In vivo hippocampal cornu ammonis 1-3 glutamatergic abnormalities are associated with temporal lobe epilepsy surgery outcomes.

OBJECTIVE: Previous positron emission tomography (PET) studies using [11 C]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [11 C]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes. METHODS: We obtained magnetic resonance imaging (MRI) and [11 C]ABP688-PET from 31 unilateral MTLE patients and 30 healthy controls. MRI hippocampal subfields were segmented using FreeSurfer. To respect the lower PET special resolution, MRI-derived anatomical subfields were combined into CA1-3, CA4/dentate gyrus, and Subiculum. Partial volume corrected [11 C]ABP688 nondisplaceable binding potential (BPND ) values were averaged across each subfield, and Z-scores were calculated. Subfield [11 C]ABP688-BPND was compared between seizure-free and non-seizure-free patients. In addition, we also assessed subfield volumes and [18 F]fluorodeoxyglucose (FDG) uptake in each clinical group. RESULTS: MTLE [11 C]ABP688-BPND was reduced in ipsilateral (epileptogenic) CA1-3 and CA4/dentate-gyrus (p < .001, 95% confidence interval [CI] = .29-.51) compared to controls, with no difference in Subiculum. [11 C]ABP688-BPND and subfield volumes were compared between seizure-free (Engel IA, n = 13) and non-seizure-free patients (Engel IC-III, n = 10). In ipsilateral CA1-3 only, [11 C]ABP688-BPND was lower in seizure-free patients than in non-seizure-free patients (p = .012, 95% CI = 1.46-11.0) independently of volume. A subset analysis of 12 patients with [11 C]ABP688-PET+[18 F]FDG-PET showed no between-group significant difference in [18 F]FDG uptake, whereas CA1-3 [11 C]ABP688-BPND remained significantly lower in the seven of 12 seizure-free patients (p = .03, 95% CI = -3.13 to -.21). SIGNIFICANCE: Reduced mGluR5 allosteric site availability in hippocampal CA1-3, measured in vivo by [11 C]ABP688-PET, is associated with postsurgery seizure freedom independent of atrophy or hypometabolism. Information derived from hippocampal CA1-3 [11 C]ABP688-PET is a promising imaging biomarker potentially impactful in surgical decisions for MRI-negative/PET-negative MTLE patients.

In vivo metabotropic glutamate receptor type 5 abnormalities localize the epileptogenic zone in mesial temporal lobe epilepsy.

OBJECTIVE: Surgical specimens from patients with mesial temporal lobe epilepsy (MTLE) show abnormalities in tissue concentrations of metabotropic glutamate receptor type 5 (mGluR5). To clarify whether these abnormalities are specific to the epileptogenic zone (EZ), we characterized in vivo whole-brain mGluR5 availability in MTLE patients using positron emission tomography (PET) and [11 C]ABP688, a radioligand that binds specifically to the mGluR5 allosteric site. METHODS: Thirty-one unilateral MTLE patients and 30 healthy controls underwent [11 C]ABP688 PET. We compared partial volume corrected [11 C]ABP688 nondisplaceable binding potentials (BPND ) between groups using region-of-interest and whole-brain voxelwise analyses. [18 F]Fluorodeoxyglucose (FDG) PET was acquired in 15 patients, for whom we calculated asymmetry indices of [11 C]ABP688 BPND and [18 F]FDG uptake to compare lateralization and localization differences. RESULTS: [11 C]ABP688 BPND was focally reduced in the epileptogenic hippocampal head and amygdala (p < 0.001). Patients with hippocampal atrophy showed more extensive abnormalities, including the ipsilateral temporal neocortex (p = 0.006). [11 C]ABP688 BPND showed interhemispheric differences of higher magnitude and discriminated the epileptogenic structures more accurately when compared to [18 F]FDG uptake, which showed more widespread hypometabolism. Among 23 of 25 operated patients with >1 year of follow-up, 13 were seizure-free (Engel Ia) and showed significantly lower [11 C]ABP688 BPND in the ipsilateral entorhinal cortex. INTERPRETATION: [11 C]ABP688 PET provides a focal biomarker for the EZ in MTLE with higher spatial accuracy compared to [18 F]FDG PET. Focally reduced mGluR5 availability in the EZ might reflect receptor internalization or conformational changes in response to excessive extracellular glutamate, supporting a potential role for mGluR5 as therapeutic target in human MTLE. Ann Neurol 2019; 1-11 ANN NEUROL 2019;85:218-228.

Characterization of age/sex and the regional distribution of mGluR5 availability in the healthy human brain measured by high-resolution [(11)C]ABP688 PET.

PURPOSE: Metabotropic glutamate receptor type 5 (mGluR5) is a G protein-coupled receptor that has been implicated in several psychiatric and neurological diseases. The radiopharmaceutical [(11)C]ABP688 allows for in vivo quantification of mGluR5 availability using positron emission tomography (PET). In this study, we aimed to detail the regional distribution of [(11)C]ABP688 binding potential (BPND) and the existence of age/sex effects in healthy individuals. METHODS: Thirty-one healthy individuals aged 20 to 77 years (men, n = 18, 45.3 ± 18.2 years; females, n = 13, 41.5 ± 19.6 years) underwent imaging with [(11)C]ABP688 using the high-resolution research tomograph (HRRT). We developed an advanced partial volume correction (PVC) method using surface-based analysis in order to accurately estimate the regional variation of radioactivity. BPND was calculated using the simplified reference tissue model, with the cerebellum as the reference region. Surface-based and volume-based analyses were performed for 39 cortical and subcortical regions of interest per hemisphere. RESULTS: We found the highest [(11)C]ABP688 BPND in the lateral prefrontal and anterior cingulate cortices. The lowest [(11)C]ABP688 BPND was observed in the pre- and post-central gyri as well as the occipital lobes and the thalami. No sex effect was observed. Associations between age and [(11)C]ABP688 BPND without PVC were observed in the right amygdala and left putamen, but were not significant after multiple comparisons correction. CONCLUSIONS: The present results highlight complexities underlying brain adaptations during the aging process, and support the notion that certain aspects of neurotransmission remain stable during the adult life span.

Academic and Geographic Employment Outcomes for Graduating Residents in Radiation Oncology: 2015-2022.

PURPOSE: Little is known about how the academic and geographic employment outcomes of new radiation oncology (RO) graduates have changed over time. In this study, we sought to trace the evolution of these outcomes for all RO residents who graduated between 2015 and 2022. METHODS AND MATERIALS: Using publicly available data sources, we identified the first permanent, clinical employment positions accepted by graduating members of the RO residency classes of 2015 to 2022. We additionally determined the medical school and residency program attended by each graduate. We then classified each clinical employment position by its rural-urban continuum code and core-based statistical area, and whether it was academic or nonacademic. RESULTS: Of 1478 RO graduates identified, 1396 first accepted clinical positions in the United States after residency. A majority accepted positions in the largest metropolitan areas (N = 878, 62.9%) and in nonacademic settings (N = 719, 51.5%). The proportion of graduates who accepted academic positions climbed steadily from 2015 to 2020 before dropping by 31% in 2021 and partially rebounding in 2022. Women and graduates of large-sized academic programs were more likely to have accepted academic positions. In contrast, graduates of small-sized residency programs were more likely than those of large-sized residency programs to have accepted positions in nonmetropolitan areas. At least 288 of the examined individuals (20.6%) had switched jobs at least once at the time of this analysis. CONCLUSIONS: Most new RO graduates in this study accepted clinical positions in large metropolitan areas. A slight majority accepted nonacademic positions. While the RO job market was able to absorb the vast majority of these new graduates between 2015 and 2022, there is no guarantee that this equilibrium will hold in the future. Additional studies aiming to refine projections of future RO demand are needed.

Gender Representation Among Academic US Radiation Oncology Department Chairs: Who are They?

Purpose: Women are underrepresented in academic radiation oncology (RO), particularly in leadership positions. In this study, we sought to better understand the characteristics of individuals who currently serve as academic RO chairpersons at institutions with an associated Accreditation Council for Graduate Medical Education-accredited RO residency training program. Methods and Materials: We created a database of academic RO chairpersons in the United States by using publicly available sources, including residency training program websites, hospital/institutional websites, Doximity, LinkedIn, the American Society for Radiation Oncology (ASTRO) website, the American College of Radiation Oncology website, and the National Plan and Provider Enumeration System National Provider Identifier Registry. We used the χ2 Goodness of Fit test, Mann-Whitney U test, and Fisher exact test via R version 4.1.1 to evaluate for statistical significance among categorical variables, medians, and proportions, respectively. Results: We identified 85 of the 90 chairpersons (94.4%) currently serving at institutions with an Accreditation Council for Graduate Medical Education-accredited RO residency training program, 5 of whom hold interim positions and were thus excluded from further analyses. Of the remaining 80 chairpersons, 9 (11.3%) are women, and 71 (88.8%) are men (P < .01). Seventy-six chairpersons (95.0%) are full professors, and 19 (23.8%) hold dual MD PhD degrees. Thirty-two chairpersons (40.0%) hold an official leadership role in a cancer center affiliated with their current institution (43.7% of men vs 11.1% of women; P = .08). Seventy-three chairpersons (91.3%) secured their current positions a median of 16 years (range, 6-33 years) after completing RO residency. Thirty-five chairpersons (43.8%) were promoted to chair from positions within their current institutions (40.8% of men vs 66.7% of women; P = .17). The majority of chairpersons are ASTRO Fellows (62.5%); notably fewer are ASTRO (5.0%) or American College of Radiation Oncology (2.5%) Gold Medalists. Eight RO residency programs trained more than half of current chairpersons. Conclusion: Significantly more men than women currently serve as RO chairpersons. Future interventions that promote the recruitment, retention, and promotion of talented women in academic RO should be considered.

Geographic Employment Outcomes for Graduating Residents in Radiation Oncology: 2021.

PURPOSE: In light of the persistent disparity in the prevalence of radiation oncologists between rural and urban areas in the United States, we sought to characterize the geographic employment outcomes of the radiation oncology (RO) residency class of 2021. METHODS AND MATERIALS: We identified the employment positions accepted by 2021 RO residency graduates using publicly available information. Then, we classified each position as academic or nonacademic and determined the rural-urban continuum code and core-based statistical area (CBSA) of each position, residency program, and medical school associated with the 2021 graduates. Last, we compared the geographic employment outcomes of the 2021 class with those of the 2019 class. RESULTS: Most 2021 graduates accepted employment positions outside of the counties, CBSAs, and states in which they attended medical school or residency. A total of 116 graduates accepted nonacademic positions, and 65 graduates accepted academic positions. Nine graduates accepted fellowships and were excluded from this analysis. As with the class of 2019, most 2021 graduates (n = 104; 57.5%) accepted positions in the largest metropolitan areas, and few (n = 11; 6.1%) accepted positions in nonmetropolitan areas. Female residents were more likely to accept academic (48.9% vs 31.3%; P = .03) and academic main site (36.2% vs 21.6%; P = .05) positions than male residents. The distribution of jobs in both the 5 and 10 largest CBSAs was not significantly different from what would have been expected if jobs were equally distributed across the country on the basis of population (P = .81 and P = .87, respectively). However, the distribution was significantly different from what would have been expected if the distribution of such positions reflected the number of residents who graduated from residency programs in those CBSAs (P < .01 and P < .01, respectively). CONCLUSIONS: As with the class of 2019, the majority of graduates in the class of 2021 accepted employment positions in large metropolitan areas. Relatively few graduates accepted positions in nonmetropolitan areas. How key RO stakeholders respond to the challenge of maintaining a stable supply of rural radiation oncologists while also ensuring that jobs available to graduating RO residents reflect their preferences will have a significant effect on the field going forward.

Gender Differences in the Research Productivity of Radiation Oncology Resident Graduates in the United States: 2015 to 2019.

Purpose: It is well-documented that gender disparities exist in academic radiation oncology departments. The purpose of this study was to analyze gender differences in research productivity during residency among recent graduates of radiation oncology training programs in the United States (US). Methods and Materials: We used several publicly available sources to create a database of US radiation oncology residents who graduated between 2015 and 2019. We systematically collected gender information from the National Plan and Provider Enumeration System National Provider Identifier Registry and Medicare claims registry. Postresidency employment information was collected using several publicly available sources. PubMed was queried to identify first-author publications of residents. A secondary analysis of metadata including impact factor, number of citations, modified Hirsch index (h index), and type of publication was performed. A multivariable linear regression was performed to evaluate the effect of gender on research productivity during residency. Results: There were 910 total graduates identified during this period and who were entered into this database, of whom all had available gender information. Female trainees comprised 29.0% (n = 264) of RO residents and had fewer first-author publications and citations, had lower mean modified h index, and were published in journals with lower impact factors. On multivariable linear regression analysis, female gender was independently associated with decreased total number of publications (P = .005), mean number of citations (P < .001), and modified h index (P = .001) when controlling for residency size and advanced (PhD or master's) degrees. Conclusions: In the US, female RO trainees had lower research productivity, which was not explained by advanced degrees or residency size. A significant gender gap in trainee research productivity persists, which has known implications in terms of academic achievement, promotions, and career trajectory. Future interventions to improve resident research productivity and mentorship are warranted.

Dynamic Amyloid and Metabolic Signatures of Delayed Recall Performance within the Clinical Spectrum of Alzheimer's Disease.

Associations between pathophysiological events and cognitive measures provide insights regarding brain networks affected during the clinical progression of Alzheimer's disease (AD). In this study, we assessed patients' scores in two delayed episodic memory tests, and investigated their associations with regional amyloid deposition and brain metabolism across the clinical spectrum of AD. We assessed the clinical, neuropsychological, structural, and positron emission tomography (PET) baseline measures of participants from the Alzheimer's Disease Neuroimaging Initiative. Subjects were classified as cognitively normal (CN), or with early (EMCI) or late (LMCI) mild cognitive impairment, or AD dementia. The memory outcome measures of interest were logical memory 30 min delayed recall (LM30) and Rey Auditory Verbal Learning Test 30 min delayed recall (RAVLT30). Voxel-based [18F]florbetapir and [18F]FDG uptake-ratio maps were constructed and correlations between PET images and cognitive scores were calculated. We found that EMCI individuals had LM30 scores negatively correlated with [18F]florbetapir uptake on the right parieto-occipital region. LMCI individuals had LM30 scores positively associated with left lateral temporal lobe [18F]FDG uptake, and RAVLT30 scores positively associated with [18F]FDG uptake in the left parietal lobe and in the right enthorhinal cortex. Additionally, LMCI individuals had LM30 scores negatively correlated with [18F]florbetapir uptake in the right frontal lobe. For the AD group, [18F]FDG uptake was positively correlated with LM30 in the left temporal lobe and with RAVLT30 in the right frontal lobe, and [18F]florbetapir uptake was negatively correlated with LM30 scores in the right parietal and left frontal lobes. The results show that the association between regional brain metabolism and the severity of episodic memory deficits is dependent on the clinical disease stage, suggesting a dynamic relationship between verbal episodic memory deficits, AD pathophysiology, and clinical disease stages.

The Rise of Open Access Journals in Radiation Oncology: Influence on Resident Research, 2015 to 2019.

Purpose: While a rising share of scientific research articles are being published in open access (OA) journals, their impact on resident research in radiation oncology is unknown. Thus, we sought to determine the number, content, and costs of first-author, PubMed-searchable articles radiation oncology residents in the United States (US) published in OA journals in recent years. Methods and Materials: We built a database of first-author, PubMed-searchable articles published by US radiation oncology residents who graduated between 2015 and 2019. We then classified each journal in which these articles appeared as either OA or non-OA and obtained the current article-processing charge (APC) for each publication that appeared in an OA journal. Results: The residents in this study published 2637 first-author, PubMed-searchable articles, 555 of which (21.0%) appeared in 138 OA journals. The number of publications in OA journals per resident increased from 0.47 for the class of 2015 to 0.79 for the class of 2019. Publications in OA journals garnered fewer citations than those in non-OA journals (8.9 vs 14.9, P < .01). Furthermore, 90.6% of OA journals levy an APC for original research reports (median, $1896), which is positively correlated with their 2019 impact factor (r = 0.63, P < .01). Aggregate APCs totaled $900,319.21 and appeared to increase over the study period. Conclusions: The number of first-author, PubMed-searchable articles published by graduating US radiation oncology residents in OA journals rose significantly between 2015 and 2019. To maximize the benefits of OA publishing in the future, US radiation oncology residents will need to ensure that they use vetted OA journals to publish their research findings and avoid predatory journals.

Moving beyond Definitive Therapy: Increasing Physical Activity in Survivors of Cancers of the Head and Neck.

As chemotherapeutic, radiation, and surgical techniques have improved, there has been a dramatic improvement in survival in patients diagnosed with cancers of the head and neck. As a result, a heightened focus on survivorship by clinicians will increasingly prove necessary. In particular, medical care teams will have to pay special attention to mitigating the long-term sequelae of definitive cancer treatments, many of which act as barriers to exercise. This is unfortunate, as the benefits of exercise in patients with cancer have become increasingly recognized. In this review, we discuss the potential benefits of and barriers to exercise in survivors of cancers of the head and neck. We also review existing exercise guidelines and strategies by which clinicians can promote exercise in this unique patient population.

Characterization of rib fracture development following liver directed stereotactic body radiation therapy.

Purpose: Rib fractures are a well-described complication following thoracic stereotactic body radiation therapy (SBRT). However, there are limited data in the setting of liver-directed SBRT. Methods: Patients who underwent liver SBRT from 2014 to 2019 were analyzed. Logistic regression models were used to identify the demographic, clinical, and dosimetric factors associated with the development of rib fractures. Results: Three hundred and forty-three consecutive patients were reviewed with median follow-up of 9.3 months (interquartile range [IQR]: 4.7-17.4 months); 81% of patients had primary liver tumors and 19% had liver metastases. Twenty-one patients (6.2%) developed rib fractures with a median time to diagnosis of 7 months following SBRT (IQR: 5-19 months). Of those patients, 11 experienced concomitant chest wall pain, while 10 patients had an incidental finding of a rib fracture on imaging. On univariate analysis, female gender (odds ratio [OR]: 2.29; p = 0.05), V30 Gy (OR: 1.02; p < 0.001), V40 Gy (OR: 1.08; p < 0.001), maximum chest wall dose (OR: 1.1; p < 0.001), and chest wall D30 cm3 (OR: 1.09; p < 0.001) were associated with an increased probability of developing a rib fracture. On multivariate analysis, maximum chest wall dose (OR: 1.1; p < 0.001) was associated with developing a rib fracture. Receipt of more than one course of SBRT (p = 0.34), left versus right sided lesion (p = 0.69), osteoporosis (p = 0.54), age (p = 0.82), and PTV volume (p = 0.55) were not significant. Conclusions: Rib fractures following liver SBRT were observed in 6.2% of patients with the majority being asymptomatic. To mitigate this risk, clinicians should minimize dose delivery to the chest wall. Female patients may be at increased risk.

Oligoprogression of Solid Tumors on Immune Checkpoint Inhibitors: The Impact of Local Ablative Radiation Therapy.

The breakthrough of a limited number of clones while on immune checkpoint inhibitors (ICIs), known as oligoprogression, has been previously described. The benefit of ablative radiation therapy (RT) directed at these clones, as opposed to changing systemic therapy, is unclear. We analyzed 30 patients with advanced solid tumors, the majority of whom (23/30, 86.7%) had either hepatocellular or urothelial carcinoma, who experienced oligoprogression on ICIs and were referred for RT. In this study, oligoprogression was defined as having experienced progression at three or fewer metastatic sites outside of the brain after achieving at least stable disease on ICIs for a minimum of three months. The median time to oligoprogression was 11.1 months from the initiation of immunotherapy. 24 patients had one oligoprogressive lesion and six had two. The median radiation dose delivered was 4650 cGy in a median of five fractions. The median progression-free survival (PFS) after RT was 7.1 months, and the time to oligoprogression was not a significant predictor of PFS2. 26 patients continued on ICIs after RT. While 17 patients subsequently progressed, 15 did so at three or fewer metastatic sites and could have theoretically stood to benefit from an additional course of salvage RT to further extend the lifespan of their ICIs. Overall survival at 6, 12, and 24 months was 100.0%, 96.3%, and 82.8%, respectively. These results suggest that RT may provide a PFS benefit and extend the lifespan of ICIs in patients who experience oligoprogression. Regardless of PFS, however, overall survival in this population appears to be excellent.

Radiation Oncology Resident Research Productivity in the United States: 2015 to 2019.

PURPOSE: Multiple efforts have been made in recent years to establish national benchmarks for research productivity among US radiation oncology residents. Morgan et al found a mean of 1.01 first-author, PubMed-searchable articles published by US radiation oncology residents over 4 years of residency between 2002 and 2007, whereas Verma et al found a mean of 1.97 first-author, PubMed-searchable articles published by members of the graduating US radiation oncology residency classes of 2014 and 2015. In this study, we sought to establish new national benchmarks for US radiation oncology resident research productivity and characterize the scholarly work produced by graduating US radiation oncology residents. METHODS AND MATERIALS: We built a database of US radiation oncology residents who graduated between 2015 and 2019 using multiple sources of publicly available data. We subsequently searched the PubMed database to identify all first-author publications for every resident in our database from the start of residency until 3 months after the completion of residency. Publications were categorized by type (original research, review, case report, or commentary) and content. We performed a secondary analysis to identify factors associated with an increased probability of publishing during residency. RESULTS: We identified 909 US radiation oncology residency graduates from 89 residency programs between 2015 and 2019. Collectively, these graduates published 2637 first-author, PubMed-searchable articles (mean: 2.90; median: 2.0; range, 0-58; interquartile range, 1-4) in 392 distinct peer-reviewed journals during their residency, and 69.7% of the first-author publications comprised original research. On multivariable analysis, only residency size was predictive of publishing a first-author manuscript during residency. Among residents with at least 1 first-author manuscript, male sex, lack of a doctorate degree, and residency size were all significant predictors of the number of first-author manuscripts published during residency. CONCLUSIONS: US radiation oncology resident research productivity, as measured by the number of first-author, PubMed-searchable publications, has increased compared with historical data. However, substantial variability exists in resident research productivity nationwide.

The Holman Research Pathway in Radiation Oncology: 2010 to 2019.

PURPOSE: There has not been an assessment of the Holman Research Pathway (HRP) in radiation oncology (RO) in nearly 10 years. In this study, we sought to review the demographic characteristics, research productivity during and after residency, job placements, and National Institutes of Health (NIH) grant funding of RO residents who completed the HRP in the modern era. METHODS AND MATERIALS: We created a comprehensive database of RO residents who completed the HRP between 2010 and 2019. Using a variety of data sources, we obtained demographic information, first-author manuscripts published in residency, and first- and last-author manuscripts published in the first 30 months after residency for each resident. In addition, we identified the first and current job and NIH grant funding for each resident. RESULTS: Ninety-seven RO residents who graduated from 50 medical schools and 25 residency programs were included. The majority were male (82.5%), had a PhD (92.8%), and identified as white (64.9%). Collectively, these residents published 212 first-author, PubMed-searchable manuscripts during residency (mean: 2.2) and 142 first- or last-author, PubMed-searchable manuscripts in the first 30 months after completion of residency (mean: 1.5). The number of first-author publications authored by HRP graduates during residency was highly correlated (r = 0.62; P < .01) with the number of first- and last-author publications they authored during the first 30 months after completing residency. Ninety-six of the 97 residents (99.0%) were employed in full-time clinical positions after completing residency. Seventy-six HRP residents (78.4%) obtained an academic position as their first job after residency, only 4 of whom have since left academia, and 20 (20.6%) obtained a nonacademic position. Of the 75 HRP graduates currently employed in an academic position, 39 (52.0%) have their own laboratories. Twenty-three of the 96 HRP residents (24.0%) who secured employment in full-time clinical positions after residency switched jobs over the study period. Lastly, 33 of the 97 HRP residents (34.0%) have thus far received 47 extramural NIH research grants, 15 of which were R-01 grants. CONCLUSIONS: Over the past decade, the HRP has proven successful in training a new cohort of physician investigators in RO. Although productive, HRP residents have had relatively homogenous sex, educational, and racial backgrounds. Ensuring sufficient representation of residents from a variety of backgrounds in the HRP in the future will be crucial.

Patterns of care and outcomes of intensity modulated radiation therapy versus three-dimensional conformal radiation therapy for anal cancer.

BACKGROUND: Definitive chemoradiation is the standard of care for anal squamous cell carcinoma. Compared to three-dimensional conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) is increasingly becoming the preferred technique in order to reduce treatment related toxicity. The objective of this study is to evaluate practice patterns and total radiation treatment times of two radiation modalities. METHODS: A total of 6,966 patients with non-metastatic squamous cell carcinoma of the anus who received definitive chemoradiation were queried from the National Cancer Database (NCDB) from 2004-2013. Logistic regression was performed to assess for predictors of IMRT receipt. The Kaplan-Meier method and multivariable Cox regression analysis was used to assess overall survival (OS). RESULTS: In total, 3,868 (55.5%) received 3DCRT and 3,098 (44.5%) received IMRT. Total radiation treatment time was <7 weeks for 54.3% of patients treated with 3DCRT versus 63.8% of patients treated with IMRT. On multivariable logistic regression, positive clinical nodes (OR =1.20, P=0.001) and treatment at an academic facility (OR =1.23, P<0.001) were associated with increased likelihood of receiving IMRT. The 5-year OS was 73.0% for 3DCRT and 73.9% for IMRT (P=0.315). On multivariable analysis, total radiation treatment time ≥7 weeks (HR =1.33, P<0.001) was associated with worse survival while radiation modality (3DCRT vs. IMRT) did not impact survival (HR =0.98, P=0.763). CONCLUSIONS: IMRT has dramatically increased in utilization from 2% to 65% during the study time period. IMRT was less likely than 3DCRT to have prolonged radiation treatment times, which was associated with worse survival.

Inferior Longitudinal Fasciculus' Role in Visual Processing and Language Comprehension: A Combined MEG-DTI Study.

The inferior longitudinal fasciculus (ILF) is a white matter tract that connects the occipital and the temporal lobes. ILF abnormalities have been associated with deficits in visual processing and language comprehension in dementia patients, thus suggesting that its integrity is important for semantic processing. However, it remains elusive whether ILF microstructural organization per se impacts the visual semantic processing efficiency in the healthy brain. The present study aims to investigate whether there is an association between ILF's microstructural organization and visual semantic processing at the individual level. We hypothesized that the efficiency of visual semantic processing positively correlates with the degree of anisotropy of the ILF. We studied 10 healthy right-handed subjects. We determined fractional anisotropy (FA) of the ILF using diffusion tensor imaging (DTI). We extracted N400m latency and amplitude from magnetoencephalography (MEG) signals during a visual semantic decision task. N400m and mean FA of the ILF were left lateralized with the higher FA value in the left hemisphere. Inter-individual analysis showed that FA of the ILF negatively correlated with the N400m latency and amplitude, which suggests that high ILF anisotropy is associated with more efficient semantic processing. In summary, our findings provide supporting evidence for a role of the ILF in language comprehension.

Resting state executive control network adaptations in amnestic mild cognitive impairment.

Executive dysfunction is frequently associated with episodic memory decline in amnestic mild cognitive impairment (aMCI) patients. Resting state executive control network (RS-ECN) represents a novel approach to interrogate the integrity of brain areas underlying executive dysfunction. The present study aims to investigate RS-ECN in aMCI and examine a possible link between changes in brain functional connectivity and declines in executive function. aMCI individuals (n = 13) and healthy subjects (n = 16) underwent cognitive assessment including executive function and high field functional magnetic resonance imaging. Individual RS-ECN maps were estimated using a seed-based cross-correlation method. Between groups RS-ECN functional connectivity comparison was assessed using voxel-wise statistic parametric mapping. aMCI individuals had reduced RS-ECN connectivity in the anterior cingulate cortex (ACC) and dorsal lateral prefrontal cortex (DLPFC), bilaterally. In contrast, aMCI showed increased connectivity in ventral lateral and anterior prefrontal cortex, bilaterally. Connectivity strength was associated with executive function in the ACC (r = 0.6213, p = 0.023) and right DLPFC (r = 0.6454, p = 0.017). Coexistence between connectivity declines and recruitment of brain regions outside the RS-ECN as reported here fits a brain reserve conceptual framework in which brain networks undergo remodeling in aMCI individuals.