A. Ianiro

Initial clinical experience with Epid-based in-vivo dosimetry for VMAT treatments of head-and-neck tumors

We evaluated an EPID-based in-vivo dosimetry algorithm (IVD) for complex VMAT treatments in clinical routine. 19 consecutive patients with head-and-neck tumors and treated with Elekta VMAT technique using Simultaneous Integrated Boost strategy were enrolled. In-vivo tests were evaluated by means of (i) ratio R between daily in-vivo isocenter dose and planned dose and (ii) γ-analysis between EPID integral portal images in terms of percentage of points with γ-value smaller than one (γ%) and mean γ-values (γmean), using a global 3%-3 mm criteria. Alert criteria of ±5% for R ratio, γ% < 90% and γmean > 0.67 were chosen. A total of 350 transit EPID images were acquired during the treatment fractions. The overall mean R ratio was equal to 1.002 ± 0.019 (1 SD), with 95.9% of tests within ±5%. The 2D portal images of γ-analysis showed an overall γmean of 0.42 ± 0.16 with 93.3% of tests within alert criteria, and a mean γ% equal to 92.9 ± 5.1% with 85.9% of tests within alert criteria. Relevant discrepancies were observed in three patients: a set-up error was detected for one patient and two patients showed major anatomical variations (weight loss/tumor shrinkage) in the second half of treatment. The results are supplied in quasi real-time, with IVD tests displayed after only 1 minute from the end of arc delivery. This procedure was able to detect when delivery was inconsistent with the original plans, allowing physics and medical staff to promptly act in case of major deviations between measured and planned dose.

Linac-based extracranial radiosurgery with Elekta volumetric modulated arc therapy and an anatomy-based treatment planning system: Feasibility and initial experience.

We reported our initial experience in using Elekta volumetric modulated arc therapy (VMAT) and an anatomy-based treatment planning system (TPS) for single high-dose radiosurgery (SRS-VMAT) of liver metastases. This study included a cohort of 12 patients treated with a 26-Gy single fraction. Single-arc VMAT plans were generated with Ergo++ TPS. The prescription isodose surface (IDS) was selected to fulfill the 2 following criteria: 95% of planning target volume (PTV) reached 100% of the prescription dose and 99% of PTV reached a minimum of 90% of prescription dose. A 1-mm multileaf collimator (MLC) block margin was added around the PTV. For a comparison of dose distributions with literature data, several conformity indexes (conformity index [CI], conformation number [CN], and gradient index [GI]) were calculated. Treatment efficiency and pretreatment dosimetric verification were assessed. Early clinical data were also reported. Our results reported that target and organ-at-risk objectives were met for all patients. Mean and maximum doses to PTVs were on average 112.9% and 121.5% of prescribed dose, respectively. A very high degree of dose conformity was obtained, with CI, CN, and GI average values equal to 1.29, 0.80, and 3.63, respectively. The beam-on-time was on average 9.3 minutes, i.e., 0.36min/Gy. The mean number of monitor units was 3162, i.e., 121.6MU/Gy. Pretreatment verification (3%-3mm) showed an optimal agreement with calculated values; mean γ value was 0.27 and 98.2% of measured points resulted with γ < 1. With a median follow-up of 16 months complete response was observed in 12/14 (86%) lesions; partial response was observed in 2/14 (14%) lesions. No radiation-induced liver disease (RILD) was observed in any patients as well no duodenal ulceration or esophagitis or gastric hemorrhage. In conclusion, this analysis demonstrated the feasibility and the appropriateness of high-dose single-fraction SRS-VMAT in liver metastases performed with Elekta VMAT and Ergo++ TPS. Preliminary clinical outcomes showed a high rate of local control and minimum incidence of acute toxicity.

Optimal beam margins in linac-based VMAT stereotactic ablative body radiotherapy: a Pareto front analysis for liver metastases

We explored the Pareto fronts mathematical strategy to determine the optimal block margin and prescription isodose for stereotactic body radiotherapy (SBRT) treatments of liver metastases using the volumetric-modulated arc therapy (VMAT) technique. Three targets (planning target volumes [PTVs] = 20, 55, and 101 cc) were selected. A single fraction dose of 26 Gy was prescribed (prescription dose [PD]). VMAT plans were generated for 3 different beam energies. Pareto fronts based on (1) different multileaf collimator (MLC) block margin around PTV and (2) different prescription isodose lines (IDL) were produced. For each block margin, the greatest IDL fulfilling the criteria (95% of PTV reached 100%) was considered as providing the optimal clinical plan for PTV coverage. Liver Dmean, V7Gy, and V12Gy were used against the PTV coverage to generate the fronts. Gradient indexes (GI and mGI), homogeneity index (HI), and healthy liver irradiation in terms of Dmean, V7Gy, and V12Gy were calculated to compare different plans. In addition, each target was also optimized with a full-inverse planning engine to obtain a direct comparison with anatomy-based treatment planning system (TPS) results. About 900 plans were calculated to generate the fronts. GI and mGI show a U-shaped behavior as a function of beam margin with minimal values obtained with a +1 mm MLC margin. For these plans, the IDL ranges from 74% to 86%. GI and mGI show also a V-shaped behavior with respect to HI index, with minimum values at 1 mm for all metrics, independent of tumor dimensions and beam energy. Full-inversed optimized plans reported worse results with respect to Pareto plans. In conclusion, Pareto fronts provide a rigorous strategy to choose clinical optimal plans in SBRT treatments. We show that a 1-mm MLC block margin provides the best results with regard to healthy liver tissue irradiation and steepness of dose fallout.

Volumetric modulated arc therapy (VMAT) and simultaneous integrated boost in head-and-neck cancer: is there a place for critical swallowing structures dose sparing?

OBJECTIVE To explore the potential of volumetric-modulated arc therapy (VMAT) to reduce the risk of swallowing problems after curative chemoradiotherapy. METHODS 20 patients with head and neck cancer who previously underwent radiotherapy were selected. Radiotherapy was prescribed according to simultaneous integrated boost technique with all targets irradiated simultaneously over 30 daily fractions. Doses of 70.5 (67.5), 60.0 and 55.5 Gy were prescribed to primary tumour, high-risk nodal regions and low-risk nodal regions, respectively. Pharyngeal constrictor muscles (PCM) and glottic and supraglottic larynx (SGL) were considered organs at risk related to swallowing dysfunction (SW-OARs). Upper pharyngeal constrictor muscles (uPCM), middle pharyngeal constrictor muscles (mPCM) and lower pharyngeal constrictor muscles (lPCM) part of PCM were also outlined separately. Clinical standard plans (standard-VMAT) and plans aiming to spare SW-OARs (swallowing dysfunction-VMAT) were also created. Normal tissue complication probabilities (NTCP) for physician-rated swallowing dysfunction were calculated using a recently predictive model developed by Christianen et al. RESULTS Planning with two strategies demonstrated comparable planning target volume coverage and no differences in sparing of parotid glands and other non-swallowing organs at risk. SW-VMAT plans provided mean dose reduction for uPCM and SGL by 3.9 and 4.5 Gy, respectively. NTCP values for Radiation Therapy Oncology Group grade 2-4 swallowing dysfunction was decreased by 9.2%. Dose reductions with SW-VMAT depended on tumour location and overlap with SW-OARs. CONCLUSION VMAT plans aiming at sparing swallowing structures are feasible, providing a significant reduction in NTCP swallowing dysfunction with respect to conventional VMAT. ADVANCES IN KNOWLEDGE Dysphagia is today considered one of the dose-limiting toxicities of chemoradiotherapy. The dose sparing of swallowing structures represents a major challenge in radiotherapy. VMAT is a complex new technology having the potential to significantly reduce the risk of dysphagia after curative chemoradiotherapy.

Partially ablative radiotherapy (PAR) for large mass tumors using simultaneous integrated boost: A dose‐escalation feasibility study

Abstract Purpose This study aimed to assess the feasibility to plan and deliver highly heterogeneous doses to symptomatic large tumors using volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) during a short course palliative accelerated radiotherapy. Methods A patient with a large symptomatic chordoma infiltrating the right gluteal region was selected. A modified SIB treatment was implemented to irradiate the central volume of the tumor (boost target volume, BTV) up to 10 Gy/fraction in a dose escalation trial while maintaining the remaining tumor volume (planning target volume, PTV) and the surrounding healthy tissues within 5 Gy/fraction in twice daily fractions for two consecutive days. Four SIB plans were generated in the dual‐arc modality; a basal dose of 20 Gy was prescribed to the PTV, while the BTV was boosted up to 40 Gy. For comparison purposes, plans obtained with a sequential boost (SEQ plans) were also generated. All plans were optimized to deliver at least 95% of the prescription dose to the targets. Dose contrast index (DCI), conformity index (CI), integral dose (ID), and the irradiated body volumes at 5, 10, and 20 Gy were evaluated. Results At equal targets coverage, SIB plans provided major improvement in DCI, CI, and ID with respect to SEQ plans. When BTV dose escalated up to 200% of PTV prescription, DCI resulted in 66% for SIB plans and 37% for SEQ plans; the ID increase was only 11% for SIB plans (vs 27% for SEQ plans) and the increase in healthy tissues receiving more than 5, 10, and 20 Gy was less than 2%. Pretreatment dose verification reported a γ‐value passing rate greater than 95% with 3%(global)‐2 mm. Conclusion A modified SIB technique is dosimetrically feasible for large tumors, where doses higher than the tolerance dose of healthy tissues are necessary to increase the therapeutic gain.

Dose escalation in extracranial stereotactic ablative radiotherapy (DESTROY-1): a multi-arm phase I trial

OBJECTIVE: A multiarm Phase I clinical trial was performed to define the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) delivered by non-coplanar conformal beams or volumetric modulated arc therapy technique in seven predefined clinical settings. METHODS: The (a) and (b) arms investigated primary and metastatic lung cancer differentiated by site of onset, arm (c) included primary or metastatic lesions outside the thorax, the (d) and (e) arms were for in-field reirradiation of recurrence, and finally, the (f) and (g) arms were for boost irradiation to the lesions after an adjuvant RT prescribed dose. A 4 months cut-off after previous irradiation course was fixed to distinguish the boost from the retreatment (<4 vs >4 months, respectively). Patients were prospectively enrolled in study arms according to tumor site, clinical stage and previous treatment. The total dose prescribed to the isocenter, ranged from 20 to 50 Gy according to the protocol design and the doses per fraction ranged from 4 to 10 Gy in 5 days. RESULTS: A total of 281 patients (M/F: 167/114; median age: 69 years) with 376 lesions underwent SBRT. No acute toxicity was reported in 175 patients (62.3%) while 106 (37.7%) experienced only low-grade (G < 2) acute toxicity. Four patients (all previously irradiated in the same site) showed >Grade 2 toxicity within 6 months from SBRT. With a median follow-up of 19 months, 204 patients (72.6%) did not experience late toxicity, and 77 (27.4%) experienced low grade late toxicity. On per-lesion basis, the 12-and 24 months actuarial local control inside the SBRT field were 84.3 and 73.7 %, respectively. CONCLUSIONS: SBRT delivered in five consecutive fractions up to the doses evaluated is well tolerated. The MTD was reached in four (a, b, c and f) of the seven study arms. Recruitment for (d), (e) and (g) arms is still ongoing. ADVANCES IN KNOWLEDGE: In a prospective dose-escalation trial, the MTD of 50 Gy/10 Gy fraction and 35 Gy/7 Gy fraction were defined for primary and metastatic lesions and as boost after prior RT dose ≤50 Gy, respectively.