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Purpose: This study aimed to evaluate the toxicity and clinical outcomes for cervical cancer patients treated definitively with intensity-modulated radiation therapy (IMRT) compared with non-IMRT treatment. Methods and Materials: This prospective cohort study included 452 patients with newly diagnosed cervical cancer treated with curative intent (135 IMRT and 317 non-IMRT). Treatment involved external irradiation and brachytherapy, and 85% of patients received concurrent chemotherapy. All IMRT patients underwent an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET/CT) simulation. A 3-month post-therapy PET was obtained to evaluate treatment response. Toxicity was scored by the Common Terminology Criteria for Adverse Events Version 3.0. Results: The IMRT and non-IMRT groups had similar stage distribution and histology. For all patients, the post-therapy FDG-PET response correlated with overall recurrence risk (p < 0.0001) and cause-specific survival (p < 0.0001). Post-treatment FDG-PET findings were not significantly different between the IMRT and non-IMRT patients (p = 0.9774). The mean follow-up for all patients alive at the time of last follow-up was 52 months (72 months non-IMRT, 22 months IMRT). At last follow-up, 178 patients (39 IMRT, 139 non-IMRT) had developed a recurrence. The difference in recurrence-free survival between the two groups did not reach statistical significance (p = 0.0738), although the IMRT group showed better overall and cause-specific survivals (p < 0.0001). Of the patients, 62 patients (8 IMRT and 54 non-IMRT) developed Grade 3 or greater bowel or bladder complications, and by cumulative hazard function analysis the risk was significantly less for patients treated with IMRT (p = 0.0351). Conclusion: Cervical cancer patients treated with FDG-PET/CT-guided IMRT have improved survival and less treatment-related toxicity compared with patients treated with non-IMRT radiotherapy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the variation in cervical cancer glucose metabolism for different tumor histologies and levels of differentiation, as measured by the uptake of 18F-fluorodeoxyglucose (FDG) by positron emission tomography (PET). Methods: The study population consisted of 240 patients with International Federation of Gynecology and Obstetrics stages Ib1 through IVb cervical cancer, who underwent a pretreatment FDG-PET. Tumor histology included 221 squamous cell (SC), 4 adenosquamous (AS), and 15 adenocarcinoma (AC) tumors. There were 14 well, 145 moderately, and 81 poorly differentiated tumors. The stage distribution was as follows: 70 stage I tumors (9 AC, 2 AS, and 59 SC), 102 stage II tumors (3 AC, 1 AS, and 98 SC), 64 stage III tumors (3 AC, 1 AS, and 60 SC), and 4 stage IV tumors (4 SC). From the FDG-PET, maximal standardized uptake value (SUVmax) was determined. The variation in SUVmax was analyzed for differences based on tumor histology and differentiation. Results: For all patients, the mean SUVmax was 11.62 (range, 2.50-50.39). The mean SUVmax by histology was as follows: SC, 11.91 (range, 2.50-50.39); AS, 8.85 (range, 6.53-11.26); and AC, 8.05 (range, 2.83-13.92). Squamous versus nonsquamous tumors demonstrated a significant difference in SUVmax (P=.0153). SUVmax and tumor volume were not found to be correlated (R2=0.013). The mean SUVmax was 8.58 for well-differentiated, 11.56 for moderately differentiated, and 12.23 for poorly differentiated tumors. The mean SUVmax was significantly different for well-differentiated versus poorly differentiated cervical tumors (P=.0474). Conclusions: Cervical tumor FDG uptake varied by histology and differentiation. SC tumors demonstrated a significantly higher SUVmax compared with nonsquamous cell tumors, and poorly differentiated tumors also had a higher SUVmax. [ABSTRACT FROM AUTHOR]

Aims: The 2023 FIGO staging criteria for endometrial cancer (EC) introduced marked changes from the 2009 version. The full implication of these changes for patient diagnosis and treatment is unknown. We evaluate the differences in staging and prognostication between the two systems, with and without inclusion of molecular classification., Methods and Results: We assigned (1) FIGO 2009, (2) 2023 molecular-agnostic and (3) 2023 molecular-informed stages to 404 fully staged and molecularly classified patients with EC. Disease-specific and progression/relapse-free survival were analysed via the Kaplan-Meier method and compared with log-rank testing; 118 of 252 (47%) FIGO 2009 stage I patients were upstaged based on histopathological findings alone. Stage I/II subgroup survival distribution analysis showed a worse prognosis in FIGO 2023 IIB and IIC patients. In the molecular-informed FIGO 2023 system, three of 15 (20%) POLE-mutated stage I/II cases were downstaged from FIGO 2009 and eight (53%) were downstaged from molecular-agnostic FIGO 2023. Fifty-one of 60 (85%) p53-abnormal tumours were upstaged from the FIGO 2009, whereas 13 of 60 (22%) were upstaged from the 2023 molecular-agnostic stage. Molecular classification improved prognostic stratification for both 2009 and 2023 FIGO systems., Conclusions: Downstaging based on POLE mutation more accurately represents patient outcomes. However, in the absence of known POLE status, applying molecular-agnostic FIGO 2023 criteria for stage I/II disease should be conducted with caution. For aggressive histotypes, additionally reporting FIGO 2009 stage should be considered. Upstaging based on substantial lymphovascular space invasion, aggressive histotype with any myometrial invasion and abnormal p53 improves prognostic discernment. Further subdivisions within stage I/II provide minimal additional prognostic information., (© 2024 John Wiley & Sons Ltd.)

Background and Purpose: Intravoxel-incoherent-motion (IVIM) magnetic-resonance-imaging (MRI) and positron-emission-tomography (PET) have been investigated independently but not voxel-wise to evaluate tumor microenvironment in cervical carcinoma patients. Whether regionally combined information of IVIM and PET offers additional predictive benefit over each modality independently has not been explored. Here, we investigated parametric-response-mapping (PRM) of co-registered PET and IVIM in cervical cancer patients to identify sub-volumes that may predict tumor shrinkage to concurrent-chemoradiation-therapy (CCRT)., Materials and Methods: Twenty cervical cancer patients (age: 63[41-85]) were retrospectively evaluated. Diffusion-weighted-images (DWIs) were acquired on 3.0 T MRIs using a free-breathing single-shot-spin echo-planar-imaging (EPI) sequence. Pre- and on-treatment (∼after four-weeks of CCRT) MRI and pre-treatment FDG-PET/CT were acquired. IVIM model-fitting on the DWIs was performed using a Bayesian-fitting simplified two-compartment model. Three-dimensional rigidly-registered maps of PET/CT standardized-uptake-value (SUV) and IVIM diffusion-coefficient ( D ) and perfusion-fraction ( f ) were generated. Population-means of PET-SUV, IVIM- D and IVIM- f from pre-treatment-scans were calculated and used to generate PRM via a voxel-wise joint-histogram-analysis to classify voxels as high/low metabolic-activity and with high/low (hi/lo) cellular-density. Similar PRM maps were generated for SUV and f ., Results: Tumor-volume (p < 0.001) significantly decreased, while IVIM- f (p = 0.002) and IVIM- D (p = 0.03) significantly increased on-treatment. Pre-treatment tumor-volume (r = -0.45,p = 0.04) and PRM-SUV hi D lo (r = -0.65,p = 0.002) negatively correlated with ΔGTV, while pre-treatment IVIM- D (r = 0.64,p = 0.002), PRM-SUV lo f hi (r = 0.52,p = 0.02), and PRM-SUV lo D hi (r = 0.74,p < 0.001) positively correlated with ΔGTV., Conclusion: IVIM and PET was performed on cervical cancer patients undergoing CCRT and we observed that both IVIM- f and IVIM- D increased during treatment. Additionally, PRM was applied, and sub-volumes were identified that were related to ΔGTV., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: The aim of this work was to report the effect of mismatch repair (MMR) status on outcomes of patients with stage I-II endometrioid endometrial adenocarcinoma (EEC) who receive adjuvant radiation therapy., Methods and Materials: This is a multi-institutional retrospective cohort study across 11 institutions in North America. Patients with known MMR status and stage I-II EEC status postsurgical staging were included. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated via the Kaplan-Meier method. Univariable and multivariable analyses were performed via Cox proportional hazard models for RFS and OS. Statistical analyses were conducted using SPSS version 27., Results: In total, 744 patients with a median age at diagnosis of 65 years (IQR, 58-71) were included. Most patients were White (69.4%) and had Federation of Obstetrics and Gynecology 2009 stage I (84%) and Federation of Obstetrics and Gynecology grade 1 to 2 (73%). MMR deficiency was reported in 234 patients (31.5%), whereas 510 patients (68.5%) had preserved MMR. External beam radiation therapy with or without vaginal brachytherapy was delivered to 186 patients (25%), whereas 558 patients (75%) received vaginal brachytherapy alone. At a median follow-up of 43.5 months, the estimated crude OS and RFS rates for the entire cohort were 92.5% and 84%, respectively. MMR status was significantly correlated with RFS. RFS was inferior for MMR deficiency compared with preserved MMR (74.3% vs 88.6%, P < .001). However, no difference in OS was seen (90.8% vs 93.2%, P = .5). On multivariable analysis, MMR deficiency status was associated with worse RFS (hazard ratio, 1.86; P = .001) but not OS., Conclusions: MMR status was independently associated with RFS but not OS in patients with early-stage EEC who were treated with adjuvant radiation therapy. These findings suggest that differential approaches to surveillance and/or treatment based on MMR status could be warranted., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Interstitial gynecologic brachytherapy necessitates precise needle placement, requiring time and expertise. We aimed to simplify interstitial procedures and facilitate optimal needle distribution with individualized vaginal templates to guide interstitial needles., Materials/methods: We developed the 3D-printed vaginal individualized applicator (VIA), a cylindrical template containing individualized internal channels that guide interstitial needles to cover the tumor extent. Eight patients underwent VIA only interstitial implants (VIA only), and five intact cervical cases were treated using tandem and customized VIA (VIA + T). Procedure length, number of needles utilized and dosimetric measures were evaluated., Results: VIA was successfully designed and used clinically for 24 procedures (8 VIA only, 16 VIA + T). Average procedure needle insertion time reduced from 80.9 min for traditional interstitial to 42.9 min for VIA only, approximately 47% shorter with a similar mean high risk CTV volume (28.3 cc VIA only vs. 32.4 cc) and excellent dosimetry with average CTV V100% (94.3% and 94.4%). VIA + T was particularly useful in patients with small vaginal canals and large tumor size. For the five VIA + T patients average tumor size was 68.0cc (range 26.6-143.5 cc). VIA + T procedures were approximately 20% shorter than hybrid procedures with other applicators with mean length of 20.1 min and an average of 6.8 needles (range 3-12)., Conclusion: Our novel 3D-printed VIA facilitates gynecologic interstitial brachytherapy by simplifying needle placement, reducing procedure time, and maintaining excellent dosimetry. VIA can be customized for various clinical scenarios, particularly beneficial for large tumors or small vaginal canals., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Historical gynecologic interstitial brachytherapy templates block direct tumor visualization during needle placement, presenting an opportunity for clinical innovation to develop a novel interstitial template allowing direct tumor visualization during needle insertion., Methods and Materials: We designed and implemented a novel interstitial template, simple needle attachment post placement interstitial template (SNAPP-IT), that allowed direct visualization of the target vaginal tumor during interstitial needle placement while maintaining the ability to individually secure needles to the template, allow a vaginal cylinder, suture holes for securing to the perineum, MRI compatibility and sterilizable for repeat use. Procedure outcomes including procedure time, needle path lengths, and plan dosimetry were prospectively captured in a patient database., Results: Forty gynecologic interstitial brachytherapy cases were recorded (20 SNAPP-IT, 20 traditional templates). Needle insertion depth was reduced using the SNAPP-IT in comparison with traditional interstitial templates (11.8 cm vs. 3.6 cm, p < 0.0001). The average CTV volume was 25.6 cc for SNAPP-IT and 20.7 cc for traditional; both methods averaged a similar number of needles (15.8, 15.6). Dosimetric constraints were similarly met in both treatment groups. Procedures performed using the SNAPP-IT were shorter compared with those performed with traditional interstitial devices (83.4 minutes vs. 100.7 minutes) and there were no post-operative infections in the SNAPP-IT group., Conclusions: Implementation of a novel gynecologic interstitial brachytherapy template (SNAPP-IT) reduced procedure times, allowed direct tumor visualization, and decreased needle insertion depth. SNAPP-IT provides a useful alternative approach for vaginal interstitial brachytherapy, may increase brachytherapist efficiency with complex procedures and potentially expands access to interstitial brachytherapy., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: We developed a 3-dimensionally (3D) printed tandem anchored radially guiding interstitial template (TARGIT) to increase the simplicity of intracavitary/interstitial technique for tandem-and-ovoid (T&O) procedures in cervical cancer brachytherapy. This study compared dosimetry and procedure logistics between T&O implants using the original TARGIT versus the next-generation TARGIT-Flexible-eXtended (TARGIT-FX) 3D-printed template designed for practice-changing ease-of-use with further simplified needle insertion and increased flexibility in needle placement., Methods and Materials: This single-institution retrospective cohort study included patients undergoing T&O brachytherapy as part of definitive cervical cancer treatment. Procedures used the original TARGIT from November 2019 through February 2022 and the TARGIT-FX from March 2022 through November 2022. The FX design features full extension to the vaginal introitus with 9 needle channels and allows for needle additions or depth adjustments intraprocedure and after computed tomography/magnetic resonance imaging., Results: A total of 148 implants were performed, 68 (46%) with TARGIT and 80 (54%) with TARGIT-FX, across 41 patients. Across implants, the TARGIT-FX achieved higher mean V100% (+2.8%, P = .0019), and across patients, the TARGIT-FX achieved higher D90 (+2.0 Gy, P = .037) and higher D98 (+2.7 Gy, P = .016) compared with the original TARGIT. Doses to organs at risk were overall similar between templates. Procedure times for TARGIT-FX implants were 30% shorter on average than for those using the original TARGIT (P < .0001), and 28% shorter on average for the subset of implants with high-risk clinical target volume ≥30 cc (P = .013). All residents (100%, N = 6) surveyed regarding the TARGIT-FX indicated ease-of-use for needle insertion and interest in applying the technique in future practice., Conclusions: The TARGIT-FX achieved shorter procedure times with increased tumor coverage and similar normal tissue sparing compared with the previously applied TARGIT and illustrates the potential of 3D printing to enhance efficiency and shorten the learning curve for intracavitary/interstitial procedure technique in cervical cancer brachytherapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The objective of this work was to evaluate dosimetric characteristics to organs at risk (OARs) from short-course adjuvant vaginal cuff brachytherapy (VCB) in early endometrial cancer compared with standard of care (SOC) in a multi-institutional prospective randomized trial., Methods and Materials: SAVE (Short Course Adjuvant Vaginal Brachytherapy in Early Endometrial Cancer Compared to Standard of Care) is a prospective, phase 3, multisite randomized trial in which 108 patients requiring VCB were randomized to an experimental short-course arm (11 Gy × 2 fractions [fx] to surface) and SOC arm. Those randomized to the SOC arm were subdivided into treatment groups based on treating physician discretion as follows: 7 Gy × 3 fx to 5 mm, 5 to 5.5 Gy × 4 fx to 5 mm, and 6 Gy × 5 fx to surface. To evaluate doses to OARs of each SAVE cohort, the rectum, bladder, sigmoid, small bowel, and urethra were contoured on planning computed tomography, and doses to OARs were compared by treatment arm. Absolute doses for each OAR and from each fractionation scheme were converted to 2 Gy equivalent dose (EQD2 3 ). Each SOC arm was compared with the experimental arm separately using 1-way analysis of variance, followed by pairwise comparisons using Tukey's honestly significant difference test., Results: The experimental arm had significantly lower doses for rectum, bladder, sigmoid, and urethra compared with the 7 Gy × 3 and 5 to 5.5 Gy × 4 fractionation schemes; however, the experimental arm did not differ from the 6 Gy × 5 fractionation scheme. For small bowel doses, none of the SOC fractionation schemes were statistically different than the experimental. The highest EQD2 3 doses to the examined OARs were observed to come from the most common dose fractionation scheme of 7 Gy × 3 fx. With a short median follow-up of 1 year, there have been no isolated vaginal recurrences., Conclusions: Experimental short-course VCB of 11 Gy × 2 fx to the surface provides a comparable biologically effective dose to SOC courses. Experimental short-course VCB was found to reduce or be comparable to D2cc and D0.1cc EQD2 3 doses to rectum, bladder, sigmoid, small bowel, and urethra critical structures. This may translate into a comparable or lower rate of acute and late adverse effects., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Emerging data suggests that abnormal (nuclear) β-catenin expression in some settings is associated with poorer outcomes. Our study aimed to verify the significance of abnormal β-catenin expression in early-stage endometrial cancer patients and determine if adjuvant radiation therapy (RT) improves local control., Methods: We identified 213 patients with FIGO 2018 stage I-II endometrioid endometrial cancer who underwent surgery from 2009 to 2021 with β-catenin expression assessed. Vaginal, regional, and distant recurrences were analyzed using competing risk methods, and overall survival was analyzed using Kaplan-Meier., Results: Median follow up was 53.2 months; 6.9% experienced vaginal, 8.2% regional, and 7.4% distant recurrence. For the entire cohort, abnormal β-catenin expression was significantly associated with vaginal recurrence and remained significant on multivariate analysis (p = 0.03). There were 114 patients in the no specific molecular profile (NSMP) subgroup, and abnormal β-catenin expression was present in 46.5%. In the NSMP subgroup, abnormal β-catenin expression was associated with increased rates of vaginal recurrence (p = 0.06). Abnormal β-catenin expression in the NSMP subgroup was significant on multivariate analysis for vaginal recurrence (p = 0.04). RT significantly decreased vaginal recurrences in the entire cohort in patients with abnormal β-catenin expression (0%) versus wild type expression (17.5%; p = 0.03). In the NSMP subgroup 0% of patients who received RT versus 20.9% of patients who did not receive RT experienced a vaginal recurrence (p = 0.03)., Conclusion: Use of adjuvant RT for stage I-II NSMP endometrial cancer with abnormal β-catenin expression improved local control. RT should be considered in these patients to decrease risk of vaginal recurrences., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To report the impact of race on clinical outcomes in patients with stage IIIC endometrial carcinoma., Materials and Methods: A retrospective multi-institutional study included 90 black and 568 non-black patients with stage IIIC endometrial carcinoma who received adjuvant chemotherapy and radiation treatments. Overall survival (OS) and recurrence-free survival (RFS) were calculated by the Kaplan-Meier method. Propensity score matching (PSM) was conducted. Statistical analyses were conducted using SPSS version 27., Results: The Median follow-up was 45.3 months. black patients were significantly older, had more nonendometrioid histology, grade 3 tumors, and were more likely to have >1 positive paraaortic lymph nodes compared with non-black patients (all P <0.0001). The 5-year estimated OS and RFS rates were 45% and 47% compared with 77% and 68% for black patients versus non-black patients, respectively ( P <0.001). After PSM, the 2 groups were well-balanced for all prognostic covariates. The estimated hazard ratios of black versus non-black patients were 1.613 ( P value=0.045) for OS and 1.487 ( P value=0.116) for RFS. After PSM, black patients were more likely to receive the "Sandwich" approach and concurrent chemoradiotherapy compared with non-black ( P =0.013) patients., Conclusions: Black patients have higher rates of nonendometrioid histology, grade 3 tumors, and number of involved paraaortic lymph nodes, worse OS, and RFS, and were more likely to receive the "Sandwich" approach compared with non-black patients. After PSM, black patients had worse OS with a nonsignificant trend in RFS. Access to care, equitable inclusion on randomized trials, and identification of genomic differences are warranted to help mitigate disparities., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Uterine clear cell and serous carcinomas have a high propensity for locoregional and distant spread, tend to be more advanced at presentation, and carry a higher risk of recurrence and death than endometrioid cancers. Limited prospective data exist to guide evidence-based management of these rare malignancies., Objective: The American Radium Society sought to summarize evidence-based guidelines developed by a multidisciplinary expert panel that help to guide the management of uterine clear cell and serous carcinomas., Methods: The American Radium Society Appropriate Use Criteria presented in this manuscript were developed by a multidisciplinary expert panel using an extensive analysis of current published literature from peer-reviewed journals. A well-established methodology (modified Delphi) was used to rate the appropriate use of diagnostic and therapeutic procedures for the management of uterine clear cell and serous carcinomas., Results: The primary treatment for non-metastatic uterine clear cell and serous carcinomas is complete surgical staging, with total hysterectomy, salpingo-oophorectomy, omentectomy, and lymph node staging. Even in early-stage disease, patients with uterine clear cell and serous carcinomas have a worse prognosis than those with type I endometrial cancers, warranting consideration for adjuvant therapy regardless of the stage. Given the aggressive nature of these malignancies, and until further research determines the most appropriate adjuvant therapy, it may be reasonable to counsel patients about combined-modality treatment with systemic chemotherapy and radiotherapy., Conclusion: Patients diagnosed with uterine clear cell and serous carcinomas should undergo complete surgical staging. Multimodal adjuvant therapies should be considered in the treatment of both early-stage and advanced-stage disease. Further prospective studies or multi-institutional retrospective studies are warranted to determine optimal sequencing of therapy and appropriate management of patients based on their unique risk factors. Long-term surveillance is indicated due to the high risk of locoregional and distant recurrence., Competing Interests: Competing interests: All panelists were required to declare all conflicts of interest for the previous 36 months prior to initiating work on this document. These complete disclosure forms are retained by the American Radium Society (ARS) in perpetuity. The ARS Appropriate Use Criteria Steering Committee reviewed these disclosures with the chair and co-chair of this document and approved participation of the panelists prior to starting development of this work. Disclosures potentially relevant to the content of this guideline are provided. List of any potentially relevant conflicts of interest for the past 3 years for guideline chair, guideline co-chair, all voting and non-voting panelists: MB: consulting fee/honoraria (Elekta, Inc.). DG: consulting fee/honoraria (AstraZeneca, Merck). RLC: grants for clinical trials (NIH, Gateway Foundation, V-Foundation, Judy Rees/Albert Pisani MD Ovarian Cancer Research Fund, AstraZeneca, Merck, Clovis, Genmab, Roche/Genentech, Janssen); consulting fee/honoraria (AstraZeneca, Tesaro, Medivation, Clovis, Gamamab, Genmab, Roche/Genentech, Janssen, Agenus, Regeneron, OncoQuest). MH: consulting fee/Honoraria (Varian Brachytherapy; AstraZeneca). SJ: consulting fee/honoraria (AstraZeneca, Varian). WS, Jr: consulting fee/honoraria (Merck, Carl Zeiss, Varian)., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: In cervical cancer brachytherapy, adding interstitial needles to intracavitary applicators can enhance dosimetry by improving target coverage while limiting normal tissue dose. However, its use is limited to a subset of practitioners with appropriate technical skill. We designed tandem anchored radially guiding interstitial templates (TARGITs) with a 3-dimensional (3D) printing workflow to optimize needle placement and facilitate greater ease-of-use of intracavitary/interstitial (IC/IS) technique. This study compared dosimetry and procedure characteristics between tandem and ovoid (T&O) implants using TARGIT technique versus non-TARGIT technique., Methods and Materials: This single-institution retrospective cohort study included patients undergoing T&O brachytherapy as part of definitive radiation treatment for cervical cancer between February 2017 and January 2021. TARGIT technique was implemented from November 2019 onwards; all prior procedures involved non-TARGIT technique using a no needle or freehand needle approach. Target coverage, dose to organs at risk, and procedure times were evaluated and compared between TARGIT technique and non-TARGIT technique., Results: The cohort included 70 patients with cervical cancer who underwent 302 T&O procedures: 68 (23%) with TARGIT technique and 234 (77%) with non-TARGIT technique, which included 133 no needle and 101 freehand needle implants. TARGIT implants involved longer average procedure times (+6.3 minutes, P < .0001). TARGIT implants achieved a higher mean high-risk clinical target volume V100% than non-TARGIT implants (+4.4%, P = .001), including for large tumors 30 cm 3 or greater (+8.1%, P = .002). Average D90 was 4.6 Gy higher and average D98 was 3.2 Gy higher for TARGIT technique compared with non-TARGIT technique (P = .006 and P = .02). Total treatment doses to rectum, bowel, and bladder were not significantly different for TARGIT versus non-TARGIT technique., Conclusions: The 3D-printed TARGIT approach to T&O brachytherapy achieved greater tumor coverage while sparing normal tissues, particularly for large tumor volumes, with only a slight increase in average procedure time. TARGIT represents a creative technological solution for increasing accessibility of advanced IC/IS brachytherapy technique for cervical cancer definitive radiation treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The comprehensive genomic analysis of endometrial carcinoma (EC) by The Cancer Genome Atlas (TCGA) led to the discovery of four distinct and prognostically significant molecular subgroups. Molecular classification has the potential to improve risk-stratification when integrated with clinicopathologic features and has recently been included in national and international patient management EC guidelines. Thus, the adoption of molecular classification into routine pathologic and clinical practice is likely to grow significantly in the upcoming years. Establishing an efficient and standardized workflow for performing molecular classification on ECs, and reporting both the molecular and histologic findings in an integrative manner, is imperative. Here we describe our effort to implement rapid and routine molecular classification on all ECs diagnosed at our institution. To this effect, we performed immunohistochemistry as a surrogate marker for identifying genetic and/or epigenetic alterations in DNA mismatch repair (e.g., MLH1, PMS2, MSH6, MSH2), and TP53 genes. In addition, we have developed and employed a single-gene POLE SNaPshot assay, which is a rapid and analytically sensitive method for detecting select POLE exonuclease domain mutations (EDMs). We report our molecular testing workflow and integrative reporting system as well as the clinicopathologic and molecular features of 310 ECs that underwent routine molecular classification at our institution. The 310 ECs were molecularly classified as follows: 15 (5%) POLE mutant (POLEmut), 79 (25%) mismatch repair-deficient (MMRd), 135 (44%) no specific molecular profile (NSMP), and 81 (26%) p53 abnormal (p53abnl). This work provides an initial framework for implementing routine molecular classification of ECs., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Gynecological cancers have particularly benefited from the increasing use of imaging to guide radiation treatment planning for both external beam radiation and brachytherapy. While the different gynecological cancers have varying use of imaging, certain trends predominate. CT represents an economical choice for evaluating initial disease extent or potential metastasis at follow-up, particularly for endometrial and ovarian cancers. F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is particularly useful for assessing the initial disease extent and longer term treatment response of squamous predominant cancers, including cervical, vaginal, and vulvar cancers. With its excellent pelvic soft tissue discrimination, MRI provides the greatest assistance in evaluating the local extent of gynecological tumors, including initial evaluation for non-operative endometrial and vulvar cancer, and assessment before, after and during brachytherapy for cervix, locally recurrent endometrial, and primary vaginal cancers. With more limited availability of MRI, ultrasound can also help guide brachytherapy, particularly during procedures. The benefits of using imaging to better spare bone marrow or earlier assessment of treatment response are topics still being explored, in particular for cervical cancer. As imaging along with radiation oncology technologies continue to evolve and develop, such as with MRI-linacs and ultra high dose rate (FLASH) radiation, we may continue to see increasing use of imaging for advancing gynecological radiation oncology., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the impact of prophylactic paraortic lymph node (PALN) radiation therapy (RT) on clinical outcomes in patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 endometrial cancer (EC)., Methods and Materials: A multi-institutional retrospective study included patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 EC lymph node assessment, status postsurgical staging, followed by adjuvant chemotherapy and RT using various sequencing regimens. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariable and multivariable analysis were performed by Cox proportional hazard models for RFS/OS. In addition, propensity score matching was used to estimate the effect of the radiation field extent on survival outcomes., Results: A total of 378 patients were included, with a median follow-up of 45.8 months. Pelvic RT was delivered to 286 patients, and 92 patients received pelvic and PALN RT. The estimated OS and RFS rates at 5 years for the entire cohort were 80% and 69%, respectively. There was no difference in the 5-year OS (77% vs 87%, P = .47) and RFS rates (67% vs 70%, P = .78) between patients treated with pelvic RT and those treated with pelvic and prophylactic PALN RT, respectively. After propensity score matching, the estimated hazard ratios (HRs) of prophylactic PALN RT versus pelvic RT were 1.50 (95% confidence interval, 0.71-3.19; P = .28) for OS and 1.24 (95% confidence interval, 0.64-2.42; P = .51) for RFS, suggesting that prophylactic PALN RT does not improve survival outcomes. Distant recurrence was the most common site of first recurrence, and the extent of RT field was not associated with the site of first recurrence (P = .79)., Conclusions: Prophylactic PALN RT was not significantly associated with improved survival outcomes in stage IIIC1 EC. Distant metastasis remains the most common site of failure despite routine use of systemic chemotherapy. New therapeutic approaches are necessary to optimize the outcomes for women with stage IIIC1 EC., (Copyright © 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Treatment of advanced ovarian cancer using PD-1/PD-L1 immune checkpoint blockade shows promise; however, current clinical trials are limited by modest response rates. Radiotherapy has been shown to synergize with PD-1/PD-L1 blockade in some cancers but has not been utilized in advanced ovarian cancer due to toxicity associated with conventional abdominopelvic irradiation. Ultrahigh-dose rate (FLASH) irradiation has emerged as a strategy to reduce radiation-induced toxicity, however, the immunomodulatory properties of FLASH irradiation remain unknown. Here, we demonstrate that single high-dose abdominopelvic FLASH irradiation promoted intestinal regeneration and maintained tumor control in a preclinical mouse model of ovarian cancer. Reduced tumor burden in conventional and FLASH-treated mice was associated with an early decrease in intratumoral regulatory T cells and a late increase in cytolytic CD8 + T cells. Compared with conventional irradiation, FLASH irradiation increased intratumoral T-cell infiltration at early timepoints. Moreover, FLASH irradiation maintained the ability to increase intratumoral CD8 + T-cell infiltration and enhance the efficacy of αPD-1 therapy in preclinical models of ovarian cancer. These data highlight the potential for FLASH irradiation to improve the therapeutic efficacy of checkpoint inhibition in the treatment of ovarian cancer., (©2021 American Association for Cancer Research.)

Background: To evaluate whether the use of the internal target volume (ITV) delineation method improves the performance of intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in terms of survival, acute toxicities, and dose-volume parameters., Methods: A total number of 477 cervical cancer patients who received concurrent chemoradiotherapy (CCRT) from January 2012 to December 2016 were retrospectively analyzed. They were divided into four groups: the non-ITV (N-ITV) + IMRT, ITV + IMRT, N-ITV + 3DCRT, and ITV + 3DCRT groups, with 76, 41, 327, and 33 patients, respectively. Survival analysis was performed with the Kaplan-Meier and the log-rank tests, and acute toxicity analysis was performed with the chi-squared test and the binary logistic regression test. Using the propensity score matching (PSM) method, 92 patients were matched among the four groups, and their dose-volume parameters were assessed with the Kruskal-Wallis method., Results: The median follow-up time was 49 months (1-119) for overall survival (OS). The 5-year OS rate was 66.4%. The ITV delineation method was an independent prognostic factor for OS (HR [95% CI]: 0.52 [0.27, 0.98], p = 0.044) and progression-free survival (PFS) (HR [95% CI]: 0.59 [0.36, 0.99], p = 0.045). The ITV + IMRT group had the lowest incidence rate (22%) and the N-ITV + IMRT group had the highest incidence rate of grade ≥3 hematological toxicity (HT) (46.1%) among the four groups. The pelvic bone marrow relative V10, V20, and V30 in the N-ITV + IMRT group was higher than those in the ITV + IMRT and N-ITV + 3DCRT groups (p < 0.05)., Conclusions: The use of ITV for IMRT treatment planning was associated with improved overall survival and progression-free survival, with lower HT rate., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes., Methods and Materials: In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method., Results: A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P < .05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P < .0001., Conclusions: The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To determine which patients with stage III endometrial cancer receiving adjuvant chemotherapy derive benefit from the addition of vaginal brachytherapy, as stage III is a highly heterogeneous population with substantial variations in practice., Methods: Patients with FIGO stage III endometrial carcinoma diagnosed 2004-2016 who underwent at least total hysterectomy and adjuvant multiagent chemotherapy were identified in the National Cancer Database. The primary outcome was overall survival according to receipt of brachytherapy, stratified by histologic type, pathological features, and status of pelvic external beam radiotherapy (EBRT), and analyzed using the Kaplan-Meier method and Cox multivariable regression., Results: In total, 9369 patients were identified (24% stage IIIA, 5% stage IIIB, 71% stage IIIC; 61% endometrioid, 39% nonendometrioid histology), and 28% received brachytherapy. In the endometrioid cohort, brachytherapy was associated with a 5% absolute increase in 3-year overall survival (87% vs. 82%, p < 0.0001), which persisted in multivariable analysis (adjusted hazard ratio 0.74, 95% confidence interval 0.64-0.84, p < 0.0001). The benefit of brachytherapy was greater in patients not also receiving EBRT, and in patients with vaginal/parametrial extension, grade 3 disease, lymphovascular invasion, and/or deep myometrial invasion. In the nonendometrioid cohort, brachytherapy was associated with a significant survival benefit in univariable but not multivariable analysis, regardless of EBRT status or pathological features., Conclusions: Factors predictive of brachytherapy benefit were endometrioid histology and pathological risk factors for local recurrence. Additionally, brachytherapy appeared more beneficial in patients not already receiving pelvic EBRT. Further research is warranted to determine which stage III patients may be best served by brachytherapy, EBRT, or both., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Urinary catheterisation is a common procedure, with approximately 15% to 25% of all people admitted to hospital receiving short-term (14 days or less) indwelling urethral catheterisation at some point during their care. However, the use of urinary catheters is associated with an increased risk of developing urinary tract infection. Catheter-associated urinary tract infection (CAUTI) is one of the most common hospital-acquired infections. It is estimated that around 20% of hospital-acquired bacteraemias arise from the urinary tract and are associated with mortality of around 10%. This is an update of a Cochrane Review first published in 2005 and last published in 2007., Objectives: To assess the effects of strategies for removing short-term (14 days or less) indwelling catheters in adults., Search Methods: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from CENTRAL, MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP, and handsearching of journals and conference proceedings (searched 17 March 2020), and reference lists of relevant articles., Selection Criteria: We included all randomised controlled trials (RCTs) and quasi-RCTs that evaluated the effectiveness of practices undertaken for the removal of short-term indwelling urethral catheters in adults for any reason in any setting., Data Collection and Analysis: Two review authors performed abstract and full-text screening of all relevant articles. At least two review authors independently performed risk of bias assessment, data abstraction and GRADE assessment., Main Results: We included 99 trials involving 12,241 participants. We judged the majority of trials to be at low or unclear risk of selection and detection bias, with a high risk of performance bias. We also deemed most trials to be at low risk of attrition and reporting bias. None of the trials reported on quality of life. The majority of participants across the trials had undergone some form of surgical procedure. Thirteen trials involving 1506 participants compared the removal of short-term indwelling urethral catheters at one time of day (early morning removal group between 6 am to 7 am) versus another (late night removal group between 10 pm to midnight). Catheter removal late at night may slightly reduce the risk of requiring recatheterisation compared with early morning (RR 0.71, 95% CI 0.53 to 0.96; 10 RCTs, 1920 participants; low-certainty evidence). We are uncertain if there is any difference between early morning and late night removal in the risk of developing symptomatic CAUTI (RR 1.00, 95% CI 0.61 to 1.63; 1 RCT, 41 participants; very low-certainty evidence). We are uncertain whether the time of day makes a difference to the risk of dysuria (RR 2.20; 95% CI 0.70 to 6.86; 1 RCT, 170 participants; low-certainty evidence). Sixty-eight trials involving 9247 participants compared shorter versus longer durations of catheterisation. Shorter durations may increase the risk of requiring recatheterisation compared with longer durations (RR 1.81, 95% CI 1.35 to 2.41; 44 trials, 5870 participants; low-certainty evidence), but probably reduce the risk of symptomatic CAUTI (RR 0.52, 95% CI 0.45 to 0.61; 41 RCTs, 5759 participants; moderate-certainty evidence) and may reduce the risk of dysuria (RR 0.42, 95% CI 0.20 to 0.88; 7 RCTs; 1398 participants; low-certainty evidence). Seven trials involving 714 participants compared policies of clamping catheters versus free drainage. There may be little to no difference between clamping and free drainage in terms of the risk of requiring recatheterisation (RR 0.82, 95% CI 0.55 to 1.21; 5 RCTs; 569 participants; low-certainty evidence). We are uncertain if there is any difference in the risk of symptomatic CAUTI (RR 0.99, 95% CI 0.60 to 1.63; 2 RCTs, 267 participants; very low-certainty evidence) or dysuria (RR 0.84, 95% CI 0.46 to 1.54; 1 trial, 79 participants; very low-certainty evidence). Three trials involving 402 participants compared the use of prophylactic alpha blockers versus no intervention or placebo. We are uncertain if prophylactic alpha blockers before catheter removal has any effect on the risk of requiring recatheterisation (RR 1.18, 95% CI 0.58 to 2.42; 2 RCTs, 184 participants; very low-certainty evidence) or risk of symptomatic CAUTI (RR 0.20, 95% CI 0.01 to 4.06; 1 trial, 94 participants; very low-certainty evidence). None of the included trials investigating prophylactic alpha blockers reported the number of participants with dysuria., Authors' Conclusions: There is some evidence to suggest the removal of indwelling urethral catheters late at night rather than early in the morning may reduce the number of people who require recatheterisation. It appears that catheter removal after shorter compared to longer durations probably reduces the risk of symptomatic CAUTI and may reduce the risk of dysuria. However, it may lead to more people requiring recatheterisation. The other evidence relating to the risk of symptomatic CAUTI and dysuria is too uncertain to allow us to draw any conclusions. Due to the low certainty of the majority of the evidence presented here, the results of further research are likely to change our findings and to have a further impact on clinical practice. This systematic review has highlighted the need for a standardised set of core outcomes, which should be measured and reported by all future trials comparing strategies for the removal of short-term urinary catheters. Future trials should also study the effects of short-term indwelling urethral catheter removal on non-surgical patients., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Gynecologic cancers are often asymmetric, yet current Ir-192 brachytherapy techniques provide only limited radial modulation of the dose. The shielded solutions investigated here solve this by providing the ability to modulate between highly asymmetric and radially symmetric dose distributions at a given location. To find applicator designs that can modulate between full dose and less than 50% dose, at the dimensions of the urethra, a 2D calculation algorithm was developed to narrow down the search space. Two shielding design types were then further investigated using Monte Carlo and Boltzmann-solver dose calculation algorithms. 3D printing techniques using ISO 10993 certified biocompatible plastics and 3D printable tungsten-loaded plastics were tested. It was also found that shadowing effects set by the shape of the shielding cannot be easily modulated out, hence careful design is required. The shielded applicator designs investigated here, allow for reduction of the dose by over 50% at 5 mm from the applicator surface in desired regions, while also allowing radially symmetric dose with isodose line deviations less than 0.5 mm from circular. The shielding designs were also chosen with treatment delivery time in mind. Treatment times for these shielded designs were found to be less than 1.4 times longer than a 6-channel unshielded cylinder for the equivalent fully symmetric dose distribution. The 2D calculation methods developed here provide a simple way to rapidly evaluate shielding designs, while the 3D printing techniques also allow for devices with novel shapes to be rapidly prototyped. Both TOPAS Monte Carlo and Acuros BV calculations show that significant dose shaping and organ at risk sparing can be achieved without significantly compromising the plan in regions that require the full dose.

Purpose: To identify subvolumes that may predict treatment response to definitive concurrent chemoradiation therapy using parametric response mapping (PRM) of coregistered positron emission tomography (PET) and dynamic contrast-enhanced (DCE) computed tomography (CT) in locally advanced cervical carcinoma., Methods and Materials: Pre- and midtreatment (after 23 ± 4 days of concurrent chemoradiation therapy) DCE CT and PET imaging were performed on 21 patients with cervical cancer who were enrolled in a pilot study to evaluate the prognostic value of CT perfusion for primary cervical cancer (NCT01805141). Three-dimensional coregistered maps of PET/CT standardized uptake value (SUV) and DCE CT blood flow (BF) were generated. PRM was performed using voxel-wise joint histogram analysis to classify voxels within the tumor as highly metabolic and perfused (SUV hi BF hi ), highly metabolic and hypoxic (SUV hi BF lo ), low metabolic activity and hypoxic (SUV lo BF lo ), or low metabolic activity and perfused (SUV lo BF hi ) tissue based on thresholds determined from population means of pretreatment PET SUV and DCE CT BF. Relationships between baseline pretreatment imaging metrics and relative changes in metabolic tumor volume (ΔMTV), calculated from before treatment and during treatment imaging, were determined using univariable and multivariable linear regression models., Results: The relative volume of three PRM subvolumes significantly changed during treatment (SUV hi BF hi : P = .04; SUV hi BF lo : P = .0008; SUV lo BF hi : P = .02), whereas SUV lo BF lo did not (P = .9). Pretreatment PET SUV max (r = -.58, P = .006), PET SUV mean (ρ = -.59, P = .005), DCE CT BF mean (r = -.50, P = .02), tumor volume (ρ = -.65, P = .001) and PRM SUV hi BF hi (ρ = -.59, P = .004) were negatively correlated with ΔMTV, whereas PRM SUV lo BF lo was positively related to ΔMTV (r = .77, P < .0001). In a multivariable model that predicted ΔMTV, PRM SUV lo BF lo , which combines both PET/CT and DCE CT, was the only significant variable (β = 1.825, P = .03), dominating both imaging modalities independently., Conclusions: PRM was applied in locally advanced cervical carcinoma treated definitively with chemoradiation, and radioresistant subvolumes were identified that correlated with changes in MTV and predicted treatment response. Identification of these subvolumes may assist in clinical decision making to tailor therapies, such as brachytherapy, in an effort to improve patient outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To better delineate optimal management of high-risk, early-stage endometrial cancer, as national guidelines permit substantial practice variations., Methods: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB grade 3 and stage II endometrioid carcinoma who underwent at least total hysterectomy were identified in SEER-Medicare. Adjuvant treatments were brachytherapy (BT), external beam radiation therapy (EBRT), and chemotherapy. Death from endometrial cancer (cancer-specific mortality [CSM]) and local recurrence were analyzed using Gray's test and Fine-Gray regression., Results: In total, 1,095 patients were identified: 52% received BT, 56% received EBRT, 16% received chemotherapy, and 29% received no adjuvant treatment. Survival outcomes were significantly worse for stage IB grade 3 and stage II grade 3 relative to stage II grades 1-2 (5-year CSM: 18% and 23% vs. 10%; p<0.001 and p=0.003, respectively), while there was no difference between stage IB grade 3 and stage II grade 3 (p=0.618). BT had a local control benefit across all patients (p<0.001) that translated into a survival benefit in stage IB grade 3 (adjusted hazard ratio [HR] for CSM=0.47, p=0.003). EBRT had a survival benefit in stage II grade 3 (adjusted HR for CSM=0.36; p=0.031), as did lymph node dissection (p=0.015). Chemotherapy was not significantly correlated with CSM., Conclusions: High-risk, early-stage endometrioid carcinoma is a heterogeneous population. BT was associated with a survival benefit in stage IB grade 3, whereas regional treatment with EBRT and lymphadenectomy was associated with a survival benefit in stage II grade 3., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Purpose: Recognizing the prognostic significance of lymph node (LN) involvement for cervical cancer, we aimed to identify genes that are differentially expressed in LN+ versus LN- cervical cancer and to potentially create a validated predictive gene signature for LN involvement., Materials and Methods: Primary tumor biopsies were collected from 74 cervical cancer patients. RNA was extracted and RNA sequencing was performed. The samples were divided by institution into a training set ( n = 57) and a testing set ( n = 17). Differentially expressed genes were identified among the training cohort and used to train a Random Forest classifier., Results: 22 genes showed > 1.5 fold difference in expression between the LN+ and LN- groups. Using forward selection 5 genes were identified and, based on the clinical knowledge of these genes and testing of the different combinations, a 2-gene Random Forest model of BIRC3 and CD300LG was developed. The classification accuracy of lymph node (LN) status on the test set was 88.2%, with an Area under the Receiver Operating Characteristic curve (ROC-AUC) of 98.6%., Conclusions: We identified a 2 gene Random Forest model of BIRC3 and CD300LG that predicted lymph node involvement in a validation cohort. This validated model, following testing in additional cohorts, could be used to create a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) tool that would be useful for helping to identify patients with LN involvement in resource-limited settings., Competing Interests: CONFLICTS OF INTEREST None.

Purpose: Brachytherapy requires multiple different steps and plays a critical role in treatment for gynecological cancer. In an effort to improve gynecologic patient experience, we investigated how different aspects of the procedure influence how long the patient has the brachytherapy applicator in place., Methods and Materials: We prospectively recorded 145 consecutive tandem and ovoid treatments for 33 patients and determined how anesthesia vs. conscious sedation, MRI or not, and the number of procedures in the day impact applicator in time. The data were analyzed in a mixed effects linear regression model to account for the within-patient correlation., Results: We found average applicator in place time was 179 minutes (range: 87-311 minutes). Patients who received anesthesia had a significant increase in length of applicator in patient time by an average of 42 minutes compared with those who received conscious sedation. Undergoing an MRI increased length of applicator in time by an average of 66 minutes, although the actual MRI performed generally took less than 30 minutes. Having three or more procedures scheduled for 1 day increased the length of time the tandem and ovoid was inserted by an average of 35 minutes., Conclusion: The use of anesthesia vs. conscious sedation, MRI scans for treatment planning, and number of procedures scheduled per day have significant influence on the duration of brachytherapy treatments. This information can help us work to optimize scheduling and thereby improve patient brachytherapy experience., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

To evaluate the correlation between p16 expression and clinical outcomes in patients with primary vaginal cancer treated with definitive radiotherapy. P16 immunohistochemical was performed on 25 patient samples and recorded from pathology reports in 7 patients. P53 immunohistochemical was performed on 3 p16-negative samples. Baseline characteristics were compared using the Fisher exact test. Outcomes were compared using log-rank tests, and cox proportional hazards models. Survival and recurrence analysis was performed with the Kaplan-Meier method and cumulative incidence estimates. P16 expression was positive in 29 patients and negative in 3 patients. Two of the p16-negative tumors showed positive expression of p53. The median overall survival, progression-free survival and 2-yr cumulative incidence of recurrence were 66 mo [95% confidence interval (CI), 31-96], 34 mo (95% CI, 21-86), and 19% (95% CI, 7%-34%), respectively. P16-positive tumors had higher median overall survival and progression-free survival compared with p16-negative tumors (82 vs. 31 mo, P=0.02 and 35 vs 16 mo, P=0.04, respectively). The 2-yr cumulative incidence of recurrence was 14% for p16-positive tumors compared with 67% for p16-negative tumors (P=0.07). On univariable analysis, p16-negative status, age older than 65, and advanced stage were associated with inferior overall survival. P16 negativity is an independent predictor of inferior overall survival. P16-positive vaginal cancers have a better prognosis and decreased incidence of recurrence compared with p16-negative tumors. These prognostic findings associated with p16-negative vaginal cancers will need to be confirmed in larger patient cohorts.

Objectives: To determine which patients with locoregionally advanced endometrial cancer may benefit from pelvic external beam radiotherapy (EBRT) in addition to chemotherapy compared to chemotherapy alone., Methods: Patients with FIGO stages III-IVA endometrial carcinoma between 2004 and 2016 who underwent at least total hysterectomy and adjuvant multiagent chemotherapy were identified in the National Cancer Database. The primary outcome was overall survival according to receipt of pelvic EBRT, analyzed using the Kaplan-Meier method and Cox multivariable regression., Results: In total, 13,270 patients were identified (62% pure endometrioid, 38% serous/clear cell or mixed histology; 22.6% stage IIIA, 4.7% stage IIIB, 71.2% stage IIIC, 1.5% stage IVA), of whom 40% received pelvic EBRT. In univariable analysis, EBRT was associated with absolute 5-year survival increases of 5% and 9% in the endometrioid and non-endometrioid cohorts, respectively (P < 0.0001). In multivariable analyses stratified by stage and histology, patients with a significant benefit from EBRT were stage IIIC (specifically IIIC2) endometrioid (adjusted hazard ratio [HR] 0.73, P = 0.01) and stages IIIB and IIIC non-endometrioid (adjusted HR 0.52, P = 0.01 and adjusted HR 0.79, P < 0.0001). The benefit of EBRT in node-positive patients persisted in those who underwent more extensive lymphadenectomy., Conclusions: Stages III-IVA endometrial cancer comprised a heterogeneous population with respect to the added benefit of radiotherapy compared to chemotherapy alone. Patients with stage IIIC2 endometrioid and stages IIIB-C non-endometrioid cancer may be most likely to benefit from pelvic EBRT., (Copyright © 2019 Elsevier Inc. All rights reserved.)