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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]

Objective To evaluate clinical outcomes, prognostic factors, and toxicity in patients with vaginal recurrence of early-stage endometrial cancer treated with definitive radiotherapy. Methods Retrospective review identified 62 patients with stage I-II endometrial cancer and vaginal recurrence treated with external beam radiotherapy and imageguided brachytherapy with definitive intent from November 2004 to July 2017. All patients had prior hysterectomy without adjuvant radiotherapy and >3 months followup. Mismatch repair (MMR) status was determined by immunohistochemical staining of the four mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6) when available in the pathology record. Rates of vaginal control, recurrence-free survival, and overall survival were calculated by Kaplan-Meier. Univariate and multivariate analyses were performed by Cox proportional hazards. Results Most patients had endometrioid histology (55, 89%), grade 1 or 2 tumor (53, 85%), and vaginal-only recurrence (55, 89%). With a median follow-up of 39 months (range, 3-167), 3-and 5-year rates of vaginal control, recurrence-free survival, and overall survival were 86% and 82%, 69% and 55%, and 80% and 61%, respectively. On multivariate analysis, non-endometrioid histology (HR 12.5, P<0.01) was associated with relapse when adjusted for chemotherapy use. Patients with nonendometrioid histology also had a 4.5-fold higher risk of death when adjusted for age (P=0.02). Twenty patients had known MMR status, all with grade 1-2 endometrioid tumors and 10 (50%) with MMR deficiency. The 3-year recurrence-free survival was 100% for MMR-proficient tumors and 52% for MMR-deficient (P=0.03). Late grade 2 and 3 gastrointestinal, genitourinary and vaginal toxicity was reported in 27% and 3%, 15% and 2%, and 16% and 2% of patients, respectively. Conclusion Definitive radiotherapy with image-guided brachytherapy resulted in 5-year local control rates exceeding 80% and late severe toxicity rates were under 3%. Distant recurrence was common and highest for those with grade 3 or non-endometrioid tumors and MMR deficient grade 1-2 disease. [ABSTRACT FROM AUTHOR]

Habitat loss is a main contributor to fish fauna declines in the southwestern USA. Several studies have defined stream‐specific habitat conditions that support the growth and survival of native fish in Arizona to inform stream restoration efforts, yet general habitat use of most individual species across the region is not established. Therefore, we evaluated habitat use of four native fishes, Speckled Dace Rhinichthys osculus, Sonora Sucker Catostomus insignis, Desert Sucker Catostomus clarkii, and Longfin Dace Agosia chrysogaster, across three Arizona streams through the development of habitat suitability criteria (HSC). We developed both stream‐specific and generalized HSC for each species. Generalized HSC were calculated as the combination of stream‐specific HSC for each species. We then assessed the utility of generalized HSC through transferability among study streams. Also, past HSC studies have not considered the occurrence of nonnative species, so we tested whether the presence of nonnative fishes influenced native fish habitat use through logistic regression models. Fish and habitat data were collected along the Mogollon Rim in Arizona during the 2017 summer field season at base flow conditions. We established minimum microhabitat use for four native Arizona fish species through developing HSC. Most generalized criteria did not transfer among study streams due to variation in habitat availability and fish community structure. Logistic regression analysis showed that the presence of nonnative fishes was inversely related to the presence of two native fish species, which could have influenced habitat use of both species. The lack of transferability across streams as demonstrated in this study confirms that only HSC developed in the stream of interest or in similar undegraded streams with comparable fish communities should be used for restoration efforts. For projects to restore native fishes in streams where nonnative competitors will not dominate, the least degraded similar streams without coexisting nonnative fishes can guide restoration efforts. [ABSTRACT FROM AUTHOR]

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. [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]

Introduction: To evaluate clinical outcomes for patients with localized recurrent ovarian cancer treated with salvage radiotherapy. Methods: In a retrospective single institutional analysis, we identified 40 patients who received salvage radiotherapy for localized ovarian cancer recurrence from January 1995 to June 2011. Recurrent disease was categorized as: pelvic peritoneal (45%, 18), extraperitoneal/nodal (35%, 14), or vaginal (20%, eight). Actuarial disease-free and overall survival estimates were calculated by Kaplan–Meier and prognostic factors evaluated by the Cox proportional hazards model. Results: Median follow-up was 42 months. Median patient age was 54 years (range, 27–78). Histologic subtypes were: serous (58%, 23), endometrioid (15%, six), clear cell (13%, five), mucinous (8%, three), and other (8%, three). At the time of salvage radiotherapy, surgical cytoreduction was performed in 60% (24) and 68% (27) had platinum-sensitive disease. Most patients (63%, 25) received salvage radiotherapy at the time of first recurrence. Relapse after salvage radiotherapy occurred in 29 patients at a median time of 16 months and was outside the radiotherapy field in 62%. 18 At 3 years, disease-free and overall survival rates were 18% and 80%, respectively. On multivariate analysis, non-serous histology (hazards ratio 0.3, 95% CI 0.1–0.7) and platinum-sensitivity (hazards ratio 0.2, 95% CI 0.1–0.5) were associated with lower relapse risk. Platinum-sensitivity was also associated with overall survival (hazards ratio 0.4, 95% CI 0.1–1.0). Four patients (10%) were long-term survivors without recurrence 5 years after salvage radiotherapy. Of the five patients with clear cell histology, none experienced relapse at the time of last follow-up. Discussion: Patients with non-serous and/or platinum-sensitive ovarian cancer had the greatest benefit from salvage radiotherapy for localized recurrent disease. Although relapse was common, radiotherapy prolonged recurrence for > 1 year in most patients and four were long-term survivors. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to report response rates and predictors of response to palliative radiotherapy (RT) for recurrent ovarian cancer. Methods/Materials: Database review identified 64 patients with symptomatic ovarian cancer recurrence who received a total of 76 courses of RT for 103 indications from March 2003 to August 2014. Radiotherapy indications were pain (44%), bleeding (32%), obstruction (15%), and other (9%). Responses were categorized as complete, partial, or none; all response (AR)was the sum of complete and partial responses. Response rates were compared using a χ² test. Multivariate analysis was performed using logistic regression. Patients were followed up for symptom recurrence and death. Results: Response rates were significantly higher for pain (AR, 87%) and bleeding (93%) than for obstruction (62%) and other (60%; P < 0.01). Patients treated for pain at nonbony sites had higher response rates (AR 96%) compared with those treated at bony sites (75%; P = 0.04). Patients with clear cell histology had the lowest response rates (AR, 60%) compared with those with serous (82%), endometrioid (95%), or other Müllerian histology (85%; P = 0.01). Platinum status at diagnosis or the time of RT was not associated with response, nor was tumor size or number of prior chemotherapy regimens. On multivariate analysis, histology, RT indication, and RT dose were independent predictors of response (all P < 0.01). Conclusions: Palliative RT provides relief of pain and bleeding in most patients with ovarian cancer recurrence. Patients with symptomatic obstruction, bony involvement, and clear cell histology may experience lower clinical response rates. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate clinical outcomes including disease-free survival (DFS) and overall survival (OS) for women with node-positive, high-grade adenocarcinoma of the uterus.Database review identified 73 patients with International Federation of Gynecology and Obstetrics stage IIIC 1/2 grade 3 endometrial cancer diagnosed from 1995 to 2009. Study inclusion required total abdominal hysterectomy/bilateral salpingo-oophorectomy and negative chest imaging. Histologic subtypes were endometrioid (22, 30%), papillary serous (20, 27%), clear cell (9, 12%), mixed (21, 29%), and undifferentiated (1, 1%). Adjuvant treatment was chemotherapy with external beam radiation therapy (EBRT) in 55 patients (75%), EBRT alone in 14 (19%), chemotherapy in 2 (3%), and no adjuvant therapy in 2 (3%).With a median follow-up of 50 months, DFS/OS rates at 5 years were 44%/53%, respectively. Intraperitoneal relapse was more common in patients with positive cytology (30% vs 6%, P = 0.02) and nonendometrioid histology (16% vs 4%, P = 0.3). By histologic subtype, 5-year DFS/OS rates were 59%/82% for grade 3 endometrioid, 25%/30% for serous, 22%/17% for clear cell, and 50%/51% for mixed histology (P = 0.1/P < 0.001). The 5-year DFS/OS rates were 56%/68% for those who received both chemotherapy and EBRT. Among patients treated with adjuvant EBRT, pelvic control was 93%.For node-positive, high-grade endometrial cancer, patients with endometrioid and mixed histologic subtypes had better clinical outcomes than did those with serous and clear cell cancers. Distinct patterns of relapse were observed with a greater risk of intraperitoneal failure for nonendometrioid histologic subtypes. Future studies are needed to define the optimal chemotherapy regimen and radiation fields. [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]

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]