The significance of partial volume effect on the estimation of hypoxic tumour volume with [18F]FMISO PET/CT.

BACKGROUND: The purpose of this study was to evaluate how a retrospective correction of the partial volume effect (PVE) in [18F]fluoromisonidazole (FMISO) PET imaging, affects the hypoxia discoverability within a gross tumour volume (GTV). This method is based on recovery coefficients (RC) and is tailored for low-contrast tracers such as FMISO. The first stage was the generation of the scanner's RC curves, using spheres with diameters from 10 to 37 mm, and the same homogeneous activity concentration, positioned in lower activity concentration background. Six sphere-to-background contrast ratios were used, from 10.0:1, down to 2.0:1, in order to investigate the dependence of RC on both the volume and the contrast ratio. The second stage was to validate the recovery-coefficient correction method in a more complex environment of non-spherical lesions of different volumes and inhomogeneous activity concentration. Finally, we applied the correction method to a clinical dataset derived from a prospective imaging trial (DRKS00003830): forty nine head and neck squamous cell carcinoma (HNSCC) cases who had undergone FMISO PET/CT scanning for the quantification of tumour hypoxia before (W0), 2 weeks (W2) and 5 weeks (W5) after the beginning of radiotherapy. Here, PVE was found to cause an underestimation of the activity in small volumes with high FMISO signal. RESULTS: The application of the proposed correction method resulted in a statistically significant increase of both the hypoxic subvolume (171% at W0, 691% at W2 and 4.60 × 103% at W5 with p < 0.001) and the FMISO standardised uptake value (SUV) (27% at W0, 21% at W2 and by 25% at W5 with p < 0.001) within the primary GTV. CONCLUSIONS: The proposed PVE-correction method resulted in a statistically significant increase of the hypoxic fraction (HF) with p < 0.001 and demonstrated results in better agreement with published HF data for HNSCC. To summarise, the proposed RC-based correction method can be a useful tool for a retrospective compensation against PVE.

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

Introduction: 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. Materials and methods: 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. Results: 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/ß 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/ß 3.0 Gy, and V68Gy[%] to V70Gy[%] for α/ß 2.3 Gy. The model with α/ß 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/ß 3.0 Gy, with a BIC value of 66.73. Conclusion: 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/ß 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.

The role of the soft palate dose regarding normal tissue toxicities in older adults with head and neck cancer undergoing definitive radiotherapy.

PURPOSE: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is continuously increasing. Older HNSCC patients may be more vulnerable to radiotherapy-related toxicities, so that extrapolation of available normal tissue complication probability (NTCP) models to this population may not be appropriate. Hence, we aimed to investigate the correlation between organ at risk (OAR) doses and chronic toxicities in older patients with HNSCC undergoing definitive radiotherapy. METHODS: Patients treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between 2009 and 2019 in a large tertiary cancer center were eligible for this analysis. OARs were contoured based on international consensus guidelines, and EQD2 doses using α/ß values of 3 Gy for late effects were calculated based on the radiation treatment plans. Treatment-related toxicities were graded according to Common Terminology Criteria for Adverse Events version 5.0. Logistic regression analyses were carried out, and NTCP models were developed and internally validated using the bootstrapping method. RESULTS: A total of 180 patients with a median age of 73 years fulfilled the inclusion criteria and were analyzed. Seventy-three patients developed chronic moderate xerostomia (grade 2), 34 moderate dysgeusia (grade 2), and 59 moderate-to-severe (grade 2-3) dysphagia after definitive radiotherapy. The soft palate dose was significantly associated with all analyzed toxicities (xerostomia: OR = 1.028, dysgeusia: OR = 1.022, dysphagia: OR = 1.027) in the multivariable regression. The superior pharyngeal constrictor muscle was also significantly related to chronic dysphagia (OR = 1.030). Consecutively developed and internally validated NTCP models were predictive for the analyzed toxicities (optimism-corrected AUCs after bootstrapping: AUCxerostomia=0.64, AUCdysgeusia=0.60, AUCdysphagia=0.64). CONCLUSIONS: Our data suggest that the dose to the soft palate is associated with chronic moderate xerostomia, moderate dysgeusia and moderate-to-severe dysphagia in older HNSCC patients undergoing definitive radiotherapy. If validated in external studies, efforts should be undertaken to reduce the soft palate dose in these patients.

Evaluation of RADIANCE Monte Carlo algorithm for treatment planning in electron based Intraoperative Radiotherapy (IOERT).

PURPOSE: To perform experimental as well as independent Monte Carlo (MC) evaluation of the MC algorithm implemented in RADIANCE version 4.0.8, a dedicated treatment planning system (TPS) for 3D electron dose calculations in intraoperative radiation therapy (IOERT). METHODS AND MATERIALS: The MOBETRON 2000 (IntraOp Medical Corporation, Sunnyvale, CA) IOERT accelerator was employed. PDD and profiles for five cylindrical plastic applicators with 50-90 mm diameter and 0°, 30° beveling were measured in a water phantom, at nominal energies of 6, 9 and 12 MeV. Additional PDD measurements were performed for all the energies without applicator. MC modeling of the MOBETRON was performed with the user code BEAMnrc and egs_chamber of the MC simulation toolkit EGSnrc. The generated phase space files of the two 0°-bevel applicators (50 mm, 80 mm) and three energies in both RADIANCE and BEAMnrc, were used to determine PDD and profiles in various set-ups of virtual water phantoms with air and bone inhomogeneities. 3D dose distributions were also calculated in image data sets of an anthropomorphic tissue-equivalent pelvis phantom. Image acquisitions were realized with a CT scanner (Philips Big Bore CT, Netherlands). Gamma analysis was applied to quantify the deviations of the RADIANCE calculations to the measurements and EGSnrc calculations. Gamma criteria normalized to the global maximum were investigated between 2%, 2 mm and 3%, 3 mm. RESULTS: RADIANCE MC calculations satisfied the gamma criteria of 3%, 3 mm with a tolerance limit of 85% passing rate compared to in- water phantom measurements, except for the dose profiles of the 30° beveled applicators. Mismatches lay in surface doses, in umbra regions and in the beveled end of the 30° applicators. A very good agreement to the EGSnrc calculations in heterogeneous media was observed. Deviations were more pronounced for the larger applicator diameter and higher electron energy. In 3D dose comparisons in the anthropomorphic phantom, gamma passing rates were higher than 96 % for both simulated applicators. CONCLUSIONS: RADIANCE MC algorithm agrees within 3%, 3 mm criteria with in-water phantom measurements and EGSnrc MC dose distributions in heterogeneous media for 0°-bevel applicators. The user should be aware of missing scattering components and the 30° beveled applicators should be used with attention.

The use of deep learning in interventional radiotherapy (brachytherapy): A review with a focus on open source and open data.

Deep learning advanced to one of the most important technologies in almost all medical fields. Especially in areas, related to medical imaging it plays a big role. However, in interventional radiotherapy (brachytherapy) deep learning is still in an early phase. In this review, first, we investigated and scrutinised the role of deep learning in all processes of interventional radiotherapy and directly related fields. Additionally, we summarised the most recent developments. For better understanding, we provide explanations of key terms and approaches to solving common deep learning problems. To reproduce results of deep learning algorithms both source code and training data must be available. Therefore, a second focus of this work is on the analysis of the availability of open source, open data and open models. In our analysis, we were able to show that deep learning plays already a major role in some areas of interventional radiotherapy, but is still hardly present in others. Nevertheless, its impact is increasing with the years, partly self-propelled but also influenced by closely related fields. Open source, data and models are growing in number but are still scarce and unevenly distributed among different research groups. The reluctance in publishing code, data and models limits reproducibility and restricts evaluation to mono-institutional datasets. The conclusion of our analysis is that deep learning can positively change the workflow of interventional radiotherapy but there is still room for improvements when it comes to reproducible results and standardised evaluation methods.

A Novel Radiotherapeutic Approach to Treat Bulky Metastases Even From Cutaneous Squamous Cell Carcinoma: Its Rationale and a Look at the Reliability of the Linear-Quadratic Model to Explain Its Radiobiological Effects.

Introduction: Metastatic cutaneous squamous cell carcinoma (cSCC) is a very rare condition. The lack of definition of an oligometastatic subgroup means that there is no consensus for its treatment, unlike the mucosal head and neck counterpart. Like the latter, the cutaneous form is able to develop bulky tumor masses. When this happens, the classic care approach is just for palliative intent due to a likely unfavorable benefit-risk balance typical of aggressive treatments. Here we proposed a novel radiotherapy (RT) technique to treat bulky metastases from cSCC in the context of an overall limited tumor burden and tried to explain its clinical outcome by the currently available mathematical radiobiological and ad hoc developed models. Methods: We treated a case of facial cSCC with three metastases: two of them by classic stereotactic RT and the other by lattice RT supported by metabolic imaging (18F-FDG PET) due to its excessively large dimensions. For the latter lesion, we compared four treatment plans with different RT techniques in order to define the best approach in terms of normal tissue complication probability (NTCP) and tumor control probability (TCP). Moreover, we developed an ad hoc mathematical radiobiological model that could fit better with the characteristics of heterogeneity of this bulky metastasis for which, indeed, a segmentation of normoxic, hypoxic, and necrotic subvolumes might have been assumed. Results: We observed a clinical complete response in all three disease sites; the bulky metastasis actually regressed more rapidly than the other two treated by stereotactic RT. For the large lesion, NTCP predictions were good for all four different plans but even significantly better for the lattice RT plan. Neither the classic TCP nor the ad hoc developed radiobiological models could be totally adequate to explain the reported outcome. This finding might support a key role of the host immune system. Conclusions: PET-guided lattice RT might be safe and effective for the treatment of bulky lesions from cSCC. There might be some need for complex mathematical radiobiological models that are able to take into account any immune system's role in order to explain the possible mechanisms of the tumor response to radiation and the relevant key points to enhance it.

Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference.

PURPOSE: Multiparametric magnetic resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET/CT) are used to guide focal radiotherapy (RT) dose escalation concepts. Besides improvements of treatment effectiveness, maintenance of a good quality of life is essential. Therefore, this planning study investigates whether urethral sparing in moderately hypofractionated RT with focal RT dose escalation influences tumour control probability (TCP) and normal tissue complication probability (NTCP). PATIENTS AND METHODS: 10 patients with primary prostate cancer (PCa), who underwent 68Ga PSMA-PET/CT and mpMRI followed by radical prostatectomy were enrolled. Intraprostatic tumour volumes (gross tumor volume, GTV) based on both imaging techniques (GTV-MRI and -PET) were contoured manually using validated contouring techniques and GTV-Union was created by summing both. For each patient three IMRT plans were generated with 60 Gy to the whole prostate and a simultaneous integrated boost up to 70 Gy to GTV-Union in 20 fractions by (Plan 1) not respecting and (Plan 2) respecting dose constraints for urethra as well as (Plan 3) respecting dose constraints for planning organ at risk volume for urethra (PRV = urethra + 2mm expansion). NTCP for urethra was calculated applying a Lyman-Kutcher-Burman model. TCP-Histo was calculated based on PCa distribution in co-registered histology (GTV-Histo). Complication free tumour control probability (P+) was calculated. Furthermore, the intrafractional movement was considered. RESULTS: Median overlap of GTV-Union and PRV-Urethra was 1.6% (IQR 0-7%). Median minimum distance of GTV-Histo to urethra was 3.6 mm (IQR 2 - 7 mm) and of GTV-Union to urethra was 1.8 mm (IQR 0.0 - 5.0 mm). The respective prescription doses and dose constraints were reached in all plans. Urethra-sparing in Plans 2 and 3 reached significantly lower NTCP-Urethra (p = 0.002) without significantly affecting TCP-GTV-Histo (p = p > 0.28), NTCP-Bladder (p > 0.85) or NTCP-Rectum (p = 0.85), resulting in better P+ (p = 0.006). Simulation of intrafractional movement yielded even higher P+ values for Plans 2 and 3 compared to Plan 1. CONCLUSION: Urethral sparing may increase the therapeutic ratio and should be implemented in focal RT dose escalation concepts.

Intraoperative radiotherapy boost as part of breast-conservation therapy for breast cancer: a single-institution retrospective analysis.

BACKGROUND: There are currently no data from randomized controlled trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost as part of a breast-conservation approach for breast cancer. This study retrospectively reviewed the safety and efficacy of IORT as a boost treatment at a tertiary cancer center. METHODS: From 2015 to 2019, patients underwent breast-conserving surgery with axillary lymph node staging and a single dose of 20 Gy IORT with 50-kV photons, followed by whole-breast irradiation (WBI) and adjuvant systemic therapy (if applicable). Patients were followed for assessment of acute and late toxicities (using the Common Terminology Criteria for Adverse Events version 5.0) at 3-6-month intervals. Outcomes included ipsilateral (IBTR) and contralateral breast progression-free survival (CBE), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: Median follow-up for the 214 patients was 28 (range 2-59) months. Most patients had T1 disease (n = 124) and were clinically node negative. Only few patients had high-grade and/or triple-negative disease. The vast majority of patients underwent sentinel node biopsy, and 32 (15%) required re-resection for initially positive margins. Finally, all tumor bed margins were clear. Nine (4.2%) and 48 (22.4%) patients underwent neoadjuvant and adjuvant chemotherapy, respectively. WBI was predominantly performed as conventionally fractionated WBI (n = 187, 87.4%), and the median time from BCS to WBI was 54.5 days. IORT was delivered with a single dose of 20 Gy. The median WBI dose was 50 Gy (range 29.4-50.4 Gy). No patients experienced grade 4 events; acute grade 3 toxicities were limited to 17 (8%) cases of radiation dermatitis. Postoperative toxicities were mild. After WBI only one case of late grade ≥ 2 events was reported. There were two recurrences in the tumor bed and one contralateral breast event. CONCLUSION: This investigation provides additional preliminary data supporting the using of IORT in the boost setting and corroborates the existing literature. These encouraging results should be prospectively validated by the eventual publication of randomized studies such as TARGIT­B.

Dosimetric Impact of the Positional Imaging Frequency for Hypofractionated Prostate Radiotherapy - A Voxel-by-Voxel Analysis.

BACKGROUND: To investigate deviations between planned and applied treatment doses for hypofractionated prostate radiotherapy and to quantify dosimetric accuracy in dependence of the image guidance frequency. METHODS: Daily diagnostic in-room CTs were carried out in 10 patients in treatment position as image guidance for hypofractionated prostate radiotherapy. Fraction doses were mapped to the planning CTs and recalculated, and applied doses were accumulated voxel-wise using deformable registration. Non-daily imaging schedules were simulated by deriving position correction vectors from individual scans and used to rigidly register the following scans until the next repositioning before dose recalculation and accumulation. Planned and applied doses were compared regarding dose-volume indices and TCP and NTCP values in dependence of the imaging and repositioning frequency. RESULTS: Daily image-guided repositioning was associated with only negligible deviations of analyzed dose-volume parameters and conformity/homogeneity indices for the prostate, bladder and rectum. Average CTV T did not significantly deviate from the plan values, and rectum NTCPs were highly comparable, while bladder NTCPs were reduced. For non-daily image-guided repositioning, there were significant deviations in the high-dose range from the planned values. Similarly, CTV dose conformity and homogeneity were reduced. While TCPs and rectal NTCPs did not significantly deteriorate for non-daily repositioning, bladder NTCPs appeared falsely diminished in dependence of the imaging frequency. CONCLUSION: Using voxel-by-voxel dose accumulation, we showed for the first time that daily image-guided repositioning resulted in only negligible dosimetric deviations for hypofractionated prostate radiotherapy. Regarding dosimetric aberrations for non-daily imaging, daily imaging is required to adequately deliver treatment.

Prostate cancer tumour control probability modelling for external beam radiotherapy based on multi-parametric MRI-GTV definition.

PURPOSE: To evaluate the applicability and estimate the radiobiological parameters of linear-quadratic Poisson tumour control probability (TCP) model for primary prostate cancer patients for two relevant target structures (prostate gland and GTV). The TCP describes the dose-response of prostate after definitive radiotherapy (RT). Also, to analyse and identify possible significant correlations between clinical and treatment factors such as planned dose to prostate gland, dose to GTV, volume of prostate and mpMRI-GTV based on multivariate logistic regression model. METHODS: The study included 129 intermediate and high-risk prostate cancer patients (cN0 and cM0), who were treated with image-guided intensity modulated radiotherapy (IMRT) ± androgen deprivation therapy with a median follow-up period of 81.4 months (range 42.0-149.0) months. Tumour control was defined as biochemical relapse free survival according to the Phoenix definition (BRFS). MpMRI-GTV was delineated retrospectively based on a pre-treatment multi-parametric MR imaging (mpMRI), which was co-registered to the planning CT. The clinical treatment planning procedure was based on prostate gland, delineated on CT imaging modality. Furthermore, we also fitted the clinical data to TCP model for the two considered targets for the 5-year follow-up after radiation treatment, where our cohort was composed of a total number of 108 patients, of which 19 were biochemical relapse (BR) patients. RESULTS: For the median follow-up period of 81.4 months (range 42.0-149.0) months, our results indicated an appropriate α/ß = 1.3 Gy for prostate gland and α/ß = 2.9 Gy for mpMRI-GTV. Only for prostate gland, EQD2 and gEUD2Gy were significantly lower in the biochemical relapse (BR) group compared to the biochemical control (BC) group. Fitting results to the linear-quadratic Poisson TCP model for prostate gland and α/ß = 1.3 Gy were D50 = 66.8 Gy with 95% CI [64.6 Gy, 69.0 Gy], and γ = 3.8 with 95% CI [2.6, 5.2]. For mpMRI-GTV and α/ß = 2.9 Gy, D50 was 68.1 Gy with 95% CI [66.1 Gy, 70.0 Gy], and γ = 4.5 with 95% CI [3.0, 6.1]. Finally, for the 5-year follow-up after the radiation treatment, our results for the prostate gland were: D50 = 64.6 Gy [61.6 Gy, 67.4 Gy], γ = 3.1 [2.0, 4.4], α/ß = 2.2 Gy (95% CI was undefined). For the mpMRI-GTV, the optimizer was unable to deliver any reasonable results for the expected clinical D50 and α/ß. The results for the mpMRI-GTV were D50 = 50.1 Gy [44.6 Gy, 56.0 Gy], γ = 0.8 [0.5, 1.2], α/ß = 0.0 Gy (95% CI was undefined). For a follow-up time of 5 years and a fixed α/ß = 1.6 Gy, the TCP fitting results for prostate gland were D50 = 63.9 Gy [60.8 Gy, 67.0 Gy], γ = 2.9 [1.9, 4.1], and for mpMRI-GTV D50 = 56.3 Gy [51.6 Gy, 61.1 Gy], γ = 1.3 [0.8, 1.9]. CONCLUSION: The linear-quadratic Poisson TCP model was better fit when the prostate gland was considered as responsible target than with mpMRI-GTV. This is compatible with the results of the comparison of the dose distributions among BR and BC groups and with the results achieved with the multivariate logistic model regarding gEUD2Gy. Probably limitations of mpMRI in defining the GTV explain these results. Another explanation could be the relatively homogeneous dose prescription and the relatively low number of recurrences. The failure to identify any benefit for considering mpMRI-GTV as the target responsible for the clinical response is confirmed when considering a fixed α/ß = 1.6 Gy, a fixed follow-up time for biochemical response at 5 years or Gleason score differentiation.

Dosimetric Impact of Interfractional Variations for Post-prostatectomy Radiotherapy to the Prostatic Fossa-Relevance for the Frequency of Position Verification Imaging and Treatment Adaptation.

Background and purpose: To analyze divergences between the planned and applied treatment doses for post-prostatectomy radiotherapy to the prostatic fossa on a voxel-by-voxel basis based on interfractional anatomic variations and imaging frequency. Materials and methods: For 10 patients receiving intensity-modulated postoperative radiotherapy to the prostatic fossa, position verification was carried out by daily in-room CT imaging in treatment position (340 fraction CTs). Applied fraction doses were recalculated on daily CT scans, and treatment doses were accumulated on a voxel-by-voxel basis after deformable image registration. To simulate weekly imaging, derived weekly position correction vectors were used to rigidly register all daily scans of the respective treatment week onto the planning CT before dose accumulation. Detailed dose statistics of the prescribed and applied treatment doses were compared in relation to the frequency of position verification imaging. Derived NTCP and Pinjury values were calculated for the rectum and bladder. Results: Despite a large variability in the pelvic anatomy, daily CT-based patient repositioning resulted in largely negligible deviations of the analyzed dose-volume, conformity, and uniformity parameters from the planned doses for post-prostatectomy radiotherapy, and only the bladder exhibited significant increases in the accumulated mean and median doses. Derived NTCP for the applied doses to the rectum and bladder and Pinjury values did not significantly deviate from the treatment plan. In contrast, weekly CT-based repositioning resulted in significant decreases of the PTV coverage and dose conformity as well as large deviations of the applied doses to the rectum and bladder from the planned doses. Consecutively, NTCP for the rectum and Pinjury were found falsely reduced for weekly patient repositioning. Conclusions: Our data indicate for the first time in a voxel-by-voxel analysis that daily imaging is required for reliable adaptive delivery of intensity-modulated radiotherapy to the prostatic fossa. This work will help guiding adaptive treatment strategies for post-prostatectomy radiotherapy.

Dosimetric Impact of Interfractional Variations in Prostate Cancer Radiotherapy-Implications for Imaging Frequency and Treatment Adaptation.

Background and purpose: To analyze deviations of the applied from the planned doses on a voxel-by-voxel basis for definitive prostate cancer radiotherapy depending on anatomic variations and imaging frequency. Materials and methods: Daily in-room CT imaging was performed in treatment position for 10 patients with prostate cancer undergoing intensity-modulated radiotherapy (340 fraction CTs). Applied fraction doses were recalculated on daily images, and voxel-wise dose accumulation was performed using a deformable registration algorithm. For weekly imaging, weekly position correction vectors were derived and used to rigidly register daily scans of that week to the planning CT scan prior to dose accumulation. Applied and prescribed doses were compared in dependence of the imaging frequency, and derived TCP and NTCP values were calculated. Results: Daily CT-based repositioning resulted in non-significant deviations of all analyzed dose-volume, conformity and uniformity parameters to the CTV, bladder and rectum irrespective of anatomic changes. Derived average TCP values were comparable, and NTCP values for the applied doses to the bladder and rectum did not significantly deviate from the planned values. For weekly imaging, the applied D2 to the CTV, rectum and bladder significantly varied from the planned doses, and the CTV conformity index and D98 decreased. While TCP values were comparable, the NTCP for the bladder erroneously appeared reduced for weekly repositioning. Conclusions: Based on daily diagnostic quality CT imaging and voxel-wise dose accumulation, we demonstrated for the first time that daily, but not weekly imaging resulted in only negligible deviations of the applied from the planned doses for prostate intensity-modulated radiotherapy. Therefore, weekly imaging may not be adequately reliable for adaptive treatment delivery techniques for prostate. This work will contribute to devising adaptive re-planning strategies for prostate radiotherapy.

Investigating the role of constrained CVT and CVT in HIPO inverse planning for HDR brachytherapy of prostate cancer.

PURPOSE: The purpose of this study is to investigate the role of the centroidal Voronoi tessellation (CVT) and constrained CVT (CCVT) in inverse planning in combination with the Hybrid Inverse Planning Optimization (HIPO) algorithm in HDR brachytherapy of prostate cancer. HIPO implemented in Oncentra© Prostate treatment planning system, is used for three-dimensional (3D)-ultrasound-based intraoperative treatment planning in high dose rate brachytherapy. HIPO utilizes a hybrid iterative process to determine the most appropriate placement of a given number of catheters to fulfil predefined dose-volume constraints. The main goals of the current investigation were to identify a way of improving the performance of HIPO inverse planning; accelerating the HIPO, and to evaluate the effect of the two CVT-based initialization methods on the dose distribution in the sub-region of prostate that is not accessible by catheters, when trying to avoid perforation of urethra. METHODS: We implemented the CVT algorithm to generate initial catheter configurations before the initialization of the HIPO algorithm. We introduced the CCVT algorithm to improve the dose distribution to the sub-volume of prostate within the bounding box of the urethra contours including its upper vertical extension (U-P). For the evaluation, we considered a total of 15 3D ultrasound-based HDRBT prostate implants. Execution time and treatment plan quality were evaluated based on the dose-volume histograms of prostate (PTV), its sub-volume U-P, and organs at risk (OARs). Furthermore, the conformity index COIN, the homogeneity index HI and the complication-free tumor control probability (P+ ) were used for our treatment plan comparisons. Finally, the plans with the recommended HIPO execution mode were compared to the clinically used intraoperative pre-plans. RESULTS: The plan quality achieved with CCVT-based HIPO initialization was superior to the default HIPO initialization method. Focusing on the U-P sub-region of the prostate, the CCVT method resulted in a significant improvement of all dosimetric indices compared to the default HIPO, when both were executed in the adaptive mode. For that recommended HIPO execution mode, and for U-P, CCVT demonstrated in general higher dosimetric indices than CVT. Additionally, the execution time of CCVT initialized HIPO was lower compared to both alternative initialization methods. This is also valid for the values of the aggregate objective function with the differences to the default initialization method being highly significant. Paired non-parametric statistical tests (Wilcoxon signed-rank) showed a significant improvement of dose-volume indices, COIN and P+ for the plans generated by the CCVT-based catheter configuration initialization in HIPO compared to the default HIPO initialization process. Furthermore, in ten out of 15 cases, the CCVT-based HIPO plans fulfilled all the clinical dose-volume constraints in a single trial without any need for further catheter position adaption. CONCLUSION: HIPO with CCVT-based initialization demonstrates better performance regarding the aggregate objective function and convergence when compared to the CVT-based and default catheter configuration initialization methods. This improved performance of HIPO inverse planning is clearly not at the cost of the dosimetric and radiobiologically evaluated plan quality. We recommend the use of the CCVT method for HIPO initialization especially in the adaptive planning mode.

Focal dose escalation for prostate cancer using 68Ga-HBED-CC PSMA PET/CT and MRI: a planning study based on histology reference.

BACKGROUND: Focal radiation therapy has gained of interest in treatment of patients with primary prostate cancer (PCa). The question of how to define the intraprostatic boost volume is still open. Previous studies showed that multiparametric MRI (mpMRI) or PSMA PET alone could be used for boost volume definition. However, other studies proposed that the combined usage of both has the highest sensitivity in detection of intraprostatic lesions. The aim of this study was to demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of radiation therapy dose painting using 68Ga-HBED-CC PSMA PET/CT, mpMRI or the combination of both in primary PCa. METHODS: Ten patients underwent PSMA PET/CT and mpMRI followed by prostatectomy. Three gross tumour volumes (GTVs) were created based on PET (GTV-PET), mpMRI (GTV-MRI) and the union of both (GTV-union). Two plans were generated for each GTV. Plan95 consisted of whole-prostate IMRT to 77 Gy in 35 fractions and a simultaneous boost to 95 Gy (Plan95PET/Plan95MRI/Plan95union). Plan80 consisted of whole-prostate IMRT to 76 Gy in 38 fractions and a simultaneous boost to 80 Gy (Plan80PET/Plan80MRI/Plan80union). TCPs were calculated for GTV-histo (TCP-histo), which was delineated based on PCa distribution in co-registered histology slices. NTCPs were assessed for bladder and rectum. RESULTS: Dose constraints of published protocols were reached in every treatment plan. Mean TCP-histo were 99.7% (range: 97%-100%) and 75.5% (range: 33%-95%) for Plan95union and Plan80union, respectively. Plan95union had significantly higher TCP-histo values than Plan95MRI (p = 0.008) and Plan95PET (p = 0.008). Plan80union had significantly higher TCP-histo values than Plan80MRI (p = 0.012), but not than Plan80PET (p = 0.472). Plan95MRI had significantly lower NTCP-rectum than Plan95union (p = 0.012). No significant differences in NTCP-rectum and NTCP-bladder were observed for all other plans (p > 0.05). CONCLUSIONS: IMRT dose escalation on GTVs based on mpMRI, PSMA PET/CT and the combination of both was feasible. Boosting GTV-union resulted in significantly higher TCP-histo with no or minimal increase of NTCPs compared to the other plans.

Influence of inhomogeneous radiosensitivity distributions and intrafractional organ movement on the tumour control probability of focused IMRT in prostate cancer.

PURPOSE: To evaluate the influence of radioresistance and intrafractional movement on the tumour control probability (TCP) in IMRT prostate treatments using simultaneous integrated boosts to PSMA-PET/CT-delineated GTVs. MATERIALS AND METHODS: 13 patients had PSMA-PET/CT prior to prostatectomy and histopathological examination. Two GTVs were available: GTV-PET and GTV-histo, which is the true cancer volume. Focused IMRT plans delivering 77 Gy in 35 fractions to the prostate and 95 Gy to PTV-PET were produced. For random portions of the true cancer volume, α and α/ß were uniformly changed to represent different radiosensitivity reductions. TCP was calculated (linear quadratic model) for the true cancer volume with and without simulated intrafractional movement. RESULTS: Intrafractional movement increased the TCP by up to 10.2% in individual cases and 1.2% averaged over all cases for medium radiosensitivity levels. At lower levels of radiosensitivity, movement decreased the TCP. Radiosensitivity reductions of 10-20% led to TCP reductions of 1-24% and 10-68% for 1% and 5% affected cancer volume, respectively. There is no linear correlation but a sudden breakdown of TCPs within a small range of radiosensitivity levels. CONCLUSION: TCP drops significantly within a narrow range of radiosensitivity levels. Intrafractional movement can increase TCP when the boost volume is surrounded by a sufficiently high dose plateau.

Evaluation of intensity modulated radiation therapy dose painting for localized prostate cancer using 68Ga-HBED-CC PSMA-PET/CT: A planning study based on histopathology reference.

PURPOSE: To demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of IMRT dose painting using 68Ga-HBED-CC PSMA PET/CT for target delineation in prostate cancer (PCa). METHODS AND MATERIALS: 10 patients had PSMA PET/CT scans prior to prostatectomy. GTV-PET was generated on the basis of an intraprostatic SUVmax of 30%. Two IMRT plans were generated for each patient: Plan77 which consisted of whole-prostate IMRT to 77Gy, and Plan95 which consisted of whole-prostate IMRT to 77Gy and a simultaneous integrated boost to the GTV-PET up to 95Gy (35 fractions). The feasibility of these plans was judged by their ability to adhere to the FLAME trial protocol. TCP-histo/-PET were calculated on co-registered histology (GTV-histo) and GTV-PET, respectively. NTCPs for rectum and bladder were calculated. RESULTS: All plans reached prescription doses whilst adhering to dose constraints. In Plan77 and Plan95 mean doses in GTV-histo were 75.8±0.3Gy and 96.9±1Gy, respectively. Average TCP-histo values for Plan77 and Plan95 were 70% (range: 15-97%), and 96% (range: 78-100%, p<0.0001). Average TCP-PET values for Plan77 and Plan95 were 55% (range: 27-82%), and 100% (range: 99-100%, p<0.0001). There was no significant difference between TCP-PET and TCP-histo in Plan95 (p=0.25). There were no significant differences in rectal (p=0.563) and bladder (p=0.3) NTCPs. CONCLUSIONS: IMRT dose painting using PSMA PET/CT was technically feasible and resulted in significantly higher TCPs without higher NTCPs.

TraumaStation: a portable telemedicine station.

TraumaStation is a portable medical device which covers the mobility of the medical doctors as well as integrates the diversity of telemedicine devices. Many portable telemedicine devices has been developed the last years in order to help patients in remote areas or in emergency situationns. The medical TraumaStation is a light portable tele-medical first-aid device, which provides the physicians with an ultrasound, electrocardiogram, blood pressure, oxygen meter apparatus all in a suitcase. In addition, the portable device is equipped with all available telecommunication gateways (e.g. GSM, UMTS, ISDN, DSL, Satellite) providing a great communication convenience to the physicians utilizing XMMP instant messaging protocols and real time video conference.

Integrated telemedicine applications and services for oncological positron emission tomography.

TENPET (Trans European Network for Positron Emission Tomography) aims to evaluate the provision of integrated teleconsultation and intelligent computer supported cooperative work services for clinical positron emission tomography (PET) in Europe at its current stage, as it is a multi-centre project financially supported by the European Commission (Information Society, eTEN Program). It addresses technological challenges by linking PET centres and developing supporting services that permit remote consultation between professionals in the field. The technological platform (CE-marked) runs on Win2000/NT/XP systems and incorporates advanced techniques for image visualization, analysis and fusion, as well as for interactive communication and message handling for off-line communications. Four PET Centres from Spain, France and Germany participate to the pilot system trials. The performance evaluation of the system is carried out via log files and user-filled questionnaires on the frequency of the teleconsultations, their duration and efficacy, quality of the images received, user satisfaction, as well as on privacy, ethical and security issues. TENPET promotes the co-operation and improved communication between PET practitioners that are miles away from their peers or on mobile units, offering options for second opinion and training and permitting physicians to remotely consult patient data if they are away from their centre. It is expected that TENPET will have a significant impact in the development of new skills by PET professionals and will support the establishment of peripheral PET units. To our knowledge, TENPET is the first telemedicine service specifically designed for oncological PET. This report presents the technical innovations incorporated in the TENPET platform and the initial pilot studies at real and diverse clinical environments in the field of oncology.