Person:

Lu, Hsiao-Ming

Purpose The delivery of post-mastectomy radiation therapy (PMRT) can be challenging for patients with left sided breast cancer that have undergone mastectomy. This study investigates the use of protons for PMRT in selected patients with unfavorable cardiac anatomy. We also report the first clinical application of protons for these patients. Methods and materials Eleven patients were planned with protons, partially wide tangent photon fields (PWTF), and photon/electron (P/E) fields. Plans were generated with the goal of achieving 95% coverage of target volumes while maximally sparing cardiac and pulmonary structures. In addition, we report on two patients with unfavorable cardiac anatomy and IMN involvement that were treated with a mix of proton and standard radiation. Results: PWTF, P/E, and proton plans were generated and compared. Reasonable target volume coverage was achieved with PWTF and P/E fields, but proton therapy achieved superior coverage with a more homogeneous plan. Substantial cardiac and pulmonary sparing was achieved with proton therapy as compared to PWTF and P/E. In the two clinical cases, the delivery of proton radiation with a 7.2 to 9 Gy photon and electron component was feasible and well tolerated. Akimbo positioning was necessary for gantry clearance for one patient; the other was treated on a breast board with standard positioning (arms above her head). LAO field arrangement was used for both patients. Erythema and fatigue were the only noted side effects. Conclusions: Proton RT enables delivery of radiation to the chest wall and regional lymphatics, including the IMN, without compromise of coverage and with improved sparing of surrounding normal structures. This treatment is feasible, however, optimal patient set up may vary and field size is limited without multiple fields/matching.

This study explores the potential of cone-beam computed tomography (CBCT) for monitoring relative beam range variations due to daily changes in patient anatomy for prostate treatment by anterior proton beams. CBCT was used to image an anthropomorphic pelvic phantom, in eight sessions on eight different days. In each session, the phantom was scanned twice, first at a standard position as determined by the room lasers, and then after it was shifted by 10 mm translation randomly along one of the X, Y, or Z directions. The filling of the phantom bladder with water was not refreshed from day to day, inducing gradual change of the water-equivalent path length (WEPL) across the bladder. MIMvista (MIM) software was used to perform image registration and re-alignment of all the scans with the scan from the first session. The XiO treatment planning system was used to perform data analysis. It was found that, although the Hounsfield unit numbers in CBCT have substantially larger fluctuations than those in diagnostic CT, CBCT datasets taken for daily patient positioning could potentially be used to monitor changes in patient anatomy. The reproducibility of the WEPL, computed using CBCT along anterior-posterior (AP) paths across and around the phantom prostate, over a volume of 360 cc, is sufficient for detecting daily WEPL variations that are equal to or larger than 3 mm. This result also applies to CBCT scans of the phantom after it is randomly shifted from the treatment position by 10 mm. limiting the interest to WEPL variation over a specific path within the same CBCT slice, one can detect WEPL variation smaller than 1 mm. That is the case when using CBCT for tracking daily change of the WEPL across the phantom bladder that was induced by spontaneous change in the bladder filling due to evaporation. In summary, the phantom study suggests that CBCT can be used for monitoring day to day WEPL variations in a patient. The method can detect WEPL variation equal to or greater than 3 mm. The study calls for further investigation using the CBCT data from real patients. If confirmed with real patients' data, CBCT could become, in addition to patient setup, a standard tool for proton therapy pretreatment beam range check. PACS number: 87.55.Tm.

Purpose

To evaluate the lifespan and risk of cancer following whole-body exposure of mice to neutrons generated by a passively scattered clinical SOBP proton beam.

Methods and Materials

Three hundred young adult female FVB/N mice, 152 test and 148 control, were entered into the experiment. Mice were placed in an annular cassette around a cylindrical phantom, which was positioned lateral to the mid SOBP of a 165 MeV, clinical proton beam. The average distance from the edge of the mid SOBP to the conscious active mice was 21.5 cm. The phantom was irradiated with once daily fractions of 25 Gy, 4 days per week, for 6 weeks. The age at death and cause of death, i.e., cancer and type vs. non-cancer causes, were assessed over the lifespan of the mice.

Results

Exposure of mice to a dose of 600 Gy of proton beam generated neutrons, reduced the median lifespan of the mice by 4.2% (Kaplan-Meier cumulative survival, P = 0.053). The relative risk of death from cancer in neutron exposed vs. control mice was 1.40 for cancer of all types (P = 0.0006) and 1.22 for solid cancers (P = 0.09). For a typical 60 Gy dose of clinical protons, the observed 22% increased risk of solid cancer would be expected to decrease by a factor of 10.

Conclusions

Exposure of mice to neutrons generated by a proton dose which exceeds a typical course of radiotherapy by a factor of 10, resulted in a statistically significant increase in the background incidence of leukemia and a marginally significant increase in solid cancer. The results indicate that the risk of out-of-field 2nd solid cancers from SOBP proton generated neutrons and typical treatment schedules, is 6 - 10 times less than is suggested by current neutron risk estimates.

Purpose

To evaluate the feasibility of a respiratory-gated proton beam therapy for liver tumors.

Materials and Methods

Fifteen patients were enrolled on a prospective IRB-approved protocol. Eligibility criteria included Childs-Pugh A/B cirrhosis, unresectablebiopsy-proven hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), or metastatic disease (solid tumors only), 1-3 lesions, and tumor size of ≤6 cm. Patients received 15 fractions to a total dose of 45-75 GyE using respiratory-gated proton beam therapy. Gating was performed with an external respiratory position monitoring (RPM) based system.

Results

Of the15 patients enrolled on this clinical trial, 11 had HCC, 3 had ICC, and 1had metastasis from another primary. Ten patients had a single lesion, 3 patients had 2 lesions, and 2 patients 3 lesions. Toxicities were: Gr 3 bilirubinemia- 2, Gr 3 gastrointestinal bleed- 1, and Gr 5 stomach perforation-1. One patient had a marginal recurrence, 3 had hepatic recurrences elsewhere in the liver, and 2 had extrahepatic recurrence. With a median follow-up for survivors of 69 months, 1-yr, 2-yr, 3-yr OS is 53%, 40%, and 33% respectively. PFS is 40%,33% and 27% at 1, 2, and 3 years, respectively.

Conclusion

Respiratory-gated proton beam therapy for liver tumors is feasible. Phase II studies for primary liver tumors and metastatic tumorsare underway.

Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangement anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS.

Monte Carlo models of proton therapy treatment heads are being used to improve beam delivery systems and to calculate the radiation field for patient dose calculations. The achievable accuracy of the model depends on the exact knowledge of the treatment head geometry and time structure, the material characteristics, and the underlying physics. This work aimed at studying the uncertainties in treatment head simulations for passive scattering proton therapy. The sensitivities of spread-out Bragg peak (SOBP) dose distributions on material densities, mean ionization potentials, initial proton beam energy spread and spot size were investigated. An improved understanding of the nature of these parameters may help to improve agreement between calculated and measured SOBP dose distributions and to ensure that the range, modulation width, and uniformity are within clinical tolerance levels. Furthermore, we present a method to make small corrections to the uniformity of spread-out Bragg peaks by utilizing the time structure of the beam delivery. In addition, we re-commissioned the models of the two proton treatment heads located at our facility using the aforementioned correction methods presented in this paper.

Purpose

To quantify daily variations in the anatomy of patients undergoing radiation therapy for prostate carcinoma, to estimate their effect on dose distribution, and to evaluate the effectiveness of current standard planning and set-up approaches employed in proton therapy.

Methods

We used series of CT data, which included the pre-treatment scan, and between 21 and 43 in-room scans acquired on different treatment days, from 10 patients treated with intensity-modulated radiation therapy at Morristown Memorial Hospital. Variations in femur rotation angles, thickness of subcutaneous adipose tissue, and physical depth to the distal surface of the prostate for lateral beam arrangement were recorded. Proton dose distributions were planned with the standard approach. Daily variations in the location of the prescription iso-dose were evaluated.

Results

In all 10 datasets, substantial variation was observed in the lateral tissue thickness (standard deviation of 1.7–3.6 mm for individual patients, variations of over 5 mm from the planning CT observed in all series), and femur rotation angle (standard deviation between 1.3–4.8°, with the maximum excursion exceeding 10° in 6 out of 10 datasets). Shifts in the position of treated volume (98% iso-dose) were correlated with the variations in the lateral tissue thickness.

Conclusions

Analysis suggests that, combined with image-guided set-up verification, the range compensator expansion technique prevents loss of dose to target due to femur rotation and soft tissue deformation, in the majority of cases. Anatomic changes coupled with the uncertainties of particle penetration in tissue restrict possibilities for margin reduction in proton therapy of prostate cancer.