A multicenter cooperative group study of late effects after high-risk neuroblastoma: COG ALTE15N2—LEAHRN study.
Bibliographic record
Abstract
10002 Background: Aggressive therapies for high-risk neuroblastoma (HRNBL) have resulted in increased survival, but late effects have not been well-characterized. Methods: Comprehensive cross-sectional evaluation of health outcomes in HRNBL survivors enrolled on the COG Neuroblastoma Biology Study after 1/1/2000 and ≥ 5 years from primary diagnosis, using medical record abstraction and in-person clinical assessments. Descriptive and multivariable analyses identified extent of and risk factors for late toxicity. Results: There were 375 participants from 88 COG centers, 205 (55%) male; 92 (26%) non-white; 45 (13%) Hispanic. Median age at neuroblastoma diagnosis was 2.5 years (range: 0.2-15.8), at enrollment was 12.0 years (range: 5.0-24.0). All had received chemotherapy; 94% received cisplatin (median dose: 398 mg/m2). Other exposures included: radiation (95%), isotretinoin (91%), anti-GD2 antibody therapy (64%), MIBG (7%), single (79%) or tandem autologous transplantation (ASCT; 20%). ASCT conditioning included: Busulfan/Melphalan (BuMel) (18%), Carboplatin/Etoposide/Melphalan (CEM) (73%), Thiotepa/Cytoxan (19%), and total body irradiation (5%). Severe ototoxicity (requiring hearing aids) was observed in 58% of participants. Physician-reported late effects included hypothyroidism (17%), pulmonary hypertension (1%), congestive heart failure (2%), and hypertension (6%). Pulmonary Function Studies revealed restrictive lung disease [RLD - Total Lung Capacity < 70% predicted] in 8% of subjects. Laboratory study showed elevated creatinine in 7% and Hemoglobin A1c in 7%. Growth failure (height Z-score < -1.7) was observed in 34%. Subsequent malignant neoplasms (SMN) developed in 15 participants (4%; 4 sarcomas, 3 MDS/t-AML, single instance of 8 other malignancies). Adjusting for sex, follow-up time, age, and race, there were no differences in risk of SMN, severe ototoxicity, growth failure, or RLD for participants who received BuMel vs. CEM-based condtioning, or among those who received anti-GD2 antibody therapy vs. those who did not. Use of carboplatin during ASCT was not assocoiated with increased ototoxicity risk for any category of cisplatin induction dose. Comparing subjects who received CEM as a component of tandem ASCT (vs. single CEM), there was increased risk of growth failure [OR (95%CI) = 4.2(2.1, 8.4); p < 0.0001], but not RLD. Exposure to isotretinoin was not associated with increased risk of growth failure. Further multivariable analyses will be presented, exploring risks for late toxicity associated with conditioning regimens, radiation therapy, surgical approaches, and acute and chronic complications of therapy. Conclusions: The burden of late toxicity in HRNBL survivors is substantial. Anti-GD2 immunotherapy and isotretinoin do not appear to be associated with SMN, ototoxicity, growth failure, or RLD.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 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".