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Laser interstitial thermal therapy (LITT) is a minimally invasive treatment option for intracranial tumors which are challenging to treat via traditional methods; however, its safety and efficacy are not yet well-validated in the literature.To assess the available evidence on the indications, adverse events (AEs) of LITT and progression-free (1Y-PFS) and overall survival (1Y-OS) in the treatment of primary and secondary brain tumors.A comprehensive literature search was conducted through the databases PubMed, Embase, and the Cochrane Library through October 2021. Comparative and descriptive studies, except for case reports, were included in the meta-analysis. Separate analyses by tumor type (high-grade gliomas, including WHO grade 4 astrocytomas [which include glioblastomas] as a specific subgroup; low-grade gliomas; and brain metastases) were conducted. Pooled effect sizes and their 95% confidence intervals (CI) were generated via random-effects models.Forty-five studies met inclusion criteria, yielding 826 patients for meta-analysis. There were 829 lesions total of which 361 lesions were classified as high-grade gliomas, 116 as low-grade gliomas, 337 as metastatic brain tumors, and 15 as non-glial tumors. Indications for offering LITT included: deep/inaccessible tumor (12 studies), salvage therapy post-failed radiosurgery (9), failures of two or more treatment options (3), in pediatrics patients (4), patient preference (1); indications were non-specific in 12 studies. Pooled incidence of all (minor or major) procedure-related AEs was 30% (95% CI: 27-40%) for all tumors. Pooled incidence of neurological deficits (minor or major) was 16% (12-22%); post-procedural edema 14% (8-22%); seizure 6% (4-9%); hematoma 20% (14-29%); deep vein thrombosis 19% (11-30%); hydrocephalus 8% (5-12%); and wound infection 5% (3-7%). 1Y-PFS was 18.6% (11.3-29.0%) in high-grade gliomas, 16.9% (11.6-24.0%) among the Grade 4 astrocytomas; and 51.2% (36.7-65.5%) in brain metastases. 1Y-OS was 43.0% (36.0-50.0%) among high-grade glioma, 45.9% (95% CI: 37.9-54%) in Grade 4 astrocytomas; 93.0% (42.3-100%) for low-grade gliomas, and 56.3% (47.0-65.3%) in brain metastases.New neurological deficits and post-procedural edema were the most reported adverse events following LITT, albeit mostly transient. This meta-analysis provides the best statistical estimates of progression and survival outcomes based on currently available information. LITT is generally a safe procedure for selected patients, and future well-designed comparative studies on its outcomes versus the current standard-of-care should be performed.

Background Leptomeningeal disease (LMD) is a relatively uncommon manifestation of advanced cancer. Patients with LMD carry a poor prognosis and often decline rapidly, complicating inclusion in clinical trials. Identification of LMD subsets of greater incidence and more favorable prognosis might facilitate dedicated clinical trials in the future. We hypothesized that patients with breast cancer may represent such a population and sought to assess the relative incidence and prognosis of LMD secondary to breast vs. non-breast primaries. Methods We identified 2411 patients with intracranial metastases secondary to breast (N = 501) and non-breast (N = 1910) primaries at Brigham and Women’s Hospital/Dana-Farber Cancer Institute between 1996 and 2020, of whom 112 presented with and an additional 161 subsequently developed LMD. A log-rank test and Cox modeling were used to compare outcomes in patients with breast vs. non-breast primaries. Results Among patients with newly diagnosed intracranial disease, the incidence proportion of concurrent LMD was 11.4% vs. 2.9% among patients with breast vs. non-breast primaries (P Conclusions Patients with breast cancer and LMD may represent an ideal population for clinical trials given the higher incidence and potentially more favorable prognosis seen in this population.

Brain metastases occur commonly in patients with advanced solid malignancies. Yet, less is known about brain metastases than cancer-related entities of similar incidence. Advances in oncologic care have heightened the importance of intracranial management. Here, in this consensus review supported by the Society for Neuro-Oncology (SNO), we review the landscape of brain metastases with particular attention to management approaches and ongoing efforts with potential to shape future paradigms of care. Each coauthor carried an area of expertise within the field of brain metastases and initially composed, edited, or reviewed their specific subsection of interest. After each subsection was accordingly written, multiple drafts of the manuscript were circulated to the entire list of authors for group discussion and feedback. The hope is that the these consensus guidelines will accelerate progress in the understanding and management of patients with brain metastases, and highlight key areas in need of further exploration that will lead to dedicated trials and other research investigations designed to advance the field.

To evaluate the epidemiology of primary and metastatic pediatric brain tumors in the United States according to the WHO CNS 4th and 5th editions classifications.Pediatric patients (age ≤ 14) presenting between 2004 and 2017 with a brain tumor were identified in the National Cancer Database and categorized by NICHD age stages. Patients' age, sex, race/ethnicity, overall survival, and tumor characteristics were evaluated according to WHO CNS 4th and 5th editions.23,978 pediatric brain tumor patients were identified. Overall, other (i.e. circumscribed) astrocytic gliomas (21%), diffuse astrocytic/oligodendroglial gliomas (21%; 64% of which were midline), and embryonal tumors (16%) predominated. A minority of brain tumors were of ependymal (6%), glioneuronalneuronal (6%), germ cell tumor (GCT; 4%), mesenchymal non-meningothelial (2%), cranial nerve (2%), choroid plexus (2%), meningioma (2%), pineal (1%), and hematolymphoid (0.4%) types. GCTs were more likely in patients of Asian/Pacific Islander race/ethnicity. Brain metastases were exceedingly rare, accounting for 1.4% overall, with the most common primary tumor being neuroblastoma (61%) and non-CNS sarcoma (16%). Brain metastatic, choroid plexus, and embryonal tumors peaked during infancy and toddlerhood; whereas diffuse gliomas peaked in middle-late childhood. GCTs and glioneuronalneuronal tumors uniquely displayed bimodal distributions, with elevated prevalence in both infancy and middle-to-late childhood.We systematically described the epidemiology of pediatric brain tumors in the context of contemporary classification schema, thereby validating our current understanding and providing key insights.

Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for WHO grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010 and 2018 were identified from the National Cancer Database. The overall survival (OS) associated with first-line single-agent temozolomide vs multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results One thousand five hundred ninety-six radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n = 1414) treated with temozolomide and 11.4% (n = 182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at the time of analysis. There was a significant difference in unadjusted OS between temozolomide (5-year OS 58.9%, 95%CI: 55.6-62.0) and PCV (5-year OS 65.1%, 95%CI: 54.8-73.5; P = .04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs temozolomide HR 0.81, 95%CI: 0.59-1.11, P = .18). PCV was more frequently used for younger Olig3s but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

Background Falls in patients with cancer harbor potential for serious sequelae. Patients with brain metastases (BrM) may be especially susceptible to falls but supporting investigations are lacking. We assessed the frequency, etiologies, risk factors, and sequelae of falls in patients with BrM using 2 data sources. Methods We identified 42 648 and 111 patients with BrM utilizing Surveillance, Epidemiology, and End Results (SEER)-Medicare data (2008-2016) and Brigham and Women’s Hospital/Dana-Farber Cancer Institute (BWH/DFCI) institutional data (2015), respectively, and characterized falls in these populations. Results Among SEER-Medicare patients, 10 267 (24.1%) experienced a fall that prompted medical evaluation, with cumulative incidences at 3, 6, and 12 months of 18.0%, 24.3%, and 34.1%, respectively. On multivariable Fine/Gray’s regression, older age (≥81 or 76-80 vs 66-70 years, hazard ratio [HR] 1.18 [95% CI, 1.11-1.25], P < .001 and HR 1.10 [95% CI, 1.04-1.17], P < .001, respectively), Charlson comorbidity score of >2 vs 0-2 (HR 1.08 [95% CI, 1.03-1.13], P = .002) and urban residence (HR 1.08 [95% CI, 1.01-1.16], P = .03) were associated with falls. Married status (HR 0.94 [95% CI, 0.90-0.98], P = .004) and Asian vs white race (HR 0.90 [95% CI, 0.81-0.99], P = .03) were associated with reduced fall risk. Identified falls were more common among BWH/DFCI patients (N = 56, 50.4% of cohort), resulting in emergency department visits, hospitalizations, fractures, and intracranial hemorrhage in 33%, 23%, 11%, and 4% of patients, respectively. Conclusions Falls are common among patients with BrM, especially older/sicker patients, and can have deleterious consequences. Risk-reduction measures, such as home safety checks, physical therapy, and medication optimization, should be considered in this population.

Surgery and radiosurgery represent the most common treatment options for vestibular schwannoma. A systematic review and meta-analysis were conducted to compare the outcomes of surgery versus stereotactic radiosurgery (SRS).The Cochrane library, PubMed, Embase, and clinicaltrials.gov were searched through 01/2021 to find all studies on surgical and stereotactic procedures performed to treat vestibular schwannoma. Using a random-effects model, pooled odds ratios (OR) and their 95% confidence intervals (CI) comparing post- to pre-intervention were derived for pre-post studies, and pooled incidence of adverse events post-intervention were calculated for case series and stratified by intervention type.Twenty-one studies (18 pre-post design; three case series) with 987 patients were included in the final analysis. Comparing post- to pre-intervention, both surgery (OR: 3.52, 95%CI 2.13, 5.81) and SRS (OR: 3.30, 95%CI 1.39, 7.80) resulted in greater odds of hearing loss, lower odds of dizziness (surgery OR: 0.10; 95%CI 0.02, 0.47 vs. SRS OR: 0.22; 95%CI 0.05, 0.99), and tinnitus (surgery OR: 0.23; 95%CI 0.00, 37.9; two studies vs. SRS OR: 0.11; 95%CI 0.01, 1.07; one study). Pooled incidence of facial symmetry loss was larger post-surgery (14.3%, 95%CI 6.8%, 22.7%) than post-SRS (7%, 95%CI 1%, 36%). Tumor control was larger in the surgery (94%, 95%CI 83%, 98%) than the SRS group (80%, 95%CI 31%, 97%) for small-to-medium size tumors.Both surgery and SRS resulted in similar odds of hearing loss and similar improvements in dizziness and tinnitus among patients with vestibular schwannoma; however, facial symmetry loss appeared higher post-surgery.

Background Older patients with brain metastases (BrM) commonly experience symptoms that prompt acute medical evaluation. We characterized emergency department (ED) visits and inpatient hospitalizations in this population. Methods We identified 17 789 and 361 Medicare enrollees diagnosed with BrM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2010-2016) and an institutional database (2007-2016), respectively. Predictors of ED visits and hospitalizations were assessed using Poisson regression. Results The institutional cohort averaged 3.3 ED visits/1.9 hospitalizations per person-year, with intracranial disease being the most common reason for presentation/admission. SEER-Medicare patients averaged 2.8 ED visits/2.0 hospitalizations per person-year. For patients with synchronous BrM (N = 7834), adjusted risk factors for ED utilization and hospitalization, respectively, included: male sex (rate ratio [RR] = 1.15 [95% CI = 1.09-1.22], P < .001; RR = 1.21 [95% CI = 1.13-1.29], P < .001); African American vs white race (RR = 1.30 [95% CI = 1.18-1.42], P < .001; RR = 1.25 [95% CI = 1.13-1.39], P < .001); unmarried status (RR = 1.07 [95% CI = 1.01-1.14], P = .02; RR = 1.09 [95% CI = 1.02-1.17], P = .01); Charlson comorbidity score >2 (RR = 1.27 [95% CI = 1.17-1.37], P < .001; RR = 1.36 [95% CI = 1.24-1.49], P < .001); and receipt of non-stereotactic vs stereotactic radiation (RR = 1.44 [95% CI = 1.34-1.55, P < .001; RR = 1.49 [95% CI = 1.37-1.62, P < .001). For patients with metachronous BrM (N = 9955), ED visits and hospitalizations were more common after vs before BrM diagnosis (2.6 vs 1.2 ED visits per person-year; 1.8 vs 0.9 hospitalizations per person-year, respectively; RR = 2.24 [95% CI = 2.15-2.33], P < .001; RR = 2.06 [95% CI = 1.98-2.15], P < .001, respectively). Conclusions Older patients with BrM commonly receive hospital-level care secondary to intracranial disease, especially in select subpopulations. Enhanced care coordination, closer outpatient follow-up, and patient navigator programs seem warranted for this population.

Background The limited availability of proton beam therapy (PBT) requires individual treatment selection strategies that can be based on normal tissue complication probability (NTCP) models. We developed and externally validated NTCP models for common late side-effects following PBT in brain tumour patients to optimise patients’ quality of life. Methods Cohorts from three PBT centres (216 patients) were investigated for several physician-rated endpoints at 12 and 24 months after PBT: alopecia, dry eye syndrome, fatigue, headache, hearing and memory impairment, and optic neuropathy. Dose-volume parameters of associated normal tissues and clinical factors were used for logistic regression modelling in a development cohort. Statistically significant parameters showing high area under the receiver operating characteristic curve (AUC) values in internal cross-validation were externally validated. In addition, analyses of the pooled cohorts and of time-dependent generalised estimating equations including all patient data were performed. Results In the validation study, mild alopecia was related to high dose parameters to the skin [e.g. the dose to 2% of the volume (D2%)] at 12 and 24 months after PBT. Mild hearing impairment at 24 months after PBT was associated with the mean dose to the ipsilateral cochlea. Additionally, the pooled analyses revealed dose–response relations between memory impairment and intermediate to high doses to the remaining brain as well as D2% of the hippocampi. Mild fatigue at 24 months after PBT was associated with D2% to the brainstem as well as with concurrent chemotherapy. Moreover, in generalised estimating equations analysis, dry eye syndrome was associated with the mean dose to the ipsilateral lacrimal gland. Conclusion We developed and in part validated NTCP models for several common late side-effects following PBT in brain tumour patients. Validation studies are required for further confirmation.

BackgroundVenous thromboembolism is common in patients with solid malignancies and brain metastases. Whether to anticoagulate such patients is controversial given the possibility of intracerebral haemorrhage (ICH). We evaluated the added risk of ICH in patients with brain metastases receiving therapeutic anticoagulation.MethodsWe performed a matched, retrospective cohort study of 291 patients (100 receiving therapeutic anticoagulation vs 191 controls) with brain metastases managed at Brigham and Women’s Hospital/Dana-Farber Cancer Institute between 1998 and 2015. For each patient, all MRI studies of the brain were reviewed to identify ICH. Propensity score matching and multivariable Cox regression were used to mitigate confounding.ResultsThe risk of ICH was comparable in patients receiving anticoagulation versus controls preanticoagulation. Postanticoagulation, we observed significant or borderline-significant associations between anticoagulation and development of any ICH (HR 1.31, 95% CI 0.96 to 1.79, p=0.09), ICH as identified by gradient echo/susceptibility-weighted imaging (HR 1.46, 95% CI 1.06 to 2.01, p=0.02), symptomatic ICH (HR 1.80, 95% CI 1.01 to 3.22, p=0.05), extralesional ICH (HR 5.82, 95% CI 1.56 to 21.7, p=0.009) and fatal ICH (HR 5.68, 95% CI 0.60 to 54.2, p=0.13). Anticoagulation was associated with differentially higher ICH risk in patients with prior ICH versus no prior ICH (HR 2.20 vs 0.68, respectively, p interaction ConclusionsAnticoagulation is associated with clinically significant ICH in patients with brain metastases, especially those with melanoma or prior ICH. The indication for anticoagulation and risk of intracerebral bleeding should be considered on an individual basis among such patients.

PURPOSE The optimal timing of adjuvant radiation therapy (RT) in the management of atypical meningiomas remains controversial. We compared the outcomes of atypical meningiomas managed with upfront adjuvant RT versus postoperative surveillance. METHODS AND MATERIALS Patients with intracranial atypical meningiomas who underwent resection between 2000 and 2015 at a single institution were identified. Patients receiving adjuvant RT (n = 51), defined as RT within the first year of surgery before tumor progression/recurrence (P/R), were compared with those undergoing initial surveillance (n = 179). The primary endpoints were radiographic evidence of P/R and time to P/R from surgery. RESULTS A total of 230 patients were identified. Fifty-one (22%) patients received upfront adjuvant RT, and 179 (78%) underwent surveillance. Compared with the surveillance group, patients who received adjuvant RT had larger tumors (5.2 cm vs 4.6 cm; P = .04), were more likely to have undergone subtotal resection (65% vs 26%; P < . 01), and more often had bone invasion (18% vs 7%; P = .02). On multivariable analysis, receipt of adjuvant RT was associated with a lower risk of P/R compared with surveillance (hazard ratio, 0.21; 95% confidence interval, 0.11-0.41; P < .01). Patients who initially underwent surveillance and then received salvage RT at time of P/R had a shorter median time to local progression after RT compared with patients who developed local P/R after upfront adjuvant RT (19 vs 64 months, respectively; P < . 01). CONCLUSION Upfront adjuvant RT was associated with improved local control in atypical meningiomas irrespective of extent of initial resection compared with surveillance. Early adjuvant RT should be strongly considered after gross total resection of atypical meningiomas.

To inform treatment decisions for patients with high-risk prostate cancer (PCa), we determined rates of adverse pathologic factors and overall survival (OS) among subgroups of high-risk men.Using the National Cancer Database, 89,450 patients with clinical N0M0 unfavorable intermediate-risk, favorable high-risk (cT1c, Gleason 6, prostate-specific antigen [PSA]20 ng/mL or cT1c, biopsy Gleason 8, PSA10 ng/mL), standard high-risk (all other cT3a, biopsy Gleason ≥ 8, or PSA20 ng/mL), or very high-risk (cT3b-T4 or biopsy primary Gleason pattern 5) PCa treated with radical prostatectomy were identified. Rates of adverse pathologic factors (positive surgical margins, T4 disease, or pathologic lymph node involvement) were compared across subgroups.Patients with unfavorable intermediate-risk (n = 31,381) and favorable high-risk (n = 10,296) disease had similar rates of adverse features (7.6% vs 8.2%, adjusted odds ratio 1.00, 95% confidence interval 0.92-1.08, P= .974). Patients with standard high-risk (n = 30,260) or very high-risk (n = 7513) disease were significantly more likely to have adverse pathologic factors (15.9% and 26.5%, P.001 for both). Patients with unfavorable intermediate-risk and favorable high-risk disease had similar 5-year OS (95.7% vs 95.1%, adjusted hazard ratio 1.06, 95% confidence interval 0.92-1.21, P = .411) but better OS compared to standard and very high-risk patients (93.4% and 88.1%, respectively; P.001).Unfavorable intermediate-risk or favorable high-risk PCa patients had low rates of adverse pathologic factors and similar OS. In contrast, standard and very high-risk PCa patients had significantly higher rates of adverse pathologic factors and worse OS. This 3-tiered subclassification of high-risk disease may allow for improved treatment selection among patients considering surgery.

Background Prognostic estimates for patients with brain metastases (BM) stem from younger, healthier patients enrolled in clinical trials or databases from academic centers. We characterized population-level prognosis in elderly patients with BM. Methods Using Surveillance, Epidemiology, and End Results (SEER)–Medicare data, we identified 9882 patients ≥65 years old with BM secondary to lung, breast, skin, kidney, esophageal, colorectal, and ovarian primaries between 2014 and 2016. Survival was assessed by primary site and evaluated with Cox regression. Results In total, 2765 versus 7117 patients were diagnosed with BM at primary cancer diagnosis (synchronous BM, median survival = 2.9 mo) versus thereafter (metachronous BM, median survival = 3.4 mo), respectively. Median survival for all primary sites was ≤4 months, except ovarian cancer (7.5 mo). Patients with non-small-cell lung cancer (NSCLC) receiving epidermal growth factor receptor (EGFR)– or anaplastic lymphoma kinase (ALK)–based therapy for synchronous BM displayed notably better median survival at 12.5 and 20.1 months, respectively, versus 2.8 months exhibited by other patients with NSCLC; survival estimates in melanoma patients based on receipt of BRAF/MEK therapy versus not were 6.7 and 2.8 months, respectively. On multivariable regression, older age, greater comorbidity, and type of managing hospital were associated with poorer survival; female sex, higher median household income, and use of brain-directed stereotactic radiation, neurosurgical resection, or systemic therapy (versus brain-directed non-stereotactic radiation) were associated with improved survival (all P Conclusions Elderly patients with BM have a poorer prognosis than suggested by prior algorithms. If prognosis is driven by systemic and not intracranial disease, brain-directed therapy with potential for significant toxicity should be utilized cautiously.

Treatment options for hydrocephalus include endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS). Some ambiguity remains regarding indications, safety, and efficacy for these procedures in different clinical scenarios. The objective of the present study was to pool the available evidence to compare outcomes among patients with hydrocephalus undergoing ETV versus VPS. A systematic search of the literature was conducted via PubMed, EMBASE, and Cochrane Library through 11/29/2018 to identify studies evaluating failure and complication rates, following ETV or VPS. Pooled effect estimates were calculated using random effects. Heterogeneity was assessed by the Cochrane Q test and the I2 value. Heterogeneity sources were explored through subgroup analyses and meta-regression. Twenty-three studies (five randomized control trials (RCTs) and 18 observational studies) were meta-analyzed. Comparing ETV to VPS, failure rate was not statistically significantly different with a pooled relative risk (RR) of 1.48, 95%CI (0.85, 2.59) for RCTs and 1.17 (0.89, 1.53) for cohort studies; P-interaction: 0.44. Complication rates were not statistically significantly different between ETV and VPS in RCTs (RR: 1.34, 95%CI: 0.50, 3.59) but were statistically significant for prospective cohort studies (RR: 0.47, 95%CI: 0.30, 0.78); P-interaction: 0.07. Length of hospital stay was no different, when comparing ETV and VPS. These results remained unchanged when stratifying by intervention type and when regressing on age when possible. No significant differences in failure rate were observed between ETV and VPS. ETV was found to have lower complication rates than VPS in prospective cohort studies but not in RCTs. Further research is needed to identify the specific patient populations who may be better suited for one intervention versus another.

Whole brain radiation therapy (WBRT) remains an important component of treatment for patients with multiple brain metastases (BrM) but is associated with significant neurotoxicity and memory impairment. Although RTOG 0614 demonstrated that administration of memantine to patients receiving WBRT may reduce radiation-associated cognitive decline, prior literature has suggested that radiation oncologists are hesitant to prescribe memantine. We sought to assess the frequency of memantine prescription in patients managed with non-stereotactic, brain-directed radiation for BrM. Patients > 65 years old with newly diagnosed BrM between 2007 and 2016 receiving non-stereotactic, brain-directed radiation (including WBRT) were identified using the SEER–Medicare database. Receipt of memantine with non-stereotactic, brain-directed radiation was defined as any Part D claim for memantine 30 days before or after initiation of non-stereotactic, brain-directed radiation. Clinical and demographic variables among patients who did and did not receive memantine were compared. Between 2007 and 2016, we identified 6220 patients with BrM receiving non-stereotactic, brain-directed radiation. Only 2.20% of patients (n = 137) received memantine with radiation. Rates were 1.10% versus 5.14% in the period preceding (2007–2013) and following (2014–2016) the publication of RTOG 0614, respectively. Overall utilization of memantine remained low across several clinical, demographic, and prognostic variables. Despite phase 3 evidence supporting memantine utilization among patients receiving WBRT, our population-based study indicates that rates of memantine prescription are strikingly low, although memantine utilization seems to be increasing since publication of RTOG 0614. Further investigation is needed to identify provider and practice-related barriers preventing incorporation of memantine into management paradigms.

There are few treatment guidelines for locally recurrent esophageal cancer after trimodality treatment (pre-operative chemoradiation followed by surgery) in patients with a poor performance status. The purpose of this single institutional, retrospective study was to evaluate the clinical outcomes and toxicities of definitive-intent re-irradiation for patients with recurrent esophageal cancer with a poor performance status [ECOG (Eastern Cooperative Oncology Group) ≥2]. Seven patients were identified with a median age of 74 years (range, 61-81 years). Four patients were ECOG 2 and three patients were ECOG 3. The median follow-up time after re-irradiation was 49 months. The median interval between initial radiotherapy and re-treatment was 32 months. Six patients received concurrent chemotherapy [carboplatin + paclitaxel in three patients; folinic acid, fluorouracil, oxaliplatin (FOLFOX) + 5-fluorouracil in one patient; FOLFOX in one patient, and capecitabine in one patient]. At the last follow-up, the six patients who underwent concurrent chemotherapy had stable disease (86%), while the one who did not receive chemotherapy progressed (14%). Two patients developed metastases. Three patients developed acute (6 months) were limited to grades 1 and 2 dysphagia and pneumonitis in four patients. In conclusion, definitive re-irradiation of recurrent esophageal cancer in patients with a poor performance status appears to be safe with acceptable acute toxicity and late complications. It also appears to result in durable local control when combined with chemotherapy, albeit with a small number of patients and limited follow-up.

While open surgery has been the primary surgical approach for adult degenerative scoliosis, minimally invasive surgery (MIS) represents an alternative option and appears to be associated with reduced morbidity. Given the lack of consensus, we aimed to conduct a systematic review on available literature comparing MIS versus open surgery for adult degenerative scoliosis. PubMed, Embase, and Cochrane databases were searched through December 16, 2019, for studies that compared both MIS and open surgery in patients with degenerative scoliosis. Four cohort studies reporting on 350 patients met the inclusion criteria. In two studies, patients undergoing open surgery were younger and had more severe disease at baseline as compared with MIS. Patients who underwent MIS had less blood loss, shorter length of stay, and a reduced rate of complications and infections. Both MIS and open surgery resulted in a significant change in pain and disability scores and both approaches provided significant correction of deformity in all studies, although open surgery was associated with a greater change in pelvic incidence-lumbar lordosis mismatch (PI-LL) and sagittal vertical axis (SVA) in two and three studies, respectively. In patients with adult degenerative scoliosis undergoing surgery, both MIS and open approaches appeared to offer comparable improvements in pain and function. However, MIS was associated with better safety outcomes, while open surgery provided greater correction of spinal deformity. Further studies are needed to identify specific subset of patients who may benefit from one approach versus the other.

Purpose The logistical burdens of appointment scheduling and travel add to the psychological and emotional distress among patients with a new cancer diagnosis. This may be heightened among patients needing radiation therapy (RT), who must travel to and from a treatment facility daily for several weeks. Here, we studied the association between RT appointment waiting time and patient-reported pain and anxiety and explored additional factors that may influence daily waiting time. Methods Ninety-four patients undergoing RT at a single, academic institution were surveyed in the first and final weeks of treatment. On the day of the survey, patients were asked to report: pain (Likert scale: 0–10), anxiety (0–10), commute mode/time, and estimated waiting time for RT. Actual waiting times were calculated per review of the electronic scheduling system. Results Increased objective waiting time was associated with higher pain scores at the start (P = .05) and end (P = 0.004) of RT, although overall pain scores were low at both time points (mean 1.4 and 1.5, respectively). Anxiety scores were also low (mean 1.2 at both time points) and were not associated with objective waiting time (P > .05). Of note, patients reported perceived waiting times that were considerably shorter than actual waiting times (mean 15 vs. 26 minutes, respectively, at first survey early in the RT course). Time of day and tumor site were not associated with waiting time. Conclusion Daily waiting time may play a role in pain and/or anxiety experienced by patients with cancer during RT. Perceived waiting time may differ substantially from actual waiting time and represents a potential area for intervention to improve patients’ quality of life.

Background A subgroup of men with favorable high-risk prostate cancer (T1c with either a Gleason score of 4 + 4 = 8 and a prostate-specific antigen [PSA] level 20 ng/mL) has been associated with improved outcomes in comparison with other standard high-risk patients. This study was designed to validate the prognostic utility of a subclassification for high-risk disease with a prospectively collected data set. Methods This study identified 3033 men from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had been diagnosed from 1993 to 2001 with clinically localized prostate cancer-either intermediate-risk disease (clinical stage T2b-c, a Gleason score of 7, or a PSA level of 10 to 20 ng/mL) or high-risk disease (clinical stage T3-T4, a Gleason score of 8-10, or a PSA level >20 ng/mL)-that was managed with radical prostatectomy or radiation therapy. Multivariable logistic regression was used to calculate adjusted odds ratios (aORs) for pathological T3 to T4 or N1 (pT3-T4/pN1) disease. Fine and Gray competing risks regression was used to determine adjusted hazard ratios (aHRs) of prostate cancer-specific mortality (PCSM). Results The median follow-up was 5.7 years. Patients with favorable high-risk disease had lower 8-year PCSM in comparison with patients with standard high-risk disease (2.2% vs 10.8%; aHR, 0.26; 95% confidence interval [CI], 0.09-0.73; P = .01) but similar PCSM in comparison with patients with intermediate-risk disease (2.2% vs 2.2%; aHR, 0.90; 95% CI, 0.32-2.54; P = .84). Among those who underwent surgery, those with favorable high-risk disease had lower odds of pT3-T4/pN1 disease than those with standard high-risk disease (46.2% vs 63.3%; aOR, 0.50; 95% CI, 0.27-0.94; P = .03). Conclusions This study validates the prognostic utility of a subclassification for high-risk disease in a prospectively collected patient cohort. Patients with favorable high-risk disease have PCSM similar to that of patients with intermediate-risk disease and significantly better than that of patients with standard high-risk disease. Future trials are needed to assess possible de-intensification of therapy for favorable high-risk disease.

Objectives Visual dysfunction in patients with pituitary adenomas is a clear indication for endoscopic endonasal transsphenoidal surgery (EETS). However, the visual outcomes vary greatly among patients and it remains unclear what tumor, patient, and surgical characteristics contribute to postoperative visual outcomes. Methods One hundred patients with pituitary adenomas who underwent EETS between January 2011 and June 2015 in a single institution were retrospectively reviewed. General patient characteristics, pre- and postoperative visual status, clinical presentation, tumor characteristics, hormone production, radiological features, and procedural characteristics were evaluated for association with presenting visual signs and visual outcomes postoperatively. Suprasellar tumor extension (SSE) was graded 0 to 4 following a grading system as formulated by Fujimoto et al. Results Sixty-six (66/100) of all patients showed visual field defects (VFD) at the time of surgery, of whom 18% (12/66) were asymptomatic. VFD improved in 35 (35%) patients and worsened in 4 (4%) patients postoperatively. Mean visual acuity (VA) improved from 0.67 preoperatively to 0.84 postoperatively (p = 0.04). Nonfunctioning pituitary adenomas (NFPAs) and Fujimoto grade were independent predictors of preoperative VFD in the entire cohort (p = 0.02 and p Conclusion EETS significantly improved both VA and VFD for most patients, although a few patients showed deterioration of visual deficits postoperatively. Higher degrees of SSE and NFPA were independent predictors of favorable visual outcomes.

Histopathological grading of meningiomas is insufficient for optimal risk stratification. The purpose of the present study was to determine the prognostic value of atypical histopathological features across all nonmalignant meningiomas (World Health Organization [WHO] grade I-II).The data from 334 patients with WHO grade I (n = 275) and grade II (n = 59) meningiomas who had undergone surgical resection from 2001 to 2015 at 2 academic centers were pooled. Progression/recurrence (P/R) was determined radiographically and measured from the date of surgery.The median follow-up was 52 months. The patients were stratified by the number of atypical features: 0 (n = 151), 1 (n = 71), 2 (n = 66), 3 (n = 22), and 4 or 5 (n = 24). The risk of P/R increased with an increasing number of atypical features (log-rank test, P = 0.001). The 5-year actuarial rates of P/R stratified by the number of atypical features were as follows: 0, 16.3% (95% confidence interval [CI], 10.7-24.4); 1, 21.7% (95% CI, 12.8-35.2); 2, 28.2% (95% CI, 18.4-41.7); 3, 30.4% (95% CI, 13.8-58.7); and 4 or 5, 51.4% (95% CI, 31.7-74.5). On univariate analysis, the presence of high nuclear/cytoplasmic ratio (P = 0.007), prominent nucleoli (P = 0.007), and necrosis (P0.00005) were associated with an increased risk of P/R. On multivariate analysis, the number of atypical features (hazard ratio [HR], 1.30; 95% CI, 1.03-1.63; P = 0.03), ≥4 mitoses per high-power fields (HR, 2.45; 95% CI, 1.17-5.15; P = 0.02), subtotal resection (HR, 3.9; 95% CI, 2.5-6.3; P0.0005), and the lack of adjuvant radiotherapy (HR, 2.40; 95% CI, 1.19-4.80; P = 0.01) were associated with an increased risk of P/R.An increased number of atypical features, ≥4 mitoses per 10 high-power fields, subtotal resection, and the lack of adjuvant radiotherapy were independently associated with P/R of WHO grade I-II meningiomas. Patients with these features might benefit from intensified therapy.

Neurologic death is the most serious consequence of intracranial disease among patients with brain metastases. Identifying patients with brain metastases at increased risk of neurologic death can improve care and guide further research. We sought to delineate factors predictive of neurologic death among patients with brain metastases.We identified 1218 patients with newly diagnosed brain metastases managed at Brigham and Women's Hospital/Dana-Farber Cancer Institute from 2008-2015. Factors predictive of neurologic death were assessed via univariable and multivariable Fine and Gray competing risks regression.On multivariable analysis, neurologic death was associated with number of brain metastases (hazard ratio [HR] 1.01 per 1 metastasis increase, 95% confidence interval [CI] 1.01-1.02, P0.001) and 3 primary tumor sites (reference=non-small cell lung cancer): melanoma (HR 4.67, 95% CI 3.27-6.68, P0.001), small cell lung cancer (HR 2.33, 95% CI 1.47-3.68, P0.001), and gastrointestinal cancer (HR 2.21, 95% CI 1.28-3.82, P = 0.005). Conversely, a reduction in neurologic death was found in patients with good Karnofsky performance status (90-100 vs. 30-80, HR 0.67, 95% CI 0.48-0.95, P = 0.03) and progressive extracranial metastases at diagnosis of intracranial disease (HR 0.50, 95% CI 0.38-0.67, P = 0.001). Among patients with breast primaries, HER2+ patients displayed increased neurologic death relative to the reference of HR+/HER2- (univariable analysis only: HR 2.41, 95% CI 1.00-5.84, P = 0.05).Patients with melanoma, small cell lung cancer, gastrointestinal cancer, and HER2+ breast cancer primaries, as well as greater intracranial versus extracranial disease burden, harbor significant risk of neurologic death. Future research investigating novel intracranial approaches should focus on these populations.

PURPOSE Although the bulk of patient-generated health data are increasing exponentially, their use is impeded because most data come in unstructured format, namely as free-text clinical reports. A variety of natural language processing (NLP) methods have emerged to automate the processing of free text ranging from statistical to deep learning–based models; however, the optimal approach for medical text analysis remains to be determined. The aim of this study was to provide a head-to-head comparison of novel NLP techniques and inform future studies about their utility for automated medical text analysis. PATIENTS AND METHODS Magnetic resonance imaging reports of patients with brain metastases treated in two tertiary centers were retrieved and manually annotated using a binary classification (single metastasis v two or more metastases). Multiple bag-of-words and sequence-based NLP models were developed and compared after randomly splitting the annotated reports into training and test sets in an 80:20 ratio. RESULTS A total of 1,479 radiology reports of patients diagnosed with brain metastases were retrieved. The least absolute shrinkage and selection operator (LASSO) regression model demonstrated the best overall performance on the hold-out test set with an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.89 to 0.94), accuracy of 83% (95% CI, 80% to 87%), calibration intercept of –0.06 (95% CI, –0.14 to 0.01), and calibration slope of 1.06 (95% CI, 0.95 to 1.17). CONCLUSION Among various NLP techniques, the bag-of-words approach combined with a LASSO regression model demonstrated the best overall performance in extracting binary outcomes from free-text clinical reports. This study provides a framework for the development of machine learning-based NLP models as well as a clinical vignette of patients diagnosed with brain metastases.

Objective To assess the efficacy and toxicity of proton radiotherapy in vestibular schwannoma. Study design Retrospective chart review and volumetric MRI-analyses. Setting Tertiary referral center. Patients Vestibular schwannoma patients treated with protons between 2003 and 2018. Intervention Proton radiotherapy. Main outcome measures Tumor control was defined as not requiring salvage treatment. Progressive hearing loss was defined as a decrease in maximum speech discrimination score below the 95% critical difference in reference to the pretreatment score. Hearing assessment includes contralateral hearing and duration of follow-up. Dizziness and/or unsteadiness and facial and trigeminal nerve function were scored. Patients who had surgery prior to proton radiotherapy were separately assessed. Results Of 221 included patients, 136 received single fraction and 85 fractionated proton radiotherapy. Actuarial 5-year local control rate was 96% (95% CI 90-98%). The median radiological follow-up was 4.5 years. Progressive postirradiation speech discrimination score loss occurred in 42% of patients with audiometric follow-up within a year. Facial paresis was found in 5% (usually mild), severe dizziness in 5%, and trigeminal neuralgia in 5% of patients receiving protons as primary treatment. Conclusions Proton radiotherapy achieves high tumor control with modest side effects aside from hearing loss in vestibular schwannoma patients. Limited and heterogeneous outcome reporting hamper comparisons to the literature. Potential sequelae of radiation therapy impacting vestibular function, cognitive function, and quality of life warrant further evaluation. Subgroups that benefit most from proton radiotherapy should be identified to optimize allocation and counterbalance its costs.

BackgroundWe previously demonstrated the effectiveness of 2nd-line immune checkpoint inhibitors (ICI) for stage 4 melanoma patients.1 2In late 2015, ICI was FDA-approved and NCCN-recommended in the 1st-line setting.3 4 Here we assess the real-world effectiveness and utilization of 1st-line ICI among advanced melanoma patients following 2015.MethodsPatients newly-diagnosed with stage 4 melanoma during 2010–2018 were identified using the U.S. National Cancer Database (comprises >70% of newly-diagnosed cancers).5 Post-approval 1st-line ICI’s overall survival (OS, estimated by Kaplan-Meier techniques) and utilization were assessed for patients diagnosed in 2016–2018, using multivariable Cox and logistic regression, respectively. To account for immortal time bias in receiving ICI, we only included those patients in regression analyses who survived at least until the landmark timepoint, defined as the median time from diagnosis to ICI initiation (49 days).1 2 The more conservative 75th percentile diagnosis-to-ICI-initiation landmark timepoint (80 days) was also evaluated. Analyses were adjusted for patient, tumor, treatment, socioeconomic, and care setting characteristics.ResultsAmong 14,912 stage 4 melanoma patients, 1st-line immunotherapy utilization increased from 8.4% in 2010 to 39.2% in 2015, and 57.9% in 2018.(Figure 1) Altogether, median OS improved from 8.0 mos (95%CI=7.3–8.8) in 2010 to 16.1 mos (95%CI=14.0–18.5) in 2017. For patients diagnosed in 2016+ who survived at least until the landmark timepoints, OS improved with 1st-line ICI (median OS=33.1 mos, 95%CI=29.4–40.5; vs just 13.6 mos for no ICI, 95%CI=12.1–16.1; HR=0.58, 99%CI=0.50–0.68; padjAbstract 246 Figure 1(A) The percent of stage 4 melanoma patients diagnosed each year who received 1st-line immune checkpoint inhibitor (ICI), with stratification by (B) brain or lung metastatic involvement, and (C) treating hospital type.Abstract 246 Table 1Multivariable Cox regression analysis of overall survival among stage 4 melanoma patients in 2016+. To account for immortal time bias, landmark timepoints were utilized, defined by the median (i.e. 49d; panels A, C, E) and 75th percentile (i.e. 80d; panels B, D, F) time from diagnosis to ICI initiation. Patients had to survive at least as long as the landmark timepoint to be included in the analysis. Results are shown for all stage 4 patients, as well as those with brain or lung metastases. p values are only displayed for the primary association of interest.ICI = immune checkpoint inhibitor. HR = hazard ratio. CI = confidence interval. LN = lymph node.Abstract 246 Table 2Multivariable logistic regression analysis of 1st-line immune checkpoint inhibitor (ICI) receipt among stage 4 melanoma patients in 2016+. To account for bias due to early mortality, landmark timepoints were utilized, defined by the median (i.e. 49d) and 75th percentile (i.e. 80d) time from diagnosis to ICI initiation. Patients had to survive at least as long as the landmark timepoint to be included in the analysis. Results are shown for all stage 4 patients, as well as those with brain or lung metastases. Variables that demonstrate a significant association with ICI receipt are highlighted in yellow.ICI = immune checkpoint inhibitor. OR = odds ratio. CI = confidence interval. LN = lymph node.Abstract 246 Figure 2Overall survival associated with 1st-line immune checkpoint inhibitors (ICI) for stage 4 melanoma patients diagnosed after 2015 (A-B), including patients with brain (C-D) and lung metastases (E-F). To account for immortal time bias, landmark timepoints were utilized, defined by the median (i.e. 49d; panels A, C, E) and 75th percentile (i.e. 80d; panels B, D, F) time from diagnosis to ICI initiation. Patients had to survive at least as long as the landmark timepoint to be included in the analysis.ConclusionsFollowing FDA-approval in 2015, 1st-line ICI was associated with dramatic improvements in OS for stage 4 melanoma patients—including those with brain or lung metastases. As of 2018, 42% of patients still weren’t receiving 1st-line ICI in the U.S.—particularly patients who were underinsured, from the poorest quartile of households, or managed at community hospitals—suggesting that disparities exist in guideline-recommended 1st-line ICI utilization for advanced melanoma patients.ReferencesDobry A, Zogg C, Hodi F, Smith T, Ott P, Iorgulescu JB. Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies. Cancer Immunol Immunother 2018 December;67(12):1833–1844.Iorgulescu JB, Harary M, Zogg C, Ligon K, Reardon D, Hodi F, Aizer A, Smith T. Improved risk-adjusted survival for melanoma brain metastases in the era of checkpoint blockade immunotherapies: results from a national cohort. Cancer Immunol Res 2018 September;6(9):1039–1045.Beaver JA, Theoret MR, Mushti S, He K, Libeg M, Goldberg K, Sridhara R, McKee AE, Keegan P, Pazdur R. FDA approval of nivolumab for the first-line treatment of patients with BRAFV600 wild-type unresectable or metastatic melanoma. Clin Cancer Res 2017 July 15;23(14):3479–3483National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Melanoma, Version 1.2016.Boffa DJ, Rosen JE, Mallin K, Loomis A, Gay G, Palis B, Thoburn K, Gress D, McKellar DP, Shulman LN, Facktor MA, Winchester DP. Using the national cancer database for outcomes research: a review. JAMA Oncol 2017 December 1;3(12):1722–1728.

Steroids are commonly used to treat peritumoral edema and increased intracranial pressure in patients with brain tumors. Despite widespread use of steroids, relatively little evidence is available about their optimal perioperative dosing scheme. This study aimed to increase insight into practice variation of perioperative steroid dosing and tapering schedules used in the neurosurgical community.An electronic survey comprising 27 questions regarding steroid dosing, tapering schedules, and adverse events was administered to neurosurgeons between December 6, 2019, and June 1, 2020. The survey was distributed through the European Association of Neurosurgical Societies and social media platforms. Collected data were assessed for quantitative and qualitative analysis.The survey obtained 175 responses from 55 countries across 6 continents, including 30 from low- or middle-income countries; 152 (87%) respondents completed all questions. Of respondents, 130 (80%) indicated prescribing perioperative steroids. Reported doses ranged from 2 to 64 mg/day in schedules ranging from 1 to 4 times daily. The most prescribed steroid was dexamethasone in doses of 16 mg/day (n = 49; 31%), 12 mg/day (n = 31; 20%), and 8 mg/day (n = 18; 12%). No significant association was found between prescribed dose and physician and institutional characteristics.Steroids are commonly prescribed perioperatively in patients with brain tumors. However, there is great practice variation in dosing and schedules among neurosurgeons. Future investigation in a prospective and preferably randomized manner is needed to identify an optimal dosing scheme and implement international/national guidelines for steroid use.

OBJECTIVELoss of pituitary function due to nonfunctional pituitary adenoma (NFPA) may be due to compression of the pituitary gland. It has been proposed that the size of the gland and relative perioperative gland expansion may relate to recovery of pituitary function, but the extent of this is unclear. This study aims to assess temporal changes in hormonal function after transsphenoidal resection of NFPA and the relationship between gland reexpansion and endocrine recovery.METHODSPatients who underwent endoscopic transsphenoidal surgery by a single surgeon for resection of a nonfunctional macroadenoma were selected for inclusion. Patients with prior pituitary surgery or radiosurgery were excluded. Patient characteristics and endocrine function were extracted by chart review. Volumetric segmentation of the pre- and postoperative (≥ 6 months) pituitary gland was performed using preoperative and long-term postoperative MR images. The relationship between endocrine function over time and clinical attributes, including gland volume, were examined.RESULTSOne hundred sixty eligible patients were identified, of whom 47.5% were female; 56.9% of patients had anterior pituitary hormone deficits preoperatively. The median tumor diameter and gland volume preoperatively were 22.5 mm (interquartile range [IQR] 18.0–28.8 mm) and 0.18 cm3 (IQR 0.13–0.28 cm3), respectively. In 55% of patients, endocrine function normalized or improved in their affected axes by median last clinical follow-up of 24.4 months (IQR 3.2–51.2 months). Older age, male sex, and larger tumor size were associated with likelihood of endocrine recovery. Median time to recovery of any axis was 12.2 months (IQR 2.5–23.9 months); hypothyroidism was the slowest axis to recover. Although the gland significantly reexpanded from preoperatively (0.18 cm3, IQR 0.13–0.28 cm3) to postoperatively (0.33 cm3, IQR 0.23–0.48 cm3; p < 0.001), there was no consistent association with improved endocrine function.CONCLUSIONSRecovery of endocrine function can occur several months and even years after surgery, with more than 50% of patients showing improved or normalized function. Tumor size, and not gland volume, was associated with preserved or recovered endocrine function.

Background The prevalence of pain among patients undergoing radiation therapy (RT) is not well described. Objectives The purpose of this study was to assess the prevalence and management of pain in patients undergoing RT. Methods 94 patients undergoing RT were surveyed at two time points during the course of their treatment. Patients reported on pain, fatigue, nausea, headache, and depressive symptoms, as well as on the use of pharmacologic and nonpharmacologic or alternative methods for symptom management. Findings The mean severity of pain did not change significantly between the first week of RT and the final week. Severity of pain was associated with worse fatigue, nausea, headaches, and depressive symptoms, providing opportunities for providers to address multiple co-occurring symptoms. Rates of opioid and marijuana use remained similar between the two time points. More than half of the patients reported use of at least one nonpharmacologic method for pain management, with use increasing during the course of RT.

Background Radiotherapy-associated cardiac toxicity studies in patients with locally advanced non–small cell lung cancer (NSCLC) have been limited by small sample size and nonvalidated cardiac endpoints. Objectives The purpose of this analysis was to ascertain whether cardiac radiation dose is a predictor of major adverse cardiac events (MACE) and all-cause mortality (ACM). Methods This retrospective analysis included 748 consecutive locally advanced NSCLC patients treated with thoracic radiotherapy. Fine and Gray and Cox regressions were used to identify predictors for MACE and ACM, adjusting for lung cancer and cardiovascular prognostic factors, including pre-existing coronary heart disease (CHD). Results After a median follow-up of 20.4 months, 77 patients developed ≥1 MACE (2-year cumulative incidence, 5.8%; 95% confidence interval [CI]: 4.3% to 7.7%), and 533 died. Mean radiation dose delivered to the heart (mean heart dose) was associated with a significantly increased risk of MACE (adjusted hazard ratio [HR]: 1.05/Gy; 95% CI: 1.02 to 1.08/Gy; p Conclusions Despite the competing risk of cancer-specific death in locally advanced NSCLC patients, cardiac radiation dose exposure is a modifiable cardiac risk factor for MACE and ACM, supporting the need for early recognition and treatment of cardiovascular events and more stringent avoidance of high cardiac radiotherapy dose.

BACKGROUND Certain patients with intermediate-risk prostate cancer (PCa) may be appropriate candidates for active surveillance (AS). In the current study, the authors sought to characterize AS use and early mortality outcomes for patients with intermediate-risk PCa in the United States. METHODS The novel Surveillance, Epidemiology, and End Results Active Surveillance/Watchful Waiting database identified 52,940 men diagnosed with National Comprehensive Cancer Network intermediate-risk PCa (cT2b-c, Gleason score of 7, or a prostate-specific antigen level of 10-20 ng/mL) and actively managed (AS, radiotherapy, or radical prostatectomy) from 2010 through 2015. The Cuzick test assessed AS time trends, and logistic multivariable regression characterized features associated with AS. Fine-Gray and Cox modeling determined PCa-specific mortality (PCSM) and overall survival, respectively. RESULTS The rate of AS increased from 3.7% in 2010 to 7.3% in 2015, and from 7.2% to 11.7% among men aged ≥70 years. Among men with favorable and unfavorable intermediate-risk disease, the use of AS increased from 7.2% to 14.9% and from 2.2% to 3.8%, respectively (all P value for trend

Patients undergoing cranial irradiation are at high risk for development of subsequent pituitary deficiencies. Patients with meningiomas can expect to live many years after treatment and are therefore particularly vulnerable to long-term sequalae of radiation therapy (RT). The purpose of this study was to determine the rates and timing of onset of pituitary dysfunction across each hypothalamic-pituitary axis in patients with meningiomas in the sellar region.Data from 74 patients with meningiomas in the sellar or perisellar region who underwent RT between 2001 and 2017 at a single academic center were analyzed. Dose-volume histograms were generated to determine the dose of radiation to the pituitary gland. Pituitary function tests were evaluated before and after completion of RT.There was a 20% risk for new hypopituitarism across any hypothalamic-pituitary axis after RT at a median follow-up of 43 months. Identified rates of dysfunction across each axis were 24% for thyroid and adrenal, 19% for growth hormone, and 10% for gonadal. Median time to develop deficiencies ranged from 11 months for growth hormone deficiency to 32 months for adrenal insufficiency. Deficiencies were likely to be correlated, with increased risk for thyroid dysfunction in patients with adrenal, gonadal, or prolactin deficiencies (P .05). On univariate analysis, mean dose to the pituitary gland and male sex were associated with increased risk for post-RT thyroid deficiency (P = .01 and P = .004, respectively). There was no difference in rates of hypothyroidism after protons compared with photons (P = .14).Cranial irradiation for sellar meningiomas carries a risk for subsequent hypopituitarism that appears to be dose dependent and may occur years after completion of RT. Growth hormone deficiency and gonadal dysfunction were likely underestimated here secondary to a lack of routine testing. Given the favorable tumor prognosis in this patient population, early and long-term endocrine follow-up is warranted.

Brain metastases from breast cancer are frequently managed with brain-directed radiation but the impact of subtype on intracranial recurrence patterns after radiation has not been well-described. We investigated intracranial recurrence patterns of brain metastases from breast cancer after brain-directed radiation to facilitate subtype-specific management paradigms. We retrospectively analyzed 349 patients with newly diagnosed brain metastases from breast cancer treated with brain-directed radiation at Brigham and Women’s Hospital/Dana-Farber Cancer Institute between 2000 and 2015. Patients were stratified by subtype: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−), HER2+ positive (HER2+), or triple-negative breast cancer (TNBC). A per-metastasis assessment was conducted. Time-to-event analyses were conducted using multivariable Cox regression. Of the 349 patients, 116 had HR+/HER2− subtype, 164 had HER2+ subtype, and 69 harbored TNBC. Relative to HR+/HER2− subtype, local recurrence was greater in HER2+ metastases (HR 3.20, 95% CI 1.78–5.75, p

Background Brain metastases commonly manifest in patients with cancer, with ∼20%–50% presenting with 1 intracranial lesion. Among patients with 1, small brain metastasis and controlled or absent extracranial disease, it remains unclear whether aggressive intracranial management using neurosurgical resection plus cavity stereotactic radiosurgery/stereotactic radiotherapy (SRS/SRT) rather than SRS/SRT alone is beneficial. In patients with controlled or absent extracranial disease and 1 brain metastasis ≤2 cm in size, we evaluated the effect of surgery plus SRS/SRT compared with SRS/SRT on oncologic outcomes, including overall survival. Methods We retrospectively identified 86 patients with controlled or absent extracranial disease and 1 brain metastasis ≤2 cm in size who had been treated from 2000 to 2015 at our institution. We examined differences in the rates of local and distant failure, use of salvage treatment, and other oncologic outcomes, including all-cause mortality. Results The baseline characteristics were similar between the 2 cohorts. The median follow-up period for the surviving patients was 38 months. On multivariable analysis, surgical resection plus cavity SRS/SRT was associated with a lower risk of all-cause mortality (hazard ratio, 0.44; 95% confidence interval, 0.19–1.00; P = 0.05) compared with SRS/SRT alone. The 1- and 2-year rates of overall survival were 100% and 88% versus 74% and 52% for surgery plus cavity SRS/SRT versus SRS/SRT alone, respectively. Conclusions Aggressive, local therapy, including neurosurgical resection, might benefit patients with 1 brain metastasis in the context of controlled or absent systemic disease, even if the lesion in question is small. Further studies are needed to evaluate these associations.

Background Up to one-third of patients with localized Ewing sarcoma (ES) develop recurrent disease, but current biomarkers do not accurately identify this high-risk group. Therefore, the objective of this study was to determine the utility of mutational burden in predicting outcomes in patients with localized ES. Methods Clinical and genomic data from 99 patients with ES, of whom 63 had localized disease at diagnosis, were obtained from the cBioPortal for Cancer Genomics. Genomic data included the type and number of somatic mutations using cBioPortal mutation calling. Primary endpoints were overall survival (OS) and the time to progression (TTP). Results Patients had a median number of 11 somatic mutations. Patients were stratified according to whether they had a lower or higher mutational burden if they had ≤11 or >11 mutations, respectively. Higher mutational burden was significantly associated with inferior OS and TTP, a finding that was confirmed by univariate and multivariable analyses. In patients who had localized disease at diagnosis, higher mutational burden was the only variable significantly associated with inferior OS and TTP. The presence of a mutation in either stromal antigen 2 (STAG2) or tumor protein 53 (TP53), both of which were correlated previously with shorter OS in patients with ES, were significantly associated with higher mutational burden. Upon stratifying patients who had localized disease based on a standard panel of cancer genes, higher risk stratification was correlated significantly with inferior TTP and trended toward significance with inferior OS. Conclusions Patients who have localized ES and a higher mutational burden have inferior OS and TTP compared with those who have lower mutation burden. The current findings suggest that the somatic mutation burden can be used to better risk stratify these patients and to guide clinical decision making.

Pituitary prolactinomas in women often lead to amenorrhea, galactorrhea, or infertility. The purpose of this study was to evaluate the effectiveness of transsphenoidal surgery (TSS) in restoring fertility in women with proloactinomas. A systematic search of the literature was conducted in accordance with PRISMA guidelines through 6/13/2017. PubMed, Embase, and Cochrane databases were utilized to select studies reporting on patients with pituitary prolactinomas removed via TSS. Outcomes extracted included pre- and post-operative rates of menses, lactation, and fertility. Pooled effect estimates were calculated using random-effects. After removal of duplicates, 900 articles remained, of which 14 were meta-analyzed. The mean difference between pre- and post-operative prolactin level was 186.9 (95% CI = 133.7, 240.1; I2 = 69.9%; P-heterogeneity 0.05). No evidence of publication bias was seen using Begg's and Egger's tests (all P > 0.05). Transsphenoidal surgery appeared to improve fertility measures in women with pituitary prolactinomas.

Brain metastases affect a significant percentage of patients with advanced extracranial malignancies. Yet, the incidence of brain metastases remains poorly described, largely due to limitations of population-based registries, a lack of mandated reporting of brain metastases to federal agencies, and historical difficulties with delineation of metastatic involvement of individual organs using claims data. However, in 2016, the Surveillance Epidemiology and End Results (SEER) program released data relating to the presence vs absence of brain metastases at diagnosis of oncologic disease. In 2020, studies demonstrating the viability of utilizing claims data for identifying the presence of brain metastases, date of diagnosis of intracranial involvement, and initial treatment approach for brain metastases were published, facilitating epidemiologic investigations of brain metastases on a population-based level. Accordingly, in this review, we discuss the incidence, clinical presentation, prognosis, and management patterns of patients with brain metastases. Leptomeningeal disease is also discussed. Considerations regarding individual tumor types that commonly metastasize to the brain are provided.

Background Nonmalignant vascular anomalies (VA) comprise a heterogeneous spectrum of conditions characterized by aberrant growth or development of blood and/or lymphatic vessels and can cause significant morbidity. Little is known about outcomes after radiotherapy in pediatric and young adult patients with nonmalignant VA. Methods Thirty patients who were diagnosed with nonmalignant VA and treated with radiotherapy prior to 2017 and before the age of 30 were identified. Clinical and treatment characteristics and outcomes were recorded. Results Median age at first radiotherapy was 15 years (range 0.02-27). Median follow-up from completion of first radiotherapy was 9.8 years (range 0.02-67.4). Lymphatic malformations (33%), kaposiform hemangioendothelioma (17%), and venous malformations (17%) were the most common diagnoses. The most common indication for first radiotherapy was progression despite standard therapy and/or urgent palliation for symptoms (57%). After first radiotherapy, 14 patients (47%) had a complete response or partial response, defined as decrease in size of treated lesion or symptomatic improvement. After first radiotherapy, 27 (90%) required additional treatment for progression or recurrence. Long-term complications included telangiectasias, fibrosis, xerophthalmia, radiation pneumonitis, ovarian failure, and central hypothyroidism. No patient developed secondary malignancies. At last follow-up, three patients (10%) were without evidence of disease, 26 (87%) with disease, and one died of complications (3.3%). Conclusions A small group of pediatric and young adult patients with nonmalignant, high-risk VA experienced clinical benefit from radiotherapy with expected toxicity; however, most experienced progression. Prospective studies are needed to characterize indications for radiotherapy in VA refractory to medical therapy, including targeted inhibitors.

INTRODUCTION Few data exist regarding the epidemiology of brain metastases (BMs) in adolescent and young adult (AYA) patients. Herein we use national cancer registry data to dissect their epidemiology and compare to the adult population. METHODS AYA patients (15 ≤ age ≤ 39) who newly presented with a BM between 2010 and 2017 were identified in the National Cancer Database (comprising >70% of all newly-diagnosed cancers in the U.S.). The epidemiology of BMs was analyzed by primary cancer of origin, and compared between AYA and adult patients. Overall survival was analyzed with multivariable Cox regression. RESULTS 2,773 AYA patients presenting with BMs were identified (98% with histopathological diagnosis), compared to 156,103 adult patients (94% with histopathological diagnosis). Whereas 39.6% of newly-diagnosed brain tumors with histopathological confirmation were BMs in adults, BMs represented only 5.8% of such tumors in AYA patients. Additionally, the distributions of primary cancer types differed substantially between adults and AYA patients: notably, NSCLC dominated in adults (64.2%) vs representing only 31.6% of BMs in AYA patients. AYA patients were more likely to present with BMs from melanoma (13.0% of AYA BMs vs 3.7% in adult), soft tissue (4.5% vs 0.3%), testicular (in males 26.2% vs 0.1%), and breast (in females 29.5% vs 7.8%) primaries. Among breast BMs in females, AYA patients were less likely to have HR+/HER2- primaries (40.2% vs 47.8%) and more likely to have HER2+ (25.2% vs 20.1%) and triple positive (11.1% vs. 9.8%) primaries than adults. Overall survival was significantly longer for AYA patients with BMs (HR=0.61 compared to adult patients, 95%CI:0.58-0.64, p< 0.001) even after adjusting for primary cancer type, patient sex. CONCLUSIONS The epidemiology and cancer types of BMs in AYA patients differ substantially from adult patients. Future research aimed at understanding the unique differences in pathophysiology and outcomes of BMs in AYA patients is warranted.

Introduction Primary intracranial germ cell tumors (GCTs) appear to be more prevalent among pediatric patients in eastern Asia than in the U.S. Herein we use cancer registry data to evaluate whether GCT prevalence differs by race/ethnicity among U.S. pediatric patients. Methods Pediatric patients (age≤14) presenting between 2004–2017 with a primary intracranial GCT were identified by ICD-O-3 histological and topographical coding from the National Cancer Database (comprising >70% of cancers newly-diagnosed cancers in the U.S.), and categorized by NICHD age stages. Patients’ age, sex, race/ethnicity, and overall survival, and tumor location and size were evaluated. Results 889 pediatric patients with primary intracranial GCTs were identified, which were overwhelmingly male (64.8%) and pure germinomas (64.0%). Non-germinomatous (24.5%) and mixed (11.5%) tumor types were in the minority. Overall, primary GCTs comprised 4.9% of intracranial tumors in pediatric males and 2.9% of intracranial tumors in pediatric females. Asian/Pacific Islander pediatric patients in the U.S. had a notably higher prevalence of GCTs: among Asian/Pacific Islander males, 10.6% of all brain tumors were GCTs, compared to only 4.5% in White non-Hispanic patients, 2.8% in Black non-Hispanic patients, and 6.0% in Hispanic patients. Despite the much lower prevalence of GCTs among female patients overall, this predominance also persisted for Asian/Pacific Islander females, among whom 7.5% of brain tumors were GCTs, compared to only 2.5% in White non-Hispanic patients, 2.4% in Black non-Hispanic patients, and 4.1% in Hispanic patients. Overall, 9.4% of pediatric primary intracranial GCTs occurred in patients of Asian/Pacific Islander race/ethnicity, in contrast to 4.0% of diffuse astrocytic/oligodendroglial tumors, 2.8% of other astrocytic tumors, or 4.6% of embryonal tumors. Conclusions Primary intracranial GCTs affect a substantially larger proportion of both male and female pediatric patients of Asian/Pacific Islander race/ethnicity in the United States.

BACKGROUND Management of advanced NSCLC has been transformed by PD-1/PD-L1 immune checkpoint inhibitors (ICI), with FDA approvals in 2015 (second-line) and 2016 (first-line). Because patients with brain metastases (BMs) were disproportionately excluded from the pioneering trials, herein we evaluated the overall survival (OS) associated with ICI in NSCLC BMs nationally. METHODS Patients newly-diagnosed with stage 4 NSCLC, including BMs, from 2010–2016 were identified from the National Cancer Database (comprising >70% of all newly-diagnosed cancers in the U.S.) Post-approval, median time from diagnosis to ICI was 58days, and this timepoint was selected for all landmark survival analyses (logrank test and multivariable Cox regression) and for multivariable logistic regression to identify predictors of ICI utilization. RESULTS 50,858 patients presented with advanced NSCLC that involved the brain: representing 27.6% of all newly-diagnosed stage 4 cases. Following initial FDA approvals in 2015, ICI rates for BM patients rose from 7.2% in 2015 to 12.7% in 2016. OS for NSCLC BMs for patients diagnosed post-approval (median 6.3 months, 95%CI: 6.0–6.6) was substantially better than those diagnosed pre-approval (median 5.5 months, 95%CI: 5.4–5.7, p< 0.001) and, in fact, than those diagnosed in 2014 (median 5.9 months, 95%CI: 5.6–6.1, p=0.002). Among patients diagnosed post-approval, ICI receipt demonstrated substantially improved OS in landmark survival analyses (median 13.8 months, 95%CI: 12.2–15.1; vs. 8.5 months, 95%CI: 8.3–8.9, p< 0.001); benefits which persisted in multivariable landmark survival analyses (HR 0.83, 95%CI: 0.71–0.96, p=0.02), independent of patient characteristics, other therapies, and extracranial disease. For patients diagnosed post-approval, who reached the landmark timepoint, ICI receipt was independent of patient demographics, socioeconomic status, and hospital type—with the exception of Medicaid-insured patients, who were less likely than privately-insured patients to receive ICI (OR 0.77, 95%CI: 0.60–0.97, p=0.03). CONCLUSIONS Nationally, the dramatic OS benefits of ICIs for advanced NSCLC were also demonstrated for patients with BMs.

INTRODUCTION Up to 10% of cancer patients experience spinal cord compression from metastatic disease. Palliation and local control were traditionally pursued with conventional external beam radiotherapy (cEBRT), but advancements in image-guidance and intensity-modulation for stereotactic body radiotherapy (SBRT) have dramatically changed the management of these lesions. Herein we evaluate the national practice patterns and outcomes associated with cEBRT vs. SBRT. METHODS U.S. patients newly diagnosed with metastatic cancer necessitating RT to the spine were identified from the National Cancer Database (2004-2016), stratified by RT modality and cancer type, and evaluated using multivariable logistic regression and Cox proportional hazards. RESULTS 34,759 U.S. patients required spinal RT within 3 months of initial stage 4 cancer presentation, primarily for lung adenocarcinoma (25%), lung small cell carcinoma (14%), and prostatic (12%) metastases. Patients overwhelming received cEBRT (30Gy/10; 50%), followed by hypo-fractionated SBRT (15-30Gy/2-6; 11%) and single-fraction SBRT (i.e. stereotactic radiosurgery, SRS; 15-24Gy/1; 0.9%); whereas 38% received another regimen (e.g. 30-37.5Gy/12-15 or 40Gy/20). From 2004→2016, the rates of single-fraction SRS (0.4→1.9%) and hypo-fractionated SBRT (13.1→23.6%) increased, whereas cEBRT (86.5→74.4%) decreased. SBRT was significantly more likely to be utilized at academic hospitals as compared to cEBRT (OR 0.57; 95% CI: 0.49-0.66; p< 0.01). SBRT was more likely utilized for elderly or high comorbidity patients and varied across cancer types. Survival analysis indicated that across all cancer types, single-fraction SRS, was independently associated with improved overall survival compared to cEBRT (HR 1.51; 95%CI: 1.31-1.74; p< 0.01) after adjusting for patient characteristics, care setting, tumor type and systemic treatment. CONCLUSIONS Through analysis of cancer registry data, we found that practice patterns of RT for spinal metastases have been evolving nationally, with an increase in the use of SBRT. Single-fraction SBRT was associated with improved adjusted OS. Notably, we found that utilization of SBRT lags in the community setting.