiation. We established a multi-institutional registry to evaluate the toxicity and efficacy of this technique across various practice settings.

Methods And Materials: Institutions using the NIBB technique were invited to participate. Data for acute/late toxicity, cosmetic outcome, and tumor recurrence were collected. Toxicity and cosmetic outcome were graded based on the Common Terminology Criteria for Adverse Events version 3.0 and NRG/Radiation Therapy Oncology Group scale, respectively. Treatment variables were analyzed for association with outcomes.

Results: A total of 252 patients from eight institutions were analyzed. The median age was 69 years. The mean tumor size was 1.1 cm (0.1-4.0 cm). Treatment was delivered 10 fractions (34-36 Gy) in 75% and five fractions (28.5 Gy) in 22%. B.i.d. fractionation was used in 9%. Acute radiation dermatitis was Grade 0-1, 2, and 3 in 77%, 19%, and 4%, respectively. One hundred ninety-one patients with a median followup of 18 months (4-72 months) were evaluable for late outcomes. Late toxicity Grades 2 and 3 were observed in 8.8% and 1%, respectively. Cosmetic outcome was excellent, good, and fair/poor in 62%, 36%, and 2%, respectively. B.i.d. fractionation was associated with higher acute and late toxicity. Second-generation applicators were associated with lower late toxicity and better cosmetic outcome. Actuarial freedom from ipsilateral breast tumor recurrence and true recurrence were 98.3% and 98.3% at 2 years and 90.9% and 95.4% at 5 years, respectively.

Conclusions: Accelerated partial breast irradiation using NIBB was well tolerated with a low rate of acute and late toxicity across various practice settings. Ipsilateral breast tumor recurrence and cosmetic outcomes were favorable. b.i.d. fractionation was associated with higher toxicity. Longer followup is needed to confirm late endpoints.
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http://dx.doi.org/10.1016/j.brachy.2021.01.002DOI Listing
February 2021

Mammographically guided noninvasive breast brachytherapy: Preoperative partial breast radiotherapy markedly improves targeting accuracy and decreases irradiated volume.

Brachytherapy 2021 Mar-Apr;20(2):339-344. Epub 2020 Dec 5.

Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI; Tufts Medical Center, Tufts University School of Medicine, Boston, MA.

Purpose: Mammographically based noninvasive image-guided breast brachytherapy (NIBB) partial breast irradiation (PBI) is ideally suited for preoperative treatment. We hypothesize that delivering NIBB PBI to the preoperative tumor volume compared with the postoperative lumpectomy bed would simplify target identification and allow for a reduction in irradiated volume along each orthogonal axis.

Methods And Materials: Patients with invasive breast cancer treated with NIBB PBI at our institution were identified. Preoperative NIBB treatments were modeled along orthogonal craniocaudal and mediolateral axes with an applicator encompassing the gross lesion plus a 1 cm clinical target volume margin. Preoperative treatment volumes were calculated along each axis using the selected applicator surface area multiplied by the preoperative mammogram separation. The actual applicator size and breast separation from the first fraction of postoperative treatment was used to calculate the postoperative treatment volume. Paired -test was used to compare the preoperative and postoperative treatment separation, area, and volume for each patient.

Results: Forty-eight patients with Stage I-II breast cancer had imaging and treatment data available for review. Along the axis, the mean preoperative treatment volume was significantly less than the mean postoperative treatment volume (116 cm vs. 204 cm , respectively; p < 0.0001). Similarly, along the mediolateral axis, the mean preoperative treatment volume was significantly less than the mean postoperative treatment volume (125 cm vs. 216 cm , respectively; p < 0001).

Conclusions: Based on our retrospective comparison, PBI delivered using NIBB to the preoperative tumor may reduce the volume of healthy breast tissue receiving radiation as compared with NIBB to the postoperative tumor bed.
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http://dx.doi.org/10.1016/j.brachy.2020.10.013DOI Listing
December 2020

Accelerated Partial Breast Radiation: Information on Dose, Volume, Fractionation, and Efficacy from Randomized Trials.

Int J Radiat Oncol Biol Phys 2020 12 18;108(5):1123-1128. Epub 2020 Nov 18.

Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island.

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http://dx.doi.org/10.1016/j.ijrobp.2020.06.064DOI Listing
December 2020

Phase 2 Trial of Accelerated Partial Breast Irradiation (APBI) Using Noninvasive Image Guided Breast Brachytherapy (NIBB).

Int J Radiat Oncol Biol Phys 2020 12 25;108(5):1143-1149. Epub 2020 Jul 25.

Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts.

Purpose: Noninvasive image guided breast brachytherapy (NIBB) is a novel approach to delivery of accelerated partial breast irradiation (APBI) that may hold advantages over established techniques. NIBB is not invasive but maintains a high level of precision by using breast immobilization via breast compression and image guidance; it therefore does not require large planning tumor volume margins. We present the primary outcomes of this prospective phase 2 study (BrUOG Br-251).

Methods And Materials: Eligible patients with early-stage breast cancer underwent NIBB APBI using a dose 34 Gy in 10 fractions delivered daily or twice a day. Treatment was delivered using an Ir-192 high-dose-rate source via specialized applicators. Two orthogonal treatment axes were used for each fraction. The primary endpoints were late toxicity and cosmesis assessed at 2 and 5 years. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Cosmesis was assessed using the NRG/Radiation Therapy Oncology Group scale. Ipsilateral breast tumor recurrence was defined as any recurrence or new primary in the treated breast.

Results: Forty patients underwent protocol treatment. Median patient age was 68 years (50-92 years). Mean tumor size was 1.1 cm (0.3-3.0 cm). Among the cohort, 62.5% had invasive carcinoma and 37.5% had ductal carcinoma in situ. Thirty-nine percent elected to receive hormone therapy. No grade ≥3 late toxicities were observed at any time point. Grade 2 toxicity was 5% and 10% at 2 and 5 years, respectively. Telangiectasia grade 1 and 2 occurred in 27.5% and 5%, respectively. Breast separation of >7 cm was associated with telangiectasia (P < .01). The rate of good to excellent cosmetic outcome was 95% at 2 years and 100% at 5 years. With a median follow-up of 68 months, the actuarial 5-year freedom from ipsilateral breast tumor recurrence was 93.3% (±4.8%), and overall survival was 93.7% (±4.4%).

Conclusions: NIBB to deliver APBI is well tolerated with a low incidence of significant late toxicity and has favorable cosmetic outcomes. Continued evaluation of the NIBB APBI technique in a larger cohort is warranted.
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http://dx.doi.org/10.1016/j.ijrobp.2020.07.2312DOI Listing
December 2020

Update on Partial Breast Irradiation.

Clin Breast Cancer 2020 Apr 17. Epub 2020 Apr 17.

Department of Radiation Oncology, Lifespan Cancer Institute, Alpert Medical School of Brown University, Providence, RI.

For early-stage breast cancer, partial breast irradiation (PBI) allows for reduction in the irradiated volume of normal tissues by confining the radiation target to the area surrounding the lumpectomy cavity after breast-conserving surgery. This approach has been supported by phase 2 data. However, widespread adoption of PBI has awaited the results of randomized controlled trials. This review discusses the results of randomized controlled trials comparing whole breast irradiation to PBI, including the recently published National Surgical Adjuvant Breast and Bowel Project (NSABP) B39/Radiotherapy Oncology Group (RTOG) 0413, and the Canadian RAPID trials. PBI techniques, dose/fractionation schedules, and patient selection are also reviewed.
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http://dx.doi.org/10.1016/j.clbc.2020.04.003DOI Listing
April 2020

Partial Breast Irradiation Is the Preferred Standard of Care for a Majority of Women With Early-Stage Breast Cancer.

J Clin Oncol 2020 07 22;38(20):2268-2272. Epub 2020 May 22.

Department of Radiation Oncology, Lifespan Cancer Institute, Alpert Medical School, Brown University, Providence, RI.

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http://dx.doi.org/10.1200/JCO.19.02594DOI Listing
July 2020

Novel and programmatic improvements to the workflow associated with the AccuBoost breast brachytherapy procedure.

Brachytherapy 2020 May - Jun;19(3):372-379. Epub 2020 Apr 2.

Department of Radiation Oncology, The Warren Alpert Medical School of Brown University, Providence, RI. Electronic address:

Purpose: While the noninvasive breast brachytherapy (NIBB) treatment procedure, known as AccuBoost, for breast cancer patients is well established, the treatment quality can be improved by the efficiency of the workflow delivery. A formalized approach evaluated the current workflow through failure modes and effects analysis and generated insight for developing new procedural workflow techniques to improve the clinical treatment process.

Methods And Materials: AccuBoost treatments were observed for several months while gathering details on the multidisciplinary workflow. A list of possible failure modes for each procedure step was generated and organized by timing within the treatment process. A team of medical professionals highlighted procedural steps that unnecessarily increased treatment time, as well as introduced quality deficiencies involving applicator setup, treatment planning, and quality control checks preceding brachytherapy delivery. Procedural improvements and their impact on the clinical workflow are discussed.

Results: The revised clinical workflow included the following key procedural enhancements. Prepatient arrival: Improvement of prearrival preparation requires advance completion of dose calculation documentation with patient-specific setup data. Patient arrival pretreatment: Physicists carry out dwell time calculations and check the plan, while the therapist concurrently performs several checks of the ensuing hardware configuration.

Treatment: An electronic method to export the associated HDR brachytherapy paperwork to the electronic medical record system with electronic signatures and captured approvals was generated. Posttreatment: The therapist confirms the applicators were appropriately positioned, and treatment was delivered as expected.

Conclusions: The procedural improvements reduced the overall treatment time, improved consistency across users, and eased performance of this special procedure for all participants.
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http://dx.doi.org/10.1016/j.brachy.2020.01.007DOI Listing
January 2021

New Cardiac Abnormalities After Radiotherapy in Breast Cancer Patients Treated With Trastuzumab.

Clin Breast Cancer 2020 06 19;20(3):246-252. Epub 2019 Dec 19.

Department of Radiation Oncology, Rhode Island Hospital, Providence, RI.

Purpose: To evaluate cardiac imaging abnormalities after modern radiotherapy and trastuzumab in breast cancer patients.

Patients And Methods: All patients treated with trastuzumab and radiotherapy for breast cancer between 2006 and 2014 with available cardiac imaging (echocardiogram or multigated acquisition scan) were retrospectively analyzed. Cardiac abnormalities included myocardial abnormalities (atrial or ventricular dilation, hypertrophy, hypokinesis, and impaired relaxation), decreased ejection fraction > 10%, and valvular abnormalities (thickening or stenosis of the valve leaflets). Breast laterality (left vs. right) and heart radiation dose volume parameters were analyzed for association with cardiac imaging abnormalities.

Results: A total of 110 patients with 57 left- and 53 right-sided breast cancers were evaluated. Overall, 37 patients (33.6%) developed a new cardiac abnormality. Left-sided radiotherapy was associated with an increase in new cardiac abnormalities (relative risk [RR] = 2.51; 95% confidence interval [CI], 1.34-4.67; P = .002). Both myocardial and valvular abnormalities were associated with left-sided radiotherapy (myocardial: RR = 2.21; 95% CI, 1.06-4.60; P = .029; valvular: RR = 3.30; 95% CI, 0.98-10.9; P = .044). There was no significant difference in decreased ejection fraction between left- and right-sided radiotherapy (9.6% vs. 2.1%; P = .207). A mean heart dose > 2 Gy as well as volume of the heart receiving 20 Gy (V20), V30, and V40 correlated with cardiac abnormalities (mean heart dose > 2 Gy: RR = 2.00; P = .040).

Conclusion: New cardiac abnormalities, including myocardial and valvular dysfunction, are common after trastuzumab and radiotherapy. The incidence of new abnormalities correlates with tumor laterality and cardiac radiation dose exposure. Long-term follow-up is needed to understand the clinical significance of these early imaging abnormalities.
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http://dx.doi.org/10.1016/j.clbc.2019.12.006DOI Listing
June 2020

Multi-institutional validation of brain metastasis velocity, a recently defined predictor of outcomes following stereotactic radiosurgery.

Radiother Oncol 2020 01 13;142:168-174. Epub 2019 Sep 13.

Department of Radiation Oncology, Wake Forest School of Medicine, USA.

Introduction: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting.

Methods: Patients from nine academic centers were treated with upfront SRS; the validation cohort consisted of data from eight institutions not previously used to define BMV. Patients were classified by BMV into low (<4 BMV), intermediate (4-13 BMV), and high-risk groups (>13 BMV). Time-to-event outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the effect of BMV and salvage modality on OS.

Results: Of 2829 patients, 2092 patients were included in the validation dataset. Of these, 921 (44.0%) experienced distant brain failure (DBF). Median OS from initial SRS was 11.2 mo. Median OS for BMV < 4, BMV 4-13, and BMV > 13 were 12.5 mo, 7.0 mo, and 4.6 mo (p < 0.0001). After multivariate regression modeling, melanoma histology (β: 10.10, SE: 1.89, p < 0.0001) and number of initial brain metastases (β: 1.52, SE: 0.34, p < 0.0001) remained predictive of BMV (adjusted R = 0.06).

Conclusions: This multi-institutional dataset validates BMV as a predictor of OS following initial SRS. BMV is being utilized in upcoming multi-institutional randomized controlled trials as a stratification variable for salvage whole brain radiation versus salvage SRS after DBF.
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http://dx.doi.org/10.1016/j.radonc.2019.08.011DOI Listing
January 2020

The American Brachytherapy Society consensus statement for electronic brachytherapy.

Brachytherapy 2019 May - Jun;18(3):292-298. Epub 2018 Nov 26.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH. Electronic address:

Purpose: Brachytherapy is utilized in the treatment of many different malignancies; although traditionally performed with low-dose-rate or high-dose-rate techniques, more recently, electronic brachytherapy (EB) has emerged as a potential alternative. At this time, there are no evidence-based guidelines to assist clinicians in patient selection for EB and concerns exits regarding differences in dosimetry as compared to traditional brachytherapy techniques. As such, the American Brachytherapy Society appointed a group of physicians and physicists to create a consensus statement regarding the use of EB.

Methods And Materials: Physicians and physicists with expertise in brachytherapy created a site-directed consensus statement for appropriate patient selection and utilization of EB based on a literature search and clinical experience.

Results: EB has been utilized to deliver accelerated partial breast irradiation with, thus far acceptable local control and toxicity rates including a randomized trial that used EB to deliver intraoperative radiotherapy; however, prospective data with large patient numbers and long-term follow up are needed. Increasing numbers of patients have been treated with EB for nonmelanomatous skin cancers; although, preliminary data are promising, there is a lack of data comparing EB to traditional radiotherapy techniques as well as a lack of long-term follow up. For treatment of the vaginal cuff with EB, small retrospective studies have been reported without long-term follow up.

Conclusions: In light of a randomized trial in breast showing higher rates of recurrence and the lack of prospective data with mature follow up with other sites, as well as concerns regarding dosimetry, it is not recommended that EB be utilized for accelerated partial breast irradiation, nonmelanomatous skin cancers, or vaginal cuff brachytherapy outside prospective clinical trials at this time.
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http://dx.doi.org/10.1016/j.brachy.2018.10.006DOI Listing
December 2019

Local failure and vertebral body fracture risk using multifraction stereotactic body radiation therapy for spine metastases.

Adv Radiat Oncol 2018 Jul-Sep;3(3):245-251. Epub 2018 Apr 10.

Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island.

Purpose: Single-fraction radiation surgery for spine metastases is highly effective. However, a high rate (20-39%) of vertebral body fracture (VBF) has been associated with large, single-fraction doses. We report our experience using multifraction stereotactic body radiation therapy (SBRT).

Methods And Materials: All patients who were treated with multifraction SBRT for spine metastases at our institution between 2009 and 2017 were retrospectively analyzed. SBRT was delivered in 2 to 5 fractions using the Cyberknife System (Accuray, Sunnyvale, CA). Patients were followed clinically and with magnetic resonance imaging every 3 to 6 months. Local control, complications (including VBF), and overall survival were evaluated. Patient, disease, and treatment variables were analyzed for a statistical association with outcomes.

Results: A total of 83 patients were treated to 98 spine lesions with a median follow-up of 7.6 months. Histologies included non-small cell lung cancer (NSCLC; 24%), renal cell carcinoma (RCC; 18%), and breast cancer (12%). Surgery or vertebroplasty were performed before SBRT in 21% of cases. Patients received a median SBRT dose of 24 Gy in a median of 3 fractions. Local control was 93% at 6 months and 84% at 1 year. Higher prescribed dose, higher biologic effective dose, higher minimum dose to 90% of the planning target volume, tumor histology, and smaller tumor volume predicted improved local control. The cumulative dose was 23 Gy versus 26 Gy for patients with and without failure ( = .02), higher biologic effective dose 39 Gy versus 46 Gy, ( = .01), and higher minimum dose to 90% of the planning target volume 23 Gy versus 26 Gy ( = .03). VBF occurred in 4.2% of all cases and 5.3% of those without surgery or vertebroplasty prior to SBRT. Only preexisting VBF predicted risk of post-SBRT VBF ( < .01).

Conclusions: Multifraction SBRT results in a high local control rate for metastatic spinal disease with a low VBF rate, which suggests a favorable therapeutic ratio compared with single-fraction SBRT.
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http://dx.doi.org/10.1016/j.adro.2018.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128022PMC
April 2018

Five fraction accelerated partial breast irradiation using noninvasive image-guided breast brachytherapy: Feasibility and acute toxicity.

Brachytherapy 2018 Sep - Oct;17(5):825-830. Epub 2018 Jun 21.

Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, RI; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, MA.

Purpose: To improve efficiency, convenience, and cost, a prospective phase II trial was initiated to evaluate accelerated partial breast irradiation delivered with noninvasive image-guided breast brachytherapy (NIBB) via five once-daily fractions.

Methods And Materials: Women ≥50 years old with early-stage breast cancer undergoing breast conserving surgery were enrolled. Eligibility criteria included invasive carcinoma ≤2.0 cm or ductal carcinoma in situ ≤3.0 cm, ER positive (if invasive), lymph node negative, LVI absent, and margins negative by 2 mm. Patients received a total dose of 28.5 Gy in five daily fractions. NIBB was delivered using two orthogonal axes for each fraction. Applicators were selected to encompass the lumpectomy cavity with a 1.0 cm clinical target volume margin and 0 to 0.5 cm planning target volume margin. Acute and late toxicity was assessed based on CTCAE v3.0.

Results: Forty patients with a mean age of 67 years underwent protocol treatment. Mean tumor size was 1.0 cm (0.3-2.0 cm). Eighty percent had invasive carcinoma and the remainder had ductal carcinoma in situ. Mean tumor bed volume was 21 cc (5-79 cc) and mean breast volume was 1319 cc (499-3044 cc). Mean breast separation with compression was 6.7 cm (3.5-8.9 cm). All patients tolerated well. Median discomfort with compression was 1 (range: 0-7) on a 10-point pain scale. Acute skin reaction was Grade 0-1 in 70%, Grade 2 in 28%, and Grade 3 in 3%. Acute skin toxicity was not associated with breast size but was associated with larger breast separation with compression (p < 0.01) and larger applicator size (p < 0.01). No Grade 3+ late toxicity or local recurrences have been observed at a median followup of 14 months.

Conclusions: Accelerated partial breast irradiation delivered using NIBB over five daily fractions is a convenient treatment option that is feasible and well tolerated.
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http://dx.doi.org/10.1016/j.brachy.2018.05.006DOI Listing
March 2019

BRCA1 Mutations Associated With Increased Risk of Brain Metastases in Breast Cancer: A 1: 2 Matched-pair Analysis.

Am J Clin Oncol 2018 12;41(12):1252-1256

Departments of Radiation Oncology.

Background: Brain metastases (BM) occur in ∼5% of breast cancer patients. BRCA1-associated cancers are often basal-like and basal-like cancers are known to have a predilection for central nervous system metastases. We performed a matched-pair analysis of breast cancer patients with and without BRCA mutations and compared the frequency of BM in both groups.

Materials And Methods: From a database of 1935 patients treated for localized breast cancer at our institution from 2009 to 2014 we identified 20 patients with BRCA1 or BRCA2 mutations and manually matched 40 patients without BRCA mutations accounting for age, stage, estrogen receptor expression, and human epidermal growth factor receptor 2 (HER2) expression. Comparisons of freedom from brain metastasis, brain metastasis-free survival, and overall survival were made using the log rank test. Testing for a basal-type phenotype using the immunohistochemistry definition (ER/PR/HER2 and either CK 5/6 or EGFR) was performed for BRCA patients who developed BM and their matched controls.

Results: We analyzed 60 patients: 20 BRCA and 40 were matched controls. Median follow-up was 37 and 49 months, respectively. Three years freedom from brain metastasis was 84% for BRCA patients and 97% for BRCA controls (P=0.049). Three years brain metastasis-free survival was 84% and 97% for the BRCA+ and controls, respectively (P=0.176). Mean time to brain failure was 11 months from diagnosis for the BRCA patients. All 3 BRCA1 patients who developed BM were of a basal-type triple negative phenotype.

Conclusions: Breast cancer patients with germline BRCA1 mutations appear to have a shorter interval to brain progression while accounting for confounding factors.
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http://dx.doi.org/10.1097/COC.0000000000000466DOI Listing
December 2018

Management approach for recurrent brain metastases following upfront radiosurgery may affect risk of subsequent radiation necrosis.

Adv Radiat Oncol 2016 Oct-Dec;1(4):294-299. Epub 2016 Aug 24.

Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, RI.

Purpose: Many patients treated with stereotactic radiosurgery (SRS) alone as initial treatment require 1 or more subsequent salvage therapies. This study aimed to determine if commonly used salvage strategies are associated with differing risks of radiation necrosis (RN).

Methods And Materials: All patients treated with upfront SRS alone for brain metastases at our institution were retrospectively analyzed. Salvage treatment details were obtained for brain failures. Patients who underwent repeat SRS to the same lesion were excluded. RN was determined based on pathological confirmation or advanced brain imaging consistent with RN in a symptomatic patient. Patients were grouped according to salvage treatment and rates of RN were compared via Fisher's exact tests.

Results: Of 284 patients treated with upfront SRS alone, 132 received salvage therapy and 44 received multiple salvage treatments. This included 31 repeat SRS alone, 58 whole brain radiation therapy (WBRT) alone, 28 SRS and WBRT, 7 surgery alone, and 8 surgery with adjuvant radiation. With a median follow-up of 10 months, the rate of RN among all patients was 3.17% (9/284), salvaged patients 4.55% (6/132), and never salvaged patients 1.97% (3/152). Receiving salvage therapy did not significantly increase RN risk ( = .31). Of the patients requiring salvage treatments, the highest RN rate was among patients that had both salvage SRS and WBRT (delivered as separate salvage therapies) (6/28, 21.42%). RN rate in this group was significantly higher than in those treated with repeat SRS alone (0/31), WBRT alone (0/58), surgery alone (0/7), and surgery with adjuvant radiation (0/8). Comparing salvage WBRT doses <30 Gy versus ≥30 Gy revealed no effect of dose on RN rate. Additionally, among patients who received multiple SRS treatments, number of treated lesions was not predictive of RN incidence.

Conclusion: Our results suggest that initial management approach for recurrent brain metastasis after upfront SRS does not affect the rate of RN. However, the risk of RN significantly increases when patients are treated with both repeat SRS and salvage WBRT. Methods to improve prediction of toxicity and optimize patient selection for salvage treatments are needed.
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http://dx.doi.org/10.1016/j.adro.2016.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514163PMC
August 2016

American Brachytherapy Society consensus report for accelerated partial breast irradiation using interstitial multicatheter brachytherapy.

Brachytherapy 2017 Sep - Oct;16(5):919-928. Epub 2017 Jul 1.

Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, RI; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, MA.

Purpose: To develop a consensus report for the quality practice of accelerated partial breast irradiation (APBI) using interstitial multicatheter brachytherapy (IMB).

Methods And Materials: The American Brachytherapy Society Board appointed an expert panel with clinical and research experience with breast brachytherapy to provide guidance for the current practice of IMB. This report is based on a comprehensive literature review with emphasis on randomized data and expertise of the panel.

Results: Randomized trials have demonstrated equivalent efficacy of APBI using IMB compared with whole breast irradiation for select patients with early-stage breast cancer. Several techniques for placement of interstitial catheters are described, and importance of three-dimensional planning with appropriate optimization is reviewed. Optimal target definition is outlined. Commonly used dosing schemas include 50 Gy delivered in pulses of 0.6-0.8 Gy/h using pulsed-dose-rate technique and 34 Gy in 10 fractions, 32 Gy in eight fractions, or 30 Gy in seven fractions using high-dose-rate technique. Potential toxicities and strategies for toxicity avoidance are described in detail. Dosimetric constraints include limiting whole breast volume that receives ≥50% of prescription dose to <60%, skin dose to ≤100% of prescription dose (≤60-70% preferred), chest wall dose to ≤125% of prescription dose, Dose Homogeneity Index to >0.75 (>0.85 preferred), V < 45 cc, and V < 14 cc. Using an optimal implant technique coupled with optimal planning and appropriate dose constraints, a low rate of toxicity and a good-to-excellent cosmetic outcome of ≥90% is expected.

Conclusions: IMB is an effective technique to deliver APBI for appropriately selected women with early-stage breast cancer. This consensus report has been created to assist clinicians in the appropriate practice of APBI using IMB.
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http://dx.doi.org/10.1016/j.brachy.2017.05.012DOI Listing
April 2018

Current Treatment of Metastatic Spine Tumors - Surgery and Stereotactic Radiosurgery.

R I Med J (2013) 2017 Jun 1;100(6):18-20. Epub 2017 Jun 1.

Surgical Director, Comprehensive Spine Center, and Director, Neurosurgical Trauma and Spinal Disorders, Rhode Island Hospital; Associate Professor of Neurosurgery (.

There has been significant progress and innovation in the treatment of patients with metastatic spinal tumors over the last two to three decades that has impacted our ability to provide individualized care that improves a patient's quality of life and degree of neurologic impairment. Advances in surgical techniques and radiation delivery modalities have dramatically improved our ability to decrease local tumor recurrence rates, improve pain control, and provide more durable spinal stability. Modern day spine tumor resection and reconstruction techniques have been shown to improve and prolong patients' ability to ambulate, maintain continence, and reduce the need for pain medications. Spinal radiosurgery, the focused delivery of radiation to a target in the spine, has significantly enhanced the ability to provide a high degree of local tumor control in a non-invasive manner, even for tumors that are deemed radioresistant by conventional radiation therapy standards. In most patients, a combination of treatment modalities, including both surgery and radiation, is the mainstay of any comprehensive treatment plan for metastatic spinal tumors. [Full article available at http://rimed.org/rimedicaljournal-2017-06.asp].
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June 2017

Postmastectomy Radiation Therapy Is Associated With Improved Survival in Node-Positive Male Breast Cancer: A Population Analysis.

Int J Radiat Oncol Biol Phys 2017 06 13;98(2):384-391. Epub 2017 Feb 13.

Department of Radiation Oncology, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island.

Purpose: Because of its rarity, there are no randomized trials investigating postmastectomy radiation therapy (PMRT) in male breast cancer. This study retrospectively examines the impact of PMRT in male breast cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.

Methods And Materials: The SEER database 8.3.2 was queried for men ages 20+ with a diagnosis of localized or regional nonmetastatic invasive ductal/lobular carcinoma from 1998 to 2013. Included patients were treated by modified radical mastectomy (MRM), with or without adjuvant external beam radiation. Univariate and multivariate analyses evaluated predictors for PMRT use after MRM. Kaplan-Meier overall survival (OS) curves of the entire cohort and a case-matched cohort were calculated and compared by the log-rank test. Cox regression was used for multivariate survival analyses.

Results: A total of 1933 patients were included in the unmatched cohort. There was no difference in 5-year OS between those who received PMRT and those who did not (78% vs 77%, respectively, P=.371); however, in the case-matched analysis, PMRT was associated with improved OS at 5 years (83% vs 54%, P<.001). On subset analysis of the unmatched cohort, PMRT was associated with improved OS in men with 1 to 3 positive nodes (5-year OS 79% vs 72% P=.05) and those with 4+ positive nodes (5-year OS 73% vs 53% P<.001). On multivariate analysis of the unmatched cohort, independent predictors for improved OS were use of PMRT: HR=0.551 (0.412-0.737) and estrogen receptor-positive disease: HR=0.577 (0.339-0.983). Predictors for a survival detriment were higher grade 3/4: HR=1.825 (1.105-3.015), larger tumor T2: HR=1.783 (1.357-2.342), T3/T4: HR=2.683 (1.809-3.978), higher N-stage: N1 HR=1.574 (1.184-2.091), N2/N3: HR=2.328 (1.684-3.218), black race: HR=1.689 (1.222-2.336), and older age 81+: HR=4.164 (1.497-11.582).

Conclusions: There may be a survival benefit with the addition of PMRT for male breast cancer with node-positive disease.
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http://dx.doi.org/10.1016/j.ijrobp.2017.02.007DOI Listing
June 2017

Repeat Stereotactic Radiosurgery for Locally Recurrent Brain Metastases.

World Neurosurg 2017 Aug 24;104:589-593. Epub 2017 Apr 24.

Department of Radiation Oncology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.

Purpose/objectives: The outcomes of repeat stereotactic radiosurgery (SRS) after failure of previous SRS are not well established. We report our overall experience using SRS for the retreatment of locally recurrent brain metastases.

Methods: Patients with brain metastases diagnosed between 2003 and 2015 who underwent repeat SRS for local tumor progression following prior SRS were identified. Rates of local control, radiation necrosis, and overall survival were analyzed. Factors affecting local failure and radiation necrosis were assessed by chi-square test.

Results: Twenty-four lesions in 22 patients underwent repeat SRS in a single fraction. Median age was 59 years. The median SRS-1 dose was 18 Gy, and the median SRS-2 dose was 15.5 Gy. The median SRS-1 target volume was 2.25 cm, and the median SRS-2 target volume was 3.30 cm. The median follow-up from SRS-2 was 8.8 months. The actuarial local controls for SRS-2 were 94.1% and 61.1% at 6 and 12 months, respectively. The incidences of actuarial radiation necrosis were 9.2% and 9.2% at 6 and 12 months, respectively. Volume of tumor >4 cm correlated with increased risk of local failure (P = 0.006) with no local failures recorded with volumes ≤4 cm. SRS-2 dose, cumulative SRS dose, receipt of whole brain radiotherapy, and use of SRS-2 as boost after surgery did not correlate with local failure or radiation necrosis. Median overall survival after SRS-2 was 8.78 months.

Conclusion: Repeat SRS is feasible for select patients, particularly for those with tumor volume ≤4 cm. Further evaluation is needed to establish the most appropriate treatment doses and volumes for this approach.
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http://dx.doi.org/10.1016/j.wneu.2017.04.103DOI Listing
August 2017

Comparison of Onsite Versus Online Chart Reviews as Part of the American College of Radiation Oncology Accreditation Program.

J Oncol Pract 2017 05 16;13(5):e516-e521. Epub 2017 Mar 16.

Rhode Island Hospital, Brown University, Providence, RI; Tufts Medical Center, Tufts University, Boston, MA; University of Pittsburgh Medical Center, University of Pittsburgh Cancer Institute, Pittsburgh; Penn State Hershey St Joseph Cancer Center, Reading, PA; University of California San Diego, La Jolla CA; University of Maryland School of Medicine, Baltimore; American College of Radiation Oncology, Bethesda, MD; Private Practice, Apex, NC; Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo, NY; University of Washington Medical Center, Seattle, WA; and Nacogdoches Medical Center, Nacogdoches, TX.

Purpose: Accreditation based on peer review of professional standards of care is essential in ensuring quality and safety in administration of radiation therapy. Traditionally, medical chart reviews have been performed by a physical onsite visit. The American College of Radiation Oncology Accreditation Program has remodeled its process whereby electronic charts are reviewed remotely.

Methods: Twenty-eight radiation oncology practices undergoing accreditation had three charts per practice undergo both onsite and online review. Onsite review was performed by a single reviewer for each practice. Online review consisted of one or more disease site-specific reviewers for each practice. Onsite and online reviews were blinded and scored on a 100-point scale on the basis of 20 categories. A score of less than 75 was failing, and a score of 75 to 79 was marginal. Any failed charts underwent rereview by a disease site team leader.

Results: Eighty-four charts underwent both onsite and online review. The mean scores were 86.0 and 86.9 points for charts reviewed onsite and online, respectively. Comparison of onsite and online reviews revealed no statistical difference in chart scores ( P = .43). Of charts reviewed, 21% had a marginal (n = 8) or failing (n = 10) score. There was no difference in failing charts ( P = .48) or combined marginal and failing charts ( P = .13) comparing onsite and online reviews.

Conclusion: The American College of Radiation Oncology accreditation process of online chart review results in comparable review scores and rate of failing scores compared with traditional on-site review. However, the modern online process holds less potential for bias by using multiple reviewers per practice and allows for greater oversight via disease site team leader rereview.
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http://dx.doi.org/10.1200/JOP.2016.015230DOI Listing
May 2017

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases.

Int J Radiat Oncol Biol Phys 2017 02 1;97(2):246-253. Epub 2016 Oct 1.

Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island. Electronic address:

Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS.

Methods And Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation.

Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(-) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62.

Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.
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http://dx.doi.org/10.1016/j.ijrobp.2016.09.043DOI Listing
February 2017

Patients with Long-Term Control of Systemic Disease Are a Favorable Prognostic Group for Treatment of Brain Metastases with Stereotactic Radiosurgery Alone.

World Neurosurg 2017 Feb 9;98:266-272. Epub 2016 Nov 9.

Department of Radiation Oncology, Rhode Island Hospital-Brown University Alpert Medical School, Providence, Rhode Island, USA; Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts, USA. Electronic address:

Background: Stereotactic radiosurgery (SRS) alone is an attractive option for treatment of brain metastases. SRS avoids whole-brain radiotherapy (WBRT)-associated morbidity, but is limited by regional central nervous system (CNS) failures and short survival in some patients. We evaluated a subgroup of patients with controlled systemic disease that could represent a favorable patient population for SRS alone.

Methods: All patients with brain metastases treated with SRS without WBRT at our institution between 2004 and 2014 were grouped into two cohorts: those with controlled systemic disease (CSD) for 1 year or longer before prior to presentation with brain metastases and those without (i.e., uncontrolled systemic disease [USD]). Rates of local and regional CNS failure, and overall survival were assessed with χ and Student t tests. Cox regression analysis was performed to evaluate independent predictors of regional control and overall survival.

Results: Two hundred ninety-four patients underwent SRS to 697 lesions, of which 65 patients had CSD. Median follow-up was 9.7 months. There was no difference in local control between the two cohorts (P = 0.795). Regional CNS control was significantly better for patients with CSD (68% vs. 48%; P = 0.001). Overall survival at 1 and 5 years for CSD were 65% and 13% with USD yielding 41% and 7%, respectively (P < 0.001). Multivariate analysis demonstrated that USD (relative CSD) independently predicts regional failure (hazard ratio [HR], 1.75; P = 0.008) and shorter overall survival (HR, 1.55; P = 0.007).

Conclusions: Patients with brain metastases after 1 year or longer of primary and systemic disease control represent a particularly favorable cohort, with lower regional CNS failure and prolonged survival, for an approach of SRS alone.
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http://dx.doi.org/10.1016/j.wneu.2016.11.010DOI Listing
February 2017

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study.

Int J Radiat Oncol Biol Phys 2016 12 31;96(5):1021-1027. Epub 2016 Aug 31.

Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts.

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD).

Methods And Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients per cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated.

Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively.

Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.
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http://dx.doi.org/10.1016/j.ijrobp.2016.08.032DOI Listing
December 2016

Stereotactic radiosurgery for large brain metastases.

J Clin Neurosci 2015 Oct 22;22(10):1650-4. Epub 2015 Jul 22.

Department of Radiation Oncology, Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA; Department of Radiation Oncology, Tufts Medical Center, Boston, MA, USA. Electronic address:

We evaluated patient outcomes following stereotactic radiosurgery (SRS)-treatment of large brain metastasis (⩾3 cm) at our institution. SRS is an established treatment for limited brain metastases. However, large tumors pose a challenge for this approach. For this study, 343 patients with 754 total brain metastases were treated with SRS, of which 93 had large tumors. The tumor size was 3-3.5, 3.5-4, and ⩾4 cm in 29%, 32%, and 39% of these patients. Surgical resection was performed prior to SRS in 68% of patients, and 53% achieved a gross total resection. The local control of large metastases was inferior compared to smaller tumors, with 1 year local control of 68 versus 86%, respectively (p<0.001). Among the patients with large metastases, no correlation between local control and surgical resection (p=0.747), or extent of surgery (gross total versus subtotal resection; p=0.120), was identified. Histology (p=0.939), tumor size (3-4 versus >4 cm; p=0.551), and SRS dose (⩽16 versus >16 Gy; p=0.539) also showed no correlation with local failure. The overall survival at 1, 2, and 5 years was 46%, 29% and 5%, respectively. Prolonged survival was seen in patients with age <65 years (p=0.009), primary treatment compared with salvage (p=0.077), and controlled primary tumors (p=0.022). Radiation necrosis developed in 10 patients (11.8%). For patients with large brain metastases, SRS is well tolerated and can achieve local central nervous system disease control in the majority of patients, and extended survival in some, though the local control rate is suboptimal. Further strategies to improve the outcomes in this subgroup of patients are needed.
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http://dx.doi.org/10.1016/j.jocn.2015.05.019DOI Listing
October 2015

In Regard to Vaidya et al.

Int J Radiat Oncol Biol Phys 2015 Aug 14;92(5):952-953. Epub 2015 Jul 14.

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1016/j.ijrobp.2015.05.032DOI Listing
August 2015

Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases.

Front Oncol 2015 11;5:110. Epub 2015 May 11.

Department of Radiation Oncology, Tufts Medical Center , Boston, MA , USA ; Department of Radiation Oncology, Rhode Island Hospital , Providence, RI , USA.

Purpose: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT) in patients with brain metastases treated with stereotactic radiosurgery (SRS) as their initial radiotherapy approach.

Materials And Methods: Patients with brain metastases treated with SRS from 2001 to 2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky performance status ≥70, and life expectancy ≥3 months. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with ≥1-year WBRT-free survival (N = 104), and those who died or required salvage WBRT within 3 months of SRS (N = 56). Differences between these groups were assessed by univariate and multivariate analyses.

Results: Median survival for all patients was 11 months. Among patients with ≥1-year WBRT-free survival, median survival was 33 months (12-107 months) with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p < 0.05) included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden (≤5 metastatic lesions). After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival.

Conclusion: A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone.
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http://dx.doi.org/10.3389/fonc.2015.00110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426730PMC
June 2015

Prescription dose evaluation for APBI with noninvasive image-guided breast brachytherapy using equivalent uniform dose.

Brachytherapy 2015 Jul-Aug;14(4):496-501. Epub 2015 Apr 18.

Department of Radiation Oncology, Rhode Island Hospital, Brown Alpert Medical School, Providence, RI; Department of Radiation Oncology, Tufts Medical Center, Boston, MA; Department of Radiation Oncology, Tufts University School of Medicine, Boston, MA.

Purpose: Noninvasive image-guided breast brachytherapy (NIBB) is an attractive novel approach to deliver accelerated partial breast irradiation (APBI). Calculations of equivalent uniform dose (EUD) were performed to identify the appropriate APBI dose for this technique.

Methods And Materials: APBI plans were developed for 15 patients: five with three-dimensional conformal APBI (3D-CRT), five with multi-lumen intracavitary balloons (m-IBB), and five simulating NIBB treatment. Prescription doses of 34.0 and 38.5 Gy were delivered in 10 fractions for m-IBB and 3D-CRT, respectively. Prescription doses ranging from 34.0 to 38.5 Gy were considered for NIBB. Dose-volume histogram data from all 3D-CRT, m-IBB, and NIBB plans were used to calculate the biologically effective EUD and corresponding EUD to the PTV_eval using the following equation: EUD = EUBED/(n [1 + EUD/α/β]). An α/β value of 4.6 Gy was assumed for breast tumor. EUD for varying NIBB prescription doses were compared with EUD values for the other APBI techniques.

Results: Mean PTV_eval volume was largest for 3D-CRT (372.9 cm(3)) and was similar for NIBB and m-IBB (88.7 and 87.2 cm(3), respectively). The EUD value obtained by prescribing 38.5 Gy with 3D-CRT APBI was 38.6 Gy. The EUD value of 34.0 Gy prescribed with m-IBB was 34.4 Gy. EUD values for NIBB ranged from 33.9 to 38.2 Gy for prescription doses ranging from 34.0 to 38.5 Gy.

Conclusions: Using EUD calculations to compare APBI techniques and treatment doses, a prescription dose of 36.0 Gy in 10 fractions using NIBB has a comparable biologic equivalent dose to other established brachytherapy techniques.
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http://dx.doi.org/10.1016/j.brachy.2015.03.007DOI Listing
February 2016

Multi-axis dose accumulation of noninvasive image-guided breast brachytherapy through biomechanical modeling of tissue deformation using the finite element method.

J Contemp Brachytherapy 2015 Feb 17;7(1):55-71. Epub 2015 Feb 17.

Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, RI, USA.

Purpose: Noninvasive image-guided breast brachytherapy delivers conformal HDR (192)Ir brachytherapy treatments with the breast compressed, and treated in the cranial-caudal and medial-lateral directions. This technique subjects breast tissue to extreme deformations not observed for other disease sites. Given that, commercially-available software for deformable image registration cannot accurately co-register image sets obtained in these two states, a finite element analysis based on a biomechanical model was developed to deform dose distributions for each compression circumstance for dose summation.

Material And Methods: The model assumed the breast was under planar stress with values of 30 kPa for Young's modulus and 0.3 for Poisson's ratio. Dose distributions from round and skin-dose optimized applicators in cranial-caudal and medial-lateral compressions were deformed using 0.1 cm planar resolution. Dose distributions, skin doses, and dose-volume histograms were generated. Results were examined as a function of breast thickness, applicator size, target size, and offset distance from the center.

Results: Over the range of examined thicknesses, target size increased several millimeters as compression thickness decreased. This trend increased with increasing offset distances. Applicator size minimally affected target coverage, until applicator size was less than the compressed target size. In all cases, with an applicator larger or equal to the compressed target size, > 90% of the target covered by > 90% of the prescription dose. In all cases, dose coverage became less uniform as offset distance increased and average dose increased. This effect was more pronounced for smaller target-applicator combinations.

Conclusions: The model exhibited skin dose trends that matched MC-generated benchmarking results within 2% and clinical observations over a similar range of breast thicknesses and target sizes. The model provided quantitative insight on dosimetric treatment variables over a range of clinical circumstances. These findings highlight the need for careful target localization and accurate identification of compression thickness and target offset.
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http://dx.doi.org/10.5114/jcb.2015.49355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371066PMC
February 2015

Local recurrence and survival following stereotactic radiosurgery for brain metastases from small cell lung cancer.

Pract Radiat Oncol 2015 Jan-Feb;5(1):e37-44. Epub 2014 May 3.

Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts; Department of Radiation Oncology, Rhode Island Hospital, Providence, Massachusetts.

Purpose: Stereotactic radiosurgery (SRS) represents a treatment option for patients with brain metastases from small cell lung cancer (SCLC) following prior cranial radiation. Inferior local control has been described. We reviewed our failure patterns following SRS treatment to evaluate this concern.

Methods And Materials: Individuals with SCLC who received SRS for brain metastases from 2004 to 2011 were identified. Central nervous system (CNS) disease was detected and followed by gadolinium-enhanced, high-resolution magnetic resonance (MR) imaging. SRS dose was prescribed to the tumor periphery. Local recurrence was defined by increasing lesion size or enhancement, MR-spectroscopy, and perfusion changes consistent with recurrent disease or pathologic confirmation. Any new enhancing lesion not identified on the SRS planning scan was considered a regional failure. Overall survival (OS) and CNS control were evaluated using the Kaplan-Meier method. Factors predicted to influence outcome were tested by univariate log-rank analysis and Cox regression.

Results: Fifteen males and 25 females (median age of 61 years [range, 36-79]) of which 39 received prior brain irradiation were identified. In all, 132 lesions (3.3 per patient) between 0.4 and 4.7 cm received a median dose of 16 Gy (12-22 Gy). Thirteen metastases (10%) ultimately recurred locally with 6- and 12-month control rates of 81% and 69%, respectively. Only 1 of 110 metastases <2 cm recurred. Local failure was more likely for size >2 cm (P < .001) and dose <16 Gy (P < .001). The median OS was 6.5 months, and the time to regional CNS recurrence was 5.2 months. For patients with single brain metastases, both OS (P = .037) and regional CNS recurrence (P = .003) were improved. CNS control (P = .001), and survival (P = .057), were also longer for patients with controlled systemic disease.

Conclusions: Local control following SRS for SCLC metastases is achievable for lesions <2 cm. For metastases >2 cm, local failure is more common than expected. Patients with controlled systemic disease and limited CNS involvement would benefit most from aggressive treatment.
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http://dx.doi.org/10.1016/j.prro.2014.03.006DOI Listing
October 2015

Erratum to: Perineural tumor spread of bladder cancer causing lumbosacral plexopathy: an anatomic explanation.

Acta Neurochir (Wien) 2015 Jan;157(1):153

Department of Neurosurgery, Warren Alpert Medical School of Brown University, Providence, RI, USA.

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http://dx.doi.org/10.1007/s00701-014-2285-4DOI Listing
January 2015