Naved Chaudhri

Target motion tracking with a scanned particle beam

Treatment of moving targets with scanned particle beams results in local over- and under-dosage due to interplay of beam and target motion. To mitigate the impact of respiratory motion, a motion tracking system has been developed and integrated in the therapy control system at Gesellschaft für Schwerionenforschung. The system adapts pencil beam positions as well as the beam energy according to target motion to irradiate the planned position. Motion compensation performance of the tracking system was assessed by measurements with radiographic films and a 3D array of 24 ionization chambers. Measurements were performed for stationary detectors and moving detectors using the tracking system. Film measurements showed comparable homogeneity inside the target area. Relative differences of 3D dose distributions within the target volume were 1 +/- 2% with a maximum of 4%. Dose gradients and dose to surrounding areas were in good agreement. The motion tracking system successfully preserved dose distributions delivered to moving targets and maintained target conformity.

Four-Dimensional Patient Dose Reconstruction for Scanned Ion Beam Therapy of Moving Liver Tumors

PURPOSE Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy. METHODS AND MATERIALS Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)-weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporal correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V95) and 107% (V107) of the planned doses. RESULTS 4D dose reconstruction based on daily measured data is possible in a clinical setting. V95 and V107 values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V95 > 87%, SD < 3%) and overdose (mean V107 < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients. CONCLUSIONS A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment.

Re-irradiation of adenoid cystic carcinoma: Analysis and evaluation of outcome in 52 consecutive patients treated with raster-scanned carbon ion therapy

BACKGROUND Treatment of local relapse in adenoid cystic carcinoma (ACC) following prior radiation remains a challenge: without the possibility of surgical salvage patients face the choice between palliative chemotherapy and re-irradiation. Chemotherapy yields response rates around 30% and application of tumouricidal doses is difficult due to proximity of critical structures. Carbon ion therapy (C12) is a promising method to minimize side-effects and maximize re-treatment dose in this indication. We describe our initial results for re-irradiation in heavily pre-treated ACC patients. METHODS Patients treated with carbon ion therapy between 04/2010 and 05/2013 (N=52pts, median age: 54 a) were retrospectively evaluated regarding toxicity (NCI CTC v.4), tumour response (RECIST) and control rates. 48pts (92.3%) received carbon ions only, 4pts received IMRT plus C12. RESULTS 4pts were treated following R1-resection, 43pts for inoperable local relapse. Most common tumour sites were paranasal sinus (36.5%), parotid (19.2%), and base of skull (17.3%). Pts received a median dose of 51GyE C12/63Gy BED and cumulative dose of 128Gy BED [67-182Gy] after a median RT-interval of 61months. Median target volume was 93ml [9-618ml]. No higher-grade (>°II) acute reactions were observed, 7pts showed blood-brain-barrier changes (°I/II: 8pts; °III: 2pts), 1 pt corneal ulceration, xerophthalmia 7pts, °IV bleeding 1 pt, tissue necrosis 2pts, otherwise no significant late reactions. Objective response rate (CR/PR) was 56.6%. With a median follow-up of 14months [1-39months] local control and distant control at 1a are 70.3% and 72.6% respectively. Of the 18pts with local relapse, 13pts have recurred in-field, 1 pt at the field edge, 3pts out of field, and one in the dose gradient. CONCLUSION Despite high applied doses, C12 re-irradiation shows moderate side-effects, response rates even in these heavily pre-treated patients are encouraging and present a good alternative to palliative chemotherapy. Though most local recurrences occur within the high-dose area, further dose escalation should be viewed with caution.

Next generation multi-scale biophysical characterization of high precision cancer particle radiotherapy using clinical proton, helium-, carbon- and oxygen ion beams

The growing number of particle therapy facilities worldwide landmarks a novel era of precision oncology. Implementation of robust biophysical readouts is urgently needed to assess the efficacy of different radiation qualities. This is the first report on biophysical evaluation of Monte Carlo simulated predictive models of prescribed dose for four particle qualities i.e., proton, helium-, carbon- or oxygen ions using raster-scanning technology and clinical therapy settings at HIT. A high level of agreement was found between the in silico simulations, the physical dosimetry and the clonogenic tumor cell survival. The cell fluorescence ion track hybrid detector (Cell-Fit-HD) technology was employed to detect particle traverse per cell nucleus. Across a panel of radiobiological surrogates studied such as late ROS accumulation and apoptosis (caspase 3/7 activation), the relative biological effectiveness (RBE) chiefly correlated with the radiation species-specific spatio-temporal pattern of DNA double strand break (DSB) formation and repair kinetic. The size and the number of residual nuclear γ-H2AX foci increased as a function of linear energy transfer (LET) and RBE, reminiscent of enhanced DNA-damage complexity and accumulation of non-repairable DSB. These data confirm the high relevance of complex DSB formation as a central determinant of cell fate and reliable biological surrogates for cell survival/RBE. The multi-scale simulation, physical and radiobiological characterization of novel clinical quality beams presented here constitutes a first step towards development of high precision biologically individualized radiotherapy.

Dosimetry auditing procedure with alanine dosimeters for light ion beam therapy

BACKGROUND AND PURPOSE In the next few years the number of facilities providing ion beam therapy with scanning beams will increase. An auditing process based on an end-to-end test (including CT imaging, planning and dose delivery) could help new ion therapy centres to validate their entire logistic chain of radiation delivery. An end-to-end procedure was designed and tested in both scanned proton and carbon ion beams, which may also serve as a dosimetric credentialing procedure for clinical trials in the future. The developed procedure is focused only on physical dose delivery and the validation of the biological dose is out of scope of the current work. MATERIALS AND METHODS The audit procedure was based on a homogeneous phantom that mimics the dimension of a head (20 × 20 × 21 cm(3)). The phantom can be loaded either with an ionisation chamber or 20 alanine dosimeters plus 2 radiochromic EBT films. Dose verification aimed at measuring a dose of 10Gy homogeneously delivered to a virtual-target volume of 8 × 8 × 12 cm(3). In order to interpret the readout of the irradiated alanine dosimeters additional Monte Carlo simulations were performed to calculate the energy dependent detector response of the particle fluence in the alanine detector. A pilot run was performed with protons and carbon ions at the Heidelberg Ion Therapy facility (HIT). RESULTS The mean difference of the absolute physical dose measured with the alanine dosimeters compared with the expected dose from the treatment planning system was -2.4 ± 0.9% (1σ) for protons and -2.2 ± 1.1% (1σ) for carbon ions. The measurements performed with the ionisation chamber indicate this slight underdosage with a dose difference of -1.7% for protons and -1.0% for carbon ions. The profiles measured by radiochromic films showed an acceptable homogeneity of about 3%. CONCLUSIONS Alanine dosimeters are suitable detectors for dosimetry audits in ion beam therapy and the presented end-to-end test is feasible. If further studies show similar results, this dosimetric audit could be implemented as a credentialing procedure for clinical proton and carbon beam delivery.

Carbon Ion irradiation in the treatment of grossly incomplete or unresectable malignant peripheral nerve sheaths tumors: acute toxicity and preliminary outcome

BackgroundTo report our early experience with carbon ion irradiation in the treatment of gross residual or unresectable malignant peripheral nerve sheath tumors (MPNST).MethodsWe retrospectively analysed 11 patients (pts) with MPNST, who have been treated with carbon ion irradiation (C12) at our institution between 2010 and 2013. All pts had measurable gross disease at the initiation of radiation treatment. Median age was 47 years (29-79). Tumors were mainly located in the pelvic/sacral (5 pts) and sinunasal/orbital region (5 pts). 5 pts presented already in recurrent situation, 3 pts had been previously irradiated, and in 3 pts MPNST were neurofibromatosis type 1 (NF1) associated. Median cumulative dose was 60 GyE. Treatment was carried out either as a combination of IMRT plus C12 boost (4 pts) or C12 only (7 pts).ResultsMedian follow-up was 17 months (3-31 months). We observed 3 local progressions, translating into estimated 1- and 2-year local control rates of 65%. One patient developed distant failure, resulting in estimated 1- and 2-year PFS rates of 56%. Two patients have died, therefore the estimated 1- and 2-year OS rates are 75%. Acute radiation related toxicities were generally mild, no grade 3 side effects were observed. Severe late toxicity (grade 3) was scored in 2 patients (trismus, wound healing delays).ConclusionCarbon ion irradiation yields very promising short term local control and overall survival rates with low morbidity in patients suffering from gross residual or unresectable malignant peripheral nerve sheath tumors and should be further investigated in a prospective trial.

Raster‐scanned intensity‐controlled carbon ion therapy for mucosal melanoma of the paranasal sinus

The purpose of this study was to evaluate the use of raster‐scanned intensity‐controlled carbon ion therapy (ICCT) in the treatment of mucosal melanoma of the paranasal sinus.

Intensity-modulated radiotherapy versus proton radiotherapy versus carbon ion radiotherapy for spinal bone metastases: a treatment planning study

Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiotherapy (SBRT). As target geometry is complex, we compared SBRT plans using step‐and‐shoot intensity‐modulated radiotherapy (IMRT), carbon ion RT, and proton RT. We prepared plans treating cervical, thoracic, and lumbar metastases for three different techniques — IMRT, carbon ion, and proton plans — to deliver a median single 24 Gy fraction such that at least 90% of the planning target volume (PTV) received more than 18 Gy and were compared for PTV coverage, normal organ sparing, and estimated delivery time. PTV coverage did not show significant differences for the techniques, spinal cord dose sparing was lowered with the particle techniques. For the cervical lesion spinal cord maximum dose, dose of 1% (D1), and percent volume receiving 10 Gy (V10Gy) were 11.9 Gy, 9.1 Gy, and 0.5% in IMRT. This could be lowered to 4.3 Gy, 2.5 Gy, and 0% in carbon ion planning and to 8.1 Gy, 6.1 Gy, and 0% in proton planning. Regarding the thoracic lesion no difference was found for the spinal cord. For the lumbar lesion maximum dose, D1 and percent volume receiving 5 Gy (V5Gy) were 13.4 Gy, 8.9 Gy, and 8.9% for IMRT; 1.8 Gy, 0.7 Gy, and 0% for carbon ions; and 0 Gy,<0.01 Gy, and 0% for protons. Estimated mean treatment times were shorter in particle techniques (6–7 min vs. 12–14 min with IMRT). This planning study indicates that carbon ion and proton RT can deliver high‐quality PTV coverage for complex treatment volumes that surround the spinal cord. PACS number: 87.55.dkOutcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiotherapy (SBRT). As target geometry is complex, we compared SBRT plans using step-and-shoot intensity-modulated radiotherapy (IMRT), carbon ion RT, and proton RT. We prepared plans treating cervical, thoracic, and lumbar metastases for three different techniques - IMRT, carbon ion, and proton plans - to deliver a median single 24 Gy fraction such that at least 90% of the planning target volume (PTV) received more than 18 Gy and were compared for PTV coverage, normal organ sparing, and estimated delivery time. PTV coverage did not show significant differences for the techniques, spinal cord dose sparing was lowered with the particle techniques. For the cervical lesion spinal cord maximum dose, dose of 1% (D1), and percent volume receiving 10 Gy (V10Gy) were 11.9 Gy, 9.1 Gy, and 0.5% in IMRT. This could be lowered to 4.3 Gy, 2.5 Gy, and 0% in carbon ion planning and to 8.1 Gy, 6.1 Gy, and 0% in proton planning. Regarding the thoracic lesion no difference was found for the spinal cord. For the lumbar lesion maximum dose, D1 and percent volume receiving 5 Gy (V5Gy) were 13.4 Gy, 8.9 Gy, and 8.9% for IMRT; 1.8 Gy, 0.7 Gy, and 0% for carbon ions; and 0 Gy,<0.01 Gy, and 0% for protons. Estimated mean treatment times were shorter in particle techniques (6-7 min vs. 12-14 min with IMRT). This planning study indicates that carbon ion and proton RT can deliver high-quality PTV coverage for complex treatment volumes that surround the spinal cord. PACS number: 87.55.dk.

4D Treatment Dose Reconstruction for Scanned Ion Beam Therapy

Purpose/Objective(s): To report the initial outcomes and toxicity of SABR for oligometastases. Materials/Methods: Fifty-three patients with a minimum potential followup of 1 year were treated with SABR directed to a total of 99 metastatic sites (lung n Z 65, liver n Z 14, bone n Z 10, lymph node n Z 9, soft tissue n Z 1). The most commonly used SABR regimen was 50 Gy in 5 consecutive daily fractions using conformal arc technique with daily image guidance using CBCT. The most common primary sites were colorectal cancer (CRC; 28%), non-small cell lung carcinoma (NSCLC; 19%), soft tissue sarcoma (STS; 15%), and renal cell carcinoma (RCC; 8%). Median time to metastatic progression from initial diagnosis was 1.2 years (range, 0-13.1 years). The majority of patients were treated for solitary metastases (59%). Prior to SABR, 45% were treated for metastatic disease with surgery, chemotherapy or both. Fourteen patients received additional SABR for limited progression. Results: Median follow-up was 1.3 years (1.4 years for living patients). Local control (LC), distant-progression free survival (DPFS), causespecific survival (CSS), and overall survival (OS) at 1 and 2 years were 92%, 56%, 87%, 85%, and 74%, 40%, 70%, 69%, respectively, after the initial course of SABR. After a second course of SABR for limited progression the 1-year DPFS was only 22%. On univariate analysis there was no significant predictor for LC, although liver metastases and CRC primaries showed a trend toward decreased LC. Two-year DFPS, CSS, and OS were worse for patients with multiple metastatic sites, multiple organ involvement, increased cumulative GTV at initial SABR course, and when all measurable disease was not treated with SABR. Grade 3+ toxicity was observed in only 3 patients. Conclusions: In selected patients with limited metastatic disease, SABR resulted in durable disease control in a significant percentage of patients with minimal toxicity. Author Disclosure: R. Dagan: None. A.R. Yeung: None. R.A. Zlotecki: None. C.G. Morris: None. P. Okunieff: None.