Multivariable model for predicting acute oral mucositis during combined IMRT and chemotherapy for locally advanced nasopharyngeal cancer patients

Oral Oncol. 2018 Nov:86:266-272. doi: 10.1016/j.oraloncology.2018.10.006. Epub 2018 Oct 11.

Abstract

Introduction/objective: Oral and oropharyngeal mucositis (OM) represents amultifactorialand complexinterplayof patient-, tumor-, and treatment-related factors. We aimed to build a predictive model for acute OM for locally advanced nasopharyngeal carcinoma (NPC) patients by combining clinical and dosimetric factors.

Materials/methods: A series of consecutive NPC patients treated curatively with IMRT/VMAT + chemotherapy at 70 Gy (2-2.12 Gy/fr) was considered. For each patient, clinical- tumor- and treatment-related data were retrospectively collected. oral cavity (OC) and parotid glands (PG, considered as a single organ) were selected as organs-at-risk (OARs). Acute OM was assessed according to CTCAE v4.0 at baseline and weekly during RT. Two endpoints were considered: grade ≥3 and mean grade ≥1.5. DVHs were reduced to Equivalent Uniform Dose (EUD). Dosimetric and clinical/treatment features selected via LASSO were inserted into a multivariable logistic model. Goodness of fit was evaluated through Hosmer-Lemeshow test and calibration plot.

Results: Data were collected for 132 patients. G ≥ 3 and mean G ≥ 1.5 OM were reported in 40 patients (30%). Analyses resulted in a 3-variables model for G ≥ 3 OM, including OC EUD with n = 0.05 (OR = 1.02), PG EUD with n = 1 (OR = 1.06), BMI ≥ 30 (OR = 3.8, for obese patients), and a single variable model for mean G ≥ 1.5 OM, i.e. OC EUD with n = 1 (mean dose) (OR = 1.07). Calibration was good in both cases.

Conclusion: OC mean dose was found to impact most on OM duration (mean G ≥ 1.5), while G ≥ 3 OM was associated to a synergic effect between PG mean dose and high dose received by small OC volumes, with BMI acting as a dose-modifying factor.

Keywords: Head and neck cancer; Intensity modulated radiation therapy; Nasopharyngeal carcinoma; Oral mucositis; Predictive model; Radiation-induced toxicity.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • Chemoradiotherapy / adverse effects*
  • Chemoradiotherapy / methods
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Biological*
  • Mouth Mucosa / radiation effects
  • Multivariate Analysis
  • Nasopharyngeal Carcinoma / therapy*
  • Nasopharyngeal Neoplasms / therapy*
  • Organs at Risk / radiation effects
  • Radiation Injuries / diagnosis
  • Radiation Injuries / etiology
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated / adverse effects*
  • Radiotherapy, Intensity-Modulated / methods
  • Retrospective Studies
  • Stomatitis / diagnosis*
  • Stomatitis / etiology
  • Time Factors
  • Young Adult