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, 2 (10), e1913619

Association of Chemoradiotherapy Regimens and Survival Among Patients With Nasopharyngeal Carcinoma: A Systematic Review and Meta-analysis

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Association of Chemoradiotherapy Regimens and Survival Among Patients With Nasopharyngeal Carcinoma: A Systematic Review and Meta-analysis

Bin Zhang et al. JAMA Netw Open.

Erratum in

  • Error in Results.
    JAMA Netw Open. 2019 Nov 1;2(11):e1917197. doi: 10.1001/jamanetworkopen.2019.17197. JAMA Netw Open. 2019. PMID: 31722019 Free PMC article. No abstract available.

Abstract

Importance: The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial.

Objectives: To update meta-analyses on the association of survival outcomes with IC and AC regimens in patients with locoregionally advanced NPC and assess whether the current evidence is conclusive by a trial sequential analysis (TSA) approach.

Data sources: PubMed, Embase, and Web of Science were searched for articles published from inception until June 1, 2019.

Study selection: Randomized clinical trials that assessed the efficacy of radiotherapy with or without chemotherapy among previously untreated patients and patients with nondistant metastatic NPC.

Data extraction and synthesis: Data were extracted by 2 investigators from each trial independently and synthesized by the 2 investigators. All trial results were combined and analyzed by a fixed- or random-effects model.

Main outcomes and measures: Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS).

Results: A total of 8036 patients (median age, 46.5 years; 5872 [73.1%] male) from 28 randomized clinical trials were included in the analysis. Pooled analyses revealed that concurrent chemoradiotherapy (CCRT) was significantly associated with improved OS, PFS, DMFS, and LRFS compared with radiotherapy across all subgroups. The TSA confirmed the treatment outcomes of CCRT compared with radiotherapy. The additional IC regimen was associated with an improvement in OS (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), PFS (HR, 0.73; 95% CI, 0.64-0.84), DMFS (HR, 0.67; 95% CI, 0.59-0.78), and LRFS (HR, 0.74; 95% CI, 0.64-0.85). These findings were consistent in subgroup analyses of multicenter trials with sample sizes greater than 250, years of survival rate of 5 or greater, median follow-up longer than 5 years, or low risk of bias. However, the additional AC regimen was not associated with a survival benefit in OS (HR, 0.98; 95% CI, 0.78-1.23), PFS (HR, 0.86; 95% CI, 0.70-1.07), DMFS (HR, 0.84; 95% CI, 0.64-1.10), or LRFS (HR, 0.80, 95% CI, 0.59-1.09). The TSA provided sound evidence on the additional benefit of IC but not AC.

Conclusions and relevance: These data suggest a significant association of survival outcomes with CCRT in patients with locoregionally advanced NPC. The addition of IC instead of AC could achieve survival benefits. The potential therapeutic gain of AC should be explored in the future.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Overall Survival With Hazard Ratios (HRs) by Timing of Chemotherapy
The center of each square is the HR for individual trial comparison, with the corresponding horizontal line showing the 95% CIs. The size of the square is proportional to the number of deaths from the trial. The center of the first 4 diamonds is the HR for different timings of chemotherapy, and the extremities are the 95% CIs. The center of the diamond at the bottom represents the overall pooled HR, with the extremities of the diamond showing the 95% CI. AC indicates adjuvant chemotherapy; AF, accelerated fractionation; AOCOA, Asian-Oceanian Clinical Oncology Association; CCRT, concomitant chemoradiotherapy; CF, conventional fractionation; GORTEC, Head and Neck Radiation Oncology Group; HeCOG, Hellenic Cooperative Oncology Group; IC, induction chemotherapy; INT-0099, Southwest Oncology Group (SWOG)–coordinated Intergroup trial (also known as SWOG 8892); NPC, nasopharyngeal carcinoma; PWHQEH, Prince of Wales Hospital, Queen Elizabeth Hospital; QMH, Queen Mary Hospital (2 × 2 design, counted twice in the analysis); SQNP, Singapore Naso-Pharynx; TCOG, Taiwan Cooperative Oncology Group; and VUMCA, International Nasopharynx Cancer Study Group.
Figure 2.
Figure 2.. Progression-Free Survival With Hazard Ratios (HRs) by Timing of Chemotherapy
The center of each square is the HR for individual trial comparison, with the corresponding horizontal line showing the 95% CI. The size of the square is proportional to the number of relapses or deaths from the trial. The center of the first 4 diamonds is the HR for different timings of chemotherapy, and the extremities are the 95% CIs. The center of the diamond at the bottom represents the overall pooled HR, with the extremities of the diamond showing the 95% CI. AC indicates adjuvant chemotherapy; AF, accelerated fractionation; AOCOA, Asian-Oceanian Clinical Oncology Association; CCRT, concomitant chemoradiotherapy; CF, conventional fractionation; GORTEC, Head and Neck Radiation Oncology Group; HeCOG, Hellenic Cooperative Oncology Group; IC, induction chemotherapy; INT-0099, SWOG (Southwest Oncology Group)–coordinated Intergroup trial (also known as SWOG 8892); NPC, nasopharyngeal carcinoma; PWHQEH, Prince of Wales Hospital, Queen Elizabeth Hospital; QMH, Queen Mary Hospital (2 × 2 design, counted twice in the analysis); SQNP, Singapore Naso-Pharynx; TCOG, Taiwan Cooperative Oncology Group; and VUMCA, International Nasopharynx Cancer Study Group.
Figure 3.
Figure 3.. Distant Metastasis–Free Survival With Hazard Ratios (HRs) by Timing of Chemotherapy
The center of each square is the HR for individual trial comparison, with the corresponding horizontal line showing the 95% CI. The size of the square is proportional to the number of distance metastasis from the trial. The center of the first 4 diamonds is the HR for different timings of chemotherapy, and the extremities are the 95% CIs. The center of the diamond at the bottom represents the overall pooled HR, with the extremities of the diamond showing the 95% CI. AC indicates adjuvant chemotherapy; AF, accelerated fractionation; AOCOA, Asian-Oceanian Clinical Oncology Association; CCRT, concomitant chemoradiotherapy; CF, conventional fractionation; GORTEC, Head and Neck Radiation Oncology Group; HeCOG, Hellenic Cooperative Oncology Group; IC, induction chemotherapy; INT-0099, SWOG (Southwest Oncology Group)–coordinated Intergroup trial (also known as SWOG 8892); NPC, nasopharyngeal carcinoma; PWHQEH, Prince of Wales Hospital, Queen Elizabeth Hospital; QMH, Queen Mary Hospital (2 × 2 design, counted twice in the analysis); SQNP, Singapore Naso-Pharynx; TCOG, Taiwan Cooperative Oncology Group; and VUMCA, International Nasopharynx Cancer Study Group.
Figure 4.
Figure 4.. Locoregional Recurrence-Free Survival With Hazard Ratios (HRs) by Timing of Chemotherapy
The center of each square is the HR for individual trial comparison, with the corresponding horizontal line showing the 95% CI. The size of the square is proportional to the number of locoregional recurrences from the trial. The center of the first 4 diamonds is the HR for different timings of chemotherapy, and the extremities are the 95% CIs. The center of the diamond at the bottom represents the overall pooled HR, with the extremities of the diamond showing the 95% CI. AC indicates adjuvant chemotherapy; AF, accelerated fractionation; CCRT, concomitant chemoradiotherapy; CF, conventional fractionation; GORTEC, Head and Neck Radiation Oncology Group; IC, induction chemotherapy; INT-0099, SWOG (Southwest Oncology Group)–coordinated Intergroup trial (also known as SWOG 8892); NPC, nasopharyngeal carcinoma; PWHQEH, Prince of Wales Hospital, Queen Elizabeth Hospital; QMH, Queen Mary Hospital; SQNP, Singapore Naso-Pharynx; TCOG, Taiwan Cooperative Oncology Group; and VUMCA, International Nasopharynx Cancer Study Group.

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  • Error in Results.
    JAMA Netw Open. 2019 Nov 1;2(11):e1917197. doi: 10.1001/jamanetworkopen.2019.17197. JAMA Netw Open. 2019. PMID: 31722019 Free PMC article. No abstract available.

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