J Farr

Neutron scattered dose equivalent to a fetus from proton radiotherapy of the mother

Scattered neutron dose equivalent to a representative point for a fetus is evaluated in an anthropomorphic phantom of the mother undergoing proton radiotherapy. The effect on scattered neutron dose equivalent to the fetus of changing the incident proton beam energy, aperture size, beam location, and air gap between the beam delivery snout and skin was studied for both a small field snout and a large field snout. Measurements of the fetus scattered neutron dose equivalent were made by placing a neutron bubble detector 10 cm below the umbilicus of an anthropomorphic Rando phantom enhanced by a wax bolus to simulate a second trimester pregnancy. The neutron dose equivalent in milliSieverts (mSv) per proton treatment Gray increased with incident proton energy and decreased with aperture size, distance of the fetus representative point from the field edge, and increasing air gap. Neutron dose equivalent to the fetus varied from 0.025 to 0.450 mSv per proton Gray for the small field snout and from 0.097 to 0.871 mSv per proton Gray for the large field snout. There is likely to be no excess risk to the fetus of severe mental retardation for a typical proton treatment of 80 Gray to the mother since the scattered neutron dose to the fetus of 69.7 mSv is well below the lower confidence limit for the threshold of 300 mGy observed for the occurrence of severe mental retardation in prenatally exposed Japanese atomic bomb survivors. However, based on the linear no threshold hypothesis, and this same typical treatment for the mother, the excess risk to the fetus of radiation induced cancer death in the first 10 years of life is 17.4 per 10,000 children.

Potentials of robust intensity modulated scanning proton plans for locally advanced lung cancer in comparison to intensity modulated photon plans

BACKGROUND AND PURPOSE The potentials of lung sparing, dose escalation, and the robustness of intensity modulated proton plans (IMPT(robust)), obtained by minimax optimization on multiple scenarios, were studied. MATERIALS AND METHODS IMPT(robust) optimization as described by Fredriksson et al. [23] was evaluated by means of comparative treatment planning using breath hold CT data from 6 non-small cell lung cancer (NSCLC) patients. IMPT(robust) and single field uniform dose (SFUD) proton plans were compared to Tomotherapy and 7-field intensity modulated photon therapy (IMXT). Plan robustness against set-up errors, range uncertainties, and between field motions were analyzed as well as lung exposure quantified by the mean lung dose (MLD) and the partial lung volumes receiving at least 20, 10, and 5 Gy(RBE) (V20, V10, V5). Robustness was analyzed with regard to stability of the effective uniform dose (EUD) and the dose level reached or exceeded in 95% of the CTV (D95). RESULTS MLD by IMPT(robust) was less than by SFUD, and Tomotherapy in each patient, on average by 14.8% and 28.5% (p<0.05, Friedman test). V20-V5 were higher with Tomotherapy compared to both proton therapy techniques, on average by a factor of >1.8. Robustness of IMPT(robust) was high. EUD and D95 values were maintained above 96% and 94% of the reference plan values for all tested scenarios. With dose escalation to 86 Gy(RBE) lung tissue tolerances were maintained. CONCLUSIONS IMPT(robust) proved advantageous in terms of lung exposure and possible dose escalation while being also markedly robust. However, motion during delivery of a field remains a major problem of IMPT(robust) to be mitigated by high scanning speed and variable spot size.

Re-irradiation of recurrent head and neck carcinomas: comparison of robust intensity modulated proton therapy treatment plans with helical tomotherapy

BackgroundTo test the hypothesis that the therapeutic ratio of intensity-modulated photon therapy using helical tomotherapy (HT) for retreatment of head and neck carcinomas can be improved by robust intensity-modulated proton therapy (IMPT).MethodsComparative dose planning with robust IMPT was performed for 7 patients retreated with HT.ResultsOn average, HT yielded dose gradients steeper in a distance ≤ 7.5 mm outside the target (p<0.0001, F-test) and more conformal high dose regions down to the 50% isodose than IMPT. Both methods proved comparably robust against set-up errors of up to 2 mm, and normal tissue exposure was satisfactory. The mean body dose was smaller with IMPT.ConclusionsIMPT was found not to be uniformly superior to HT and the steeper average dose fall-off around the target volume is an argument pro HT under the methodological implementations used. However, looking at single organs at risk, the normal tissue sparing of IMPT can surpass tomotherapy for an individual patient. Therefore, comparative dose planning is recommended, if both methods are available.

Proton beam therapy: a fad or a new standard of care.

Purpose of review Newer methods and advances in radiation therapy promise to reduce the risk of complications in children who require irradiation. They have secured the role of radiation therapy in the treatment of a variety of pediatric central nervous system and solid tumors and for young patients enrolled on clinical trials. Recent findings Proton therapy is the latest advancement in radiation therapy. Its availability is increasing as new centers are built throughout the United States. Pediatric specialists should understand that proton therapy is in its pioneering stage of development and that advantages have not been quantitatively demonstrated. Proton therapy clearly reduces collateral radiation dose to normal tissue when compared with photon (X-ray)-based methods of irradiation and has the potential to selectively and safely escalate dose to high-risk tumors; however, research results are lacking in both of these areas, leading to some confusion among pediatric specialists with regard to indications and the need to refer patients for this limited resource and expensive form of radiation therapy. Summary This review highlights a number of issues surrounding proton therapy in children and supports the use of proton therapy in clinical trials.

Dosimetric impact of intrafraction motion for compensator-based proton therapy of lung cancer

Compensator-based proton therapy of lung cancer using an un-gated treatment while allowing the patient to breathe freely requires a compensator design that ensures tumor coverage throughout respiration. Our investigation had two purposes: one is to investigate the dosimetric impact when a composite compensator correction is applied, or is not, and the other one is to evaluate the significance of using different respiratory phases as the reference computed tomography (CT) for treatment planning dose calculations. A 4D-CT-based phantom study and a real patient treatment planning study were performed. A 3D MIP dataset generated over all phases of the acquired 4D-CT scans was adopted to design the field-specific composite aperture and compensator. In the phantom study, the MIP-based compensator design plan named plan D was compared to the other three plans, in which average intensity projection (AIP) images in conjunction with the composite target volume contour copied from the MIP images were used. Relative electron densities within the target envelope were assigned either to original values from the AIP image dataset (plan A) or to predetermined values, 0.8 (plan B) and 0.9 (plan C). In the patient study, the dosimetric impact of a compensator design based on the MIP images (plan ITV(MIP)) was compared to designs based on end-of-inhale (EOI) (plan ITV(EOI)) and middle-of-exhale (MOE) CT images (plan ITV(MOE)). The dose distributions were recalculated for each phase. Throughout the ten phases, it shows that D(GTV)(min) changed slightly from 86% to 89% (SD = 0.9%) of prescribed dose (PD) in the MIP plan, while varying greatly from 10% to 79% (SD = 26.7%) in plan A, 17% to 73% (SD = 22.5%) in plan B and 53% to 73% (SD = 6.8%) in plan C. The same trend was observed for D(GTV)(mean) and V95 with less amplitude. In the MIP-based plan ITV(MIP), D(GTV)(mean) was almost identically equal to 95% in each phase (SD = 0.5%). The patient study verified that the MIP approach increased the minimum value of D99 of the clinical target volume (CTV) by 58.8% compared to plan ITV(EOI) and 12.9% compared to plan ITV(MOE). Minimum values of D99 were 37.60%, 83.50% and 96.40% for plan ITV(EOI), plan ITV(MOE) and plan ITV(MIP), respectively. Standard deviations of D99 were significantly decreased (SD = 0.5%) in the MIP plan as compared to plan ITV(EOI) (SD = 18.9%) or plan ITV(MOE) (SD = 4.0%). These studies demonstrate that the use of MIP images to design the patient-specific composite compensators provide superior and consistent tumor coverage throughout the entire respiratory cycle whilst maintaining a low average normal lung dose. The additional benefit of the MIP-based design approach is that the dose calculation can be implemented on any single phase as long as it uses the aperture and compensator optimized from the MIP images. This also reduces the requirement for contouring on all breathing phases down to just one.

Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort

Context Long-term follow-up data on premature ovarian insufficiency (POI) in childhood cancer survivors are limited. Objective To describe the prevalence of POI, its risk factors, and associated long-term adverse health outcomes. Design Cross-sectional. Setting The St. Jude Lifetime Cohort Study, an established cohort in a tertiary care center. Patients Nine hundred twenty-one participants (median age, 31.7 years) were evaluated at a median of 24.0 years after cancer diagnosis. Main Outcome Measure POI was defined by persistent amenorrhea combined with a follicle-stimulating hormone level >30 IU/L before age 40. Multivariable Cox regression was used to study associations between demographic or treatment-related risk factors and POI. Multivariable logistic regression was used to study associations between POI and markers for cardiovascular disease, bone mineral density (BMD), and frailty. Exposure to alkylating agents was quantified using the validated cyclophosphamide equivalent dose (CED). Results The prevalence of POI was 10.9%. Independent risk factors for POI included ovarian radiotherapy at any dose and CED ≥8000 mg/m2. Patients with a body mass index ≥30 kg/m2 at the time of the St. Jude Lifetime Cohort assessment were less likely to have a diagnosis of POI. Low BMD and frailty were independently associated with POI. Conclusion High-dose alkylating agents and ovarian radiotherapy at any dose are associated with POI. Patients at the highest risk should be offered fertility preservation whenever feasible. POI contributes to poor general health outcomes in childhood cancer survivors; further studies are needed to investigate the role of sex hormone replacement in improving such outcomes.

Determining the optimal dosimetric leaf gap setting for rounded leaf‐end multileaf collimator systems by simple test fields

Individual QA for IMRT/VMAT plans is required by protocols. Sometimes plans cannot pass the institutes QA criteria. For the Eclipse treatment planning system (TPS) with rounded leaf‐end multileaf collimator (MLC), one practical way to improve the agreement of planned and delivered doses is to tune the value of dosimetric leaf gap (DLG) in the TPS from the measured DLG. We propose that this step may be necessary due to the complexity of the MLC system, including dosimetry of small fields and the tongue‐and‐groove (T&G) effects, and report our use of test fields to obtain linac‐specific optimal DLGs in TPSs. More than 20 original patient plans were reoptimized with the linac‐specific optimal DLG value. We examined the distribution of gaps and T&G extensions in typical patient plans and the effect of using the optimal DLG on the distribution. The QA pass rate of patient plans using the optimal DLG was investigated. The dose‐volume histograms (DVHs) of targets and organs at risk were checked. We tested three MLC systems (Varian millennium 120 MLC, high‐definition 120 MLC, and Siemens 160 MLC) installed in four Varian linear accelerators (linacs) (TrueBEAM STx, Trilogy, Clinac 2300 iX, and Clinac 21 EX) and 1 Siemens linac (Artiste). With an optimal DLG, the individual QA for all those patient plans passed the institutes criteria (95% in DTA test or gamma test with 3%/3 mm/10%), even though most of these plans had failed to pass QA when using original DLGs optimized from typical patient plans or from the optimization process (automodeler) of Pinnacle TPS. Using either our optimal DLG or one optimized from typical patient plans or from the Pinnacle optimization process yielded similar DVHs. PACS number: 87.55Qr

Range and modulation dependencies for proton beam dose per monitor unit calculations

Calculations of dose per monitor unit (D/MU) are required in addition to measurements to increase patient safety in the clinical practice of proton radiotherapy. As in conventional photon and electron therapy, the D/MU depends on several factors. This study focused on obtaining range and modulation dependence factors used in D/MU calculations for the double scattered proton beam line at the Midwest Proton Radiotherapy Institute. Three dependencies on range and one dependency on modulation were found. A carefully selected set of measurements was performed to discern these individual dependencies. Dependencies on range were due to: (1) the stopping power of the protons passing through the monitor chamber; (2) the reduction of proton fluence due to nuclear interactions within the patient; and (3) the variation of proton fluence passing through the monitor chamber due to different source-to-axis distances (SADs) for different beam ranges. Different SADs are produced by reconfigurations of beamline elements to provide different field sizes and ranges. The SAD effect on the D/MU varies smoothly as the beam range is varied, except at the beam range for which the first scatterers are exchanged and relocated to accommodate low and high beam ranges. A geometry factor was devised to model the SAD variation effect on the D/MU. The measured D/MU variation as a function of range can be predicted within 1% using the three modeled dependencies on range. Investigation of modulated beams showed that an analytical formula can predict the D/MU dependency as a function of modulation to within 1.5%. Special attention must be applied when measuring the D/MU dependence on modulation to avoid interplay between range and SAD effects.

Microdosimetric measurements for neutron-absorbed dose determination during proton therapy

This work presents microdosimetric measurements performed at the Midwest Proton Radiotherapy Institute in Bloomington, Indiana, USA. The measurements were done simulating clinical setups with a water phantom and for a variety of stopping targets. The water phantom was irradiated by a proton spread out Bragg peak (SOBP) and by a proton pencil beam. Stopping target measurements were performed only for the pencil beam. The targets used were made of polyethylene, brass and lead. The objective of this work was to determine the neutron-absorbed dose for a passive and active proton therapy delivery, and for the interactions of the proton beam with materials typically in the beam line of a proton therapy treatment nozzle. Neutron doses were found to be higher at 45° and 90° from the beam direction for the SOBP configuration by a factor of 1.1 and 1.3, respectively, compared with the pencil beam. Meanwhile, the pencil beam configuration produced neutron-absorbed doses 2.2 times higher at 0° than the SOBP. For stopping targets, lead was found to dominate the neutron-absorbed dose for most angles due to a large production of low-energy neutrons emitted isotropically.

The effects of motion on the dose distribution of proton radiotherapy for prostate cancer

Proton radiotherapy of the prostate basal or whole seminal vesicles using scattering delivery systems is an effective treatment of prostate cancer that has been evaluated in prospective trials. Meanwhile, the use of pencil beam scanning (PBS) can further reduce the dose in the beam entrance channels and reduce the dose to the normal tissues. However, PBS dose distributions can be affected by intra‐ and interfractional motion. In this treatment planning study, the effects of intra‐ and interfractional organ motion on PBS dose distributions are investigated using repeated CT scans at close and distant time intervals. The minimum dose (Dmin) and the dose to 2% and 98% of the volumes (D2% and D98%), as well as EUD in the clinical target volumes (CTV), is used as measure of robustness. In all patients, D98% was larger than 96% and D2% was less than 106% of the prescribed dose. The combined information from Dmin, D98% and EUD led to the conclusion that there are no relevant cold spots observed in any of the verification plans. Moreover, it was found that results of single field optimization are more robust than results from multiple field optimizations. PACS numbers: 87.55.D‐, 87.55.de, 87.53.Bn, 87.55.dk, 87.55.ne