Clinical investigation
Lung
Stereotactic body radiation therapy of early-stage non–small-cell lung carcinoma: Phase I study

https://doi.org/10.1016/j.ijrobp.2005.03.073Get rights and content

Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer.

Methods and Materials: All patients had non–small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 × 8 Gy fractions) using 7–10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods.

Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy), but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses ≤16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally.

Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.

Introduction

Lung cancer remains in North America the most frequent cause of cancer death in both men and women. It was estimated that there will be 173,770 new lung cancer cases in the United States in the year 2004 with an estimated 160,440 deaths due to this highly lethal malignancy. This accounts for approximately 13% of all cancers diagnosed but 28% of all cancer deaths (2). Approximately 25% of patients present with Stage I or II disease. Optimally, the definitive management of these cases of early-stage lung carcinoma is considered to be surgical with a 50%–80% 5-year survival (3, 4). In contrast, the management of those patients with early-stage bronchogenic carcinoma deemed medically inoperable is less clear. Involved-field radiotherapy is generally considered the treatment of choice for those patients who cannot undergo surgery (4, 5), but 5-year survival after radiotherapy alone is less than approximately half of that achieved by wide surgical resection.

In a preliminary report, we presented the outcome of the first 33 patients entered on a Phase I study of high-dose-per-fraction, stereotactically targeted radiation therapy for patients with Stage I lung cancer who were considered medically inoperable (13). With a median follow-up of 15.2 months, patients had tolerated the therapy well. We now present further results from the completed trial, which included 47 patients, with an assessment of patterns of failure in these frail patients.

Section snippets

Patients

Patients included were diagnosed with non–small-cell lung carcinoma (NSCLC) by biopsy, or they were cytologically staged as AJCC Stage 1A or 1B. Eligible diagnoses included squamous cell carcinoma, adenocarcinoma, large-cell carcinoma, bronchoalveolar cell carcinoma, or non–small-cell not otherwise specified. Patients had no direct evidence of regional or distant metastases after appropriate staging studies. All patients were assessed for surgery by a thoracic surgeon and deemed medically

Patient characteristics

Between January 2000 and January 2003, 47 patients were accrued to the study. The median Karnofsky performance score was 70 with 14 oxygen-dependent patients. Demographics and main reasons for medical inoperability are shown in Table 1. For Stage T1 patients, the mean GTV treated was 8.51 cc, and for Stage T2 patients, mean GTV was 50.5 cc.

For the T1 tumor group, partial responses were seen in all tumors with complete responses in 7/19 patients. Tumor shrinkage greater than 50% was seen in

Discussion

Surgery is the preferred form of treatment for early-stage NSCLC with many reviews showing a 50%–80% 5-year survival (4, 5). Local radiotherapy to a limited volume of tissue is considered the standard therapy for patients with Stage I or II NSCLC who do not receive surgery, because of refusal or medical comorbidity; however, no randomized trials to compare the outcome of radiotherapy to observation only have been done. McGarry et al. (8) reviewed early-stage NSCLC patients managed by

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