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We report an updated analysis of the outcomes and toxicities of MRI-based brachytherapy for locally advanced cervical cancer from a U.S. academic center. A retrospective review was performed on patients treated with MRI-based brachytherapy for cervical cancer. EBRT was standardly 45 Gy in 25 fractions with weekly cisplatin. MRI was performed with the brachytherapy applicator in situ. Dose specification was most commonly 7 Gy for 4 fractions with optimization aim of D90 HR-CTV EQD2 of 85–95 Gy α/β=10 Gy in 2 implants each delivering 2 fractions. Ninety-eight patients were included with median follow up of 24.5 months (IQR 11.9–39.8). Stage IIIA-IVB accounted for 31.6% of cases. Dosimetry results include median GTV D98 of 101.0 Gy (IQR 93.3–118.8) and HR-CTV D90 of 89 Gy (IQR 86.1–90.6). Median D2cc bladder, rectum, sigmoid, and bowel doses were 82.1 Gy (IQR 75.9–88.0), 65.9 Gy (IQR 59.6–71.2), 65.1 Gy (IQR 57.7–69.6), and 55 Gy (IQR 48.9–60.9). Chronic grade 3+ toxicities were seen in the bladder (8.2%), rectosigmoid (4.1%), and vagina (1.0%). Three-year LC, PFS, and OS were estimated to be 84%, 61.7%, and 76.1%, respectively. MRI-based brachytherapy demonstrates excellent local control and acceptable rates of high-grade morbidity. These results are possible in our population with relatively large volume primary tumors and extensive local disease. • Local control, overall survival, and progression-free survival at our institution are similar to larger studies. • Dose planning limits to organs-at-risk were met in a population with a higher proportion of stage IIIA-IVB patients. • Chronic grade 3+ toxicities were seen in 13.3% of patients, mostly in stage IIIB and IVA patients. [ABSTRACT FROM AUTHOR]

Curative-intent radiotherapy for locally advanced and select early stage cervical cancer in the US includes external beam radiotherapy (EBRT) with brachytherapy. Although there are guidelines for brachytherapy dose and fractionation regimens, there are limited data on practice patterns. This study aims to evaluate the contemporary utilization of cervical cancer brachytherapy in the US and its association with patient demographics and facility characteristics. We retrospectively analyzed clinical covariates of cervical cancer patients diagnosed and treated in 2018–2020 with curative-intent radiotherapy from the 2020 National Cancer Database. Associations between patient and institutional factors with the number of brachytherapy fractions were identified with logistic regression. Factors with association (p < 0.10) were then included in a multivariable logistic regression model. All tests were two-sided with significance <0.05 unless specified otherwise. Among the eligible 2517 patients, 97.3% received HDR or LDR and is further analyzed. More patients received HDR than LDR brachytherapy (98.9% vs 1.1%) and intracavitary than interstitial brachytherapy (86.4% vs 13.6%). The most common number of HDR fractions prescribed were 5 (51.0%), 4 (32.9%), and 3 (8.6%). After adjusting for the other variables in the model, ethnicity, private insurance status, overall insurance status, and facility type were the only factors that were significantly associated with the number of brachytherapy factions (p < 0.0001, p = 0.028, p = 0.001, and p < 0.0001, respectively, n = 2184). In the US, various HDR brachytherapy regimens are utilized depending on patient and institutional factors. Future research may optimize cervical cancer brachytherapy by correlating specific dose and fractionation regimens with patient outcomes. • Curative-intent radiotherapy for cervical cancer in the US may include external beam radiotherapy and brachytherapy. • This is the first assessment of physician practice pattern of curative-intent brachytherapy for cervical cancer in the US. • Most patients received HDR intracavitary brachytherapy and completed their radiotherapy as prescribed. • Patient ethnicity, insurance, and facility type are significantly associated with number of HDR brachytherapy fractions. [ABSTRACT FROM AUTHOR]

Uterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterine serous carcinoma. This multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or any mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher's exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free and overall survival. There were 737 patients included. Most patients had Stage IA disease (75%), 49% of which had no myometrial invasion. Only 164 (24%) tumors had lymphatic/vascular space invasion. Adjuvant treatment varied: 22% received no adjuvant therapy, 17% had chemotherapy alone, 19% had cuff brachytherapy, 35% had cuff brachytherapy with chemotherapy, and 6% underwent pelvic radiation. Adjuvant treatment was significantly associated with a decreased risk of recurrence (p = 0.04). Compared with no adjuvant therapy, patients who received brachytherapy or brachytherapy/chemotherapy had improved recurrence-free survival (HR 0.59, 95% CI 0.40–0.86; HR 0.65, 95% CI 0.49–0.88, respectively) and overall survival (HR 0.53, 95% CI 0.35–0.79; HR 0.49, 95% CI 0.35–0.69, respectively). Improved survival with brachytherapy and brachytherapy/chemotherapy persisted on multivariable analyses. Chemotherapy alone was also associated with improved overall survival compared with no adjuvant treatment (HR 0.55, 95% CI 0.37–0.81). Adjuvant therapy was associated with a decreased risk of recurrence relative to observation alone. Adjuvant cuff brachytherapy with and without chemotherapy was associated with improved survival outcomes in patients with early stage uterine serous carcinoma. • Treatment approaches for patients with early stage uterine serous carcinoma vary. • Use of adjuvant therapy is associated with decreased risk of recurrence relative to surveillance. • Vaginal cuff brachytherapy both with and without chemotherapy is associated with improved survival outcomes. • Patients with early stage uterine serous carcinoma should be offered vaginal cuff brachytherapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the clinical outcome in locally advanced cervical cancer (LACC) after image-guided adaptive brachytherapy (IGABT) with combined intracavitary and interstitial (IC/IS) techniques using the hybrid Venezia applicator (Elekta AB, Sweden). LACC patients (UICC Stage IIB – IVB) treated with radiochemotherapy followed by IGABT with the hybrid IC/IS Venezia applicator at a single institution were retrospectively analyzed. Treatment comprised EBRT of the pelvis with 45 Gy and concomitant weekly cisplatin chemotherapy (40 mg/m2) followed by MRI-based IGABT. Dosimetry, oncological outcome and toxicity were investigated. Forty-six patients underwent a total of 184 fractions of IGABT between 2017 and 2020. Median follow-up was 24 months. Combined IC/IS techniques were used in 40 patients (87%). The median HRCTV volume was 31.2 cm3 and the median HRCTV D 90% was 92.3 Gy (EQD2 10). The median D 2cm 3 was 74.8 Gy for bladder, 57.9 Gy for rectum, 60.0 Gy for sigmoid and 52.2 Gy for bowel (EQD2 3). The 3-yr actuarial rates were 97.6% for local control, 97.6% for pelvic control, 59.9% for distant metastasis-free survival and 81.6% for overall survival. The crude rate for G2 and G3 late toxicity was 21.7% and 4.3%. IGABT with the hybrid Venezia applicator and a pronounced use of a combined IC/IS technique achieved high target doses, while maintaining low doses to organs at risk, leading to excellent local control and overall survival rates with acceptable toxicity. • Combined intracavitary and interstitial brachytherapy achieves high target doses. • This leads to excellent local control. • Toxicity with this combined approach is acceptable. • Distant recurrence is common; improvements in distant control are warranted. [ABSTRACT FROM AUTHOR]

Since dose escalation allowed by image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer (LACC), local relapses have become a rare event. Only scarce data are available on the outcome of patients experiencing a local relapse after IGABT. Between 2004 and 2016, all consecutive patients treated at Gustave Roussy Institute for LACC and receiving concomitant chemoradiation and IGABT were analysed. Clinical and treatment-related prognostic factors for survival after local relapse were searched, in order to potentially identify patients requiring salvage treatment. Two hundred and fifty-nine patients were treated during this period. With a median follow-up of 4.1 years, 10.8% (n = 28) had a local relapse. Among these patients, 53.6% had synchronous lymph nodes or distant metastatic relapse and only 13 patients (5% of all patients) had isolated local relapse. After local relapse, median survival was 47 months and three patients were alive at last follow-up. Only three patients with local relapse could receive salvage surgery (10.7%). Metastases occurrence and pelvic wall involvement were the main contraindications (67.9%) for salvage surgery. Among the three patients treated with surgery, two are still alive at last follow-up without significant complication. Improved survival was observed among the two patients who could have surgery (p =.02). Local progression led to serious symptoms in 75% of patients. Only the time interval between brachytherapy and relapse (<1 year) was prognostic for 2-year overall survival (p =.005). Salvage surgery is feasible in a very low number of highly selected patients with local relapse following IGABT. Local failure is a major cause of severe local symptoms, confirming that every effort should be done to achieve long-term local control through dose escalation. • In locally advanced cervical cancer, local relapse is a rare event due to dose escalation allowed by brachytherapy. • Feasibility of salvage surgery is uncertain and is feasible in a low number of highly selected patients. • Salvage surgery, however, appears to improve overall survival without significant complication. [ABSTRACT FROM AUTHOR]

To analyze the clinical outcomes and the safety of radiochemotherapy (RCT) and image-guided adaptive brachytherapy (IGABT) and to evaluate the impact of hysterectomy (HT) as completion of treatment for cervical cancer. 145 patients with locally advanced cervical cancer were treated at our institution. Patients underwent RCT and IGABT, then hysterectomy (HT) as completion of treatment was performed, with the exception of patients with surgical contraindications, para aortic metastatic disease or patients who refused surgery. Clinical outcomes and morbidity were retrospectively reviewed in both groups. Local relapse free survival (LRFS), pelvic relapse free survival (PRFS) and overall survival (OS) were analyzed. Completion HT was performed in 90 (62.1%) patients. Complete histological response and microscopic disease were found in 77 patients (85.6%). Local relapse was observed in 14 patients (9.6%) without differences between completion HT group and the definitive RCT and IGABT group (Odds Ratio OR = 1.73 [0.57–5.23], p = 0.33). The estimated 3-year LRFS and PRFS for the entire population were respectively 90% [84%–94%] and 93% [87%–96%], with no significant differences between them (respectively Hazard Ratio HR = 0.57 [0.20–1.64], p = 0.30 and HR = 0.37 [0.10–1.31], p = 0.12). The estimated 3-year OS rate for the whole population was 84% [75%–91%] with no significant differences between groups (HR = 0.81 [0.32–2.06], p = 0.65). Regarding morbidity, grade ≥ 2 vaginal toxicity was more frequent in the definitive RCT and IGABT group (43.6% vs 26.7%, p = 0.04). All grade 4 toxicity events were reported in the completion HT group. Due to high severe toxicity, RCT and IGABT with dose escalation followed by completion hysterectomy don't seem compatible. No benefit and increased severe late morbidity were observed. Combined intracavitary/interstitial technique is mandatory in large target volume at brachytherapy. • Locally advanced cervical cancer in the modern era of Image-guided adaptive brachytherapy. • Impact of hysterectomy as completion of treatment. • Incompatibility of treatments: high grade toxicity without clinical benefits. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate the efficacy, feasibility and safety of image-based, inversely and adaptively planned high-dose rate interstitial brachytherapy (HDR-ISBT) to treat advanced primary or recurrent gynecologic malignancy in a single implant, three-consecutive-day regimen. Methods Clinical demographics and outcome data were abstracted from all patients with primary and recurrent gynecologic malignancies who received HDR-ISBT boost from 2014 to 2017. Treatment consisted of a single implant (~7 Gy × 4 fractions) of interstitial needles using the Syed-Neblett template over a three-day hospital admission. CT-based (3D) simulation with inverse and adaptive planning was utilized for each fraction. MR prior to and MR immediately after external beam therapy were fused for HDR-ISBT target delineation. Results Forty women with an overall median follow-up of 18 months (range: 6–54 months) received an HDR-ISBT boost. Of the 30 primary cases (83% cervix, 10% vaginal, 7% uterine), 44% had organ invasion (bladder, rectal or both) on MRI. Median coverage and dose are reported (V 100 : 98%, HR-CTV EQD 2 : 85.1 Gy, D 90 : 92 Gy). A significant association existed between rectal doses exceeding GEC-ESTRO recommendations (D 2cc < 75 Gy) and the development of grade 3 gastrointestinal toxicity with a relative risk of 1.4 [1.1–1.8] (p =.046). Actuarial two-year overall survival (OS), local control (LC) and progression-free survival (PFS) were 81%, 81% and 64%, respectively. Conclusions A four fraction, inversely and adaptively planned, single-implant approach of image-based HDR-ISBT provides excellent coverage, minimal toxicity and effective local control in patients with advanced and recurrent disease. Graphical abstract Unlabelled Image Highlights • A condensed regimen of single implant interstitial brachytherapy is safe and effective. • An inverse and adaptive planning technique for each fraction is feasible. • One of the most locally advanced gynecologic cohorts treated with brachytherapy [ABSTRACT FROM AUTHOR]

Objectives: There are significant disparities in access to care and treatment among cervical cancer patients. Less than half of patients with locally advanced cervical cancer receive the standard of care therapy consisting of concurrent chemoradiation, followed by brachytherapy, despite significantly improved overall survival based on an analysis of the National Cancer Database. The recommended time to complete radiation therapy in advanced cervical cancer patients is < 56 days, with both pelvic control and survival decreasing when the duration of treatment is lengthened. This study explored the relationship between social vulnerability and clinical variables, including radiation treatment duration in cervical cancer patients undergoing definitive chemoradiation, including brachytherapy over a nine-year period at a single institution. Methods: By querying a cohort discovery tool, data were obtained from 108 patients with cervical cancer from 2012 to 2021 who received brachytherapy in addition to external beam radiation. Patients' census tracts were matched to indices from the Centers for Disease Control's (CDC) Social Vulnerability Index (SVI). The SVI rankings range from least vulnerable, 0, to most vulnerable, 1, for four themes: socioeconomic status, household composition and disability, minority status and language, and housing type and transportation. Clinical data, such as stage, histology, and demographic factors, were investigated. Results were analyzed using the Kruskal-Wallis rank-sum test Fisher's exact test, and Spearman's correlation. Results: Of patients included, 69% were Caucasian, 20% African American, 6.5% Hispanic, 1.9% Asian, and 1.9% American Indian/ Alaskan Native. The median SVI value when comparing patients to all census tracts in the United States was 0.43 (range: 0.0001-0.9907) in this population. Median SVI values suggested that African American patients were most vulnerable with an SVI of 0.86 (Interquartile Range [IQR]: 0.77-0.94), followed by Hispanic 0.59 (IQR: 0.46-0.79), American Indian or Alaska Native 0.56 (IQR: 0.43-0.69), Asian 0.33 (IQR: 0.22-0.44), and Caucasian 0.31 (IQR: 0.11-0.53) (p <0.001). Using 2018 FIGO staging, 58% of patients were stage III. Stage IV patients had the highest social vulnerability (0.77, IQR: 0.6-0.9). In a subset analysis of radiation treatment duration, the median time from start to end of radiation was 53 days (range: 35-127 days). There was no significant difference in length of time of radiation treatment by race (p=0.3) or stage (p>0.9). There was no relationship between SVI and radiation treatment duration (Rs =0.1). Conclusions: While social vulnerability appears to impact cervical cancer patients in regards to race and stage, increased social vulnerability was not associated with increased radiation treatment duration. Other factors, such as time to diagnosis, initiation of treatment, or accessibility to follow-up, may be more reflective of social vulnerability than treatment duration when a committed team works to mitigate obstacles to care during the course of radiation. [ABSTRACT FROM AUTHOR]