Search

To report clinical outcomes and dosimetric predictors of late toxicity for patients with vaginal recurrence of endometrial cancer treated with brachytherapy in the re-irradiation setting. On retrospective review, 32 patients with vaginal recurrence of endometrial cancer received salvage brachytherapy with or without pelvic radiotherapy (RT) from 06/2003–12/2017. Prior RT modalities were vaginal brachytherapy (19, 59%), pelvic RT (7, 22%) or both (6, 19%). Image-guided brachytherapy was performed with CT- (25, 78%) or MR-guidance (7, 22%). Vaginal control, recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier method. Late toxicity was graded by Common Toxicity Criteria for Adverse Events. Median time from prior RT to re-irradiation was 22 months (range, 4–140). Salvage RT modalities were pelvic RT and brachytherapy (25, 78%) or brachytherapy alone (7, 22%). With median follow-up of 47 months, 3/5-year vaginal control, RFS and OS rates were 64/56%, 47/41% and 68/42%, respectively. Six patients (19%) had no evidence of disease at 85–155 months. Late grade 2/3 GI, GU and vaginal toxicity rates were 13%/16%, 19%/13%, and 9%/16%. Cumulative D2cc rectum (sum of prior and salvage RT courses) was predictive of grade 2+ and grade 3 GI toxicity. Cumulative D2cc rectum for an estimated 10% risk of late grade 2+ and 3 GI toxicity was 86 Gy and 92 Gy, respectively. Salvage image-guided brachytherapy in the re-irradiation setting results in modest local control and increased late toxicity for localized recurrent endometrial cancer. With long-term disease control, cumulative D2cc rectum may be used to reduce late GI complication risk. [ABSTRACT FROM AUTHOR]

In patients with node-positive endometrial cancer, adjuvant radiation therapy with chemotherapy decreases local-regional recurrence compared with chemotherapy alone. However, the optimal radiation field borders and extent of nodal coverage have not been well studied. In a multi-institutional cohort, survival outcomes and sites of failure were analyzed for patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IIIC endometrioid endometrial cancer treated with pelvic radiation therapy (PRT) versus extended-field radiation therapy (EFRT), which encompassed high para-aortic lymph nodes. In a multi-institutional retrospective study, 143 patients with FIGO stage IIIC1 or IIIC2 endometrioid endometrial cancer treated with adjuvant radiation therapy from 2000 to 2016 were identified. Patient subgroups were classified by substage and radiation field extent: stage IIIC1 received EFRT, stage IIIC1 received PRT, and stage IIIC2 received EFRT. Recurrence-free survival (RFS), overall survival (OS), and out-of-field recurrence were calculated by the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards model. Sites of failure were categorized as within or outside the radiation field. The median follow-up was 59 months; 87% of patients received chemotherapy. The 5-year RFS and OS rates were 73% and 87%, respectively. By subgroup, 5-year RFS rates were 79% for stage IIIC1 EFRT, 73% for stage IIIC1 PRT, and 69% for stage IIIC2 EFRT (P =.4). On multivariate analysis, the recurrence risk was highest for stage IIIC2 EFRT, although this result was not statistically significant (adjusted hazard ratio, 2.0; P =.4). In-field vaginal and nodal recurrences were observed in 2 patients (1%) and 4 patients (3%), respectively. Of 78 patients with stage IIIC1 cancer treated with PRT, 5 (6%) had isolated para-aortic nodal relapse outside the radiation field; 3 were long-term survivors (more than 6 years after salvage therapy). For patients with para-aortic recurrence, 86% had lymphovascular invasion, 71% had myometrial invasion of ≥50%, and 57% had grade 3 disease. Adjuvant chemoradiation therapy resulted in excellent survival outcomes for patients with FIGO stage IIIC endometrioid endometrial cancer. For patients with positive pelvic nodes, isolated para-aortic relapse outside the PRT field was uncommon and amenable to salvage therapy. [ABSTRACT FROM AUTHOR]

Our purpose was to evaluate outcomes and sites of failure for women with early stage endometrial adenocarcinoma treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) with a low dose scheme. Retrospective review identified 318 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II endometrioid endometrial cancer who received adjuvant HDR VB to a dose of 24 Gray (Gy) in 6 fractions from 2005 to 2017. Patients with <6 months follow-up were excluded. Dose was prescribed to cylinder surface and computerized tomography (CT) imaging was performed before each fraction to assess cylinder placement. Rates of vaginal relapse (VR), pelvic nodal relapse, distant metastasis, recurrence-free survival, and overall survival were calculated by Kaplan-Meier method. Univariate analysis was performed by log rank test or Cox proportional hazards. Pretreatment CT images were analyzed for patients with VR. Median follow-up was 42 months for 243 patients. The 3-year rates of VR, pelvic nodal relapse, distant metastasis, recurrence-free survival, and overall survival were 1.9%, 1.5%, 4.3%, 94.1%, and 98.9%, respectively. The 3-year VR rates by Gynecologic Oncology (GOG)-99 risk groups were 0%, 1.4%, and 3.2% for low risk, low-intermediate risk, and high-intermediate risk (HIR) disease (P =.5). By Post-operative Radiation Therapy in Endometrial Carcinoma (PORTEC) risk stratification, 3-year VR rate was 1.3% for HIR disease. On review of pretreatment CT images of the 6 patients with VR, 3 patients had relapse at the introitus outside of the treated vaginal length, and 3 had in-field recurrence at the vaginal apex. Higher body mass index (BMI) was associated with VR, with a 14% increase in risk per BMI unit (kg/m2, P =.02). There were no reported grade 2 GI or any grade 3 toxicities. Adjuvant HDR VB with a low-dose regimen results in excellent clinical outcomes for patients with early stage endometrioid endometrial cancer. Patients with higher BMI may be at increased risk of VR, and additional study is needed to optimize brachytherapy treatment parameters. [ABSTRACT FROM AUTHOR]

Purpose To increase intraprocedural efficiency in the use of clinical resources and to decrease planning time for cervical cancer brachytherapy treatments through redesign of the procedure's process map. Methods and Materials A multidisciplinary team identified all tasks and associated resources involved in cervical cancer brachytherapy in our institution and arranged them in a process map. A redesign of the treatment planning component of the process map was conducted with the goal of minimizing planning time. Planning time was measured on 20 consecutive insertions, of which 10 were performed with standard procedures and 10 with the redesigned process map, and results were compared. Statistical significance ( p < 0.05) was measured with a two-tailed t test. Results Twelve tasks involved in cervical cancer brachytherapy treatments were identified. The process map showed that in standard procedures, the treatment planning tasks were performed sequentially. The process map was redesigned to specify that contouring and some planning tasks are performed concomitantly. Some quality assurance tasks were reorganized to minimize adverse effects of a possible error on procedure time. Test dry runs followed by live implementation confirmed the applicability of the new process map to clinical conditions. A 29% reduction in planning time ( p < 0.01) was observed with the introduction of the redesigned process map. Conclusions A process map for cervical cancer brachytherapy was generated. The treatment planning component of the process map was redesigned, resulting in a 29% decrease in planning time and a streamlining of the quality assurance process. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate clinical outcomes of CT-guided high-dose-rate (HDR) interstitial brachytherapy for primary and recurrent gynecologic cancer. Methods and Materials: Records were reviewed for 68 women (34 with primary disease and 34 with recurrence) treated with CT-guided HDR interstitial brachytherapy between May 2005 and September 2011. Interstitial application was performed under general anesthesia using an iterative approach of catheter insertion and adjustment with serial image acquisition by CT in a dedicated brachytherapy suite. The median fractional brachytherapy dose was 3.9Gy delivered twice daily in seven fractions. The median cumulative dose in equivalent 2-Gy fractions was 74.8Gy. Actuarial survival estimates were calculated using the Kaplan–Meier method, and toxicity was reported by Common Toxicity Criteria. Results: Primary disease sites were endometrial (34), cervical (17), vaginal (11), ovarian (3), and vulvar (3). Median age was 61.5 years, and tumor size at diagnosis was 3.4cm. Median D 90 and V 100 were 73.6Gy and 87.5%, respectively; median D 2cc for bladder, rectum, and sigmoid were 67.1, 64.6, and 53.7Gy, respectively. With a median followup of 17 months, actuarial rates of local control, progression-free survival, and overall survival at 2 years for all patients were 86%, 60%, and 64%, respectively. There were 9 grade 3 late toxicities (six gastrointestinal and three vulvovaginal). Conclusions: HDR interstitial brachytherapy with CT-guided catheter placement results in acceptable local control, toxicity, and survival rates for women with primary or recurrent gynecologic cancer. Durable pelvic control may be achieved in most patients with this specialized brachytherapy technique. [Copyright &y& Elsevier]

Purpose: To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer. Methods and Materials: Records were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adverse Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method. Results: At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). Discussion: Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure adequate tumor coverage while minimizing the D2cc to the rectum. [Copyright &y& Elsevier]

Abstract: Purpose: To develop a guideline for quality practice of low-dose-rate (LDR) and pulsed-dose-rate (PDR) brachytherapy for locally advanced cervical cancer. Methods: Members of the American Brachytherapy Society (ABS) with expertise in cervical cancer brachytherapy formulated updated guidelines for LDR and PDR brachytherapy for locally advanced (International Federation of Gynecology and Obstetrics [FIGO] Stages IB2–IVA) cervical cancer based on literature review and clinical experience. Results: The ABS strongly recommends the use of brachytherapy as a component of the definitive treatment of locally advanced cervical carcinoma. Precise applicator placement is necessary to maximize the probability of achieving local control without major side effects. The ABS recommends a cumulative delivered dose of approximately 80–90Gy for definitive treatment. Dosimetry must be performed after each insertion before treatment delivery. The dose delivered to point A should be reported for all intracavitary brachytherapy applications regardless of treatment planning technique. The ABS also recommends adoption of the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology guidelines for contouring, image-based treatment planning and dose reporting. Interstitial brachytherapy may be considered for a small proportion of patients whose disease cannot be adequately encompassed by intracavitary application and should be performed by practitioners with special expertise in these procedures. Quality management measures must be performed, and follow-up information should also be obtained. Conclusions: Updated ABS guidelines are provided for LDR and PDR brachytherapy for locally advanced cervical cancer. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their clinical practices and to adopt dose-reporting policies that are critical for outcome analysis. [Copyright &y& Elsevier]

Purpose: To compare high dose rate (HDR) point B to pelvic lymph node dose using three-dimensional–planned brachytherapy for cervical cancer. Methods and Materials: Patients with FIGO Stage IB–IIIB cervical cancer received 70 tandem HDR applications using CT-based treatment planning. The obturator, external, and internal iliac lymph nodes (LN) were contoured. Per fraction (PF) and combined fraction (CF) right (R), left (L), and bilateral (Bil) nodal doses were analyzed. Point B dose was compared with LN dose–volume histogram (DVH) parameters by paired t test and Pearson correlation coefficients. Results: Mean PF and CF doses to point B were R 1.40 Gy ± 0.14 (CF: 7 Gy), L 1.43 ± 0.15 (CF: 7.15 Gy), and Bil 1.41 ± 0.15 (CF: 7.05 Gy). The correlation coefficients between point B and the D100, D90, D50, D2cc, D1cc, and D0.1cc LN were all less than 0.7. Only the D2cc to the obturator and the D0.1cc to the external iliac nodes were not significantly different from the point B dose. Significant differences between R and L nodal DVHs were seen, likely related to tandem deviation from irregular tumor anatomy. Conclusions: With HDR brachytherapy for cervical cancer, per fraction nodal dose approximates a dose equivalent to teletherapy. Point B is a poor surrogate for dose to specific nodal groups. Three-dimensional defined nodal contours during brachytherapy provide a more accurate reflection of delivered dose and should be part of comprehensive planning of the total dose to the pelvic nodes, particularly when there is evidence of pathologic involvement. [Copyright &y& Elsevier]

Summary: The EBCTCG has clearly demonstrated that the use of RT after either breast conserving surgery (BCS) or after mastectomy in node-positive patients not only reduces local recurrence (LR), but also improves long-term survival. The EBCTCG specifically found that the absolute reduction in the 5-year rate of LR was proportional to the absolute reduction in 15-year breast cancer mortality with a 4:1 ratio. Studies from the EBCTCG have also clearly shown that when RT for breast cancer inadvertently delivers ‘excessive’ dose to the heart, there is an increased rate of late cardiac deaths. Over time, LR rates with RT have decreased, particularly after BCS, and this is largely due to a favorable interaction of RT with adjuvant systemic therapy. There is new information emerging about the effectiveness of RT based on newer biologic classification of breast cancer and about how the 4:1 ratio might change in the face of increasingly effective systemic therapy and with a better understanding of the importance of biologic classification and of the competing risks of local and distant recurrence. Technical innovations in RT include the development of techniques that minimize cardiac irradiation. It is critical that CT simulation be done during which the heart should be contoured and the radiation dose-cardiac volume relationship be determined. In the EBCTCG''s preliminary analysis, increased late cardiac deaths were most closely linked to mean cardiac doses >5 Gy. A number of techniques are available to minimize cardiac dose both after BCS and mastectomy and these will be described. There has also been development of fractionation and treatment techniques to complete RT faster for purposes of patient convenience and to assure its optimal level of use. There are now 10-year results from a Canadian trial showing equivalent LR and cosmetic outcome with RT using the convential 25 treatments to the whole breast compared to 16 treatments using a higher dose per day. Few randomized patients, however, were treated with adjuvant chemotherapy and a boost was not used. The generalizability of the Canadian trial results to patients treated with adjuvant chemotherapy or requiring a boost is not known. For patients treated after BCS, there has been great interest in the use of accelerated partial breast irradiation (APBI), which can be accomplished using interstitial, intracavitary, external-beam or intraoperative techniques. Clinical trials are now underway to compare APBI to conventional techniques, but mature results from these trials will not be available for some time. In the U.S., ASTRO has developed a consensus statement based on an expert panel as to when APBI can be reasonably used outside of a clinical trial and this will be described. [Copyright &y& Elsevier]

Interstitial and intracavitary gynecological HDR brachytherapy involve precise, localized delivery to targets with high dose gradients, sparing adjacent organs at risk (OAR). Due to the proximity of the rectum, bowel and bladder to the target, deviations in the applicator or catheter with respect to patient anatomy can significantly increase dose to OAR. The magnitude and direction of applicator and catheter migration at each fraction was assessed for template interstitial and tandem and ring (T&R) cohorts. The cohort included twelve gynecological patients with intact cervical lesions treated with external beam and brachytherapy. Pre-treatment CT images were registered to the simulation CT with respect to the target. Treatment catheter positions transformed into the planning CT coordinate system to evaluate localized catheter displacement and dose distributions calculated at each fraction. Dose was evaluated on the planning CT with planning contours and dwell locations at treatment position. Absolute deviation, depth and deflection angle for all patients were 4.6 ± 4.2 mm, -1.4 ± 4.0 mm, and 3.1 ± 2.3° respectively (n = 516 catheter positions for all treatment fractions and patients, mean ± SD). Absolute catheter deviation and deflection magnitude for interstitial treatments increased overall with each subsequent fraction with an overall increase of catheter retraction at each fraction (p < 0.005, n = 492 catheters, Kruskal-Wallis). A target EQD2 D90 reduction of 10 ± 10% and 7.7 ± 8.7% of the planned dose for interstitial and T&R cohorts respectively. There was an overall increase in bladder and rectal doses at each fraction. Catheter tracking in interstitial and intracavitary gynecological treatments with CT imaging revealed significant changes in catheter positioning with respect to the target volume. Overall deviations increased in magnitude with each subsequent fraction in the interstitial treatments. This caused patient dosimetry deviations, including target dose reduction and adjacent OAR doses changes. [ABSTRACT FROM AUTHOR]

Brachytherapy is critical for the curative treatment of locally advanced cervical cancer. Although brachytherapy use is declining in the United States (U.S.), novel interstitial or intracavitary applicators and advances in image guidance for applicator placement and treatment planning have allowed for tumor dose escalation while reducing normal tissue toxicity. Recent survey data have suggested insufficient brachytherapy training for radiation oncology trainees in the United States. This study aimed to address these gaps by developing and piloting a simulation-based education (SBE) workshop for MR-guided cervical cancer brachytherapy. An SBE workshop was developed for graduate medical education (GME) trainees focusing on MR-guided brachytherapy for cervical cancer. Four hands-on stations, simulating aspects of the procedure, were led by a team of gynecological brachytherapy experts. The learners were radiation oncology residents and fellows in a U.S. GME training program. The primary outcome was feasibility, assessed by completion of the workshop within the time constraints of the curriculum. Learners completed preworkshop and postworkshop surveys to provide information on efficacy. The workshop was successfully completed in a 1-h block of GME didactic time. Ten trainees completed all four stations, and all completed preworkshop and postworkshop surveys, which showed improvements in knowledge and technical proficiency. Feedback was positive, and trainees requested additional learning opportunities. This study showed that GME-focused SBE in MR-guided cervical cancer brachytherapy was feasible. SBE provided a nonclinical environment in which to practice aspects of MR-guided brachytherapy. Ongoing work includes collaboration with other U.S. institutions. Future studies should focus on international adaptation. [ABSTRACT FROM AUTHOR]

Abstract Purpose External beam radiation therapy (EBRT) with low-dose-rate (LDR) brachytherapy boost has been associated with improved biochemical progression–free survival and overall survival (OS) compared with dose-escalated EBRT (DE-EBRT) alone for unfavorable-risk prostate cancer. However, it is not known whether high-dose-rate (HDR) boost provides a similar benefit. We compare HDR boost against LDR boost and DE-EBRT with respect to OS. Methods Using the National Cancer Database, we identified 122,896 patients who were diagnosed with National Comprehensive Cancer Network intermediate- or high-risk prostate cancer between 2004 and 2014 and treated with DE-EBRT (75.6–86.4 Gy), LDR boost, or HDR boost. We compared the OS among the three groups using multivariable Cox proportional hazards regression. Inverse probability treatment weighting was used to adjust for covariate imbalance. Results On multivariable Cox proportional hazards regression, HDR boost was associated with a similar OS to LDR boost (adjusted hazard ratio [AHR] 1.03 [0.96, 1.11]; p = 0.38) but significantly better OS than DE-EBRT (AHR 1.36 [1.29, 1.44]; p < 0.001). Inverse probability treatment weighting analysis yielded similar results. There was no significant difference between LDR and HDR boosts for National Comprehensive Cancer Network intermediate-risk (AHR 1.05 [0.96, 1.15]; p = 0.32) and high-risk (AHR 1.00 [0.89, 1.12]; p = 0.98) subgroups (p -interaction = 0.55). Conclusions Our results suggest that HDR brachytherapy boost yields similar OS benefits compared with LDR brachytherapy boost for unfavorable-risk prostate cancer. HDR boost may be a suitable alternative to LDR boost. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the survival endpoints in women with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrial cancer who received adjuvant vaginal brachytherapy (VBT) alone using multi-institutional pooled data.Methods and Materials: We performed a multi-institutional analysis of surgically staged patients with FIGO stage II endometrioid-type endometrial cancer treated with VBT alone. Patient, tumor, and treatment characteristics were collected and analyzed. Univariable and multivariable frailty survival models were performed to assess clinicopathologic risk factors for recurrence and death.Results: One hundred six patients were included (92 VBT alone and 14 VBT with chemotherapy) with median follow-up of 39.0 months. Pelvic node dissection was performed in 89.6% of patients. One hundred four patients (98.1%) and 2 patients (1.9%) had microscopic and macroscopic cervical stromal invasion, respectively. Grade 1 or 2 disease occurred in 88.6% of patients. For patients treated with VBT without chemotherapy, the 5-year estimates of vaginal failure, pelvic nodal failure, and distant metastases were 2.6%, 4.2%, and 7.2%, respectively. Five-year progression-free survival and overall survival were 74.0% and 76.2%, respectively. On univariable and multivariable models for progression-free survival, increasing age and lack of pelvic node resection were hazardous (P < .05).Conclusions: Vaginal and pelvic failure rates were low in this selected population of stage II patients receiving adjuvant VBT without external beam radiation therapy. It is reasonable to consider adjuvant VBT alone in selected patients with grade 1 or 2 disease and microscopic cervical stromal invasion who underwent pelvic lymphadenectomy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose To investigate the dose–volume histogram metrics and optimization results of the contoured bowel in cervical cancer brachytherapy. Methods and Materials Treatment plans of cervical cancer patients treated with image-guided high dose rate were retrospectively analyzed with institutional review board approval. In addition to the clinical target volume, rectum, bladder, and sigmoid, the bowel was contoured at the time of planning (Group 1) or at the time of this analysis (Group 2). Results Thirty-two patients treated with 145 insertions were included. Before optimization, mean ± 1 standard deviation overall bowel minimum dose to the most irradiated 2 cm 3 volume of an organ ( D 2cc ) was 67.8 Gy α/β3 ± 13.7 Gy α/β3 (Group 1: 72.6 ± 13.2 Gy α/β3 ; Group 2: 57.3 ± 8.0 Gy α/β3 ). Before optimization, one patient in Group 1 presented a bowel D 2cc metric exceeding 100 Gy α/β3 . After optimization, bowel D 2cc mean ± 1 standard deviation was 59.4 ± 6.7 Gy α/β3 (Group 1: 61.4 ± 6.0 Gy α/β3 , p < 0.001; Group 2: 55.2 ± 6.5 Gy α/β3 , p = 0.026). Conclusions Given the potentially high doses and the benefit of optimization in reducing dose to the organs at risk, we recommend consideration of systematic contouring of the bowel when bowel is present in the pelvis. [ABSTRACT FROM AUTHOR]

Objective Uterine carcinosarcoma (CS) is an aggressive malignancy and the optimal adjuvant treatment is not well-established. We report outcomes with vaginal brachytherapy (VB) for women with early-stage CS. Methods and Materials A multi-institutional retrospective study of Stage I-II CS treated with hysterectomy, surgical staging, and adjuvant high-dose-rate VB without external-beam pelvic radiotherapy was performed. Rates of vaginal control, pelvic control, locoregional control, disease-free survival, and overall survival were determined using the Kaplan-Meier method. Results 33 patients were identified. Prescribed VB dose was 21 Gy in three fractions ( n = 15 [45%]) or 24 Gy in six fractions ( n = 18 [55%]). Eighteen patients (55%) received chemotherapy. Median followup was 2.0 years. Twenty-seven patients (82%) underwent pelvic lymphadenectomy, 5 (15%) had nodal sampling, and 1 (3%) had no lymph node assessment. Relapse occurred in 11 patients (33%), all of whom had lymph node evaluation. Locoregional relapse was a component of failure in 6 patients (18%), of whom 3 (9%) failed in the pelvis alone. Three patients (9%) had simultaneous distant and locoregional relapse (two vaginal, one pelvic). Five additional patients (15%) had distant relapse. Six of the 11 patients (55%) with disease recurrence received chemotherapy. Two-year vaginal control and pelvic control were 94% and 87%. Two-year locoregional control, disease-free survival, and overall survival were 81%, 66%, and 79%. Conclusions Despite having early-stage disease and treatment with VB, patients in this series had relatively high rates of local and distant relapse. Patients who undergo lymphadenectomy and VB remain at risk for relapse. Novel treatment strategies are needed. [ABSTRACT FROM AUTHOR]

Background and purpose The goals of this study were to determine the rate and risk factors of rectal bleeding (RB) after external beam radiotherapy and vaginal brachytherapy (EBRT + VB), and to compare these data to previously unreported RB rates from PORTEC-2 patients receiving EBRT or VB alone. Materials and methods Retrospective chart review identified 212 endometrial cancer patients receiving adjuvant EBRT + VB between 2006 and 2013. Patient-reported RB data were also obtained from PORTEC-2 patients randomized to EBRT ( n = 166) or VB ( n = 182). The two populations were compared using an RB scale of symptom severity. Results After a median 35 months, 17.9% of EBRT + VB patients ( n = 38) experienced any RB with 1.9% ( n = 4) having bleeding requiring intervention. Age ⩽70 years was the only predictor of RB (OR 2.8; 95% CI 1.1–8.7; p = 0.027). Rates of patient-reported RB after EBRT were similar with 15.0% ( n = 25) having any RB and 0.6% ( n = 1) having “very much” bleeding. On regression analysis, any EBRT (either EBRT alone or EBRT + VB) increased the risk of RB compared to those who received VB alone (OR 3.0; p = 0.0028; 95% CI 1.4–6.7). The rates of more severe RB were low and did not significantly differ between treatments. Conclusions Significant RB is rare after radiation. EBRT has higher rates of rectal bleeding than VB. The addition of VB to EBRT does not significantly alter bleeding rates. [ABSTRACT FROM AUTHOR]

Objective To create and compare consensus clinical target volume (CTV) contours for computed tomography (CT) and 3-Tesla (3-T) magnetic resonance (MR) image-based cervical-cancer brachytherapy. Methods and Materials Twenty-three experts in gynecologic radiation oncology contoured the same 3 cervical cancer brachytherapy cases: 1 stage IIB near-complete response (CR) case with a tandem and ovoid, 1 stage IIB partial response (PR) case with tandem and ovoid with needles, and 1 stage IB2 CR case with a tandem and ring applicator. The CT contours were completed before the MRI contours. These were analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with κ statistics as a measure of agreement between participants. The conformity index was calculated for each of the 6 data sets. Dice coefficients were generated to compare the CT and MR contours of the same case. Results For all 3 cases, the mean tumor volume was smaller on MR than on CT ( P <.001). The κ and conformity index estimates were slightly higher for CT, indicating a higher level of agreement on CT. The Dice coefficients were 89% for the stage IB2 case with a CR, 74% for the stage IIB case with a PR, and 57% for the stage IIB case with a CR. Conclusion In a comparison of MR-contoured with CT-contoured CTV volumes, the higher level of agreement on CT may be due to the more distinct contrast medium visible on the images at the time of brachytherapy. MR at the time of brachytherapy may be of greatest benefit in patients with large tumors with parametrial extension that have a partial or complete response to external beam. On the basis of these results, a 95% consensus volume was generated for CT and for MR. Online contouring atlases are available for instruction at http://www.nrgoncology.org/Resources/ContouringAtlases/GYNCervicalBrachytherapy.aspx . [ABSTRACT FROM AUTHOR]

Purpose: To investigate the dosimetric variability associated with interobserver organ-at-risk delineation differences on computed tomography in patients undergoing gynecologic interstitial brachytherapy. Methods and Materials: The rectum, bladder, and sigmoid of 14 patients treated with gynecologic interstitial brachytherapy were retrospectively contoured by 13 physicians. Geometric variability was calculated using κ statistics, conformity index (CIgen), and coefficient of variation (CV) of volumes contoured across physicians. Dosimetric variability of the single-fraction D0.1cc and D2cc was assessed through CV across physicians, and the standard deviation of the total EQD2 (equivalent dose in 2 Gy per fraction) brachytherapy dose (SDTOT) was calculated. Results: The population mean ± 1 standard deviation of κ, CIgen, and volume CV were, respectively: 0.77 ± 0.06, 0.70 ± 0.08, and 20% ± 6% for bladder; 0.74 ± 06, 0.67 ± 0.08, and 20% ± 5% for rectum; and 0.33 ± 0.20, 0.26 ± 0.17, and 82% ± 42% for sigmoid. Dosimetric variability was as follows: for bladder, CV = 31% ± 19% (SDTOT = 72 ± 64 Gy) for D0.1cc and CV = 16% ± 10% (SDTOT = 9 ± 6 Gy) for D2cc; for rectum, CV = 11% ± 5% (SDTOT = 16 ± 17 Gy) for D0.1cc and CV = 7% ± 2% (SDTOT = 4 ± 3 Gy) for D2cc; for sigmoid, CV = 39% ± 28% (SDTOT = 12 ± 18 Gy) for D0.1cc and CV = 34% ± 19% (SDTOT = 4 ± 4 Gy) for D2cc. Conclusions: Delineation of bladder and rectum by 13 physicians demonstrated substantial geometric agreement and resulted in good dosimetric agreement for all dose-volume histogram parameters except bladder D0.1cc. Small delineation differences in high-dose regions by the posterior bladder wall may explain these results. The delineation of sigmoid showed fair geometric agreement. The higher dosimetric variability for sigmoid compared with rectum and bladder did not correlate with higher variability in the total brachytherapy dose but rather may be due to the sigmoid being positioned in low-dose regions in the cases analyzed in this study. [ABSTRACT FROM AUTHOR]

The androgen receptor (AR) activates target gene expression in the presence of agonist ligands via the recruitment of transcriptional coactivators, but recent work shows that overexpression of the nuclear corepressors NCoR and SMRT attenuates this agonist-mediated AR activation. Here we demonstrate using NCoR siRNA and chromatin immunoprecipitation that endogenous NCoR is recruited to and represses the dihydrotestosterone (DHT)-liganded AR. Furthermore this study shows that NCoR and coactivators compete for AR in the presence of DHT. AR antagonists such as bicalutamide that are currently in use for prostate cancer treatment can also mediate NCoR recruitment, but mifepristone (RU486) at nanomolar concentrations is unique in its ability to markedly enhance the AR-NCoR interaction. The RU486-liganded AR interacted with a C-terminal fragment of NCoR, and this interaction was mediated by the two most C-terminal nuclear receptor interacting domains (RIDs) present in NCoR.. Significantly, in addition to the AR ligand binding domain, the AR N terminus was also required for this interaction. Mutagenesis studies demonstrate that the N-terminal surface of the AR-mediating NCoR recruitment was distinct from tau5 and from the FXXLF motif that mediates agonist-induced N-C-terminal interaction. Taken together these data demonstrate that NCoR is a physiological regulator of the AR and reveal a new mechanism for AR antagonism that may be exploited for the development of more potent AR antagonists. [ABSTRACT FROM AUTHOR]