Neoadjuvant versus adjuvant therapy in patients with stage III or IV resectable melanoma: A systematic review and meta-analysis.
Bibliographic record
Abstract
e21542 Background: Neoadjuvant therapy (NAT) has emerged as a promising strategy to treat resectable melanoma patients by generating a robust immune response and longer immunologic memory. We performed a systematic review and meta-analysis evaluating the survival benefit of NAT compared to standard adjuvant therapy (AT) for melanoma patients. Methods: We searched for randomized clinical trials (RCT) comparing NAT versus AT in resectable stages IIIB/C or IV melanoma patients on PubMed, Scopus, and Cochrane Library databases. We assessed event-free survival (EFS), distant metastasis-free survival (DMFS), overall survival (OS), and safety. Studies included were limited to RCTs with an adjuvant control arm and reporting at least one of the outcomes of interest. Heterogeneity was examined with the I2 statistics, and the random effects model was fitted. Results: Four RCTs met inclusion criteria for a total of 504 patients. Most patients had stage IIIB/C (79.1%), and received NAT with immunotherapy (66%), target therapy (4.2%) and talimogene laherparepvec (TVEC) (29.8%). In the pooled analysis of 2-year follow-up: 71.3% of patients in the NAT arm and 53.2% in AT arm were event-free [Risk Ratio (RR): 0.57 95%Cl 0.39-0.83 p=0.003]. Albeit the difference in therapies, NAT decreased by 44% the risk of death compared to AT, with 89.4% and 81.2% of patients alive at two years, respectively (RR 0.56 95%Cl 0.36-0.87 p=0.01). DMFS was reported in three studies (n=191). Patients on NAT had numerically higher DMFS rate (44%) compared to AT (28.6%) (p=0.23). Two studies (n=170) have published 5-year follow-up results: OS rate has remained statistically significant, favoring NAT (RR 0.58 95%Cl 0.34-0.97 p=0.04). Significant differences were not observed in EFS (p=0.06) and DMFS (p=0.08). Adverse events were similar in both groups, and there were no treatment-related deaths. In these studies, there were no significant delays in surgery due to toxicity or unexpected perioperative complications. Combined immunotherapy caused the highest incidence of grade 3/4 toxicity (90%) among the therapies. Conclusions: This systematic review and meta-analysis indicate a significant survival benefit from NAT for stages IIIB/C and resectable stage IV melanoma. NAT induces better anti-tumor activity, leading to improved EFS and OS compared to AT, with similar safety profile. Phase 3 clinical trials with longer follow-up are warranted. [Table: see text]
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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 | 0.010 | 0.020 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.017 | 0.036 |
| Bibliometrics | 0.005 | 0.006 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".