Table 4.
Review of carbon ion therapy pancreatic cancer clinical studies (2000–current).
| Author | Disease | Sample Size | Study Design | Chemotherapy | Total Dose and Fractionation | Acute Side Effects Criteria for Adverse Events Version |
Late Side Effects | MST Months | 1-year OS Rate | 2-year OS Rate | PFS | FFLP | Median FU Period Months (Range) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Shinoto, et al. [68] Φ | Unresectable LAPC | 64 | Retrospective, single institute. | Gemcitabine or S-1 | 55.2 Gy (RBE) in 12 | Grade 2 = 26% Grade 3 = 6% V4 [99] |
Grade 2 = 6% Grade ≥3 = 0% |
25.1 | 84% | 53% | 2-year = 23% | 2-year LC = 82% | 24.4 (5.1–46.1) |
| Kawashiro, et al. [17] Φ | Unresectable LAPC | 72 | Retrospective, non-randomized, multi- institutional study. | 68% received concurrent gemcitabine (1000 mg/m2 weekly) | 52.8 Gy (RBE) or 55.2 Gy (RBE) in 12 | Grade 2 = 44% Grade 3 = 28.1% Grade 4 = 1% V4 [99] |
Grade 1 = 99% Grade 2 = 0% Grade 3 = 1% |
21.5 | 73% | 46% | Local recurrence incidence at 1- year and 2- year = 16% and 24% | Distant metastasis-free survival at 1-year and 2-year = 41% and 28%. Median distant metastasis-free survival = 8.3 months |
13.6 (2.8–37.9) For surviving patients 14.7 (3.2–37.5) |
| Combs, et al. [102] | LAPC | 33 | Prospective, phase I, single institute. | Concurrent gemcitabine (300 mg/m2) | 45–53 GyE in 3 | PHOENIX-01 trial withdrawn (before enrolment). | |||||||
| Shinoto, et al. [67] Φ | Unresectable LAPC | 72 | Prospective, single institute. | Concurrent gemcitabine (400–100 mg/m2) on days 1,8 and 15. | 43.2–55.2 GyE in 12 | Grade 1 ≥ GI ulcer = 15% Grade ≥ 3 haematologic toxicities = 53% V3 [90] |
Grade 3 = 1.4% | 19.6 | 73% | 35% overall For ≥ 45.6 GyE group 2-year OS = 48% |
The median time to progression was 5.9 months. 86% experienced distant metastases |
1-year = 92% 2-year = 83% |
≥ 2 years |
| Shinoto, et al. [70] Φ | Potentially resectable LAPC | 26 | Phase 1, single institute. | NR | 30–36.8 GyE in 8 | Grade 1 = 3.8% Grade 3 = 3.8% V2 [93] |
Grade 4 = 3.8% | 18.6 | 69% For patient who underwent surgical resection = 81% |
NR | No patients experienced local recurrence. distant metastasis in 65% of patients |
81% of patients underwent surgery. 5-year survival rates for all 26 patients and for those who underwent surgery were 42% and 52% |
33.8 |
| Shinoto, et al. [103] | LAPC | 45 | Phase II, single institute. | Concurrent S-1 administered orally twice a day (80 mg/m2) for 28 days every 6 weeks. | 55.2 GyE in 12 | Currently recruiting | |||||||
RBE: relative biological effectiveness, GI: gastrointestinal, MST: median survival time, OS: overall survival, RT: radiation therapy, FU: follow up, NR: not reported, LAPC: locally advanced pancreatic cancer, PFS: Progression-free survival. Φ: OS measured from start of treatment. Dose to target volumes: RBE: relative biological effective dose. GyE: Gray equivalents (carbon physical dose (in Gray) × (RBE)).