Neuroscience Education Institute

Abstract Background: Recurrent pediatric ependymoma remains a major therapeutic challenge with few evidence-based systemic options. NCCN guidelines emphasize maximal safe resection and radiotherapy, without systemic chemotherapy and which should generally be reserved for recurrence due to limited and unpredictable benefit. However, personalized functional profiling may provide actionable, patient-specific evidence by directly measuring tumor drug sensitivity and resistance ex vivo. Methods: Fresh surgical specimens from three pediatric recurrent ependymomas were processed into viable tumor fragments and 3D microtumors analyzed using the SAGE Oncotest™, a multiplexed ex- vivo functional profiling assay measuring both cytotoxicity and antiproliferation. NCCN-relevant agents were tested at standardized and physiologically representative concentrations over several logs. Cytotoxicity (loss of viability) and antiproliferation (inhibition of DNA synthesis) were quantified using our proprietary algorithmic drug sensitivity score (DSS) with percent effect relative to untreated controls. Results: Responses were highly patient-specific and frequently uncoupled between growth arrest and cell death, indicating distinct underlying dependencies. Cytotoxic chemotherapies: Topoisomerase I–based therapy showed the most consistent dual activity, consistent with replication stress vulnerability. Irinotecan produced cytotoxicity across cases (20–77%) with strong antiproliferation (85–99%). Gemcitabine produced strong antiproliferation (96–99%) with variable cytotoxicity (0–45%), consistent with S-phase suppression without uniform tumor kill. CDK4/6 inhibitors: Intra-class divergence suggested differences in target selectivity and pathway reliance. Ribociclib produced strong antiproliferation (72–96%) with minimal cytotoxicity (5–33%), consistent with cytostatic CDK4/6 blockade, whereas abemaciclib showed in one tumor a striking dual activity (cytotoxicity 81%, antiproliferation 97%), consistent with broader kinase activity beyond CDK4/6. With the exception of venetoclax, most other targeted agents were largely inactive or cytostatic only. Combinations: Combinations did not reliably exceed the best single agent and occasionally reduced cytotoxicity, consistent with independent and sometimes antagonistic interactions. Conclusions: Current NCCN guidelines for ependymoma emphasize surgical resection and radiotherapy without routine systemic therapy, a strategy supported by broad drug resistance across most tumors. However, multiplex ex vivo profiling revealed patient-specific vulnerabilities, including strong antiproliferative effects and, in selected cases, measurable cytotoxicity. Functional profiling may therefore enable rational selection of individualized systemic therapies in recurrent ependymoma, with the potential to improve quality of life, prolong progression-free survival, and possibly overall survival. Citation Format: Rajeshwar Nitiyanandan, Ivan Trus, Chiara Maestri, Shawn Mahoney, Ricardo J. Parker, John Norko, Sheila Singh, William Cance, Chris Apfel. Functional precision oncology in recurrent ependymoma: Multiplexed functional profiling reveals unexpected cytotoxic and anti-proliferative drug activity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr A054.

Although Jackson Pollock is most famous for his drip drawings, these occurred late in his career, starting around 1947. Prior to that he produced some “surrealist inflected” paintings and “gestural abstraction.” Troubled Queen in 1945 is considered Pollock’s masterful transitional work from the regionalist figurative paintings of his early years to the passionate “drip paintings” for which he is best known. As stated by Elliot Bostwick Davis et al (mfashop.com/9020398034), “As Troubled Queen shows, Pollock had begun to work in a very large scale by this time; his paint was dragged over, dripped on, and flung at the canvas. His subject matter was no less highly wrought: emerging from the churning coils and jagged lines of this life-sized canvas are two facelike forms, one a leering mask, the other a one-eyed diamond shape. Their nightmarish presences reflect not only Pollock’s agitated psyche but also the years of violence that had torn the world apart through war.” Thus, Troubled Queen shows that Pollock included images in his painting prior to his “drip paintings,” rendering it feasible that he continued to include images in his “drip paintings” using that new technique. We have coined the term “Polloglyphs TM” to name the images that are encrypted in his “drip paintings” and that tell a story about Pollock’s inner being, camouflaged yet hiding in plain sight.Here, in order to establish the basis for Polloglyphs in his later “drip paintings,” we have deconstructed the multiple images in Troubled Queen by first showing the image on a white background and then transposing it upon the painting. In this way, the observer can begin to see how images were incorporated into Pollock’s pre-drip paintings. These are not Rorschach ink blots with fractal edges that are fooling the eyes and only in the mind of the viewer, but images purposely put on canvas as the observer can see. Clearly, there is a “troubled queen” in Troubled Queen. Beyond that there are images of war possibly inspired by Picasso’s famous Guernica painted in 1937 and first seen by Pollock in 1939. A character is also seen to her left. Pollock had a trick that can be used to better visualize and uncover his images by rotating this painting 90 degrees counterclockwise. In this case, a small angel of mercy with her sword can be seen in the upper left quadrant. Another character, possibly a soldier with a hatchet and gun with bullet in the barrel can also be seen. Several other images can also be deciphered including a Picasso-like rooster and many others. Together, these images suggest a theme of war during the midst of World War II and may have triggered Pollock’s long standing feelings of inadequacy as his psychiatrist and his draft board found him unfit to serve as a soldier and he was exempted from serving. We encourage the observer to look carefully at Troubled Queen and to develop an opinion on which if any of the images are seen and to ponder as well what they may mean.FundingNo Funding

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The purpose of this study was to evaluate the safety and efficacy of a posterior facet replacement device, the Total Posterior Spine (TOPS) System, for the treatment of one-level symptomatic lumbar stenosis with grade I degenerative spondylolisthesis. Posterior lumbar arthroplasty with facet replacement is a motion-preserving alternative to lumbar decompression and fusion. The authors report the preliminary results from the TOPS FDA investigational device exemption (IDE) trial. The study was a prospective, randomized controlled FDA IDE trial comparing the investigational TOPS device with transforaminal lumbar interbody fusion (TLIF) and pedicle screw fixation. The minimum follow-up duration was 24 months. Validated patient-reported outcome measures included the Oswestry Disability Index (ODI) and visual analog scale (VAS) for back and leg pain. The primary outcome was a composite measure of clinical success: 1) no reoperations, 2) no device breakage, 3) ODI reduction of ≥ 15 points, and 4) no new or worsening neurological deficit. Patients were considered a clinical success only if they met all four measures. Radiographic assessments were made by an independent core laboratory. A total of 249 patients were evaluated (n = 170 in the TOPS group and n = 79 in the TLIF group). There were no statistically significant differences between implanted levels (L4-5: TOPS, 95% and TLIF, 95%) or blood loss. The overall composite measure for clinical success was statistically significantly higher in the TOPS group (85%) compared with the TLIF group (64%) (p = 0.0138). The percentage of patients reporting a minimum 15-point improvement in ODI showed a statistically significant difference (p = 0.037) favoring TOPS (93%) over TLIF (81%). There was no statistically significant difference between groups in the percentage of patients reporting a minimum 20-point improvement on VAS back pain (TOPS, 87%; TLIF, 64%) and leg pain (TOPS, 90%; TLIF, 88%) scores. The rate of surgical reintervention for facet replacement in the TOPS group (5.9%) was lower than the TLIF group (8.8%). The TOPS cohort demonstrated maintenance of flexion/extension range of motion from preoperatively (3.85°) to 24 months (3.86°). This study demonstrates that posterior lumbar decompression and dynamic stabilization with the TOPS device is safe and efficacious in the treatment of lumbar stenosis with degenerative spondylolisthesis. Additionally, decompression and dynamic stabilization with the TOPS device maintains segmental motion.