Clinical Introduction of Stem Cell Sparing Radiotherapy to Reduce the Risk of Xerostomia in Patients with Head and Neck Cancer.

Background/objectives: Studies have shown that dose to the parotid gland stem cell rich (SCR) regions should be reduced to lower the risk of xerostomia after radiotherapy (RT). This study aimed to assess whether stem cell sparing (SCS)-RT can be adopted in routine clinical practice.

Methods: Multiple planning studies were performed to compare SCS-RT with standard (ST)-RT using 30 head and neck cancer patients.

Protocol compliance in a multicentric phase III trial investigating scheduled adaptive radiotherapy and dose painting in head and neck cancer.

Purpose: To report on quality assurance (QA) and protocol adherence (PA) in a multicentre phase III trial for head and neck cancer, evaluate patterns of protocol deviations and investigate the effect of PA on study outcomes.

Methods: All 221 patients from the ARTFORCE trial (NCT01504815) were included in this study. Pre- and per-treatment QA measures included protocol guidelines, a dummy run, early case reviews and trial meetings.

Merkel-cell carcinoma: ESMO-EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up.

• This ESMO Clinical Practice Guideline provides key recommendations for managing Merkel-cell carcinoma (MCC). • Recommendations are based on available scientific data and the multidisciplinary group of experts’ collective opinion. • The guideline covers clinical and pathological diagnosis, staging and risk assessment, treatment and follow-up.

A multicentric randomized controlled phase III trial of adaptive and 18F-FDG-PET-guided dose-redistribution in locally advanced head and neck squamous cell carcinoma (ARTFORCE).

Background And Purpose: This multicenter randomized phase III trial evaluated whether locoregional control of patients with LAHNSCC could be improved by fluorodeoxyglucose-positron emission tomography (FDG-PET)-guided dose-escalation while minimizing the risk of increasing toxicity using a dose-redistribution and scheduled adaptation strategy.

Materials And Methods: Patients with T3-4-N0-3-M0 LAHNSCC were randomly assigned (1:1) to either receive a dose distribution ranging from 64-84 Gy/35 fractions with adaptation at the 10thfraction (rRT) or conventional 70 Gy/35 fractions (cRT). Both arms received concurrent three-cycle 100 mg/mcisplatin.

Surgical site complications of isolated salvage neck dissection post-radiotherapy and post-chemoradiotherapy - A cohort analysis (1997-2017).

Introduction: This study aims to quantify surgical site complications (SSC) after isolated salvage neck dissection (ND) compared with primary ND.

Patients And Methods: Between 1997 and 2017 in the Netherlands Cancer Institute - Antoni van Leeuwenhoek, a total of 323 isolated NDs were performed in 308 patients: primary ND (n = 144), post-radiotherapy (RT) ND (n = 53) and post-chemoradiotherapy (CRT) ND (n = 126). Patient, tumor and therapy characteristics were recorded.

Postoperative radiotherapy in stage I-III Merkel cell carcinoma.

Background: Postoperative radiotherapy (PORT) is currently recommended for the treatment of Merkel cell carcinoma. Nevertheless, deviations occur frequently due to the generally elderly and frail patient population. We aimed to evaluate the influence of PORT on survival in stage I-III MCC patients treated in the Netherlands.

Comparisons of normal tissue complication probability models derived from planned and delivered dose for head and neck cancer patients.

Background And Purpose: Normal tissue complication probability (NTCP) models are typically derived from the planned dose distribution, which can deviate from the delivered dose due to anatomical day-to-day variations. The aim of this study was to compare NTCP models derived from the planned and the delivered dose for head and neck cancer (HNC) patients.

Material And Method: 322 HNC patients who received radiotherapy with daily CBCT guidance were included in this retrospective study.

Deterioration of Intended Target Volume Radiation Dose Due to Anatomical Changes in Patients with Head-and-Neck Cancer.

Delivered radiation dose can differ from intended dose. This study quantifies dose deterioration in targets, identifies predictive factors, and compares dosimetric to clinical patient selection for adaptive radiotherapy in head-and-neck cancer patients. One hundred and eighty-eight consecutive head-and-neck cancer patients treated up to 70 Gy were analyzed.

Reduction of GTV to high-risk CTV radiation margin in head and neck squamous cell carcinoma significantly reduced acute and late radiation-related toxicity with comparable outcomes.

Background And Purpose: We aim to retrospectively investigate whether reducing GTV to high-risk CTV margin will significantly reduce acute and late toxicity without jeopardizing outcome in head-and-neck squamous cell carcinoma (HNSCC) treated with definitive (chemo)radiation.

Materials And Methods: Between April 2015 and April 2019, 155 consecutive patients were treated with GTV to high-risk CTV margin of 10 mm and subsequently another 155 patients with 6 mm margin. The CTV-PTV margin was 3 mm for both groups.

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.

Defining High-Quality Integrated Head and Neck Cancer Care Through a Composite Outcome Measure: Textbook Outcome.

Objectives/hypothesis: To further improve the quality of head and neck cancer (HNC) care, we developed a composite measure defined as "textbook outcome" (TO).

Methods: We analyzed a retrospective cohort of patients after curvative-intent primary surgery, radiotherapy (RT), or chemoradiation (CRT) for HNC between 2015 and 2018 at the Netherlands Cancer Institute. TO was defined as 1) the start of treatment within 30 days, 2a) satisfactory pathologic outcomes, without 30-day postoperative complications, for the surgically treated group, and 2b), for RT and CRT patients, no unexpected or prolonged hospitalization and toxicity after the completion of treatment as planned.

Non-invasive imaging prediction of tumor hypoxia: A novel developed and externally validated CT and FDG-PET-based radiomic signatures.

Background: Tumor hypoxia increases resistance to radiotherapy and systemic therapy. Our aim was to develop and validate a disease-agnostic and disease-specific CT (+FDG-PET) based radiomics hypoxia classification signature.

Material And Methods: A total of 808 patients with imaging data were included: N = 100 training/N = 183 external validation cases for a disease-agnostic CT hypoxia classification signature, N = 76 training/N = 39 validation cases for the H&N CT signature and N = 62 training/N = 36 validation cases for the Lung CT signature.

Randomized controlled trial to identify the optimal radiotherapy scheme for palliative treatment of incurable head and neck squamous cell carcinoma.

Background: No randomized controlled trials (RCT) have yet identified the optimal palliative radiotherapy scheme in patients with incurable head and neck squamous cell carcinoma (HNSCC). We conducted RCT to compare two radiation schemes in terms of efficacy, toxicity and quality-of-life (QoL).

Materials And Methods: Patients with locally-advanced HNSCC who were ineligible for radical treatment and those with limited metastatic disease were randomly assigned in 1:1 ratio to arm 1 (36 Gy in 6 fractions, twice a week) or arm 2 (50 Gy in 16 fractions, four times a week).

[F]-HX4 PET/CT hypoxia in patients with squamous cell carcinoma of the head and neck treated with chemoradiotherapy: Prognostic results from two prospective trials.

Introduction: The presence of hypoxia in head-and-neck squamous cell carcinoma is a negative prognostic factor. PET imaging with [18F] HX4 can be used to visualize hypoxia, but it is currently unknown how this correlates with prognosis. We investigated the prognostic value of [18F] HX4 PET imaging in patients treated with definitive radio(chemo)therapy (RTx).

Privacy-preserving distributed learning of radiomics to predict overall survival and HPV status in head and neck cancer.

A major challenge in radiomics is assembling data from multiple centers. Sharing data between hospitals is restricted by legal and ethical regulations. Distributed learning is a technique, enabling training models on multicenter data without data leaving the hospitals ("privacy-preserving" distributed learning).

Long-term swallowing, trismus, and speech outcomes after combined chemoradiotherapy and preventive rehabilitation for head and neck cancer; 10-year plus update.

Background: The objective of this study was to explore the 10-year plus outcomes of Intensity Modulated Radiotherapy with concomitant chemotherapy (CRT) combined with preventive swallowing rehabilitation (CRT+) for head and neck cancer (HNC).

Methods: Subjective and objective swallowing, trismus, and speech related outcomes were assessed at 10-year plus after CRT+. Outcomes were compared to previously published 6-year results of the same cohort.

Protocolised way to cope with anatomical changes in head & neck cancer during the course of radiotherapy.

Introduction: During a course of radiotherapy for head-and-neck-cancer (HNC), non-rigid anatomical changes can be observed on daily Cone Beam CT (CBCT). To objectify responses to these changes, we use a decision support system (traffic light protocol). Action levels orange and red may lead to re-planning.

Biological Determinants of Chemo-Radiotherapy Response in HPV-Negative Head and Neck Cancer: A Multicentric External Validation.

Tumor markers that are related to hypoxia, proliferation, DNA damage repair and stem cell-ness, have a prognostic value in advanced stage HNSCC patients when assessed individually. Here we aimed to evaluate and validate this in a multifactorial context and assess interrelation and the combined role of these biological factors in determining chemo-radiotherapy response in HPV-negative advanced HNSCC. RNA sequencing data of pre-treatment biopsy material from 197 HPV-negative advanced stage HNSCC patients treated with definitive chemoradiotherapy was analyzed.

Impact of setup and range uncertainties on TCP and NTCP following VMAT or IMPT of oropharyngeal cancer patients.

Setup and range uncertainties compromise radiotherapy plan robustness. We introduce a method to evaluate the clinical effect of these uncertainties on the population using tumor control probability (TCP) and normal tissue complication probability (NTCP) models. Eighteen oropharyngeal cancer patients treated with curative intent were retrospectively included.

FDG-PET/CT improves detection of residual disease and reduces the need for examination under anaesthesia in oropharyngeal cancer patients treated with (chemo-)radiation.

Purpose: Early detection of residual disease (RD) after (chemo)radiation for oropharyngeal (OPC) is crucial. Surveillance of neck nodes with FDG-PET/CT has been studied extensively, whereas its value for local RD remains less clear. We aim to evaluate the diagnostic value of post-treatment FDG-PET/CT in detecting local RD and the outcome of patients with local RD.

Improving decision making in larynx cancer by developing a decision aid: A mixed methods approach.

Objective: Patients diagnosed with advanced larynx cancer face a decisional process in which they can choose between radiotherapy, chemoradiotherapy, or a total laryngectomy with adjuvant radiotherapy. Clinicians do not always agree on the best clinical treatment, making the decisional process for patients a complex problem.

Methods: Guided by the International Patient Decision Aid (PDA) Standards, we followed three developmental phases for which we held semi-structured in-depth interviews with patients and physicians, thinking-out-loud sessions, and a study-specific questionnaire.

Radiation dose to the masseter and medial pterygoid muscle in relation to trismus after chemoradiotherapy for advanced head and neck cancer.

Background: We studied the relationship between trismus (maximum interincisor opening [MIO] ≤35 mm) and the dose to the ipsilateral masseter muscle (iMM) and ipsilateral medial pterygoid muscle (iMPM).

Methods: Pretreatment and post-treatment measurement of MIO at 13 weeks revealed 17% of trismus cases in 83 patients treated with chemoradiation and intensity-modulated radiation therapy. Logistic regression models were fitted with dose parameters of the iMM and iMPM and baseline MIO (bMIO).

SPECT/CT-guided elective nodal irradiation for head and neck cancer: Estimation of clinical benefits using NTCP models.

Background And Purpose: The great majority of patients with lateralized head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy routinely undergo bilateral elective nodal irradiation (ENI), even though the incidence of contralateral regional failure after unilateral ENI is low. Excluding the contralateral neck from elective irradiation could reduce radiation-related toxicity and improve quality-of-life. The current study investigated the dosimetric benefits of a novel approach using lymph drainage mapping by SPECT/CT to select patients for unilateral ENI.

The impact of margin reduction on outcome and toxicity in head and neck cancer patients treated with image-guided volumetric modulated arc therapy (VMAT).

Background And Purpose: In recent decades, outcomes of patients with head and neck cancer (HNC) have improved as a result of implementing several strategies, such as chemoradiation. However, these improvements were achieved at the cost of increased toxicity. One way to reduce radiation-related toxicity is by reducing the margins.

Biological PET-guided adaptive radiotherapy for dose escalation in head and neck cancer: a systematic review.

Introduction: In recent years, the possibility of adapting radiotherapy to changes in biological tissue parameters has emerged. It is hypothesized that early identification of radio-resistant parts of the tumor during treatment provides the possibility to adjust the radiotherapy plan to improve outcome. The aim of this systematic literature review was to evaluate the current state of the art of biological PET-guided adaptive radiotherapy, focusing on dose escalation to radio-resistant tumor.