A multicenter, randomized, controlled, pivotal trial of microbubble-enhanced transcranial focused ultrasound for patients with NSCLC brain metastases (LIMITLESS).
Bibliographic record
Abstract
TPS2089 Background: The efficacy of systemic therapies for brain metastases (BM) is hindered by the blood-brain barrier (BBB) and brain-tumor barrier. Transcranial low-intensity focused ultrasound combined with IV microbubble oscillators (MB-FUS), allows for localized, controlled, non-invasive and temporary BBB opening, which has been shown to enhance tumor drug delivery of systemic therapies, as well as impro efficacy of immunotherapies. Non-small cell lung cancer (NSCLC) is the most common cause of BM, and this randomized controlled trial (RCT) aims to evaluate the safety and efficacy of MB-FUS-mediated BBB opening combined with standard of care (SOC) systemic therapy versus systemic therapy alone for patients with NSCLC BM. Methods: LIMITLESS is prospective, multicenter, parallel-arm, RCT, ongoing at up to 30 centers, that randomizes patients with NSCLC BM, in a 2:1 ratio to either: (i) Arm 1: MR-guided MB-FUS plus all FDA approved on-label use of immune checkpoint inhibitors (ICIs) with or without chemotherapy regimen (SOC systemic therapy), or (ii) Arm 2: SOC systemic therapy alone. Included patients are ≥18 years aged, with normal organ function, KPS ≥70, and have ≥0.5 cm size BM meeting measurable disease criteria as per RANO-BM. Patients on both arms receive standard-of-care therapy, while those on arm 1 also undergo MB-FUS. Patients undergo pre-treatment brain MRI, followed by IV administration of microbubbles for enhanced sonication effects. BBB opening is performed using a transcranial 220 kHz device with 1024-element phased array transducer with real-time acoustic feedback-based power control for maintaining effective microbubble activation. The primary study outcome is the overall objective response rate (ORR) at 6 months as assessed using RANO-BM criteria. Using a Bayesian design for power analysis, a superior ORR of 60% is assumed for MB-FUS arm versus 30% in the control arm for a total sample size of N = 96, 64 participants in MB-FUS and 32 in control arm, for 80% power using a two-sided chi-square test with an alpha of 0.05. For the upper-bound estimate, ORR of 45% in MB-FUS arm and 30% in the control arm, the study needs N = 369 participants: 246 in LIFU arm and 123 in control arm. The secondary outcomes are best objective response rate and median time-to-response per treatment arm. Exploratory outcomes are median progression-free survival (PFS), overall survival (OS), median intracranial PFS, median extracranial PFS, and quality of life. Patient enrollment commenced in 2022 and is ongoing (ClinicalTrials.Gov Registration: NCT05317858). Clinical trial information: NCT05317858 .
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".