Stereotactic body radiation therapy (SBRT) for lung malignancies: preliminary toxicity results using a flattening filter-free linear accelerator operating at 2400 monitor units per minute

Abstract

Background: Flattening filter-free (FFF) linear accelerators (linacs) are capable of delivering dose rates more than 4-times higher than conventional linacs during SBRT treatments, causing some to speculate whether the higher dose rate leads to increased toxicity owing to radiobiological dose rate effects. Despite wide clinical use of this emerging technology, clinical toxicity data for FFF SBRT are lacking. In this retrospective study, we report the acute and late toxicities observed in our lung radiosurgery experience using a FFF linac operating at 2400 MU/min.

Methods: We reviewed all flattening filter-free (FFF) lung SBRT cases treated at our institution from August 2010 through July 2012. Patients were eligible for inclusion if they had at least one clinical assessment at least 30 days following SBRT. Pulmonary, cardiac, dermatologic, neurologic, and gastrointestinal treatment related toxicities were scored according to CTCAE version 4.0. Toxicity observed within 90 days of SBRT was categorized as acute, whereas toxicity observed more than 90 days from SBRT was categorized as late. Factors thought to influence risk of toxicity were examined to assess relationship to grade > =2 toxicity.

Results: Sixty-four patients with >30 day follow up were eligible for inclusion. All patients were treated using 10 MV unflattened photons beams with intensity modulated radiation therapy (IMRT) inverse planning. Median SBRT dose was 48 Gy in 4 fractions (range: 30-60 Gy in 3-5 fractions). Six patients (9%) experienced > = grade 2 acute pulmonary toxicity; no non-pulmonary acute toxicities were observed. In a subset of 49 patients with greater than 90 day follow up (median 11.5 months), 11 pulmonary and three nerve related grade > =2 late toxicities were recorded. Pulmonary toxicities comprised six grade 2, three grade 3, and one each grade 4 and 5 events. Nerve related events were rare and included two cases of grade 2 chest wall pain and one grade 3 brachial plexopathy which spontaneously resolved. No grade > =2 late gastrointestinal, skin, or cardiac toxicities were observed. Tumor size, biologically effective dose (BED10, assuming α/β of 10), and tumor location (central vs peripheral) were not significantly associated with grade > =2 toxicity.

Conclusions: In this early clinical experience, lung SBRT using a FFF linac operating at 2400 MU/min yields minimal acute toxicity. Preliminary results of late treatment related toxicity suggest reasonable rates of grade > =2 toxicities. Further assessment of late effects and confirmation of the clinical efficacy of FFF SBRT is warranted.

Figure 1

Cross-beam profile. Cross beam profile of a conventional 10 megavolt photon beam (dashed line) is compared to the cross beam profile of an unflattened photon beam (solid line) of equivalent energy. The unflattened beam has approximately four times higher dose rate at central axis.

Figure 2

Radiation associated imaging changes. Panels A and B show typical radiation changes that are apparent on chest CT approximately 3–9 months following SBRT. Images on the left show pre-treatment tumor and images on the right show post-SBRT changes. Both axial and coronal planes are provided. The imaging changes depicted above are considered grade 1 radiation pneumonitis by the CTCAE v4.o criteria if they are not associated with clinical symptomatology.