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OBJECTIVE: Insular gliomas pose a significant surgical challenge due to the complex surrounding functional and vascular anatomy. The authors report their experience using a novel framework for the treatment of insular gliomas with laser interstitial thermal therapy (LITT) and provide representative case examples emphasizing indications, rationale, and technical pearls. METHODS: A prospectively gathered institutional database was used to identify patients with newly diagnosed insular gliomas who underwent LITT between 2015 and 2023. The proposed framework of insular glioma management is guided by tumor size and extent of extra-insular tumor involvement. Patients with tumors localized to the insula (insula-only) were treated with single-session or staged LITT. Patients with insular tumors with frontotemporal involvement (insular+) were treated with insular LITT and standard frontotemporal resection of extra-insular tumor. Clinical and volumetric lesional characteristics were analyzed, with particular emphasis on extent of cytoreductive treatment and safety. RESULTS: Of the 261 patients treated at the authors' institution with LITT between 2015 and 2023, 33 LITT procedures were identified involving 22 unique patients with treatment-naive insular gliomas. Of the 22 patients, 12 had insular-only tumors and were treated with LITT alone, while 10 patients had insular+ lesions and were treated with LITT and resection. The median tumor volume for insular-only tumors was 13.4 cm3 (IQR 10.6, 26.3 cm3), with a median extent of treatment of 100% (IQR 92.1%, 100%). Insular+ lesions were significantly larger, with a median volume of 81.2 cm3 (IQR 51.9, 97 cm3) and median extent of treatment of 96.6% (IQR 93.7%, 100%). All patients with insular-only tumors were discharged the day after ablation, while insular+ patients had significantly longer hospital stays, with 50% staying more than 3 days. Overall, 8% of insular-only patients had permanent neurological deficits compared with 33% of insular+ patients. Two patients' tumors progressed during follow-up: one patient with WHO grade 4 astrocytoma and the other with diffuse glioma not otherwise specified. Patients with grade 4 tumors had the highest rate of permanent neurological deficit (43%) and a larger decline in postoperative Karnofsky Performance Status score (p = 0.046). CONCLUSIONS: The authors present their experience using a novel insular glioma treatment paradigm that incorporates LITT into the broader framework of insular glioma surgery. Their findings suggest that insular LITT is feasible and may allow for high rates of cytoreduction while potentially ameliorating the risks of conventional insular glioma surgery.
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PURPOSE: Laser interstitial thermal therapy (LITT) is a minimally invasive cytoreductive treatment option for brain tumors with a risk of vascular injury from catheter placement or thermal energy. This may be of concern with deep-seated tumors that have surrounding end-artery perforators and critical microvasculature. The purpose of this study was to assess the risk of distal ischemia following LITT for deep-seated perivascular brain tumors. METHODS: A retrospective review of a multi-institution database was used to identify patients who underwent LITT between 2013 and 2022 for tumors located within the insula, thalamus, basal ganglia, and anterior perforated substance. Demographic, clinical and volumetric tumor characteristics were collected. The primary outcome was radiographic evidence of distal ischemia on post-ablation magnetic resonance imaging (MRI). RESULTS: 61 LITT ablations for deep-seated perivascular brain tumors were performed. Of the tumors treated, 24 (39%) were low-grade gliomas, 32 (52%) were high-grade gliomas, and 5 (8%) were metastatic. The principal location included 31 (51%) insular, 14 (23%) thalamic, 13 (21%) basal ganglia, and 3 (5%) anterior perforated substance tumors. The average tumor size was 19.6 cm3 with a mean ablation volume of 11.1 cm3. The median extent of ablation was 92% (IQR 30%, 100%). Two patients developed symptomatic intracerebral hemorrhage after LITT. No patient had radiographic evidence of distal ischemia on post-operative diffusion weighted imaging. CONCLUSION: We demonstrate that LITT for deep-seated perivascular brain tumors has minimal ischemic risks and is a feasible cytoreductive treatment option for otherwise difficult to access intracranial tumors.
Subject(s)
Brain Neoplasms , Glioma , Laser Therapy , Humans , Laser Therapy/methods , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Glioma/surgery , Magnetic Resonance Imaging/methods , Retrospective Studies , LasersSubject(s)
Brain Neoplasms , Radiosurgery , Humans , Brain Neoplasms/surgery , Brain Neoplasms/secondaryABSTRACT
BACKGROUND: Laser interstitial thermal therapy (LITT) for glioblastoma (GBM) has been reserved for poor surgical candidates and deep "inoperable" lesions. We present the first reported series of LITT for surgically accessible recurrent GBM (rGBM) that would otherwise be treated with surgical resection. OBJECTIVE: To evaluate the use of LITT for unifocal, lobar, first-time rGBM compared with a similar surgical cohort. METHODS: A retrospective institutional database was used to identify patients with unifocal, lobar, first-time rGBM who underwent LITT or resection between 2013 and 2020. Clinical and volumetric lesional characteristics were compared between cohorts. Subgroup analysis of patients with lesions ≤20 cm 3 was also completed. Primary outcomes were overall survival and progression-free survival. RESULTS: Of the 744 patients with rGBM treated from 2013 to 2020, a LITT cohort of 17 patients were compared with 23 similar surgical patients. There were no differences in baseline characteristics, although lesions were larger in the surgical cohort (7.54 vs 4.37 cm 3 , P = .017). Despite differences in lesion size, both cohorts had similar extents of ablation/resection (90.7% vs 95.1%, P = .739). Overall survival (14.1 vs 13.8 months, P = .578) and progression-free survival (3.7 vs 3.3 months, P = 0. 495) were similar. LITT patients had significantly shorter hospital stays (2.2 vs 3.0 days, P = .004). Subgroup analysis of patients with lesions ≤20 cm 3 showed similar outcomes, with LITT allowing for significantly shorter hospital stays. CONCLUSION: We found no difference in survival outcomes or morbidity between LITT and repeat surgery for surgically accessible rGBM while LITT resulted in shorter hospital stays and more efficient postoperative care.
Subject(s)
Brain Neoplasms , Glioblastoma , Laser Therapy , Humans , Laser Therapy/methods , Lasers , Magnetic Resonance Imaging , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: Neurosurgeons generate an enormous amount of data daily. Within these data lie rigorous, valid, and reproducible evidence. Such evidence can facilitate healthcare reform and improve quality of care. To measure the quality of care provided objectively, evaluating the safety and efficacy of clinical activities should occur in real time. Registries must be constructed and collected data analyzed with the precision akin to that of randomized clinical trials to accomplish this goal. METHODS: The Quality Outcomes Database (QOD) Tumor Registry was launched in February 2019 with 8 sites in its initial 1-year pilot phase. The Tumor Registry was proposed by the AANS/CNS Tumor Section and approved by the QOD Scientific Committee in the fall of 2018. The initial pilot phase aimed to assess the feasibility of collecting outcomes data from 8 academic practices across the United States; these outcomes included length of stay, discharge disposition, and inpatient complications. RESULTS: As of November 2019, 923 eligible patients have been entered, with the following subsets: intracranial metastasis (17.3%, n = 160), high-grade glioma (18.5%, n = 171), low-grade glioma (6%, n = 55), meningioma (20%, n = 184), pituitary tumor (14.3%, n = 132), and other intracranial tumor (24%, n = 221). CONCLUSIONS: The authors have demonstrated here, as a pilot study, the feasibility of documenting demographic, clinical, operative, and patient-reported outcome characteristics longitudinally for 6 common intracranial tumor types.
Subject(s)
Brain Neoplasms , Glioma , Meningeal Neoplasms , Brain Neoplasms/surgery , Humans , Pilot Projects , Registries , United StatesABSTRACT
OBJECTIVE: Greater extent of resection (EOR) is associated with longer overall survival in patients with high-grade gliomas (HGGs). 5-Aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). When administered orally, 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue 400-nm light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative imaging agent for HGG tissue. In this first-ever, to the authors' knowledge, multicenter 5-ALA FGS study conducted in the United States, the primary objectives were the following: 1) assess the diagnostic accuracy of 5-ALA-induced PPIX fluorescence for HGG histopathology across diverse centers and surgeons; and 2) assess the safety profile of 5-ALA FGS, with particular attention to neurological morbidity. METHODS: This single-arm, multicenter, prospective study included adults aged 18-80 years with Karnofsky Performance Status (KPS) score > 60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3-5 samples per tumor were taken and their fluorescence status was recorded by the surgeon. Specimens were submitted for histopathological analysis. Patients were followed for 6 weeks postoperatively for adverse events, changes in the neurological exam, and KPS score. Multivariate analyses were performed of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables. RESULTS: Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG histopathology of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events due to intraoperative neurological injury, which may have resulted from FGS, occurred at a rate of 4.3%. There were 2 deaths unrelated to FGS. Compared to preoperative KPS scores, postoperative KPS scores were significantly lower at 48 hours and 2 weeks but were not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume. CONCLUSIONS: PPIX fluorescence, as judged by the surgeon, has a high sensitivity and PPV for HGG. 5-ALA was well tolerated in terms of drug-related adverse events, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity.
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BACKGROUND: Opioids are prescribed routinely after cranial surgery despite a paucity of evidence regarding the optimal quantity needed. Overprescribing may adversely contribute to opioid abuse, chronic use, and diversion. OBJECTIVE: To evaluate the effectiveness of a system-wide campaign to reduce opioid prescribing excess while maintaining adequate analgesia. METHODS: A retrospective cohort study of patients undergoing a craniotomy for tumor resection with home disposition before and after a 2-mo educational intervention was completed. The educational initiative was composed of directed didactic seminars targeting senior staff, residents, and advanced practice providers. Opioid prescribing patterns were then assessed for patients discharged before and after the intervention period. RESULTS: A total of 203 patients were discharged home following a craniotomy for tumor resection during the study period: 98 who underwent surgery prior to the educational interventions compared to 105 patients treated post-intervention. Following a 2-mo educational period, the quantity of opioids prescribed decreased by 52% (median morphine milligram equivalent per day [interquartile range], 32.1 [16.1, 64.3] vs 15.4 [0, 32.9], P < .001). Refill requests also decreased by 56% (17% vs 8%, P = .027) despite both groups having similar baseline characteristics. There was no increase in pain scores at outpatient follow-up (1.23 vs 0.85, P = .105). CONCLUSION: A dramatic reduction in opioids prescribed was achieved without affecting refill requests, patient satisfaction, or perceived analgesia. The use of targeted didactic education to safely improve opioid prescribing following intracranial surgery uniquely highlights the ability of simple, evidence-based interventions to impact clinical decision making, lessen potential patient harm, and address national public health concerns.
Subject(s)
Analgesics, Opioid , Pharmaceutical Preparations , Analgesics, Opioid/therapeutic use , Brain , Humans , Pain, Postoperative/drug therapy , Practice Patterns, Physicians' , Prescription Drugs , Retrospective StudiesABSTRACT
OBJECTIVE: Examine the effect of a universal facemask policy for healthcare workers (HCW) and incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity. METHODS: Daily number of symptomatic HCW tested, SARS-CoV-2 positivity rates, and HCW job-descriptions were collected pre and post Universal HCW facemask policy (March 26, 2020). Multiple change point regression was used to model positive-test-rate data. SARS-CoV-2 testing and positivity rates were compared for pre-intervention, transition, post-intervention, and follow-up periods. RESULTS: Between March 12 and August 10, 2020, 19.2% of HCW were symptomatic for COVID-19 and underwent SARS-CoV-2 testing. A single change point was identified â¼March 28-30 (95% probability). Before the change point, the odds of a tested HCW having a positive result doubled every 4.5 to 7.5âdays. Post-change-point, the odds of a tested HCW having a positive result halved every 10.5 to 13.5âdays. CONCLUSIONS: Universal facemasks were associated with reducing HCW's risk of acquiring COVID-19.
Subject(s)
COVID-19/epidemiology , Health Personnel/statistics & numerical data , Health Policy/legislation & jurisprudence , Masks , SARS-CoV-2/isolation & purification , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19 Testing , Delivery of Health Care , Health Personnel/classification , Humans , Michigan/epidemiologyABSTRACT
PURPOSE: Liquid biopsy offers a minimally invasive tool to diagnose and monitor the heterogeneous molecular landscape of tumors over time and therapy. Detection of TERT promoter mutations (C228T, C250T) in cfDNA has been successful for some systemic cancers but has yet to be demonstrated in gliomas, despite the high prevalence of these mutations in glioma tissue (>60% of all tumors). EXPERIMENTAL DESIGN: Here, we developed a novel digital droplet PCR (ddPCR) assay that incorporates features to improve sensitivity and allows for the simultaneous detection and longitudinal monitoring of two TERT promoter mutations (C228T and C250T) in cfDNA from the plasma of patients with glioma. RESULTS: In baseline performance in tumor tissue, the assay had perfect concordance with an independently performed clinical pathology laboratory assessment of TERT promoter mutations in the same tumor samples [95% confidence interval (CI), 94%-100%]. Extending to matched plasma samples, we detected TERT mutations in both discovery and blinded multi-institution validation cohorts with an overall sensitivity of 62.5% (95% CI, 52%-73%) and a specificity of 90% (95% CI, 80%-96%) compared with the gold-standard tumor tissue-based detection of TERT mutations. Upon longitudinal monitoring in 5 patients, we report that peripheral TERT-mutant allele frequency reflects the clinical course of the disease, with levels decreasing after surgical intervention and therapy and increasing with tumor progression. CONCLUSIONS: Our results demonstrate the feasibility of detecting circulating cfDNA TERT promoter mutations in patients with glioma with clinically relevant sensitivity and specificity.
Subject(s)
Biomarkers, Tumor/genetics , Brain Neoplasms/diagnosis , Glioma/diagnosis , Telomerase/genetics , Adult , Aged , Brain Neoplasms/blood , Brain Neoplasms/therapy , Cell Line, Tumor , Cohort Studies , DNA Mutational Analysis/methods , Feasibility Studies , Female , Glioma/blood , Glioma/therapy , Humans , Liquid Biopsy/methods , Male , Middle Aged , Mutation , Polymerase Chain Reaction , Promoter Regions, Genetic , Sensitivity and SpecificityABSTRACT
QUESTION: What is the role of temozolomide in the management of adult patients (aged 65 and under) with newly diagnosed glioblastoma? TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. RECOMMENDATION: Level I: Concurrent and post-irradiation Temozolomide (TMZ) in combination with radiotherapy and post-radiotherapy as described by Stupp et al. is recommended to improve both PFS and OS in adult patients with newly diagnosed GBM. There is no evidence that alterations in the dosing regimen have additional beneficial effect. QUESTION: Is there benefit to adjuvant temozolomide treatment in elderly patients (> 65 years old?). TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. RECOMMENDATION: Level III: Adjuvant TMZ treatment is suggested as a treatment option to improve PFS and OS in adult patients (over 70 years of age) with newly diagnosed GBM. QUESTION: What is the role of local regional chemotherapy with BCNU biodegradable polymeric wafers in adult patients with newly diagnosed glioblastoma? TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. RECOMMENDATION: Level III: There is insufficient evidence for the use of BCNU wafers following resection in patients with newly diagnosed glioblastoma who undergo the Stupp protocol after surgery. Further studies of higher quality are suggested to understand the role of BCNU wafer and other locoregional therapy in the setting of Stupp Protocol. QUESTION: What is the role of bevacizumab in the adult patient with newly diagnosed glioblastoma? TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. RECOMMENDATION: Level I: Bevacizumab in general is not recommended in the initial treatment of adult patients with newly diagnosed GBM. It continues to be strongly recommended that patients with newly diagnosed GBM be enrolled in properly designed clinical trials to assess the benefit of novel chemotherapeutic agents compared to standard therapy.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Evidence-Based Practice/standards , Glioblastoma/drug therapy , Practice Guidelines as Topic/standards , Adult , Disease Management , Glioblastoma/diagnosis , HumansABSTRACT
The American Board of Neurological Surgery (ABNS) was incorporated in 1940 in recognition of the need for detailed training in and special qualifications for the practice of neurological surgery and for self-regulation of quality and safety in the field. The ABNS believes it is the duty of neurosurgeons to place a patient's welfare and rights above all other considerations and to provide care with compassion, respect for human dignity, honesty, and integrity. At its inception, the ABNS was the 13th member board of the American Board of Medical Specialties (ABMS), which itself was founded in 1933. Today, the ABNS is one of the 24 member boards of the ABMS.To better serve public health and safety in a rapidly changing healthcare environment, the ABNS continues to evolve in order to elevate standards for the practice of neurological surgery. In connection with its activities, including initial certification, recognition of focused practice, and continuous certification, the ABNS actively seeks and incorporates input from the public and the physicians it serves. The ABNS board certification processes are designed to evaluate both real-life subspecialty neurosurgical practice and overall neurosurgical knowledge, since most neurosurgeons provide call coverage for hospitals and thus must be competent to care for the full spectrum of neurosurgery.The purpose of this report is to describe the history, current state, and anticipated future direction of ABNS certification in the US.
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OBJECTIVE: We aimed to characterize the socioeconomic impact of glioma for patients with clinical and radiographic evidence of disease stability, using the standardized Medical Expenditure Panel Survey-Household Component (MEPS-HC). METHODS: The MEPS-HC questionnaire was used to investigate the degree of economic hardship referable to the patient's brain tumor and treatment. The questionnaire included demographic variables such as age at diagnosis, ethnicity, highest level of education, and annual household income. Descriptive statistics were used to characterize variables and between-group comparisons were evaluated using Fisher exact test. RESULTS: Of 127 prescreened patients, 89 of 107 eligible patients completed the survey. Pathology at diagnosis was predominantly low grade (60%). Most patients were insured at time of diagnosis (91%), married (76%), and employed (79%), with annual household incomes slightly higher than the national average. Despite this, nearly a quarter incurred debt referable to brain tumor care (24%), 53% required extended unpaid time off, and 46% retired or were no longer working. Financial burden and workforce morbidity were insensitive to tumor location, laterality, and annual household income. Patients with gross total resection at initial surgery were less likely to report ongoing limitations in daily activities (45% vs 83%, p = 0.004). CONCLUSIONS: Even in a population of stable, high-functioning glioma survivors, financial burden and workforce morbidity was ubiquitous across all tumor subtypes, treatment paradigms, and income levels.
Subject(s)
Cost of Illness , Glioma/economics , Glioma/psychology , Survivorship , Adolescent , Adult , Aged , Female , Glioma/diagnosis , Humans , Male , Middle Aged , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Predicting survival of patients with spinal metastases would help stratify treatments from aggressive to palliation. OBJECTIVE: To evaluate whether sarcopenia predicts survival in patients with lung, breast, prostate, or multiple myeloma spinal metastases. METHODS: Psoas muscle measurements in patients with spinal metastasis were taken from computed tomography scans at 2 time points: at first episode of stereotactic body radiation therapy (SBRT) and from the most recent scan available. Overall survival and hazard ratios were calculated with multivariate cox proportional hazards regression analyses. RESULTS: In 417 patients with spinal metastases, 40% had lung cancer, 27% breast, 21% prostate, and 11% myeloma. Overall survival was not associated with age, sex, ethnicity, levels treated, or SBRT volume. Multivariate analysis showed patients in the lowest psoas tertile had shorter survival (222 d, 95% CI = 185-323 d) as compared to the largest tertile (579 d, 95% CI = 405-815 d), (HR1.54, P = .005). Median psoas size as a cutoff value was also strongly predictive for survival (HR1.48, P = .002). Survival was independent of tumor histology. The psoas/vertebral body ratio was also successful in predicting overall survival independent of tumor histology and gender (HR1.52, P < .01). Kaplan-Meier survival curves visually represent survival (P = .0005). CONCLUSION: In patients with spine metastases, psoas muscle size as a hallmark of frailty/sarcopenia is an objective, simple, and effective way to identify patients who are at risk for shorter survival, regardless of tumor histology. This information can be used to help with surgical decision making in patients with advanced cancer, as patients with small psoas sizes are at higher risk of death.
Subject(s)
Frailty , Sarcopenia , Spinal Neoplasms/mortality , Spinal Neoplasms/secondary , Adult , Aged , Aged, 80 and over , Breast Neoplasms/complications , Breast Neoplasms/pathology , Female , Frailty/etiology , Humans , Kaplan-Meier Estimate , Lung Neoplasms/complications , Lung Neoplasms/pathology , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/pathology , Multivariate Analysis , Proportional Hazards Models , Prostatic Neoplasms/complications , Prostatic Neoplasms/pathology , Psoas Muscles/pathology , Radiosurgery/methods , Retrospective Studies , Sarcopenia/etiology , Sarcopenia/pathologyABSTRACT
QUESTION: Do steroids improve neurological symptoms and/or quality of life in patients with metastatic brain tumors compared to supportive care only or other treatment options? If steroids are given, what dose should be used? TARGET POPULATION: These recommendations apply to adults diagnosed with brain metastases. RECOMMENDATIONS: STEROID THERAPY VERSUS NO STEROID THERAPYAsymptomatic brain metastases patients without mass effectInsufficient evidence exists to make a treatment recommendation for this clinical scenario.Brain metastases patients with mild symptoms related to mass effect Level 3: Corticosteroids are recommended to provide temporary symptomatic relief of symptoms related to increased intracranial pressure and edema secondary to brain metastases. It is recommended for patients who are symptomatic from metastatic disease to the brain that a starting dose of 4 to 8 mg/d of dexamethasone be considered.Brain metastases patients with moderate to severe symptoms related to mass effect Level 3: Corticosteroids are recommended to provide temporary symptomatic relief of symptoms related to increased intracranial pressure and edema secondary to brain metastases. If patients exhibit severe symptoms consistent with increased intracranial pressure, it is recommended that higher doses such as 16 mg/d or more be considered. CHOICE OF STEROID: Level 3: If corticosteroids are given, dexamethasone is the best drug choice given the available evidence.Duration of Corticosteroid Administration Level 3: Corticosteroids, if given, should be tapered as rapidly as possible but no faster than clinically tolerated, based upon an individualized treatment regimen and a full understanding of the long-term sequelae of corticosteroid therapy.Given the very limited number of studies (2) which met the eligibility criteria for the systematic review, these are the only recommendations that can be offered based on this methodology.The full guideline can be found at https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_7.
Subject(s)
Brain Neoplasms/drug therapy , Evidence-Based Medicine/standards , Neurosurgeons/standards , Practice Guidelines as Topic/standards , Steroids/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Adult , Brain Neoplasms/surgery , Congresses as Topic/standards , Female , Humans , Male , Quality of LifeABSTRACT
TARGET POPULATION: Adult patients (older than 18 yr of age) with newly diagnosed brain metastases. QUESTION: If whole brain radiation therapy (WBRT) is used, is there an optimal dose/fractionation schedule? RECOMMENDATIONS: Level 1: A standard WBRT dose/fractionation schedule (ie, 30 Gy in 10 fractions or a biological equivalent dose [BED] of 39 Gy10) is recommended as altered dose/fractionation schedules do not result in significant differences in median survival or local control. Level 3: Due to concerns regarding neurocognitive effects, higher dose per fraction schedules (such as 20 Gy in 5 fractions) are recommended only for patients with poor performance status or short predicted survival. Level 3: WBRT can be recommended to improve progression-free survival for patients with more than 4 brain metastases. QUESTION: What impact does tumor histopathology or molecular status have on the decision to use WBRT, the dose fractionation scheme to be utilized, and its outcomes? RECOMMENDATIONS: There is insufficient evidence to support the choice of any particular dose/fractionation regimen based on histopathology. Molecular status may have an impact on the decision to delay WBRT in subgroups of patients, but there is not sufficient data to make a more definitive recommendation. QUESTION: Separate from survival outcomes, what are the neurocognitive consequences of WBRT, and what steps can be taken to minimize them? RECOMMENDATIONS: Level 2: Due to neurocognitive toxicity, local therapy (surgery or SRS) without WBRT is recommended for patients with ≤4 brain metastases amenable to local therapy in terms of size and location. Level 2: Given the association of neurocognitive toxicity with increasing total dose and dose per fraction of WBRT, WBRT doses exceeding 30 Gy given in 10 fractions, or similar biologically equivalent doses, are not recommended, except in patients with poor performance status or short predicted survival. Level 2: If prophylactic cranial irradiation (PCI) is given to prevent brain metastases for small cell lung cancer, the recommended WBRT dose/fractionation regimen is 25 Gy in 10 fractions, and because this can be associated with neurocognitive decline, patients should be told of this risk at the same time they are counseled about the possible survival benefits. Level 3: Patients having WBRT (given for either existing brain metastases or as PCI) should be offered 6 mo of memantine to potentially delay, lessen, or prevent the associated neurocognitive toxicity. QUESTION: Does the addition of WBRT after surgical resection or radiosurgery improve progression-free or overall survival outcomes when compared to surgical resection or radiosurgery alone? RECOMMENDATIONS: Level 2: WBRT is not recommended in WHO performance status 0 to 2 patients with up to 4 brain metastases because, compared to surgical resection or radiosurgery alone, the addition of WBRT improves intracranial progression-free survival but not overall survival. Level 2: In WHO performance status 0 to 2 patients with up to 4 brain metastases where the goal is minimizing neurocognitive toxicity, as opposed to maximizing progression-free survival and overall survival, local therapy (surgery or radiosurgery) without WBRT is recommended. Level 3: Compared to surgical resection or radiosurgery alone, the addition of WBRT is not recommended for patients with more than 4 brain metastases unless the metastases' volume exceeds 7 cc, or there are more than 15 metastases, or the size or location of the metastases are not amenable to surgical resection or radiosurgery.The full guideline can be found at: https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_3.