Single versus Multifraction Stereotactic Radiosurgery for Large Brain Metastases: An International Meta-analysis of 24 Trials

Quantitative Systems Pharmacology: An Exemplar Model‐Building Workflow With Applications in Cardiovascular, Metabolic, and Oncology Drug Development

“…Moreover, such a model‐based evaluation of preclinical results may provide a basis for useful inferences in support of early clinical programs. For example, preclinical simulations of various RT and anti‐PD‐(L)1 combination schedules, based on realistic baseline conditions of immune cells and tumor size at start of treatment, point in favor of a concurrent schedule in terms of response optimization, consistent with the results obtained in early clinical trials . The value of such a preclinical‐to‐clinical translation is, at most, of a qualitative nature.…”

“…For example, preclinical simulations of various RT and anti-PD-(L)1 combination schedules, based on realistic baseline conditions of immune cells and tumor size at start of treatment, point in favor of a concurrent schedule in terms of response optimization, consistent with the results obtained in early clinical trials. 85,86 The value of such a preclinical-to-clinical translation is, at most, of a qualitative nature. Building a quantitative inference to the clinic using such a population QSP model would require adjustments of the model in two specific aspects.…”

Two-session Radiosurgery as Initial Treatment for Newly Diagnosed Large, Symptomatic Brain Metastases from Breast and Lung Histology

“…Ten patients had a total of 36 tumors; of these, 22 lesions with a mean volume of 12.3 ml (range, 7-78.4 ml) underwent two-session radiosurgery. The mean prescription dose for the first treatment was 13 Gy (range, [9][10][11][12][13][14][15][16][17][18] to the 50% isodose line, and the intratumoral mean dose was 17.9 Gy (12-22.9). All 10 patients had neurological symptoms, with a mean Karnofsky physical score (KPS) of 60 (range, 50-70) on the day of treatment.…”

“…These histology subtypes are considered more radioresistant than the histology here presented and thus may limit the extrapolation of the results here described. Several recent studies have described different fractionation schemes that are intended to safely increase the biologically effective dose to large lesions, thereby improving long-term local control and survival when compared with historical reports of tumor control at one year of 45 and 49% in patients that received a lower dose in a single fraction such as 15 and 18 Gy, respectively [14,[16][17][18][19][20][22][23]. Recent results suggest that the classical scheme of surgery followed by SRS may be comparable to staged (two-session) radiosurgery with local tumor failure rate at one year of 8% [26].…”

“…Shaw et al recommend that radiosurgery doses to large lesions be limited, with reference doses of 24 Gy recommended for lesions <2 cm in diameter, doses of 18 Gy recommended for lesions >2 cm and <3 cm in diameter, and doses of 15 Gy recommended for lesions >3 cm [12]. Nevertheless, doses below 20 Gy were found insufficient to provide long-term (i.e., one-year) control by several authors [13][14][15][16].…”