Abstract 767: Cyclosporin-modulated intensified-dosage chemotherapy for saving eyes with Group D intraocular retinoblastoma
Bibliographic record
Abstract
Abstract PURPOSE: Cyclosporin (CSA) inhibits the multidrug resistance P-glycoprotein. Since 2000, we tested increased carboplatin and increased etoposide dosages in a cyclosporin-modulated carboplatin-etoposide-vincristine protocol, followed by focal laser/cryotherapy consolidation, to avoid elective radiation of newly diagnosed retinoblastoma (RB) patients, since radiation increases the secondary cancer risk in patients with heritable RB. We report the results for International Classification Groups A, B, C and D intraocular eyes (Ophthalmol Clinic North Am 2005; 18:41-53). METHOD: When Neupogen support became available, we increased the predominantly myelotoxic carboplatin to 28 mg/kg (from 18.7 mg/kg in our previous trial) and etoposide to 12 mg/kg (from 7.7 mg/kg in our previous trial), but kept the predominantly neurotoxic vincristine unchanged at 0.05 mg/kg, modulated by the same cyclosporin schedule (33 mg/kg over 3 hours on each of the 2 days per cycle). We treated 34 eyes in 23 patients: 2 A eyes, 11 B eyes, 6 C eyes and 15 D eyes. This report focuses only on the most difficult to save Group D eyes, and compares results with a non-cyclosporin carboplatin (26 mg/kg) and etoposide (10 mg/kg), vincristine (0.05 mg/kg) regimen. Radiation or enucleation for recurrence was considered failure. RESULTS: We report the long-term results of 15 Group D eyes in 10 patients, at mean followup of 11.1 years and median followup of 10.8 years (range 5.7-13.4 years). Eye event-free rate was 53% for Group D (8/15) eyes. Seven D eyes failed, and 6 were enucleated and 1 radiated. No child lost both eyes. Toxicity rates were acceptable with 15.7% fever-and-neutropenia, 0.7% bacterial sepsis, 9.7% blood transfusion and 27.6% platelet transfusion, and no long-term renotoxicity or ototoxicity. In comparison, at mean followup of 4.5 years (range 0.4-9.8 years), in a previously reported (Pediatr Blood Cancer 2013; 60:688-693) non-cyclosporin regimen, the non-radiation eye event-free rate was 47% for Group D (26/55) eyes, with 5 eyes enucleated, and 24 eyes radiated (19 irradiated eyes retained; 5 irradiated eyes required enucleation). CONCLUSION: This cyclosporin-modulated intensified-dosage protocol was well-tolerated, with a non-radiation eye salvage rate of 53%, and 60% overall if the one irradiated but retained eye was included, in the most difficult to save Group D eyes. No child lost both eyes, and most avoided radiation. This same protocol is being tested in a multicenter trial. Citation Format: Helen S.L. Chan, Elise Héon, A Linn Murphree, Paulita P. Astudillo, Helen Dimaras, Furqan Shaikh, Brenda L. Gallie. Cyclosporin-modulated intensified-dosage chemotherapy for saving eyes with Group D intraocular retinoblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 767. doi:10.1158/1538-7445.AM2014-767
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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) | 0.001 | 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) | 0.002 | 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".