Background and purpose:Intrafraction motion degrades the efficacy of radiation therapy. We reported on the implementation of focal dose-escalated stereotactic body radiation therapy (HypoFocal-SBRT) for prostate carcinoma on standard linear accelerator, and assessed whether periodic intrafraction image guidance (PIF-IG) improved the accuracy of treatment. Materials and methods:Twenty prostate cancer patients underwent HypoFocal-SBRT. Treatment planning prioritized plan robustness and efficiency accommodating image guidance as-needed for treatment on standard accelerator. A three-dose level planning target volume (PTV) SBRT regime with focal boost was prescribed: PTV30 (seminal vesicles), PTV35 (prostate), and PTV40-42 (intraprostatic tumor lesion) in 5 fractions. Fiducial marker-based PIF-IG, triggered at pre-defined imaging control point(s) (ICPs), was performed using 1 mm (translations)/1° (rotations) action thresholds for online couch corrections. Applied marker registration values were compared to estimated ground-truth, as well as simulated treatment with no PIF-IG and effect on delivered dose estimated. Results:Interventions occurred at least once in 95% of patients and 83% of fractions. PIF-IG reduced the geometric uncertainty (root-mean-square error) from 1.6 mm, 2.3 mm, and 2.2 mm for the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions to 0.6 mm, 0.9 mm, and 0.8 mm, respectively. With PIF-IG, target volumes D98% doses with 5% less than planned were observed in 2% of fractions for PTV30 and PTV35, and 0% for PTV40-42, compared to 16%, 12%, and 6% without PIF-IG. Conclusions:Focal dose-escalated SBRT for prostate cancer can be efficiently and accurately performed on standard accelerator. PIF-IG improved the geometric and delivered dose accuracy.

BACKGROUND:O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET has a higher specificity than contrast-enhanced T1-weighted MRI (CE-T1MRI) in diagnosing recurrent glioblastoma. We aimed to evaluate whether a FET-PET-based target volume delineation, compared with CE-T1MRI, improves outcomes in patients with recurrent glioblastoma scheduled for re-irradiation. METHODS:GLIAA was a multicentre, open-label, parallel randomised study done in 15 radiation oncology centres in Germany. Patients aged 18 years or older with a Karnofsky performance score greater than 60% and a macroscopic WHO grade IV recurrent glioblastoma (1-6 cm) were randomly assigned (1:1) to receive either FET-PET-based or CE-T1MRI-based target volume delineation followed by re-irradiation with 39 Gy in 13 fractions. Randomisation was performed centrally, using a minimisation technique with a random element and a computer-assisted randomisation tool, stratified by time since first radiotherapy, previous chemotherapy, tumour diameter, MGMT status, and planned chemotherapy. The primary endpoint was progression-free survival from randomisation, assessed in the per-protocol population (patients who initiated treatment per their assigned group). Adverse events were systematically assessed in all patients who commenced therapy. The trial was registered with ClinicalTrials.gov (NCT01252459), German Clinical Trials Registry (DRKS00000634), and European Clinical Trials Database (EudraCT 2012-001121-27), and is completed. FINDINGS:Between Nov 22, 2013, and Aug 18, 2021, 271 patients were recruited and screened for eligibility, 200 of whom were randomly assigned to re-irradiation based on FET-PET (n=100) or CE-T1MRI (n=100). 85 (43%) participants were female and 115 (58%) were male. 98 patients in the FET-PET group and 97 in the CE-T1MRI group were treated per protocol. Median follow-up for censored patients was 12·2 months (IQR 6·6-20·7). Median progression-free survival was 4·0 months (95% CI 3·7-5·2) in the FET-PET group and 4·9 months (3·7-6·0) in the CE-T1MRI group (one-sided stratified log-rank p=0·98; adjusted hazard ratio 1·14 [95% CI 0·85-1·52]; p=0·39; median follow-up for six censored patients 4·1 months [IQR 2·3-6·6]). The most common grade 3-4 adverse event was radionecrosis (eight [8%] of 99 in the FET-PET group vs seven [7%] of 99 in the CE-T1MRI group). Acute and subacute serious adverse events occurred in 15 (15%) of 99 patients in each group; possibly re-irradiation-related late serious adverse events occurred in ten (10%) of 97 patients in the FET-PET group and 18 (19%) of 96 in the CE-T1MRI group. There were no treatment-related deaths. INTERPRETATION:FET-PET-based target volume delineation for re-irradiation did not lead to a significant clinical benefit compared with CE-T1MRI-based treatment in patients with recurrent glioblastoma. Thus, CE-T1MRI remains the preferred delineation method in this setting. FUNDING:Deutsche Krebshilfe.

IntroductionTo evaluate the outcomes after stereotactic body radiotherapy (SBRT) for locally advanced primary liver cancer.Materials and methodsPatients with locally advanced liver cancer unsuitable for other loco-regional treatments were treated with SBRT with 50–60 Gy in 3–12 fractions in two consecutive prospective trials.ResultsA total of 83 patients were included, of whom 14 were excluded, leaving 69 evaluable patients with 74 treated lesions. A total of 50 patients had hepatocellular carcinoma (HCC), and 11 patients had cholangiocarcinoma (CCC). Approximately 76% had a Child-Pugh (CP) score of A, while 54% had an albumin–bilirubin (ALBI) score of 1. With a median follow-up of 29 months, the median overall survival (OS) was 11 months, and the progression-free survival (PFS) was 18 months. The ALBI score was an important predictor of overall survival (HR 2.094, p = 0.001), which remained significant also in the multivariate analysis. Patients with an ALBI grade of ≥1 had an OS of 4 months versus 23 months in patients with an ALBI grade of 1 (p ≤ 0.001). The local control at 1 and 2 years was 91%. Thirteen patients developed grade ≥ 3 toxicities, of whom nine patients experienced liver toxicities. Patients with a higher ALBI score had a high risk for developing hepatic failure (OR 6.136, p = 0.006).DiscussionSBRT is a very effective treatment with low toxicity and should be considered as a local treatment option in patients with HCC and CCC. Patients with a higher ALBI grade are at risk for developing toxicities after SBRT and have a significantly lower survival rate.

2021 Background: Re-irradiation is an important treatment option for recurrent glioblastoma (rGBM). Here, we aimed to compare the oncological outcome of a re-irradiation target volume delineation based on O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) with the one of a treatment based on contrast enhanced T1-weighted magnetic resonance imaging (T1Gd-MRI). Methods: GLIAA was a prospective, multicenter, randomized trial (NOA 10/ARO 2013-1, DKTK-a.). Patients with rGBM recurrence of 1-6 cm following initial radiotherapy were recruited at 14 centers in Germany and randomized 1:1 between a FET-PET- (arm A) and a T1Gd-MRI-based target volume delineation (arm B). The treatment consisted in a high-precision stereotactic re-irradiation with 39 Gy in 13 fractions. The primary endpoint was progression-free survival (PFS) from randomization. Secondary endpoints included overall survival (OS), local tumor control, and toxicity. Results: From November 26, 2013, to September 2, 2021, 271 patients were assessed for eligibility and 200 were randomized. 98 patients in the FET-PET arm and 97 patients in the T1Gd-MRI arm were treated per protocol. Median PFS was 4.0 months (95% confidence interval [CI] 3.7-5.2) in the FET-PET arm and 4.9 months (95% CI 3.7-6.0) in the GdT1-MRI arm (one-sided stratified log-rank test p=0.98; adjusted HR for the experimental versus the control arm 1.14 [95% CI 0.85-1.52], p=0.39). Median OS was 9.4 months (95% CI 7.8-11.1) in arm A and 9.0 months (95% CI 7.6-10.5) in arm B (HR 1.01 [95% CI 0.75-1.37], p=0.92). Local control rate at 12 months was 22% in the FET-PET arm (95% CI 14%-31%) and 20% in the GdT1-MRI arm (95% CI 12%-29%). Radiation necrosis as adverse event was documented in 25.5% of cases in arm A and in 21.6% in arm B. Of the 239 patients who received the FET tracer, 3 reported 5 severe adverse events in the timespan of 7 days after PET. No event was related to the application of the tracer. Conclusions: In this trial, FET-PET-based re-irradiation of rGBM was not superior to the GdT1-MRI-based treatment. Consequently, both options remain valid in this setting. Stereotactic re-irradiation with 39 Gy in 3 Gy fractions was shown to be safe and the FET-PET investigation was well tolerated in all cases. Due to the inclusion of FET-PET-positive patients only, our results do not impact the known diagnostic role of FET-PET in differentiating rGBM progression from post-therapeutic changes. Clinical trial information: NCT01252459 .

PURPOSE:Our purpose was to investigate whether liver stereotactic body radiation therapy treatment planning can be harmonized across different treatment planning systems, delivery techniques, and institutions by using a specific prescription method and to minimize the knowledge gap concerning intersystem and interuser differences. We provide best practice guidelines for all used techniques. METHODS AND MATERIALS:A multiparametric specification of target dose (gross target volume [GTV]D50%, GTVD0.1cc, GTVV90%, planning target volume [PTV]V70%) with a prescription dose of GTVD50% = 3 × 20 Gy and organ-at-risk (OAR) limits were distributed with computed tomography and structure sets from 3 patients with liver metastases. Thirty-five institutions provided 132 treatment plans using different irradiation techniques. These plans were first analyzed for target and OAR doses. Four different renormalization methods were performed (PTVDmin, PTVD98%, PTVD2%, PTVDmax). The resulting 660 treatments plans were evaluated regarding target doses to study the effect of dose renormalization to different prescription methods. A relative scoring system was used for comparisons. RESULTS:GTVD50% prescription can be performed in all systems. Treatment plan harmonization was overall successful, with standard deviations for Dmax, PTVD98%, GTVD98%, and PTVDmean of 1.6, 3.3, 1.9, and 1.5 Gy, respectively. Primary analysis showed 55 major deviations from clinical goals in 132 plans, whereas in only <20% of deviations GTV/PTV dose was traded for meeting OAR limits. GTVD50% prescription produced the smallest deviation from target planning objectives and between techniques, followed by the PTVDmax, PTVD98%, PTVD2%, and PTVDmin prescription. Deviations were significant for all combinations but for the PTVDmax prescription compared with GTVD50% and PTVD98%. Based on the various dose prescription methods, all systems significantly differed from each other, whereas GTVD50% and PTVD98% prescription showed the least difference between the systems. CONCLUSIONS:This study showed the feasibility of harmonizing liver stereotactic body radiation therapy treatment plans across different treatment planning systems and delivery techniques when a sufficient set of clinical goals is given.

Hippocampus-avoidance whole brain radiotherapy with simultaneous integrated boost (HA-WBRT+SIB) is a complex treatment option for patients with multiple brain metastases, aiming to prevent neurocognitive decline and simultaneously increase tumor control. Achieving efficient hippocampal dose reduction in this context can be challenging. The aim of the current study is to present and analyze the efficacy of complete directional hippocampal blocking in reducing the hippocampal dose during HA-WBRT+SIB. A total of 30 patients with multiple metastases having undergone HA-WBRT+SIB were identified. The prescribed dose was 30 Gy in 12 fractions to the whole brain, with 98% of the hippocampus receiving ≤ 9 Gy and 2% ≤ 17 Gy and with SIB to metastases/resection cavities of 36–51 Gy in 12 fractions. Alternative treatment plans were calculated using complete directional hippocampal blocking and compared to conventional plans regarding target coverage, homogeneity, conformity, dose to hippocampi and organs at risk. All alternative plans reached prescription doses. Hippocampal blocking enabled more successful sparing of the hippocampus, with a mean dose of 8.79 ± 0.99 Gy compared to 10.07 ± 0.96 Gy in 12 fractions with the conventional method (p < 0.0001). The mean dose to the whole brain (excluding metastases and hippocampal avoidance region) was 30.52 ± 0.80 Gy with conventional planning and 30.28 ± 0.11 Gy with hippocampal blocking (p = 0.11). Target coverage, conformity and homogeneity indices for whole brain and metastases, as well as doses to organs at risk were similar between planning methods (p > 0.003). Complete directional hippocampal blocking is an efficient method for achieving improved hippocampal sparing during HA-WBRT+SIB.

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.

The aim was to evaluate stereotactic body radiation therapy (SBRT) treatment planning variability for early stage nonsmall cell lung cancer (NSCLC) with respect to the published guidelines of the Stereotactic Radiotherapy Working Group of the German Society for Radiation Oncology (DEGRO).

PurposeTo 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 materials10 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 77 Gy, and Plan95 which consisted of whole-prostate IMRT to 77 Gy and a simultaneous integrated boost to the GTV-PET up to 95 Gy (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.ResultsAll plans reached prescription doses whilst adhering to dose constraints. In Plan77 and Plan95 mean doses in GTV-histo were 75.8 ± 0.3 Gy and 96.9 ± 1 Gy, 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.ConclusionsIMRT dose painting using PSMA PET/CT was technically feasible and resulted in significantly higher TCPs without higher NTCPs.

Introduction: Stereotactic radiosurgery (SRS) has been increasingly advocated for 1-3 small brain metastases. The goal of this study was to evaluate the clinical results in patients with brain metastases treated with LINAC-based SRS using a thermoplastic mask (non-invasive fixation system) and Image-Guided Radiotherapy (IGRT). Material and Methods: In this single-institution study 48 patients with 77 brain metastases were treated between February 2012 and January 2014. The prescribed dose was 20 Gy or 18 Gy as a single fraction. SRS was performed with a True Beam STX Novalis Radiosurgery LINAC (Varian Medical Systems). The verification of positioning was done using the BrainLAB ExacTrac (R) X-ray 6D system and cone-beam CT. Results: In 69 of 77 treated brain metastases (90%) the follow-up was documented on MR imaging performed every 3 months. Mean follow-up time was 10.86 months. Estimated 1-year local control was 83%, using the Kaplan-Meier method. In 7/69 brain metastases (10%) local failure (LF) was diagnosed. Median progression free survival (PFS) was 3.73 months, largely due to distant brain relapse. A GTV of <= 2.0 cm(3) was significantly associated with a better PFS than a GTV >2.0 cm(3). Extracranial stable disease and GTV <= 2.5 cm(3) were significant predictors of OS. We observed 2 cases of radiation necrosis diagnosed by histology after surgical resection. No other cases of severe side effects (CTACE >= 3) were observed. Conclusion: LINAC-based frameless SRS with the BrainLAB Mask using the BrainLAB ExacTrac (R) X-ray 6D system for patient positioning is well tolerated, safe and leads to favorable crude local control of 90%. In our experience, local control after frameless (ringless) SRS is as good as ring-based SRS reported in literature. Without invasive head fixation, radiotherapy is more comfortable for patients. (C) 2017 The Authors. Published by Elsevier Ireland Ltd on behalf of European Society for Radiotherapy and Oncology.

Stereotactic radiotherapy near serial organs at risk (OAR) requires special caution. A novel intensity-modulated radiotherapy (IMRT) prescription concept termed simultaneous integrated protection (SIP) for quantifiable and comparable dose prescription to targets very close to OAR is described.

PURPOSE:Rotational IMRT is a new technique, whose value still has to be assessed. We evaluated its adequacy for the treatment of head and neck (H&N) cancer compared to the well-established step-and-shoot IMRT.MATERIALS AND METHODS:A total of 15 patients, who were treated with either IMRT (13 patients) or VMAT (2 patients) in the H&N region, were chosen. For each patient, a treatment plan with the respective other technique was calculated. To compare the resulting dose distributions, the dose-volume histograms (DVHs) were evaluated. To quantify the differences, a new quality index (QI) was introduced, as a measure of the planning target volume (PTV) coverage and homogeneity. A conformity function (CF) was defined to estimate normal tissue sparing.RESULTS:The QI for VMAT amounts to 36.3, whereas for IMRT the mean value is 66.5, indicating better PTV coverage as well as less overdosage for the rotational technique. While the sparing of organs at risk (OAR) was similar for both techniques, the CF shows a significantly better sparing of healthy tissue for all doses with VMAT treatment.CONCLUSIONS:VMAT results in dose distributions for H&N patients that are at least comparable with treatments performed with step-and-shoot IMRT. Two new tools to quantify the quality of dose distributions are presented and have proven to be useful.