Imaging and AI based chromatin biomarkers for diagnosis and therapy evaluation from liquid biopsies.

Multiple genomic and proteomic studies have suggested that peripheral blood mononuclear cells (PBMCs) respond to tumor secretomes and thus could provide possible avenues for tumor prognosis and treatment evaluation. We hypothesized that the chromatin organization of PBMCs obtained from liquid biopsies, which integrates secretome signals with gene expression programs, provides efficient biomarkers to characterize tumor signals and the efficacy of proton therapy in tumor patients. Here, we show that chromatin imaging of PBMCs combined with machine learning methods provides such robust and predictive chromatin biomarkers.

Pencil Beam Scanning Proton Therapy for Adolescents and Young Adults with Head and Neck Sarcomas.

Purpose: To assess clinical outcomes of adolescents and young adults (AYAs) with head and neck sarcomas (HNSs) treated with pencil beam scanning proton therapy (PBSPT) and to report quality of life (QoL).

Materials And Methods: Twenty-eight AYAs (aged 15 to 39 years) with HNS treated between January 2001 and July 2022 at our institution were included. The median age was 21.

Oncological Outcomes, Long-Term Toxicities, Quality of Life and Sexual Health after Pencil-Beam Scanning Proton Therapy in Patients with Low-Grade Glioma.

Purpose: To assess oncological outcomes, toxicities, quality of life (QoL) and sexual health (SH) of low-grade glioma (LGG) patients treated with pencil-beam scanning proton therapy (PBS-PT).

Material And Methods: We retrospectively analyzed 89 patients with LGG (Neurofibromatosis type 1; = 4 (4.5%) patients) treated with PBS-PT (median dose 54 Gy (RBE)) from 1999 to 2022 at our institution.

Quality of Life, Clinical, and Patient-Reported Outcomes after Pencil Beam Scanning Proton Therapy Delivered for Intracranial Grade WHO 1-2 Meningioma in Children and Adolescents.

Purpose: The purpose of this study was to report the clinical and patient-reported outcomes of children and adolescents with intracranial meningioma treated with pencil beam scanning proton therapy (PBS-PT).

Material And Methods: Out of a total cohort of 207 intracranial meningioma patients treated with PBS-PT between 1999 and 2022, 10 (4.8%) were children or adolescents aged < 18 years.

Extraction of Interoperable Data from Healthcare Documents by Identifying Common Data Elements: An Analysis of Radiation Therapy Planning CT Physician Order Entry Records.

Introduction: Documentation as well as IT-based management of medical data is of ever-increasing relevance in modern medicine. As radiation oncology is a rather technical, data-driven discipline, standardization, and data exchange are in principle possible. We examined electronic healthcare documents to extract structured information.

Long Term Outcome and Quality of Life of Intracranial Meningioma Patients Treated with Pencil Beam Scanning Proton Therapy.

The aim of this study was to assess the clinical outcome, including QoL, of patients with intracranial meningiomas WHO grade 1-3 who were treated with Pencil Beam Scanning Proton Therapy (PBS PT) between 1997 and 2022. Two hundred patients (median age 50.4 years, 70% WHO grade 1) were analyzed.

Clinical outcome after pencil beam scanning proton therapy and dysphagia/xerostomia NTCP calculations of proton and photon radiotherapy delivered to patients with cancer of the major salivary glands.

Objectives: The purpose of this study is to report the oncological outcome, observed toxicities and normal tissue complication probability (NTCP) calculation for pencil beam scanning (PBS) PT delivered to salivary gland tumour (SGT) patients.

Methods: We retrospectively reviewed 26 SGT patients treated with PBSPT (median dose, 67.5 Gy(RBE)) between 2005 and 2020 at our institute.

Therapy Resistance of Glioblastoma in Relation to the Subventricular Zone: What Is the Role of Radiotherapy?

Glioblastoma is a highly heterogeneous primary malignant brain tumor with marked inter-/intratumoral diversity and a poor prognosis. It may contain a population of neural stem cells (NSC) and glioblastoma stem cells that have the capacity for migration, self-renewal and differentiation. While both may contribute to resistance to therapy, NSCs may also play a role in brain tissue repair.

Hearing Loss in Cancer Patients with Skull Base Tumors Undergoing Pencil Beam Scanning Proton Therapy: A Retrospective Cohort Study.

To assess the incidence and severity of changes in hearing threshold in patients undergoing high-dose pencil-beam-scanning proton therapy (PBS-PT). This retrospective cohort study included fifty-one patients (median 50 years (range, 13-68)) treated with PBS-PT for skull base tumors. No chemotherapy was delivered.

Clinical Outcome After Pencil Beam Scanning Proton Therapy of Patients With Non-Metastatic Malignant and Benign Peripheral Nerve Sheath Tumors.

Objective: Peripheral nerve sheath tumors (PNSTs) commonly arise from peripheral nerve roots and grow locally invasive. Malignant PNSTs (mPNSTs) represent aggressive sarcomas of neural origin that can originate from PNSTs. Radiation therapy is commonly used as part of the required multimodal treatment.

Correction: Role of caveolin-1 as a biomarker for radiation resistance and tumor aggression in lung cancer.

[This corrects the article DOI: 10.1371/journal.pone.

NTCP Modeling for High-Grade Temporal Radionecroses in a Large Cohort of Patients Receiving Pencil Beam Scanning Proton Therapy for Skull Base and Head and Neck Tumors.

Purpose: To develop a normal tissue complication probability model including clinical and dosimetric parameters for high-grade temporal lobe radionecroses (TRN) after pencil beam scanning proton therapy.

Methods And Materials: We included data on 299 patients with skull base and head and neck tumors treated with pencil-beam scan proton therapy, with a total dose of ≥60 Gy (relative biological effectiveness) from May 2004 to November 2018. We considered 9 clinical and 27 dosimetric parameters for the structure-wise modeling of high-grade (grade ≥2) TRN.

Role of caveolin-1 as a biomarker for radiation resistance and tumor aggression in lung cancer.

Radiation therapy plays a major role in the treatment of lung cancer patients. However, cancer cells develop resistance to radiation. Tumor radioresistance is a complex multifactorial mechanism which may be dependent on DNA damage and repair, hypoxic conditions inside tumor microenvironment, and the clonal selection of radioresistant cells from the heterogeneous tumor site, and it is a major cause of treatment failure in non-small cell lung cancer (NSCLC).

Assessment of Tumor Volume Dynamics and Outcome After Radiosurgery for the Treatment of Vestibular Schwannoma: A Single-Center Experience.

Objective: To assess the factors affecting early local and audiometric outcomes in vestibular schwannoma (VS) patients treated with stereotactic radiosurgery (SRS).

Study Design: A retrospective review of medical records.

Setting: Tertiary referral center.

Vestibular dose correlates with dizziness after radiosurgery for the treatment of vestibular schwannoma.

Background: Stereotactic radiosurgery (SRS) has been recognized as a first-line treatment option for small to moderate sized vestibular schwannoma (VS). Our aim is to evaluate the impact of SRS doses and other patient and disease characteristics on vestibular function in patients with VS.

Methods: Data on VS patients treated with single-fraction SRS to 12 Gy were retrospectively reviewed.

Outcomes of adolescents and young adults treated for brain and skull base tumors with pencil beam scanning proton therapy.

Background: The use of proton therapy (PT) in adolescents and young adults (AYAs) is becoming increasingly popular. This study aims to assess the outcomes and late toxicity consequences in AYAs (15-39 years) with brain/skull base tumors treated with pencil beam scanning proton therapy.

Methods: One hundred seventy six AYAs treated curatively at the Paul Scherrer Institute (PSI) were identified.

Radiosurgery of vestibular schwannoma: prognostic factors for hearing outcome using 3D-constructive interference in steady state (3D-CISS).

Purpose: Stereotactic radiosurgery (SRS) is an effective treatment for vestibular schwannoma (VS). Three-dimensional (3D) constructive interference in steady state (CISS) is the preferred magnetic resonance imaging (MRI) sequence for evaluating signal changes in the inner ear endolymph. Previous studies demonstrated a correlation between pretreatment cochlear signal intensity in 3D-CISS and posttherapeutic hearing outcomes.

Identification of a MET-eIF4G1 translational regulation axis that controls HIF-1α levels under hypoxia.

Poor oxygenation is a common hallmark of solid cancers that strongly associates with aggressive tumor progression and treatment resistance. While a hypoxia-inducible factor 1α (HIF-1α)-associated transcriptional overexpression of the hepatocyte growth factor (HGF) receptor tyrosine kinase (RTK) MET has been previously documented, any regulation of the HIF-1α system through MET downstream signaling in hypoxic tumors has not been yet described. By using MET-driven in vitro as well as ex vivo tumor organotypic fresh tissue models we report that MET targeting results in depletion of HIF-1α and its various downstream targets.

Outcome of proximal esophageal cancer after definitive combined chemo-radiation: a Swiss multicenter retrospective study.

Objective: To report oncological outcomes and toxicity rates, of definitive platin-based chemoradiadiationtherapy (CRT) in the management of proximal esophageal cancer.

Methods: We retrospectively reviewed the medical records of patients with cT1-4 cN0-3 cM0 cervical esophageal cancer (CEC) (defined as tumors located below the inferior border of the cricoid cartilage, down to 22 cm from the incisors) treated between 2004 and 2013 with platin-based definitive CRT in four Swiss institutions. Acute and chronic toxicities were retrospectively scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.

Clinical and Radiologic Outcomes in Adults and Children Treated with Pencil-Beam Scanning Proton Therapy for Low-Grade Glioma.

Purpose: We assessed clinical and radiologic outcomes in adults and children with low-grade glioma (LGG) of the brain treated with pencil-beam scanning (PBS) proton therapy (PT).

Materials And Methods: Between 1997 and 2014, 28 patients were treated with PBS PT, 20 (71%) of whom were younger than 18 years. Median age at start of PT was 12.

High-dose irradiation of bone chips preserves the in vitro activity of bone-conditioned medium.

Extracorporeal irradiation sterilizes resected tumor bone used as autografts in reconstruction surgery. Therapeutic irradiation is a standard technique in head and neck cancer therapy that aims to preserve organ function. Bone irradiation has a complex, mostly inhibitory, effect on remodeling and regeneration, although the underlying mechanisms are still not fully understood.

Tumour control and Quality of Life in children with rhabdomyosarcoma treated with pencil beam scanning proton therapy.

Purpose: To assess clinical outcomes in children with rhabdomyosarcoma (RMS) treated with pencil beam scanning (PBS) proton therapy (PT).

Methods And Materials: Eighty-three RMS (embryonal, n=74; 89%) patients treated between January 2000 and December 2014 were included. The median age was 4.

KRAS and HRAS mutations confer resistance to MET targeting in preclinical models of MET-expressing tumor cells.

The MET receptor tyrosine kinase is often deregulated in human cancers and several MET inhibitors are evaluated in clinical trials. Similarly to EGFR, MET signals through the RAS-RAF-ERK/MAPK pathway which plays key roles in cell proliferation and survival. Mutations of genes encoding for RAS proteins, particularly in KRAS, are commonly found in various tumors and are associated with constitutive activation of the MAPK pathway.

Definitive intensity modulated radiotherapy in locally advanced hypopharygeal and laryngeal squamous cell carcinoma: mature treatment results and patterns of locoregional failure.

Purpose: To assess clinical outcomes and patterns of loco-regional failure (LRF) in relation to clinical target volumes (CTV) in patients with locally advanced hypopharyngeal and laryngeal squamous cell carcinoma (HL-SCC) treated with definitive intensity modulated radiotherapy (IMRT) and concurrent systemic therapy.

Methods: Data from HL-SCC patients treated from 2007 to 2010 were retrospectively evaluated. Primary endpoint was loco-regional control (LRC).