The median age was 78 years (range, 62-89) and six of the 15 patients (40%) had an ECOG performance status of 2-3 (). Severe COPD or interstitial lung disease was present in eight patients and five patients had at least two primary tumors. In five cases, prior thoracic radiation therapy, and in one case central location of the tumor, were also factors in the selection of protons as treatment modality. The median tumor size was 15 mm (range, 10-31 mm) (). Four patients did not undergo biopsy because they either refused or were judged to be at unacceptably high procedural risk. Bronchoscopy or mediastinoscopy to assess nodal stations were not performed in any patients prior to SBRT. Eleven tumors were within 1 cm of the chest wall, and two were within 2 cm of the mediastinal pleura. The average respiratory tumor motion was 2 mm (range, 0-10 mm).
Tumor characteristics (n = 20)
The median total dose was 45 Gy(RBE) (range, 42-50 Gy(RBE)) and the median fraction size was 14 Gy(RBE) (range, 10-16 Gy(RBE)) corresponding to a BED10 of at least 100 Gy(RBE). The number of fractions was 3 for 17 out of 20 tumors. Four patients were treated with two or more courses of therapy, each for separate and distinct tumors (). The average V5 and V20 for the ipsilateral lung for these patients were 20.5% (range, 5-39%) and 9.5% (range, 2-27%) respectively. The ipsilateral mean lung dose was 5.12 Gy(RBE) (range, 1.37 – 12.56). The contralateral lung in all cases received no dose due to the lack of exit dose of protons. An example dose distribution is shown in . One patient had a pacemaker at the same level as his lung lesion and dose to this area was avoided by employing only two beams (see ).
Figure 1 Sample proton SBRT dose distributions. (A) Limitation of dose to central structures. Radiation dose to the right bronchial tree (yellow) was limited by using a two beam arrangement. The dose falloff of the anterior beam results in a relatively small dose (more ...)
Treatments were well tolerated with only one case of grade 2 dermatitis (). There was one case of grade 3 pneumonitis in a patient with severe COPD which responded to prednisone. This patient had an ipsilateral mean lung dose of 3.36 Gy(RBE). One patient had a symptomatic rib fracture and two had asymptomatic fractures. For these patients, chest wall V30 and maximum doses were 11.1-24.9 cc and 44.3-48.6 Gy(RBE), respectively. No grade 4 or 5 toxicities were observed.
Radiation associated toxicity (n = 20)
There were six deaths (). Of these, two were attributable to lung cancer progression while the other four were due to other causes. Two patients developed both regional and distant metastases, one developed only regional metastases, and one developed only distant metastases. No local failures within the radiation field were observed. With a median follow-up time of 24.1 months, 2-year Kaplan Meier estimates of overall survival, local control, regional control, and distant control were 64% (95% confidence limits, 34-83%), 100% (83-100%), 78% (38-93%), and 86% (56-95%), respectively. Three patients developed metachronous primary tumors.