Late Gastrointestinal Toxicity Research Articles

Stereotactic body radiotherapy with a focal boost to the intraprostatic tumor for intermediate and high risk prostate cancer: 5-year efficacy and toxicity in the hypo-FLAME trial

BackgroundThe addition of an integrated focal boost to the intraprostatic lesion is associated with improved biochemical disease-free survival (bDFS) in patients with intermediate- and high-risk prostate cancer (PCa) in conventionally fractionated radiotherapy. Furthermore, whole gland stereotactic body radiotherapy (SBRT) demonstrated to be non-inferior to conventional radiotherapy for low- and intermediate-risk PCa. To investigate the combination of ultra-hypofractionated prostate SBRT with iso-toxic focal boosting for intermediate- and high-risk PCa, we performed the hypo-FLAME trial. MethodsPatients with intermediate- or high-risk PCa were enrolled in the phase II hypo-FLAME trial. All patients were treated with 35 Gy in 5 weekly fractions to the whole prostate gland with an iso-toxic integrated boost up to 50 Gy to the multiparametric MRI-defined tumor(s). If the dose constraints to the normal tissues would be exceeded, these were prioritised over the focal boost dose. The current analysis reports on the 5-year bDFS, late toxicity and health-related quality of life (HRQoL). ResultsBetween 2016 and 2018, 100 men were treated with a median follow-up of 61 months. The estimated 5-year bDFS (95 % CI) was 93 % (86 % to 97 %). At 5 years, the prevalence of grade 2 + genitourinary and gastrointestinal toxicity was 12 % and 4 %, respectively. ConclusionUltra-hypofractionated focal boost SBRT is associated with encouraging biochemical control rates up to 5-year follow-up in patients with intermediate- and high-risk PCa. Furthermore, prostate SBRT with iso-toxic focal boosting is associated with acceptable late genitourinary and gastrointestinal toxicity rates.

Physician reported toxicities and patient reported quality of life of transperineal ultrasound-guided radiotherapy of prostate cancer

PurposeThis study aims to address therapy-related toxicities and quality of life in prostate cancer patients undergoing transperineal ultrasound (TPUS) guided radiotherapy (RT). MethodsAcute and late gastrointestinal (GI) and genitourinary (GU) toxicities were assessed by physicians using CTCAE v5.0. Patient-reported quality of life outcomes were evaluated using EORTC QLQ-C30, -PR25 and IPSS. We utilized Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) as the RT technique for this study. The assessments were carried out before RT, at RT end, 3 months after RT and subsequently at 1-year intervals. Prostate-specific antigen (PSA) was also evaluated at each follow-up. ResultsIn this study, a total of 164 patients were enrolled, while among them, 112 patients delivered quality-of-life data in a prospective evaluation. The median pre-treatment PSA was 7.9 ng/mL (range: 1.8–169 ng/ml). At the median follow-up of 19 months (3–82 months), the median PSA decreased to 0.22 ng/ml. Acute grade II GI and GU toxicities occurred in 8.6 % and 21.5 % patients at RT end. Regarding late toxicities, 2.2 % patients experienced grade II GI toxicities at 27 months and only one patient at 51 months, whereas no grade II GU late toxicities were reported at these time points. Quality of life scores also indicated a well-tolerated treatment. Patients mainly experienced acute clinically relevant symptoms of fatigue, pain, as well as deterioration in bowel and urinary symptoms. However, most symptoms normalized at 3 months and remained stable thereafter. Overall functioning showed a similar decline at RT end but improved over time. ConclusionThe outcomes of TPUS-guided RT demonstrated promising results in terms of minimal physician-reported toxicities and satisfactory patient-reported QoL.

Utilizing CT imaging for evaluating late gastrointestinal tract side effects of radiotherapy in uterine cervical cancer: a risk regression analysis

BackgroundRadiotherapy (RT) is effective for cervical cancer but causes late side effects (SE) to nearby organs. These late SE occur more than 3 months after RT and are rated by clinical findings to determine their severity. While imaging studies describe late gastrointestinal (GI) SE, none demonstrate the correlation between the findings and the toxicity grading. In this study, we demonstrated the late GI toxicity prevalence, CT findings, and their correlation.MethodsWe retrospectively studied uterine cervical cancer patients treated with RT between 2015 and 2018. Patient characteristics and treatment(s) were obtained from the hospital’s databases. Late RTOG/EORTC GI SE and CT images were obtained during the follow-up. Post-RT GI changes were reviewed from CT images using pre-defined criteria. Risk ratios (RR) were calculated for CT findings, and multivariable log binomial regression determined adjusted RRs.ResultsThis study included 153 patients, with a median age of 57 years (IQR 49–65). The prevalence of ≥ grade 2 RTOG/EORTC late GI SE was 33 (27.5%). CT findings showed 91 patients (59.48%) with enhanced bowel wall (BW) thickening, 3 (1.96%) with bowel obstruction, 7 (4.58%) with bowel perforation, 6 (3.92%) with fistula, 0 (0%) with bowel ischemia, and 0 (0%) with GI bleeding. Adjusted RRs showed that enhanced BW thickening (RR 9.77, 95% CI 2.64–36.07, p = 0.001), bowel obstruction (RR 5.05, 95% CI 2.30–11.09, p < 0.001), and bowel perforation (RR 3.82, 95% CI 1.96–7.44, p < 0.001) associated with higher late GI toxicity grades.ConclusionsOur study shows CT findings correlate with grade 2–4 late GI toxicity. Future research should validate and refine these findings with different imaging and toxicity grading systems to assess their potential predictive value.

Long-term Results of Hypofractionated Radiotherapy With Intra-prostatic Boosts in Men With Intermediate- and High-risk Prostate Cancer: A Phase II Trial

AimsIn the conventionally fractionated phase III FLAME prostate trial, focal boosts improved local control and biochemical disease-free survival (bDFS). We explored the toxicity and effectiveness of a moderately hypofractionated schedule with focal boosts. Material and methodsBIOPROP20 is a phase II single-arm non-randomised trial for intermediate- to very high-risk localised prostate cancer patients with bulky tumour volumes. Multi-parametric magnetic resonance imaging (MRI) and 18F-choline positron emission tomography-computed tomography (PET-CT) scans were used for staging and boost volume definition. Patients were treated with 60Gy in 20 fractions with a boost dose up to 68Gy. Five patients with positive lymph nodes on the PET-CT scan received radiotherapy to pelvic lymph nodes (45Gy to elective nodes, boosted up to 50Gy to involved nodes). Primary outcomes were acute (≤18 weeks) and late urinary and gastrointestinal toxicity, prospectively recorded up to 5 years with Common Terminology Criteria for Adverse Events v4 (CTCAE). Secondary outcomes were biochemical or clinical progression, metastasis-free survival (MFS), and overall survival (OS). Results61 patients completed radiotherapy with hormone therapy (range: 6–36 months). Cumulative acute and late gastrointestinal toxicity was low at 6.6% and 5.0%, respectively. Cumulative acute and late urinary toxicity was 49.2% and 30.1%, respectively; the prevalence reduced to 5.9% at 5 years. At 5 years: 6 patients had biochemical progression (bDFS: 88.5%; 95% CI: 80.2–97.6%), the MFS was 82.4% (95% CI: 73.0–92.9%), 5 patients died (OS: 91.2%; 95% CI: 84.1–98.9%), one with prostate cancer. The prostate, boost, nodal planning volumes, and the organs at risk (rectum, bowel, urethra, and bladder) met the optimal protocol dose constraints. There was a trend to increased urinary toxicity with increasing urethral (RR: 1.95, 95% CI: 0.73–5.22, p = 0.18), but not bladder dose. ConclusionFocal boosts with a 20 fraction hypofractionated prostate radiotherapy schedule are associated with an acceptable risk of gastrointestinal and urinary toxicity and achieve good cancer control. ClinicalTrials.gov identifierNCT02125175.

Clinical Outcome Comparison between CT-Guided Versus all MRI-Guided Scenarios in Brachytherapy for Cervical Cancer: A Single-Institute Experience

ObjectivesImage-guided adaptive brachytherapy (IGABT) is the standard of care for patients with cervical cancer. The objective of this study was to compare the treatment outcomes and adverse effects of computed tomography (CT)-guided and magnetic resonance imaging (MRI)-guided scenarios. Materials and MethodsData of patients with cervical cancer treated using external beam radiotherapy followed by IGABT from 2012 to 2016 were retrospectively reviewed. CT-guided IGABT was compared with the three modes of MRI-guided IGABT: pre-brachytherapy (MRI Pre-BT) without applicator insertion for fusion, planning MRI with applicator in-place in at least 1 fraction (MRI ≥1Fx), and MRI in every fraction (MRI EveryFx). Patient characteristics, oncologic outcomes, and late radiation toxicity were analyzed using descriptive, survival, and correlation statistics. ResultsOverall, 354 patients were evaluated with a median follow-up of 60 months. The 5-year overall survival (OS) rates were 61.5%, 65.2%, 54.4%, and 63.7% with CT-guided, MRI PreBT, MRI ≥1Fx, and MRI EveryFx IGABT, respectively with no significant differences (p = 0.522). The 5-year local control (LC) rates were 92.1%, 87.8%, 80.7%, and 76.5% (p = 0.133), respectively, with a significant difference observed between the CT-guided and MRI ≥1Fx (p = 0.018). The grade 3–4 late gastrointestinal toxicity rates were 6% in the CT-guided, MRI ≥1Fx, and MRI EveryFx, and 8% in MRI PreBT. The grade 3–4 late genitourinary toxicity rates were 4% in the CT-guided, 2% in MRI PreBT, 1% in MRI ≥1Fx, and none in MRI EveryFx. No significant differences were observed in the oncologic and toxicity outcomes among MRI PreBT, MRI ≥1Fx, and MRI EveryFx. ConclusionsCT-guided IGABT yielded an acceptable 5-year OS, LC, and toxicity profile compared with all MRI scenarios and is a potentially feasible option in resource-limited settings.

Dosimetric predictors of acute and late gastrointestinal toxicities in stereotactic online adaptive magnetic resonance-guided radiotherapy (SMART) for locally advanced pancreatic adenocarcinoma

Background and purposeA retrospective evaluation of dosimetric predictors and leveraged dose-volume data for gastrointestinal (GI) toxicities for locally-advanced pancreatic cancer (LAPC) treated with daily stereotactic MRI-guided online-adaptive radiotherapy (SMART). Materials and methods147 patients with LAPC were treated with SMART at our institution between 2018 and 2021. Patients were evaluated using CTCAE V5.0 for RT-related acute (≤3 months) and late (>3 months) toxicities. Each organ at risk (OAR) was matched to a ≥ grade 2 (Gr2+) toxicity endpoint composite group. A least absolute shrinkage selector operator regression model was constructed by dose-volumes per OAR to account for OAR multicollinearity. A receiver operator curve (ROC) analysis was performed for the combined averages of significant toxicity groups to identify critical volumes per dose levels. Results18 of 147 patients experienced Gr2+ GI toxicity. 17 Gr2+ duodenal toxicities were seen; the most significant predictor was a V33Gy odds ratio (OR) of 1.69 per cc (95 % CI 1.14–2.88). 17 Gr2+ small bowel (SB) toxicities were seen; the most significant predictor was a V33Gy OR of 1.60 per cc (95 % CI 1.01–2.53). The AUC was 0.72 for duodenum and SB. The optimal duodenal cut-point was 1.00 cc (true positive (TP): 17.8 %; true negative (TN); 94.9 %). The SB cut-point was 1.75 cc (TP: 16.7 %; TN: 94.3 %). No stomach or large bowel dose toxicity predictors were identified. ConclusionsFor LAPC treated with SMART, the dose-volume threshold of V33Gy for duodenum and SB was associated with Gr2+ toxicities. These metrics can be utilized to guide future dose-volume constraints for patients undergoing upper abdominal SBRT.

Escalade de dose en radiothérapie modérément hypofractionnée pour les cancers de la prostate localisés, ESHYPRO : résultats d’une série monocentrique rétrospective évaluant la toxicité et l’efficacité

PurposeProstate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated. Material and methodsThe study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75Gy in 30 fractions of 2.5Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46Gy in 23 fractions with simultaneous integrated boost. ResultsA total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4years and 3.96years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6months, 1year and 5years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6months, 1year and 5years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P=0.0028 for both). ConclusionExternal radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses.

Evaluating a hypofractionated radiotherapy schedule for prostate cancer at an institution in South Africa

Background: Hypofractionated radiotherapy (HFRT) in the treatment of prostate cancer (PCa) has logistical and cost advantages, especially in a resource constrained setting. Studies have demonstrated equivalent efficacy with HFRT schedules using Intensity Modulated Radiation Therapy (IMRT) as treatment modality. However, higher rates of acute and late gastrointestinal (GI) and genitourinary (GU) toxicity have been reported when compared to conventionally fractionated radiotherapy (CFRT). In this study, we evaluate the efficacy and toxicity rates of a HFRT schedule using 3D conformal radiotherapy (RT) as treatment modality.Aim: With this study, we aim to describe the safety and outcomes of a definitive HFRT schedule used for localised PCa. We hypothesise that there is no difference in the biochemical relapse rate and incidence rates of normal tissue toxicities between patients receiving CFRT and HFRT schedules.Setting: This RT schedule was used at Tygerberg Academic Hospital in South Africa for the treatment of localised prostate cancer.Methods: This is a retrospective study in which the records of patients diagnosed with localised PCa were reviewed. Patients were treated with either CFRT regimen to a total of 74Gy in 37 daily fractions for 5 days a week or a HFRT regimen to a total of 65Gy in 26 daily fractions for 4 days per week.Results: In all, 116 patients were included in the study with a median follow-up of 57.2 months from the start of RT. No statistically significant differences in overall survival (OS) and biochemical relapse-free survival were found between the two schedules. A significant difference in acute GI toxicity was observed, with a higher incidence noted in the HFRT schedule. No significant differences were observed in late GI toxicity or in early and late GU toxicities.Conclusion: This study observes a hypofractionated regimen using three-dimensional conformal radiation therapy (3DCRT) with similar efficacy and RT-related toxicities to CFRT.Contribution: The HFRT schedule used in this study could be useful in hospitals with limited access to resources.

Ablative Radiation Therapy for Unfavorable Prostate Tumors (ABRUPT): Preliminary Analysis of Toxicity and Quality of Life from a Prospective Study

To assess late gastrointestinal (GI) and genitourinary (GU) side effects in patients with organ-confined unfavorable prostate cancer (PCa) treated with single-dose ablative radiation therapy (SDRT). Thirty patients enrolled in a single-arm prospective trial received 24 Gy SDRT to the whole prostate with urethra-sparing and organ motion control delivered on a Linac platform with a 10 MV flattening filter-free single partial arc. Androgen deprivation therapy was prescribed as per standard of care. Treatment-related acute and late GU and GI toxicities (Common Terminology Criteria for Adverse Events_v5 scale) and quality of life (QoL) outcomes (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-PR25/C30, International Prostate Symptom Score [IPSS]) were assessed at different time points. Minimal important difference (MID) was established as a change of >0.5 pooled standard deviations from baseline. Statistical analysis included analysis of variance and logistic regression. Median follow-up was 18 months (range, 6-31 months), with no ≥G3 late side effects observed. G2 late GI and G2 late GU toxicities occurred in 1 and 2 patients, respectively. GI toxicity of any grade correlated with maximum rectal dose (P = .021). Lower baseline QoL score (P = .025), higher baseline IPSS score (P = .049), acute GU toxicity (P = .029), and acute urinary domain MID (P = .045) predicted GU toxicity of any grade. In multivariate analysis (MVA), only baseline QoL score (odds ratio [OR], 0.95, P = .031) and acute GU toxicity (OR, 8.4, P = .041) remained significant. Significant QoL change was observed only in the urinary domain (P = .005), with a median increase from 8 to 17. Late urinary MID correlated with acute urinary MID (P = .003), acute QoL MID (P = .029), acute GU toxicity (P = .030), and lower baseline urinary score (P = .033). In MVA, only acute urinary MID predicted late urinary MID (OR, 9.7, P = .035). Our findings provide promising data on the feasibility and safety of 24 Gy whole-gland SDRT with urethra-sparing and organ motion control, in association with androgen deprivation therapy and an adequate prophylactic medication, in organ-confined unfavorable PCa. Long-term follow-up is needed to confirm these results.

Hypofractionated radiation therapy combined with androgen deprivation therapy for clinically node-positive prostate cancer.

This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive prostate cancer. Medical records of 60 patients with clinically suspected metastatic lymph nodes on radiological examination were retrospectively analyzed. Eight patients (13.3%) were suspected to have metastatic common iliac or para-aortic lymph nodes. All patients underwent definitive RT with a dose fractionation of 70 Gy in 28 fractions. ADT was initiated 2-3 months before RT and continued for at least 2 years. Biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS), and prostate cancer-specific survival (PCSS) were calculated, and genitourinary and gastrointestinal adverse events were recorded. The median follow-up period was 5.47 years. The 5-year BFR, CFR, OS, and PCSS rates were 19.1%, 11.3%, 89.0%, and 98.2%, respectively. The median duration of ADT was 2.30 years. BFR and CFR increased after 3 years, and 11 out of 14 biochemical failures occurred after the cessation of ADT. Grade 2 and beyond late genitourinary and gastrointestinal toxicity rates were 5.0% and 13.3%, respectively. However, only two grade 3 adverse events were reported, and no grade 4-5 adverse events were reported. Patients with non-regional lymph node metastases did not have worse BFR, CFR, or adverse event rates. This study reported the efficacy and tolerable toxicity of hypofractionated definitive RT combined with ADT for clinically node-positive prostate cancer. Additionally, selected patients with adjacent non-regional lymph node metastases might be able to undergo definitive RT combined with ADT.

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.

Dosimetric and toxicity comparison between Syed-Neblett and Fletcher-Suit-Delclos Tandem and Ovoid applicators in high dose rate cervix cancer brachytherapy

PURPOSETo compare patient and tumor characteristics, dosimetry, and toxicities between interstitial Syed-Neblett and intracavitary Fletcher-Suit-Delclos Tandem and Ovoid (T&O) applicators in high dose rate (HDR) cervical cancer brachytherapy. METHODSA retrospective analysis was performed for cervical cancer patients treated with 3D-based HDR brachytherapy from 2011 to 2023 at a single institution. Dosimetric parameters for high-risk clinical target volume and organs at risk were obtained. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. RESULTSA total of 115 and 58 patients underwent Syed and T&O brachytherapy, respectively. Patients treated with Syed brachytherapy were more likely to have larger tumors and FIGO stage III or IV disease. The median D2cc values to the bladder, small bowel, and sigmoid colon were significantly lower for Syed brachytherapy. Patients treated with Syed brachytherapy were significantly more likely to be free of acute gastrointestinal (44% vs. 21%, p = 0.003), genitourinary (58% vs. 36%, p = 0.01), and vaginal toxicities (60% vs. 33%, p = 0.001) within 6 months following treatment compared to patients treated with T&O applicators. In contrast, Syed brachytherapy patients were more likely to experience late gastrointestinal (68% vs. 49%, p = 0.082), genitourinary (51% vs. 35%, p = 0.196), and vaginal toxicities (70% vs. 57%, p = 0.264). CONCLUSIONSSyed-Neblett and T&O applicators are suitable for HDR brachytherapy for cervical cancer in distinct patient populations. Acute toxicities are more prevalent with T&O applicators, while patients treated with Syed-Neblett applicators are more likely to develop late toxicities.

A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8months was mandatory for patients with intermediate or high-risk prostate cancer. From 20 institutions, 134 patients enrolled. The median follow-up was 5.16years (range, 1.43-6.47years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

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.

Probability of normal tissue complications for hematologic and gastrointestinal toxicity in postoperative whole pelvic radiotherapy for gynecologic malignancies using intensity-modulated proton therapy with robust optimization.

This retrospective treatment-planning study was conducted to determine whether intensity-modulated proton therapy with robust optimization (ro-IMPT) reduces the risk of acute hematologic toxicity (H-T) and acute and late gastrointestinal toxicity (GI-T) in postoperative whole pelvic radiotherapy for gynecologic malignancies when compared with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated X-ray (IMXT) and single-field optimization proton beam (SFO-PBT) therapies. All plans were created for 13 gynecologic-malignancy patients. The prescribed dose was 45 GyE in 25 fractions for 95% planning target volume in 3D-CRT, IMXT and SFO-PBT plans and for 99% clinical target volume (CTV) in ro-IMPT plans. The normal tissue complication probability (NTCP) of each toxicity was used as an in silico surrogate marker. Median estimated NTCP values for acute H-T and acute and late GI-T were 0.20, 0.94 and 0.58 × 10-1 in 3D-CRT; 0.19, 0.65 and 0.24 × 10-1 in IMXT; 0.04, 0.74 and 0.19 × 10-1 in SFO-PBT; and 0.06, 0.66 and 0.15 × 10-1 in ro-IMPT, respectively. Compared with 3D-CRT and IMXT plans, the ro-IMPT plan demonstrated significant reduction in acute H-T and late GI-T. The risk of acute GI-T in ro-IMPT plan is equivalent with IMXT plan. The ro-IMPT plan demonstrated potential clinical benefits for reducing the risk of acute H-T and late GI-T in the treatment of gynecologic malignances by reducing the dose to the bone marrow and bowel bag while maintaining adequate dose coverage to the CTV. Our results indicated that ro-IMPT may reduce acute H-T and late GI-T risk with potentially improving outcomes for postoperative gynecologic-malignancy patients with concurrent chemotherapy.

Simultaneous Focal Boost With Stereotactic Radiation Therapy for Localized Intermediate- to High-Risk Prostate Cancer: Primary Outcomes of the SPARC Phase 2 Trial

Purpose: Dose escalated radiotherapy is associated with better biochemical control at the expense of toxicity. Stereotactic body radiotherapy (SBRT) with dose escalation to the dominant intraprostatic lesion (DIL) provides a logical approach to improve outcomes in high-risk disease whilst limiting toxicity. This study evaluated the toxicity and quality of life (QOL) with CyberKnife-based SBRT and simultaneous integrated boost in localised prostate cancer. Methods and Materials: Eligible participants included newly diagnosed, biopsy-proven unfavourable intermediate to high risk localised prostate cancer (at least one of the following: Gleason ≥ 4+3, MRI defined T3a N0, PSA ≥ 20) with up to two MRI-identified DILs. Participants received 36.25Gy in 5 fractions on alternative days with a simultaneous boost to DIL up to 47.5Gy as allowed by organs at risk constraints delivered by CyberKnife. All participants received androgen deprivation therapy. The primary outcome measure was acute grade 2 + genitourinary toxicity. Acute and late genitourinary and gastrointestinal toxicity using RTOG scoring, biochemical parameters, IPSS, IIEF5, EQ5D QOL outcomes were assessed. Results: Between 2013 and 2023, 20 participants were enrolled with a median follow-up of 30 months. The median D95 dose to DIL was 47.43Gy. Cumulative acute grade 2 + genitourinary and gastrointestinal toxicity was 25% and 30%, respectively. One patient developed acute grade 3 genitourinary toxicity (5%). There is no late grade 3 genitourinary or gastrointestinal toxicity to date. IPSS score and urinary QOL scores recovered to baseline by 6months. Patient-reported outcomes showed no significant change in EQ-5D QOL scores at 12 weeks and 1 year. There are no cases of biochemical relapse reported to date. Conclusions: CyberKnife SBRT delivered dose of 36.25Gy to the prostate with a simultaneous integrated boost up to 47.5Gy is well tolerated. Acute and late GU and GI toxicity rates are comparable to other contemporary SBRT trials and series with focal boost.

Five-year clinical outcomes of scanning carbon-ion radiotherapy for prostate cancer.

Carbon-ion radiotherapy (CIRT) has been associated with favorable clinical outcomes in patients with prostate cancer. At our facility, all patients are treated using scanning CIRT (sCIRT). We retrospectively analyzed five-year clinical outcomes of prostate cancer treated with sCIRT to investigate treatment efficacy and toxicity. In this study, we included 253 consecutive prostate cancer patients treated with sCIRT at the Kanagawa Cancer Center from December 2015 to December 2017. The total dose of sCIRT was set at 51.6 Gy (relative biological effect) in 12 fractions over three weeks. We employed the Phoenix definition for biochemical relapse. The overall survival (OS), biochemical relapse-free (bRF) rate, and cumulative incidence of late toxicity were estimated using the Kaplan-Meier method. Toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. The median age of the patients was 70 years (range: 47-86 years). The median follow-up duration was 61.1 months (range: 4.1-80.3 months). Eight (3.2%), 88 (34.8%), and 157 (62.1%) patients were in the low-risk, intermediate-risk, and high-risk groups, respectively, according to the D'Amico classification system. The five-year OS and bRF were 97.5% and 93.3%, respectively. The five-year bRF rates for the low-risk, intermediate-risk, and high-risk groups were 87.5%, 93.7%, and 93.4%, respectively (p = 0.7215). The five-year cumulative incidence of Grade 2 or more late genitourinary and gastrointestinal toxicity was 7.4% and 1.2%, respectively. The results of this study show that sCIRT has a favorable therapeutic effect and low toxicity in the treatment of prostate cancer.

Secondary analysis of late major gastrointestinal and genitourinary toxicities in unfavorable-risk prostate cancer patients receiving docetaxel: Insights from a randomized trial.

This study sought to evaluate the late toxicity associated with neoadjuvant and concurrent docetaxel and radiation therapy in patients with prostate cancer. A secondary analysis was performed of the phase 3 multicenter randomized trial (Dana-Farber Cancer Institute 05-043) including 350 patients with nonmetastatic unfavorable-risk prostate cancer. Patients were randomized 1:1 to receive androgen deprivation therapy, radiation therapy, and docetaxel versus androgen deprivation therapy and radiation therapy. The study assessed the cumulative incidence rates of grade 2 and grade 3 or higher gastrointestinal, genitourinary, and sexual toxicity. A multivariable Fine and Gray's competing risks regression model adjusted for age at randomization and pelvic lymph node radiation therapy was used to evaluate the treatment effect of docetaxel on time to late genitourinary and gastrointestinal toxicities. The study included 338 patients who primarily had minimal or no comorbidity (74.9%) and median age 66 years (interquartile range: 61,71). At a median follow-up of 10.2 years, docetaxel was not associated with increased risk of any grade 3 or higher (adjusted hazard ratio [AHR], 0.98; 95% confidence interval [CI], 0.36-2.67; p=.96) or grade 2 gastrointestinal (p=.75), genitourinary (p=.44), and sexual (p=.29) toxicity. Age was associated with increased grade 3 or higher (AHR, 1.08; 95% CI, 1.01-1.16; p=.03) and grade 2 gastrointestinal toxicity (AHR, 1.11; 95% CI, 1.03-1.20; p=.005). A nonsignificant trend (p=.09) toward increased late grade 3 or higher toxicity was observed for pelvic radiation therapy use. Docetaxel combined with radiotherapy has an acceptable long-term toxicity profile.

Evaluation of the safety and efficacy of high-dose rate brachytherapy for radiorecurrent prostate cancer: asystematic review and meta-analysis.

High-dose-rate brachytherapy (HDR-BT) plays an important role in the treatment of locally recurrent prostate cancer after definitive treatment. The objective of this study is to summarize the efficacy and toxicity of HDR-BT in these patients. We performed asystematic review of PubMed and EMBASE from inception to July 2023. The primary endpoint was relapse-free survival (RFS) in different subgroups, and the secondary endpoint was gastrointestinal (GI) and genitourinary (GU) toxicity. Asemi-automated tool (WebPlotDigitizer) and anew Shiny application combined with Rsoftware (R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria; https://www.R-project.org/ ) helped to reconstruct survival curves. Twenty-six studies met the inclusion criteria for quantitative analysis, including 1447 patients. Atotal of 761 patients from 13studies were included in survival reconstruction, and the median RFS time was 61.2 months (57.6-72.0months). The estimated 2‑, 3‑, and 5‑year rates were 75.9% (95% confidence interval [CI] 72.8 ~ 79.2%), 66.7% (95% CI 63.0 ~ 70.5%), and 52.3% (95% CI 47.5 ~ 57.4%), respectively. Whole-gland irradiation with multiple fractions (≥ 2F) resulted in better RFS compared with focal gland irradiation with fewer fractions (1F mostly; hazard ratio [HR]: 0.60, 95% CI 0.47-0.77, p < 0.0001). According to the different median time from primary treatment to salvage therapy (TRS) and median age at recurrence, short median TRS (56-67.2 months vs. 70-120 months; HR 0.52, 95% CI 0.68-0.40; p < 0.0001) and younger median age (60-70years vs. 71-75years; HR 0.58, 95% CI 0.46-0.74; p < 0.0001) were positive factors for RFS. The cumulative incidences estimated for grade ≥ 3 acute and late GU toxicities were 1% (95% CI 0 ~ 1%) and 5% (95% CI 4 ~ 7%), respectively. Three patients (3/992) experienced grade ≥ 3 late GI toxicity, and no cases of grade ≥ 3 acute GI toxicity were reported. HDR-BT has ahigh safety profile and good RFS benefit for salvage treatment of radiorecurrent prostate cancer. In terms of RFS, whole-gland irradiation with multiple fractions seems to be better than focal gland irradiation with fewer fractions, while short TRS and younger age are good prognostic factors. In view of the low level of evidence in the included studies and the large heterogeneity of each study, these conclusions still need to be confirmed by randomized controlled trials.

Image-guided moderately hypofractionated radiotherapy for localized prostate cancer: a multicentric retrospective study (IPOPROMISE)

BackgroundModerate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series.Materials and methodsWe retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan–Meier survival curves and fitted univariate and multivariable Cox’s proportional hazards regression models to study the association between the clinical variables and each survival type.ResultsAt the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3–99.6%) and 85.5% (95%CI 81.9–89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4–6%) and 6% (95%CI 4–8%), respectively.ConclusionReal-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.