Publications by authors named "Kristin J Redmond"

67 Publications

Reducing Radiation-Induced Cognitive Toxicity: Sparing the Hippocampus and Beyond.

Int J Radiat Oncol Biol Phys 2021 Apr;109(5):1131-1136

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.

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http://dx.doi.org/10.1016/j.ijrobp.2021.01.001DOI Listing
April 2021

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

Tumor Control Probability of Radiosurgery and Fractionated Stereotactic Radiosurgery for Brain Metastases.

Int J Radiat Oncol Biol Phys 2020 Dec 31. Epub 2020 Dec 31.

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, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature.

Methods And Materials: PubMed-indexed studies published between January 1995 and September 2017 were used to evaluate dosimetric and clinical predictors of TCP after SRS or fSRS for brain metastases. Eligible studies had ≥10 patients and included detailed dose-fractionation data with corresponding ≥1-year local control (LC) data, typically evaluated as a >20% increase in diameter of the targeted lesion using the pre-SRS diameter as a reference.

Results: Of 2951 potentially eligible manuscripts, 56 included sufficient dose-volume data for analyses. Accepting that necrosis and pseudoprogression can complicate the assessment of LC, for tumors ≤20 mm, single-fraction doses of 18 and 24 Gy corresponded with >85% and 95% 1-year LC rates, respectively. For tumors 21 to 30 mm, an 18 Gy single-fraction dose was associated with 75% LC. For tumors 31 to 40 mm, a 15 Gy single-fraction dose yielded ∼69% LC. For 3- to 5-fraction fSRS using doses in the range of 27 to 35 Gy, 80% 1-year LC has been achieved for tumors of 21 to 40 mm in diameter.

Conclusions: TCP for SRS and fSRS are presented. For small lesions ≤20 mm, single doses of ≈18 Gy appear generally associated with excellent rates of LC; for melanoma, higher doses seem warranted. For larger lesions >20 mm, local control rates appear to be ≈ 70% to 75% with usual doses of 15 to 18 Gy, and in this setting, fSRS regimens should be considered. Greater consistency in reporting of dosimetric and LC data is needed to facilitate future pooled analyses. As systemic and biologic therapies evolve, updated analyses will be needed to further assess the necessity, efficacy, and toxicity of SRS and fSRS.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.034DOI Listing
December 2020

The Judicious Use of Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy in the Management of Large Brain Metastases.

Cancers (Basel) 2020 Dec 29;13(1). Epub 2020 Dec 29.

Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA 98195, USA.

Brain metastases are the most common intracranial malignant tumor in adults and are a cause of significant morbidity and mortality for cancer patients. Large brain metastases, defined as tumors with a maximum dimension >2 cm, present a unique clinical challenge for the delivery of stereotactic radiosurgery (SRS) as patients often present with neurologic symptoms that require expeditious treatment that must also be balanced against the potential consequences of surgery and radiation therapy-namely, leptomeningeal disease (LMD) and radionecrosis (RN). Hypofractionated stereotactic radiotherapy (HSRT) and pre-operative SRS have emerged as novel treatment techniques to help improve local control rates and reduce rates of RN and LMD for this patient population commonly managed with post-operative SRS. Recent literature suggests that pre-operative SRS can potentially half the risk of LMD compared to post-operative SRS and that HSRT can improve risk of RN to less than 10% while improving local control when meeting the appropriate goals for biologically effective dose (BED) and dose-volume constraints. We recommend a 3- or 5-fraction regimen in lieu of SRS delivering 15 Gy or less for large metastases or resection cavities. We provide a table comparing the BED of commonly used SRS and HSRT regimens, and provide an algorithm to help guide the management of these challenging clinical scenarios.
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http://dx.doi.org/10.3390/cancers13010070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795798PMC
December 2020

Evaluation of Definitive Stereotactic Body Radiotherapy and Outcomes in Adults With Extracranial Oligometastasis.

JAMA Netw Open 2020 11 2;3(11):e2026312. Epub 2020 Nov 2.

Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.

Importance: The outcomes and factors that influence survival in patients with oligometastasis (OM) are not well understood and have not been well described in large-scale studies.

Objective: To evaluate overall progression-free survival (PFS), widespread progression (WSP) outcomes, and survival factors from a pooled data set of 1033 patients with OM treated with stereotactic body radiotherapy (SBRT).

Design, Setting, And Participants: Case series from January 1, 2008, to December 31, 2016. The dates of analysis were April 2019 to May 2020. The setting was multi-institutional tertiary care hospitals. Participants were consecutive patients with 5 or fewer extracranial OMs whose primary tumor was treated curatively.

Exposure: Definitive SBRT.

Main Outcomes And Measures: Overall survival (OS), progression-free survival, rate of WSP, patterns of failure, and factors altering OS.

Results: In the largest international OM case series to date (1033 participants) (mean age, 68.0 years [range, 18.0-94.3 years]; 601 [58.2%] men), 1416 SBRT courses were delivered to patients with 1 OM (596 [57.7%]), 2 OMs (245 [23.7%]), 3 OMs (105 [10.2%]), 4 OMs (55 [5.3%]), and 5 OMs (32 [3.1%]). The median follow-up was 24.1 months (range, 0.3-104.7 months), and the median OS was 44.2 months (95% CI, 39.2-48.8 months). The median PFS was 12.9 months (95% CI, 11.6-14.2 months), and the median time to WSP was 42.5 months (95% CI, 36.8-53.5 months). The OS rates were 84.1% (95% CI, 81.7%-86.2%) at 1 year, 56.7% (95% CI, 53.0%-60.2%) at 3 years, and 35.2% (95% CI, 30.1%-40.3%) at 5 years. The 3-year OS, PFS, and WSP rates were 56.7% (95% CI, 53.0%-60.2%), 23.0% (95% CI, 20.2%-25.9%), and 45.2% (95% CI, 41.4%-48.9%), respectively. The 5-year OS, PFS, and WSP rates were 35.2% (95% CI, 30.1%-40.3%), 14.8% (95% CI, 11.9%-17.9%), and 54.5% (95% CI, 49.8%-59.2%), respectively. At the time of first progression, 342 patients (33.1%) had recurrence of OM disease, and 230 patients (22.3%) underwent subsequent ablative therapies to all known metastatic sites. Multivariable analyses identified primary tumor type (hazard ratio [HR], 3.73; 95% CI, 1.75-7.94; P < .001 for breast; 5.75; 95% CI, 2.88-11.46; P < .001 for colorectal; 4.67; 95% CI, 2.12-10.31; P < .001 for kidney; 10.61; 95% CI, 5.36-20.99; P < .001 for lung; and 12.00; 95% CI, 6.06-23.76; P < .001 for other [with prostate being the reference group]), metachronous OM presentation more than 24 months since initial diagnosis (HR, 0.63; 95% CI, 0.49-0.80; P < .001), metastases confined to the lung only (HR, 0.58; 95% CI, 0.48-0.72; P < .001), and nodal or soft-tissue metastases only (HR, 0.49; 95% CI, 0.26-0.90; P = .02) as survival factors. Sixty-six (6.4%) grade 3 or higher toxic effects were observed, including 1 (0.1%) grade 5 event.

Conclusions And Relevance: This study found favorable long-term OS and WSP rates associated with extracranial OM ablated with SBRT; however, modest PFS rates were observed. A substantial proportion of patients with OM developed progressive disease and were treated with local ablation. Factors that can inform clinical decision-making and clinical trial design include primary tumor type, a metachronous presentation more than 24 months since diagnosis, and the site of OM presentation.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.26312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670310PMC
November 2020

Clinician Experiences in Treatment Decision-Making for Patients with Spinal Metastases: A Qualitative Study.

J Bone Joint Surg Am 2021 Jan;103(1):e1

Departments of Orthopaedic Surgery (L.B.B., K.R.A., J.A.B., E.L., J.N.K., and A.J.S.), Neurosurgery (D.L.S.), and Radiation Oncology (T.A.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Effective management of metastatic disease requires multidisciplinary input and entails high risk of disease-related and treatment-related morbidity and mortality. The factors that influence clinician decision-making around spinal metastases are not well understood. We conducted a qualitative study that included a multidisciplinary cohort of physicians to evaluate the decision-making process for treatment of spinal metastases from the clinician's perspective.

Methods: We recruited operative and nonoperative clinicians, including orthopaedic spine surgeons, neurosurgeons, radiation oncologists, and physiatrists, from across North America to participate in either a focus group or a semistructured interview. All interviews were audiorecorded and transcribed verbatim. We then performed a thematic analysis using all of the available transcript data. Investigators sequentially coded transcripts and identified recurring themes that encompass overarching patterns in the data and directly bear on the guiding study question. This was followed by the development of a thematic map that visually portrays the themes, the subthemes, and their interrelatedness, as well as their influence on treatment decision-making.

Results: The thematic analysis revealed that numerous factors influence provider-based decision-making for patients with spinal metastases, including clinical elements of the disease process, treatment guidelines, patient preferences, and the dynamics of the multidisciplinary care team. The most prominent feature that resonated across all of the interviews was the importance of multidisciplinary care and the necessity of cohesion among a team of diverse health-care providers. Respondents emphasized aspects of care-team dynamics, including effective communication and intimate knowledge of team-member preferences, as necessary for the development of appropriate treatment strategies. Participants maintained that the primary role in decision-making should remain with the patient.

Conclusions: Numerous factors influence provider-based decision-making for patients with spinal metastases, including multidisciplinary team dynamics, business pressure, and clinician experience. Participants maintained a focus on shared decision-making with patients, which contrasts with patient preferences to defer decisions to the physician, as described in prior work.

Clinical Relevance: The results of this thematic analysis document the numerous factors that influence provider-based decision-making for patients with spinal metastases. Our results indicate that provider decisions regarding treatment are influenced by a combination of clinical characteristics, perceptions of patient quality of life, and the patient's preferences for care.
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http://dx.doi.org/10.2106/JBJS.20.00334DOI Listing
January 2021

Multi-institutional Analysis of Prognostic Factors and Outcomes After Hypofractionated Stereotactic Radiotherapy to the Resection Cavity in Patients With Brain Metastases.

JAMA Oncol 2020 Oct 15. Epub 2020 Oct 15.

Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany.

Importance: For brain metastases, the combination of neurosurgical resection and postoperative hypofractionated stereotactic radiotherapy (HSRT) is an emerging therapeutic approach preferred to the prior practice of postoperative whole-brain radiotherapy. However, mature large-scale outcome data are lacking.

Objective: To evaluate outcomes and prognostic factors after HSRT to the resection cavity in patients with brain metastases.

Design, Setting, And Participants: An international, multi-institutional cohort study was performed in 558 patients with resected brain metastases and postoperative HSRT treated between December 1, 2003, and October 31, 2019, in 1 of 6 participating centers. Exclusion criteria were prior cranial radiotherapy (including whole-brain radiotherapy) and early termination of treatment.

Exposures: A median total dose of 30 Gy (range, 18-35 Gy) and a dose per fraction of 6 Gy (range, 5-10.7 Gy) were applied.

Main Outcomes And Measures: The primary end points were overall survival, local control (LC), and the analysis of prognostic factors associated with overall survival and LC. Secondary end points included distant intracranial failure, distant progression, and the incidence of neurologic toxicity.

Results: A total of 558 patients (mean [SD] age, 61 [0.50] years; 301 [53.9%] female) with 581 resected cavities were analyzed. The median follow-up was 12.3 months (interquartile range, 5.0-25.3 months). Overall survival was 65% at 1 year, 46% at 2 years, and 33% at 3 years, whereas LC was 84% at 1 year, 75% at 2 years, and 71% at 3 years. Radiation necrosis was present in 48 patients (8.6%) and leptomeningeal disease in 73 patients (13.1%). Neurologic toxic events according to the Common Terminology Criteria for Adverse Events grade 3 or higher occurred in 16 patients (2.8%) less than 6 months and 24 patients (4.1%) greater than 6 months after treatment. Multivariate analysis identified a Karnofsky Performance Status score of 80% or greater (hazard ratio [HR], 0.61; 95% CI, 0.46-0.82; P < .001), 22 to 33 days between resection and radiotherapy (HR, 1.50; 95% CI, 1.07-2.10; P = .02), and a controlled primary tumor (HR, 0.69; 95% CI, 0.52-0.90; P = .007) as prognostic factors associated with overall survival. For LC, a single brain metastasis (HR, 0.57; 95% CI, 0.35-0.93; P = .03) and a controlled primary tumor (HR, 0.59; 95% CI, 0.39-0.92; P = .02) were significant in the multivariate analysis.

Conclusions And Relevance: To date, this cohort study includes one of the largest series of patients with brain metastases and postoperative HSRT and appears to confirm an excellent risk-benefit profile of local HSRT to the resection cavity. Additional studies will help determine radiation dose-volume parameters and provide a better understanding of synergistic effects with systemic and immunotherapies.
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http://dx.doi.org/10.1001/jamaoncol.2020.4630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563677PMC
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

Isolated progression of metastatic lung cancer: Clinical outcomes associated with definitive radiotherapy.

Cancer 2020 Oct 30;126(20):4572-4583. Epub 2020 Jul 30.

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

Background: Progressive, metastatic non-small cell lung cancer (NSCLC) often requires the initiation of new systemic therapy. However, in patients with NSCLC that is oligoprogressive (≤3 lesions), local radiotherapy (RT) may allow for the eradication of resistant microclones and, therefore, the continuation of otherwise effective systemic therapy.

Methods: Patients treated from 2008 to 2019 with definitive doses of RT to all sites of intracranial or extracranial oligoprogression without a change in systemic therapy were identified. Radiographic progression-free survival (rPFS) and time to new therapy (TNT) were measured. Associations between baseline clinical and treatment-related variables were correlated with progression-free survival via Cox proportional hazards modeling.

Results: Among 198 unique patients, 253 oligoprogressive events were identified. Intracranial progression occurred in 51% of the patients, and extracranial progression occurred in 49%. In the entire cohort, the median rPFS was 7.9 months (95% CI, 6.5-10.0 months), and the median TNT was 8.8 months (95% CI, 7.2-10.9 months). On adjusted modeling, patients with the following disease characteristics were associated with better rPFS: better performance status (P = .003), fewer metastases (P = .03), longer time to oligoprogression (P = .009), and fewer previous systemic therapies (P = .02). Having multiple sites of oligoprogression was associated with worse rPFS (P < .001).

Conclusions: In select patients with oligoprogression, definitive RT is a feasible treatment option to delay the initiation of next-line systemic therapies, which have more limited response rates and efficacy. Further randomized prospective data may help to validate these findings and identify which patients are most likely to benefit.
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http://dx.doi.org/10.1002/cncr.33109DOI Listing
October 2020

The IMPACT of Molecular Grading of Gliomas on Contemporary Clinical Practice.

Int J Radiat Oncol Biol Phys 2020 08;107(5):859-862

Department of Radiation Oncology, Stanford University, Stanford, California.

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http://dx.doi.org/10.1016/j.ijrobp.2020.05.043DOI Listing
August 2020

Normal tissue complication probability of vertebral compression fracture after stereotactic body radiotherapy for de novo spine metastasis.

Radiother Oncol 2020 09 12;150:142-149. Epub 2020 Jun 12.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, United States. Electronic address:

Objective: Stereotactic body radiotherapy (SBRT) for spine metastases is associated with post-treatment vertebral compression fracture (VCF). The purpose of this study is to identify clinical and radiation planning characteristics that predict post-SBRT VCF through a novel normal tissue complication probability (NTCP) analysis.

Methods: Patients with de novo spine metastases treated with SBRT between 2009 and 2018 at a single institution were included. Those who had surgical stabilization or radiation to the same site prior to SBRT were excluded. VCF was defined as new development or progression of existing vertebral body height loss not attributable to tumor growth. Probit NTCP models were constructed and fitted using a maximum likelihood approach. A multivariate proportional hazard model was used to estimate time to VCF using the Fine and Gray method.

Results: Three hundred and two vertebral segments from 193 patients were treated with a median dose of 24 Gy in 3 fractions (range 15-30 Gy in 1-5 fractions). With a median follow up of 13.9 months, local control was 89.3% at 1 year. A total of 26 SBRT-induced VCFs were observed, with 1 and 2-year cumulative incidences of 4.6% and 6.7%. NTCP modeling demonstrated a steep response of VCF risk to the dose to 80% and 50% volume of the planning target volume (PTV D80% and D50%), but not maximum dose or dose to 1 cc or 10% of PTV. D80% of 25 Gy and D50% of 28 Gy in 3 fractions corresponded to 10% VCF risk. On multivariate analysis, lower body mass index (HR 0.90 per unit increase, p = 0.04), total spinal instability neoplastic score (SINS, HR 2.44 unstable vs stable, p = 0.04), and PTV D80% (HR 1.11 for every Gy increase, p = 0.003) were associated with increased VCF risk.

Conclusions: SBRT provides excellent tumor control for spinal metastases and is associated with low rate of VCF in our cohort. NTCP modeling suggests that the larger volume of spine receiving lower doses are more closely associated with post-SBRT VCF than high dose regions. Under current target delineation methods, common SBRT regimens such as 24 Gy in 2 fractions or 27 Gy in 3 fractions may be inherently associated with VCF risk of 10% or greater. Consensus contouring guidelines should be reevaluated to minimize the volume of irradiated spine in light of these new data.
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http://dx.doi.org/10.1016/j.radonc.2020.06.009DOI Listing
September 2020

A Prospective Cohort Study of Neural Progenitor Cell-Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed Patients With Glioblastoma.

Neurosurgery 2020 07;87(1):E31-E40

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

Background: In treating glioblastoma, irradiation of the neural progenitor cell (NPC) niches is controversial. Lower hippocampal doses may limit neurocognitive toxicity, but higher doses to the subventricular zones (SVZ) may improve survival.

Objective: To prospectively evaluate the impact of limiting radiation dose to the NPC niches on tumor progression, survival, and cognition in patients with glioblastoma.

Methods: Patients with glioblastoma received resection followed by standard chemoradiation. Radiation dose to the NPC niches, including the bilateral hippocampi and SVZ, was minimized without compromising tumor coverage. The primary outcome was tumor progression in the spared NPC niches. Follow-up magnetic resonance imaging was obtained bimonthly. Neurocognitive testing was performed before treatment and at 6- and 12-mo follow-up. Cox regression evaluated predictors of overall and progression-free survival. Linear regression evaluated predictors of neurocognitive decline.

Results: A total of 30 patients enrolled prospectively. The median age was 58 yr. Median mean doses to the hippocampi and SVZ were 49.1 and 41.8 gray (Gy) ipsilaterally, and 16.5 and 19.9 Gy contralaterally. Median times to death and tumor progression were 16.0 and 7.6 mo, and were not significantly different compared to a matched historical control. No patients experienced tumor progression in the spared NPC-containing regions. Overall survival was associated with neurocognitive function (P ≤ .03) but not dose to the NPC niches. Higher doses to the hippocampi and SVZ predicted greater decline in verbal memory (P ≤ .01).

Conclusion: In treating glioblastoma, limiting dose to the NPC niches may reduce cognitive toxicity while maintaining clinical outcomes. Further studies are needed to confirm these results.
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http://dx.doi.org/10.1093/neuros/nyaa107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293896PMC
July 2020

Stereotactic Body Radiation Therapy for Nonspine Bone Metastases: International Practice Patterns to Guide Treatment Planning.

Pract Radiat Oncol 2020 Nov - Dec;10(6):e452-e460. Epub 2020 Mar 11.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Purpose: Stereotactic body radiation therapy (SBRT) is increasingly used for nonspine bone metastases (NSBM); however, there are limited data informing treatment planning. We surveyed international experts to better understand worldwide practice patterns in delivering NSBM-SBRT.

Methods And Materials: Nine international radiation oncologists were invited to participate based on demonstrated expertise with NSBM-SBRT. Experts were sent gross tumor volume contours and planning computed tomography and magnetic resonance images for 11 NSBM cases that covered a range of bony sites, including metastases to long bones (femur, humerus), pelvic bones (ilium, ischium, acetabulum, pubic symphysis), and thoracic bones (rib, sternum, scapula, clavicle). Experts were surveyed regarding treatment planning decisions and dose-fractionation selection. Descriptive analysis was conducted on the survey data.

Results: All experts participated and completed the survey. Most (56%) routinely fused magnetic resonance imaging with planning computed tomography imaging for target delineation. Dose fractionation schedules included single-fraction (18-24 Gy/1), 2 fractions (24 Gy/2), 3 fractions (28-30 Gy/3), 5 fractions (30-50 Gy/5), and 10 fractions (42-50 Gy/10). Although doses varied considerably, all had a biological equivalent dose of ≤100 Gy. Five-fraction schedules were most common, specifically 35 Gy/5, with 56% opting for this dose-fractionation in at least 1 case. Other dose-fractionation schedules used by at least 3 experts were 20 Gy/1, 30 Gy/3, and 30 Gy/5. Three experts prescribed 2 dose volumes using a simultaneous integrated boost. The 2 dose volumes were either the gross tumor volume and clinical target volume (CTV) or a smaller CTV (CTV1) encompassed within a larger CTV (CTV2) (eg, 30 Gy/3 to gross tumor volume or CTV1 and 15-24 Gy/3 to CTV or CTV2). Dose de-escalation was recommended by all experts in the setting of previous SBRT and by most in the context of previous convevoltherapy or in weight-bearing bones, especially if moderate-to-severe cortical erosion was present.

Conclusions: Significant heterogeneity exists worldwide in radiation technique and dose-fractionation for NSBM-SBRT, which supports the need for consensus guidelines to inform practice and trial design. Nonetheless, these data demonstrate expert agreement on selecting dose schedules with a biologically effective dose ≤100 Gy, reasons for dose de-escalation, and in determining acceptable dose schedules based on bony site.
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http://dx.doi.org/10.1016/j.prro.2020.02.011DOI Listing
March 2020

Tumor-Treating Field Arrays Do Not Reduce Target Volume Coverage for Glioblastoma Radiation Therapy.

Adv Radiat Oncol 2020 Jan-Feb;5(1):62-69. Epub 2019 Aug 28.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland.

Purpose: To inform development of procedures for using tumor-treating field arrays (TTFields) during glioblastoma radiation therapy by determining whether the placement and repositioning of arrays affects target volume coverage and cranial skin dose.

Methods And Materials: Radiation plans from 10 consecutive patients treated for glioblastoma were copied to a cranial phantom and reoptimized for phantom anatomy. Dose distributions were then recalculated on 3 additional computed tomographic scans of the phantom with the TTFields electrode arrays placed over distinct locations on the phantom scalp to compare planning target volume (PTV) coverage and skin dose with and without TTFields in place in varying positions. Percent depth dose curves were also measured for radiation beams passing through the electrodes and compared with commonly used bolus material.

Results: The presence of TTFields arrays decreased PTV V97% and D97% by as much as 1.7% and 2.7%, respectively, for a single array position, but this decrease was mitigated by array repositioning. On averaging the 3 array positions, there was no statistically significant difference in any dosimetric parameter of PTV coverage (V95-97%, D95-97%) across all cases compared with no array. Mean increases in skin D1cc and D20cc of 3.1% were calculated for the cohort. Surface dose for TTFields electrodes was less than that with a 5-mm superflab bolus.

Conclusions: Our work demonstrates that placement of TTFields arrays does not significantly affect target volume coverage. We show that repositioning of TTFields arrays, as is required in clinical use, further minimizes any dosimetric changes and eliminates the need for replanning when arrays are moved. A slight, expected bolus effect is observed, but the calculated increases in skin dose are not clinically significant. These data support the development of clinical trials to assess the safety and efficacy of combining concurrent chemoradiotherapy with TTFields therapy for glioblastoma.
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http://dx.doi.org/10.1016/j.adro.2019.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004938PMC
August 2019

Stereotactic body radiotherapy for benign spinal tumors: Meningiomas, schwannomas, and neurofibromas.

J Radiosurg SBRT 2019 ;6(3):167-177

Department of Radiation Oncology, Princess Alexandra Hospital, University of Queensland, Woolloongabba, QLD, Australia.

Stereotactic body radiation therapy (SBRT) is a relatively new technology, and its use among patients with benign spinal tumors has limited prospective data. Similar to intracranial benign tumors treated successfully with SBRT, benign spinal tumors of the same histology can also develop, and SBRT may be an effective treatment alternative in inoperable or recurrent cases. Outcomes in patients with neurofibromatosis type 1, neurofibromatosis type 2, or schwannomatosis treated with SBRT have also been reported. Single institution reports have shown local control rates over 90% and improvement in clinical symptoms. The optimum dose and fractionation to maximize local control and minimize toxicity is unknown, with few incidences of radiation treatment-related toxicities. Given the location and benign nature of these tumors, careful management of dose to critical organs is essential. With continued follow-up, the optimum use of SBRT in patients with benign spinal tumors can be better defined.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774487PMC
January 2019

International consensus recommendations for target volume delineation specific to sacral metastases and spinal stereotactic body radiation therapy (SBRT).

Radiother Oncol 2020 04 23;145:21-29. Epub 2019 Dec 23.

Department of Radiation Oncology, BC Cancer - Vancouver Centre, Canada.

Background And Purpose: To interrogate inter-observer variability in gross tumour volume (GTV) and clinical target volume (CTV) delineation specific to the treatment of sacral metastases with spinal stereotactic body radiation therapy (SBRT) and develop CTV consensus contouring recommendations.

Materials And Methods: Nine specialists with spinal SBRT expertise representing 9 international centres independently contoured the GTV and CTV for 10 clinical cases of metastatic disease within the sacrum. Agreement between physicians was calculated with an expectation minimisation algorithm using simultaneous truth and performance level estimation (STAPLE) and with kappa statistics. Optimised confidence level consensus contours were obtained using a voxel-wise maximum likelihood approach and the STAPLE contours for GTV and CTV were based on an 80% confidence level.

Results: Mean GTV STAPLE agreement sensitivity and specificity was 0.70 (range, 0.54-0.87) and 1.00, respectively, and 0.55 (range, 0.44-0.64) and 1.00 for the CTV, respectively. Mean GTV and CTV kappa agreement was 0.73 (range, 0.59-0.83) and 0.59 (range, 0.41-0.70), respectively. Optimised confidence level consensus contours were identified by STAPLE analysis. Consensus recommendations for the CTV include treating the entire segment containing the disease in addition to the immediate adjacent bony anatomic segment at risk of microscopic extension.

Conclusion: Consensus recommendations for CTV target delineation specific to sacral metastases treated with SBRT were established using expert contours. This is a critical first step to achieving standardisation of target delineation practice in the sacrum and will serve as a baseline for meaningful pattern of failure analyses going forward.
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http://dx.doi.org/10.1016/j.radonc.2019.11.026DOI Listing
April 2020

A novel MRI-based score assessing trabecular bone quality to predict vertebral compression fractures in patients with spinal metastasis.

J Neurosurg Spine 2019 Dec 20:1-8. Epub 2019 Dec 20.

Departments of1Neurosurgery.

Objective: Vertebral compression fractures (VCFs) in patients with spinal metastasis can lead to destabilization and often carry a high risk profile. It is therefore important to have tools that enable providers to predict the occurrence of new VCFs. The most widely used tool for bone quality assessment, dual-energy x-ray absorptiometry (DXA), is not often available at a patient's initial presentation and has limited sensitivity. While the Spinal Instability Neoplastic Score (SINS) has been associated with VCFs, it does not take patients' baseline bone quality into consideration. To address this, the authors sought to develop an MRI-based scoring system to estimate trabecular vertebral bone quality (VBQ) and to assess this system's ability to predict the occurrence of new VCFs in patients with spinal metastasis.

Methods: Cases of adult patients with a diagnosis of spinal metastasis, who had undergone stereotactic body radiation therapy (SBRT) to the spine or neurosurgical intervention at a single institution between 2012 and 2019, were retrospectively reviewed. The novel VBQ score was calculated for each patient by dividing the median signal intensity of the L1-4 vertebral bodies by the signal intensity of cerebrospinal fluid (CSF). Multivariable logistic regression analysis was used to identify associations of demographic, clinical, and radiological data with new VCFs.

Results: Among the 105 patients included in this study, 56 patients received a diagnosis of a new VCF and 49 did not. On univariable analysis, the factors associated with new VCFs were smoking status, steroid use longer than 3 months, the SINS, and the novel scoring system-the VBQ score. On multivariable analysis, only the SINS and VBQ score were significant predictors of new VCFs and, when combined, had a predictive accuracy of 89%.

Conclusions: As a measure of bone quality, the novel VBQ score significantly predicted the occurrence of new VCFs in patients with spinal metastases independent of the SINS. This suggests that baseline bone quality is a crucial factor that requires assessment when evaluating these patients' conditions and that the VBQ score is a novel and simple MRI-based measure to accomplish this.
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http://dx.doi.org/10.3171/2019.9.SPINE19954DOI Listing
December 2019

A Phase 2 Study of Post-Operative Stereotactic Body Radiation Therapy (SBRT) for Solid Tumor Spine Metastases.

Int J Radiat Oncol Biol Phys 2020 02 16;106(2):261-268. Epub 2019 Oct 16.

Neurological Surgery, The John Hopkins University, Baltimore, Maryland.

Purpose: In patients with spinal instability, cord compression, or neurologic deficits, the standard of care is surgery followed by radiation therapy (RT). Recurrence rates after conventional RT remain high. The purpose of this study is to prospectively examine the efficacy of postoperative stereotactic body RT (SBRT) in patients who have undergone surgical intervention for spine metastases. We hypothesize that postoperative SBRT to the spine would be associated with higher local control than historical rates after conventional RT.

Methods And Materials: Thirty-five adult patients with a Karnofsky Performance Status score ≥40 and spine metastases from solid tumors with no prior overlapping RT and target volumes ≤3 consecutive vertebral levels were enrolled. Thirty-three patients were treated. Two patients underwent treatment to 2 target volumes for a total of 35 target volumes. All patients received SBRT 30 Gy in 5 fractions. Patients were followed with neurological examinations and computed tomography and/or magnetic resonance imaging every 3 months. Neurologic function was assessed at the same time points using the American Spinal Injury Association (ASIA) impairment score. Pain was rated according to the 10-point visual analogue scale and MD Anderson Cancer Center brief pain index. Toxicity was recorded according to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4. The primary objective was the rate of radiographic local recurrence at 12 months after completion of SBRT.

Results: Patient characteristics were as follows: 34.3% had radioresistant primaries; 71.4% were ASIA E and the remainder ASIA D; and the median baseline Karnofsky Performance Status score was 70 (range, 50-100). Radiographic and symptomatic local control at 1 year were 90% (95% confidence interval, 76%-98%). The median time to recurrence in these 3 patients was 3.5 months (range, 3.4-5.8 months), all had radiosensitive tumors, and all recurrences were epidural. No patients experienced wound dehiscence, hardware failure, or spinal cord myelopathy. The median time to return to systemic therapy was 0.5 months (range, 0-9.4 months).

Conclusions: This prospective study of postoperative spine SBRT demonstrates excellent local control with low toxicity. These data suggest superior rates of local control compared with conventional RT; however, a formal comparative study is warranted.
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http://dx.doi.org/10.1016/j.ijrobp.2019.10.011DOI Listing
February 2020

Updated risk models demonstrate low risk of symptomatic radionecrosis following stereotactic radiosurgery for brain metastases.

Surg Neurol Int 2019 15;10:32. Epub 2019 Mar 15.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, 401 N Broadway Suite 1440, Baltimore, MD, USA.

Background: Improvements in systemic therapy continue to increase survival for patients with brain metastases. Updated dosimetric models are required to optimize long-term safety of stereotactic radiosurgery (SRS) for this indication.

Methods: Patients at a single institution receiving SRS from December 2011 to December 2014 were retrospectively reviewed. Patients with radiographic progression of at least one lesion, and with at least 6 months of follow-up from the start of SRS were included. Grade 3 necrosis was defined as requiring surgical intervention. This data were combined with two additional published datasets to construct logistic models describing necrosis risk as a function of dose and volume.

Results: From our institution, 294 brain metastases across 57 patients in 139 treatment plans met inclusion criteria. Primary histologies included non-small cell lung cancer ( = 19), melanoma ( = 13), breast carcinoma ( = 9), renal cell carcinoma ( = 7), and other ( = 9). Median follow-up from SRS of first cranial metastasis was 21.7 months (range: 6.3-56.6) and median overall survival was 25.6 months (range: 6.5-56.6). There were eight cases of Grade 1-2 and two cases of Grade 3 necrosis. As a useful clinical reference point, 20 cc of total brain receiving a single-fraction equivalent dose ≥14 Gy corresponded to 12.1% risk for Grade 1-3 ( < 0.003) and 3.4% risk for Grade 3 necrosis ( < 0.001).

Conclusions: These results compare favorably with the QUANTEC brain tolerance estimates for radiosurgery, providing optimism for lower toxicity in the modern era. Additional studies are needed to determine dose tolerance parameters across a broad spectrum of patients.
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http://dx.doi.org/10.4103/sni.sni_303_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499458PMC
March 2019

Prospective acceleration of parallel RF transmission-based 3D chemical exchange saturation transfer imaging with compressed sensing.

Magn Reson Med 2019 11 17;82(5):1812-1821. Epub 2019 Jun 17.

Divison of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, Maryland.

Purpose: To develop prospectively accelerated 3D CEST imaging using compressed sensing (CS), combined with a saturation scheme based on time-interleaved parallel transmission.

Methods: A variable density pseudo-random sampling pattern with a centric elliptical k-space ordering was used for CS acceleration in 3D. Retrospective CS studies were performed with CEST phantoms to test the reconstruction scheme. Prospectively CS-accelerated 3D-CEST images were acquired in 10 healthy volunteers and 6 brain tumor patients with an acceleration factor (R ) of 4 and compared with conventional SENSE reconstructed images. Amide proton transfer weighted (APTw) signals under varied RF saturation powers were compared with varied acceleration factors.

Results: The APTw signals obtained from the CS with acceleration factor of 4 were well-preserved as compared with the reference image (SENSE R = 2) both in retrospective phantom and prospective healthy volunteer studies. In the patient study, the APTw signals were significantly higher in the tumor region (gadolinium [Gd]-enhancing tumor core) than in the normal tissue (p < .001). There was no significant APTw difference between the CS-accelerated images and the reference image. The scan time of CS-accelerated 3D APTw imaging was dramatically reduced to 2:10 minutes (in-plane spatial resolution of 1.8 1.8 mm ; 15 slices with 4-mm slice thickness) as compared with SENSE (4:07 minutes).

Conclusion: Compressed sensing acceleration was successfully extended to 3D-CEST imaging without compromising CEST image quality and quantification. The CS-based CEST imaging can easily be integrated into clinical protocols and would be beneficial for a wide range of applications.
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http://dx.doi.org/10.1002/mrm.27875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660350PMC
November 2019

Commentary: Image-Guided, Linac-Based, Surgical Cavity-Hypofractionated Stereotactic Radiotherapy in 5 Daily Fractions for Brain Metastases.

Neurosurgery 2019 11;85(5):E870-E871

Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington.

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http://dx.doi.org/10.1093/neuros/nyz189DOI Listing
November 2019

Assessing the Effectiveness of Systemic Therapy after Stereotactic Radiosurgery on Cancer Recurrence and All-Cause Mortality.

World Neurosurg 2019 Sep 31;129:e572-e581. Epub 2019 May 31.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Electronic address:

Background: Patients with cancer often present with brain metastases in the setting of controlled extracranial disease, for which they receive stereotactic radiosurgery (SRS) and surgical resection. The role of systemic therapy after SRS is unclear. Brain metastasis indicates active cancer dissemination, and microscopic systemic disease may be present despite absence of gross disease as assessed by conventional imaging modalities.

Objective: The aim was to determine if post-SRS systemic therapy reduces the risk of brain relapse, systemic relapse, and death in patients with brain metastases and controlled extracranial disease.

Methods: We retrospectively reviewed the medical records of 67 patients with controlled extracranial disease who received SRS for brain metastases. Kaplan-Meier analysis and Cox proportional hazards regression were used to assess how post-SRS systemic therapy affected the risk of brain relapse, systemic relapse, and all-cause mortality.

Results: In our sample, 31% of patients received systemic therapy after SRS. Post-SRS systemic therapy did not affect median time to brain relapse (P = 0.43), systemic relapse (P = 0.16), or death (P = 0.33) by univariate analysis. After accounting for confounding factors such as cancer histology and age, post-SRS systemic therapy significantly reduced the risk of brain relapse (hazard ratio [HR], 0.22; P = 0.002) but not systemic relapse (HR, 0.38; P = 0.09) or all-cause mortality (HR, 2.16; P = 0.09).

Conclusions: Only a minority of patients with brain metastases and controlled extracranial disease receive adjuvant systemic therapy after SRS, but those that do have a reduced risk of brain relapse. Post-SRS systemic therapy may act prophylactically to reduce the risk of intracranial cancer recurrence.
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http://dx.doi.org/10.1016/j.wneu.2019.05.218DOI Listing
September 2019

Extracranial Abscopal Responses after Radiation Therapy for Intracranial Metastases: A Review of the Clinical Literature and Commentary on Mechanism.

Cureus 2019 Mar 8;11(3):e4207. Epub 2019 Mar 8.

Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, USA.

The current literature contains a small number of case series and individual case reports that describe radiographic regression of extracranial tumors after treatment of one or more brain metastases with radiation therapy. These observations suggest an abscopal effect that traverses the blood-brain barrier. The purpose of this review is to describe the clinical evidence for this phenomenon and potential mechanistic relationships between radiation, the blood-brain barrier, and the abscopal effect. Among reported cases, the majority of patients received systemic immunotherapy, which is consistent with an immunologic mechanism underlying abscopal responses. Preclinical data suggest that radiation may play multiple roles in this process, including the release of tumor-associated antigens and disruption of the blood-brain barrier. Future studies investigating the abscopal effect would benefit from more rigorous methods to control for patient and treatment factors that may affect distant tumor response.
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http://dx.doi.org/10.7759/cureus.4207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505720PMC
March 2019

In Reply to Ryu.

Int J Radiat Oncol Biol Phys 2019 06;104(2):464-465

Department of Neurological Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1016/j.ijrobp.2019.02.016DOI Listing
June 2019

Association of a Simulated Institutional Gender Equity Initiative With Gender-Based Disparities in Medical School Faculty Salaries and Promotions.

JAMA Netw Open 2018 12 7;1(8):e186054. Epub 2018 Dec 7.

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

Importance: Despite progress in narrowing gender-based salary gaps, notable disparities persist in the scientific community. The significance of pay difference may be underestimated, with little data evaluating its effect on lifetime wealth after accounting for factors like time to promotion and savings.

Objectives: To characterize gender disparities in salary and assess the outcomes associated with a gender equity initiative (GEI).

Design, Setting, And Participants: Quality improvement study with simulations of salary and additional accumulated wealth (AAW) using retrospectively reviewed Johns Hopkins University School of Medicine annual salary and promotion data. All academic faculty were included in the faculty salary analysis from 2005 (n = 1481) and 2016 (n = 1885).

Main Outcomes And Measures: Salary and longitudinal promotion data from 2005 to 2016 were used to estimate gender-based differences in salary and time to promotion. The effect of these differences on total salary and AAW, including retirement and salary-based investments, was simulated for a representative male and female faculty member over a 30-year career in 3 scenarios: (1) pre-GEI, (2) post-GEI, and (3) in real time for GEI, beginning with and progressing through these initiatives.

Results: Analyses of salaries of 1481 faculty (432 women) in 2005 and 1885 faculty (742 women) in 2016 revealed that a decade after GEI implementation, the overall mean (SE) salary gap by gender decreased from -2.6% (1.2%) (95% CI, -5.6% to -0.3%) to -1.9% (1.1%) (95% CI, -4.1% to 0.3%). Simulation of pre-GEI disparities correlated with male faculty collecting an average lifetime AAW of $501 416 more than the equivalent woman, with disparities persisting past retirement. The AAW gap decreased to $210 829 in the real-time GEI simulation and to $66 104 using post-GEI conditions, reflecting success of GEI efforts.

Conclusions And Relevance: Even small gender-based salary gaps are associated with substantial differences in lifetime wealth, but an institutional commitment to achieving equitable promotion and compensation for women can appreciably reduce these disparities. The findings of this study support broad implementation of similar initiatives without delay, as results may take more than a decade to emerge. A modifiable version of the simulation is provided so that external users may assess the potential disparities present within their own institutions.
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http://dx.doi.org/10.1001/jamanetworkopen.2018.6054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324345PMC
December 2018

Embolize, Resect, Irradiate.

Int J Radiat Oncol Biol Phys 2019 01 12;103(1):16. Epub 2018 Dec 12.

Department of Neurological Surgery, The Johns Hopkins University, Baltimore, Maryland.

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http://dx.doi.org/10.1016/j.ijrobp.2018.03.041DOI Listing
January 2019

Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system.

Oncoimmunology 2018;7(12):e1500108. Epub 2018 Sep 6.

Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, USA.

Immune checkpoint blockade targeting programmed cell death protein 1 (PD-1) is emerging as an important treatment strategy in a growing list of cancers, yet its clinical benefits are limited to a subset of patients. Further investigation of tumor-intrinsic predictors of response and how extrinsic factors, such as iatrogenic immunosuppression caused by conventional therapies, impact the efficacy of anti-PD-1 therapy are paramount. Given the widespread use of corticosteroids in cancer management and their immunosuppressive nature, this study sought to determine how corticosteroids influence anti-PD-1 responses and whether their effects were dependent on tumor location within the periphery versus central nervous system (CNS), which may have a more limiting immune environment. In well-established anti-PD-1-responsive murine tumor models, corticosteroid therapy resulted in systemic immune effects, including severe and persistent reductions in peripheral CD4+ and CD8 + T cells. Corticosteroid treatment was found to diminish the efficacy of anti-PD-1 therapy in mice bearing peripheral tumors with responses correlating with peripheral CD8/Treg ratio changes. In contrast, in mice bearing intracranial tumors, corticosteroids did not abrogate the benefits conferred by anti-PD-1 therapy. Despite systemic immune changes, anti-PD-1-mediated antitumor immune responses remained intact during corticosteroid treatment in mice bearing intracranial tumors. These findings suggest that anti-PD-1 responses may be differentially impacted by concomitant corticosteroid use depending on tumor location within or outside the CNS. As an immune-specialized site, the CNS may potentially play a protective role against the immunosuppressive effects of corticosteroids, thus sustaining antitumor immune responses mediated by PD-1 blockade.
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http://dx.doi.org/10.1080/2162402X.2018.1500108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279341PMC
September 2018

Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage.

Adv Radiat Oncol 2018 Oct-Dec;3(4):582-590. Epub 2018 Jul 10.

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

Purpose: Reirradiation for recurrent glioma remains controversial without knowledge of optimal patient selection, dose, fractionation, and normal tissue tolerances. We retrospectively evaluated outcomes and toxicity after conventionally fractionated reirradiation for recurrent high-grade glioma, along with the impact of concurrent chemotherapy.

Methods And Materials: We conducted a retrospective review of patients reirradiated for high-grade glioma recurrence between 2007 and 2016 (including patients with initial low-grade glioma). Outcome metrics included overall survival (OS), prognostic factors for survival, and treatment-related toxicity.

Results: Patients (n = 118; median age 47 years; median Karnofsky performance status score: 80) were re-treated at a median of 28 months (range, 5-214 months) after initial radiation therapy. The median reirradiation dose was 41.4 Gy (range, 12.6-54.0 Gy) to a median lesion volume of 202 cm (range, 20-901 cm). The median cumulative (initial radiation and reirradiation combined) potential maximum brainstem dose was 76.9 Gy (range, 5.0-108.3 Gy) and optic apparatus dose was 56.0 Gy (range, 4.5-90.9 Gy). Of the patients, 56% received concurrent temozolomide, 14%, bevacizumab, and 11%, temozolomide plus bevacizumab; 19% had no chemotherapy. The planned reirradiation was completed by 90% of patients. Median OS from the completion of reirradiation was 9.6 months (95% confidence interval [CI], 7.5-11.7 months) for all patients and 14.0, 11.5, and 6.7 months for patients with initial grade 2, 3, and 4 glioma, respectively. On multivariate analysis, better OS was observed with a >24-month interval between radiation treatments (hazard ratio [HR]: 0.3; 95% CI, 0.2-0.5; < .001), reirradiation dose >41.4 Gy (HR: 0.6; 95% CI, 0.4-0.9; = .03), and gross total resection before reirradiation (HR: 0.6, 95% CI, 0.3-0.9; = .02). Radiation necrosis and grade ≥3 late neurotoxicity were both minimal (<5%). No symptomatic persistent brainstem or optic nerve/chiasm injury was identified.

Conclusions: Salvage reirradiation, even at doses >41.4 Gy in conventional fractionation, along with chemotherapy, was safe and well tolerated with meaningful survival duration. These data provide information that may be useful in implementing safe reirradiation treatments for appropriately selected patients and guiding future studies to define optimal reirradiation doses, maximal safe doses to critical structures, and the role of systemic therapy.
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http://dx.doi.org/10.1016/j.adro.2018.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200913PMC
July 2018

Commentary: Stereotactic Body Radiotherapy for Spinal Metastases at the Extreme Ends of the Spine: Imaging-Based Outcomes for Cervical and Sacral Metastases.

Neurosurgery 2019 11;85(5):E804-E805

Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington.

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http://dx.doi.org/10.1093/neuros/nyy428DOI Listing
November 2019

Outcomes of Metastatic Brain Lesions Treated with Radioactive Cs-131 Seeds after Surgery: Experience from One Institution.

Cureus 2018 Jul 30;10(7):e3075. Epub 2018 Jul 30.

Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, USA.

Introduction Brain metastases are common in patients with advanced systemic cancer and often recur despite treatment with surgical resection and radiotherapy. Whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) have significantly improved local control rates but are limited by complications including neurocognitive deficits and radiation necrosis. These risks can be higher in the re-irradiation setting. Brachytherapy may be an alternative method of additional targeted adjuvant radiotherapy with acceptable rates of toxicity. Methods A retrospective chart review of all patients undergoing resection for metastatic brain lesions and permanent low-dose rate Cs-131 brachytherapy was performed for one institution over a 10-year period. All patients had previous radiation therapy already and, after surgery, were followed with imaging every three months. Patient demographics, disease characteristics, intracranial disease, peri- and post-operative complications, and outcomes were recorded. The primary outcome of interest was local tumor recurrence at the site of brachytherapy while secondary outcomes included distant disease progression (within the brain) and complications such as radiation necrosis. Results During the study period, nine cases of individual patients met inclusion criteria. The median preoperative lesion diameter was 3 cm (0.8-4.1). The median overall survival after surgery and brachytherapy was 10.3 months, after excluding two patients who were lost to follow-up. Six of nine patients had no local recurrence, while three patients had development or progression of distant lesions. No patients experienced acute or delayed complications. Conclusion Cs-131 brachytherapy is a promising alternative method for controlling brain metastases after previous radiation interventions and surgical resection. In this case series, there were no incidences of local tumor recurrence or complications such as radiation necrosis.
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http://dx.doi.org/10.7759/cureus.3075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166914PMC
July 2018