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To assess whether R2* mapping with a standard Monoexponential (ME) or a Gaussian Augmentation of the Monoexponential (GAME) decay model better characterizes gradient-echo signal decays in gynecological cancers after external beam radiation therapy at 3T, and evaluate implications of modeling for noninvasive identification of intratumoral hypoxia.Multi-gradient-echo signals were acquired on 25 consecutive patients with gynecologic cancers and three healthy participants during inhalation of different oxygen concentrations at 3T. Data were fitted with both ME and GAME models. Models were compared using F-tests in tumors and muscles in patients, muscles, cervix, and uterus in healthy participants, and across oxygenation levels.GAME significantly improved fitting over ME (P0.05): Improvements with GAME covered 34% of tumor regions-of-interest on average, ranging from 6% (of a vaginal tumor) to 68% (of a cervical tumor) in individual tumors. Improvements with GAME were more prominent in areas that would be assumed hypoxic based on ME alone, reaching 90% as ME R2* approached 100 Hz. Gradient echo decay parameters at different oxygenation levels were not significantly different (P = 0.81).R2* may prove sensitive to hypoxia; however, inaccurate representations of underlying data may limit the success of quantitative assessments. Although the degree to which R2 or σ values correlate with hypoxia remains unknown, improved characterization with GAME increases the potential for determining any correlates of fit parameters with biomarkers, such as oxygenation status. J. MAGN. RESON. IMAGING 2016;44:1020-1030.

The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer.Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and 29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The primary endpoint was grade ≥3 AEs occurring within the first 90 days (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]).A total of 34 patients were accrued from November 2009 through December 2011, 30 of whom were eligible and received study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval, 10.6%-36.0%) developed grade ≥3 treatment-related nonhematologic toxicities within 90 days; an additional 6 patients experienced grade ≥3 toxicities between 90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease-free survival rate was 79.1%. No patient developed a within-field pelvic failure and no patients with International Federation of Gynecology and Obstetrics stage I to IIIA disease developed disease recurrence after a median follow-up of 26 months.Postoperative bevacizumab added to chemotherapy and pelvic IMRT appears to be well tolerated and results in high OS rates at 2 years for patients with high-risk endometrial carcinoma.

PURPOSE: Given the complicated nature of an interstitial gynecologic brachytherapy treatment plan, the use of a quantitative tool to evaluate the quality of the achieved metrics compared to clinical practice would be advantageous. For this purpose, predictive mathematical models to predict the D(2cc) of rectum and bladder in interstitial gynecologic brachytherapy are discussed and validated. METHODS: Previous plans were used to establish the relationship between D2cc and the overlapping volume of the organ at risk with the targeted area (C0) or a 1-cm expansion of the target area (C1). Three mathematical models were evaluated: D(2cc) = α*C(1) + β (LIN); D(2cc) = α – exp(–β*C(0)) (EXP); and a mixed approach (MIX), where both C(0) and C(1) were inputs of the model. The parameters of the models were optimized on a training set of patient data, and the predictive error of each model (predicted D(2cc) − real D(2cc)) was calculated on a validation set of patient data. The data of 20 patients were used to perform a K-fold cross validation analysis, with K = 2, 4, 6, 8, 10, and 20. RESULTS: MIX was associated with the smallest mean prediction error

This report presents an update to the American Brachytherapy Society (ABS) high-dose-rate (HDR) brachytherapy guidelines for locally advanced cervical cancer.Members of the ABS with expertise in cervical cancer formulated updated guidelines for HDR brachytherapy using tandem and ring, ovoids, cylinder, or interstitial applicators for locally advanced cervical cancer. These guidelines were written based on medical evidence in the literature and input of clinical experts in gynecologic brachytherapy.The ABS affirms the essential curative role of tandem-based brachytherapy in the management of locally advanced cervical cancer. Proper applicator selection, insertion, and imaging are fundamental aspects of the procedure. Three-dimensional imaging with magnetic resonance or computed tomography or radiographic imaging may be used for treatment planning. Dosimetry must be performed after each insertion before treatment delivery. Applicator placement, dose specification, and dose fractionation must be documented, quality assurance measures must be performed, and followup information must be obtained. A variety of dose/fractionation schedules and methods for integrating brachytherapy with external-beam radiation exist. The recommended tumor dose in 2-Gray (Gy) per fraction radiobiologic equivalence (normalized therapy dose) is 80-90Gy, depending on tumor size at the time of brachytherapy. Dose limits for normal tissues are discussed.These guidelines update those of 2000 and provide a comprehensive description of HDR cervical cancer brachytherapy in 2011.

Inactivation of the PTEN suppressor gene has been shown to occur in the majority of endometrial cancer cases. Somatic PTEN inactivation by deletion and/or mutation, the first detectible change of endometrial carcinogenesis, has been reported to occur at a high frequency in the endometrium of normal premenopausal women, although few of these cases progress to cancer. It was hypothesized that the 50% to 60% reduced cancer risk attributed to oral contraceptives (OCPs) and intrauterine devices (IUDs) occurred in part through their activity as negative selection factors for these subclinical mutated glands.A total of 71 women with a history of OCP use and 80 with a history of IUD use were age matched with 191 and 119 controls, respectively. Endometrial biopsy specimens were immunostained for PTEN, and each was scored for the presence or absence of PTEN-null glands (latent precancer).The frequency of latent precancers was found to be significantly reduced in OCP-exposed (13%; odds ratio [OR], 0.19 [P.001]) and IUD-exposed (18%; OR, 0.42 [P = .015]) women compared with respective matched controls (43% and 34%). The presence or absence of endometritis did not appear to be significantly correlated with PTEN status within the IUD-exposed group (P = .24).Normal-appearing PTEN mutated endometrial glands, which are highly prevalent in the normal population, may be targets of endometrial cancer risk-modulating exposures. Some exposures reported to diminish the incidence of endometrial cancer in epidemiologic outcome studies, including OCP and IUD use, are associated with a proportionate decline in the frequency of latent precancers. Involution of pre-existing endometrial latent precancers, as evaluated by PTEN analysis, may provide an accessible surrogate marker for long-term endometrial cancer risk.