A phase I trial of intratumoral (i.t.) administration of reovirus in patients with histologically confirmed recurrent malignant gliomas (MGs)
Bibliographic record
Abstract
1563 Background: Reovirus is an oncolytic virus which replicates preferentially in transformed cells possessing activated Ras signaling pathways. Promising activity was found in in vivo models of MGs and in a phase I trial in patients (pts.) with cutaneous metastases from systemic cancer. We performed this dose-escalation trial of i.t. administration of reovirus to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) in pts. with recurrent MG. Response, survival and time to progression (TTP) were secondary aims. Methods: Pts. were ≥ 18 yrs old, had a KPS ≥ 60, received prior radiotherapy ± chemotherapy, a histologically proven recurrence of MG and recurred ≤ 3 times. Reovirus was administered i.t. stereotactically at one of three dose levels (1 × 107, 1 × 108 or 1 × 109 TCID50) in a volume of 0.9 mls. Results: Twelve pts. were treated at 3 dose levels; seven were men, the median (mdn) KPS was 80, mdn age was 53.5 yrs, 10 had glioblastoma multiforme, one anaplastic astrocytoma and another anaplastic oligoastrocytoma. There were the 1st, 2nd or 3rd recurrences in 6, 5 and 1 pts., respectively. During i.t. viral administration all pts. were treated with prophylactic anticonvulsants and 6 (50%) were receiving corticosteroids. The 1st, 2nd and 3rd cohorts contained 3, 6 and 3 pts., respectively. There were no grade 3 or 4 adverse events definitely or probably related to the administration of reovirus. A transient increase in GGT was possibly related to reovirus administration and a patient experienced grade 3 motor weakness that could be related to post-injection edema. Viral shedding and systemic immune responses were examined but results are pending. There were no CR, or PR; a pt. had SD, 10 PD and one was not evaluable. The mdn survival was 20 weeks (range, 6–171), 6 pts. survived > 6 months and 3 are alive 6, 7 and 40 months from the reovirus injection. The mdn TTP was 4.3 weeks (range: 3.4–39). Conclusions: A MTD was not reached. The intratumoral administration or reovirus was well tolerated in patients with recurrent MGs. Phase 2 studies in MGs are planned. [Table: see text]
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 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".