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Objective: Observation, radiotherapy and surgery are treatment options in vestibular schwannomas (VS). Decision making differs between centers and is usually based on tumor characteristics (e.g., size) and the expected physical health (PH) outcome (i.e., hearing and facial function). However, mental health (MH) is often under-reported. The objective of the present study was to ascertain the impact of VS treatment on PH and MH. Methods: PH and MH were assessed in a prospective cross-sectional study including 226 patients with unilateral sporadic VS before and after surgical removal (SURG). Quality-of-life (QoL) was estimated by self-rating questionnaires: general Short-Form Health Survey (SF-36), Penn Acoustic Neuroma Quality-of-Life Scale (PANQOL), Dizziness Handicap Inventory (DHI), Hearing Handicap Inventory (HHI), Tinnitus Handicap Inventory (THI), and Facial Disability Index (FDI). QoL changes over time as well as predictive factors were accessed by multivariate analyses of covariance (MANCOVA). Results: In total, 173 preoperative and 80 postoperative questionnaires were analyzed. There was a significant PH deterioration related to facial function (FDI, PANQOL-face) after surgery. In line with facial rehabilitation, however, FDI improved within the first five years after surgery and did not differ compared to the preoperative patient cohort, eventually. In contrast, MH (i.e., PANQOLanxiety) and general health (i.e., PANQOL-GH) improved with surgery and correlated with the extent-of-resection. Conclusion: Physical and mental health is significantly influenced by VS surgery. While PH might decrease after surgery, MH potentially increases when patient is cured. Practitioners should take MH into account before advising an incompletely VS treatment (e.g., subtotal resection, observation or radiosurgery). [ABSTRACT FROM AUTHOR]

Spring floods trigger spawning in many native fishes of the desert Southwest (USA), but less is known about fish community response when native fishes are rare. Here, we document change to native and nonnative fish captures and instream habitat features following a decade-high flooding event (2019) in the Verde River (AZ) where native fish captures were rare in the years pre-flood. Using prepositioned areal electrofishing devices (PAEDs), we sampled the fish community at 90 sampling units pre-flood (2017) and resampled those same units post-flood (2019) to compare and identify changes to catch and habitat features. Relative abundance of native fishes increased from 0.6% pre-flood (0.01 fish/PAED) to 53.0% post-flood (1.66 fish/PAED) and was largely attributable to the presence of juvenile Roundtail Chub Gila robusta (≤ 70 mm total length (TL)) and juvenile Sonora Sucker Catostomus insignis (≤ 100 mm TL). Juvenile Desert Sucker Catostomus clarkii experienced a lesser increase. One adult native fish was captured in 2017 and adult native fishes were absent from 2019 sampling. The catch of adult/subadult Common Carp Cyprinus carpio (> 100 mm TL) declined; however, this could be related to reservoir management and not the flood. The abundance of all size-classes of Black Bass Micropterus spp., Red Shiner Cyprinella lutrensis and other nonnative fishes did not change. The majority (97%) of juvenile native fishes were captured at the uppermost sampling reach. A 54% reduction to canopy cover across all sampling reaches and an increase of fine sediments at the most downstream reach demonstrates how floods can restructure the river environment. This case-study adds evidence that protection of spring floods is vital to the persistence and recolonization of fishes native to the desert Southwest, especially where they are rare. The continued presence of nonnative species may preclude juvenile native fishes from recruiting to adults. [ABSTRACT FROM AUTHOR]

Effluent discharge from wastewater treatment plants can be a substantial source of microplastics in receiving water bodies including rivers. Despite growing concern about microplastic pollution in freshwater habitats, the literature has not yet addressed effluent-dependent rivers, which derive 100% of their baseflow from effluent. The objective of this study was to document and explore trends in microplastic pollution within the effluent-dependent lower Santa Cruz River near Tucson, Arizona (USA). We examined microplastic concentrations in the water column and benthic sediment and microplastic consumption by mosquitofish (Gambusia affinis) at 10 sites along a ~40 km stretch of the lower Santa Cruz River across two time periods: baseflow (effluent only) and post-flood (effluent immediately following urban runoff). In total, across both sampling periods, we detected microplastics in 95% of water column samples, 99% of sediment samples, and 6% of mosquitofish stomachs. Flow status (baseflow vs post-flood) was the only significant predictor of microplastic presence and concentrations in our models. Microplastic fragment concentrations in the water column were higher post-flood, microplastic fiber concentrations in benthic sediment were lower post-flood, and mosquitofish were more likely to have consumed microplastics post-flood than during baseflow. The additional microplastics detected after flooding was likely due to a combination of allochthonous material entering the channel via runoff and bed scour that exhumed microplastics previously buried in the riverbed. Effluent-dependent urban streams are becoming increasingly common; more work is needed to identify microplastic pollution baselines and trends in effluent rivers worldwide. [ABSTRACT FROM AUTHOR]

Problem: Cervical cancer screening strategies in the United States include cotesting (human papillomavirus (HPV) with cytology), primary HPV with genotyping and reflex cytology, and cytology alone. An ongoing challenge is the appropriate triage of patients to colposcopy to those at highest risk. We investigated whether incorporation of p16INK4a immunodetection by enzyme‐linked immunosorbent assay (ELISA) on fresh cervical samples obtained at the time of screening could improve appropriate referral to colposcopy. Method of Study: A derivation group comprised of cervical swabs collected from subjects with high‐grade dysplasia or cancer (positive control) and from subjects with negative screening history (negative control). Samples collected from colposcopy were used to evaluate the existing screening strategies individually and with incorporation of p16INK4a ELISA. Histology was used as the gold standard. Results: Among 163 subjects recruited, 138 were included. In the derivation group, mean p16INK4a level was 2.86 ng/mL (n = 31) and 0.58 ng/mL (n = 20) among positive and negative controls respectively (p = 0.002) with an area under the receiver operator characteristic curve of 0.79 (p < 0.001). Among colposcopy subjects, sensitivity/specificity for cotesting, primary HPV, and cytology were 94%/42%, 88%/45%, and 88%/49%, respectively. Incorporation of p16INK4a resulted in similar sensitivity and improved specificity (cotesting+p16 88%/58%, primary HPV+p16 88%/57%, cytology+p16 81%/62%; p = 0.23/p = 0.008) with decrease in colposcopy referrals by 15% to 22% (p = 0.01). Conclusions: These results demonstrate the feasibility of quantifying p16INK4a by ELISA in fresh cervical samples, and its potential as an adjunct to existing screening strategies in the identification of high grade‐dysplasia while reducing the number of colposcopic referrals. [ABSTRACT FROM AUTHOR]

SCCOHT: PATHOGENESIS AND HISTORICAL TREATMENT SCCOHT is a rare, aggressive malignancy primarily affecting young women; mean age at diagnosis is 24 years.[3] Tumors are large, averaging 15.7 cm,[4] and hypercalcemia is present in approximately 65% of patients. SCCOHT is typified by genomic stability, with a low tumor mutational burden and few chromosomal abnormalities.[13],[14] Despite this, these tumors have immunogenic microenvironments with strong PD-L1 expression and increased tumor-infiltrating lymphocytes (TILs).[15] Given the rarity of this malignancy, treatment beyond cytoreductive surgery is heterogeneous and unstandardized. MOLECULAR TUMOR BOARD CASE DISCUSSION AND PERSPECTIVES ON MATCHED THERAPIES To our knowledge, this is the first report of this I SMARCA4 i germline mutation in SCCOHT[11],[21] and the first report of treatment with either ponatinib or combination CDK4/6 inhibition and immune checkpoint blockade (ICB) in SCCOHT. Ann Oncol 29:viii576-viii595, 2018 36 Soldi R, Ghosh Halder T, Weston A, et al: The novel reversible LSD1 inhibitor SP-2577 promotes anti-tumor immunity in SWItch/Sucrose-NonFermentable (SWI/SNF) complex mutated ovarian cancer [Internet]. bioRxiv 2020.01.10.902528, 2020 37 Sheng W, LaFleur MW, Nguyen TH, et al: LSD1 Ablation stimulates anti-tumor immunity and enables checkpoint blockade. [Extracted from the article]

Purpose: To evaluate MRI characteristics in vaginal recurrence of endometrial cancer (EC) including tumor volume shrinkage during salvage radiotherapy, and to identify imaging features associated with survival. Methods: Patients with vaginal recurrence of EC treated with external beam radiotherapy (EBRT) followed by brachytherapy (BT), and with available pelvic MRI at two time points: baseline and/or before BT were retrospectively identified from 2004 to 2017. MRI features including recurrence location and tissue characteristics on T2- and T1-weighted images were evaluated at baseline only. Tumor volumes were measured both at baseline and pre-BT. Survival rates and associations were evaluated by Cox regression and Fisher's exact test, respectively. Results: Sixty-two patients with 36 baseline and 50 pre-BT pelvic MRIs were included (24/62 with both MRIs). Vaginal recurrence of EC was most commonly located in the vaginal apex (27/36, 75%). Tumors with a post-contrast enhancing peripheral rim or low T2 signal rim at baseline showed longer recurrence-free survival (RFS) (HR 0.2, 95% CI 0.1–0.9, P < 0.05 adjusted for histology; HR 0.2, 95% CI 0.1–0.8, P < 0.05, respectively). The median tumor shrinkage at pre-BT was 69% (range 1–99%). Neither absolute tumor volumes nor volume regression at pre-BT were associated with RFS. Lymphovascular space invasion (LVSI) at hysterectomy and adjuvant RT were associated with recurrence involving the distal vagina (both P < 0.05). Conclusion: Vaginal recurrences with rim enhancement at baseline MRI predicted improved RFS, while tumor volume shrinkage at pre-BT did not. Distal vaginal recurrence was more common in patients with LVSI and adjuvant RT at EC diagnosis. [ABSTRACT FROM AUTHOR]

Cervical cancer outcomes remain poor among disadvantaged populations, including ethnic minorities, low-income, and underinsured women. The aim of this study was to evaluate the mechanisms that underlie the observed association between race/ethnicity and cervical cancer survival. We identified 13,698 women, ages 21 to 64 years, diagnosed with stages I-III primary cervical cancer between 2007–2013 in Surveillance, Epidemiology, and End Results (SEER). Multivariable Cox proportional hazards regression models evaluated associations between race/ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Other) and cervical cancer-specific mortality. We conducted mediation analysis to calculate the mediation proportion and its 95% confidence interval. Non-Hispanic black women had an increased risk of cervical cancer-specific mortality (HR: 1.23, 95% CI: 1.08–1.39), and Hispanic women a decreased risk of dying from their disease (HR: 0.82, 95% CI: 0.72–0.93), compared with non-Hispanic white. The estimated proportion of excess cervical cancer mortality for non-Hispanic black women relative to non-Hispanic white women that was mediated by insurance was 18.6% and by treatment was 47.2%. Furthermore, non-Hispanic black women were more likely to receive radiation and less likely to receive surgery for early-stage disease. In this population-based study we found that some of the excess cervical cancer-specific mortality for non-Hispanic black women is mediated by factors such as insurance status and treatment. These findings suggest that enhancing existing insurance coverage and ensuring equal and adequate treatment in all women may be a key strategy for improving cervical cancer outcomes. [ABSTRACT FROM AUTHOR]

Radiation therapy is a critical treatment modality in the management of patients with gynecologic tumors. New highly conformal external-beam and brachytherapy techniques have led to important reductions in recurrence and patient morbidity and mortality. However, patients who receive pelvic radiation for gynecologic malignancies may experience a unique constellation of toxicity because of the anatomic locations, combination with concurrent chemotherapy and/or surgery, as well as potential surgical interventions. Although side effects are often categorized into acute versus late toxicities, several late toxicities represent continuation and evolution of the same pathologic process. Comorbidities and radiation dose can significantly increase the risk of morbidity. Current understanding of the incidence of various morbidities in patients treated with current radiation techniques for gynecologic malignancies, the impact of chemotherapy and surgery, treatment options for those effects, and future areas of research are highlighted. Cancer 2014;120:3870-3883. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

The majority of breast cancers developing in BRCA1 mutation carriers are triple negative breast cancers (TNBC), an aggressive subtype that accounts for 15-20 % of sporadic breast cancer. We compare the clinical outcome and sites of relapse of TNBC in BRCA1 mutation carriers and non-carriers who received adjuvant chemotherapy. Women with stage I-III TNBC who had BRCA1 testing within 36 months of diagnosis and received adjuvant chemotherapy were identified from clinical databases at two academic institutions. Sites of relapse, freedom from distant metastasis (FFDM), and breast cancer-specific survival (BCSS) were determined. RCA1 carriers ( n = 89) were significantly younger at diagnosis ( P < 0.0001) than non-carriers ( n = 175). FFDM at 5 years was 80.5 % for carriers and 76.9 % for non-carriers; with median follow-up of 55 months, hazard ratio (HR) was 0.90, P = 0.71. Sites of recurrence, including brain, did not differ significantly. BCSS at 5 years was 88.1 % for carriers and 81.4 % for non-carriers; HR 0.60; P = 0.15 at 55 months follow-up. BRCA1 carriers who underwent oophorectomy had a significantly lower rate of death from TNBC, with an adjusted HR of 0.30 (95 % CI 0.10-0.94). Adjusting for age, oophorectomy, and prophylactic mastectomy, BRCA1 mutation status was not an independent predictor of survival (HR 2.1; P = 0.13). BRCA1 mutation carriers with TNBC had similar survival rates and sites of recurrence to non-carriers after treatment with conventional chemotherapy. Carriers who underwent oophorectomy had a significantly lower rate of breast cancer-related death; this finding should be studied further in all women with TNBC. [ABSTRACT FROM AUTHOR]

Objective: To explore the association of a functional germline variant in the 3′-UTR of KRAS with endometrial cancer risk, as well as the association of microRNA (miRNA) signatures and the KRAS-variant with clinical characteristics and survival outcomes in two prospective RTOG endometrial cancer trials. Methods/Materials: The association of the KRAS-variant with endometrial cancer risk was evaluated by case-control analysis of 467 women with type 1 or 2 endometrial cancer and 582 age-matched controls. miRNA and DNA were isolated for expression profiling and genotyping from tumor specimens of 46 women with type 1 endometrial cancer enrolled in RTOG trials 9708 and 9905. miRNA expression levels and KRAS-variant genotype were correlated with patient and tumor characteristics, and survival outcomes were evaluated by variant allele type. Results: The KRAS-variant was not significantly associated with overall endometrial cancer risk (14% controls and 17% type 1 cancers), although was enriched in type 2 endometrial cancers (24%, p = 0.2). In the combined analysis of RTOG 9708/9905, miRNA expression differed by age, presence of lymphovascular invasion and KRAS-variant status. Overall survival rates at 3 years for patients with the variant and wild-type alleles were 100% and 77% (HR 0.3, p = 0.24), respectively, favoring the variant. Conclusions: The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology. [ABSTRACT FROM AUTHOR]

Due to its rarity, treatment guidelines for vaginal cancer are extrapolated from institutional reports and prospective studies of cervical and anal cancer. An expert panel was convened to reach consensus on the selection of imaging and the rapeutic modalities. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) used by the panel to rate the appropriateness of imaging and treatment procedures. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Four variants were developed to represent clinical scenarios in vaginal cancer managem ent. Group members reached consensus on the appropriateness of the pretreatment evaluation and the rapeutic interventions. This article represents the consensus opinion of an expert panel and may be used to in form clinical recommendations in vaginal cancer management. [ABSTRACT FROM AUTHOR]

Background: Women with BRCA1 mutations develop breast cancer with similar pathologic features to sporadic triple negative (TN) breast cancer, a subtype associated with early disease relapse and poor outcome. The clinical outcome of women with and without BRCA1 mutations who had TN breast cancer treated with conventional chemotherapy were compared.Methods: Women with stage I to III TN breast cancer who had BRCA1 testing within 36 months of diagnosis and received alkylating chemotherapy were identified from clinical databases and a Specialized Program of Research Excellence (SPORE) specimen bank. BRCA2 mutation carriers were excluded, resulting in a study cohort of 46 BRCA1 carriers and 71 noncarriers. Sites of metastasis, relapse rates, and survival were compared among carriers and noncarriers. The median follow-up was 75 months.Results: BRCA1 carriers were younger at diagnosis (P < .001) and had smaller tumors (P = .03) than noncarriers. Freedom from distant metastasis at 5 years was 76% for carriers and 70% for noncarriers (hazard ratio [HR] 0.79, P = .5). Sites of distant recurrence did not differ significantly (P = .15), although BRCA1 carriers had a propensity for brain relapse (58% vs 24%, P = .06). Overall survival at 5 years was 82% for carriers and 74% for noncarriers (HR 0.64, P = .25). Adjusting for age and stage, BRCA1 mutation status was not an independent predictor of survival (HR 0.73, P = .48).Conclusions: BRCA1 mutation carriers with TN disease had similar survival rates to noncarriers when treated with alkylating chemotherapy. Women with BRCA1-related breast cancer may benefit from novel therapies that target DNA repair, and further study is needed to identify sporadic TN breast cancers with a BRCA-deficient phenotype. [ABSTRACT FROM AUTHOR]

The thyroid hormone receptor (TR) has been proposed to regulate expression of target genes in the absence of triiodothyronine (T[sub3]) through the recruitment of the corepressors, NCoR and SMRT. Thus, NCoR and SMRT may play an essential role in thyroid hormone action, although this has never been tested in vivo. To accomplish this, we developed mice that express in the liver a mutant NC0R protein (L-NCoRΔID) that cannot interact with the TR. L-NCoRΔlD mice appear grossly normal, however, when made hypothyroid the repression of many positively regulated T[sub3]-target genesis abrogated, demonstrating that NCoR plays a specific and sufficient role in repression by TR in the absence of T[sub3]. Remarkably, in the euthyroid state, expression of many T[sub3]-targets is also up-regulated in L-NCoRΔID mice, demonstrating that NCoR also determines the magnitude of the response to T[sub3] in euthyroid animals. Although positive T[sub3] targets were up-regulated in L-NCoRΔID mice in the hypoand euthyroid state, there was little effect seen on negatively regulated T[sub3] target genes. Thus, NCoR is a specific regulator of T[sub3]-action in vivo and mediates repression by the unliganded TR in hypothyroidism. Furthermore. NCoR appears to play a key role in determining the tissue-specific responses to similar levels of circulating T[sub3]. Interestingly, NCoR recruitment to LXR is also impaired in this model, leading to activation of LXRtarget genes, further demonstrating that NCoR recruitment regulates multiple nuclear receptor signaling pathways. [ABSTRACT FROM AUTHOR]