Fig. 1

Therapeutic response. a Contrast-enhanced T1-weighted MRI images. Images were obtained on Day 2, 18, 94, 122, 227, and 367. Baseline MRI (Day 2) showed LM in the suprasellar region (T1) and dorsal medulla (T2) and recurrence of the thoracic tumor (T3). Foci of linear leptomeningeal and periventricular enhancement are highlighted with arrowheads. Notably, in cycle 1, his consciousness recovered to drowsiness after thoracic tumor resection, but 10 days later he developed diabetes insipidus and hyponatremia due to increased volume of the suprasellar nodule from a baseline of 1905 to 2606 mm³ (see Supplementary Fig. 2a and Table 3 for details). Leptomeningeal and periventricular enhancement also progressed. The electrolyte and fluid imbalance were transient and resolved within 2 cycles of treatment. His consciousness fully recovered since cycle 3 with concurrent improvement of global neurocognitive function (See Supplementary Fig. 9 and Table 4 for details). When radiotherapy was completed in cycle 6, the volume of all lesions had remarkably diminished, from a baseline of 1905 mm³ for T1 and 829 mm³ for T2, to 1615 and 265 mm³ on Day 122, respectively. Interestingly, in cycle 11 (Day 227), without any neurological symptom, the involvement of periventricular enhancement was slightly increased due to the reduced dose of panobinostat within this cycle, but decreased after dose increase in cycle 12 (Day 256) (see Supplementary Figs. 2a, 5–7 and Table 3 for details). b Differentially expressed proteins in CSF through the course of therapy. CSF proteins differentially expressed through the treatment course (ANOVA adjusted p < 0.05) were grouped into 20 clusters based on expression profiles (see Supplementary Fig. 10 for cluster characteristics). Heatmaps illustrating the relative expression of selected proteins that had a consistent trend in protein expression in CSF samples collected at various time points during treatment are shown. Refer to Supplementary Fig. 11 for the full list of proteins in each of the four clusters. Time points A–E represented Day 26, 72, 169, 321, and 340, respectively