Clinical outcomes with utilization of high-potency topical steroids in patients with lichen sclerosus-associated vulvar cancer.

OBJECTIVES: To evaluate the impact of high-potency topical steroid use on risk of recurrence of lichen sclerosus-associated vulvar cancer. METHODS: This is a retrospective cohort study evaluating patients with lichen sclerosus (LS)- associated vulvar squamous cell cancer (VSCC). Demographic and clinical outcome data were compared between two comparison groups: patients who received steroids, mainly clobetasol, and patients who did not receive steroids following treatment of LS-related vulvar cancer. Categorical variables were compared using Fisher's exact test or chi-square test. Continuous variables were compared using a two-sided student's t-test. Time to recurrence (TTR) and overall survival (OS) were analyzed using Kaplan-Meier survival plot and compared using Mantel-Cox log rank test. Cox proportional hazard regression models were conducted to generate hazard ratios for both TTR and OS. A p value of <0.05 was considered statistically significant. RESULTS: A total of 49 patients were included, with 36 patients receiving steroid treatment and 13 patients in the expectant management group. The median age of diagnosis was 68. The average BMI was 31.7 +/- 7.0. The median length of follow up was 41 months. The majority of patients were diagnosed with stage I VSCC. There was no difference in demographics or oncologic management of vulvar cancer between the two cohorts. Overall recurrence was decreased among patients who received steroid treatment when compared to patients who did not, 12 patients (33.3%) versus 9 patients (69.2%) respectively (p = 0.048). CONCLUSIONS: High-potency topical steroid use following treatment of lichen sclerosus-associated vulvar squamous cell carcinoma is associated with decreased risk of recurrence and prolonged median time to recurrence.

Tyrosine kinase inhibitor toxicities: A society of gynecologic oncology review and recommendations.

OBJECTIVE: Oral tyrosine kinase inhibitors (TKIs) have new indications for treatment in gynecologic malignancies. These targeted drugs have both unique and overlapping toxicities, which require careful attention and management. New combination therapies with immune-oncology agents have demonstrated promise in endometrial cancer. This review examines common adverse events associated with TKIs and provides readers with an evidence-based review on current uses and strategies for the management of these medications. METHODS: A comprehensive review of the medical literature on TKI use in gynecologic cancer was undertaken by a committee approach. Details of each drug, its molecular target, and relevant data on both clinical efficacy and side effects were compiled and organized for clinical use. Information on drug-related secondary effects and management strategies for specific toxicities, including dose reduction and concomitant medications, were gathered. RESULTS: TKIs can potentially offer improved response rates and durable responses for a group of patients who were previously without an effective standard second-line therapy. The combination of lenvatinib and pembrolizumab represents a more targeted approach to the drivers of endometrial cancer; however, there remains significant drug-related toxicity, and thus dose reduction and dose delay are frequently required. Toxicity management requires frequent check-ins and management strategies to help patients find the highest tolerable dose. TKIs are expensive and patient financial toxicity is as critical a measure of a drug's utility as any drug side effect. Many of these drugs have patient assistance programs, which should be fully utilized to minimize cost. CONCLUSIONS: Future studies are needed to expand the role of TKIs into new molecularly driven groups. Attention to cost, durability of response, and long-term toxicity management is needed to ensure all eligible patients have access to treatment.

Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer.

BACKGROUND: Stage III or IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence. METHODS: In this randomized phase 3 trial, we tested whether 6 months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapse-free survival (primary end point) than six cycles of combination chemotherapy alone in patients with stage III or IVA endometrial carcinoma. Secondary end points included overall survival, acute and chronic toxic effects, and quality of life. RESULTS: Of the 813 patients enrolled, 736 were eligible and were included in the analysis of relapse-free survival; of those patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy and 361 received chemotherapy only). The median follow-up period was 47 months. At 60 months, the Kaplan-Meier estimate of the percentage of patients alive and relapse-free was 59% (95% confidence interval [CI], 53 to 65) in the chemoradiotherapy group and 58% (95% CI, 53 to 64) in the chemotherapy-only group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with a lower 5-year incidence of vaginal recurrence (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and pelvic and paraaortic lymph-node recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than chemotherapy alone, but distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Grade 3, 4, or 5 adverse events were reported in 202 patients (58%) in the chemoradiotherapy group and 227 patients (63%) in the chemotherapy-only group. CONCLUSIONS: Chemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00942357.).

Patient reported outcomes for cisplatin and radiation followed by carboplatin/paclitaxel versus carboplatin/paclitaxel for locally advanced endometrial carcinoma: An NRG oncology study.

INTRODUCTION: Chemotherapy plus radiation (Cis-RT + CP) did not demonstrate superiority in prolonging relapse-free survival compared to chemotherapy alone in patients with stage III or IVA endometrial carcinoma. The impact of treatment on quality of life (QOL), neurotoxicity (NTX) and psychometric properties of the gastrointestinal (GI) symptoms subscale during treatment and up to 1 year are described herein. METHODS: QOL assessments were scheduled at baseline, 6 weeks (post completion of RT (Cis-RT + CP) or prior to cycle 3 (CP)), then 18 weeks (end of treatment) and 70 weeks (1 year after the end of treatment) after starting treatment. QOL instruments included the FACT-En TOI, FACT/GOG-neurotoxicity (Ntx) subscale (short), and the gastrointestinal (GI) symptoms subscale. RESULTS: At the end of treatment, patients receiving Cis-RT + CP reported a statistically significant decreased QOL when compared to CP. The decline in QOL was reflected in physical well-being, functional well-being, and endometrial cancer specific concerns, but the minimally important differences (MID) were not considered clinically meaningful. Patients in both groups reported increased chemotherapy-induced Ntx symptoms with the CP group having worse scores and reaching peak symptoms at the time of chemotherapy completion. Patients on Cis-RT + CP reported statistically significantly worse GI symptoms after radiation therapy compared to patients on CP, this occurred across assessment intervals, though the MID was not meaningful. Psychometric evaluations indicated that the GI symptom scale is reliable, valid, and responsive to change. CONCLUSIONS: PROs indicate that the chemoradiotherapy group experienced worse HRQoL and GI toxicity compared to patients randomized to chemotherapy alone for locally advanced endometrial cancer though based on the MID, these were not clinically meaningful differences. The GI symptom subscale was a reliable and valid scale that has value for future trials. TRIAL REGISTRATION: NCT00942357.

Abdominopelvic MR to CT registration using a synthetic CT intermediate.

Accurate coregistration of computed tomography (CT) and magnetic resonance (MR) imaging can provide clinically relevant and complementary information and can serve to facilitate multiple clinical tasks including surgical and radiation treatment planning, and generating a virtual Positron Emission Tomography (PET)/MR for the sites that do not have a PET/MR system available. Despite the long-standing interest in multimodality co-registration, a robust, routine clinical solution remains an unmet need. Part of the challenge may be the use of mutual information (MI) maximization and local phase difference (LPD) as similarity metrics, which have limited robustness, efficiency, and are difficult to optimize. Accordingly, we propose registering MR to CT by mapping the MR to a synthetic CT intermediate (sCT) and further using it in a sCT-CT deformable image registration (DIR) that minimizes the sum of squared differences. The resultant deformation field of a sCT-CT DIR is applied to the MRI to register it with the CT. Twenty-five sets of abdominopelvic imaging data are used for evaluation. The proposed method is compared to standard MI- and LPD-based methods, and the multimodality DIR provided by a state of the art, commercially available FDA-cleared clinical software package. The results are compared using global similarity metrics, Modified Hausdorff Distance, and Dice Similarity Index on six structures. Further, four physicians visually assessed and scored registered images for their registration accuracy. As evident from both quantitative and qualitative evaluation, the proposed method achieved registration accuracy superior to LPD- and MI-based methods and can refine the results of the commercial package DIR when using its results as a starting point. Supported by these, this manuscript concludes the proposed registration method is more robust, accurate, and efficient than the MI- and LPD-based methods.

Adjusting to the new reality: Evaluation of early practice pattern adaptations to the COVID-19 pandemic.

OBJECTIVE: We aim to define national practice patterns to assess current clinical practice, anticipated delays and areas of concern that potentially could lead to deviations from the normal standard of care. METHODS: Anonymous surveys were emailed to members of the Society of Gynecologic Oncology (SGO). The spread of COVID-19 and its impact on gynecologic oncology care in terms of alterations to normal treatment patterns and anticipated challenges were assessed. The Wilcoxon rank sum test was performed to determine risk factors for COVID-19 infection. RESULTS: We analyzed the responses of 331 gynecologic oncology providers. COVID-19 is present in 99.1% of surveyed communities with 99.7% reporting mitigation efforts in effect. The infection rate differs significantly between regions (p≪0.001) with the Northeast reporting the highest number of COVID-19 cases. Practice volume has dropped by 61.6% since the start of the pandemic with most cancellations being provider initiated. A majority of responders (52.8%) believed that ovarian cancer will be the most affected cancer by COVID-19. >94% of responders are proceeding with gynecologic cancer surgeries with exception of grade 1, endometrioid endometrial adenocarcinoma (36.3%). Surgical backlog (58.6%), delayed cancer diagnosis (43.2%) and re-establishing normal care with delayed patient (37.8%) were identified as the top 3 challenges after COVID-19 has abated. CONCLUSIONS: COVID-19 is widespread and has radically altered normal practice patterns. Despite COVID-19 related concerns, most gynecologic oncology care is proceeding. However, the steep decline in clinical volume shows there is a large group of patients who are not being diagnosed or are deferring care.

Prophylactic Gynecologic Surgery at Time of Colectomy Benefits Women with Lynch Syndrome and Colon Cancer: A Markov Cost-Effectiveness Analysis.

BACKGROUND: Women with Lynch syndrome who have completed childbearing should be offered prophylactic hysterectomy and bilateral salpingo-oophorectomy for gynecologic cancer prevention. The benefit of prophylactic gynecologic surgery at the time of colon cancer resection is unclear. OBJECTIVE: This study aimed to compare the cost, quality of life, and likelihood of being alive and free from colon, endometrial, and ovarian cancer between operative choices for patients with Lynch syndrome undergoing surgery for colon cancer. DESIGN: A Markov decision tree spanning 40 years was constructed for a hypothetical cohort of 30-year-old women with Lynch syndrome who had been diagnosed with colon cancer. Outcomes of 6 surgical strategies were compared, including segmental or total abdominal colectomy with or without hysterectomy alone or combined with bilateral salpingo-oophorectomy. SETTINGS: A Markov cost-effectiveness analysis was performed at a single center. PATIENTS: A literature search was performed identifying studies of patients with genetically diagnosed Lynch syndrome that described cost, risk of mortality, and quality of life after colon cancer resection and prophylactic gynecologic surgery. MAIN OUTCOME MEASURES: The primary outcomes measured were quality-adjusted life-years and the likelihood of being alive and free from colon, endometrial, and ovarian cancer 40 years after surgery. RESULTS: Women with Lynch syndrome who underwent a total abdominal colectomy and hysterectomy with bilateral salpingo-oophorectomy had the highest likelihood of being alive and cancer free. Total abdominal colectomy with hysterectomy was a close second, but yielded the largest amount of quality-adjusted life-years and lowest cost. LIMITATIONS: This study is limited by the statistical method and quality of studies used. CONCLUSIONS: Total abdominal colectomy with prophylactic hysterectomy at 30 years of age was the most cost-effective surgical choice in women with Lynch syndrome and colon cancer. The addition of bilateral salpingo-oophorectomy offered the highest event-free survival and lowest mortality. However, the additional morbidity of premature menopause of prophylactic salpingo-oophorectomy for younger women outweighed the benefit of ovarian cancer prevention. See Video Abstract at http://links.lww.com/DCR/B287. LA CIRUGÍA GINECOLÓGICA PROFILÁCTICA EN EL MOMENTO DE LA COLECTOMÍA BENEFICIA A LAS MUJERES CON SÍNDROME DE LYNCH Y CÁNCER DE COLON: UN ANÁLISIS DE COSTO-EFECTIVIDAD DE MARKOV: Las mujeres con síndrome de Lynch que han completado la maternidad deberían recibir histerectomía profiláctica y salpingooforectomía bilateral para la prevención del cáncer ginecológico. El beneficio de la cirugía ginecológica profiláctica en el momento de la resección del cáncer de colon no está claro.Comparar el costo, la calidad de vida y la probabilidad de estar viva y libre de cáncer de colon, endometrio y ovario entre las opciones quirúrgicas para pacientes con síndrome de Lynch sometidos a cirugía por cáncer de colon.Se construyó un árbol de decisión de Markov que abarca cuarenta años para una cohorte hipotética de mujeres de 30 años con síndrome de Lynch diagnosticadas con cáncer de colon. Se compararon los resultados de seis estrategias quirúrgicas, incluida la colectomía abdominal segmentaria o total con o sin histerectomía sola o combinada con salpingooforectomía bilateral.Se realizó un análisis de costo-efectividad de Markov en un solo centro.se realizó una búsqueda bibliográfica para identificar estudios de pacientes con síndrome de Lynch con diagnóstico genético que describieron el costo, el riesgo de mortalidad y la calidad de vida después de la resección del cáncer de colon y la cirugía ginecológica profiláctica.años de vida ajustados por calidad y probabilidad de estar vivo y libre de cáncer de colon, endometrio y ovario 40 años después de la cirugía.Las mujeres con síndrome de Lynch que se sometieron a una colectomía e histerectomía abdominal total con salpingooforectomía bilateral tuvieron la mayor probabilidad de estar vivas y libres de cáncer. La colectomía abdominal total con histerectomía fue un segundo lugar cercano, pero produjo la mayor cantidad de años de vida ajustados por calidad y el costo más bajo.Este estudio está limitado por el método estadístico y la calidad de los estudios utilizados.La colectomía abdominal total con histerectomía profiláctica a los 30 años fue la opción quirúrgica más rentable en mujeres con síndrome de Lynch y cáncer de colon. La adición de salpingooforectomía bilateral ofreció la mayor supervivencia libre de eventos y la menor mortalidad. Sin embargo, la morbilidad adicional de la menopausia prematura de la salpingooforectomía profiláctica para las mujeres más jóvenes superó el beneficio de la prevención del cáncer de ovario. Consulte Video Resumen en http://links.lww.com/DCR/B287. (Traducción-Dr. Yesenia Rojas-Khalil).

The association between progesterone receptor expression and survival in women with adult granulosa cell tumors.

BACKGROUND: Granulosa cell tumors (GCT) variably express estrogen receptors (ER) and progesterone receptors (PR). The goal of this study is to evaluate the relationship between ER and PR expression patterns and clinical outcomes in women with GCT. METHODS: A multicenter, retrospective analysis was performed of all cases of GCT diagnosed between 1989 and 2012. Immunohistochemical staining for ER and PR was performed on formalin-fixed paraffin embedded (FFPE) tumor tissue and interpreted using a semiquantitative scoring system that incorporated tumor cell staining proportion and intensity. Demographics, disease status, and survival information were collected. Associations between ER and PR staining scores and recurrence-free and overall survival were assessed using univariate Cox proportional hazards models. RESULTS: FFPE tumor blocks were available for 149/186 GCT patients. The majority of the women had clinical stage I disease (76%). ER and PR expression was present in 52% and 98% of subjects, respectively. The median composite scores of ER and PR staining were 1 (range 0-8) and 9 (range 0-15), respectively. In univariate analysis, PR composite score >9 was strongly associated with decreased recurrence-free survival (HR = 2.9, 95% CI = 1.5-5.5) and decreased overall survival (HR = 3.7, CI 1.3-10.2). ER composite score was not a significant predictor of recurrence-free survival or overall survival (p = 0.7, HR = 1.1, 95% CI 0.6-2.0 and p = 0.06, HR = 1.1, 95% CI 0.4-2.9, respectively). CONCLUSIONS: Our results reveal that high PR composite score (≥9) was associated with both decreased recurrence-free and overall survival in patients with GCT while ER expression was not associated with survival outcomes.

Prior breast cancer and tamoxifen exposure does not influence outcomes in women with uterine papillary serous carcinoma.

OBJECTIVES: To evaluate progression-free survival (PFS) and overall survival (OS) outcomes in women diagnosed with uterine papillary serous carcinoma (UPSC) who have had (UPSCBR+) or have not had (UPSCBR-) an antecedent history of breast cancer and to correlate their outcomes to prior tamoxifen exposure. METHODS: Data were collected for women diagnosed with UPSC at two academic institutions between January 1997 and July 2012. Patient demographics, tumor histology, stage, and treatments were recorded. Patients were divided into two groups: those with and without a personal history of breast cancer. Within the UPSCBR+ cohort, we identified those with a history of tamoxifen use. Cox regression modeling was used to explore associations between selected covariates of interest and the time-to-event outcomes of PFS and OS. RESULTS: Of 323 patients with UPSC, 46 (14%) were UPSCBR+. Of these, 15 (33%) had a history of tamoxifen use. UPSCBR+ patients were older than UPSCBR- (median years, 72 vs. 68, p=0.004). UPSCBR+ women showed no significant difference in PFS or OS compared to UPSCBR- (p=0.64 and p=0.73 respectively), even after controlling for age (p=0.15 and p=0.48 respectively). Within the UPSCBR+ cohort, there was no difference in PFS or OS with or without tamoxifen exposure (p=0.98 and p=0.94 respectively). CONCLUSIONS: There was no difference in PFS or OS between the UPSCBR+ and UPSCBR- cohorts. We did not demonstrate significant OS or PFS differences in women who took tamoxifen prior to their endometrial cancer diagnosis. These findings have implications for counseling, and should be encouraging to women who are facing their second cancer diagnosis.

Continuous epidural infusion anesthesia and analgesia in gynecologic oncology patients: less pain, more gain?

OBJECTIVE: There is a lack of consistent data regarding gynecologic oncology (GO) patients and the use of neuraxial anesthesia for post-operative pain management. Our objective was to compare the use of continuous epidural infusion (CEI) as part of post-operative pain management to more traditional management schemes. METHODS: GO patients undergoing laparotomy from July 1st, 2011 through July 31st, 2012 were identified. Patient demographic data and peri-operative details were abstracted from the medical record. The primary outcome was a mean patient visual analog pain score. Secondary outcomes included length of stay, post-operative urinary tract infection (UTI) and venous thromboembolic (VTE) events. RESULTS: There were 237 laparotomies during the study time period. Fifty-six women had CEI for post-operative pain management and 181 did not. Patients with CEI had lower pain scores on POD #0 (3.8 vs 5.3, p < 0.01), #1 (2.6 vs 4.0, p < 0.01) and #2 (2.5 vs 3.5, p < 0.01) compared to women without CEI. There was no difference in the length of stay between those with and without CEI (103 vs 94 h, p = 0.32). Women with CEI did have a longer length of urinary catheterization (56 vs 26 h, p = 0.01) but not an increased rate of UTI (5.5% vs 1.8%, p = 0.24). There was a higher rate of post-operative VTE events among women with CEI (8.9% vs 1.7%, p = 0.02). CONCLUSIONS: In this small series, GO patients undergoing laparotomy had improved post-operative pain control when their analgesia regimen included CEI. However, the higher rate of VTE events among CEI users is concerning and merits further investigation.

The Risk Factors of Readmission in Postoperative Gynecologic Oncology Patients at a Single Institution.

INTRODUCTION: Hospital readmission rates are an important measure of quality care and have recently been tied to reimbursement. This study seeks to identify the risk factors for postoperative readmission in patients treated by a gynecologic oncology service. METHODS: A 7-year retrospective review (2007-2013) of all patients operated on by the University of Virginia gynecologic oncology service who were readmitted within 30 days of discharge was performed. Abstracted data included demographics, dates of surgery, operative details, cancer history, and relevant medical history. The readmitted patients (n = 166) were compared with randomly selected controls (n = 168) from the same service in a matching time frame and analyzed using univariate and multivariate models. RESULTS: In the study period, 2993 operations were performed. One hundred sixty-six unique patients (5.5%) were readmitted within 30 days of discharge from their operative procedure. On multivariate analysis, the factors that were associated with a higher risk of readmission were a history of psychiatric disease, postoperative complication, type of insurance, surgical modality, and lysis of adhesions at the time of surgery. The most common readmission diagnoses were infection (44%), nausea/vomiting (28%), thrombosis (6%), bowel leak (4%), and bleeding (4%). CONCLUSIONS: Postoperative readmissions are a common problem and are increasingly important as a measure of quality. Although patients were generally admitted for infections or gastrointestinal complaints, we also found that individual factors such as mental health and socioeconomic status also contributed. Our data suggest that we can preoperatively identify high-risk individuals for whom extra resources can be directed postoperatively to avoid unnecessary readmissions.

Up-Front Multigene Panel Testing for Cancer Susceptibility in Patients With Newly Diagnosed Endometrial Cancer: A Multicenter Prospective Study.

PURPOSE: Clinical utility of up-front multigene panel testing (MGPT) is directly related to the frequency of pathogenic variants (PVs) in the population screened and how genetic findings can be used to guide treatment decision making and cancer prevention efforts. The benefit of MGPT for many common malignancies remains to be determined. In this study, we evaluated up-front MGPT in unselected patients with endometrial cancer (EC) to determine the frequency of PVs in cancer susceptibility genes. METHODS: Patients with EC were prospectively enrolled at nine Ohio institutions from October 1, 2017, to December 31, 2020. Nine hundred and sixty-one patients with newly diagnosed EC underwent clinical germline MGPT for 47 cancer susceptibility genes. In addition to estimating the prevalence of germline PVs, the number of individuals identified with Lynch syndrome (LS) was compared between MGPT and tumor-based screening. RESULTS: Likely pathogenic variants or PVs were identified in 97 of 961 women (10.1%). LS was diagnosed in 29 of 961 patients (3%; 95% CI, 2.1 to 4.3), with PVs in PMS2 most frequent. MGPT revealed nine patients with LS in addition to the 20 identified through routine tumor-based screening. BRCA1 and BRCA2 PVs were found in 1% (10 of 961; 95% CI, 0.6 to 1.9) of patients and that group was significantly enriched for type II ECs. CONCLUSION: This prospective, multicenter study revealed potentially actionable germline variants in 10% of unselected women with newly diagnosed EC, supporting the use of up-front MGPT for all EC patients. The discovery that BRCA1 or BRCA2 heterozygotes frequently had type II cancers points to therapeutic opportunities for women with aggressive histologic EC subtypes.

An analysis of vulvar necrotizing fasciitis in the unique and ethnically diverse Hawaiian population.

Vulvar necrotizing fasciitis is a surgical emergency with a high rate of morbidity and mortality. Our case series adds seven patients to the literature and presents the first group that is predominantly of Pacific-Islander origin. This study not only confirms traditional risk factors such as diabetes mellitus, obesity and hypertension but investigates ethnicity and socioeconomic status as risk factors. Also presented is a case of recurrent necrotizing fasciitis initially involving the vulva, then the back. In any patient for which there is suspicion of vulvar necrotizing fasciitis, surgical diagnosis remains the gold standard and facilitates rapid debridement of all necrotic tissues. Aggressive surgical debridement with broad spectrum antibiotic coverage is required to minimize mortality.

3T multiparametric MRI-guided high-dose-rate combined intracavitary and interstitial adaptive brachytherapy for the treatment of cervical cancer with a novel split-ring applicator.

PURPOSE: To evaluate the role of 3T-MRI-guided adaptive high-dose-rate (HDR) combined intracavitary and interstitial brachytherapy for cervical cancer using a novel intracavitary split-ring (ICSR) applicator adapter. METHODS AND MATERIALS: We retrospectively reviewed all HDR brachytherapy cases from 2013 to 2015 using an ICSR applicator. Initial optimization was performed using 3T multiparametric MRI (mpMRI) series with an applicator in place. The mpMRI series were discretionarily acquired before subsequent fractions for possible target adaptation. When necessary, interstitial needles (ISNs) were inserted through a novel ICSR adapter or freehand. Dosimetric parameters, clinical outcomes, and toxicities were compared between groups. RESULTS: Seventeen patients were included, with a mean followup of 32 months. An mpMRI series preceded each initial fraction and 52.9% of patients underwent ≥1 additional pretreatment mpMRI. Among these subsequent fractions, the high-risk clinical target volume was reduced in 80% vs. 41% without pretreatment mpMRI. Five patients had ISN placement (seven insertions) to improve extracervical target coverage. Mean D90 (Gy) per fraction to the high-risk clinical target volume and intermediate-risk clinical target volume with and without an ISN were 7.51 ± 1.07 vs. 6.14 ± 0.52 (p = 0.028) and 6.35 ± 0.75 vs. 5.21 ± 0.49 (p = 0.007), respectively. Mean fractional D2cc (Gy) for organs at risk was comparable. No Grades 3-4 toxicity was reported. Disease-free survival and local control for the ICSR-ISN and ICSR-alone groups were 29.8 months/80.0% and 31.2 months/83.3%, respectively. CONCLUSIONS: The mpMRI acquisition with ICSR applicator in place immediately before HDR brachytherapy for cervical cancer guided successful adaptive treatment optimization and delivery. Our initial experience with a novel interstitial adapter for the split-ring applicator demonstrated excellent target coverage without compromising organs at risk, resulting in good local control and disease-free survival.

A case report of adult croup: a new old problem.

Larnygeotracheobronchitis is a common disease of childhood most often associated with infection by parainfluenza virus. Although rare, adult cases have been reported. Adult croup presents similarly to the childhood version; however, the severity is usually much worse, often leading to hospitalization. Presented is the case of an 80-year-old woman with croup, which is the twelfth reported in the English literature.

Decreased peritoneal ovarian cancer growth in mice lacking expression of lipid phosphate phosphohydrolase 1.

Lysophosphatidic acid (LPA) is a bioactive lipid that enhances ovarian cancer cell proliferation, migration and invasion in vitro and stimulates peritoneal metastasis in vivo. LPA is generated through the action of autotaxin or phospholipases, and degradation begins with lipid phosphate phosphohydrolase (LPP)-dependent removal of the phosphate. While the effects of LPA on ovarian cancer progression are clear, the effects of LPA metabolism within the tumor microenvironment on peritoneal metastasis have not been reported. We examined the contribution of lipid phosphatase activity to ovarian cancer peritoneal metastasis using mice deficient in LPP1 expression. Homozygous deletion of LPP1 (LPP1 KO) results in elevated levels and decreased turnover of LPA in vivo. Within 2 weeks of intraperitoneal injection of syngeneic mouse ovarian cancer cells, we observed enhanced tumor seeding in the LPP1 KO mice compared to wild type. However, tumor growth plateaued in the LPP1 KO mice by 3 weeks while tumors continued to grow in wild type mice. The decreased tumor burden was accompanied by increased apoptosis and no change in proliferation or angiogenesis. Tumor growth was restored and apoptosis reversed with exogenous administration of LPA. Together, these observations demonstrate that the elevated levels of LPA per se in LPP1 KO mice do not inhibit tumor growth. Rather, the data support the notion that either elevated LPA concentration or altered LPA metabolism affects other growth-promoting contributions of the tumor microenvironment.

Desmoplastic small round cell tumor of the ovary: A rare but devastating disease in young women.

•Desmoplastic small round cell tumor of the ovary is a rare clinical entity with poor prognosis.•Accurate diagnosis utilizes a combination of histological, immunohistological, and cytogenetic findings.•This disease should be kept on the differential diagnosis in young women with widespread disease on presentation.

High poly(adenosine diphosphate-ribose) polymerase expression and poor survival in advanced-stage serous ovarian cancer.

OBJECTIVE: To estimate the range of poly(adenosine diphosphate [ADP]-ribose) polymerase expression in serous ovarian cancers and to determine whether expression is associated with response to therapy and outcome. METHODS: Immunostaining for poly(ADP-ribose) polymerase was performed in 186 paraffin-embedded, serous ovarian cancers. Nuclear poly(ADP-ribose) polymerase expression was quantified using a scoring system that assesses both staining intensity and percentage of cells staining. Kaplan-Meier analysis was performed to evaluate the relationship between poly(ADP-ribose) polymerase expression and overall survival. RESULTS: High poly(ADP-ribose) polymerase expression was present in 54% of serous cancers but was not associated with stage or grade. There was no difference in the rate of complete clinical response to primary chemotherapy between cases with low poly(ADP-ribose) polymerase expression (70%) compared with those with high poly(ADP-ribose) polymerase expression (71%). However, high poly(ADP-ribose) polymerase expression was associated with significantly worse median overall survival (36 compared with 43 months, P=.04, hazard ratio 0.71). CONCLUSION: Expression of poly(ADP-ribose) polymerase in ovarian cancers is heterogeneous, and high expression in serous ovarian cancers is associated with worse overall survival. These data suggest that evaluation of poly(ADP-ribose) polymerase expression in the primary cancer could potentially allow selective use of poly(ADP-ribose) polymerase inhibitors in patients most likely to respond. LEVEL OF EVIDENCE: III.