Survival Outcomes in T3N0 versus N1 in Head and Neck Cutaneous Squamous Cell Carcinoma – Implications for Neoadjuvant Immune Checkpoint Inhibitor Immunotherapy
Bibliographic record
Abstract
Background: Based on encouraging clinical outcomes in unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC), the role of immune checkpoint inhibitor (ICI) immunotherapy in the (neo)adjuvant setting for earlier-stage [AJCC stage II-IV (M0)] disease is being investigated. Although pN1 disease is not included in current adjuvant trials, including C-POST (NCT03969004) and Keynote 630 (NCT03833167) where postoperative adjuvant radiotherapy remains a prerequisite, pathological staging is unavailable for neoadjuvant clinical trials and therefore, patients with isolated cN1 disease will still be included. Our anecdotal experience suggests significant differences in prognosis between the T3N0 and isolated N1 subgroups of stage III disease, with the latter having a significantly favourable outcome. Better risk-stratification of T3N0 versus isolated N1 disease is warranted to enable improved communication of the longer-term risks and benefits of neoadjuvant ICI, and critical appraisal of clinical trial data. The objective of this study is to undertake a systematic review and meta-analysis of survival outcomes in pT3N0 versus pN1 head and neck cSCC (HNcSCC). Methods: Five databases were searched for studies reporting survival outcomes (disease free survival; DFS or disease specific survival; DSS) in either pT3N0 or isolated pN1 HNcSCC between 2010 and January 2024. Two reviewers independently extracted data. Risk of bias was estimated with the Newcastle-Ottawa Scale. Kaplan-Meier curves were extracted, digitised and aggregated as per established procedure. The Kaplan-Meier method, log-rank test and univariate Cox analysis were used to describe and compare survival outcomes for aggregated pT3N0 and pN1 cohorts. Results: The aggregated groups contained 405 pT3N0 and 161 isolated pN1 patients. DFS could not be assessed due to lack of data. DSS was significantly worse for pT3N0 disease compared to pN1 disease (HR 1.800, 95% CI 1.168-2.774, log rank p-value = 0.007) with 5-year DSS of 69.3% [standard error (SE) 3.5%] for pT3N0 disease versus 81.6% (SE 3.0%) for pN1 disease (Figure 1). Figure 1 - Kaplan-Meier curve for disease specific survival in aggregated groups of patients with N1 versus T3N0 cutaneous squamous cell carcinoma of the head and neck Conclusions: The risk-benefit implications from ICI immunotherapy differ for T3N0 versus isolated N1 patients. Appreciation of the significant survival outcome difference between these two stage III subgroups is critical when designing neoadjuvant ICI clinical trials and interpreting trial data.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 teacher head, 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".