Histopathologic image-based deep learning classifier for predicting platinum-based treatment responses in high-grade serous ovarian cancer.

Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image-based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model's decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.

Ultrasonographic evaluation of endometrial stripe thickness is insufficient to rule out uterine serous carcinoma.

PURPOSE: Uterine serous carcinoma (USC) is a rare endometrial cancer representing less than 10% of uterine cancers but contributing to up to 50% of the mortality. Delay in diagnosis with this high-grade histology can have significant clinical impact. USC is known to arise in a background of endometrial atrophy. We investigated endometrial stripe (EMS) thickness in USC to evaluate current guidelines for postmenopausal bleeding in the context of this histology. METHODS: Retrospective chart review was conducted using ICD-9 and ICD-10 codes over an 18-year period. We included 139 patients with USC and compared characteristics of patients with EMS ≤ 4 mm and EMS > 4 mm. Chi-square or Fisher's exact tests were used to compare proportions and two-tailed t-tests to compare means. A p-value of < 0.05 was considered statistically significant. RESULTS: Most patients were white, obese, and multiparous. Thirty-two (23%) had an EMS ≤ 4 mm; 107 (77%) had an EMS > 4 mm. There were no statistically significant differences in age at diagnosis or presenting symptoms between groups, and postmenopausal bleeding was the most common symptom in each group. CONCLUSION: Nearly 25% of patients with USC initially evaluated with transvaginal ultrasound were found to have an EMS ≤ 4 mm. If transvaginal ultrasound is used to triage these patients, one in four women will potentially experience a delay in diagnosis that may impact their prognosis.

Histopathological subtyping of high-grade serous ovarian cancer using whole slide imaging.

OBJECTIVE: We have established 4 histopathologic subtyping of high-grade serous ovarian cancer (HGSOC) and reported that the mesenchymal transition (MT) type has a worse prognosis than the other subtypes. In this study, we modified the histopathologic subtyping algorithm to achieve high interobserver agreement in whole slide imaging (WSI) and to characterize the tumor biology of MT type for treatment individualization. METHODS: Four observers performed histopathological subtyping using WSI of HGSOC in The Cancer Genome Atlas data. As a validation set, cases from Kindai and Kyoto Universities were independently evaluated by the 4 observers to determine concordance rates. In addition, genes highly expressed in MT type were examined by gene ontology term analysis. Immunohistochemistry was also performed to validate the pathway analysis. RESULTS: After algorithm modification, the kappa coefficient, which indicates interobserver agreement, was greater than 0.5 (moderate agreement) for the 4 classifications and greater than 0.7 (substantial agreement) for the 2 classifications (MT vs. non-MT). Gene expression analysis showed that gene ontology terms related to angiogenesis and immune response were enriched in the genes highly expressed in the MT type. CD31 positive microvessel density was higher in the MT type compared to the non-MT type, and tumor groups with high infiltration of CD8/CD103 positive immune cells were observed in the MT type. CONCLUSION: We developed an algorithm for reproducible histopathologic subtyping classification of HGSOC using WSI. The results of this study may be useful for treatment individualization of HGSOC, including angiogenesis inhibitors and immunotherapy.

Metastatic spread of serous ovarian carcinoma to the bilateral breasts: a rare presentation.

A woman presented with a mass in her right breast. She had previously been treated with carboplatin, paclitaxel and bevacizumab for serous ovarian carcinoma diagnosed 5 years previously and was currently on maintenance olaparib. A right breast mammogram demonstrated periareolar skin thickening and the physical examination revealed an erythematous, non-blanching cutaneous lesion. A punch biopsy revealed high-grade serous carcinoma of ovarian origin, positive for PAX-8, WT-1 and p53. Positron emission tomogram-CT scan showed diffusely increased fluorodeoxyglucose uptake in the right breast. She was treated with external beam radiation therapy to the right breast and regional lymphatics and received 5200 cGy in 20 fractions to the right breast and supraclavicular region with good response. Two weeks after completing radiation therapy, she presented with a new lesion inferior to her left areola, concerning for metastasis to the contralateral breast. Subsequent biopsy of the left breast identified metastatic serous ovarian carcinoma for which she received an additional 5200 cGy in 20 fractions to the breast.

Multimodal data integration using machine learning improves risk stratification of high-grade serous ovarian cancer.

Patients with high-grade serous ovarian cancer suffer poor prognosis and variable response to treatment. Known prognostic factors for this disease include homologous recombination deficiency status, age, pathological stage and residual disease status after debulking surgery. Recent work has highlighted important prognostic information captured in computed tomography and histopathological specimens, which can be exploited through machine learning. However, little is known about the capacity of combining features from these disparate sources to improve prediction of treatment response. Here, we assembled a multimodal dataset of 444 patients with primarily late-stage high-grade serous ovarian cancer and discovered quantitative features, such as tumor nuclear size on staining with hematoxylin and eosin and omental texture on contrast-enhanced computed tomography, associated with prognosis. We found that these features contributed complementary prognostic information relative to one another and clinicogenomic features. By fusing histopathological, radiologic and clinicogenomic machine-learning models, we demonstrate a promising path toward improved risk stratification of patients with cancer through multimodal data integration.

Synchronous uterine serous carcinoma and ovarian sex cord stromal tumor (thecoma)-A rare first case report.

Synchronous endometrial and ovarian carcinoma is a rare instance and it accounts for 50 to 70% of all synchronous female genital tract tumors. However, it is very rare to find synchronous endometrial carcinoma and ovarian sex cord-stromal tumor (thecoma). The present case is a 75-year-old woman with a complaint of post-menopausal vaginal bleeding. Radiologically, the magnetic resonance imaging (MRI) pelvis revealed altered signal intensity mass in the uterus. Frozen section and routine histopathological examination were done on radical hysterectomy. Microscopically, serous carcinoma involving uterine corpus and left Fallopian tube was identified along with the unusual finding of contralateral ovarian sex cord-stromal tumor (thecoma), which was confirmed on immunohistochemical examination. It is a very rare association and is first reported in the present study after a thorough search of the published literature. Their relationship based on a high level of estrogen produced by the hyperactive ovary is controversial as serous carcinomas are less hormone-dependent.

Pancreatic serous cystadenocarcinoma diagnosed with liver metastasis at 7 years after the resection of the primary serous neoplastic lesion.

Pancreatic serous neoplasms are rare tumors that are usually benign. However, histopathological differentiation between benign (serous cystadenoma) and malignant (serous cystadenocarcinoma) lesions is difficult. We present the case of a patient with pancreatic serous cystadenocarcinoma that was diagnosed with liver metastasis 7 years after the resection of the primary serous neoplastic lesion. A woman in her 60 s was diagnosed with pancreatic serous cystadenoma based on imaging and histopathological examination findings. The tumor was resected, and the patient was followed up every 6 months to monitor tumor progression. At 7 years after the resection of the primary lesion, liver tumors showing marked flare-like contrast enhancements were detected on arterial phase computed tomography findings and on dynamic magnetic resonance imaging findings acquired 60 s after the administration of a contrast agent. Laparoscopic segmental hepatectomy of S4 and S6 was performed to resect these tumors. Histopathological examination revealed that these tumors were metastatic and developed from the primary lesion. Therefore, a diagnosis of serous cystadenocarcinoma was confirmed. The flare-like contrast enhancement around the metastatic liver lesions on computed tomography and dynamic magnetic resonance images may be an indicator of serous cystadenocarcinoma with liver metastasis that could assist in diagnosis.

Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma.

Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. Here, we establish a murine model of HGSOC and utilize image-guided microinjections of retrograde neuro-tracer to label tumor-infiltrating peripheral neurons, mapping their source and circuitry. We show that regional sensory neurons innervate HGSOC tumors. Interestingly, the axons within the tumor trace back to local dorsal root ganglia as well as jugular-nodose ganglia. Further manipulations of these tumor projecting neurons may define the neuronal contributions in tumor growth, invasion, metastasis, and responses to therapeutics.

Can addition of frozen section analysis to preoperative endometrial biopsy and MRI improve identification of high-risk endometrial cancer patients?

BACKGROUND: Surgeons sometimes have difficulty determining which result to favor when preoperative results (MRI + preoperative endometrial biopsy [pre-op EB]) differ from intraoperative frozen section histology (FS) results. Investigation of how FS can complement ordinary preoperative examinations like MRI and pre-op EB in identification of patients at high risk of lymph node metastasis (high-risk patients) could provide clarity on this issue. Therefore, the aim of this study is to assess the utility of pre-op EB, MRI and FS results and determine how to combine these results in identification of high-risk patients. METHODS: The subjects were 172 patients with endometrial cancer. Patients with a histological high-grade tumor (HGT), namely, grade 3 endometrioid cancer, clear cell carcinoma or serous cell carcinoma, or with any type of cancer invading at least half of the uterine myometrium were considered high-risk. Tumors invading at least half of the uterine myometrium were classified as high-stage tumors (HST). We compared (a) detection of HGT using pre-op EB versus FS, (b) detection of HST using MRI versus FS, and (c) identification of high-risk patients using MRI + pre-op EB versus FS. Lastly, we determined to what degree addition of FS results improves identification of high-risk patients by routine MRI + pre-op EB. RESULTS: (a) Sensitivity, specificity, and accuracy for detecting HGT were 59.6, 98.4 and 87.8% for pre-op EB versus 55.3, 99.2 and 87.2% for FS (P = 0.44). (b) These figures for detecting HST were 74.4, 83.0 and 80.8% for MRI versus 46.5, 99.2 and 86.0% for FS (P < 0.001). (c) These figures for identifying high-risk patients were 78.3, 85.4 and 82.6% for MRI + pre-op EB versus 55.1, 99.0 and 81.2% for FS (P < 0.001). The high specificity of FS improved the sensitivity of MRI + pre-op EB from 78.3 to 81.2%, but this difference was not statistically significant (P < 0.16). CONCLUSION: Frozen section enables identification of high-risk patients with nearly 100% specificity. This advantage can be used to improve sensitivity for identification of high-risk patients by routine MRI + pre-op EB, although this improvement is not statistically significant.

Cell-stiffness and morphological architectural patterns in clinical samples of high grade serous ovarian cancers.

High grade serous ovarian carcinoma (HGSOC) is recognized as the most frequent type of ovarian cancer and the main cause of ovarian cancer related deaths worldwide. Although homologous recombination deficiency testing has been adopted in the clinical workflow, morphological analysis remains the main diagnostic tool. In this study Atomic Force Microscopy (AFM) was tested in standard hematoxylin and eosin (H&E) stained sections to investigate the biomechanical properties of different architectural growing patterns of HGSOC. Our results showed that AFM was able to discriminate HGSOC morphological growing patterns as well as patients' stage. Micropapillary pattern, which has been associated to poor outcome, had lower Young's moduli. In addition stage IV HGSOC was significantly softer than stage III cancers. Based on our results, AFM analysis could represent an additional tool in HGSOC morphological diagnosis as the biomechanical proprieties of HGSOC were quantitatively associated to tumor staging and architectural pattern.

Added value of contrast-enhanced ultrasound (CEUS) in the diagnosis of primary retroperitoneal serous adenocarcinoma: a case report.

BACKGROUND: Primary retroperitoneal serous adenocarcinoma (PRSA) is a rare malignant disease. Given the rarity of the disease, the imaging features of PRSA are unclear. Contrast-enhanced ultrasound (CEUS) also plays an important role in the evaluation of the differential diagnosis of retroperitoneal lesions. CASE PRESENTATION: We report the case of a 62-year-old woman of with increased CA125 levels for 1 year who was referred to our hospital. After conducting contrast-enhanced computed tomography and magnetic resonance imaging, the mass was misdiagnosed as a chocolate cyst. After transvaginal ultrasound (TUS) combined with CEUS, cystadenocarcinoma was considered as the initial diagnosis. Pathology results confirmed PRSA as the final diagnosis. CONCLUSIONS: CEUS features of PRSA are reported for the first time based on this case, potentially aiding in the differential diagnosis of this rare entity before surgery.

Pretreatment maximum standardized uptake value in 18F-fluorodeoxyglucose positron emission tomography-computed tomography as a prognostic factor for ovarian clear cell carcinoma and low-grade serous carcinoma.

OBJECTIVE: The maximum standardized uptake value (SUVmax) derived by positron emission tomography-computed tomography (PET/CT) can be an index of biological tumor aggressiveness, which is assessed using noninvasive tools before the treatment of epithelial ovarian cancer (EOC). This study aimed to evaluate the prognostic value of the pretreatment SUVmax in patients with EOC. MATERIALS AND METHODS: We reviewed the data of patients with EOC who underwent pretreatment 18F-FDG PET/CT between June 2006 and September 2016. The relationships between pretreatment SUVmax and histological subtypes of EOC were determined. Moreover, progression-free survival (PFS) and overall survival (OS) were evaluated according to the pretreatment SUVmax. Risk factors associated with progression or death were also analyzed. RESULTS: Of 148 patients, 66 (44.6%), 11 (7.4%), 34 (23.0%), 19 (12.8%), 15 (10.1%), and three (2.0%) were diagnosed with high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), clear cell carcinoma (CCC), endometrioid carcinoma, mucinous carcinoma, and others, respectively. The median SUVmax was marginally lower in LGSC (6.80 vs. 10.5; P = 0.059) and significantly lower in CCC (5.92 vs. 10.5; P = 0.001) than in HGSC. A high pretreatment SUVmax (≥9.30) was a prognostic factor for OS in patients with LGSC (P = 0.046). Furthermore, multivariate analysis revealed that a high SUVmax (≥5.85) was an independent prognostic factor for OS (P = 0.046) in patients with CCC. However, a high SUVmax (≥7.77) was a poor predictor of PFS and OS in patients with EOC (P = 0.156 and P = 0.158, respectively). CONCLUSION: Our findings suggest that the pretreatment SUVmax is not only an independent predictor of survival in patients with CCC but also a significant predictor of survival in patients with LGSC.

Are CT and MRI useful tools to distinguish between micropapillary type and typical type of ovarian serous borderline tumors?

PURPOSE: To investigate the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of ovarian serous borderline tumors (SBTs), and evaluate whether CT and MRI can be used to distinguish micropapillary from typical subtypes. MATERIALS AND METHODS: We retrospectively reviewed the clinical features and CT and MR imaging findings of 47 patients with SBTs encountered at our institute from September 2013 to December 2019. 30 patients with 58 histologically proven typical SBT and 17 patients with 26 micropapillary SBT were reviewed. Preoperative CT and MR images were evaluated, by two observers in consensus for the laterality, maximum diameter (MD), morphology patterns, internal architecture, attenuation or signal intensity, ADC value, enhancement patterns of solid portions (SP), and extra-ovarian imaging features. RESULTS: The median age were similar between typical SBT and SBT-MP (32.5 years, 36 years, respectively, P>0.05). Morphology patterns between two subtypes were significantly different on CT and MR images (P < 0.001). Irregular solid tumor (21/37, 56.76%) was the major morphology pattern of typical SBT tumor, while unilocular cyst with mural nodules (14/20, 70%) was the major morphology pattern of SBT-MP on CT images. Similarly, papillary architecture with internal branching (PA&IB) (17/21, 80.95%) was the major morphology pattern of typical SBT tumor, while unilocular cyst with mural nodules (4/6, 66.67%) was the major pattern of SBT-MP on MR images. PA&IB all showed slightly hyperintense papillary architecture with hypointense internal branching on T2-weighted MRI. More calcifications were found in typical SBT (24/37, 64.86%) than SBT-MP mass lesion (6/20, 30%) (P < 0.05). Hemorrhage was less frequently visible in (20/37, 54.05%) typical SBT lessons than SBT-MP mass lesion (18/20, 90%) (P < 0.05). The ovarian preservation is more seen in typical SBT (38/58, 65.52%) than SBT-MP (12/28, 42.86%) in our series (P < 0.05). Mean ADC value of solid portions (papillary architecture and mural nodules) was 1.68 (range from 1.44 to 1.85) × 10-3 mm2/s for typical SBT and 1.62 (range from 1.45 to 1.7) × 10-3 mm2/s for that of SBT-MP. The solid components of the two SBT subtypes showed wash-in appearance enhancements after contrast injection both in CT and MR images except 2 of SBT-MP with no enhancement as complete focal hemorrhage on MR images. CONCLUSION: Morphology and internal architecture are two major imaging features that can help to distinguish between SBT-MP and typical SBT.

The "Far Left" of the Morphologic Spectrum of Ovarian High-grade Serous Carcinoma: Case Report of a Purely Noninvasive High-grade Serous Carcinoma Mimicking an Ovarian Serous Borderline Tumor.

High-grade serous carcinoma has a variety of different growth patterns, but is typically easily recognizable to pathologists and rarely confused with serous borderline tumors. We report a case of a 71-yr-old woman with a unilateral 5.1 cm ovarian cyst with small papillary projections on contrast-enhanced magnetic resonance imaging of the pelvis. Histologic examination showed a noninvasive papillary neoplasm with hierarchical branching and epithelial proliferation, and thus, at low magnification, bearing a striking resemblance to a serous borderline tumor. However, a more careful examination demonstrated high-grade cytologic features, nuclear pleomorphism, and abundant mitotic activity, suggestive of high-grade serous carcinoma. The morphology and immunohistochemical profile of this lesion is consistent with a rare, purely noninvasive growth pattern of high-grade serous carcinoma. This lesion represents the "far left" of the high-grade ovarian serous carcinoma morphologic spectrum and can mimic a serous borderline tumor.

Misdiagnosis of High-grade Serous Ovarian Cancer With BRCA Mutation as Endometriotic Cyst Due to Its Unique Gross Morphology: A Case Report and Literature Review.

It is believed that high-grade serous ovarian cancer (HGSOC) is a solid or multilocular-solid cancer. Here, we report the case of a 40-yr-old woman with a left ovarian unilocular cyst. Ultrasonography and computed tomographic examination confirmed that the cyst was thin-walled and homogenous in thickness without mural nodules. It was considered to be an endometriotic cyst. Left ovarian cyst excision specimens proved it to be HGSOC after pathologic examination. Therefore, the patient underwent radical surgery for HGSOC. Pathologic examination of radical resection specimens confirmed that the HGSOC was still in FIGO stage IA and no fallopian tube lesion was found. Considering that the patient had a history of breast cancer in both the breasts at a young age, it was hypothesized that the breast cancer susceptibility gene (BRCA) gene may have a germline mutation. Next-generation sequencing confirmed the BRCA1 (c.3770_3771delAG) germline mutation in this patient. Previous studies have reported the special morphological characteristics and growth pattern of HGSOC with BRCA mutation in the advanced stage. Our case demonstrates that HGSOC with the BRCA mutation can also be a unilocular cyst with a thin wall and uniform thickness without a mural nodule, and in the early stage, may have unique gross morphology.

Carcinosarcoma of the ovary: MR and clinical findings compared with high-grade serous carcinoma.

PURPOSE: To clarify imaging and clinical characteristics of ovarian carcinosarcoma (CS) compared with high-grade serous carcinoma (HGSC). METHODS: We retrospectively reviewed MR imagings of 12 patients with CS and 30 patients with HGSC and evaluated tumor size, shape, appearance, nature of cystic and solid components, hemorrhage, and necrosis. Age, premenopausal or postmenopausal, histologic subtype, presence of endometriosis, tumor markers, and stage were also evaluated. These parameters were compared using the Mann-Whitney U test and the chi-square test/Fisher's exact test. RESULTS: The mean size of CSs was 13.6 cm, and significantly larger than that of HGSCs (mean 9.0 cm, p = 0.022). The stained-glass appearance (67% vs. 23%, p = 0.013), hemorrhage (100% vs. 50%, p = 0.003), necrosis (75.0% vs. 13%, p = 0.000), and endometriosis (33% vs. 7%, p = 0.012) were significantly more common in CSs. The postmenopausal ratio of CSs was 100% and significantly higher than that of HGSCs (70.0%, p = 0.041). Among the tumor makers, only CA-125 was significantly lower in CSs than in HGSCs (mean 715.1 U/ml vs. 1677.1 U/ml, p = 0.009). The stage distribution was similar and was not significantly different. CONCLUSION: CSs formed larger masses, and the stained-glass appearance, hemorrhage, and necrosis were more frequently observed in CSs.

A case of a malignant serous neoplasm of the pancreas with synchronous vascular invasion and metachronous metastases.

Serous neoplasms (SNs) of the pancreas are usually considered benign tumors. However, they rarely manifest malignant behaviors. Here we present a case of malignant SN and review the literature of malignant SN. A 71-year-old woman presented to our hospital with a palpable abdominal mass. Imaging studies revealed a 7 cm mass with a cluster of microcysts having a honeycomb appearance in the head of the pancreas, which invaded the superior mesenteric vein (SMV). After being clinically diagnosed with SN, pancreaticoduodenectomy was performed with resection of limited SMV. Microscopically, the tumor was diagnosed as an SN concomitant with the tumor thrombus in the SMV. Four years after the surgery, two liver tumors and two peritoneal nodules were detected and three of them were surgically resected. All of those lesions had a honeycomb appearance in their cut surfaces and they were microscopically indistinguishable from the originally resected SN. A review of the literature identified 22 cases of malignant metastatic SNs published to date. Even though extremely rare, metachronous metastasis could occur in SNs of the pancreas. Local invasion indicated an increased likelihood of future metastasis. Thus, periodic surveillance should be considered for SNs after resection, especially when they have a local invasion.

Low-dose adjuvant vaginal cylinder brachytherapy for early-stage non-endometrioid endometrial cancer: recurrence risk and survival outcomes.

OBJECTIVE: The aim of this study was to evaluate recurrence patterns and survival outcomes for patients with early-stage non-endometrioid endometrial adenocarcinoma treated with adjuvant high-dose rate vaginal brachytherapy with a low-dose scheme. METHODS: A retrospective review was performed of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II non-endometrioid endometrial cancer who received adjuvant vaginal brachytherapy with a low-dose regimen of 24 Gy in six fractions from November 2005 to May 2017. All patients had >6 months of follow-up. Rates of recurrence-free survival, overall survival, vaginal, pelvic, and distant recurrence were calculated by the Kaplan-Meier method. Prognostic factors for recurrence and survival were evaluated by Cox proportional hazards modeling. RESULTS: A total of 106 patients were analyzed. Median follow-up was 49 months (range 9-119). Histologic subtypes were serous (47%, n=50), clear cell (10%, n=11), mixed (27%, n=29), and carcinosarcoma (15%, n=16). Most patients (79%) had stage IA disease, 94% had surgical nodal assessment, and 13% had lymphovascular invasion. Adjuvant chemotherapy was delivered to 75%. The 5-year recurrence-free and overall survival rates were 74% and 83%, respectively. By histology, 5-year recurrence-free/overall survival rates were: serous 73%/78%, clear cell 68%/88%, mixed 88%/100%, and carcinosarcoma 56%/60% (p=0.046 and p<0.01). On multivariate analysis, lymphovascular invasion was significantly associated with recurrence (HR 3.3, p<0.01). The 5-year vaginal, pelvic, and distant recurrence rates were 7%, 8%, and 21%, respectively. Vaginal and pelvic recurrence rates were highest for patients with carcinosarcoma, lymphovascular invasion and/or FIGO stage IB/II disease. At 5 years, vaginal and pelvic recurrence rates for patients with lymphovascular invasion were 33% and 40%, respectively. Patients with stage IA disease or no lymphovascular invasion had 5-year vaginal recurrence rates of 4% and pelvic recurrence rates of 6% and 3%, respectively. CONCLUSIONS: Adjuvant high-dose rate brachytherapy with a low-dose scheme is effective for most patients with early-stage non-endometrioid endometrial cancer, particularly stage IA disease and no lymphovascular invasion. Pelvic radiation therapy should be considered for those with carcinosarcoma, lymphovascular invasion and/or stage IB/II disease.