MLC tracking for lung SABR is feasible, efficient and delivers high-precision target dose and lower normal tissue dose.

BACKGROUND AND PURPOSE: The purpose of this work is to present the clinical experience from the first-in-human trial of real-time tumor targeting via MLC tracking for stereotactic ablative body radiotherapy (SABR) of lung lesions. METHODS AND MATERIALS: Seventeen patients with stage 1 non-small cell lung cancer (NSCLC) or lung metastases were included in a study of electromagnetic transponder-guided MLC tracking for SABR (NCT02514512). Patients had electromagnetic transponders inserted near the tumor. An MLC tracking SABR plan was generated with planning target volume (PTV) expanded 5 mm from the end-exhale gross tumor volume (GTV). A clinically approved comparator plan was generated with PTV expanded 5 mm from a 4DCT-derived internal target volume (ITV). Treatment was delivered using a standard linear accelerator to continuously adapt the MLC based on transponder motion. Treated volumes and reconstructed delivered dose were compared between MLC tracking and comparator ITV-based treatment. RESULTS: All seventeen patients were successfully treated with MLC tracking (70 successful fractions). MLC tracking treatment delivery time averaged 8 minutes. The time from the start of CBCT to the end of treatment averaged 22 minutes. The MLC tracking PTV for 16/17 patients was smaller than the ITV-based PTV (range -1.6% to 44% reduction, or -0.6 to 18 cc). Reductions in mean lung dose (27 cGy) and V20Gy (50 cc) were statistically significant (p < 0.02). Reconstruction of treatment doses confirmed a statistically significant improvement in delivered GTV D98% (p < 0.05) from planned dose compared with the ITV-based plans. CONCLUSION: The first treatments with lung MLC tracking have been successfully performed in seventeen SABR patients. MLC tracking for lung SABR is feasible, efficient and delivers high-precision target dose and lower normal tissue dose.

Geometric uncertainty analysis of MLC tracking for lung SABR.

PURPOSE: The purpose of this work was to report on the geometric uncertainty for patients treated with multi-leaf collimator (MLC) tracking for lung SABR to verify the accuracy of the system. METHODS: Seventeen patients were treated as part of the MLC tracking for lung SABR clinical trial using electromagnetic beacons implanted around the tumor acting as a surrogate for target motion. Sources of uncertainties evaluated in the study included the surrogate-target positional uncertainty, the beam-surrogate tracking uncertainty, the surrogate localization uncertainty, and the target delineation uncertainty. Probability density functions (PDFs) for each source of uncertainty were constructed for the cohort and each patient. The total PDFs was computed using a convolution approach. The 95% confidence interval (CI) was used to quantify these uncertainties. RESULTS: For the cohort, the surrogate-target positional uncertainty 95% CIs were ±2.5 mm (-2.0/3.0 mm) in left-right (LR), ±3.0 mm (-1.6/4.5 mm) in superior-inferior (SI) and ±2.0 mm (-1.8/2.1 mm) in anterior-posterior (AP). The beam-surrogate tracking uncertainty 95% CIs were ±2.1 mm (-2.1/2.1 mm) in LR, ±2.8 mm (-2.8/2.7 mm) in SI and ±2.1 mm (-2.1/2.0 mm) in AP directions. The surrogate localization uncertainty minimally impacted the total PDF with a width of ±0.6 mm. The target delineation uncertainty distribution 95% CIs were ±5.4 mm. For the total PDF, the 95% CIs were ±5.9 mm (-5.8/6.0 mm) in LR, ±6.7 mm (-5.8/7.5 mm) in SI and ±6.0 mm (-5.5/6.5 mm) in AP. CONCLUSION: This work reports the geometric uncertainty of MLC tracking for lung SABR by accounting for the main sources of uncertainties that occurred during treatment. The overall geometric uncertainty is within ±6.0 mm in LR and AP directions and ±6.7 mm in SI. The dominant uncertainty was the target delineation uncertainty. This geometric analysis helps put into context the range of uncertainties that may be expected during MLC tracking for lung SABR (ClinicalTrials.gov registration number: NCT02514512).

Interim Results of a Prospective Prostate-Specific Membrane Antigen-Directed Focal Stereotactic Reirradiation Trial for Locally Recurrent Prostate Cancer.

PURPOSE: To report the feasibility, toxicity, and preliminary outcomes (metabolic and biochemical) of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-directed focal prostate reirradiation using linear accelerator (LINAC)-based stereotactic body radiation treatment (SBRT). METHODS AND MATERIALS: From March 2016 to March 2019, 25 patients were enrolled in a prospective single institution trial (ACTRN12617000035325). Eligibility criteria included patients with biopsy proven isolated prostate recurrence after definitive irradiation, with concordant multiparametric MRI and 68Ga-PSMA PET/CT findings, and a prostate-specific antigen of less than 15 ng/mL at the time of recurrence. The study included a sequential dose escalation component with the first 18 patients receiving 36 Gy in 6 fractions on alternate days with subsequent patients receiving 38 Gy in 6 fractions assuming acceptable toxicity. RESULTS: Median age was 72 years (range, 62-83) with a median time between first radiation treatment and salvage SBRT of 8.3 years (range, 4.5- 13.6). Median prostate-specific antigen at reirradiation was 4.1 (range, 1.1-16.6). The median follow-up was 25 months (range, 13-46). Acute grade 1 and 2 genitourinary (GU) toxicity occurred in 6 (24%) and 1 (4%) men, respectively. Acute grade 1 gastrointestinal (GI) toxicity occurred in 8% with one acute grade 3 GI toxicity (4%) due to a rectal ulcer overlying the hydrogel. Late grade 1 and 2 GU toxicity occurred in 28% and 4%. Late grade 1 GI toxicity occurred in 8% with no grade 2 or greater toxicity. Twenty-four patients have undergone per-protocol 12-month 68Ga-PSMA PET/CT, of which 23 (92%) demonstrated a complete metabolic response. Biochemical freedom from failure was 80% at 2 years with 3 out of 4 of the biochemical failures exhibiting recurrent local disease. CONCLUSIONS: PSMA-directed salvage focal reirradiation to the prostate using linear accelerator-based SBRT is feasible and safe. Toxicity was low, with very favorable short term local and biochemical control in a carefully selected cohort of patients.

Both four-dimensional computed tomography and four-dimensional cone beam computed tomography under-predict lung target motion during radiotherapy.

BACKGROUND AND PURPOSE: To test the hypothesis that 4DCT and 4DCBCT-measured target motion ranges predict target motion ranges during lung cancer SABR. MATERIALS AND METHODS: Ten lung SABR patients were implanted with Calypso beacons. 4DCBCT was reconstructed for 29 fractions (1-4fx/patient) from a 1 min CBCT scan. The beacon centroid motion segmented for all 4DCT and 4DCBCT bins was compared with the real-time imaging and treatment beacon centroid ("target") motion range (4SDs) for each fraction. We tested the hypotheses that (1) 4DCT and 4CBCT predict treatment motion range and (2) there is no difference between 4DCT and 4DCBCT for predicting treatment motion range. Phase-wise root-mean-square errors (RMSEs) between imaging and treatment motion and reconstructed motion (4DCT, 4DCBCT) were calculated. Relationships between motion ranges in 4DCT and 4DCBCT and imaging and treatment motion ranges were investigated for the superior-inferior (SI), left-right (LR) and anterior-posterior (AP) directions. Baseline drifts and amplitude variability were investigated as potential factors leading to motion misrepresentation. RESULTS: SI 4DCT, 4DCBCT, imaging and treatment motion ranges were 6.3 ±â€¯3.6 mm, 7.1 ±â€¯4.5 mm, 11.1 ±â€¯7.5 mm and 10.9 ±â€¯6.9 mm, respectively. Similar 4DCT and 4DCBCT under-predictions were observed in the LR and AP directions. Hypothesis (1) was rejected (p < 0.0001). Treatment target motion range was under-predicted in 4DCT by factors of 1.7, 1.9 and 1.7 and in 4DCBCT by factors of 1.5, 1.6 and 1.6 in the SI, LR, and AP directions, respectively. RMSEs were generally lower for end-exhale than inhale. 4DCBCT showed higher correlations with the imaging and treatment target motion than 4DCT and testing hypothesis (2) a statistically significant difference between 4DCT and 4DCBCT was shown in the SI direction (p = 0.03). CONCLUSION: For lung SABR patients both 4DCT and 4DCBCT significantly under-predict treatment target motion ranges.

MLC tracking for lung SABR reduces planning target volumes and dose to organs at risk.

PURPOSE: Assess the dosimetric impact of multi-leaf collimator (MLC) tracking and mid-ventilation (midV) planning compared with the internal target volume (ITV)-based planning approach for lung Stereotactic Ablative Body Radiotherapy (SABR). METHOD: Ten lung SABR patients originally treated with an ITV-based plan were re-planned according to MLC tracking and midV planning schemes. All plans were delivered on a linac to a motion phantom in a simulated treatment with real lung motions. Delivered dose was reconstructed in patient planning scans. ITV-based, tracking and midV regimes were compared at the planning and delivered stages based on PTV volume and dose metrics for the GTV and OAR. RESULTS: MLC tracking and midV schemes yielded favourable outcomes compared with ITV-based plans. Average reduction in PTV volume was (MLC tracking/MidV) 33.9%/22%. GTV dose coverage performed better with MLC tracking than the other regimes. Reduction in dose to OAR were for the lung (mean lung dose, 0.8Gy/0.2Gy), oesophagus (D3cc, 1.9Gy/1.4Gy), great vessels (D10cc, 3.2Gy/1.3Gy), trachea (D4cc, 1.1Gy/0.9Gy), heart (D1cc, 2.0Gy/0.5Gy) and spinal cord (D0.03cc, 0.5Gy/-0.1Gy). CONCLUSION: MLC tracking showed reduction in PTV volume, superior GTV dose coverage and organ dose sparing than MidV and ITV-based strategies.

The first patient treatment of electromagnetic-guided real time adaptive radiotherapy using MLC tracking for lung SABR.

BACKGROUND AND PURPOSE: Real time adaptive radiotherapy that enables smaller irradiated volumes may reduce pulmonary toxicity. We report on the first patient treatment of electromagnetic-guided real time adaptive radiotherapy delivered with MLC tracking for lung stereotactic ablative body radiotherapy. MATERIALS AND METHODS: A clinical trial was developed to investigate the safety and feasibility of MLC tracking in lung. The first patient was an 80-year old man with a single left lower lobe lung metastasis to be treated with SABR to 48Gy in 4 fractions. In-house software was integrated with a standard linear accelerator to adapt the treatment beam shape and position based on electromagnetic transponders implanted in the lung. MLC tracking plans were compared against standard ITV-based treatment planning. MLC tracking plan delivery was reconstructed in the patient to confirm safe delivery. RESULTS: Real time adaptive radiotherapy delivered with MLC tracking compared to standard ITV-based planning reduced the PTV by 41% (18.7-11cm3) and the mean lung dose by 30% (202-140cGy), V20 by 35% (2.6-1.5%) and V5 by 9% (8.9-8%). CONCLUSION: An emerging technology, MLC tracking, has been translated into the clinic and used to treat lung SABR patients for the first time. This milestone represents an important first step for clinical real-time adaptive radiotherapy that could reduce pulmonary toxicity in lung radiotherapy.