Key challenges in normal tissue complication probability model development and validation:towards a comprehensive strategy

Normal Tissue Complication Probability (NTCP) models can be used for treatment plan optimisation and patient selection for emerging treatment techniques. We discuss and suggest methodological approaches to address key challenges in NTCP model development and validation, including: missing data, non-linear response relationships, multicollinearity between predictors, overfitting, generalisability and the prediction of multiple complication grades at multiple time points. The methodological approaches chosen are aimed to improve the accuracy, transparency and robustness of future NTCP-models. We demonstrate our methodological approaches using clinical data

Comprehensive toxicity risk profiling in radiation therapy for head and neck cancer:A new concept for individually optimised treatment

Background and purpose: A comprehensive individual toxicity risk profile is needed to improve radiation treatment optimisation, minimising toxicity burden, in head and neck cancer (HNC) patients. We aimed to develop and externally validate NTCP models for various toxicities at multiple time points. Materials and methods: Using logistic regression, we determined the relationship between normal tissue irradiation and the risk of 22 toxicities at ten time points during and after treatment in 750 HNC patients. The toxicities involved swallowing, salivary, mucosal, speech, pain and general complaints. Studied pre-dictors included patient, tumour and treatment characteristics and dose parameters of 28 organs. The resulting NTCP models were externally validated in 395 HNC patients. Results: The NTCP models involved 14 organs that were associated with at least one toxicity. The oral cavity was the predominant organ, associated with 12 toxicities. Other important organs included the parotid and submandibular glands, buccal mucosa and swallowing muscles. In addition, baseline toxicity, treatment modality, and tumour site were common predictors of toxicity. The median discrimination performance (AUC) of the models was 0.71 (interquartile range: 0.68-0.75) at internal validation and 0.67 (interquartile range: 0.62-0.71) at external validation. Conclusion: We established a comprehensive individual toxicity risk profile that provides essential insight into how radiation exposure of various organs translates into multiple acute and late toxicities. This comprehensive understanding of radiation-induced toxicities enables a new radiation treatment optimisation concept that balances multiple toxicity risks simultaneously and minimises the overall tox-icity burden for an individual HNC patient who needs to undergo radiation treatment. (C) 2021 The Author(s). Published by Elsevier B.V

National Protocol for Model-Based Selection for Proton Therapy in Head and Neck Cancer

In the Netherlands, the model-based approach is used to identify patients with head and neck cancer who may benefit most from proton therapy in terms of prevention of late radiation-induced side effects in comparison with photon therapy. To this purpose, a National Indication Protocol Proton therapy for Head and Neck Cancer patients (NIPP-HNC) was developed, which has been approved by the health care authorities. When patients qualify according to the guidelines of the NIPP-HNC, proton therapy is fully reimbursed. This article describes the procedures that were followed to develop this NIPP-HNC and provides all necessary information to introduce model-based selection for patients with head and neck cancer into routine clinical practice.</p

Weekly kilovoltage cone-beam computed tomography for detection of dose discrepancies during (chemo)radiotherapy for head and neck cancer

<div><p>ABSTRACT</p><p><b>Background</b>. Use of highly conformal radiotherapy in patients with head and neck carcinoma may lead to under-/overdosage of gross target volume (GTV) and organs at risk (OAR) due to changes in patients’ anatomy. A method to achieve more effective radiation treatment combined with less toxicity is dose-guided radiotherapy (DGRT). The aim of this study was to evaluate discrepancies between planned and actually delivered radiation dose in head and neck patients and to identify predictive factors.</p><p><b>Methods.</b> In this retrospective analysis, 20 patients with cT2-4 N0-3 M0 carcinoma originating from oropharynx, oral cavity, larynx and hypopharynx (Cohort 1), and seven patients with cT1-4 N0-3 M0 nasopharyngeal carcinoma (Cohort 2) treated with primary (chemo)radiotherapy and undergoing weekly kV-CBCT scans were included. Radiation dose was recalculated on 184 kV-CBCT images, which was quantified by D_95% (GTV), D_mean (parotid and submandibular glands) and D_2% (spinal cord). Predictive factors investigated for changes in these dose metrics were: gender, age, cT/N-stage, tumor grade, HPV-status, systemic therapy, body mass index at start of treatment, weight loss and volume change over the duration of the radiotherapy.</p><p><b>Results.</b> There was no significant difference between the planned and delivered dose for GTV and OARs of Week 1 to subsequent weeks for Cohort 1. In Cohort 2, actually delivered D_mean to parotid glands was significant higher than planned dose (1.1 Gy, p = 0.002). No clinically relevant correlations between dose changes and predictive factors were found.</p><p><b>Conclusion.</b> Weekly dose calculations do not seem to improve dose delivery for patients with tumors of the oral cavity, oropharynx, larynx and hypopharynx. In patients with nasopharyngeal carcinoma, however, mid-treatment imaging may facilitate DGRT.</p></div

Prognostic value of primary tumor volume after concurrent chemoradiation with daily low-dose cisplatin for advanced-stage head and neck carcinoma

BACKGROUND: The purpose of this study was to evaluate the prognostic value of tumor volume in head and neck squamous cell carcinoma treated with chemoradiation. METHODS: Forty-six patients were treated with radiotherapy and cisplatin (6 mg/m(2) IV x 20, daily). Baseline primary tumor volume was recorded from MRI scans. The prognostic impact of tumor volume and other factors for locoregional control, disease-free survival (DFS), and overall survival (OS) was tested. RESULTS: Mean tumor volume was 28 cm(3) (median 23 cm(3); range, 3-112). The locoregional control rate at 3 years was 81% for patients with tumor volumes or = median (p = .036). At multivariate analysis, it appeared that tumor volume remained an independent determinant of locoregional control and survival when adjusted for other factors. CONCLUSIONS: In advanced-stage head and neck squamous cell carcinoma treated with concurrent chemoradiation, primary tumor volume is associated with locoregional control and survival. Larger studies are needed to confirm whether incorporation of tumor volume in the staging system improves prediction of treatment outcome and can serve as a tool to guide treatment option