Dosimetric impact of applicator displacement on three-dimensional image-guided high-dose-rate brachytherapy treatments for cervical cancer.

Purpose: To determine the dosimetric impact of brachytherapy applicator displacement during intracavitary (IC) and combined intracavitary/interstitial (IC/IS) high-dose-rate brachytherapy in the treatment of cervical cancer. Material and methods: Data from 27 consecutively treated patients undergoing IC or IC/IS high-dose-rate brachytherapy with tandem and ovoid-based applicators at a single academic medical center were analyzed. Virtual applicator displacements (a single shift of whole applicator with tandem/ovoid/associated needles) of 0 (clinical position), 2, 5, 7, and 10 mm in the inferior direction were modeled on treatment planning CT or MRI scans, with maintaining the same dwell times. Radiation dose to target volumes (D90 of high-risk clinical target volume) and organs at risk (OARs) (D0.1cc, D1cc, and D2cc of bladder, rectum, and sigmoid) were calculated for each virtual applicator shift, and significance of displacements was assessed using general linear model and Kruskal-Wallis test. Results: Mean dose to high-risk clinical target volume (HR-CTV) D90 was 95.7%, 88.9%, 84.6%, and 77.1% of the prescribed dose in clinical position with displacements of 2, 5, 7, and 10 mm, respectively. Rectal D2cc significantly increased by 28% and 44% at displacement of 7 mm and 10 mm, respectively. IC/IS cases showed relatively greater dosimetric differences than IC cases, with HR-CTV D90 doses of 94.4%, 85.8%, 80.4%, and 72.4% at virtual displacements of 2, 5, 7, and 10 mm, respectively. Conclusions: Applicator displacements of 5 mm or greater result in statistically significant and clinically meaningful decreases in radiation dose to HR-CTV during 3-dimensional high-dose-rate brachytherapy treatment planning, with corresponding increase in radiation dose to the rectum. IC/IS applicator displacements lead to relatively greater differences than those of IC applicators.

Lattice position optimization for LATTICE therapy.

BACKGROUND: LATTICE radiation therapy delivers 3D heterogenous dose of high peak-to-valley dose ratio (PVDR) to the tumor target, with peak dose at lattice vertices inside the target and valley dose for the rest of the target. Although the lattice vertex positions can impact PVDR inside the target and sparing of organs-at-risk (OAR), they are fixed as constants and not optimized during treatment planning in current clinical practice. PURPOSE: This work proposes a new LATTICE plan optimization method that can optimize lattice vertex positions during LATTICE treatment planning, which is the first lattice position optimization study to the best of our knowledge. METHODS: The new LATTICE treatment planning method optimizes lattice vertex positions as well as other plan variables (e.g., photon fluences or proton spot weights), with optimization objectives for target PVDR and OAR sparing. To satisfy mathematical differentiability, the lattice vertices are approximated in sigmoid functions. For geometric feasibility, proper geometry constraints are enforced onto lattice vertex positions. The lattice position optimization problem is solved by iterative convex relaxation (ICR) method and alternating direction method of multipliers (ADMM), and lattice vertex positions and photon/proton plan variables are jointly updated via the Quasi-Newton method. RESULTS: Both photon and proton LATTICE RT were considered, and the optimal lattice vertex positions in terms of plan objectives were found by solving all possible combinations on given discrete positions via exhaustive searching based on standard IMRT/IMPT, which served as the ground truth for validating the new LATTICE method. The results show that the new method indeed provided the optimal lattice vertex positions with the smallest optimization objective, the largest target PVDR, and the best OAR sparing. CONCLUSIONS: A new LATTICE treatment planning method is proposed and validated that can optimize lattice vertex positions as well as other photon or proton plan variables for improving target PVDR and OAR sparing.

Correlation of clinical outcome, radiobiological modeling of tumor control, normal tissue complication probability in lung cancer patients treated with SBRT using Monte Carlo calculation algorithm.

PURPOSE/BACKGROUND: We analyzed the predictive value of non-x-ray voxel Monte Carlo (XVMC)-based modeling of tumor control probability (TCP) and normal tissue complication probability (NTCP) in patients treated with stereotactic body radiotherapy (SBRT) using the XVMC dose calculation algorithm. MATERIALS/METHODS: We conducted an IRB-approved retrospective analysis in patients with lung tumors treated with XVMC-based lung SBRT. For TCP, we utilized tumor size-adjusted biological effective dose (s-BED) TCP modeling validated in non-MC dose calculated SBRT to: (1) verify modeling as a function of s-BED in patients treated with XVMC-based SBRT; and (2) evaluate the predictive potential of different PTV dosimetric parameters (mean dose, minimum dose, max dose, prescription dose, D95, D98, and D99) for incorporation into the TCP model. Correlation between observed local control and TCPs was assessed by Pearson's correlation coefficient. For NTCP, Lyman NTCP Model was utilized to predict grade 2 pneumonitis and rib fracture. RESULTS: Eighty-four patients with 109 lung tumors were treated with XVMC-based SBRT to total doses of 40 to 60 Gy in 3 to 5 fractions. Median follow-up was 17 months. The 2-year local and local-regional control rates were 91% and and 78%, respectievly. All estimated TCPs correlated significantly with 2-year actuarial local control rates (P < 0.05). Significant corelations between TCPs and tumor control rate according to PTV dosimetric parameters were observed. D99 parameterization demonstrated the most robust correlation between observed and predicted tumor control. The incidences of grade 2 pneumonitis and rib fracture vs. predicted were 1% vs. 3% and 10% vs. 13%, respectively. CONCLUSION: Our TCP results using a XVMC-based dose calculation algorithm are encouraging and yield validation to previously described TCP models using non-XVMC dose methods. Furthermore, D99 as potential predictive parameter in the TCP model demonstrated better correlation with clinical outcome.

Brachial plexopathy after stereotactic body radiation therapy for apical lung cancer: Dosimetric analysis and preliminary clinical outcomes.

PURPOSE: The treatment of apical lung tumors with stereotactic body radiation therapy (SBRT) is challenging due to the proximity of the brachial plexus and the concern for nerve damage. METHODS AND MATERIALS: Between June 2009 and February 2017, a total of 75 consecutive patients underwent SBRT for T1-T3N0 non-small cell lung cancer involving the upper lobe of the lung. All patients were treated with 4-dimensional computed tomography (CT)-based image guided SBRT to a dose of 40 to 60 Gy in 3 to 5 fractions. For dosimetric analysis, only apical tumors as defined by the location of the tumor epicenter superior to the aortic arch were included. The anatomical brachial plexus was delineated using the Radiation Therapy Oncology Group atlas. RESULTS: Thirty-one patients with 31 apical lung tumors satisfied the anatomical criteria for inclusion. The median age was 73 years (range, 58-89). The median planning target volume was 26.5 cc (range, 8.2-81.4 cc). The median brachial plexus, brachial plexus maximum dose (Dmax), Dmax per fraction, V22 (cc, 3-4 fractions), V30 (cc, 5 fractions), and biologically effective dose 3 Gy were 15.8 Gy (range, 1.7-66.5 Gy), 3.4 Gy (range, 0.6-14.7 Gy), 0.0 cc (range, 0-0.9 cc), 0.06 cc (range, 0-2.5 cc), and 31.5 Gy (range, 3.3-133.1 Gy), respectively. At a median follow-up of 17 months, the observed incidence of brachial plexopathy was 0%. CONCLUSIONS: There is significant variation in dose to the brachial plexus for patients treated with SBRT for apical lung tumors. Although the incidence of neuropathic symptoms in this series was zero, further attention should be focused on the clinical implications of these findings.

Dosimetric assessment of an air-filled balloon applicator in HDR vaginal cuff brachytherapy using the Monte Carlo method.

PURPOSE: As an alternative to cylindrical applicators, air-inflated balloon applicators have been introduced into high-dose-rate (HDR) vaginal cuff brachytherapy to achieve sufficient dose to the vagina mucosa as well as to spare organs at risk, mainly the rectum and bladder. Commercial treatment planning systems which employ formulae in the AAPM Task Group No. 43 (TG 43) report do not take into account tissue inhomogeneity. Consequently, the low-density air in a balloon applicator induces different doses delivered to the mucosa from planned by these planning systems. In this study, we investigated the dosimetric effects of the air in a balloon applicator using the Monte Carlo (MC) method. METHODS: The thirteen-catheter Capri™ applicator by Varian™ for vaginal cuff brachytherapy was modeled together with the Ir-192 radioactive source for the microSelectron™ Digital (HDR-V3) afterloader by Elekta™ using the MCNP MC code. The validity of charged particle equilibrium (CPE) with an air balloon present was evaluated by comparing the kerma and the absorbed dose at various distances from the applicator surface. By comparing MC results with and without air cavity present, dosimetric effects of the air cavity were studied. Clinical patient cases with optimized multiple Ir-192 source dwell positions were also explored. Four treatment plans by the Oncentra Brachy™ treatment planning system were re-calculated with MCNP. RESULTS: CPE fails in the vicinity of the air-water interface. One millimeter beyond the air-water boundary the kerma and the absorbed dose are equal (0.2% difference), regardless of air cavity dimensions or iridium source locations in the balloon. The air cavity results in dose increase, due to less photon absorption in the air than in water or solid materials. The extent of the increase depends on the diameter of the air balloon. The average increment is 3.8%, 4.5% and 5.3% for 3.0, 3.5, and 4.0 cm applicators, respectively. In patient cases, the dose to the mucosa is also increased with the air cavity present. The point dose difference between Oncentra Brachy and MC at 5 mm prescription depth is 8% at most and 5% on average. CONCLUSIONS: Except in the vicinity of the air-mucosa interface, the dosimetric difference is not significant enough to mandate tissue inhomogeneity correction in HDR treatment planning.

Volumetric modulated arc therapy treatment planning of thoracic vertebral metastases using stereotactic body radiotherapy.

PURPOSE/OBJECTIVES: To retrospectively evaluate the plan quality, treatment efficiency, and accuracy of volumetric modulated arc therapy (VMAT) plans for thoracic spine metastases using stereotactic body radiotherapy (SBRT). MATERIALS/METHODS: Seven patients with thoracic vertebral metastases treated with noncoplanar hybrid arcs (NCHA) (1 to 2 3D-conformal partial arcs +7 to 9 IMRT beams) were re-optimized with VMAT plans using three coplanar arcs. Tumors were located between T2 and T7 and PTVs ranged between 24.3 and 240.1 cc (median 48.1 cc). All prescriptions were 30 Gy in 5 fractions with 6 MV beams treated using the Novalis Tx linac equipped with high definition multileaf collimators (HDMLC). MR images were fused with planning CTs for target and OAR contouring. Plans were compared for target coverage using conformality index (CI), homogeneity index (HI), D90, D98, D2, and Dmedian. Normal tissue sparing was evaluated by comparing doses to the spinal cord (Dmax, D0.35, and D1.2 cc), esophagus (Dmax and D5 cc), heart (Dmax, D15 cc), and lung (V5 and V10). Data analysis was performed with a two-sided t-test for each set of parameters. Dose delivery efficiency and accuracy of each VMAT plan was assessed via quality assurance (QA) using a MapCHECK device. The Beam-on time (BOT) was recorded, and a gamma index was used to compare dose agreement between the planned and measured doses. RESULTS: VMAT plans resulted in improved CI (1.02 vs. 1.36, P = 0.05), HI (0.14 vs. 0.27, P = 0.01), D98 (28.4 vs. 26.8 Gy, P = 0.03), D2 (32.9 vs. 36.0 Gy, P = 0.02), and Dmedian (31.4 vs. 33.7 Gy, P = 0.01). D90 was improved but not statistically significant (30.4 vs. 31.0 Gy, P = 0.38). VMAT plans showed statistically significant improvements in normal tissue sparing: Esophagus Dmax (22.5 vs. 27.0 Gy, P = 0.03), Esophagus 5 cc (17.6 vs. 21.5 Gy, P = 0.02), and Heart Dmax (13.1 vs. 15.8 Gy, P = 0.03). Improvements were also observed in spinal cord and lung sparing as well but were not statistically significant. The BOT showed significant reduction for VMAT, 4.7 ± 0.6 min vs. 7.1 ± 1 min for NCHA (not accounting for couch kicks). VMAT plans demonstrated an accurate dose delivery of 95.5 ± 1.0% for clinical gamma passing rate of 3%/3 mm criteria, which was similar to NCHA plans. CONCLUSIONS: VMAT plans have shown improved dose distributions and normal tissue sparing compared to NCHA plans. Significant reductions in treatment time could potentially minimize patient discomfort and intrafraction movement errors. VMAT planning for SBRT is an attractive option for the treatment of metastases to thoracic vertebrae, and further investigation using alternative fractionation schedules is warranted.

Volumetric-modulated arc therapy (VMAT) for whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to organs at risk.

A prospective clinical trial, Radiation Therapy Oncology Group (RTOG) 0933, has demonstrated that whole brain radiotherapy (WBRT) using conformal radiation delivery technique with hippocampal avoidance is associated with less memory complications. Further sparing of other organs at risk (OARs) including the scalp, ear canals, cochleae, and parotid glands could be associated with reductions in additional toxicities for patients treated with WBRT. We investigated the feasibility of WBRT using volumetric-modulated arc therapy (VMAT) to spare the hippocampi and the aforementioned OARs. Ten patients previously treated with nonconformal WBRT (NC-WBRT) using opposed lateral beams were retrospectively re-planned using VMAT with hippocampal sparing according to the RTOG 0933 protocol. The OARs (scalp, auditory canals, cochleae, and parotid glands) were considered as dose-constrained structures. VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions. Comparison of the dosimetric parameters achieved by VMAT and NC-WBRT plans was performed using paired t-tests using upper bound p-value of < 0.001. Average beam on time and monitor units (MUs) delivered to the patients on VMAT were compared with those obtained with NC-WBRT. All VMAT plans met RTOG 0933 dosimetric criteria including the dose to hippocampi of 100% of the volume (D100%) of 8.4 ± 0.3 Gy and maximum dose of 15.6 ± 0.4 Gy, respectively. A statistically significant dose reduction (p < 0.001) to all OARs was achieved. The mean and maximum scalp doses were reduced by an average of 9 Gy (32%) and 2 Gy (6%), respectively. The mean and maximum doses to the auditory canals were reduced from 29.5 ± 0.5 Gy and 31.0 ± 0.4 Gy with NC-WBRT, to 21.8 ± 1.6 Gy (26%) and 27.4 ± 1.4 Gy (12%) with VMAT. VMAT also reduced mean and maximum doses to the cochlea by an average of 4 Gy (13%) and 2 Gy (6%), respectively. The parotid glands mean and maximum doses with VMAT were 4.4 ± 1.9 Gy and 15.7 ± 5.0 Gy, compared to 12.8 ± 4.9 Gy and 30.6 ± 0.5 Gy with NC-WBRT, respectively. The average dose reduction of mean and maximum of parotid glands from VMAT were 65% and 50%, respectively. The average beam on time and MUs were 2.3minutes and 719 on VMAT, and 0.7 minutes and 350 on NC-WBRT. This study demonstrated the feasibility of WBRT using VMAT to not only spare the hippocampi, but also significantly reduce dose to OARs. These advantages of VMAT could potentially decrease the toxicities associated with NC-WBRT and improve patients' quality of life, especially for patients with favorable prognosis receiving WBRT or patients receiving prophylactic cranial irradiation (PCI).

Linac-based stereotactic radiosurgery (SRS) in the treatment of refractory trigeminal neuralgia: Detailed description of SRS procedure and reported clinical outcomes.

PURPOSE/OBJECTIVES: To present our linac-based SRS procedural technique for medically and/or surgically refractory trigeminal neuralgia (TN) treatment and simultaneously report our clinical outcomes. MATERIALS AND METHODS: Twenty-seven refractory TN patients who were treated with a single fraction of 80 Gy to TN. Treatment delivery was performed with a 4 mm cone size using 7-arc arrangement with differential-weighting for Novalis-TX with six MV-SRS (1000 MU/min) beam and minimized dose to the brainstem. Before each treatment, Winston-Lutz quality assurance (QA) with submillimeter accuracy was performed. Clinical treatment response was evaluated using Barrow Neurological Institute (BNI) pain intensity score, rated from I to V. RESULTS: Out of 27 patients, 22 (81%) and 5 (19%) suffered from typical and atypical TN, respectively, and had median follow-up interval of 12.5 months (ranged: 1-53 months). For 80 Gy prescriptions, delivered total average MU was 19440 ± 611. Average beam-on-time was 19.4 ± 0.6 min. Maximum dose and dose to 0.5 cc of brainstem were 13.4 ± 2.1 Gy (ranged: 8.4-15.9 Gy) and 3.6 ± 0.4 Gy (ranged: 3.0-4.9 Gy), respectively. With a median follow-up of 12.5 months (ranged: 1-45 months) in typical TN patients, the proportion of patients achieving overall pain relief was 82%, of which half achieved a complete pain relief with BNI score of I-II and half demonstrated partial pain reduction with BNI score of IIIA-IIIB. Four typical TN patients (18%) had no response to radiosurgery treatment. Of the patients who responded to treatment, actuarial pain recurrence free survival rates were approximately 100%, 75%, and 50% at 12 months, 15 months, and 24 months, respectively. Five atypical TN patients were included, who did not respond to treatment (BNI score: IV-V). However, no radiation-induced cranial-toxicity was observed in all patients treated. CONCLUSION: Linac-based SRS for medically and/or surgically refractory TN is a fast, effective, and safe treatment option for patients with typical TN who had excellent response rates. Patients, who achieve response to treatment, often have durable response rates with moderate actuarial pain recurrence free survival. Longer follow-up interval is anticipated to confirm our clinical observations.

On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery.

To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12. Contrast-enhanced T1/T2-weighted magnetic resonance images were coregistered with planning computed tomography and planning target volumes (PTV) were between 14.4 and 230.1cc (median = 38.0cc). Prescription dose was 16Gy in 1 fraction with 6MV beams at Novalis-TX linear accelerator consisting of micro multileaf collimators. Each plan was assessed for target coverage using conformality index, the conformation number, the ratio of the volume receiving 50% of the prescription dose over PTV, R50%, homogeneity index (HI), and PTV_1600 coverage per RTOG 0631 requirements. Organs-at-risk doses were evaluated for maximum doses to spinal cord (D0.03cc, D0.35cc), partial spinal cord (D10%), esophagus (D0.03cc and D5cc), heart (D0.03cc and D15cc), and lung (V5, V10, and maximum dose to 1000cc of lung). Dose delivery efficiency and accuracy of each VMAT-SBRS plan were assessed using quality assurance (QA) plan on MapCHECK device. Total beam-on time was recorded during QA procedure, and a clinical gamma index (2%/2mm and 3%/3mm) was used to compare agreement between planned and measured doses. All 10 VMAT-SBRS plans met RTOG 0631 dosimetric requirements for PTV coverage. The plans demonstrated highly conformal and homogenous coverage of the vertebral PTV with mean HI, conformality index, conformation number, and R50% values of 0.13 ± 0.03 (range: 0.09 to 0.18), 1.03 ± 0.04 (range: 0.98 to 1.09), 0.81 ± 0.06 (range: 0.72 to 0.89), and 4.2 ± 0.94 (range: 2.7 to 5.4), respectively. All 10 patients met protocol guidelines with maximum dose to spinal cord (average: 8.83 ± 1.9Gy, range: 5.9 to 10.9Gy); dose to 0.35cc of spinal cord (average: 7.62 ± 1.7Gy, range: 5.4 to 9.6Gy); and dose to 10% of partial spinal cord (average 6.31 ± 1.5Gy, range: 3.5 to 8.5Gy) less than 14, 10, and 10Gy, respectively. For all 10 patients, the maximum dose to esophagus (average: 9.41 ± 4.3Gy, range: 1.5 to 14.9Gy) and dose to 5cc of esophagus (average: 7.43 ± 3.8Gy, range: 1.1 to 11.8Gy) were kept less than protocol requirements 16Gy and 11.9Gy, respectively. In a similar manner, all 10 patients met protocol compliance criteria with maximum dose to heart (average: 4.62 ± 3.5Gy, range: 1.3 to 10.2Gy) and dose to 15cc of heart (average: 2.23 ± 1.8Gy, range: 0.3 to 5.6Gy) less than 22 and 16Gy, respectively. The dose to the lung was retained much lower than protocol guidelines for all 10 patients. The total number of monitor units was, on average, 6919 ± 1187. The average beam-on time was 11.5 ± 2.0 minutes. The VMAT plans demonstrated dose delivery accuracy of 95.8 ± 0.7%, on average, for clinical gamma passing rate with 2%/2mm criteria and 98.3 ± 0.8%, on average, with 3%/3mm criteria. All VMAT-SBRS plans were considered clinically acceptable per RTOG 0631 dosimetric compliance criteria. VMAT planning provided highly conformal and homogenous dose distributions for the lower-dose vertebral PTV and the spinal cord as well as organs-at-risk such as esophagus, heart, and lung. Higher QA pass rates and shorter beam-on time suggest that VMAT-SBRS is a clinically feasible, fast, and effective treatment option for patients with thoracic vertebral metastases.

Treatment planning strategy for whole-brain radiotherapy with hippocampal sparing and simultaneous integrated boost for multiple brain metastases using intensity-modulated arc therapy.

PURPOSE: To retrospectively evaluate the accuracy, plan quality and efficiency of intensity-modulated arc therapy (IMAT) for hippocampal sparing whole-brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in patients with multiple brain metastases (m-BM). MATERIALS AND METHODS: A total of 5 patients with m-BM were retrospectively replanned for HS-WBRT with SIB using IMAT treatment planning. The hippocampus was contoured on diagnostic T1-weighted magnetic resonance imaging (MRI) which had been fused with the planning CT image set. The hippocampal avoidance zone (HAZ) was generated using a 5-mm uniform margin around the paired hippocampi. The m-BM planning target volumes (PTVs) were contoured on T1/T2-weighted MRI registered with the 3D planning computed tomography (CT). The whole-brain planning target volume (WB-PTV) was defined as the whole-brain tissue volume minus HAZ and m-BM PTVs. Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis-TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5-mm leaf width at isocenter) and 6-MV beam. Prescription dose was 30Gy for WB-PTV and 45Gy for each m-BM in 10 fractions. Three full coplanar arcs with orbit avoidance sectors were used. Treatment plans were evaluated using homogeneity (HI) and conformity indices (CI) for target coverage and dose to organs at risk (OAR). Dose delivery efficiency and accuracy of each IMAT plan was assessed via quality assurance (QA) with a MapCHECK device. Actual beam-on time was recorded and a gamma index was used to compare dose agreement between the planned and measured doses. RESULTS: All 5 HS-WBRT with SIB plans met WB-PTV D2%, D98%, and V30Gy NRG-CC001 requirements. The plans demonstrated highly conformal and homogenous coverage of the WB-PTV with mean HI and CI values of 0.33 ± 0.04 (range: 0.27 to 0.36), and 0.96 ± 0.01 (range: 0.95 to 0.97), respectively. All 5 hippocampal sparing patients met protocol guidelines with maximum dose and dose to 100% of hippocampus (D100%) less than 16 and 9Gy, respectively. The dose to the optic apparatus was kept below protocol guidelines for all 5 patients. Highly conformal and homogenous radiosurgical dose distributions were achieved for all 5 patients with a total of 33 brain metastases. The m-BM PTVs had a mean HI = 0.09 ± 0.02 (range: 0.07 to 0.19) and a mean CI = 1.02 ± 0.06 (range: 0.93 to 1.2). The total number of monitor units (MU) was, on average, 1677 ± 166. The average beam-on time was 4.1 ± 0.4 minute . The IMAT plans demonstrated accurate dose delivery of 95.2 ± 0.6%, on average, for clinical gamma passing rate with 2%/2-mm criteria and 98.5 ± 0.9%, on average, with 3%/3-mm criteria. CONCLUSIONS: All hippocampal sparing plans were considered clinically acceptable per NRG-CC001 dosimetric compliance criteria. IMAT planning provided highly conformal and homogenous dose distributions for the WB-PTV and m-BM PTVs with lower doses to OAR such as the hippocampus. These results suggest that HS-WBRT with SIB is a clinically feasible, fast, and effective treatment option for patients with a relatively large numbers of m-BM lesions.

Assessment of Monte Carlo algorithm for compliance with RTOG 0915 dosimetric criteria in peripheral lung cancer patients treated with stereotactic body radiotherapy.

The purpose of the study was to evaluate Monte Carlo-generated dose distributions with the X-ray Voxel Monte Carlo (XVMC) algorithm in the treatment of peripheral lung cancer patients using stereotactic body radiotherapy (SBRT) with non-protocol dose-volume normalization and to assess plan outcomes utilizing RTOG 0915 dosimetric compliance criteria. The Radiation Therapy Oncology Group (RTOG) protocols for non-small cell lung cancer (NSCLC) currently require radiation dose to be calculated using tissue density heterogeneity corrections. Dosimetric criteria of RTOG 0915 were established based on superposition/convolution or heterogeneities corrected pencil beam (PB-hete) algorithms for dose calculations. Clinically, more accurate Monte Carlo (MC)-based algorithms are now routinely used for lung stereotactic body radiotherapy (SBRT) dose calculations. Hence, it is important to determine whether MC calculations in the delivery of lung SBRT can achieve RTOG standards. In this report, we evaluate iPlan generated MC plans for peripheral lung cancer patients treated with SBRT using dose-volume histogram (DVH) normalization to determine if the RTOG 0915 compliance criteria can be met. This study evaluated 20 Stage I-II NSCLC patients with peripherally located lung tumors, who underwent MC-based SBRT with heterogeneity correction using X-ray Voxel Monte Carlo (XVMC) algorithm (Brainlab iPlan version 4.1.2). Total dose of 50 to 54 Gy in 3 to 5 fractions was delivered to the planning target vol-ume (PTV) with at least 95% of the PTV receiving 100% of the prescription dose (V100% ≥ 95%). The internal target volume (ITV) was delineated on maximum intensity projection (MIP) images of 4D CT scans. The PTV included the ITV plus 5 mm uniform margin applied to the ITV. The PTV ranged from 11.1 to 163.0 cc (mean = 46.1 ± 38.7 cc). Organs at risk (OARs) including ribs were delineated on mean intensity projection (MeanIP) images of 4D CT scans. Optimal clinical MC SBRT plans were generated using a combination of 3D noncoplanar conformal arcs and nonopposing static beams for the Novalis-TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5 mm leaf width at isocenter) and 6 MV-SRS (1000 MU/min) beam. All treatment plans were evaluated using the RTOG 0915 high- and intermediate-dose spillage criteria: conformity index (R100%), ratio of 50% isodose volume to the PTV (R50%), maximum dose 2 cm away from PTV in any direction (D2cm), and percent of normal lung receiving 20Gy (V20) or more. Other OAR doses were documented, including the volume of normal lung receiving 5 Gy (V5) or more, dose to < 0.35 cc of spinal cord, and dose to 1000 cc of total normal lung tissue. The dose to < 1 cc, < 5 cc, < 10 cc of ribs, as well as maximum point dose as a function of PTV, prescription dose, and a 3D distance from the tumor isocenter to the proximity of the rib contour were also examined. The biological effective dose (BED) with α/ß ratio of 3 Gy for ribs was analyzed. All 20 patients either fully met or were within the minor deviation dosimetric compliance criteria of RTOG 0915 while using DVH normalization. However, only 5 of the 20 patients fully met all the criteria. Ten of 20 patients had minor deviations in R100% (mean = 1.25 ± 0.09), 13 in R50% (mean = 4.5 ± 0.6), and 11 in D2cm (mean = 61.9 ± 8.5). Lung V20, dose to 1000 cc of normal lung, and dose to < 0.35 cc of spinal cord were met in accordance with RTOG criteria in 95%, 100%, and 100%, respectively, with exception of one patient who exhibited the largest PTV (163 cc) and experienced a minor deviation in lung V20 (mean = 4.7±3.4%). The 3D distance from the tumor isocenter to the proximal rib contour strongly correlated with maximum rib dose. The average values of BED3Gy for maximum point dose and dose to < 1 cc of ribs were higher by a factor of 1.5 using XVMC compared to RTOG 0915 guidelines. The preliminary results for our iPlan XVMC dose analyses indicate that the majority (i.e., 75% of patient population) of our patients had minor deviations when compared to the dosimetric guidelines set by RTOG 0915 protocol. When using an exclusively sophisticated XVMC algorithm and DVH normalization, the RTOG 0915 dosimetric compliance criteria such as R100%, R50%, and D2cm may need to be revised. On average, about 7% for R100%, 13% for R50%, and 14% for D2cm corrections from the mean values were necessary to pass the RTOG 0915 compliance criteria. Another option includes rescaling of the prescription dose. No further adjustment is necessary for OAR dose tolerances including normal lung V20 and total normal lung 1000 cc. Since all the clinical MC plans were generated without compromising the target coverage, rib dose was on the higher side of the protocol guidelines. As expected, larger tumor size and proximity to ribs correlated to higher absolute dose to ribs. These patients will be clinically followed to determine whether delivered MC-computed dose to PTV and the ribs dose correlate with tumor control and severe chest wall pain and/or rib fractures. In order to establish new specific MC-based dose parameters, further dosimetric studies with a large cohort of MC lung SBRT patients will need to be conducted.

Monte Carlo evaluation of tissue heterogeneities corrections in the treatment of head and neck cancer patients using stereotactic radiotherapy.

The purpose of this study was to generate Monte Carlo computed dose distributions with the X-ray voxel Monte Carlo (XVMC) algorithm in the treatment of head and neck cancer patients using stereotactic radiotherapy (SRT) and compare to heterogeneity corrected pencil-beam (PB-hete) algorithm. This study includes 10 head and neck cancer patients who underwent SRT re-irradiation using heterogeneity corrected pencil-beam (PB-hete) algorithm for dose calculation. Prescription dose was 24-40 Gy in 3-5 fractions (treated 3-5 fractions per week) with at least 95% of the PTV volume receiving 100% of the prescription dose. A stereotactic head and neck localization box was attached to the base of the thermoplastic mask fixation for target localization. The gross tumor volume (GTV) and organs-at-risk (OARs) were contoured on the 3D CT images. The planning target volume (PTV) was generated from the GTV with 0 to 5 mm uniform expansion; PTV ranged from 10.2 to 64.3 cc (average = 35.0±17.5 cc). OARs were contoured on the 3D planning CT and consisted of spinal cord, brainstem, optic structures, parotids, and skin. In the BrainLab treatment planning system (TPS), clinically optimal SRT plans were generated using hybrid planning technique (combination of 3D conformal nonco-planar arcs and nonopposing static beams) for the Novalis-Tx linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5 mm leaf width at isocenter) and 6 MV-SRS (1000 MU/min) beam. For the purposes of this study, treatment plans were recomputed using XVMC algorithm utilizing identical beam geometry, multileaf positions, and monitor units and compared to the corresponding clinical PB-hete plans. The Monte Carlo calculated dose distributions show small decreases (< 1.5%) in calculated dose for D99, Dmean, and Dmax of the PTV coverage between the two algorithms. However, the average target volume encompassed by the prescribed percent dose (Vp) was about 2.5% less with XVMC vs. PB-hete and ranged between -0.1 and 7.8%. The averages for D100 and D10 of the GTV were lower by about 2% and ranged between -0.8 and 3.1%. For the spinal cord, both the maximal dose difference and the dose to 0.35 cc of the structure were higher by an average of 4.2% (ranged 1.2 to -13.6%) and 1.4% (ranged 7.5 to -11.3%), respectively, with XVMC calculation. For the brainstem, the maximal dose dif-ferences and the dose to 0.5 cc of the structure were, on average, higher by 2.4% (ranged 6.4 to -8.0%) and 3.6% (ranged 6.4 to -9.0%), respectively. For the parotids, both the mean dose and the dose to 20 cc of parotids were higher by an average of 3% (ranged -0.2 to -5.9%) and 4% (ranged -0.2 to -8%), respectively, with XVMC calculation. For the optic apparatus, results from both algorithms were similar. However, the mean dose to skin was 3% higher (ranged 0 to -6%), on average, with XVMC compared to PB-hete, although the maximum dose to skin was 2% lower (ranged -5% to 15.5%). The results from our XVMC dose calculations for head and neck SRT patients indicate small to moderate underdosing of the tumor volume when compared to PB-hete calculation. However, Vp was up to 7.8% less for the lower-neck patient with XVMC. Critical structures, such as spinal cord, brainstem, or parotids, could potentially receive higher doses when using XVMC algorithm. Given the proximity to critical structures and the smaller volumes treated with SRT in the region of the head and neck, the differences between XVMC and PB-hete calculation methods may be of clinical interest.

Potential for reduced radiation-induced toxicity using intensity-modulated arc therapy for whole-brain radiotherapy with hippocampal sparing.

The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity-modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole-brain radiotherapy (NC-WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1-weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole-brain planning target volume (WB-PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam-on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB-PTV, mean WB-PTV D2%, and mean WB-PTV D98% were 34.9 ± 0.3 Gy, 33.2 ± 0.4 Gy, and 26.0± 0.4Gy, respectively. Accordingly, WB-PTV received the prescription dose of 30Gy and mean V30 was 90.5% ± 0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4 ± 0.3 Gy, 11.2 ± 0.3 Gy, and 15.6 ± 0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23 ± 0.02 and 0.96 ± 0.02, respectively. The maximum point dose to WB-PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC-WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC-WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719 ± 44 and 2.34 ± 0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1 ± 0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per RTOG 0933 criteria. IMAT planning provided highly conformal and homogenous plan with a fast and effective treatment option for WBRT patients, sparing not only hippocampi but also other OARs, which could potentially result in an additional improvement of the quality life (QoL). In the future, we plan to evaluate the clinical potential of IMAT planning and treatment option with hippocampal and other OARs avoidance in our patient's cohort and asses the QoL of the WBRT patients, as well as simultaneous integrated boost (SIB) for the brain metastases diseases.

Technical Note: Dosimetric evaluation of Monte Carlo algorithm in iPlan for stereotactic ablative body radiotherapy (SABR) for lung cancer patients using RTOG 0813 parameters.

For stereotactic ablative body radiotherapy (SABR) in lung cancer patients, Radiation Therapy Oncology Group (RTOG) protocols currently require radiation dose to be calculated using tissue heterogeneity corrections. Dosimetric criteria of RTOG 0813 were established based on the results obtained from non-Monte Carlo (MC) algorithms, such as superposition/convolutions. Clinically, MC-based algorithms are now routinely used for lung SABR dose calculations. It is essential to confirm that MC calculations in lung SABR meet RTOG guidelines. This report evaluates iPlan MC plans for SABR in lung cancer patients using dose-volume histogram normalization per current RTOG 0813 compliance criteria. Eighteen Stage I-II non-small cell lung cancer (NSCLC) patients with centrally located tumors, who underwent MC-based lung SABR with heterogeneity correction using X-ray Voxel Monte Carlo (XVMC) algorithm (BrainLAB iPlan version 4.1.2), were analyzed. Total dose of 60 Gy in 5 fractions was delivered to planning target volume (PTV) with at least V100% = 95%. Internal target volumes (ITVs) were delineated on maximum intensity projection (MIP) images of 4D CT scans. PTV (ITV + 5 mm margin) volumes ranged from 10.0 to 99.9 cc (mean = 36.8 ± 20.7 cc). Organs at risk (OARs) were delineated on average images of 4D CT scans. Optimal clinical MC SABR plans were generated using a combination of non-coplanar conformal arcs and beams for the Novalis-TX consisting of high definition multileaf collimators (MLCs) and 6 MV-SRS (1000 MU/min) mode. All plans were evaluated using the RTOG 0813 high and intermediate dose spillage criteria: conformity index (R100%), ratio of 50% isodose volume to the PTV (R50%), maximum dose 2 cm away from PTV in any direction (D2 cm), and percent of normal lung receiving 20 Gy (V20) or more. Other organs-at-risk (OARs) doses were tabulated, including the volume of normal lung receiving 5 Gy (V5), maximum cord dose, dose to < 15 cc of heart, and dose to <5 cc of esophagus. Only six out of 18 patients met all RTOG 0813 compliance criteria. Eight of 18 patients had minor deviations in R100%, four in R50%, and nine in D2 cm. However, only one patient had minor deviation in V20. All other OARs doses, such as maximum cord dose, dose to < 15 cc of heart, and dose to < 5 cc of esophagus, were satisfactory for RTOG criteria, except for one patient, for whom the dose to < 15 cc of heart was higher than RTOG guidelines. The preliminary results for our limited iPlan XVMC dose calculations indicate that the majority (i.e., 2/3) of our patients had minor deviations in the dosimetric guidelines set by RTOG 0813 protocol in one way or another. When using an exclusive highly sophisticated XVMC algorithm, the RTOG 0813 dosimetric compliance criteria such as R100% and D2 cm may need to be revisited. Based on our limited number of patient datasets, in general, about 6% for R100% and 9% for D2 cm corrections could be applied to pass the RTOG 0813 compliance criteria in most of those patients. More patient plans need to be evaluated to make recommendation for R50%. No adjustment is necessary for OAR dose tolerances, including normal lung V20. In order to establish new MC specific dose parameters, further investigation with a large cohort of patients including central, as well as peripheral lung tumors, is anticipated and strongly recommended.

A comparative study to evaluate the efficacy of on board imaging with cone beam CT using target registration in patients with lung tumors undergoing stereotactic body radiation therapy and comparison with ExacTrac using skeletal registration on Novalis Tx.

BACKGROUND: Stereotactic body radiation therapy is an advanced technique, which delivers ablative doses to lung lesions. Target verification is done either by orthogonal x-rays or cone beam CT. This study was undertaken to compare these two verification methods. AIM: To evaluate the efficacy of ExacTrac and Cone Beam Computed Tomography (CBCT) for target repositioning while delivering Stereotactic Body Radiation Therapy (SBRT) for lung lesions and derive the population-based margin. MATERIALS AND METHODS: All patients who had undergone SBRT for lung lesions from February to September 2009 were involved. Patients were immobilized using the BodyFix double vacuum immobilization system, indexed to the computed tomography (CT) simulator and treatment machine. Four-dimensional (3-D) scan was done to generate internal target volume (ITV) and a free breathing CT scan for planning was done on the BrainLab iPlan 4.1 software. During treatment, patient's position was verified using ExacTrac and CBCT. The resulting vertical, lateral, and longitudinal shifts were noted. The random and systematic error were calculated and the margin recipe derived using the Van Herk formula. RESULTS: Sixteen patients had undergone SBRT for lung tumors from February to September 2009. Data from eight patients who had undergone 34 sessions of SBRT was analyzed. The systematic error for lateral, longitudinal, and vertical shifts for ExacTrac and CBCT were 3.68, 4.27, 3.5 mm and 0.53, 0.38, 0.70 mm, respectively. The random error were 1.10, 1.51, 1.96 mm and 0.32, 0.81, 0.59 mm. The lateral, longitudinal and vertical Van Herk margin recipe for ExacTrac were 9.98, 11.72, 10.18 mm, respectively, and for CBCT was 2.17, 1.53,1.55 mm. CONCLUSIONS: The systematic and random errors for CBCT were significantly lesser as compared to the errors with Exactrac.