Impact of MRI on target volume definition in head and neck cancer patients.

Background: Target volume definition for curative radiochemotherapy in head and neck cancer is crucial since the predominant recurrence pattern is local. Additional diagnostic imaging like MRI is increasingly used, yet it is usually hampered by different patient positioning compared to radiotherapy. In this study, we investigated the impact of diagnostic MRI in treatment position for target volume delineation.

Plasma sICAM-1 correlates with tumor volume before primary radiochemotherapy of head and neck squamous cell carcinoma patients.

Background: Biomarkers are of major interest to optimize diagnosis, prognosis and to guide treatment in head and neck cancer patients. Especially blood-based biomarkers appear promising as they can be easily collected and repeatedly analyzed during the course of radiochemotherapy.

Patients And Methods: At first, for a broad overview, multiple immune markers were evaluated in six plasma samples of three head and neck squamous cell carcinoma (HNSCC) patients at the beginning and the end of radio-chemotherapy.

Dose escalation to hypoxic subvolumes in head and neck cancer: A randomized phase II study using dynamic [F]FMISO PET/CT.

Background And Purpose: Tumor hypoxia is a major cause of resistance to radiochemotherapy in locally advanced head-and-neck cancer (LASCCHN). We present results of a randomized phase II trial on hypoxia dose escalation (DE) in LASCCHN based on dynamic [F]FMISO (dynFMISO) positron emission tomography (PET). The purpose was to confirm the prognostic value of hypoxia PET and assess feasibility, toxicity and efficacy of hypoxia-DE.

Dynamics of HMBG1 (High Mobility Group Box 1) during radiochemotherapy correlate with outcome of HNSCC patients.

Purpose: High Mobility Group Box 1 (HMGB1) protein has been described as a consensus marker for immunogenic cell death (ICD) in cancer. To personalize treatments, there is a need for biomarkers to adapt dose prescription, concomitant chemotherapy, and follow-up in radiation oncology. Thus, we investigated the levels of HMGB1 in plasma of patients with head and neck squamous cell carcinoma (HNSCC) during the course of radiochemotherapy and follow-up in correlation with oncologic outcome and clinical confounders.

Comparison of patient stratification by computed tomography radiomics and hypoxia positron emission tomography in head-and-neck cancer radiotherapy.

Background And Purpose: Hypoxia Positron-Emission-Tomography (PET) as well as Computed Tomography (CT) radiomics have been shown to be prognostic for radiotherapy outcome. Here, we investigate the stratification potential of CT-radiomics in head and neck cancer (HNC) patients and test if CT-radiomics is a surrogate predictor for hypoxia as identified by PET.

Materials And Methods: Two independent cohorts of HNC patients were used for model development and validation, HN1 (n = 149) and HN2 (n = 47).

Dynamics of cell-free tumour DNA correlate with treatment response of head and neck cancer patients receiving radiochemotherapy.

Purpose: Definitive radiochemotherapy (RCTX) with curative intent is one of the standard treatment options in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Despite this intensive therapy protocol, disease recurrence remains an issue. Therefore, we tested the predictive capacity of liquid biopsies as a novel biomarker during RCTX in patients with HNSCC.

ERCC2 gene single-nucleotide polymorphism as a prognostic factor for locally advanced head and neck carcinomas after definitive cisplatin-based radiochemotherapy.

Identifying patients with locally advanced head and neck carcinoma on high risk of recurrence after definitive concurrent radiochemotherapy is of key importance for the selection for consolidation therapy and for individualized treatment intensification. In this multicenter study we analyzed recurrence-associated single-nucleotide polymorphisms (SNPs) in DNA repair genes in tumor DNA from 132 patients with locally advanced head and neck carcinoma (LadHnSCC). Patients were treated with definitive radiotherapy and simultaneous cisplatin-based chemotherapy at six partner sites of the German Cancer Consortium (DKTK) Radiation Oncology Group from 2005 to 2011.

PET/MRI and genetic intrapatient heterogeneity in head and neck cancers.

Purpose: The relation between functional imaging and intrapatient genetic heterogeneity remains poorly understood. The aim of our study was to investigate spatial sampling and functional imaging by FDG-PET/MRI to describe intrapatient tumour heterogeneity.

Methods: Six patients with oropharyngeal cancer were included in this pilot study.

Radiogenomics in head and neck cancer: correlation of radiomic heterogeneity and somatic mutations in TP53, FAT1 and KMT2D.

Purpose: Genetic tumour profiles and radiomic features can be used to complement clinical information in head and neck squamous cell carcinoma (HNSCC) patients. Radiogenomics imply the potential to investigate complementarity or interrelations of radiomic and genomic features, and prognostic factors might be determined. The aim of our study was to explore radiogenomics in HNSCC.

Prospective Evaluation of a Tumor Control Probability Model Based on Dynamic F-FMISO PET for Head and Neck Cancer Radiotherapy.

Our purpose was to evaluate an imaging parameter-response relationship between the extent of tumor hypoxia quantified by dynamic F-fluoromisonidazole (F-FMISO) PET/CT and the risk of relapse after radiotherapy in patients with head and neck cancer. Before a prospective cohort of 25 head and neck cancer patients started radiotherapy, they were examined with dynamic F-FMISO PET/CT 0-240 min after tracer injection. F-FMISO image parameters, including a hypoxia metric, derived from pharmacokinetic modeling of dynamic F-FMISO and maximum tumor-to-muscle ratio (TMR) at 4 h after injection, gross tumor volume (GTV), relative hypoxic volume based on and a logistic regression model combining GTV and TMR, were assessed and compared with a previous training cohort ( = 15).

Circulating cell-free DNA: A potential biomarker to differentiate inflammation and infection during radiochemotherapy.

Background And Purpose: Radiochemotherapy is a standard treatment option for patients with head and neck cancer (HNSCC). During radiation, local toxicities are common and need to be differentiated from infections. As levels of circulating cell-free DNA (cfDNA) are known to be elevated during infections, cfDNA might complement clinical parameters.

Assessment of image quality of a radiotherapy-specific hardware solution for PET/MRI in head and neck cancer patients.

Background And Purpose: Functional PET/MRI has great potential to improve radiotherapy planning (RTP). However, data integration requires imaging with radiotherapy-specific patient positioning. Here, we investigated the feasibility and image quality of radiotherapy-customized PET/MRI in head-and-neck cancer (HNC) patients using a dedicated hardware setup.

Resolution of atelectasis during radiochemotherapy of lung cancer with serious implications for further treatment. A case report.

Local failure is a major cause for low overall survival rates in advanced non small cell lung cancer (NSCLC). Among others, radioresistant tumor clones as well as geographical miss can explain these high local failure rates. One reason for geographical miss is a change of tumor related atelectasis in the course of radiotherapy.

SDF-1/CXCR4 expression in head and neck cancer and outcome after postoperative radiochemotherapy.

Introduction: Outcome after postoperative radiochemotherapy (RT-CT) for patients with advanced head and neck squamous cell carcinomas (HNSCC) remains unsatisfactory, especially among those with HPV negative tumours. Therefore, new biomarkers are needed to further define subgroups for individualised therapeutic approaches. Preclinical and first clinical observations showed that the chemokine receptor CXCR4 and its ligand SDF-1 (CXCL12) play an important role in tumour cell proliferation, survival, cancer progression, metastasis and treatment resistance.

Voxel-wise correlation of functional imaging parameters in HNSCC patients receiving PET/MRI in an irradiation setup.

Purpose: The purpose of this study was to demonstrate the feasibility of voxel-wise multiparametric characterization of head and neck squamous cell carcinomas (HNSCC) using hybrid multiparametric magnetic resonance imaging and positron emission tomography with [F]-fluorodesoxyglucose (FDG-PET/MRI) in a radiation treatment planning setup.

Methods: Ten patients with locally advanced HNSCC were examined with a combined FDG-PET/MRI in an irradiation planning setup. The multiparametric imaging protocol consisted of FDG-PET, T2-weighted transverse short tau inversion recovery sequence (STIR) and diffusion-weighted MRI (DWI).

SDF-1/CXCR4 expression is an independent negative prognostic biomarker in patients with head and neck cancer after primary radiochemotherapy.

Introduction: Preclinical and clinical data suggest that the chemokine pathway governed by SDF-1 and CXCR4 contributes to a resistant phenotype. This retrospective biomarker study aims to explore the specific prognostic value of SDF-1 and CXCR4 expression in locally advanced head and neck squamous cell carcinomas (HNSCC) treated with primary radiochemotherapy (RT-CT).

Material And Methods: Biopsies from 141 HNSCC tumours of the oral cavity, oropharynx and hypopharynx were evaluated for SDF-1 and CXCR4 expression by immunofluorescence.

Geometric analysis of loco-regional recurrences in relation to pre-treatment hypoxia in patients with head and neck cancer.

Introduction: A previous pattern-of-failure study has suggested that up to 50% of the loco-regional failures (LRF) in head and neck squamous cell carcinoma (HNSCC) occur outside the initial hypoxic volume determined by [F]-fluoromisonidazole-PET ([F]-FMISO-PET). The aim of the present analysis was to correlate spatial patterns of failure with respect to the pretherapeutic dynamic [F]-FMISO-PET/CT in HNSCC after radiochemotherapy (RCT).

Material And Methods: Within a running phase 2 trial using [F]-FMISO-PET imaging prior to RCT in HNSCC patients (n = 54), we have observed so far 11 LRF with a minimum follow-up of 12 months.

Overlap of highly FDG-avid and FMISO hypoxic tumor subvolumes in patients with head and neck cancer.

Background: PET imaging may be used to personalize radiotherapy (RT) by identifying radioresistant tumor subvolumes for RT dose escalation. Using the tracers [F]-fluorodeoxyglucose (FDG) and [F]-fluoromisonidazole (FMISO), different aspects of tumor biology can be visualized. FDG depicts various biological aspects, e.

The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: A multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).

We examined the prognostic role of PD-1+ and CD8+ tumor infiltrating lymphocytes (TILs), and PD-L1+ cells in patients with squamous cell carcinoma of the head and neck (SCCHN) treated with surgery and postoperative chemoradiotherapy (CRT). FFPE samples from 161 patients were immunohistochemically stained for PD-1, CD8 and PD-L1. The immune marker expression was correlated with clinicopathologic characteristics, and overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of HPV16 DNA/p16 status.

Prognostic value of dynamic hypoxia PET in head and neck cancer: Results from a planned interim analysis of a randomized phase II hypoxia-image guided dose escalation trial.

Background And Purpose: To prospectively assess the prognostic value of tumour hypoxia determined by dynamic [F]Fluoromisonidazole (dynFMISO) PET/CT, and to evaluate both feasibility and toxicity in patients with locally advanced squamous cell carcinomas of the head and neck (LASCCHN) treated with dynFMISO image-guided dose escalation (DE) using dose-painting by contours.

Patients And Methods: We present a planned interim analysis of a randomized phase II trial. N=25 patients with LASCCHN received baseline dynFMISO PET/CT to derive hypoxic volumes (HV).

Comparison of DCE-MRI kinetic parameters and FMISO-PET uptake parameters in head and neck cancer patients.

Purpose: Tumor hypoxia is a major cause of radiation resistance, often present in various solid tumors. Dynamic [ F]-fluoromisonidazole (FMISO) PET imaging is able to reliably assess tumor hypoxia. Comprehensive characterization of tumor microenvironment through FMISO-PET and dynamic contrast enhanced (DCE) MR multimodality imaging might be a valuable alternative to the dynamic FMISO-PET acquisition.