Clinical Investigation
Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403

This work was presented in part at the 52nd Annual Meeting of the American Society for Radiation Oncology, October 31-November 4, 2010, San Diego, CA; and at the 54th Annual Meeting of the American Society for Radiation Oncology, October 29-November 1, 2012, Boston, MA.
https://doi.org/10.1016/j.ijrobp.2015.07.2278Get rights and content

Purpose

To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC).

Methods and Materials

Eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients.

Results

Between July 2004 and November 2008, 169 patients from 15 institutions were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed.

Conclusions

Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC.

Introduction

Stereotactic radiation therapy for extracranial tumors was introduced by Blomgren et al (1), Lax et al (2), Uematsu et al (3), and Arimoto et al (4). This technique has been referred to as stereotactic body radiation therapy (SBRT) 5, 6 or stereotactic ablative radiation therapy and has been recently applied to treat inoperable primary lung cancer.

The advantage of SBRT with a smaller irradiated volume enabled by greater setup precision is hypofractionated radiation therapy, leading to a shorter treatment course. Disadvantages are the uncertain effects of altered fractionation and the theoretical risk of worsening the ratio of normal tissue to tumor tissue through use of a high dose in each treatment session.

The current standard choice of treatment for stage I non-small cell lung cancer (NSCLC) is lobectomy and mediastinal lymph nodal dissection (7). However, lobectomy is not indicated for the patients with severe comorbidity. Even without comorbidity, some patients prefer treatment by a less-invasive procedure. Stereotactic body radiation therapy as a new radiation technique is an alternative choice for this population. A multi-institutional retrospective study (8) demonstrated a result potentially comparable to surgery for operable stage I NSCLC.

The purpose of Japan Clinical Oncology Group (JCOG) study 0403 was to evaluate the safety and efficacy of SBRT in patients with operable or inoperable T1N0M0 NSCLC (Union for International Cancer Control staging criteria, 6th edition, 2002). Answers to the following 2 clinical questions were sought by this trial: (1) Can SBRT be an alternative standard treatment modality for inoperable patients? (2) Is SBRT promising as an alternative to lobectomy for operable patients? This report presents the results of the analysis for both the inoperable and operable population.

Section snippets

Study design and participants

Eligibility criteria for the patients were (1) histologically or cytologically proven NSCLC; (2) clinical T1N0M0 (Union for International Cancer Control staging criteria, 6th edition) staged by bronchoscopy and computed tomography (CT), but 18-fluorodeoxyglucose–positron emission tomography not mandatory; (3) Eastern Cooperative Oncology Group performance status 0 to 2; (4) age ≥20 years; (5) PaO2 ≥60 torr (under room air); (6) forced expiratory volume 1.0 ≥700 mL; (7) no history of radiation

Results

From 15 institutions of the JCOG Radiation Therapy Study Group, 72 inoperable patients were registered between July 2004 and November 2008, and 97 operable patients were registered between July 2004 and January 2007. After the restratification, 104 inoperable patients and 65 operable patients were available for analyses, as shown in Figure 1. Characteristics of the patients are shown in Table 2. Both in the inoperable population and operable populations, all patients completed the protocol

Discussion

The purpose of this study was to evaluate the safety and efficacy of SBRT in patients with inoperable or operable T1N0M0 NSCLC. Because no upper age limit was included in the eligibility criteria for this trial, a relatively older population than those for surgery was entered in this trial, with a median age of 78 years for the inoperable and 79 years for the operable population.

In the inoperable population, the % 3-year OS was 59.9% (95% CI 49.6%-68.8%). The expected % 3-year survival of

Conclusion

Stereotactic body radiation therapy as delivered in this trial for both inoperable and operable stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC, and it also has a potential to be an alternative to surgery for operable stage I NSCLC.

Acknowledgments

The authors thank data managers Hidenobu Yamada and Chikako Aibara; and biostatisticians Junki Mizusawa and Naoki Ishizuka.

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Note—An online CME test for this article can be taken at http://astro.org/MOC.

This work was supported in part by the National Cancer Center Research and Development Fund (23-A-16, 23-A-21, and 26-A-4); a Grant-in-Aid for Cancer Research (14S-4, 17S-5, 20S-5, and 20S-6); and a Health and Labor Sciences Research Grant for Clinical Cancer Research (H15-41, H18-014) from the Japanese Ministry of Health, Labor and Welfare. The principal investigator of this study is Masahiro Hiraoka.

This trial was registered as NCT00238875 by Clinicaltrials.gov and C000000029 by UMIN-CTR (www.umin.ac.jp/ctr/).

Conflict of interest: none.

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