Jay S Loeffler

Harvard University, Cambridge, Massachusetts, United States

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Publications (394)2049.16 Total impact

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    ABSTRACT: Background: Risk stratification of meningiomas by histopathological grade alone does not reliably predict which patients will progress/recur after treatment. We sought to determine whether preoperative imaging and clinical characteristics could predict histopathological grade and/or improve prognostication of progression/recurrence (P/R). Methods: We retrospectively reviewed preoperative MR and CT imaging features of 144 patients divided into low-grade (2007 WHO grade I; n = 118) and high-grade (2007 WHO grades II/III; n = 26) groups that underwent surgery between 2002 and 2013 (median follow-up of 49 months). Results: Multivariate analysis demonstrated that the risk factors most strongly associated with high-grade histopathology were male sex, low apparent diffusion coefficient (ADC), absent calcification, and high peritumoral edema. Remarkably, multivariate Cox proportional hazards analysis demonstrated that, in combination with extent of resection, ADC outperformed WHO histopathological grade for predicting which patients will suffer P/R after initial treatment. Stratification of patients into 3 risk groups based on non-Simpson grade I resection and low ADC as risk factors correlated with the likelihood of P/R (P < .001). The high-risk group (2 risk factors; n = 39) had a 45% cumulative incidence of P/R, whereas the low-risk group (0 risk factors; n = 31) had no P/R events at 5 years after treatment. Independent of histopathological grade, high-risk patients who received adjuvant radiotherapy had a lower 5-year crude rate of P/R than those without (17% vs 59%; P = .04). Conclusions: Patients with non-Simpson grade I resection and low ADC meningiomas are at significantly increased risk of P/R and may benefit from adjuvant radiotherapy and/or additional surgery.
    Full-text · Article · Nov 2015 · Neuro-Oncology
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    Full-text · Article · Nov 2015
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    ABSTRACT: To understand neurocognitive effects of proton radiation therapy (PRT) in patients with low-grade glioma, we evaluated 20 patients who received this therapy prospectively and over 5 years with a comprehensive neuropsychological battery. 20 patients were evaluated at baseline and at yearly intervals for up to 5 years with a battery of neuropsychological measures that assessed intellectual, attention, executive, visuospatial and memory functions as well as mood and functional status. We evaluated change in cognitive functioning over time. We analyzed the relationship between cognitive performance and tumor location and also examined whether patients' performance differed from that reported in a study of normative practice effects. Overall, patients exhibited stability in cognitive functioning. Tumor location played a role in performance; those with tumors in the left hemisphere versus in the right hemisphere were more impaired at baseline on verbal measures (p < .05). However, we found greater improvement in verbal memory over time in patients with left than with right hemisphere tumors (p < .05). Results of our study, the first to investigate, in depth, neurocognitive effects of PRT in adults with low-grade gliomas, are promising. We hypothesize that the conformal advantage of PRT may contribute to preservation of cognitive functioning, although larger sample sizes and a longer period of study are required. Our study also highlights the need to consider normative practice effects when studying neurocognitive functioning in response to treatment over time, and the need to utilize comprehensive neuropsychological batteries given our findings that differentiate patients with left and right hemisphere tumors.
    No preview · Article · Oct 2015 · Journal of Neuro-Oncology
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    Full-text · Article · Oct 2015 · Acta Neuropathologica
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    ABSTRACT: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System (CNS) Cancers provide interdisciplinary recommendations for managing adult CNS cancers. Primary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. These NCCN Guidelines Insights summarize the NCCN CNS Cancers Panel's discussion and highlight notable changes in the 2015 update. This article outlines the data and provides insight into panel decisions regarding adjuvant radiation and chemotherapy treatment options for high-risk newly diagnosed low-grade gliomas and glioblastomas. Additionally, it describes the panel's assessment of new data and the ongoing debate regarding the use of alternating electric field therapy for high-grade gliomas. © National Comprehensive Cancer Network, Inc. 2015, All rights reserved.
    Full-text · Article · Oct 2015 · Journal of the National Comprehensive Cancer Network: JNCCN
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    ABSTRACT: OBJECT World Health Organization (WHO) Grade I (benign) meningiomas with atypical features may behave more aggressively than similarly graded tumors without atypical features. Here, the prognostic significance of atypical features in benign meningiomas was determined. METHODS Data from patients diagnosed with WHO Grade I benign meningiomas per the 2007 WHO criteria and who underwent surgery between 2002 and 2012 were retrospectively reviewed. Patients were stratified by the absence or presence of 1 to 2 atypical features with review of the clinical and histological factors. RESULTS A total of 148 patients met the inclusion criteria (n = 77 with atypia; n = 71 without atypia). The median follow-up duration after pathological diagnosis was 37.5 months. Thirty patients had progression/recurrence (P/R) after initial treatment, and 22 (73%) of 30 patients with P/R had 1-2 atypical features. The presence of atypical features was significantly associated with P/R (p = 0.03) and independent of the MIB-1 labeling index. The 1-year and 5-year actuarial rates of P/R were 9.6% versus 1.4% and 30.8% versus 13.8% fortumors with and without atypical features, respectively. Higher Simpson grade resection (II-IV vs I) was associated with the increased risk of P/R (p < 0.001). Stratification of patients into low-risk (Simpson Grade I), intermediate-risk (Simpson Grade II-IV with no atypical features), and high-risk groups (Simpson Grade II-IV with atypical features) was significantly correlated with increased risk of P/R (p < 0.001). CONCLUSIONS Patients with benign meningiomas with atypical features and those undergoing Simpson Grade II-IV resection are at significantly increased risk of P/R. Patients with these features may benefit from the consideration of additional surgery and/or radiation therapy.
    No preview · Article · Aug 2015 · Journal of Neurosurgery
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    ABSTRACT: Recurrent aggressive falcine meningiomas are uncommon tumors that recur despite receiving extensive surgery and radiation therapy (RT). We have utilized brachytherapy as a salvage treatment in two such patients with a unique implantation technique. Both patients had recurrence of WHO Grade II falcine meningiomas despite multiple prior surgical and RT treatments. Radioactive I-125 seeds were made into strands and sutured into a mesh implant, with 1 cm spacing, in a size appropriate to cover the cavity and region of susceptible falcine dura. Following resection the vicryl mesh was implanted and fixed to the margins of the falx. Implantation in this interhemispheric space provides good dose conformality with targeting of at-risk tissue and minimal radiation exposure to normal neural tissues. The patients are recurrence free 31 and 10 months after brachytherapy treatment. Brachytherapy was an effective salvage treatment for the recurrent aggressive falcine meningiomas in our two patients.
    No preview · Article · Aug 2015 · Journal of Neuro-Oncology
  • Kevin S. Oh · Jay S. Loeffler

    No preview · Article · Jul 2015
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    ABSTRACT: We present a unique patient with delayed onset, acute demyelination that occurred distant to the effective field of radiation after proton beam radiotherapy for an optic nerve sheath meningioma. The use of stereotactic radiotherapy as an effective treatment modality for some brain tumors is increasing, given technological advances which allow for improved targeting precision. Proton beam radiotherapy improves the precision further by reducing unnecessary radiation to surrounding tissues. A 42-year-old woman was diagnosed with an optic nerve sheath meningioma after initially presenting with vision loss. After biopsy of the lesion to establish diagnosis, the patient underwent stereotactic proton beam radiotherapy to a small area localized to the tumor. Subsequently, the patient developed a large enhancing mass-like lesion with edema in a region outside of the effective radiation field in the ipsilateral frontal lobe. Given imaging features suggestive of possible primary malignant brain tumor, biopsy of this new lesion was performed and revealed an acute demyelinating process. This patient illustrates the importance of considering delayed onset acute demyelination in the differential diagnosis of enhancing lesions in patients previously treated with radiation. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Apr 2015 · Journal of Clinical Neuroscience
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    ABSTRACT: We perform a systematic review of repeat radiosurgery for cerebral arteriovenous malformations (AVM) with an emphasis on lesion obliteration rates and complications. Radiosurgery is an accepted treatment modality for AVM located in eloquent cortex or deep brain structures. For residual or persistent lesions, repeat radiosurgery can be considered if sufficient time has passed to allow for a full appreciation of treatment effects, usually at least 3years. A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. References for this review were identified by searches of MEDLINE, Web of Science and Google Scholar databases. A total of 14 studies comprising 733 patients met the review criteria and were included. For series that reported target dose at both first and repeat treatments, the weighted means were 19.42Gy and 19.06Gy, respectively. The mean and median obliteration rate for the repeat radiosurgery treatments were 61% (95% confidence interval 51.9-71.7%) and 61.5%, respectively. The median follow up following radiosurgery ranged from 19.5 to 80months. Time to complete obliteration after the repeat treatment ranged from 21 to 40.8months. The most common complications of repeat radiosurgery for AVM included hemorrhage (7.6%) and radiation-induced changes (7.4%). Repeat radiosurgery can be used to treat incompletely obliterated AVM with an obliteration rate of 61%. Complications are related to treatment effect latency (hemorrhage risk) as well as radiation-induced changes. Repeat radiosurgery can be performed at 3 years following the initial treatment, allowing for full realization of effects from the initial treatment prior to commencing therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Apr 2015 · Journal of Clinical Neuroscience

  • No preview · Article · Apr 2015

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  • No preview · Article · Apr 2015
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    ABSTRACT: Treatment of glioblastoma (GBM), the most common primary malignant brain tumor in adults, remains a significant unmet need in oncology. Historically, cytotoxic treatments provided little durable benefit, and tumors recurred within several months. This has spurred a substantial research effort to establish more effective therapies for both newly diagnosed and recurrent GBM. In this context, antiangiogenic therapy emerged as a promising treatment strategy because GBMs are highly vascular tumors. In particular, GBMs overexpress vascular endothelial growth factor (VEGF), a proangiogenic cytokine. Indeed, many studies have demonstrated promising radiographic response rates, delayed tumor progression, and a relatively safe profile for anti-VEGF agents. However, randomized phase III trials conducted to date have failed to show an overall survival benefit for antiangiogenic agents alone or in combination with chemoradiotherapy. These results indicate that antiangiogenic agents may not be beneficial in unselected populations of patients with GBM. Unfortunately, biomarker development has lagged behind in the process of drug development, and no validated biomarker exists for patient stratification. However, hypothesis-generating data from phase II trials that reveal an association between increased perfusion and/or oxygenation (ie, consequences of vascular normalization) and survival suggest that early imaging biomarkers could help identify the subset of patients who most likely will benefit from anti-VEGF agents. In this article, we discuss the lessons learned from the trials conducted to date and how we could potentially use recent advances in GBM biology and imaging to improve outcomes of patients with GBM who receive antiangiogenic therapy. © 2015 by American Society of Clinical Oncology.
    No preview · Article · Feb 2015 · Journal of Clinical Oncology
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    ABSTRACT: In this prospective study, the authors evaluated potential treatment toxicity and progression-free survival in patients with low-grade glioma who received treatment with proton radiation therapy. Twenty patients with World Health Organization grade 2 glioma who were eligible for radiation therapy were enrolled in a prospective, single-arm trial of proton therapy. The patients received proton therapy at a dose of 54 Gy (relative biological effectiveness) in 30 fractions. Comprehensive baseline and regular post-treatment evaluations of neurocognitive function, neuroendocrine function, and quality of life (QOL) were performed. All 20 patients (median age, 37.5 years) tolerated treatment without difficulty. The median follow-up after proton therapy was 5.1 years. At baseline, intellectual functioning was within the normal range for the group and remained stable over time. Visuospatial ability, attention/working memory, and executive functioning also were within normal limits; however, baseline neurocognitive impairments were observed in language, memory, and processing speed in 8 patients. There was no overall decline in cognitive functioning over time. New endocrine dysfunction was detected in 6 patients, and all but 1 had received direct irradiation of the hypothalamic-pituitary axis. QOL assessment revealed no changes over time. The progression-free survival rate at 3 years was 85%, but it dropped to 40% at 5 years. Patients with low-grade glioma tolerate proton therapy well, and a subset develops neuroendocrine deficiencies. There is no evidence for overall decline in cognitive function or QOL. Cancer 2015. © 2015 American Cancer Society. © 2014 American Cancer Society.
    No preview · Article · Jan 2015 · Cancer

  • No preview · Article · Nov 2014 · International journal of radiation oncology, biology, physics
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    ABSTRACT: BACKGROUND: This is a prospective study to evaluate potential treatment toxicity and progression free survival (PFS) of low grade glioma patients treated with proton radiation therapy. METHODS: Twenty WHO grade II glioma patients indicated for radiation therapy (8 new high risk diagnoses; 12 recurrent/progressive disease) were enrolled on a prospective single arm trial of proton therapy receiving 54 Gy(RBE) in 30 fractions. Comprehensive baseline and regular post treatment evaluations of neurocognitive function, neuroendocrine function, and quality of life (QOL) were performed. RESULTS: All 20 patients (median age 37.5 years) tolerated treatment without difficulty. Median follow up after proton therapy was 5.1 years. Baseline level of intellectual functioning on a standardized IQ measure was within the normal range for the group and remained stable over time. Performances in the cognitive domains of visuospatial ability, language function, attention/working memory, and processing speed were also in the normal range at baseline and did not decline over time. New endocrine dysfunction was detected in six patients and all but one had direct irradiation of the hypothalamic-pituitary axis. QOL assessment showed no change over time with the extended follow up. PFS at 3 years was 85% and at 5 years was 40%. CONCLUSIONS: Low grade glioma patients tolerate proton therapy well and a subset develops neuroendocrine deficiencies. There was no evidence for decline in cognitive function or QOL which may be partially attributable to reduced radiation dose to the normal brain by use of proton therapy. PFS was similar to that of photon based therapy.
    No preview · Article · Nov 2014 · Neuro-Oncology
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    ABSTRACT: Purpose/Objective(s) This study evaluated the efficacy and toxicity of proton therapy for functional pituitary adenomas (FPAs). Methods and Materials We analyzed 165 patients with FPAs who were treated at a single institution with proton therapy between 1992 and 2012 and had at least 6 months of follow-up. All but 3 patients underwent prior resection, and 14 received prior photon irradiation. Proton stereotactic radiosurgery was used for 92% of patients, with a median dose of 20 Gy(RBE). The remainder received fractionated stereotactic proton therapy. Time to biochemical complete response (CR, defined as ≥3 months of normal laboratory values with no medical treatment), local control, and adverse effects are reported. Results With a median follow-up time of 4.3 years (range, 0.5-20.6 years) for 144 evaluable patients, the actuarial 3-year CR rate and the median time to CR were 54% and 32 months among 74 patients with Cushing disease (CD), 63% and 27 months among 8 patients with Nelson syndrome (NS), 26% and 62 months among 50 patients with acromegaly, and 22% and 60 months among 9 patients with prolactinomas, respectively. One of 3 patients with thyroid stimulating hormone—secreting tumors achieved CR. Actuarial time to CR was significantly shorter for corticotroph FPAs (CD/NS) compared with other subtypes (P=.001). At a median imaging follow-up time of 43 months, tumor control was 98% among 140 patients. The actuarial 3-year and 5-year rates of development of new hypopituitarism were 45% and 62%, and the median time to deficiency was 40 months. Larger radiosurgery target volume as a continuous variable was a significant predictor of hypopituitarism (adjusted hazard ratio 1.3, P=.004). Four patients had new-onset postradiosurgery seizures suspected to be related to generously defined target volumes. There were no radiation-induced tumors. Conclusions Proton irradiation is an effective treatment for FPAs, and hypopituitarism remains the primary adverse effect.
    Full-text · Article · Nov 2014 · International journal of radiation oncology, biology, physics
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    ABSTRACT: The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases.
    Full-text · Article · Nov 2014 · Journal of the National Comprehensive Cancer Network: JNCCN
  • Itai Pashtan · Kevin S Oh · Jay S Loeffler
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    ABSTRACT: Radiation therapy in the form of fractionated treatment or radiosurgery has an important role in the management of pituitary adenomas. Radiation is a reliable way of gaining local control for radiographically progressing pituitary adenomas. For functioning adenomas that are biochemically recurrent or persistent, radiation therapy is less consistent in offering biochemical normalization and often requires a latency period of years or decades. The decision of when to use radiation therapy is a delicate balance between its benefits and late sequelae, especially in the context of benign disease. Recent technological advances in radiation oncology hold the potential to minimize dose to uninvolved normal tissue and therefore reduce the risk of toxicity.
    No preview · Article · Sep 2014 · Handbook of Clinical Neurology

Publication Stats

18k Citations
2,049.16 Total Impact Points


  • 1993-2015
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1991-2015
    • Massachusetts General Hospital
      • • Department of Radiation Oncology
      • • Department of Neurology
      Boston, Massachusetts, United States
  • 1985-2015
    • Harvard Medical School
      • Department of Radiation Oncology
      Boston, Massachusetts, United States
  • 2003-2010
    • National Institutes of Health
      • Division of Cancer Epidemiology and Genetics
      Bethesda, MD, United States
  • 1985-2010
    • Dana-Farber Cancer Institute
      • Center for Neuro-Oncology
      Boston, Massachusetts, United States
  • 2009
    • GSI Helmholtzzentrum für Schwerionenforschung
      Darmstadt, Hesse, Germany
  • 2004
    • Massachusetts Eye and Ear Infirmary
      • Department of Otolaryngology
      Boston, Massachusetts, United States
  • 2001
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      Bethesda, MD, United States
  • 2000
    • Washington University in St. Louis
      San Luis, Missouri, United States
    • University of Colorado
      Denver, Colorado, United States
    • Henry Ford Hospital
      Detroit, Michigan, United States
  • 1990-2000
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Department of Surgery
      • • Department of Radiation Oncology
      Boston, Massachusetts, United States
  • 1998
    • Jefferson College
      Хиллсборо, Missouri, United States
  • 1997
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 1989-1997
    • Boston Children's Hospital
      • Department of Radiology
      Boston, Massachusetts, United States
  • 1996
    • University of California, San Francisco
      San Francisco, California, United States
  • 1986
    • Radiation Therapy and Cancer Institute
      San Juan, Texas, United States