Late Rectal Toxicity Research Articles

Image-guided brachytherapy for pediatric bladder and/or prostate rhabdomyosarcoma: toward an increased personalization of treatment.: Brachytherapy in uro-pediatric rhabdomyosarcoma

IntroductionRhabdomyosarcoma (RMS) is the most common soft tissue cancer in children. Around 15% of RMS involve the bladder and/or prostate (BP). Overall survival is around 85%. After chemotherapy, patients receive local treatment based on surgery and/or radiotherapy. In recent decades, image guidance and pulsed dose-rate (PDR) brachytherapy have made it possible to personalize treatment, reduce radiation-related toxicity, while maintaining a good tumor control. We report one of the largest series of image-guided brachytherapy for pediatric RMS BP. Material and methodsThe clinical and dosimetric parameters of children treated with brachytherapy for BP RMS between July 2014 and September 2020 were retrospectively reviewed. Patients were treated with a multimodal conservative approach, combining partial conservative surgery (preservation of the bladder neck and urethra), followed by an interstitial brachytherapy procedure. Iridium-192 PDR treatment was administered on the basis of CT and MRI planning. Toxicities were reported according to version 4.0 of the Common Terminology Criteria for Adverse Events. ResultsA total of 75 patients were identified, with a median age of 29 months (range 2–84) at diagnosis. The median brachytherapy dose was 60.06 Gy (143 pulses, 0.42 Gy/pulse). With a median follow-up of 44.1 months (range 0.7–90), the 5-year OS and PFS rates were 97.3% and 92% respectively. Median D50% for the bladder and D1cc for the rectum were 38.6 Gy and 49 Gy respectively. The 5-year probability of survival without severe late urinary toxicity (grade 3 or higher) was estimated at 78.8% (CI95%: 68.1–91.1). A total of 9.3% of children experienced grade 2 or 3 late rectal toxicity. ConclusionsImage-guided PDR brachytherapy offers a personalized treatment for pediatric BP RMS, with a favorable therapeutic index. No prognostic factors for urinary toxicity have been identified. Multicenter studies with larger numbers of patients are needed to clarify these data.

Impact of neoadjuvant androgen deprivation therapy on toxicity in intensity-modulated radiation therapy for prostate cancer.

This study aimed to compare toxicities, prostate volume and dosimetry, between patients who underwent intensity-modulated radiation therapy (IMRT) combined with ≥3months of neoadjuvant androgen deprivation therapy (NADT) and those without NADT for prostate cancer. In total, 449 patients with intermediate- and high-risk prostate cancer received 78Gy IMRT in 39 fractions, of which 129 were treated without any ADT (non-ADT group) and 320 with NADT ≥3months (NADT group). Adverse events and dose-volume indices were compared between the two groups retrospectively. The NADT group had a lower rate of acute grade 2 gastrointestinal (GI) toxicities (17% vs 25%, P = 0.063) and late grade 2 GI toxicities (P = 0.055), including a significantly lower rate of late grade 2 rectal hemorrhage (P = 0.033), compared with the non-ADT group. There were no cases of late grade 3 or higher GI toxicities. The average volume of the prostate in the NADT group was 38% smaller than that in the non-ADT group (43.7 vs 27.0cm3, P < 0.001). Bladder V40Gy and V50Gy, and rectum V40Gy, V50Gy, V60Gy and V70Gy were significantly smaller in the NADT group. In the NADT group, no significant difference was observed in adverse events or dosimetry between the subgroups with NADT ≥12 and <12months. Acute and late rectal toxicities were reduced by NADT within ≥3months in accordance with reduced prostate volume and improved rectal dosimetry. This suggests a merit of administering neoadjuvant ADT ≥3months for reducing rectal toxicities.

Helical Tomotherapy Versus 3-Dimensional Conformal Radiation Therapy in High-Risk Prostate Cancer: A Phase 3 Randomized Controlled Trial

We present long-term outcomes from a phase 3 randomized controlled trial that compared helical tomotherapy with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of high-risk prostate cancer. Newly diagnosed patients with high-risk prostate cancer were randomly allocated to receive radical radiation therapy (RT) using 3D-CRT or helical tomotherapy. In both arms, patients received an initial dose of 46 Gy in 23 fractions to the prostate and pelvic lymph nodes, followed by an additional boost to the prostate of 32 Gy in 16 fractions. RT was combined with 3 years of adjuvant androgen deprivation. The primary endpoint was late (>90 days since RT initiation) rectal toxicity. Overall,123 patients were randomly assigned to either the 3D-CRT (n = 60) or tomotherapy (n = 63) arms. The median follow-up was 161 months. Overall, the proportion of patients with grade ≥ 2 late rectal toxicity was 8.3% (95% CI, 3.1-19.1; n = 5) in the 3D-CRT arm and 11.1% (95% CI, 5.0-22.2; n = 7) in the tomotherapy arm with no significant between-arm difference (P = .83). There was no significant difference (P = .17) in the proportion of patients with late grade ≥ 2 genitourinary toxicity:10.0% (95% CI, 4.1-21.2) in the 3D-CRT arm and 20.6% (95% CI, 11.9-33.0) in the tomotherapy arm. There was no significant difference in the hazard of biochemical progression or death between the 2 groups (hazard ratio for the tomotherapy arm: 0.72; 95% CI, 0.46-1.15; P = .17). In this phase 3 trial, the overall incidence of grade ≥ 2 rectal toxicity was low and was not significantly different between the 2 arms. There was no significant evidence of improved biochemical progression-free survival in patients treated with tomotherapy. These findings should be interpreted considering the possibility of type II errors due to limited sample size and low event rates.

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.

Predictors of radiation-induced late rectal toxicity in prostate cancer treatment: a volumetric and dosimetric analysis.

Prostate cancer (PCa) is a prevalent malignancy in European men, often treated with radiotherapy (RT) for localized disease. While modern RT achieves high success rates, concerns about late gastrointestinal (GI) toxicities persist. This retrospective study aims to identify predictors for late GI toxicities following definitive conventionally fractionated external beam RT (EBRT) for PCa, specifically exploring the dose to the rectal wall. A cohort of 96 intermediate- to high-risk PCa patients underwent EBRT between 2008 and 2016. Rectum and rectum wall contours were delineated, and 3D dose matrices were extracted. Volumetric and dosimetric indices were computed, and statistical analyses were performed to identify predictors using the Mann-Whitney U-rank test, logistic regression, and recursive feature elimination. In our cohort, 15 out of 96 patients experienced grade II late proctitis. Our analysis reveals distinct optimal predictors for rectum and rectum wall (RW) structures varying with α/β values (3.0 and 2.3 Gy) across prescribed doses of 68 to 76 Gy. Despite variability, RW predictors demonstrate greater consistency, notably V68Gy[%] to V74Gy[%] for α/β 3.0 Gy, and V68Gy[%] to V70Gy[%] for α/β 2.3 Gy. The model with α/β 2.3 Gy, featuring RW volume receiving 70 Gy (V70Gy[%]), stands out with a BIC value of 62.92, indicating its superior predictive effectiveness. Finally, focusing solely on the rectum structure, the V74Gy[%] emerges the best predictor for α/β 3.0 Gy, with a BIC value of 66.73. This investigation highlights the critical role of V70Gy[%] in the rectum wall as a robust predictor for grade II late gastrointestinal (GI) toxicity following external beam radiation therapy (EBRT) for prostate cancer (PCa). Furthermore, our findings suggest that focusing on the rectum wall specifically, rather than the entire rectum, may offer improved accuracy in assessing proctitis development. A V70Gy (in EQD2 with α/β 2.3 Gy) of ≤5% and if possible ≤1% for the rectal wall should be achieved to minimize the risk of late grade II proctitis.

Comprehensive 3DCRT Hypofractionated Radiotherapy Schedule for Localized Prostate Adenocarcinoma in the Era of IMRT: Dosimetric and Endoscopic Analysis.

Background: Moderate hypofractionated radiotherapy (MHRT) has emerged as the preferred treatment modality for localized prostate cancer based on randomized controlled studies regarding efficacy and toxicity using contemporary radiotherapy techniques. In the setting of MHRT, available data on dosimetric parameters and late rectal toxicity are limited. Aim: To present the effects of MHRT on late rectal toxicity while conducting an extensive dosimetric analysis in conjunction with rectoscopy results. Methods: This is a prospective study including patients with intermediate-risk prostate adenocarcinoma. All patients were treated with MHRT 44 Gy in 16 fractions to the seminal vesicles and to the prostate, followed by a sequential boost to the prostate alone of 16.5 Gy in 6 fractions delivered with three-dimensional conformal radiation therapy (3DCRT). Acute and late toxicity were assessed. Endoscopy was performed at baseline, every 3 months post-therapy for the first year, and every 6 months for the year after. The Vienna Rectoscopy Score (VRS) was used to assess rectal mucosal injury related to radiotherapy. Dosimetric analysis for the rectum, rectal wall, and its subsegments (upper, mid, and low 1/3) was performed. Results: Between September 2015 and December 2019, 20 patients enrolled. Grade 1 late gastrointestinal toxicity occurred in 10% of the patients, whereas 5% had a grade ≥2. Twelve months post radiotherapy: 4 (20%) patients had VRS 1; 2 (10%) patients had VRS 2; 1(5%) patient had VRS 3. 24 months post radiotherapy, VRS 1 was observed in 4 patients (20%) and VRS 2 in 3 (15%) patients. The dosimetric analysis demonstrated noticeable variations between the rectum, rectal wall, and rectal wall subsegments. The dosimetric analysis of the rectum, rectal wall, and its mid and low segments with respect to rectoscopy findings showed that the higher dose endpoints V52.17Gy and V56.52Gy are associated with rectal mucosal injury. Conclusions: A thorough delineation of the rectal wall and its subsegments, together with the dosimetric analysis of these structures, may reduce late rectal toxicity. Dosimetric parameters such as V52.17Gy and V56.52Gy were identified to have a significant impact on rectal mucosal injury; additional dose endpoint validation and its relation to late GI toxicity is needed.

Neoadjuvant short-course radiotherapy or chemoradiation plus consolidative chemotherapy followed by radical operation for locally advanced rectal cancer.

Limited evidence compares short-course radiotherapy (SCRT) and long-course chemoradiotherapy (LCCRT), both of which are followed by consolidative chemotherapy before radical rectal surgery. We conducted a retrospective cohort study to assess treatment response, survival outcomes, and toxicity in patients with locally advanced rectal cancer. Patients (cT3-4 and/or N+) treated with SCRT or LCCRT, consolidative chemotherapy, or total mesorectal excision between 2013 and 2021 were identified. the cause-specific cumulative incidence of disease-related treatment failure, locoregional recurrence, distant metastases, and overall survival were evaluated using flexible parametric competing risk analysis and Kaplan-Meier methods, adjusted for treatment regimens and clinicopathological factors. A pathological complete response (pCR), tumor downstaging, and toxicity have been reported. Among the 144 patients, 115 (80%) underwent curative rectal surgery. The LCCRT and SCRT groups achieved pCR in 10 (18%) and seven (12%) patients, respectively (odds ratio, 1.68; 95% confidence interval [CI], 0.59-4.78). The adjusted cause-specific hazard ratio for disease-related treatment failure with LCCRT versus SCRT was 0.26 (95% CI, 0.08-0.87). Three-year cumulative probability of disease-related treatment failure was 10.0% and 25.6% for LCCRT and SCRT, respectively. No significant differences in T-downstaging, N-downstaging, significant pathologic downstaging (ypT0-2N0), locoregional failure, distant metastasis, or overall survival were found. Late rectal toxicity occurred in 10 (15%) LCCRT and two (3%) SCRT patients, respectively. LCCRT with consolidative chemotherapy demonstrated improved disease-related treatment failure compared with SCRT, despite higher late rectal toxicity. Further research is needed to assess the long-term oncologic outcomes and toxicity.

Toxicity profile and Patient-Reported outcomes following salvage Stereotactic Ablative Radiation Therapy to the prostate Bed: The POPART multicentric prospective study

BackgroundWhile SBRT to the prostate has become a valuable option as a radical treatment, limited data support its use in the postoperative setting. Here, we report the updated results of the multicentric Post-Prostatectomy Ablative Radiation Therapy (POPART) trial, investigating possible predictors of toxicities and patient-reported outcomes. MethodsPatients with PSA levels between 0.1–2.0 ng/mL after radical prostatectomy received Linac-based SBRT to the prostate bed in five fractions every other day for a total dose of 32.5 Gy (EQD21.5 = 74.3 Gy). Late toxicity was assessed using CTCAE v.5 scale, while EPIC-CP, ICIQ-SF, IIEF 5 questionnaires and PSA levels measured quality of life and biochemical control. Pre- and post-treatment scores were compared using a paired t-test, with MID established at > 0.5 pooled SD from the baseline. A logistic regression analysis was performed to evaluate potential associations between specific patient/tumor/treatment factors and outcome deterioration. ResultsFrom April 2021 to April 2023 a total of 50 pts were enrolled and treated. Median follow-up was 12.2 (3–27) months. No late ≥ G2 GI or GU toxicity was registered. Late G1 urinary and rectal toxicities occurred in 46 % and 4 % of patients, respectively. Among 47 patients completing all EPIC-CP domains, four (9 %) showed worsened QoL, and eleven (26 %) developed erectile dysfunction correlating with PTV D2% (P = 0.032). At Multivariate analysis bladder wall D10cc independently correlated with late G1 GU toxicity (P = 0.034). Median post-treatment PSA nadir was 0.04 ng/mL (0.00 – 0.84). At the last follow-up, six patients presented with biochemical failure, including two nodal relapses. ConclusionsOur findings show that post-prostatectomy SBRT did not result in increased toxicity nor a significant decline in QoL measures, thus showing that it can be safely extended to the postoperative setting. Long-term follow-up and randomized comparisons with different RT schedules are needed to validate this approach.

Stereotactic body radiotherapy with CyberKnife® System for low- and intermediate-risk prostate cancer: clinical outcomes and toxicities of CyPro Trial.

Stereotactic body radiotherapy (SBRT) of 35-36.25 Gy in five fractions with the CyberKnife System yields excellent control with low toxicity in low-intermediate-risk prostate cancer patients. We found no differences in biochemical control and overall survival in relation to dose. There were no significant differences in toxicity or quality of life between the two groups. Stereotactic body radiotherapy (SBRT) is an emerging therapeutic approach for low- and intermediate-risk prostate cancer. We present retrospective data on biochemical control, toxicity, and quality of life of CyPro Trial. A total of 122 patients with low- and intermediate-risk prostate cancer were treated with the CyberKnife System at a dose of 35 Gy or 36.25 Gy in five fractions. Biochemical failure (BF)/biochemical disease-free survival (bDFS) was defined using the Phoenix method (nadir + 2 ng/ml). Acute/late rectal and urinary toxicities were assessed by the Radiation Therapy Oncology Group (RTOG) toxicity scale. Quality of life (QoL) was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and PR25. International Erectile Function Index-5 (IIEF5) and International Prostate Symptom Score (IPSS) questionnaires were administered at baseline, every 3 months after treatment during the first years, and then at 24 months and 36 months. The 1-, 2-, and 5-year DFS rates were 92.9%, 92.9%, and 92.3%, respectively, while the 1-, 2-, and 5-year bDFS rates were 100%, 100%, and 95.7%, respectively. With regard to risk groups or doses, no statistically significant differences were found in terms of DFS or bDFS. Grade 2 urinary toxicity was acute in 10% and delayed in 2% of patients. No Grade 3 acute and late urinary toxicity was observed. Grade 2 rectal toxicity was acute in 8% and late in 1% of patients. No Grade 3-4 acute and late rectal toxicity was observed. Grade 2 acute toxicity appeared higher in the high-dose group (20% in the 36.25-Gy group versus 3% in the 35-Gy group) but was not statistically significant. Our study confirms that SBRT of 35-36.25 Gy in five fractions with the CyberKnife System produces excellent control with low toxicity in patients with low-intermediate-risk prostate cancer. We found no dose-related differences in biochemical control and overall survival. Further confirmation of these results is awaited through the prospective phase of this study, which is still ongoing.

Assessment of rectal toxicities after radiation therapy for localized prostate cancer: experience of the Akanda Cancer Institute in Gabon.

The purpose was to evaluate the incidence of acute and late rectal toxicities and their correlation with the clinical and dosimetric parameters of patients who underwent curative radiotherapy for localized prostate cancer at the Akanda Cancer Institute, Gabon. Between 2013 and 2021, a cohort of 46 patients with clinically localized stage cT1c-T4 prostate cancer was treated with three-dimensional conformal radiation therapy (3D-CRT) at the national cancer institute with doses ranging from 66 to 80 Gy. Post-radiation gastrointestinal (GI) toxicities were classified and graded according to the Common Terminology Criteria for Adverse Events CTCAE v4.0. In our study, 17.4% (8/46) developed acute GI. Grades 1 and 3 acute GI complications were seen in 13.0% (6/46) and 4.3% (2/46), respectively. No patient developed acute grade 2 or grade higher than 3 complications. Late GI side effects were limited. The median time to the development of late GI Grade ≥ 1 toxicities was 12 months (range: 9-19 months). 10.9% (5/46) had experience late GI. Among them, grade 1 and 2 were seen in 6.5% (3/46), and 4.3% (2/46), respectively. There was no grade 3 or higher complications. Statistically, we did not find any correlation between the presence of rectal toxicity and clinical factors or the presence of comorbidity. On the dosimetric level, the Mann-Whitney statistical test found a correlation between the presence of late GI toxicity and rectal volume irradiated at the prescribed dose (p = 0.02). Despite the high radiation doses involved, our results showed an acceptable complication rate.

Dose Escalation Using Magnetic Resonance Guided High-Dose-Rate Endorectal Brachytherapy to Enhance Clinical Response after Neoadjuvant Radiotherapy in Rectal Adenocarcinoma

To assess the proportion of patients with rectal adenocarcinoma achieving clinical complete response after neoadjuvant chemoradiation (NACTRT) and MR guided endorectal brachytherapy boost (MR-ERBT) MATERIALS/METHODS: Patients with rectal cancers (T2-T4/N0-N+) treated with concurrent chemoradiotherapy (50Gy/25# with Capecitabine) between June-2017 to April-2022. Post RT, patients having residual non-circumferential lesions <8cm in length were administered escalated-dose MR-ERBT with Ir192 HDR source. A median dose of 12Gy (8-15Gy) in 3 (2-3) fractions at 3-5 day intervals was delivered using MR-ERBT after external radiation. Data on near complete/complete clinical response (nCR/cCR) rates, local regrowth rates and clinical outcome were collected for analysis. Of the 145 patients who received MR-ERBT, majority were staged as T3(78.7%) and N1-2 (77.5%) rectal cancers. Median tumor length was 4cm and 123 (85%) of the tumors were located in the lower rectum (0-5cm from anal verge). Seventy-six (52%) patients achieved cCR or nCR (37 cCR, 39 nCR) and were advised observation or watch and wait (WW) management. The 69 patients having partial response were advised surgery. The patients having nCR 16 (29%) underwent resection, of these 10 (62%) had pathological complete response (pCR). The patients with partial or poor response, 57 underwent resection and of these 11 (19%) had pCR, 12 patients refused surgery due to fear of permanent stoma and continued to be on follow up. Of the 79 patients undergoing resection, 36 (45.5%) had sphincter preserving surgeries. At the median follow up of 30 months, local regrowth was seen in 8 (10.5%) of patients on WW and 6 were surgically salvaged while other 2 had synchronous metastatic relapse. Thus, 56 (41%) achieved organ preservation and continued to be on WW management. Twelve (8,2%) patients developed distant metastasis in the entire cohort, 3 in the WW group and 9 in the resected group. There were no pelvic recurrences seen in the resected patients. The disease-free survival at 3 years were (96.1% vs 89% Observation vs. resected (p_0.05) respectively. The overall survival at 3 years were (93% vs 98% Observation vs. resected (p_0.44) respectively. Late rectal toxicity was observed in 16(11%) patients on observation CONCLUSION: Dose Escalated MR-EBRT is an effective and safe method to enhance complete clinical response, thus improving the rate of organ preservation for distal rectal cancers.

Long-Term Anorectal Function in Rectal Cancer Patients Managed by a Watch-and-Wait Strategy after Neoadjuvant Therapy: A Cross-Sectional Study

Rectal cancer patients reaching complete clinical response (cCR) after neoadjuvant chemoradiotherapy can be offered a nonoperative watch-and-wait (W&W) strategy. As evidence of good oncological outcomes accumulates, the functional outcomes remain less explored. The aim of this study is to comprehensively assess the long-term rectal toxicity and anorectal function in patients managed by a W&W strategy and to investigate the clinical risk factors for anorectal dysfunction. Seventy W&W patients who were disease-free at the moment of recruitment were included. A minimum 2-year follow-up was considered. We graded late rectal toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale and the Late Effects of Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) system. Long-term anorectal function was assessed with the Wexner score, the Low Anterior Resection Syndrome score (LARS score), and the Memorial Sloan Kettering Bowel Function Instrument (MSK BFI). All patients received standard chemoradiotherapy consisting of a total dose of 5000 cGy in 25 fractions. The median tumor distance from the anal verge was 3 (IQR 2-4) cm. After a median follow-up of 43 (IQR 28-66) months, less than half of patients developed Grade 1 (40.0%) or Grade 2 (1.4%) late rectal toxicity, and no patients complained of higher grades. LENT/SOMA criteria also identified more patients with mild symptoms. The most frequent symptoms were sphincter control problems, mainly manifested as fecal urgency, reported by 60.0% of patients. For long-term anorectal function, the median LARS score was 16 (IQR 4-25). 17.1% of patients reported minor LARS and 15.7% reported major LARS. The median Wexner score was 2 (IQR 0-3). The median MSK BFI total score was 82 (IQR 77-86). Smoking history was an independent risk factor for anorectal dysfunction in multivariate analyses (OR = 6.491, 95% CI 1.536-27.432). Rectal cancer patients managed by a watch-and-wait strategy after neoadjuvant chemoradiotherapy have retained satisfactory anorectal function. However, fecal urgency might be a common problem. Smoking history was an independent risk factor for long-term anorectal dysfunction. Prospective studies with emphasis on bowel function outcomes containing a larger number of patients are needed.

Effect of Daikenchuto Therapy on Risk of Rectal Bleeding after IMRT for Prostate Cancer

Rectal bleeding due to radiation proctitis after treatment in radiation therapy for prostate cancer is a typical late toxicity symptom. The rate of rectal bleeding has been reduced by using IMRT, IGRT and peri-rectal hydrogel spacer. On the other hand, few reports have attempted to reduce the rate of rectal bleeding by medication. It has been reported that Daikenchuto (DKT), a traditional Japanese herbal medicine, has the effects of accelerating gastrointestinal motility and anti-fibrosis. We retrospectively investigated the rate of rectal bleeding in patients between concurrently administered and not administered DKT for bowel control during IMRT for prostate cancer. The subjects were 102 patients who underwent definitive IMRT for prostate cancer between 2014 and 2021 in our hospital. The DKT therapy concurrent use group were included 46 patients (45%), who were administered DKT per 10.0 g / day or 15.0 g / day. The irradiation was carried out, confirming the rectal volume every time by the image-guided radiotherapy using cone beam CT in all cases. The curative doses fractionation of IMRT were 78 Gy in 2 Gy per fraction (40%) or 70 Gy in 2.5 Gy per fraction (60%). We compared the rate of rectal bleeding after IMRT with and without DKT. Late rectal bleeding toxicity was scored using the Common Terminology Criteria for Adverse Events ver. 5.0 criteria. The associated factors of rectal bleeding were examined using the Cox proportional hazard model for multivariate analysis. In the DKT therapy group, the median follow-up period was 31 months (Range: 17-84 months), and the rectal bleeding rate was Grade 1 in 2 patients (4%) and Grade ≥ 2 in none. The median observation period in the non-DKT therapy group was 48 months (Range: 17-101 months), and the rectal bleeding rate was Grade 1 in 12 patients (21%), Grade 2 in 6 patients (10%), and there were no events of Grade ≥ 3. In univariate analysis, DKT therapy, dose fractionation and planned rectal doses (V50, V55, V60, V65, V70 and V75 converted to EQD23) were significant factors for rectal bleeding. Multivariate analysis showed that the DKT therapy was a significant independent factor in reducing the rate of rectal bleeding (HR: 0.105, 95% CI: 0.01-0.50, P = 0.003). It was statistically suggested in this study that the DKT therapy further reduced the rate of rectal bleeding in IMRT for prostate cancer.

Reirradiation with advanced brachytherapy techniques in recurrent GYN cancers

PurposeTo evaluate clinical outcomes of recurrent gynaecological cancers treated with reirradiation (reRT) using advanced brachytherapy (BT) technique. Methods and MaterialsSeventy-six women who underwent reRT with BT for gynaecological cancers at our institute between January 2000 and December 2019 were analysed to determine patient, disease and treatment characteristics and clinical outcomes. Descriptive analysis was used for demographics, and the Kaplan Meir method was used for survival analysis. ResultsMedian age at recurrence was 55 years (Range: 35–73). Forty-three patients had recurrent cervical cancer with intact uterus, and 33 had recurrent vault/vaginal cancers post adjuvant RT. Eight patients received EBRT prior to BT (Range: 30–50Gy). Twenty-two patients (28.9%) received salvage chemotherapy before consideration of brachytherapy. Brachytherapy application was done using MUPIT in 38, Vienna applicator in 20, Syed Neblett in 8, central vaginal cylinder in 3, multicatheter intravaginal applicator in 2, tandem-ovoids in 4 and Houdek applicator in 1 patient. Median cumulative EQD2 for all courses of radiation was 108 Gy (IQR 92-123 Gy). At median follow up of 39 months, local control (LC), progression-free survival (PFS) and Overall survival (OS) at 2-years was 60%, 56.3%, and 72.9 respectively. Patients who had recurrences beyond 2 years had significantly better OS compared to early recurrences. Patients who received BT doses >40 Gy had a higher LC and PFS. Grade 3 to 4 late rectal toxicity was seen in 10 (13%), bladder toxicity in 6 (8%) and vaginal fibrosis in 24 (31%) patients. ConclusionThe use of advanced BT approach in reirradiation setting is a feasible and safe option in treatment of post-treatment recurrent cervical, endometrial, and vaginal cancers.

Locally advanced cervical cancer: how the improvement in techniques in external beam radiotherapy and brachytherapy impacts on survival outcomes and long-term toxicities.

Platinum-based chemoradiotherapy and brachytherapy are the standard treatment for locally advanced cervical cancer. Reported long-term outcomes for treated with both IMRT and 3D-Image-guided-adaptive brachytherapy are lacking. This retrospective study included 165 patients with FIGO Stage IB-IVB cervical cancer, treated with chemoradiotherapy in combination with brachytherapy. External beam radiotherapy was delivered as IMRT/VMAT/TOMO helical or 3DCRT. The intracavitary brachytherapy treatment (ICBT) was performed using two different planning system (with or without optimization). Among the patient subgroups, comprising those who received IMRT/VMAT/Tomo helical and 3DCRT, as well as those who underwent ICBT planning optimization and those who did not, homogeneity was observed in terms of age, performance status, T stage, N status, TNM stage, and histology. With a median follow-up time of 60.5months, the 5-year overall survival (OS) in the 3DCRT and IMRT groups was 74.9% and 92.8%, respectively (p = 0.033). The 5-year OS in the ICBT planning optimization group was 93.7%, compared to 75% in the non-optimization group (p = 0.014). Regarding late radiation toxicities, patients in the IMRT group had a lower incidence of chronic rectal toxicity compared to those in the 3DCRT group (6.5% vs. 34.1%, p = 0.001). The group with ICBT planning optimization had a lower incidence of late urinary toxicities (10.4%) compared to the non-optimized ICBT planning group (18.2%, p = 0.012). Similarly, the ICBT planning optimization group had a lower incidence of late rectal toxicity (6.5% with 80% grade 1 and 20% grade 2) compared to the non-optimized ICBT planning group (34.1%, p = 0.001). In this series, the group of patients receiving optimized ICBT had an advantage in terms of OS and CSS suggesting that the use of new Treatment Planning Systems associated with 3D imaging, improves the long-term survival. Additionally, a significant reduction in late rectal and urinary toxicity has been observed.

Retrospective Analysis of Clinical Outcomes of Stereotactic Body Radiation Therapy for Localized Prostate Cancer at an Asian Cancer Specialist Centre.

The current treatment options for localized prostate cancer are radical prostatectomy and external beam radiotherapy (EBRT) with stereotactic body radiation therapy (SBRT) gaining interest as a treatment option compared to standard fractionation radiation therapy. This present study is a retrospective study evaluating the correlations between the biochemical efficacy, and treatment toxicity in SBRT for localized prostate cancer. All organ-confined prostate cancer patients treated with SBRT from 2010 to 2018, at Beacon Hospital, Malaysia were included in this study. Patient demographics, dosimetric parameters, and disease information were retrospectively collected. The primary endpoint was biochemical recurrence-free survival assessed using the Phoenix definition (Nadir + 2 ng/mL). Toxicity outcomes were scored using the Radiation Therapy Oncology Group scale. Fourty-nine patients who met the inclusion criteria (5 low-, 13 intermediate- and 31 high-risk according to the D'amico Risk Classification) received SBRT. The most common dose regime was 34-35Gy in 5 fractions (n=18). Other dose regimes were 24Gy in 3 fractions and 25-33Gy in 5 fractions. Median follow-up was 45.4 months. The median pre-treatment prostate-specific antigen (PSA) was 11.22 ng/mL, which decreased to a median PSA of 0.1 ng/mL by 2 years post-treatment. Out of the 49 cases, only 1 case of biochemical recurrence occurred, yielding a 3- and 5-year overall survival of 100%, and a 3- and 5- year biochemical recurrence-free rate of 100% and 95.2%. Acute grade III urinary toxicities occurred in 1 (2%); whereas acute grade I urinary and rectal toxicities were seen in 22 (44.9%) and 7 (14.3%) patients respectively. Grade I and grade III late rectal toxicities occurred in 3 and 1 patients respectively, while 3 and 1 patient reported late grade I and III urethral stricture respectively. SBRT for clinically-localized and locally advanced prostate cancer provided promising outcomes with low toxicity and good biochemical control.

Quality Metric to Assess Adequacy of Hydrogel Rectal Spacer Placement for Prostate Radiation Therapy and Association of Metric Score With Rectal Toxicity Outcomes

Although hydrogel spacer placement (HSP) minimizes rectal dose during prostate cancer radiation therapy, its potential benefit for modulating rectal toxicity could depend on the achieved prostate-rectal separation. We therefore developed a quality metric associated with rectal dose reduction and late rectal toxicity among patients treated with prostate stereotactic body radiation therapy (SBRT). A quality metric consisting of prostate-rectal interspace measurements from axial T2-weighted magnetic resonance imaging simulation images was applied to 42 men enrolled in a multi-institutional phase 2 study using HSP with prostate SBRT (45 Gy in 5 fractions). A score of 0, 1, or 2 was assigned to a prostate-rectal interspace measurement of <0.3 cm, 0.3 to 0.9 cm, or ≥1 cm, respectively. An overall spacer quality score (SQS) was computed from individual scores at rectal midline and ±1 cm laterally, located at the prostate base, midgland, and apex. Associations of SQS with rectal dosimetry and late toxicity were evaluated. The majority of the analyzed cohort had an SQS of 1 (n=17; 41%) or 2 (n=18; 43%). SQS was associated with maximum rectal point dose (rectal Dmax; P=.002), maximum dose to 1 cc of rectum (D1cc; P=.004), and volume of rectum receiving ≥100% of prescription dose (V45; P=.046) and ≥40 Gy (V40; P=.005). SQS was also associated with a higher incidence of (P=.01) and highest-graded late rectal toxicity (P=.01). Among the 20 men who developed late grade ≥1 rectal toxicity, 57%, 71%, and 22% had an SQS of 0, 1, and 2, respectively. Men with an SQS of 0 or 1 compared with 2 had 4.67-fold (95% CI, 0.72-30.11) or 8.40-fold (95% CI, 1.83-38.57) greater odds, respectively, of developing late rectal toxicity. We developed a reliable and informative metric for assessing HSP, which appears to be associated with rectal dosimetry and late rectal toxicity after prostate SBRT.

Is an Endorectal Balloon Beneficial for Rectal Sparing after Spacer Implantation in Prostate Cancer Patients Treated with Hypofractionated Intensity-Modulated Proton Beam Therapy? A Dosimetric and Radiobiological Comparison Study.

The aim of this study is to examine the dosimetric influence of endorectal balloons (ERB) on rectal sparing in prostate cancer patients with implanted hydrogel rectum spacers treated with dose-escalated or hypofractionated intensity-modulated proton beam therapy (IMPT). Ten patients with localized prostate cancer included in the ProRegPros study and treated at our center were investigated. All patients underwent placement of hydrogel rectum spacers before planning. Two planning CTs (with and without 120 cm3 fluid-filled ERB) were applied for each patient. Dose prescription was set according to the h strategy, with 72 Gray (Gy)/2.4 Gy/5× weekly to prostate + 1 cm of the seminal vesicle, and 60 Gy/2 Gy/5× weekly to prostate + 2 cm of the seminal vesicle. Planning with two laterally opposed IMPT beams was performed in both CTs. Rectal dosimetry values including dose-volume statistics and normal tissue complication probability (NTCP) were compared for both plans (non-ERB plans vs. ERB plans). For ERB plans compared with non-ERB, the reductions were 8.51 ± 5.25 Gy (RBE) (p = 0.000) and 15.76 ± 11.11 Gy (p = 0.001) for the mean and the median rectal doses, respectively. No significant reductions in rectal volumes were found after high dose levels. The use of ERB resulted in significant reduction in rectal volume after receiving 50 Gy (RBE), 40 Gy (RBE), 30 Gy (RBE), 20 Gy (RBE), and 10 Gy (RBE) with p values of 0.034, 0.008, 0.003, 0.001, and 0.001, respectively. No differences between ERB and non-ERB plans for the anterior rectum were observed. ERB reduced posterior rectal volumes in patients who received 30 Gy (RBE), 20 Gy (RBE), or 10 Gy (RBE), with p values of 0.019, 0.003, and 0.001, respectively. According to the NTCP models, no significant reductions were observed in mean or median rectal toxicity (late rectal bleeding ≥ 2, necrosis or stenosis, and late rectal toxicity ≥ 3) when using the ERB. ERB reduced rectal volumes exposed to intermediate or low dose levels. However, no significant reduction in rectal volume was observed in patients receiving high or intermediate doses. There was no benefit and also no disadvantage associated with the use of ERB for late rectal toxicity, according to available NTCP models.

Predictive modelling for late rectal and urinary toxicities after prostate radiotherapy using planned and delivered dose.

Normal tissue complication probability (NTCP) parameters derived from traditional 3D plans may not be ideal in defining toxicity outcomes for modern radiotherapy techniques. This study aimed to derive parameters of the Lyman-Kutcher-Burman (LKB) NTCP model using prospectively scored clinical data for late gastrointestinal (GI) and genitourinary (GU) toxicities for high-risk prostate cancer patients treated using volumetric-modulated-arc-therapy (VMAT). Dose-volume-histograms (DVH) extracted from planned (DP) and accumulated dose (DA) were used. DP and DA obtained from the DVH of 150 prostate cancer patients with pelvic-lymph-nodes irradiation treated using VMAT were used to generate LKB-NTCP parameters using maximum likelihood estimations. Defined GI and GU toxicities were recorded up to 3-years post RT follow-up. Model performance was measured using Hosmer-Lemeshow goodness of fit test and the mean area under the receiver operating characteristics curve (AUC). Bootstrapping method was used for internal validation. For mild-severe (Grade ≥1) GI toxicity, the model generated similar parameters based on DA and DP DVH data (DA-D50:71.6 Gy vs DP-D50:73.4; DA-m:0.17 vs DP-m:0.19 and DA/P-n 0.04). The 95% CI for DA-D50 was narrower and achieved an AUC of >0.6. For moderate-severe (Grade ≥2) GI toxicity, DA-D50 parameter was higher and had a narrower 95% CI (DA-D50:77.9 Gy, 95% CI:76.4-79.6 Gy vs DP-D50:74.6, 95% CI:69.1-85.4 Gy) with good model performance (AUC>0.7). For Grade ≥1 late GU toxicity, D50 and n parameters for DA and DP were similar (DA-D50: 58.8 Gy vs DP-D50: 59.5 Gy; DA-n: 0.21 vs DP-n: 0.19) with a low AUC of<0.6. For Grade ≥2 late GU toxicity, similar NTCP parameters were attained from DA and DP DVH data (DA-D50:81.7 Gy vs DP-D50:81.9 Gy; DA-n:0.12 vs DP-n:0.14) with an acceptable AUCs of >0.6. The achieved NTCP parameters using modern RT techniques and accounting for organ motion differs from QUANTEC reported parameters. DA-D50 of 77.9 Gy for GI and DA/DP-D50 of 81.7-81.9 Gy for GU demonstrated good predictability in determining the risk of Grade ≥2 toxicities especially for GI derived D50 and are recommended to incorporate as part of the DV planning constraints to guide dose escalation strategies while minimising the risk of toxicity.

Multi-Factor Analysis and Prediction of Late Rectal Toxicity after Radiotherapy for Cervical Cancer

<h3>Purpose/Objective(s)</h3> This study is to explore the role of clinical and dosimetric parameters in predicting grade 2-4 rectal toxicity after intensity modulated radiotherapy and three-dimensional image-guided brachytherapy for patients with locally advanced cervix cancer. <h3>Materials/Methods</h3> A total of 104 patients with cervical cancer who were treated with radiotherapy and experienced late rectal toxicity from January 2016 to October 2021 were collected. late toxicity was defined as toxicity occurring or lasting more than 3 months after initiation of treatment and graded according to Common Toxicity Criteria for Adverse Events (CTCAE version 5.0). Collect the general clinical characteristics (age, pathological type, clinical stage, history of Cardiovascular diseases, radiotherapy type(radical/adjuvant radiotherapy), the dose of External therapy and brachytherapy, cycles of concurrent or adjuvant chemotherapy, etc.),and dosimetric factors data of the rectum(V5-V50, Dmin, Dmean, Dmax, D0.1 cc, D1 cc, D2 cc, D5 cc, etc.) of patients after radiotherapy, and statistically analyze the relationship between clinical factors, dosimetric factors, and grade 2-4 rectal toxicity. the statistical methods we used include independent sample t test, chi-square test, non-parametric rank sum test, binary logistic regression analysis, etc. <h3>Results</h3> The ratio of grade 2-4 rectal toxicity in the whole group was 42.31%(44/104).Univariate analysis showed that the occurrence of grade 2-4 rectal toxicity was significantly correlated with radiotherapy type (radical/adjuvant radiotherapy),brachytherapy dose, rectum V45,D2cc and D5cc.Factors with statistical significance (P <0.05) from univariate analysis were included in the multivariate analysis to show that rectum V45,D2cc and D5cc were independent risk factors for late rectal toxicity of grade 2-4(P=0.04,0.032 and 0.014).The ROC curve analysis is used to evaluate the combined detection of rectum V45,D2cc and D5cc,the area under the ROC curve for the dose, rectum occurrence of grade 2-4 rectal toxicity was 0.727 (95 %CI: 0.630-0.823,P<0.001),the best cut-off value was 0.355, the sensitivity was 0.707, and the specificity was 0.650. <h3>Conclusion</h3> In this study, V45, D2cc and D5cc were independent risk factors for late grade 2-4 rectal toxicity. A prediction mode was created on multivariable analysis, with three dose-volume parameters predictive of late grade 2-4 rectal toxicity.