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

Abstract

The safety and efficacy of carbon-ion radiotherapy for advanced non-small cell lung cancer have not been established. We evaluated the clinical outcomes and dose-volume histogram parameters of carbon-ion radiotherapy compared with photon therapy in T2b–4N0M0 non-small cell lung cancer. Twenty-three patients were treated with carbon-ion radiotherapy between May 2011 and December 2015. Seven, 14, and 2 patients had T2b, T3, and T4, respectively. The median age was 78 (range, 53−91) years, with 22 male patients. There were 12 adenocarcinomas, 8 squamous cell carcinomas, 1 non-small cell lung carcinoma, and 2 clinically diagnosed lung cancers. Eleven patients were operable, and 12 patients were inoperable. Most patients (91%) were treated with carbon-ion radiotherapy of 60.0 Gy relative biological effectiveness (RBE) in 4 fractions or 64.0 Gy (RBE) in 16 fractions. Local control and overall survival rates were calculated. Dose-volume histogram parameters of normal lung and tumor coverages were compared between carbon-ion radiotherapy and photon therapies, including three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). The median follow-up of surviving patients was 25 months. Three patients experienced local recurrence, and the 2-year local control rate was 81%. During follow-up, 5 patients died of lung cancer, and 1 died of intercurrent disease. The 2-year overall survival rate was 70%. Operable patients had a better overall survival rate compared with inoperable patients (100% vs. 43%; P = 0.04). There was no grade ≥2 radiation pneumonitis. In dose-volume histogram analysis, carbon-ion radiotherapy had a significantly lower dose to normal lung and greater tumor coverage compared with photon therapies. Carbon-ion radiotherapy was effectively and safely performed for T2b–4N0M0 non-small cell lung cancer, and the dose distribution was superior compared with those for photon therapies. A Japanese multi-institutional study is ongoing to prospectively evaluate these patients and establish the use of carbon-ion radiotherapy.

Dosimetric evaluation of 4D‐CBCT reconstructed by Simultaneous Motion Estimation and Image Reconstruction (SMEIR) for carbon ion therapy of lung cancer

“…Radiation therapy delivered with heavy ions, such as carbon ions, has unique biological and physical advantages that may improve local control, while reducing radiation exposure to nontarget organs at risk such as the heart . Because of characteristics such as the Bragg peak, lower oxygen enhancement ratio (OER), and higher relative biological effectiveness, heavy ions could provide patient‐specific treatment options for lung cancer . Excellent dose localization for deep‐seated tumors with critical organ dose sparing can be achieved by treating with heavy ions .…”

“…The additional benefit that carbon ions have, over other charged particles like protons, is an increased biological effectiveness because of dense ionization and the resulting complex DNA damage . Carbon ion treatment can also improve tumor control without increasing toxicity and is considered a radical nonsurgical therapy that achieves high local control rates without severe adverse effects . Charged particle therapy, especially with carbon ions, is known to be effective for various treatment sites including lung and may even be a safer option than photon SBRT and protons in case of large or central tumors and poor pulmonary function …”

“…1,2 Because of characteristics such as the Bragg peak, lower oxygen enhancement ratio (OER), and higher relative biological effectiveness, heavy ions could provide patient-specific treatment options for lung cancer. 1,3 Excellent dose localization for deep-seated tumors with critical organ dose sparing can be achieved by treating with heavy ions. 4,5 The additional benefit that carbon ions have, over other charged particles like protons, is an increased biological effectiveness because of dense ionization and the resulting complex DNA damage.…”

“…6,7 Carbon ion treatment can also improve tumor control without increasing toxicity 8,9 and is considered a radical nonsurgical therapy that achieves high local control rates without severe adverse effects. 3 Charged particle therapy, especially with carbon ions, is known to be effective for various treatment sites including lung 10 and may even be a safer option than photon SBRT and protons in case of large or central tumors and poor pulmonary function. 11 Lung cancer is one of the leading causes of cancer-related deaths in both men and women worldwide 12 with respirationrelated motion providing the biggest challenge to an efficient treatment.…”

The Potential of Heavy-Ion Therapy to Improve Outcomes for Locally Advanced Non-Small Cell Lung Cancer

“…These advantages are particularly relevant to recent findings in RTOG 0617 where the importance of radiation conformity to prevent pneumonitis and reduce cardiac doses has been established ( 10 , 11 ). Just as proton therapy can reduce cardiac doses in comparison to photon therapy ( 12 ), heavy ions also have the potential to further reduce cardiac and pulmonary doses ( 9 , 13 ). First, the Bragg Peak can reduce radiation doses distal to the target to a far greater degree than photon irradiation.…”