L. Placidi

Long-Term Clinical Safety of High-Dose Proton Radiation Therapy Delivered With Pencil Beam Scanning Technique for Extracranial Chordomas and Chondrosarcomas in Adult Patients: Clinical Evidence of Spinal Cord Tolerance

PURPOSEnTo assess the radiation dose tolerance of the spinal cord by reviewing our institutional experience regarding the incidence of radiation-induced spinal cord toxicity after high-dose pencil beam scanning proton therapy (PBSPT).nnnMETHODS AND MATERIALSnSeventy-six patients (median age 53xa0years; range, 23-79xa0years) treated for spinal chordoma (n=55) or chondrosarcoma (n=21) met the following criteria and were retrospectively analyzed: PBSPT only, no reirradiation or concomitant chemotherapy, maximum dose (Dmax) to the spinal cord of ≥45xa0Gy(relative biological effectiveness [RBE]), ≥18xa0years of age, and follow-up of ≥12xa0months. The delivered dose was 59.4 to 75.2xa0Gy(RBE) [median 73.9xa0Gy(RBE)] delivered with conventional fractionation between 2000 and 2014. The Dmax, D2%, and V40-V60 of the surface (sSC) and center (cSC) of the spinal cord were recorded. Toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 4.03.nnnRESULTSnMedian follow-up was 65.5xa0months (range, 13-173xa0months). Patients received a mean Dmax and D2% to the sSC of 59.0 (median 58.7; range, 48.3-75.9) and 55.3 (median 52.7; range, 43.1-73.8) Gy(RBE), respectively. The corresponding values for the cSC were 52.3 (median 52.7; range, 32.3-73.3) and 51.1 (median 52.0; range, 25.3-73.1) Gy(RBE), respectively. Four patients (5%) developed acute radiation-induced neurotoxicity (grade [G] 1, n=1; G2, n=3). Twelve patients (16%) experienced late neurologic toxicities (G1, n=7; G2, n=4; G4, n=1). One patient with a history of pre-PBSPT symptomatic spinal cord compression redeveloped tetraplegia (G4) after receiving a Dmax of 57.8xa0Gy(RBE) to the sSC and 54.1xa0Gy(RBE) to the cSC. No significant correlation was found between sSC Dmax and D2%, cSC Dmax and D2%, or the length of CTV and toxicity.nnnCONCLUSIONSnHigh-dose conformal PBSPT may be delivered safely in close proximity to the spinal cord with minimal neurotoxicity. Dose constraints of 64xa0Gy(RBE) as D2% for the sSC and 54xa0Gy(RBE) for the cSC seem appropriate for clinical use.

Effect of Anatomic Changes on Pencil Beam Scanned Proton Dose Distributions for Cranial and Extracranial Tumors

PURPOSEnToxa0estimate the frequency and impact of anatomic changes on the delivered dose in pencil beam scanning proton therapy, to assess the need for repeat CT scanning and adaptive replanning.nnnMETHODS AND MATERIALSnA total of 730 patients treated at Paul Scherrer Institut between 2007 and 2014 were included in this study, for which the number of patients who had control CT scans and who were replanned as a result of anatomic changes was analyzed. For those that were replanned, the nominal dose distributions (originally optimized on the planning CT scan) were recalculated on the replanning CT scan and differences evaluated using standard dose metrics for planning target volumes and clinical target volumes and organs at risk (OARs).nnnRESULTSnControl CT studies were acquired for 244 patients (33.5%), and replanning was deemed clinically necessary for 40 (16%) of these (5.5% of the total cohort). The OARs and target dose differences between the nominal and recalculated dose distributions were found to be strongly dependent on the subgroup of patients. Nevertheless, dose differences were found to be ≤ 5% for 88% of all analyzed OARs, and planning target volume/clinical target volume V95% was reduced byxa0≤5% in 87%/90% of cases.nnnCONCLUSIONSnDespite anatomic variations, clinically delivered plans have been found to be robust to anatomic changes, with replanning being deemed necessary in only a small number of cases. However, because the dosimetric effect of such changes can be quite large for some cases, they have to be monitored and evaluated on an individual basis.

Range resolution and reproducibility of a dedicated phantom for proton PBS daily quality assurance

PURPOSEnWedge phantoms coupled with a CCD camera are suggested as a simple means to improve the efficiency of quality assurance for pencil beam scanning (PBS) proton therapy, in particular to verify energy/range consistency on a daily basis. The method is based on the analysis of an integral image created by a pencil beam (PB) pattern delivered through a wedge. We have investigated the reproducibility of this method and its dependence on setup and positional beam errors for a commercially available phantom (Sphinx®, IBA Dosimetry) and CCD camera (Lynx®, IBA Dosimetry) system.nnnMATERIAL AND METHODSnThe phantom includes 4 wedges of different thickness, allowing verification of the range for 4 energies within one integral image. Each wedge was irradiated with a line pattern of clinical energies (120, 150, 180 and 230MeV). The equipment was aligned to the isocenter using lasers, and the delivery was repeated for 5 consecutive days, 4 times each day. Range was computed using the myQA software (IBA Dosimetry) and inter- and intra-setup uncertainty were calculated. Dependence of range on energy was investigated delivering the same pencil beam pattern but with energy variations in steps of ±0.2MeV for all the nominal energies, up to ±1.0MeV. Possible range uncertainties, caused by setup and positional errors, were then simulated including inclination of the phantom, pencil beam and couch shifts.nnnRESULTSnIntra position setup (based on in-room laser system) shows a maximum in plane difference within 1.5mm. Range reproducibility (standard deviation) was less than 0.14mm. Setup and beam errors did not affect significantly the results, except for a vertical shift of 10mm which leads to an error in the range computation.nnnCONCLUSIONnTaking into account different day-to-day setup and beam errors, day-to-day determination of range has been shown to be reproducible using the proposed system.

Long-Term Outcomes and Prognostic Factors After Pencil-Beam Scanning Proton Radiation Therapy for Spinal Chordomas: A Large, Single-Institution Cohort

PURPOSEnTo evaluate the efficacy and safety of high-dose pencil-beam scanning proton therapy (PBS-PT) in the adjuvant treatment of spinal chordomas.nnnMETHODS AND MATERIALSnBetween 1997 and 2015, 100 patients with spinal chordomas (median age, 56xa0years; range, 25-81xa0years) were treated with adjuvant PBS-PT at the Paul Scherrer Institute: cervical (nxa0=xa046), thoracic (nxa0=xa04), lumbar (nxa0=xa012), and sacral (nxa0=xa038). The majority (88%) received PBS-PT alone rather than combined photon-proton therapy. The median radiation therapy dose prescribed was 74 Gy (relative biological effectiveness [RBE]) (range, 59.4-77xa0Gy [RBE]). Thirty-nine patients (39%) had undergone surgical stabilization, primarily with titanium hardware, before radiation therapy.nnnRESULTSnWith a median follow-up of 65xa0months (range, 13-175xa0months), 5-year local control, disease control, and overall survival rates were 63% (95% confidence interval [CI] 57.7-68.7%; median, 103xa0months), 57% (95% CI 50.9-62.1%; median, 82xa0months), and 81% (95% CI 76.8-85.6%; median, 157xa0months), respectively. On univariate and multivariate analyses, the presence of surgical stabilization was highly prognostic for worsened outcomes. Multivariate analysis also revealed the extent of treatment volumes and presence of gross residual disease to be important in predicting outcomes. High-grade (grade ≥3) toxicities were rare in both the acute (8%) and late (6%) settings.nnnCONCLUSIONnFor spinal chordomas, PBS-PT remains a highly effective and safe method for delivery of dose-escalated adjuvant radiation therapy. The presence of metallic surgical stabilization prognosticates for worsened outcomes. Further investigation is warranted to characterize ideal treatment volumes and effect of surgical stabilization on therapy for these challenging tumors.

Positioning of head and neck patients for proton therapy using proton range probes: a proof of concept study

To exploit the full potential of proton therapy, accurate and on-line methods to verify the patient positioning and the proton range during the treatment are desirable. Here we propose and validate an innovative technique for determining patient misalignment uncertainties through the use of a small number of low dose, carefully selected proton pencil beams (range probes) (RP) with sufficient energy that their residual Bragg peak (BP) position and shape can be measured on exit. Since any change of the patient orientation in relation to these beams will result in changes of the density heterogeneities through which they pass, our hypothesis is that patient misalignments can be deduced from measured changes in Bragg curve (BC) shape and range. As such, a simple and robust methodology has been developed that estimates average proton range and range dilution of the detected residual BC, in order to locate range probe positions with optimal prediction power for detecting misalignments. The validation of this RP based approach has been split into two phases. First we retrospectively investigate its potential to detect translational patient misalignments under real clinical conditions. Second, we test it for determining rotational errors of an anthropomorphic phantom that was systematically rotated using an in-house developed high precision motion stage. Simulations of RPs in these two scenarios show that this approach could potentially predict translational errors tou2009lower than1.5u2009mm and rotational errors tou2009smaller than 1° using only three or five RPs positions respectively.

Radiation Necrosis and White Matter Lesions in Pediatric Patients With Brain Tumors Treated With Pencil Beam Scanning Proton Therapy.

PURPOSEnTo assess the rate of radiation necrosis (RN) and white matter lesions (WMLs) in pediatric patients with primary brain tumors treated with pencil beam scanning (PBS) proton therapy (PT) with or without concomitant chemotherapy at the PSI.nnnMETHODS AND MATERIALSnBetween 1999 and 2015, 171 pediatric patients (age <18xa0years) were treated with PT. Median age at diagnosis was 3.3xa0years (range, 0.3-17.0xa0years), and the median delivered dose was 54xa0Gy (relative biological effectiveness) (range, 40.0-74.1xa0Gy). Radiation necrosis and WMLs were defined as a new area of abnormal signal intensity on T2-weighted images or increased signal intensity on T2-weighted images, and contrast enhancement on T1 occurring in the brain parenchyma included in the radiation treatment field, which did not demonstrate any abnormality before PT. Radiation necrosis and WMLs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up period for the surviving patients was 49.8xa0months (range, 5.9-194.7xa0months).nnnRESULTSnTwenty-nine patients (17%) developed RN at a median time of 5xa0months (range, 1-26xa0months), most of them (n = 17; 59%) being asymptomatic (grade 1). Grade 2, 4, and 5 toxicities occurred in 8, 2, and 2 patients, respectively. Eighteen patients (11%) developed WMLs at a median time of 14.5xa0months (range, 2-62xa0months), most of them (n = 13; 72%) being asymptomatic (grade 1). White matter lesion grade 2 and 3 toxicities occurred in 4 and 1 patient(s), respectively. The 5-year RN-free andxa0WML-free survival was 83% and 87%, respectively. In univariate analysis, neoadjuvant (P = .025) or any (P = .03) chemotherapy, hydrocephalus before PT (P = .035), and ependymoma (P = .026) histology were significant predictors of RN.nnnCONCLUSIONSnChildren treated with PT demonstrated a low prevalence of symptomatic RN (7%) or WML (3%) compared with similar cohorts treated with either proton or photon radiation therapy. Chemotherapy, ependymomal tumors and hydrocephalus as an initial symptom were significant risk factors for RN.

PO-0805: Proton radiography for the clinical commissioning of the new Gantry2 head support at PSI

In figure a comparison of TPS and MC planar dose distribution with 2DQA measurements is shown. In our protocol, if the passing rate (PR) is above 95% the field is accepted. If it is between 95 and 90% a justification must be added to the QA report to flag the field as accepted. A passing rate below 90% makes the field unacceptable. In the graph 27 fields belonging to 10 patients are analysed. MC has a PR always greater than 95% for every depth showing a good agreement with measurements. TPS results are always in the “grey” area between 90 and 95%. The execution time of a 2DQA with an array of ICs takes almost 1 hour and half; simulations, that can be performed in parallel, take 11 minutes on average.