Person:

Wolfgang, John

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.

Intrafractional motion and interfractional changes affect the accuracy of the delivered dose in radiotherapy, particularly in charged-particle radiotherapy. Most recent studies are focused on intrafractional motion (respiratory motion). Here, we report a quantitative simulation analysis of the effects of interfractional changes on water-equivalent pathlength (WEL) in charged-particle lung therapy. Serial four-dimensional (4D) CT scans were performed under free breathing conditions; the time span between the first and second 4DCT scans was five weeks. We quantified WEL changes between the first and second CT scans due to interfractional changes (tumor shrinkage and tissue density changes) and compared the particle-beam-stopping point between the serial 4DCT scans with use of the same initial bolus. Both tumor-shrinkage and lung-density changes were observed in a single patient over the course of therapy. The lung density decreased by approximately 0.1 g/cm3 between the first and second-CT scans, resulting in a 1.5 cm WEL changes. Tumor shrinkage resulted in approximately 3 cm WEL changes. If the same initial bolus and plan were used through the treatment course, an unexpected significant beam overshoot would occur by interfractional changes due to tumor shrinkage and lung density variation.