Efficacy and mucosal toxicity of concomitant chemo-radiotherapy in patients with locally-advanced squamous cell carcinoma of the head-and-neck in the light of a novel mathematical model

Abstract

Background: In the last several decades, combined radiotherapy (RT) and chemotherapy (CT) have beenrecognized as feasible in locally-advanced-squamous-cell-carcinoma of the head-and-neck (LA-HNSCC).Several meta-analyses identified concurrent RT + CT (CRT) most likely effective approach respect toRT-alone. However, radiobiological models comparing different chemotherapeutic schedules againstdelivered RT fractionation schedule for overall survival and toxicity are still needed.Methods and materials: Based on 9 randomized trials (2785 patients), radiobiological models andmultivariate logistic regression model were used to derive dose-response curves and estimate the 5-year-overall survival (OS) and ≥G3 acute mucositis rate of CRT or RT-alone.Results: Equivalent dose at 2 Gy/fraction (EQD2) was calculated using the linear quadratic model. Theeffect of CRT schedules, considering the CT type and its administration schedule and the HPV status oftumors were estimated using the univariate/multivariate logistic regression. The multivariate logisticregression model for 5y-OS indicated EQD2 and the type of CT, the chemo-sensitization fraction and theHPV status significant prognostic factors, while for toxicity both EQD2 and the concomitant adminis-tration of 5-fluorouracil (5Fu) resulted as significant prognostic factors. Combined schedules cisplatin(DDP)+/−5Fu + RT produced the higher OS compared with combined carboplatin+/−5Fu + RT or RT-alone

Upfront DPD Deficiency Detection to Secure 5-FU Administration: Part 2- Application to Head-and-Neck Cancer Patients

“…Overall, 12.8% of severe toxicities were registered, a value markedly lower than previously published data regarding the safety of 5-FU-based therapy with or without radiotherapy in head-and-neck cancer, i.e. 25%–50%, including frequent cases of febrile neutropenia [12–14]. Of note, it is not possible to attribute the 12.8% remaining toxic events to a specific drug, including 5-FU, because patients were all treated with multiple therapies associating mostly platinum derivatives, or paclitaxel, with possible combined effects in terms of cumulative toxicities.…”

Local Irradiation Modulates the Pharmacokinetics of Metabolites in 5-Fluorouracil—Radiotherapy–Pharmacokinetics Phenomenon

“…However, 31% to 34% of treated patients have doselimiting toxicities (Meta-Analysis Group . Concomitant administration of 5-FU and RT increases the rate of observed grade 3 or higher acute mucositis (Strigari et al, 2016). Bazan et al (2013) reported that acute hematologic toxicity in patients treated with pelvic RT concomitant with 5-FU was 8% higher than in those undergoing RT alone.…”

Assessing Novel Drugs and Radiation Technology in the Chemoradiation of Oropharyngeal Cancer

“…In the era of 2D radiotherapy and early 3D conformal radiotherapy, potential for sparing of the oral cavity was limited. Models derived from trials conducted in this era show clear relationships between prescription dose converted to biologically effective dose (BED) or an equivalent dose in 2 Gray (Gy) fractions (EQD 2 ) and the rate of grade 3 mucositis [ 23 , 24 ]. Attempts have also been made to model the additional effect on oral mucositis of synchronous chemotherapy [ 25 , 26 ].…”

“…Such systems have the advantage of being simple to use. In addition, early radiobiological models linking mucositis and prescription dose were based on such physician scored objective systems [ 23 , 24 ]. More complex systems for scoring mucositis such as the Oral Mucositis Assessment Scale (OMAS) where the extent of mucositis is incorporated by assigning a grade to different anatomical regions within the mouth have subsequently been developed [ 37 ].…”