A Phase I/II Trial of Stereotactic Body Radiation Therapy (SBRT) Dose Escalation in the Treatment of Patients With Inoperable Stage I/II Non-Small Cell Lung Cancer Arising Within the Zone of the Proximal Bronchial Tree

Stage I Non-small Cell Lung Cancer Lung cancer is the most frequent cause of cancer death in both men and women in North America, accounting for approximately 13% of all cancers diagnosed and 28% of all cancer deaths. There will be an estimated 173,770 new lung cancer cases in the United States in the year 2004 with an estimated 160,440 deaths due to lung cancer.1 Seventy-five percent of patients with bronchogenic carcinoma will be diagnosed with non-small cell lung cancer (NSCLC). The number of patients with early or localized disease (currently an estimated 15-20% of NSCLC patients)2 is expected to rise over the next several years due to widespread screening with CT scanning.

The treatment of choice for stage I (T1-T2N0) NSCLC is surgical resection which results in 5-year survival rates of approximately 60 to 70%.3-5 Occasionally, however, there are patients with early-stage NSCLC that are unable to tolerate surgical resection or the postoperative recovery period due to various comorbidities.

While conventionally fractionated radiation therapy has been utilized as nonsurgical therapy for these medically inoperable patients, close observation with no specific cancer therapy has also been advocated in highly selected cases. McGarry, et. al., reviewed outcomes in 75 patients who had received no specific cancer therapy for stage I NSCLC, and the cause of death was progressive cancer in 53% of cases with a median survival time of 14.2 ± 2.4 months.6

Definitive conventionally fractionated RT for early-stage NSCLC is considered reasonable non-surgical therapy but yields poor 5-year survival rates ranging from 10 to 30%.7-11 Several studies have suggested a dose-response relationship reporting a benefit to dose escalation above the standard conventionally fractionated 4,500 to 6,600 cGy. This benefit was evident in both survival and local control in these patients.10-14 Sibley, et. al., reviewed 156 medically inoperable patients with stage I NSCLC treated with primary RT at Duke University between 1980 and 1995. They reported a 5-year, cause-specific survival rate of 32%. There was a trend toward improved survival in those patients achieving local control which approached significance for higher RT doses (p = 0.07).13 At this institution, we have published a series treating 56 patients with medically inoperable NSCLC with a median dose of 70 Gy using conformal radiotherapy techniques.15 Actuarial local control rates were 69% and 63% at two- and three years of follow up, respectively. These data serve as the estimate for statistical power calculations for this trial.

Radiation fields have historically encompassed the primary tumor as well as the regional lymphatics in the ipsilateral hilum and mediastinum. This elective treatment was based on the identified risk of occult lymph node involvement ranging up to 20% in some surgical series.16 In recent years, elimination of elective nodal irradiation, which is potentially poorly tolerated in this population,17 has been validated by several retrospective studies permitting treatment of the primary tumor alone with limited fields.18-21 Slotman, et. al., in a study from the Netherlands, reported the use of limited "postage-stamp" fields to treat early stage lung cancer patients using hypofractionated RT (i.e., 4,800 cGy in 400-cGy fractions). Reported 3-year overall and disease-specific survival rates were 42% and 76%, respectively.20