Publications by authors named "Joshua D Palmer"

54 Publications

The role of VEGF receptor inhibitors in preventing cerebral radiation necrosis: a retrospective cohort study.

Neurooncol Pract 2021 Feb 17;8(1):75-80. Epub 2020 Oct 17.

Department of Neurology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Radiation necrosis (RN) is a potential complication after radiation therapy for brain tumors. It is hypothesized that VEGF plays an important role in the pathophysiology of RN. Bevacizumab, a monoclonal antibody against VEGF-A, is often successful in the management of RN. The objective of this study is to assess whether VEGF receptor (VEGFR) inhibitors, a group of oral tyrosine kinase inhibitors (TKIs), can prevent or reverse RN.

Methods: We retrospectively studied a cohort of 102 patients with renal cell carcinoma and brain metastases seen at The Ohio State University James Cancer Center between January 1, 2011 and April 30, 2019. We identified those who developed RN and analyzed the temporal relationship between the use of VEGFR TKIs and the development of RN.

Results: The cumulative incidence of RN is 13.7% after radiation treatments that included LINAC-based stereotactic radiosurgery, fractionated stereotactic radiotherapy, or Gamma Knife radiosurgery. There was no statistically significant difference in the cumulative incidence of RN between patients taking TKIs and patients who were off TKIs (9.9% and 11.5% respectively,  = .741). The median time to development of RN was only numerically shorter in patients taking TKIs (151 vs 315 days,  = .315). One patient developed RN after stopping cabozantinib. Eight patients developed RN while on cabozantinib, pazopanib, or sunitinib. One patient was started on axitinib during active RN without significant improvement subsequently.

Conclusions: VEGFR TKIs do not consistently prevent RN. The therapeutic effects of VEGFR TKIs against RN warrant further research.
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http://dx.doi.org/10.1093/nop/npaa067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906267PMC
February 2021

Postoperative Stereotactic Body Radiotherapy for Spinal Metastasis and Predictors of Local Control.

Neurosurgery 2021 Feb 11. Epub 2021 Feb 11.

Department of Neurosurgery, The James Cancer Hospital at the Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Background: Spine surgery is indicated for select patients with mechanical instability, pain, and/or malignant epidural spinal cord compression, with or without neurological compromise. Stereotactic body radiotherapy (SBRT) is an option for durable local control (LC) for metastatic spine disease.

Objective: To determine factors associated with LC and progression-free survival (PFS) for patients receiving postoperative stereotactic spine radiosurgery.

Methods: We analyzed consecutive patients from 2013 to 2019 treated with surgical intervention followed by SBRT. Surgical interventions included laminectomy and vertebrectomy. SBRT included patients treated with 1 to 5 fractions of radiosurgery. We analyzed LC, PFS, overall survival (OS), and toxicity. Univariate and multivariate analyses were performed.

Results: A total of 63 patients were treated with a median follow-up of 12.5 mo. Approximately 75% of patients underwent vertebrectomy and 25% underwent laminectomy. One-year cumulative incidence of local failure was 19%. LC was significantly improved for patients receiving radiosurgery ≤40 d from surgery compared to that for patients receiving radiosurgery ≥40 d from surgery, 94% vs 75%, respectively, at 1 yr (P = .03). Patients who received preoperative embolization had improved LC with 1-yr LC of 88% vs 76% for those who did not receive preoperative embolization (P = .037). Significant predictors for LC on multivariate analysis were time from surgery to radiosurgery, higher radiotherapy dose, and preoperative embolization. The 1-yr PFS and OS was 56% and 60%, respectively.

Conclusion: Postoperative radiosurgery has excellent and durable LC for spine metastasis. An important consideration when planning postoperative radiosurgery is minimizing delay from surgery to radiosurgery. Preoperative embolization and higher radiotherapy dose were associated with improved LC warranting further study.
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http://dx.doi.org/10.1093/neuros/nyaa587DOI Listing
February 2021

Suboptimal outcome for patients with biliary rhabdomyosarcoma treated on low-risk clinical trials: A report from the Children's Oncology Group.

Pediatr Blood Cancer 2021 Apr 26;68(4):e28914. Epub 2021 Jan 26.

Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.

Background: Biliary rhabdomyosarcoma (RMS) is the most common biliary tumor in children. The biliary tract is classified as a favorable primary site. Therefore, patients with localized biliary RMS were included in two consecutive low-risk studies, D9602 and ARST0331, by the Children's Oncology Group (COG). The outcome for these patients treated with low-risk therapy has not been reported.

Procedure: Patients with biliary RMS enrolled on COG low-risk trials D9602 or ARST0331 were analyzed. All patients received systemic chemotherapy and those with Group II (microscopic residual) or Group III (macroscopic residual) disease received 36-50.4 Gy adjuvant radiotherapy (RT). Delayed primary excision (DPE) was allowed on both studies.

Results: Seventeen patients with biliary RMS were treated on D9602 (n = 7) or ARST0331 (n = 10). Median age was 3.5 years (range 1.7-10.3). Ten (59%) patients had tumors >5 cm and 14 (82%) had Group III disease. Fifteen (88%) patients received RT. The 5-year event-free survival (EFS) and overall survival (OS) were 70.6% (95% confidence interval [CI]: 46.9-94.3%) and 76.5% (95% CI: 54.6-98.4%), respectively. The majority of patients (80%) who received RT did not have disease recurrence while both patients who did not receive RT had local relapse. Five (36%) of 14 patients with Group III disease underwent DPE; two experienced a local relapse. In the nine patients without DPE, two developed local relapse.

Conclusions: Patients with localized biliary RMS treated on low-risk studies had suboptimal outcomes. These patients may benefit from therapy on intermediate-risk studies.
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http://dx.doi.org/10.1002/pbc.28914DOI Listing
April 2021

Resected WHO grade I meningioma and predictors of local control.

J Neurooncol 2021 Mar 9;152(1):145-151. Epub 2021 Jan 9.

Department of Radiation Oncology, Sidney Kimmel Medical College, Philadelphia, PA, USA.

Introduction: Despite optimal surgical resection, meningiomas may recur, with increasing grade and the degree of resection being predictive of risk. We hypothesize that an increasing Ki67 correlates with a higher risk of recurrence of resected WHO grade I meningiomas.

Methods: The study population consisted of patients with resected WHO grade 1 meningiomas in locations outside of the base of skull. Digitally scanned slides stained for Ki67 were analyzed using automatic image analysis software in a standardized fashion.

Results: Recurrence was observed in 53 (17.7%) of cases with a median follow up time of 25.8 months. Ki67 ranged from 0 to 30%. Median Ki67 was 5.1% for patients with recurrence and 3.5% for patients without recurrence. In unadjusted analyses, high Ki-67 (≥ 5 vs. < 5) vs. ≥ 5) was associated with over a twofold increased risk of recurrence (13.1% vs. 27% respectively; HR 2.1731; 95% CI [1.2534, 3.764]; p = 0.006). After Adjusting for patient or tumor characteristics, elevated Ki-67 remained significantly correlated with recurrence. Grade 4 Simpson resection was noted in 71 (23.7%) of patients and it was associated with a significantly increased risk of recurrence (HR 2.56; 95% CI [1.41, 4.6364]; p = 0.002).

Conclusions: WHO grade 1 meningiomas exhibit a significant rate of recurrence following resection. While Ki-67 is not part of the WHO grading criteria of meningiomas, a value greater than 5% is an independent predictor for increased risk of local recurrence following surgical resection.
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http://dx.doi.org/10.1007/s11060-020-03688-1DOI Listing
March 2021

Pediatric Gliosarcoma With and Without Neurofibromatosis Type 1: A Whole-exome Comparison of 2 Patients.

J Pediatr Hematol Oncol 2020 Nov 23. Epub 2020 Nov 23.

Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

Gliosarcoma is rare among pediatric patients and among individuals with Neurofibromatosis Type 1 (NF1). Here we compare 2 pediatric gliosarcoma patients, one of whom has NF1. We performed whole-exome sequencing, methylation, and copy number analysis on tumor and blood for both patients. Whole-exome sequencing showed higher mutational burden in the tumor of the patient without NF1. Copy number analysis showed differences in chromosomal losses/gains between the tumors. Neither tumor showed O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. The NF1 patient survived without progression while the other expired. This is the first reported case of gliosarcoma in a child with NF1.
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http://dx.doi.org/10.1097/MPH.0000000000002020DOI Listing
November 2020

Characterizing benefit from temozolomide in MGMT promoter unmethylated and methylated glioblastoma: a systematic review and meta-analysis.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa082. Epub 2020 Oct 30.

Division of Neuro-Oncology, Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Background: The current standard of care for the management of patients with newly diagnosed glioblastoma (GBM) includes maximal safe resection followed by radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). While it is well established that TMZ has better efficacy in patients with promoter methylation, it remains an area of debate whether TMZ should be omitted when treating GBM patients with unmethylated .

Methods: We conducted a systematic review and meta-analysis to provide separate estimates of median overall survival (OS) and progression-free survival (PFS) for patients with methylated and unmethylated GBM treated with RT with or without TMZ. We searched multiple databases from inception to January 13, 2020.

Results: The median OS for patients with unmethylated GBM treated with RT/TMZ pooled from 5 phase III studies ( = 655) was 14.11 months (95% confidence interval [CI], 13.18-15.04) with a median PFS of 4.99 months (95% CI, 4.25-5.72). In contrast, the median OS for patients with methylated GBM pooled from 6 studies ( = 753) was 24.59 months (95% CI, 22.19-26.99) with a median PFS pooled from 7 studies ( = 805) of 9.51 months (95% CI, 7.41-11.61). There is a paucity of prospective data pertaining to OS/PFS in unmethylated patients treated with RT only and therefore a direct comparison was not possible.

Conclusions: This meta-analysis provides estimates of survival for patients with methylated or unmethylated GBM treated with RT/TMZ. Further research is needed to delineate whether TMZ should be withheld for patients with unmethylated GBM outside of the setting of clinical trials.
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http://dx.doi.org/10.1093/noajnl/vdaa082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596890PMC
October 2020

Radiotherapy and Late Effects.

Pediatr Clin North Am 2020 12;67(6):1051-1067

Department of Radiation Oncology, University of Rochester, Rochester, NY, USA; Department of Pediatrics, University of Rochester, Rochester, NY, USA; Department of Radiation Oncology, The Judy DiMarzo Cancer Survivorship Program, James P. Wilmot Cancer Institute, University of Rochester Medical Center, PO Box 647, Rochester, NY 14642, USA. Electronic address:

Advances in multimodality care for patients with pediatric cancer continues to improve long-term survival. The use of surgery, chemotherapy, and radiotherapy may lead to debilitating late effects in childhood cancer survivors. It is critically important to understand, mitigate, and screen for late effects to improve the quality of life in childhood cancer survivors. This review summarizes the use of radiotherapy in children, radiobiology of tissue injury, impact of age on late effects, important organ systems affected by radiotherapy during survivorship, and screening for radiotherapy late effects.
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http://dx.doi.org/10.1016/j.pcl.2020.08.001DOI Listing
December 2020

Improving the Pediatric Patient Experience During Radiation Therapy-A Children's Oncology Group Study.

Int J Radiat Oncol Biol Phys 2021 Feb 12;109(2):505-514. Epub 2020 Sep 12.

Department of Radiation Oncology, University of Colorado, Aurora, Colorado.

Purpose: Treatment with radiation therapy (RT) can cause anxiety and distress for pediatric patients and their families. Radiation oncology teams have developed strategies to reduce the negative psychological impact. This survey study aimed to characterize these methods.

Methods And Materials: A 37-item questionnaire was sent to all radiation oncology members of the Children's Oncology Group to explore strategies to improve the pediatric patient experience. The Wilcoxon rank-sum test was used to assess factors associated with use of anesthesia for older children.

Results: Surveys were completed by 106 individuals from 84/210 institutions (40%). Respondents included 89 radiation oncologists and 17 supportive staff. Sixty-one percent of centers treated ≤50 children per year. Respondents described heterogenous interventions. The median age at which most children no longer required anesthesia was 6 years (range: ≤3 years to ≥8 years). Routine anesthesia use at an older age was associated with physicians' lack of awareness of these strategies (P = .04) and <10 years of pediatric radiation oncology experience (P = .04). Fifty-two percent of respondents reported anesthesia use added >45 minutes in the radiation oncology department daily. Twenty-six percent of respondents planned to implement new strategies, with 65% focusing on video-based distraction therapy and/or augmented reality/virtual reality.

Conclusions: Many strategies are used to improve children's experience during RT. Lack of awareness of these interventions is a barrier to their implementation and is associated with increased anesthesia use. This study aims to disseminate these methods with the goal of raising awareness, facilitating implementation, and, ultimately, improving the experience of pediatric cancer patients and their caregivers.
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http://dx.doi.org/10.1016/j.ijrobp.2020.09.002DOI Listing
February 2021

In response to Bolukbasi et al.

Radiother Oncol 2020 Sep 8. Epub 2020 Sep 8.

Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, United States; Department of Neurological Surgery, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, United States. Electronic address:

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http://dx.doi.org/10.1016/j.radonc.2020.09.006DOI Listing
September 2020

Health-Related Quality of Life and Patient-Reported Outcomes in Radiation Oncology Clinical Trials.

Curr Treat Options Oncol 2020 Aug 29;21(11):87. Epub 2020 Aug 29.

Department of Radiation Oncology, University of Maryland Medical Center, 22 S. Greene Street, Baltimore, MD, 21201, USA.

Opinion Statement: The importance of assessing health-related quality of life (HRQoL) and patient-reported outcomes (PROs) is now well recognized as an essential measure when evaluating the effectiveness of new cancer therapies. Quality of life measures provide for a multi-dimensional understanding of the impact of cancer treatment on measures ranging from functional, psychological, and social aspects of a patient's health. Patient-reported outcomes provide for an assessment of physical and functional symptoms that are directly elicited from patients. Collection of PROs and HRQoL data has been shown to not only be feasible but also provide for reliable measures that correlate with established outcomes measures better than clinician-scored toxicities. The importance of HRQoL measures has been emphasized by both patients and clinicians, as well as policy makers and regulatory bodies. Given the benefits associated with measuring HRQoL and PROs in oncology clinical trials, it is increasingly important to establish methods to effectively incorporate PROs and HRQoL measures into routine clinical practice.
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http://dx.doi.org/10.1007/s11864-020-00782-4DOI Listing
August 2020

Multidisciplinary patient-centered management of brain metastases and future directions.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa034. Epub 2020 Mar 16.

Department of Radiation Oncology, Centre Hospitalier de l' Université de Montreal, Montreal, Quebec, Canada.

The incidence of brain metastasis is increasing as improvements in systemic therapy lead to increased survival. This provides new and challenging clinical decisions for patients who are trying to balance the risk of recurrence or progression with treatment-related side effects, and it requires appropriate management strategies from multidisciplinary teams. Improvements in prognostic assessment and systemic therapy with increasing activity in the brain allow for individualized care to better guide the use of local therapies and/or systemic therapy. Here, we review the current landscape of brain-directed therapy for the treatment of brain metastasis in the context of recent improved systemic treatment options. We also discuss emerging treatment strategies including targeted therapies for patients with actionable mutations, immunotherapy, modern whole-brain radiation therapy, radiosurgery, surgery, and clinical trials.
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http://dx.doi.org/10.1093/noajnl/vdaa034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415255PMC
March 2020

A nomogram to predict symptomatic epilepsy in patients with radiation-induced brain necrosis.

Neurology 2020 09 6;95(10):e1392-e1403. Epub 2020 Jul 6.

From the Department of Neurology Bioland Laboratory (X.H., X. Zhang, X.R., Y.L., H.L., J.J., J.C., X. Zhuo, X.P., J.L., Z.Y., Y.T.) and Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center (Y.T.), Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University; Guangdong Province Key Laboratory of Brain Function and Disease (Y.T.), Zhongshan School of Medicine, Sun Yat-Sen University; Department of Oncology (X.W.), The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China; Division of Radiation Oncology and Medical Sciences (M.L.K.C.), National Cancer Centre Singapore; Oncology Academic Programme (M.L.K.C.), Duke-NUS Medical School, Singapore; Department of Neurology (A.A.A.), Saint Andrew's State General Hospital of Patras, Greece; Neurological Clinic, Department of Experimental and Clinical Medicine (S.L.), Marche Polytechnic University, Italy; New York Proton Center (C.B.S.), New York; Thomas Jefferson University (J.G.), Philadelphia, PA; Departments of Radiation Oncology (J.D.P.) and Neurosurgery (J.D.P.), The James Cancer Hospital at The Ohio State University Comprehensive Cancer Center, Columbus; Sunnybrook Health Sciences Centre (E.C.), University of Toronto, Canada; and Radiation Oncology (P.D.B.), Mayo Clinic, Rochester, MN.

Objective: To develop and validate a nomogram to predict epilepsy in patients with radiation-induced brain necrosis (RN).

Methods: The nomogram was based on a retrospective analysis of 302 patients who were diagnosed with symptomatic RN from January 2005 to January 2016 in Sun Yat-sen Memorial Hospital using the Cox proportional hazards model. Discrimination of the nomogram was assessed by the concordance index ( index) and the calibration curve. The results were internally validated using bootstrap resampling and externally validated using 128 patients with RN from 2 additional hospitals.

Results: A total of 302 patients with RN with a median follow-up of 3.43 years (interquartile range 2.54-5.45) were included in the training cohort; 65 (21.5%) developed symptomatic epilepsy during follow-up. Seven variables remained significant predictors of epilepsy after multivariable analyses: MRI lesion volume, creatine phosphokinase, the maximum radiation dose to the temporal lobe, RN treatment, history of hypertension and/or diabetes, sex, and total cholesterol level. In the validation cohort, 28 out of 128 (21.9%) patients had epilepsy after RN within a median follow-up of 3.2 years. The nomogram showed comparable discrimination between the training and validation cohort (corrected index 0.76 [training] vs 0.72 [95% confidence interval 0.62-0.81; validation]).

Conclusion: Our study developed an easily applied nomogram for the prediction of RN-related epilepsy in a large RN cohort.

Classification Of Evidence: This study provides Class III evidence that a nomogram predicts post-RN epilepsy.
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http://dx.doi.org/10.1212/WNL.0000000000010190DOI Listing
September 2020

Brain extraction on MRI scans in presence of diffuse glioma: Multi-institutional performance evaluation of deep learning methods and robust modality-agnostic training.

Neuroimage 2020 10 27;220:117081. Epub 2020 Jun 27.

Center for Biomedical Image Computing and Analytics (CBICA), University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Brain extraction, or skull-stripping, is an essential pre-processing step in neuro-imaging that has a direct impact on the quality of all subsequent processing and analyses steps. It is also a key requirement in multi-institutional collaborations to comply with privacy-preserving regulations. Existing automated methods, including Deep Learning (DL) based methods that have obtained state-of-the-art results in recent years, have primarily targeted brain extraction without considering pathologically-affected brains. Accordingly, they perform sub-optimally when applied on magnetic resonance imaging (MRI) brain scans with apparent pathologies such as brain tumors. Furthermore, existing methods focus on using only T1-weighted MRI scans, even though multi-parametric MRI (mpMRI) scans are routinely acquired for patients with suspected brain tumors. In this study, we present a comprehensive performance evaluation of recent deep learning architectures for brain extraction, training models on mpMRI scans of pathologically-affected brains, with a particular focus on seeking a practically-applicable, low computational footprint approach, generalizable across multiple institutions, further facilitating collaborations. We identified a large retrospective multi-institutional dataset of n=3340 mpMRI brain tumor scans, with manually-inspected and approved gold-standard segmentations, acquired during standard clinical practice under varying acquisition protocols, both from private institutional data and public (TCIA) collections. To facilitate optimal utilization of rich mpMRI data, we further introduce and evaluate a novel ''modality-agnostic training'' technique that can be applied using any available modality, without need for model retraining. Our results indicate that the modality-agnostic approach obtains accurate results, providing a generic and practical tool for brain extraction on scans with brain tumors.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597856PMC
October 2020

Neuro-Oncology Practice Clinical Debate: stereotactic radiosurgery or fractionated stereotactic radiotherapy following surgical resection for brain metastasis.

Neurooncol Pract 2020 Jun 1;7(3):263-267. Epub 2019 Oct 1.

Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal, Quebec, Canada.

The treatment of resected brain metastasis has shifted away from the historical use of whole-brain radiotherapy (WBRT) toward adjuvant radiosurgery (stereotactic radiosurgery [SRS]) based on a recent prospective clinical trial demonstrating less cognitive decline with the use of SRS alone and equivalent survival as compared with WBRT. Whereas all level 1 evidence to date concerns single-fraction SRS for postoperative brain metastasis, there is emerging evidence that fractionated stereotactic radiotherapy (FSRT) may improve local control at the resected tumor bed. The lack of direct comparative data for SRS vs FSRT results in a diversity in clinical practice. In this article, Greenspoon and Roberge defend the use of SRS as the standard of care for resected brain metastasis, whereas Palmer and Brown argue for FSRT.
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http://dx.doi.org/10.1093/nop/npz047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274181PMC
June 2020

Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases: The FIRE-SCLC Cohort Study.

JAMA Oncol 2020 07;6(7):1028-1037

University of Colorado School of Medicine, Department of Radiation Oncology, Aurora.

Importance: Although stereotactic radiosurgery (SRS) is preferred for limited brain metastases from most histologies, whole-brain radiotherapy (WBRT) has remained the standard of care for patients with small cell lung cancer. Data on SRS are limited.

Objective: To characterize and compare first-line SRS outcomes (without prior WBRT or prophylactic cranial irradiation) with those of first-line WBRT.

Design, Setting, And Participants: FIRE-SCLC (First-line Radiosurgery for Small-Cell Lung Cancer) was a multicenter cohort study that analyzed SRS outcomes from 28 centers and a single-arm trial and compared these data with outcomes from a first-line WBRT cohort. Data were collected from October 26, 2017, to August 15, 2019, and analyzed from August 16, 2019, to November 6, 2019.

Interventions: SRS and WBRT for small cell lung cancer brain metastases.

Main Outcomes And Measures: Overall survival, time to central nervous system progression (TTCP), and central nervous system (CNS) progression-free survival (PFS) after SRS were evaluated and compared with WBRT outcomes, with adjustment for performance status, number of brain metastases, synchronicity, age, sex, and treatment year in multivariable and propensity score-matched analyses.

Results: In total, 710 patients (median [interquartile range] age, 68.5 [62-74] years; 531 men [74.8%]) who received SRS between 1994 and 2018 were analyzed. The median overall survival was 8.5 months, the median TTCP was 8.1 months, and the median CNS PFS was 5.0 months. When stratified by the number of brain metastases treated, the median overall survival was 11.0 months (95% CI, 8.9-13.4) for 1 lesion, 8.7 months (95% CI, 7.7-10.4) for 2 to 4 lesions, 8.0 months (95% CI, 6.4-9.6) for 5 to 10 lesions, and 5.5 months (95% CI, 4.3-7.6) for 11 or more lesions. Competing risk estimates were 7.0% (95% CI, 4.9%-9.2%) for local failures at 12 months and 41.6% (95% CI, 37.6%-45.7%) for distant CNS failures at 12 months. Leptomeningeal progression (46 of 425 patients [10.8%] with available data) and neurological mortality (80 of 647 patients [12.4%] with available data) were uncommon. On propensity score-matched analyses comparing SRS with WBRT, WBRT was associated with improved TTCP (hazard ratio, 0.38; 95% CI, 0.26-0.55; P < .001), without an improvement in overall survival (median, 6.5 months [95% CI, 5.5-8.0] for SRS vs 5.2 months [95% CI, 4.4-6.7] for WBRT; P = .003) or CNS PFS (median, 4.0 months for SRS vs 3.8 months for WBRT; P = .79). Multivariable analyses comparing SRS and WBRT, including subset analyses controlling for extracranial metastases and extracranial disease control status, demonstrated similar results.

Conclusions And Relevance: Results of this study suggest that the primary trade-offs associated with SRS without WBRT, including a shorter TTCP without a decrease in overall survival, are similar to those observed in settings in which SRS is already established.
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http://dx.doi.org/10.1001/jamaoncol.2020.1271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273318PMC
July 2020

Epidemiology of synchronous brain metastases.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa041. Epub 2020 Apr 24.

Department of Radiation Oncology, Penn State Cancer Institute, Hershey, Pennsylvania, USA.

Background: The objectives of this study were to characterize (1) epidemiology of brain metastases at the time of primary cancer diagnosis, (2) incidence and trends of synchronous brain metastases from 2010 to 2015, and (3) overall survival (OS) of patients with synchronous brain metastases.

Methods: A total of 42 047 patients with synchronous brain metastases from 2010 to 2015 were identified from the Surveillance, Epidemiology, and End Results database. Descriptive analysis was utilized to analyze demographics and incidence. The Kaplan-Meier method and a Cox proportional hazards model were utilized to evaluate potential prognostic factors for OS.

Results: The majority of patients were diagnosed from age older than 50 (91.9%). Common primary sites included lung (80%), melanoma (3.8%), breast (3.7%), and kidney/renal pelvis (3.0%). Among pediatric patients, common primaries included kidney/renal pelvis and melanomas. The incidence was roughly 7.3 persons/100 000. Synchronous brain metastases were associated with significantly poorer OS compared to extracranial metastases alone (hazard ratio [HR] =1.56; 95% CI: 1.54-1.58; < .001). Among patients with brain metastases, male gender (HR = 1.60 vs 1.52), age older than 65 years (HR = 1.60 vs 1.46), synchronous liver, bone, or lung metastases (HR = 1.61 vs 1.49), and earlier year of diagnosis (HR = 0.98 for each year following 2010) were associated with significantly poorer OS.

Conclusions: The vast majority of brain metastases are from lung primaries. Synchronous brain metastases are associated with poorer OS compared to extracranial metastases alone.
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http://dx.doi.org/10.1093/noajnl/vdaa041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182307PMC
April 2020

Linear accelerator-based radiosurgery is associated with lower incidence of radionecrosis compared with gamma knife for treatment of multiple brain metastases.

Radiother Oncol 2020 Jun 30;147:136-143. Epub 2020 Mar 30.

Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, USA; Department of Neurological Surgery, The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, USA. Electronic address:

Background: Gamma knife (GK) and linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) both offer excellent local control in the management of multiple brain metastases. The efficacy and toxicity of LINAC and GK SRS have not been directly compared in the modern era. We studied outcomes in patients treated with LINAC SRS and GK at two separate institutions.

Methods: We identified patients treated with either LINAC or GK who were treated to ≥2 lesions and had available follow up. LINAC patients were treated using single-isocenter multitarget technique. We used Cox regression, Fine and Gray competing risks regression, and nearest neighbor propensity score matching to account for confounders and imbalance between cohorts. Kaplan-Meier curves were used to estimate overall survival and rates of radionecrosis.

Results: We identified 391 patients who were treated in 537 courses to a total 2699 lesions (LINAC: 1014, GK: 1685). After propensity score matching, GK was associated with similar overall survival (HR = 0.86; 95% CI 0.59-1.24; p = 0.41) and higher rate of radionecrosis (HR = 3.83; 95% CI 1.66-8.84; p = 0.002) compared to LINAC. In a secondary propensity score matched analysis comparing radionecrosis in single-fraction LINAC and GK, GK remained associated with higher incidence of radionecrosis (HR = 4.42; 95% CI 1.28-15.29; p = 0.019).

Conclusions: In this multi-institutional study, we found similar overall survival with lower incidence of radionecrosis in patients treated with LINAC compared to GK SRS. These findings are hypothesis generating and should be validated in an independent cohort.
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http://dx.doi.org/10.1016/j.radonc.2020.03.024DOI Listing
June 2020

Initial experience with scalp sparing radiation with concurrent temozolomide and tumor treatment fields (SPARE) for patients with newly diagnosed glioblastoma.

J Neurooncol 2020 May 23;147(3):653-661. Epub 2020 Mar 23.

Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.

Introduction: Standard of care for glioblastoma includes concurrent chemoradiation and maintenance temozolomide with tumor treatment fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We report our initial experience evaluating toxicity and tolerability of scalp-sparing radiation with concurrent TTFields.

Methods: This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed glioblastoma were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent temozolomide (75 mg/m daily), and TTFields. Maintenance therapy included standard temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity for concurrent TTFields with chemoradiation in newly diagnosed glioblastoma.

Results: We report the first ten patients on the trial. Eight were male, and two were female, with median age 61 years (range 49 to 73 years). Median KPS was 90 (range 70-90). Median follow-up was 7.9 months (2.8 to 17.9 months). Nine (90%) patients with unmethylated MGMT promotor, and one with methylated. Median time from surgery to radiation was 33 days (28 to 49 days). All patients completed concurrent chemoradiation plus TTFields without radiation or TTFields treatment interruption or discontinuation. Scalp dose constraints were achieved for all patients, with mean dose having a median value of 7.7 Gy (range 4.9 to 13.2 Gy), D20cc median 22.6 Gy (17.7 to 36.8 Gy), and D30cc median 19.8 Gy (14.8 to 33.4 Gy). Average daily use during concurrent phase had median value of 83.5% and 77% for maintenance. There was no related ≥ Grade 3 toxicity. Skin toxicity (erythema, dermatitis, pruritus) was noted in 80% of patients, however, these were limited to Grade 1 or 2 events which resolved spontaneously or responded to topical medications. Eight patients (80%) had progression, with median PFS of 6.9 months (range 2.8 to 9.6 months).

Conclusions: Concurrent TTFields with scalp-sparing chemoradiation is a safe and feasible treatment option with limited toxicity. Future randomized prospective trial is warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.

Trial Registration: Clinicaltrials.gov Identifier NCT03477110.
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http://dx.doi.org/10.1007/s11060-020-03466-zDOI Listing
May 2020

Single fraction radiosurgery, fractionated radiosurgery, and conventional radiotherapy for spinal oligometastasis (SAFFRON): A systematic review and meta-analysis.

Radiother Oncol 2020 May 28;146:76-89. Epub 2020 Feb 28.

Department of Radiation Oncology, Mayo Clinic, Jacksonville, USA. Electronic address:

Background And Purpose: To perform a systematic review/meta-analysis of outcomes for patients with spinal metastases treated with stereotactic radiosurgery (SRS) (either single-fraction (SF-SRS) or multiple-fraction (MF-SRS)) or conventional radiotherapy (RT).

Materials And Methods: Thirty-seven studies were identified. Primary outcomes were 1-year local control (LC) and acute/late grade 3-5 toxicities (including vertebral compression fractures (VCF)). Weighted random effects meta-analyses using the DerSimonian and Laird methods and meta-regressions were conducted to characterize and compare effect sizes. Mixed effects regression models were used in dose analyses.

Results: A total of 3237 patients with 4911 lesions were included; 43.8%, 19.7%, and 36.5% of lesions received SF-SRS, MF-SRS, or RT, respectively. SF-SRS resulted in improved 1-year LC (92.9% (95% CI: 86.4-97.4%); p = 0.007) compared to RT (81.0% (95% CI: 69.2-90.5%)) with no difference between MF-SRS (82.1%; p = 0.86) and RT. On subgroup analysis of de novo metastases, superior 1-year LC following SF-SRS (95.5% (95% CI: 87.4-99.6%)) was maintained compared to RT (83.6% (95% CI: 70.4-93.5%); p = 0.007). A 4.7% increase in LC was noted for each 10 Gy increase in biologically effective dose (BED, assuming an alpha/beta = 10) with SRS (p < 0.001). No difference in toxicities were found between SF-SRS (0.4%), MF-SRS (0.2%), or RT (0%). Higher VCF rates were noted following SF-SRS (19.5%) vs. MF-SRS (9.6%; p = 0.039)) with no correlation between dose and VCF rates.

Conclusion: SF-SRS resulted in superior LC with a roughly 5% LC benefit for every 10 Gy increase in BED with higher VCF rates compared to MF-SRS. If LC is the goal of treatment, then SRS may be a preferred treatment modality. However, these results are hypothesis-generating, and prospective randomized clinical trials are indicated to definitively address the question of whether SRS results in improved LC compared to RT.
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http://dx.doi.org/10.1016/j.radonc.2020.01.030DOI Listing
May 2020

Outcomes after stereotactic radiosurgery for CNS lymphoma.

J Neurooncol 2020 Apr 27;147(2):465-476. Epub 2020 Feb 27.

Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, USA.

Background: The standard of care for CNS lymphoma typically includes high dose methotrexate followed by whole brain radiation therapy, but there is an increased risk of neurotoxicity with this regimen. In our institution, we offered stereotactic radiosurgery (SRS) for disease refractory to HD-MTX in a subset of patients. A search of the literature on this modality for CNS lymphoma was also conducted.

Methods: Medical records of six patients who received partial brain radiation therapy for persistent CNS lymphoma were reviewed. SRS was given via 1-3 fractions to doses of 21 or 24 Gy. PubMed, SCOPUS, and Cochrane Library databases were systematically searched for articles reporting on outcomes for CNS lymphoma treated with SRS.

Results: Six patients (eleven lesions) were treated with SRS for CNS lymphomas. Median follow up was 15.6 months (range 3.3-37.8). Median RT dose per lesion was 21 Gy and median time to progression was 12.7 months. Median overall survival was not reached. Four patients had distant intracranial failure with two developing local recurrence. The search strategy yielded 16 studies of which only one was prospective and included a control group. 183 out of 256 evaluated lesions (69%) responded completely to treatment and 13 of 204 patients (6%) recurred within the treatment area at last follow-up. Overall, the treatment was well tolerated.

Conclusion: SRS may provide favorable local control in patients with refractory CNS lymphomas. A prospective trial is warranted to validate the efficacy of such an approach.
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http://dx.doi.org/10.1007/s11060-020-03444-5DOI Listing
April 2020

Single-Isocenter Multitarget Stereotactic Radiosurgery Is Safe and Effective in the Treatment of Multiple Brain Metastases.

Adv Radiat Oncol 2020 Jan-Feb;5(1):70-76. Epub 2019 Sep 16.

Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus Ohio.

Purpose: Multiple studies have reported favorable outcomes for stereotactic radiosurgery (SRS) in the treatment of limited brain metastases. An obstacle of SRS in the management of numerous metastases is the longer treatment time using traditional radiosurgery. Single-isocenter multitarget (SIMT) SRS is a novel technique that permits rapid therapy delivery to multiple metastases. There is a lack of clinical evidence regarding its efficacy and safety. We report the outcomes of patients treated with this technique.

Methods And Materials: We reviewed the records of patients with intact or resected brain metastases treated with SRS in 1 to 5 fractions using SIMT technique at our institution, with at least 1 available follow-up brain magnetic resonance imaging. Survival, disease control, and toxicity were evaluated using Cox regression, logistic regression, and Kaplan-Meier analysis.

Results: We identified 173 patients with 1014 brain metastases. Median follow up was 12.7 months. Median beam-on time was 4.1 minutes. The median dose to the brain was 219.4 cGy. Median overall survival and freedom from intracranial progression were 13.2 and 6.3 months, respectively. Overall survival did not differ between patients treated with greater than or less than 4 lesions (hazard ratio, 1.03; 95% confidence interval 0.66-1.61;  = .91). Actuarial 1- and 2-year local control were 99.0% and 95.1%, respectively. Rates of grade 2 and grade 3 or higher radionecrosis were 1.4% and 0.9%, respectively.

Conclusions: SIMT radiosurgery delivered in 1 to 5 fractions offers excellent local control and acceptable toxicity in the treatment of multiple intact and postoperative brain metastases. This technique should be evaluated prospectively.
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http://dx.doi.org/10.1016/j.adro.2019.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004936PMC
September 2019

Rapid Early Tumor Progression is Prognostic in Glioblastoma Patients.

Am J Clin Oncol 2019 05;42(5):481-486

Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.

Objectives: Determine the prognostic significance of rapid early tumor progression before radiation and chemotherapy for glioblastoma patients.

Methods: A retrospective review of glioblastoma patients was performed. Rapid early progression (REP) was defined as new enhancing tumor or >25% increase in enhancement before radiotherapy. The pre/postoperative magnetic resonance imaging was compared with the preradiation magnetic resonance imaging to determine REP. A blinded review of imaging was performed. Kaplan-Meier curves were generated to compare progression-free and overall survival (OS). Univariate analysis was performed using the log-rank test for categorical variables and Cox proportional hazards for continuous variables. Multivariable logistic regression was performed to assess factors related to early progression and Cox proportional hazards model was used for multivariate analysis of OS.

Results: Eighty-seven patients met entry criteria. A total of 52% of patients developed REP. The OS in the REP group was 11.5 months (95% confidence interval [CI]: 7.4-17.6) and 20.1 months (95% CI: 17.8-26.1) without REP (P=0.013). On multivariate analysis including significant prognostic factors, presence of REP was found to increase the risk of death (hazard ratio: 2.104, 95% CI: 1.235-3.583, P=0.006). A total of 74% of patients recurred in the site of REP.

Conclusions: REP was common and independently predicted for a worse OS. Integrating REP with MGMT promotor methylation improved prognostic assessment. The site of REP was a common site of tumor progression. Our findings are hypothesis generating and may indicate a particular subset of glioblastoma patients who are resistant to current standard of care therapy. Further study to determine other molecular features of this group are underway.
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http://dx.doi.org/10.1097/COC.0000000000000537DOI Listing
May 2019

Treatment of Glioblastoma (GBM) with the Addition of Tumor-Treating Fields (TTF): A Review.

Cancers (Basel) 2019 Feb 2;11(2). Epub 2019 Feb 2.

Department of Neuro-Oncology, The Ohio State University, Columbus, OH 43210, USA.

Glioblastoma (GBM) is the most common primary brain tumor. Despite aggressive treatment, GBM almost always recurs. The current standard-of-care for treatment of newly diagnosed GBM has remained relatively unchanged since 2005: maximal safe resection followed by concomitant chemoradiation (CRT) with temozolomide (TMZ), and subsequent adjuvant TMZ. In 2011, the first-generation tumor treating fields (TTF) device, known at the time as the NovoTTF-100A System (renamed Optune), was approved by the Food and Drug Administration (FDA) for treatment of recurrent GBM. The TTF device was subsequently approved as an adjuvant therapy for newly-diagnosed GBM in 2015. The following is a review of the TTF device, including evidence supporting its use and limitations.
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http://dx.doi.org/10.3390/cancers11020174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406491PMC
February 2019

Germinoma Involving the Retina: An Unusual Presentation of Recurrent Intracranial Mixed Germ Cell Tumor.

World Neurosurg 2019 Jan 7. Epub 2019 Jan 7.

The Department of Pathology & Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH 43205 and The Department of Pathology, The Ohio State University, College of Medicine, Columbus, OH 43210 USA.

Background: We report a patient with primary central nervous system mixed malignant germ cell tumor (GCT) who presented with recurrent malignant germinomatous infiltration of the retina.

Case Description: A ten-year-old girl initially presented with a large suprasellar mixed malignant GCT with a near-complete response after initial induction chemotherapy and irradiation. Three and half years after initial therapy, she presented with progressively worsening vision in her left eye. Magnetic resonance imaging showed infiltrative changes within the left optic nerve but no discrete mass. Serum and cerebrospinal fluid (CSF) tumor markers were not elevated and CSF cytology was negative. Left optic nerve biopsy confirmed the presence of mature teratoma and pure germinoma components. She was treated with gross-total resection of the left eye and optic nerve and chemotherapy. Histopathologic evaluation of the optic nerve showed only mature teratoma elements but with pure germinoma cells infiltrating the inner layers of the retina.

Conclusions: Loco-regional extension of suprasellar GCT to the optic nerve is not uncommon; however, infiltration of the tumor into the retina is not reported in the literature. Early detection of optic pathway involvement and proper delineation of the irradiation field may prevent GCT infiltration of the retina with subsequent vision loss.
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http://dx.doi.org/10.1016/j.wneu.2018.12.143DOI Listing
January 2019

Bevacizumab and re-irradiation for recurrent high grade gliomas: does sequence matter?

J Neurooncol 2018 Dec 4;140(3):623-628. Epub 2018 Sep 4.

Department of Radiation Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Purpose/objectives: We report the outcomes of the largest cohort to date of patients receiving both bevacizumab (BEV) and fractionated stereotactic radiotherapy (FSRT) for progressive or recurrent high grade glioma (HGG). Furthermore, the sequence of these two treatment regimens was analyzed to determine an optimal treatment paradigm for recurrent HGG.

Materials/methods: After Institutional Review Board approval, patients with pathologically confirmed WHO grade III anaplastic astrocytoma (AA) or IV glioblastoma multiforme (GBM) glioma who subsequently underwent re-irradiation at recurrence with FSRT were retrospectively reviewed. Patients from this group who had received BEV were also identified. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were analyzed as study endpoints. Date of recurrence was defined as the date of radiographic evidence of progressive/recurrent disease. Kaplan-Meier curves were generated utilizing a log-rank test with a p-value ≤ 0.05 considered significant to compare treatment sequences in terms of survival outcomes.

Results: A total of 118 patients with recurrent/progressive HGG (GBM = 87, AA = 31) had received both BEV and FSRT. Patient characteristics were as follows: median KPS at recurrence was 80 (range 50-100); median age at recurrence was 57 years; median time to radiographic recurrence/progression was 10.8 months (mo) and 33.1% of patients had surgery for recurrence. The median time from the start of BEV to FSRT was 6.4 months and from FSRT to the start of BEV was 5.1 months. For the entire cohort, median overall survival (OS) was 26.7 months and median survival time (MST) from recurrence was 13.8 months (24.4 months and 11.9 months for GBM only). In patients that received BEV prior to FSRT (n = 50), median OS and MST from recurrence were 25.2 and 13.3 months respectively. In patients receiving FSRT first (n = 56), median OS and MST from recurrence were 28.8 months and 13.9 months, respectively. Sequencing of BEV and FSRT at recurrence was not significantly associated with OS (p = 0.08) or median survival from recurrence (p = 0.75).

Conclusions: The combination of FSRT and BEV for recurrent/progressive HGG provides promising results in terms of overall survival and survival from recurrence. Combining these treatment modalities appears to improve upon the historic outcomes of either treatment alone. The outcomes data from this study support the ongoing RTOG trial exploring the combination of BEV and FSRT for recurrent HGG.
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http://dx.doi.org/10.1007/s11060-018-2989-zDOI Listing
December 2018

A consensus on the role of osimertinib in non-small cell lung cancer from the AME Lung Cancer Collaborative Group.

J Thorac Dis 2018 Jul;10(7):3909-3921

Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.

The first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have brought substantial clinical benefit to patients with advanced non-small cell lung cancer (NSCLC) and sensitizing mutation. However, acquired resistance is inevitable since the vast majority of patients experience disease relapse within ~1-2 years. Osimertinib is a novel irreversible, covalent third-generation EGFR-TKI and potent inhibitor of T790M mutation, the most common mechanism of acquired resistance to first-generation EGFR-TKIs. Several trials have consistently demonstrated the superior clinical activity and safety of osimertinib in patients with advanced NSCLC and acquired T790M mutation after treatment with a first-generation EGFR-TKI. Recently, the efficacy of osimertinib in a first-line setting was demonstrated to be clearly superior to standard-first line treatment in patients with -mutant NSCLC regardless of T790M mutation status. Nevertheless, this advance, several unresolved issues of osimertinib should be emphasized including the molecular mechanisms of acquired resistance to osimertinib, the feasibility of testing T790M mutation from plasma circulating tumor DNA, its efficacy to patients with central nervous system (CNS) metastases or exon 20 mutations, its combination with other therapeutic strategies such as immune checkpoint inhibitors and its role in adjuvant therapy.
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http://dx.doi.org/10.21037/jtd.2018.07.61DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106007PMC
July 2018

Treatment recommendations for elderly patients with newly diagnosed glioblastoma lack worldwide consensus.

J Neurooncol 2018 Nov 7;140(2):421-426. Epub 2018 Aug 7.

Department of Radiation Oncology, Sidney Kimmel Medical College and Cancer Center at Thomas Jefferson University, Philadelphia, PA, USA.

Background: Glioblastoma predominantly occurs in the 6th and 7th decades of life. The optimal treatment paradigm for elderly patients is not well established. We sampled current worldwide management strategies for elderly patients with newly diagnosed glioblastoma.

Methods: A web-based survey was developed and distributed to 168 radiation oncologists, neuro-oncologists and neurosurgeons identified through the United Council for Neurologic Subspecialties and the CNS committees for North American, European and Asian Organizations. Questions addressed treatment recommendations in order to determine whether management consensus exists in this patient subset.

Results: There were 68 (40%) respondents. Across respondents, the most important factors directing treatment were KPS (94%) and MGMT methylation status (71%). Only 37% of respondents strictly factor in age when making treatment recommendations with 59% defining elderly as greater than 70 years-old. The most common treatment recommendations for MGMT-methylated elderly patients with KPS > 70 were as follows: standard chemoRT (49%), short course chemoRT (39%), and temozolomide alone (30%). The most common treatment recommendations for MGMT-unmethylated patients with KPS > 70 were as follows: short course RT alone (51%), standard chemoRT (38%), and short course chemoRT (28%). Treatment recommendations for patients with KPS < 50 were short course RT alone (40%), best supportive care (57%), or TMZ alone (17%). Individuals practicing in North America were significantly more likely to recommend standard chemoradiation for patients compared to their European counterparts.

Conclusion: Worldwide treatment recommendations for elderly patients with newly diagnosed GBM vary widely. Further randomized studies are needed to elucidate the optimal treatment strategy for this subset of patients.
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http://dx.doi.org/10.1007/s11060-018-2969-3DOI Listing
November 2018

In Reply to McClelland III and Jaboin.

Int J Radiat Oncol Biol Phys 2018 07 20;101(4):1000-1002. Epub 2018 Jun 20.

Department of Radiation Oncology, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1016/j.ijrobp.2018.04.019DOI Listing
July 2018