Pelvic External Beam Radiotherapy Research Articles

The value of magnetic resonance imaging in predicting vesicovaginal fistula in cervical cancer with bladder invasion treated with definitive chemoradiotherapy.

To assess the predictive value of magnetic resonance imaging for vesicovaginal fistula development in cervical cancer patients with bladder invasion treated with definitive chemoradiotherapy. A retrospective review was conducted of the medical records of 43 cervical cancer patients with bladder invasion between 1999 and 2015. Bladder invasion was confirmed through magnetic resonance imaging (scores ≥3) or cystoscopic findings, with or without biopsy. Treatment included weekly cisplatin plus pelvic external beam radiotherapy, with extended-field radiotherapy. After external beam radiotherapy, patients received intracavitary brachytherapy or an external beam boost. Vesicovaginal fistula was diagnosed based on reported symptoms and relevant imaging tests during follow-up. The median follow-up period was 67.4months. The 5-year disease-free and overall survival rates were 66.4%, and 71.8%, respectively. Vesicovaginal fistula developed in five patients (12.8%), with three cases occurring within 1year post-treatment and two others at 16.7 and 64.5months, respectively. In multivariate analysis, the height of bladder wall involvement on magnetic resonance imaging was the only significant predictor of vesicovaginal fistula (p=0.041). Specifically, Vesicovaginal fistula occurred in 25% of cases when bladder wall involvement was ≥20.3mm, in 50% of cases at ≥31.1mm, and in 75% of cases at ≥41mm. The height of bladder wall involvement on magnetic resonance imaging is a significant predictor of vesicovaginal fistula formation in cervical cancer patients with bladder invasion. This finding can aid clinicians in better predicting this complication, improving patient counseling and management strategies.

Patterns of Care in Adjuvant Radiation Therapy for Stage II Endometrioid Endometrial Adenocarcinoma: a National Cancer Database Analysis

PurposeTreating stage II endometrial cancer involves total hysterectomy, bilateral salpingo-oophorectomy (TH/BSO), and risk-adapted adjuvant therapy. Professional guidelines support various adjuvant treatments, but high-level data supporting specific options are conflicting. We sought to evaluate adjuvant radiation (RT) trends for these patients, hypothesizing increased utilization of external beam pelvic radiation (EBRT) over time. Methods and MaterialsPatients diagnosed in 2004-2019 with stage II endometrioid endometrial cancer who underwent TH/BSO and surgical staging were identified in the National Cancer Database. Patient characteristics per adjuvant RT received were compared using Wilcoxon Rank Sum and analysis of variance testing. Multivariable regression analysis (MVA) identified variables associated with EBRT, vaginal brachytherapy (VBT), or RT omission. P-value <0.05 was significant, except in MVA where Bonferoni correction was employed (p-value <0.017). ResultsPatients meeting criteria totaled 18,798; 19% received adjuvant EBRT alone, 25% VBT alone, 24% EBRT+VBT, and 32% no RT. Adjuvant RT use increased from 2004-2019, particularly EBRT+VBT (p<0.05). On MVA, community hospital treatment (OR 1.8, p<0.001) Midwest location (OR 1.2, p=0.02), single-agent chemotherapy receipt (OR 6.9, p<0.001), lympho-vascular space invasion (LVSI) (OR 1.4, p<0.001), and positive surgical margins (+SM) (OR 1.8, p<0.001) were positively associated with EBRT. No variables were positively associated with VBT. Black race (OR 1.2, p=0.03), community hospital treatment (OR 1.4, p=0.04), South (OR 2.2, p<0.001) or West (OR 2.1, p<0.001) location, distance >50 miles from treatment center (OR 1.5, p<0.001), and grade 2 (OR 1.2, p<0.001) or 3 (OR 1.3, p=0.01) disease were associated with RT omission. ConclusionAdjuvant RT for stage II endometrial cancer increased over time, particularly EBRT+VBT. Patient-related factors such as race, region, and distance from treatment center were associated with RT omission, suggesting sociodemographic barriers to care. Tumor-related factors such as +SM and LVSI were associated with EBRT receipt, suggesting consideration of high-risk factors for locoregional recurrence in adjuvant RT approaches.

Friday, July 12, 20241:30 PM - 2:45 PM PL01 Presentation Time: 1:30 PM: A Randomized Comparison of LDR or HDR Brachytherapy Boost Combined with Pelvic External Beam Radiation for Unfavorable Intermediate or High-Risk Prostate Cancer. Efficacy Results at Median 6 Years Follow Up

Friday, July 12, 20241:30 PM - 2:45 PM PL01 Presentation Time: 1:30 PM: A Randomized Comparison of LDR or HDR Brachytherapy Boost Combined with Pelvic External Beam Radiation for Unfavorable Intermediate or High-Risk Prostate Cancer. Efficacy Results at Median 6 Years Follow Up

69 A Randomized Comparison of LDR or HDR Brachytherapy Boost Combined with Pelvic External Beam Radiation for Unfavourable Intermediate or High-Risk Prostate Cancer: Efficacy Results at Median 6 Years Follow Up

69 A Randomized Comparison of LDR or HDR Brachytherapy Boost Combined with Pelvic External Beam Radiation for Unfavourable Intermediate or High-Risk Prostate Cancer: Efficacy Results at Median 6 Years Follow Up

The Clinical Course of the Late Toxicity of Definitive Radiotherapy in Cervical Cancer.

Background and Objectives: This study aimed to investigate the clinical course and characteristics of late toxicity over time following the completion of definitive radiotherapy (RT) in patients with cervical cancer. Materials and Methods: We retrospectively reviewed the medical records of 60 patients with cervical cancer who underwent pelvic external beam radiotherapy followed by intracavitary brachytherapy. Late toxicity was assessed for the lower gastrointestinal (GI) tract and bladder organ at 6, 12, 24, 36, and >36 months post-RT. We examined the onset and prevalence of late toxicity at each time point. Clinical remission and interventions for managing late toxicity were also investigated. Results: The peak onset of lower GI toxicity occurred 12 months after RT completion, with a median symptom duration of 9.9 months (range, 0.1-26.3 months), and exhibited its highest prevalence rate of 15.5% at 24 months post-RT. Most GI toxicities developed and resolved within three years post-RT, with a prevalence rate of 8.1% at three years, followed by a decreasing trend. Bladder toxicity first peaked at 24 months post-RT and continued to occur beyond 36 months, showing the re-increasing pattern in the prevalence rate after 36 months (23.5%). In terms of clinical remission, 66.7% of lower GI toxicities (12 of 18 patients) and 60% of bladder toxicities (9 of 15 patients) achieved complete remission by the last follow-up date. Conclusions: Late toxicities of the GI and bladder following definitive RT in cervical cancer are partially reversible and exhibit distinct patterns of onset and prevalence over time. A systematic follow-up strategy should be established for the early detection and timely intervention of late toxicity by understanding these clinical courses.

Adjuvant Therapy for Endometrial Cancer in the Era of Molecular Classification.

Endometrial cancer primarily undergoes surgical intervention, with adjuvant treatments such as external beam pelvic radiotherapy, vaginal brachytherapy, chemotherapy, and combined therapy investigated in randomized trials. Treatment decisions hinge on clinicopathological risk factors. Low-risk cases usually require surgery alone, whereas high-intermediate risk often benefit from adjuvant vaginal brachytherapy for enhanced local control with minimal side effects. Recent trials advocate pelvic radiotherapy for high-risk cases, particularly in Stage I-II tumors with risk factors. Chemoradiation proves advantageous for serous cancers and Stage III disease, improving recurrence-free, and overall survival. Molecular studies, notably the Cancer Genome Atlas project, identified four distinct molecular classes, transcending stages, and histological types. These molecular subtypes exhibit a stronger prognostic impact than histopathological characteristics, heralding a shift toward molecular-integrated diagnostics and treatments. Incorporating molecular factors into adjuvant strategies, including targeted therapies, marks a new paradigm in endometrial cancer management, underpinning ongoing research, and clinical trials. This review outlines current adjuvant approaches, underscores the emergence of molecular-integrated risk profiling, and touches on developments in targeted therapy.

A single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer.

Pre-operative chemoradiation for rectal cancer is often associated with severe gastrointestinal (GI) toxicity which can interrupt, delay, and/or lead to termination of treatment. In this study, we evaluated whether the addition of YIV-906, a novel herbal medicine proven to reduce GI toxicity associated with chemotherapy could also reduce GI side effects during standard pre-operative capecitabine and pelvic radiation therapy (RT) in the neoadjuvant setting for the treatment of locally advanced rectal cancer. This single arm clinical study enrolled 24 patients between Dec 23, 2014-Sep 17, 2018 at Smilow Cancer Hospital, a comprehensive cancer center at Yale New Haven Hospital. All patients were age ≥18 years, Eastern Cooperative Oncology Group 0-1 and with histologically confirmed T3-T4 and N0-N2, M0 adenocarcinoma of the rectum. Median follow-up was 61.9 months. All patients received concurrent pelvic external beam RT (50.4 Gy in 28 fractions), YIV-906 (taken orally 800 mg twice daily on days 1-4 of RT each week), and oral capecitabine delivered in a neo-adjuvant fashion, followed by definitive surgery. Toxicity was assessed weekly during radiation and until acute symptoms resolved and then at 28 days, 4 months, 7 months and 10 months. Toxicities were graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. At the time of surgery, 4 patients (16.7%) had a complete or near-complete response. At a median follow-up of 61.9 months, the mean overall survival (OS) of our patient cohort was 74.9 months [95% confidence interval (CI): 67.3-82.5]. The estimated 5-year OS was 82.0%. We observed 0% acute grade 4 toxicities, and only two cases of acute grade 3 diarrhea (8.3%). The addition of YIV-906 to capecitabine based chemoradiation for locally advanced rectal cancer led to reduced rates of GI toxicity compared to historical controls, in particular grade 3 or greater diarrhea. These findings suggest YIV-906 should be evaluated in a randomized clinical trial to further assess potential reductions in the toxicity profile of chemoradiation for GI cancers.

Adjuvant Treatment of Stage I-II Serous Endometrial Cancer: A Single Institution 20-Year Experience.

Background: Serous endometrial carcinoma (SEC) is a high-risk subtype of endometrial cancer. The effectiveness of multiple adjuvant therapies, namely chemotherapy (CT), radiotherapy (RT), and sequential/concurrent chemotherapy with radiotherapy (CRT), have previously been investigated. However, optimal management of early-stage SEC remains unclarified. Methods: All cases of early-stage SEC (FIGO 2009 stages I-II) treated in our institution from 2002 to 2019 were identified. Patient data were documented until September 2023. Overall survival (OS) and disease-free survival (DFS) were computed using Kaplan-Meier estimates and Cox's proportional hazard model; descriptive statistical analysis was performed. Results: A total of 50 patients underwent total hysterectomy-bilateral salpingo-oophorectomy and omentectomy, displaying stage IA (60%), IB (24%), and II (16%) disease. The median follow-up was 90.9 months. Patients underwent adjuvant CRT (n = 36, 72%), CT (n = 6, 12%), or RT (n = 6, 12%). Two patients were observed and excluded from analyses. The 42 patients who received radiotherapy had pelvic external beam radiotherapy (n = 10), vaginal brachytherapy (n = 21), or both (n = 11). CRT had better OS (HR 0.14, 95%CI 0.04-0.52, p < 0.005) and DFS (HR 0.25, 95%CI 0.07-0.97, p = 0.05) than CT alone. RT displayed no OS or DFS benefits compared to CT/CRT. Recurrences were mostly distant. Acute and late G3-4 toxicities were primarily hematologic. Conclusions: Our data underline the challenge of treating SEC. CRT appears to be superior to CT alone but not to RT. Most recurrences were distant, highlighting the need for optimized systemic treatment options.

Advances in research on organ-at-risk protection in pelvic tumor external beam radiotherapy

The simultaneous objectives of destroying tumor cells while protecting normal pelvic organs present a dual clinical and technical challenge within the realm of pelvic tumor radiotherapy. This article reviews the latest literatures, focusing on technological innovations in key aspects of radiotherapy such as positioning, planning, and delivery. These include positioning fixation techniques, organ-at-risk avoidance irradiation, non-coplanar irradiation techniques, as well as organ displacement protection and image-guided adaptive techniques. It summarizes and discusses the research progress made in the protection of critical organs during pelvic tumor radiotherapy. The paper emphasizes technological advancements in the protection of critical organs throughout the processes of radiotherapy positioning, planning, and implementation, aiming to provide references for further research on the protection of critical organs in the external irradiation treatment of pelvic tumors.

Impact of cachexia on disease recurrence and survival outcomes in endometrial cancer patients

ObjectiveCancer cachexia is progressive weight loss due to muscle/adipose tissue wasting and inadequate intake that occurs in response to malignancy. It is an independent predictor of disease recurrence and reduced survival in several cancers. However, cachexia’s relationship with gynecologic malignancy outcomes has only been examined in small studies with limited follow-up and inconsistent definitions of cachexia. This study investigated the impact of cachexia on disease recurrence and overall survival in high-risk endometrial carcinoma patients. MethodsThis retrospective cohort study examined data from patients with high-risk non-metastatic primary endometrial carcinoma treated at a single institution from 2015 to 2020. Treatment for all subjects included total hysterectomy, surgical staging, pelvic external beam radiotherapy with or without adjuvant chemotherapy. Radiation planning CT datasets were used to measure skeletal musculature at the L3 vertebral level. Skeletal muscle index (SMI) was defined as total L3 skeletal muscle cross sectional area (cm2)/height2 (m2), and cachexia was defined based on SMI. Results55 patients were eligible for analysis. Several SMI thresholds were used to define cachexia, and analysis was performed for each definition. Kaplan-Meier and Cox-proportional hazards regression analysis yielded no significant reduction in overall survival (OS) or progression-free survival (PFS) in patients with cachexia, regardless of threshold chosen. However, 4 of 13 definitions of cachexia showed significantly improved OS in patients without cachexia, relative to those with cachexia. There were no significant differences in disease recurrence. ConclusionsCachexia as defined in this study was not associated with poor outcomes in endometrial carcinoma patients based on OS, PFS, or disease recurrence.

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China’s real world

BackgroundEndometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China’s real world.MethodsThis retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT.ResultsThe study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone.ConclusionsIn the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

A Review of the Efficacy of the Low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) Diet in Managing Gastrointestinal Symptoms Related to Cancer Treatment.

The low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, designed to alleviate symptoms in individuals with irritable bowel syndrome (IBS), focuses on limiting the consumption of poorly absorbed fermentable carbohydrates known as FODMAP. These FODMAP are believed to be the primary triggers for food-related gastrointestinal symptoms in functional gastrointestinal disorders. However, there is currently insufficient direct evidence investigating the role of low FODMAP diets in cancer patients undergoing treatment. This review aims to summarize the current evidence on the low FODMAP diet and its potential implications for cancer patients in terms of treatment outcomes, alleviating gastrointestinal symptoms, and overall health. A systematic literature search was conducted using databases, including PubMed, Scopus, Google Scholar, Web of Science, and Cochrane. Five studies met the criteria for inclusion in the review, and these studies covered rectal toxicity during radiotherapy, gastrointestinal symptoms in colorectal cancer patients, acute gastrointestinal toxicity during pelvic external beam radiotherapy, symptoms in patients with radiation-induced enteropathy, and chronic gastrointestinal sequelae resulting from pelvic organ cancer treatment. The available evidence suggests that a low FODMAP diet may offer advantages in reducing rectal gas and volume during radiotherapy, alleviating diarrhea symptoms, reducing symptom deterioration, and improving quality of life. However, these studies highlight the need for large-scale randomized trials, long-term follow-up, and guidelines to establish the efficacy, safety, and implementation strategies of the low FODMAP diet in different cancer contexts and patient populations. While preliminary findings reported some possible benefits of a low FODMAP diet for certain cancer patients, rigorous studies with large sample sizes are needed to provide more robust evidence. Further research is warranted to optimize the utilization of this diet as an adjunctive intervention for managing gastrointestinal symptoms in this population.

A Randomized Trial Comparing Quality of Life After Low-Dose Rate or High-Dose Rate Prostate Brachytherapy Boost With Pelvic External Beam Radiation Therapy

Purpose/ObjectivesTo compare health-related Quality of Life (QoL) in urinary, bowel and sexual domains after combined external beam radiotherapy (EBRT) and either low dose rate (LDR) or high dose rate (HDR) prostate brachytherapy (BT). Materials/MethodsEligible men with intermediate or high-risk prostate cancer, treated with combined pelvic EBRT and BT were randomly assigned to either HDR (15 Gy) or LDR (110 Gy) boost. International Prostate Symptom Score (IPSS), Index of Erectile Function (IIEF), Expanded Prostate Cancer Composite (EPIC-26) were collected at baseline, 1,3,6 and 12 months, q6 months to 3 years and then annually along with PSA/testosterone. Fisher's exact test compared categorical variables and the Mann Whitney U test EPIC domain scores. ResultsFrom 01/2014 to 12/2019, a random number generator assigned 195 men: 108 to HDR and 87 to LDR. Median age was 71 years. Risk group was high in 57% and unfavorable intermediate in 43%. Androgen deprivation (used in 74%) began with 3 months neoadjuvant and continued for median 12 months. Baseline EPIC scores were similar for the LDR/HDR cohorts: 89/88 for GU and 92/93 for GI. EPIC urinary scores decreased at one month for HDR but recovered promptly to a steady state by 6 months. LDR scores reached a nadir at 3 months with slow recovery to 18 months, after which urinary QoL was similar for HDR and LDR. Bowel QOL scores fell in both cohorts reaching respective nadirs at 12 months. HDR patients recovered close to baseline and maintained higher scores than LDR patients to 5 years. The decline for LDR patients remained > the MCID out to 5 years. ConclusionsPatient experience for combined EBRT and prostate BT is improved with HDR BT. Urinary QoL improves over time to be equivalent between the 2 modalities after 18 months, but LDR patients report lasting bowel symptoms.

Low-dose-rate, high-dose-rate, and pulsed-dose-rate intra-cavitary brachytherapy for cervical cancer: The very first comparison study.

For cervical cancer patients, intra-cavitary brachytherapy (ICBT) is utilized with various dose-rate systems, such as low-dose-rate (LDR), high-dose-rate (HDR), and pulsed-dose-rate (PDR). This retrospective analysis aimed to compare the therapeutic outcomes of cervical cancer patients treated with either LDR-, HDR-, or PDR-ICBT. A total of 613 patients were treated with pelvic external beam radiation therapy (EBRT), followed by either LDR- (271 patients), HDR- (259 patients), or PDR- (83 patients) ICBT. Point-based planning was performed according to orthogonal radiographs in LDR patients, and computed tomography (CT) imaging in HDR and PDR patients. ICBT prescribed dose was as follows: for LDR treatment, 30 Gy in a single-session; for HDR: 7 Gy × 3 fractions (once a week fraction); and for PDR: 27 Gy in an hourly pulse of 70 cGy, with all the doses prescribed at point A. Radioactive source used was cesium-137 for LDR, and iridium-192 for HDR and PDR treatments. Loco-regional control (LRC) rate was 74%, 75%, and 77% in LDR, HDR, and PDR groups, respectively (p = 0.80). The 5-year overall survival (OS) in the three groups, i.e., LDR, HDR, and PDR was 63%, 64%, and 68%, respectively (p = 0.77). Severe late toxicity (RTOG grade ≥ 3) rate in the three groups was comparable (LDR, 12%; HDR, 8%; and PDR, 8.9%, p = 0.36). Our study revealed comparable LRC, 5-year OS, and late toxicity rates using three dose-rate systems. Lower OS rates were observed in LDR group for stage III patients compared with patients in HDR and PDR groups. Therefore, we suggest that LDR should be used with caution while treating stage III patients.

Previous external beam radiation therapy for pelvic malignancy increases complications of total hip arthroplasty.

External beam radiation therapy (EBRT) has known effects on bone health. No large database studies have looked at the effects of pelvic EBRT on total hip arthroplasty (THA) outcomes. The purpose of this study was to evaluate 90-day and long-term (>2 years) complication rates following THA in patients with a history of pelvic malignancy and EBRT. Patients were retrospectively identified using a national insurance claims database. Subjects who underwent THA for osteoarthritis or avascular necrosis were included if they had at least 2-year follow-up and were stratified into 3 cohorts: (1) prior pelvic malignancy diagnosis (prostate, cervical, uterine, ovarian, or rectal) and EBRT (Group A); (2) prior malignancy diagnosis but no EBRT (Group B); and (3) neither prior malignancy diagnosis nor EBRT (Group C). Univariate and multivariate analyses were conducted to evaluate for an association between prior EBRT and the incidence of 90-day and 2-year complication rates using chi-square, student t-tests, and logistic regression analyses where appropriate. 671,554 patients met the inclusion criteria. Group A had higher odds of all-cause revision, septic revision, and loosening with revision after 2 years when compared to Group C and Group B (p < 0.001). Group A subjects had higher rates of 90-day deep vein thrombosis, sepsis, and stroke (p < 0.001) than groups B and C. Prior EBRT for pelvic malignancy was associated with significantly increased rates of all-cause revision, septic revision, and loosening as well as 90-day medical complications.

Online Adaptive Magnetic Resonance-guided Radiation Therapy for Gynaecological Cancers: Preliminary Results of Feasibility and Outcome

AimsTo present the preliminary results on the clinical utilisation of an online daily adaptive magnetic resonance-guided radiation therapy (MRgRT) for various gynaecological cancers. Materials and methodsTwelve patients treated between September 2018 and June 2022 were included. Six patients (50%) were treated with pelvic radiation therapy followed by MRgRT boost as brachytherapy boost was ineligible or unavailable, three patients (25%) were treated with pelvic MRgRT followed by high dose rate brachytherapy, two patients (16.7%) were treated with only MRgRT, one patient (8.3%) was treated with linear accelerator-based radiation therapy followed by MRgRT boost for bulky iliac lymph nodes. ResultsThe median age was 56.5 years (range 31–86 years). Eight patients (66.7%) had a complete response, three patients (25%) had a partial response and one patient (8.3%) died due to acute renal failure. The mean follow-up time was 11.2 months (range 3.1–42.6 months). The estimated 1-year overall survival was 88.9%. The median treatment time was 47 days (range 10–87 days). During external beam radiation therapy, 10 (83.3%) patients had concomitant chemoradiotherapy. Pelvic external beam radiation therapy doses for all cohorts were 45–50.4 Gy with a fraction dose of 1.8 Gy. The median magnetic resonance-guided boost dose was 32 Gy (range 20–50 Gy) and fraction doses ranged between 4 and 10 Gy. Three patients were treated with intracavitary high dose rate brachytherapy (26–28 Gy in four to five fractions). None of the patients had grade >3 late genitourinary toxicities. ConclusionMRgRT is reliable and clinically feasible for treating patients with gynaecological cancers alone or in combination with brachytherapy with an acceptable toxicity and outcome. MRgRT boost could be an option when brachytherapy is not available or ineligible.

Effect of Pelvic External Beam Radiation Therapy on Bone Mineral Density: A Secondary Analysis of a Phase 3 Randomized Controlled Trial

Pelvic radiation therapy may lead to decreased bone mineral density (BMD) and increased risk of fracture that could be of particular concern in patients with prostate cancer who also receive androgen deprivation therapy (ADT). We performed an exploratory analysis of a randomized, double-masked, placebo-controlled trial to determine whether exposure to prior pelvic external beam radiation therapy (XRT) affects BMD and risk of fracture in patients with prostate cancer treated with ADT. Patients with nonmetastatic prostate cancer aged ≥70 years or <70 years with low BMD (T-score < -1) or osteoporotic fracture who had been receiving ADT for ≥12 months were randomly assigned to receive densoumab or placebo every 6 months for 3 years. BMD was measured at baseline and at months 1, 3, 6, 12, 24, and 36. We applied multivariable linear mixed-effects models with an interaction term between the treatment arm and exposure to prior pelvic XRT to evaluate differential XRT effect on percent BMD change between the 2 treatment arms. Among 1407 eligible patients, 31% (n = 447) received prior pelvic XRT. There was no significant difference in any clinical fractures among patients with (5.8%, 26 of 447) or without (5.2%, 50 of 960) prior pelvic XRT (P = .42). Prior pelvic XRT was associated with a significant (0.54%) improvement in BMD (95% CI, 0.05-1.02) in the placebo group and a nonsignificant (0.04%) decline in BMD (95% CI, -0.47 to -0.35) in the denosumab group (interaction P = .007). There was no significant difference in pelvic XRT effect on percent BMD change in the lumbar spine (P = .65) or total hip (P = .39) between the 2 treatment groups. We did not find sufficient evidence to suggest any detrimental effect of pelvic XRT on the treatment effect from denosumab on percent BMD change, with only an approximately 5% incidence of clinical fractures.

The Prognostic Impact of Substantial Lymphovascular Space Invasion in Women with FIGO Stage I Uterine Endometrioid Carcinoma with Pathologically Negative Nodal Evaluation

Substantiallymphovascular space invasion (LVSI) is an important predictor of lymph node involvement in women with endometrial carcinoma. However, its prognostic significance in women with stage I who had pathologic negative nodal evaluation (PNNE) was not fully evaluated. We aimed to evaluate the prognostic significance of substantial LVSI on recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) in women with FIGO stage I uterine endometrioid adenocarcinoma (EC). Our uterine cancer database was queried for women with stage I EC who had a hysterectomy and PNNE at our institution between 1/1990 and 11/2022. Postoperatively, patients were managed with observation or adjuvant radiation therapy (RT) with pelvic external beam RT or vaginal cuff brachytherapy (VB). Women with synchronous malignancies and those who received adjuvant chemotherapy were excluded. Pathologic specimens were retrieved and LVSI was quantified by Gynecology pathologists (none, focal or substantial). Patients' demographics, surgical and pathologic variables were analyzed. Predictors of RFS, DSS and OS using univariate (UVA) and multivariate analysis (MVA) were studied. One thousand fifty-two patients were identified with a median age of 63 years and median follow-up of 9.7 years. Median number of examined lymph node (LN) were 9 (range 4-18). 907 patients (86.2%) had no LVSI, 87 (8.3%) had focal and 58 (5.5%) had substantial LVSI. In patients with focal LVSI, 32.2% received pelvic RT and 39.1% received VB. In patients with substantial LVSI, 20.7% received pelvic RT and 58.6% received VB.Recurrence was diagnosed in 86 patients (8.2%). While any LVSI was associated with tumor recurrence, there was no significant difference for the site of initial recurrence between patients with focal vs. substantial LVSI. 5-year RFS was 93.3% (95% CI 91.5-95.1), 76.8% (67.2-87.7) and 79.1% (67.6-95.3) for no, focal and substantial LVSI. The 5-year DSS was 97.6% (96.5-98.7), 83.5% (75-93.1), and 90% (81.8-99.9); and 5-year OS was 90.7% (88.7-92.8), 72.8% (62.9-84.2) and 86% (76.2-97.2), respectively. Independent predictors of worse 5-year RFS and DSS include any LVSI, age > 60 years, higher tumor grade. Independent predictors of worse 5- year OS include any LVSI, age > 60, high comorbidity burden, and higher tumor grade. Our large data suggest similar recurrence-free, disease specific and OS for women with stage I uterine endometrioid carcinoma who had pathologically negative nodal evaluation and substantial or focal LVSI. There was no significant difference for the site of initial recurrence between patients with focal or substantial LVSI. Multi-institutional pooled analyses may be needed to validate our results.

Prospective Evaluation of MRI-Based Endoluminal Brachytherapy with Novel Applicator for Anorectal Cancer

To present results of patients treated on a prospective dose escalation trial of MRI-based endoluminal high dose rate (HDR) brachytherapy (BT) and concurrent chemotherapy utilizing a novel double-balloon applicator for recurrent or inoperable rectal and anal cancer. A total of 15 patients were enrolled on a prospective, institutional review board-approved dose escalation protocol evaluating endoluminal HDR-BT with concurrent chemotherapy. Inclusion criteria were histologically confirmed locally residual or recurrent cancer of the rectum or anus and prior pelvic external beam radiation therapy (EBRT). BT was delivered with a novel anorectal applicator consisting of an inner balloon, which supported 8 channels for the radioactive source, and a compliant outer balloon for optimal deformation against exophytic lesions. Applicator insertion and treatment delivery were performed under general anesthesia in 3 weekly sessions. MRI-based treatment planning was performed while under anesthesia during the first session only. Capecitabine (825 mg/m2 BID) was administered Monday-Friday on the weeks of BT. Efficacy and toxicity were evaluated by clinical assessment and MRI examinations at pre-defined intervals (3, 6, and 12 months for the first year) after the procedure. From 1/2015 to 4/2018 15 patients at a median age of 65 years (43-86) with recurrent or residual cancer (9 rectal, 6 anal) were enrolled and treated at the initial dose level of 15 Gy in 3 fractions (n = 6), the intermediate dose level of 18 Gy in 3 fractions (n = 3), and the highest dose level of 21 Gy in 3 fractions (n = 6). Treatment was delivered as planned for 14 patients; 1 patient was treated with a single-channel Bougie applicator for the third fraction due to the development of severe circumferential narrowing that prevented insertion of the endorectal applicator. On first MRI imaging post-BT, 7 patients had a complete response, 5 patients had a partial response, 1 patient had progressive disease, and 2 patients had indeterminate imaging. At a median follow up of 26 months (7-88), 10 patients (6 rectal and 4 anal) have developed a local recurrence (2 also with distant disease) which were treated with surgery (4), systemic therapy (1), or no known therapy (3). Acute (<6 months post-RT) grade 2 and 3 toxicities were observed in 1 (rectal bleeding) and 2 (anorectal pain) patients, respectively, and the only late grade 3 toxicity observed was rectal bleeding in 1 patient. Endoluminal HDR BT with MRI-based treatment planning and a novel double-balloon applicator was feasible up to a dose level of 21Gy in 3 fractions in patients with non-operable rectal or anal cancers and history of prior EBRT. The clinical efficacy and toxicity associated with this treatment should be more clearly defined with analyses of larger cohorts of patients.

Correlation of Post-Treatment Biopsy and Fluorodeoxyglucose PET/CT Findings Following Definitive Chemotherapy and Radiation for Cervical Cancer

Concurrent chemotherapy and external beam radiation with brachytherapy boost is considered standard of care for treatment of locally advanced cervical cancer. Post treatment surveillance fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging is recommended 3-6 months after completion of therapy. Persistent FDG avidity is commonly observed at the cervix on surveillance scans, indeterminate for residual malignancy versus post treatment inflammatory change. To better understand the clinical significance of residual hypermetabolic activity, we performed an analysis of surveillance FDG-PET/CT images, correlating findings with post treatment cervical biopsy results after completion of therapy. The medical records of all patients treated with definitive chemotherapy and radiation for locally advanced (FIGO IB3 to IVA) cervical cancer at a single academic medical center between 2017 and 2022 were reviewed. Patients were treated with curative intent using a combination of pelvic external beam radiation with concurrent cisplatin chemotherapy followed by intracavitary or combined intracavitary/interstitial brachytherapy boost. Patients underwent FDG-PET/CT imaging at 3-6 months upon completion of therapy, followed by biopsy either for suspected residual disease or equivocal findings on physical exam or FDG-PET/CT scans. Biopsies were obtained within 100 days of FDG-PET/CT imaging (median, 14 days). Twenty-three patients met inclusion criteria. One patient was excluded from analysis due to lack of FDG avidity on her pre-treatment FDG-PET/CT. Among the 22 evaluable scans, median pre-treatment FDG- PET/CT SUVmax of the cervix was 16.3 (range, 4.9-55). Median post-treatment SUVmax was 4.4 (range, 2.1-7.4). Median change in SUVmax from pre-treatment to post-treatment was 11.8 (range, 1.1 to 50.6). Twenty patients had a post-treatment SUVmax of greater than 3. Among post treatment scans, eight showed no residual uptake; two showed uptakes equal to the liver; eleven showed uptakes moderately higher than liver; and one showed uptake markedly increased relative to liver. None of the biopsy specimens showed evidence of residual malignancy, instead showing fibroinflammatory necrosis and reactive changes. None of the patients developed clinical evidence of disease progression at the cervix within one year of treatment completion. Residual hypermetabolic activity at the cervix is common following definitive chemotherapy and radiation for cervical cancer. This is unlikely to represent residual viable malignancy. Post treatment FDG-PET/CT imaging remains valuable for detecting locoregional or distant disease progression/persistence following therapy.