Outcomes and relapse patterns of stage IB grade 2 or 3 endometrial cancer treated with adjuvant vaginal brachytherapy.

INTRODUCTION: Risk factors for pelvic recurrence in early stage endometrial cancer are poorly understood. We sought to describe outcomes, patterns of failure, and risk factors for recurrence among patients with grade 2-3 endometrial cancer with deep myometrial invasion who were treated with vaginal brachytherapy as sole adjuvant therapy after hysterectomy and lymph node dissection. METHODS: We retrospectively reviewed the records of stage I patients with grade 2-3 endometrioid histology and ≥50% myometrial invasion treated at an academic institution from January 2005 to December 2017. Only patients with endometrioid histology were included. Mixed histologies, including papillary serous or clear cell components, were excluded. Further exclusion criteria were International Federation of Gynecology and Obstetrics stage IB grade 1 patients, follow-up time less than 3 months, receipt of pelvic irradiation or any form of systemic therapy (chemotherapy, aromatase inhibitor). Overall survival, disease-free survival, and pelvic recurrence-free survival were calculated with Kaplan-Meier methods. Multivariable Cox proportional hazards regression was used to analyze factors associated with overall survival and disease-free survival. RESULTS: Among 131 consecutive patients identified, 111 (85%) patients met the inclusion criteria. The majority (98.2%) underwent lymph node dissection with ≥10 lymph nodes removed in 78.9%. With a median follow-up of 36 months (IQR 12-70 months), the 3-year overall survival, disease-free survival, and pelvic recurrence-free survival were 89.6%, 90.1%, and 92.8%, respectively. Histologic grade 3, older age, and lymphovascular invasion were not associated with inferior outcomes; however, lower uterine segment involvement (p=0.031), tumor size >4 cm (p=0.024), and <10 lymph nodes removed (p=0.032) were associated with reduced disease-free survival on multivariable analysis. Pelvic recurrence occurred in 12 (11%) patients, most often in the setting of synchronous distant disease (n=9), and was significantly more likely with lower uterine segment involvement. CONCLUSION: Among patients with stage IB grade 2-3 endometrial cancer treated with vaginal brachytherapy, the risk factors for recurrence (larger tumor size and lower uterine segment involvement) in conjunction with established risk factors (high grade, ≥50% myometrial invasion, and lymphovascular invasion) may identify a group of high-risk patients who might benefit from pelvic radiotherapy.

Patient-Reported Outcomes and Cosmesis in a Feasibility Study of 4-Dimensional Simulated Image Guided Accelerated Partial Breast Irradiation.

PURPOSE: Three-dimensional conformal accelerated partial breast irradiation (APBI) is a treatment option for well selected women with breast cancer, despite reports of adverse cosmetic outcome with this technique. Dose-volume relationships may be responsible for this poor cosmesis. We aimed to determine the feasibility of limiting the exposure of nontarget breast tissue to radiation through smaller planning target volumes achieved through daily image guidance and 4-dimensional computed tomography simulation. METHODS AND MATERIALS: Eligibility criteria included the following: women, age ≥50 years, Karnofsky performance status score ≥70, stage 0 and I breast cancer treated with breast-conserving surgery, margins clear by ≥2 mm, pathologic tumor size ≤2 cm, and 4-dimensional computed tomography with planning target volumes of 0.2 cm rather than the standard 1.0 cm. A dose of 3850 cGy was prescribed in 10 fractions. The study was considered successful if ≥50% of enrollees met dosimetric constraints on the breast (V50 < 45% and V100 < 23.5%). RESULTS: The study achieved its primary endpoint of feasibility of reducing the nontarget breast dose with a breast median of V50 = 31% and V100 = 11%. There were no recurrences and no toxicity grade >3. At baseline, fair/poor cosmesis was low (2.2%). By year 3, adverse cosmesis post-APBI had increased by 13.2% (to 15.4%). Patient decisional satisfaction was reached completely in 84.2% of patients. CONCLUSIONS: This study demonstrated that with 4-dimensional simulated APBI that uses stringent dosimetric constraints and image guidance radiation therapy, it is possible to obtain acceptable cosmetic outcomes. We report no locoregional recurrences in 3 years and no toxicity grade >3. The observed decline in cosmesis was acceptable compared with that of prior published studies, and patient satisfaction with APBI was excellent.

Paxillin and embryonic PolyAdenylation Binding Protein (ePABP) engage to regulate androgen-dependent Xenopus laevis oocyte maturation - A model of kinase-dependent regulation of protein expression.

Steroid-triggered Xenopus laevis oocyte maturation is an elegant physiologic model of nongenomic steroid signaling, as it proceeds completely independent of transcription. We previously demonstrated that androgens are the main physiologic stimulator of oocyte maturation in Xenopus oocytes, and that the adaptor protein paxillin plays a crucial role in mediating this process through a positive feedback loop in which paxillin first enhances Mos protein translation, ensued by Erk2 activation and Erk-dependent phosphorylation of paxillin on serine residues. Phosphoserine-paxillin then further augments Mos protein translation and downstream Erk2 activation, resulting in meiotic progression. We hypothesized that paxillin enhances Mos translation by interacting with embryonic PolyAdenylation Binding Protein (ePABP) on polyadenylated Mos mRNA. Knockdown of ePABP phenocopied paxillin knockdown, with reduced Mos protein expression, Erk2 and Cdk1 activation, as well as oocyte maturation. In both Xenopus oocytes and mammalian cells (HEK-293), paxillin and ePABP constitutively interacted. Testosterone (Xenopus) or EGF (HEK-293) augmented ePABP-paxillin binding, as well as ePABP binding to Mos mRNA (Xenopus), in an Erk-dependent fashion. Thus, ePABP and paxillin work together in an Erk-dependent fashion to enhance Mos protein translation and promote oocyte maturation.

Radiation Dermatitis: Recognition, Prevention, and Management.

Radiation therapy (RT) is a frequently used modality for cancer treatment. Acute and/or chronic skin changes may occur and carry risk of influencing quality of life during and after completion of RT. Radiation reactions may lead to delays in treatment, diminished cosmesis, and functional deficits. Lifestyle factors, treatment modalities, topical agents, and, in some cases, wound dressings may be utilized to help prevent or ameliorate radiation-induced skin reactions. While rigorous evidence supporting specific interventions may be lacking or contradictory, this article summarizes the current knowledge of the etiology, manifestations, and interventions available for prevention and management of radiation dermatitis. Further well-designed studies are needed to confirm the efficacy of current recommendations and facilitate development of novel strategies for optimal care of patients with radiation dermatitis.

Adjuvant carboplatin, paclitaxel, and vaginal cuff brachytherapy for stage III endometrial cancer: analysis of outcomes and patterns of recurrence based on pathologic characteristics.

OBJECTIVE: The aim of this study was to evaluate outcomes of patients with stage III endometrial adenocarcinoma treated with surgery followed by adjuvant chemotherapy and vaginal cuff brachytherapy. METHODS: We retrospectively identified 83 patients treated for 1988 International Federation of Gynecology and Obstetrics (FIGO) stage III endometrial adenocarcinoma at our institution between 2003 and 2010. All patients underwent comprehensive surgical staging. Adjuvant therapy was carboplatin and paclitaxel for 6 cycles and vaginal cuff brachytherapy. For analysis, patients were grouped into type I (FIGO grade 1-2 endometrioid histology, n = 41) or type II (FIGO grade 3, clear cell or papillary serous histology, n = 42) disease. Forty-three patients (52%) had node-positive disease, with similar node-positive rates for type I (n = 21, 51.2%) and type II (n = 22, 52.4%). RESULTS: The median follow-up was 38.6 months. There were no isolated vaginal failures. The estimated 3-year disease-free survival (DFS) and overall survival (OS) for type I versus type II were 92.4% versus 58.0% (P = 0.001) and 97.2% versus 65.8% (P = 0.002), respectively. The 3-year DFS and OS for node negative versus node positive were 85.0% versus 63.6% (P = 0.02) and 84.2% versus 78.0% (P = 0.02), respectively. Associations between type I histology and node-negative disease with improved DFS and OS persisted on multivariate analysis. CONCLUSIONS: Our institutional approach of adjuvant chemotherapy and vaginal cuff brachytherapy for stage III endometrial cancer seemed acceptable for patients with low-risk histology or node-negative disease. In contrast, higher rates of failure among those with high-risk histology and/or node-positive disease support intensification of therapy in these subsets.