Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases.

BACKGROUND: The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). METHODS: Ninety-nine patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. RESULTS: After a median follow-up of 11.9 months (range 0.7-29.7), there was no significant difference between the two groups. However, patients who received concurrent IT (n = 30) had better 1-year LC, OS, FFDBM but a higher RN rate compared to patients who did not: 96% versus 78% (p = 0.02), 89% versus 77% (p = 0.02), 76% versus 53% (p = 0.004) and 80% versus 90% (p = 0.03), respectively. In multivariate analysis, concurrent IT (p = 0.022) and tumor volume < 2.07 cc (p = 0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p = 0.03). CONCLUSION: SRT delivered concurrently with IT seems to be associated with improved LC, FFDBM and OS as well as with a higher rate of RN.

Examining the Inter Hemispheric Transfer Time Test: A new computerized cognitive test to incorporate into therapeutic strategy for patients with brain metastases? A pilot study.

OBJECTIVE: To evaluate the computerized Inter Hemispheric Transfer Time Test (IHTTT), a cognitive test designed for the detection of information processing speed impairment in patients undergoing stereotactic radiation therapy for brain metastases. METHODS: Inclusion criteria: age ≥18 years, brain metastases treated by stereotactic radiotherapy (SRT) with dose schedule: 33 Gy in 3 fractions, solid tumour, ≥70 Karnofsky Performance Status, Mini-Mental State Evaluation (MMSE) ≥ 24, no history of stroke brain injury. Twenty-nine patients were recruited from June 2014 to April 2015. All recruited patients were administered Frontal Assessment Battery at Bedside (FAB), IHTTT and QLQ-C30 quality of life questionnaire before SRT, at one-month, six-month and one-year follow-up. The primary endpoint was Interhemispheric Transfer Index (IHTI). Secondary endpoints included Interhemispheric Transfer Time (IHTT), MMSE, FAB, and quality of life. RESULTS: A significant evolution of cognitive function over time was assessed by the IHTTT: IHTT = 720 ±â€¯27 ms at baseline, 728 ±â€¯20 at one month, 736 ±â€¯36 at 6 months, 799 ±â€¯111 at one-year follow-up (p = 0.0010); IHTI = 13.1 ±â€¯31.4, 11.5 ±â€¯24.3, 50.6 ±â€¯57.9, 91.0 ±â€¯59.4 (p < 0.0001). There was also a significant evolution over time for MMSE (p = 0.014) but neither for FAB score nor the quality of life scores. IHTI was strongly related to progression-free survival (p = 0.0091). CONCLUSION: Our results suggest that IHTTT is able to detect the evolution of cognitive function over time. IHTTT could be an interesting sensitive cognitive test to include in evaluation of patients with brain metastases irradiated by SRT.

[Brain metastases: Focal treatment (surgery and radiation therapy) and cognitive consequences]. / Métastases cérébrales : rôle des traitements focaux (chirurgie et radiothérapie) et leur impact cognitif.

Brain metastases represent the first cause of malignant brain tumor. Without radiation therapy, prognosis was poor with fast neurological deterioration, and a median overall survival of one month. Nowadays, therapeutic options depend on brain metastases presentation, extra brain disease, performance status and estimated prognostic (DS GPA). Therefore, for oligometastatic brain patients with a better prognosis, this therapeutic modality is controversial. In fact, whole-brain radiation therapy improves neurological outcomes, but it can also induce late neuro-cognitive sequelae for long-term survivors of brain metastases. Thus, in this strategy for preserving good cognitive functions, stereotactic radiation therapy is a promising treatment. Delivering precisely targeted radiation in few high-doses in one to four brain metastases, allows to reduce radiation damage to normal tissues and it should allow to decrease radiation-induced cognitive decline. In this paper, we will discuss about therapeutic strategies (radiation therapy and surgery) with their neuro-cognitive consequences for brain metastases patients and future concerning preservation of cognitive functions.