Status of particle therapy for lung cancer

Figures & data

Figure 1. Proton Beam dosimetry is sensitive to lung density changes. A) Axial CT imaging of the proton beam dose distribution of the original plan for the treatment of a patient with stage III NSCLC. During the second week of a routine weekly verification resimulation CT, there was evidence of atelectasis in the right upper lobe (B). C) DVH analysis of the initial plan compared to the dosimetric alteration due to the atelectasis. Except for the brachial plexus, there was an overall increase in mean and absolute doses to all the indicated normal structures (esophagus, heart, spinal cord) and a slight under dosing of the ITV and PTV. Compared to D, panel E is an adaptive plan that was done in order to improve tumor coverage. However in order to achieve this, there had to be a compromise in the dose to normal tissues with a slightly increased doses compared to the initial plan. This is reflective in the DVH in panel F.

Figure 2. Proton Beam dosimetry is sensitive to tumor response to treatment. A) Axial CT imaging of a proton beam dose distribution from the original plan in a patient with T3N2 adenocarcinoma. B-C) During week 4 of routine repeat CT simulation, there was clear evidence of response to therapy with necrotic hollowing of the tumor center. This alters the proton beam dose distribution, with increased dose to adjacent normal structures but without a compromise to tumor coverage. D-E) Adaptive plan was done on the week 5 CT simulation scan in order to improve the dose distribution, with DVH in F) showing reduced normal tissue doses compared to what would have been delivered if no adaptive planning was performed.

Table I. Results of high-dose proton therapy, carbon-ion therapy, and stereotactic body radiotherapy for stage I non-small cell lung cancer.

Study and Reference	No. of Patients (IA/IB)	Modality	Total Dose	Dose per Fraction	Median Follow-Up Time, months	Local Control Rates	Overall Survival Rates	Severe (grade ≥3) Toxicity
Miyamoto 2007 [34]	50 (29/21)	Carbonion	72 Gy (RBE)	8 GyE	59	5-yr 95%	5-yr 50%	None
Miyamoto 2007 [35]	79 (42/37)	Carbonion	52.8/60 Gy (RBE)	13.2/15 GyE	39	3-yr 98%	3-yr 78%	None
Iwata 2010 [31]	21 (14/7)	Carbonion	52.8 GyE	13.2 GyE	24	2-yr 86%	2-yr 87%	None
Bush 2004 [26]	68 (29/39)	Protons	51/60 Gy (RBE)	5.1/6 GyE	30	3-yr 74%	3-yr 44%	None
Nihei 2006 [29]	37 (17/20)	Protons	70–94 Gy (RBE)	3.5–4.7 GyE	24	2-yr 80%	2-yr 84%	RP 8%
Iwata 2010 [31]	57 (27/30)	Protons	80/60 Gy (RBE)	4/6 GyE	40	3-yr 81%	3-yr 73%	RP 2%
Chang 2010 [30]	18 (4/13/1)	Protons	87.5 Gy (RBE)	2.5 GyE	16.3	2-yr 89%	2-yr 54.5%	None
Onishi 2007 [19]	257 (164/9)	SBRT	30–84 Gy	4.4–35Gy	38	3-yr 80%	3-yr 57%	None
Baumann 2009 [33]	57 (40/17)	SBRT	45 Gy	15 Gy	35	3-yr 92%	3-yr 60%	RP 2%
Timmerman 2006 [24]	70 (35/35)	SBRT	60/66 Gy	20/22Gy	33	2-yr 95%	2-yr 55%	RP14%
Timmerman 2010 [22]	55	SBRT	54 Gy	18 Gy	34.4	3-yr 97.6%	55.80%	Any 13%

Gy (RBE), unit that refers to the modification of the physical dose of a charged particle by its relative biological effectiveness; the RBE for protons is 1.1, and that for carbon ions ranges from 1.5 to 3.

Miyamoto T, Baba M, Yamamoto N, Koto M, Sugawara T, Yashiro T, . for the Working Group for Lung Cancer. Curative treatment of stage I non-small-cell lung cancer with carbon ion beams using a hypofractionated regimen. Int J Radiat Oncol Biol Phys 2007;67:750–8.

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Miyamoto T, Baba M, Sugane T, Nakajima M, Yashiro T, Kagei K, . for Working Group for Lung Cancer. Carbon ion radiotherapy for stage I non-small cell lung cancer using a regimen of four fractions during 1 week. J Thorac Oncol 2007;2:916–26.

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Bush DA, Slater JD, Shin BB, Cheek G, Miller DW, Slater JM. Hypofractionated proton beam radiotherapy for stage I lung cancer. Chest 2004;126:1198–203.

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Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, . Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: Updated results of 257 patients in a Japanese multi-institutional study. J Thorac Oncol 2007;2:S94–100.

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Baumann P, Nyman J, Hoyer M, Wennberg B, Gagliardi G, Lax I, . Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy. J Clin Oncol 2009;27:3290–6. Epub 2009 May 4.

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Timmerman R, McGarry R, Yiannoutsos C, Papiez L, Tudor K, DeLuca J, . Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol 2006;24:4833–9.

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