Carbon Ion Radiotherapy in Hypo-Fractionation Regimen and Single Dose for Stage I Non-small-Cell Lung Cancer

  • T. Miyamoto
  • N. Yamamoto
  • M. Baba
  • T. Kamada
Part of the Medical Radiology book series (MEDRAD)


It has been more than one decade since we started carbon ion radiation therapy (CIRT) for non-small-cell lung cancer (NSCLC) in November 1994. From 1994 to 1999, we conducted a phase I/II clinical trial for stage I NSCLC with CIRT and demonstrated an optimal dose of 90 GyE in 18 fractions over 6 weeks and 72 GyE in 9 fractions over 3 weeks for achieving more than 90% local control with minimal pulmonary damage. In the following phase II study from 1999 to 2003, the total dose was fixed at 72 GyE in 9 fractions over 3 weeks and at 52.8 GyE for stage IA and at 60 GyE for stage 1B in 4 fractions over 1 week. Targets were irradiated from four oblique directions. A respiratory-gated irradiation system was used for all irradiation sessions. On these two phase II schedules combined, the 5-year local control rate for 131 primary tumors of 129 patients was 91.5%. The local control rate for T1 and T2 tumors was 96.3 and 84.7%, respectively. While there was significant difference in control rate between T1 and T2, there was no significant difference in histology between squamous and non-squamous type. The 5-year cause-specific survival rate of the patients was 67.0% (IA: 84.4, IB: 43.7), and their overall survival was 45.3% (IA: 53.9, 1B: 34.2). No adverse effects greater than grade III occurred in the lung. In this way, the treatment period and fractionation were shortened and lessened from 18 fractions over 6 weeks to 9 fractions over 3 weeks and further to 4 fractions over one week. Finally it reached a single dose. Since 2003, 210 patients have already been treated with CIRT in single dose increasing 28, 32, 34, 36, 38, 40, 42, 44, 46, and 48 GyE. Compared with the previous fractionation regimen, CIRT in single-dose is demonstrating low morbidity and high QOL. The 5-year local control rate of 131 tumors with doses more than 36 GyE was higher than 80%. The 5-year cause-specific and overall survival rate of 131 patients were 1.5 and 52.6%, respectively. Of the whole evaluate, we will finally recommend that CIRT in single dose is the best for the treatment of the peripheral type of stage I NSCLC.


Local Control Rate Linear Energy Transfer Radiation Pneumonitis Lung Cancer Death Digital Reconstructed Radiograph 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank the following doctors who participated in this long-term study: Hideki Nisimura, Masasi Koto, Toshiyuki Sugawara, Tomoyasu Yasiro, Naoki Hirasawa, Kenji Kagei, Mio Nakajima, Toshio Sugane, Kyousan Yosikawa, Susumu Kandatsu, Hidefumi Ezawa and Kennosuke Kadono. We also thank the doctors who constantly supported and advised: Hirohiko Tujii, Jun-etsu Mizoe, Suhou Sakata, Kozo Morita, Takeshi Iinuma, and Toru Matzumoto, and Takehiko Fujisawa of the Working group for lung cancer.


  1. ACRIN (2010) For immediate release. Screening of people at high-risk for lung cancer with low dose CT significantly reduces lung cancer deathGoogle Scholar
  2. Bush DA, Slater JD, Bonnet R et al (1999) Proton-beam radiotherapy for early stage lung cancer. Chest 116:1313–1319PubMedCrossRefGoogle Scholar
  3. Endo M, Koyama-Ito H, Minohara S et al (1996) Hiplan-a heavy ion treatment planning system at HIMAC. J Jpn Soc Ther Radiol Oncol 8:231–238Google Scholar
  4. Harpole DH, Herndon JE, Yung WG et al (1995) Stage I nonsmall cell lung cancer. A multivariate analysis of treatment methods and patterns of recurrence. Cancer 76:787–796PubMedCrossRefGoogle Scholar
  5. Hirao Y, Ogawa H, Yamada S et al (1992) Heavy ion synchrotron for medical use—HIMAC project at NIRS-JAPAN. Nucl Phys A 538:541c–550cCrossRefGoogle Scholar
  6. Jeremic B, Classen J, Bamberg M (2002) Radiotherapy alone technically operable, medically inoperable, early-stage (I/II) non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 54:119–130PubMedCrossRefGoogle Scholar
  7. Kanai T, Furusawa Y, Fukutsu K et al (1997) Irradiation of mixed beam and design of spread out Bragg peak for heavy-ion radiotherapy. Radiat Res 147:78–85PubMedCrossRefGoogle Scholar
  8. Kanai T, Endo M, Minohara S et al (1999) Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy. Int J Radiat Oncol Biol Phys 44:201–210PubMedCrossRefGoogle Scholar
  9. Koto M, Miyamoto T, Yamamoto N, et al (2004) Local control and recurrence of stage I non-small cell lung cancer after carbon ion radiotherapy. Radiother Oncol 71:147–156 PubMedCrossRefGoogle Scholar
  10. Ludwig Seitz, Hermann Wintz (1920) Unsere Methode der Rontgen-Tiefentherapie und ihre ihre Erforge. Verlag von Uaban & Schwarzenberg, Berlin N24, Wien I, 1920Google Scholar
  11. Martini N, Bains MS, Burt ME et al (1995) Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 109:120–129 PubMedCrossRefGoogle Scholar
  12. Minohara S, Kanai T, Endo M et al (2000) Respiratory gated irradiation system for heavy ion radiotherapy. Int J Radiat Oncol Biol Phys 47:1097–1103PubMedCrossRefGoogle Scholar
  13. Miyamoto T (2004) Carbon beam therapy for lung cancer. Jpn J Lung Cancer 44:741–751CrossRefGoogle Scholar
  14. Miyamoto T, Yamamoto N, Nishimura H et al (2003) Carbon ion radiotherapy for stage I non-small-cell lung cancer. Radiother Oncol 66:127–140PubMedCrossRefGoogle Scholar
  15. Miyamoto T, Baba M, Yamamoto N, Koto M et al (2007a) Curative treatment of stage I non-small-cell lung cancer with carbon ion beams using a hypo-fractionated. Int J Radiat. Oncol Biol Phys 67:750–758PubMedCrossRefGoogle Scholar
  16. Miyamoto T, Baba M, Yamamoto N, Sugane T et al (2007b) Carbon ion radiotherapy for stage I non-small-cell lung cancer using a regimen of four fraction during 1 week. J Thorac Oncol 2:916–926PubMedCrossRefGoogle Scholar
  17. Mountain CF (1997) Revisions in the international system for staging lung cancer. Chest 111:1710–1717 PubMedCrossRefGoogle Scholar
  18. Nagata Y, Takayama K, Matuo Y et al (2005) Clinical outcomes of a phase I/II study of 48 Gy of stereotactic body radiotherapy in 4 fractions for primary lung cancer using a stereotactic body frame. Int J Radiat Oncol Biol Phys 63:1427–1431PubMedCrossRefGoogle Scholar
  19. Nakajima T, Yasufuku K, Fujiwara T et al (2008) Endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis of intrapulmonary lesions. J Thorac Oncol 3(9):985–988PubMedCrossRefGoogle Scholar
  20. Naruke T, Tsuchiya R, Kondo H et al (2001) Prognosis and survival after resection for bronchogenic carcinoma based on the 1997 TNM-staging classification: the Japanese experience. Ann Thorac Surg 71:1759–1764PubMedCrossRefGoogle Scholar
  21. Onishi H, Araki T, Shirato H et al (2004) Stereotactic hypofractionated high-dose irradiation for stageI nonsmall cell lung carcinoma. Cancer 101:1623–1631PubMedCrossRefGoogle Scholar
  22. Shioyama Y, Tokuuye K, Okumuma T et al (2003) Clinical evaluation of proton radiotherapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 56:7–13PubMedCrossRefGoogle Scholar
  23. Iinuma T, Miyamoto T (2006) A new paradigm for medical practice for lung cancer: A combination of lung cancer screening by LSCT (lung cancer screening CT) and radiosurgery by single-dose carbon irradiation. JJLC 46:309–314CrossRefGoogle Scholar
  24. Yamamoto N, Miyamoto T, Nishimura H et al (2003) Preoperative carbon ion radiotherapy for non-small-cell lung cancer with chest wall invasion-pathological findings concerning tum response and radiation induced lung injury in the resected organs. Lung Cancer 42:87–95PubMedCrossRefGoogle Scholar
  25. Yasukawa T, Yamaguchi Y, Aoyagi H et al (1996) Diagnosis of hilar and mediastinal lymph node metastasis of lung cancer by positoron emission tomography using 11C-methionine. Jpn J Lung Cancer 36:919–926CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Research Center Hospital for Charged Particle TherapyNational Institute of Radiological Sciences (NIRS)ChibaJapan

Personalised recommendations