Conference Report: Review of Clinical Implementation of Advanced Quantitative Imaging Techniques for Personalized Radiotherapy.

The topic of quantitative imaging in radiation therapy was presented as a "Masterclass" at the 2023 annual meeting of the American Society of Radiation Oncology (ASTRO). Dual-energy computed tomography (CT) and single-positron computed tomography were reviewed in detail as the first portion of the meeting session, with data showing utility in many aspects of radiation oncology including treatment planning and dose response. Positron emission tomography/CT scans evaluating the functional volume of lung tissue so as to provide optimal avoidance of healthy lungs were presented second.

Risk of late radiation necrosis more than 5 years after stereotactic radiosurgery.

Objective: Radiation necrosis (RN) is a well-recognized late complication most commonly occurring within 2 years of stereotactic radiosurgery (SRS); however, late RN (LRN), RN occurring or recurring > 5 years after SRS, has been poorly described. This study analyzes the incidence of and risk factors for LRN occurring > 5 years after SRS.

Methods: This retrospective analysis included patients treated with linear accelerator-based SRS for tumors or arteriovenous malformations with > 5 years of clinical and serial MRI follow-up.

Radiomic Analysis of Treatment Effect for Patients with Radiation Necrosis Treated with Pentoxifylline and Vitamin E.

Background: The combination of oral pentoxifylline (Ptx) and vitamin E (VitE) has been used to treat radiation-induced fibrosis and soft tissue injury. Here, we review outcomes and perform a radiomic analysis of treatment effects in patients prescribed Ptx + VitE at our institution for the treatment of radiation necrosis (RN).

Methods: A total of 48 patients treated with stereotactic radiosurgery (SRS) had evidence of RN and had MRI before and after starting Ptx + VitE.

The Utility of Spectroscopic MRI in Stereotactic Biopsy and Radiotherapy Guidance in Newly Diagnosed Glioblastoma.

Current diagnostic and therapeutic approaches for gliomas have limitations hindering survival outcomes. We propose spectroscopic magnetic resonance imaging as an adjunct to standard MRI to bridge these gaps. Spectroscopic MRI is a volumetric MRI technique capable of identifying tumor infiltration based on its elevated choline (Cho) and decreased N-acetylaspartate (NAA).

A Fully Automated Post-Surgical Brain Tumor Segmentation Model for Radiation Treatment Planning and Longitudinal Tracking.

Glioblastoma (GBM) has a poor survival rate even with aggressive surgery, concomitant radiation therapy (RT), and adjuvant chemotherapy. Standard-of-care RT involves irradiating a lower dose to the hyperintense lesion in T2-weighted fluid-attenuated inversion recovery MRI (T2w/FLAIR) and a higher dose to the enhancing tumor on contrast-enhanced, T1-weighted MRI (CE-T1w). While there have been several attempts to segment pre-surgical brain tumors, there have been minimal efforts to segment post-surgical tumors, which are complicated by a resection cavity and postoperative blood products, and tools are needed to assist physicians in generating treatment contours and assessing treated patients on follow up.

Spectroscopic MRI-Based Biomarkers Predict Survival for Newly Diagnosed Glioblastoma in a Clinical Trial.

Despite aggressive treatment, glioblastoma has a poor prognosis due to its infiltrative nature. Spectroscopic MRI-measured brain metabolites, particularly the choline to N-acetylaspartate ratio (Cho/NAA), better characterizes the extent of tumor infiltration. In a previous pilot trial (NCT03137888), brain regions with Cho/NAA ≥ 2x normal were treated with high-dose radiation for newly diagnosed glioblastoma patients.

Applying a Radiation Therapy Volume Analysis Pipeline to Determine the Utility of Spectroscopic MRI-Guided Adaptive Radiation Therapy for Glioblastoma.

Accurate radiation therapy (RT) targeting is crucial for glioblastoma treatment but may be challenging using clinical imaging alone due to the infiltrative nature of glioblastomas. Precise targeting by whole-brain spectroscopic MRI, which maps tumor metabolites including choline (Cho) and N-acetylaspartate (NAA), can quantify early treatment-induced molecular changes that other traditional modalities cannot measure. We developed a pipeline to determine how spectroscopic MRI changes during early RT are associated with patient outcomes to provide insight into the utility of adaptive RT planning.

Mutant Isocitrate Dehydrogenase 1 Expression Enhances Response of Gliomas to the Histone Deacetylase Inhibitor Belinostat.

Histone deacetylase inhibitors (HDACis) are drugs that target the epigenetic state of cells by modifying the compaction of chromatin through effects on histone acetylation. Gliomas often harbor a mutation of isocitrate dehydrogenase (IDH) 1 or 2 that leads to changes in their epigenetic state presenting a hypermethylator phenotype. We postulated that glioma cells with IDH mutation, due to the presence of epigenetic changes, will show increased sensitivity to HDACis.

Using Brain Tumor MRI Structured Reporting to Quantify the Impact of Imaging on Brain Tumor Boards.

Multidisciplinary tumor boards (TB) are an essential part of brain tumor care, but quantifying the impact of imaging on patient management is challenging due to treatment complexity and a lack of quantitative outcome measures. This work uses a structured reporting system for classifying brain tumor MRIs, the brain tumor reporting and data system (BT-RADS), in a TB setting to prospectively assess the impact of imaging review on patient management. Published criteria were used to prospectively assign three separate BT-RADS scores (an initial radiology report, secondary TB presenter review, and TB consensus) to brain MRIs reviewed at an adult brain TB.

A Novel Approach to Determining Tumor Progression Using a Three-Site Pilot Clinical Trial of Spectroscopic MRI-Guided Radiation Dose Escalation in Glioblastoma.

Glioblastoma (GBM) is a fatal disease, with poor prognosis exacerbated by difficulty in assessing tumor extent with imaging. Spectroscopic MRI (sMRI) is a non-contrast imaging technique measuring endogenous metabolite levels of the brain that can serve as biomarkers for tumor extension. We completed a three-site study to assess survival benefits of GBM patients when treated with escalated radiation dose guided by metabolic abnormalities in sMRI.

Development and validation of a prognostic gene expression signature for lower-grade glioma following surgery and adjuvant radiotherapy.

Background And Purpose: Standard of care for lower-grade glioma (LGG) is maximal safe resection and risk-adaptive adjuvant therapy. While patients who benefit the most from adjuvant chemotherapy have been elucidated in prospective randomized studies, comparable insights for adjuvant radiotherapy (RT) are lacking. We sought to identify and validate patterns of gene expression that are associated with differential outcomes among LGG patients treated by RT from two large genomics databases.

A multi-institutional pilot clinical trial of spectroscopic MRI-guided radiation dose escalation for newly diagnosed glioblastoma.

Background: Glioblastomas (GBMs) are aggressive brain tumors despite radiation therapy (RT) to 60 Gy and temozolomide (TMZ). Spectroscopic magnetic resonance imaging (sMRI), which measures levels of specific brain metabolites, can delineate regions at high risk for GBM recurrence not visualized on contrast-enhanced (CE) MRI. We conducted a clinical trial to assess the feasibility, safety, and efficacy of sMRI-guided RT dose escalation to 75 Gy for newly diagnosed GBMs.

Final Report on Clinical Outcomes and Tumor Recurrence Patterns of a Pilot Study Assessing Efficacy of Belinostat (PXD-101) with Chemoradiation for Newly Diagnosed Glioblastoma.

Glioblastoma (GBM) is highly aggressive and has a poor prognosis. Belinostat is a histone deacetylase inhibitor with blood-brain barrier permeability, anti-GBM activity, and the potential to enhance chemoradiation. The purpose of this clinical trial was to assess the efficacy of combining belinostat with standard-of-care therapy.

Modern Linear Accelerator-Based Radiotherapy Is Safe and Effective in the Treatment of Secretory and Nonsecretory Pituitary Adenomas.

Background: Adjuvant radiotherapy (RT) can help achieve local control (LC) and reduce hormonal overexpression for pituitary adenomas (PAs). Prior reports involved Gamma Knife or older linear accelerator (LINAC) techniques. The aim of this study was to report long-term outcomes for modern LINAC RT.

3D whole-brain metabolite imaging to improve characterization of low-to-intermediate grade gliomas.

Purpose: MRI is the standard imaging modality used for diagnosis, treatment planning, and post-treatment management of gliomas. Contrast-enhanced T1-weighted (CE-T1w) MRI is used to plan biopsy and radiation for grade IV gliomas but is less effective for grade II and III gliomas (i.e.

Co-Occurrence Conundrum: Brain Metastases from Lung Adenocarcinoma, Radiation Necrosis, and Gliosarcoma.

Non-small cell lung cancer (NSCLC) commonly presents with metastasis to the brain. When brain metastases are treated with stereotactic radiosurgery (SRS), longitudinal imaging to monitor treatment response may identify radiation necrosis, metastasis progression, and/or another primary brain malignancy. A 60-year-old female with metastatic NSCLC involving the brain underwent treatment with systemic therapy and SRS.

Quantitation of cancer treatment response by 2-[F]FDG PET/CT: multi-center assessment of measurement variability using AUTO-PERCIST™.

Background: The aim of this study was to assess the reader variability in quantitatively assessing pre- and post-treatment 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography/computed tomography ([F]FDG PET/CT) scans in a defined set of images of cancer patients using the same semi-automated analytical software (Auto-PERCIST™), which identifies tumor peak standard uptake value corrected for lean body mass (SUL) to determine [F]FDG PET quantitative parameters.

Methods: Paired pre- and post-treatment [F]FDG PET/CT images from 30 oncologic patients and Auto-PERCIST™ semi-automated software were distributed to 13 readers across US and international sites. One reader was aware of the relevant medical history of the patients (read), whereas the 12 other readers were blinded to history but had access to the correlative images.

Moderately Hypofractionated Radiation for Benign Meningiomas and Schwannomas: A Report of 70 Patients Treated Between 2008 and 2018.

Purpose: Radiosurgery and fractionated intensity modulated radiation therapy (IMRT) are effective treatment modalities for meningiomas and schwannomas. Although fractionated IMRT yields favorable tumor control, daily treatments for 5 to 6 weeks can be burdensome for patients and health care systems. Thus, hypofractionated radiation may be a reasonable alternative.

The Longitudinal Imaging Tracker (BrICS-LIT):A Cloud Platform for Monitoring Treatment Response in Glioblastoma Patients.

Glioblastoma is a common and aggressive form of brain cancer affecting up to 20,000 new patients in the US annually. Despite rigorous therapies, current median survival is only 15-20 months. Patients who complete initial treatment undergo follow-up imaging at routine intervals to assess for tumor recurrence.

Genomic copy number variation correlates with survival outcomes in WHO grade IV glioma.

Allele-specific copy number analysis of tumors (ASCAT) assesses copy number variations (CNV) while accounting for aberrant cell fraction and tumor ploidy. We evaluated if ASCAT-assessed CNV are associated with survival outcomes in 56 patients with WHO grade IV gliomas. Tumor data analyzed by Affymetrix OncoScan FFPE Assay yielded the log ratio (R) and B-allele frequency (BAF).

Optimal timing of chemoradiotherapy after surgical resection of glioblastoma: Stratification by validated prognostic classification.

Background: Previous studies examining the time to initiate chemoradiation (CRT) after surgical resection of glioblastoma have been conflicting. To better define the effect that the timing of adjuvant treatment may have on outcomes, the authors examined patients within the National Cancer Database (NCDB) stratified by a validated prognostic classification system.

Methods: Patients with glioblastoma in the NCDB who underwent surgery and CRT from 2004 through 2013 were analyzed.

Remarkable response of a patient with secondary glioblastoma to a histone deacetylase inhibitor.

Secondary glioblastoma is a rare brain tumor characterized by a mutation in isocitrate dehydrogenase, which is reported to lead to epigenetic modification. Patients with secondary glioblastoma experience poor survival and quality-of-life outcomes due to the disease's aggressiveness and a lack of targeted therapies. In this report, a patient with a secondary glioblastoma was treated with a histone deacetylase inhibitor, an epigenetic drug with potent anti-inflammatory properties, in addition to the standard regimen.

Outcomes of whole-brain radiation with simultaneous in-field boost (SIB) for the treatment of brain metastases.

Purpose: Prospective studies have demonstrated increased local control with the addition of a radiosurgery (SRS) boost to whole-brain irradiation (WBRT) in patients with brain metastases. However, the clinical application of SRS boost can be limited by several factors, including tumor size, numbers of lesions, and high cost of care. Here, we investigate the use of WBRT with a simultaneous integrated boost (SIB) to visible lesions in patients with brain metastases.

Dosimetric Factors Related to Radiation Necrosis After 5-Fraction Radiosurgery for Patients With Resected Brain Metastases.

Purpose: Stereotactic radiosurgery (SRS) is increasingly used in the management of patients with resected brain metastases (rBMs). A significant complication of this therapy can be radiation necrosis (RN). Despite radiation therapy dose de-escalation and the delivery of several rather than a single dose fraction, rates of RN after SRS for rBMs remain high.