Breast cancer subtype and intracranial recurrence patterns after brain-directed radiation for brain metastases.

PURPOSE: Brain metastases from breast cancer are frequently managed with brain-directed radiation but the impact of subtype on intracranial recurrence patterns after radiation has not been well-described. We investigated intracranial recurrence patterns of brain metastases from breast cancer after brain-directed radiation to facilitate subtype-specific management paradigms. METHODS: We retrospectively analyzed 349 patients with newly diagnosed brain metastases from breast cancer treated with brain-directed radiation at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2000 and 2015. Patients were stratified by subtype: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), HER2+ positive (HER2+), or triple-negative breast cancer (TNBC). A per-metastasis assessment was conducted. Time-to-event analyses were conducted using multivariable Cox regression. RESULTS: Of the 349 patients, 116 had HR+/HER2- subtype, 164 had HER2+ subtype, and 69 harbored TNBC. Relative to HR+/HER2- subtype, local recurrence was greater in HER2+ metastases (HR 3.20, 95% CI 1.78-5.75, p < 0.001), while patients with TNBC demonstrated higher rates of new brain metastases after initial treatment (HR 3.16, 95% CI 1.99-5.02, p < 0.001) and shorter time to salvage whole brain radiation (WBRT) (HR 3.79, 95% CI 1.36-10.56, p = 0.01) and salvage stereotactic radiation (HR 1.86, 95% CI 1.11-3.10, p = 0.02). CONCLUSIONS: We identified a strong association between breast cancer subtype and intracranial recurrence patterns after brain-directed radiation, particularly local progression for HER2+ and distant progression for TNBC patients. If validated, the poorer local control in HER2+ brain metastases may support evaluation of novel local therapy-based approaches, while the increased distant recurrence in TNBC suggests the need for improved systemic therapy and earlier utilization of WBRT.

Only visible flicker helps flutter: Tactile-visual integration breaks in the absence of visual awareness.

Combining information from multiple senses enhances our perception of the world. Whether we need to be aware of all stimuli to benefit from multisensory integration, however, is still under investigation. Here, we tested whether tactile frequency perception benefits from the presence of congruent visual flicker even if the flicker is so rapid that it is perceptually fused into a steady light and therefore invisible. Our participants completed a tactile frequency discrimination task given either unisensory tactile or congruent tactile-visual stimulation. Tactile and tactile-visual test frequencies ranged from far below to far above participants' flicker fusion threshold (determined separately). For frequencies distinctively below their flicker fusion threshold, participants performed significantly better given tactile-visual stimulation than when presented with only tactile stimuli. Yet, for frequencies above their flicker fusion threshold, participants' tactile frequency perception did not profit from the presence of congruent but likely fused and thus invisible visual flicker. The results matched the predictions of an ideal-observer model in which tactile-visual integration is conditional on awareness of both stimuli. In contrast, it was impossible to reproduce the observed results with a model that assumed tactile-visual integration proceeds irrespective of stimulus awareness. In sum, we revealed that the benefits of congruent visual stimulation for tactile flutter frequency perception depend on the visibility of the visual flicker, suggesting that multisensory integration requires awareness.