Direct dose correlation of MRI morphologic alterations of healthy liver tissue after robotic liver SBRT.

PURPOSE: For assessing healthy liver reactions after robotic SBRT (stereotactic body radiotherapy), we investigated early morphologic alterations on MRI (magnetic resonance imaging) with respect to patient and treatment plan parameters. PATIENTS AND METHODS: MRI data at 6-17 weeks post-treatment from 22 patients with 42 liver metastases were analyzed retrospectively. Median prescription dose was 40 Gy delivered in 3-5 fractions. T2- and T1-weighted MRI were registered to the treatment plan. Absolute doses were converted to EQD2 (Equivalent dose in 2Gy fractions) with α/ß-ratios of 2 and 3 Gy for healthy, and 8 Gy for modelling pre-damaged liver tissue. RESULTS: Sharply defined, centroid-shaped morphologic alterations were observed outside the high-dose volume surrounding the GTV. On T2-w MRI, hyperintensity at EQD2 isodoses of 113.3 ± 66.1 Gy2, 97.5 ± 54.7 Gy3, and 66.5 ± 32.0 Gy8 significantly depended on PTV dimension (p = 0.02) and healthy liver EQD2 (p = 0.05). On T1-w non-contrast MRI, hypointensity at EQD2 isodoses of 113.3 ± 49.3 Gy2, 97.4 ± 41.0 Gy3, and 65.7 ± 24.2 Gy8 significantly depended on prior chemotherapy (p = 0.01) and total liver volume (p = 0.05). On T1-w gadolinium-contrast delayed MRI, hypointensity at EQD2 isodoses of 90.6 ± 42.5 Gy2, 79.3 ± 35.3 Gy3, and 56.6 ± 20.9 Gy8 significantly depended on total (p = 0.04) and healthy (p = 0.01) liver EQD2. CONCLUSIONS: Early post-treatment changes in healthy liver tissue after robotic SBRT could spatially be correlated to respective isodoses. Median nominal doses of 10.1-11.3 Gy per fraction (EQD2 79-97 Gy3) induce characteristic morphologic alterations surrounding the lesions, potentially allowing for dosimetric in-vivo accuracy assessments. Comparison to other techniques and investigations of the short- and long-term clinical impact require further research.

MRI morphologic alterations after liver SBRT : Direct dose correlation with intermodal matching.

AIM: CT morphologic and histopathologic alterations have been reported after SBRT. We analyzed the correlation of MRI morphologic alterations with radiation doses to assess the potential for MRI-based dose-effect correlation in healthy liver tissue. PATIENTS AND METHODS: MRI data of 24 patients with liver metastases 7±3 weeks after image-guided SBRT in deep-inspiration breath-hold were retrospectively analyzed. MRI images were intermodally matched to the planning CT and corresponding dose distribution. Absolute doses were converted to EQD2,α/ß =x with α/ß values of 2, 3 for healthy liver tissue, 8 Gy for modelled predamaged liver tissue and 10 Gy for tumor tissue. RESULTS: A central nonenhancing area was observed within the isodose lines of nominally 48.2 ± 15.2 Gy, EQD2Gy/α/ß =10 92.5 ± 27.7 Gy. Contrast-enhancement around the central nonenhancing area was observed within the isodose lines of nominally 46.9 ± 15.3 Gy, EQD2Gy/α/ß =10 90.5 ± 28.3 Gy. Outside the high-dose volume, in the beam path, characteristic sharply defined, nonblurred MRI morphologic alterations were observed that corresponded with the following isodose lines: T1-intensity changes occurred at isodose lines of nominally 21.9 ± 6.7 Gy (EQD2,α/ß =2 42.5 ± 8.7 Gy, EQD2,α/ß =3 38.5 ± 7.6 Gy, EQD2,α/ß =8 30.2 ±6.3 Gy). T2-hyper/hypointensity was observed within isodose lines of nominally 22.4 ± 6.6 Gy (EQD2,α/ß=2 42.7 ± 8.1 Gy, EQD2,α/ß=3 38.7 ± 7 Gy; EQD2,α/ß=8 30.5 ± 5.9 Gy). CONCLUSIONS: Using deformable matching, direct spatial/dosimetric correlation of SBRT-induced changes in liver tissue was possible. In the PTV high-dose region, a central nonenhancing area and peripheral contrast medium accumulation was observed. Beam path doses of 38-42 Gy (EQD2,α/ß =2-3) induce characteristic MRI morphologic alterations.

Automatically gated image-guided breath-hold IMRT is a fast, precise, and dosimetrically robust treatment for lung cancer patients.

BACKGROUND: High-dose radiotherapy of lung cancer is challenging. Tumors may move by up to 2 cm in craniocaudal and anteroposterior directions as a function of breathing cycle. Tumor displacement increases with treatment time, which consequentially increases the treatment uncertainty. OBJECTIVE: This study analyzed whether automatically gated cone-beam-CT (CBCT)-controlled intensity modulated fast deep inspiration breath hold (DIBH) stereotactic body radiation therapy (SBRT) in flattening filter free (FFF) technique and normofractionated lung DIBH intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT) treatments delivered with a flattening filter can be applied with sufficient accuracy within a clinically acceptable timeslot. MATERIALS AND METHODS: Plans of 34 patients with lung tumors were analyzed. Of these patients, 17 received computer-controlled fast DIBH SBRT with a dose of 60 Gy (5 fractions of 12 Gy or 12 fractions of 5 Gy) in an FFF VMAT technique (FFF-SBRT) every other day and 17 received conventional VMAT with a flattening filter (conv-VMAT) and 2-Gy daily fractional doses (cumulative dose 50-70 Gy). RESULTS: FFF-SBRT plans required more monitor units (MU) than conv-VMAT plans (2956.6 ± 885.3 MU for 12 Gy/fraction and 1148.7 ± 289.2 MU for 5 Gy/fraction vs. 608.4 ± 157.5 MU for 2 Gy/fraction). Total treatment and net beam-on times were shorter for FFF-SBRT plans than conv-VMAT plans (268.0 ± 74.4 s vs. 330.2 ± 93.6 s and 85.8 ± 25.3 s vs. 117.2 ± 29.6 s, respectively). Total slot time was 13.0 min for FFF-SBRT and 14.0 min for conv-VMAT. All modalities could be delivered accurately despite multiple beam-on/-off cycles and were robust against multiple interruptions. CONCLUSION: Automatically gated CBCT-controlled fast DIBH SBRT in VMAT FFF technique and normofractionated lung DIBH VMAT can be applied with a low number of breath-holds in a short timeslot, with excellent dosimetric accuracy. In clinical routine, these approaches combine optimally reduced lung tissue irradiation with maximal delivery precision for patients with small and larger lung tumors.

Cone Beam CT-Based Daily Adaptive Planning or Defined-Filling Protocol for Neoadjuvant Gastric Cancer Radiation Therapy: A Comparison.

PURPOSE: This study aimed to investigate, in the setting of neoadjuvant gastric irradiation with integrated boost, whether cone beam computed tomography (CBCT)-based adaptive radiation therapy compared with a defined-filling protocol would be beneficial in terms of feasibility and achieving daily reproducible dose volume indexes of the planning target volume (PTV) and organs at risk (OARs) and workflow. METHODS AND MATERIALS: Planning computed tomography (PCT) and 25 CBCT scans of a previously treated patient were used, and neoadjuvant therapy of gastric carcinoma was simulated offline. PTVs and OARs were defined per the TOPGEAR protocol (PTV: 45 Gy/1.8 Gy), and an integrated boost (gross tumor volume [GTV]: 50.4 Gy/2.016 Gy) was added. The patient followed a filling regimen consisting of 12-hour fasting followed by 200 mL of water intake (2 glasses of water) immediately before irradiation. OARs and PTVs were newly contoured on each CBCT. Nonrigid registration of PCT and CBCT scans was performed. Nonadapted plans were recalculated on each CBCT (R-CBCT). Furthermore, an adapted plan was created for the new anatomy (A-CBCT). Dose parameters and comparison of R-CBCT and A-CBCT for the kidneys, liver, and heart were analyzed using a paired t test. RESULTS: A total of 200 plans for R-CBCT and A-CBCT were obtained. Mean gastric volumes were 277.32 cm3 (±54.40 cm3) in CBCT scans and 519.2 cm3 in PCT. Mean doses to the PTV did not differ meaningfully within the CBCT scans, with an average of 1.54%. The D95 improved in GTV coverage by 5.26% compared with the R-CBCT plan. Mean heart, liver, and right kidney doses were reduced with the A-CBCT plan by 35.74%, 10.71% and 29.47%, respectively. The R- and A-CBCT comparison for GTV and OARs was significantly different in all cases (P < .0001). CONCLUSIONS: Adaptive radiation therapy through deformable registration represents an important tool in neoadjuvant gastric irradiation, encompassing daily variability and organ motion, compared with the defined-filling protocol while improving OAR sparing.

In-vivo treatment accuracy analysis of active motion-compensated liver SBRT through registration of plan dose to post-therapeutic MRI-morphologic alterations.

BACKGROUND/PURPOSE: In-vivo-accuracy analysis (IVA) of dose-delivery with active motion-management (gating/tracking) was performed based on registration of post-radiotherapeutic MRI-morphologic-alterations (MMA) to the corresponding dose-distributions of gantry-based/robotic SBRT-plans. METHODS: Forty targets in two patient cohorts were evaluated: (1) gantry-based SBRT (deep-inspiratory breath-hold-gating; GS) and (2) robotic SBRT (online fiducial-tracking; RS). The planning-CT was deformably registered to the first post-treatment contrast-enhanced T1-weighted MRI. An isodose-structure cropped to the liver (ISL) and corresponding to the contoured MMA was created. Structure and statistical analysis regarding volumes, surface-distance, conformity metrics and center-of-mass-differences (CoMD) was performed. RESULTS: Liver volume-reduction was -43.1 ±â€¯148.2 cc post-RS and -55.8 ±â€¯174.3 cc post-GS. The mean surface-distance between MMA and ISL was 2.3 ±â€¯0.8 mm (RS) and 2.8 ±â€¯1.1 mm (GS). ISL and MMA volumes diverged by 5.1 ±â€¯23.3 cc (RS) and 16.5 ±â€¯34.1 cc (GS); the median conformity index of both structures was 0.83 (RS) and 0.80 (GS). The average relative directional errors were ≤0.7 mm (RS) and ≤0.3 mm (GS); the median absolute 3D-CoMD was 3.8 mm (RS) and 4.2 mm (GS) without statistically significant differences between the two techniques. Factors influencing the IVA included GTV and PTV (p = 0.041 and p = 0.020). Four local relapses occurred without correlation to IVA. CONCLUSIONS: For the first time a method for IVA was presented, which can serve as a benchmarking-tool for other treatment techniques. Both techniques have shown median deviations <5 mm of planned dose and MMA. However, IVA also revealed treatments with errors ≥5 mm, suggesting a necessity for patient-specific safety-margins. Nevertheless, the treatment accuracy of well-performed active motion-compensated liver SBRT seems not to be a driving factor for local treatment failure.

Neoadjuvant gene delivery of feline granulocyte-macrophage colony-stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial.

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have high recurrence rates. Immunostimulatory gene therapy is a promising approach in veterinary oncology. This phase I dose-escalation study was performed to determine toxicity and feasibility of gene therapy with feline granulocyte-macrophage colony-stimulating factor (feGM-CSF) in cats with fibrosarcomas. Twenty cats were treated with plasmid coding for feGM-CSF attached to magnetic nanoparticles in doses of 50, 250, 750 and 1250 microg. Two preoperative intratumoral injections followed by magnetofection were given. Four control cats received only surgical treatment. Adverse events were recorded and correlated according to the veterinary co-operative oncology group toxicity scale. An enzyme-linked immunosorbent assay was performed to detect plasma feGM-CSF concentrations. No significant treatment related toxicity was observed. Preliminary recurrence results were encouraging as, on day 360, ten of 20 treated cats were recurrence-free. In conclusion, 1250 microg of feGM-CSF plasmid DNA applied by magnetofection is safe and feasible for phase II testing.

Deep Inspiration Breath Hold-Based Radiation Therapy: A Clinical Review.

Several recent developments in linear accelerator-based radiation therapy (RT) such as fast multileaf collimators, accelerated intensity modulation paradigms like volumeric modulated arc therapy and flattening filter-free (FFF) high-dose-rate therapy have dramatically shortened the duration of treatment fractions. Deliverable photon dose distributions have approached physical complexity limits as a consequence of precise dose calculation algorithms and online 3-dimensional image guided patient positioning (image guided RT). Simultaneously, beam quality and treatment speed have continuously been improved in particle beam therapy, especially for scanned particle beams. Applying complex treatment plans with steep dose gradients requires strategies to mitigate and compensate for motion effects in general, particularly breathing motion. Intrafractional breathing-related motion results in uncertainties in dose delivery and thus in target coverage. As a consequence, generous margins have been used, which, in turn, increases exposure to organs at risk. Particle therapy, particularly with scanned beams, poses additional problems such as interplay effects and range uncertainties. Among advanced strategies to compensate breathing motion such as beam gating and tracking, deep inspiration breath hold (DIBH) gating is particularly advantageous in several respects, not only for hypofractionated, high single-dose stereotactic body RT of lung, liver, and upper abdominal lesions but also for normofractionated treatment of thoracic tumors such as lung cancer, mediastinal lymphomas, and breast cancer. This review provides an in-depth discussion of the rationale and technical implementation of DIBH gating for hypofractionated and normofractionated RT of intrathoracic and upper abdominal tumors in photon and proton RT.

Radiation protection for an intraoperative X-ray source compared to C-arm fluoroscopy.

BACKGROUND: Intraoperative radiotherapy (IORT) using the INTRABEAM(®) system promises a flexible use regarding radiation protection compared to other approaches such as electron treatment or HDR brachytherapy with (192)Ir or (60)Co. In this study we compared dose rate measurements of breast- and Kypho-IORT with C-arm fluoroscopy which is needed to estimate radiation protection areas. MATERIALS AND METHODS: C-arm fluoroscopy, breast- and Kypho-IORTs were performed using phantoms (silicon breast or bucket of water). Dose rates were measured at the phantom's surface, at 30 cm, 100 cm and 200 cm distance. Those measurements were confirmed during 10 Kypho-IORT and 10 breast-IORT patient treatments. RESULTS: The measured dose rates were in the same magnitude for all three paradigms and ranges from 20 µSv/h during a simulated breast-IORT at two meter distance up to 64 mSv/h directly at the surface of a simulated Kypho-IORT. Those measurements result in a circle of controlled area (yearly doses >6 mSv) for each paradigm of about 4 m±2 m. DISCUSSION/CONCLUSIONS: All three paradigms show comparable dose rates which implies that the radiation protection is straight forward and confirms the flexible use of the INTRABEAM(®) system.

Arc therapy for total body irradiation--a robust novel treatment technique for standard treatment rooms.

BACKGROUND AND PURPOSE: We developed a simple and robust total body irradiation (TBI) method for standard treatment rooms that obviates the need for patient translation devices. METHODS AND MATERIALS: Two generic arcs with rectangular segments for a patient thickness of 16 and 20 cm (arc16/arc20) were generated. An analytical fit was performed to determine the weights of the arc segments depending on patient thickness and gantry angle. Stability and absolute dose for both arcs were measured using EBT3 films in a range of solid water slab phantom thicknesses. Additionally ionization chamber measurements were performed every 10 cm at a source surface distance (SSD) of ∼ 200 cm. RESULTS: The measured standard deviation for arc16 is ± 3% with a flatness ⩽ 9.0%. Arc20 had a standard deviation of ± 3% with a flatness ⩽ 7.3% for all measured thicknesses. The theoretical curves proved to be accurate for the prediction of the segment weightings for the two arcs. In vivo measurements for the first 22 clinical patients showed a dose deviation of less than 3%. CONCLUSIONS: Arc therapy is a convenient and stable method for TBI. This cost-effective approach has been introduced clinically, obviating the need for field patches and to physically move the patient.