Background: The timing of return to play after anterior cruciate ligament (ACL) reconstruction is still controversial due to uncertainty of true ACL graft state at the time of RTP. Recent work utilizing ultra-short echo T2* (UTE-T2*) magnetic resonance imaging (MRI) as a scanner-independent method to objectively and non-invasively assess the status of in vivo ACL graft remodeling has produced promising results. Purpose/Hypothesis: The purpose of this study was to prospectively and noninvasively investigate longitudinal changes in T2* within ACL autografts at incremental time points up to 12 months after primary ACL reconstruction in human patients. We hypothesized that (1) T2* would increase from baseline and initially exceed that of the intact contralateral ACL, followed by a gradual decline as the graft undergoes remodeling, and (2) remodeling would occur in a region-dependent manner. Study Design: Case series; Level of evidence, 4. Methods: Twelve patients (age range, 14-45 years) who underwent primary ACL reconstruction with semitendinosus tendon or bone–patellar tendon–bone autograft (with or without meniscal repair) were enrolled. Patients with a history of previous injury or surgery to either knee were excluded. Patients returned for UTE MRI at 1, 3, 6, 9, and 12 months after ACL reconstruction. Imaging at 1 month included the contralateral knee. MRI pulse sequences included high-resolution 3-dimensional gradient echo sequence and a 4-echo T2-UTE sequence (slice thickness, 1 mm; repetition time, 20 ms; echo time, 0.3, 3.3, 6.3, and 9.3 ms). All slices containing the intra-articular ACL were segmented from high-resolution sequences to generate volumetric regions of interest (ROIs). ROIs were divided into proximal/distal and core/peripheral sub-ROIs using standardized methods, followed by voxel-to-voxel registration to generate T2* maps at each time point. This process was repeated by a second reviewer for interobserver reliability. Statistical differences in mean T2* values and mean ratios of T2*inj/T2*intact (ie, injured knee to intact knee) among the ROIs and sub-ROIs were assessed using repeated measures and one-way analyses of variance. P < .05 represented statistical significance. Results: Twelve patients enrolled in this prospective study, 2 withdrew, and ultimately 10 patients were included in the analysis (n = 7, semitendinosus tendon; n = 3, bone–patellar tendon–bone). Interobserver reliability for T2* values was good to excellent (intraclass correlation coefficient, 0.84; 95% CI, 0.59-0.94; P < .001). T2* values increased from 5.5 ± 2.1 ms (mean ± SD) at 1 month to 10.0 ± 2.9 ms at 6 months ( P = .001), followed by a decline to 8.1 ± 2.0 ms at 12 months ( P = .129, vs 1 month; P = .094, vs 6 months). Similarly, mean T2*inj/T2*intact ratios increased from 62.8% ± 22.9% at 1 month to 111.1% ± 23.9% at 6 months ( P = .001), followed by a decline to 92.8% ± 29.8% at 12 months ( P = .110, vs 1 month; P = .086, vs 6 months). Sub-ROIs exhibited similar increases in T2* until reaching a peak at 6 months, followed by a gradual decline until the 12-month time point. There were no statistically significant differences among the sub-ROIs ( P > .05). Conclusion: In this preliminary study, T2* values for ACL autografts exhibited a statistically significant increase of 82% between 1 and 6 months, followed by an approximate 19% decline in T2* values between 6 and 12 months. In the future, UTE-T2* MRI may provide unique insights into the condition of remodeling ACL grafts and may improve our ability to noninvasively assess graft maturity before return to play.

Clinical studies treating pediatric and adult solid tumors, such as glioblastoma (GBM), with a triple-drug regimen of temozolomide (TMZ), bevacizumab (BEV), and irinotecan (IRI) [TBI] have demonstrated various efficacies, but with no unexpected toxicities. The TBI regimen has never been studied in recurrent GBM (rGBM) patients. In this retrospective study, we investigated the outcomes and side effects of rGBM patients who had received the TBI regimen. We identified 48 adult rGBM patients with a median age of 56 years (range: 26–76), who received Tumor Treating Fields (TTFields) treatment for 30 days or longer, and concurrent salvage chemotherapies. The patients were classified into two groups based on chemotherapies received: TBI with TTFields (TBI+T, N = 18) vs. bevacizumab (BEV)-based chemotherapies with TTFields (BBC+T, N = 30). BBC regimens were either BEV monotherapy, BEV+IRI or BEV+CCNU. Patients in TBI+T group received on average 19 cycles of TMZ, 26 and 21 times infusions with BEV and IRI, respectively. Median overall survival (OS) and progression-free survival (PFS) for rGBM (OS-R and PFS-R) patients who received TBI+T were 18.9 and 10.7 months, respectively. In comparison, patients who received BBC+T treatment had OS-R and PFS-R of 11.8 (P > 0.05) and 4.7 (P < 0.05) months, respectively. Although the median PFS results were significantly different by 1.5 months (6.6 vs. 5.1) between TBI+T and BBC+T groups, the median OS difference of 14.7 months (32.5 vs. 17.8) was more pronounced, P < 0.05. Patients tolerated TBI+T or BBC+T treatments well and there were no unexpected toxicities. The most common side effects from TBI+T treatment included grade III hypertension (38.9%) and leukopenia (22.2%). In conclusion, the TBI regimen might play a role in the improvement of PFS-R and OS-R among rGBM patients. Prospective studies with a larger sample size are warranted to study the efficacy and toxicity of TBI+T regimen for rGBM.

Central nervous system (CNS) malignancies can be difficult to diagnose and many do not respond satisfactorily to existing therapies. Monitoring patients with CNS malignancies for treatment response and tumour recurrence can be challenging because of the difficulty and risks of brain biopsies, and the low specificity and sensitivity of the less invasive methodologies that are currently available. Uncertainty about tumour diagnosis or whether a tumour has responded to treatment or has recurred can cause delays in therapeutic decisions that can impact patient outcome. Therefore, there is an urgent need to develop and validate reliable and minimally invasive biomarkers for CNS tumours that can be used alone or in combination with current clinical practices. Blood-based biomarkers can be informative in the diagnosis and monitoring of various types of cancer. However, blood-based biomarkers have proven suboptimal for analysis of CNS tumours. In contrast, circulating biomarkers in cerebrospinal fluid (CSF), including circulating tumour DNA, microRNAs and metabolites, hold promise for accurate and minimally invasive assessment of CNS tumours. This review summarises the current understanding of these three types of CSF biomarkers and their potential use in neuro-oncologic clinical practice.

We report a case of a patient with newly diagnosed, locally extensive and cystic, suprasellar papillary craniopharyngioma successfully treated with single-agent Dabrafenib. The patient was symptomatic with gait imbalance with falls, lethargic episodes, fatigue and incontinence. Diagnostic imaging demonstrated a cystic suprasellar tumor extending into the third ventricle causing obstructive hydrocephalus. The tumor was partially debulked, and bilateral shunts were placed. NGS sequencing demonstrated BRAF V600E mutation, and the patient was prescribed dual agent Dabrafenib and Trametinib. However, due to insurance denial for Trametinib, he only received single-agent Dabrafenib (150mg BID). The treatment resulted in a major response (over two years), including reduction of the tumor cyst, and improvement of the clinical symptoms. No adverse events have been reported. The patient continues on Dabrafenib (150 mg BID) with a steady reduction in tumor size, and improvement in cognitive function leading to independent living.

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s vi147 NEURO-ONCOLOGY • NOVEMBER 2017artifact that complicates interpretation. The ideal system of intraoperative histology would be built on a rapid, standardized workflow with minimal tissue processing and diagnostic-quality images. Stimulated Raman histology (SRH) is a new label-free imaging technique that provides intraoperative histologic images of fresh, unprocessed surgical specimens. Here, we evaluate the capacity of SRH for use in the intraoperative diagnosis of pediatric brain tumors. SRH revealed key diagnostic features in fresh tissue specimens collected from 33 prospectively enrolled pediatric brain tumor patients, preserving tumor cytology and histoarchitecture in all specimens. We simulated an intraoperative neuropathology consultation for 25 patients with specimens imaged using both SRH and standard H&E histology. SRH-based diagnoses achieve near-perfect diagnostic concordance (Cohen's kappa, κ > 0.90) and an accuracy of 92-96%. Leveraging the image contrast generated by the intrinsic biochemical data embedded in SRH images, we developed a quantitative histologic method that allows for rapid image feature extraction. Nuclear density, tumor-associated macrophage infiltration, and nuclear morphology parameters extracted from 3337 SRH fields of view were used to develop and train a decision tree machine-learning model. Using SRH image features, our model correctly identified normal versus lesional tissue and low-grade versus high-grade tumors in 25 fresh pediatric surgical specimens with 100% accuracy. Our results provide insight into how SRH can deliver rapid diagnostic histologic data during pediatric brain tumor surgery.

2021 Background: Microtubule inhibitors, including taxanes, are active in preclinical models of glioblastoma (GBM), however, clinical benefit is hampered by poor blood-brain barrier (BBB) accumulation. TPI 287, a third-generation taxane designed to evade P-glycoprotein mediated efflux, readily penetrates the BBB and overcomes this limitation. CB-017 is a multi-center phase 1/2 trial designed to determine the optimal dose of TPI 287 and potential efficacy in patients treated with this drug plus bevacizumab (BEV) for treatment of recurrent GBM. Final results of the dose escalation Phase 1 stage of this trial are reported. Methods: GBM patients at first or second relapse after standard therapy and without prior exposure to anti-angiogenic agents were eligible for enrollment. BEV was administered at 10 mg/kg every 2 weeks and TPI 287 every 3 weeks via IV infusion. MRIs were obtained every six weeks with response assessed via RANO criteria. TPI 287 dose escalation was based on a traditional 3+3 design. Results: Twenty-four patients were enrolled in 7 TPI 287 dose-escalation cohorts (140-220 mg/m2) from 6 U.S. centers. Twenty and 23 patients were evaluable for response and survival, respectively. Median follow-up was 28 months. Results are shown in the table below. Of the 9 patients from which biomarker data was available, tumors from 8 patients (89%) harbored an unmethylated MGMT promoter, an established negative prognostic indicator for survival. No DLTs were reported and myelosuppression (n=3) was the only drug-related grade 3/4 adverse event. Conclusions: TPI 287 in combination with BEV is safe and well tolerated at doses up to 220 mg/m2. Final survival results from the Phase 1 portion of this study compare favorably with historical controls and support further investigation of TPI 287 plus BEV for treatment of recurrent GBM. Clinical trial information: NCT01933815. [Table: see text]

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