Publications by authors named "Eric L Chang"

157 Publications

Stereotactic Radiosurgery for Perioptic Meningiomas: An International, Multicenter Study.

Neurosurgery 2021 Jan 20. Epub 2021 Jan 20.

Department of Neurosurgery, University of Virginia, Charlottesville, Virginia.

Background: Stereotactic radiosurgery (SRS) is increasingly used for management of perioptic meningiomas.

Objective: To study the safety and effectiveness of SRS for perioptic meningiomas.

Methods: From 12 institutions participating in the International Radiosurgery Research Foundation (IRRF), we retrospectively assessed treatment parameters and outcomes following SRS for meningiomas located within 3 mm of the optic apparatus.

Results: A total of 438 patients (median age 51 yr) underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) perioptic meningiomas. Median treatment volume was 8.01 cm3. Median prescription dose was 12 Gy, and median dose to the optic apparatus was 8.50 Gy. A total of 405 patients (93%) underwent single-fraction SRS and 33 patients (7%) underwent hypofractionated SRS. During median imaging follow-up of 55.6 mo (range: 3.15-239 mo), 33 (8%) patients experienced tumor progression. Actuarial 5-yr and 10-yr progression-free survival was 96% and 89%, respectively. Prescription dose of ≥12 Gy (HR: 0.310; 95% CI [0.141-0.679], P = .003) and single-fraction SRS (HR: 0.078; 95% CI [0.016-0.395], P = .002) were associated with improved tumor control. A total of 31 (10%) patients experienced visual decline, with actuarial 5-yr and 10-yr post-SRS visual decline rates of 9% and 21%, respectively. Maximum dose to the optic apparatus ≥10 Gy (HR = 2.370; 95% CI [1.086-5.172], P = .03) and tumor progression (HR = 4.340; 95% CI [2.070-9.097], P < .001) were independent predictors of post-SRS visual decline.

Conclusion: SRS provides durable tumor control and quite acceptable rates of vision preservation in perioptic meningiomas. Margin dose of ≥12 Gy is associated with improved tumor control, while a dose to the optic apparatus of ≥10 Gy and tumor progression are associated with post-SRS visual decline.
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http://dx.doi.org/10.1093/neuros/nyaa544DOI Listing
January 2021

Stereotactic radiosurgery for treatment of radiation-induced meningiomas: a multiinstitutional study.

J Neurosurg 2021 Jan 1:1-9. Epub 2021 Jan 1.

1Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Radiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs.

Methods: From 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS.

Results: Fifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm3, and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4-195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3-45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm3 predicted progression (HR 8.226, 95% CI 1.028-65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS.

Conclusions: SRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.
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http://dx.doi.org/10.3171/2020.7.JNS202064DOI Listing
January 2021

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

Automatic detection and segmentation of multiple brain metastases on magnetic resonance image using asymmetric UNet architecture.

Phys Med Biol 2021 Jan 13;66(1):015003. Epub 2021 Jan 13.

Department of Radiation Oncology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States of America.

Detection of brain metastases is a paramount task in cancer management due both to the number of high-risk patients and the difficulty of achieving consistent detection. In this study, we aim to improve the accuracy of automated brain metastasis (BM) detection methods using a novel asymmetric UNet (asym-UNet) architecture. An end-to-end asymmetric 3D-UNet architecture, with two down-sampling arms and one up-sampling arm, was constructed to capture the imaging features. The two down-sampling arms were trained using two different kernels (3 × 3 × 3 and 1 × 1 × 3, respectively) with the kernel (1 × 1 × 3) dominating the learning. As a comparison, vanilla single 3D UNets were trained with different kernels and evaluated using the same datasets. Voxel-based Dice similarity coefficient (DSC), sensitivity (S ), precision (P ), BM-based sensitivity (S ), and false detection rate (F ) were used to evaluate model performance. Contrast-enhanced T1 MR images from 195 patients with a total of 1034 BMs were solicited from our institutional stereotactic radiosurgery database. The patient cohort was split into training (160 patients, 809 lesions), validation (20 patients, 136 lesions), and testing (15 patients, 89 lesions) datasets. The lesions in the testing dataset were further divided into two subgroups based on the diameters (small S = 1-10 mm, large L = 11-26 mm). In the testing dataset, there were 72 and 17 BMs in the S and L sub-groups, respectively. Among all trained networks, asym-UNet achieved the highest DSC of 0.84 and lowest F of 0.24. Although vanilla 3D-UNet with a single 1 × 1 × 3 kernel achieved the highest sensitivities for the S group, it resulted in the lowest precision and highest false detection rate. Asym-UNet was shown to balance sensitivity and false detection rate as well as keep the segmentation accuracy high. The novel asym-UNet segmentation network showed overall competitive segmentation performance and more pronounced improvement in hard-to-detect small BMs comparing to the vanilla single 3D UNet.
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http://dx.doi.org/10.1088/1361-6560/abca53DOI Listing
January 2021

Radiotherapy to the brain: what are the consequences of this age-old treatment?

Ann Palliat Med 2021 Jan 29;10(1):936-952. Epub 2020 Jul 29.

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

Radiotherapy (RT) has been widely used in the management of benign and malignant brain tumors for decades. However, complications can develop as a result of adjacent structures being exposed to radiation. As such, careful selection of patients and deciding on the most suitable modality of RT are crucial to minimize complications. In general, complications can be subdivided based on its timeline of onset; acute (few days to weeks), early delayed (1-6 months) and late (>6 months). Late complications such as cognitive decline and radiation necrosis can be debilitating and negatively impacts quality-of-life. New strategies to reduce RT-related complications such as with hippocampal sparing-WBRT, memantine, and focal RT (e.g., stereotactic radiosurgery) have had promising results and are being adopted in clinical practice. This review will focus on RT-related complications in the brain, with a focus on WBRT or SRS-related late adverse events, as well as measures to mitigate these complications.
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http://dx.doi.org/10.21037/apm-20-856DOI Listing
January 2021

Executive summary from American Radium Society's appropriate use criteria on neurocognition after stereotactic radiosurgery for multiple brain metastases.

Neuro Oncol 2020 12;22(12):1728-1741

Department of Radiation Oncology, Keck School of Medicine of University of Southern California, Los Angeles, CA.

Background: The American Radium Society (ARS) Appropriate Use Criteria brain malignancies panel systematically reviewed (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) published literature on neurocognitive outcomes after stereotactic radiosurgery (SRS) for patients with multiple brain metastases (BM) to generate consensus guidelines.

Methods: The panel developed 4 key questions (KQs) to guide systematic review. From 11 614 original articles, 12 were selected. The panel developed model cases addressing KQs and potentially controversial scenarios not addressed in the systematic review (which might inform future ARS projects). Based upon quality of evidence, the panel confidentially voted on treatment options using a 9-point scale of appropriateness.

Results: The panel agreed that SRS alone is usually appropriate for those with good performance status and 2-10 asymptomatic BM, and usually not appropriate for >20 BM. For 11-15 and 16-20 BM there was (between 2 case variants) agreement that SRS alone may be appropriate or disagreement on the appropriateness of SRS alone. There was no scenario (among 6 case variants) in which conventional whole-brain radiotherapy (WBRT) was considered usually appropriate by most panelists. There were several areas of disagreement, including: hippocampal sparing WBRT for 2-4 asymptomatic BM; WBRT for resected BM amenable to SRS; fractionated versus single-fraction SRS for resected BM, larger targets, and/or brainstem metastases; optimal treatment (WBRT, hippocampal sparing WBRT, SRS alone to all or select lesions) for patients with progressive extracranial disease, poor performance status, and no systemic options.

Conclusions: For patients with 2-10 BM, SRS alone is an appropriate treatment option for well-selected patients with good performance status. Future study is needed for those scenarios in which there was disagreement among panelists.
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http://dx.doi.org/10.1093/neuonc/noaa192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746939PMC
December 2020

Low risk of radiation myelopathy with relaxed spinal cord dose constraints in de novo, single fraction spine stereotactic radiosurgery.

Radiother Oncol 2020 Nov 31;152:49-55. Epub 2020 Jul 31.

Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, United States.

Background And Purpose: Spine stereotactic radiosurgery (SSRS) offers high rates of local control in a critical anatomic area by delivering precise, ablative doses of radiation for treatment of spine metastases. However, the dose tolerance of the spinal cord (SC) after SSRS with relation to radiation myelopathy (RM) is not well-described.

Materials And Methods: We reviewed patients who underwent single fraction, de novo SSRS from 2012-2017 and received >12 Gy Dmax to the SC, defined using MRI-CT fusion without PRV expansion. The standard SC constraint was D0.01cc ≤ 12 Gy. Local control was estimated with the Kaplan-Meier method. Bayesian analysis was used to compute posterior probabilities for RM.

Results: A total of 146 SSRS treatments among 132 patients were included. The median SC Dmax was 12.6 Gy (range, 12.1-17.1 Gy). The SC Dmax was >12 and <13 Gy for 109 (75%) treatments, ≥13 and <14 Gy for 28 (19%) treatments, and ≥14 Gy for 9 (6%) treatments. The 1-year local control rate was 94%. With a median follow-up time of 42 months, there were zero (0) RM events observed. Assuming a prior 4.3% risk of RM, the true rate of RM for SC Dmax of ≤14 Gy was computed as <1% with 98% probability.

Conclusion: In one of the largest series of patients treated with single fraction, de novo SSRS, there were no cases of RM observed with a median follow-up of 42 months. These data support safe relaxation of MRI-defined SC dose up to D0.01cc ≤ 12 Gy, which corresponds to <1% risk of RM.
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http://dx.doi.org/10.1016/j.radonc.2020.07.050DOI Listing
November 2020

Commentary: Mature Imaging-Based Outcomes Supporting Local Control for Complex Reirradiation Salvage Spine Stereotactic Body Radiotherapy.

Neurosurgery 2020 09;87(4):E498-E499

Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington.

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http://dx.doi.org/10.1093/neuros/nyaa159DOI Listing
September 2020

Neuro-oncology Management During the COVID-19 Pandemic With a Focus on WHO Grade III and IV Gliomas.

Neuro Oncol 2020 May 5. Epub 2020 May 5.

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

Background: Because of the increased risk in cancer patients of developing complications caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), physicians have to balance the competing risks of the negative impact of the pandemic and the primary tumor. In this consensus statement, an international group of experts present mitigation strategies and treatment guidance for patients suffering from high grade gliomas (HGG) during the coronavirus disease 2019 (COVID-19) pandemic.

Method / Results: 16 international experts in the treatment of HGG contributed to this consensus-based practice recommendation including neuro-oncologists, neurosurgeons, radiation -oncologists and a medical physicist. Generally, treatment of neuro-oncological patients cannot be significantly delayed and initiating therapy should not be outweighed by COVID-19. We present detailed interdisciplinary treatment strategies for molecular subgroups in two pandemic scenarios, a scale-up phase and a crisis phase.

Conclusion: This practice recommendation presents a pragmatic framework and consensus-based mitigation strategies for the treatment of HGG patients during the SARS-CoV-2 pandemic.
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http://dx.doi.org/10.1093/neuonc/noaa113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239150PMC
May 2020

Quantifying vascular invasion in pancreatic cancer-a contrast CT based method for surgical resectability evaluation.

Phys Med Biol 2020 06 1;65(10):105012. Epub 2020 Jun 1.

Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, United States of America.

Pancreatic cancer (PC) is one of the most lethal cancers, with frequent local therapy resistance and dismal 5-year survival rate. To date, surgical resection remains to be the only treatment option offering potential cure. Unfortunately, at diagnosis, the majority of patients demonstrate varying levels of vascular infiltration, which can contraindicate surgical resection. Patients unsuitable for immediate resection are further divided into locally advanced (LA) and borderline resectable (BR), with different treatment goals and therapeutic designs. Accurate definition of resectability is thus critical for PC patients, yet the existing methods to determine resectability rely on descriptive abutment to surrounding vessels rather than quantitative geometric characterization. Here, we aim to introduce a novel intra-subject object-space support-vector-machine (OsSVM) method to quantitatively characterize the degree of vascular involvement-the main factor determining the PC resectability. Intra-subject OsSVMs were applied on 107 contrast CT scans (56 LA, BR and 26 resectable (RE) PC cases) for optimized tumor-vessel separations. Nine metrics derived from OsSVM margins were calculated as indicators of the overall vascular infiltration. The combined sets of matrics selected by the elastic net yielded high classification capability between LA and BR (AUC = 0.95), as well as BR and RE (AUC = 0.98). The proposed OsSVM method may provide an improved quantitative imaging guideline to refine the PC resectability grading system.
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http://dx.doi.org/10.1088/1361-6560/ab8106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316342PMC
June 2020

Current approaches to the management of brain metastases.

Nat Rev Clin Oncol 2020 05 20;17(5):279-299. Epub 2020 Feb 20.

Department of Radiation Oncology, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.

Brain metastases are a very common manifestation of cancer that have historically been approached as a single disease entity given the uniform association with poor clinical outcomes. Fortunately, our understanding of the biology and molecular underpinnings of brain metastases has greatly improved, resulting in more sophisticated prognostic models and multiple patient-related and disease-specific treatment paradigms. In addition, the therapeutic armamentarium has expanded from whole-brain radiotherapy and surgery to include stereotactic radiosurgery, targeted therapies and immunotherapies, which are often used sequentially or in combination. Advances in neuroimaging have provided additional opportunities to accurately screen for intracranial disease at initial cancer diagnosis, target intracranial lesions with precision during treatment and help differentiate the effects of treatment from disease progression by incorporating functional imaging. Given the numerous available treatment options for patients with brain metastases, a multidisciplinary approach is strongly recommended to personalize the treatment of each patient in an effort to improve the therapeutic ratio. Given the ongoing controversies regarding the optimal sequencing of the available and expanding treatment options for patients with brain metastases, enrolment in clinical trials is essential to advance our understanding of this complex and common disease. In this Review, we describe the key features of diagnosis, risk stratification and modern paradigms in the treatment and management of patients with brain metastases and provide speculation on future research directions.
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http://dx.doi.org/10.1038/s41571-019-0320-3DOI Listing
May 2020

Identifying Disparities in Care in Treating Glioblastoma: A Retrospective Cohort Study of Patients Treated at a Safety-net Versus Private Hospital Setting.

World Neurosurg 2020 05 27;137:e213-e220. Epub 2020 Jan 27.

Department of Neurosurgery, University of Southern California Keck School of Medicine, Los Angeles, California, USA.

Background: Patients of lower socioeconomic status (SES) may experience barriers to their oncologic care, but current data conflict over whether SES affects the prognosis of patients with glioblastoma (GB).

Objective: We sought to determine whether SES disparities impaired delivery of neuro-oncologic care and affected the prognosis of GB patients.

Methods: The records of GB patients treated from 2010 to 2014 at a safety-net hospital (SNH) or private hospital (PH), both served by 1 academic medical institution, were retrospectively reviewed and compared. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.

Results: A total of 55 SNH and 39 PH GB patients were analyzed with median 11-month follow-up. SNH patients were predominantly Hispanic, low income, enrolled in Medicaid, were less likely to receive radiation (89% vs. 100%), took longer to start radiation (41 vs. 29 days), and were less likely to complete radiation treatment (80% vs. 95%). Concurrent and adjuvant temozolomide use were also lower (85% vs. 94% and 60% vs. 71%, respectively). OS and PFS were not significantly different (15 vs. 16 months and 8 vs. 11 months, respectively). On multivariate analysis, adjuvant chemotherapy and RT completion predicted for better OS, whereas hospital type, income, and insurance did not.

Conclusion: Although GB patients at our SNH received less adjuvant treatment compared with PH, outcomes were similar. Access to multidisciplinary care staffed by academic physicians may play an important role in overcoming socioeconomic barriers to treatment availability and quality at SNHs.
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http://dx.doi.org/10.1016/j.wneu.2020.01.133DOI Listing
May 2020

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 Apr 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

Effectiveness of Gamma Knife Radiosurgery in the Treatment of Refractory Trigeminal Neuralgia: A Case Series.

Oper Neurosurg (Hagerstown) 2020 06;18(6):571-576

Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.

Background: Medical management is the first line of treatment for trigeminal neuralgia (TN). Patients with medically refractory TN may undergo a variety of invasive surgical interventions with varying success rates. Management of TN refractory to both medical and surgical intervention remains somewhat controversial.

Objective: To assess the effectiveness of Gamma Knife radiosurgery (GKRS; Elekta Instruments AB) for medically refractory TN.

Methods: A retrospective review was conducted for 57 cases (47 patients) who underwent GKRS for refractory TN at our institution between 2005 and 2018. TN pain outcomes were evaluated using the Barrow Neurological Institute (BNI) Pain Scale. A good outcome was defined by post-GKRS BNI score of I-III, whereas treatment failure was defined BNI score IV-V.

Results: Of the total 57 GKRS procedures, 47 (82.5%) had good outcomes. A total of 22 patients (46.8%) experienced complete pain relief off medications (BNI I). The average time to pain relief was 30 d (range 1-120 d). Prior invasive surgical treatment for TN was not found to have a significant impact on GKRS outcomes (P = .32). Target and treatment volumes were not found to correlate significantly with GKRS outcomes (.47 and .47, respectively). Complications included 2 cases (4.2%) of facial numbness. A total of 37 patients (78.7%) did not have any additional invasive surgical interventions following GKRS treatment.

Conclusion: GKRS is a safe and effective treatment modality for both medically and surgically refractory TN. Complete symptom relief was possible in patients with prior surgical or GKRS treatments. Recurrent symptoms following surgery or GKRS should not exclude a patient from future GKRS consideration.
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http://dx.doi.org/10.1093/ons/opz311DOI Listing
June 2020

Bevacizumab is more effective in nasopharyngeal carcinoma patients with lower maximum radiation dose to the temporal lobe.

Chin Clin Oncol 2019 Oct 17;8(S1):S20. Epub 2019 Apr 17.

Department of Radiation Oncology, Norris Cancer Hospital, Keck School of Medicine of USC, Los Angeles, CA, USA.

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http://dx.doi.org/10.21037/cco.2019.02.06DOI Listing
October 2019

Strategies to Mitigate Toxicities From Stereotactic Body Radiation Therapy for Spine Metastases.

Neurosurgery 2019 12;85(6):729-740

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

Improvements in systemic therapy are translating into more patients living longer with metastatic disease. Bone is the most common site of metastasis, where spinal lesions can result in significant pain impacting quality of life and possible neurological dysfunction resulting in a decline in performance status. Stereotactic body radiation therapy (SBRT) of the spine has emerged as a promising technique to provide durable local control, palliation of symptoms, control of oligoprogressive sites of disease, and possibly augment the immune response. SBRT achieves this by delivering highly conformal radiation therapy to allow for dose escalation due to a steep dose gradient from the planning target volume to nearby critical organs at risk. In our review, we provide an in-depth review and expert commentary regarding seminal literature that defined clinically meaningful toxicity endpoints with actionable dosimetric limits and/or clinical management strategies to mitigate toxicity potentially attributable to SBRT of the spine. We placed a spotlight on radiation myelopathy (de novo, reirradiation after conventional external beam radiation therapy or salvage after an initial course of spinal SBRT), plexopathy, vertebral compression fracture, pain flare, esophageal toxicity, myositis, and safety regarding combination with concurrent targeted or immune therapies.
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http://dx.doi.org/10.1093/neuros/nyz213DOI Listing
December 2019

Updates in the management of intradural spinal cord tumors: a radiation oncology focus.

Neuro Oncol 2019 06;21(6):707-718

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

Primary spinal cord tumors represent a hetereogeneous group of central nervous system malignancies whose management is complex given the relatively uncommon nature of the disease and variety of tumor subtypes, functional neurologic deficits from the tumor, and potential morbidities associated with definitive treatment. Advances in neuroimaging; integration of diagnostic, prognostic, and predictive molecular testing into tumor classification; and developments in neurosurgical techniques have refined the current role of radiotherapy in the multimodal management of patients with primary spinal cord tumors, and corroborated the need for prospective, multidisciplinary discussion and treatment decision making. Radiotherapeutic technological advances have dramatically improved the entire continuum from treatment planning to treatment delivery, and the development of stereotactic radiosurgery and proton radiotherapy provides new radiotherapy options for patients treated in the definitive, adjuvant, or salvage setting. The objective of this comprehensive review is to provide a contemporary overview of the management of primary intradural spinal cord tumors, with a focus on radiotherapy.
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http://dx.doi.org/10.1093/neuonc/noz014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556849PMC
June 2019

Preserve the Facial Nerve.

Int J Radiat Oncol Biol Phys 2019 03;103(4):798-799

Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, California.

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http://dx.doi.org/10.1016/j.ijrobp.2018.11.024DOI Listing
March 2019

Lens Dose-Response Prediction Modeling and Cataract Incidence in Patients With Retinoblastoma After Lens-Sparing or Whole-Eye Radiation Therapy.

Int J Radiat Oncol Biol Phys 2019 04 8;103(5):1143-1150. Epub 2018 Dec 8.

Department of Radiation Oncology, Keck School of Medicine of USC and Children's Hospital Los Angeles, Los Angeles, California. Electronic address:

Purpose: We retrospectively assessed the incidence of cataracts in patients with retinoblastoma (Rb) treated with either lens-sparing radiation therapy (LSRT) or whole-eye radiation therapy (WERT). A secondary aim of this study was to model the dose-response risk of cataract.

Methods And Materials: We reviewed 65 patients with Rb treated with radiation therapy (RT) at Children's Hospital, Los Angeles from 1997 to 2015. Eyes that were enucleated before RT or lacked follow-up eye examinations were excluded. All patients underwent computed tomography simulation, and mean lens dose data were collected. Follow-up ophthalmologic examinations and intraocular lens implant history were reviewed for cataracts. The primary event-free survival (EFS) outcome was cataract development. Eyes without cataracts were censored on the last date of eye examination or post-RT enucleation, if applicable. Kaplan-Meier estimates were used to compare EFS outcomes, and dose response was projected with Cox regression and logistic regression models.

Results: Sixty-one patients (94 eyes) were analyzed with a median follow-up of 51.8 months. For eyes treated with WERT, cataracts developed in 71.7% versus 35.3% for LSRT. Median EFS for WERT and LSRT were 20.8 and 67.9 months, respectively. Compared with WERT, a significant EFS benefit was demonstrated for LSRT (P < .001). Mean lens dose had a significant effect on cataracts in both Cox regression and logistic regression models (P < .01). The mean lens dose of 7 Gy was projected to have a 5-year cataract incidence of 20% and 25% with the logistic and Cox regression models, respectively.

Conclusions: We report the first clinical data demonstrating significantly improved EFS in patients with Rb treated with LSRT. Through lens dose-response modeling, we validate a mean lens dose threshold of 7 Gy to keep cataract risk below 25%. Although RT is used less often for Rb owing to advances in chemotherapy delivery options, these findings are relevant for refining lens dose constraints, particularly in children who have received radiation dose near the orbit.
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http://dx.doi.org/10.1016/j.ijrobp.2018.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667833PMC
April 2019

Long-Term Tumor Control Rates Following Gamma Knife Radiosurgery for Acoustic Neuroma.

World Neurosurg 2019 Feb 15;122:366-371. Epub 2018 Nov 15.

Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Background: Acoustic neuromas (ANs) are benign intracranial tumors that arise from myelin-forming Schwann cells surrounding the vestibular branch of the vestibulocochlear nerve (cranial nerve VIII). Treatment options for AN include observation, radiosurgery, and microsurgical resection. Gamma Knife radiosurgery (GKRS) for AN has well-documented short-term safety and efficacy for carefully selected patients. Recent innovations in GKRS technology may improve long-term outcomes. The aim of this study was to report long-term tumor control and complication rates after GKRS for sporadic AN.

Methods: A retrospective review was performed of patients with sporadic ANs at Keck Hospital of USC who underwent GKRS from 1995 to 2015 with a minimum follow-up of 12 months.

Results: Median age at treatment was 63.7 years (range, 19.4-84.2 years). Median follow-up time was 69 months. Median tumor diameter was 17.5 mm (range, 5.0-29.0 mm), and median treatment volume was 2.41 cm (range, 0.09-12.8 cm). Median prescribed dose was 12.50 Gy. Tumor control was achieved in 51 (98.1%) patients over the follow-up period (12-192 months). One patient experienced tumor progression at 22 months after GKRS, requiring surgical intervention, which ultimately resulted in remission. Complications included hearing loss (17.3%), worsened balance/ataxia (7.7%), and hydrocephalus (1.92%).

Conclusions: Patients undergoing GKRS for sporadic ANs had high rates of tumor control over a median follow-up time of >5 years. Improvements in radiosurgery treatment planning were seen in the most recent cohort of patients. GKRS is a safe and effective modality for treating sporadic ANs in selected patients.
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http://dx.doi.org/10.1016/j.wneu.2018.11.009DOI Listing
February 2019

Commentary: Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors.

Neurosurgery 2019 11;85(5):E840-E841

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

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http://dx.doi.org/10.1093/neuros/nyy460DOI Listing
November 2019

Phase 1 Study of Spinal Cord Constraint Relaxation With Single Session Spine Stereotactic Radiosurgery in the Primary Management of Patients With Inoperable, Previously Unirradiated Metastatic Epidural Spinal Cord Compression.

Int J Radiat Oncol Biol Phys 2018 12 9;102(5):1481-1488. Epub 2018 Aug 9.

Department of Neurosurgery, MD Anderson Cancer Center, University of Texas, Houston, Texas.

Purpose: We seek to establish the feasibility of using spine stereotactic radiosurgery (SSRS), allowing for spinal cord dose constraint relaxation, as the primary management of metastatic epidural spinal cord compression (MESCC) in inoperable patients.

Methods And Materials: Inoperable patients with thoracic MESCC and no history of radiation were enrolled on this prospective phase 1 single-institution protocol. SSRS was delivered to a histology-dependent prescription dose of 18 or 24 Gy. Incremental spinal cord constraint relaxation was performed from a Dmax cohort of 10 Gy up to 16 Gy only if tumor progression occurred and the risk of radiation-induced myelopathy (RM) remained lower than the risk of tumor progression.

Results: Thirty-two patients enrolled on the trial; 4, 12, 9, and 7 patients were in the 10 Gy, 12 Gy, 14 Gy, and 16 Gy cord Dmax cohorts, respectively. At baseline, there were 2 sites with MESCC grade 1A, 10 sites with grade 1B, 10 sites with grade 1C, 9 sites with grade 2, and 1 site with grade 3 disease. Among the 28 evaluable patients, the median overall survival was 28.6 months (95% confidence interval [CI], 9.2-48.0 months), and the 1-year local control was 89% (95% CI, 74%- 97%). With a median follow-up of 17 months, there were no cases of RM (upper 95% CI, 12%). In the cohort receiving a cord Dmax of 16 Gy, there were no cases of RM (upper 95% CI, 39%) with a median follow-up of 17 months (range, 12.7-21.0 months).

Conclusions: SSRS is a safe and effective tool in patients with MESCC. In high-risk inoperable patients with MESCC receiving SSRS, dose constraint relaxation of the cord constraint dmax to 16 Gy may be considered to optimize local control, with the acknowledgment that this is based on 6 evaluable patients who received this dose in this trial.
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http://dx.doi.org/10.1016/j.ijrobp.2018.07.2023DOI Listing
December 2018

Commentary: Clinical Outcomes of Upfront Stereotactic Radiosurgery Alone for Patient With 5 to 15 Brain Metastases.

Neurosurgery 2019 08;85(2):E247-E248

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

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http://dx.doi.org/10.1093/neuros/nyy278DOI Listing
August 2019

The evolution and rise of stereotactic body radiotherapy (SBRT) for spinal metastases.

Expert Rev Anticancer Ther 2018 09 3;18(9):887-900. Epub 2018 Jul 3.

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

Introduction: Owing to improvements in clinical care and systemic therapy, more patients are being diagnosed with, and living longer with, spinal metastases (SM). In parallel, tremendous technological progress has been made in the field of radiation oncology. Advances in both software and hardware are able to integrate three- (and four-) dimensional body imaging with spatially accurate treatment delivery methods. This leads to improved efficacy, shortened treatment schedule, and potentially reduced treatment-related toxicity. Areas covered: In this review, we will look at the progress made by stereotactic body radiotherapy (SBRT) in the management of SM. We will review the technological factors which have enabled the widespread use of SBRT. The efficacy of SBRT, in various clinical scenarios, and associated toxicities will be reviewed. Lastly, we will discuss about patient selection and provide a five-year roadmap. Expert commentary: Spine SBRT is a safe and efficacious treatment option. Practice guidelines recommend the use of SBRT in oligometastatic patients especially those with radio-resistant cancer types, and in scenarios involving re-irradiation. SBRT offers patients dose-intensification over a short schedule which may allow less time off systemic therapy. The results of the phase III trials are eagerly awaited.
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http://dx.doi.org/10.1080/14737140.2018.1493381DOI Listing
September 2018

Novel multidisciplinary approaches in the management of metastatic epidural spinal cord compression.

Future Oncol 2018 Jul 25;14(17):1665-1668. Epub 2018 Jun 25.

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

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http://dx.doi.org/10.2217/fon-2018-0133DOI Listing
July 2018

Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity.

J Neurooncol 2018 Sep 25;139(2):421-429. Epub 2018 Apr 25.

Department of Radiation Oncology, Keck School of Medicine of USC, Los Angeles, CA, USA.

Introduction: There is evidence that the combination of ipilimumab and stereotactic radiosurgery (SRS) for brain metastases improves outcomes. We investigated clinical outcomes, radiation toxicity, and impact of ipilimumab timing in patients treated with SRS for melanoma brain metastases.

Methods: We retrospectively identified 91 patients treated with SRS at our institution for melanoma brain metastases from 2006 to 2015. Concurrent ipilimumab administration was defined as within ± 4 weeks of SRS procedure. Acute and late toxicities were graded with CTCAE v4.03. Overall survival (OS), local failure, distant brain failure, and failure-free survival were analyzed with the Kaplan-Meier method. OS was analyzed with Cox regression.

Results: Twenty-three patients received ipilimumab concurrent with SRS, 28 patients non-concurrently, and 40 patients did not receive ipilimumab. The median age was 62 years and 91% had KPS ≥ 80. The median follow-up time was 7.4 months. Patients who received ipilimumab had a median OS of 15.1 months compared to 7.8 months in patients who did not (p = 0.02). In multivariate analysis, ipilimumab (p = 0.02) and diagnosis-specific graded prognostic assessment (p = 0.02) were associated with OS. There were no differences in intracranial control by ipilimumab administration or timing. The incidence of radiation necrosis was 5%, with most events occurring in patients who received ipilimumab.

Conclusions: Patients who received ipilimumab had improved OS even after adjusting for prognostic factors. Ipilimumab did not appear to increase risk for acute toxicity. The majority of radiation necrosis events, however, occurred in patients who received ipilimumab. Our results support the continued use of SRS and ipilimumab as clinically appropriate.
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http://dx.doi.org/10.1007/s11060-018-2880-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469981PMC
September 2018

Population description and clinical response assessment for spinal metastases: part 2 of the SPIne response assessment in Neuro-Oncology (SPINO) group report.

Neuro Oncol 2018 08;20(9):1215-1224

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

Background: Approximately 40% of metastatic cancer patients will develop spinal metastases. The current report provides recommendations for standardization of metrics used for spinal oncology patient population description and outcome assessment beyond local control endpoints on behalf of the SPIne response assessment in Neuro-Oncology (SPINO) group.

Methods: The SPINO group survey was conducted in order to determine the preferences for utilization of clinician-based and patient-reported outcome measures for description of patients with spinal metastases. Subsequently, ClinicalTrials.gov registry was searched for spinal oncology clinical trials, and measures for patient description and outcome reporting were identified for each trial. These two searches were used to identify currently used descriptors and instruments. A literature search was performed focusing on the measures identified in the survey and clinical trial search in order to assess their validity in the metastatic spinal tumor patient population. References for this manuscript were identified through PubMed and Medline searches.

Results: Published literature, expert survey, and ongoing clinical trials were used to synthesize recommendations for instruments for reporting of spinal stability, epidural tumor extension, neurological and functional status, and symptom severity.

Conclusions: Accurate description of patient population and therapy effects requires a combination of clinician-based and patient-reported outcome measures. The current report provides international consensus recommendations for the systematic reporting of patient- and clinician-reported measures required to develop trials applicable to surgery for spinal metastases and postoperative spine stereotactic body radiotherapy (SBRT).
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http://dx.doi.org/10.1093/neuonc/noy047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071663PMC
August 2018

Stereotactic Radiosurgery for Multiple Brain Metastases: Two Cases of Preserved Quality of Life.

Cureus 2017 Dec 28;9(12):e1995. Epub 2017 Dec 28.

Department of Radiation Oncology, Keck School of Medicine of the University of Southern California, Los Angeles, CA.

Brain metastases are the most common intracranial tumors in the adult population and have been historically treated with whole brain radiation therapy (WBRT). However, as medical advances improve life expectancy, stereotactic radiosurgery (SRS) has replaced WBRT as the standard of care for limited (one to three) brain metastases due to the relative sparing of neurocognitive function (NCF) and therefore quality of life (QoL). The use of SRS has been less documented in the case of multiple (four or more) brain metastases, with literature limited to non-randomized studies showing comparable survival and local control. In this series, we detail the case of two individuals who received SRS at our institution for multiple brain metastases and demonstrated remarkable response. The first patient is a 78-year-old woman who received Gamma Knife (GK) treatment to 17 lesions at our institution. This patient responded very well to treatment and maintains an excellent quality of life, with no deficits on serial neurological examination as she continues to travel and drive for ridesharing businesses. The second patient is an active 44-year-old woman who received SRS to 24 lesions at our institution. The patient has now been free of intracranial failures for two years and continues fulfilling her love for travel and long-distance biking. SRS is emerging as an acceptable alternative to WBRT in treating multiple brain metastases due to its preservation of NCF. Because omission of WBRT may lead to increased probability of distant brain metastasis failure, it is critical to follow these patients closely with frequent neuroimaging. In the event of a failure, it is also possible to use SRS salvage therapy with good response. Some patients who receive SRS alone demonstrate exceptional outcomes with excellent QoL, and it is possible that certain prognostication factors such as performance status, tumor histology, and tumor volume may play a role in identifying these patients. The decision to treat a patient with SRS alone for multiple brain metastases should be made carefully with consideration of systemic therapeutic options, overall prognosis, and the patient's goals of care, with adherence to a careful follow-up plan by the physician and patient.
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http://dx.doi.org/10.7759/cureus.1995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832392PMC
December 2017