Hippocampal Avoidance During Prophylactic Cranial Irradiation for Patients With Small Cell Lung Cancer: Randomized Phase II/III Trial NRG-CC003
Bibliographic record
Abstract
PURPOSE Hippocampal avoidance (HA) during therapeutic whole-brain radiotherapy reduces the risk of neurocognitive function (NCF) toxicity in patients with brain metastasis. This trial hypothesized that HA during prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) leads to noninferior intracranial relapse (ICR) and reduction in NCF toxicity. METHODS This randomized phase II/III trial enrolled patients with SCLC, no brain metastases, and response to chemotherapy. The primary end points were 12-month ICR (noninferiority design, randomized phase II) and 6-month Hopkins Verbal Learning Test–Revised (HVLT-R) Delayed Recall (DR) failure (phase III). Secondary end points were failure in any NCF test, health-related quality of life (HRQOL), overall survival (OS), and toxicity. RESULTS From December 2015 to June 2022, 393 patients were randomly assigned. The median age was 64 years. Stage and memantine usage were balanced. The median follow-up was 17.0 months (all patients) and 30.8 months (alive patients). HA-PCI had noninferior 12-month ICR rate (PCI 14.8% v HA-PCI 14.7%, P < .0001). Six-month HVLT-R DR deterioration was not significantly different (PCI 30.0% v HA-PCI 25.5%, P = .28). Addition of HA to PCI reduced the risk of failure in any NCF test (adjusted hazard ratio [HR], 0.78; 95% CI [0.61 to 0.99]; P = .039). Addition of HA to PCI was not associated with longitudinal change in any HRQOL domain. There were no differences in OS (adjusted HR, 0.88 [95% CI, 0.67 to 1.14]; P = .33) or grade ≥3 toxicity (PCI 31.4% v HA-PCI 30.7%, P = .88). CONCLUSION Although the study did not meet its primary end point of DR preservation, HA during PCI reduces the risk of overall neurocognitive toxicity with noninferior ICR risk and similar survival.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.010 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".