Cremers, Florian

In Radiation Therapy Oncology Group 90-05, the maximum tolerated dose of single-fraction radiosurgery (SRS) for brain metastases of 21–30 mm was 18 Gy (biologically effective dose (BED) 45 Gy12). Since the patients in this study received prior brain irradiation, tolerable BED may be >45 Gy12 for de novo lesions. We investigated SRS and fractionated stereotactic radiotherapy (FSRT) with a higher BED for radiotherapy-naive lesions. Patients receiving SRS (19–20 Gy) and patients treated with FSRT (30–48 Gy in 3–12 fractions) with BED > 49 Gy12 for up to 4 brain metastases were compared for grade ≥ 2 radiation necrosis (RN). In the entire cohort (169 patients with 218 lesions), 1-year and 2-year RN rates were 8% after SRS vs. 2% and 13% after FSRT (p = 0.73) in per-patient analyses, and 7% after SRS vs. 7% and 10% after FSRT (p = 0.59) in per-lesion analyses. For lesions ≤ 20 mm (137 patients with 185 lesions), the RN rates were 4% (SRS) vs. 0% and 15%, respectively, (FSRT) (p = 0.60) in per-patient analyses, and 3% (SRS) vs. 0% and 11%, respectively, (FSRT) (p = 0.80) in per-lesion analyses. For lesions > 20 mm (32 patients with 33 lesions), the RN rates were 50% (SRS) vs. 9% (FSRT) (p = 0.012) in both per-patient and per-lesion analyses. In the SRS group, a lesion size > 20 mm was significantly associated with RN; in the FSRT group, lesion size had no impact on RN. Given the limitations of this study, FSRT with BED > 49 Gy12 was associated with low RN risk and may be safer than SRS for brain metastases > 20 mm.

A modern approach for brain metastases includes whole-brain radiotherapy plus simultaneous boost (WBRT+SIB). We developed a survival score in 128 patients treated with WBRT+SIB. Three models, each including three prognostic groups, were created. Positive predictive values (PPVs) for death ≤6 and survival ≥6 months were calculated. On multivariate analyses, performance score (KPS) and the number of brain metastases were significantly associated with survival. On univariate analyses, age showed a strong trend, and extra-cerebral cranial metastases a trend. In Model 1 (KPS, number of lesions), compared groups had 6-month survival rates of 15%, 38% and 57%. In Model 2 (KPS, lesions, age), rates were 17%, 33% and 75%, and in Model 3 (KPS, lesions, age, extra-cerebral metastases), 14%, 34% and 78%. PPVs for death ≤6 and survival ≥6 months were 85% and 57% (Model 1), 83% and 75% (Model 2), and 86% and 78% (Model 3). Thus, all models were accurate in predicting death ≤ 6 months; poor-prognosis patients may not benefit from SIB. Models 2 and 3 were superior in predicting survival ≥ 6 months. Given that Model 3 requires more data (including extensive staging), Model 2 is considered favorable for many patients. If extra-cerebral metastases are already known or extensive staging has been performed, Model 3 can also be used.

Estimating post-treatment ambulatory status can improve treatment personalization of patients irradiated for malignant spinal cord compression (MSCC). A new clinical score was developed from data of 283 patients treated with radiotherapy alone in prospective trials. Radiotherapy regimen, age, gender, tumor type, interval from tumor diagnosis to MSCC, number of affected vertebrae, other bone metastases, visceral metastases, time developing motor deficits, ambulatory status, performance score, sensory deficits, and sphincter dysfunction were evaluated. For factors with prognostic relevance in the multivariable logistic regression model after backward stepwise variable selection, scoring points were calculated (post-radiotherapy ambulatory rate in % divided by 10) and added for each patient. Four factors (primary tumor type, sensory deficits, sphincter dysfunction, ambulatory status) were used for the instrument that includes three prognostic groups (17–21, 22–31, and 32–37 points). Post-radiotherapy ambulatory rates were 10%, 65%, and 97%, respectively, and 2-year local control rates were 100%, 75%, and 88%, respectively. Positive predictive values to predict ambulatory and non-ambulatory status were 97% and 90% using the new score, and 98% and 79% using the previous instrument. The new score appeared more precise in predicting non-ambulatory status. Since patients with 32–37 points had high post-radiotherapy ambulatory and local control rates, they may not require surgery.