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Abstract Background We aimed to assess the feasibility of a dose painting (DP) procedure, known as simultaneous integrated boost intensity modulated radiation Therapy (SIB-IMRT), for treating prostate cancer with dominant intraprostatic lesions (DILs) based on multi-parametric magnetic resonance (mpMR) images and hierarchical clustering with a machine learning technique. Methods The mpMR images of 120 patients were used to create hierarchical clustering and draw a dendrogram. Three clusters were selected for performing agglomerative clustering. Then, the DIL acquired from the mpMR images of 20 patients were categorized into three groups to have them treated with a DP procedure being composed of three planning target volumes (PTVs) determined as PTV1, PTV2, and PTV3 in treatment plans. The DP procedure was carried out on the patients wherein a total dose of 80, 85 and 91 Gy were delivered to the PTV1, PTV2, and PTV3, respectively. Dosimetric and radiobiologic parameters [Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)] of the DP procedure were compared with those of the conventional IMRT and Three-Dimensional Conformal Radiation Therapy (3DCRT) procedures carried out on another group of 20 patients. A post-treatment follow-up was also made four months after the radiotherapy procedures. Results All the dosimetric variables and the NTCPs of the organs at risks (OARs) revealed no significant difference between the DP and IMRT procedures. Regarding the TCP of three investigated PTVs, significant differences were observed between the DP versus IMRT and also DP versus 3DCRT procedures. At post-treatment follow-up, the DIL volumes and apparent diffusion coefficient (ADC) values in the DP group differed significantly (p-value 0.05) between the DP versus IMRT. Conclusions The results of this comprehensive clinical trial illustrated the feasibility of our DP procedure for treating prostate cancer based on mpMR images validated with acquired patients’ dosimetric and radiobiologic assessment and their follow-ups. This study confirms significant potential of the proposed DP procedure as a promising treatment planning to achieve effective dose escalation and treatment for prostate cancer. Trial registration: IRCT20181006041257N1; Iranian Registry of Clinical Trials, Registered: 23 October 2019, https://en.irct.ir/trial/34305 .

Background: We aimed to assess the feasibility of a dose painting (DP) procedure, known as simultaneous integrated boost intensity modulated radiation Therapy (SIB-IMRT), for treating prostate cancer with dominant intraprostatic lesions (DILs) based on multi-parametric magnetic resonance (mpMR) images and hierarchical clustering with a machine learning technique.Methods: The mpMR images of 120 patients were used to create hierarchical clustering and draw a dendrogram. Three clusters were selected for performing agglomerative clustering. Then, the DIL acquired from the mpMR images of 20 patients were categorized into three groups to have them treated with a DP procedure being composed of three planning target volumes (PTVs) determined as PTV1, PTV2, and PTV3 in treatment plans. The DP procedure was carried out on the patients wherein a total dose of 80, 85 and 91 Gy were delivered to the PTV1, PTV2, and PTV3, respectively. Dosimetric and radiobiologic parameters [Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)] of the DP procedure were compared with those of the conventional IMRT and Three-Dimensional Conformal Radiation Therapy (3DCRT) procedures carried out on another group of 20 patients. A post-treatment follow-up was also made four months after the radiotherapy procedures.Results: All the dosimetric variables and the NTCPs of the organs at risks (OARs) revealed no significant difference between the DP and IMRT procedures. Regarding the TCP of three investigated PTVs, significant differences were observed between the DP versus IMRT and also DP versus 3DCRT procedures. At post-treatment follow-up, the DIL volumes and apparent diffusion coefficient (ADC) values in the DP group differed significantly (p-value < 0.001) from those of the IMRT. However, the whole prostate ADC and prostate-specific antigen (PSA) indicated no significant difference (p-value > 0.05) between the DP versus IMRT.Conclusions: The results of this comprehensive clinical trial illustrated the feasibility of our DP procedure for treating prostate cancer based on mpMR images validated with acquired patients' dosimetric and radiobiologic assessment and their follow-ups. This study confirms significant potential of the proposed DP procedure as a promising treatment planning to achieve effective dose escalation and treatment for prostate cancer.Trial Registration: IRCT20181006041257N1; Iranian Registry of Clinical Trials, Registered: 23 October 2019, https://en.irct.ir/trial/34305 . [ABSTRACT FROM AUTHOR]

Background: Patients with large, locally advanced cervical cancers (LACC) are challenging to treat. The purpose of this work is to use 18F-FDG PET as planning basis for a short-course simultaneous integrated boost (SIB) in external beam radiotherapy of LACC in order to increase tumour shrinkage and likelihood of local control.Methods: Ten previously treated patients with LACC were included, all with pre-treatment FDG PET/CT images available. The FDG avid tumour volume, MTV50, was dose escalated in silico by intensity modulated radiotherapy from the standard 1.8 Gy to 2.8 Gy per fraction for the 10 first fractions; a short-course SIB. For the 18 remaining external fractions, standard pelvic treatment followed to total PTV and MTV50 doses of 50.4 Gy and 60.4 Gy, respectively. Photon and proton treatment were considered using volumetric modulated arc treatment (VMAT) and intensity-modulated proton therapy (IMPT), respectively. All treatment plans were generated using the Eclipse Treatment Planning System (TPS). The impact of tumour shrinkage on doses to organs at risk (OARs) was simulated in the TPS for the SIB plans.Results: Dose escalation could be implemented using both VMAT and IMPT, with a D98 ≥ 95 % for MTV50 being achieved in all cases. The sum of the 10 fraction short-course SIB and subsequent 18 standard fractions was compared to the standard non-SIB approach by dose volume histogram (DVH) analysis. Only marginal increase of dose to OARs was found for both modalities and a small further increase estimated from tumour shrinkage. Most DVH parameters showed a mean difference below 2 %. IMPT had, compared to VMAT, reduced OAR doses in the low to intermediate dose range, but showed no additional advantage in dose escalation.Conclusions: Planning of dose escalation based on a FDG avid boost volume was here demonstrated feasible. The concept may allow time for enhanced tumour shrinkage before brachytherapy. Thus, this strategy may prove clinically valuable, in particular for patients with large tumours. [ABSTRACT FROM AUTHOR]

Background: Newly diagnosed WHO grade II-III or any WHO grade recurrent meningioma exhibit an aggressive behavior and thus are considered as high- or intermediate risk tumors. Given the unsatisfactory rates of disease control and survival after primary or adjuvant radiation therapy, optimization of treatment strategies is needed. We investigated the potential of dose-painting intensity-modulated proton beam-therapy (IMPT) for intermediate- and high-risk meningioma. Material and methods: Imaging data from five patients undergoing proton beam-therapy were used. The dose-painting target was defined using [68]Ga-[1,4,7,10-tetraazacyclododecane tetraacetic acid]' d-Phe1,Tyr3-octreotate ([68]Ga-DOTATATE)-positron emission tomography (PET) in target delineation. IMPT and photon intensity-modulated radiation therapy (IMRT) treatment plans were generated for each patient using an in-house developed treatment planning system (TPS) supporting spot-scanning technology and a commercial TPS, respectively. Doses of 66 Gy (2.2 Gy/fraction) and 54 Gy (1.8 Gy/fraction) were prescribed to the PET-based planning target volume (PTVPET) and the union of PET- and anatomical imaging-based PTV, respectively, in 30 fractions, using simultaneous integrated boost. Results: Dose coverage of the PTVsPET was equally good or slightly better in IMPT plans: dose inhomogeneity was 10 ± 3% in the IMPT plans vs. 13 ± 1% in the IMRT plans (p = 0.33). The brain Dmean and brainstem D50 were small in the IMPT plans: 26.5 ± 1.5 Gy(RBE) and 0.002 ± 0.0 Gy(RBE), respectively, vs. 29.5 ± 1.5 Gy (p = 0.001) and 7.5 ± 11.1 Gy (p = 0.02) for the IMRT plans, respectively. The doses delivered to the optic structures were also decreased with IMPT. Conclusions: Dose-painting IMPT is technically feasible using currently available planning tools and resulted in dose conformity of the dose-painted target comparable to IMRT with a significant reduction of radiation dose delivered to the brain, brainstem and optic apparatus. Dose escalation with IMPT may improve tumor control and decrease radiation-induced toxicity. [ABSTRACT FROM AUTHOR]

Background Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The purpose of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[18 F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N4)-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models. Methods Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and 64Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes for dose escalation were defined by a thresholdbased method for both tracers and five dose escalation levels were formed in each subvolume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions for each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with construction of dose distribution density maps and quality volume histograms (QVH). Correlation between highdose regions was investigated with Dice correlation coefficients. Results Comparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. 64Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions. Conclusion Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, 64Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64Cu-ATSM at two different time-points and FDG provide different biological information that has to be taken into account when using the dose painting strategy in radiotherapy treatment planning. [ABSTRACT FROM AUTHOR]

Background: To integrate 3D MR spectroscopy imaging (MRSI) in the treatment planning system (TPS) for glioblastoma dose painting to guide simultaneous integrated boost (SIB) in intensity-modulated radiation therapy (IMRT). Methods: For sixteen glioblastoma patients, we have simulated three types of dosimetry plans, one conventional plan of 60-Gy in 3D conformational radiotherapy (3D-CRT), one 60-Gy plan in IMRT and one 72-Gy plan in SIB-IMRT. All sixteen MRSI metabolic maps were integrated into TPS, using normalization with color-space conversion and threshold-based segmentation. The fusion between the metabolic maps and the planning CT scans were assessed. Dosimetry comparisons were performed between the different plans of 60-Gy 3D-CRT, 60-Gy IMRT and 72-Gy SIB-IMRT, the last plan was targeted on MRSI abnormalities and contrast enhancement (CE). Results: Fusion assessment was performed for 160 transformations. It resulted in maximum differences <1.00 mm for translation parameters and ⩽1.15° for rotation. Dosimetry plans of 72-Gy SIB-IMRT and 60-Gy IMRT showed a significantly decreased maximum dose to the brainstem (44.00 and 44.30 vs. 57.01 Gy) and decreased high dose-volumes to normal brain (19 and 20 vs. 23% and 7 and 7 vs. 12%) compared to 60-Gy 3D-CRT (p < 0.05). Conclusions: Delivering standard doses to conventional target and higher doses to new target volumes characterized by MRSI and CE is now possible and does not increase dose to organs at risk. MRSI and CE abnormalities are now integrated for glioblastoma SIB-IMRT, concomitant with temozolomide, in an ongoing multi-institutional phase-III clinical trial. Our method of MR spectroscopy maps integration to TPS is robust and reliable; integration to neuronavigation systems with this method could also improve glioblastoma resection or guide biopsies. [ABSTRACT FROM AUTHOR]