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Background: The incidence of early-onset colorectal cancer (eoCRC) diagnosed among individuals under age 50 has been rising. However, risk factors for eoCRC are unclear. We investigated whether metabolic abnormalities are risk factors for eoCRC adenocarcinoma. Methods: Invasive colorectal adenocarcinoma cases diagnosed between ages 15 and 49 from 2008 to 2018 at Kaiser Permanente Southern California (KPSC) were identified. Those with a history of inflammatory bowel disease were excluded. Noncancer controls were selected 5:1 for each case matched by age, sex, and length of membership prior to index date. Data were collected from KSPC's electronic medical records. The exposures of interest included obesity, type II diabetes, hypertension, and dyslipidemia, assessed from ≥1 year prior to eoCRC diagnosis/index date. Conditional logistic regressions were used to evaluate the associations between these metabolic risk factors and risk of eoCRC adenocarcinoma, adjusting for race/ethnicity, smoking, family history, neighborhood socioeconomic status, and health care utilization. Results: A total of 1,032 cases and 5,128 controls were included. Risk of colorectal adenocarcinoma was significantly associated with obesity [odds ratio (OR) = 1.41; 95% confidence interval (CI), 1.15–1.74], but not diabetes, hypertension or dyslipidemia. In analysis stratified by tumor location, obesity was significantly associated with risk of colon adenocarcinoma OR = 1.56 (1.17–2.07), but its association with rectal adenocarcinoma was less clear OR = 1.19 (0.85–1.68). No significant interaction was detected between obesity and age (≥40 vs. Conclusions: Obesity was associated with risk for eoCRC adenocarcinoma. Impact: This finding could help inform early-onset colorectal adenocarcinoma screening and prevention recommendations. See related commentary by Hayes, p. 1775

Objective The role of adjuvant radiotherapy (ART) in patients with World Health Organization Grade II atypical meningiomas (AMs) remains controversial. Methods We retrospectively reviewed 149 patients with newly diagnosed resected AMs from 2000 to 2012. Gross total resection (GTR) was defined as Simpson Grades I–III and subtotal resection (STR) as Grades IV and V. Kaplan-Meier analyses of local control (LC), progression-free survival (PFS), and overall survival were performed with the log-rank test, and risk factors for progression/recurrence (P/R) were analyzed with multivariate Cox regression. Results Median follow-up was 74.2 months. GTR was achieved in 98 patients and STR in 51 patients. Fifty-three (35%) patients received ART. Overall, 46 patients (31%) experienced P/R with a median time to P/R of 32.4 months. ART was associated with a trend toward improved PFS (P = 0.0669) in the GTR subset but significantly improved LC (P = 0.0183) and PFS (P = 0.0034) in the STR subset. Age, tumor size, and STR were significant risk factors for worse PFS, whereas receiving ART was associated with improved PFS on multivariate analyses. Thirty-nine of the 46 progressive/recurrent patients underwent salvage therapy with only 22 patients experiencing long-term control. Five patients experienced transformation to World Health Organization Grade III malignant meningioma. Conclusions Patients who undergo STR for newly diagnosed AM should receive ART based on improvements in LC and PFS. GTR patients should be considered for ART, but active surveillance is a reasonable management approach with the recognition that progressive/recurrent disease can act aggressively. Prospective, randomized trials are currently underway to evaluate the role of ART.

BACKGROUND The updated AJCC Cancer Staging Manual groups all p16-positive oropharyngeal squamous cell carcinoma (OPSCC) with unilateral nodal involvement within 6 cm into the new clinical N1 classification, consolidating a heterogeneous group of disease with varying radiographic findings. METHODS A central radiological review was conducted identifying 233 patients with stage I node-positive (cT1-2N1) disease who underwent definitive concurrent chemoradiation. Factors evaluated included lymph node size, low-neck lymphadenopathy, retropharyngeal lymphadenopathy, overt radiographic extracapsular extension, and matted lymphadenopathy. RESULTS On multivariate analysis adjusted for age, smoking history, and chemotherapy regimen, low-neck lymphadenopathy (hazard ratio (HR) = 6.55; P

Objectives This study aims to report tumor control rates and cranial nerve function after low dose (11.0 Gy) Gamma knife radiosurgery (GKRS) in patients with vestibular schwannomas. Methods A retrospective chart review was performed on 30 consecutive patients with vestibular schwannomas treated from March 2004 to August 2010 with GKRS at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The marginal dose for all patients was 11.0 Gy prescribed to the 50% isodose line. Median follow-up time was 42 months. The median treatment volume was 0.53 cm 3 . Hearing data were obtained from audiometry reports before and after radiosurgery. Results The actuarial progression free survival (PFS) based on freedom from surgery was 100% at 5 years. PFS based on freedom from persistent growth was 91% at 5 years. One patient experienced tumor progression requiring resection at 87 months. Serviceable hearing, defined as Gardner–Robertson score of I–II, was preserved in 50% of patients. On univariate and multivariate analyses, only higher mean and maximum dose to the cochlea significantly decreased the proportion of patients with serviceable hearing. Conclusion Vestibular schwannomas can be treated with low doses (11.0 Gy) of GKRS with good tumor control and cranial nerve preservation.

The epithelial-mesenchymal transition (EMT) is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs) are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy.