Relationship between Radiation Treatment Parameters and Overall Survival following Induction Chemotherapy in a Sequential Regimen for Locally Advanced Head and Neck Carcinoma (LAHNC): A Subset Analysis of TAX324

Abstract

Purpose/Objective(s)The importance of radiotherapy treatment time (RTT) and technique has never been assessed when treating LAHNC after induction chemotherapy (IC). We analyzed the relationship between overall survival (OS) and RTT and technique when using chemoradiotherapy (CRT) following IC.Materials/MethodsTAX324 is a phase III study comparing TPF with PF IC, with both arms followed by CRT in LAHNC patients. Prospective quality assurance was performed, and this analysis includes all patients who received ≥70 Gy, per protocol. RTT was analyzed as binary (< 8 weeks vs. greater) and continuous (number of days beyond 8 weeks) functions. RT plans with cord dose greater than 45 Gy were considered “inappropriate.” The primary endpoint was OS. Significant univariable predictors (UVA) of OS were placed into a Cox stepwise regression multivariable analysis (MVA).ResultsA total of 350 (of 501) TAX324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in patient age, gender, performance status (PS), disease site, stage, reason for inoperability, RTT (median: 7.3 weeks, interquartile range, 7-8 weeks) or inappropriate RT plans (total: 30%). On UVA, type of IC, PS, disease site (oropharynx vs. other), T stage (T3/4 vs. other), nodal stage (N3 vs. other), duration of RTT (median OS: 86 vs. 36 months [mo], p = 0.01), and inappropriate technique (median OS: 85 mo vs. 40 mo, p = 0.03) were significantly associated with OS. On MVA, PF IC (HR 1.41, p = 0.025), PS of 1 (HR 1.49, p = 0.011), non-oropharynx site (HR 1.53, p = 0.0064), T3/4 stage (HR 1.62, p = 0.018), N3 status (HR 1.70, p = 0.01), and longer RTT (HR 1.52, p = 0.0118) were associated with statistically significant inferior survival. When evaluating RTT by number of days beyond 8 weeks, each increase in RTT by 1 day was associated with a relative 4% decrease in OS (p = 0.0028).ConclusionsIn this TAX324 secondary analysis, TPF IC remains superior to PF IC after controlling for RT delivery. However, even with optimal IC, RTT is a crucial determinant of treatment success. Aggressive sequential therapy for LAHNC should be reserved for patients who can complete CRT without breaks. Appropriate delivery of RT following IC is essential for optimizing OS in this disease. Purpose/Objective(s)The importance of radiotherapy treatment time (RTT) and technique has never been assessed when treating LAHNC after induction chemotherapy (IC). We analyzed the relationship between overall survival (OS) and RTT and technique when using chemoradiotherapy (CRT) following IC. The importance of radiotherapy treatment time (RTT) and technique has never been assessed when treating LAHNC after induction chemotherapy (IC). We analyzed the relationship between overall survival (OS) and RTT and technique when using chemoradiotherapy (CRT) following IC. Materials/MethodsTAX324 is a phase III study comparing TPF with PF IC, with both arms followed by CRT in LAHNC patients. Prospective quality assurance was performed, and this analysis includes all patients who received ≥70 Gy, per protocol. RTT was analyzed as binary (< 8 weeks vs. greater) and continuous (number of days beyond 8 weeks) functions. RT plans with cord dose greater than 45 Gy were considered “inappropriate.” The primary endpoint was OS. Significant univariable predictors (UVA) of OS were placed into a Cox stepwise regression multivariable analysis (MVA). TAX324 is a phase III study comparing TPF with PF IC, with both arms followed by CRT in LAHNC patients. Prospective quality assurance was performed, and this analysis includes all patients who received ≥70 Gy, per protocol. RTT was analyzed as binary (< 8 weeks vs. greater) and continuous (number of days beyond 8 weeks) functions. RT plans with cord dose greater than 45 Gy were considered “inappropriate.” The primary endpoint was OS. Significant univariable predictors (UVA) of OS were placed into a Cox stepwise regression multivariable analysis (MVA). ResultsA total of 350 (of 501) TAX324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in patient age, gender, performance status (PS), disease site, stage, reason for inoperability, RTT (median: 7.3 weeks, interquartile range, 7-8 weeks) or inappropriate RT plans (total: 30%). On UVA, type of IC, PS, disease site (oropharynx vs. other), T stage (T3/4 vs. other), nodal stage (N3 vs. other), duration of RTT (median OS: 86 vs. 36 months [mo], p = 0.01), and inappropriate technique (median OS: 85 mo vs. 40 mo, p = 0.03) were significantly associated with OS. On MVA, PF IC (HR 1.41, p = 0.025), PS of 1 (HR 1.49, p = 0.011), non-oropharynx site (HR 1.53, p = 0.0064), T3/4 stage (HR 1.62, p = 0.018), N3 status (HR 1.70, p = 0.01), and longer RTT (HR 1.52, p = 0.0118) were associated with statistically significant inferior survival. When evaluating RTT by number of days beyond 8 weeks, each increase in RTT by 1 day was associated with a relative 4% decrease in OS (p = 0.0028). A total of 350 (of 501) TAX324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in patient age, gender, performance status (PS), disease site, stage, reason for inoperability, RTT (median: 7.3 weeks, interquartile range, 7-8 weeks) or inappropriate RT plans (total: 30%). On UVA, type of IC, PS, disease site (oropharynx vs. other), T stage (T3/4 vs. other), nodal stage (N3 vs. other), duration of RTT (median OS: 86 vs. 36 months [mo], p = 0.01), and inappropriate technique (median OS: 85 mo vs. 40 mo, p = 0.03) were significantly associated with OS. On MVA, PF IC (HR 1.41, p = 0.025), PS of 1 (HR 1.49, p = 0.011), non-oropharynx site (HR 1.53, p = 0.0064), T3/4 stage (HR 1.62, p = 0.018), N3 status (HR 1.70, p = 0.01), and longer RTT (HR 1.52, p = 0.0118) were associated with statistically significant inferior survival. When evaluating RTT by number of days beyond 8 weeks, each increase in RTT by 1 day was associated with a relative 4% decrease in OS (p = 0.0028). ConclusionsIn this TAX324 secondary analysis, TPF IC remains superior to PF IC after controlling for RT delivery. However, even with optimal IC, RTT is a crucial determinant of treatment success. Aggressive sequential therapy for LAHNC should be reserved for patients who can complete CRT without breaks. Appropriate delivery of RT following IC is essential for optimizing OS in this disease. In this TAX324 secondary analysis, TPF IC remains superior to PF IC after controlling for RT delivery. However, even with optimal IC, RTT is a crucial determinant of treatment success. Aggressive sequential therapy for LAHNC should be reserved for patients who can complete CRT without breaks. Appropriate delivery of RT following IC is essential for optimizing OS in this disease.