Stereotactic body radiation therapy of primary lung cancer and metastases

Stereotactic body radiation therapy (SBRT) has been assessed by both retrospective and prospective studies showing excellent treatment outcome with acceptable toxicity and high grade of local control. However, late presenting effects as well as further evaluating toxic effects in relation to dose-volume parameters at high-fraction doses and clinical characteristics is of the utmost importance in order to further develop the clinical application of this method.

Study I is a retrospective study of 29 patients (32 lesions) who were treated between 1994 and 2004 with reirradiation with SBRT of a previously treated SBRT-lung target. Reirradiation was defined as >50% overlap of the previously treated target. The primary aim was to evaluate toxicity. Serious toxicity was scored in 11 patients, with the toxic effects being lethal for three patients. Noted risk factors for serious toxicity were central location, large CTV and shorter time between the first treatment and the reirradiation. As concluded from the analysis, reirradiation of a peripherally located lung target is feasible, whereas careful consideration should be taken before reirradiating a centrally located target.

In study II, we reported on an extended follow-up of a prospectively collected patient cohort with medically inoperable stage I non-small cell lung cancer (NSCLC) treated curatively with SBRT, 15Gyx3. Between 2003 and 2005, 57 patients were included in this study. Long-term follow-up aimed to evaluate late presenting (def. >36 months) effects and toxicity. Five-yearlocal control and overall survival were 79% and 30% respectively. Three patients had late presenting grade 3 toxicity possibly attributed to their treatment. In conclusion, long-term results of SBRT are excellent and support the further use of SBRT for medically inoperable cases, the shorter survival however, is a limitation, possibly hiding late presenting effects.

Study III is a retrospective study of SBRT-treated adrenal metastases, whose objective was an evaluation of local control and toxicity. Fifty-eight patients with 62 adrenal metastases from various origins were treated between 1999 and 2013 and are included in this analysis. The median prescribed BED10 was 80Gy (24-113). Two-year local control rate (based on 60 evaluable tumors) was 87% and grade 3-4 toxicity occurred in 12% of the patients, the majority emanating from gastrointestinal organs. Treating adrenal metastases could render a high grade of local control, which has to be balanced against the risk of toxicity. The clinical challenge is to select the patients truly benefiting from the treatment with disease control and long-term survival.

In study IV, 57 patients with 61 SBRT-treated apically located lung tumors, defined as the center of the tumor located above the aortic arch, were retrospectively collected. Here the primary aim was to evaluate radiation induced brachial plexopathy (RIBP). Seven patients presented grade 2-3 RIBP; 3 suffering from sensory/motor deficit and 4 from isolated pain. A normal tissue complication probability (NTCP) model was fitted to the data, the BED3,max NTCP-model did show the best fit. As concluded from this analysis, the brachial plexus has to be considered as a risk organ and a dose-constraint of D-max ≤30Gy to the plexus for a threefraction treatment may be advisable.

List of scientific papers

I. Peulen H, Karlsson K, LINDBERG K, Tullgren O, Baumann P, Lax I, Lewensohn R, Wersäll P. . Radiotherapy and Oncology, 2011, volume 101, pp 260-266.
https://doi.org/10.1016/j.radonc.2011.09.012

II. LINDBERG K, Nyman J, Riesenfeld Källskog V, Hoyer M, Lund JÅ, Lax I, Wersäll P, Karlsson K, Friesland S, Lewensohn R. Long-term results of a prospective phase II trial of medically inoperable stage I NSCLC treated with SBRT – the Nordic experience. Acta Oncologica, 2015. Early online:1-9.
https://doi.org/10.3109/0284186X.2015.1020966

III. LINDBERG K, Grozman V, Haasbeek C, Westman G, Lax I, Wersäll P, Andersson A, Lewensohn R. Stereotactic body radiation therapy of adrenal gland metastases – results of a multicenter retrospective analysis of 60 tumor lesions. I[Manuscript]

IV. LINDBERG K, Grozman V, Lindberg S, Onjukka E, Lax I, Lewensohn R, Wersäll P. Radiation induced brachial plexus toxicity after SBRT of apically located lung lesions. [Manuscript]