A cost-effective, machine learning-based new unified risk-classification score (NU-CATS) for patients with endometrial cancer.

INTRODUCTION: Treatment for endometrial cancer (EC) is increasingly guided by molecular risk classifications. Here, we aimed at using machine learning (ML) to incorporate clinical and molecular risk factors to optimize risk assessment. METHODS: The Cancer Genome Atlas-Uterine Corpus Endometrial Carcinoma (n = 596), Memorial Sloan Kettering-Metastatic Events and Tropisms (n = 1315) and the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (n = 4561) datasets were used to identify genetic alterations and clinicopathological features. Software packages including Keras, Pytorch, and Scikit Learn were tested to build artificial neural networks (ANNs) with a binary output as either intra-abdominal metastatic progression ('1') vs. non-metastatic ('0'). RESULTS: Black patients with EC have worse prognosis than White patients, adjusting for TP53 or POLE mutation status. Over 75% of Black patients carry TP53 mutations as compared to approximately 40% of White patients. Older age is associated with an increasing likelihood of TP53 mutation, high risk histology, and distant metastasis. For patients above age 70, 91% of Black and 60% of White EC patients carry TP53 mutations. A ML-based New Unified classifiCATion Score (NU-CATS) that incorporates age, race, histology, mismatch repair status, and TP53 mutation status showed 75% accuracy in prognosticating intra-abdominal progression. A higher NU-CATS is associated with an increasing risk of having positive pelvic or para-aortic lymph nodes and distant metastasis. NU-CATS was shown to outperform Leiden/TransPORTEC model for estimating risk of FIGO Stage I/II disease progression and survival in Black EC patients. CONCLUSION: The NU-CATS, a ML-based, cost-effective algorithm, incorporates diverse clinicopathologic and molecular variables of EC and yields superior prognostication of the risk of nodal involvement, distant metastasis, disease progression, and overall survival.

Treatment Strategies for Oligometastatic Breast Cancer.

OPINION STATEMENT: Oligometastatic breast cancer, typically defined as the presence of 1-5 metastases, represents an intermediate state between locally advanced and widely metastatic disease. Emerging research suggests that oligometastatic cancer has a unique molecular signature distinct from widely metastatic disease, and that it carries a superior prognosis. Owing to its more limited capacity for widespread progression, oligometastatic disease may benefit from aggressive ablative therapy to known metastases. Options for ablation include surgical excision, radiofrequency ablation, and hypofractionated image-guided radiotherapy (HIGRT). The phase II SABR-COMET trial, which enrolled patients with oligometastatic disease of multiple histologies and randomized them to HIGRT vs. standard of care, found a notable survival advantage in favor of HIGRT. Other data suggest that HIGRT may synergize with immunotherapy by releasing powerful cytokines that increase anti-tumor immune surveillance and by recruiting tumor infiltrating lymphocytes, helping to overcome resistance to therapy. There are many ongoing trials exploring the role of ablative therapy, most notably HIGRT, with or without immunotherapy, for the treatment of oligometastatic breast cancer.We believe that patients with oligometastatic breast cancer should be offered enrollment on prospective clinical trials when possible. Outside the context of a clinical trial, we recommend that select patients with oligometastatic breast cancer be offered treatment with a curative approach, including ablative therapy to all sites of disease if it can be safely accomplished. Currently, selection criteria to consider for ablative therapy include longer disease-free interval from diagnosis to metastasis (>2 years), fewer metastases, and fewer involved organs. Undoubtedly, new data will refine or even upend our understanding of the definition and optimal management of oligometastatic disease.

Association of chemotherapy and radiotherapy sequence with overall survival in locoregionally advanced endometrial cancer.

OBJECTIVE: The optimal adjuvant management of women with FIGO Stage III-IVA endometrial cancer (EC) is unclear. While recent prospective data suggest that treatment with pelvic radiotherapy (RT) prior to chemotherapy (CT) is not associated with a survival benefit compared to CT alone, no prospective randomized trial has included a treatment arm in which CT is given before RT. METHODS: An observational cohort study was performed on women with FIGO Stage III-IVA Type 1 (grade 1-2, endometrioid) EC who underwent hysterectomy and received multi-agent CT and/or RT from 2004 to 2014 at Commission on Cancer-accredited hospitals. Multivariable parametric accelerated failure time models were performed to estimate the association of sequence of adjuvant CT and RT with overall survival (OS) using propensity score-adjusted matched cohorts. RESULTS: Of 5795 women identified, 1260 (21.7%) received RT only, 2465 (42.5%) received CT only, 593 (9.7%) received RT before CT, and 1506 (26.0%) received RT after CT. Women who received RT after CT experienced significantly longer 5-year OS than women who received RT before CT (5-year OS: 80.1% vs 73.3%; time-ratio (TR) = 1.37, 95% CI = 1.18-1.58, P < 0.001), CT only (68.9%; TR = 1.33, 95% CI = 1.19-1.48, P < 0.001), or RT only (64.5%, TR = 1.50, 95% CI = 1.32-1.70, P < 0.001). CONCLUSIONS: For women with advanced EC, treatment with multi-agent CT followed by RT is associated with longer OS compared with treatment with RT followed by CT or either treatment alone. These hypothesis-generating data support inclusion in future prospective trials of regimens in which multi-agent CT starts prior to RT.

Updates on adjuvant chemotherapy and radiation therapy for endometrial cancer.

PURPOSE OF REVIEW: This article will provide an opinion on adjuvant treatment of stage I-III endometrial cancer based on existing and evolving evidence. RECENT FINDINGS: For early-stage (I and II) intermediate risk endometrial cancer, vaginal brachytherapy reduces the risk of locoregional relapse. Recent studies have investigated the use of chemotherapy in early stage, high-risk patient population, but did not demonstrate a survival benefit. As such, chemotherapy is only recommended for selected patients at high risk for distant recurrence. On the other hand, for stage III disease, chemotherapy has a well established role. A landmark trial recently reported confirmed that chemoradiation improves recurrence-free survival compared with radiation alone in stage III endometrial cancer. However, in another randomized phase III trial, chemoradiotherapy was not superior to chemotherapy alone in this group, raising questions as to whether addition of radiation is necessary. Therefore, improved risk stratification using molecular markers in addition to traditional pathological criteria is critically needed to better predict the risk of local and systemic recurrence and to assist therapy decision-making. SUMMARY: Endometrial cancer care is evolving and recent pivotal trials highlight the significance of chemotherapy to the treatment of stage III endometrial cancer and not to the approach for stage I and II cancer. The role of radiation therapy for stage III disease is raised into question.

Clinical implementation, logistics and workflow guide for MRI image based interstitial HDR brachytherapy for gynecological cancers.

Interstitial brachytherapy (IBT) is often utilized to treat women with bulky endometrial or cervical cancers not amendable to intracavitary treatments. A modern trend in IBT is the utilization of magnetic resonance imaging (MRI) with a high dose rate (HDR) afterloader for conformal 3D image-based treatments. The challenging part of this procedure is to properly complete many sequenced and co-related physics preparations. We presented the physics preparations and clinical workflow required for implementing MRI-based HDR IBT (MRI-HDR-IBT) of gynecologic cancer patients in a high-volume brachytherapy center. The present document is designed to focus on the clinical steps required from a physicist's standpoint. Those steps include: (a) testing IBT equipment with MRI scanner, (b) preparation of templates and catheters, (c) preparation of MRI line markers, (d) acquisition, importation and registration of MRI images, (e) development of treatment plans and (f) treatment evaluation and documentation. The checklists of imaging acquisition, registration and plan development are also presented. Based on the TG-100 recommendations, a workflow chart, a fault tree analysis and an error-solution table listing the speculated errors and solutions of each step are provided. Our workflow and practice indicated the MRI-HDR-IBT is achievable in most radiation oncology clinics if the following equipment is available: MRI scanner, CT (computed tomography) scanner, MRI/CT compatible templates and applicators, MRI line markers, HDR afterloader and a brachytherapy treatment planning system capable of utilizing MRI images. The OR/procedure room availability and anesthesiology support are also important. The techniques and approaches adopted from the GEC-ESTRO (Groupe Européen de Curiethérapie - European Society for Therapeutic Radiology and Oncology) recommendations and other publications are proven to be feasible. The MRI-HDR-IBT program can be developed over time and progressively validated through clinical experience, this document is expected to serve as a reference workflow guideline for implementing and performing the procedure.

Development of a nomogram to predict the clinical impact of a postexcision preirradiation mammogram.

We aimed to better quantify the impact of a postexcision preirradiation mammogram (PPM), first by identifying factors associated with abnormal results and then incorporating these findings into a nomogram. Beginning February 2011, our institution made a practice change to obtain a PPM on all patients with any calcifications identified. A total of 530 patients underwent a PPM. Suspicious abnormalities were reported in 61 patients (11.5%), with the PPM leading to a change in management in 47 instances (8.9%). A nomogram was created based on patient and tumor characteristics to identify patients most likely to have an abnormal PPM.

Stage I uterine carcinosarcoma: Matched cohort analyses for lymphadenectomy, chemotherapy, and brachytherapy.

OBJECTIVE: To determine if lymphadenectomy, chemotherapy and radiotherapy are associated with survival benefit among women with stage I uterine carcinosarcoma. METHODS: Women with stage I uterine carcinosarcoma (n=5614) were identified from the 1998-2013 National Cancer Data Base. Kaplan-Meier survival estimates and Cox proportional-hazards regression models were used to evaluate predictors of overall survival. Effects of these predictors were also estimated using propensity score matched analyses for lymphadenectomy, adjuvant chemotherapy, and radiotherapy. RESULTS: 42.0% (2360/5614) of women in the cohort received no adjuvant radiation or chemotherapy. Black race and positive surgical margin status were associated with decreased survival by multivariable Cox regression. Among women with pathologically node-negative disease, the hazard of death increased 5% (4-7%) per each one centimeter increase in tumor size (P=1.9×10-10). From matched cohort analyses, omitting lymphadenectomy was associated with decreased median (interquartile range) survival: 45.2 (36.4-57.6) versus 73.9 (63.8-91.6) months, hazard ratio (HR) (95% CI) 1.38 (1.20-1.59), P=9.4×10-6. Hazard of death decreased by 3% (1-5%) for each five lymph nodes removed (P=0.01). Multiagent chemotherapy and vaginal brachytherapy were associated with decreased hazard of death (HR (95% CI) 0.62 (0.54-0.73), P=1.1×10-9 and HR (95% CI) 0.83 (0.70-0.97), P=0.02, respectively). Highest five-year survival was observed after brachytherapy and multiagent chemotherapy (74.1% (68.3-80.3%), P<2.0×10-16). CONCLUSION: Lymphadenectomy to at least 15-20 removed nodes is associated with increased survival of women with node-negative uterine carcinosarcoma. Adjuvant "cuff and chemo" with vaginal brachytherapy and multiagent chemotherapy is associated with increased survival.

Receipt of vaginal brachytherapy is associated with improved survival in women with stage I endometrioid adenocarcinoma of the uterus: A National Cancer Data Base study.

BACKGROUND: Randomized controlled trials have consistently shown that the use of postoperative radiotherapy (RT) for stage I endometrial cancer leads to a reduction in the incidence of pelvic recurrences without a corresponding reduction in overall mortality. It was hypothesized that a reduction in mortality associated with the receipt of RT could be identified in a large data set with greater statistical power. METHODS: Women with surgically staged IA or IB endometrial adenocarcinoma who were treated with total hysterectomy between 2003 and 2011 were identified in the National Cancer Data Base. Chi-square tests and multivariate logistic regression were performed to analyze factors associated with the treatment type. A survival analysis was performed with log-rank testing, Cox proportional hazards regression, and Kaplan-Meier estimates. RESULTS: A total of 44,309 eligible women were identified (33,380 at stage IA and 10,929 at stage IB): 88.4% of the women with stage IA tumors and 51.6% of the women with stage IB tumors received no RT. Older age, comorbid disease, a higher histologic grade, and a larger tumor size were independently associated with an increase in mortality. The receipt of vaginal brachytherapy (VB) was independently associated with a reduction in mortality for both stage IA disease (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.67-0.97) and stage IB disease (HR, 0.62; 95% CI, 0.51-0.74). CONCLUSIONS: Analyses of this large database support the utility of postoperative VB for many women with stage I endometrial cancer. Unfortunately, RT appears to be underused in this population. Greater adherence to consensus guidelines may lead to improved outcomes. Cancer 2016;122:3724-31. © 2016 American Cancer Society.

National Evaluation of the New Commission on Cancer Quality Measure for Postmastectomy Radiation Treatment for Breast Cancer.

BACKGROUND: Current guidelines recommend postmastectomy radiotherapy (PMRT) for patients with ≥4 positive lymph nodes and suggest strong consideration of PMRT in those with 1-3 positive nodes. These recommendations were incorporated into a Commission on Cancer quality measure in 2014. However, national adherence with these recommendations is unknown. Our objectives were to describe PMRT use in the United States in patients with stage I to III invasive breast cancer and to examine possible factors associated with the omission of PMRT. METHODS: From the National Cancer Data Base, 753,536 mastectomies at 1123 hospitals were identified from 1998 to 2011. PMRT use over time was examined using random effects logistic regression analyses, adjusting for patient, tumor, and hospital characteristics. Analyses were stratified by nodal status (≥4 nodes positive, 1-3 nodes positive, node negative). RESULTS: The proportion of patients receiving PMRT increased from 1998 to 2011 (>4 positive nodes: 56.2 to 66.6 %; 1-3 positive nodes: 28.0 to 39.1 %; node-negative: 8.3 to 10.0 %, p < 0.001 for all). In adjusted analyses, patients with ≥4 positive nodes were more likely to have PMRT omitted if they had smaller tumors. Patients with 1-3 positive nodes were more likely to have PMRT omitted if they had lower grade or smaller tumors. Irrespective of patients' nodal status, PMRT utilization rates decreased as age increased. CONCLUSIONS: Though PMRT rates increased over time in patients with ≥4 and 1-3 positive nodes, PMRT in patients with ≥4 positive nodes remains underutilized. Feedback to hospitals using the new Commission on Cancer PMRT measure may help to improve adherence rates.

Patterns of recurrence and role of pelvic radiotherapy in ovarian clear cell adenocarcinoma.

OBJECTIVE(S): The aims of this study were to analyze patterns of recurrence in patients with ovarian clear cell adenocarcinoma (CCA) and to evaluate the role of pelvic radiotherapy (RT). METHODS AND MATERIALS: All patients with ovarian CCA treated at a single institution between 1989 and 2012 were identified, and their medical records were reviewed. Eligibility criteria included histologic diagnosis of pure CCA of the ovary, surgical staging for International Federation of Gynecology and Obstetrics stage I-to-IIIC disease, and adjuvant or neoadjuvant chemotherapy. Selected end points were 3-, 5-, and 8-year cumulative incidence of pelvic recurrence (CIPR). RESULTS: Fifty-six patients met eligibility criteria. Most received intravenous carboplatin and paclitaxel for a median of 6 cycles. Six patients (10.7%) received pelvic RT, and 50 (89.3%) did not. Pelvic RT patients had stage I-to-IIC disease. Median follow-up was 39 months (range, 1-69 months). For the group as a whole, 14 patients (25%) had initial disease recurrence involving the pelvis, whereas 6 (10.7%) had first recurrence outside the pelvis. Three-, 5- and 8-year CIPR were 28.2%, 38.5%, and 43.2%, respectively. There was no significant difference in 3-, 5-, or 8-year CIPR between the group of patients receiving RT (20%, 20%, and 20%) and a group of patients with stages I to IIC who did not receive RT (9.9%, 22.4%, and 30.2%), P = 0.22. During RT, patients developed mild grade 1-to-2 side effects. After RT, 1 patient developed lower extremity lymphedema with recurrent cellulitis. One patient who developed small bowel obstruction before RT developed small bowel radiation enteritis and obstruction after RT, ultimately requiring surgical intervention. CONCLUSIONS: These findings suggest that ovarian CCA exhibits a propensity for pelvic recurrence after surgery and chemotherapy. RT, a local treatment that can effectively sterilize microscopic tumor cells, may benefit patients with this disease. Prospective studies with sufficient statistical power are warranted to further evaluate the role of RT.

Race, Prevalence of POLE and POLD1 Alterations, and Survival Among Patients With Endometrial Cancer.

Importance: Black patients with endometrial cancer (EC) in the United States have higher mortality than patients of other races with EC. The prevalence of POLE and POLD1 pathogenic alterations in patients of different races with EC are not well studied. Objective: To explore the prevalence of and outcomes associated with POLE and POLD1 alterations in differential racial groups. Design, Setting, and Participants: This retrospective cohort study incorporated the largest available data set of patients with EC, including American Association for Cancer Research Project GENIE (Genomics Evidence Neoplasia Information Exchange; 5087 participants), Memorial Sloan Kettering-Metastatic Events and Tropisms (1315 participants), and the Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (517 participants), collected from 2015 to 2023, 2013 to 2021, and 2006 to 2012, respectively. The prevalence of and outcomes associated with POLE or POLD1 alterations in EC were evaluated across self-reported racial groups. Exposure: Patients of different racial groups with EC and with or without POLE or POLD1 alterations. Main Outcomes and Measures: The main outcome was overall survival. Data on demographic characteristics, POLE and POLD1 alteration status, histologic subtype, tumor mutation burden, fraction of genome altered, and microsatellite instability score were collected. Results: A total of 6919 EC cases were studied, of whom 444 (6.4%), 694 (10.0%), and 4869 (70.4%) patients were self-described as Asian, Black, and White, respectively. Within these large data sets, Black patients with EC exhibited a lower weighted average prevalence of pathogenic POLE alterations (0.5% [3 of 590 cases]) compared with Asian (6.1% [26 of 424]) or White (4.6% [204 of 4520]) patients. By contrast, the prevalence of POLD1 pathogenic alterations was 5.0% (21 cases), 3.2% (19 cases), and 5.6% (255 cases) in Asian, Black, and White patients with EC, respectively. Patients with POLD1 alterations had better outcomes regardless of race, histology, and TP53 alteration status. For a total of 241 clinically annotated Black patients with EC, a composite biomarker panel of either POLD1 or POLE alterations identified 7.1% (17 patients) with positive outcomes (1 event at 70 months follow up) in the small sample of available patients. Conclusions and Relevance: In this retrospective clinicopathological study of patients of different racial groups with EC, a composite biomarker panel of either POLD1 or POLE alteration could potentially guide treatment de-escalation, which is especially relevant for Black patients.

Oligometastatic Breast Cancer.

Oligometastatic breast cancer is typically defined as the presence of 1-5 metastases and represents an intermediate state between locally advanced and widely metastatic disease. Oligometastatic cancer appears have a molecular signature that is distinct from widely metastatic disease and is associated with a superior prognosis. Due to its more limited capacity for widespread progression, oligometastatic disease could potentially benefit from aggressive ablative therapy to known sites of disease. The phase II SABR-COMET trial enrolled patients with oligometastatic disease of multiple histologies and randomized them to HIGRT vs. standard of care, finding a notable survival advantage in favor of HIGRT. There are many ongoing trials exploring the role of HIGRT for the treatment of oligometastatic breast cancer. Future studies may identify optimal candidates for ablative therapy by molecular signature; current clinically-based selection criteria include longer disease-free interval from diagnosis to metastasis (>2 years), fewer metastases, and fewer involved organs.

Should uterine tandem applicators ever be placed without ultrasound guidance? No: a brief report and review of the literature.

BACKGROUND: Brachytherapy is an integral component of the curative treatment of locally advanced cervical cancer. Optimal applicator placement is associated with improvements in local control and treatment-related toxicity. Uterine perforation by the tandem is common and often undetected by orthogonal radiographs. The role of ultrasound in guiding tandem placement remains controversial. METHODS: A 55-year-old woman with International Federation of Gynecology and Obstetrics stage IIB cervix cancer underwent placement of a Fletcher-Suit-Delcos tandem and ovoids applicator. Postoperative computed tomography was used for treatment planning. RESULTS: The applicator appeared to be appropriately placed on clinical exam and orthogonal radiographs. Postoperative computed tomography revealed the tandem had perforated the anterior uterine wall. In a second procedure, the tandem was placed correctly under intraoperative ultrasonography. CONCLUSIONS: A review of the literature finds a relatively high rate of uterine perforation of the uterus that is undetected by orthogonal radiographs or clinical examination. Multiple reports support the use of real-time ultrasound for patients with especially challenging anatomy. As this report illustrates, uterine perforation is possible in any patient. Therefore, routine real-time ultrasonography should be considered for all uterine tandem insertions.

Adaptability and Resilience of Academic Radiation Oncology Personnel and Procedures during COVID-19 Pandemic.

BACKGROUND: A comprehensive response to the unprecedented SARS-CoV-2 (COVID-19) challenges for public health and its impact on radiation oncology patients and personnel for resilience and adaptability is presented. METHODS: The general recommendations included working remotely when feasible, implementation of screening/safety and personal protective equipment (PPE) guidelines, social distancing, regular cleaning of treatment environment, and testing for high-risk patients/procedures. All teaching conferences, tumor boards, and weekly chart rounds were conducted using a virtual platform. Additionally, specific recommendations were given to each section to ensure proper patient treatments. The impact of these measures, especially adaptability and resilience, were evaluated through specific questionnaire surveys. RESULTS: These comprehensive COVID-19-related measures resulted in most staff expressing a consistent level of satisfaction in regard to personal safety, maintaining a safe work environment, continuing quality patient care, and continuing educational activities during the pandemic. There was a significant reduction in patient treatments and on-site patient visits with an appreciable increase in the number of telemedicine e-visits. CONCLUSIONS: Survey results demonstrated substantial adaptability and resilience, including in the rapid recovery of departmental activities during the reactivation phase. In the event of a future public health emergency, the measures implemented may be adopted with good outcomes by radiation oncology departments across the globe.

Impact of p53, HIF1a, Ki-67, CA-9, and GLUT1 Expression on Treatment Outcomes in Locally Advanced Cervical Cancer Patients Treated With Definitive Chemoradiation Therapy.

PURPOSE/OBJECTIVE: The objective of this study was to assess the association between pretreatment p53, hypoxia inducible factor 1a (HIF1a), Ki-67, carbonic anhydrase-9 (CA-9), and glucose transporter 1 (GLUT1) expression in locally advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), local-regional control (LC), and distant metastases-free survival (DMFS). PATIENTS AND METHODS: Twenty-eight patients treated definitively and consecutively for cervical cancer with CRT had p53, HIF1a, Ki-67, CA-9, and GLUT1 protein expression assessed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes. Outcomes were stratified by p53 (H-score: <15 vs. ≥15), HIF1a (H-score: <95 vs. ≥95), Ki-67 (labeling index <41% vs. ≥41%), CA-9 (H-score: <15 vs. ≥15), and GLUT1 (H-score: <175 vs. ≥175) expression. OS, PFS, LC, and DMFS rates were calculated using the Kaplan-Meier method, and differences between groups were evaluated by the log-rank test. RESULTS: Notable clinical characteristics of the cohort included median age of 51 years (range: 32 to 74 y), FIGO stage IIB disease (57.2%), clinical node-negative disease (64.3%), squamous cell carcinoma (89.3%), and adenocarcinoma (10.7%). Treatment outcomes included 5-year OS (57.2%), PFS (48.1%), LC (72.1%), and DMFS (62.9%). For HIF1a H-score <95 and ≥95, the 5-year OS (52.0% and 68.4%, P=0.58), PFS (53.0% and 40.9%, P=0.75), LC (71.6% and 68.2%, P=0.92), and DMFS (59.7% and 52.0%, P=0.91) were not significantly different. For Ki-67 labeling index <41% and ≥41%, the 5-year OS (44.9% and 66.6%, P=0.35), PFS (38.9% and 55.4%, P=0.53), LC (57.7% and 85.7%, P=0.22), and DMFS (67.3% and 61.0%, P=0.94) were not significantly different. For CA-9 H-score <15 and ≥15, the 5-year OS (54.4% and 66.7%, P=0.39), PFS (57.3% and 40.0%, P=0.87), LC (70.0% and 70.0%, P=0.95), and DMFS (70.0% and 46.7%, P=0.94) were not significantly different. For GLUT1 H-score <175 and ≥175, the 5-year OS (43.6% and 43.6%, P=0.32), PFS (55.6% and 49.5%, P=0.72), LC (72.9% and 71.5%, P=0.97), and DMFS (62.5% and 59.6%, P=0.76) were not significantly different. For p53, H-score <15 and ≥15, the 5-year OS (62% and 53%), PFS (63% and 30.3%), LC (87.5% and 52%), and DMFS (79.6% and 41.6%). CONCLUSIONS: In this study population, HIF1a, Ki-67, CA-9, and GLUT1 expression did not predict treatment response or outcomes in locally advanced cervical cancer patients treated definitively with CRT. There was a nonstatistically significant trend towards worse outcomes with p53 expression.

NRG Oncology/RTOG Consensus Guidelines for Delineation of Clinical Target Volume for Intensity Modulated Pelvic Radiation Therapy in Postoperative Treatment of Endometrial and Cervical Cancer: An Update.

PURPOSE: Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions. METHODS AND MATERIALS: An international consensus guideline working group discussed modifications of the current atlas and areas of controversy. A document was prepared to assist in contouring definitions. A sample case abdominopelvic computed tomographic image was made available, on which experts contoured targets. Targets were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement between observers. RESULTS: Sixteen participants provided 13 sets of contours. Participants were asked to provide separate contours of the following areas: vaginal cuff, obturator, internal iliac, external iliac, presacral, common iliac, and para-aortic regions. There was substantial agreement for the common iliac region (sensitivity 0.71, specificity 0.981, kappa 0.64), moderate agreement in the external iliac, para-aortic, internal iliac and vaginal cuff regions (sensitivity 0.66, 0.74, 0.62, 0.59; specificity 0.989, 0.966, 0.986, 0.976; kappa 0.60, 0.58, 0.52, 0.47, respectively), and fair agreement in the presacral and obturator regions (sensitivity 0.55, 0.35; specificity 0.986, 0.988; kappa 0.36, 0.21, respectively). A 95% agreement contour was smoothed and a final contour atlas was produced according to consensus. CONCLUSIONS: Agreement among the participants was most consistent in the common iliac region and least in the presacral and obturator nodal regions. The consensus volumes formed the basis of the updated NRG/RTOG Oncology postoperative atlas. Continued patterns of recurrence research are encouraged to refine these volumes.

Radiation dermatitis in patients treated with concurrent trastuzumab emtansine (T-DM1).

Trastuzumab Emtansine (T-DM1) improves outcomes for patients with HER2+ breast cancer, and is given concurrently with radiation. We have noted increased radiation dermatitis in these patients, which may have been underreported on the KATHERINE clinical trial, and call for clinicians to remain vigilant of unexpected toxicities with newly approved therapies.

Development of a gynecologic brachytherapy curriculum and simulation modules to improve radiation oncology trainees' skills and confidence.

PURPOSE: Brachytherapy in the management of cervical cancer is directly linked to improved survival. Unfortunately, we continue to see a decline in its utilization. A recent survey of U.S. residents demonstrated limited caseload as the greatest barrier to achieving independence in brachytherapy practice. To improve residents' brachytherapy skills and confidence in performing brachytherapy independently, a gynecologic brachytherapy simulation course was developed and tested. METHODS AND MATERIALS: The gynecologic brachytherapy curriculum and simulation modules were developed using a combination of didactic education, self-study, practicums, and patient-centered cases. The simulation modules consisted of 2-h sessions. The first hour occurred within a simulated OR environment, where residents independently performed all aspects of applicator insertion in a cadaver model. The second hour consisted of contouring, dosimetric planning, and treatment evaluation. A brachytherapy training survey developed by the Association of Residents in Radiation Oncology was given before and after the course. RESULTS: The perceived ability to perform brachytherapy independently for a given disease site correlated directly with number of cases performed. Most residents believed that after performing five cases they would be capable of performing additional cases independently (10 of 18). All strongly agreed (8 of 18) or agreed (10 of 18) this to be true after 15 cases. Compared with survey data before the brachytherapy simulation course, trainees felt that their ability to independently perform brachytherapy (p < 0.001) improved. CONCLUSIONS: A brachytherapy simulation course can be used to gain further experience in a controlled environment. Our results demonstrate that gynecologic brachytherapy simulation increased trainees' confidence in performing the procedures independently.

Radiation recall reaction with docetaxel administration after accelerated partial breast irradiation with electronic brachytherapy.

PURPOSE: Accelerated partial breast irradiation (APBI) offers several advantages over whole breast irradiation. Electronic brachytherapy may further reduce barriers to breast conserving therapy by making APBI more available. However, its toxicity profile is not well characterized. METHODS AND MATERIALS: A 60-year-old woman was treated with APBI using Axxent (Xoft, Sunnyvale, CA) electronic brachytherapy. One month after APBI, a cycle of docetaxel and cyclophosphamide was given. Within 3 weeks, the patient developed an ulcerative radiation recall reaction in the skin overlying the lumpectomy cavity. To investigate this toxicity, the skin dose from electronic brachytherapy was compared with the dose that would have been delivered by an iridium-192 ((192)Ir) source. Additionally, a dose equivalent was estimated by adjusting for the increased relative biologic effectiveness (RBE) of low energy photons generated by the electronic source. RESULTS: Using electronic brachytherapy, the skin dose was 537cGy per fraction compared with 470cGy for an (192)Ir source. Given an RBE for a 40kV source of 1.28 compared with (192)Ir, the equivalent dose at the skin for an electronic source was 687cGy-equivalents, a 46% increase. CONCLUSIONS: We present a case of an ulcerative radiation recall reaction in a patient receiving APBI with electronic brachytherapy followed by chemotherapy. Our analysis shows that the use of electronic brachytherapy resulted in the deposition of significantly higher equivalent dose at the skin compared with (192)Ir. These findings suggest that standard guidelines (e.g., surface-to-skin distance) that apply to (192)Ir-based balloon brachytherapy may not be applicable to electronic brachytherapy.

Mechanical properties of the shoulder and pectoralis major in breast cancer patients undergoing breast-conserving surgery with axillary surgery and radiotherapy.

Breast-conserving surgery (BCS) and radiotherapy reduce breast cancer recurrence but can cause functional deficits in breast cancer survivors. A cross-sectional study quantified the long-term pathophysiological impact of these treatments on biomechanical measures of shoulder stiffness and ultrasound shear wave elastography measures of the shear elastic modulus of the pectoralis major (PM). Nine node-positive patients treated with radiotherapy to the breast and regional nodes after BCS and axillary lymph node dissection (Group 1) were compared to nine node-negative patients treated with radiotherapy to the breast alone after BCS and sentinel node biopsy (Group 2) and nine healthy age-matched controls. The mean follow-up for Group 1 and Group 2 patients was 988 days and 754 days, respectively. Shoulder stiffness did not differ between the treatment groups and healthy controls (p = 0.23). The PM shear elastic modulus differed between groups (p = 0.002), with Group 1 patients exhibiting a stiffer PM than Group 2 patients (p < 0.001) and healthy controls (p = 0.027). The mean prescribed radiotherapy dose to the PM was significantly correlated with passive shear elastic modulus (p = 0.018). Breast cancer patients undergoing more extensive axillary surgery and nodal radiotherapy did not experience long-term functional deficits to shoulder integrity but did experience long-term mechanical changes of the PM.