Abstract 3535: Retinoblastoma cerebrospinal fluid metastases treatable by intensive intraventricular and multidrug resistance-reversal systemic chemotherapy without radiation
Bibliographic record
Abstract
Abstract PURPOSE: Despite combining chemotherapy with peripheral stem cell transplant, cerebrospinal fluid (CSF) metastasis is the most difficult type of retinoblastoma (RB) metastasis to cure, since most drugs that can be given safely into the CSF are anti-leukemia agents that are ineffective against solid tumors. Most metastatic RB cells also express P-glycoprotein causing multidrug resistance (MDR). Drugs do not readily enter into the central nervous system because of the blood-brain barrier formed by P-glycoprotein-rich blood vessels. High-dose craniospinal radiation is too morbid for treatment of young children. Radiation also greatly increases the secondary malignancy risk for patients with germline RB1 mutations. To cure CSF metastases without craniospinal radiation, we designed an intensive multimodality chemotherapy regimen. METHOD: Since 2000, we treated 4 children with CSF metastases: Child A, with germline bilateral RB, and optic nerve involvement (1 eye enucleated but no radiation); Child B, with germline trilateral RB (no enucleation and no surgery or radiation for the huge suprasellar tumor); Child C, with germline trilateral RB (1 eye enucleated but no surgery or radiation for the huge suprasellar tumor); and Child D, with nongermline unilateral RB with orbital and intracranial recurrence (only localized orbital radiation). All children were treated with 6 or 7-cycle high-dose carboplatin and etoposide, standard-dose vincristine, and high-dose/3-hour-infusion cyclosporine to inhibit both tumor-cell and blood-brain barrier P-glycoprotein. Intraventricular drugs, cytarabine, which is not a substrate of P-glycoprotein but effective against RB cell line in vitro, and topotecan, which is less susceptible to MDR, contributed to treatment of the CSF metastases. On achieving significant responses, supralethal-dosage carboplatin, etoposide and cyclophosphamide were used for consolidation, with the bone marrow rescued with autologous peripheral blood stem cells. RESULTS: Child A and C are relapse-free 9.1 and 2.3 years post-diagnosis (8.6 and 1.8 years post-transplant). Child B and D died of disease 2.7 and 1.8 years post-diagnosis (2 and 1.4 years post-transplant). CONCLUSION: Two of the 4 children with CSF metastases, who in the past would have died, are now surviving after intensive multimodality chemotherapy without radiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3535.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".