Publications by authors named "Anand Mahadevan"

74 Publications

Potential Clinical Significance of Overall Targeting Accuracy and Motion Management in the Treatment of Tumors That Move With Respiration: Lessons Learnt From a Quarter Century of Stereotactic Body Radiotherapy From Dose Response Models.

Front Oncol 2020 9;10:591430. Epub 2021 Feb 9.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, United States.

Objective: To determine the long-term normal tissue complication probability with stereotactic body radiation therapy (SBRT) treatments for targets that move with respiration and its relation with the type of respiratory motion management (tracking . compression or gating).

Methods: A PubMed search was performed for identifying literature regarding dose, volume, fractionation, and toxicity (grade 3 or higher) for SBRT treatments for tumors which move with respiration. From the identified papers logistic or probit dose-response models were fitted to the data using the maximum-likelihood technique and confidence intervals were based on the profile-likelihood method in the dose-volume histogram (DVH) Evaluator.

Results: Pooled logistic and probit models for grade 3 or higher toxicity for aorta, chest wall, duodenum, and small bowel suggest a significant difference when live motion tracking was used for targeting tumors with move with respiration which was on the average 10 times lower, in the high dose range.

Conclusion: Live respiratory motion management appears to have a better toxicity outcome when treating targets which move with respiration with very steep peripheral dose gradients. This analysis is however limited by sparsity of rigorous data due to poor reporting in the literature.
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http://dx.doi.org/10.3389/fonc.2020.591430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900559PMC
February 2021

Maximizing Tumor Control and Limiting Complications With Stereotactic Body Radiation Therapy for Pancreatic Cancer.

Int J Radiat Oncol Biol Phys 2020 Dec 24. Epub 2020 Dec 24.

Department of Radiation Oncology, Northwell Health, New York, New York.

Purpose: Stereotactic body radiation therapy (SBRT) and stereotactic ablative body radiation therapy is being increasingly used for pancreatic cancer (PCa), particularly in patients with locally advanced and borderline resectable disease. A wide variety of dose fractionation schemes have been reported in the literature. This HyTEC review uses tumor control probability models to evaluate the comparative effectiveness of the various SBRT treatment regimens used in the treatment of patients with localized PCa.

Methods And Materials: A PubMed search was performed to review the published literature on the use of hypofractionated SBRT (usually in 1-5 fractions) for PCa in various clinical scenarios (eg, preoperative [neoadjuvant], borderline resectable, and locally advanced PCa). The linear quadratic model with α/β= 10 Gy was used to address differences in fractionation. Logistic tumor control probability models were generated using maximum likelihood parameter fitting.

Results: After converting to 3-fraction equivalent doses, the pooled reported data and associated models suggests that 1-year local control (LC) without surgery is ≈79% to 86% after the equivalent of 30 to 36 Gy in 3 fractions, showing a dose response in the range of 25 to 36 Gy, and decreasing to less than 70% 1-year LC at doses below 24 Gy in 3 fractions. The 33 Gy in 5 fraction regimen (Alliance A021501) corresponds to 28.2 Gy in 3 fractions, for which the HyTEC pooled model had 77% 1-year LC without surgery. Above an equivalent dose of 28 Gy in 3 fractions, with margin-negative resection the 1-year LC exceeded 90%.

Conclusions: Pooled analyses of reported tumor control probabilities for commonly used SBRT dose-fractionation schedules for PCa suggests a dose response. These findings should be viewed with caution given the challenges and limitations of this review. Additional data are needed to better understand the dose or fractionation-response of SBRT for PCa.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.017DOI Listing
December 2020

Dose-Volume Predictors of Radiation Pneumonitis After Lung Stereotactic Body Radiation Therapy (SBRT): Implications for Practice and Trial Design.

Cureus 2020 Oct 5;12(10):e10808. Epub 2020 Oct 5.

Radiation Medicine and Applied Sciences, University of California San Diego Moores Cancer Center, La Jolla, USA.

Background and purpose Recently published HyTEC report summarized lung toxicity data and proposed guidelines of mean lung dose (MLD) <8 Gy and normal lung receiving at least 20 Gy, V<10-15% to avoid lung toxicity. Support for preferred use of a particular dosimetric parameter has been limited. We performed a detailed dose-volume analysis of data on radiation pneumonitis (RP) following lung stereotactic body radiation therapy (SBRT) to search for parameters showing the strongest correlation with RP. Materials and methods Two patient cohorts (primary and metastatic lung tumor patients) from previously reported studies were analyzed. Total number of patients was 96, and incidence of grade ≥2 RP was 13.5% (13/96). Fitting to the logistic function was performed to investigate correlation between incidence of RP and reported dosimetric and volumetric parameters. Another independent cohort was used to explore correlation between dosimetric parameters. Results Among normal lung parameters (MLD and reported V), only MLD consistently showed significant correlation with incidence of RP. Gross tumor volume (GTV), internal target volume, planning target volume (PTV), and minimum dose covering 95% of GTV or PTV did not show statistical significance. A significant correlation between reported V and MLD was observed in all cohorts. Conclusions In considering tumor- and target-specific (e.g., GTV, PTV) and normal lung-specific (e.g., MLD, V) metrics, MLD was the only parameter that consistently correlated with incidence of RP across both cohorts. Because SBRT planning constraints allow small normal lung volumes to receive high doses, utility of MLD is not obvious. The parallel structure of lung is one possible explanation, but correlation between dosimetric parameters obscures elucidation of the preferred or mechanistically based parameter to guide radiotherapy planning.
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http://dx.doi.org/10.7759/cureus.10808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641492PMC
October 2020

Single- and Multifraction Stereotactic Radiosurgery Dose/Volume Tolerances of the Brain.

Int J Radiat Oncol Biol Phys 2020 Sep 11. Epub 2020 Sep 11.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Purpose: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS).

Methods And Materials: Eligible studies provided NTCPs for the endpoints of radionecrosis, edema, or symptoms after cranial SRS/fSRS and quantitative dose-volume metrics. Studies of patients with only glioma, meningioma, vestibular schwannoma, or brainstem targets were excluded. The data summary and analyses focused on arteriovenous malformations (AVM) and brain metastases.

Results: Data from 51 reports are summarized. There was wide variability in reported rates of radionecrosis. Available data for SRS/fSRS for brain metastases were more amenable to NTCP modeling than AVM data. In the setting of brain metastases, SRS/fSRS-associated radionecrosis can be difficult to differentiate from tumor progression. For single-fraction SRS to brain metastases, tissue volumes (including target volumes) receiving 12 Gy (V1) of 5 cm, 10 cm, or >15 cm were associated with risks of symptomatic radionecrosis of approximately 10%, 15%, and 20%, respectively. SRS for AVM was associated with modestly lower rates of symptomatic radionecrosis for equivalent V12. For brain metastases, brain plus target volume V20 (3-fractions) or V24 (5-fractions) <20 cm was associated with <10% risk of any necrosis or edema, and <4% risk of radionecrosis requiring resection.

Conclusions: The risk of radionecrosis after SRS and fSRS can be modeled as a function of dose and volume treated. The use of fSRS appears to reduce risks of radionecrosis for larger treatment volumes relative to SRS. More standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses that can refine predictive models of brain toxicity risks.
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http://dx.doi.org/10.1016/j.ijrobp.2020.08.013DOI Listing
September 2020

Early imaging marker of progressing glioblastoma: a window of opportunity.

J Neurooncol 2020 Jul 29;148(3):629-640. Epub 2020 Jun 29.

Division of Neuro-Oncology, The OH State University Comprehensive Cancer Center - James and OSU Neurological Institute, Columbus, OH, 43210, USA.

Purpose: Therapeutic intervention at glioblastoma (GBM) progression, as defined by current assessment criteria, is arguably too late as second-line therapies fail to extend survival. Still, most GBM trials target recurrent disease. We propose integration of a novel imaging biomarker to more confidently and promptly define progression and propose a critical timepoint for earlier intervention to extend therapeutic exposure.

Methods: A retrospective review of 609 GBM patients between 2006 and 2019 yielded 135 meeting resection, clinical, and imaging inclusion criteria. We qualitatively and quantitatively analyzed 2000+ sequential brain MRIs (initial diagnosis to first progression) for development of T2 FLAIR signal intensity (SI) within the resection cavity (RC) compared to the ventricles (V) for quantitative inter-image normalization. PFS and OS were evaluated using Kaplan-Meier curves stratified by SI. Specificity and sensitivity were determined using a 2 × 2 table and pathology confirmation at progression. Multivariate analysis evaluated SI effect on the hazard rate for death after adjusting for established prognostic covariates. Recursive partitioning determined successive quantifiers and cutoffs associated with outcomes. Neurological deficits correlated with SI.

Results: Seventy-five percent of patients developed SI on average 3.4 months before RANO-assessed progression with 84% sensitivity. SI-positivity portended neurological decline and significantly poorer outcomes for PFS (median, 10 vs. 15 months) and OS (median, 20 vs. 29 months) compared to SI-negative. RC/V ratio ≥ 4 was the most significant prognostic indicator of death.

Conclusion: Implications of these data are far-reaching, potentially shifting paradigms for glioma treatment response assessment, altering timepoints for salvage therapeutic intervention, and reshaping glioma clinical trial design.
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http://dx.doi.org/10.1007/s11060-020-03565-xDOI Listing
July 2020

Stereotactic Ablative Radiotherapy for ≥T1b Primary Renal Cell Carcinoma: A Report From the International Radiosurgery Oncology Consortium for Kidney (IROCK).

Int J Radiat Oncol Biol Phys 2020 11 17;108(4):941-949. Epub 2020 Jun 17.

Department of Radiation Oncology, London Regional Cancer Program, London, Ontario, Canada; Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.

Purpose: Patients with larger (T1b, >4 cm) renal cell carcinoma (RCC) not suitable for surgery have few treatment options because thermal ablation is less effective in this setting. We hypothesize that SABR represents an effective, safe, and nephron-sparing alternative for large RCC.

Methods And Materials: Individual patient data from 9 institutions in Germany, Australia, USA, Canada, and Japan were pooled. Patients with T1a tumors, M1 disease, and/or upper tract urothelial carcinoma were excluded. Demographics, treatment, oncologic, and renal function outcomes were assessed using descriptive statistics. Kaplan-Meier estimates and univariable and multivariable Cox proportional hazards regression were generated for oncologic outcomes.

Results: Ninety-five patients were included. Median follow-up was 2.7 years. Median age was 76 years, median tumor diameter was 4.9 cm, and 81.1% had Eastern Cooperative Oncology Group performance status of 0 to 1 (or Karnofsky performance status ≥70%). In patients for whom operability details were reported, 77.6% were defined as inoperable as determined by the referring urologist. Mean baseline estimated glomerular filtration rate (eGFR) was 57.2 mL/min (mild-to-moderate dysfunction), with 30% of the cohort having moderate-to-severe dysfunction (eGFR <45mL/min). After SABR, eGFR decreased by 7.9 mL/min. Three patients (3.2%) required dialysis. Thirty-eight patients (40%) had a grade 1 to 2 toxicity. No grade 3 to 5 toxicities were reported. Cancer-specific survival, overall survival, and progression-free survival were 96.1%, 83.7%, and 81.0% at 2 years and 91.4%, 69.2%, 64.9% at 4 years, respectively. Local, distant, and any failure at 4 years were 2.9%, 11.1%, and 12.1% (cumulative incidence function with death as competing event). On multivariable analysis, increasing tumor size was associated with inferior cancer-specific survival (hazard ratio per 1 cm increase: 1.30; P < .001).

Conclusions: SABR for larger RCC in this older, largely medically inoperable cohort, demonstrated efficacy and tolerability and had modest impact on renal function. SABR appears to be a viable treatment option in this patient population.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.014DOI Listing
November 2020

Dosimetric Limitations in Treating Breast Cancer with Accelerated Partial Breast Irradiation Using Strut Adjusted Volume Implant (SAVI).

Cureus 2020 Apr 3;12(4):e7528. Epub 2020 Apr 3.

Surgery, Geisinger/Holy Spirit, Mechanicsburg, USA.

We present one case of accelerated partial breast irradiation (APBI) using strut adjusted volume implant (SAVI) where there were limitations in delivering the dose as per the standard guidelines. The device was placed close to both the chest wall and the skin with little tissue surrounding the tip. Two plans were made in an attempt to achieve the standard therapeutic doses without over-treating the chest wall or the skin. Similar cases reported in the literature were reviewed. The dosimetry of the two plans was compared to the cases discussed in the literature.
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http://dx.doi.org/10.7759/cureus.7528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198095PMC
April 2020

Understanding High-Dose, Ultra-High Dose Rate, and Spatially Fractionated Radiation Therapy.

Int J Radiat Oncol Biol Phys 2020 07 13;107(4):766-778. Epub 2020 Apr 13.

Department of Radiation Oncology, University of California-Irvine, Irvine, California. Electronic address:

The National Cancer Institute's Radiation Research Program, in collaboration with the Radiosurgery Society, hosted a workshop called Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy on August 20 and 21, 2018 to bring together experts in experimental and clinical experience in these and related fields. Critically, the overall aims were to understand the biological underpinning of these emerging techniques and the technical/physical parameters that must be further defined to drive clinical practice through innovative biologically based clinical trials.
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http://dx.doi.org/10.1016/j.ijrobp.2020.03.028DOI Listing
July 2020

Indications, feasibility, safety, and efficacy of CyberKnife radiotherapy for the treatment of olfactory groove meningiomas: a single institutional retrospective series.

Radiat Oncol 2020 Mar 12;15(1):63. Epub 2020 Mar 12.

Department of Radiology, Division of Neuroradiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Purpose: To assess the safety and efficacy of CyberKnife® radiotherapy (CKRT) for the treatment of olfactory groove meningiomas (OGMs).

Methods: A retrospective review was performed of 13 patients with OGM treated with CKRT from September 2005 to May 2018 at our institution. Nine patients were treated primarily with CKRT, 3 for residual disease following resection, and 1 for disease recurrence.

Results: Five patients were treated with stereotactic radiosurgery (SRS), 6 with hypofractionated stereotactic radiotherapy (HSRT), and 2 with fractionated stereotactic radiotherapy (FSRT). The median tumor volume was 8.12 cm. The median prescribed dose was 14.8 Gy for SRS, 27.3 Gy for HSRT, and 50.2 Gy for FSRT. The median maximal dose delivered was 32.27 Gy. Median post treatment follow-up was 48 months. Twelve of 13 patients yielded a 100% regional control rate with a median tumor volume reduction of 31.7%. Six of the 12 patients had reduced tumor volumes while the other 6 had no changes. The thirteenth patient had significant radiation-induced edema requiring surgical decompression. Twelve patients were alive and neurologically stable at the time of the review. One patient died from pneumonia unrelated to his CKRT treatment.

Conclusions: CKRT appears to be safe and effective for the treatment of OGMs.
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http://dx.doi.org/10.1186/s13014-020-01506-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069021PMC
March 2020

Feasibility, safety, and utility of brain MRI for patients with non-MRI-conditioned CIED.

Neurosurg Rev 2020 Dec 17;43(6):1539-1546. Epub 2019 Oct 17.

Neurosurgical Service, McMaster University and Hamilton Health Services, Hamilton, ON, Canada.

Feasibility, safety, and utility of brain MRI for patients with non-MRI-conditioned cardiac implantable electrical devices (CIEDs) remains controversial. While a growing number of studies have shown safe employment in select patients under strict protocols, there is an increasing clinical need for further off-label investigations. To assess the feasibility and utility of brain MRI in neurological and neurosurgical patients with non-MRI-conditioned CIEDs using off-label protocol. We retrospectively evaluated 126 patients with non-MRI-conditioned CIEDs referred to our hospital between 2014 to 2018 for MRI under an IRB-approved protocol. A total of 126 off-label brain MRI scans were performed. The mean age was 67.5 ± 13.0. Seventy percent of scans were performed on female patients. Indications for MRI are neurosurgical (45.2%), neurological (51.6%), and others (3.2%). MRI utilization for tumor cases was highest for tumor cases (68.3%), but employment was valuable for vascular (12.7%), deep brain stimulators (3.2%), and other cases (15.9%). In the tumor category, (37.2%) of the scans were performed for initial diagnosis and pre-surgical planning, (47.7%) for post-intervention evaluation/surveillance, (15.1%) for stereotactic radiosurgery treatment (CyberKnife). No clinical complications were encountered. No functional device complications of the CIED were identified during and after the MRI in 96.9% of the studies. A 49.6% of the off-label brain MRI scans performed led to a clinically significant decision and/or intervention for the patients. A 42.9% of obtained MRI studies did not change the plan of care. A 7.9% of post-scan decision-making data was not available. We demonstrate that off-label brain MRI scans performed on select patients under a strict protocol is feasible, safe, and relevant. Almost 50% of scans provided critical information resulting in clinical intervention of the patients.
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http://dx.doi.org/10.1007/s10143-019-01149-6DOI Listing
December 2020

The Emerging Role of Stereotactic Ablative Radiotherapy for Primary Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

Eur Urol Focus 2019 Nov 24;5(6):958-969. Epub 2019 Jun 24.

Division of Radiation Oncology & Cancer Imaging, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne, Australia. Electronic address:

Context: Stereotactic ablative radiotherapy (SABR) is an emerging treatment option for primary renal cell carcinoma (RCC).

Objective: To systematically review the literature on SABR for primary RCC and perform a meta-analysis evaluating local control (LC), toxicity, and renal function.

Evidence Acquisition: A PROSPERO-registered (#115573), Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA)-based systematic review of the literature was conducted (1995-2019). Studies of SABR targeting primary RCC tumors were included, while those targeting only metastases were excluded. The primary outcome was LC defined as tumor size reduction and/or absence of local progression. Secondary outcomes included toxicity (Common Terminology Criteria for Adverse Events) and renal function (change in estimated glomerular filtration rate [eGFR]). Weighted random-effect meta-analyses using the DerSimonian and Laird method were conducted for primary and secondary outcomes. The I statistic and Cochran's Q test were used to assess heterogeneity.

Evidence Synthesis: From 2386 PubMed entries and 924 meeting abstracts, 26 studies were identified (11 prospective trials), including 383 tumors in 372 patients, most of whom were deemed inoperable. Weighted averages (ranges) of median follow-up, median age, and mean tumor size were 28.0 (5.8-79.2)mo, 70.4 (62-83)yr, and 4.6 (2.3-9.5)cm, respectively. RCC histology was confirmed in 78.9% of patients who underwent pretreatment biopsy. Dose fractionation varied, but 26Gy in one fraction and 40Gy in five fractions were most common. The random-effect estimates for LC, grade 3-4 toxicity, and post-SABR eGFR change were 97.2% (95% confidence interval [CI]: 93.9-99.5%, I=20%), 1.5% (95% CI: 0-4.3%, I=0%), and -7.7ml/min (95% CI: -12.5 to -2.8, I=2%), respectively, and heterogeneity was minimal. Six patients with pre-existing renal dysfunction (2.9%) required dialysis.

Conclusions: Renal SABR is locally effective and associated with low toxicity rates for primary RCC, despite treatment of larger tumors in older, mostly medically inoperable patients.

Patient Summary: Stereotactic ablative radiotherapy is a high-precision, noninvasive radiation treatment requiring few outpatient visits, and represents a safe and effective management option for primary renal cell carcinoma.
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http://dx.doi.org/10.1016/j.euf.2019.06.002DOI Listing
November 2019

Stereotactic Radiotherapy as a Treatment Option for Renal Tumors in the Solitary Kidney: A Multicenter Analysis from the IROCK.

J Urol 2019 06;201(6):1097-1104

Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre and University of Melbourne , Melbourne , Australia.

Purpose: Stereotactic ablative radiotherapy is an emerging treatment for renal cell carcinoma. Our study objective was to evaluate this therapy in patients with a solitary kidney, focusing on oncologic and renal function outcomes.

Materials And Methods: We pooled individual patient data from 9 IROCK (International Radiosurgery Oncology Consortium for Kidney) institutions in Germany, Australia, the United States of America, Canada and Japan. Median followup was 2.6 years. Baseline characteristics and outcomes were compared between the solitary and bilateral kidney cohorts. Predictors of renal function after stereotactic ablative radiotherapy were assessed by logistic regression modeling.

Results: A total of 81 patients with a solitary kidney underwent stereotactic ablative radiotherapy. Mean age was 67.3 years and 97.5% of patients had good performance status, including ECOG (Eastern Cooperative Oncology Group) 0-1 or KPS (Karnofsky Performance Status) 70% or greater. Median tumor diameter was 3.7 cm (IQR 2.5-4.3) and 37% of tumors were 4 cm or greater. The 138 patients in the bilateral cohort harbored larger tumors and were older (p <0.001) with a lower baseline estimated glomerular filtration rate (p = 0.024). After stereotactic ablative radiotherapy in the solitary kidney cohort the mean ± SD estimated glomerular filtration rate decrease was -5.8 ± 10.8 ml per minute (-9%). No patient with a solitary kidney required dialysis. After stereotactic ablative radiotherapy a tumor size of 4 cm or greater was associated with an estimated glomerular filtration rate decrease of 15 ml per minute or greater (OR 4.2, p = 0.029). At 2 years the rates of local control, and progression-free, cancer specific and overall survival in the solitary cohort were 98.0%, 77.5%, 98.2% and 81.5%, respectively. There was no significant difference in renal function or oncologic outcomes between the cohorts (p >0.05).

Conclusions: In this analysis of the IROCK database stereotactic ablative radiotherapy in patients with a solitary kidney had an acceptable impact on renal function and achieved excellent oncologic outcomes, similar to those in patients with bilateral kidneys. Thus, stereotactic ablative radiotherapy represents a viable treatment option in patients with renal cell carcinoma in a solitary kidney.
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http://dx.doi.org/10.1097/JU.0000000000000111DOI Listing
June 2019

Stereotactic Body Radiotherapy (SBRT) for liver metastasis - clinical outcomes from the international multi-institutional RSSearch® Patient Registry.

Radiat Oncol 2018 Feb 13;13(1):26. Epub 2018 Feb 13.

The Radiosurgery Society, San Mateo, CA, USA.

Background: Stereotactic body radiotherapy (SBRT) is an emerging treatment option for liver metastases in patients unsuitable for surgery. We investigated factors associated with clinical outcomes for liver metastases treated with SBRT from a multi-center, international patient registry.

Methods: Patients with liver metastases treated with SBRT were identified in the RSSearch® Patient Registry. Patient, tumor and treatment characteristics associated with treatment outcomes were assessed. Dose fractionations were normalized to BED. Overall survival (OS) and local control (LC) were evaluated using Kaplan Meier analysis and log-rank test.

Results: The study included 427 patients with 568 liver metastases from 25 academic and community-based centers. Median age was 67 years (31-91 years). Colorectal adenocarcinoma (CRC) was the most common primary cancer. 73% of patients received prior chemotherapy. Median tumor volume was 40 cm (1.6-877 cm), median SBRT dose was 45 Gy (12-60 Gy) delivered in a median of 3 fractions [1-5]. At a median follow-up of 14 months (1-91 months) the median overall survival (OS) was 22 months. Median OS was greater for patients with CRC (27 mo), breast (21 mo) and gynecological (25 mo) metastases compared to lung (10 mo), other gastro-intestinal (GI) (18 mo) and pancreatic (6 mo) primaries (p < 0.0001). Smaller tumor volumes (< 40 cm) correlated with improved OS (25 months vs 15 months p = 0.0014). BED ≥ 100 Gy was also associated with improved OS (27 months vs 15 months p < 0.0001). Local control (LC) was evaluable in 430 liver metastases from 324 patients. Two-year LC rates was better for BED ≥ 100 Gy (77.2% vs 59.6%) and the median LC was better for tumors < 40 cm (52 vs 39 months). There was no difference in LC based on histology of the primary tumor.

Conclusions: In a large, multi-institutional series of patients with liver metastasis treated with SBRT, reasonable LC and OS was observed. OS and LC depended on dose and tumor volume, while OS varied by primary tumor. Future prospective trials on the role of SBRT for liver metastasis from different primaries in the setting of multidisciplinary management including systemic therapy, is warranted.

Trial Registration: Clinicaltrials.gov: NCT01885299 .
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http://dx.doi.org/10.1186/s13014-018-0969-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811977PMC
February 2018

Pooled analysis of stereotactic ablative radiotherapy for primary renal cell carcinoma: A report from the International Radiosurgery Oncology Consortium for Kidney (IROCK).

Cancer 2018 03 20;124(5):934-942. Epub 2017 Dec 20.

Cyberknife Center, University of Munich Hospitals, Munich, Germany.

Background: Stereotactic ablative radiotherapy (SABR) is an emerging therapy for primary renal cell carcinoma. The authors assessed safety, efficacy, and survival in a multi-institutional setting. Outcomes between single-fraction and multifraction SABR were compared.

Methods: Individual patient data sets from 9 International Radiosurgery Oncology Consortium for Kidney institutions across Germany, Australia, the United States, Canada, and Japan were pooled. Toxicities were recorded using Common Terminology Criteria for Adverse Events, version 4.0. Patient, tumor, and treatment characteristics were stratified according to the number of radiotherapy fractions (single vs multiple). Survival outcomes were examined using Kaplan-Meier estimates and Cox proportional-hazards regression.

Results: Of 223 patients, 118 received single-fraction SABR, and 105 received multifraction SABR. The mean patient age was 72 years, and 69.5% of patients were men. There were 83 patients with grade 1 and 2 toxicity (35.6%) and 3 with grade 3 and 4 toxicities (1.3%). The rates of local control, cancer-specific survival, and progression-free survival were 97.8%, 95.7%, and 77.4%, respectively, at 2 years; and they were 97.8%, 91.9%, and 65.4%, respectively, at 4 years. On multivariable analysis, tumors with a larger maximum dimension and the receipt of multifraction SABR were associated with poorer progression-free survival (hazard ratio, 1.16 [P < .01] and 1.13 [P = .02], respectively) and poorer cancer-specific survival (hazard ratio, 1.28 [P < .01] and 1.33 [P = .01], respectively). There were no differences in local failure between the single-fraction cohort (n = 1) and the multifraction cohort (n = 2; P = .60). The mean ( ± standard deviation) estimated glomerular filtration rate at baseline was 59.9 ± 21.9 mL per minute, and it decreased by 5.5 ± 13.3 mL per minute (P < .01).

Conclusions: SABR is well tolerated and locally effective for treating patients who have primary renal cell carcinoma and has an acceptable impact on renal function. An interesting observation is that patients who receive single-fraction SABR appear to be less likely to progress distantly or to die of cancer. Cancer 2018;124:934-42. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.31156DOI Listing
March 2018

The impact of different stereotactic radiation therapy regimens for brain metastases on local control and toxicity.

Adv Radiat Oncol 2017 Jul-Sep;2(3):391-397. Epub 2017 Jun 6.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.

Purpose: Stereotactic radiation therapy (SRT) enables focused, short course, high dose per fraction radiation delivery to brain tumors that are less ideal for single fraction treatment because of size, shape, or close proximity to sensitive structures. We sought to identify optimal SRT treatment regimens for maximizing local control while minimizing morbidity.

Methods And Materials: We performed a retrospective review of patients treated with SRT for solid brain metastases using variable dose schedules between 2001 and 2011 at 3 academic hospitals. Endpoints included (1) local control, (2) acute toxicity (Common Toxicity Criteria for Adverse Events v3.0), and (3) symptomatic radionecrosis. Kaplan-Meier and a competing risks methodology were used to estimate the actuarial rate of local failure and assess the association of clinical and treatment covariates with time to local failure.

Results: A total of 156 patients was identified. Common tumor histologies included breast (21%), non-small cell lung (32%), melanoma (22%), small cell lung (9%), and renal cell carcinoma (6%). The majority of lesions were supratentorial (57%). Median target volume was 3.99 mL (range, 0.04-58.42). Median total SRT dose was 25 Gy (range, 12-36), median fractional dose was 5 Gy (range, 2.5-11), and median number of fractions was 5 (range, 2-10). Cumulative incidence of local progression at 3, 6, 12, 18, and 24 months was 11%, 22%, 29%, 34%, and 36%. Total prescription dose was the only factor significantly associated with time to local progression on univariate ( = .02) and multivariable analysis ( = .01, adjusted hazards ratio, 0.87). Five patients experienced seizures within 10 days of SRT and 5 patients developed radionecrosis. All patients with documented radionecrosis received prior radiation to the index lesion.

Conclusions: Our series of SRT for brain metastases found total prescription dose to be the only factor associated with local control. Both acute and long-term toxicity events from SRT were modest.
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http://dx.doi.org/10.1016/j.adro.2017.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605319PMC
June 2017

Surgery for posterior fossa ependymomas in adults.

J Neurosurg Sci 2018 Feb 22;62(1):63-70. Epub 2017 Sep 22.

Department of Surgery, Division of Neurosurgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Ependymomas of the posterior fossa in adults are relatively rare, represent less than 1% of adult intracranial gliomas. Most of the cases are WHO grade II. Due to their rarity, there are no randomized studies regarding the best management of these tumors. It seems that surgical resection has a major role in their management. Unlike the scenario in children, these tumors can be cured by gross total resection without adjuvant therapy in the majority of cases. Hence, knowing the different surgical approaches, with their pros and cons, is important in order to offer the patient the best treatment. In this paper, we review the current literature on surgery for ependymomas of the posterior fossa in adults, and the advantages and risks of the principal surgical approaches, namely the telo-velar and the transvermian, are discussed.
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http://dx.doi.org/10.23736/S0390-5616.17.04190-XDOI Listing
February 2018

Tanycytic ependymoma of the brain stem, presentations of rare cystic disease variants and review of literature.

J Neurosurg Sci 2018 Feb 7;62(1):78-88. Epub 2017 Sep 7.

Department of Radiation Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Introduction: The aim of this paper was to systematically review the evidence linking Propionibacterium acnes (P. acnes) with the develop Tanycytic ependymoma (tcE) is a rare variant of ependymoma and management guidelines for patients with this disease are not established.

Evidence Acquisition: We performed a systematic search on Pubmed complimented by hand-searching citation lists to identify patients with pathologically confirmed tcE. Signs and symptoms, radiological and specific pathological findings as well as reported treatment modalities and outcomes were recorded and analyzed.

Evidence Synthesis: Fifty-one studies involving a total of 77 patients were identified and included in this review. Most cases of tcEs occurred in the spinal cord (50.6%), followed by lesions located in upper intracranial sites (36.4%) and only a few at the cervicomedullary junction (3.9%). Female to male ratio was calculated as about 1:1.5, with a mean age at diagnosis of approximately 36.1±18 years. Complete resection of the tumor without further additional therapy was the treatment of choice in most cases (63.6%), radiotherapy was considered in 10 cases (13.0%). In 18 reported cases of tcE (23.4%), the treatment was not documented. Defined follow-up periods for patients with tcE were only documented in 44 cases (57.1%), the mean follow-up was 22.3 months. 36 cases (46.8%) had no recurrence of tumor after treatment (26 months mean follow-up).

Conclusions: This comprehensive review on tcEs supports surgery as the initial treatment modality of choice. Radiotherapy can be considered when total gross resection cannot be achieved and allows for prolonged progression-free survival. Given the benign nature of this subtype of ependymoma, aggressive treatment such as chemotherapy is usually not indicated.
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http://dx.doi.org/10.23736/S0390-5616.17.04194-7DOI Listing
February 2018

Stereotactic body radiotherapy for unresected pancreatic cancer: A nationwide review.

Cancer 2017 Nov 14;123(21):4158-4167. Epub 2017 Jul 14.

Surgical Outcomes Analysis and Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Background: The role of conventional radiotherapy in the management of pancreatic cancer has yet to be elucidated. Over the past decade, stereotactic body radiotherapy (SBRT) has emerged as a novel therapeutic option in pancreatic cancer care. This study evaluated the survival impact of SBRT on patients with unresected pancreatic cancer.

Methods: The National Cancer Data Base was queried for unresected patients who received chemotherapy for nonmetastatic pancreatic adenocarcinoma between 2004 and 2012. Four treatment groups were identified: chemotherapy alone, chemotherapy combined with external-beam radiotherapy (EBRT), chemotherapy combined with intensity-modulated radiotherapy (IMRT), and chemotherapy combined with SBRT. Propensity score models predicting the odds of receiving SBRT were created to control for potential selection bias, and patients were matched by propensity scores. The survival analysis was performed with the Kaplan-Meier method.

Results: A total of 14,331 patients met the inclusion criteria. Chemotherapy alone was delivered to 5464 patients (38.1%); 6418 (44.8%), 322 (2.3%), and 2127 (14.8%) received chemotherapy along with EBRT, IMRT, and SBRT, respectively. The unadjusted median survival before matching was 9.9, 10.9, 12.0, and 13.9 months for patients treated with chemotherapy, EBRT, IMRT, and SBRT, respectively. In separate matched analyses, SBRT remained superior to chemotherapy alone (log-rank P < .0001) and EBRT (log-rank P = .0180). After matching, survival did not differ between patients receiving IMRT and patients receiving SBRT (log-rank P = .0492).

Conclusions: SBRT is associated with a significantly better outcome than chemotherapy alone or in conjunction with traditional EBRT. These results support the idea that SBRT is a promising treatment approach for patients with unresected pancreatic cancer. Cancer 2017;123:4158-4167. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30856DOI Listing
November 2017

Regional variation in the treatment of pancreatic adenocarcinoma: Decreasing disparities with multimodality therapy.

Surgery 2017 08 6;162(2):275-284. Epub 2017 May 6.

Surgical Outcomes Analysis & Research, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Electronic address:

Background: Survival in pancreatic cancer remains poor with curative potential dependent on operative resection. We reviewed national adherence to practice guidelines to evaluate regional variation in the treatment and survival of patients with pancreatic cancer.

Methods: Retrospective cohort review of adults with pancreatic adenocarcinoma using the National Cancer Data Base from 2006 to 2013. Overall survival was compared by the Kaplan-Meier method and Cox proportional hazards models. Sequential multivariate logistic regression models were generated for odds of: a) diagnosis in stage I/II, b) resection, and c) receipt of multimodality therapy, defined as operative resection plus chemotherapy with or without radiation. Five geographic regions of the United States were used for analyses.

Results: A total of 115,952 patients were identified. At least 22% of patients in all stages received no treatment, with only 38.4% and 32.3% of stage I and II patients receiving multimodality therapy. On unadjusted analysis, the Northeast had the greatest survival for all stages of disease, most pronounced for stage I where patients lived 2 to 3 more months (log-rank P < .0001). While adjusted odds of early diagnosis and resection were comparable or greater across regions relative to the Northeast, patients who underwent resection in the Northeast were significantly more likely to receive multimodality therapy. Multivariate Cox modeling for patients receiving multimodality therapy accounted for differences in 3 of 4 remaining regions.

Conclusion: Regional variations exist in pancreatic cancer treatment and survival. While providing multimodality cancer-directed therapy can help mitigate these differences, survival with pancreatic cancer needs to be interpreted in the context of overall health, underlying risk factors, and life expectancy.
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http://dx.doi.org/10.1016/j.surg.2017.03.009DOI Listing
August 2017

Stereotactic radiosurgery for brain metastasis from gynecological malignancies.

Oncol Lett 2017 Mar 18;13(3):1525-1528. Epub 2017 Jan 18.

Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Brain metastases are relatively uncommon in gynecological malignancies, and there is limited available data on their management. The present study reports the outcomes of patients with brain metastasis from gynecological malignancies who were treated with stereotactic radiosurgery (SRS). Patients with brain metastasis from a gynecological primary site were treated with SRS using the Cyberknife™ frameless SRS system. Primary lesions were treated with a single fraction of 16-22 Gy. A total of 3 resection cavities were treated with 8 Gy 3 times, meaning a total of 24 Gy, and 1 recurrent lesion was re-irradiated with 5 Gy 5 times, meaning a total of 25 Gy. All patients were followed up with regular magnetic resonance imaging and clinical examinations 1 month after treatment and every 2 months thereafter. A total of 20 lesions in 8 patients were included in this study; 1 patient presented with metastatic endometrial cancer and the remaining 7 presented with metastatic ovarian cancer. The median age was 61 years (range, 48-78 years). All patients had received systemic therapy prior to developing brain metastasis. A total of 3 patients underwent surgical resection and 1 patient was administered re-irradiation for recurrence. There were 3 local failures in 2 patients. The actuarial 1-, 2- and 3-year local control rates were 91, 91 and 76%, respectively. The median overall survival time was 29 months. No SRS-associated toxicities or neurological mortalities were observed. In conclusion, brain metastasis from gynecological malignancies is uncommon, however, SRS is a safe and effective treatment modality for local control as a primary or adjuvant treatment in patients with this disease.
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http://dx.doi.org/10.3892/ol.2017.5621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403471PMC
March 2017

Meningiomas in pregnancy: timing of surgery and clinical outcomes as observed in 104 cases and establishment of a best management strategy.

Acta Neurochir (Wien) 2018 08 22;160(8):1521-1529. Epub 2017 Mar 22.

Department of Surgery, Division of Neurosurgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Background: There is a strong correlation between the level of circulating female sex hormones and the parturient growth of meningiomas. As a result, rapid changes in meningioma size occur during pregnancy, putting both the mother and fetus at risk. Large, symptomatic meningiomas require surgical resection, regardless of the status of pregnancy. However, the preferred timing of such complex intervention is a matter of debate. The rarity of this clinical scenario and the absence of prospective trials make it difficult to reach evidence-based conclusions. The aim of this study was to create evidence-based management guidelines for timing of surgery for pregnancy-related intracranial meningiomas.

Method: The English literature from 1990 to 2016 was systematically reviewed according to PRISMA guidelines for all surgical cases of pregnancy-related intracranial meningiomas. Cases were divided into two groups: patients who have had surgery during pregnancy and delivered thereafter (group A) and patients who delivered first (group B). Groups were compared for demographic, clinical and radiological features, as well as for neurosurgical, obstetrical and neonatological outcomes. Statistical analysis was performed to assess differences.

Results: A total of 104 surgical cases were identified and reviewed, of which 86 were suitable for comparison and statistical analysis. Thirty-five patients (40%) underwent craniotomy for resection during pregnancy or at delivery (group A) and 51 patients (60%) underwent surgery after delivery (group B). Groups showed no significant differences in characteristics such as age at diagnosis, number of gestations, presenting symptoms, tumor site and tumor size. Despite a comparable distribution over the gestational trimesters, group A had significantly more patients diagnosed prior to the 27th gestational week (46 vs 17.5%, p = 0.0075). Group A was also associated with a significantly higher rate of both emergent craniotomies (40 vs 19.6%, p = 0.0048) and emergent Caesarian deliveries (47 vs 17.8%, p = 0.00481). The time from diagnosis to surgery was significantly longer in group B (11 weeks vs 1 week in group A, p = 0.0013). The rate of premature delivery was high but similar in both groups (∼70%). Risks of maternal mortality or fetal mortality were associated with group A (odds ratio = 14.7), but did not reach statistical significance.

Conclusions: While surgical resection of meningioma during pregnancy may be associated with increased maternal and fetal mortalities, the overall neurosurgical, obstetrical and neonatological outcomes, as well as many clinical characteristics, are similar to patients undergoing resection postpartum. We believe that fetal survival chances have a significant impact on decision-making, as patients diagnosed at a later stage in pregnancy (≥27th week of gestation) were more likely to undergo delivery first. This complicated clinical scenario requires the close cooperation of multiple disciplines. While the mother's health and well-being should always be paramount in guiding management, we hope that the overall good outcomes observed by this systematic review will encourage colleagues to aim for term pregnancies whenever possible in order to reduce prematurity-related problems.
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http://dx.doi.org/10.1007/s00701-017-3146-8DOI Listing
August 2018

Schwannoma of the trochlear nerve-an illustrated case series and a systematic review of management.

Neurosurg Rev 2018 Jul 1;41(3):699-711. Epub 2016 Sep 1.

Department of Surgery, Division of Neurosurgery, Beth Israel Deaconess Medical Center, Harvard Medical School, West Campus, Lowry Medical Office Building, Suite 3B, 110 Francis St., Boston, MA, 02215, USA.

Schwannomas of cranial nerves in the absence of systemic neurofibromatosis are relatively rare. Among these, schwannomas of the trochlear nerve are even less common. They can be found incidentally or when they cause diplopia or other significant neurological deficits. Treatment options include observation only, neuro-ophthalmological intervention, and/or neurosurgical management via resection or sterotactic radiosurgery (SRS). In recent years, the latter has become an attractive therapeutic tool for a number of benign skull base neoplasm including a small number of reports on its successful use for trochlear Schwannomas. However, no treatment algorithm for the management of these tumors has been proposed so far. The goal of this manuscript is to illustrate a case series of this rare entity and to suggest a rational treatment algorithm for trochlear schwannomas, based on our institutional experience of recent cases, and a pertinent review of the literature. Including our series of 5 cases, a total of 85 cases reporting on the management of trochlear schwannomas have been published. Of those reported, less than half (40 %) of patients underwent surgical resection, whereas the remainder were managed conservatively or with SRS. Seventy-six percent (65/85) of the entire cohort presented with diplopia, which was the solitary symptom in over half of the cases (n = 39). All patients who presented with symptoms other than diplopia or headaches as solitary symptoms underwent surgical resection. Patients in the non-surgical group were mostly male (M/F = 3.5:1), presented at an older age and had shorter mean diameter (4.6 vs. 30.4 mm, p < 0.0001) when compared to the surgical group. Twelve patients in the entire cohort were treated with SRS, none of whom had undergone surgical resection before or after radiation treatment. Trochlear schwannoma patients without systemic neurofibromatosis are rare and infrequently reported in the literature. Of those, patients harboring symptomatic trochlear Schwannomas do not form a single homogenous group, but fall into two rather distinct subgroups regarding demographics and clinical characteristics. Among those patients in need of intervention, open microsurgical resection as well as less invasive treatment options exist, which all aim at safe relief of symptoms and prevention of progression. Both open microsurgical removal as well as SRS can achieve good long-term local control. Consequently, a tailored multidisciplinary treatment algorithm, based on the individual presentation and tumor configuration, is proposed.
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http://dx.doi.org/10.1007/s10143-016-0783-yDOI Listing
July 2018

Post operative stereotactic radiosurgery for positive or close margins after preoperative chemoradiation and surgery for rectal cancer.

J Gastrointest Oncol 2016 Jun;7(3):315-20

1 Department of Radiation Oncology, Istanbul University, Istanbul, Turkey ; 2 Radiation Oncology, 3 Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Background: The incidence of positive margins after neoadjuvant chemoradiation and adequate surgery is very low. However, when patients do present with positive or close margins, they are at a risk of local failure and local therapy options are limited. We evaluated the role of stereotactic body radiotherapy (SBRT) in patients with positive or close margins after induction chemoradiation and total mesorectal excision.

Methods: This is a retrospective evaluation of patients treated with SBRT after induction chemoradiation and surgery for positive or close margins. Seven evaluable patients were included. Fiducial seeds were place at surgery. The Cyberknife(TM) system was used for planning and treatment. Patients were followed 1 month after treatment and 3-6 months thereafter. Descriptive statistics and Kaplan-Meir method was used to repot the findings.

Results: Seven patients (3 men and 4 women) were included in the study with a median follow-up of 23.5 months. The median initial radiation dose was 5,040 cGy (in 28 fractions) and the median SBRT dose was 2,500 cGy (in 5 fractions). The local control at 2 years was 100%. The overall survival at 1 and 2 years was 100% and 71% respectively. There was no Grade III or IV toxicity.

Conclusions: SBRT reirradiation is an effective and safe method to address positive or close margins after neoadjuvant chemoradiation and surgery for rectal cancer.
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http://dx.doi.org/10.21037/jgo.2015.11.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880783PMC
June 2016

Stereotactic Body Radiotherapy (SBRT) Reirradiation for Recurrent Pancreas Cancer.

J Cancer 2016 10;7(3):283-8. Epub 2016 Jan 10.

1. Department of Radiation Oncology;

Objectives: After adjuvant or definitive radiation for pancreas cancer, there are limited conventional treatment options for recurrent pancreas cancer. We explored the role of (Stereotactic Body Radiotherapy) SBRT for reirradiation of recurrent pancreas Cancer.

Methods: This is a retrospective study of patients reirradiated with SBRT for recurrent pancreas cancer. All patients were deemed unresectable and treated with systemic therapy. Fiducial gold markers were used. CT simulation was performed with oral and IV contrast and patients were treated with respiratory motion tracking in the Cyberknife(TM) system.

Results: 30 patients (17 men and 13 women) with a median age of 67 years were included in the study. The median target volume was 41.29cc. The median prescription dose was 25Gy (24-36Gy) in a median of 5 fractions prescribed to a mean 78% isodose line. The median overall survival was 14 months. The 1 and 2 year local control was 78%. The worst toxicity included 3/30(10%) Grade III acute toxicity for pain, bleeding and vomiting. There was 2/30 (7%) Grade III long-term bowel obstructions.

Conclusions: SBRT can be a useful and tolerable option for patients with recurrent pancreas cancer after prior radiation.
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http://dx.doi.org/10.7150/jca.13295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747882PMC
February 2016

Steroid and anticonvulsant prophylaxis for stereotactic radiosurgery: Large variation in physician recommendations.

Pract Radiat Oncol 2016 Jul-Aug;6(4):e89-e96. Epub 2015 Nov 10.

Department of Radiation Oncology, Dana-Farber/Brigham & Women's Cancer Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose/objective(s): The risk of developing symptomatic edema or seizure following stereotactic radiosurgery (SRS) is poorly defined, and many practitioners prescribe prophylactic corticosteroids and/or anticonvulsants. Because there are no clear guidelines regarding appropriate use, we sought to characterize prescribing practices and factors associated with these recommendations.

Methods And Materials: We conducted a 1-time, internet-based survey among 500 randomly selected radiation oncologists self-described as specializing in central nervous system diseases who were registered in the American Society for Radiation Oncology directory. Physicians were contacted by e-mail and invited to complete the 22-question survey.

Results: The response rate was 32% (n = 161). Sixty-six percent of respondents had been in practice for >10 years, and 45% of respondents practiced at an academic medical center. During/after SRS, 53% of respondents "always" or "usually" recommended corticosteroids, whereas 47% "never," "rarely," or "sometimes" recommended them. When prescribing corticosteroids, the recommended duration of use was <1 week, 1-2 weeks, or >2 weeks among 49%, 33%, and 18% of respondents, respectively. Respondents who worked in an academic medical center were less likely to prescribe corticosteroids, although this did not reach significance (P = .09). Seizure prophylaxis was less common overall, as 79% of respondents "rarely" or "never" prescribed anticonvulsants for SRS. Respondents who prescribed anticonvulsants more frequently had higher estimations of the risk of seizure within 2 weeks of SRS (P < .001), and their recommended duration of anticonvulsant use was <1 week, 1-2 weeks, and >2 weeks among 35%, 25%, and 41% of respondents, respectively.

Conclusions: There is extreme variation in physician recommendations regarding prophylactic corticosteroid and anticonvulsant use for patients undergoing SRS. Further investigation of the risks and benefits of these medications for SRS is warranted, which may promote guideline development and more patient-centered, rational prescribing practices.
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http://dx.doi.org/10.1016/j.prro.2015.11.004DOI Listing
March 2017

Consensus statement from the International Radiosurgery Oncology Consortium for Kidney for primary renal cell carcinoma.

Future Oncol 2016 Mar 3;12(5):637-45. Epub 2016 Feb 3.

University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, OH, USA.

Aim: To provide a multi-institutional consensus document for stereotactic body radiotherapy of primary renal cell carcinoma.

Materials & Methods: Eight international institutions completed a 65-item survey covering patient selection, planning/treatment aspects and response evaluation.

Results: All centers treat patients with pre-existing hypertension and solitary kidneys. Five institutions apply size constraints of 5-8 cm. The total planning target volume expansion is 3-10 mm. All institutions perform pretreatment imaging verification, while seven institutions perform some form of intrafractional monitoring. Number of fractions used are 1-12 to a total dose of 25 Gy-80 GyE. Imaging follow-up for local tumor response includes computed tomography (n = 8), PET-computed tomography (n = 1) and MRI (n = 5). Follow-up frequency is 3-6 months for the first 2 years and 3-12 months for subsequent 3 years.

Conclusion: Key methods for safe implementation and practice for stereotactic body radiotherapy kidney have been identified and may aid standardization of treatment delivery.
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http://dx.doi.org/10.2217/fon.16.2DOI Listing
March 2016

Stereotactic Radiosurgery for Renal Cancer Brain Metastasis: Prognostic Factors and the Role of Whole-Brain Radiation and Surgical Resection.

J Oncol 2015 19;2015:636918. Epub 2015 Nov 19.

Department of Neurosurgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02445, USA.

Background. Renal cell carcinoma is a frequent source of brain metastasis. We present our consecutive series of patients treated with Stereotactic Radiosurgery (SRS) and analyse prognostic factors and the interplay of WBRT and surgical resection. Methods. This is a retrospective study of 66 patients with 207 lesions treated with the Cyberknife radiosurgery system in our institution. The patients were followed up with imaging and clinical examination 1 month and 2-3 months thereafter for the brain metastasis. Patient, treatment, and outcomes characteristics were analysed. Results. 51 male (77.3%) and 15 female (22.7%) patients, with a mean age of 58.9 years (range of 31-85 years) and a median Karnofsky Performance Status (KPS) of 90 (range of 60-100), were included in the study. The overall survival was 13.9 months, 21.9 months, and 5.9 months for the patients treated with SRS only, additional surgery, and WBRT, respectively. The actuarial 1-year Local Control rates were 84%, 94%, and 88% for SRS only, for surgery and SRS, and for WBRT and additional SRS, respectively. Conclusions. Stereotactic radiosurgery is a safe and effective treatment option in patients with brain metastases from RCC. In case of a limited number of brain metastases, surgery and SRS might be appropriate.
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http://dx.doi.org/10.1155/2015/636918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668321PMC
December 2015

Ipilmumab and cranial radiation in metastatic melanoma patients: a case series and review.

J Immunother Cancer 2015 15;3:50. Epub 2015 Dec 15.

Department of Radiation Oncology, Beth Israel Deaconess Hospital, Boston, MA USA.

Background: Ipilimumab improves survival in metastatic melanoma patients. This population frequently develops brain metastases, which have been associated with poor survival and are often treated with radiation. Therefore, outcomes following ipilimumab and radiation are of interest, especially given case reports and animal studies suggest combined treatment may generate abscopal responses outside the radiation field.

Findings: We reviewed sixteen consecutive melanoma patients who received 1 to 8 courses of radiation, with a sum total of 51, systematically evaluating abscopal responses by following the largest extra-cranial lesion. We also reviewed other series of patients treated with cranial radiation and ipilimumab. Our patients received between 1 and 8 courses of cranial radiation. Four patients received radiation concurrently with ipilimumab. Median survival was 14 months, and 17 months in patients initially treated with SRS. Interestingly, after radiotherapy, there was a 2.8-fold increased likelihood that the rate of extra-cranial index lesion response improved that didn't reach statistical significance (p = 0.07); this was more pronounced when ipilimumab was administered within three months of radiation (p < 0.01).

Conclusion: Our experience and review of recently published series suggest ipilimumab and cranial radiation is well tolerated and can result in prolonged survival. Timing of ipilimumab administration in relation to radiation may impact outcomes. Additionally, our results demonstrate a trend for favorable systemic response following radiotherapy worthy of further evaluation in studies powered to detect potential synergies between radiation and immunotherapy.
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http://dx.doi.org/10.1186/s40425-015-0095-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678639PMC
December 2015