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American Journal of Clinical Oncology Nov 2023Distinguishing between radiation necrosis (RN) and metastatic progression is extremely challenging due to their similarity in conventional imaging. This is crucial from...
OBJECTIVES
Distinguishing between radiation necrosis (RN) and metastatic progression is extremely challenging due to their similarity in conventional imaging. This is crucial from a therapeutic point of view as this determines the outcome of the treatment. This study aims to establish an automated technique to differentiate RN from brain metastasis progression using radiomics with machine learning.
METHODS
Eighty-six patients with brain metastasis after they underwent stereotactic radiosurgery as primary treatment were selected. Discrete wavelets transform, Laplacian-of-Gaussian, Gradient, and Square were applied to magnetic resonance post-contrast T1-weighted images to extract radiomics features. After feature selection, dataset was randomly split into train/test (80%/20%) datasets. Random forest classification, logistic regression, and support vector classification were trained and subsequently validated using test set. The classification performance was measured by area under the curve (AUC) value of receiver operating characteristic curve, accuracy, sensitivity, and specificity.
RESULTS
The best performance was achieved using random forest classification with a Gradient filter (AUC=0.910±0.047, accuracy 0.8±0.071, sensitivity=0.796±0.055, specificity=0.922±0.059). For, support vector classification the best result obtains using wavelet_HHH with a high AUC of 0.890±0.89, accuracy of 0.777±0.062, sensitivity=0.701±0.084, and specificity=0.85±0.112. Logistic regression using wavelet_HHH provides a poor result with AUC=0.882±0.051, accuracy of 0.753±0.08, sensitivity=0.717±0.208, and specificity=0.816±0.123.
CONCLUSION
This type of machine-learning approach can help accurately distinguish RN from recurrence in magnetic resonance imaging, without the need for biopsy. This has the potential to improve the therapeutic outcome.
PubMed: 37580873
DOI: 10.1097/COC.0000000000001036 -
Cancer Research Communications Aug 2023Glioblastoma multiforme (GBM) is a hypoxic tumor resistant to radiotherapy. The purpose of this study was to assess the safety and efficacy of a novel oxygen...
PURPOSE
Glioblastoma multiforme (GBM) is a hypoxic tumor resistant to radiotherapy. The purpose of this study was to assess the safety and efficacy of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM.
EXPERIMENTAL DESIGN
In this multicenter phase Ib/II dose-escalation study, patients were administered DDFPe via intravenous infusion (0.05, 0.10, or 0.17 mL/kg) while breathing supplemental oxygen prior to each 2 Gy fraction of radiotherapy (30 fractions over 6 weeks). Patients also received standard-of-care chemotherapy [temozolomide (TMZ)]. Serial MRI scans were taken to monitor disease response. Adverse events were recorded and graded. TOLD (tissue oxygenation level-dependent) contrast MRI was obtained to validate modulation of tumor hypoxia.
RESULTS
Eleven patients were enrolled. DDFPe combined with radiotherapy and TMZ was well tolerated in most patients. Two patients developed delayed grade 3 radiation necrosis during dose escalation, one each at 0.1 and 0.17 mL/kg of DDFPe. Subsequent patients were treated at the 0.1 mL/kg dose level. Kaplan-Meier analysis showed a median overall survival of 19.4 months and a median progression-free survival of 9.6 months, which compares favorably to historical controls. Among 6 patients evaluable for TOLD MRI, a statistically significant reduction in tumor T was observed after DDFPe treatment.
CONCLUSIONS
This trial, although small, showed that the use of DDFPe as a radiosensitizer in patients with GBM was generally safe and may provide a survival benefit. This is also the first time than TOLD MRI has shown reversal of tumor hypoxia in a clinical trial in patients. The recommended dose for phase II evaluation is 0.1 mL/kg DDFPe.Trial Registration: NCT02189109.
SIGNIFICANCE
This study shows that DDFPe can be safely administered to patients, and it is the first-in-human study to show reversal of hypoxia in GBM as measured by TOLD MRI. This strategy is being used in a larger phase II/III trial which will hopefully show a survival benefit by adding DDFPe during the course of fractionated radiation and concurrent chemotherapy.
Topics: Humans; Glioblastoma; Emulsions; Radiation-Sensitizing Agents; Temozolomide; Hypoxia; Oxygen
PubMed: 37609003
DOI: 10.1158/2767-9764.CRC-22-0433 -
Frontiers in Immunology 2023The prevalence of brain cancer has been increasing in recent decades, posing significant healthcare challenges. The introduction of immunotherapies has brought forth... (Review)
Review
The prevalence of brain cancer has been increasing in recent decades, posing significant healthcare challenges. The introduction of immunotherapies has brought forth notable diagnostic imaging challenges for brain tumors. The tumor microenvironment undergoes substantial changes in induced immunosuppression and immune responses following the development of primary brain tumor and brain metastasis, affecting the progression and metastasis of brain tumors. Consequently, effective and accurate neuroimaging techniques are necessary for clinical practice and monitoring. However, patients with brain tumors might experience radiation-induced necrosis or other neuroinflammation. Currently, positron emission tomography and various magnetic resonance imaging techniques play a crucial role in diagnosing and evaluating brain tumors. Nevertheless, differentiating between brain tumors and necrotic lesions or inflamed tissues remains a significant challenge in the clinical diagnosis of the advancements in immunotherapeutics and precision oncology have underscored the importance of clinically applicable imaging measures for diagnosing and monitoring neuroinflammation. This review summarizes recent advances in neuroimaging methods aimed at enhancing the specificity of brain tumor diagnosis and evaluating inflamed lesions.
Topics: Humans; Neuroinflammatory Diseases; Precision Medicine; Brain Neoplasms; Positron-Emission Tomography; Molecular Imaging; Tumor Microenvironment
PubMed: 37533851
DOI: 10.3389/fimmu.2023.1211900 -
European Radiology Experimental Dec 2023Renal ischemia-reperfusion injury (IRI) frequently occurs clinically. We investigated the value of contrast-enhanced ultrasonography (CEUS) in the evaluation of renal...
BACKGROUND
Renal ischemia-reperfusion injury (IRI) frequently occurs clinically. We investigated the value of contrast-enhanced ultrasonography (CEUS) in the evaluation of renal IRI levels in mice.
METHODS
Thirty-six healthy adult male C57BL/6 mice (20-22 g) were randomly divided into the sham, 10 min, 20 min, 30 min, 40 min, and 50 min groups based on the time of renal warm ischemia by blocking the left renal pedicle, approved by the Institutional Animal Ethics Committee. Time-intensity curve (TIC)-derived parameters such as peak enhancement (PE) and wash-in perfusion index (WiPI) were produced using CEUS at 1 h and 24 h after IRI. The severity of kidney injury was detected by the renal tubular necrosis rate which was analyzed by hematoxylin and eosin staining at 24 h after IRI. The Spearman correlation coefficient was used to describe the correlations between PE and WiPI values and the renal tubular necrosis rate.
RESULTS
The PE and WiPI values decreased after IRI in the groups with a warm ischemia time ≥ 20 min. The renal tubular necrosis rate was significantly correlated with the PE value at 1 h (ρ = -0.802) and 24 h (ρ = -0.861) after IRI and the WiPI value at 1 h (ρ = -0.814) and 24 h (ρ = -0.853) after IRI (all p < 0.001).
CONCLUSION
TIC-derived parameters, including PE and WiPI values, can be used to evaluate the severity of renal IRI in mice. CEUS is a safe and effective technology for the detection of renal IRI.
RELEVANCE STATEMENT
CEUS can evaluate the severity of renal ischemia-reperfusion injury by peak enhancement and wash-in perfusion index values selected from various time-intensity curve-derived parameters.
KEY POINTS
• Contrast-enhanced ultrasonography can evaluate the level of renal ischemia-reperfusion injury. • Peak enhancement and wash-in perfusion index are correlated with the renal tubular necrosis rate. • CEUS can detect changes in unilateral renal function without radiation.
Topics: Mice; Male; Animals; Mice, Inbred C57BL; Kidney; Reperfusion Injury; Ultrasonography; Necrosis
PubMed: 38110603
DOI: 10.1186/s41747-023-00392-3 -
Nature Communications May 2024With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority....
With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.
Topics: Radiosurgery; Humans; Brain Neoplasms; Male; Female; Middle Aged; Aged; Magnetic Resonance Imaging; Melanoma; Adult; Treatment Outcome; Tumor Burden; Aged, 80 and over; Treatment Failure; Retrospective Studies
PubMed: 38697991
DOI: 10.1038/s41467-024-47998-8 -
Cancers Oct 2023Drug resistance remains a significant challenge in the treatment of colorectal cancer (CRC). In recent years, the emerging field of ferroptosis, a unique form of... (Review)
Review
Drug resistance remains a significant challenge in the treatment of colorectal cancer (CRC). In recent years, the emerging field of ferroptosis, a unique form of regulated cell death characterized by iron-dependent lipid peroxidation, has offered new insights and potential therapeutic strategies for overcoming drug resistance in CRC. This review examines the role of ferroptosis in CRC and its impact on drug resistance. It highlights the distinctive features and advantages of ferroptosis compared to other cell death pathways, such as apoptosis and necrosis. Furthermore, the review discusses current research advances in the field, including novel treatment approaches that target ferroptosis. These approaches involve the use of ferroptosis inducers, interventions in iron metabolism and lipid peroxidation, and combination therapies to enhance the efficacy of ferroptosis. The review also explores the potential of immunotherapy in modulating ferroptosis as a therapeutic strategy. Additionally, it evaluates the strengths and limitations of targeting ferroptosis, such as its selectivity, low side effects, and potential to overcome resistance, as well as challenges related to treatment specificity and drug development. Looking to the future, this review discusses the prospects of ferroptosis-based therapies in CRC, emphasizing the importance of further research to elucidate the interaction between ferroptosis and drug resistance. It proposes future directions for more effective treatment strategies, including the development of new therapeutic approaches, combination therapies, and integration with emerging fields such as precision medicine. In conclusion, harnessing ferroptosis represents a promising avenue for overcoming drug resistance in CRC. Continued research efforts in this field are crucial for optimizing therapeutic outcomes and providing hope for CRC patients.
PubMed: 37958383
DOI: 10.3390/cancers15215209 -
Cancers Sep 2023Radiation necrosis (RN) is a possible late complication of stereotactic radiosurgery (SRS), but only a few risk factors are known. The aim of this study was to assess...
BACKGROUND
Radiation necrosis (RN) is a possible late complication of stereotactic radiosurgery (SRS), but only a few risk factors are known. The aim of this study was to assess tumor location in correlation to the development of radiation necrosis for skull base (SB) and non-skull base tumors.
METHODS
All patients treated with radiosurgery for benign neoplasms (2004-2020) were retrospectively evaluated. The clinical, imaging and medication data were obtained and the largest axial tumor diameter was determined using MRI scans in T1-weighted imaging with gadolinium. The diagnosis of RN was established using imaging parameters. Patients with tumors located at the skull base were compared to patients with tumors in non-skull base locations.
RESULTS
205 patients could be included. Overall, 157 tumors (76.6%) were located at the SB and compared to 48 (23.4%) non-SB tumors. Among SB tumors, the most common were vestibular schwannomas (125 cases) and meningiomas (21 cases). In total, 32 (15.6%) patients developed RN after a median of 10 (IqR 5-12) months. Moreover, 62 patients (30.2%) had already undergone at least one surgical resection. In multivariate Cox regression, SB tumors showed a significantly lower risk of radiation necrosis with a Hazard Ratio (HR) of 0.252, < 0.001, independently of the applied radiation dose. Furthermore, higher radiation doses had a significant impact on the occurrence of RN (HR 1.372, = 0.002).
CONCLUSIONS
The risk for the development of RN for SB tumors appears to be low but should not be underestimated. No difference was found between recurrent tumors and newly diagnosed tumors, which may support the value of radiosurgical treatment for patients with recurrent SB tumors.
PubMed: 37835452
DOI: 10.3390/cancers15194760 -
Brain, Behavior, and Immunity Feb 2024Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair,...
Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6C, CD43, PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke.
Topics: Humans; Mice; Animals; Monocytes; Ischemic Stroke; Brain Edema; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Infarction, Middle Cerebral Artery
PubMed: 38070624
DOI: 10.1016/j.bbi.2023.12.007 -
Cureus Aug 2023Solitary fibrous tumors (SFTs) are rare spindle cell neoplasms of mesenchymal origin that are most commonly found in the pleura, although they have also been documented...
Solitary fibrous tumors (SFTs) are rare spindle cell neoplasms of mesenchymal origin that are most commonly found in the pleura, although they have also been documented in extrapleural locations. SFTs affect males and females in equal distribution, and they typically occur between the fourth and seventh decades of life. Since SFTs are usually benign and asymptomatic, the majority of them are discovered incidentally on computed tomography (CT) or magnetic resonance imaging (MRI) imaging, unless they grow to a size that causes mass effect symptoms on other organs. Nonetheless, imaging is not sufficient to diagnose an SFT, and therefore, biopsy is recommended for further analysis. Advances in immunohistochemistry and molecular diagnostics have identified CD34 and NAB2-STAT6, respectively, as the most consistent markers for SFTs. The risk of SFT metastasis can be determined through the use of a four-variable risk-stratification model developed by Demicco et al., which is based upon the risk factors of patient age, tumor size, mitotic count per 10 high-power fields, and the degree of tumor necrosis. The management of SFTs involves a wide surgical resection of the tumor while preserving surrounding organs and structures. Post-operative surveillance involves imaging the primary tumor site for up to five years due to the risk of local recurrence. At this time, neither radiation therapy nor chemotherapy after resection have yet to show benefit, and therefore, they are not currently recommended. This case report discusses the management of a 68-year-old woman who was diagnosed with a malignant extrapleural SFT in her right medial upper thigh.
PubMed: 37605717
DOI: 10.7759/cureus.43750 -
Cancers Sep 2023Intrahepatic cholangiocarcinoma (ICC) is a rare disease with a rising incidence. While surgical resection is the only curative option, the disease process is often... (Review)
Review
Intrahepatic cholangiocarcinoma (ICC) is a rare disease with a rising incidence. While surgical resection is the only curative option, the disease process is often identified in advanced stages, as this malignancy often remains clinically silent in early development. Only one-third of patients are eligible for resection at the time of diagnosis. For patients who cannot undergo resection, intra-arterial therapies are reasonable palliative treatment options; in rare occasions, these may be bridging therapies, as well. The premise of bland embolization and most chemoembolization intra-arterial therapies is that the arterial supply of the tumor is occluded to induce tumor necrosis, while radioembolization utilizes the arterial flow of the tumor to deliver radiation therapy. In this review, we discuss the use of transarterial embolization, transarterial chemoembolization, and selective internal radiation therapy for the treatment of ICC. Phase III randomized controlled clinical trials are difficult to tailor to this extremely rare and aggressive disease, but ultimately, further investigation should be pursued to define the patient population that will derive the greatest benefit from each modality.
PubMed: 37835420
DOI: 10.3390/cancers15194727