Optimal hypofractionated conformal radiotherapy for large brain metastases in patients with high risk factors: a single-institutional prospective study

Abstract

BackgroundA single-institutional prospective study of optimal hypofractionated conformal radiotherapy for large brain metastases with high risk factors was performed based on the risk prediction of radiation-related complications.MethodsEighty-eight patients with large brain metastases ≥10 cm3 in critical areas treated from January 2010 to February 2014 using the CyberKnife were evaluated. The optimal dose and number of fractions were determined based on the surrounding brain volume circumscribed with a single dose equivalent (SDE) of 14 Gy (V14) to be less than 7 cm3 for individual lesions. Univariate and multivariate analyses were conducted.ResultsAs a result of optimal treatment, 92 tumors ranging from 10 to 74.6 cm3 (median, 16.2 cm3) in volume were treated with a median prescribed isodose of 57% and a median fraction number of five. In order to compare the results according to the tumor volume, the tumors were divided into the following three groups: 1) 10–19.9 cm3, 2) 20–29.9 cm3 and 3) ≥30 cm3. The lesions were treated with a median prescribed isodose of 57%, 56% and 55%, respectively, and the median fraction number was five in all three groups. However, all tumors ≥20 cm3 were treated with ≥ five fractions. The median SDE of the maximum dose in the three groups was 47.2 Gy, 48.5 Gy and 46.5 Gy, respectively. Local tumor control was obtained in 90.2% of the patients, and the median survival was nine months, with a median follow-up period of seven months (range, 3-41 months). There were no significant differences in the survival rates among the three groups. Six tumors exhibited marginal recurrence 7-36 months after treatment. Ten patients developed symptomatic brain edema or recurrence of pre-existing edema, seven of whom required osmo-steroid therapy. No patients developed radiation necrosis requiring surgical resection.ConclusionOur findings demonstrate that the administration of optimal hypofractionated conformal radiotherapy based on the dose-volume prediction of complications (risk line for hypofractionation), as well as Kjellberg’s necrosis risk line used in single-session radiosurgery, is effective and safe for large brain metastases or other lesions in critical areas.

Brain metastases treated with hypofractionated stereotactic radiotherapy: 8 years experience after Cyberknife installation

“…Some authors suggested the use of a further fractionated treatment. Determining optimal dose is a controversial debate [31]. Partly this can be explained by fundamental radiobiology [29].…”

Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm

“…56 More recently, in an attempt to overcome the modest LC observed in the management of LBM and also to decrease the radiation toxicity associated with SRS treatment, several novel strategies have been explored. Retrospective and prospective studies evaluating both hypofractionated SRS (hypo-FSRS), typically delivered in 3-6 fractions, 18,19,25,27,28,38,39,[42][43][44]46,71,72 and staged SRS 24,74,75 have been investigated in the management of LBM. The rationale was to increase the prescribed dose and hence the LC while decreasing the morbidity of radiation injury, by distributing the dose over time and perhaps to smaller targets at the time of second treatment.…”

Adaptive hypofractionated gamma knife radiosurgery for a large brainstem metastasis

“…Hypofractionated regimens have proved effective in the management of brain malignancies in high- and low-risk areas. [ 11 20 21 35 36 47 52 58 ] Furthermore, the role of radiotherapy in the management of NSCLC has been widely documented. [ 2 3 9 12 33 35 45 ] Understanding the relation between dose-volume values, clinical data, and local anatomical traits remains critical in terms of achieving local tumor control and avoiding/limiting normal tissue toxicity.…”