clinical outcome of stereotactic body radiation therapy for patients
with inoperable Stage I/II non–small-cell lung cancer
|Patients were immobilized using a vacuum
bag covering them from the head to the pelvis. Each patient underwent
slow CT simulation at 10 s/slide with a CT-slide thickness of 5 mm and
CT-slide interval of 5 mm to take into consideration tumor motion.
Selected patients with significant tumor motion (>1 cm) were evaluated
fluoroscopically; additional margins for tumor motion were added based
on the results of the fluoroscopic analysis.
The GTV was delineated in the
lung window, and a minimum margin of 1 cm was used to form the PTV from
the GTV. Either a single focus or multiple foci of radiation
beams were used based on the size of the PTV. A radiation dose of 50 Gy
was prescribed to the 50% isodose line covering at least 95% of the PTV
(5 Gy/fraction). Also, delivery of a total dose of 70 Gy (70% isodose
line) covering at least 90% of the GTV (7 Gy/fraction) was required.
Three-dimensional imaging of isodose coverage of GTV and PTV was used to
select aperture diameter, and number and location of target foci
depending on the size and shape of the target volume.
Radiotherapy was delivered over
2 weeks in 5 fractions per week. Prophylactic lymph node
irradiation was not performed in any of the cases. To reduce the
potential toxicity in central structures in patients with N1 disease as
indicated by CT/positron emission tomography (PET), 40 Gy was prescribed
to the 50% isodose line covering at least 95% of the PTV in
cancer-positive lymph nodes (4 Gy/fraction), and covering of 95% of the
gross cancer-positive lymph nodes by the 75% isodose line (6 Gy/fraction)
was required. In general, the volume of the lung receiving at least 20
Gy was required to be less than 20%. Also, the dose delivered to
critical structures such as the main bronchi, esophagus, trachea, heart,
and major blood vessels was required to be below 50 Gy (5 Gy/fraction),
and the dose delivered to the spinal cord was required to be below 30 Gy
Emerging clinical data show that omitting prophylactic lymph node irradiation does not reduce the local control rate for patients receiving definitive radiotherapy, with isolated outside-field (field of radiotherapy) local recurrence rates less than 8%, particularly in patients with Stage I disease and those who undergo PET scanning for staging.
The toxicity of body gamma-knife radiosurgery in our study was very tolerable. Only 2.3% of the patients experienced Grade 2 pneumonitis, and only 2.3% of the patients had Grade 3 pneumonitis. The patients who had Grade 3 pneumonitis had a significant history of chronic obstructive pulmonary disease before SBRT. Also, 4% of the patients with a tumor located close to a central structure had Grade 2 esophagitis. We detected no symptomatic late side effects of body gamma-knife radiosurgery. The cases of radiation-induced pneumonitis were related to the lung volume irradiated, dose received, and baseline lung-function status. In all of our cases, the volume of the lung receiving at least 20 Gy was less than 20%. However, when the target volume was large, a significant portion of normal lung tissue may have received a significant low dose of radiation, and the risk of toxic effects may have been higher when compared with smaller target volumes. Currently, there are no proven SBRT clinical data that establish a dose that normal tissues can tolerate. All current guidelines for the SBRT tolerance of normal tissue are based on previous experience using conventional fractionated radiotherapy and conversion to SBRT using BED calculation. Based on our experience and the results reported in the literature, use of body gamma-knife radiosurgery is safe and effective in treating periphery tumors smaller than 5 cm up to a total dose of 50 Gy delivered to the 50% isodose line in 10 fractions at 5 Gy/fraction. With better consideration of tumor motion and on-board imaging technology, use of higher doses per fraction or lower fraction numbers is also possible and may achieve even better results. However, for centrally located lung tumors that are close to critical structures, such as the main bronchi, trachea, esophagus, and spinal cord, individualized fraction sizes and numbers should be considered. Our delivery of 50 Gy in 10 fractions may be one option for SBRT in patients with centrally located lung tumors.
Stereotactic body gamma-knife radiosurgery with delivery of 50 Gy to the 50% isodose line is feasible and safe in the treatment of inoperable Stage I/II NSCLC. The 3-year local control and overall survival rates seem to be much better than those for conventional radiotherapy, and the toxicity is minimal. This technology provides a novel approach to treating early-stage NSCLC, and further dose escalation with better tumor-motion-tracking techniques may further improve clinical outcomes, particularly in patients with peripheral lesions. Radiation oncologists should administer this procedure to patients with central lung lesions only after careful selection. Although exposure of normal lung tissue to low doses of radiation is a concern, our patient selection criteria and body gamma-knife technique do not seem to result in significant acute or chronic toxic effects in the lung.