Dataset Information

Efficacy and Toxicity of Three Induction Chemotherapy Regimens in Locoregionally Advanced Nasopharyngeal Carcinoma: Outcomes of 10-Year Follow-Up

ABSTRACT:

Background/Objective

We aimed to compare the 10-year survival outcomes of induction docetaxel plus cisplatin and 5-fluorouracil (TPF), docetaxel plus cisplatin (TP), and cisplatin plus 5-fluorouracil (PF) regimens additional to concurrent chemoradiotherapy (CRT) in locoregionally advanced nasopharyngeal carcinoma (NPC).

Methods

Eligible patients with newly diagnosed stage III-IVA NPC were included. Propensity score matching (PSM) was used to balance prognostic covariates. Survival outcomes and toxicities between different groups were compared.

Results

A total of 855 patients between 2009 and 2012 were included, with 395 (46.2%), 258 (30.2%), and 202 (23.6%) receiving TPF plus CRT, TP plus CRT, and PF plus CRT regimens, respectively. After a median follow-up of 111.8 months, multivariate analysis both in the whole cohort and PSM selected 202 pairs showed that TPF plus CRT and TP plus CRT achieved significantly better 10-year overall survival (OS) than PF plus CRT. Sensitivity analysis after excluding patients with T3-4N0 disease demonstrated that TPF plus CRT still achieved significantly better OS than PF plus CRT (HR, 0.580; 95% CI, 0.395-0.852; P = 0.005), while the difference between TP plus CRT and PF plus CRT was marginally significant (HR, 0.712; 95% CI, 0.503-1.008; P = 0.056). With regard to toxicity profile, PF regimen achieved the lowest grade 3–5 toxicities (27.3%).

Conclusion

TPF plus CRT and TP plus CRT were better than PF plus CRT in improving the 10-year OS of patients with stage III-IVA NPC.

SUBMITTER: Peng H

PROVIDER: S-EPMC8551638 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundInduction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) for non-metastatic locoregionally advanced nasopharyngeal carcinoma (NPC) has gained considerable attention. However, the most efficacious IC regimens remain investigational. We aimed to compare the survival benefits of all available IC regimens followed by CCRT in this network meta-analysis.MethodsAll randomized-controlled trials of CCRT with or without IC in non-metastatic locoregionally advanced NPC were included, with an overall nine trials of 2,705 patients counted in the analysis. CCRT alone was the reference category. Eight IC regimens followed by CCRT were analyzed: docetaxel + cisplatin (DC), gemcitabine + carboplatin + paclitaxel (GCP), gemcitabine + cisplatin (GP), mitomycin + epirubicin + cisplatin + fluorouracil + leucovorin (MEPFL), cisplatin + epirubicin + paclitaxel (PET), cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX) and cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX). Fixed-effects frequentist network meta-analysis models was applied and P-score was used to rank the treatments.ResultsDC, GP, and PX were the top three IC regimens with the highest probability of benefit on overall survival (OS). Their corresponding hazard ratios (HRs) (95% CIs) compared with CCRT alone were of 0.24 (0.08-0.73), 0.43 (0.24-0.77), and 0.54 (0.27-1.09) and the respective P-scores were 94%, 82%, and 68%. The first three IC regimens showing significantly improved progression-free survival (PFS) were PX, followed by GP and DC with respective HRs of 0.46 (0.24-0.88), 0.51 (0.34-0.77), and 0.49 (0.20-1.20), and P-scores of 82%, 78%, and 74%. Among the studies in the intensity-modulated radiation therapy (IMRT) era, GP and PX were the best performed IC regimens, whilst DC performed the best among non-IMRT studies. Doublet and gemcitabine-based IC regimens had better survival benefits compared to triplet and taxane-based IC regimens, respectively.ConclusionsGiven its consistent superiority in both OS and PFS, DC, GP, and PX ranked among the three most efficacious IC regimens in both the overall and subgroup analysis of IMRT or non-IMRT studies. Exploratory analyses suggested that doublet and gemcitabine-based IC regimens showed better survival performance.

Project description:BackgroundInduction chemotherapy (IC) can alleviate locoregionally advanced nasopharyngeal carcinoma (LA-NPC), but effectiveness differs between patients, toxicity is problematic, and effective blood-based IC efficacy predictors are lacking. Here, we aimed to identify biomarkers for early identification of IC beneficiaries.MethodsSixty-four pairs of matched plasma samples collected before and after IC from LA-NPC patients including 34 responders and 30 non-responders, as well as 50 plasma samples of healthy individuals, were tested using data-independent acquisition mass spectrometry. The proteins associated with clinical traits or IC benefits were investigated by weighted gene co-expression network analysis (WGCNA) and soft cluster analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional annotations were performed to determine the potential function of the identified proteins. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of candidate biomarkers in predicting IC beneficiaries.ResultsCompared with healthy individuals, 1027 differentially expressed proteins (DEPs) were found in the plasma of LA-NPC patients. Based on feedback from IC outcomes, 463 DEPs were identified in the pre-IC plasma between responders and non-responders. A total of 1212 DEPs represented the proteomic changes before and after IC in responders, while 276 DEPs were identified in post-IC plasma between responders and non-responders. WGCNA identified nine protein co-expression modules correlated with clinical traits. Soft cluster analysis identified four IC benefits-related protein clusters. Functional enrichment analysis showed that these proteins may play a role in IC via immunity, complement, coagulation, glycosaminoglycan and serine. Four proteins differentially expressed in all group comparisons, paraoxonase/arylesterase 1 (PON1), insulin-like growth factor-binding protein 3 (IGFBP-3), rheumatoid factor D5 light chain (v-kappa-3) and RNA helicase (DDX55), were associated with clinical traits or IC benefits. A four-protein model accurately identified potential IC beneficiaries (AUC=0.95) while diagnosing LA-NPC (AUC=0.92), and the prediction performance was verified using the models to confirm the effective IC (AUC=0.97) and evaluate IC outcome (AUC=0.94).ConclusionThe plasma protein profiles among IC responders and non-responders were different. PON1, IGFBP3, v-kappa-3 and DDX55 could serve as potential biomarkers for early identification of IC beneficiaries for individualised treatment of LA-NPC.