Association of allostatic load with overall survival in epithelial ovarian cancer.

OBJECTIVE: Elevated allostatic load (AL), an integrated, cumulative marker of physiologic damage due to socioenvironmental stress, is associated with increased mortality in patients with breast, lung, and other cancers. The relationship between allostatic load and mortality in ovarian cancer patients remains unknown. We examined the relationship between allostatic load and overall survival in ovarian cancer patients. METHODS: This cross-sectional study used data from 201 patients enrolled in a prospective observational ovarian cancer cohort study at a National Cancer Institute-designated Comprehensive Cancer Center from October 2012 through June 2022. All patients underwent debulking surgery and completed a full course of standard-of-care platinum-based chemotherapy. Follow-up was completed through January 2024. Allostatic load was calculated as a summary score by assigning one point to the worst sample quartile for each of ten biomarkers measured within 45 days before the ovarian cancer diagnosis. High allostatic load was defined as having an allostatic load in the top quartile of the summary score. A Cox proportional hazard model with robust variance tested the association between allostatic load and overall survival. RESULTS: There were no associations between allostatic load and ovarian cancer clinical characteristics. After accounting for demographic, clinical, and treatment factors, high allostatic load was associated with a significant increase in mortality (hazard ratio 2.17 [95%CI, 1.13-4.15]; P = 0.02). CONCLUSION: Higher allostatic load is associated with worse survival among ovarian cancer patients. Allostatic load could help identify patients at risk for poorer outcomes who may benefit from greater socioenvironmental support during treatment.

Image-based multichannel vaginal cylinder brachytherapy for the definitive treatment of gynecologic malignancies in the vagina.

PURPOSE: Brachytherapy is integral to vaginal cancer treatment and is typically delivered using an intracavitary single-channel vaginal cylinder (SCVC) or an interstitial brachytherapy (ISBT) applicator. Multi-channel vaginal cylinder (MCVC) applicators allow for improved organ-at-risk (OAR) sparing compared to SCVC while maintaining target coverage. We present clinical outcomes of patients treated with image-based high dose-rate (HDR) brachytherapy using a MCVC. METHODS AND MATERIALS: Sixty patients with vaginal cancer (27% primary vaginal and 73% recurrence from other primaries) were treated with combination external beam radiotherapy (EBRT) and image-based HDR brachytherapy utilizing a MCVC if residual disease thickness was 7 mm or less after EBRT. All pts received 3D image-based BT to a total equivalent dose of 70-80 Gy. RESULTS: The median high-risk clinical target volume was 24.4 cm3 (interquartile range [IQR], 14.1), with a median dose to 90% of 77.2 Gy (IQR, 2.8). After a median follow-up of 45 months (range, 11-78), the 4-year local-regional control, distant control, DFS, and OS rates were 92.6%, 76.1%, 64.0%, and 67.2%, respectively. The 4-year LRC rates were similar between the primary vaginal (92%) and recurrent (93%) groups (p = 0.290). Pts with lymph node positive disease had a lower rate of distant control at 4 years (22.7% vs. 89.0%, p < 0.001). There were no Grade 3 or higher acute complications. The 4-year rate of late Grade 3 or higher toxicity was 2.7%. CONCLUSIONS: Clinical outcomes of pts with primary and recurrent vaginal cancer treated definitively in a systematic manner with combination EBRT with image-guided HDR BT utilizing a MCVC applicator demonstrate high rates of local control and low rates of severe morbidity. The MCVC technique allows interstitial implantation to be avoided in select pts with ≤7 mm residual disease thickness following EBRT while maintaining excellent clinical outcomes with extended 4-year follow-up in this rare malignancy.

Outcomes of stage II endometrial cancer: The UPMC Hillman Cancer Center experience.

PURPOSE: Previous studies of stage II endometrial cancer have included cancers with cervical glandular involvement, a factor no longer associated with risk of recurrence. In order to better assess relapse patterns and the impact of adjuvant therapy, a retrospective analysis was conducted for patients with modern stage II endometrial cancer, defined as cervical stromal invasion. MATERIALS AND METHODS: Patients diagnosed with surgically staged FIGO stage II endometrial cancer at the UPMC Hillman Cancer Center from 1990-2013 were reviewed. Factors associated with rates of locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were analyzed using the log rank test. RESULTS: 110 patients with FIGO stage II disease were identified. Most (84.5%) received EBRT±BT, with 13.6% receiving BT alone. With a median follow-up of 64.6months, the 5-year actuarial rates of LRC, DM, DFS, and OS were 94.9%, 85.1%, 67.9%, and 75.0%, respectively. With 5 locoregional failures, the only factor predictive of LRC was pelvic lymph node dissection. Characteristics associated with DM included age, LVSI, depth of myometrial invasion, and receipt of chemotherapy. Factors predictive of both DFS and OS were age, grade, adverse histology, LVSI, depth of myometrial invasion, and receipt of chemotherapy. CONCLUSIONS: This represents the largest single-institution study for modern stage II endometrial cancer, confirming high rates of pelvic disease control after surgery and adjuvant therapy. With most patients receiving adjuvant radiotherapy, the predominant mode of failure, albeit low in absolute number, remains distant metastases.

Image-guided tandem and cylinder brachytherapy as monotherapy for definitive treatment of inoperable endometrial carcinoma.

OBJECTIVES: Management of endometrial cancer consists of surgical staging with adjuvant therapy guided by risk factors, though some women cannot undergo surgery due to comorbidities. We present a series of women treated with definitive high-dose rate image-guided tandem and cylinder brachytherapy (HDR-IGBT) alone. METHODS: Patients with grade 1-2, clinical stage I endometrial adenocarcinoma, <50% myometrial invasion, and tumor≤2cm were reviewed. Definitive treatment consisted of 5-6 fractions HDR-IGBT alone with CT- or MRI-based planning. Local-regional control (LRC) was defined as complete imaging response and/or cessation of vaginal bleeding. RESULTS: From 2007 to 2016, 45 patients were treated to a median dose of 37.5Gy. The median gross tumor volume (GTV) and clinical target volume (CTV) were 5.9cm3 (range, 0.7-18.7) and 80.9cm3 (17.2-159.0), respectively. The median cumulative dose to 90% (D90) of the GTV was 132.8Gy (76.5-295.6) equivalent 2Gy dose, and the median CTV D90 was 49.7Gy (34.5-57.2). Median follow-up among living patients was 18.6months (3.0-64.3). Cessation of vaginal bleeding occurred in 98%. Among those with post-treatment MRI (64%), complete radiographic response was demonstrated in 90%. The 2-year LRC, cancer-specific survival, and overall survival rates were 90%, 86%, and 97%, respectively. No grade 3+ acute or late toxicity was observed. CONCLUSIONS: HDR-IGBT alone for treatment of early-stage, medically inoperable endometrial cancer is feasible with excellent response rates and clinical results. This approach also allows sparing of critical organs and ensures target coverage, which contributed to the low toxicity rate and high LRC in comparison with 2D point-based series.

Surgical Outcomes of Patients Undergoing Extrafascial Hysterectomy After Neoadjuvant Radiotherapy With or Without Chemotherapy for Locally Advanced Endometrial Cancer Clinically Extending to the Cervix or Parametria.

OBJECTIVES: Recent data have shown high rates of clinical and pathologic responses to neoadjuvant radiation therapy for locally advanced endometrial cancer. There are limited data on the surgical outcomes of these patients in the era of modern radiation and surgical techniques. We sought to characterize surgical outcomes after extrafascial hysterectomy in this population. METHODS: Patients with endometrial cancer of all histologies clinically involving the cervix or parametria treated with neoadjuvant brachytherapy followed by extrafascial hysterectomy from 1999 to 2014 were identified. Patient charts were reviewed for data regarding treatment characteristics and postoperative outcomes. Pearson χ and logistic regression analyses were used to assess correlations between surgical complications and treatment-related variables. RESULTS: Twenty-nine patients met inclusion criteria. Mean operating time for the cohort was 115 minutes. Mean estimated blood loss was 100 mL. No visceral injuries occurred. Mean length of hospital stay was 1 and 4 days for the minimally invasive and laparotomy groups, respectively. Rates of postoperative ileus, blood transfusion, wound infection, and readmission were 3%, 3%, 6%, and 3%, respectively. No case of prolonged urodynamic dysfunction was noted. The rate of vaginal complications was significantly higher in the group of patients who underwent minimally invasive surgery as compared with laparotomy (33% vs 5%, P < 0.041). CONCLUSIONS: These data support adjuvant extrafascial hysterectomy after neoadjuvant radiotherapy for endometrial cancer with cervical or parametrial involvement as a safe and viable procedure, with low rates of postoperative complications. Extra care should be taken when closing the vaginal cuff to reduce the risk of vaginal cuff complications.

The effect of groin treatment modality and sequence on clinically significant chronic lymphedema in patients with vulvar carcinoma.

OBJECTIVE: Chronic lymphedema (CL) after inguinal lymph node dissection (ILND) or radiotherapy (RT) is a significant problem for vulvar cancer survivors. The treatment modality or combination of therapies that poses the greatest risk is not known. The objective of this study was to describe rates of clinically significant CL conferred by different groin treatment modalities. METHODS: Medical records of vulvar cancer patients who had groin treatment with ILND, RT, or both were retrospectively reviewed. Each treated groin was considered individually, and divided into 4 treatment groups: ILND alone, ILND with adjuvant RT, neoadjuvant chemoradiation therapy (NCRT), or NCRT followed by ILND. Clinically significant CL was defined as that which required treatment and was recorded by laterality. Differences among groups were evaluated with χ(2) and Fisher exact test. RESULTS: Between 2000 and 2010, 146 patients with vulvar cancer who underwent therapy to 1 or both groins were identified for a total of 266 treated groins. The rates of CL for single-modality treatment, ILND or NCRT, were 10.9% and 6.7%, respectively. Multimodal treatment resulted in higher rates of CL, 13.5% for ILND followed by RT and 17.2% for NCRT followed by ILND, although differences were not significant (P = 0.37). CONCLUSIONS: Clinically significant CL was not different between treatment modalities in this study, but is underpowered. The results provide valuable information about treatment complications that will be useful for patient-centered counseling. Prospective evaluation of CL and its impact on quality of life is warranted.

Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria.

PURPOSE: For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. MATERIALS AND METHODS: Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. RESULTS: All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. CONCLUSIONS: Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response.

USA endometrial cancer projections to 2030: should we be concerned?

AIM: As the incidence of endometrial cancer (EC) increased considerably since 2007, this study aimed to project the burden of EC to the year 2030. METHODS: Multivariate linear regression was used to project EC incidence by modeling trends in EC incidence from 1990 to 2013, while accounting for temporal changes in obesity, hysterectomy and smoking. RESULTS: The best-fitting model predicting EC rates included a time effect plus effects for hysterectomy (12-year lag), severe obesity (3-year lag) and smoking (9-year lag). The best-fitting model projected an increase to 42.13 EC cases per 100,000 by the year 2030, a 55% increase over 2010 EC rates. CONCLUSION: The projected increase of EC over next 16 years indicates the need for close monitoring of EC trends.

Pediatric radical abdominal trachelectomy for solitary fibrous tumor of the uterine cervix.

OBJECTIVE: Solitary fibrous tumor is a rare mesenchymal tumor initially described arising in the pleura but now reported in many other thoracic and extrathoracic sites. Here we report the first case of a 14-year-old girl who was discovered to have a large solitary fibrous tumor of the uterine cervix, an unusual site for these tumors, to highlight the diagnosis and management of these tumors. METHODS: Case report and review of the literature on extrapleural solitary fibrous tumors. RESULTS: The median age of occurrence is in the late 50's and there is only one previous report in the literature of a solitary fibrous tumor in a patient less than 18 years old. Most patients will be cured by complete surgical resection though late local and distant relapse will occur in a minority of patients, many of whom have indicative histological features. Complete surgical resection of this tumor arising in the uterine cervix, was achieved by performing a radical abdominal trachelectomy. CONCLUSIONS: Review of the literature confirms the good long-term outcome of the majority of these patients with complete surgical resection but emphasizes the importance of close long-term follow-up.

Magnetic resonance imaging response in patients treated with definitive radiation therapy for medically inoperable endometrial cancer-Does it predict treatment response?

PURPOSE: Many patients with endometrial cancer cannot undergo surgery and instead receive definitive radiation therapy (RT). We investigate the correlation between MRI response to RT and clinical outcomes. METHODS AND MATERIALS: Women with inoperable, clinical Stage I endometrial cancer were treated with definitive brachytherapy (BT) with/without pelvic RT (PRT). Patients underwent MRI with functional diffusion-weighted imaging before and after RT. A radiologist retrospectively classified cases as complete, partial, or indeterminate response (CR, PR, or IR, respectively) vs. disease progression. Local control was clinicopathologically defined. RESULTS: From 2007 to 2017, 50 women underwent definitive RT. Thirty-five (70%) received BT alone (median dose 37.5 Gy). For combined therapy, the median PRT and BT doses were 45 and 25 Gy, respectively. Median gross tumor volume and high-risk clinical target volume were 7.1 cc and 90.0 cc, respectively. Median followup among living patients was 20 months. All patients underwent post-RT MRI with T1/T2 sequencing at a median of 3.2 months after RT; 40 patients (80%) underwent functional diffusion-weighted imaging sequences. On initial post-RT MRI, CR was documented in 42 patients (84%), IR in 1 patient (2%), and PR in seven patients (14%). At median followup of 16.3 months, no CR patients had uterine failure. Among eight patients with initial PR/IR, all were found to be clinicopathologically no evidence of disease at the uterus on further evaluation. CONCLUSIONS: Definitive RT with BT or BT + PRT is associated with high response rates on MRI. Overall, initial CR predicted for excellent outcome with no infield failure.

Single-Institution Experience in 3D MRI-Based Brachytherapy for Cervical Cancer for 239 Women: Can Dose Overcome Poor Response?

PURPOSE: Recent Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology guidelines recommend that the dose to 90% (D90) of the high-risk clinical target volume (HRCTV) in cervical cancer be at least 85 Gy, with higher doses for poor response to radiation therapy. METHODS AND MATERIALS: A retrospective review of brachytherapy delivered at a single institution was evaluated for dosimetry and outcomes. Significance of tumor parameters on local control was evaluated with Kaplan-Meier and univariable and multivariable Cox regression analysis. Correlations were determined with a linear regression model. RESULTS: A total of 239 women underwent high-dose-rate brachytherapy for cervical cancer between 2007 and 2018 with evaluable dosimetry. Median follow-up was 28.6 months. The median prescribed dose was 27.5 Gy in 5 fractions, with a median HRCTV D90 of 83.9 Gy (range, 81.9-85.7 Gy), HRCTV volume of 31 cm3 (range, 14.9-121.9 cm3), and treatment time of 51 days (range, 36-83 days). Local control for the entire cohort at 5 years was 90.8%. Local control was worse with adenocarcinomas, HRCTV >40 cm3 at brachytherapy, requirement for a higher brachytherapy dose, and treatment >51 days. On multivariable analysis, local control was worse with adenocarcinoma (hazard ratio, 4.141; 95% confidence interval, 1.498-11.444; P = .006) and HRCTV >40 cm3 (hazard ratio, 3.640; 95% confidence interval, 1.316-10.069; P = .013). HRCTV EQD2 D90 > 85 Gy did not statistically improve outcomes for any subset. The 2-year progression-free survival for HRCTV >40 cm3 was 66.2% versus 84.1% if ≤40 cm3 (P < .001). Overall survival was predicted by HRCTV and overall treatment time in multivariable analysis. For women with HRCTV ≤40 cm3, overall survival at 2 years was 90.4% versus 68.5% if >40 cm3 (P < .001). CONCLUSION: Local control was excellent with magnetic resonance imaging-based planning in the entire cohort of patients. A poor response to external beam radiation (larger HRCTV) and adenocarcinoma histology predicted for worse local control despite association with higher brachytherapy prescription. Women with these risk factors face higher rates of extrapelvic progression and poorer overall survival.

The Prognostic Significance of p16 Status in Patients With Vulvar Cancer Treated With Vulvectomy and Adjuvant Radiation.

PURPOSE: Vulvar squamous cell carcinoma (VSCC) is a relatively rare malignancy. Human papillomavirus has been implicated as a causative factor for a subset of these patients. The purpose of this study was to evaluate whether p16-positivity (a human papillomavirus surrogate) predicts for better response rates in women who undergo surgery followed by adjuvant radiation therapy (RT). METHODS AND MATERIALS: We retrospectively analyzed data from women with VSCC who were treated with adjuvant RT. p16-Positivity was defined as diffuse strong immunoreactivity within the tumor. Time to event outcomes was performed with Kaplan-Meier and cumulative incidence methodologies. RESULTS: Thirty-nine women were identified. Ten had positive results for p16 (p16+), and 29 had negative results (p16-). The median follow-up was 25.7 months. The median age at diagnosis was 59 years for women with p16+ tumors and 74 years for women with p16- tumors (P = .022). The distribution of stage did not differ by p16 status. The indications for adjuvant RT were close/positive margins in 19 women, positive nodes in 9 women, and both in 11 women. There were 21 recurrences: 15 vulvar, 3 isolated nodal, 2 synchronous vulvar/nodal, and 1 distant metastasis. In-field relapse rates at 3 years were lower in p16+ patients (32.5%) than in p16- patients (59.1%, P = .072). This trend was also observed in progression-free survival (P = .062). A p16+ status and a lower International Federation of Gynecology and Obstetrics stage were associated with fewer in-field relapses and improved progression-free survival in multivariable analyses. The p16 status was not a predictor of overall survival. CONCLUSIONS: p16-Positivity appears to be a prognostic factor for in-field relapse rates in patients with VSCC appropriately treated with adjuvant RT.

Neoadjuvant Chemoradiation Therapy Followed by Extrafascial Hysterectomy in Locally Advanced Type II Endometrial Cancer Clinically Extending to Cervix.

PURPOSE: The role of neoadjuvant chemoradiation therapy in locally advanced type II endometrial cancer is controversial. We thus aimed to present our experience with the hypothesis that neoadjuvant chemoradiation therapy is associated with similarly high rates of downstaging and locoregional control for type II endometrial cancer and type I endometrial cancer. METHODS AND MATERIALS: Thirty-four patients with type II endometrial cancer with clinical evidence of cervical ± parametrium involvement treated with neoadjuvant external beam radiation therapy (45-50.4 Gy in 25-28 fractions) and high-dose-rate brachytherapy with a median total dose of 20 Gy (range, 15-27.5) in 4 fractions (range, 3-5) and concurrent platinum chemotherapy ± adjuvant chemotherapy from 2008 to 2018 were retrospectively reviewed. Patients with type I pathologic diagnoses and those treated with definitive (rather than preoperative) intent were excluded. RESULTS: Pathologic characteristics were as follows: 38% were carcinosarcoma, 18% serous, and 24% clear cell. Ninety-four percent of patients were downstaged to an extrafascial hysterectomy, and 94% had negative surgical margins. The 2-year local control, regional control, distant control, disease-free survival, and overall survival were 87.8%, 81.3%, 76.3%, 52.5%, and 63.7%, respectively. There was 1 subacute grade 3 and 1 late grade 3 small bowel obstruction, directly attributable to radiation therapy. CONCLUSIONS: Neoadjuvant chemoradiation therapy effectively downstages the majority of locally advanced type II endometrial cancers, thereby increasing the likelihood of achieving complete resection with negative margins.

Super-Utilization of Health Care Resources Among Gynecologic Oncology Patients.

Super-utilizers account for many emergency department visits (EDV) and hospitalizations. Among Medicare/Medicaid patients, 5% to 10% account for >50% of spending. Little is known about super-utilization in gynecologic oncology. Charts of 64 gynecologic oncology patients with ≥3 EDV and/or admissions over 12 months were reviewed retrospectively. Cancer type distribution was 47% ovarian, 23% cervical, 23% endometrial, and 6% vulvar. Treatment at index visit was 61% chemotherapy, 16% no treatment, 8% recent surgery, and 6% radiation. Mean visits was 5.7 (SD 3.9, range 3-28). Most common presenting complaints were gastrointestinal and pain. Patients near end of life were more likely to be admitted. EDV frequently occurred outside standard work hours (63%). EDV/admissions resulted in total variable expenses of $1 462 581 ($982 933 direct expense, $479 648 service expense). Interventions to decrease super-utilization could target symptom management, off-hour support, patients on chemotherapy, and end of life. Approaches could include multidisciplinary resources, palliative care teams, extending office hours, and earlier initiation of hospice.

Racial and Socioeconomic Disparities in Hysterectomy Route for Benign Conditions.

BACKGROUND: The aim of this paper was to explore disparities associated with the route of hysterectomy in the University of Pittsburgh Medical Center (UPMC) health system and to evaluate whether the hysterectomy clinical pathway implementation impacted disparities in the utilization of minimally invasive hysterectomy (MIH). METHODS: We performed a retrospective medical record review of all the patients who have undergone hysterectomy for benign indications at UPMC-affiliated hospitals between fiscal years (FY) 2012 and 2014. RESULTS: A total number of 6373 hysterectomy patient cases were included in this study: 88.7% (5653) were European American (EA), 11.02% (702) were African American (AA), and the remaining 0.28% (18) were of other ethnicities. We found that non-EA, women aged 45-60, traditional Medicaid, and traditional Medicare enrollees were more likely to have a total abdominal hysterectomy (TAH). Residence in higher median income zip code (> $61,000) was associated with 60% lower odds of undergoing TAH. Both FY 2013 and 2014 were associated with significantly lower odds of TAH. Logistic regression results from the model for non-EA patients for FY 2012 and FY 2014 demonstrated that FY and zip code income group were not significant predictors of surgery type in this subgroup. Pathway implementation did not reduce racial disparity in MIH utilization. CONCLUSION: This study demonstrated that there is a significant disparity in MIH utilization, where non-EA and Medicaid/Medicare recipients had higher odds of undergoing TAH. Further research is needed to investigate how care standardization may alleviate healthcare disparities.

Single-institutional outcomes of adjuvant brachytherapy for Stage I endometrial cancer-Are outcomes consistent with randomized studies?

PURPOSE: Vaginal brachytherapy (VBT) alone has been shown to be a viable adjuvant treatment strategy for most patients with Stage I endometrioid endometrial cancer. We sought to examine our institutional data following practice pattern changes resulting from the publications of GOG-99 and PORTEC-2. METHODS AND MATERIALS: We retrospectively analyzed women who underwent adjuvant VBT after surgical staging for Stage 1 endometrioid endometrial cancer at our institution from 2007 to 2014. RESULTS: We identified 297 women. Median time to last followup or death was 52.3 months (interquartile range: 32.3-72.3 months). By International Federation of Gynecology and Obstetrics 2009 staging, 162 patients (54.5%) had Stage IA and 128 (43.1%) had Stage IB disease. Ninety-nine (33.3%) patients had Grade 1, 153 (51.5%) had Grade 2, and 45 (15.2%) had Grade 3 disease. According to GOG-249 and PORTEC-2 criteria, 167 (56.2%) and 127 (42.7%) patients were with high-intermediate-risk disease. Two women had Stage IB Grade 3 disease. The most common high-dose-rate-VBT regimen was 2100 cGy/three fractions to a depth of 5 mm. Four (two acute and two late) (1.3%) Grade 3 genitourinary toxicities were reported: three episodes of vaginal dehiscence (after second course of VBT, 2 months after completion of VBT, and 1 year after completion of VBT) and one episode of radiation necrosis. Twenty-one (7%) women recurred: three recurred in the vagina, two recurred in the pelvic lymph nodes, and 16 recurred distantly. CONCLUSIONS: Outcomes appear consistent with published randomized data in women with high-intermediate-risk endometrial cancer who are treated with brachytherapy alone. Recurrence and complication rates were minimal.

Inflammatory biomarker in adipose stem cells of women with endometrial cancer.

AIM: To explore inflammatory biomarkers secreted by adipose stem cells (ASCs) in omental, retroperitoneal and subcutaneous adipose tissues of women with endometrial cancer. PATIENTS & METHODS: ASCs were collected from 22 women, aged 35-83 years, undergoing hysterectomy for endometrial cancer. Angiopoietin-2, EGF, IL-8, leptin, VEGFA, VEGFC and VEFGD levels in the ASC-conditioned media were analyzed by Luminex. RESULTS: We found a significant difference between the three depots for IL-8 (p < 0.0001), with the highest levels of IL-8 in the omental depot. VEGFA levels were highest in the retroperitoneal depot. CONCLUSION: This is one of the first studies to explore biomarker expression in ASC-conditioned media in adipose tissue. ASC characteristics may be important to evaluate in relation to cancer risk.

Percent surface area involvement is a predictor of lymph node metastasis in endometrial cancer.

OBJECTIVE: To determine if percent surface area involvement (SAI) of tumor in endometrial cancer is predictive of lymph node metastasis. METHODS: A retrospective study was performed of all patients diagnosed with endometrial cancer at Magee Women's Hospital between January 1990 and December of 1995. Papillary serous and clear cell histologic subtypes were excluded. Pathology reports were reviewed for percent SAI, myometrial invasion, grade, histologic subtype, lymphovascular space invasion, and lymph node metastasis. Percent SAI was categorized into three groups: <35%, 35-80%, and >80%. The primary outcome variables were pelvic or periaortic lymph node metastasis. Univariate and multivariate analysis logistic regression models were used to determine predictors of nodal metastasis. RESULTS: Of 558 patient records reviewed, 319 had lymph node dissections performed and 42 (13%) of those patients had positive lymph nodes. Two of 79 (3%) patients with <35% SAI had lymph node metastasis, 17 of 165 (10%) patients with 35-80% SAI had lymph node metastasis, and 23 of 75 (31%) patients with >80% SAI had lymph node metastasis. The percent SAI was significantly associated with lymph node metastasis (p<0.001). Multivariate logistic regression indicated that for patients with >80% SAI, the odds of having lymph node metastasis were 10.8 times (CI 1.3-90.4) that for patients with similar tumor histology, grade, and invasion, but <35% SAI (p=0.03). A subset analysis of patients with superficial myometrial invasion was performed and 16% of patients with <50% myometrial invasion and >80% SAI had positive lymph nodes, while only 1.4% of patients with <50% myometrial invasion and <35% SAI had positive lymph nodes (p=0.02). CONCLUSION: Our analysis indicates that percent SAI is an independent risk factor for lymph node metastasis. Furthermore, assessing SAI with myometrial invasion gives a more accurate prediction of lymph node metastasis than myometrial invasion alone. This becomes clinically relevant when assessing risk factors for lymph node metastasis intraoperatively.

Hysterectomy Pathway as the Global Engine of Practice Change: Implications for Value in Care.

INTRODUCTION: In 2012, University of Pittsburgh Medical Center (UPMC) introduced a hysterectomy clinical pathway to reduce the number of total abdominal hysterectomies performed for benign gynecological indications. This study focused on exploring physician and patient factors impacting the utilization of hysterectomy clinical pathways. METHODS: An online survey with 24 questions was implemented to explore physicians' attitudes and perceived barriers toward implementing the pathway. A survey consisting of 27 questions was developed for patients to determine the utility of a pathway-based educational tool for making surgery decisions and to measure satisfaction with the information provided. Descriptive statistics were used to describe survey results, while thematic analysis was performed on verbal feedback submitted by respondents. RESULTS: Physician respondents found the clinical pathway to be practical, beneficial to patients, and up-to-date with the latest evidence-based literature. Key barriers to the use of the pathway that were identified by physicians included perceived waste of time, inappropriateness for some of the patient groups, improper incentive structure, and excessive bureaucracy surrounding the process. Overall, patient respondents were satisfied with the tool and found it to be helpful with the decision-making process of choosing a hysterectomy route. CONCLUSIONS: Physicians and patients found the developed tools to be practical and beneficial. Findings of this study will help to use pathways as a unifying framework to shape future care of patients needing hysterectomy and add value to their care.

Long-term outcomes using adjuvant pelvic intensity modulated radiation therapy (IMRT) for endometrial carcinoma.

PURPOSE: We evaluated the long-term outcome and toxicity of adjuvant intensity modulated radiation therapy (IMRT) for high-risk endometrial carcinoma via a retrospective institutional review of patients treated in this setting with extended follow-up. METHODS AND MATERIALS: Patients with endometrial cancer who underwent comprehensive surgical staging followed by adjuvant IMRT with or without sequential chemotherapy between 1999 and 2010 were reviewed. Median doses delivered with IMRT and brachytherapy were 45 Gy in 25 fractions and 10 Gy in 2 fractions; 10.2% received extended field and 94.5% received vaginal brachytherapy. Kaplan-Meier estimates are provided for rates of locoregional (in-field) relapse, distant metastasis, and disease-free survival, and overall survival. Gastrointestinal (GI) and genitourinary (GU) toxicity reported were graded with the Common Terminology Criteria for Adverse Events, version 4.03. RESULTS: A total of 128 patients were identified. Median age at diagnosis was 64 years. Most patients (82.8%) had endometrioid adenocarcinoma followed by papillary serous (10.2%), clear cell (4.7%), and carcinosarcoma (2.3%). International Federation of Gynecology and Obstetrics staging distribution was as follows: IA, 13.3%; IB, 32.8%; II, 30.4%; IIIA, 5.5%; IIIC1, 9.4%; and IIIC2, 8.6%. Most (85.9%) underwent nodal dissections (28.1% pelvic only and 57.8% pelvic and para-aortic). Two patients (1.6%) experienced acute grade 3 GI toxicity; no other acute grade ≥3 GI/GU toxicities were noted. With a median follow-up of 57.0 months, 5-year locoregional relapse was 2.5%: vagina (n = 3), parametrium (n = 1), pelvic node (n = 1). Five-year estimates of distant metastasis, disease-free survival, and overall survival were 16.5%, 73.4%, and 77.4%, respectively. Five-year actuarial rates of late grade 3 GI and GU toxicities were 3.2% and 0.0%. The 5-year rate of symptomatic pelvic insufficiency fracture was 4.4%. CONCLUSIONS: This study represents the largest cohort of endometrial cancer patients with extended follow-up receiving adjuvant IMRT. High rates of pelvic disease control and limited late toxicities demonstrate safety and efficacy of this approach in the setting of extended follow-up.