Radiomics signature for dynamic monitoring of tumor inflamed microenvironment and immunotherapy response prediction.

Background: The efficacy of immune checkpoint inhibitors (ICIs) depends on the tumor immune microenvironment (TIME), with a preference for a T cell-inflamed TIME. However, challenges in tissue-based assessments via biopsies have triggered the exploration of non-invasive alternatives, such as radiomics, to comprehensively evaluate TIME across diverse cancers. To address these challenges, we develop an ICI response signature by integrating radiomics with T cell-inflamed gene-expression profiles.

Adenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications.

Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels.

Methods: Whole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelic MUTYH cases, on 7 adenomas and 2 CRCs from 5 biallelic NTHL1 cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants.

First families with spinocerebellar ataxia type 7 in Poland.

Introduction: We present the first two Polish families diagnosed with spinocerebellar ataxia type 7 (SCA7) and draw attention to cardiac involvement as a new potential manifestation of this disease.

Material And Methods: Two well-documented kindreds are presented.

Results: The proband from Family 1 presented aged 54 years with vision worsening followed by progressive imbalance.

RNF43 mutations predict response to anti-BRAF/EGFR combinatory therapies in BRAF metastatic colorectal cancer.

Anti-BRAF/EGFR therapy was recently approved for the treatment of metastatic BRAF colorectal cancer (mCRC). However, a large fraction of patients do not respond, underscoring the need to identify molecular determinants of treatment response. Using whole-exome sequencing in a discovery cohort of patients with mCRC treated with anti-BRAF/EGFR therapy, we found that inactivating mutations in RNF43, a negative regulator of WNT, predict improved response rates and survival outcomes in patients with microsatellite-stable (MSS) tumors.

Radiomic Signatures Associated with CD8 Tumour-Infiltrating Lymphocytes: A Systematic Review and Quality Assessment Study.

The tumour immune microenvironment influences the efficacy of immune checkpoint inhibitors. Within this microenvironment are CD8-expressing tumour-infiltrating lymphocytes (CD8 TILs), which are an important mediator and marker of anti-tumour response. In practice, the assessment of CD8 TILs via tissue sampling involves logistical challenges.

Patient with Phenylketonuria and Intellectual Disability-Problem Not Always Caused Exclusively by Insufficient Metabolic Control (Coexistence of PKU and Alazami Syndrome).

The authors present a case report of a boy with a classical form of phenylketonuria and Alazami syndrome. The inborn error of phenylalanine metabolism was diagnosed in the neonatal period based on population new-born screening. Despite early implementation of a low-phenylalanine diet and good biochemical control, the patient developed behavioural disorders and intellectual disability.

Diffusion MRI signal cumulants and hepatocyte microstructure at fixed diffusion time: Insights from simulations, 9.4T imaging, and histology.

Purpose: Relationships between diffusion-weighted MRI signals and hepatocyte microstructure were investigated to inform liver diffusion MRI modeling, focusing on the following question: Can cell size and diffusivity be estimated at fixed diffusion time, realistic SNR, and negligible contribution from extracellular/extravascular water and exchange?

Methods: Monte Carlo simulations were performed within synthetic hepatocytes for varying cell size/diffusivity / , and clinical protocols (single diffusion encoding; maximum b-value: {1000, 1500, 2000} s/mm ; 5 unique gradient duration/separation pairs; SNR = { , 100, 80, 40, 20}), accounting for heterogeneity in and perfusion contamination. Diffusion ( ) and kurtosis ( ) coefficients were calculated, and relationships between and were visualized. Functions mapping to were computed to predict unseen values, tested for their ability to classify discrete cell-size contrasts, and deployed on 9.

Robust imaging habitat computation using voxel-wise radiomics features.

Tumor heterogeneity has been postulated as a hallmark of treatment resistance and a cure constraint in cancer patients. Conventional quantitative medical imaging (radiomics) can be extended to computing voxel-wise features and aggregating tumor subregions with similar radiological phenotypes (imaging habitats) to elucidate the distribution of tumor heterogeneity within and among tumors. Despite the promising applications of imaging habitats, they may be affected by variability of radiomics features, preventing comparison and generalization of imaging habitats techniques.

Minimizing acquisition-related radiomics variability by image resampling and batch effect correction to allow for large-scale data analysis.

Objective: To identify CT-acquisition parameters accounting for radiomics variability and to develop a post-acquisition CT-image correction method to reduce variability and improve radiomics classification in both phantom and clinical applications.

Methods: CT-acquisition protocols were prospectively tested in a phantom. The multi-centric retrospective clinical study included CT scans of patients with colorectal/renal cancer liver metastases.

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration.

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR).

An anthropomorphic breathing phantom of the thorax for testing new motion mitigation techniques for pencil beam scanning proton therapy.

Motion-induced range changes and incorrectly placed dose spots strongly affect the quality of pencil-beam-scanned (PBS) proton therapy, especially in thoracic tumour sites, where density changes are large. Thus motion-mitigation techniques are necessary, which must be validated in a realistic patient-like geometry. We report on the development and characterisation of a dynamic, anthropomorphic, thorax phantom that can realistically mimic thoracic motions and anatomical features for verifications of proton and photon 4D treatments.

Respiratory motion-management in stereotactic body radiation therapy for lung cancer - A dosimetric comparison in an anthropomorphic lung phantom (LuCa).

Background And Purpose: The objective of this study was to compare the latest respiratory motion-management strategies, namely the internal-target-volume (ITV) concept, the mid-ventilation (MidV) principle, respiratory gating and dynamic couch tracking.

Materials And Methods: An anthropomorphic, deformable and dynamic lung phantom was used for the dosimetric validation of these techniques. Stereotactic treatments were adapted to match the techniques and five distinct respiration patterns, and delivered to the phantom while radiographic film measurements were taken inside the tumor.

The impact of breathing guidance and prospective gating during thoracic 4DCT imaging: an XCAT study utilizing lung cancer patient motion.

Two interventions to overcome the deleterious impact irregular breathing has on thoracic-abdominal 4D computed tomography (4DCT) are (1) facilitating regular breathing using audiovisual biofeedback (AVB), and (2) prospective respiratory gating of the 4DCT scan based on the real-time respiratory motion. The purpose of this study was to compare the impact of AVB and gating on 4DCT imaging using the 4D eXtended cardiac torso (XCAT) phantom driven by patient breathing patterns. We obtained simultaneous measurements of chest and abdominal walls, thoracic diaphragm, and tumor motion from 6 lung cancer patients under two breathing conditions: (1) AVB, and (2) free breathing.

Four-Dimensional Dose Reconstruction for Scanned Proton Therapy Using Liver 4DCT-MRI.

Purpose: Four-dimensional computed tomography-magnetic resonance imaging (4DCT-MRI) is an image-processing technique for simulating many 4DCT data sets from a static reference CT and motions extracted from 4DMRI studies performed using either volunteers or patients. In this work, different motion extraction approaches were tested using 6 liver cases, and a detailed comparison between 4DCT-MRI and 4DCT was performed.

Methods And Materials: 4DCT-MRI has been generated using 2 approaches.

Quantifying the impact of respiratory-gated 4D CT acquisition on thoracic image quality: a digital phantom study.

Purpose: Prospective respiratory-gated 4D CT has been shown to reduce tumor image artifacts by up to 50% compared to conventional 4D CT. However, to date no studies have quantified the impact of gated 4D CT on normal lung tissue imaging, which is important in performing dose calculations based on accurate estimates of lung volume and structure. To determine the impact of gated 4D CT on thoracic image quality, the authors developed a novel simulation framework incorporating a realistic deformable digital phantom driven by patient tumor motion patterns.

Comparative study of layered and volumetric rescanning for different scanning speeds of proton beam in liver patients.

In recent years, particle therapy has become a widely accepted form of cancer treatment and technological advances in beam delivery technology (i.e. pencil beam scanning (PBS)) have enabled the application of highly conformal dose distributions to static targets.