RESUMEN
Radiation therapy, a common treatment for central nervous system cancers, can negatively impact cognitive function, resulting in radiation-induced cognitive decline (RICD). RICD involves a decline in cognitive abilities such as memory and attention, likely due to damage to brain white matter, inflammation, and oxidative stress. The multifactorial nature of RICD poses challenges including different mechanisms of injury (neurogenesis, oxidative stress and neuroinflammation, dendritic structure alterations and vascular effects) and confounding factors like advanced age, and pre-existing conditions. Despite these challenges, several potential solutions exist. Neuroprotective agents like antioxidants can mitigate radiation damage, while cognitive rehabilitation techniques such as cognitive training and memory strategies improve cognitive function. Advanced imaging techniques like magnetic resonance imaging (MRI) help identify vulnerable brain areas, and proton therapy offers precise targeting of cancer cells, sparing healthy tissue. Multidisciplinary care teams are crucial for managing RICD's cognitive and psychological effects. Personalized medicine, using genetic and molecular data, can identify high-risk patients and tailor treatments accordingly. Emerging therapies, including stem cell therapy and regenerative medicine, offer hope for repairing or replacing damaged brain tissue. Addressing RICD is vital for cancer survivors, necessitating consideration of cognitive function and provision of appropriate support and resources for those experiencing cognitive decline.
RESUMEN
Purpose: We report on the feasibility and outcomes of liver stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) with single-photon emission computed tomography (SPECT) functional treatment planning in patients with Child-Pugh (CP) B/C cirrhosis. Methods and Materials: Liver SPECT with 99mTc-sulfur colloid was coregistered to treatment planning computed tomography (CT) for the guided avoidance of functional hepatic parenchyma during SBRT. Functional liver volumes (FLVs) obtained from SPECT were compared with anatomic liver volumes defined on the planning CT. Radiation dose constraints were adapted exclusively to FLV. Local control, toxicity, and survival were reported with at least 6 months of radiographic follow-up. Pre- and posttransplant outcomes were analyzed in a subset of patients who completed SBRT as a bridge to liver transplant. Model of End-Stage Liver Disease was used to score hepatic function before and after SBRT completion. Results: With a median follow-up of 32 months, 45 patients (58 lesions) with HCC and CP-B/C cirrhosis received SBRT to a median dose of 45 Gy (3-5 fractions). FLV loss (34%, P < .001) was observed in all patients, and the functional and anatomic liver volumes matched well in a control group of noncirrhotic/non-HCC patients. Despite marked functional parenchyma retraction, the amount of FLV on SPECT exposed to the threshold irradiation was significantly less than the CT liver volumes (P < .001) because of the optimized beam placement during dosimetry planning. Twenty-three patients (51%) successfully completed orthotopic liver transplant, with a median time to transplant of 9.2 months. With 91% in-field local control, the overall 2-year survival was 65% (90% after the orthotopic liver transplant), with no incidence of radiation-induced liver disease observed within 3 to 4 months or accelerated CP class migration from B to C within the first 6 months post-SBRT. Mean Model of End-Stage Liver Disease-Na score was not significantly elevated at 3-month intervals after SBRT completion. Conclusions: Functional treatment planning with 99mTc sulfur colloid SPECT/CT allows identification and avoidance of functional hepatic parenchyma in patients with CP-B/C cirrhosis, leading to low toxicity and satisfactory transplant outcomes.
RESUMEN
Recent studies identified distinct genomic subtypes of lower-grade gliomas that could potentially be used to guide patient treatment. This study aims to determine whether there is an association between genomics of lower-grade glioma tumors and patient outcomes using algorithmic measurements of tumor shape in magnetic resonance imaging (MRI). We analyzed preoperative imaging and genomic subtype data from 110 patients with lower-grade gliomas (WHO grade II and III) from The Cancer Genome Atlas. Computer algorithms were applied to analyze the imaging data and provided five quantitative measurements of tumor shape in two and three dimensions. Genomic data for the analyzed cohort of patients consisted of previously identified genomic clusters based on IDH mutation and 1p/19q co-deletion, DNA methylation, gene expression, DNA copy number, and microRNA expression. Patient outcomes were quantified by overall survival. We found that there is a strong association between angular standard deviation (ASD), which measures irregularity of the tumor boundary, and the IDH-1p/19q subtype (p < 0.0017), RNASeq cluster (p < 0.0002), DNA copy number cluster (p < 0.001), and the cluster of clusters (p < 0.0002). The RNASeq cluster was also associated with bounding ellipsoid volume ratio (p < 0.0005). Tumors in the IDH wild type cluster and R2 RNASeq cluster which are associated with much poorer outcomes generally had higher ASD reflecting more irregular shape. ASD also showed association with patient overall survival (p = 0.006). Shape features in MRI were strongly associated with genomic subtypes and patient outcomes in lower-grade glioma.