Proton radiotherapy significantly reduces pneumonia in oesophageal cancer patients.

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection is the current standard of care for oesophageal cancer (EC) patients. This treatment is associated with a variety of complications, with pneumonia being the most common. We hypothesize that proton radiotherapy (PRT) can significantly reduce the incidence of pneumonia compared to photon radiotherapy (PhRT).

Blood biomarkers for cardiac damage during and after radiotherapy for esophageal cancer: A prospective cohort study.

Purpose: The aim of this study was to test the hypothesis that the levels of High Sensitive Troponin T (HS-TNT) and N-terminal Brain Natriuretic Peptide (NT-ProBNP) increase after radiation therapy in a dose dependent way and are predictive for clinical cardiac events.

Materials And Methods: Blood samples during and after radiotherapy of 87 esophageal cancer patients were analysed regarding the course of HS-TNT and NT-ProBNP levels and their relationship with clinical toxicity endpoints and radiation dose volume parameters.

Results: HS-TNT values at the end of treatment correlated with the mean heart dose (p = 0.

External validation of NTCP-models for radiation pneumonitis in lung cancer patients treated with chemoradiotherapy.

Purpose: Normal tissue complication probability (NTCP) models can be used to estimate the risk of radiation pneumonitis (RP). The aim of this study was to externally validate the most frequently used prediction models for RP, i.e.

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.

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.

Role of mTOR through Autophagy in Esophageal Cancer Stemness.

Esophageal cancer (EC) is a highly aggressive disease with a poor prognosis. Therapy resistance and early recurrences are major obstacles in reaching a better outcome. Esophageal cancer stem-like cells (CSCs) seem tightly related with chemoradiation resistance, initiating new tumors and metastases.

Late cardiac toxicity of neo-adjuvant chemoradiation in esophageal cancer survivors: A prospective cross-sectional pilot study.

Purpose: Although cure rates in esophageal cancer (EC) have improved since the introduction of neoadjuvant chemoradiation (nCRT), evidence for treatment-related cardiac toxicity is growing, of which the exact mechanisms remain unknown. The primary objective of this study was to identify (subclinical) cardiac dysfunction in EC patients after nCRT followed by surgical resection as compared to surgery alone.

Materials And Methods: EC survivors followed for 5-15 years after curative resection with (n = 20) or without (n = 20) nCRT were enrolled in this prospective cross-sectional pilot study.

Current status and application of proton therapy for esophageal cancer.

Esophageal cancer remains one of the leading causes of death from cancer across the world despite advances in multimodality therapy. Although early-stage disease can often be treated surgically, the current state of the art for locally advanced disease is concurrent chemoradiation, followed by surgery whenever possible. The uniform midline tumor location puts a strong importance on the need for precise delivery of radiation that would minimize dose to the heart and lungs, and the biophysical properties of proton beam makes this modality potential ideal for esophageal cancer treatment.

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.

Re-Irradiation in Patients with Recurrent Rectal Cancer is Safe and Feasible.

Background: There is no consensus yet for the best treatment regimen in patients with recurrent rectal cancer (RRC). This study aims to evaluate toxicity and oncological outcomes after re-irradiation in patients with RRC in our center. Clinical (cCR) and pathological complete response (pCR) rates and radicality were also studied.

Clinical selection strategy for and evaluation of intra-operative brachytherapy in patients with locally advanced and recurrent rectal cancer.

Background And Purpose: A radical resection of locally advanced rectal cancer (LARC) or recurrent rectal cancer (RRC) can be challenging. In case of increased risk of an R1 resection, intra-operative brachytherapy (IOBT) can be applied. We evaluated the clinical selection strategy for IOBT.

Radiation-Induced Myocardial Fibrosis in Long-Term Esophageal Cancer Survivors.

Purpose: Radiation-induced cardiac toxicity is a potential lethal complication. The aim of this study was to assess whether there is a dose-dependent relationship between radiation dose and myocardial fibrosis in patients who received neoadjuvant chemoradiation (nCRT) for esophageal cancer (EC).

Methods And Materials: Forty patients with EC treated with a transthoracic esophagectomy with (n = 20) or without (n = 20) nCRT (CROSS study regimen) were included.

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.

Evaluation of continuous beam rescanning versus pulsed beam in pencil beam scanned proton therapy for lung tumours.

The treatment of moving targets with pencil beam scanned proton therapy (PBS-PT) may rely on rescanning strategies to smooth out motion induced dosimetric disturbances. PBS-PT machines, such as Proteus®Plus (PPlus) and Proteus®One (POne), deliver a continuous or a pulsed beam, respectively. In PPlus, scaled (or no) rescanning can be applied, while POne implies intrinsic 'rescanning' due to its pulsed delivery.

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).

Investigation of inter-fraction target motion variations in the context of pencil beam scanned proton therapy in non-small cell lung cancer patients.

Purpose: For locally advanced-stage non-small cell lung cancer (NSCLC), inter-fraction target motion variations during the whole time span of a fractionated treatment course are assessed in a large and representative patient cohort. The primary objective is to develop a suitable motion monitoring strategy for pencil beam scanning proton therapy (PBS-PT) treatments of NSCLC patients during free breathing.

Methods: Weekly 4D computed tomography (4DCT; 41 patients) and daily 4D cone beam computed tomography (4DCBCT; 10 of 41 patients) scans were analyzed for a fully fractionated treatment course.

Can we safely reduce the radiation dose to the heart while compromising the dose to the lungs in oesophageal cancer patients?

Purpose: The aim of this study was to evaluate which clinical and treatment-related factors are associated with heart and lung toxicity in oesophageal cancer patients treated with chemoradiation (CRT). The secondary objective was to analyse whether these toxicities are associated with overall survival (OS).

Materials And Methods: The study population consisted of a retrospective cohort of 216 oesophageal cancer patients treated with curative CRT.

Organ sparing potential and inter-fraction robustness of adaptive intensity modulated proton therapy for lung cancer.

The aim of this study was to compare adaptive intensity modulated proton therapy (IMPT) robustness and organ sparing capabilities with that of adaptive volumetric arc photon therapy (VMAT). Eighteen lung cancer patients underwent a planning 4DCT (p4DCT) and 5 weekly repeated 4DCT (r4DCT) scans. Target volumes and organs at risk were manually delineated on the three-dimensional (3D) average scans of the p4DCT (av_p4DCT) and of the r4DCT scans (av_r4DCT).

Small Cell Carcinoma of the Esophagus: A Nationwide Analysis of Treatment and Outcome at Patient Level in Locoregional Disease.

Background And Purpose: Small cell carcinoma of the esophagus (SCEC) is a rare subtype of esophageal cancer for which optimal treatment is unknown. We analyzed the impact of treatment factors on outcome in patients with nonmetastasized SCEC.

Methods: Patients with a histologically confirmed SCEC without distant metastases were analyzed in a nationwide multicenter retrospective cohort.