Carbon ion radiotherapy with pencil beam scanning for hepatocellular carcinoma: Long-term outcomes from a phase I trial.

This study evaluates the feasibility of the pencil beam scanning technique of carbon ion radiotherapy (CIRT) in the setting of hepatocellular carcinoma (HCC) and establishes the maximum tolerated dose (MTD) calculated by the Local Effect Model version I (LEM-I) with a dose escalation plan. The escalated relative biological effectiveness-weighted dose levels included 55, 60, 65, and 70 Gy in 10 fractions. Active motion management techniques were employed, and several measures were applied to mitigate the interplay effect induced by a moving target. CIRT was planned with the LEM-I-based treatment planning system and delivered by raster scanning. Offline PET/CT imaging was used to verify the beam range. Offline adaptive replanning was performed whenever required. Twenty-three patients with a median tumor size of 4.3 cm (range, 1.7-8.5 cm) were enrolled in the present study. The median follow-up time was 56.1 months (range, 5.7-74.4 months). No dose limiting toxicity was observed until 70 Gy, and MTD had not been reached. No patients experienced radiation-induced liver disease within 6 months after the completion of CIRT. The overall survival rates at 1, 3, and 5 years were 91.3%, 81.9%, and 67.1% after CIRT, respectively. The local progression-free survival and progression-free survival rates at 1, 3 and 5 years were 100%, 94.4%, and 94.4% and 73.6%, 59.2%, and 37.0%, respectively. The raster scanning technique could be used to treat HCC. However, caution should be exercised to mitigate the interplay effect. CIRT up to 70 Gy in 10 fractions over 2 weeks was safe and effective for HCC.

Technical Note: A simple and fast daily quality assurance solution for modulated scanning proton and carbon ion beams.

PURPOSE: A typical ion beam treatment facility has multiple treatment rooms and may treat with more than one ion species, thus requiring a significant quality assurance (QA) effort. The goal of this work was to perform daily QA using a single irradiation per ion species to obtain the beam dosimetry parameters of dose per monitor unit (D/MU), range, and spot position. The X-ray alignment system should also be checked and the entire procedure performed by therapists. METHODS: This goal was achieved by designing a jig for the Sun Nuclear Daily QA™ 3 device and combining it with specific brass boluses, a standard QA plan, and a cuboid polyethylene phantom for positioning/repositioning tests. The design of the plan used for each ion species delivery ensured that there was no interference between the tests of the various characteristics. RESULTS: The 1-year monitoring results showed the proposed daily QA procedure was reliable and able to reflect each of the specified QA items of the proton and carbon ion beams. To simplify the daily analysis, the tolerances for the D/MU, beam range, and spot position (±1.5%, ±0.3 mm, ±1.5 mm, respectively) are checked using only the detector readings without the need for additional data processing. CONCLUSIONS: The proposed daily QA procedure was clinically implemented in our facility in April 2019 and has run smoothly for the first 2 years of operation. The total daily QA time for the four-room facility decreased from 1 to 1.5 h to 30 to 40 min and was achieved not by reducing QA tests but rather by implementing new technology and procedures permitting acquisition of multiple beam information.

Biological Guided Carbon-Ion Microporous Radiation to Tumor Hypoxia Area Triggers Robust Abscopal Effects as Open Field Radiation.

Recently, a growing number of studies focus on partial tumor irradiation to induce the stronger non-target effects. However, the value of partial volume carbon ion radiotherapy (CIRT) targeting hypoxic region of a tumor under imaging guidance as well as its effect of inducing radiation induced abscopal effects (RIAEs) have not been well investigated. Herein, we developed a technique of carbon ion microporous radiation (CI-MPR), guided by 18F-FMISO PET/computerized tomography (CT), for partial volume radiation targeting the hypoxia area of a tumor and investigated its capability of inducing abscopal effects. Tumor-bearing mice were inoculated subcutaneously with breast cancer 4T1 cells into the flanks of both hind legs of mouse. Mice were assigned to three groups: group I: control group with no treatment; group II: carbon ion open field radiation (CI-OFR group) targeting the entire tumor; group III: partial volume carbon ion microporous radiation (CI-MPR group) targeting the hypoxia region. The tumors on the left hind legs of mice were irradiated with single fraction of 20 Gy of CIRT. Mice treated with CI-MPR or CI-OFR showed that significant growth delay on both the irradiated and unirradiated of tumor as compared to the control groups. Tumor regression of left tumor irradiated with CI-OFR was more prominent as compared to the tumor treated with CI-MPR, while the regression of the unirradiated tumor in both CI-MPR and CI-OFR group was similar. Biological-guided CIRT using the newly developed microporous technique targeting tumor hypoxia region could induce robust abscopal effects similar to CIRT covering the entire tumor.

Evaluating dosimetric constraints for carbon ion radiotherapy in the treatment of locally advanced pancreatic cancer.

OBJECTIVE: To identify a safe carbon ion radiotherapy (CIRT) regimen for patients with locally advanced pancreatic cancer (LAPC). METHODS: We generated treatment plans for 13 consecutive, unselected patients who were treated for LAPC with CIRT at our center using three dose and fractionation schedules: 4.6 GyRBE × 12, 4.0 GyRBE × 14, and 3.0 GyRBE × 17. We tested the ability to meet published dose constraints for the duodenum, stomach, and small bowel as a function of dose schedule and distance between the tumor and organs at risk. RESULTS: Using 4.6 GyRBE × 12 and 4.0 GyRBE × 14, critical (high-dose) constraints could only reliably be achieved when target volumes were not immediately adjacent to organs at risk. Critical constraints could be met in all cases using 3.0 GyRBE × 17. Low-dose constraints could not uniformly be achieved using any dose schedule. CONCLUSION: While selected patients with LAPC may be treated safely with a CIRT regimen of 4.6 GyRBE × 12, our dosimetric analyses indicate that a more conservative schedule of 3.0 GyRBE × 17 may be required to safely treat a broader population of LAPC patients, including those with large tumors and tumors that approach gastrointestinal organs at risk. The result of this work was used to guide an ongoing clinical trial.

Proton and carbon ion radiation therapy for locally advanced pancreatic cancer: A phase I dose escalation study.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of proton and carbon ion radiation therapy (PCRT) for locally advanced pancreatic cancer (LAPC). METHODS: A single-institution, phase I dose escalation study was performed. The proton dose of 50.4 GyE in 28 fractions was delivered to clinical target volume, and carbon ion as a boost dose to gross tumor volume escalated from 12 GyE to 18 GyE with 3 GyE per fraction in 3 dose levels. The dose limiting toxicity (DLT) was defined as any treatment-related grade (G)3 or higher of non-hematological toxicity. The MTD was exceeded if ≥2 patients in a dose level developed DLT. RESULTS: From May 2015 to July 2016, ten patients were enrolled, 3 in dose level 1, 4 in dose level 2, and 3 in dose level 3. With a median follow-up of 17.4 months, no patient developed a DLT, and the acute G1-2 of gastrointestinal (GI) and hepatic toxicity occurred in 40% of patients, and G1 of GI late toxicity, in 30%. The median overall survival was 17.3 months. CONCLUSION: Higher than 50.4 GyE could be given by PCRT with slight toxicity and good tolerance for LAPC, and the tumor control and survival had been improved, but not significantly. Better outcome may be achieved using carbon ion radiation therapy with higher biological equivalent dose.

Comparison of photon volumetric modulated arc therapy, intensity-modulated proton therapy, and intensity-modulated carbon ion therapy for delivery of hypo-fractionated thoracic radiotherapy.

PURPOSE: The aim of the present study was to compare the dose distribution generated from photon volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT), and intensity modulated carbon ion therapy (IMCIT) in the delivery of hypo-fractionated thoracic radiotherapy. METHODS AND MATERIALS: Ten selected patients who underwent thoracic particle therapy between 2015 and 2016 were re-planned to receive a relative biological effectiveness (RBE) weighted dose of 60 Gy (i.e., GyE) in 15 fractions delivered with VMAT, IMPT, or IMCIT with the same optimization criteria. Treatment plans were then compared. RESULTS: There were no significant differences in target volume dose coverage or dose conformity, except improved D95 was found with IMCIT compared with VMAT (p = 0.01), and IMCIT was significantly better than IMPT in all target volume dose parameters. Particle therapy led to more prominent lung sparing at low doses, and this result was most prominent with IMCIT (p < 0.05). Improved sparing of other thoracic organs at risk (OARs) was observed with particle therapy, and IMCIT further lowered the D1cc and D5cc for major blood vessels, as compared with IMPT (p = 0.01). CONCLUSION: Although it was comparable to VMAT, IMCIT led to significantly better tumor target dose coverage and conformity than did IMPT. Particle therapy, compared with VMAT, improved thoracic OAR sparing. IMCIT, compared with IMPT, may further improve normal lung and major blood vessel sparing under limited respiratory motion.