Postoperative Radiotherapy for pT1- and pT2-Classified Squamous Cell Carcinoma of the External Auditory Canal.

Background: There is no consensus regarding the indication for postoperative radiotherapy (PORT) for T1- and T2-classified squamous cell carcinoma (SCC) of the external auditory canal (EAC) even with negative surgical margins. This study aimed to evaluate whether PORT provides additional benefits for these cases.

Methods: We collected retrospective data from fourteen international hospitals, including resected pT1- and pT2-classified EAC SCC with negative surgical margins.

Sentinel node identification in laryngeal and pharyngeal carcinoma after flexible endoscopy-guided tracer injection under topical anesthesia: A feasibility study.

Background: The aim of this study was to investigate the feasibility of flexible endoscopy-guided tracer injection for sentinel lymph node (SLN) identification in patients with laryngeal and pharyngeal carcinoma.

Methods: Sixteen cT1-4N0-2M0 patients with laryngeal or pharyngeal carcinoma underwent intra- and peritumoral [ Tc]Tc-nanocolloid injections after topical anesthesia under endoscopic guidance. SPECT-CT scans were performed at two time points.

High-Accuracy Nodal Staging of Head and Neck Cancer With USPIO-Enhanced MRI: A New Reading Algorithm Based on Node-to-Node Matched Histopathology.

Objectives: Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) is a potential diagnostic tool for lymph node assessment in patients with head and neck cancer. Validation by radiologic-pathologic correlation is essential before the method is evaluated in clinical studies. In this study, MRI signal intensity patterns of lymph nodes are correlated to their histopathology to develop a new USPIO-enhanced MRI reading algorithm that can be used for nodal assessment in head and neck cancer patients.

Validation of In Vivo Nodal Assessment of Solid Malignancies with USPIO-Enhanced MRI: A Workflow Protocol.

Background: In various cancer types, the first step towards extended metastatic disease is the presence of lymph node metastases. Imaging methods with sufficient diagnostic accuracy are required to personalize treatment. Lymph node metastases can be detected with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI), but this method needs validation.

Excessive toxicity of cabozantinib in a phase II study in patients with recurrent and/or metastatic salivary gland cancer.

Aim: Because the tyrosine kinases c-MET and vascular endothelial growth factor receptors (VEGFR) are often overexpressed in salivary gland cancer (SGC), this study evaluated the efficacy and safety of cabozantinib in patients with recurrent/metastatic (R/M) SGC.

Patients And Methods: A single-centre phase II study was conducted. Patients with immunohistochemical c-MET-positive R/M SGC were included in three cohorts: adenoid cystic carcinoma (ACC); salivary duct carcinoma (SDC) and other miscellaneous SGCs.

Novel Diagnostic Approaches for Assessment of the Clinically Negative Neck in Head and Neck Cancer Patients.

In head and neck cancer, the presence of nodal disease is a strong determinant of prognosis and treatment. Despite the use of modern multimodality diagnostic imaging, the prevalence of occult nodal metastases is relatively high. This is why in clinically node negative head and neck cancer the lymphatics are treated "electively" to eradicate subclinical tumor deposits.

Advances in cancer imaging require renewed radiotherapy dose and target volume concepts.

Advances in diagnostic imaging create opportunities for improved therapeutic targeting of cancer but conceptual thinking about radiotherapy target volume definition and dose-prescription is not keeping up. In this opinion paper we discuss how modern imaging can contribute to new concepts for radiotherapy dose-prescription and target volume definition illustrated by the example of head and neck cancer. These new insights have the potential to significantly reduce radiation associated toxicity and may have important impact on the combination of radiotherapy with systemic cancer therapies.

F-FDG-PET/CT-based treatment planning for definitive (chemo)radiotherapy in patients with head and neck squamous cell carcinoma improves regional control and survival.

Background And Purpose: Multimodality imaging including F-FDG-PET has improved the detection threshold of nodal metastases in head and neck squamous cell carcinoma (HNSCC). The aim of this retrospective analysis is to investigate the impact of FDG-PET/CT-based nodal target volume definition (FDG-PET/CT-based NTV) on radiotherapy outcomes, compared to conventional CT-based nodal target volume definition (CT-based NTV).

Materials And Methods: Six-hundred-thirty-three patients treated for HNSCC with definitive (chemo)radiotherapy using IMRT/VMAT techniques between 2008 and 2017 were analyzed.

Tumor to cervical spinal cord standardized uptake ratio (SUR) improves the reproducibility of F-FDG-PET based tumor segmentation in head and neck squamous cell carcinoma in a multicenter setting.

Background: In quantitative FDG-PET data analysis, normalization of the standardized uptake value (SUV) with an internal image-derived standard improves its reproducibility. In this study, the cervical spinal cord is proposed as an internal standard that is within the field of view of the radiotherapy planning PET/CT-scan in head and neck cancer. The aim is to evaluate if the tumor to cervical spinal cord standardized uptake ratio (SUR) can improve the reproducibility of a model to determine the metabolic tumor volume (MTV) on FDG-PET/CT in a multicenter setting.

Implications of improved diagnostic imaging of small nodal metastases in head and neck cancer: Radiotherapy target volume transformation and dose de-escalation.

Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes.

Uniform FDG-PET guided GRAdient Dose prEscription to reduce late Radiation Toxicity (UPGRADE-RT): study protocol for a randomized clinical trial with dose reduction to the elective neck in head and neck squamous cell carcinoma.

Background: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary.

Reirradiation of head and neck cancer: Long-term disease control and toxicity.

Background: The purpose of this study was to report long-term disease control and late radiation toxicity for patients reirradiated for head and neck cancer.

Methods: We conducted a retrospective analysis of 137 patients reirradiated with a prescribed dose ≥45 Gy between 1986 and 2013 for a recurrent or second primary malignancy. Endpoints were locoregional control, overall survival (OS), and grade ≥4 late complications according to European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria.

Cross-institutional knowledge-based planning (KBP) implementation and its performance comparison to Auto-Planning Engine (APE).

Background And Purpose: To investigate (1) whether a plan library established at one institution can be applied for another institution's knowledge-based planning (KBP); (2) the performance of cross-institutional KBP compared to Auto-Planning Engine (APE).

Material And Methods: Radboud University Medical Center (RUMC) provided 35 oropharyngeal cancer patients (68Gy to PTV and 50.3Gy to PTV) with clinically-delivered and comparative APE plans.

Patterns of Recurrence in Electively Irradiated Lymph Node Regions After Definitive Accelerated Intensity Modulated Radiation Therapy for Head and Neck Squamous Cell Carcinoma.

Purpose: To provide a comprehensive risk assessment on the patterns of recurrence in electively irradiated lymph node regions after definitive radiation therapy for head and neck cancer.

Methods And Materials: Two hundred sixty-four patients with stage cT2-4N0-2M0 squamous cell carcinoma of the oropharynx, larynx, or hypopharynx treated with accelerated intensity modulated radiation therapy between 2008 and 2012 were included. On the radiation therapy planning computed tomography (CT) scans from all patients, 1166 lymph nodes (short-axis diameter ≥5 mm) localized in the elective volume were identified and delineated.

Xerostomia: a day and night difference.

Purpose: To compare patient-reported xerostomia during daytime and during nighttime with objectively measured parotid and submandibular gland function in a cohort of head-and-neck cancer (HNC) patients treated with RT.

Materials And Methods: A cohort of 138 HNC patients underwent objective measurements of parotid (PF) and submandibular (SMF) gland function and completed a xerostomia questionnaire (XQ) before RT, at 6 weeks, 6 months and 1 year after RT. No attempt was made to spare the submandibular gland(s).

MUC5B levels in submandibular gland saliva of patients treated with radiotherapy for head-and-neck cancer: a pilot study.

Background: The salivary mucin MUC5B, present in (sero)mucous secretions including submandibular gland (SMG) saliva, plays an important role in the lubrication of the oral mucosa and is thought to be related to the feeling of dry mouth. We investigated if MUC5B levels in SMG saliva could distinguish between the presence or absence of severe dry mouth complaints 12  months after radiotherapy (RT) for head-and-neck cancer (HNC).

Findings: Twenty-nine HNC patients with a residual stimulated SMG secretion rate of ≥ 0.

Parotid gland function after radiotherapy: the combined michigan and utrecht experience.

Purpose: To analyze the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head-and-neck (HN) cancer.

Patients And Methods: A total of 222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and 1 year after RT using Lashley cups at both centers.

A comparison of dose-response models for the parotid gland in a large group of head-and-neck cancer patients.

Purpose: The dose-response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy.

Sparing the contralateral submandibular gland in oropharyngeal cancer patients: a planning study.

Background And Purpose: The submandibular glands are proposed to be important in preventing xerostomia in head-and-neck cancer patients. We investigated the feasibility of sparing the contralateral submandibular gland (cSMG) by reducing the dose to the contralateral planning target volume (PTV) and by reducing the clinical target volume (CTV)-to-PTV margin.

Materials And Methods: Ten oropharyngeal cancer patients with a contralateral elective PTV were included in this planning study, using intensity modulated radiotherapy (IMRT).

Large cohort dose-volume response analysis of parotid gland function after radiotherapy: intensity-modulated versus conventional radiotherapy.

Purpose: To compare parotid gland dose-volume response relationships in a large cohort of patients treated with intensity-modulated (IMRT) and conventional radiotherapy (CRT).

Methods And Materials: A total of 221 patients (64 treated with IMRT, 157 with CRT) with various head-and-neck malignancies were prospectively evaluated. The distribution of tumor subsites in both groups was unbalanced.

Pharmacokinetics of two generic fixed-dose combinations for HIV-infected children (Pedimune Baby & Pedimune Junior) are similar to the branded products in healthy adults.

Objectives: Cipla Pharmaceuticals have developed generic fixed-dose combinations of stavudine, lamivudine and nevirapine for HIV-infected children (Pedimune Baby and Junior). We determined the pharmacokinetic profiles of stavudine, lamivudine and nevirapine in Pedimune and compared these with the branded products.

Methods: This Phase I, comparative, single-centre, open-label, three-period, single-dose study was designed as a pilot study to exclude large differences in pharmacokinetics.

Brief report: enzyme inducers reduce elimination half-life after a single dose of nevirapine in healthy women.

Objective: Single-dose nevirapine (SD-NVP) to prevent mother-to-child transmission (MTCT) of HIV is associated with development of NVP resistance, probably because of its long half-life in combination with a low genetic barrier to resistance. The objective of this study was to find enzyme inducers to reduce the NVP half-life.

Design: The design of this phase 1 pharmacokinetic study was a single-center, open-label, 2-period, 9-group study.