Abstract
The therapeutic landscape of the management of low- and high-grade infiltrating gliomas continues to evolve. Daily clinical decision making in neuro-oncology clinics across the US is ...frequently challenging, especially for anaplastic and low grade primary brain tumors. The focus of this review is centered on treatments which are approved by the FDA and/or featured in the NCCN Guidelines. Systemic therapy trials using a variety of agents such as temozolomide, bevacizumab, and procarbazine, lomustine, vincristine (PCV), and lastly trials of local therapies including surgical trials using carmustine impregnated wafers as well as trials investigating the administration of tumor treating fields are evaluated. Pivotal trials on the treatment of the primary brain tumors are discussed in detail along with associated correlative studies.
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.
Meningiomas are extraaxial central nervous system tumors most often discovered in middle to late adult life, and are more often seen in women. Ninety percent of meningiomas are benign, 6% are ...atypical, and 2% are malignant. Most patients in whom a meningioma is diagnosed undergo resection to relieve neurological symptoms. Complete resection is often curative. For the majority of incompletely resected or recurrent tumors not previously irradiated, radiotherapy is administered. Radiotherapy may be administered as either conventional external-beam radiation therapy or stereotactically by linear accelerator, Leksell Gamma Knife, or Cyberknife radiosurgery. Advocates of stereo-tactic radiotherapy have suggested this therapy in lieu of surgery particularly in high-risk patients, those with meningiomas in eloquent or surgically inaccessible locations, and elderly patients. When the meningioma is unresectable or all other treatments (surgery and radiotherapy) have failed, hormonal therapy or chemotherapy may be considered. Notwithstanding limited data, hydroxyurea has been modestly successful in patients with recurrent meningiomas.
To validate the dose calculation accuracy and dose distribution of GammaTiles for brain tumors, and to suggest a surgically targeted radiation therapy (STaRT) workflow for planning, delivery, ...radiation safety documentation, and posttreatment validation.
Novel surgically targeted radiation therapy, GammaTiles, uses Cs-131 radiation isotopes embedded in collagen-based tiles that can be resorbed after surgery. GammaTile target delineation and dose calculation were performed on MIM Symphony software. Point-based and complex seed distribution calculations in MIM Symphony were verified with hand calculations and BrachyVision calculations. Vendor-provided 2-dimensional dose distribution calculation accuracy was validated using gafchromic EBT3 film measurements at various depths. A workflow was established for safe and effective GammaTile implants.
Good agreement was observed between different calculations. Calculation accuracy of less than 0.5% was achieved for all points except one, which had rounding issues for very low doses and resulted in just below 5% difference. Differences in anisotropy and geometry positioning were noticed in the delineation of Cs-131 IsoRay seeds in the compared systems, resulting in minor discrepancies in the calculated dosimetry distributions. Film measurements showed profiles with relatively good agreement of 0% to 5% in nongradient regions with higher differences between 5% to 10% in the sharp dose fall-off regions.
A comprehensive evaluation of GammaTile geometry, dose distribution, and clinical workflow was conducted. Safe intro-operative implantation of GammaTiles requires extensive preplanning and interdisciplinary collaboration. A STaRT workflow was outlined to provide a guideline for an accurate treatment planning and safe implant process at other institutions.
BACKGROUND: Neuroanatomic locations of gliomas may influence clinical presentations, molecular profiles, and patients’ prognoses. METHODS: We investigated our institutional cancer registry to include ...patients with glioma over a 10-year period. Statistical tests were used to compare demographic, genetic, and clinical characteristics among patients with gliomas in different locations. Survival analysis methods were then used to assess associations between location and overall survival in the full cohort, as well as in relevant subgroups. RESULTS: 182 gliomas were identified. Of the tumours confined to a single lobe, there were 51 frontal (28.0%), 50 temporal (27.5%), 22 parietal (12.1%), and seven occipital tumours (3.8%) identified. Tumours affecting the temporal lobe were associated with reduced overall survival when compared to all other tumours (11 months vs. 13 months, log-rank p = 0.0068). In subgroup analyses, this result was significant for males HR (95%CI) 2.05 (1.30, 3.24), p = 0.002, but not for females HR (95%CI) 1.12 (0.65, 1.93), p = 0.691. Out of 82 cases tested for IDH-1, 10 were mutated (5.5%). IDH-1 mutation was present in six frontal, two temporal, one thalamic, and one multifocal tumour. Out of 21 cases tested for 1p19q deletions, 12 were co-deleted, nine of which were frontal lobe tumours. MGMT methylation was assessed in 45 cases; 7/14 frontal tumours and 6/13 temporal tumours were methylated. CONCLUSION: Our results support the hypothesis that the anatomical locations of gliomas influence patients’ clinical courses. Temporal lobe tumours were associated with poorer survival, though this association appeared to be driven by these patients’ more aggressive tumour profiles and higher risk baseline demographics. Independently, female patients who had temporal lobe tumours fared better than males. Molecular analysis was limited by the low prevalence of genetic testing in the study sample, highlighting the importance of capturing this information for all gliomas. IMPORTANCE OF THIS STUDY: The specific neuroanatomic location of tumours in the brain is thought to be predictive of treatment options and overall prognosis. Despite evidence for the clinical significance of this information, there is relatively little information available regarding the incidence and prevalence of tumours in the different anatomical regions of the brain. This study has more fully characterised tumour prevalence in different regions of the brain. Additionally, we have analysed how this information may affect tumours’ molecular characteristics, treatment options offered to patients, and patients’ overall survival. This information will be informative both in the clinical setting and in directing future research.
The introduction of methotrexate (MTX)-based chemotherapy has improved median survival for patients with primary CNS lymphoma (PCNSL). Older age is a negative prognostic marker in patients with PCNSL ...and may increase the likelihood of MTX toxicity. We studied the response and adverse effects of intravenous high-dose MTX in patients who were 70 or more years of age at the time of diagnosis. We identified 31 patients at our institution diagnosed with PCNSL at age > or =70 years (median, 74 years) who were treated with high-dose MTX (3.5-8 g/m(2)) as initial therapy from 1992 through 2006. The best response to MTX was determined by contrast-enhanced MRI. Toxicity was analyzed by chart review. These 31 patients received a total of 303 cycles of MTX (median, eight cycles per patient). Overall, 87.9% of the cycles required dose reduction because of impaired creatinine clearance. In 30 evaluable patients, the overall radiographic response rate was 96.7%, with 18 complete responses (60%) and 11 partial responses (36.7%). Progression-free survival and overall survival were 7.1 months and 37 months, respectively. Grade I-IV toxicities were observed in 27 of 31 patients and included gastrointestinal disturbances in 58% (3.2% grade III), hematological complications in 80.6% (6.5% grade III), and renal toxicity in 29% (0% grade III/IV). High-dose MTX is associated with a high proportion of radiographic responses and a low proportion of grade III/IV toxicity in patients 70 or more years of age. High-dose MTX should be considered as a feasible treatment option in elderly patients with PCNSL.
Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed ...the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN.
We reviewed 63 patients with LC and ICM who received RT (radiosurgery stereotactic radiosurgery with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes.
Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%, P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality.
This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.
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