Clinical investigation
Lung
Selective mediastinal node irradiation based on FDG-PET scan data in patients with non–small-cell lung cancer: A prospective clinical study

https://doi.org/10.1016/j.ijrobp.2004.12.019Get rights and content

Purpose: To evaluate the patterns of recurrence when selective mediastinal node irradiation based on FDG-PET scan data is used in patients with non-small-cell lung cancer (NSCLC).

Methods and Materials: A prospective Phase I/II study was undertaken on 44 patients with NSCLC without detectable distant metastases on CT and FDG-PET scan, delivering either 61.2 Gy in 34 fractions over 23 days or 64.8 Gy in 36 fractions over 24 days (1.8 Gy b.i.d. with 8-h interval). Only the primary tumor and the positive mediastinal areas on the pretreatment FDG-PET scan were irradiated. Isolated nodal failure was defined as recurrence in the regional nodes outside of the clinical target volume, in the absence of in-field failure.

Results: The CT and FDG-PET stage distribution was as follows: Stage I: 8 patients (18%) and 13 patients (29%); Stage II: 6 patients (14%) and 10 patients (23%); Stage IIIA: 15 patients (34%) and 7 patients (16%); Stage IIIB: 15 patients (34%) and 14 patients (32%), respectively. After a median follow-up time of 16 months (95% confidence interval [CI], 11–21 months) postradiotherapy, 11 patients (25%) developed a local recurrence. Only 1 patient (crude rate, 2.3%; upper bound of 95% CI, 10.3%), with a Stage II tumor on both CT and PET, developed an isolated nodal failure. The median actuarial overall survival was 21 months (95% CI, 14–28 months), and the median actuarial progression-free survival was 18 months (95% CI, 12–24 months).

Conclusions: Selective mediastinal node irradiation based on FDG-PET scan data in patients with NSCLC results in low isolated nodal failure rates. In the Phase I component of this trial, radiation dose escalation up to 64.8 Gy in 36 fractions over 24 days is feasible.

Introduction

In recent years, the prognosis of patients with non-small-cell lung cancer (NSCLC) has significantly improved (1, 2, 3, 4). This has mainly been because of a better integration of chemotherapy and radiotherapy, more effective drugs, and improvements in radiotherapy schedules. Local tumor failure still occurs in the overwhelming majority of patients, but radiation-induced esophagitis and pneumonitis are common dose-limiting toxicities. Thus, dose escalation or intensification, which might be needed to improve the prognosis, is not straightforward, and approaches to decrease toxicity are therefore of great clinical interest.

An obvious way to reduce toxicity due to radiotherapy is to reduce the volume of dose-limiting organs, such as the lungs and esophagus, included in the planning target volume (PTV). Previous studies have shown that it is safe to irradiate only mediastinal lymph nodes enlarged on the CT scan, hence omitting elective nodal irradiation, with <5% of patients experiencing an isolated nodal failure (5, 6, 7, 8, 9, 10). Because the diagnostic accuracy of the mediastinal staging is better with 18F-deoxy-D-glucose (FDG) positron emission tomography (PET) than with CT scan, we hypothesized that irradiating only the FDG-positive mediastinal areas in patients suffering from NSCLC would not result in a higher incidence of isolated nodal failure (11, 12, 13, 14, 15). Moreover, in a previous theoretical modeling study (16), we showed that selective irradiation of FDG-PET-positive mediastinal areas would result in smaller radiation fields than those based on CT scan data, leading to less morbidity and hence allowing dose escalation. We therefore initiated a prospective clinical Phase I/II study to investigate whether selective irradiation of the FDG-PET-positive mediastinal areas would be safe and whether radiation dose escalation in a short overall treatment would be feasible.

Section snippets

Patient population

The entry criteria were as follows: cytologically or histologically proved NSCLC, with the exclusion of mixed pathology between NSCLC and small-cell cancer and bronchioloalveolar carcinoma; Union Internationale Contre Cancer Stages I–III, with the exclusion of T4 lesions because of a malignant pleural effusion; World Health Organization performance status 0–1; measurable disease; age ≥18 years; adequate pulmonary function (forced expiratory volume in 1 s > 1 L); no severe recent cardiac disease

Patient characteristics

From November 2001 to December 2003, 44 patients were entered in the study. Their characteristics are summarized in Table 1. The median age was 68 years (range, 51–89 years). All patients were in a good general condition (100% World Health Organization performance status 0 or 1), with a preponderance of men (61%). All patients had to have no detectable distant metastases both on CT and on FDG-PET scan, but because of the latter the mediastinal staging changed in 11 of 44 patients (25%; 95% CI,

Discussion

To the best of our knowledge, this is the first clinical study reporting on selective mediastinal irradiation based on FDG-PET scan data in patients with NSCLC. The rationale is obvious: The diagnostic accuracy for the staging of the mediastinum with the FDG-PET scan is higher than with the CT scan; thus, it is more logical to delineate the mediastinal lymph node areas for radiotherapy based on FDG-PET rather than on CT scan data (11, 12, 13, 14, 15). With a follow-up time sufficient to detect

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