Whole Pelvic Radiotherapy Research Articles

Microbiome and metabolome dynamics during radiotherapy for prostate cancer

BackgroundProstate cancer patients treated with radiotherapy are susceptible to acute gastrointestinal (GI) toxicity due to substantial overlap of the intestines with the radiation volume. Due to their intimate relationship with GI toxicity, faecal microbiome and metabolome dynamics during radiotherapy were investigated. Material & methodsThis prospective study included 50 prostate cancer patients treated with prostate (bed) only radiotherapy (PBRT) (n = 28) or whole pelvis radiotherapy (WPRT) (n = 22) (NCT04638049). Longitudinal sampling was performed prior to radiotherapy, after 10 fractions, near the end of radiotherapy and at follow-up. Patient symptoms were dichotomized into a single toxicity score. Microbiome and metabolome fingerprints were analyzed by 16S rRNA gene sequencing and ultra-high-performance liquid chromatography hybrid high-resolution mass spectrometry, respectively. ResultsThe individual α-diversity did not significantly change over time. Microbiota composition (β-diversity) changed significantly over treatment (PERMANOVA p-value = 0.03), but there was no significant difference in stability when comparing PBRT versus WPRT. Levels of various metabolites were significantly altered during radiotherapy. Baseline α-diversity was not associated with any toxicity outcome. Based on the metabolic fingerprint, no natural clustering according to toxicity profile could be achieved. ConclusionsRadiation dose and treatment volume demonstrated limited effects on microbiome and metabolome fingerprints. In addition, no distinctive signature for toxicity status could be established. There is an ongoing need for toxicity risk stratification tools for diagnostic and therapeutic purposes, but the current evidence implies that the translation of metabolic and microbial biomarkers into routine clinical practice remains challenging.

Impact of Prophylactic Pelvic Lymph Node Irradiation in De-Novo Oligometastatic Prostate Cancer.

To evaluate the impact of prophylactic pelvic nodal irradiation in de-novo oligometastatic prostate cancer treated with radiotherapy (RT) for both primary tumor and all metastatic lesions. This was a single-center prospective cohort study. De novo oligometastatic prostate cancer patients with RT for both primary tumor and all metastatic lesions were included. Kaplan-Meier method, log rank test and cox regression were used to calculate OS and PFS. PFS included PSA failure, local or distant failure assessed by imaging. This study analyzed 202 patients from 10/2011 to 1/2022 with median follow-up of 48 months. A total of 126 (62.4%) patients were treated with pelvic lymph node RT. The dose was 47.5 Gy with 1.9 Gy per fraction. Among them, 66 (32.7%) patients were treated with whole pelvic RT (WPRT), which the upper limit was at the aortic bifurcation. 60 (29.7%) patients were treated with mini-WPRT, which the upper limit was at the lower margin of obturator foramen. The incidence of diarrhea (P = 0.038) and leukocyte reduction (P = 0.040) in the WPRT subgroup during radiotherapy was significantly higher than that in the mini-WPRT and non-pelvic RT subgroup. For the whole cohort, the median OS and PFS were not reached. The subgroup analysis showed that the elective pelvic nodal irradiation could improve PFS (P = 0.042). However, there was no difference of PFS between standard WPRT and mini-WPRT. The study suggests that for de-novo oligometastatic prostate cancer, elective pelvic nodal irradiation may improve PFS. For patients who cannot tolerate WPRT, mini-WPRT may be an alternative option. However, it needs to be verified in the prospective RCT study.

Late Urinary Toxicity and QoL with Curative Radiotherapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase III Trial

Whole pelvic radiotherapy (WPRT) showed better biochemical failure-free survival and metastasis-free survival than prostate-only radiotherapy (PORT) in the phase III randomized POP-RT trial for high and very high-risk prostate cancer, albeit with higher RTOG grade 2 late urinary toxicity. We report updated long term, symptom-wise comparison and dose-effect relations from this trial. Late urinary toxicity, and cumulative severity of each symptom over the follow-up period was graded using CTCAE v5.0. Grade 2+ toxicities were compared between the trial arms by chi square test. Bladder dosimetry in 5-Gy increments (V5, V10, V15...V65 Gy, V68 Gy) from the trial database of approved radiotherapy plans, was compared for each urinary symptom and overall late gr2+ toxicity by student t-test. Observed differences in dosimetric parameters were tested using multivariable logistic regression analysis, including age at diagnosis, known diabetes, tumor stage, trial arm, and prior transurethral resection of prostate (TURP). Urinary QOL scores were compared between arms using generalised linear mixed model. Combined late symptom-wise toxicity and dose-volume data were available for analysis for 193/224 patients. At a median follow-up of 75 months, cumulative CTCAE gr2+ late urinary toxicity remained higher with WPRT than PORT, though not statistically significant (36.5% vs 26.8%, p = 0.15). Grade 3 toxicity was low and similar in both arms. Symptom-wise cumulative rates showed no significant difference between arms (Table 1). Dosimetric comparison showed significantly higher bladder V5-V15 in patients with gr2+ toxicity over those with <gr2 urinary toxicity. On symptom-wise analysis, V5-V40 range was significantly higher for presence of dysuria, hematuria, and urgency. No significant differences were observed over higher dose range for any urinary symptom. On multivariable analysis, no significant association was identifiable between bladder dosimetry and urinary symptoms. Urinary QOL scores was similar between both the arms for all the symptoms. Compared to prostate-only radiotherapy, whole pelvic radiotherapy resulted similar Grade 3 urinary toxicity of about 5% with about 10% higher cumulative grade 2+ urinary toxicity over long term follow up. This difference was not reflected in patient-reported QOL. WPRT particularly increased urgency and hematuria. Larger bladder volume being irradiated with 5Gy to 15Gy dose range could contribute to increase in urinary symptoms.

Prospective Dosimetric Comparison Study Between Volumetric Modulated Arc Therapy and Intracavitary Brachytherapy for Cervical Cancer

Although volumetric modulated arc therapy (VMAT) boost can achieve highly conformal dose distributions for cervical cancer, VMAT has the disadvantage of requiring set-up and organ motion margins. This study prospectively recruited patients with the cervical cancer and compared VMAT plan with intracavitary brachytherapy (ICBT) plan. All patients treated with ICBT for locally advanced cervical cancer between April 2020 and September 2022 were enrolled. Patients had whole-pelvis radiotherapy, followed by CT scans with and without the tandem and ovoid in the same session (for the planning of ICBT and VMAT, respectively). ICBT planning characterizes the high-risk clinical target volume (HR-CTV) as the target volume and the bladder, rectum, sigmoid colon and small bowel loop as the organ at risk (OAR). VMAT planning defines the HR-CTV + 3 mm as the target volume and bladder, rectum + 3 mm (planning organ at risk volume (PRV) rectum), sigmoid colon + 3 mm (PRV sigmoid) and bowel bag as the OAR to account for set-up and organ motion. ICBT and VMAT plans were optimized for maximal dose received by at least 90% (D90%) of the target volume without impairing the dose constraints for the OARs. The prescribed dose (PD) was 26 Gy in 4 fractions. The dose constraints were determined as 25.2 Gy for D2 ml in the bladder and 20 Gy for D2 ml in the other OARs. The D90% and D100% of the target volume and D2 ml of OARs were compared between 2 plans using paired two-tailed Student's t test. Seventeen patients were enrolled. Dose and volume parameters for the 2 plans are shown in Table 1. Of the 17 patients, D90% of the target volume received 100% PD in 4 cases with ICBT plans, in 6 cases for VMAT plans, and in 2 cases with both methods. For D90% of the target volume, ICBT plans were greater than VMAT plans in 4 cases, with a maximum difference of 5.6 Gy (ICBT: 26.0 Gy, SBRT: 20.4 Gy). VMAT plans were higher than ICBT plans in 11 cases, with a maximum difference of 10.3 Gy (ICBT: 14.5 Gy, SBRT: 24.8 Gy). The dose-limiting OARs to attain D90% of target volume were bladder in 12 cases and small bowel loop in 1 case for ICBT plans, while PRV rectum in 11 cases, PRV sigmoid in 4 cases and bowel bag in 1 case for VMAT plans. This prospective study with 17 ICBT-eligible patients revealed D90% of the target volume demonstrated no substantial difference between VMAT and ICBT plans, while D100% showed a significant increase in VMAT plan compared to ICBT plan. Even with a set-up and organ motion margins on the HR-CTV and OARs, VMAT may have a dosimetric advantage over ICBT if the target geometry is complicated and close to the OARs.

Adaptive Ultra-Hypofractionated Whole-Pelvic Radiotherapy in High-Risk and Very High-Risk Prostate Cancer on 1.5-1.5 MR Linac: The Estimated Delivered Dose and Early Toxicity Results

To study the feasibility and safety for patients with high-risk (HR) and very high-risk (VHR) prostate cancer treated with adaptive ultra-hypofractionated whole-pelvic radiotherapy (UHF-WPRT) on 1.5 magnetic resonance (MR)-Linac. Sevenpatients with clinical stage T3a-4N0-1M0-1c consecutively treated with UHF-WPRT on a 1.5-T MR-Linac were recruited prospectively in a phase II trial (NCT05183074, ChiCTR2000033382). A 36.25 Gy dose in five fractions was delivered every other day with a boost of 40 Gy to the whole prostate, as well as 25 Gy to whole pelvic nodal area with a concomitant boost of 35 Gy to metastatic regional nodes. To estimate the delivered dose, we collected data by 3D-MR for the following stages: pre-MR, position verification-MR (PV-MR) in the Adapt-To-Shape (ATS) workflow, and 3D-MR during the beam-on phase (Bn-MR) and at the end of RT (post-MR). The target and organ-at-risk contours in the PV-MR, Bn-MR, and post-MR stages were projected from the pre-MR data by deformable image registration and manually adapted by the physician, followed by dose recalculation for the ATS plan. The cumulative acute genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated as per NCI-CTCAE 5.0 criteria. The primary endpoints were acute ≥grade 3 genitourinary (GU) and gastrointestinal (GI) toxicities during the first 3 months. Overall, 133 MR scans were collected (35 pre-MR, 35 PV-MR, 31 Bn-MR and 32 post-MR scans). With a median on-couch time of 61 minutes, the mean prostate and pelvic planning target volume (PTV)-V95% of all scans was 96.98 ± 3.06% and 96.44 ± 2.85%, respectively. The corresponding mean prostate clinical target volume (CTV)-V100% was 99.89 ± 0.32%, 98.71 ± 1.90%, 97.77 ± 2.89%, and 98.56 ± 1.72%, and the mean pelvic CTV-V100% was 97.57% ± 3.70%, 96.54 ± 3.80%, 95.43 ± 4.31%, and 94.39 ± 4.47% on pre-MR, PV-MR, Bn-MR and post-MR scans, respectively. For the 4 patients with positive nodes, the mean V100% of metastatic regional nodes was 99.89 ± 0.81%. The median V29 Gy change in the rectal wall was -1% (-18%-20%). The V29 Gy of the rectal wall increased by >15% was observed in one scan. A slight increase in the high dose of bladder wall was noted due to gradual bladder growth during the workflow. With median follow-up time of 7.3 (4.6-12.2) months, all patients were followed-up for more than 3 months. No patient was observed with acute CTCAE grade 2 or more severe GU or GI toxicities (0%). UHF-RT to prostate and pelvic with ATS workflow is well tolerated by patients with HR and VHR prostate cancer, with only mild GU and GI toxicities. The 3D-MR-based dosimetry analysis demonstrated clinically acceptable estimated dose coverage of target volumes during the beam-on period.

Long-term outcomes of whole-pelvis radiation therapy using volumetric modulated arc therapy for high-risk prostate cancer†.

This study investigated the outcomes of whole-pelvis radiation therapy (WPRT) using volumetric modulated arc therapy (VMAT) for high-risk prostate cancer. We retrospectively analysed 112 patients with high-risk prostate cancer who started WPRT at our hospital between August 2011 and August 2015. The prescribed dose was 78Gy in 39 fractions to the prostate and 46.8Gy in 26 fractions to the pelvic lymph node (LN) area. All patients received long-term androgen deprivation therapy. We evaluated late gastrointestinal (GI) and genitourinary (GU) toxicities using the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period for censored cases was 97 (interquartile range [IQR] = 85-108) months. The median age was 72 (IQR = 67-75) years. The high-risk and very-high-risk groups included 41 (36.6%) and 71 patients (63.4%), respectively. The median risk of LN invasion calculated by the Roach formula was 36.9 (IQR = 26.6-56.3) %. The 8-year overall survival, biochemical failure-free survival, disease-free survival and distant metastasis-free survival rates were 88.4, 91.9, 83.8 and 98.0%, respectively. Only one patient experienced common iliac LN recurrence, which was outside the pelvic irradiation area. All patients with recurrent disease were categorized into the very-high-risk group. The 8-year cumulative rates of ≥Grade 2 late GI and GU toxicities were 12.8 and 11.8%, respectively. No patients experienced Grade 4 or higher toxicities. WPRT using VMAT for high-risk prostate cancer was well tolerated and effective.

112 Is Hypofractionated Whole-Pelvis Radiotherapy (WPRT) as Well Tolerated as Conventionally Fractionated WPRT in Prostate Cancer Patients? An Early Analysis of the Hope-Trial

112 Is Hypofractionated Whole-Pelvis Radiotherapy (WPRT) as Well Tolerated as Conventionally Fractionated WPRT in Prostate Cancer Patients? An Early Analysis of the Hope-Trial

Whole-pelvic irradiation with boost to involved nodes and prostate in node-positive prostate cancer-long-term data from the prospective PLATIN-2trial.

Node-positive prostate cancer is apotentially curable disease. Definitive radiotherapy to the prostate and lymphatic drainage is an effective treatment option but prospective long-term outcome data are scarce. Thus, the current study aimed to evaluate the toxicity and efficacy of definitive radiation therapy for men with prostate cancer and nodal metastases using modern irradiation techniques. A total of 40treatment-naïve men with node-positive prostate cancer were allocated to the trial. All patients received definitive radiation therapy at two German university hospitals between 2009 and 2018. Radiation was delivered as intensity-modulated radiation therapy (IMRT) with 51 Gy to the lymphatic drainage with simultaneous integrated boost (SIB) up to 61.2 Gy to involved nodes and 76.5 Gy to the prostate in 34fractions. Feasibility and safety, overall and progression-free survival, toxicity, and quality of life measurements were analyzed. During amedian follow-up of 79months, median overall survival was 107 months and progression-free survival was 78months. Based on imaging follow-up, no infield relapse was reported during the first 24months of follow-up. There were 3(8%) potentially treatment-related grade3 toxicities. Common iliac node involvement was associated with ahigher risk of progression (HR 15.8; 95% CI 2.1-119.8; p = 0.007). Definitive radiation to the lymphatic drainage with SIB to the involved nodes and prostate is asafe and effective treatment approach for patients with treatment-naïve, node-positive prostate cancer with excellent infield tumor control rates and tolerable toxicity. Location rather than number of involved nodes is amajor risk factor for progression.

The impact of boost radiation therapy after hysterectomy on cervical cancer patients with close or positive resection margins.

We investigated the effect of boost radiation therapy (RT) in addition to whole pelvis RT (WPRT) on treatment outcome and safety of cervical cancer patients following hysterectomy with close/positive resection margins (RM). We retrospectively analyzed 51 patients with cervical cancer who received WPRT with or without boost-RT as adjuvant treatment between July 2006 and June 2022. Twenty patients (39.2%) were treated with WPRT-alone, and 31 (60.8%) received boost-RT after WPRT using brachytherapy or intensity-modulated RT. The median follow-up period was 41months. According to RT modality, the 4-year local control (LC) and locoregional control (LRC) rates of patients treated with WPRT-alone were 61% and 61%, respectively, whereas those in LC and LRC rates in patients who underwent WPRT with boost-RT were 93.2% and 75.3%, with p-values equal to 0.005 and 0.090, respectively. Seven patients (35.0%) had local recurrence in the WPRT-treated group compared to only two out of the 31 patients (6.5%) in the WPRT with boost-RT-treated counterparts (p = 0.025). Boost-RT was a significantly good prognostic factor for LC (p = 0.013) and LRC (p = 0.013). Boost-RT did not result in statistically-significant improvements in progression-free survival or overall survival. The acute and late toxicity rates were not significantly different between groups. Boost RT following WPRT is a safe and effective treatment strategy to improve LC without increasing toxicity in patients with cervical cancer with close/positive RM after hysterectomy.

Salvage Whole-Pelvic Radiation and Long-Term Androgen-Deprivation Therapy in the Management of High-Risk Prostate Cancer: Long-Term Update of the McGill 0913 Study.

To report the long-term outcomes of the McGill 0913 study and the potential benefits of combining prostate-bed radiotherapy (PBRT), pelvic-lymph-node radiotherapy (PLNRT), and long term ADT (LT-ADT). From 2010 to 2016, 46 high-risk prostate cancer patients who experienced biochemical recurrence (BCR) after radical prostatectomy (RP) were enrolled in this single-arm phase II clinical trial. The patients were eligible if they had a Gleason score > 8, locally advanced disease (≥pT3), a preoperative PSA of >20 ng/mL, or positive lymph nodes (LN). The patients were treated with a combination of 24 months of ADT, PBRT, and PLNRT. The primary outcome was biochemical progression-free survival (bPFS) and the predefined secondary endpoints included distant-metastasis-free survival (DMFS), overall survival (OS), and toxicity. In this update, we also report the median follow-up of 8.8 years and 10 years OS. At a median follow-up of 8.8 years, 43 patients were eligible for analysis. The median pre-salvage PSA was 0.30 μg/L. Half (51%) of the patients (n = 22) had positive margins, 40% (n = 17) had Gleason scores > 8, 63% (n = 27) had extracapsular extension, 42% (n = 18) had seminal vesicle invasion, and 19% (n = 8) had LN involvement. The 10-year bPFS was 68.3 %. The 10-year DMFS was 72.9%. The 10-year OS was 97%. There were two non-cancer-related deaths. The first patient died of congestive heart failure while the other died of an unknown cause. No new toxicity was observed after the initial report. Our study demonstrates that treatment escalation with PBRT, PLNRT, and LT-ADT improves long term outcomes. In view of the recently published SPPORT study, we conclude that this novel approach of treatment intensification in high-risk post-prostatectomy patients is safe and effective, and that it should be offered as the standard of care.

Assessing the toxicity after moderately hypofractionated prostate and whole pelvis radiotherapy compared to conventional fractionation.

To evaluate acute and late gastrointestinal (GI) and genitourinary (GU) toxicities after moderately hypofractionated (HF) or conventionally fractionated (CF) primary whole-pelvis radiotherapy (WPRT). Primary prostate-cancer patients treated between 2009 and 2021 with either 60 Gy at 3 Gy/fraction to the prostate and 46 Gy at 2.3 Gy/fraction to the whole pelvis (HF), or 78 Gy at 2 Gy/fraction to the prostate and 50/50.4 Gy at 1.8-2 Gy/fraction to the whole pelvis (CF). Acute and late GI and GU toxicities were retrospectively assessed. 106patients received HF and 157 received CF, with amedian follow-up of 12and 57months. Acute GI toxicity rates in the HF and CF groups were, respectively, grade2: 46.7% vs. 37.6%, and grade3: 0% vs. 1.3%, with no significant difference (p = 0.71). Acute GU toxicity rates were, respectively, grade2: 20.0% vs. 31.8%, and grade3: 2.9% vs. 0%, (p = 0.04). We compared prevalence of late GI and GU toxicities between groups after 3,12, and 24months and did not find any significant differences (respectively, p = 0.59, 0.22, and 0.71 for GI toxicity; p = 0.39, 0.58, and 0.90 for GU toxicity). Moderate HF WPRT was well tolerated during the first 2years. Randomized trials are needed to confirm these findings.

In silico comparison of whole pelvis intensity-modulated photon versus proton therapy for the postoperative management of prostate cancer

Background Limited data exist comparing intensity-modulated photon (IMRT) and proton (IMPT) radiation therapy when treating the prostate bed and pelvic lymph nodes in the postoperative setting for prostate cancer. The aim of this study was to evaluate dosimetric differences between IMRT and IMPT when treating with whole pelvis radiation therapy (WPRT) postoperatively. Materials and methods IMRT and IMPT plans were generated for 10 post-prostatectomy patients treated between July and August 2020. The prescription was 50 Gy radiobiologic equivalent (GyE) (proton radiobiological effective dose 1.1) to the pelvis and 70 GyE to the prostate bed in 2 GyE per fraction. Paired 2-sided Wilcoxon signed-rank tests were used to compare clinical target volume (CTV) coverage and dose to organs at risk (OARs). Results CTV coverage was met for all plans with 99% of CTVs receiving ≥99% of prescription doses. Dose to OARs was significantly higher with IMRT than IMPT for the following endpoints: bladder V5-V65; bowel V5-V45; sigmoid V5-V50; rectum V5-V70; femoral head V40 and maximum dose; bone V5-V65. Select endpoints with significant differences included bladder V30 (63.5 vs. 44.4%, p < .001), bowel V15 (949 vs. 191 cc, p = .001) and V30 (386 vs. 121 cc, p < .001), rectum V40 (81.8 vs. 32.1%, p < .001) and V50 (47.6 vs. 24.9%, p < .001), femoral head maximum doses (46.4–47.1 vs. 38.3–38.6GyE, p < .001), and bone V10 (93.3 vs. 85.4%, p < . 001). Mean doses for all OARs were significantly higher with IMRT, including bladder (41.9 vs. 29.7GyE, p < .001), bowel (21.2 vs. 5.5GyE, p < .001), and rectum (50.8 vs. 27.3GyE, p < .001). Integral dose to ‘Body – CTV’ was significantly higher with IMRT (32.8 vs. 18.4 J, p < .001). Conclusion IMPT provides comparable target coverage to IMRT when treating prostate cancer with WPRT in the postoperative setting while significantly reducing dose to OARs. These data can inform the future clinical management and delivery of post-prostatectomy irradiation for prostate cancer.

RT-PACE: Phase I/II study of adjuvant whole pelvic hypofractionated radiotherapy for non-metastatic cervical and endometrial cancer.

TPS5631 Background: Whole pelvic radiation therapy (WPRT) improves locoregional control in women with high-intermediate and high-risk endometrial cancer. The standard treatment course consists of 25-28 fractions (5-5.5 weeks) of 1.8-2 Gy/fraction, and is delivered using intensity-modulated radiation therapy (IMRT), which allows for superior sparing of normal tissue with a subsequent lower rate of acute and late toxicity compared to less conformal treatment techniques. Moderate hypofractionation (HF, &gt;2 Gy/fraction) has been studied in other disease sites, such as breast and prostate cancer, and is associated with lower or comparable toxicity, improved patient convenience, and greater cost savings compared to standard fractionation. However, HF has not been well-studied in the setting of WPRT for gynecologic cancers. Methods: This phase I/II multi-institutional study evaluates the feasibility, safety, and toxicity profile of HF-WPRT in women with non-metastatic cervical or endometrial cancers who have undergone curative hysterectomy and are recommended adjuvant WPRT by their treating physician. Concurrent chemotherapy is not allowed, but can be administered sequentially prior to or after WPRT. Para-aortic radiation or nodal boosts are not allowed, however vaginal brachytherapy boost is permissible. Phase I is a safety study of increasing dose-per-fraction. All treatment regimens have an approximate biologic effective dose of 53 Gy (α/β =10). A keyboard design is utilized to identify the maximum tolerated dose-per-fraction (MTD), defined in this study as the regimen that is associated with a CTCAE grade 3+ gastrointestinal/genitourinary toxicity rate of ≤10% on the last day of WPRT. There are 3 dose cohorts of increasing dose-per-fraction. Phase II will accrue 64 evaluable patients to HF-WPRT using the MTD determined in phase I. The primary endpoint is to evaluate the change in patient-reported gastrointestinal toxicity from baseline to the last day of WPRT using the EPIC bowel score. The study is powered to compare results to the RTOG 1203 IMRT standard fractionation arm. The phase 1 portion of the study completed accrual; the phase II portion opened in April 2022 with a fractionation of 42.56 Gy in 16 fractions. Secondary endpoints include genitourinary toxicity (EPIC, CTCAE), quality of life (FACT-Cx, PRO-CTCAE), financial toxicity (FACIT-COST), and decision-making (Decision Regret Scale). Pelvic control at 2 years is an exploratory endpoint. Clinical trial information: NCT04683653 .

Integrating CT-based radiomic model with clinical features improves long-term prognostication in high-risk prostate cancer.

High-risk prostate cancer (PCa) is often treated by prostate-only radiotherapy (PORT) owing to its favourable toxicity profile compared to whole-pelvic radiotherapy. Unfortunately, more than 50% patients still developed disease progression following PORT. Conventional clinical factors may be unable to identify at-risk subgroups in the era of precision medicine. In this study, we aimed to investigate the prognostic value of pre-treatment planning computed tomography (pCT)-based radiomic features and clinical attributes to predict 5-year progression-free survival (PFS) in high-risk PCa patients following PORT. A total of 176 biopsy-confirmed PCa patients who were treated at the Hong Kong Princess Margaret Hospital were retrospectively screened for eligibility. Clinical data and pCT of one hundred eligible high-risk PCa patients were analysed. Radiomic features were extracted from the gross-tumour-volume (GTV) with and without applying Laplacian-of-Gaussian (LoG) filter. The entire patient cohort was temporally stratified into a training and an independent validation cohort in a ratio of 3:1. Radiomics (R), clinical (C) and radiomic-clinical (RC) combined models were developed by Ridge regression through 5-fold cross-validation with 100 iterations on the training cohort. A model score was calculated for each model based on the included features. Model classification performance on 5-year PFS was evaluated in the independent validation cohort by average area-under-curve (AUC) of receiver-operating-characteristics (ROC) curve and precision-recall curve (PRC). Delong's test was used for model comparison. The RC combined model which contains 6 predictive features (tumour flatness, root-mean-square on fine LoG-filtered image, prostate-specific antigen serum concentration, Gleason score, Roach score and GTV volume) was the best-performing model (AUC = 0.797, 95%CI = 0.768-0.826), which significantly outperformed the R-model (AUC = 0.795, 95%CI = 0.774-0.816) and C-model (AUC = 0.625, 95%CI = 0.585-0.665) in the independent validation cohort. Besides, only the RC model score significantly classified patients in both cohorts into progression and progression-free groups regarding their 5-year PFS (p< 0.05). Combining pCT-based radiomic and clinical attributes provided superior prognostication value regarding 5-year PFS in high-risk PCa patients following PORT. A large multi-centre study will potentially aid clinicians in implementing personalised treatment for this vulnerable subgroup in the future.

Radiation-based Therapy for Muscle-invasive Bladder Cancer: Contemporary Outcomes Across Tertiary Centers

BackgroundRadiation therapy (RT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). ObjectiveTo analyze predictors of complete response (CR) and survival after RT for MIBC. Design, setting, and participantsThis was a multicenter retrospective study of 864 patients with nonmetastatic MIBC who underwent curative-intent RT from 2002 to 2018. Outcome measurements and statistical analysisRegression models were used to explore prognostic factors associated with CR, cancer-specific survival (CSS), and overall survival (OS). Results and limitationsThe median patient age was 77 yr and median follow-up was 34 mo. Disease stage was cT2 in 675 patients (78%) and cN0 in 766 (89%). Neoadjuvant chemotherapy (NAC) was given to 147 patients (17%) and concurrent chemotherapy to 542 (63%). A CR was experienced by 592 patients (78%). cT3–4 stage (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29–0.63; p < 0.001) and hydronephrosis (OR 0.50, 95% CI 034–0.74; p = 0.001) were significantly associated with lower CR. The 5-yr survival rates were 63% for CSS and 49% for OS. Higher cT stage (HR 1.93, 95% CI 1.46–2.56; p < 0.001), carcinoma in situ (HR 2.10, 95% CI 1.25–3.53; p = 0.005), hydronephrosis (HR 2.36, 95% CI 1.79–3.10; p < 0.001), NAC use (HR 0.66, 95% CI 0.46–0.95; p = 0.025), and whole-pelvis RT (HR 0.66, 95% CI 0.51–0.86; p = 0.002) were independently associated with CSS; advanced age (HR 1.03, 95% CI 1.01–1.05; p = 0.001), worse performance status (HR 1.73, 95% CI 1.34–2.22; p < 0.001), hydronephrosis (HR 1.50, 95% CI 1.17–1.91; p = 0.001), NAC use (HR 0.69, 95% CI 0.49–0.97; p = 0.033), whole-pelvis RT (HR 0.64, 95% CI 0.51–0.80; p < 0.001), and being surgically unfit (HR 1.42, 95% CI 1.12–1.80; p = 0.004) were associated with OS. The study is limited by the heterogeneity of different treatment protocols. ConclusionsRT for MIBC yields a CR in most patients who elect for curative-intent bladder preservation. The benefit of NAC and whole-pelvis RT require prospective trial validation. Patient summaryWe investigated outcomes for patients with muscle-invasive bladder cancer treated with curative-intent radiation therapy as an alternative to surgical removal of the bladder. The benefit of chemotherapy before radiotherapy and whole-pelvis radiation (bladder plus the pelvis lymph nodes) needs further study.

Benefit of whole-pelvis radiation for patients with muscle-invasive bladder cancer: An inverse probability treatment-weighted analysis.

449 Background: Pelvic lymph node irradiation is still under debate for patients with muscle-invasive bladder cancer (MIBC) planned for curative-intent radiation-based therapy (RT). A previous randomized trial suggested bladder-only (BO)-RT was effective in reducing RT-related toxicity, while associated with non-inferior oncological outcomes – bladder preservation rates, disease-free survival, and overall survival (OS) – compared to whole-pelvis (WP)-RT. In this study, we sought to evaluate the impact of the radiation volume (BO-RT vs. WP-RT) on main oncological outcomes in patients with MIBC. Methods: This nationwide study included patients with urothelial MIBC (cT2-4aN0-2M0) who underwent curative RT at 10 academic centers across Canada. Patients clinically staged with pelvic or abdominal wall invasion (cT4b) or enlarged lymph nodes beyond the common iliac bifurcation (cN3) before RT were excluded. Patients were divided into two groups based on the RT volume: WP-RT vs. BO-RT. Inverse probability of treatment weighting (IPTW) and absolute standardized differences (ASDs) were used to balance baseline covariates across treatment groups. Regression models were used to assess the impact of the RT volume on the rates of complete response (CR) to treatment, cancer-specific survival (CSS), and OS while adjusting for potential confounding variables in the weighted cohorts. Results: A total of 599 patients were analyzed, out of whom 369 (61.6%) underwent WP-RT. Patients in the WP-RT group were younger (mean age 73.2 vs. 77.4; ASD 0.41), and more likely to have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (82.1% vs. 73.5%; ASD 0.21), clinical node-positive disease (12.5% vs. 2.2%; ASD 0.40), and lymphovascular invasion (26.3% vs. 16.1%; ASD 0.25), compared to BO-RT. In addition, WP-RT patients were more commonly treated with neoadjuvant chemotherapy (20.9% vs. 10.4%; ASD 0.29) and concurrent chemotherapy (76.7% vs. 56.5%; ASD 0.44), compared to BO-RT. In the IPTW cohort, age, gender, ECOG PS, clinical staging, the proportion of patients with carcinoma in situ, lymphovascular invasion, variant urothelial histologies, hydronephrosis, and whose tumours were completely resected before RT, treated with NAC, and treated with concurrent chemotherapy were well balanced across groups (all ASDs &lt; 0.10). In multivariable analysis, WP-RT did not impact CR rates post-RT (OR 1.14; p=0.526) but was associated with both CSS (HR 0.66; p=0.016) and OS (HR 0.68; p=0.002), independently of other prognostic factors (Table). Conclusions: Our study demonstrated a significant survival benefit with the use of WP-RT compared to BO-RT in patients with MIBC treated with curative intent. Additional randomized controlled trials are needed to confirm our findings.

Benefit of whole-pelvis radiation for patients with muscle-invasive bladder cancer: An inverse probability treatment weighted analysis

Benefit of whole-pelvis radiation for patients with muscle-invasive bladder cancer: An inverse probability treatment weighted analysis

Sentinel Node Procedure to Select Clinically Localized Prostate Cancer Patients with Occult Nodal Metastases for Whole Pelvis Radiotherapy

BackgroundAccurate identification of men who harbor nodal metastases is necessary to select patients who most likely benefit from whole pelvis radiotherapy (WPRT). Limited sensitivity of diagnostic imaging approaches for the detection of nodal micrometastases has led to the exploration of the sentinel lymph node biopsy (SLNB). ObjectiveTo evaluate whether SLNB can be used as a tool to select pathologically node-positive patients who likely benefit from WPRT. Design, setting, and participantsWe included 528 clinically node-negative primary prostate cancer (PCa) patients with an estimated nodal risk of >5% treated between 2007 and 2018. InterventionA total of 267 patients were directly treated with prostate-only radiotherapy (PORT; non-SLNB group), while 261 patients underwent SLNB to remove lymph nodes directly draining from the primary tumor prior to radiotherapy (SLNB group); pN0 patients were treated with PORT, while pN1 patients were offered WPRT. Outcome measurements and statistical analysisBiochemical recurrence–free survival (BCRFS) and radiological recurrence-free survival (RRFS) were compared using propensity score weighted (PSW) Cox proportional hazard models. Results and limitationsThe median follow-up was 71 mo. Occult nodal metastases were found in 97 (37%) SLNB patients (median metastasis size: 2 mm). Adjusted 7-yr BCRFS rates were 81% (95% confidence interval [CI] 77–86%) in the SLNB group and 49% (95% CI 43–56%) in the non-SLNB group. The corresponding adjusted 7-yr RRFS rates were 83% (95% CI 78–87%) and 52% (95% CI 46–59%), respectively. In the PSW multivariable Cox regression analysis, SLNB was associated with improved BCRFS (hazard ratio [HR] 0.38, 95% CI 0.25–0.59, p < 0.001) and RRFS (HR 0.44, 95% CI 0.28–0.69, p < 0.001). Limitations include the bias inherent to the study’s retrospective nature. ConclusionsSLNB-based selection of pN1 PCa patients for WPRT was associated with significantly improved BCRFS and RRFS compared with (conventional) imaging-based PORT. Patient summarySentinel node biopsy can be used to select patients who will benefit from the addition of pelvis radiotherapy. This strategy results in a longer duration of prostate-specific antigen control and a lower risk of radiological recurrence.

Variability of radiotherapy volume delineation: PSMA PET/MRI and MRI based clinical target volume and lymph node target volume for high-risk prostate cancer

PurposeA comparative retrospective study to assess the impact of PSMA Ligand PET/MRI ([68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 PET/MRI) as a new method of target delineation compared to conventional imaging on whole-pelvis radiotherapy for high-risk prostate cancer (PCa).Patients and methodsForty-nine patients with primary high-risk PCa completed the whole-pelvis radiotherapy plan based on PSMA PET/MRI and MRI. The primary endpoint compared the size and overlap of clinical target volume (CTV) and nodal gross tumour volume (GTVn) based on PSMA PET/MRI and MRI. The diagnostic performance of two methods for pelvic lymph node metastasis (PLNM) was evaluated.ResultsIn the radiotherapy planning for high-risk PCa patients, there was a significant correlation between MRI-CTV and PET/MRI-CTV (P = 0.005), as well as between MRI-GTVn and PET/MRI-GTVn (P < 0.001). There are non-significant differences in the CTV and GTVn based on MRI and PET/MRI images (P = 0.660, P = 0.650, respectively). The conformity index (CI), lesion coverage factor (LCF) and Dice similarity coefficient (DSC) of CTVs were 0.999, 0.953 and 0.954. The CI, LCF and DSC of GTVns were 0.927, 0.284, and 0.32. Based on pathological lymph node analysis of 463 lymph nodes from 37 patients, the sensitivity, specificity of PET/MRI in the diagnosis of PLNM were 77.78% and 99.76%, respectively, which were higher than those of MRI (P = 0.011). Eight high-risk PCa patients who finished PSMA PET/MRI changed their N or M stage.ConclusionThe CTV delineated based on PET/MRI and MRI differ little. The GTVn delineated based on PET/MRI encompasses metastatic pelvic lymph nodes more accurately than MRI and avoids covering pelvic lymph nodes without metastasis. We emphasize the utility of PET/MRI fusion images in GTVn delineation in whole pelvic radiotherapy for PCa. The use of PSMA PET/MRI aids in the realization of more individual and precise radiotherapy for PCa.

VMAT partial arc technique decreases dose to organs at risk in whole pelvic radiotherapy for prostate cancer when compared to full arc VMAT and IMRT.

Whole pelvic radiotherapy (WPRT) can sterilize microscopic lymph node metastases in treatment of prostate cancer. WPRT, compared to prostate only radiotherapy (PORT), is associated with increased acute gastrointestinal, and hematological toxicities. To further explore minimizing normal tissue toxicities associated with WPRT in definitive IMRT for prostate cancer, this planning study compared dosimetric differences between static 9-field-IMRT, full arc VMAT, and mixed partial-full arc VMAT techniques. In this retrospective study, 12 prostate cancer patients who met the criteria for WPRT were randomly selected for this study. The initial volume, PTV46, included the prostate, seminal vesicles, and pelvic nodes with margin and was prescribed to 4600cGy. The cone-down volume, PTV78, included the prostate and proximal seminal vesicles with margin to a total dose of 7800cGy. For each CT image set, 3 plans were generated for each of the PTVs: an IMRT plan, a full arc (FA) VMAT plan, and a mixed partial-full arc (PFA) VMAT plan, using 6MV photons energy. According to RTOG protocols none of the plans had a major Conformity Index (CI) violation by any of the 3 planning techniques. PFA plan had the best mean CI index of 1.00 and significantly better than IMRT (p = 0.03) and FA (p = 0.007). For equivalent PTV coverage, the average composite gradient index of the PFA plans was better than the IMRT and the FA plans with values 1.92, 2.03, and 2.01 respectively. The defference was statistically significant between PFA/IMRT and PFA/FA, with p- values of < 0.001. The IMRT plans and the PFA plans provided very similar doses to the rectum, bladder, sigmoid colon, and femoral heads, which were lower than the dose in the FA plans. There was a significant decrease in the mean dose to the rectum from 4524 cGy with the FA to 4182cGy with the PFA and 4091cGy with IMRT (p < 0.001). The percent of rectum receiving 4000cGy was also the highest with FA at 66.1% compared to 49.9% (PFA) and 47.5% (IMRT). There was a significant decrease in the mean dose to the bladder from 3922cGy (FA) to 3551cGy (PFA) and 3612cGy (IMRT) (p < 0.001). The percent of bladder receiving 4000cGy was also the highest with FA at 45.4% compared to 36.6% (PFA) and 37.4% (IMRT). The average mean dose to the sigmoid colon decreased from 4177cGy (FA) to 3893cGy (PFA) and 3819cGy (IMRT). The average mean dose to the femoral heads decreased from 2091cGy (FA) to 2026cGy (PFA) and 1987cGy (IMRT). Considering the improvement in plan quality indices recorded in this study including the dose gradient and the dose to organs at risk, mixed partial-full arc plans may be the preferred VMAT treatment technique over full arc plans for prostate cancer treatments that include nodal volumes.