Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours.

Hypoxia is a common feature of solid tumours affecting their biology and response to therapy. One of the main transcription factors activated by hypoxia is hypoxia-inducible factor (HIF), which regulates the expression of genes involved in various aspects of tumourigenesis including proliferative capacity, angiogenesis, immune evasion, metabolic reprogramming, extracellular matrix (ECM) remodelling, and cell migration. This can negatively impact patient outcomes by inducing therapeutic resistance.

Esophageal wall dose-surface maps do not improve the predictive performance of a multivariable NTCP model for acute esophageal toxicity in advanced stage NSCLC patients treated with intensity-modulated (chemo-)radiotherapy.

In our previous work, a multivariable normal-tissue complication probability (NTCP) model for acute esophageal toxicity (AET) Grade  ⩾2 after highly conformal (chemo-)radiotherapy for non-small cell lung cancer (NSCLC) was developed using multivariable logistic regression analysis incorporating clinical parameters and mean esophageal dose (MED). Since the esophagus is a tubular organ, spatial information of the esophageal wall dose distribution may be important in predicting AET. We investigated whether the incorporation of esophageal wall dose-surface data with spatial information improves the predictive power of our established NTCP model.

Is selective nodal irradiation in non-small cell lung cancer still safe when using IMRT? Results of a prospective cohort study.

Background And Purpose: Isolated nodal failures (INF) are rare after 3D-conformal radiotherapy (3D-CRT) for stage III non-small cell lung cancer (NSCLC). Since incidental nodal irradiation doses are lower with Intensity Modulated Radiation Therapy (IMRT) than with 3D-CRT, INF may be higher after IMRT. We therefore investigated the incidence of INF after IMRT in stage III NSCLC patients.

PRONTOX - proton therapy to reduce acute normal tissue toxicity in locally advanced non-small-cell lung carcinomas (NSCLC): study protocol for a randomised controlled trial.

Background: Primary radiochemotherapy with photons is the standard treatment for locally advanced-stage non-small cell lung cancer (NSCLC) patients. Acute radiation-induced side effects such as oesophagitis and radiation pneumonitis limit patients' quality of life, and the latter can be potentially life-threatening. Due to its distinct physical characteristics, proton therapy enables better sparing of normal tissues, which is supposed to translate into a reduction of radiation-induced side effects.

[18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches.

Purpose: Nitroglycerin (NTG) is a vasodilating drug, which increases tumor blood flow and consequently decreases hypoxia. Therefore, changes in [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG PET) uptake pattern may occur. In this analysis, we investigated the feasibility of [18F]FDG PET for response assessment to paclitaxel-carboplatin-bevacizumab (PCB) treatment with and without NTG patches.

FMISO as a Biomarker for Clinical Radiation Oncology.

Tumour hypoxia is a well-known negative prognostic marker in almost all solid tumours. [18F]Fluoromisonidazole (FMISO)-positron emission tomography (PET) is a non-invasive method to detect tumour hypoxia. Compared to other methods of hypoxia assessment it possesses some considerable advantages: It is non-invasive, it delivers spatial information on the hypoxia distribution within the entire tumour volume, and it can be repeated during the course of radio(chemo)therapy.

Evaluation of tumour hypoxia during radiotherapy using [F]HX4 PET imaging and blood biomarkers in patients with head and neck cancer.

Background And Purpose: Increased tumour hypoxia is associated with a worse overall survival in patients with head and neck squamous cell carcinoma (HNSCC). The aims of this study were to evaluate treatment-associated changes in [F]HX4-PET, hypoxia-related blood biomarkers, and their interdependence.

Material And Methods: [F]HX4-PET/CT scans of 20 patients with HNSCC were acquired at baseline and after ±20Gy of radiotherapy.

Prognostic value of blood-biomarkers related to hypoxia, inflammation, immune response and tumour load in non-small cell lung cancer - A survival model with external validation.

Aim: Improve the prognostic prediction of clinical variables for non-small cell lung cancer (NSCLC), by selecting from blood-biomarkers, non-invasively describing hypoxia, inflammation and tumour load.

Methods: Model development and validation included 182 and 181 inoperable stage I-IIIB NSCLC patients treated radically with radiotherapy (55.2%) or chemo-radiotherapy (44.

The Diagnostic Value of MR Imaging in Determining the Lymph Node Status of Patients with Non-Small Cell Lung Cancer: A Meta-Analysis.

Purpose To summarize existing evidence of thoracic magnetic resonance (MR) imaging in determining the nodal status of non-small cell lung cancer (NSCLC) with the aim of elucidating its diagnostic value on a per-patient basis (eg, in treatment decision making) and a per-node basis (eg, in target volume delineation for radiation therapy), with results of cytologic and/or histologic examination as the reference standard. Materials and Methods A systematic literature search for original diagnostic studies was performed in PubMed, Web of Science, Embase, and MEDLINE. The methodologic quality of each study was evaluated by using the Quality Assessment of Diagnostic Accuracy Studies 2, or QUADAS-2, tool.

Early Weight Loss during Chemoradiotherapy Has a Detrimental Impact on Outcome in NSCLC.

Objectives: The aim of this study was to assess the effect of early weight loss before the onset of radiation esophagitis on overall survival (OS) in patients with non-small cell lung cancer treated with concurrent chemoradiotherapy.

Methods: Characteristics (e.g.

Improved progression free survival for patients with diabetes and locally advanced non-small cell lung cancer (NSCLC) using metformin during concurrent chemoradiotherapy.

Background And Purpose: The aim was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome.

Material And Methods: A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients). All received cCRT in one of three participating radiation oncology departments in the Netherlands between January 2008 and January 2013.

Emerging Role of MRI for Radiation Treatment Planning in Lung Cancer.

Magnetic resonance imaging (MRI) provides excellent soft-tissue contrast and allows for specific scanning sequences to optimize differentiation between various tissue types and properties. Moreover, it offers the potential for real-time motion imaging. This makes magnetic resonance imaging an ideal candidate imaging modality for radiation treatment planning in lung cancer.

Increasing the Therapeutic Ratio of Stereotactic Ablative Radiotherapy by Individualized Isotoxic Dose Prescription.

To obtain a favorable tradeoff between treatment benefits and morbidity ("therapeutic ratio"), radiotherapy (RT) dose is prescribed according to the tumor volume, with the goal of controlling the disease while respecting normal tissue tolerance levels. We propose a new paradigm for tumor dose prescription in stereotactic ablative radiotherapy (SABR) based on organ-at-risk (OAR) tolerance levels called isotoxic dose prescription (IDP), which is derived from experiences and limitations of conventionally fractionated radiotherapy. With IDP, the radiation dose is prescribed based on the predefined level of normal tissue complication probability of a nearby dose-limiting OAR at a prespecified dose-volume constraint.

Imaging-Based Treatment Adaptation in Radiation Oncology.

In many tumor types, significant effort is being put into patient-tailored adaptation of treatment to improve outcome and preferably reduce toxicity. These opportunities first arose with the introduction of modern irradiation techniques (e.g.

Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy.

Background And Purpose: The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to distinct dosimetric characteristics of intensity-modulated radiation therapy (IMRT), 3D-CRT based models need revision. We established a multivariable NTCP model for AET in 149 AS-NSCLC patients undergoing IMRT.

The effect of SUV discretization in quantitative FDG-PET Radiomics: the need for standardized methodology in tumor texture analysis.

FDG-PET-derived textural features describing intra-tumor heterogeneity are increasingly investigated as imaging biomarkers. As part of the process of quantifying heterogeneity, image intensities (SUVs) are typically resampled into a reduced number of discrete bins. We focused on the implications of the manner in which this discretization is implemented.

PET-based dose painting in non-small cell lung cancer: Comparing uniform dose escalation with boosting hypoxic and metabolically active sub-volumes.

Background And Purpose: We compared two imaging biomarkers for dose-escalation in patients with advanced non-small cell lung cancer (NSCLC). Treatment plans boosting metabolically active sub-volumes defined by FDG-PET or hypoxic sub-volumes defined by HX4-PET were compared with boosting the entire tumour.

Materials And Methods: Ten NSCLC patients underwent FDG- and HX4-PET/CT scans prior to radiotherapy.

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

Background: 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.

Imaging of tumour hypoxia and metabolism in patients with head and neck squamous cell carcinoma.

Background: Tumour hypoxia and a high tumour metabolism increase radioresistance in patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to evaluate the correlation between hypoxia ([(18)F]HX4 PET) and glucose metabolism ([(18)F]FDG PET) molecular imaging.

Material And Methods: [(18)F]HX4 and [(18)F]FDG PET/CT images of 20 HNSCC patients were acquired prior to (chemo)radiotherapy, in an immobilisation mask, with a median time interval of seven days (NCT01347281).

Comparison of [18F]-FMISO, [18F]-FAZA and [18F]-HX4 for PET imaging of hypoxia--a simulation study.

Background: To investigate the effect of hypoxia tracer properties on positron emission tomography (PET) image quality for three tracers [18F]-fluoromisonidazole (FMISO), [18F]-fluoroazomycinarabinoside (FAZA) and [18F]-flortanidazole (HX4), using mathematical simulations based on microscopic tumor tissue sections.

Material And Methods: Oxygen distribution and tracer binding was mathematically simulated on immunohistochemically stained cross-sections of tumor xenografts. Tracer diffusion properties were determined based on available literature.

Is integrated transit planar portal dosimetry able to detect geometric changes in lung cancer patients treated with volumetric modulated arc therapy?

Background: Geometric changes are frequent during the course of treatment of lung cancer patients. This may potentially result in deviations between the planned and actual delivered dose. Electronic portal imaging device (EPID)-based integrated transit planar portal dosimetry (ITPD) is a fast method for absolute in-treatment dose verification.