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Item does not contain fulltext, PURPOSE: The FLAME trial (NCT01168479) showed that isotoxic focal boosting to the intraprostatic lesion(s) in patients with intermediate- and high-risk prostate cancer improves 5-year disease-free survival (DFS). Although the near-minimum dose to the gross tumor volume (D98%) was associated with improved outcomes, a closer look suggested that this might not be the same for all patients. Therefore, we investigated whether risk factors that are associated with a benefit of focal boosting can be identified. METHODS AND MATERIALS: We described the distribution of clinical characteristics and the number of high-risk factors with respect to the D98% in 526 FLAME trial patients. We used penalized Cox regression to develop a prediction model. To investigate a potential benefit in patient subgroups, we compared the model-based predictions of 5-year DFS assuming standard whole-gland radiation therapy of 77 Gy to the predictions assuming an additional focal boost with D98% of 95 Gy. RESULTS: Patients with high-risk factors were well represented in the group of 120 patients that received D98% > 85 Gy and showed fewer recurrences compared with the group that received 77 Gy. Applying the model simulating a standard dose of 77 Gy, we predicted a high DFS for grade group (GG) 1 patients, whereas patients with high-risk characteristics appeared to show a low DFS. All risk groups showed a high level of DFS when simulating D98% of 95 Gy. CONCLUSIONS: Our results suggest that GG 1 patients already show a low level of failure at a standard dose of 77 Gy, limiting the additional benefit of focal boosting. In contrast, patients with high-risk characteristics, especially GG 4 or 5, show a low 5-year DFS, while focal boosting might improve this substantially. This suggests that reaching a high focal boost dose may be particularly beneficial for these patients.

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Contains fulltext : 292741.pdf (Publisher’s version ) (Open Access), The post-treatment imaging surveillance of gliomas is challenged by distinguishing tumor progression (TP) from treatment-related abnormalities (TRA). Sophisticated imaging techniques, such as perfusion-weighted magnetic resonance imaging (MRI PWI) and positron-emission tomography (PET) with a variety of radiotracers, have been suggested as being more reliable than standard imaging for distinguishing TP from TRA. However, it remains unclear if any technique holds diagnostic superiority. This meta-analysis provides a head-to-head comparison of the diagnostic accuracy of the aforementioned imaging techniques. Systematic literature searches on the use of PWI and PET imaging techniques were carried out in PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and the reference lists of relevant papers. After the extraction of data on imaging technique specifications and diagnostic accuracy, a meta-analysis was carried out. The quality of the included papers was assessed using the QUADAS-2 checklist. Nineteen articles, totaling 697 treated patients with glioma (431 males; mean age ± standard deviation 50.5 ± 5.1 years) were included. The investigated PWI techniques included dynamic susceptibility contrast (DSC), dynamic contrast enhancement (DCE) and arterial spin labeling (ASL). The PET-tracers studied concerned [S-methyl-(11)C]methionine, 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG), O-(2-[(18)F]fluoroethyl)-L-tyrosine ([(18)F]FET) and 6-[(18)F]-fluoro-3,4-dihydroxy-L-phenylalanine ([(18)F]FDOPA). The meta-analysis of all data showed no diagnostic superior imaging technique. The included literature showed a low risk of bias. As no technique was found to be diagnostically superior, the local level of expertise is hypothesized to be the most important factor for diagnostically accurate results in post-treatment glioma patients regarding the distinction of TRA from TP.

Item does not contain fulltext, BACKGROUND: Germline and tumour genetic testing in prostate cancer (PCa) is becoming more broadly accepted, but testing indications and clinical consequences for carriers in each disease stage are not yet well defined. OBJECTIVE: To determine the consensus of a Dutch multidisciplinary expert panel on the indication and application of germline and tumour genetic testing in PCa. DESIGN SETTING AND PARTICIPANTS: The panel consisted of 39 specialists involved in PCa management. We used a modified Delphi method consisting of two voting rounds and a virtual consensus meeting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consensus was reached if ≥75% of the panellists chose the same option. Appropriateness was assessed by the RAND/UCLA appropriateness method. RESULTS AND LIMITATIONS: Of the multiple-choice questions, 44% reached consensus. For men without PCa having a relevant family history (familial PCa/BRCA-related hereditary cancer), follow-up by prostate-specific antigen was considered appropriate. For patients with low-risk localised PCa and a family history of PCa, active surveillance was considered appropriate, except in case of the patient being a BRCA2 germline pathogenic variant carrier. Germline and tumour genetic testing should not be done for nonmetastatic hormone-sensitive PCa in the absence of a relevant family history of cancer. Tumour genetic testing was deemed most appropriate for the identification of actionable variants, with uncertainty for germline testing. For tumour genetic testing in metastatic castration-resistant PCa, consensus was not reached for the timing and panel composition. The principal limitations are as follows: (1) a number of topics discussed lack scientific evidence, and therefore the recommendations are partly opinion based, and (2) there was a small number of experts per discipline. CONCLUSIONS: The outcomes of this Dutch consensus meeting may provide further guidance on genetic counselling and molecular testing related to PCa.

01 augustus 2023, Contains fulltext : 294962.pdf (Publisher’s version ) (Closed access), BACKGROUND AND PURPOSE: The hypo-FLAME trial showed that once-weekly (QW) focal boosted prostate stereotactic body radiotherapy (SBRT) is associated with acceptable acute genitourinary (GU) and gastrointestinal (GI) toxicity. Currently, we investigated the safety of reducing the overall treatment time (OTT) of focal boosted prostate SBRT from 29 to 15 days. MATERIAL AND METHODS: Patients with intermediate- and high-risk prostate cancer were treated with SBRT delivering 35 Gy in 5 fractions to the whole prostate gland with an iso-toxic boost up to 50 Gy to the intraprostatic lesion(s) in a semi-weekly (BIW) schedule. The primary endpoint was radiation-induced acute toxicity (CTCAE v5.0). Changes in quality of life (QoL) were examined in terms of proportions achieving a minimal clinically important change (MCIC). Finally, acute toxicity and QoL scores of the BIW schedule were compared with the results of the prior QW hypo-FLAME schedule (n = 100). RESULTS: Between August 2020 and February 2022, 124 patients were enrolled and treated BIW. No grade ≥3 GU or GI toxicity was observed. The 90-days cumulative incidence of grade 2 GU and GI toxicity rates were 47.5% and 7.4%, respectively. Patients treated QW scored significant less grade 2 GU toxicity (34.0%, p = 0.01). No significant differences in acute GI toxicity were observed. Furthermore, patients treated QW had a superior acute bowel and urinary QoL. CONCLUSION: Semi-weekly prostate SBRT with iso-toxic focal boosting is associated with acceptable acute GU and GI toxicity. Based on the comparison between the QW and BIW schedule, patients should be counselled regarding the short-term advantages of a more protracted schedule. Registration number ClinicalTrials.gov: NCT04045717.

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Item does not contain fulltext, PURPOSE OR OBJECTIVES: The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractionated EBRT in the treatment of localized prostate cancer, the five-year biochemical disease-free survival increased, without significantly increasing toxicity. The aim of the present study was to investigate the association between radiation dose to the bladder and urethra and genitourinary (GU) toxicity grade ≥2 in the entire cohort. MATERIAL AND METHODS: The dose-effect relations of the urethra and bladder dose, separately, and GU toxicity grade ≥2 (CTCAE 3.0) up to five years after treatment were assessed. A mixed model analysis for repeated measurements was used, adjusting for age, diabetes mellitus, T-stage, baseline GU toxicity grade ≥1 and institute. Additionally, the association between the dose and separate GU toxicity subdomains were investigated. RESULTS: Dose-effect relations were observed for the dose (Gy) to the bladder D2 cm(3) and urethra D0.1 cm(3), with adjusted odds ratios of 1.14 (95% CI 1.12-1.16, p < 0.0001) and 1.12 (95% CI 1.11-1.14, p < 0.0001), respectively. Additionally, associations between the dose to the urethra and bladder and the subdomains urinary frequency, urinary retention and urinary incontinence were observed. CONCLUSION: Further increasing the dose to the bladder and urethra will result in a significant increase in GU toxicity following EBRT. Focal boost treatment plans should incorporate a urethral dose-constraint. Further treatment optimization to increase the focal boost dose without increasing the dose to the urethra and other organs at risk should be a focus for future research, as we have shown that a focal boost is beneficial in the treatment of prostate cancer.

Item does not contain fulltext, BACKGROUND AND PURPOSE: Currently, automatic approaches for radiotherapy planning are widely used, however creation of high quality treatment plans is still challenging. In this study, two independent dose prediction methods were used to personalize the initial settings for the automated planning template for optimizing prostate cancer treatment plans. This study evaluated the dose metrics of these plans comparing both methods with the current clinical automated prostate cancer treatment plans. MATERIAL AND METHODS: Datasets of 20 high-risk prostate cancer treatment plans were taken from our clinical database. The prescription dose for these plans was 70 Gy given in fractions of 2.5 Gy. Plans were replanned using the current clinical automated treatment and compared with two personalized automated planning methods. The feasibility dose volume histogram (FDVH) and modified filter back projection (mFBP) methods were used to calculate independent dose predictions. Parameters for the initial objective values of the planning template were extracted from these predictions and used to personalize the optimization of the automated planning process. RESULTS: The current automated replanned clinical plans and the automated plans optimized with the personalized template methods fulfilled the clinical dose criteria. For both methods a reduction in the average mean dose of the rectal wall was found, from 22.5 to 20.1 Gy for the FDVH and from 22.5 to 19.6 Gy for the mFBP method. CONCLUSIONS: With both dose-prediction methods the initial settings of the template could be personalized. Hereby, the average dose to the rectal wall was reduced compared to the standard template method.

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Contains fulltext : 249327.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 283430.pdf (Publisher’s version ) (Open Access), BACKGROUND: In a considerable subgroup of glioma patients treated with (chemo) radiation new lesions develop either representing tumor progression (TP) or treatment-related abnormalities (TRA). Quantitative diffusion imaging metrics such as the Apparent Diffusion Coefficient (ADC) and Fractional Anisotropy (FA) have been reported as potential metrics to noninvasively differentiate between these two phenomena. Variability in performance scores of these metrics and absence of a critical overview of the literature contribute to the lack of clinical implementation. This meta-analysis therefore critically reviewed the literature and meta-analyzed the performance scores. METHODS: Systematic searching was carried out in PubMed, EMBASE and The Cochrane Library. Using predefined criteria, papers were reviewed. Diagnostic accuracy values of suitable papers were meta-analyzed quantitatively. RESULTS: Of 1252 identified papers, 10 ADC papers, totaling 414 patients, and 4 FA papers, with 154 patients were eligible for meta-analysis. Mean ADC values of the patients in the TP/TRA groups were 1.13 × 10(-3)mm(2)/s (95% CI 0.912 × 10(-3)-1.32 × 10(-3)mm(2)/s) and 1.38 × 10(-3)mm(2)/s (95% CI 1.33 × 10(-3)-1.45 × 10(-3)mm(2)/s, respectively. Mean FA values of TP/TRA was 0.19 (95% CI 0.189-0.194) and 0.14 (95% CI 0.137-0.143) respectively. A significant mean difference between ADC and FA values in TP versus TRA was observed (p = 0.005). CONCLUSIONS: Quantitative ADC and FA values could be useful for distinguishing TP from TRA on a meta-level. Further studies using serial imaging of individual patients are warranted to determine the role of diffusion imaging in glioma patients.

Item does not contain fulltext, BACKGROUND: Focal dose escalation in external beam radiotherapy (EBRT) showed an increase in 5-yr biochemical disease-free survival in the Focal Lesion Ablative Microboost in Prostate Cancer (FLAME) trial. OBJECTIVE: To analyze the effect of a focal boost to intraprostatic lesions on local failure-free survival (LFS) and regional + distant metastasis-free survival (rdMFS). DESIGN, SETTING, AND PARTICIPANTS: Patients with intermediate- or high-risk localized prostate cancer were included in FLAME, a phase 3, multicenter, randomized controlled trial. INTERVENTION: Standard treatment of 77 Gy to the entire prostate in 35 fractions was compared to an additional boost to the macroscopic tumor of up to 95 Gy during EBRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: LFS and rdMFS, measured via any type of imaging, were compared between the treatment arms using Kaplan-Meier and Cox regression analyses. Dose-response curves were created for local failure (LF) and regional + distant metastatic failure (rdMF) using logistic regression. RESULTS AND LIMITATIONS: A total of 571 patients were included in the FLAME trial. Over median follow-up of 72 mo (interquartile range 58-86), focal boosting decreased LF (hazard ratio [HR] 0.33, 95% confidence interval [CI] 0.14-0.78) and rdMF (HR 0.58, 95% CI 0.35-0.93). Dose-response curves showed that a greater dose to the tumor resulted in lower LF and rdMF rates. CONCLUSIONS: A clear dose-response relation for LF and rdMF was observed, suggesting that adequate focal dose escalation to intraprostatic lesions prevents undertreatment of the primary tumor, resulting in an improvement rdMF. PATIENT SUMMARY: Radiotherapy is a treatment option for high-risk prostate cancer. The FLAME trial has shown that a high dose specifically targeted at the tumor within the prostate will result in better disease outcome, with less likelihood of regional and distant disease spread. The FLAME trial is registered on ClinicalTrials.gov as NCT01168479.

Contains fulltext : 244248.pdf (Publisher’s version ) (Open Access), PURPOSE: External Beam Radiotherapy (EBRT) techniques dramatically changed over the years. This may have affected the risk of radiation-induced second primary cancers (SPC), due to increased irradiated low dose volumes and scatter radiation. We investigated whether patterns of SPC after EBRT have changed over the years in prostate cancer (PCa) survivors. MATERIALS AND METHODS: PCa survivors diagnosed between 1990-2014 were selected from the Netherlands Cancer Registry. Patients treated with EBRT were divided in three time periods, representing 2-dimensional Radiotherapy (RT), 3-dimensional conformal RT (3D-CRT), and the advanced RT (AdvRT) era. Standardized incidence ratios (SIR) and absolute excess risks (AER) were calculated to estimate relative and excess absolute SPC risks. Sub-hazard ratios (sHRs) were calculated to compare SPC rates between the EBRT and prostatectomy cohort. SPCs were categorized by subsite and anatomic region. RESULTS: PCa survivors who received EBRT had an increased risk of developing a solid SPC (SIR=1.08; 1.05-1.11), especially in patients aged <70 years (SIR=1.13; 1.09-1.16). Pelvic SPC risks were increased (SIR=1.28; 1.23-1.34), with no obvious differences between the three EBRT eras. Non-pelvic SPC were only significantly increased in the AdvRT era (SIR=1.08; 1.02-1.14), in particular for the 1-5 year follow-up period. Comparing the EBRT cohort to the prostatectomy cohort, again an increased pelvic SPC risk was found for all EBRT periods (sHRs= 1.61, 1.47-1.76). Increased non-pelvic SPC risks were present for all RT eras and highest for the AdvRT period (sHRs=1.17, 1.06-1.29). CONCLUSION: SPC risk in patients with EBRT is increased and remained throughout the different EBRT eras. The risk of developing a SPC outside the pelvic area changed unfavorably in the AdvRT era. Prolonged follow-up is needed to confirm this observation. Whether this is associated with increased irradiated low-dose volumes and scatter, or other changes in clinical

Contains fulltext : 235310.pdf (Publisher’s version ) (Closed access), PURPOSE: [(177)Lu]Lu-PSMA-617 radioligand therapy ((177)Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of (177)Lu-PSMA in pateints with low-volume mHSPC. PATIENTS AND METHODS: Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on [(68)Ga]Ga-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of (177)Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS. RESULTS: All patients received two cycles of (177)Lu-PSMA without complications. No treatment-related grade III-IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease. CONCLUSIONS: (177)Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC.

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Contains fulltext : 232798.pdf (Publisher’s version ) (Open Access), BACKGROUND AND PURPOSE: Proton therapy is expected to outperform photon-based treatment regarding organs at risk (OAR) sparing but to date there is no method to practically measure clinical benefit. Here, we introduce the novel ROCOCO Performance Scoring System (RPSS) translating dose differences into clinically relevant endpoints and apply this to a treatment plan comparison of volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) in 20 pilocytic astrocytoma patients. MATERIAL AND METHODS: The RPSS was developed on the basis of expert-based weighting factors and toxicity scores per OAR. The imaging datasets of 20 pilocytic astrocytoma patients having undergone radiotherapy were included in this in silico dosimetric comparison trial as proof of principle. For each of these patients, treatment plans to a total dose of 54 Gy (RBE) were generated for VMAT and IMPT and these were compared regarding radiation dose to the clinical target volume (CTV) and OARs. The RPSS was calculated for each treatment plan comparing VMAT and IMPT. RESULTS: In 40 analysed treatment plans, the average and low dose volumes to various OARs were significantly reduced when using IMPT compared to VMAT (p < 0.05). Using the RPSS, a significant difference between both treatment modalities was found, with 85% of the patients having a lower RPSS in favour of the IMPT plan. CONCLUSION: There are dosimetric differences between IMPT and VMAT in pilocytic astrocytoma patients. In absence of clinically validated NTCP models we introduce the RPSS model in order to objectively compare treatment modalities by translating dosimetric differences in potential clinical differences.

Item does not contain fulltext, PURPOSE: This study proposes optimal tracer-specific threshold-based window levels for PSMA PET-based intraprostatic gross tumour volume (GTV) contouring to reduce interobserver delineation variability. METHODS: Nine (68)Ga-PSMA-11 and nine (18)F-PSMA-1007 PET scans including GTV delineations of four expert teams (GTV(manual)) and a majority-voted GTV (GTV(majority)) were assessed with respect to a registered histopathological GTV (GTV(histo)) as the gold standard reference. The standard uptake values (SUVs) per voxel were converted to a percentage (SUV%) relative to the SUV(max). The statistically optimised SUV% threshold (SOST) was defined as those that maximises accuracy for threshold-based contouring. A leave-one-out cross-validation receiver operating characteristic (ROC) curve analysis was performed to determine the SOST for each tracer. The SOST analysis was performed twice, first using the GTV(histo) contour as training structure (GTV(SOST-H)) and second using the GTV(majority) contour as training structure (GTV(SOST-MA)) to correct for any limited misregistration. The accuracy of both GTV(SOST-H) and GTV(SOST-MA) was calculated relative to GTV(histo) in the 'leave-one-out' patient of each fold and compared with the accuracy of GTV(manual). RESULTS: ROC curve analysis for (68)Ga-PSMA-11 PET revealed a median threshold of 25 SUV% (range, 22-27 SUV%) and 41 SUV% (40-43 SUV%) for GTV(SOST-H) and GTV(SOST-MA), respectively. For (18)F-PSMA-1007 PET, a median threshold of 42 SUV% (39-45 SUV%) for GTV(SOST-H) and 44 SUV% (42-45 SUV%) for GTV(SOST-MA) was found. A significant pairwise difference was observed when comparing the accuracy of the GTV(SOST-H) contours with the median accuracy of the GTV(manual) contours (median, - 2.5%; IQR, - 26.5-0.2%; p = 0.020), whereas no significant pairwise difference was found for the GTV(SOST-MA) contours (median, - 0.3%; IQR, - 4.4-0.6%; p = 0.199). CONCLUSIONS: Threshold-based contouring using GTV(majority)-trained SOSTs achie

Contains fulltext : 232628.pdf (Publisher’s version ) (Open Access), PURPOSE: This study investigates whether focal boosting of the macroscopic visible tumor with external beam radiotherapy increases biochemical disease-free survival (bDFS) in patients with localized prostate cancer. PATIENTS AND METHODS: In the phase III, multicenter, randomized controlled Focal Lesion Ablative Microboost in Prostate Cancer trial, 571 patients with intermediate- and high-risk prostate cancer were enrolled between 2009 and 2015. Patients assigned to standard treatment received 77 Gy (fractions of 2.2 Gy) to the entire prostate. The focal boost arm received an additional simultaneous integrated focal boost up to 95 Gy (fractions up to 2.7 Gy) to the intraprostatic lesion visible on multiparametric magnetic resonance imaging. Organ at risk constraints were prioritized over the focal boost dose. The primary end point was 5-year bDFS. Secondary end points were disease-free survival (DFS), distant metastases-free survival, prostate cancer-specific survival, overall survival, toxicity, and health-related quality of life. RESULTS: Median follow-up was 72 months. Biochemical DFS was significantly higher in the focal boost compared with the standard arm (hazard ratio 0.45, 95% CI, 0.28 to 0.71, P < .001). At 5-year follow-up bDFS was 92% and 85%, respectively. We did not observe differences in prostate cancer-specific survival (P = .49) and overall survival (P = .50). The cumulative incidence of late genitourinary and GI toxicity grade ≥ 2 was 23% and 12% in the standard arm versus 28% and 13% in the focal boost arm, respectively. Both for late toxicity as health-related quality of life, differences were small and not statistically significant. CONCLUSION: The addition of a focal boost to the intraprostatic lesion improved bDFS for patients with localized intermediate- and high-risk prostate cancer without impacting toxicity and quality of life. The Focal Lesion Ablative Microboost in Prostate Cancer study shows that a high focal boost strategy to improve tum

Contains fulltext : 232771.pdf (Publisher’s version ) (Open Access), Radiotherapy has an important role in the curative and palliative treatment settings for bladder cancer. As a target for radiotherapy the bladder presents a number of technical challenges. These include poor tumor visualization and the variability in bladder size and position both between and during treatment delivery. Evidence favors the use of magnetic resonance imaging (MRI) as an important means of tumor visualization and local staging. The availability of hybrid systems incorporating both MRI scanning capabilities with the linear accelerator (MR-Linac) offers opportunity for in-room and real-time MRI scanning with ability of plan adaption at each fraction while the patient is on the treatment couch. This has a number of potential advantages for bladder cancer patients. In this article, we examine the technical challenges of bladder radiotherapy and explore how magnetic resonance (MR) guided radiotherapy (MRgRT) could be leveraged with the aim of improving bladder cancer patient outcomes. However, before routine clinical implementation robust evidence base to establish whether MRgRT translates into improved patient outcomes should be ascertained.

Contains fulltext : 233507.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 235318.pdf (Publisher’s version ) (Open Access), BACKGROUND AND PURPOSE: For irradiation of localized prostate-cancer, moderately-hypofractionated regimens with a variety of dose per fraction are used. We adopted a regimen of 70 Gy in 28 fractions of 2.5 Gy, using state of the art radiotherapy (RT) and closely monitored the efficacy, toxicity and health-related quality of life (HRQoL) in a large cohort, using patient-reported outcomes. MATERIALS AND METHODS: Between 2008 and 2016, 462 patients with intermediate- to high-risk localized prostate cancer were treated with RT, 28 fractions of 2.5 Gy, using IMRT/VMAT, an online fiducial-maker based correction protocol and a daily inserted endorectal balloon. Overall freedom from failure (no biochemical or clinical recurrence) , as well as self-reported genitourinary (GU) and gastrointestinal (GI) related toxicity and HRQoL are reported. RESULTS: Overall freedom from failure rates at 3 and 5 years were 92.0% (89.1-94.9%) and 83.5% (78.6-88.4%), respectively. Prevalence rates of grade ≥ 2 GU/GI-toxicity were 16.3%/6.3% and 22,1%/3.2% after 3 and 5 years respectively. The 5-year actuarial incidences of grade ≥ 2 GU/GI-toxicity were 43.5%/18.5%. HRQoL worsened during RT and gradually recovered thereafter, In accordance with the prevalence rates. CONCLUSION: Treatment of intermediate- or high-risk localized prostate cancer with RT to 70 Gy in 28 fractions with IMRT/VMAT, using fiducial markers and an endorectal balloon leads to good long-term tumor control rates and acceptable patient reported toxicity rates. Furthermore, patient-reported outcomes, including HRQoL, are essential for a good comparison between different studies. Finally, prevalence rates show a better correlation with HRQoL than actuarial incidence rates do and might therefore better represent the burden of toxicity.

Item does not contain fulltext, BACKGROUND AND PURPOSE: The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade >/=2). MATERIAL AND METHODS: All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose-effect relation of the anorectal dose parameters (D2cm(3) and D50%) and GI toxicity grade >/=2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade >/=1, hormonal therapy and institute. RESULTS: A dose-effect relation for D2cm(3) and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13-1.21, p < 0.0001) and 1.20 (95% CI 1.14-1.25, p < 0.0001) for GI toxicity, respectively. CONCLUSION: Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose-effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer.

Contains fulltext : 226250.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 220466.pdf (Publisher’s version ) (Closed access), BACKGROUND AND PURPOSE: Local recurrences after radiotherapy for prostate cancer (PCa) often originate at the location of the macroscopic tumour(s). Since PCa cells are known to be sensitive to high fraction doses, hypofractionated whole gland stereotactic body radiotherapy (SBRT) in conjunction with a simultaneous ablative microboost to the macroscopic tumour(s) within the prostate could be a way to reduce the risk of local failure. We investigated the safety of this treatment strategy. MATERIALS AND METHODS: Patients with intermediate or high risk PCa were enrolled in a prospective phase II trial, called hypo-FLAME. All patients were treated with extreme hypofractionated doses of 35 Gy in 5 weekly fractions to the whole prostate gland with an integrated boost up to 50 Gy to the multiparametric (mp) MRI-defined tumour(s). Treatment-related toxicity was measured using the CTCAE v4.0. The primary endpoint of the trial was treatment-related acute toxicity. RESULTS: Between April 2016 and December 2018, 100 men were treated in 4 academic centres. All patients were followed up for a minimum of 6 months. The median mean dose delivered to the visible tumour nodule(s) on mpMRI was 44.7 Gy in this trial. No grade ≥3 acute genitourinary (GU) or gastrointestinal (GI) toxicity was observed. Furthermore, 90 days after start of treatment, the cumulative acute grade 2 GU and GI toxicity rates were 34.0% and 5.0%, respectively. CONCLUSION: Simultaneous focal boosting to the macroscopic tumour(s) in addition to whole gland prostate SBRT is associated with acceptable acute GU and GI toxicity.