Pelvic External Beam Radiotherapy Research Articles

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.

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-blind, 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.

Hypomagnesemia and Survival in Patients with Cervical Cancer Treated with Definitive Chemoradiotherapy

Hypomagnesemia is a common side effect of platinum-based chemotherapy regimens. Although there are data reporting that hypomagnesemia is associated with worse survival in patients receiving platinum-based chemotherapy or chemoradiotherapy (CRT), this has not been documented in patients with cervical cancer treated with definitive CRT. We hypothesized that in patients with cervical cancer undergoing definitive CRT, on-treatment hypomagnesemia would be associated with longer treatment duration and worse cancer-specific survival (CSS). Patients with cervical cancer treated with definitive CRT from 1999 to 2015 were identified from a single cancer center's clinicopathologic database. Lowest on-treatment magnesium value was recorded and categorized as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grading (grade 1: <0.7 - 0.5 mmol/L, grade 2: <0.5 - 0.4 mmol/L, grade 3: <0.4-0.3 mmol/L, and grade 4 <0.3 mmol/L). Grade 0 was defined as ≥ 0.7 mmol/L. Treatment duration was defined as the number of days between the first day of radiotherapy until the last day of pelvic treatment (either brachytherapy or pelvic external beam radiotherapy boost). Prolonged treatment was considered as any treatment duration greater than 63 days. CSS for patients with either grade 0-1 or grade ≥ 2 CTCAE v5.0 magnesium toxicity was estimated using the Kaplan-Meier method, and the Peto & Peto modification to the generalized Gehan-Wilcoxon was used to determine statistical significance between groups. Associations with prolonged treatment duration was explored using logistic regression. P-values of <0.05 were considered statistically significant. A total of 186 patients were identified; median follow-up was 7 (IQR 2-11) years. 125 (67%) had stage I-II disease and 61 (33%) stage III-IV. Median treatment duration was 51 (IQR 48-57) days. All patients received concurrent weekly cisplatin-based chemotherapy with RT: the majority (n = 133; 72%) received 5 or 6 cycles. 147 (79%) patients received routine IV magnesium infusion with their chemotherapy and 173 (93%) received routine IV mannitol. During treatment the highest CTCAE v5.0 magnesium toxicity score was grade 0-1 in 158 (85%) and grade ≥ 2 in 28 (15%). Magnesium grade ≥ 2 was associated with worse 5-year CSS [grade 0-1: 5yr CSS 67.2%, (95% CI 60.1-75.1); grade ≥ 2: 5yr CSS 50%, (95% CI 34.5-72.4); p = 0.039]. Magnesium status was not associated with an increase in treatment duration [OR 1.465 (95% CI 0.3177 - 6.753); p = 0.625]. On-treatment hypomagnesemia ≥ grade 2 (CTCAE v5.0) was associated with worse CSS but did not predict longer treatment duration. This is the first study that shows a detrimental survival impact of on-treatment hypomagnesemia in this patient population. These findings highlight the need to ensure adequate monitoring, support and correction of magnesium during definitive CRT.

PO05: The Utility of a Vaginal Brachytherapy Boost Following Pelvic External Beam Radiotherapy for Uterine Cancer

PO05: The Utility of a Vaginal Brachytherapy Boost Following Pelvic External Beam Radiotherapy for Uterine Cancer

Practice patterns of adjuvant radiotherapy in women with stage I to II endometrial carcinoma: a real-world multi-institutional analysis in China

BackgroundThis study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers.MethodsWe included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014).ResultsA total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients.There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3–5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy.ConclusionWe report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China.Trial registrationThe clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139).

Molecular Classification Predicts Response to Radiotherapy in the Randomized PORTEC-1 and PORTEC-2 Trials for Early-Stage Endometrioid Endometrial Cancer.

The molecular classification of endometrial cancer (EC) has proven to have prognostic value and is predictive of response to adjuvant chemotherapy. Here, we investigate its predictive value for response to external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) in early-stage endometrioid EC (EEC). Data of the randomized PORTEC-1 trial (n = 714) comparing pelvic EBRT with no adjuvant therapy in early-stage intermediate-risk EC and the PORTEC-2 trial (n = 427) comparing VBT with EBRT in early-stage high-intermediate-risk EC were used. Locoregional (including vaginal and pelvic) recurrence-free survival was compared between treatment groups across the four molecular classes using Kaplan-Meier's methodology and log-rank tests. A total of 880 molecularly classified ECs, 484 from PORTEC-1 and 396 from PORTEC-2, were included. The majority were FIGO-2009 stage I EEC (97.2%). The median follow-up was 11.3 years. No locoregional recurrences were observed in EC with a pathogenic mutation of DNA polymerase-ε (POLEmut EC). In mismatch repair-deficient (MMRd) EC, locoregional recurrence-free survival was similar after EBRT (94.2%), VBT (94.2%), and no adjuvant therapy (90.3%; P = .74). In EC with a p53 abnormality (p53abn EC), EBRT (96.9%) had a substantial benefit over VBT (64.3%) and no adjuvant therapy (72.2%; P = .048). In EC with no specific molecular profile (NSMP EC), both EBRT (98.3%) and VBT (96.2%) yielded better locoregional control than no adjuvant therapy (87.7%; P < .0001). The molecular classification of EC predicts response to radiotherapy in stage I EEC and may guide adjuvant treatment decisions. Omitting radiotherapy seems to be safe in POLEmut EC. The benefit of radiotherapy seems to be limited in MMRd EC. EBRT yields a significantly better locoregional recurrence-free survival than VBT or no adjuvant therapy in p53abn EC. VBT is the treatment of choice for NSMP EC as it is as effective as EBRT and significantly better than no adjuvant therapy for locoregional tumor control.

A phase I study of the Wee1 kinase inhibitor adavosertib (AZD1775) in combination with chemoradiation in cervical, upper vaginal, and uterine cancers

ObjectiveWee1 kinase is a crucial regulator of the G2/M checkpoint which prevents entry of damaged DNA into mitosis. Adavosertib (AZD1775), a selective inhibitor of Wee1, induces G2 escape and increases...

Abstract 2800: Pharmacokinetics, bioavailability, and pharmacodynamics of oral triapine

Abstract Background: Locally advanced cervical cancer accounts for most deaths from disease. Standard of care includes treatment with cisplatin-based chemoradiation with a 70% response rate. The addition of intravenous (IV) triapine to chemoradiation has shown promising clinical activity in phase 1 and 2 studies but comes with a more intensive treatment regimen. An ongoing phase 1 trial has finished the escalation phase, and we report the pharmacokinetics (PK) and pharmacodynamics (PD) of oral (PO) triapine. Methods: This phase 1 study followed a 3+3 design for dose escalation of oral triapine, starting with initial dose of 100 mg five days a week for five weeks combined with external beam pelvic radiation and weekly IV cisplatin. PK was determined by LC-MS/MS, and PD included methemoglobin levels at 4 h post dose. Within patient PK variability after IV and PO dosing and PO bioavailability were calculated. Results: PK data were available for 10 patients at 100 (the MTD) and 150 mg. PO parameter values were Tmax 1.3 h, t1/2 1.4 h, CL/F 104 L/h, and Vz/F 214 L. There was no discernable difference between triapine exposure at 100 vs. 150 mg PO (Cmax 520 (2.5) vs. 344 (1.9) µg/L; AUC 1209 (2.53) vs. 1034 (1.41) µg/L•h), and between patient variability at each dose level was substantial. The correlation of PO Vz/F vs Cl/F was high at R2=0.86, suggesting that the apparent clearance and volume variability is primarily due to variability in the oral bioavailability F. PO within patient variability of Cmax and AUC was also large at 43% and 55%. IV PK was less variable with lower geometric standard deviations across all parameters, including within patients where variability of Cmax and AUC was modest at 10 and 12% coefficient of variation, respectively. Oral bioavailability was estimated at 66%. We found a non-significant trend of smoking almost doubling triapine oral clearance from 68 to 156 L/h (p=0.056). There was no apparent relationship between occurrence of DLT and either IV or PO triapine AUC. Methemoglobin levels directly correlated with triapine exposure expressed as AUC or Cmax. Conclusions: Triapine PK parameter values for PO and IV administration and PO bioavailability values observed in this trial were comparable to previous reports. Correlation of methemoglobin with exposure highlights the importance of optimizing triapine exposure. Additional data may support the exploration of a dose specific to current smokers. Citation Format: Jan H. Beumer, Sarah Behr, Holly Gallion, John Vargo, Frederick Ueland, Haider Mahdi, Brian Orr, Eugenia Girda, Susan Christner, Edward Chu, Charles Kunos, Percy S. Ivy, Sarah Taylor. Pharmacokinetics, bioavailability, and pharmacodynamics of oral triapine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2800.

Concomitant chemoradiotherapy, brachytherapy, and parametrial boost versus concomitant chemoradiation and brachytherapy alone in locally advanced cervical carcinoma: A prospective and comparative study

Background: The inherent property of brachytherapy is its steep dose gradient and parametrium, near the pelvic wall, which gets little contribution in dose from brachytherapy. As parametria are the common sites for treatment failure, parametrial boost (PMB) may increase the disease control in case of locally advanced cervical carcinomas after 45–50 Gy of external-beam radiotherapy (EBRT) to the whole pelvis. Aims and Objectives: This study aimed to find whether a satisfactory control of the parametrial disease can be achieved with acceptable toxicity. Materials and Methods: Between December 2014 and December 2017, 92 patients were treated by concomitant chemoradiation with whole pelvic EBRT of 50 Gy in 25 fractions and weekly Cisplatin (40 mg/m2) followed by brachytherapy. Out of 89 patients, 46 patients were given an additional PMB of 10 Gy in five fractions and 46 were given no boost. Results: The local control of the disease in terms of CR or PR was comparable in the two arms (i.e., with or without PMB), with P=0.542. The central recurrences between the two arms were also comparable, 13.9% without PMB, and 9.76% with PMB, P=0.726. When parametrial recurrence is concerned, there were four parametrial recurrences (11.11%) in the arm without boost, in comparison to no parametrial recurrence (0%) in the boost arm, and this was statistically significant (P=0.044). Conclusion: In locally advanced carcinoma cervix patients, in terms of parametrial recurrence, this study showed a significant clinical benefit of an additional external beam PMB.

Long-Term Efficacy and Toxicity of Intensity-Modulated Radiotherapy in Bulky Cervical Cancer.

Treatment of bulky cervical cancer is associated with both high adverse effects and local recurrence rates with traditional box method radiotherapy. Intensity-modulated radiotherapy (IMRT) has been adopted for the treatment of cervical cancer in order to deliver more precise radiation doses to the target region. We retrospectively enrolled a total of 98 patients with cervical cancer ≥4 cm who completed IMRT and point A-based brachytherapy treatment. The median follow-up time of the cohort was 6.84 years, with the 5-year OS and DFS being 66.33% and 75.12%, respectively. In addition, 7.14% of patients experienced local recurrence, 12.24% had distant recurrence, 6.12% had both local and distant recurrence, and 3.06% had persistent disease. In the univariate analysis, lymph node metastasis, higher creatinine levels, higher initial CA-125 and receiving chemotherapy other than cisplatin were all associated with a worse PFS. A tumor size ≥6 cm was associated with an increased incidence of higher grade of acute diarrhea. Grade 3 late radiation proctitis and cystitis developed in 11.22% and 13.27% of patients, respectively. The local recurrence rates and overall efficiencies were not inferior to other studies involving traditional pelvic external beam radiation therapy with concurrent chemotherapy. The safety and efficacy of IMRT for bulky cervical cancer were acceptable.

Outcomes of salvage high dose-rate brachytherapy with or without pelvic external beam radiotherapy in patients with palpable local recurrence of prostate cancer after radical prostatectomy

PurposeThis study aims to evaluate the outcomes and toxicities in patients with palpable local recurrence of prostate cancer after radical prostatectomy (RP), who were treated with salvage high dose-rate brachytherapy (HDR-BT) with or without pelvic external beam radiotherapy (EBRT). MethodsThis retrospective review included patients with palpable local recurrence of prostate cancer after RP who underwent salvage HDR-BT at a single institution between 2002 and 2020. HDR-BT regimens included 950 cGy x 2 (N = 4) or 1500 cGy x 1 (N = 2) combined with EBRT; or monotherapy with 950 cGy x 4 (N = 1) or 800 cGy x 2 (N = 1). Toxicity was graded according to CTCAE Version 5.0. ResultsA total of 8 patients were included. Median follow-up was 49 months (range: 9–223 months). Median age at time of salvage brachytherapy was 68 years (range: 59–85 years). Seven out of 8 patients were alive at last follow-up. There have been no locoregional recurrences. Three patients developed distant metastatic disease. One patient developed acute grade 3 urinary obstruction requiring catheterization, which lasted for 1 day postbrachytherapy. One patient developed late grade 3 urinary incontinence 18 months after brachytherapy. There were no other grade 2+ toxicities. ConclusionsThis study demonstrates the safety and efficacy of salvage HDR-BT in the setting of palpable local recurrence of prostate cancer after RP, with durable locoregional control and acceptable rates of toxicity. HDR-BT should be further explored as an option for dose-escalated salvage radiotherapy after prior radical prostatectomy.

Reviewing Stereotactic Body Radiation Therapy Boost after Neoadjuvant Chemoradiation as an Alternative to Brachytherapy Boost for Locally Advanced Cervical Cancer

It is generally agreed upon that concurrent chemoradiotherapy (CCRT) is the treatment of choice for locally advanced cervical cancer (LACC). Radiotherapy consists of pelvic external beam radiation therapy (EBRT) and intracavitary brachytherapy (BT) to boost the cervix with coexisting residual tumors. Both of these treatments are administered simultaneously. In developing countries, however, there is a trend toward favoring surgery over other sorts of therapy. This preference can be attributed to several factors, including the fact that surgery is more readily available, socially acceptable, and culturally understood. On the other hand, with the development of more advanced techniques for external beam radiation treatment (EBRT), the usage of brachytherapy (BT), which is intended to boost the cervix in patients diagnosed with cervical cancer (CC), has been steadily decreasing in industrialized countries. The manner in which LACC has been treated as of late has become a contentious issue. In women who have locally advanced CC, we do not have any prospective evidence to support the idea that surgery or current EBRT, or stereotactic body radiation therapy (SBRT), may be substituted for intracavitary BT boost as a treatment option. This study aims to review SBRT as an alternative to brachytherapy following neoadjuvant concurrent chemotherapy and radiation therapy.