Update in the classification and the role of intra‐arterial stenting in the management of carotid body paragangliomas

Abstract

Background

To review the Shamblin classification of carotid body paragangliomas (CBPs) and the role of intra‐arterial stenting in their surgical management.

Methods

Retrospective case series of 20 patients with 28 CBPs that were surgically resected at our center. Intra‐arterial stenting was performed in Shamblin II and II classes.

Results

The mean follow‐up was 47.8 months. Five (17.9%) tumors were Shamblin class I, 15 (53.6%) were class II, and 8 (28.6%) were class III. Thirteen (68.4%) CBPs were associated with other paragangliomas. The internal carotid artery (ICA) was stented preoperatively in eight (28.6%) cases and occluded in four (14.3%) cases. The tumor extended to the jugular foramen in six cases (21.4%). Intraoperatively, there was an ICA injury in one case of Shamblin II CBP in the present era.

Conclusions

The proposed classification enables the clinician to plan the management of the ICA and the right approach. Stenting of the ICA gives a chance for complete tumor removal with arterial preservation.

http://bit.ly/2GuTxuS

Adenoid cystic carcinoma with high-grade transformation forming spindle cell component of the submandibular gland

Publication date: Available online 16 February 2019

Source: Auris Nasus Larynx

Author(s): Masaru Miyazaki, Mikiko Aoki, Kaori Koga, Makoto Hamasaki, Yoshikazu Sugiyama, Kensuke Midorikawa, Daisuke Hamatake, Michio Masaki, Yasushi Takamatsu, Akinori Iwasaki, Toshifumi Sakata, Toshitaka Nagao, Kazuki Nabeshima

Abstract

Adenoid cystic carcinoma (AdCC) with high-grade transformation (AdCC-HGT) is rare, and AdCC-HGT with spindle cell component is particularly rare. The patient was a 65-year-old man with a 5 cm sized swelling of the right submandibular gland. Submandibular sialoadenectomy was performed. Histopathological findings mainly showed conventional AdCC, and minorly showed two other components: (1) the pleomorphic component, a proliferation of atypical pleomorphic epithelial cells forming solid or small clusters and accompanied by necrosis; (2) the spindle cell component, containing atypical spindle cells invading the stroma. Postoperative chemoradiotherapy was performed. Multiple right lung nodular lesions were found on the contrast-enhanced chest CT one month after the surgery. Thoracoscopic pulmonary resection was performed. The lung tumors exhibited a proliferation of atypical spindle cells, accompanied by necrosis. We considered that the spindle cell component of the AdCC-HGT of the submandibular gland developed lung metastases. The patient died seven months after submandibular sialoadenectomy due to respiratory failure. Although rare, our case highlights the importance of recognising spindle cell components in conventional AdCC; even if the area is small, these high-grade transformation areas can metastasise and become prognostic factors.

http://bit.ly/2tqq38Q

Whole-exome sequencing identification of a novel splicing mutation of RUNX2 in a Chinese family with cleidocranial dysplasia

Publication date: Available online 15 February 2019

Source: Archives of Oral Biology

Author(s): Tingting Zhang, Wu Jing, Xiaoxue Zhao, Feifei Hou, Tengfei Ma, Huijuan Wang, Xu Zhang, Xiangyu Zhang

Abstract

Objectives

Cleidocranial dysplasia (CCD) is a congenital autosomal dominant skeletal disease characterized by multiple craniofacial and dental anomalies. Here, we investigated mutation of the runt-related transcription factor 2 (RUNX2) gene, which is considered responsible for most instances of CCD in patients, in a Chinese family with CCD.

Methods

Genomic DNA was extracted from the peripheral blood lymphocytes of all participants, and mutation analysis was performed using whole-exome and Sanger sequencing. Biophysical predictions of the altered protein were analyzed using various bioinformatics tools, and direct sequencing via reverse transcription polymerase chain reaction (PCR) was performed for functional analysis of the mutation. To determine the function of the mutated protein, expression of RUNX2 and integrin-binding sialoprotein (IBSP) was investigated via quantitative PCR.

Results

We identified a novel splicing mutation (c.581–9 T > G) in all affected members, with this RUNX2 mutation incorporating in a new splice site to replace the canonical splice site, thereby resulting in insertion of an 8-bp fragment within the terminal exon 5 splice-acceptor site and premature translation termination. qPCR results confirmed attenuated RUNX2 expression and IBSP overexpression in the peripheral blood lymphocytes of patients.

Conclusions

These results suggested that the newly identified splice-site mutation (c.581–9 T > G) in RUNX2 was responsible for CCD in this family through its alteration of RUNX2 activity and upregulated IBSP levels. These findings extend the mutational spectrum of the RUNX2 gene and might contribute to genetic diagnosis and counseling of families with CCD.

http://bit.ly/2SBexGF

Home environment of infants with risk indicators for hearing loss tends to be less stimulating

Publication date: Available online 16 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Danielle Mendonça Araujo, Denise Castilho Cabrera Santos, Maria Cecília Marconi Pinheiro Lima

Abstract

Objective

To verify the home opportunities to the motor development offered to infants with and without risk indicators for hearing loss (RIHL).

Methods

Observational transversal study was done with infants between 8 and 10 months, being 77 with RIHL (Study Group-SG) and 77 without RIHL (Control Group-CG) The instrument used to characterize the sample and obtain information about the home affordances was the questionnaire Affordances in the Home Environment for the Motor Development - Infant Scale (AHEMD-IS). The results of the AHEMD-IS between the groups were compared using the Mann-Whitney and Chi-Squared tests. The significance test adopted for the study was 5%.

Results

Absolute values in the frequency of homes considered "moderately adequate" and "less than adequate" were greater in the SG in the most part of the categories, except the item Toys for Fine Motricity. It was possible to observe a statistically significant difference in the Total Score of the groups (p-value = 0.01346). Even with better results when compared with the SG, the number of homes of the CG group with affordances below expected is more than half of the sample.

Conclusions

It was possible to verify that home of infants with risk indicators for hearing loss have statistically less affordances when compared to the homes of infants without the indicators. The results alert us to the need of orientation to the infant's responsible/caretakers regarding to the importance of a favorable environment with stimulation of the infant motor development.

http://bit.ly/2TRuxAT

Annual hearing screening in girls with Turner Syndrome: results from the first three years in Glasgow

Publication date: Available online 15 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Haytham Kubba, Kerrie McAllister, Karen Hunter, Avril Mason

Abstract

Background

Hearing loss is prevalent in girls with Turner Syndrome (TS). A number of cross-sectional studies have confirmed that conductive hearing loss due to middle ear disease and permanent, progressive sensorineural hearing loss are both very common and often unrecognised in TS. Hearing screening has been suggested by many authors and is recommended in some recent national audiology guidelines (every 3-5 years in an international consensus statement, every 1-2 years in the USA and every year in the UK). The effectiveness of such regular hearing screening has not been assessed before.

Study aims and methods

In January 2016 we began a programme of annual hearing screening for all girls attending the West of Scotland TS clinic. We have collected data on age, karyotype, ear and hearing symptoms, otoscopy findings, audiometric test results and subsequent outcomes for the first three years of our programme. Our aim is to assess whether this screening programme is an effective use of resources, with a worthwhile rate of detecting new otological problems and without an excessive additional workload for the audiology department.

Results

Twenty-six girls participated in the screening programme and 8 of these had no hearing issues or ear abnormalities at any time over the 3 years. Two girls had cholesteatoma, 4 had tympanic membrane retractions and/or perforations, and 9 had OME (of which 6 were transient and 3 persistent, with 2 of these requiring treatment). One cholesteatoma, one perforation and one persistent OME were already known about but all other diagnoses were new as a result of the screening programme. Five girls have persistent conductive hearing loss (plus another 6 who had a transient episode of conductive loss due to middle ear fluid) and 6 have some degree of sensorineural hearing loss (3 purely sensorineural, 3 mixed). At the time that a hearing loss was diagnosed, the parents had concerns about the hearing in 4 cases and no concerns in 12. Six girls have been fitted with hearing aids since we started the screening programme, each for different indications (sensorineural hearing loss in two cases, and one case each of persistent OME, post cholesteatoma surgery, tympanic membrane perforation and unilateral tympanic membrane retraction respectively). Two girls have had ear surgery as a result of referral from the programme (one for ventilation tubes, one for cholesteatoma).

Conclusions

The screening programme has picked up ear disease in 69% of girls with TS with only a small additional workload for the audiology department. The ongoing detection of new problems in the second and third years of the programme attests to the value of continued regular hearing screening for girls with TS.

http://bit.ly/2BypGgT

Childhood hearing loss: Impact on parents and family life

Publication date: Available online 15 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Jesper Dammeyer, Anja Toft Hansen, Kathryn Crowe, Marc Marschark

Abstract

Background

Studies investigating the impact of having a child with hearing loss on the lives of parents and families have shown divergent results. Where some studies have reported that childhood hearing loss is associated with parental mental health problems, such as depression and stress, other studies report no impact on parental mental health and/or wellbeing.

Objective

The aim of this study was to examine the association between child-related variables—degree of hearing loss, additional disabilities, sign language abilities, cochlear implants (CI), externalizing and internalizing emotional and behavioral difficulties measured by the Strength and Difficulties Questionnaire (SDQ)—and parent-related variables—parents living together, parents' mental health, spouse activities without children, and parents' experience of the child as being a burden for the family.

Method

Data of 257 parents of children with hearing loss from a national survey were included.

Results

Only 18% of the children with hearing loss did not live with both parents, a figure significantly lower than that of the general population. The child variables of degree of hearing loss, having a CI or not, and sign language ability were not significantly associated with any of the parent variables investigated. The child having a disability in addition to hearing loss was found to be significantly associated with the frequency of spouses engaging in activities without children and reports that the child was a burden for the family. Both higher externalizing and internalizing scores on the SDQ were significantly associated with parental mental health problems, frequency of spouse activities without children, and the degree to which the child's difficulties were experienced as a burden for the family.

Conclusion

Children's hearing loss, per se, was found not to be significantly related to several key parent and family variables. However, children having additional disabilities and behavioral and emotional difficulties were significant with parent and family variables. This study thus underlines the need for further studies concerning relationships among factors related to childhood hearing loss and various family factors in order to better understand their impact on child development and family life.

http://bit.ly/2TRunJN

Survival outcomes after treatment of cancer of the oral cavity (1985–2015)

Publication date: March 2019

Source: Oral Oncology, Volume 90

Author(s): Daniella Karassawa Zanoni, Pablo H. Montero, Jocelyn C. Migliacci, Jatin P. Shah, Richard J. Wong, Ian Ganly, Snehal G. Patel

Abstract

Objectives

To present treatment results of oral squamous cell carcinoma (OSCC) at a tertiary cancer care center from 1985 to 2015.

Materials and methods

A total of 2082 patients were eligible for this study. Main outcomes measured were overall survival (OS) and disease specific survival (DSS). Prognostic variables were identified with bivariate analyses using Kaplan-Meier curves and log-rank testing for comparison. A p-value < 0.05 was considered statistically significant and significant factors were entered into multivariate analysis. Median age was 62 years (16–100), 56% were men, 66% reported a history of tobacco use and 71% of alcohol consumption. The most common subsite was tongue (51%). Seventy-three percent of patients had cT1-2 and 71% had clinically negative necks (cN0). Surgery alone was performed in 1348 patients (65%), adjuvant postoperative radiotherapy in 608 patients (29%) and postoperative chemoradiation in 126 patients (6%). Neck dissection was performed in 920 patients with cN0, and in 585 patients with a clinically involved neck. The median follow-up was 37.6 months (range 1–382).

Results

The 5-year OS and DSS were 64.4% and 79.3%, respectively. Age, comorbidities, margin status, vascular invasion, perineural invasion, AJCC 8th edition pT, and pN were independent prognostic factors of OS (p < 0.05). History of alcohol consumption, margin status, vascular invasion, perineural invasion, pT, and pN were independent prognostic factors of DSS (p < 0.05).

Conclusion

pN stage is the most powerful and consistent predictor of outcome in patients with OSCC treated with primary surgery and appropriate adjuvant therapy.

http://bit.ly/2V0ePUf

Can topical 5-fluorouracil be used as a viable treatment option for oral premalignant lesions and tumors?

Publication date: Available online 15 February 2019

Source: Oral Oncology

Author(s): Samapika Routray, Punit S. Dikhit, B.C. Rajani, Mohd. Musab Khan

http://bit.ly/2EdoHnO

Regarding clinical implications of magnetic resonance imaging in temporomandibular disorder patients presenting ear fullness

http://bit.ly/2GMo06K

In reference to management and follow‐up results of salivary fistulas treated with botulinum toxin

http://bit.ly/2tq9cmA

Surgery versus radiation for T1 glottic carcinoma: Second primary considerations

Although early glottic carcinoma is managed with radiation therapy (RT) or surgery, there is limited data on differences in second primary cancers of the larynx. We utilized the Surveillance, Epidemiology, and End Results (SEER) database to query T1 glottic carcinomas and assess the incidence of second primary laryngeal malignancies. Cumulative hazard for second primary laryngeal malignancies was compared with the log‐rank method. Among 844 surgical and 2,272 RT cases, observed‐to‐expected incidence ratios of laryngeal second primaries were 10.19 (5.89–16.55) and 6.87 (4.64–9.81) per 10 thousand person‐years, respectively. Mean person‐years at risk were comparable at 8.16 years (surgery) and 8.01 years (RT), and relative increased risk of laryngeal second primary was 20.95 (surgery) versus 14.09 (RT) per 10 thousand person‐years. Mean times to development of a second primary were also comparable (304 vs. 305 months, P = 0.898). Thus, second laryngeal primary development is analogous between cases treated with surgery alone versus RT. Continued discussion and investigation of surgery versus RT for early glottic squamous cell carcinoma will need to leverage these findings, along with ongoing investigation of voice and survival outcomes, to develop more well‐informed treatment algorithms. Laryngoscope, 2019

http://bit.ly/2GMpCgI

Investigating the Nasal Cycle Using Unilateral Peak Nasal Inspiratory Flow and Acoustic Rhinometry Minimal Cross‐Sectional Area Measurements

Abstract

Objective

To plot the nasal cycle using unilateral peak nasal inspiratory flow (UPNIF) and unilateral minimal cross‐sectional area (UMCA) readings demonstrating a linear relationship in normal nasal function. Additionally, to determine how this changes in abnormal nasal function.

Design

A cross‐sectional study measuring UPNIF and UMCA in controls demonstrating normal nasal function and in patients with nasal obstruction.

Setting

Royal National Throat Nose and Ear Hospital, London.

Participants

39 participants, 26 controls and 13 patients, were recruited. Controls exhibited normal nasal function with SNOT‐22 <5. Patients nasal obstruction symptoms secondary to inflammation or structural abnormality with SNOT‐22 >9.

Main Outcome Measures and Results

Airflow rates and resistance values were derived from UPNIF and UMCA measurements respectively based on Poiseuille's laws. Ratios between right and left UPNIF and UMCA values were taken to adjust for confounding factors. The relationship of 1/Resistance Ratio and Airflow Rate Ratio demonstrated a linear of direct proportionality of strong correlation and statistical significance (correlation coefficient =0.76, p<<0.01). This suggests that data points from controls with a normal nasal cycle lie closely along the regressed line, while those lying significantly away were shown to belong to patients with nasal dysfunction. Olfactory dysfunction appears to be a sensitive discriminator in predicting this.

Conclusion

This study demonstrates the directly proportional relationship of 1/Resistance Ratio and Airflow Rate Ratio in normal nasal function. Furthermore, nasal pathology can be predicted if data points lie significantly outside these normal limits. Further studies are needed to validate exact normal and abnormal thresholds.

This article is protected by copyright. All rights reserved.

http://bit.ly/2S5I6er

“Cold turkey” or pharmacotherapy: Examination of tobacco cessation methods tried among smokers prior to developing head and neck cancer

Abstract

Background

Tobacco cessation methods employed by patients with head and neck cancer (HNSCC) are previously unstudied and have the potential to inform choice of cessation method and necessary abstinence support.

Methods

A total of 130 current smokers with HNSCC were queried regarding prior unsuccessful tobacco cessation techniques, product used (cold turkey, varenicline, and nicotine patch/gum), and maximum time abstained from smoking.

Results

One hundred six smokers retrospectively reported using one of the four main quit methods. Unassisted cessation ("cold turkey") was the most commonly used method (P < .001). A multiple ordinal logistic general estimating equation analysis revealed that cold turkey had increased odds [5.2 (95% confidence interval [CI]: 2.2, 11.8) and 4.3 (95% CI: 1.5, 12.9)] of achieving a longer quit duration than the nicotine patch or varenicline, respectively.

Conclusions

Among smokers developing HNSCC, previous cessation attempts were most commonly unassisted. This method was associated with longest abstinence periods. These data suggest insufficient support and education regarding behavioral and pharmacologic cessation therapies.

http://bit.ly/2EduhH6

Neuro-Oncology Diet and risk of glioma

Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool Abstract Background Brain metastases are a common complication of renal cell carcinoma (RCC). Our group previously published the Renal Graded Prognostic Assessment (GPA) tool. In our prior RCC study (n = 286, 1985–2005), we found marked heterogeneity and variation in outcomes. In our recent update in a larger, more contemporary cohort, we identified additional significant prognostic factors. The purpose of this study is to update the original Renal-GPA based on the newly identified prognostic factors. Methods A multi-institutional retrospective institutional review board–approved database of 711 RCC patients with new brain metastases diagnosed from January 1, 2006 to December 31, 2015 was created. Clinical parameters and treatment were correlated with survival. A revised Renal GPA index was designed by weighting the most significant factors in proportion to their hazard ratios and assigning scores such that the patients with the best and worst prognoses would have a GPA of 4.0 and 0.0, respectively. Results The 4 most significant factors were Karnofsky performance status, number of brain metastases, extracranial metastases, and hemoglobin. The overall median survival was 12 months. Median survival for GPA groups 0–1.0, 1.5–2.0, 2.5–3, and 3.5–4.0 (% n = 25, 27, 30 and 17) was 4, 12, 17, and 35 months, respectively. Conclusion The updated Renal GPA is a user-friendly tool that will help clinicians and patients better understand prognosis, individualize clinical decision making and treatment selection, provide a means to compare retrospective literature, and provide more robust stratification of future clinical trials in this heterogeneous population. To simplify use of this tool in daily practice, a free online application is available at brainmetgpa.com. Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients Abstract Background Peptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC in HLA-A2 + glioma patients. Methods Adult patients with newly diagnosed glioblastoma (n=16) and grade III astrocytoma (n=3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination. The first 6 patients received IMA950 (9 MHC class I and 2 MHC class II peptides) i.d. and poly-ICLC i.m. After protocol amendment, IMA950 and poly-ICLC were mixed and injected s.c. (n=7) or i.m. (n=6). Primary endpoints were safety and immunogenicity. Secondary endpoints were overall survival, progression-free survival at 6 and 9 months, and vaccine-specific peripheral CD4 and CD8 T cell responses. Results The IMA950/poly-ICLC vaccine was safe and well tolerated. Four patients presented cerebral edema with rapid recovery. For the first 6 patients, vaccine-induced CD8 T cell responses were restricted to a single peptide and CD4 responses were absent. After optimization of vaccine formulation, we observed multipeptide CD8 and sustained Th1 CD4 T cell responses. For the entire cohort, CD8 T cell responses to a single or multiple peptides were observed in 63.2% and 36.8% of patients, respectively. Median overall survival was 19 months for glioblastoma patients. Conclusion We provide, in a clinical trial, using cell surface-presented antigens, insights into optimization of vaccines generating effector T cells for glioma patients. Trial registration Clinicaltrials.gov NCT01920191. Recent Developments and Future Directions in Adult Lower-Grade Gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) Consensus Abstract The finding that most grade II and III gliomas harbor isocitrate dehydrogenase (IDH) mutations conveying a relatively favorable and fairly similar prognosis in both tumor grades highlights that these tumors represent a fundamentally different entity from IDH wild-type gliomas exemplified in most glioblastoma. Herein we review the most recent developments in molecular neuropathology leading to reclassification of these tumors based upon IDH and 1p/19q status, as well as the potential roles of methylation profiling and CDKN2A/B deletional analysis. We discuss the epidemiology, clinical manifestations, benefit of surgical resection, and neuroimaging features of lower-grade gliomas as they relate to molecular subtype, including advanced imaging techniques such as 2-hydroxyglutarate magnetic resonance spectroscopy and amino acid PET scanning. Recent, ongoing and planned studies of radiation therapy and both cytotoxic and targeted chemotherapies are summarized, including both small molecule and immunotherapy approaches specifically targeting the mutant IDH protein. Diet and risk of glioma: combined analysis of three large prospective studies in the UK and USA Abstract Background Available evidence on diet and glioma risk comes mainly from studies with retrospective collection of dietary data. To minimise possible differential dietary recall between those with and without glioma, we present findings from three large prospective studies. Methods Participants included 692,176 from (UK) Million Women Study, 470,780 from (US) NIH-AARP Study, and 99,148 from (US) PLCO Study. Cox regression yielded study-specific adjusted relative risks for glioma in relation to 15 food groups, 14 nutrients, and 3 dietary patterns, which were combined, weighted by inverse-variances of the relative risks. Separate analyses by <5 and ≥5 years follow-up assessed potential biases related to changes of diet before glioma diagnosis. Results The 1,262,104 participants, mean age 60.6 (SD5.5) at baseline, were followed for 15.4 million person-years (mean 12.2 years/participant), during which 2,313 incident gliomas occurred, at mean age 68.2 (SD6.4). Overall, there was weak evidence for increased glioma risks associated with increasing intakes of total fruit, citrus fruit, and fibre, and healthy dietary patterns, but these associations were generally null after excluding the first 5 years of follow-up. There was little evidence for heterogeneity of results by study or by sex. Conclusions The largest prospective evidence to date suggests little, if any, association between major food groups, nutrients, or common healthy dietary patterns, and glioma incidence. With the statistical power of this study and the comprehensive nature of the investigation here, it seems unlikely we have overlooked major effects of diet on risk of glioma that would be of public health concern.

Highlights from the Literature

Forthcoming Meetings Edited by Albert H. Kim and Jennie W. Taylor

Glioblastoma: a prognostic value of AMT-PET? See the article by John et al, pp. 264–273.

Old meet new—the path to combination treatments in pediatric low-grade gliomas See the article by Poore et al, pp. 252–263.

Disparities along the glioblastoma clinical trials landscape We read with interest the recent work by Vanderbeek et al1 regarding the current clinical trials landscape for glioblastoma (GBM) patients. An unexplored dimension of their analysis centers on disparities and demographic discrepancies between clinical trial participants and the broader GBM population. We therefore examined clinical trials with published results as highlighted by the authors, totaling 51 trials.1 While most of these trials reported details regarding patient age (48/51, 94%) and gender (47/51, 92%), only 14 trials (27%) provided information regarding ethnicity and/or race in either peer-reviewed publications or ClinicalTrials.gov. The rate of reporting ethnicity/race was particularly low among phase I/II studies (9/43, 21%) compared with phase III trials (5/8, 63%, chi-squared test P = 0.02).

Multimodal imaging-defined subregions in newly diagnosed glioblastoma: impact on overall survival Abstract Background Although glioblastomas are heterogeneous brain-infiltrating tumors, their treatment is mostly focused on the contrast-enhancing tumor mass. In this study, we combined conventional MRI, diffusion-weighted imaging (DWI), and amino acid PET to explore imaging-defined glioblastoma subregions and evaluate their potential prognostic value. Methods Contrast-enhanced T1, T2/fluid attenuated inversion recovery (FLAIR) MR images, apparent diffusion coefficient (ADC) maps from DWI, and alpha-[11C]-methyl-L-tryptophan (AMT)-PET images were analyzed in 30 patients with newly diagnosed glioblastoma. Five tumor subregions were identified based on a combination of MRI contrast enhancement, T2/FLAIR signal abnormalities, and AMT uptake on PET. ADC and AMT uptake tumor/contralateral normal cortex (T/N) ratios in these tumor subregions were correlated, and their prognostic value was determined. Results A total of 115 MRI/PET-defined subregions were analyzed. Most tumors showed not only a high-AMT uptake (T/N ratio > 1.65, N = 27) but also a low-uptake subregion (N = 21) within the contrast-enhancing tumor mass. High AMT uptake extending beyond contrast enhancement was also common (N = 25) and was associated with low ADC (r = −0.40, P = 0.05). Higher AMT uptake in the contrast-enhancing tumor subregions was strongly prognostic for overall survival (hazard ratio: 7.83; 95% CI: 1.98–31.02, P = 0.003), independent of clinical and molecular genetic prognostic variables. Nonresected high-AMT uptake subregions predicted the sites of tumor progression on posttreatment PET performed in 10 patients. Conclusions Glioblastomas show heterogeneous amino acid uptake with high-uptake regions often extending into non-enhancing brain with high cellularity; nonresection of these predict the site of posttreatment progression. High tryptophan uptake values in MRI contrast-enhancing tumor subregions are a strong, independent imaging marker for longer overall survival.

Supratotal resection in glioma: a systematic review Abstract Background Emerging evidence suggests survival benefit from resection beyond all MRI abnormalities present on T1-enhanced and T2‒fluid attenuated inversion recovery (FLAIR) modalities in glioma (supratotal resection); however, the quality of evidence is unclear. We addressed this question via systematic review of the literature. Methods EMBASE, MEDLINE, Scopus, and Web of Science databases were queried. Case studies, reviews or editorials, non-English, abstract-only, brain metastases, and descriptive works were excluded. All others were included. Results Three hundred and nine unique references yielded 41 studies for full-text review, with 7 included in the final analysis. Studies were mostly of Oxford Center for Evidence-Based Medicine Level 4 quality. A total of 88 patients underwent supratotal resection in a combined cohort of 492 patients (214 males and 278 females, age 18 to 82 years). Fifty-one supratotal resections were conducted on high-grade gliomas, and 37 on low-grade gliomas. Karnofsky performance status, overall survival, progression-free survival, neurological deficits postoperatively, and anaplastic transformation were the main measured outcomes. No randomized controlled trials were identified. Preliminary low-quality support was found for supratotal resection in increasing overall survival and progression-free survival for both low-grade and high-grade glioma. Conclusion The literature suggests insufficient evidence for carte blanche application of supratotal resection, particularly in lower-grade gliomas where neurological deficits can result in long-term disability. While the preliminary studies discussed here, containing data from only a few centers, have reported increased progression-free and overall survival, these claims require validation in prospective research studies involving larger patient populations with clearly defined appropriate outcome metrics in order to reduce potential bias.

Uncommon low-grade brain tumors Abstract The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors includes numerous uncommon (representing ≤1% of tumors) low-grade (grades I–II) brain neoplasms with varying clinical behaviors and outcomes. Generally, gross tumor or maximal safe resection is the primary treatment. Adjuvant treatments, though their exact role is unknown, may be considered individually based on pathological subtypes and a proper assessment of risks and benefits. Targetable mutations such as BRAF (proto-oncogene B-Raf), TRAIL (tumor necrosis factor apoptosis inducing ligand), and PDGFR (platelet derived growth factor receptor) have promising roles in future management.

Outcomes following stereotactic radiosurgery for small to medium-sized brain metastases are exceptionally dependent upon tumor size and prescribed dose Abstract Background At our institution, we have historically treated brain metastasis (BM) ≤2 cm in eloquent brain with a radiosurgery (SRS) lower prescription dose (PD) to reduce the risk of radionecrosis (RN). We sought to evaluate the impact of this practice on outcomes. Methods We analyzed a prospective registry of BM patients treated with SRS between 2008 and 2017. Incidences of local failure (LF) and RN were determined and Cox regression was performed for univariate and multivariate analyses (MVAs). Results We evaluated 1533 BM ≤2 cm. Median radiographic follow-up post SRS was 12.7 months (1.4–100). Overall, the 2-year incidence of LF was lower for BM treated with PD ≥21 Gy (9.3%) compared with PD ≤15 Gy (19.5%) (sub–hazard ratio, 2.3; 95% CI: 1.4–3.7; P = 0.0006). The 2-year incidence of RN was not significantly higher for the group treated with PD ≥21 Gy (9.5%) compared with the PD ≤15 Gy group (7.5%) (P = 0.16). MVA demonstrated that PD (≤15 Gy) and tumor size (>1 cm) were significantly correlated (P < 0.05) with higher rates of LF and RN, respectively. For tumors ≤1 cm, when comparing PD ≤15 Gy with ≥21 Gy, the risks of LF and RN are equivalent. However, for lesions >1 cm, PD ≥21 Gy is associated with a lower incidence of LF without significantly increasing the risk of RN. Conclusion Our results indicate that rates of LF or RN following SRS for BM are strongly correlated with size and PD. Based on our results, we now, depending upon the clinical context, consider increasing PD to 21 Gy for BM in eloquent brain, excluding the brainstem.

Sex difference of mutation clonality in diffuse glioma evolution Abstract Background Sex differences in glioma incidence and outcome have been previously reported but remain poorly understood. Many sex differences that affect the cancer risk were thought to be associated with cancer evolution. Methods In this study, we used an integrated framework to infer the timing and clonal status of mutations in ~600 diffuse gliomas from The Cancer Genome Atlas (TCGA) including glioblastomas (GBMs) and low-grade gliomas (LGGs), and investigated the sex difference of mutation clonality. Results We observed higher overall and subclonal mutation burden in female patients with different grades of gliomas, which could be largely explained by the mutations of the X chromosome. Some well-established drivers were identified showing sex-biased clonality, such as CDH18 and ATRX. Focusing on glioma subtypes, we further found a higher subclonal mutation burden in females than males in the majority of glioma subtypes, and observed opposite clonal tendency of several drivers between male and female patients in a specific subtype. Moreover, analysis of clinically actionable genes revealed that mutations in genes of the mitogen-activated protein kinase (MAPK) signaling pathway were more likely to be clonal in female patients with GBM, whereas mutations in genes involved in the receptor tyrosine kinase signaling pathway were more likely to be clonal in male patients with LGG. Conclusions The patients with diffuse glioma showed sex-biased mutation clonality (eg, different subclonal mutation number and different clonal tendency of cancer genes), highlighting the need to consider sex as an important variable for improving glioma therapy and clinical care.