The prognostic impact of substantial lymphovascular space invasion in women with node negative FIGO stage I uterine carcinoma.

OBJECTIVE: Substantial lymphovascular space invasion (LVSI) is an important predictor of lymph node (LN) involvement in women with endometrial carcinoma. We studied the prognostic significance of substantial LVSI in patients with 2009-FIGO stage-I uterine endometrioid adenocarcinoma (EC) who all had pathologic negative nodal evaluation (PNNE). METHODS: Pathologic specimens were retrieved and LVSI was quantified (focal or substantial) in women with stage-I EC who had a hysterectomy and PNNE. In addition to multivariate analysis (MVA), recurrence-free (RFS), disease-specific (DSS), and overall (OS) survival was compared between women with focal vs. substantial LVSI. RESULTS: 1052 patients were identified with a median follow-up of 9.7 years. 358 women (34%) received adjuvant radiotherapy. 907 patients (86.2%) had no LVSI, 87 (8.3%) had focal, and 58 (5.5%) had substantial LVSI. Five-year RFS was 93.3% (95% CI: 91.5-95.1), 76.8% (95% CI: 67.2-87.7) and 79.1% (95% CI: 67.6-95.3) for no, focal, and substantial LVSI(p < 0.0001). There was no statistically significant difference in 5-year RFS, DSS, OS, and in the patterns of initial recurrence between women with focal vs substantial LVSI. On MVA with propensity score matching, substantial LVSI was not independently associated with any survival endpoint compared to focal LVSI, albeit both were detrimental when compared to no LVSI. Age ≥ 60 years and higher grade were predictors of worse RFS, DSS, and OS. Additionally, comorbidity burden was an independent predictor for OS. CONCLUSIONS: Our results suggest that substantial LVSI does not predict worse survival endpoints or different recurrence patterns in women with stage-I EC with PNNE when compared to focal LVSI.

Radiation therapy margin reduction for patients with localized prostate cancer: A prospective study of the dosimetric impact and quality of life.

OBJECTIVES: To investigate the impact of reducing Clinical Target Volume (CTV) to Planning Target Volume (PTV) margins on delivered radiation therapy (RT) dose and patient reported quality-of-life (QOL) for patients with localized prostate cancer. METHODS: Twenty patients were included in a single institution IRB-approved prospective study. Nine were planned with reduced margins (4 mm at prostate/rectum interface, 5 mm elsewhere), and 11 with standard margins (6/10 mm). Cumulative delivered dose was calculated using deformable dose accumulation. Each daily CBCT dataset was deformed to the planning CT (pCT), dose was computed, and accumulated on the resampled pCT using a parameter-optimized, B-spline algorithm (Elastix, ITK/VTK). EPIC-26 patient reported QOL was prospectively collected pre-treatment, post-treatment, and at 2-, 6-, 12-, 18-, 24-, 36-, 48-, and 60-month follow-ups. Post -RT QOL scores were baseline corrected and standardized to a [0-100] scale using EPIC-26 methodology. Correlations between QOL scores and dosimetric parameters were investigated, and the overall QOL differences between the two groups (QOLMargin-reduced -QOLcontrol ) were calculated. RESULTS: The median QOL follow-up length for the 20 patients was 48 months. Difference between delivered dose and planned dose did not reach statistical significance (p > 0.1) for both targets and organs at risk between the two groups. At 4 years post-RT, standardized mean QOLMargin-reduced -QOLcontrol were improved for Urinary Incontinence, Urinary Irritative/Obstructive, Bowel, and Sexual EPIC domains by 3.5, 14.8, 10.2, and 16.1, respectively (higher values better). The control group showed larger PTV/rectum and PTV/bladder intersection volumes (7.2 ± 5.8, 18.2 ± 8.1 cc) than the margin-reduced group (2.6 ± 1.8, 12.5 ± 8.3 cc), though the dose to these intersection volumes did not reach statistical significance (p > 0.1) between the groups. PTV/rectum intersection volume showed a moderate correlation (r = -0.56, p < 0.05) to Bowel EPIC domain. CONCLUSIONS: Results of this prospective study showed that margin-reduced group exhibited clinically meaningful improvement of QOL without compromising the target dose coverage.

The impact of race, comorbid conditions and obesity on survival endpoints in women with high grade endometrial carcinoma.

OBJECTIVE: To estimate overall survival, disease-specific survival, and progression-free survival among high grade endometrial carcinoma cases and to determine factors impacting survival for non-Hispanic white and non-Hispanic black women. METHODS: We identified high grade endometrial carcinoma cases among non-Hispanic white and non-Hispanic black women from ongoing institutional studies, and determined eligibility through medical record and pathologic review. We estimated effects of demographic and clinical variables on survival outcomes using Kaplan Meier methods and Cox proportional hazards modelling. RESULTS: Non-Hispanic Black women with BMI <25.0 had poorest overall survival compared to non-Hispanic white women with BMI <25.0 (HR 3.03; 95% CI [1.35, 6.81]), followed by non-Hispanic black women with BMI 25.0+ (HR 2.43; 95% CI [1.28, 4.60]). A similar pattern emerged for disease-specific survival. Non-Hispanic black women also had poorer progression-free survival than non-Hispanic white women (HR 1.40; 95% CI [1.01, 1.93]). Other significant factors impacting survival outcomes included receipt of National Cancer Center Network (NCCN) guideline-concordant treatment (GCT), earlier stage at diagnosis, and fewer comorbid conditions. CONCLUSIONS: BMI and race interact and modify the association with high grade endometrial carcinoma survival. Other potentially modifiable factors, such as reducing comorbidities and increasing access to GCT will potentially improve survival after diagnosis of high grade endometrial carcinomas. A better understanding of the molecular drivers of these high grade carcinomas may lead to targeted therapies that reduce morbidity and mortality associated with these aggressive tumors.

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.

Charlson Comorbidity score influence on prostate cancer survival and radiation-related toxicity.

INTRODUCTION: In addition to survival endpoints, we explored the impact of Charlson Comorbidity-Index (CCI) on the acute and late toxicities in men with localized prostate cancer who received dose-escalated definitive radiotherapy (RT). MATERIALS AND METHODS: CCI scores at diagnosis and survival outcomes were identified for men with intermediate/high-risk prostate cancer treated with RT (1/2007-12/2012). Study-cohort was accordingly grouped into no, mild and severe comorbidity (CCI-0, 1 or 2+). CCI-groups were compared for demographics, prognostic-factors; and RT-related toxicities based on RTOG/CTCAE criteria. Kaplan-Meier curves and Uni/multivariate (MVA) analyses were used to examine the influence of CCI-group on overall (OS), disease-specific (DSS) and biochemical-relapse free (BRFS) survival. RESULTS: We included 257 patients with median age 73 years (48-85), 53% African-American and 67% had intermediate-risk. Median prostate RT-dose was 76 Gy; and 47% received androgen-deprivation therapy. CCI-0,1,2+ groups encompassed 76 (30%), 54 (21%) and 127 (49%) patients, respectively and were well-balanced. Ten and 15-years OS were significantly different (76% versus 46% versus 55% for 10-years OS and 53% versus 31% versus 14% for 15-years OS for CCI-0 versus CCI-1[HR:2.25; CI[1.31-3.87]] versus CCI-2+[HR:2.73; CI[1.73-4.31]]; p < 0.001. CCI-0 had better DSS than CCI-2+ (HR:2.23; CI[1.06-4.68]; p = 0.03) and BRFS was similar (p = 0.99). Late G2/3 RT-toxicities were more common in CCI-2+ (47%) than CCI-1 (44%) and CCI-0 (29%), p = 0.032; with non-different acute-toxicities (p = 0.62). On MVA, increased CCI was deterministic for OS (HR:3.65; CI [1.71:7.79]; p < 0.001) and was only marginal for DSS (HR:2.55; CI [0.98-6.6]; p = 0.05) with no impact on BRFS (p > 0.05). CONCLUSIONS: Higher CCI is a significant predictor for late RT-related side-effects and shorter OS in men with localized prostate cancer. Baseline comorbidities should be considered during initial counseling and follow up visits.

A Matched Analysis on the Prognostic Impact of Race on Survival Endpoints of Women with Early-Stage Endometrial Cancer.

OBJECTIVE: To compare survival endpoints between African American (AA) and non-AA (NAA) women with endometrial carcinoma (EC) stage I-II using a robust matching analysis. METHODS AND MATERIALS: Patients were matched by stage, grade, adjuvant management (surveillance, vaginal brachytherapy or pelvic radiation treatment), age, and year of hysterectomy. Recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) were calculated. RESULTS: A total of 758 patients were included. Body mass index and Age-Adjusted Charlson comorbidity index was significantly higher in AA compared to NAA women. There were no significant differences between the AA and NAA groups in regard to 5-year RFS (94 vs. 93%), DSS (96 vs. 98%) or 5-year OS (90 vs. 92%). On multivariate analysis of survival endpoints for the entire study cohort, it was found that race (AA vs. NAA) was not a significant predictor of RFS, DSS, or OS. Grade 3 tumors and the presence of lymphovascular space invasion (LVSI) were the only 2 independent predictors of RFS and DSS, while age-adjusted Charlson comorbidity score, grade 3, stage II and the presence of LVSI were independent predictors of shorter OS. CONCLUSIONS: When matched based on the tumor stage, grade, adjuvant treatment, age, and year of surgery, our study suggests that there is no statistically significant difference in any survival endpoints between AA and NAA women with early-stage EC. Based on these data, disparities in outcome likely do not stem from uterine cancer-related causes. The increased comorbidity burden in AA women is likely a factor contributing to the racial disparity in endometrial cancer.

Geometric and dosimetric impact of anatomical changes for MR-only radiation therapy for the prostate.

PURPOSE: With the move towards magnetic resonance imaging (MRI) as a primary treatment planning modality option for men with prostate cancer, it becomes critical to quantify the potential uncertainties introduced for MR-only planning. This work characterized geometric and dosimetric intra-fractional changes between the prostate, seminal vesicles (SVs), and organs at risk (OARs) in response to bladder filling conditions. MATERIALS AND METHODS: T2-weighted and mDixon sequences (3-4 time points/subject, at 1, 1.5 and 3.0 T with totally 34 evaluable time points) were acquired in nine subjects using a fixed bladder filling protocol (bladder void, 20 oz water consumed pre-imaging, 10 oz mid-session). Using mDixon images, Magnetic Resonance for Calculating Attenuation (MR-CAT) synthetic computed tomography (CT) images were generated by classifying voxels as muscle, adipose, spongy, and compact bone and by assignment of bulk Hounsfield Unit values. Organs including the prostate, SVs, bladder, and rectum were delineated on the T2 images at each time point by one physician. The displacement of the prostate and SVs was assessed based on the shift of the center of mass of the delineated organs from the reference state (fullest bladder). Changes in dose plans at different bladder states were assessed based on volumetric modulated arc radiotherapy (VMAT) plans generated for the reference state. RESULTS: Bladder volume reduction of 70 ± 14% from the final to initial time point (relative to the final volume) was observed in the subject population. In the empty bladder condition, the dose delivered to 95% of the planning target volume (PTV) (D95%) reduced significantly for all cases (11.53 ± 6.00%) likely due to anterior shifts of prostate/SVs relative to full bladder conditions. D15% to the bladder increased consistently in all subjects (42.27 ± 40.52%). Changes in D15% to the rectum were patient-specific, ranging from -23.93% to 22.28% (-0.76 ± 15.30%). CONCLUSIONS: Variations in the bladder and rectal volume can significantly dislocate the prostate and OARs, which can negatively impact the dose delivered to these organs. This warrants proper preparation of patients during treatment and imaging sessions, especially when imaging required longer scan times such as MR protocols.

Impact of age at diagnosis on racial disparities in endometrial cancer patients.

INTRODUCTION: Although black patients with endometrial cancer (EC) have worse survival compared with white patients, the interaction between age/race has not been examined. The primary objective was to evaluate the impact of age at diagnosis on racial disparities in disease presentation and outcome in EC. METHODS: We evaluated women diagnosed with EC between 1991 and 2010 from the Surveillance, Epidemiology, and End Results. Mutation status for TP53 or PTEN, or with the aggressive integrative, transcript-based, or somatic copy number alteration-based molecular subtype were acquired from the Cancer Genome Atlas. Logistic regression model was used to estimate the interaction between age and race on histology. Cox regression model was used to estimate the interaction between age and race on survival. RESULTS: 78,184 white and 8518 black patients with EC were analyzed. Median age at diagnosis was 3-years younger for black vs. white patients with serous cancer and carcinosarcoma (P<0.0001). The increased presentation of non-endometrioid histology with age was larger in black vs. white patients (P<0.0001). The racial disparity in survival and cancer-related mortality was more prevalent in black vs. white patients, and in younger vs. older patients (P<0.0001). Mutations in TP53, PTEN and the three aggressive molecular subtypes each varied by race, age and histology. CONCLUSIONS: Aggressive histology and molecular features were more common in black patients and older age, with greater impact of age on poor tumor characteristics in black vs. white patients. Racial disparities in outcome were larger in younger patients. Intervention at early ages may mitigate racial disparities in EC.

The role of adjuvant therapy in stage IA serous and clear cell uterine cancer: A multi-institutional pooled analysis.

OBJECTIVE: As the optimal adjuvant management of stage IA serous or clear cell endometrial cancer is controversial, a multi-institutional review was conducted with the objective of evaluating the appropriateness of various strategies including observation. METHODS: Retrospective chart reviews for 414 consecutive patients who underwent hysterectomy for FIGO stage IA endometrial cancer with serous, clear cell or mixed histology between 2004 and 2015 were conducted in 6 North American centers. Time-to-event outcomes were analyzed by Kaplan-Meier estimates, log-rank test, univariable and multivariable cox proportional hazard regression models. RESULTS: Post-operative management included observation (50%), chemotherapy and radiotherapy (RT) (27%), RT only (16%) and chemotherapy only (7%). The 178 RT patients received external beam (EBRT, 16%), vaginal vault brachytherapy (VVB, 56%) or both (28%). Among patients without any adjuvant treatment, 5-year local control (LC), disease free survival (DFS) and cancer-specific survival (CSS) were 82% (95% confidence interval: 74-88), 70% (62-78) and 90% (82-94), respectively. CSS in patients without adjuvant treatment was improved with adequate surgical staging (100% vs. 87% (77-92), log-rank p=0.022). Adjuvant VVB was associated with improved LC (5-year 96% (91-99) vs. 84% (76-89), log-rank p=0.007) and DFS (5-year 79% (66-88) vs. 71% (63-77), log-rank p=0.033). Adjuvant chemotherapy was associated with better LC (5-year 96% (90-98) vs. 84% (77-89), log-rank p=0.014) and DFS (5-year 84% (74-91) vs. 69% (61-76), log-rank p=0.009). On multivariable analysis, adjuvant chemotherapy and VVB were associated with improved LC while adjuvant chemotherapy and age were significant for DFS. CONCLUSIONS: In stage IA serous or clear cell uterine cancer, adjuvant RT and chemotherapy were associated with better LC and DFS. Observation may be appropriate in patients who have had adequate surgical staging.

What Is the Optimal Adjuvant Treatment Sequence for Node-Positive Endometrial Cancer? Results of a National Cancer Database Analysis.

OBJECTIVE: The optimal sequence of administering chemotherapy (CT) and radiation treatment (RT) in women with node-positive endometrial carcinoma (EC) remains controversial. We used the National Cancer Database to evaluate overall survival (OS) in women with advanced EC receiving different sequences of adjuvant therapy. METHODS: The National Cancer Database was queried for female adults with International Federation of Gynecology and Obstetrics 2009 stage IIIC1 to IIIC2 EC diagnosed from 2004 to 2012 treated with hysterectomy and adjuvant CT and RT. Overall survival was compared between sequential treatment (CT followed by RT) and concurrent treatment (CT and RT within 4 weeks). χ tests assessed differences by sequence and various clinical variables. Log-rank test and Cox proportional hazards models evaluated OS. Risk factors related to OS were identified by univariate and multivariate analyses. RESULTS: Of 1826 patients, 67% (1218) received sequential treatment and 33% (608) received concurrent treatment. The median follow-up was 49.2 months. The sequential treatment group had a better 5-year OS (67% [95% confidence interval = 64%-70%]) than the concurrent treatment group (62% [95% confidence interval = 57%-66%]) (P = 0.004). On multivariate analysis, the strongest predictors of worse OS were increasing age (hazard ratio [HR] = 1.04 [1.02-1.06], P = 0.0003), type 2 versus type 1 EC (HR = 1.60 [1.06-2.43], P = 0.03), grade 3 versus 1 (HR = 2.64 [1.23-5.67], P = 0.01), residual disease or positive margin versus negative margin (HR = 2.25 [1.43-3.56], P = 0.0005), and concurrent versus sequential treatment (HR = 1.67 [1.15-2.40], P = 0.006). CONCLUSIONS: This study suggests that upfront CT followed by RT may be a better treatment sequence for adjuvant therapy in women with advanced EC.

Does Age-Adjusted Charlson Comorbidity Score Impact Survival Endpoints in Women with Federation of Gynecology and Obstetrics-Stage III Endometrial Cancer?

OBJECTIVES: We sought to evaluate the impact of age-adjusted Charlson comorbidity index (AACCI) score on survival endpoints for women with advanced stage endometrial carcinoma (EC). METHODS AND MATERIALS: We identified 238 women with stage III EC. AACCI score was calculated and 3 groups were created accordingly; group 1 with a score of 0-2, group 2 with score 3-4, and group 3 with score ≥5. Significant predictors of recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were analyzed. RESULTS: Median follow-up was 54 months and median age was 65 years. Stage IIIC was the most common stage (69%). The 3 groups were well-balanced except for less utilization of adjuvant chemotherapy in group 3 (p = 0.01). Five-year OS was significantly lower in group 3 compared to groups 1 and 2 (23 vs. 65 and 51%, respectively). Similarly, 5-year RFS was 54, 41, and 33% and DSS was 65, 54, and 35% for groups 1, 2, and 3 respectively. On multivariate analyses, AACCI group 3, cervical stromal involvement, positive peritoneal cytology, and higher tumor grade were predictors for shorter OS. Cervical stromal involvement and higher grade were independent predictors for worse RFS and DSS. Additionally, positive cytology, lymphovascular space invasion, and stage IIIC2 were significantly detrimental for RFS. CONCLUSIONS: Our study suggests that comorbidity burden is a strong predictor of worse OS in women with stage III EC. Women with higher AACCI are less likely to receive adjuvant chemotherapy. Comorbidity score can significantly impact survival endpoints for women with advanced EC.

Revisiting Milan cervical cancer study: Do the original findings hold in the era of chemotherapy?

BACKGROUND: The primary treatment of early stage cervical carcinoma (IB-IIA) is either surgery or radiation therapy based on the pivotal Milan randomized study published twenty years ago. In the presence of high-risk features, the gold standard treatment is concurrent chemotherapy and radiation therapy (CRT) whether it is the in the postoperative or the definitive setting. Using the National Cancer Data Base (NCDB), the goal of our study is to compare the outcomes of surgery and radiation therapy in the chemotherapy era. METHODS: Between 2004 and 2013, 5478 patients diagnosed with early stage cervical cancer were divided into 2 groups based on their primary treatment: non-surgical (n=1980) and surgical groups (n=3498). The distribution of patient/tumor characteristics and treatment variables with their relation to overall survival and proportional regression models were assessed to investigate the superiority of one approach over the other. Propensity score analysis adjusted for imbalance of covariates to create a well-matched-patient cohort. FINDINGS: At 46months median follow-up, the 5-year overall survival was similar between both groups (73·8% vs. 75.7%; p=0.619) after applying propensity score analysis. On multivariate analysis, high Charlson comorbidity score, stage IIA disease, larger tumor size, positive lymph nodes and high-grade disease were significant predictors of poor outcome while older age and treatment approach were not. INTERPRETATION: Our analysis suggests that surgery (followed by adjuvant RT or CRT) and definitive radiotherapy (with or without chemotherapy) result in equivalent survival. Prospective studies are warranted to establish this paradigm in the chemotherapy era.

The Impact of Androgen Receptor Expression on Endometrial Carcinoma Recurrence and Survival.

Endometrial carcinomas (ECs) are the most common gynecologic cancers in the western world. The impact of androgen receptor (AR) on clinicopathologic parameters of EC is not well studied. The aim of our study is to assess the role of AR expression in ECs and correlate its expression with estrogen (ER) and progesterone (PR). A retrospective review of 261 EC was conducted. H&E slides were reviewed and clinicopathologic parameters were analyzed. Immunohistochemical stains for AR, ER, and PR were performed on a tissue microarray. The hormonal expression was evaluated and the data were analyzed using the Fisher exact test and Kaplan-Meier survival analysis. Patients' age ranged from 31 to 91 (median=65 y). Type I EC included 202 endometrioid and 7 mucinous carcinoma, whereas type II included 34 serous, 16 carcinosarcoma, and 2 clear cell carcinoma. Although not significant, AR expression showed more frequent association with type I EC, early tumor stage (I-II), and low FIGO grade (1-2) EC. AR expression significantly correlated with absence of lymphovascular invasion (P=0.041) and decreased LN involvement (P=0.048). Patients with AR expression showed increased disease-free survival (208 vs. 165 mo, P=0.008) and late disease recurrence (P=0.009). AR expression had a positive significant correlation with PR (P<0.001) and ER (P=0.037) expression. AR might play a role as a prognostic marker for ECs.

Is Older Age a Real Adverse Prognostic Factor in Women With Early-Stage Endometrial Carcinoma? A Matched Analysis.

OBJECTIVES: The aim of this study was to evaluate if older age alone negatively impacts survival endpoints in women with early-stage uterine endometrioid carcinoma (EC), or its reported prognostic impact is due to an interaction with other well-known adverse factors using matched-analysis methodology. METHODS: We identified 1254 patients with International Federation of Gynecology and Obstetrics stage I-II EC who underwent hysterectomy at our institution. We created 2 matched groups based on International Federation of Gynecology and Obstetrics stage, tumor grade, lymph node dissection status, and the type of adjuvant management. Recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were calculated. RESULTS: A total 297 women 70 years or older were matched with 297 women younger than 70 years. The 2 groups were well balanced except for age and higher body mass index in younger patients. There were no significant difference between older and younger patients in regard to 5-year RFS (85% vs 87%; P = 0.52) or DSS (93% for both groups with P = 0.77). Five-year OS was shorter in older patients (76% vs 88% with P < 0.001). On multivariate analysis for RFS and DSS, high tumor grade and the presence of lymphovascular space invasion (LVSI) were the only 2 predictors of shorter RFS and DSS (P = 0.01 and P = 0.02, and P = 0.01 and P = 0.01, respectively). Tumor grade and LVSI also were predictors of shorter OS. CONCLUSIONS: Our study suggests that when older patients with EC are matched with younger patients based on tumor stage, grade, and adjuvant management the prognostic impact of old age disappears. High tumor grade and LVSI remained as independent predictors of survival endpoints.

Management of gynaecologic plasmacytoma: A review article.

In contrast to multiple myeloma (MM) which exhibits diffuse bone marrow and other organ involvement, solitary plasmacytomas carry a favourable prognosis. Extramedullary plasmacytomas (EMP) are a unique form of plasma cell neoplasms. These tumours are rare in the female reproductive tract. Only 24 cases of gynaecologic plasmacytomas were reported to date (7 cases were solitary plasmacytomas and 17 cases were either part of disseminated MM with involvement of a gynaecologic organ or were lacking complete work-up to rule out MM). The standard care of gynaecologic solitary EMP is surgical resection alone when feasible. Adjuvant radiation therapy may be considered for adverse prognostic factors such as positive resection margins. MM with gynaecologic organ involvement should be managed with systemic therapy and defer local therapies to symptomatic progression.

Can chemotherapy boost the survival benefit of adjuvant radiotherapy in early stage cervical cancer with intermediate risk factors? A population based study.

PURPOSE: The Gynecologic Oncology group (GOG) 0263 trial is currently exploring whether adding chemotherapy to adjuvant radiotherapy improves recurrence-free and/or overall survival in stage IB-IIA cervical cancer patients with pathologic intermediate-risk factors. Using the National Cancer Data Base, we evaluated the benefit of adjuvant chemoradiotherapy over adjuvant radiotherapy alone in the community practice setting. MATERIALS: The analysis included 869 stage IB-IIA cervical cancer patients who underwent radical hysterectomy retrieving intermediate-risk factors justifying adjuvant therapy. Adjuvant chemoradiotherapy and adjuvant radiotherapy were delivered in 440 and 429 patients, respectively. Chi-square test assessed the distribution of variables in each group and the overall survival was estimated using the Kaplan-Meier method. Proportional hazard models were performed to evaluate the impact of the different prognostic factors on survival and propensity score analysis adjusted variables imbalanced distribution. RESULTS: Adding chemotherapy to ART did not show a survival benefit at 48months median follow-up; the 5-year overall survival was 87% and 81% (p=0.6) in the adjuvant chemoradiotherapy and adjuvant radiotherapy groups, respectively. On univariate analysis, age older than 60, a higher comorbidity score, and stage IIA were significantly associated with worse survival, while none of the other covariates were significant prognosticator on multivariate analysis. The same findings held after propensity score analysis. CONCLUSION: Our analysis could not detect a significant survival benefit for adjuvant chemoradiotherapy over adjuvant radiotherapy in women with intermediate-risk factors. Until GOG 0263 results become available, the benefits of adjuvant chemoradiotherapy should be considered on an individual basis within a multidisciplinary approach.

ACR Appropriateness Criteria® Adjuvant Management of Early-Stage Endometrial Cancer.

These consensus guidelines on adjuvant radiotherapy for early-stage endometrial cancer were developed from an expert panel convened by the American College of Radiology. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method; and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. After a review of the published literature, the panel voted on three variants to establish best practices for the utilization of imaging, radiotherapy, and chemotherapy after primary surgery for early-stage endometrial cancer.

Predictors of Survival After Recurrence in Women With Early-Stage Endometrial Carcinoma.

OBJECTIVE: Factors predictive of survival after recurrent early-stage endometrial carcinoma have not been thoroughly investigated. The purpose of this study was to explore factors that impact disease-specific survival (DSS) and overall survival (OS) after recurrence in women with early-stage endometrial carcinoma. MATERIALS AND METHODS: After institutional review board approval, we identified 104 women with 2009 International Federation of Gynecology and Obstetrics stage I to II uterine endometrioid carcinoma who developed disease recurrence between January 1990 and December 2014. The Kaplan-Meier approach and Cox regression analysis were used to assess DSS and OS after recurrence and to determine factors influencing these survival end points. RESULTS: Median age of the study cohort was 65 years with a median follow-up time of 42.8 months after hysterectomy. Median time to recurrence was 15.8 months. Recurrences were diagnosed in 60 patients (57.7%) who were originally managed with observation after hysterectomy and in 44 patients (42.3%) who were initially managed with adjuvant radiation treatment. Fifty-six patients (54%) had pelvic recurrence (vaginal and/or pelvic), whereas 48 (46%) had extrapelvic recurrence. Five-year DSS and OS for the entire study population was 44% and 37%, respectively. Five-year DSS and OS were longer for patients with pelvic recurrence compared with patients with extrapelvic recurrence (66% vs 18% and 55% vs 17%, P < 0.0001). Five-year DSS was also longer for radiation-naive patients than for radiation-treated patients (51% vs 34%, P = 0.023). On multivariate analysis of DSS and OS, pelvic recurrence (P < 0.001) was the only significant predictor of longer DSS and OS. CONCLUSIONS: In women with recurrent early-stage endometrioid carcinoma, our study suggests that site of recurrence (pelvic vs extra pelvic) is the only predictor of survival. In addition, we found that radiation naivete and pelvic recurrence correlated with longer DSS and OS.

Salvage Versus Adjuvant Radiation Treatment for Women With Early-Stage Endometrial Carcinoma: A Matched Analysis.

OBJECTIVES: Adjuvant radiation treatment (ART) has been shown to reduce local recurrences in early-stage endometrial carcinoma (EC); however, this has not translated into improved overall survival (OS) benefit. As a result, some physicians forgo ART, citing successful salvage rates in cases of recurrence. Survival end points were compared between women treated with salvage RT (SRT) for locoregional recurrence and similarly matched women treated upfront with ART. MATERIALS AND METHODS: We identified 40 patients with stage I to II type 1 EC who underwent hysterectomy and received no adjuvant RT but later developed locoregional recurrence and subsequently received SRT. An additional 374 patients who underwent hysterectomy followed by ART during the same period were identified. Patients in the SRT group were matched to those in the ART group based on FIGO (International Federation of Gynecology and Obstetrics) stage and tumor grade in a 1:3 ratio. Disease-specific survival (DSS) and OS were calculated. RESULTS: A total of 156 women were matched (39:117). Median follow-up was 56 months. The 2 groups were generally well balanced. With regard to the site of tumor recurrence, it was commonly vaginal in the SRT group (74.3% vs 28.6%, P = 0.01). More SRT patients received a combination of pelvic external-beam RT with vaginal brachytherapy (94.8% vs 35%, P < 0.001). The ART group had significantly better 5-year DSS (95% vs 77%, P < 0.001) and 5-year OS (79% vs 72%, P = 0.005) compared with those of the SRT group. CONCLUSIONS: Our study suggests that women who receive SRT for their locoregional recurrence have worse DSS and OS compared with those matched patients who received ART. Further studies are warranted to develop a high-quality cost-effectiveness analysis as well as accurate predictive models of tumor recurrence. Until then, ART should at least be considered in the management of early-stage EC patients with adverse prognostic factors.

The Impact of Adjuvant Therapy on Survival and Recurrence Patterns in Women With Early-Stage Uterine Carcinosarcoma: A Multi-institutional Study.

OBJECTIVE: The aim of the study was to characterize the impact of adjuvant therapy on survival in women with stage I/II uterine carcinosarcoma after primary surgery. METHODS: We reviewed records of 118 consecutively treated women with 2009 International Federation of Gynecology and Obstetrics stage I/II uterine carcinosarcoma who underwent hysterectomy between 1990 and 2014 at 4 academic institutions. Patients were categorized by adjuvant treatment group into observation, chemotherapy only, radiation only, and combined chemotherapy and radiation. Survival analyses were conducted using Kaplan-Meier and Cox proportional hazards models. RESULTS: Median follow-up was 28 months (range, 1-244 months). Lymphadenectomy was performed in 94 patients (80%). Postoperative management included observation (n = 37 [31%]), chemotherapy alone (n = 19 [16%]), radiation therapy (RT) alone (n = 24 [20%]), and combined RT and chemotherapy (n = 38 [32%]). Radiation therapy modality included vaginal brachytherapy in 22 patients, pelvic external beam RT in 21 patients, and combination in 19 patients. In 58% of women, chemotherapy consisted of carboplatin/paclitaxel. Median overall survival for all women was 97 months. On univariate analysis, adjuvant treatment group was associated with improved overall survival (hazard ratio [HR], 0.74; confidence interval [CI], 0.58-0.96; p = 0.02), freedom from vaginal recurrence (HR, 0.55; CI, 0.37-0.82]; p = 0.004), and freedom from any recurrence (HR, 0.70; CI, 0.54-0.92; p = 0.01). Pairwise comparisons demonstrated a significant benefit to chemoradiation over other adjuvant treatments. Adjuvant treatment group remained a significant covariate for all 3 end points on multivariate analysis as well. In addition, lymphadenectomy improved overall survival on multivariate analysis (HR, 0.24; CI, 0.09-0.61; p = 0.003). Of patients under observation only who had a recurrence, 8 (44%) of 18 had a recurrence in the vagina as the sole site of recurrence. By contrast, of women who received vaginal brachytherapy, significantly fewer had a recurrence in the vagina (1/42 [2.3%]; p < 0.003, log-rank test). CONCLUSIONS: In women with early-stage uterine carcinosarcoma, our data suggest superior survival end points with combined RT and chemotherapy. The frequency of vaginal recurrence suggests a role for incorporating vaginal brachytherapy in the adjuvant management of this disease.