Optimization of hippocampus sparing during whole brain radiation therapy with simultaneous integrated boost-tutorial and efficacy of complete directional hippocampal blocking.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Complete directional hippocampal blocking is an efficient method for achieving improved hippocampal sparing during HA-WBRT+SIB.

Planning Benchmark Study for Stereotactic Body Radiation Therapy of Liver Metastases: Results of the DEGRO/DGMP Working Group on Stereotactic Radiation Therapy and Radiosurgery.

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.

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.

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.

Planning benchmark study for SBRT of early stage NSCLC : Results of the DEGRO Working Group Stereotactic Radiotherapy.

PURPOSE: 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). MATERIALS AND METHODS: Planning computed tomography (CT) scan and the structure sets (planning target volume, PTV; organs at risk, OARs) of 3 patients with early stage NSCLC were sent to 22 radiotherapy departments with SBRT experience: each department was asked to prepare a treatment plan according to the DEGRO guidelines. The prescription dose was 3 fractions of 15 Gy to the 65% isodose. RESULTS: In all, 87 plans were generated: 36 used intensity-modulated arc therapy (IMAT), 21 used three-dimensional conformal radiation therapy (3DCRT), 6 used static field intensity-modulated radiation therapy (SF-IMRT), 9 used helical radiotherapy and 15 used robotic radiosurgery. PTV dose coverage and simultaneously kept OARs doses were within the clinical limits published in the DEGRO guidelines. However, mean PTV dose (mean 58.0 Gy, range 52.8-66.4 Gy) and dose conformity indices (mean 0.75, range 0.60-1.00) varied between institutions and techniques (p ≤ 0.02). OARs doses varied substantially between institutions, but appeared to be technique independent (p = 0.21). CONCLUSION: All studied treatment techniques are well suited for SBRT of early stage NSCLC according to the DEGRO guidelines. Homogenization of SBRT practice in Germany is possible through the guidelines; however, detailed treatment plan characteristics varied between techniques and institutions and further homogenization is warranted in future studies and recommendations. Optimized treatment planning should always follow the ALARA (as low as reasonably achievable) principle.

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.

Local control and overall survival after frameless radiosurgery: A single center experience.

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 ® 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 cm3 was significantly associated with a better PFS than a GTV >2.0 cm3. Extracranial stable disease and GTV ≤2.5 cm³ 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 ® 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.

Simultaneous integrated protection : A new concept for high-precision radiation therapy.

OBJECTIVE: 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. MATERIALS AND METHODS: An intersection volume of a planning risk volume (PRV) with the total planning target volume (PTV) defined the protection volume (PTVSIP). The remainder of the PTV represented the dominant PTV (PTVdom). Planning was performed using IMRT. Dose was prescribed to PTVdom according to ICRU in 3, 5, 8, or 12 fractions. Constraints to OARs were expressed as absolute and as equieffective doses at 2 Gy (EQD2). Dose to the gross risk volume of an OAR was to respect constraints. Violation of constraints to OAR triggered a planning iteration at increased fractionation. Dose to PTVSIP was required to be as high as possible within the constraints to avoid local relapse. RESULTS: SIP was applied in 6 patients with OAR being large airways (n = 2) or bowel (n = 4) in 3, 5, 8, and 12 fractions in 1, 3, 1, and 1 patients, respectively. PTVs were 14.5-84.9 ml and PTVSIP 1.8-3.9 ml (2.9-13.4 % of PTV). Safety of the plans was analyzed from the absolute dose-volume histogram (dose to ml). The steepness of dose fall-off could be determined by comparing the dose constraints to the PRVs with those to the OARs (Wilcoxon test p = 0.001). Constraints were respected for the corresponding OARs. All patients had local control at a median 9 month follow-up and toxicity was low. CONCLUSION: SIP results in a median dose of ≥100 % to PTV, to achieve high local control and low toxicity. Longer follow-up is required to verify results and a prospective clinical trial is currently testing this new approach in chest and abdomen stereotactic body radiotherapy.

VMAT and step-and-shoot IMRT in head and neck cancer: a comparative plan analysis.

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.

On the accuracy of isocenter verification with kV imaging in stereotactic radiosurgery.

BACKGROUND AND PURPOSE: Modern medical linear accelerators (linacs) are equipped with X-ray systems, which allow to check the patient's position just prior to treatment. Their usefulness for stereotactic radiosurgery (SRS) depends on how accurately they allow to determine the deviation between the actual and planned isocenter positions. This accuracy was investigated with measurements using two different phantoms (Figures 1 and 2). MATERIAL AND METHODS: After precisely aligning a phantom onto the linac isocenter, two perpendicular X-rays or a cone-beam CT (CBCT) are taken, and the isocenter position is deduced from this data. The deviation of the thereby gained position from the setup isocenter is taken as a measure for the uncertainty of this method. RESULTS: Isocenter verification with two orthogonal X-rays (Figure 4) achieves accuracies of better than 1 mm (Table 3). The distance between the isocenters of the CBCT and the linac (Figure 3) is in the order of 1 mm, but remains constant on the time scale of 1 week (Table 1) and may therefore be taken into account. The uncertainty after correction is below 0.2 mm. CONCLUSION: kV imaging with the patient in treatment position allows to verify the isocenter position with submillimeter precision, and therefore offers a supplemental test, suitable for SRS, which takes all positional uncertainties into account.