ESTRO 2024 - Abstract Book

S1239

Clinical - Head & neck

ESTRO 2024

Purpose/Objective:

Head-and-neck squamous cell carcinoma (HNSCC) is a challenging malignancy, and its management becomes particularly complex in older adults for whom frailty and comorbidities have to be considered. While cisplatin-based chemoradiation is the standard treatment for patients with locoregionally advanced HNSCC (LA-HNSCC), many older adults with LA-HNSCC cannot tolerate concomitant cisplatin. Cumulative cisplatin doses of at least 200 mg/m² have demonstrated a strong prognostic significance in the context of definitive chemoradiation for HNSCC patients, with suboptimal dosing leading to an increased risk of locoregional treatment failure and diminished overall survival. Despite the evident clinical significance, factors that predict cisplatin treatment tolerability in older adults with HNSCC are largely lacking. This multicenter cohort analysis therefore aimed to reveal predictive parameters for cisplatin tolerability in this population.

Material/Methods:

The present study involves a subset of patients included in an international registry consisting of currently (October 2023) 1269 older adults with LA-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx. Data collection was performed retrospectively in 15 academic centers in Europe and the United States. Patients who received definitive cisplatin-based chemoradiation between 2005 and 2019 were eligible for this analysis. Cisplatin, either alone or in combination with other chemotherapeutic agents, was administered in 543 patients, of whom 522 patients had data on their cumulative cisplatin dose available. Baseline blood values were determined at maximum 5 days before the start of radiotherapy.

Results:

Median age of the cohort was 70 years (IQR, 67-74). Median ECOG performance status was 1 (IQR, 0-1), and median age-adjusted Charlson Comorbidity Index was 4 points (IQR, 3-5). Out of 290 patients with an oropharyngeal carcinoma, 141 (49%) had a p16/HPV-positive oropharyngeal carcinoma. Four hundred seventy-five patients (91%) completed radiotherapy with the prescribed radiation dose. The median cumulative cisplatin dose administered during radiotherapy was 180 mg/m2 (IQR, 120-200 mg/m2). Two hundred forty-five patients (47%) achieved a cumulative cisplatin dose of ≥200 mg/m2. Patients receiving single -agent cisplatin (n=363) were exposed to significantly higher cumulative cisplatin doses than patients treated with multi-agent cisplatin regimens (n=159; median 200 mg/m2 versus 180 mg/m2, p <0.001, unpaired t- test). Year of treatment (Pearson’s r=0.17, p <0.001) as well as the treatment center itself ( p <0.001, one-way ANOVA) had an influence on the cumulative cisplatin dose in this cohort. In the univariate analysis, positive p16/HPV status (median 200 mg/m2 versus 160 mg/m2, p <0.001), oropharyngeal carcinoma (median 200 mg/m2 versus 175 mg/m2, p <0.01), T1/2 carcinoma (median 200 mg/m2 versus 180 mg/m2, p <0.001), and superior ECOG performance status (median 200 mg/m2 (ECOG 0) versus 175 mg/m2 (ECOG 1) versus 160 mg/m2 (ECOG 2-3), p <0.001, one-way ANOVA) correlated with higher cumulative cisplatin doses, while sex, N stage, and smoking status had no impact. The cumulative cisplatin dose inversely correlated with higher age (r=-0.10, p <0.05) but not with the age-adjusted CCI (r=-0.01, p =0.77). Of the analyzed routine blood values, higher hemoglobin concentration (r=0.16, p <0.01) and eGFR values (r=0.16, p <0.01) were also associated with higher cumulative cisplatin doses, whereas absolute leukocyte counts (r=0.02, p =0.74) and baseline CRP (r=0.03, p =0.63) had no influence on cisplatin tolerability. Baseline anemia (<12 mg/L, n=107) was linked to a reduced cumulative cisplatin dose (median 160 mg/m2 versus 180 mg/m2, p <0.001), whereas both leukopenia (<4000/µL) and leukocytosis (>10.000/µL) were not ( p =0.38, and p =0.90, respectively). Depending on the eGFR, 31% (eGFR 50-<60 mL/min/1.73m2), 36% (eGFR 60-<70 mL/min/1.73m2), 52% (eGFR 70-<80 mL/min/1.73m2), and 58%

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