- Present status and actual results
- Actual results of heavy ion radiotherapy
Actual results of heavy ion radiotherapy
Even with a short irradiation time, hope is possible for local control and increased survival of cancer
Treatment results: Five-year survival rates after heavy ion radiotherapy
HIMAC therapy began in 1994 at the National Institute of Radiological Sciences, and the good results can be seen in the five-year survival rates. These results can be regarded as highly favorable, considering that mainly inoperable cancer, advanced cancer, and recurrent cancer were targeted in the early clinical studies (Phase I/II).
Treatment results: Histological types for which heavy ion radiotherapy is effective
Effectiveness against the following tissue-type cancers has been confirmed.
- ･Adenocarcinomas (adenocarcinoma, adenoid cystic carcinoma, and hepatoma)
- ･Sarcomas (malignant melanoma, bone and soft tissue sarcoma, etc.)
Treatment period: Short-term hypofractionation is being verified.
Owing to its high dose concentration, heavy ion radiotherapy can have therapeutic effects despite a low irradiation fraction, and so short-term hypofractionation for various cancers is being studied. At present, the irradiation fraction with heavy ion radiotherapy can be approximately half that for conventional radiotherapy, when treating prostate cancer, uterine cancer (estimated irradiation fractions: 20/3-5 weeks), head and neck cancer, or bone and soft tissue tumors (estimated irradiation fractions: 16/4 weeks).
Adverse reactions: Serious adverse reactions are not observed
Heavy ion radiotherapy began in Japan in 1994. In the earliest clinical studies (Phase I/II), some patients with prostate cancer, cervical cancer, and esophageal cancer who were treated with high doses showed severe adverse reactions occurring in the digestive tract. Due to the subsequent clinical research, however, a safe dose and irradiation regimen were improved, and now such adverse reactions are not observed.
The results of heavy ion radiotherapy in Japan (June 1994 to February 2007, National Institute of Radiological Sciences)
| Protocol | Phase | Target | Irradiation regimen [fractions/weeks] | Number of patients | 3-year local control rate | Survival rate | Notes | |
|---|---|---|---|---|---|---|---|---|
| 3-year | 5-year | |||||||
| Head and neck–1+2 | I/II | Locally advanced cancer | 49–70/16–18/4–6 | 34 | 81% | 48% | 37% | * 4-year survival rate |
| Head and neck–3 (9602) |
II | Locally advanced cancer | 57.6/16/4 | 284 | 73% | 57% | 43% | |
| –Adenoid cystic carcinoma | 85 | 89% | 77% | 67% | ||||
| –Adenocarcinoma | 37 | 81% | 63% | 47% | ||||
| Head and neck–4 | –Malignant melanoma | 93 | 86% | 58% | 44% | |||
| Head and neck–5 | I/II | –Other | 69 | 50% | 42% | 33% | ||
| Sarcoma | 70.4/16/4 | 23 | 100% | 61% | 41%* | |||
| Malignant melanoma | 57.6/16/4 | 63 | 76% | 56% | 49%* | |||
| –Carbon beam + Chemotherapy | 54 | 83% | 59% | 59%* | ||||
| Skull base/Paracervical | I/II | Skull base/Paracervical | 48.0–60.8/16/4 | 42 | 93% | 94% | 88% | |
| - Chordoma | 25 | 89% | 100% | 88% | ||||
| Lung–1 (9303) | I/II | Stage I (lung field type) | 59.4–95.4/18/6 | 47 | 65% | 64% | 41%（61%）* | ( )* Cause-specific survival rate ** Dose escalation under |
| Lung–2 (9701) | I/II | Stage I (lung field type) | 72.0–79.2/9/3 | 34 | 91% | 55% | 40%（58%）* | |
| Lung–3 (9802) | II | Stage I (lung field type) | 72.0/9/3 | 50 | 95% | 66% | 50%（76%）* | |
| Lung–4 (0001) | I/II | Stage I (lung field type) | 52.8–60.0/4/1 | 79 | 90% | 62% | 36%（69%）* | |
| Lung–3+4 | - | Stage I (lung field type) | 4- and 9-fractionated irradiation | 129 | 93% | 64% | 43%（73%）* | |
| –IA (≤3 cm) | 71 | 99% | 78% | 55%（88%）* | ||||
| –IB (>3 cm) | 58 | 85% | 47% | 29%（51%）* | ||||
| Lung–5 (0201)** | I/II | Stage I (lung field type) | 36–50 Gy (single irradiation) | 151 | 83% | 76% | 55% | |
| Lung–6 (9801) | I/II | Stage I (hilus type) | 57.6–61.2/9/3 | 23 | 91% | 64% | 31%（68%） | |
| Lung–7 (9903) | I/II | Locally advanced cancer | 68–76/16/4 | 37 | 88% | 38% | 38%（56%） | |
| Liver-1 | I/II | T2–4M0N0 | 49.5–79.5/15/5 | 24（24） | 81% | 50% | 25% | ( ) Number of lesions |
| Liver-2 | I/II | T2–4M0N0 | 48–69.6/4–12/1–3 | 82（86） | 87% | 48% | 26% | |
| Liver-3 | II | T2–4M0N0 | 52.8/4/1 | 44（47） | 96% | 58% | 35% | |
| Liver-2+3 | - | 52.8 Gy/4 times | 52.8/4/1 | 61（69） | 94% | 57% | 34% | |
| 52.8 Gy/4 times (single, 3–5 cm) | 52.8/4/1 | 20（22） | 91% | 75% | 70% | |||
| Liver-4 | I/II | T2–4M0N0 | 32.0–38.8/2 fr/2 days | 36（36） | 84% | 77% | - | |
| Prostate-1 | I/II | B2–C | 54–72/20/5 | 35 | 97% | 94% | 89% | 5-year relapse-free survival, 91% |
| Prostate-2 | I/II | A2–C | 60–66/20/5 | 61 | 100% | 97% | 90% | 5-year relapse-free survival, 78% |
| Prostate-3 | II | T1C–C | 66/20/5 | 365 | 99% | 94% | 92% | 5-year relapse-free survival, 90% |
| Prostate-2+3 | All cases | A2–C | 66.0–63/20/5 57.6/16/4 51.6/12/3 |
1704 | 99% | 97% | 96% | 5-year relapse-free survival, 91% |
| –Low risk | 226 | 98% | 97% | 97% | 5-year relapse-free survival, 92% | |||
| –Moderate risk | 678 | 100% | 98% | 98% | 5-year relapse-free survival, 92% | |||
| –High risk | 800 | 100% | 95% | 94% | 5-year relapse-free survival, 87% | |||
| Uterus-1 | I/II | III–IVa (squamous cell carcinoma) | 53–72/24/6 | 30 | 49% | 40% | 37% | |
| Uterus-2+3 | I/II | II–IVa (squamous cell carcinoma) | 64–72/20–24/5 | 36 | 72% | 60% | 60% | |
| Uterine adenocarcinoma | I/II | II–IVa (adenocarcinoma) | 62.4–71.2/20/5 | 39 | 55% | 55% | 38% | |
| Bone and soft tissue-1 | I/II | Nonresectable | 52.8–73.6/16/4 | 57 | 63% | 47% | 36% | Including pelvic and paravertebral |
| Bone and soft tissue-2 | II | Nonresectable | 70.4–73.6/16/4 | 650 | 78% | 70% | 58% | |
| Bone and soft tissue-1+2 | - | Osteosarcoma | 52.8–73.6/16/4 | 78 | - | - | 33% | |
| Chordoma | 52.8–73.6/16/4 | 214 | 92% | 93% | 80% | |||
| Rectum-1 | I/II | Postoperative recurrence in the pelvis | 67.2–73.6/16/4 | 229 | 90% | 67% | 45% | |
| Pancreas: Preoperative–1 | I/II | Resectable All |
44.8–48.0/16/4 | 22 | - | 23.8%（36.3）* | * 2-year survival rate ( ) Resection case |
|
| Preoperative–2 | I/II | Resectable All |
30.0–36.8/8/2 | 35 | 89% | 56% | 40% | |
| Locally advanced | I/II | Nonresectable All |
38.4–55.2/12/3 | 82 | 36% | 36% | 36%* | |
| Esophagus: Preoperative With chemotherapy |
I/II | Stage II・III (Excluding T4) | 33.6～35.2/8/2 | 5 | - | 100%* | * 2-year survival rate | |
| Complete cure by irradiation only | I/II | T1bN0 | 43.2～50.4/12/3 | 29 | - | 84% | 78% | |
| Protocol Name | Registration No. |
Phase | Treatment-favorable disease and fractions (number of fractions/period) | No. of Patients | 3-year Local Control Rate Survival Rate |
Survival Rate | Remarks | ||
|---|---|---|---|---|---|---|---|---|---|
| 3-year | 5-year | ||||||||
| ○ | Head and neck tumor III | (9602) | II | 16/4 weeks | 520 | 80% | 71% | 57% | Advanced medical care From 2003 |
| ○ | Head and neck tumor IV (Bone and soft tissue) | (0006) | I/II | 16/4 weeks | 53 | 84% | 72% | 56% | Advanced medical care From 2008 Covered by insurance from April 2016 |
| ○ | Head and neck tumor V (Malignant melanoma) | (0007) | II | 16/4 weeks With chemotherapy |
140 | 84% | 65% | 51% | Advanced medical care From 2003 |
| ○ | Non-small lung cancer III | (9801) | I/II | Central type 9/3 weeks |
23 | 91% | 64% | 31% | Advanced medical care From 2003 |
| ○ | Non-small lung cancer V | (9903) | I/II | Locally advanced 16/4 weeks |
37 | 93% | 38% | 32% | Advanced medical care From 2003 |
| Non-small lung cancer Ⅵ | (0001) | I/II | Lung field peripheral type 4/1 week |
79 | 90% | 62% | 36% | ||
| ○ | Non-small lung cancer Ⅷ | (0201) | I/II | Lung field type (48 Gy to 50 Gy) 1/1 day |
20 | 95% | 85% | 69% | Advanced medical care From 2012 |
| Non-small lung cancer IX | (0503) | I/II | Hilar and near-hilar type 12/3 weeks |
18 | 100% | 60% | 34% | ||
| Hepatoma | (9401) | I/II | 15/5 weeks | 24 | 75% | 50% | 19% | ||
| Hepatoma II | (9603) | I/II | 12/3 weeks → 8/2 weeks → 4/1 week | 82 | 82% | 45% | 25% | ||
| Hepatoma III | (0004) | II | 4/1 week | 44 | 92% | 48% | 24% | ||
| ○ | Hepatoma IV | (0202) | I/II | 2/2 days | 144 | 81% | 61% | 37% | Advanced medical care From 2006 |
| Metastatic liver cancer | (0506) | I/II | 1/1 day | 28 | 51% | 80% | 53% | MST65M | |
| Prostate cancer | (9402) | I/II | Heavy ion + Hormone | 35 | 97% | 94% | 89% | ||
| Prostate cancer II | (9703) | I/II | Heavy ion alone and Heavy ion + hormone | 61 | 100% | 97% | 90% | ||
| ○ | Prostate cancer III | (9904) | II | 20/5 weeks → 16/4 weeks → 12/3 weeks | 1704 | 99% | 97% | 96% | Advanced medical care From 2003 |
| ○ | Prostate cancer V | (1002) | I/II | 12/3 weeks | 457 | 100% | 98% | Advanced medical care From 2013 |
|
| Kidney cancer I | (1203) | I/II | 12/3 weeks | 7 | Just started | ||||
| Cervical cancer | (9403) | I/II | Equally divided | 30 | 49% | 40% | 37% | ||
| Cervical cancer II | (9702) | I/II | Increase of dosage to primary region | 36 | 72% | 60% | 60% | ||
| ○ | Cervical cancer III | (9902) | I/II | 20/5 weeks | Advanced medical care From 2014 |
||||
| ○ | Uterine cancer IV | (0508) | I/II | 20/5 weeks | 26 | 84% | 68% | 68% | Advanced medical care From 2012 |
| Uterine cancer VI | (1302) | I/II | 20/5 weeks With chemotherapy |
22 | Clinical test From June 2013 Advanced medical care From April 2016 |
||||
| ○ | Uterine adenocarcinoma | (9704) | I/II | 12/3 weeks + 8/2 weeks (for boost) |
67 | 55% | 55% | 38% | Advanced medical care From 2012 |
| ○ | Uterine adenocarcinoma II | (1001) | I/II | 12/3 weeks + 8/2 weeks (for boost) |
19 | Advanced medical care From 2014 |
|||
| Mammary gland cancer I | (1301) | I/II | 4/1 week | 3 | Clinical test From 2013 |
||||
| Bone and soft tissue tumor | (9501) | I/II | 16/4 weeks | 57 | 63% | 47% | 36% | ||
| ○ | Bone and soft tissue tumor II | (9901) | II | 16/4 weeks | 650 | 78% | 70% | 58% | Advanced medical care From 2003 |
| Esophageal cancer (Before operation) |
(9502) | I/II | 20/5 weeks | 7 | *14% | *Two-year survival rate | |||
| Esophageal cancer (Completely cured) |
(9503) | I/II | 24/6 weeks | 14 | *7% | *Two-year survival rate | |||
| Esophageal cancer (After operation) |
(9905) | I/II | 12/3 weeks Not excised |
2 | |||||
| Esophageal cancer (Short term before operation) |
(0301) | I/II | 8/2 weeks | 31 | 74% | 59% | |||
| Esophageal cancer With chemotherapy (Before operation) |
(1206) | I/II | 8/2 weeks With chemotherapy |
8 | *100% | From Sep. 2012 *Two-year survival rate |
|||
| Esophageal cancer I (Completely cured) | (0701) | I/II | 12/3 weeks | 30 | 75% | 84% | 78% | ||
| ○ | Rectal cancer (Recurrence after operation) |
(0003) | I/II | 16/4 weeks | 229 | 90% | 67% | 45% | Advanced medical care From 2004 |
| ○ | Skull base tumor | (9601) | I/II | 16/4 weeks | 90 | 92% | 92% | 82% | Partial coverage by insurance From April 2016 |
| Pancreatic cancer I (Before operation) |
(9906) | I/II | 16/4 weeks | 22 | *86% | *20% | *2-year control and survival rate | ||
| ○ | Pancreatic cancer II (Before operation) |
(0203) | I/II | 8/2 weeks | 35 | 89% | 56% | 40% | Advanced medical care From 2011 |
| Pancreatic cancer V (Before operation) |
(1205) | I | 8/2 weeks With chemotherapy |
9 | From September 2012 | ||||
| Pancreatic cancer III | (0204) | I/II | Locally advanced 12/3 weeks |
47 | *70% | *11% | *2-year control and survival rate | ||
| ○ | Pancreatic cancer IV With chemotherapy (Completely cured) |
(0513) | I/II | Locally advanced 12/3 weeks |
76 | 36% | 34% | Advanced medical care From 2012 |
|
| ○ | Ocular tumor II | (0002)+ (0002(2)) |
I/II | Heavy ion 5/8 days |
175 | 95% | 90% | 82% | Advanced medical care From 2004 |
| ○ | Lachrymal gland tumor I | (0102) | I/II | 12/3 weeks | 31 | 72% | 79% | 70% | Advanced medical care From 2011 |
○ Protocol as advanced medical care
[Reference data]
Hirohiko Tsujii et al. Radiological Sciences. 2007;50(7):4–19.
"Results of Research to Date at NIRS" (Past and Future of Heavy Ion Radiotherapy: HIMAC 20th Anniversary Lecture)
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