Trading mental and physical health in vestibular schwannoma treatment decision.

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., PANQOL-anxiety) 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).

The Impact of Racial Disparities on Outcome in Patients With Stage IIIC Endometrial Carcinoma: A Pooled Data Analysis.

OBJECTIVE: To report the impact of race on clinical outcomes in patients with stage IIIC endometrial carcinoma. MATERIALS AND METHODS: A retrospective multi-institutional study included 90 black and 568 non-black patients with stage IIIC endometrial carcinoma who received adjuvant chemotherapy and radiation treatments. Overall survival (OS) and recurrence-free survival (RFS) were calculated by the Kaplan-Meier method. Propensity score matching (PSM) was conducted. Statistical analyses were conducted using SPSS version 27. RESULTS: The Median follow-up was 45.3 months. black patients were significantly older, had more nonendometrioid histology, grade 3 tumors, and were more likely to have >1 positive paraaortic lymph nodes compared with non-black patients (all P <0.0001). The 5-year estimated OS and RFS rates were 45% and 47% compared with 77% and 68% for black patients versus non-black patients, respectively ( P <0.001). After PSM, the 2 groups were well-balanced for all prognostic covariates. The estimated hazard ratios of black versus non-black patients were 1.613 ( P value=0.045) for OS and 1.487 ( P value=0.116) for RFS. After PSM, black patients were more likely to receive the "Sandwich" approach and concurrent chemoradiotherapy compared with non-black ( P =0.013) patients. CONCLUSIONS: Black patients have higher rates of nonendometrioid histology, grade 3 tumors, and number of involved paraaortic lymph nodes, worse OS, and RFS, and were more likely to receive the "Sandwich" approach compared with non-black patients. After PSM, black patients had worse OS with a nonsignificant trend in RFS. Access to care, equitable inclusion on randomized trials, and identification of genomic differences are warranted to help mitigate disparities.

Clinical outcomes and dosimetric predictors of toxicity for re-irradiation of vaginal recurrence of endometrial cancer.

OBJECTIVE: To report clinical outcomes and dosimetric predictors of late toxicity for patients with vaginal recurrence of endometrial cancer treated with brachytherapy in the re-irradiation setting. METHODS: On retrospective review, 32 patients with vaginal recurrence of endometrial cancer received salvage brachytherapy with or without pelvic radiotherapy (RT) from 06/2003-12/2017. Prior RT modalities were vaginal brachytherapy (19, 59%), pelvic RT (7, 22%) or both (6, 19%). Image-guided brachytherapy was performed with CT- (25, 78%) or MR-guidance (7, 22%). Vaginal control, recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier method. Late toxicity was graded by Common Toxicity Criteria for Adverse Events. RESULTS: Median time from prior RT to re-irradiation was 22 months (range, 4-140). Salvage RT modalities were pelvic RT and brachytherapy (25, 78%) or brachytherapy alone (7, 22%). With median follow-up of 47 months, 3/5-year vaginal control, RFS and OS rates were 64/56%, 47/41% and 68/42%, respectively. Six patients (19%) had no evidence of disease at 85-155 months. Late grade 2/3 GI, GU and vaginal toxicity rates were 13%/16%, 19%/13%, and 9%/16%. Cumulative D2cc rectum (sum of prior and salvage RT courses) was predictive of grade 2+ and grade 3 GI toxicity. Cumulative D2cc rectum for an estimated 10% risk of late grade 2+ and 3 GI toxicity was 86 Gy and 92 Gy, respectively. CONCLUSIONS: Salvage image-guided brachytherapy in the re-irradiation setting results in modest local control and increased late toxicity for localized recurrent endometrial cancer. With long-term disease control, cumulative D2cc rectum may be used to reduce late GI complication risk.

Interfraction dose deviation and catheter position in cervical interstitial and intracavitary image guided HDR brachytherapy.

Interstitial and intracavitary gynecological HDR brachytherapy involve precise, localized delivery to targets with high dose gradients, sparing adjacent organs at risk (OAR). Due to the proximity of the rectum, bowel and bladder to the target, deviations in the applicator or catheter with respect to patient anatomy can significantly increase dose to OAR. The magnitude and direction of applicator and catheter migration at each fraction was assessed for template interstitial and tandem and ring (T&R) cohorts. The cohort included twelve gynecological patients with intact cervical lesions treated with external beam and brachytherapy. Pre-treatment CT images were registered to the simulation CT with respect to the target. Treatment catheter positions transformed into the planning CT coordinate system to evaluate localized catheter displacement and dose distributions calculated at each fraction. Dose was evaluated on the planning CT with planning contours and dwell locations at treatment position. Absolute deviation, depth and deflection angle for all patients were 4.6 ± 4.2 mm, -1.4 ± 4.0 mm, and 3.1 ± 2.3° respectively (n = 516 catheter positions for all treatment fractions and patients, mean ± SD). Absolute catheter deviation and deflection magnitude for interstitial treatments increased overall with each subsequent fraction with an overall increase of catheter retraction at each fraction (p < 0.005, n = 492 catheters, Kruskal-Wallis). A target EQD2 D90 reduction of 10 ± 10% and 7.7 ± 8.7% of the planned dose for interstitial and T&R cohorts respectively. There was an overall increase in bladder and rectal doses at each fraction. Catheter tracking in interstitial and intracavitary gynecological treatments with CT imaging revealed significant changes in catheter positioning with respect to the target volume. Overall deviations increased in magnitude with each subsequent fraction in the interstitial treatments. This caused patient dosimetry deviations, including target dose reduction and adjacent OAR doses changes.

Effect of Mismatch Repair Status on Outcome of Early-Stage Grade 1 to 2 Endometrial Cancer Treated With Vaginal Brachytherapy.

OBJECTIVES: The objective of this study was to determine if deficiency of mismatch repair (dMMR) proteins in patients with early-stage favorable endometrial cancer treated with vaginal brachytherapy (VB) is associated with increased recurrence. MATERIALS AND METHODS: A multi-institutional retrospective cohort study of 141 patients with stage I to II grade 1 and 2 endometrioid adenocarcinoma treated with surgery and adjuvant VB was performed to compare recurrence risk in dMMR (n=41) versus MMR-preserved (pMMR) (n=100). Additional clinical and pathologic risk factors were also collected. Univariate analysis and multivariable analysis Cox regression analysis was performed to identify factors associated with any recurrence. Kaplan-Meier method and log rank test were used to compare recurrence free survival and overall survival (OS). RESULTS: Median follow up was 42 months. Forty-one patients (29%) were dMMR. There were 7 recurrences (17%) in dMMR versus 4 recurrences (4%) in pMMR (P=0.009). On univariate analysis of any recurrence, both dMMR (hazard ratio: 5.3, P=0.008) and stage (hazard ratio: 3.8, P=0.05) were statistically significantly associated with time to first recurrence. The 5-year recurrence free survival was 90% (95% CI: 73%-96%) in pMMR versus 61.0% (95% CI: 19%-86%) in dMMR (P=0.003). Five-year OS was 96% (95% CI: 76%-99%) in pMMR versus 86% (95% CI: 62%-95%) in dMMR (P=0.03). CONCLUSIONS: MMR deficiency in stage I to II grade 1 to 2 endometrial cancer patients treated with adjuvant VB alone was associated with statistically significant increased risk for any recurrence and worse OS. MMR status may be an important prognosticator in this cohort of patients warranting adjuvant treatment intensification in the clinical trial setting.

Does Prophylactic Paraortic Lymph Node Irradiation Improve Outcomes in Women With Stage IIIC1 Endometrial Carcinoma?

PURPOSE: To evaluate the impact of prophylactic paraortic lymph node (PALN) radiation therapy (RT) on clinical outcomes in patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 endometrial cancer (EC). METHODS AND MATERIALS: A multi-institutional retrospective study included patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 EC lymph node assessment, status postsurgical staging, followed by adjuvant chemotherapy and RT using various sequencing regimens. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariable and multivariable analysis were performed by Cox proportional hazard models for RFS/OS. In addition, propensity score matching was used to estimate the effect of the radiation field extent on survival outcomes. RESULTS: A total of 378 patients were included, with a median follow-up of 45.8 months. Pelvic RT was delivered to 286 patients, and 92 patients received pelvic and PALN RT. The estimated OS and RFS rates at 5 years for the entire cohort were 80% and 69%, respectively. There was no difference in the 5-year OS (77% vs 87%, P = .47) and RFS rates (67% vs 70%, P = .78) between patients treated with pelvic RT and those treated with pelvic and prophylactic PALN RT, respectively. After propensity score matching, the estimated hazard ratios (HRs) of prophylactic PALN RT versus pelvic RT were 1.50 (95% confidence interval, 0.71-3.19; P = .28) for OS and 1.24 (95% confidence interval, 0.64-2.42; P = .51) for RFS, suggesting that prophylactic PALN RT does not improve survival outcomes. Distant recurrence was the most common site of first recurrence, and the extent of RT field was not associated with the site of first recurrence (P = .79). CONCLUSIONS: Prophylactic PALN RT was not significantly associated with improved survival outcomes in stage IIIC1 EC. Distant metastasis remains the most common site of failure despite routine use of systemic chemotherapy. New therapeutic approaches are necessary to optimize the outcomes for women with stage IIIC1 EC.

MicroRNA profiling in a case-control study of African American women with uterine serous carcinoma.

OBJECTIVE: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer associated with worse survival outcomes in African American (AA) patients. This study evaluated tumor miRNA expression by race, clinical and tumor characteristics, and survival outcomes. METHODS: FFPE tumor tissue from hysterectomy specimens was identified for 29 AA cases. Case matching was performed by computer-based random assignment in a 1:1 ratio with Caucasian controls based on age, stage and histologic subtype (pure vs. mixed). RNA was extracted from 77 specimens (54 tumors and 23 matched normal endometrium). MicroRNA array profiling was performed by microRNA Hi-Power Labeling (Hy3/Hy5) and hybridization to miRCURY LNA microRNA Array 7th Gen. RESULTS: Clinical and treatment characteristics were similar for cases and controls, although use of adjuvant radiation was less common in African Americans (p = 0.03). Of 968 miRNAs analyzed, 649 were differentially expressed in normal endometrium vs. tumor. When compared by race, histologic subtype, stage or presence of LVI, no differentially expressed miRNAs were identified. In patients with disease recurrence at 3 years, the three most upregulated miRNAs were miR-1, miR-21-5p and miR-223. Of these, increased miR-223 expression (>median) was associated with worse OS (p = 0.0496) in an independent dataset (TCGA dataset) comprising of 140 patients with USC (mixed or pure serous). After adjusting for age, ethnicity and BMI, upregulation of miR-223 remained risk factor for death (adjusted HR 2.87, 95% CI 1.00-8.27). CONCLUSIONS: MiRNA profiling did not identify biological differences between AA and Caucasian patients with USC. Upregulation of miR-223 may be a prognostic factor in USC.

Adjuvant Radiation Field Extent and Sites of Failure in Node Positive Endometrioid Endometrial Cancer.

PURPOSE: In patients with node-positive endometrial cancer, adjuvant radiation therapy with chemotherapy decreases local-regional recurrence compared with chemotherapy alone. However, the optimal radiation field borders and extent of nodal coverage have not been well studied. In a multi-institutional cohort, survival outcomes and sites of failure were analyzed for patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIIC endometrioid endometrial cancer treated with pelvic radiation therapy (PRT) versus extended-field radiation therapy (EFRT), which encompassed high para-aortic lymph nodes. METHODS AND MATERIALS: In a multi-institutional retrospective study, 143 patients with FIGO stage IIIC1 or IIIC2 endometrioid endometrial cancer treated with adjuvant radiation therapy from 2000 to 2016 were identified. Patient subgroups were classified by substage and radiation field extent: stage IIIC1 received EFRT, stage IIIC1 received PRT, and stage IIIC2 received EFRT. Recurrence-free survival (RFS), overall survival (OS), and out-of-field recurrence were calculated by the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards model. Sites of failure were categorized as within or outside the radiation field. RESULTS: The median follow-up was 59 months; 87% of patients received chemotherapy. The 5-year RFS and OS rates were 73% and 87%, respectively. By subgroup, 5-year RFS rates were 79% for stage IIIC1 EFRT, 73% for stage IIIC1 PRT, and 69% for stage IIIC2 EFRT (P = .4). On multivariate analysis, the recurrence risk was highest for stage IIIC2 EFRT, although this result was not statistically significant (adjusted hazard ratio, 2.0; P = .4). In-field vaginal and nodal recurrences were observed in 2 patients (1%) and 4 patients (3%), respectively. Of 78 patients with stage IIIC1 cancer treated with PRT, 5 (6%) had isolated para-aortic nodal relapse outside the radiation field; 3 were long-term survivors (more than 6 years after salvage therapy). For patients with para-aortic recurrence, 86% had lymphovascular invasion, 71% had myometrial invasion of ≥50%, and 57% had grade 3 disease. CONCLUSIONS: Adjuvant chemoradiation therapy resulted in excellent survival outcomes for patients with FIGO stage IIIC endometrioid endometrial cancer. For patients with positive pelvic nodes, isolated para-aortic relapse outside the PRT field was uncommon and amenable to salvage therapy.

Definitive radiotherapy for vaginal recurrence of early-stage endometrial cancer: survival outcomes and effect of mismatch repair status.

OBJECTIVE: To evaluate clinical outcomes, prognostic factors, and toxicity in patients with vaginal recurrence of early-stage endometrial cancer treated with definitive radiotherapy. METHODS: Retrospective review identified 62 patients with stage I-II endometrial cancer and vaginal recurrence treated with external beam radiotherapy and image-guided brachytherapy with definitive intent from November 2004 to July 2017. All patients had prior hysterectomy without adjuvant radiotherapy and >3 months follow-up. Mismatch repair (MMR) status was determined by immunohistochemical staining of the four mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6) when available in the pathology record. Rates of vaginal control, recurrence-free survival, and overall survival were calculated by Kaplan-Meier. Univariate and multivariate analyses were performed by Cox proportional hazards. RESULTS: Most patients had endometrioid histology (55, 89%), grade 1 or 2 tumor (53, 85%), and vaginal-only recurrence (55, 89%). With a median follow-up of 39 months (range, 3-167), 3- and 5-year rates of vaginal control, recurrence-free survival, and overall survival were 86% and 82%, 69% and 55%, and 80% and 61%, respectively. On multivariate analysis, non-endometrioid histology (HR 12.5, P<0.01) was associated with relapse when adjusted for chemotherapy use. Patients with non-endometrioid histology also had a 4.5-fold higher risk of death when adjusted for age (P=0.02). Twenty patients had known MMR status, all with grade 1-2 endometrioid tumors and 10 (50%) with MMR deficiency. The 3-year recurrence-free survival was 100% for MMR-proficient tumors and 52% for MMR-deficient (P=0.03). Late grade 2 and 3 gastrointestinal, genitourinary and vaginal toxicity was reported in 27% and 3%, 15% and 2%, and 16% and 2% of patients, respectively. CONCLUSION: Definitive radiotherapy with image-guided brachytherapy resulted in 5-year local control rates exceeding 80% and late severe toxicity rates were under 3%. Distant recurrence was common and highest for those with grade 3 or non-endometrioid tumors and MMR deficient grade 1-2 disease.

Impacts of baseflow and flooding on microplastic pollution in an effluent-dependent arid land river in the USA.

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.

Race- and Age-Related Disparities in Cervical Cancer Mortality.

BACKGROUND: Although the incidence of cervical cancer among younger Black women is now equivalent to that of White women, it is unknown whether the reduced incidence has affected survival rates among younger Black women. The goal of this study was to assess differences in survival by age and race. PATIENTS AND METHODS: A retrospective cohort study was performed using the National Cancer Database to analyze women with nonmetastatic cervical cancer diagnosed between 2004 and 2014. Women with unknown survival data and those who died within 3 months of diagnosis were excluded. Multivariable logistic regression models evaluated interactions between age and race (Black vs non-Black) for presentation with stage I disease and receipt of optimal treatment. A multivariable Cox regression model was used to evaluate survival differences by age and race. RESULTS: Of 55,659 women included, 16.4% were Black. Compared with their non-Black counterparts, fewer Black women presented with stage I disease (37.8% vs 47.8%; P<.01) and received optimal treatment (46.2% vs 58.3%; P<.01). Fewer Black women had private insurance if they were aged <65 years (39.6% vs 55.7%; P<.01), but not if they were aged ≥65 years (11.7% vs 12.4%; P=.43). According to multivariable logistic regression, Black women aged ≤39 years were less likely to present with stage I disease, with a significant interaction term between age and race (P<.01 for interaction). Disparities in overall survival by race were greatest for Black women aged ≤39 years (adjusted hazard ratio, 1.32; 95% CI, 1.20-1.46; P<.01) but decreased with increasing age interval until no disparity was noted for women aged ≥65 years (P<.01 for interaction). CONCLUSIONS: Younger Black women with cervical cancer are at risk for presenting with higher-stage disease and having worse overall survival. These findings may be related to insurance-related disparities and inadequate follow-up for abnormal Papanicolaou test results. Younger Black women with cervical cancer may be a particularly vulnerable population.

A Multi-Institutional Analysis of Adjuvant Chemotherapy and Radiation Sequence in Women With Stage IIIC Endometrial Cancer.

PURPOSE: Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes. METHODS AND MATERIALS: In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. RESULTS: A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P < .05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P < .0001. CONCLUSIONS: The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens.

Triaging abnormal cervical cancer screening tests using p16INK4a detection by ELISA on fresh cervical samples.

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.

Simulation-based graduate medical education in MR-guided brachytherapy for cervical cancer.

PURPOSE: Brachytherapy is critical for the curative treatment of locally advanced cervical cancer. Although brachytherapy use is declining in the United States (U.S.), novel interstitial or intracavitary applicators and advances in image guidance for applicator placement and treatment planning have allowed for tumor dose escalation while reducing normal tissue toxicity. Recent survey data have suggested insufficient brachytherapy training for radiation oncology trainees in the United States. This study aimed to address these gaps by developing and piloting a simulation-based education (SBE) workshop for MR-guided cervical cancer brachytherapy. METHODS AND MATERIALS: An SBE workshop was developed for graduate medical education (GME) trainees focusing on MR-guided brachytherapy for cervical cancer. Four hands-on stations, simulating aspects of the procedure, were led by a team of gynecological brachytherapy experts. The learners were radiation oncology residents and fellows in a U.S. GME training program. The primary outcome was feasibility, assessed by completion of the workshop within the time constraints of the curriculum. Learners completed preworkshop and postworkshop surveys to provide information on efficacy. RESULTS: The workshop was successfully completed in a 1-h block of GME didactic time. Ten trainees completed all four stations, and all completed preworkshop and postworkshop surveys, which showed improvements in knowledge and technical proficiency. Feedback was positive, and trainees requested additional learning opportunities. CONCLUSIONS: This study showed that GME-focused SBE in MR-guided cervical cancer brachytherapy was feasible. SBE provided a nonclinical environment in which to practice aspects of MR-guided brachytherapy. Ongoing work includes collaboration with other U.S. institutions. Future studies should focus on international adaptation.

Low-dose adjuvant vaginal cylinder brachytherapy for early-stage non-endometrioid endometrial cancer: recurrence risk and survival outcomes.

OBJECTIVE: The aim of this study was to evaluate recurrence patterns and survival outcomes for patients with early-stage non-endometrioid endometrial adenocarcinoma treated with adjuvant high-dose rate vaginal brachytherapy with a low-dose scheme. METHODS: A retrospective review was performed of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II non-endometrioid endometrial cancer who received adjuvant vaginal brachytherapy with a low-dose regimen of 24 Gy in six fractions from November 2005 to May 2017. All patients had >6 months of follow-up. Rates of recurrence-free survival, overall survival, vaginal, pelvic, and distant recurrence were calculated by the Kaplan-Meier method. Prognostic factors for recurrence and survival were evaluated by Cox proportional hazards modeling. RESULTS: A total of 106 patients were analyzed. Median follow-up was 49 months (range 9-119). Histologic subtypes were serous (47%, n=50), clear cell (10%, n=11), mixed (27%, n=29), and carcinosarcoma (15%, n=16). Most patients (79%) had stage IA disease, 94% had surgical nodal assessment, and 13% had lymphovascular invasion. Adjuvant chemotherapy was delivered to 75%. The 5-year recurrence-free and overall survival rates were 74% and 83%, respectively. By histology, 5-year recurrence-free/overall survival rates were: serous 73%/78%, clear cell 68%/88%, mixed 88%/100%, and carcinosarcoma 56%/60% (p=0.046 and p<0.01). On multivariate analysis, lymphovascular invasion was significantly associated with recurrence (HR 3.3, p<0.01). The 5-year vaginal, pelvic, and distant recurrence rates were 7%, 8%, and 21%, respectively. Vaginal and pelvic recurrence rates were highest for patients with carcinosarcoma, lymphovascular invasion and/or FIGO stage IB/II disease. At 5 years, vaginal and pelvic recurrence rates for patients with lymphovascular invasion were 33% and 40%, respectively. Patients with stage IA disease or no lymphovascular invasion had 5-year vaginal recurrence rates of 4% and pelvic recurrence rates of 6% and 3%, respectively. CONCLUSIONS: Adjuvant high-dose rate brachytherapy with a low-dose scheme is effective for most patients with early-stage non-endometrioid endometrial cancer, particularly stage IA disease and no lymphovascular invasion. Pelvic radiation therapy should be considered for those with carcinosarcoma, lymphovascular invasion and/or stage IB/II disease.

Retinoblastoma protein expression and its predictors in triple-negative breast cancer.

Retinoblastoma protein (Rb) is a product of the RB tumor suppressor gene. Its expression is highly prevalent in luminal breast cancers and is critical to the success of cyclin-dependent kinase (CDK) 4/6 inhibitor therapy. Expression of Rb in triple-negative breast cancer (TNBC), tumors generally associated with basal biology, is not well known. However, heterogeneity among TNBC and presence of subtypes with luminal features are well described. The purpose of this study was to determine prevalence and predictors of Rb protein expression in BRCA1-associated and sporadic TNBCs. We studied 180 TNBC patients (70 BRCA1-associated and 110 sporadic). The clinical and pathologic features of these cases were previously assessed and reported. For this study, immunohistochemical stains for Rb were performed on tissue microarray sections. Details of treatment and outcome were abstracted from medical records. Fifty-one percent of TNBC were Rb positive (≥10% nuclei staining), and 85% of these cases had ≥50% nuclei staining. Rb expression was significantly associated with sporadic TNBC (71.4% vs 49.4%; p < 0.001), androgen receptor (AR) expression (16.5% vs 3.4%; p = 0.007), histologic grade 1 or 2 (9.9% vs 2.2%; p = 0.04), and first recurrence in bone (8.8% vs 1.1%; p = 0.03). Expression of p53 was not associated with Rb expression. Expression of Rb in TNBC was significantly associated with sporadic TNBC, AR expression, lower histologic grade, and metastasis to bone. These observations characterize a TNBC subtype with features suggestive of luminal-like biology and the potential to benefit from CDK 4/6 inhibition.

Executive summary of the American Radium Society® Appropriate Use Criteria for management of uterine carcinosarcoma.

OBJECTIVE: Uterine carcinosarcomas (UCS) represent a rare but aggressive subset of endometrial cancers, comprising <5% of uterine malignancies. To date, limited prospective trials exist from which evidence-based management of this rare malignancy can be developed. METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript are evidence-based guidelines developed by a multidisciplinary expert panel for management of women with UCS. An extensive analysis of current medical literature from peer-reviewed journals was performed. A well-established methodology (modified Delphi) was used to rate the appropriate use of imaging and treatment procedures for the management of UCS. These guidelines are intended for the use of all practitioners who desire information about the management of UCS. RESULTS: The majority of patients with UCS will present with advanced extra uterine disease, with 10% presenting with metastatic disease. They have worse survival outcomes when compared to uterine high-grade endometrioid adenocarcinomas. The primary treatment for non-metastatic UCS is complete surgical staging with total hysterectomy, salpingo-oophorectomy and lymph node staging. Patients with UCS appear to benefit from adjuvant multimodality therapy to reduce the chance of tumor recurrence with the potential to improve overall survival. CONCLUSION: Women diagnosed with uterine UCS should undergo complete surgical staging. Adjuvant multimodality therapies should be considered in the treatment of both early- and advanced stage patients. Long-term surveillance is indicated as many of these women may recur. Prospective clinical studies of women with UCS are necessary for optimal management.

Vaginal recurrence of endometrial cancer: MRI characteristics and correlation with patient outcome after salvage radiation therapy.

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.