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The American Radium Society (ARS) Central Nervous System (CNS) committee reviewed literature on epidermal growth factor receptor mutated (EGFRm) and ALK-fusion (ALK+) tyrosine kinase inhibitors (TKIs) for the treatment of brain metastases (BrMs) from non-small cell lung cancers (NSCLC) to generate appropriate use guidelines addressing use of TKIs in conjunction with or in lieu of radiotherapy (RT). The panel developed three key questions to guide systematic review: can radiotherapy be deferred in patients receiving EGFR or ALK TKIs at (1) diagnosis or (2) recurrence? Should TKI be administered concurrently with RT (3)? Two literature searches were performed (May 2019 and December 2023). The panel developed 8 model cases and voted on treatment options using a 9-point scale, with 1-3, 4-6 and 7-9 corresponding to usually not appropriate, may be appropriate, and usually appropriate (respectively), per the UCLA/RAND Appropriateness Method. Consensus was achieved in only 4 treatment scenarios, all consistent with existing ARS-AUC guidelines for multiple BrM. The panel did not reach consensus that RT can be appropriately deferred in patients with BrM receiving CNS penetrant ALK or EGFR TKIs, though median scores indicated deferral may be appropriate under most circumstances. Whole brain RT with concurrent TKI generated broad disagreement except in cases with 2-4 BrM, where it was considered usually not appropriate. We identified no definitive studies dictating optimal sequencing of TKIs and RT for EGFRm and ALK+ BrM. Until such studies are completed, the committee hopes these cases guide decision- making in this complex clinical space., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Purpose: To develop and compare tumor-control probability (TCP) models for single-fraction stereotactic radiosurgery (SRS) for brain metastasis (BMs) with and without retreatment., Methods and Materials: We developed three different schemas to model TCP of BMs treated with linear accelerator-based SRS. Dose to 99% of each planning target volume (PTV D 99 ) and 6-month local control were fit using linear-quadratic-linear (LQ-L) models based on equivalent-dose conversions in 2 Gy (EQD2). The M1 schema had separate LQ-L TCP models for initial dose (M1-initial) and retreatment dose (M1-retreat), and the M2 schema had an LQ-L model using the sum of 50% of the initial SRS dose plus the retreatment SRS dose. The M1-initial and M1-retreat schema modeled local control after first SRS to 48 lesions (patients = 22) and second SRS to 46 lesions (patients = 21). The M0 schema included a whole data set of 349 lesions (patients = 136) receiving first SRS (no retreatment and M1-initial)., Results: LQ-L models fitted the data well (χ 2  = 0.059-0.525 and P = 0.999-1.000). For M0 and M1-retreat, the fitted models EQD2 50 and γ 50 parameters were similar. The LQ-L fitted EQD2 50 was ∼8.0 Gy for M0 and M1-retreat, ∼24 Gy for M1-initial, and ∼19 Gy for M2. The model fitted γ 50 was 0.1 Gy for M0, M1-retreat, and M2 and 0.5 for M1-initial. For the PTV D 99 of 10 and 20 Gy, the steepest to shallowest dose-response or largest change in TCP, that is, TCP 20Gy - TCP 10Gy , was observed in M1-initial (0.49) and M2 (0.17). M0 and M1-retreat showed a similar change in TCP of 0.21., Conclusions: The model-fitted parameters predicted the recurrent BMs required a higher threshold dose and had a steeper dose-response for first SRS versus second SRS and M0. Alternatively, the recurrent BMs required ∼2 Gy higher predicted PTV D 99 dose for first SRS to achieve the same TCP of 0.75 compared with second SRS and M0. Further investigations on larger patient cohorts are needed for validating our findings in predictive modeling of recurrent BMs., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Postoperative management of lower grade gliomas (grade 2 and 3) is heterogeneous. The American Radium Society's brain malignancies panel systematically reviewed and evaluated the literature to develop consensus guidelines addressing timing of postoperative therapy, monotherapy versus combined modality therapy, type of chemotherapy used with radiotherapy, and radiotherapy dose. Thirty-six studies were included. Using consensus methodology (modified Delphi), the panel voted upon representative case variants using a 9-point appropriateness scale to address key questions. Voting results were collated to develop summarized recommendations. Following gross-total surgical resection, close surveillance is appropriate for well-selected grade 2, IDH-mutant oligodendrogliomas or astrocytomas with low-risk features. For grade 2 gliomas with high-risk features or any grade 3 glioma, immediate adjuvant therapy is recommended. When postoperative therapy is administered, radiation and planned chemotherapy is strongly recommended over monotherapy. For grade 2 and 3 IDH-mutant oligodendrogliomas and astrocytomas, either adjunctive PCV (procarbazine, lomustine, vincristine) or temozolomide is appropriate. For grade 3 IDH-mutant astrocytomas, radiotherapy followed by temozolomide is strongly recommended. The recommended radiotherapy dose for grade 2 gliomas is 45-54 Gy/1.8-2.0 Gy, and for grade 3 gliomas is 59.4-60 Gy/1.8-2.0 Gy. While multiple appropriate treatment options exist, these consensus recommendations provide an evidence-based framework to approach postoperative management of lower grade gliomas., Competing Interests: Declaration of interests The text is the sole product of the authors. The ARS provided administrative support and facilitated teleconferences and live conferences at the annual ARS meeting., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS)., Methods and Materials: Eligible studies provided NTCPs for the endpoints of radionecrosis, edema, or symptoms after cranial SRS/fSRS and quantitative dose-volume metrics. Studies of patients with only glioma, meningioma, vestibular schwannoma, or brainstem targets were excluded. The data summary and analyses focused on arteriovenous malformations (AVM) and brain metastases., Results: Data from 51 reports are summarized. There was wide variability in reported rates of radionecrosis. Available data for SRS/fSRS for brain metastases were more amenable to NTCP modeling than AVM data. In the setting of brain metastases, SRS/fSRS-associated radionecrosis can be difficult to differentiate from tumor progression. For single-fraction SRS to brain metastases, tissue volumes (including target volumes) receiving 12 Gy (V12) of 5 cm 3 , 10 cm 3 , or >15 cm 3 were associated with risks of symptomatic radionecrosis of approximately 10%, 15%, and 20%, respectively. SRS for AVM was associated with modestly lower rates of symptomatic radionecrosis for equivalent V12. For brain metastases, brain plus target volume V20 (3-fractions) or V24 (5-fractions) <20 cm 3 was associated with <10% risk of any necrosis or edema, and <4% risk of radionecrosis requiring resection., Conclusions: The risk of radionecrosis after SRS and fSRS can be modeled as a function of dose and volume treated. The use of fSRS appears to reduce risks of radionecrosis for larger treatment volumes relative to SRS. More standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses that can refine predictive models of brain toxicity risks., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature., Methods and Materials: PubMed-indexed studies published between January 1995 and September 2017 were used to evaluate dosimetric and clinical predictors of TCP after SRS or fSRS for brain metastases. Eligible studies had ≥10 patients and included detailed dose-fractionation data with corresponding ≥1-year local control (LC) data, typically evaluated as a >20% increase in diameter of the targeted lesion using the pre-SRS diameter as a reference., Results: Of 2951 potentially eligible manuscripts, 56 included sufficient dose-volume data for analyses. Accepting that necrosis and pseudoprogression can complicate the assessment of LC, for tumors ≤20 mm, single-fraction doses of 18 and 24 Gy corresponded with >85% and 95% 1-year LC rates, respectively. For tumors 21 to 30 mm, an 18 Gy single-fraction dose was associated with 75% LC. For tumors 31 to 40 mm, a 15 Gy single-fraction dose yielded ∼69% LC. For 3- to 5-fraction fSRS using doses in the range of 27 to 35 Gy, 80% 1-year LC has been achieved for tumors of 21 to 40 mm in diameter., Conclusions: TCP for SRS and fSRS are presented. For small lesions ≤20 mm, single doses of ≈18 Gy appear generally associated with excellent rates of LC; for melanoma, higher doses seem warranted. For larger lesions >20 mm, local control rates appear to be ≈ 70% to 75% with usual doses of 15 to 18 Gy, and in this setting, fSRS regimens should be considered. Greater consistency in reporting of dosimetric and LC data is needed to facilitate future pooled analyses. As systemic and biologic therapies evolve, updated analyses will be needed to further assess the necessity, efficacy, and toxicity of SRS and fSRS., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To investigate wait time (WT) for chemoradiation and survival in post-op high-grade glioma (HGG) patients admitted to inpatient rehabilitation compared with those discharged home. Materials & methods:  A total of 291 HGG patients (14.4% grade III and 84.9% grade IV) were included in this retrospective cohort study. Patients were grouped by disposition following surgery. Results: Median length of stay was longer in acute inpatient rehabilitation facility (AIRF) patients (10d) compared with patients discharged home (3d). AIRF admission was associated with higher odds of excessive treatment delay. Median survival for AIRF patients less than for patients discharged home (42.9 vs 72.71 weeks). WT was not associated with survival even after adjusting for prognostic factors. Conclusion: HGG patients discharged to rehabilitation facilities have longer length of stay, longer WT and shorter survival compared with patients discharged home.

Background/aim: Whether adding tumor treating fields (TTF) to the Stupp protocol increases survival for glioblastoma (GBM) patients in routine clinical care remains unknown., Patients and Methods: We retrospectively identified adult patients with newly diagnosed GBM (n=104) treated with the Stupp protocol or TTF at our Institution., Results: Thirty-six percent (37/104) of patients received TTF in conjunction with the Stupp protocol and these patients had increased 6-month (p=0.006) and 1-year (p=0.170), but not 2-year survival rates compared to the 67-patients who received Stupp alone. The improvement of survival rate at 6-month was further confirmed by a modified Poisson model (p=0.010). However, we did not observe any improvement in overall survival (OS) with a Cox model., Conclusion: While adding TTF to the Stupp protocol appeared to benefit patients with newly diagnosed GBM, this effect was mild and may be largely due to selection bias., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: For brain metastases, surgical resection with postoperative stereotactic radiosurgery is an emerging standard of care. Postoperative cavity stereotactic radiosurgery is associated with a specific, underrecognized pattern of intracranial recurrence, herein termed nodular leptomeningeal disease (nLMD), which is distinct from classical leptomeningeal disease. We hypothesized that there is poor consensus regarding the definition of LMD, and that a formal, self-guided training module will improve interrater reliability (IRR) and validity in diagnosing LMD., Methods and Materials: Twenty-two physicians at 16 institutions, including 15 physicians with central nervous system expertise, completed a 2-phase survey that included magnetic resonance imaging and treatment information for 30 patients. In the "pretraining" phase, physicians labeled cases using 3 patterns of recurrence commonly reported in prospective studies: local recurrence (LR), distant parenchymal recurrence (DR), and LMD. After a self-directed training module, participating physicians completed the "posttraining" phase and relabeled the 30 cases using the 4 following labels: LR, DR, classical leptomeningeal disease, and nLMD., Results: IRR increased 34% after training (Fleiss' Kappa K = 0.41 to K = 0.55, P < .001). IRR increased most among non-central nervous system specialists (+58%, P < .001). Before training, IRR was lowest for LMD (K = 0.33). After training, IRR increased across all recurrence subgroups and increased most for LMD (+67%). After training, ≥27% of cases initially labeled LR or DR were later recognized as nLMD., Conclusions: This study highlights the large degree of inconsistency among clinicians in recognizing nLMD. Our findings demonstrate that a brief self-guided training module distinguishing nLMD can significantly improve IRR across all patterns of recurrence, and particularly in nLMD. To optimize outcomes reporting, prospective trials in brain metastases should incorporate central imaging review and investigator training., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate the correlation between the FA parameters and Ki-67 labeling index, and their diagnostic performance in grading supratentorial non-enhancing gliomas and neuronal-glial tumors (GNGT)., Methods: This institutional review board-approved, Health Insurance Portability and Accountability (HIPAA) compliant retrospective study enrolled 35 patients, including 19 with low grade GNGT and 16 with high grade GNGT. The mean FA, maximal FA and mean maximal FA values derived from diffusion tensor imaging were measured. The correlation between the FA parameters and the Ki-67 labeling index was assessed by Spearman rank test. The receiver operating characteristic curve analysis and multivariate logistic regression analysis were performed to detect the optimal imaging parameters in grading GNGT., Results: The three FA parameters of low grade GNGT were significantly lower than the high grade GNGT (p < 0.001). The mean FA, maximal FA and mean maximal FA had significant positive correlation with Ki-67 labeling index (p = 0.001, p < 0.001, p < 0.001 respectively). The maximal FA showed a higher sensitivity and specificity in grading of non-enhancing GNGT with specificity of 78.9%, sensitivity of 100.0%, respectively., Conclusions: The FA parameters correlated with Ki-67 labeling index, and were useful surrogates in preoperative grading supratentorial non-enhancing GNGT., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Metastatic prostate cancer (MPC) prognosis is variable. Few population-based studies have examined the impact of particular visceral metastatic sites on MPC survival outcomes. We investigated this using the Surveillance, Epidemiology, and End Results (SEER) database., Materials and Methods: We analyzed the overall survival (OS) and prostate cancer mortality (PCM) risk of 12,180 patients, from SEER 18 registries, diagnosed with MPC from 2010 to 2014. We identified those with metastatic disease in bone, brain, liver, and lung. Kaplan-Meier analyses, competing risks regression, and Cox proportional hazards models were used to assess the impact of visceral metastatic disease sites on OS and PCM., Results: Most patients were coded as having metastatic disease in the bone without disease in the brain, liver, or lung (bone group, n = 10,620; 87% of total). On Cox multivariable regression analysis, patients with lung metastases, with or without bone metastases, did not differ significantly from patients in the bone group with respect to OS (hazard ratio, 0.82; 95% confidence interval, 0.63-1.06; P = .13 and hazard ratio, 1.12; 95% confidence interval, 0.98-1.28; P = .10, respectively). These patients also did not differ from the bone group with respect to PCM incidence on competing risks regression analysis., Conclusions: This study suggests that patients with MPC confined to bone and/or lung may have improved survival relative to those with MPC affecting other visceral sites. Although it was anticipated that patients with bone metastases would represent a favorable subgroup, the favorable outcomes in patents with lung metastases (with or without bone metastases) was unexpected. These findings may inform future therapeutic investigations to improve the prognosis of patients with MPC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Optimal doses for single-fraction stereotactic radiosurgery (SRS) in the treatment of brain metastases are not well established. Our institution utilized conservative dosing compared to maximum-tolerated doses from the Radiation Therapy Oncology Group 90-05 Phase I study., Objective: To report individual lesion control (LC) from conservative single-fraction doses and determine factors affecting LC., Methods: From 2003 to 2015, patients who underwent linear accelerator-based single-fraction SRS for cerebral/cerebellar metastases and receiving at least 1 follow-up magnetic resonance imaging (MRI) were identified. Lesion response was assessed by a size-based rating system and modified "Response Assessment in Neuro-Oncology Brain Metastases" (RANO-BM) criteria., Results: Among 188 patients with 519 lesions, median survival was 13.1 mo; median follow-up time with MRI was 9.6 mo per course. Median tumor-periphery dose was 15 Gy (range: 7.5-20.7). Median lesion volume was 0.5 cc and diameter was 9 mm (range: 2-45). Concordance between RANO-BM and size-based system was 93%. Crude 1-yr LC was 80%, 73%, 56%, and 38% for lesions 1 to 10, 11 to 20, 21 to 30, >31 mm, respectively. On multivariate analysis, increased size, melanoma and colorectal histology, and progression after whole brain radiation therapy predicted worse LC. When excluding lesions treated as a boost, dose was a significant predictor of LC in multivariate models (hazard ratio 0.89, P = .01). Symptomatic radiation necrosis occurred in 10 lesions in 10 patients., Conclusion: Histology predicts LC after conservative SRS doses with evidence of a dose-response relationship. Conservative single-fraction SRS doses confer minimal toxicity and acceptable control in certain subgroups (breast cancer, <5 mm), with suboptimal control in larger lesions and in combination with whole brain radiation therapy.

Objectives: Radiotherapy remains the standard approach for brain metastases from renal cell carcinoma (RCC). Kinase inhibitors (KI) have become standard of care for metastatic RCC. They also increase the radiosensitivity of various tumor types in preclinical models. Data are lacking regarding the effect of KIs among RCC patients undergoing radiotherapy for brain metastases. We report our experience of radiotherapy for brain metastatic RCC in the era of targeted therapy and analyzed effects of concurrent KI therapy., Methods: We retrospectively analyzed 25 consecutive patients who received radiotherapy for brain metastases from RCC with whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or both. Kaplan-Meier rates of overall survival (OS) and brain progression-free survival (BPFS) were calculated and univariate analyses performed., Results: Lower diagnosis-specific graded prognostic assessment (DS-GPA) score and multiple intracranial metastases were associated with decreased OS and BPFS on univariate analysis; DS-GPA is also a prognostic factor on multivariate analysis. There was no significant difference in OS or BPFS for SRS compared with WBRT or WBRT and SRS combined. The concurrent use of KI was not associated with any change in OS or BPFS., Conclusions: This hypothesis-generating analysis suggests among patients with brain metastatic RCC treated with the most current therapies, those selected to undergo SRS did not experience significantly different survival or control outcomes than those selected to undergo WBRT. From our experience to date, limited in patient numbers, there seems to be neither harm nor benefit in using concurrent KI therapy during radiotherapy. Given that most patients progress systemically, we would recommend considering KI use during brain radiotherapy in these patients.

Patients with brain metastasis from melanoma have poor outcomes. Radiation is used both for prognostic and symptomatic value. We aimed to further clarify the role of stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT) as well as the prognostic implication of various sites of extracranial disease. The records of 73 consecutive patients treated at the University of Rochester Medical Center for brain-metastatic melanoma from January 2004 to October 2013 were reviewed. The median overall survival (OS) was 3.0 months. Patients treated with WBRT alone had decreased OS compared to those treated with SRS alone (HR = 0.38, p = 0.001) or WBRT and SRS (HR = 0.51, p = 0.039). The mean number of brain metastasis differed (p = 0.002) in patients in patients who received WBRT (4.0) compared to those who did not (2.0). Among patients with extracranial disease (n = 63), bone metastasis (HR = 1.86, p = 0.047, n = 15) was a negative prognostic factor; liver (HR = 1.59, p = 0.113, n = 17), lung (HR = 1.51, p = 0.23, n = 51) and adrenal metastasis (HR = 1.70, p = 0.15, n = 10) were not. In patients with concurrent brain and lung metastasis, those with disease limited to those two sites (OS = 8.7 mo, n = 13) had improved OS (HR = 0.44, p = 0.014) compared to those with additional disease (OS = 1.8 mo, n = 50). Based on this hypothesis-generating retrospective analysis, SRS may offer survival benefit compared to WBRT alone in patients with brain metastatic melanoma. Bone metastasis appears to confer a particularly poor prognosis. Those with disease confined to the lung and brain may represent a population with improved prognosis.

Brain metastases are the most common form of intracranial tumor in adults and an increasingly important cause of morbidity and mortality. Rising incidence is attributed to advanced radiographic imaging and prolonged survival due to improvements in cancer therapy (including systemic therapies) that are not as effective in treating intracranial disease. Standard treatment options for brain metastases include resection, whole-brain radiation therapy (WBRT), stereotactic radiosurgery, or a combination of these modalities. Most patients with brain metastases receive some form of radiation therapy during the course of their illness, and for the majority of them, the prognosis is poor and WBRT remains the standard. However, within this very diverse patient population, subgroups exist in which prolonged survival is possible. In recent years, several randomized controlled trials have clearly demonstrated the efficacy of stereotactic radiosurgery in well-selected patients. This, along with an increased recognition of the late neurocognitive effects of WBRT, has led many to question the role of upfront WBRT in patients with limited intracranial metastases. In this review, we summarize the evolving role of radiotherapy in the management of brain metastases and then discuss the issues related to neurotoxicity from radiation and future areas of investigation.

The purpose of this study was to determine whether dynamic susceptibility contrast MR perfusion relative cerebral blood volume (rCBV) correlates with prognosis of World Health Organization (WHO) grade III glial tumors and their different subtypes. Retrospective evaluation of pre-treatment tumor rCBV derived from dynamic susceptibility contrast MR perfusion was performed in 34 patients with histopathologically diagnosed WHO grade III glial tumors (anaplastic astrocytomas (n = 20), oligodendrogliomas (n = 4), and oligoastrocytomas (n = 10)). Progression free survival was correlated with rCBV using Spearman rank analysis. ROC curve analysis was performed to determine the operating point for rCBV in patients with anaplastic astrocytomas dichotomized at the median progression free survival time. For all grade III tumors (n = 34) the mean rCBV was 2.51 with a progression free survival of 705.5 days. The mean rCBV of anaplastic astrocytomas was 2.47 with progression free survival 495.2 days. In contrast, the mean rCBV for oligodendroglial tumors was 2.56 with a progression free survival of 1005.6 days. Although there was no significant correlation between rCBV and progression free survival among all types of grade III gliomas (P = 0.12), among anaplastic astrocytomas there was a significant correlation between pretreatment rCBV and progression free survival with correlation coefficient of -0.51 (P = 0.02). The operating point for rCBV in patients with anaplastic astrocytomas dichotomized at the median progression free survival time (446.5 days) was 2.86 with 78 % accuracy and there was a significant difference between the survival of patients with anaplastic astrocytomas in the dichotomized groups (P = 0.0009). Pre-treatment rCBV may serve as a prognostic imaging biomarker for anaplastic astrocytomas, but not grade III oligodendroglioma tumors.

In this study, we sought to characterize post-therapy MRI changes mimicking progression, which we refer to as "spurious progression" (SP) in children with brain tumors. We analyzed whether SP is associated with particular tumor types or therapeutic modalities. Between 2000 and 2009, we identified 181 consecutive children <21 years of age at our center who were treated for brain tumors and had at least three MRI scans within a year after completing therapy. SP was defined as MRI abnormalities characterized by increase in size, enhancement, edema, or cystic changes within 12 months following therapy, and stabilization or improvement on subsequent imaging. One-hundred forty-one patients with brain tumors were evaluable. Fifty-six (40%) had imaging abnormalities initially suggestive of disease progression; of these, 34 (24%) had true disease progression (TP). The remaining 22 (16%) had SP based on either stability, decrease in enhancement, edema, size, or disappearance of these cystic or non-cystic abnormalities. SP occurred in patients with low grade (n = 20) and high grade lesions (n = 2). Median time to SP was 2.4 months (range, 0.7-8.3 months), with time to stability, decrease, or disappearance at a median of 4 months (range 1.4-7.7 months). Five patients were clinically symptomatic from SP and were treated with steroids, cyst drainage, and/or surgery. Therefore, SP occurs more commonly in children with low grade tumors, but can also occur with high grade brain tumors, regardless of therapeutic approach.

Single-fraction stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (SRT) are radiation planning and delivery techniques used for the treatment of intracranial and spine/spinal cord tumors and targets. For cranial SRS and SRT, critical normal tissues/structures include the brainstem, cranial nerves, cochlea and normal brain parenchyma. For spine SRS/SRT, critical normal tissues/structures include the spinal cord, cauda equina as well as neighboring organs. This paper reviews clinical studies investigating central nervous system dose tolerances after cranial or spinal SRS/SRT. The impact of dose, volume, fractionation, and other relevant clinic-pathologic variables are discussed, as are limitations of the published data., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: To determine recurrence patterns of glioblastoma treated with temozolomide-based chemoradiation., Methods: Pretreatment and serial posttreatment magnetic resonance imaging scans of 54 patients were retrospectively evaluated. Central recurrence (i.e., local progression) and the development of new (i.e., interval appearance of discrete enhancing lesion) in-field, marginal, and distant recurrences were assessed, with the pattern of recurrence of individual lesions defined relative to the 95% isodose line (D(95)). Distant recurrences were defined as lesions completely outside D(95), marginal recurrences crossed D(95), and in-field recurrences were completely inside D(95)., Results: At a median follow-up of 17 months, 39 of 54 (72%) patients developed recurrent glioblastoma. Among these 39 patients, central recurrence occurred in 80% (at a median of 7 months from diagnosis); new in-field recurrence developed in 33% (at a median of 14 months); marginal recurrences developed in 15% (at a median of 18 months); and distant recurrences developed in 20% (at a median of 11 months). The actuarial rates of central, new in-field, marginal, distant, and any new recurrences at 1-year were 46%, 15%, 3%, 14%, and 25% respectively, whereas at 2 years, the rates were 68%, 60%, 32%, 28%, and 66%, reflecting an increasing probability of new lesions developing at later time points. Ten patients developed subependymal recurrences, of whom 7 developed multiple subependymal lesions., Conclusions: Whereas central recurrence of glioblastoma treated with radiation and temozolomide predominates and persists over time, new in-field, marginal, and distant recurrences commonly develop, particularly at later time points in patients with longer survival., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To evaluate perfusion parameter changes in patients with glioblastoma multiforme by comparing the perfusion magnetic resonance (MR) imaging measurements obtained before combined radiation and temozolomide therapy (RT-TMZ) with the follow-up MR imaging measurements obtained 1 month after completion of this treatment., Materials and Methods: Institutional review board approval was obtained, and HIPAA guidelines were followed. The data of 36 patients (24 male [median age, 63 years]; 12 female [median age, 59 years]) with glioblastoma multiforme who were treated with RT-TMZ were retrospectively reviewed. The hypothesis was that a change in relative cerebral blood volume (rCBV) 1 month after RT-TMZ is predictive of overall survival. Linear regression analysis was performed to correlate changes in tumor size and perfusion parameters with overall survival. Receiver operating characteristic (ROC) curves were evaluated for 1-year survival. Overall survival was assessed with Kaplan-Meir survival curves and log-rank testing., Results: Percentage change in rCBV at 1 month after RT-TMZ correlated with overall survival. Increased rCBV after treatment was a strong predictor of poor survival (median survival, 235 days versus 529 days with decreased rCBV) (P < .008, log-rank test). The ROC curves for 1-year survival showed a greater area under the curve (0.806; 95% confidence interval [CI]: 0.698, 0.970) (P = .005) with rCBV than with tumor size (0.556; 95% CI: 0.342, 0.729) (P = .382). The overall survival for patients with increased tumor size, based on Macdonald criteria, was shorter than that for patients who showed no progression (stable or partial response), but the difference was not significant (median survival, 442 days versus 598 days) (P = .761, log-rank test)., Conclusion: Change in rCBV after RT-TMZ appears to correlate with overall survival.

Purpose: Prospective pilot study to assess patient outcome after stereotactic body radiation therapy (SBRT) for limited metastases from breast cancer., Methods: Forty patients with < or =5 metastatic lesions received curative-intent SBRT, while 11 patients with >5 lesions, undergoing SBRT to < or =5 metastatic lesions, were treated with palliative-intent., Results: Among those treated with curative-intent, 4-year actuarial outcomes were: overall survival of 59%, progression-free survival of 38% and lesion local control of 89%. On univariate analyses, 1 metastatic lesion (versus 2-5), smaller tumor volume, bone-only disease, and stable or regressing lesions prior to SBRT were associated with more favorable outcome. Patients treated with palliative-intent SBRT were spared morbidity and mortality from progression of treated lesions, though all developed further metastatic progression shortly (median 4 months) after enrollment., Conclusions: SBRT may yield prolonged survival and perhaps cure in select patients with limited metastases. Palliative-intent SBRT may be warranted for symptomatic or potentially symptomatic metastases.

Purpose: This retrospective study was done to better understand the conditions for which stereotactic radiosurgery (SRS) for glioblastoma may be efficacious., Methods: Between 2000 and 2007, 33 patients with a pathological diagnosis of glioblastoma received SRS with the Novalis Shaped Beam Radiosurgery system. Eighteen patients (54%) underwent salvage SRS for recurrence while 15 (45%) patients received upfront SRS following standard fractionated RT for newly diagnosed glioblastoma., Results: There were no RTOG grade >2 acute side effects. The median survival after SRS was 6.7 months (range 1.4 - 74.7). There was no significant difference in overall survival (from the time of initial diagnosis) with respect to the timing of SRS (p = 0.2). There was significantly better progression free survival in patients treated with SRS as consolidation versus at the time of recurrence (p = 0.04). The majority of patients failed within or at the margin of the SRS treatment volume (21/26 evaluable for recurrence)., Conclusion: SRS is well tolerated in the treatment of glioblastoma. As there was no difference in survival whether SRS is delivered upfront or at recurrence, the treatment for each patient should be individualized. Future studies are needed to identify patients most likely to respond to SRS.

Purpose: To characterize oligometastases in patients enrolled on two prospective pilot studies, treating oligometastases with hypofractionated stereotactic body radiotherapy and stereotactic radiosurgery to cranial lesions., Methods and Materials: We describe the characteristics and local control (LC) of 293 lesions in 121 patients with five or fewer metastases treated with stereotactic body radiation and/or cranial stereotactic radiosurgery. For each lesion, the primary cancer site, tumor histology, site of metastasis, gross tumor volume, and prescribed dose were ascertained. The prescribed dose is expressed by the biologically effective dose in 2-Gy fractions (BED2), calculated using the linear quadratic model, assuming an alpha/beta ratio of 10., Results: Lung lesions were significantly smaller than other lesions in our cohort, whereas liver lesions were significantly larger, possibly reflecting a detection and/or referral bias. The 2-year and 4-year tumor LC rates were 77% and 73% respectively. A larger gross tumor volume was significantly (p < 0.0001) correlated with worse lesion LC. Lesions originating from primary pancreatic, biliary or liver cancer exhibited significantly poorer LC, as did lesions from colorectal cancer. Lesions from breast cancer were better controlled. A higher BED2 did not correlate with improved tumor control., Conclusions: Stereotactic body radiation to aggressively treat oligometastatic lesions results in good local tumor control. Bulkier lesions are more difficult to control and may benefit from dose escalation.