Comprehensive therapy for trilateral retinoblastoma
Bibliographic record
Abstract
229 Purpose: We had reported that carboplatin-etoposide-vincristine modulated by cyclosporine (CSA), which inhibits the multidrug resistance (MDR) P-glycoprotein, could cure newly diagnosed and relapsed children with intraocular retinoblastoma (RB). We propose determining the success of this protocol, combined with autologous peripheral stem cell transplant for marrow rescue after supralethal chemotherapy, for curing babies with the very rare trilateral RB. Methods: Since 2004, we treated 3 babies with trilateral RB with systemic carboplatin-etoposide-vincristine, with high-dose, short 3-hour CSA infusions aimed at inhibiting both RB cell and blood-brain barrier vascular P-glycoprotein, concurrently with Ommaya reservoir-delivery of intraventricular topotecan-cytarabine, which kill RB cells in vitro. Since the babies were too young to receive craniospinal radiation without devastating long-term sequelae, and had germline disease greatly predisposing to radiation-induced secondary malignancies, the intracranial tumor responses were consolidated with autologous peripheral stem cell transplant after supralethal chemotherapy, and intraocular tumor responses, with focal cryo/laser therapy. Results: Patient 1, a 4-month-old girl with hypothalamic overgrowth syndrome and central blindness, had tumor cells in the cerebrospinal fluid (CSF) after, but not before biopsy of the suprasellar tumor. Both the suprasellar tumor, eye tumors and CSF responded to chemotherapy, and the blindness resolved. Twenty months after diagnosis and 12 months after transplant, she developed tumor recurrence along the needle biopsy track, and died 32 months after diagnosis. Patient 2, a 6-month-old boy with central blindness, had tumor cells in the CSF despite no biopsy of the suprasellar tumor. The suprasellar tumor and CSF responded to chemotherapy, the blindness resolved, and he will be transplanted after 6 cycles of chemotherapy. Patient 3, a 9-week-old girl with central blindness, hydrocephalus and diabetes insipidis, had tumor cells in the CSF despite no biopsy of the suprasellar tumor. She just started chemotherapy. Conclusions: In the literature, babies with trilateral RB die of their disease because surgery and radiation are not treatment options, and chemotherapy alone rarely cures brain tumors. Few drugs are non-toxic and yet effective for treating RB cells in the CSF. Our comprehensive therapy offers hope of cure. CSA, which reverses MDR in tumor cells, also increases drugs crossing the blood-brain barrier, may make the difference between success or failure of chemotherapy for these intracranial tumor. We recommend checking for pineal/suprasellar masses in babies with RB, albeit that trilateral RB is rare. Conversely, if pineal/suprasellar masses are found in babies, check the eyes for RB, since this may avoid biopsies of the intracranial tumor, which may track difficult-to-treat RB cells through the brain, disseminating them into the CSF.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".