A Polygenic Risk Score for Late Bladder Toxicity Following Radiotherapy for Non-Metastatic Prostate Cancer.

Background: Late bladder toxicity is a concern for patients receiving prostate cancer radiotherapy and negatively impacts survivors. Few risk factors are known beyond the radiation dose and volume of bladder exposed. A polygenic risk score (PRS) could identify susceptible patients.

Association between dose to cardiac structures and overall survival: A multivariable analysis in a large, multi-institutional database of stage III NSCLC patients with external validation.

Background And Purpose: Inconsistencies in identifying dose-limiting cardiovascular substructures for treating stage III non-small cell lung cancer (NSCLC) have hindered the implementation of cardiac sparing treatment planning guidelines. This study aims to address these inconsistencies by performing a multivariable survival analysis with overall survival as the endpoint using a large, multinational database, followed by external validation.

Materials And Methods: Clinical and dosimetric parameters from 1587 stage III NSCLC patients treated at five institutes were analyzed.

Impact of Immune Checkpoint Inhibitors and Local Radical Treatment on Survival Outcomes in Synchronous Oligometastatic NSCLC.

Introduction: The impact of an immune checkpoint inhibitor (ICI)-based systemic treatment strategy with or without local radical treatment (LRT) on outcomes for patients with NSCLC and synchronous oligometastatic disease (sOMD) is unknown.

Methods: Multicenter retrospective study including adequately staged patients, with sOMD NSCLC (maximum five metastases in three organs [European Organization for Research and Treatment of Cancer definition]) between January 1, 2015 and December 31, 2022, treated with a first-line ICI-based versus chemotherapy-only regimen. Primary end points were progression-free survival and overall survival (OS) for an ICI-based versus chemotherapy-only strategy.

Comparative efficacy of immunotherapy-based treatment versus chemotherapy-only in patients with unresectable NSCLC with disease progression post chemoradiation and durvalumab.

Introduction: The current standard of care for fit patients with unresectable stage III NSCLC involves concurrent chemoradiation (CRT) followed by durvalumab. Disease recurrence occurs in approximately 2/3 of patients, often necessitating subsequent systemic therapy. The only available data about re-challenge immune checkpoint blockers (ICB) in this setting derives from small retrospective series.

An assay for assessing 1-aminocyclopropane-1-carboxylate malonyl (MACC) transferase (AMT) activity and its regulation by ethylene.

Background: N-malonyl 1-aminocyclopropane-1-carboxylic acid (MACC) is a major conjugate of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) and may therefore play an important role in regulating ethylene production, as well as ethylene-independent ACC signalling. While the enzyme responsible for this derivatization, ACC malonyltransferase (AMT), has been studied in the past, its identity remains unknown. Methods to assay AMT activity are not well established, and no standardized assay has been described.

Risk factors and prognostic factors of pleural metastases in thymic epithelial tumors: A narrative review.

Introduction: Pleural metastases are common in thymic epithelial tumors (TET), which include pleural recurrence and stage IVa at initial diagnosis. However, the specific risk factors predicting its recurrence (i.e.

Proton therapy of lung cancer patients - Treatment strategies and clinical experience from a medical physicist's perspective.

Purpose: Proton therapy of moving targets is considered a challenge. At Maastro, we started treating lung cancer patients with proton therapy in October 2019. In this work, we summarise the developed treatment strategies and gained clinical experience from a physics point of view.

Association of radiation-induced normal tissue toxicity with a high genetic risk for rheumatoid arthritis.

Purpose: Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesised that patients with a high polygenic risk score (PRS) for RA will have an increased risk of radiotherapy (RT) toxicity given the involvement of DNA repair.

Methods: Primary analysis was performed on 1494 prostate cancer, 483 lung cancer and 1820 breast cancer patients assessed for development of RT toxicity in the REQUITE study.

Professional-patient discrepancies in assessing lung cancer radiotherapy symptoms: An international multicentre study.

Background And Purpose: We investigate discrepancies in the assessment of treatment-related symptoms in lung cancer between healthcare professionals and patients, and factors contributing to these discrepancies.

Materials And Methods: Data from 515 participants in the REQUITE study were analysed. Five symptoms (cough, dyspnoea, bronchopulmonary haemorrhage, chest wall pain, dysphagia) were evaluated both before and after radiotherapy.

Prognostic and Predictive Biomarkers of Oligometastatic NSCLC: New Insights and Clinical Applications.

This review discusses the current data on predictive and prognostic biomarkers in oligometastatic NSCLC and discusses whether biomarkers identified in other stages and widespread metastatic disease can be extrapolated to the oligometastatic disease (OMD) setting. Research is underway to explore the prognostic and predictive value of biological attributes of tumor tissue, circulating cells, the tumor microenvironment, and imaging findings as biomarkers of oligometastatic NSCLC. Biomarkers that help define true OMD and predict outcomes are needed for patient selection for oligometastatic treatment, and to avoid futile treatments in patients that will not benefit from locoregional treatment.

Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small cell lung cancer better preserves white matter networks compared to conventional PCI.

Background: Hippocampal avoidance during prophylactic cranial irradiation (HA-PCI) is proposed to reduce neurocognitive decline, while preserving the benefits of PCI. We evaluated whether (HA-)PCI induces changes in white matter (WM) microstructure and whether sparing the hippocampus has an impact on preserving brain network topology. Additionally, we evaluated associations between topological metrics with hippocampal volume and neuropsychological outcomes.

An international and multidisciplinary EORTC survey on resectability of stage III non-small cell lung cancer.

Introduction: The EORTC-Lung Cancer Group initiated a Delphi consensus process to establish a consensual definition of resectable stage III non-small cell lung cancer (NSCLC) for the use in clinical trials, including a systematic review, survey, and review of clinical cases. Here, the survey results are presented, aimed to identify areas of controversy.

Methods: A survey was distributed among the members of six international organizations related to lung cancer.

Ninety-day mortality following curative intent radiotherapy for stage I-III lung cancer in the Netherlands.

Background And Purpose: The 90-day mortality following lung cancer treatment is a common performance indicator. The aim of this study was to investigate 90-day mortality following (chemo)radiotherapy for stage I-III lung cancer to evaluate the applicability of this outcome indicator in this patient population.

Materials And Methods: The Netherlands National Cancer Registry was queried for this retrospective population-based study.

Impact of HA-PCI on self-reported cognitive functioning and brain metastases in small-cell lung cancer: Pooled findings of NCT01780675 and PREMER trials.

Background: Cognitive decline is an arising concern in patients who need cranial irradiation. We used the pooled longitudinal individual patient data of two phase III trials: NCT01780675 and PREMER to investigate whether hippocampal avoidance (HA)-PCI is associated with improved self-reported cognitive functioning (SRCF) compared with PCI without increasing brain metastases (BM) development within the HA area.

Methods: Patients with stage I-IV small cell lung cancer (SCLC) were randomized to PCI or HA-PCI.

Improved prognostication of overall survival after radiotherapy in lung cancer patients by an interpretable machine learning model integrating lung and tumor radiomics and clinical parameters.

Background: Accurate prognostication of overall survival (OS) for non-small cell lung cancer (NSCLC) patients receiving definitive radiotherapy (RT) is crucial for developing personalized treatment strategies. This study aims to construct an interpretable prognostic model that combines radiomic features extracted from normal lung and from primary tumor with clinical parameters. Our model aimed to clarify the complex, nonlinear interactions between these variables and enhance prognostic accuracy.

Reirradiation - still navigating uncharted waters?

With the emergence of high-precision radiotherapy technologies such as stereotactic ablative radiotherapy (SABR), MR guided brachytherapy, image guided intensity modulated photon and proton radiotherapy and most recently daily adaptive radiotherapy, reirradiation is increasingly recognized as a viable treatment option for many patients. This includes those with recurrent, metastatic or new malignancies post initial radiotherapy. The primary challenge in reirradiation lies in balancing tumor control against the risk of severe toxicity from cumulative radiation doses to previously irradiated normal tissue.

Prediction of new-onset atrial fibrillation in patients with non-small cell lung cancer treated with curative-intent conventional radiotherapy.

Background: Atrial fibrillation (AF) is an important side effect of thoracic Radiotherapy (RT), which may impair quality of life and survival. This study aimed to develop a prediction model for new-onset AF in patients with Non-Small Cell Lung Cancer (NSCLC) receiving RT alone or as a part of their multi-modal treatment.

Patients And Methods: Patients with stage I-IV NSCLC treated with curative-intent conventional photon RT were included.

Association of Serum Biomarkers With Neurocognitive Decline After PCI in Small Cell Lung Cancer: An Exploratory Study of the Phase III NCT01780675 Trial.

Introduction: Blood samples were collected to explore potential serum biomarkers associated with neurocognitive function in small-cell lung cancer (SCLC) patients who received prophylactic cranial irradiation (PCI).

Methods: This pre-specified study included patients with blood samples available, who participated in a phase III trial (NCT01780675). Blood samples were collected before PCI and 3-days post-initiating PCI.

Towards a fully automatic workflow for investigating the dynamics of lung cancer cachexia during radiotherapy using cone beam computed tomography.

Cachexia is a devastating condition, characterized by involuntary loss of muscle mass with or without loss of adipose tissue mass. It affects more than half of patients with lung cancer, diminishing treatment effects and increasing mortality. Cone-beam computed tomography (CBCT) images, routinely acquired during radiotherapy treatment, might contain valuable anatomical information for monitoring body composition changes associated with cachexia.

Survivorship program including long-term toxicities and quality-of-life development over 10 years in a randomized trial in operable stage III non-small-cell lung cancer (ESPATUE).

Over 40% stage-III non-small-cell lung cancer (NSCLC) patients (pts) experience 5-year survival following multimodality treatment. Nevertheless, little is known about relevant late toxicities and quality-of-life (QoL) in the further long-term follow-up. Therefore, we invited pts from our randomized phase-III trial (Eberhardt et al.

Residual breast tissue after mastectomy and reconstruction: A substudy of the Spatial location of breast cancer local rECurRence aftEr masTectomy (SECRET) project.

Unlabelled: The current project is part of the Spatial location of breast cancer local rECurRence aftEr masTectomy (SECRET) study (NCT06130111). Herein we compared the chest wall thickness after non-skin sparing mastectomy (non-SSM) with the chest wall thickness after SSM, as a surrogate for residual breast tissue after mastectomy.

Methods: The study was approved by the ethics committee of relevant institutions.

Treatment of unresectable stage III non-small cell lung cancer for patients who are under-represented in clinical trials.

Concurrent chemoradiotherapy (cCRT) followed by one year of consolidation durvalumab is the current standard-of-care for patients with unresectable stage III non-small cell lung cancer (NSCLC), of good functional status. However, cCRT and consolidation durvalumab may be challenging to administer for selected patient populations underrepresented or even excluded in clinical trials: older and/or frail patients; those with cardiovascular or respiratory comorbidities in which treatment-related adverse events may be higher, and patients with pre-existing autoimmune disorders for whom immunotherapy use is controversial. In this narrative review, we discuss the current evidence, challenges, ongoing clinical trials and potential future treatment scenarios in relevant subgroups of patients with locally advanced NSCLC, who are underrepresented in clinical trials.

Enhanced radiation sensitivity, decreased DNA damage repair, and differentiation defects in airway stem cells derived from patients with chronic obstructive pulmonary disease.

Radiation therapy (RT) is a common treatment for lung cancer. Still, it can lead to irreversible loss of pulmonary function and a significant reduction in quality of life for one-third of patients. Preexisting comorbidities, such as chronic obstructive pulmonary disease (COPD), are frequent in patients with lung cancer and further increase the risk of complications.

Complex situations in lung cancer: multifocal disease, oligoprogression and oligorecurrence.

With the emergence of lung cancer screening programmes and newly detected localised and multifocal disease, novel treatment compounds and multimodal treatment approaches, the treatment landscape of non-small cell lung cancer is becoming increasingly complex. In parallel, in-depth molecular analyses and clonality studies are revealing more information about tumorigenesis, potential therapeutical targets and the origin of lesions. All can play an important role in cases with multifocal disease, oligoprogression and oligorecurrence.