Differential impact of cisplatin dose intensity on human papillomavirus (HPV)-related (+) and HPV-unrelated (−) locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC).
Bibliographic record
Abstract
6020 Background: Definitive radiotherapy with concurrent cisplatin (CDDP) is a standard treatment for patients (pts) with LAHNSCC. We evaluated the impact of CDDP dose intensity (mg/m2) on overall survival (OS) of HPV+ and HPV- LAHNSCC pts. Methods: Princess Margaret Cancer Centre (PM) and Istituto Nazionale dei Tumori (INT) LAHNSCC cohorts treated from 2000 to 2012 were reviewed. Kaplan-Meier method was used to estimate the 5-year (yr) OS in HPV+ vs HPV− pts. HPV status was determined by p16 staining or in situ hybridization HPV DNA for all oropharyngeal (OPC), unknown primary (UNK), and ≤ 10 pack-year (PY) smoking laryngo-hypopharyngeal cancer (LHC). Untested p16, >10 PY LHC pts were assumed HPV−. Multivariable analysis (MVA) with Cox regression identified OS predictors for HPV+ and HPV− pts. Results: A total of 659 pts (584 PM; 75 INT) were evaluated. Pts characteristics included: median age 58 (range: 27-81); primary site: OPC 73%, LHC 24%, UNK 3%; non-smokers 27%; stage: T4 25%, N2c-N3 60%; HPV+ 404 (61%), HPV− 255 (39%) pts. Median CDDP dose was 200 mg/m2 for both HPV+ and HPV− cohorts. Median follow-up was 4.3 yrs. Five year OS was inferior for HPV− CDDP ≤ 200 vs > 200 mg/m2 (44 vs 62%, p < 0.01), while no difference was detected in HPV+ CDDP ≤ 200 vs > 200 mg/m2 (83 vs 87%, p = 0.30), confirmed by MVA (Table). In N3 or T4 HPV+ pts, a trend on OS in CDDP >200 mg/m2(HR = 0.62, 95% CI: 0.30-1.31) was observed. Conclusions: In this large multicenter cohort study, CDDP dose intensity ≤ 200 mg/m2had a detrimental impact on OS in HPV− LAHNSCC pts. The impact of CDDP dose intensity on HPV+ pts was not significant. These results warrant prospective validation. MVA for OS in HPV+ and HPV– pts. HR (95% CI) & p value CDDP (mg/m2) > 200 vs ≤ 200 Age 1 yr increment Smoking 10 PY increment T HPV+: T4 vs T0-3 HPV–: T3-4 vs T1-2 N HPV+: N2c-3 vs N0-2b HPV–: N2b-3 vs N0-2a Disease Site Non-OPC vs OPC HPV+ 0.8 (0.4-1.4) p = 0.46 0.98 (0.95-1.01) p = 0.25 1.2 (1.02-1.3) p = 0.03 2.5 (1.3-4.5) p < 0.01 2.4 (1.3-4.4) p < 0.01 NA HPV– 0.5 (0.3-0.8) p < 0.01 1.00 (0.98-1.02) p = 0.93 1.1 (0.98-1.2) p = 0.12 1.4 (0.9-2.1) p = 0.13 2.4 (1.5-3.9) p < 0.01 1.2 (0.8-1.8) p = 0.38
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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 | 0.001 |
| 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".