Treatment with heavy charged particles: Systematic review of clinical data and current clinical (comparative) trials

Figures & data

Table I. Carbon ion radiotherapy for brain and skull base tumours.

Publication	Number of patients	Tumour	Treatment	Median follow-up	Local control	Overall survival
Combs et al., 2013	70	Meningioma	Proton; Carbon ion; Photon + Carbon boost	6 (range 2–22 months)	92% local control at 17 months (high-risk meningioma; Carbon boost for primary RT)	100%
Rieken et al., 2012	26 Carbon	Glioma, meningioma	50 Gy Photon, Carbon ion boost 18 Gy E/6 fractions	Not reported	–	–
Schulz-Ertner et al., 2007	54	Skull base chondrosarcoma	60 Gy E, 20 fractions	33 (range 3–82 months)	96.2% at 3 and 89.8% at 4 years	98.2% at 5 years
Schulz-Ertner et al., 2007	96	Skull base chordoma	60 Gy E, 20 fractions	31 (range 3–91 months)	70% at 5 years	91.8% at 3 and 88.5% at 5 years
Tsujii et al., 2012	47	Skull base chordoma	60.8 Gy E, 16 fractions	3.7 years	88% at 5 and 80% at 10 years	87% at 5 years
Mizoe et al., 2009	33	Skull base chordoma	Dose escalation: 16 fractions/4 weeks, 48–60.8 Gy E	4.7 years	85.1% at 5 years, 63.8% at 10 years	87.7% at 5 years, 67% at 10 years
Mizoe et al., 2007	48	Anaplastic glioma; Glioblastoma	50 Gy E Photons; Carbon boost 16.8–24.8 Gy E	Not reported	Median progression-free survival: 7 months for glioblastoma, 15 months for anaplastic astrocytoma	Median overall survival: 17 months for glioblastoma, 35 months for anaplastic astrocytoma

Table II. Carbon ion radiotherapy for tumors in the head-and-neck region.

Publication	Number of patients	Tumour	Treatment	Median follow-up	Local control	Overall survival
Jingo et al., 2012	27	Head-and-neck sarcoma	70.4 Gy E/16 fractions	37 months (range 4.1–73 months)	91.8% at 3 years	74.1% at 3 years
Schulz-Ertner et al., 2005	29	Adenoid-cystic-carcinoma	Photon 50 Gy E, Carbon Boost 18 Gy E/6 fractions	16 months (2–60 months)	78% at 5 years	76% at 5 years
Yanagi et al., 2009	102	Mucosal melanoma	Carbon ions	49.2 months (range 16.8–108.5)	84.1% at 5 years	27% at 5 years
Mizoe et al., 2012	236	Malignant melanoma, adenocarcinoma, squamous cell carcinoma, adenoid-cystic carcinoma	Carbon ion radiotherapy	54 months (mean; range 3–162 months)	5-years: 75% for malignant melanoma, 73% for adenoid cystic carcinoma, 73% for adenocarcinoma, 61% for papillary adenocarcinoma, 61% for squamous cell carcinoma and 24% for the 14 with sarcomas	5-years: 68% for adenoid cystic carcinoma, 56% for adenocarcinoma, 35% for malignant melanoma

Table III. Carbon ion radiotherapy for lung cancer.

Publication	Number of patients	Tumor	Treatment	Median follow-up	Local control	Overall survival
Miyamoto et al., 2003	81	NSCLC	Carbon ion 59.4–95.4 Gy E/18 fractions/6 weeks 68.4–79.2 Gy E/9 fractions	52.6 months (minimum 30 months)	59% at 5 years	42% at 5 years
Miyamoto et al., 2007	50	NSCLC	Carbon ion 72 Gy E/9 fractions/3 weeks	59.2 months (range 6–83 months)	95% at 5 years	50% at 5 years
Miyamoto et al., 2007	79	NSCLC	Carbon ion T1: 52.8 Gy E/4 fractions/1 week T2: 60 Gy E/4 fractions/1 week	38.6 months (range 2.5–72.2 months)	T1: 98% at 5 years T2: 80% at 5 years	45% at 5 years
Iwata et al., 2013	27	NSCLC	60 Gy E/10 fractions; 52.8 Gy E/4 fractions; 66 Gy E/10 fractions; 80 Gy E/20 fractions	51 months (range 24–103 months)	75% at 4 years	58% at 4 years
Yamamoto et al., 2012	91	Metastatic lung tumors	40–80 Gy E, 1–16 fractions	2.3 years (range 0.3–13.1 years)	91.9% at 2 years	71.2% at 2 years

Table IV. Carbon ion radiotherapy for gastrointestinal tumors.

Publication	Number of patients	Tumor	Treatment	Median follow-up	Local control	Overall survival
Akutsu et al., 2012	31	Thoracic oesophageal cancer	28.8–36.8 Gy E	Not reported	38.7%: clinical complete response (CR); 41.9% a partial response. 38.7% pathological CR	Stage I: 81% at 3 years and 61% at 5 years Stage II: 85% at 3 years and 77% at 5 years Stage III: 43% at 3 years and 29% at 5 years
Shinoto et al., 2013	26	Pancreatic cancer	Carbon ion 30–36.8 Gy E	33.8 months (survivors)	–	42% at 5 years; 52% at 5 years after surgery

Table V. Carbon ion radiotherapy for hepatocellular carcinoma (HCC).

Publication	Number of patients	Tumor	Treatment	Median follow-up	Local control	Overall survival
Kato et al., 2004	69	HCC	Carbon ions 52.8 Gy E/4 fractions	71 months (range 63–83 months)	94% at 3 and 81% at 5 years	33% at 5 years
Imada et al., 2010	40	HCC	Carbon ions 42.8–45 Gy E/2 fractions	34 months (range 6–90 months)	87.8% at 5 years (porta hepatis) 95.7% at 5 years (non-porta hepatis)	22.2% at 5 years (porta hepatis) 34.8% at 5 years (non-porta hepatis)

Table VI. Carbon ion radiotherapy for prostate cancer, gynaecological malignancies and recurrent rectal cancer.

Publication	Number of patients	Tumor	Treatment	Median follow-up	Local control	Overall survival
Okada et al., 2012	740	Prostate cancer	57.6 Gy E, 16–20 fractions	59.3 months	89.7% at 5 years (biochemical-relapse free): 16 fractions – 88.5%; 20 fractions – 90.2%	95.2% at 5 years
Shimazaki et al., 2012	728	Prostate cancer	Protocol 9402: 54–72 Gy E; Protocol 9703: 60–66 Gy E; Protocol 9903-1.2; fixed dose 66 Gy E; Protocol 9904-03: fixed dose 57.6 Gy E	87 months (range 16–153 months)	Biochemical failure rates: 12%, 6%, and 15% in low-, intermediate- and high-risk patients	–
Ishikawa et al., 2012; Tsujii et al., 2011	855	Prostate cancer	Carbon + Hormones: 66.63 Gy E/20 fractions; 57.6 Gy E/16 fractions	Minimum 6 months	–	87–99% at 5 years (Group 2–4)

Table VII. Carbon ion radiotherapy for soft-tissue sarcomas as well as chordomas and chondrosarcomas of the trunk and the extremities.

Publication	Number of patients	Tumor	Treatment	Median follow-up	Local control	Overall survival
Matsunobu et al., 2012	78	Osteosarcoma of the trunk	Carbon ion	Minimum follow-up: 14 months	–	32% at 5 years
Imai et al., 2009	95	Sacral chordoma	Carbon ion	42 (range 13–112)	88% at 5 years	86% at 5 and 74% at 10 years