Carbon-ion radiotherapy for lung cancer: Current status and future directions

━━ Recent advances in high-precision photon radiotherapy represented by stereotactic body radiotherapy (SBRT) and intensity-modulated radiotherapy (IMRT) have helped improve the treatment outcomes of lung cancers, both in disease control and side effect reduction, for normal tissues, including lung and heart, compared with conventional radiotherapy. However, photon radiotherapy is inherently limited by the physical properties of the photon beam, which result in unavoidable low to moderate irradiation to normal tissues, even at substantial distances from the tumor. The unavoidable spread of radiation sometimes leads to acute or late side effects. Efforts have been made to develop charged particle radiotherapy as an effective and less-invasive new radiation modality. Charged particle radiotherapy has the physical advantage of the dose being focused on the tumor with only minimal exposure of the surrounding normal tissues. This physical advantage of improved dose localization helps to reduce the toxicity of normal tissue, such as lung and heart, even further. Carbon ion, which is categorized as a heavy ion, not only has favorable physical properties but also a biologic advantage compared with photons and protons. Carbon ion has a strong cell-killing effect, and this effect is not markedly influenced by the oxygen concentration or the cell cycle. These physical and biological advantages of carbon-ion radiotherapy have been confirmed by a number of clinical studies, although many of these are single-institutional studies. Many multi-institutional studies for carbon-ion radiotherapy are now being vigorously conducted, including studies in lung cancer patients. The clinical superiority of carbon-ion radiotherapy to conventional techniques is expected to become clearer in the near future. (JJLC. 2017;57:723-732) KEY WORDS━━ Lung cancer, Non-small-cell lung cancer, Radiotherapy, Carbon-ion radiotherapy, Less-invasive Corresponding author: Yoshiyuki Shioyama. 要旨━━体幹部定位放射線治療(SBRT)や強度変調放 射線治療(IMRT)に代表される線量集中性を向上させた 高精度エックス線治療が急速に普及し,肺癌領域におい ても,I期肺癌に対する高線量局所照射の有用性が確認 されるとともに,局所進行期肺癌においては心毒性など の低減に有効な可能性が示唆されている.現在,さらな る治療効果の向上を目指した線量増加などの治療法開発 が進められている.しかし一方で,放射線治療の対象は, 心肺予備能の低い患者や高齢者を対象とすることが多 く,肺臓炎,心毒性などの有害事象には十分留意する必 要もあるが,局所進行期肺癌に対する第 III 相比較試験 の結果,線量増加は有害事象も避けられず,生存率改善 に寄与しないことが判明するなど,エックス線治療の限 界もうかがわせる.陽子線や炭素イオン線を用いた荷電 粒子線治療は,本格的な臨床応用,普及の段階に入り, さらなる有害事象の軽減ならびに治療効果向上を可能と する新たな放射線治療として期待されている.荷電粒子 線の最大の特徴は,ある一定の深さで高線量域(Bragg peak:ブラッグ・ピーク)を形成したうえで止まるとい う特徴を有し,このピークを腫瘍の位置や大きさに合わ 1公益財団法人佐賀国際重粒子線がん治療財団九州国際重粒子線 がん治療センター. 論文責任者:塩山善之. (肺癌.2017;57:723-732) 2017 The Japan Lung Cancer Society Carbon-ion Radiotherapy for Lung Cancer―Shioyama et al 724 Japanese Journal of Lung Cancer―Vol 57, No 6, Oct 20, 2017―www.haigan.gr.jp せて調節することで標的に集中した高線量領域を形成で きることである.そのため,粒子線治療では少ない方向 からの照射によって癌病巣へ線量を集中することがで き,中低線量域の拡がりを最小限に抑えることが可能と なり,肺臓炎や心毒性などの有害事象リスクの軽減に寄 与する.また,炭素イオン線においては殺細胞効果が高 く,低酸素状態や細胞周期などの影響を受けにくいとい う生物学的特徴もある.このような粒子線治療の理論的 有用性は,単施設による検討ではあるものの,数々の臨 床研究によって裏づけられてきた.現在は,多施設共同 臨床研究も精力的に行われており,臨床的有用性に関す るエビデンスが今後さらに明確となることが期待されて いる. 索引用語━━肺癌,非小細胞肺癌,放射線治療,重粒子 線治療,低侵襲

[1]  Y. Shioyama,et al.  Carbon-ion radiotherapy for patients with advanced stage non–small-cell lung cancer at multicenters , 2017, Journal of radiation research.

[2]  K. Shirai,et al.  Clinical outcomes using carbon-ion radiotherapy and dose-volume histogram comparison between carbon-ion radiotherapy and photon therapy for T2b-4N0M0 non-small cell lung cancer—A pilot study , 2017, PloS one.

[3]  H. Tsujii,et al.  A Dose Escalation Clinical Trial of Single‐Fraction Carbon Ion Radiotherapy for Peripheral Stage I Non–Small Cell Lung Cancer , 2017, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[4]  Y. Shioyama,et al.  Multi-institutional Retrospective Study of Carbon Ion Radiation Therapy for Stage I Non-Small Cell Lung Cancer: Japan Carbon Ion Radiation Oncology Study Group , 2016 .

[5]  T. Fujisawa,et al.  Single-Fraction Carbon-Ion Radiation Therapy for Patients 80 Years of Age and Older With Stage I Non-Small Cell Lung Cancer. , 2016, International journal of radiation oncology, biology, physics.

[6]  R. Onimaru,et al.  Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403. , 2015, International journal of radiation oncology, biology, physics.

[7]  H. Honda,et al.  Impact of Interstitial Changes on Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Lung Cancer. , 2015, Anticancer research.

[8]  T. Fujisawa,et al.  A prospective nonrandomized phase I/II study of carbon ion radiotherapy in a favorable subset of locally advanced non–small cell lung cancer (NSCLC) , 2015, Cancer.

[9]  K. Shirai,et al.  Dosimetric analysis between carbon ion radiotherapy and stereotactic body radiotherapy in stage I lung cancer. , 2014, Anticancer research.

[10]  James M. Galvin,et al.  RTOG 0618: Stereotactic body radiation therapy (SBRT) to treat operable early-stage lung cancer patients. , 2013 .

[11]  R. Okayasu,et al.  Effects of carbon ion beam on putative colon cancer stem cells and its comparison with X-rays. , 2011, Cancer research.

[12]  Yuta Shibamoto,et al.  High‐dose proton therapy and carbon‐ion therapy for stage I nonsmall cell lung cancer , 2010, Cancer.

[13]  Umberto Ricardi,et al.  Stereotactic body radiation therapy for early stage non-small cell lung cancer: results of a prospective trial. , 2010, Lung cancer.

[14]  Andrea Bezjak,et al.  Stereotactic body radiation therapy for inoperable early stage lung cancer. , 2010, JAMA.

[15]  Lech Papiez,et al.  Stereotactic body radiation therapy for early-stage non-small-cell lung carcinoma: four-year results of a prospective phase II study. , 2009, International journal of radiation oncology, biology, physics.

[16]  Y. Akino,et al.  Carbon-ion beam irradiation effectively suppresses migration and invasion of human non-small-cell lung cancer cells. , 2009, International journal of radiation oncology, biology, physics.

[17]  Susumu Kandatsu,et al.  Carbon Ion Radiotherapy for Stage I Non-small Cell Lung Cancer Using a Regimen of Four Fractions during 1 Week , 2007, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[18]  H. Tsujii,et al.  Curative treatment of Stage I non-small-cell lung cancer with carbon ion beams using a hypofractionated regimen. , 2007, International journal of radiation oncology, biology, physics.

[19]  N. Kobayashi,et al.  Accelerated reoxygenation of a murine fibrosarcoma after carbon-ion radiation. , 1999, International journal of radiation biology.