Interfractional Target Volume Changes in Brain Metastases during 13-Fraction Stereotactic Radiotherapy

Abstract

Advances in systemic therapy have greatly improved the prognosis of patients with brain metastases (BMs); long-term local control and reduced radiation toxicity are important. Fractionated stereotactic radiotherapy (SRT) seems to be associated with a reduced risk of radiation necrosis while providing equivalent local control compared to single-fraction or hypofractionated radiosurgery and is used in our institution for patients with a good prognosis or large BMs. As 13-fraction SRT lasts at least 17 days, we conduct adaptive replanning as necessary, based on contrast-enhanced mid-treatment magnetic resonance imaging (MRI) performed during 13-fraction SRT. We retrospectively analyzed interfractional volume changes and clinical outcomes of BMs treated with 13-fraction SRT. In total, this study included 23 patients with 27 BMs who received 13-fraction SRT with dynamic conformal arc therapy between July 2015 and November 2018. We excluded patients who received postoperative radiotherapy for the surgical cavity, no contrast-enhanced mid-treatment MRI, or single isocenter volumetric-modulated arc therapy for multiple BMs. The median patient age was 70 years and the median Karnofsky Performance Status was 90. There were 15 lung-cancer patients. The planning target volume (PTV) was established by adding a 1-mm margin to the gross tumor volume (GTV), defined as the volume of the contrast-enhancing lesion. The peripheral dose prescribed to the PTV was 39–44.2 Gy in 13 fractions. The GTV of the initial SRT plan (initial GTV) and the modified GTV based on the mid-treatment MRI scan (mid-treatment GTV) were compared. The median initial GTV was 3.8 (range 0.2–26.7) cm3 and the median period from the start of SRT to the mid-treatment MRI scan was 6 (range 3–11) days. In 10 lesions, the mid-treatment GTV had changed by more than 20% (5 had increased and 5 decreased) relative to the initial GTV. Adaptive replanning was conducted for 14 lesions. Of the 10 lesions that had increased or decreased in size by more than 20%, 8 received adaptive replanning. There was no significant relationship between an interfractional GTV volume change of more than 20%, primary disease (lung cancer vs. other cancers), and the presence of necrotic or cystic components. Regarding clinical outcomes, both overall survival rates and local control rates at 6 months were 95.0%, with a median follow-up period of 7.2 months. Two patients experienced grade 3 cerebral edema, two experienced grade 3 seizures, and four experienced grade 1 brain necrosis (CTCAE v5). The mid-treatment GTV changed by more than 20% relative to the initial GTV in almost one-third of lesions receiving 13-fraction SRT. More cases and long-term follow up are required to verify the impact of interfractional volume changes and adaptive replanning on clinical outcomes.