Pelvic Radiotherapy Research Articles

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.

Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis

PurposeDespite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT.MethodsA propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test.ResultsMedian follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2α/β=1.5 Gy) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis.ConclusionsOverall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity.

Comparison of setup errors between two immobilization techniques for image-guided pelvic radiotherapy: Can an ankle fixator be used as an alternative to a thermoplastic mask for immobilization without compromising treatment?

Comparison of setup errors between two immobilization techniques for image-guided pelvic radiotherapy: Can an ankle fixator be used as an alternative to a thermoplastic mask for immobilization without compromising treatment?

Utilization of machine learning methods for prediction of acute and late rectal toxicity due to curative prostate radiotherapy.

Rectal toxicity is one of the primary dose-limiting side effects of prostate cancer radiotherapy, and consequential impairment on quality of life in these patients with long survival is an important problem. In this study, we aimed to evaluate the possibility of predicting rectal toxicity with artificial intelligence model which was including certain dosimetric parameters. One hundred and thirty-seven patients with a diagnosis of prostate cancer who received curative radiotherapy for prostate +/- pelvic lymphatics were included in the study. The association of the clinical data and dosimetric data between early and late rectal toxicity reported during follow-up was evaluated. The sample size was increased to 274 patients by synthetic data generation method. To determine suitable models, 15 models were studied with machine learning algorithms using Python 2.3, Pycaret library. Random forest classifier was used with to detect active variables. The area under the curve and accuracy were found to be 0.89-0.97 and 95%-99%, respectively, with machine learning algorithms. The sensitivity values for acute and toxicity were found to be 0.95 and 0.99, respectively. Early or late rectal toxicity can be predicted with a high probability via dosimetric and physical data and machine learning algorithms of patients who underwent prostate +/- pelvic radiotherapy. The fact that rectal toxicity can be predicted before treatment, which may result in limiting the dose and duration of treatment, makes us think that artificial intelligence can enter our daily practice in a short time in this sense.

Investigating the relationship between postoperative radiotherapy and intestinal flora in rectal cancer patients: a study on efficacy and radiation enteritis.

This study aimed to investigate the impact of radiation therapy and radiation enteritis on intestinal flora, providing insights for treatment and prevention. Fecal samples were collected from 16 patients undergoing pelvic radiotherapy at Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital). Samples were collected before and after radiotherapy (27-30Gy), and analyzed using DNA sequencing and biostatistical methods. Patients with radiation enteritis showed increased α-diversity and β-diversity of intestinal flora compared to those without radiation enteritis. Differences in flora composition were observed, with higher abundance of secondary pathways such as amino acid metabolism, carbohydrate metabolism, cofactors and vitamins metabolism, and lipid metabolism. The study revealed that patients developing radiation enteritis during pelvic radiation therapy had increased diversity and abundance of intestinal flora compared to those who did not develop radiation enteritis. Additionally, patients without radiation enteritis showed significantly higher diversity and abundance of intestinal flora post-radiation compared to pre-radiation.

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.

Dose equivalent consideration from neutron contamination in modified radiotherapy vault: a Monte Carlo study

Laminated barriers incorporating metal sheets provide effective protection for space-restricted radiotherapy centers. This study aimed to assess photoneutron contamination in smaller vaults protected by different compositions of multilayer barriers during simulated pelvic radiotherapy with 18 MV photon beams. Monte Carlo Simulations of 18 MV LINAC (Varian 2100 C/D) and Medical Internal Radiation Dose (MIRD) phantom were used to assess photoneutron contamination within reconstructed vaults incorporating different combinations of metal sheet and borated polyethylene (BPE) during pelvic radiotherapy. The findings highlight a 3.27 and 2.91 times increase in ambient neutron dose Hn* (10) along the maze of reconstructed vaults that use lead and steel sheets, respectively, compared to concrete. The Hn* (10) outside the treatment room increased after incorporating a metal sheet, but it remained within the permissible limit of 20 μSv/week for uncontrolled areas adjacent to the LINAC bunker, even with a workload of 1000Gy/week. Neutron equivalent doses in the patient’s organs ranged from 0.22 to 0.96 mSv Gy−1. There is no notable distinction in the organ’s neutron equivalent dose, fatal cancer risk, secondary radiation-induced cancer risk, and cancer mortality for various laminated barrier compositions. Furthermore, the use of metal sheets for vault wall reconstruction keeps the variation in cancer risk induced by photoneutrons below 6%, while risks of fatal cancer and cancer mortality vary less than 11%. While the metal portion of the laminated barrier raises the neutron dose, the addition of a BPE plate reduces concerns of increased effective dose and secondary malignancy risk.

Late Urinary Toxicity After Extreme or Moderate Hypofractionated Prostate Radiation Therapy in Patients With Prior Transurethral Resection of Prostate

PurposeTo study the late urinary toxicity in patients with prostate cancer with prior transurethral resection of prostate (TURP) and treated with hypofractionated prostate radiotherapy. MethodsPatients diagnosed with prostate cancer, with a prior TURP, and treated with moderate or extreme hypofractionated intensity modulated radiotherapy (MHRT or SBRT), were included in this study. Severity and duration of urinary symptoms observed during serial follow up after at least three months from radiotherapy were graded per CTCAE v5.0 using information from prospectively maintained institutional database. Impact of hypofractionation and other potential contributory factors on cumulative grade 2+ late urinary toxicity was analysed with univariable and multivariable binary logistic regression. ResultsTotal 203 eligible patients were included (MHRT=114, 64-68Gy/25#; SBRT=89, 35-37.5Gy/5#). Median time from TURP to radiotherapy was 10 months (IQR 7-16), similar for MHRT and SBRT. Overall, mean cavity volume was 1.17cc (IQR 0.5-1.35), while in MHRT and SBRT groups was 1.03 cc (IQR 0.4-1.15) and 1.27 cc (IQR 0.5-1.4), respectively. At a median follow up of 37 months, cumulative grade 3 and grade 2 late urinary toxicity was 8.4% (n=17) and 23.2% (n=47) respectively. Grade 3 symptoms were observed at median 29 months (IQR 19-62) after radiotherapy completion, lasting for a median duration of 8 months (IQR 2-14). Hematuria (6.4%) and urinary obstruction (3.4%) were the chief grade 3 symptoms. Multivariable analysis for age, diabetes, pelvic radiotherapy, fraction size, prostate volume, TURP to radiotherapy duration, and TURP cavity volume showed no significant association with late grade 2+ urinary toxicity. Conclusion: In this large cohort of patients with prior TURP and treated with hypofractionated prostate radiotherapy, incidence of severe late urinary adverse effects was <10%, mainly hematuria or urinary obstruction. Most of these were temporary, and no significant contributory factors were identified for late urinary morbidity after TURP and radiotherapy.

Reply to Editorial Comment on “Incidence and Management of Radiation Cystitis After Pelvic Radiotherapy for Prostate Cancer: Analysis From a National Database"

Reply to Editorial Comment on “Incidence and Management of Radiation Cystitis After Pelvic Radiotherapy for Prostate Cancer: Analysis From a National Database"

T Cell-Derived Apoptotic Extracellular Vesicles Hydrolyze cGAMP to Alleviate Radiation Enteritis via Surface Enzyme ENPP1.

Radiation enteritis is the most common complication of pelvic radiotherapy, but there is no effective prevention or treatment drug. Apoptotic T cells and their products play an important role in regulating inflammation and maintaining physiological immune homeostasis. Here it is shown that systemically infused T cell-derived apoptotic extracellular vesicles (ApoEVs) can target mice irradiated intestines and alleviate radiation enteritis. Mechanistically, radiation elevates the synthesis of intestinal 2'3' cyclic GMP-AMP (cGAMP) and activates cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) proinflammatory pathway. After systemic infusion of ApoEVs, the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) enriches on the surface of ApoEVs hydrolyze extracellular cGAMP, resulting in inhibition of the cGAS-STING pathway activated by irradiation. Furthermore, after ApoEVs are phagocytosed by phagocytes, ENPP1 on ApoEVs hydrolyzed intracellular cGAMP, which serves as an intracellular cGAMP hydrolyzation mode, thereby alleviating radiation enteritis. The findings shed light on the intracellular and extracellular hydrolysis capacity of ApoEVs and their role in inflammation regulation.

(005) MRI TECHNIQUES FOR IMAGING BIOMARKERS OF RADIATION-INDUCED DAMAGE TO FEMALE ERECTILE TISSUES AND OTHER GENITOPELVIC ORGANS

Abstract Introduction Difficulties with arousal and orgasm are common in female patients after pelvic radiation. Yet, current classifications of toxicity and normal tissues in radiation oncology account poorly for the anatomy and critical function of female erectile tissues (arousal and orgasm) with respect to patients’ capacities to continue to engage in pleasurable sexual behaviors after cancer treatment. MRI imaging biomarkers of dose-volume dependent radiation damage can provide objective measures of the impact of interventions, help predict sexual dysfunction, and allow for re-optimization of therapy for early mitigation of radiation damage to female erectile tissues. Objective The aim of this project is to develop and optimize MRI imaging techniques for female erectile tissues and other genitopelvic organs. Optimization of this MRI protocol will allow us to establish quantitative and qualitative indices of radiation damage to specific sexual organs, providing mechanistic insights into how to measure radiation damage of current and future therapies. Methods This prospective study includes two female-identifying volunteers with healthy female pelvic anatomy who underwent MRI scans using a 3.0T MRI (Prisma, Siemens Healthcare) scanner. The protocol (Table 1) included 2D T2-weighted turbo spin-echo (TSE) sequences in the axial (spatial resolution 0.5x0.5x2mm), coronal (spatial resolution 0.5x0.5x3mm), and sagittal planes (spatial resolution 0.3x0.3x2mm), T2-weighted with fat saturation in the axial plane (spatial resolution: 0.8x0.8x4mm) diffusion-weighted tensor imaging (DTI, axial plane with 30 diffusion directions and b-values 0s/mm2 and 400s/mm2, TR/TE: 3000/57ms, spatial resolution 1.3x1.3x5mm). Protocol optimization in healthy volunteers consisted of imaging without gadolinium contrast, while future imaging in patients will also include dynamic contrast-enhanced MRI (3D T1-weighted radial acquisition in the axial plane, with 4.7s temporal resolution, 20 slices, spatial resolution 0.8x0.8x2mm) and T1 mapping (axial plane variable flip angle, B1-corrected acquisition with 5 flip angles: 5, 10, 15, 20, 30 degrees, TR/TE: 5.9/2.4ms, with 0.8x0.8x2mm spatial resolution). The sexual regions of interest (ROIs) included the female external genitalia, vagina, bulboclitoris (clitoris and vestibular bulbs), pelvic neurovasculature, and pelvic floor muscles which were visualized and contoured per standard protocols. Results The axial T2-weighted TSE sequences in 2mm slices provided clear visualization of the female erectile tissues for contouring the bulboclitoris, vaginal canal, and external genitalia (Figure 1). The T2-weighted sequences with fat saturation allows us to conduct MR neurography to evaluate the three-dimensional visibility of the nerves (plexus, pudendal and cavernous), enabling us to localize and characterize nerve abnormalities with dose-dependent radiation damage (Figure 2). Perfusion time intensity curves created with the T1 DCE scans can assess changes in vasculature, and the initial areas under the time to signal intensity curve (IAUC) will act as biomarkers for erectile tissue perfusion and permeability. Additional biomarkers include ROI intensity and volume/thickness for both erectile tissues and the vagina wall, as well as fractional anisotropy for the vagina alone. Lastly, we explore the clinical applications of DTI with fiber tractography to evaluate pelvic floor musculature. Conclusions These MRI techniques will be the first to validate normal tissue toxicity imaging biomarkers for radiation damage, allowing us to objectively measure dose-dependent inflammatory, fibrotic and vasculogenic effects of radiotherapy. Disclosure No.

The Value and Safety of Adjuvant Radiation Therapy After Radical Cystectomy in Locally Advanced Urothelial Bladder Cancer: A Controlled Randomized Study

BackgroundAdjuvant radiotherapy after radical cystectomy in locally advanced bladder cancer was revived after the advancement in precise radiotherapy that decreased the normal pelvic tissue radiation hazards. However, there are still scarce controlled randomized studies addressing this issue. Patients and methodsOne hundred thirty-one cystectomized urothelial bladder cancer patients were enrolled; a hundred and twenty-two were randomized to receive adjuvant radiotherapy (ART) 50 Gy/25 fractions, 4 weeks’ post-cystectomy or cystectomy alone (CY). Sixty-two were included in the ART arm and sixty in the CY arm. Twenty-four ART and 30 CY patients received Neoadjuvant chemotherapy. Eleven patients (9%) had cotenant neo-bladder diversion, 6 in ART, and 5 in CY arms. All ART patients were treated with intensity-modulated radiotherapy (IMRT) with daily verification cone-beam CT (CBCT). The median follow-up was 42.7 months. ResultsThe 3-year adjusted Locoregional relapse-free survival (LRFS) rate was higher in the ART arm, measuring 81% (95%CI: 69-94) compared to 71% (95% CI: 60-80) (p=0.0457). ART significantly improved the locoregional relapse-free rate in the cystectomy bed and the pelvic side wall (p= 0.016 and 0.001, respectively). The overall survival, event-free, and distant metastasis-free survival did not rank to the level of statistical significance in the 2 arms. Even though the acute side effects were slightly higher in ART, the late toxicities were almost equal in the two groups. ConclusionsAdjuvant radiotherapy is safe and quite tolerable after radical cystectomy when using precise radiation techniques. These techniques significantly improved the LRFS but had insignificant improvement on the overall survival. ART did not affect the distant metastasis-free survival. Similar studies are performed in different centers around the world to confirm the value of ART in urothelial bladder cancer.

Minimally invasive versus open ileal ureter with ileocystoplasty: comparative outcomes and 5-year experience

PurposeTo present the experience of ileal ureter with ileocystoplasty (IUC), and compare the outcomes of IUC in minimally invasive procedures to open procedures.Patients and methodsFrom December 2017 to April 2023, twenty patients underwent IUC in open or minimally invasive (including laparoscopic and robotic) procedures. The baseline characteristics, perioperative data and follow-up outcomes were collected. Success was defined as relief of clinical symptoms, stable postoperative serum creatine and absence of radiographic obstruction. The perioperative and follow-up outcomes of open procedures and minimally invasive procedures were compared.ResultsThe etiology included pelvic irradiation (14/20), urinary tuberculosis (3/20) and surgical injury (3/20). Bilateral ureter strictures were repaired in 15 cases. The surgeries conducted consisted of open procedures in 9 patients and minimally invasive procedures in 11 patients. Compared to open procedures, minimally invasive surgeries had less median estimated blood loss (EBL) (100 ml vs. 300 min, p = 0.010) and shorter postoperative hospitalization (27 d vs. 13 d, p = 0.004). Two patients in the open group experienced grade 3 complications (sigmoid fistula and acute cholecystitis in one patient, and pulmonary embolism in another patient). Over a median follow-up period of 20.1 months, the median bladder functional capacity was 300 ml, with a 100% success rate of IUC.ConclusionIUC is feasible in both open and minimally invasive procedures, with acceptable complications and a high success rate. Minimally invasive procedures can have less EBL and shorter postoperative hospitalization than open procedure. However, prospective studies with larger groups and longer follow-up are needed.

Kidney transplantation after pelvic radiotherapy: Increased morbidity?

IntroductionThe impact of pelvic irradiation on kidney transplant surgery is still unclear. The main objective of our study is to evaluate the feasibility and the safety of renal transplantation following pelvic radiotherapy. MethodsWe collected characteristics and kidney transplant data from patients with a history of pelvic cancer treated with pelvic irradiation between 2005 and 2021. These data were collected via the prospective information system “Computerized Data Validated in Transplantation” (DIVAT) and medical records. We carried out a comparative study with a non-irradiated matched control group to compare the data of intraoperative surgeries, complications reported postoperatively as well as survival of the graft and the patient. Patients were matched on age, sex, side of graft implantation, and graft rank. ResultsTwenty-four patients were collected with an average age of 65, 18 patients were treated for prostatic adenocarcinoma, 4 for gynecological cancer and 2 testicular cancers. Twenty-one patients were treated by radiotherapy, 3 by brachytherapy. Eight patients had a target dose on the iliac lymph nodes. The comparative study showed a significant difference in operative difficulty (n=15 versus n=1, P<0.01), operative duration (190min versus 149min, P=0.005), occurrence of lymphocele (P=0.041). Urinary anastomosis surgical techniques were different, 83.3% of control patients had an uretero-vesical anastomosis against 58.3% of patients with a history of irradiation (P=0.057) and about 29% of irradiated patients had an uretero-ureteral anastomosis. There was no other significant difference in per and postoperative criteria or survival. DiscussionA history of pelvic irradiation significantly increases the technical complexity of kidney transplantation without impacting safety and kidney graft survival. A history of pelvic irradiation should not be a contraindication to kidney transplant. Level of evidence3.

A phase II trial of apalutamide for intermediate-risk prostate cancer and molecular correlates.

To determine whether 6 months of preoperative apalutamide for intermediate-risk prostate cancer (IRPCa) reduces the aggregate postoperative radiotherapy risk and to evaluate associations of molecular perturbations with clinical outcomes in this study cohort. Between May 2018 and February 2020, eligible patients with IRPCa (Gleason 3 + 4 or 4 + 3 and clinical T2b-c or prostate-specific antigen level of 10-20 ng/mL) were treated with apalutamide 240 mg/day for 6 months followed by radical prostatectomy (RP) in this single-arm, phase II trial. The primary endpoint was presence of any adverse pathological feature at risk of pelvic radiation (pathological T stage after neoadjuvant therapy [yp]T3 or ypN1 or positive surgical margins). Translational studies, including germline and somatic DNA alterations and RNA and protein expression, were performed on post-apalutamide RP specimens, and assessed for associations with clinical outcomes. A total of 40 patients underwent a RP, and only one patient discontinued apalutamide prior to 6 months. In all, 40% had adverse pathological features at time of RP, and the 3-year biochemical recurrence (BCR) rate was 15%, with 27.5% being not evaluable. Genomic alterations frequently seen in metastatic PCas, such as androgen receptor (AR), tumour protein p53 (TP53), phosphatase and tensin homologue (PTEN), or BReast CAncer associated gene (BRCA1/2) were underrepresented in this localised cohort. Adverse pathological features and BCR at 3-years were associated with increased expression of select cell cycle (e.g., E2F targets: adjusted P value [Padj] < 0.001, normalised enrichment score [NES] 2.47) and oxidative phosphorylation (Padj < 0.001, NES 1.62) pathways. Preoperative apalutamide did not reduce the aggregate postoperative radiation risk to the pre-specified threshold in unselected men with IRPCa. However, transcriptomic analysis identified key dysregulated pathways in tumours associated with adverse pathological outcomes and BCR, which warrant future study. Further investigation of preoperative therapy is underway for men with high-risk PCa.

Biochemical control in intermediate- and high-risk prostate cancer after EBRT with and without brachytherapy boost.

External beam radiotherapy (EBRT) with or without brachytherapy boost (BTB) has not been compared in prospective studies using guideline-recommended radiation dose and recommended androgen-deprivation therapy (ADT). In this multicenter retrospective analysis, we compared modern-day EBRT with BTB in terms of biochemical control (BC) for intermediate-risk (IR) and high-risk (HR) prostate cancer. Patients were treated for primary IR or HR prostate cancer during 1999-2019 at three high-volume centers. Inclusion criteria were prescribed ≥ 76 Gy EQD2 (α/β = 1.5 Gy) for IR and ≥ 78 Gy EQD2 (α/β = 1.5 Gy) for HR as EBRT alone or with BTB. All HR patients received ADT and pelvic irradiation, which were optional in IR cases. BC between therapies was compared in survival analyses. Of 2769 initial patients, 1176 met inclusion criteria: 468 HR (260 EBRT, 208 BTB) and 708 IR (539 EBRT, 169 BTB). Median follow-up was 49and 51months for HR and IR, respectively. BTB patients with ≥ 113 Gy EQD2Gy experienced astable, good BC outcome compared with BTB at lower doses. Patients treated with ≥ 113 Gy EQD2Gy also experienced significantly improved BC compared with EBRT (10-year BC failure rates after ≥ 113 Gy BTB and EBRT: respectively 20.4 and 41.8% for HR and 7.5and 20.8% for IR). In patients with IR and HR prostate cancer, BTB with ≥ 113 Gy EQD2Gy offered aBC advantage compared with dose-escalated EBRT and lower BTB doses.

Role of the gel spacer in safely delivering whole pelvic radiation therapy without central shielding in computed tomography-based image-guided adaptive brachytherapy for uterine cervical cancer patients

BackgroundTo protect the rectum and bladder from high dose exposure, the Japanese guidelines for managing uterine cervical carcinoma recommend pelvic irradiation with central shielding (CS). Conversely, the European Society for Radiotherapy and Oncology (ESTRO) and the American Brachytherapy Society (ABS) guidelines recommend delivering ≥ 85 Gy to high-risk clinical target volume D90 (CTVHR D90%). In this study, we investigated whether a gel spacer can enable the safe delivery of the ESTRO/ABS-recommended doses to the target while observing dose constraints for the OARs without using CS in external beam radiation therapy (EBRT). Materials and MethodsTwenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between April 2017 and May 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy expressed in the form of the equivalent dose in 2 Gy fractions (EQD2) were calculated. Treatment outcomes and incidence of adverse events were also examined. ResultsThe median cumulative CTVHR D90%, rectum D2cm3, and bladder D2cm3 were 86.6 Gy (range, 69.8–103.7), 62.9 Gy (range, 55.3–72.5), and 72.0 Gy (range, 62.9–84.1), respectively. The median follow-up was 35.9 months (range, 10.9–70.3). The 2-year local control rate was 95% (95% CI: [69–99%]). There were no CTCAE ≥Grade 3 late gastrointestinal or genitourinary adverse events. ConclusionsThe use of gel spacer can enable ESTRO/ABS-recommended dose constraints even without using CS in EBRT, with favorable outcomes and low adverse event rates.

Analysis of the fecal metagenome in pelvic radiation survivors with or without chronic gastrointestinal toxicity.

e24041 Background: Whole pelvis radiation therapy (WPRT) is often used as a definitive or adjuvant treatment in patients with genitourinary, gynecologic, and gastrointestinal (GI) malignancies. Irradiation of nearby bowel can cause acute and chronic GI symptoms, which can affect patients’ quality of life. Radiation therapy has been shown to alter the microbial flora and may select for pathogenic species, which may enhance toxicity. Characteristics of the fecal metagenome in patients with or without chronic GI toxicity is unknown. Severity of GI symptoms can vary between patients who receive a similar radiation dose to normal bowel; therefore, there is a critical need to evaluate the interaction of RT and microbial species in the development of toxicity. Methods: An institutional database was used to identify survivors that completed WPRT for prostate, gynecologic, and anal cancer within the last 5 years. Patients were excluded if they had evidence of recurrent disease requiring additional therapy. Eligible patients were asked to participate via telephone. Consenting patients provided a stool sample and completed a customized PRO-CTCAE form (scale 1-5) assessing chronic GI symptoms. Comprehensive shotgun metagenomics were performed on stool. Stool was sequenced using an Illumina NextSeq500. The fecal metagenome in patients with or without chronic GI symptoms were compared. Patients were dichotomized by PRO-CTCAE diarrhea score (0-1 [mild] vs ≥2 [moderate-severe]). Raw reads were processed with Kneaddata for trimming, Kracken2 for taxonomic profiling, and Bracken for abundance estimation for bacterial, fungal and viral genomes using sequences from the National Center for Bioinformatics to determine quantitative genus and species differences. For microbial diversity assessments, estimated inverse Simpson and Shannon indices were performed. Results: Fecal metagenome and PRO-CTCAE results were available for 13 survivors. Thirty percent (n = 4) of patients reported moderate to severe diarrhea. The mean age was 66 years, 38% were male, 46% received concurrent or adjuvant chemotherapy, and the mean time from completion of WPRT to stool analysis was 34 months (range 14-62 months). Conventional radiation bowel constraints were met for each patient. Several species were enriched in patients with mild GI toxicity. Notably, Akkermansia muciniphilia had the largest differential enrichment in patients with without chronic GI toxicity. Conclusions: In this cohort of patients, A. muciniphilia, a mucin-degrading bacteria that modulates the gut barrier integrity and mucin layer thickness, was enriched in patients with no to mild diarrhea compared to patients with moderate to severe diarrhea. A. muciniphilia supplementation has been shown to decrease systemic inflammation in Western diet-fed mice. Evaluation of A. muciniphilia as a radioprotective gut bacterium warrants further evaluation.

A prospective double-blind clinical study: Effect of probiotics and thalidomide on radiation enteritis in patients with pelvic cancer undergoing concurrent chemoradiotherapy.

e23013 Background: Radiation induced diarrhea (RID) is one of the commonest and most distressing side effects during and after radiotherapy predominantly in patients whose irradiation region is pelvis. Thalidomide reduces severity as well as the frequency indicated in RID but mechanism of action is not elucidated. Probiotics are beneficial microorganisms that may regulate flora of intestines to increase immunity and have a protective effect on RID. This pilot study was designed to ascertain effects of thalidomide and probiotics on RID in patients being subjected to pelvic irradiation. Methods: A double-blind, single-center, randomized pilot study was conducted. Patients were classified into two groups as thalidomide plus probiotics (Lactobacillus rhamnosus + Probio-M9, ) group (TP group) or plus placebo group (P group).Incidence of grade 3/4 diarrhea, was a primary endpoint of the study. Other secondary endpoints analyzed were rates and severity of diarrhea, antibiotics use, body weight, albumin, and lymphocyte changes. 31 patients undergoing pelvic radiotherapy with or without concurrent chemotherapy were randomly selected from government tertiary general hospital. Results: The incidence of grade 3/4 diarrhea was 9.5% (95% CI: 0 to 24.5%) in TP, which was significantly different from historical data of 30% to 60%. The incidence of grade 3/4 diarrhea in group P was 19.8% (95% CI: 0~41.3%). The frequency and severity of diarrhea in group TP were little less than in group P. There is no significant difference between them. Basically, the time for antibiotic use in groups P and TP was the same, with a slightly longer time from first antibiotic exposure in group TP as compared to group P. The moment of first antibiotics have been prescribed in our study patients, this was better than that of a clinical routine treatment experience and other research data according to the literature. The changes in body weight, albumin level, and lymphocyte at different stages before and after radiotherapy in group TP were not statistically significant, and the level of body weight and albumin in group P was slightly reduced compared with before radiotherapy but increased compared with group TP after radiotherapy. Furthermore, there were no severe adverse effects regarding thalidomide as well as probiotics reported among patients who participated in this study. Conclusions: The combined treatment with thalidomide and probiotics is beneficial to ameliorate RID in patients receiving pelvic radiotherapy, yet this study can't represent whole conclusion due to small size of patients. We will also need larger, multicenter double-blind placebo-controlled trials to confirm exact efficacy and safety of this combined treatment. Clinical trial information: NCT05059613 .

Natural History of Artificial Urinary Sphincter Erosion: Long-term Lower Urinary Tract Outcomes and Incontinence Management

ObjectivesTo describe long-term lower urinary tract outcomes and incontinence management after AUS erosion, including risk factors associated with each outcome. MethodsWe retrospectively reviewed our prospectively maintained AUS database for men undergoing device explantation for urethral erosion from 1/1/1986-10/31/2023. Outcomes included development of urethral stricture and management of post explant incontinence (e.g. pads/clamp, catheter, salvage AUS, supravesical diversion). Risk factors were tested for association with stricture formation and repeat AUS erosion using logistic regression. Results1943 unique patients underwent AUS implantation during the study period, and 217 (11%) had a device explantation for urethral erosion. Of these, 194 had complete records available and were included for analysis. Median follow-up from implantation was 7.5 yrs (IQR 2.7-13.7) and median time to erosion was 2 yrs (IQR 0-6). 96 patients (49%) underwent salvage AUS placement. Of those, 38/96 (40%) were explanted for subsequent erosion. On multivariable analysis, no factors were significantly associated with risk of salvage AUS erosion. On multivariable model, pelvic radiation (OR 2.7; 95% CI 1.0-7.4) and urethral reapproximation during explant for erosion (OR 4.2; 95% CI 1.5-11.2) were significantly associated with increased risk of urethral stricture (p<0.05). At the time of last follow-up, 69/194 (36%) patients had a functioning salvage AUS, including both initial and subsequent salvage implants. ConclusionsFollowing AUS erosion, radiation history and urethral reapproximation at explantation were risk factors for development of urethral stricture. Salvage AUS replacement can be performed, but has a higher rate of repeat urethral erosion.