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Purpose: To compare clinical outcomes of MR-based versus CT-based high-dose-rate interstitial brachytherapy (ISBT) for vaginal recurrence of endometrioid endometrial cancer (EC)., Methods and Materials: We reviewed 66 patients with vaginal recurrent EC; 18 had MR-based ISBT on a prospective clinical trial and 48 had CT-based treatment. Kaplan-Meier survival modeling was used to generate estimates for local control (LC), disease-free interval (DFI), and overall survival (OS), and multivariate Cox modeling was used to assess prognostic factors. Toxicities were evaluated and compared., Results: Median followup was 33 months (CT 30 months, MR 35 months). Median cumulative equivalent dose in 2-Gy fractions was 75.5 Gy for MR-ISBT and 73.8 Gy for CT-ISBT (p = 0.58). MR patients were older (p = 0.03) and had larger tumor size (>4 cm vs. ≤ 4 cm) compared to CT patients (p = 0.04). For MR-based versus CT-based ISBT, 3-year KM rate for local control was 100% versus 78% (p = 0.04), DFI was 69% versus 55% (p = 0.1), and OS was 63% versus 75% (p = 0.81), respectively. On multivariate analysis, tumor Grade 3 was associated with worse OS (HR 3.57, 95% CI 1.25, 11.36) in a model with MR-ISBT (HR 0.56, 95% CI 0.16, 1.89). Toxicities were not significantly different between the two modalities., Conclusion: Despite worse patient prognostic features, MR-ISBT was associated with a significantly better (100%) 3-year local control, comparable survival, and improved DFI rates compared to CT. Toxicities did not differ compared to CT-ISBT patients. Tumor grade contributed as the most significant predictor for survival. Larger prospective studies are needed to assess the impact of MR-ISBT on survival outcomes., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objective: Lower extremity lymphedema adversely affects quality of life by causing discomfort, impaired mobility and increased risk of infection. The goal of this study is to investigate factors that influence the likelihood of lymphedema in patients with endometrial cancer who undergo adjuvant radiation with or without chemotherapy., Methods: A retrospective chart review identified all stage I-III endometrial cancer patients who had a hysterectomy with or without complete staging lymphadenectomy and adjuvant radiation therapy between January 2006 and February 2013. Patients with new-onset lymphedema after treatment were identified. Logistic regression was used to find factors that influenced lymphedema risk., Results: Of 212 patients who met inclusion criteria, 15 patients (7.1%) developed new-onset lymphedema. Lymphedema was associated with lymph-node dissection (odds ratio [OR], 5.6; 95% CI, 1.01 to 105.5; p=0.048) and with the presence of pathologically positive lymph nodes (OR, 4.1; 95% CI, 1.4 to 12.3; p=0.01). Multivariate logistic regression confirmed the association with lymph-node positivity (OR, 3.2; 95% CI, 1.0007 to 10.7; p=0.0499) when controlled for lymph-node dissection. Median time to lymphedema onset was 8 months (range, 1 to 58 months) with resolution or improvement in eight patients (53.3%) after a median of 10 months., Conclusion: Lymph-node positivity was associated with an increased risk of lymphedema in endometrial cancer patients who received adjuvant radiation. Future studies are needed to explore whether node-positive patients may benefit from early lymphedema-controlling interventions.

Purpose: To present evidence-based guidelines for adjuvant radiation in the treatment of endometrial cancer., Methods and Materials: Key clinical questions to be addressed in this evidence-based guideline on endometrial cancer were identified. A comprehensive literature review was performed to identify studies that included no adjuvant therapy, or pelvic radiation or vaginal brachytherapy with or without systemic chemotherapy. Outcomes included local control, survival rates, and overall assessment of quality of life., Results: Patients with grade 1 or 2 cancers with either no invasion or <50% myometrial invasion (MI), especially when no other high risk features are present, can be safely observed after hysterectomy. Vaginal cuff brachytherapy is as effective as pelvic radiation therapy at preventing vaginal recurrence for patients with grade 1 or 2 cancers with ≥50% MI or grade 3 tumors with <50% MI. Patients with grade 3 cancer with ≥50% MI or cervical stroma invasion may benefit from pelvic radiation to reduce the risk of pelvic recurrence. There is limited evidence for a benefit to vaginal cuff brachytherapy following pelvic radiation. Multimodality treatment is recommended for patients with positive nodes or involved uterine serosa, ovaries or fallopian tubes, vagina, bladder, or rectum., Conclusions: External beam and vaginal brachytherapy remain integral aspects of adjuvant therapy for endometrial cancer., (Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine rates of nodal control and survival in patients with endometrial cancer treated with intensity modulated radiation therapy (IMRT) with dose escalation to unresected nodal disease., Methods and Materials: Between November 2005 and April 2011, 22 endometrial-cancer patients received IMRT with dose escalation to gross nodal disease with curative intent. Twelve were treated for recurrent disease (RD) and 10 in the primary setting, of whom 5 had a hysterectomy. The boost area included pelvic nodes in 9 patients (41%), paraaortic nodes (PAN) in 6 (27%) and both pelvic and PAN in 7 (32%). The median gross nodal dose was 63 Gy (range, 55-65). Rates of local control, disease-free survival (DFS) and overall survival (OS) were determined using the Kaplan-Meier method., Results: Median follow-up time was 37.6 months (range, 10-88). Median nodal size was 2.25 cm (range, 1-6.9). The median time to first relapse after IMRT was 12 months (range, 6-49). Relapses occurred in 5/12 RD (42%), 1/5 hysterectomy (20%), and 5/5 inoperable cases. Nodal relapses occurred in-field in 3/12 RD and 1/5 hysterectomy patients. At 3 years, nodal control was 86%, DFS was 58% and OS was 68%. Three patients experienced grade 3 late hematologic toxicity (anemia). No late grade ≥3 gastrointestinal or genitourinary toxicity occurred., Conclusions: In endometrial cancer, the use of IMRT for dose escalation to gross nodal disease is feasible with acceptable rates of toxicity. Patients with nodal recurrence or unresectable nodal disease after a hysterectomy may benefit from radiation dose escalation., (© 2013.)

Purpose: To evaluate clinical outcomes for women with recurrent endometrial cancer treated with 3D image-guided brachytherapy, Methods and Materials: 44 women, of whom 13 had received prior RT, received salvage RT for vaginal recurrence from 9/03 to 8/11. HDR or LDR interstitial brachytherapy was performed under MR or CT guidance in 35 patients (80%); 9 (20%) had CT-guided HDR cylinder brachytherapy. The median cumulative dose in EQD2 was 75.5 Gy. Actuarial estimates of local failure (LF), disease-free (DFS) and overall survival (OS) were calculated by Kaplan-Meier., Results: Histologic subtypes were endometrioid (EAC, 33), papillary serous/clear cell (UPSC/CC, 5) and carcinosarcoma (CS, 6). The 2-year DFS/OS rates were 75%/89% for EAC and 11%/24% for UPSC/CC/CS (both p<0.01). On MVA, high tumor grade was associated with recurrence (HR 3.2 for grade 2, 9.6 for grade 3, p<0.01). The LF rate at 2 years was 4% for patients without versus 39% for those with prior RT (p=0.1). Patients who had prior RT received lower cumulative doses at recurrence (66.5 Gy vs. 74.4 Gy, p<0.01). The 2-year DFS/OS rates with and without prior RT were 26%/55% and 72%/80% (both p=0.1). Four patients (9%) experienced grade 3 late toxicity, including 3 of 13 (23%) in the re-irradiation setting and 1 of 31 (3%) with no prior radiotherapy., Discussion: 3D image-guided brachytherapy results in excellent local control for women with recurrent endometrial cancer, particularly with cumulative EQD2 doses greater than 70 Gy. Successful salvage of vaginal recurrence is related to tumor grade and histologic subtype., (© 2013.)

Objective: To report clinical outcomes following adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) for early-stage uterine papillary serous (UPSC) and clear cell (CC) endometrial cancer., Methods: A retrospective study of Stage I and II papillary serous and clear cell endometrial cancer treated with post-operative HDR VB between October 2005 and May 2012 was performed. A total of 37 patients were identified, 26 with UPSC, 9 with CC and 2 with mixed UPSC/CC. After total hysterectomy and bilateral salpingo-oophorectomy, VB was administered without external-beam radiation with a dose of 24 Gy in 6 fractions prescribed to the vaginal surface. Chemotherapy was given to 30 patients (75%)., Results: The median follow up time was 24.8 months (range, 2.0 to 71.5 months). Four patients relapsed, 2 with UPSC and 2 with CC. The initial site of relapse was concurrent vagina, pelvic/para-aortic nodes and abdominal wall (1), pelvic/para-aortic nodes (1) and para-aortic nodes alone (2). The 2-year vaginal-control rate was 96.8%. The pelvic-control rate including vaginal and nodal relapse was 93.5%. The 2-year disease-free and overall survival rates were 89.3% and 100%, respectively., Conclusion: HDR VB as the sole adjuvant treatment modality for early-stage UPSC/CC is associated with a low rate of vaginal relapse and excellent survival outcomes. This novel low-dose regimen for VB is safe and effective., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities., Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneum plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity., Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity., Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy., (Copyright © 2013 Elsevier Inc. All rights reserved.)