A planning study of proton therapy dose escalation for non-small cell lung cancer.

In non-small-cell lung cancer (NSCLC), improving local control through radiotherapy dose escalation might improve survival. However, a photon-based RCT showed increased organ at risk dose exposure and worse overall survival in the dose escalation arm. In this study, intensity-modulated proton therapy plans with dose escalation to the primary tumour were created for 20 NSCLC patients.

Clinical 3D/4D cumulative proton dose assessment methods for thoracic tumours with large motion.

Purpose: Despite the anticipated clinical benefits of intensity-modulated proton therapy (IMPT), plan robustness may be compromised due to its sensitivity to patient treatment uncertainties, especially for tumours with large motion. In this study, we investigated treatment course-wise plan robustness for intra-thoracic tumours with large motion comparing a 4D pre-clinical evaluation method (4DREM) to our clinical 3D/4D dose reconstruction and accumulation methods.

Materials And Methods: Twenty patients with large target motion (>10 mm) were treated with five times layered rescanned IMPT.

Robustness assessment of clinical adaptive proton and photon radiotherapy for oesophageal cancer in the model-based approach.

Purpose: In the Netherlands, oesophageal cancer (EC) patients are selected for intensity modulated proton therapy (IMPT) using the expected normal tissue complication probability reduction (ΔNTCP) when treating with IMPT compared to volumetric modulated arc therapy (VMAT). In this study, we evaluate the robustness of the first EC patients treated with IMPT in our clinic in terms of target and organs-at-risk (OAR) dose with corresponding NTCP, as compared to VMAT.

Materials And Methods: For 20 consecutive EC patients, clinical IMPT and VMAT plans were created on the average planning 4DCT.

Deep learning-based 4D-synthetic CTs from sparse-view CBCTs for dose calculations in adaptive proton therapy.

Background: Time-resolved 4D cone beam-computed tomography (4D-CBCT) allows a daily assessment of patient anatomy and respiratory motion. However, 4D-CBCTs suffer from imaging artifacts that affect the CT number accuracy and prevent accurate proton dose calculations. Deep learning can be used to correct CT numbers and generate synthetic CTs (sCTs) that can enable CBCT-based proton dose calculations.

Treatment planning comparison in the PROTECT-trial randomising proton versus photon beam therapy in oesophageal cancer: Results from eight European centres.

Purpose: To compare dose distributions and robustness in treatment plans from eight European centres in preparation for the European randomized phase-III PROTECT-trial investigating the effect of proton therapy (PT) versus photon therapy (XT) for oesophageal cancer.

Materials And Methods: All centres optimized one PT and one XT nominal plan using delineated 4DCT scans for four patients receiving 50.4 Gy (RBE) in 28 fractions.

Diaphragm-Based Position Verification to Improve Daily Target Dose Coverage in Proton and Photon Radiation Therapy Treatment of Distal Esophageal Cancer.

Purpose: In modern conformal radiation therapy of distal esophageal cancer, target coverage can be affected by variations in the diaphragm position. We investigated if daily position verification (PV) extended by a diaphragm position correction would optimize target dose coverage for esophageal cancer treatment.

Methods And Materials: For 15 esophageal cancer patients, intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans were computed.

Assessment of a diaphragm override strategy for robustly optimized proton therapy planning for esophageal cancer patients.

Purpose: To ensure target coverage in the treatment of esophageal cancer, a density override to the region of diaphragm motion can be applied in the optimization process. Here, we evaluate the benefit of this approach during robust optimization for intensity modulated proton therapy (IMPT) planning.

Materials And Methods: For 10 esophageal cancer patients, two robustly optimized IMPT plans were created either using (WDO) or not using (NDO) a diaphragm density override of 1.

Genetic polymorphism in is associated with effectiveness and toxicity of pemetrexed in non-small-cell lung cancer.

Patients with advanced non-small-cell lung cancer who are treated with pemetrexed display a wide variation in clinical response and toxicity. In this prospective, multicentre cohort study, we investigated the association with treatment effectiveness and toxicity of 10 polymorphisms in nine candidate genes, covering the folate pathway (), cell transport (), intracellular metabolism () and target enzymes () of pemetrexed. Adjusted for sex, ECOG performance score and disease stage, the association between (rs12995526) and overall survival (HR 1.

Dosimetric influence of deformable image registration uncertainties on propagated structures for online daily adaptive proton therapy of lung cancer patients.

Purpose: A major burden of introducing an online daily adaptive proton therapy (DAPT) workflow is the time and resources needed to correct the daily propagated contours. In this study, we evaluated the dosimetric impact of neglecting the online correction of the propagated contours in a DAPT workflow.

Material And Methods: For five NSCLC patients with nine repeated deep-inspiration breath-hold CTs, proton therapy plans were optimised on the planning CT to deliver 60 Gy-RBE in 30 fractions.

Towards the clinical implementation of intensity-modulated proton therapy for thoracic indications with moderate motion: Robust optimised plan evaluation by means of patient and machine specific information.

Purpose: Compared to volumetric modulated arc therapy (VMAT), clinical benefits are anticipated when treating thoracic tumours with intensity-modulated proton therapy (IMPT). However, the current concern of plan robustness as a result of motion hampers its wide clinical implementation. To define an optimal protocol to treat lung and oesophageal cancers, we present a comprehensive evaluation of IMPT planning strategies, based on patient 4DCTs and machine log files.

A comprehensive motion analysis - consequences for high precision image-guided radiotherapy of esophageal cancer patients.

Background And Purpose: When treating patients for esophageal cancer (EC) with photon or proton radiotherapy (RT), breathing motion of the target and neighboring organs may result in deviations from the planned dose distribution. The aim of this study was to evaluate the magnitude and dosimetric impact of breathing motion. Results were based on comparing weekly 4D computed tomography (4D CT) scans with the planning CT, using the diaphragm as an anatomical landmark for EC.

Weekly robustness evaluation of intensity-modulated proton therapy for oesophageal cancer.

Background And Purpose: Intensity-modulated proton therapy (IMPT) is expected to result in clinical benefits by lowering radiation dose to organs-at-risk (OARs). However, there are concerns about plan robustness due to motion. To address this uncertainty we evaluated the robustness of IMPT compared to the widely clinically used volumetric modulated arc therapy (VMAT) on weekly repeated computed tomographies (CT).

The association of depressive symptoms, personality traits, and sociodemographic factors with health-related quality of life and quality of life in patients with advanced-stage lung cancer: an observational multi-center cohort study.

Background: Identification of patient-related factors associated with Health-Related Quality of Life (HRQoL) and Quality of Life (QoL) at the start of treatment may identify patients who are prone to a decrease in HRQoL and/or QoL resulting from chemotherapy. Identification of these factors may offer opportunities to enhance patient care during treatment by adapting communication strategies and directing medical and psychological interventions. The aim was to examine the association of sociodemographic factors, personality traits, and depressive symptoms with HRQoL and QoL in patients with advanced-stage lung cancer at the start of chemotherapy.

Renal Toxicity From Pemetrexed and Pembrolizumab in the Era of Combination Therapy in Patients With Metastatic Nonsquamous Cell NSCLC.

The combination of chemotherapy and immune checkpoint inhibition (ICI) therapy is the current standard of care for most patients who are fit to undergo treatment for metastatic NSCLC. With this combination, renal toxicity was slightly higher than with chemotherapy alone in initial clinical trials. However, in recent real-world data, loss of kidney function is reported to be more frequent.

Influence of Genetic Variation in on Cisplatin-Induced Nephrotoxicity in Cancer Patients.

Cisplatin is a chemotherapeutic agent widely used for multiple indications. Unfortunately, in a substantial set of patients treated with cisplatin, dose-limiting acute kidney injury (AKI) occurs. Here, we assessed the association of 3 catechol-O-methyltransferase ( single nucleotide polymorphisms (SNPs) with increased cisplatin-induced nephrotoxicity.

A limited sampling schedule to estimate individual pharmacokinetics of pemetrexed in patients with varying renal functions.

Purpose: Pemetrexed is a widely used cytostatic agent with an established exposure-response relationship. Although dosing is based on body surface area (BSA), large interindividual variability in pemetrexed plasma concentrations is observed. Therapeutic drug monitoring (TDM) can be a feasible strategy to reduce variability in specific cases leading to potentially optimized pemetrexed treatment.

Frequency of low-grade adverse events and quality of life during chemotherapy determine patients' judgement about treatment in advanced-stage thoracic cancer.

Purpose: In lung cancer, the preservation of well-being is warranted given the limited prognosis. Chemotherapy may negatively influence health-related quality of life (HRQoL) due to adverse events. However, patients' judgement about this negative impact is not well understood.

Satisfactory results of a psychometric analysis and calculation of minimal clinically important differences of the World Health Organization quality of life-BREF questionnaire in an observational cohort study with lung cancer and mesothelioma patients.

Background: To determine the psychometric properties and minimal clinically important differences (MCIDs) of the World Health Organization Quality of Life-BREF (WHOQOL-BREF) in advanced stage lung cancer patients.

Methods: Patients (n = 153) completed the WHOQOL-BREF and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Confirmatory factor analysis (CFA) was performed and reliability and construct validity determined.

Renal impairment during pemetrexed maintenance in patients with advanced nonsmall cell lung cancer: a cohort study.

Optimal survival benefit from different lines of anticancer treatment in advanced nonsmall cell lung cancer (NSCLC) requires conservation of renal function. We evaluated the development of renal impairment during pemetrexed maintenance.In a prospective multicentre cohort study, we evaluated the incidence of acute/chronic kidney disease (AKD/CKD), its related treatment discontinuation frequency and associated clinical variables with AKD in patients with stage IIIB/IV NSCLC treated with pemetrexed maintenance.

Treatment Satisfaction of Patients With Advanced Non-Small-cell Lung Cancer Receiving Platinum-based Chemotherapy: Results From a Prospective Cohort Study (PERSONAL).

Introduction: In patients with advanced non-small-cell lung cancer, the treatment benefits and risks need to be constantly weighed. We explored patient-reported satisfaction with therapy (SWT) and assessed its value in addition to quality of life (QoL) and adverse events (AEs).

Patients And Methods: In a prospective multicenter cohort study, patients with stage IIIB/IV non-small-cell lung cancer received platinum-pemetrexed chemotherapy.

High and individually variable enzymatic activity precludes accurate determination of pemetrexed, methotrexate and their polyglutamate metabolite concentrations in plasma.

Most drugs are metabolized in the human body. Therefore, it is essential for therapeutic drug monitoring studies to also take into account the concentrations of drug metabolites. One of the possible metabolic activities on drugs such as pemetrexed or methotrexate is (poly)glutamation.

A new quantification method for assessing plasma concentrations of pemetrexed and its polyglutamate metabolites.

Currently no quantification method exists for potentially therapeutically relevant polyglutamate metabolites of the drug pemetrexed which is used for the treatment of lung carcinoma patients. We developed and tested an LC-MS/MS-based analytical assay that uses isotope-labeled internal standards to quantify pemetrexed and its (poly)glutamate metabolites in clinical human plasma samples of lung carcinoma patients. UHPLC chromatography and triple quadrupole mass spectrometry showed an LLOQ of 0.