Normal tissue complication probability (NTCP) modelling using spatial dose metrics and machine learning methods for severe acute oral mucositis resulting from head and neck radiotherapy

Abstract

Background and purpose: Severe acute mucositis commonly results from head and neck (chemo)radiotherapy. A predictive model of mucositis could guide clinical decision-making and inform treatment planning. We aimed to generate such a model using spatial dose metrics and machine learning.

Materials and methods: Predictive models of severe acute mucositis were generated using radiotherapy dose (dose-volume and spatial dose metrics) and clinical data. Penalised logistic regression, support vector classification and random forest classification (RFC) models were generated and compared. Internal validation was performed (with 100-iteration cross-validation), using multiple metrics, including area under the receiver operating characteristic curve (AUC) and calibration slope, to assess performance. Associations between covariates and severe mucositis were explored using the models.

Results: The dose-volume-based models (standard) performed equally to those incorporating spatial information. Discrimination was similar between models, but the RFCstandard had the best calibration. The mean AUC and calibration slope for this model were 0.71 (s.d.=0.09) and 3.9 (s.d.=2.2), respectively. The volumes of oral cavity receiving intermediate and high doses were associated with severe mucositis.

Conclusions: The RFCstandard model performance is modest-to-good, but should be improved, and requires external validation. Reducing the volumes of oral cavity receiving intermediate and high doses may reduce mucositis incidence.

Keywords: Dose–response modelling; Head and neck radiotherapy; Machine learning; NTCP modelling; Oral mucositis; Spatial dose metrics.

Figure 1

Bootstrapped (2000 replicates) odds ratios for PLR_standard model. Whiskers show 95 percentiles (non-normal distributions). definitiveRT – definitive radiotherapy (versus post-operative radiotherapy); indChemo – induction chemotherapy; noConChemo – no concurrent chemotherapy; cisCarbo – one cycle of cisplatin followed by one cycle of carboplatin; Vx – volume of organ receiving x cGy of radiation per fraction. None of the covariates are significantly associated with severe mucositis.

Figure 2

Bootstrapped (2000 replicates) odds ratios for PLR_spatial model. Whiskers show 95 percentiles (non-normal distributions). definitiveRT – definitive radiotherapy (versus post-operative radiotherapy); indChemo – induction chemotherapy; noConChemo – no concurrent chemotherapy; cisCarbo – one cycle of cisplatin followed by one cycle of carboplatin; Vx – volume of organ receiving x cGy of radiation per fraction. None of the covariates are significantly associated with severe mucositis.

Figure 3

Bootstrapped (2000 replicates) feature importance measures for RFC_standard model. Whiskers show 95 percentiles (non-normal distributions). definitiveRT – definitive radiotherapy (versus post-operative radiotherapy); indChemo – induction chemotherapy; noConChemo – no concurrent chemotherapy; cisCarbo – one cycle of cisplatin followed by one cycle of carboplatin; Vx – volume of organ receiving x cGy of radiation per fraction. The feature importance of the dose metrics increases with increasing dose up to V220, which has the highest feature importance of any covariate.

Figure 4

Bootstrapped (2000 replicates) feature importance measures for RFC_spatial model. Whiskers show 95 percentiles (non-normal distributions). definitiveRT – definitive radiotherapy (versus post-operative radiotherapy); indChemo – induction chemotherapy; noConChemo – no concurrent chemotherapy; cisCarbo – one cycle of cisplatin followed by one cycle of carboplatin; Vx – volume of organ receiving x cGy of radiation per fraction. The feature importance of the dose metrics increases with increasing dose up to V220, which has the highest feature importance of any covariate.