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1.
Magn Reson Imaging ; 111: 74-83, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38604347

ABSTRACT

PURPOSE: To assess whether diffusion-weighted imaging (DWI) with Compressed SENSE (CS) and deep learning (DL-CS-DWI) can improve image quality and lesion detection in patients at risk for hepatocellular carcinoma (HCC). METHODS: This single-center prospective study enrolled consecutive at-risk participants who underwent 3.0 T gadoxetate disodium-enhanced MRI. Conventional DWI was acquired using parallel imaging (PI) with SENSE (PI-DWI). In CS-DWI and DL-CS-DWI, CS but not PI with SENSE was used to accelerate the scan with 2.5 as the acceleration factor. Qualitative and quantitative image quality were independently assessed by two masked reviewers, and were compared using the Wilcoxon signed-rank test. The detection rates of clinically-relevant (LR-4/5/M based on the Liver Imaging Reporting and Data System v2018) liver lesions for each DWI sequence were independently evaluated by another two masked reviewers against their consensus assessments based on all available non-DWI sequences, and were compared by the McNemar test. RESULTS: 67 participants (median age, 58.0 years; 56 males) with 197 clinically-relevant liver lesions were enrolled. Among the three DWI sequences, DL-CS-DWI showed the best qualitative and quantitative image qualities (p range, <0.001-0.039). For clinically-relevant liver lesions, the detection rates (91.4%-93.4%) of DL-CS-DWI showed no difference with CS-DWI (87.3%-89.8%, p = 0.230-0.231) but were superior to PI-DWI (82.7%-85.8%, p = 0.015-0.025). For lesions located in the hepatic dome, DL-CS-DWI demonstrated the highest detection rates (94.8%-97.4% vs 76.9%-79.5% vs 64.1%-69.2%, p = 0.002-0.045) among the three DWI sequences. CONCLUSION: In patients at high-risk for HCC, DL-CS-DWI improved image quality and detection for clinically-relevant liver lesions, especially for the hepatic dome.


Subject(s)
Carcinoma, Hepatocellular , Deep Learning , Diffusion Magnetic Resonance Imaging , Liver Neoplasms , Humans , Liver Neoplasms/diagnostic imaging , Male , Female , Middle Aged , Diffusion Magnetic Resonance Imaging/methods , Prospective Studies , Carcinoma, Hepatocellular/diagnostic imaging , Aged , Liver/diagnostic imaging , Liver/pathology , Contrast Media , Image Interpretation, Computer-Assisted/methods , Adult , Gadolinium DTPA , Image Enhancement/methods
2.
J Liver Cancer ; 23(2): 284-299, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37710379

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and represents a significant global health burden with rising incidence rates, despite a more thorough understanding of the etiology and biology of HCC, as well as advancements in diagnosis and treatment modalities. According to emerging evidence, imaging features related to tumor aggressiveness can offer relevant prognostic information, hence validation of imaging prognostic features may allow for better noninvasive outcomes prediction and inform the selection of tailored therapies, ultimately improving survival outcomes for patients with HCC.

3.
Nat Cancer ; 4(9): 1258-1272, 2023 09.
Article in English | MEDLINE | ID: mdl-37537301

ABSTRACT

The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8+ T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, a classically described mechanism of tumor immune escape is tumor MHC-I downregulation. Here, we report that CD8+ T cells maintain the capacity to kill tumor cells that are entirely devoid of MHC-I expression. This capacity proves to be dependent instead on interactions between T cell natural killer group 2D (NKG2D) and tumor NKG2D ligands (NKG2DLs), the latter of which are highly expressed on MHC-loss variants. Necessarily, tumor cell killing in these instances is antigen independent, although prior T cell antigen-specific activation is required and can be furnished by myeloid cells or even neighboring MHC-replete tumor cells. In this manner, adaptive priming can beget innate killing. These mechanisms are active in vivo in mice as well as in vitro in human tumor systems and are obviated by NKG2D knockout or blockade. These studies challenge the long-advanced notion that downregulation of MHC-I is a viable means of tumor immune escape and instead identify the NKG2D-NKG2DL axis as a therapeutic target for enhancing T cell-dependent anti-tumor immunity against MHC-loss variants.


Subject(s)
CD8-Positive T-Lymphocytes , Neoplasms , Animals , Humans , Mice , Antigens/metabolism , CD8-Positive T-Lymphocytes/pathology , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/metabolism , Neoplasms/genetics , NK Cell Lectin-Like Receptor Subfamily K/genetics , NK Cell Lectin-Like Receptor Subfamily K/metabolism
5.
Neurosurgery ; 93(1): 198-205, 2023 07 01.
Article in English | MEDLINE | ID: mdl-36790207

ABSTRACT

BACKGROUND: The management of intracranial oncological disease remains a significant challenge despite advances in systemic cancer therapy. Laser interstitial thermal therapy (LITT) represents a novel treatment for local control of brain tumors through photocoagulation with a stereotactically implanted laser fiber. Because the use of laser interstitial thermal therapy continues to increase within neurosurgery, characterization of LITT is necessary to improve outcomes. OBJECTIVE: To quantify the risk of tumor seeding along the laser fiber tract in patients receiving LITT for primary or metastatic brain tumors at a high-volume treatment center. METHODS: We retrospectively reviewed all patients receiving LITT from 2015 to 2021 at our medical center. Patients with biopsy-confirmed tumors were included in this study. Tract seeding was identified as discontinuous, newly enhancing tumor along the LITT tract. RESULTS: Fifty-six patients received LITT for biopsy-confirmed tumors from 2015 to 2021, with tract seeding identified in 3 (5.4%). Twenty-nine (51.8%) patients had gliomas, while the remainder had metastases, of which lung was the most common histology (20 patients, 74%). Tract seeding was associated with ablation proceeding inward from superficial tumor margin closest to the cranial entry point ( P = .03). Patients with tract seeding had a shorter median time to progression of 1.1 (0.1-1.3) months vs 4.2 (2.2-8.6) months ( P = .03). CONCLUSION: Although the risk of tract seeding after LITT is reassuringly low, it is associated with decreased progression-free survival. This risk may be related to surgical technique or experience. Follow-up radiosurgery to the LITT tract has the potential to prevent this complication.


Subject(s)
Brain Neoplasms , Laser Therapy , Humans , Retrospective Studies , Brain Neoplasms/pathology , Progression-Free Survival , Laser Therapy/methods , Lasers
6.
Adv Radiat Oncol ; 7(6): 101054, 2022.
Article in English | MEDLINE | ID: mdl-36420187

ABSTRACT

Purpose: Stereotactic radiosurgery (SRS) is a highly effective therapy for newly diagnosed brain metastases. Prophylactic antiepileptic drugs are no longer routinely used in current SRS practice, owing to a perceived low overall frequency of new-onset seizures and potential side effects of medications. It is nonetheless desirable to prevent unwanted side effects following SRS. Risk factors for new-onset seizures after SRS have not been well established. As such, we aimed to characterize variables associated with increased seizure risk. Methods and Materials: Patients treated with SRS for newly diagnosed brain metastases between 2013 and 2016 were retrospectively reviewed at a single institution. Data on baseline demographics, radiation parameters, and clinical courses were collected. Results: The cohort consisted of 305 patients treated with SRS without prior seizure history. Median age and baseline Karnofsky Performance Scale score were 64 years (interquartile range, 55-70) and 80 (interquartile range, 80-90), respectively. Twenty-six (8.5%) patients developed new-onset seizures within 3 months of SRS. There was no association between new-onset seizures and median baseline Karnofsky Performance Scale score, prior resection, or prior whole brain radiation therapy. There were significant differences in the combined total irradiated volume (12.5 vs 3.7 cm3, P < .001), maximum single lesion volume (8.8 vs 2.8 cm3, P = .003), lesion diameter (3.2 vs 2.0 cm, P = .003), and number of lesions treated (3 vs 1, P = .018) between patients with and without new-onset seizures, respectively. On multivariate logistic regression, total irradiated volume (odds ratio, 1.09 for every 1-cm1 increase in total volume; confidence interval, 1.02-1.17; P = .016) and pre-SRS neurologic symptoms (odds ratio, 3.08; 95% confidence interval, 1.19-7.99; P = .020) were both significantly correlated with odds of seizures following SRS. Conclusions: Our data suggest that larger total treatment volume and the presence of focal neurologic deficits at presentation are associated with new-onset seizures within 3 months of SRS. High-risk patients undergoing SRS may benefit from counseling or prophylactic antiseizure therapy.

7.
Adv Drug Deliv Rev ; 185: 114311, 2022 06.
Article in English | MEDLINE | ID: mdl-35489652

ABSTRACT

Immunotherapies, such as immune checkpoint inhibition (ICI), have had limited success in treating intracranial malignancies. These failures are due partly to the restrictive blood-brain-barrier (BBB), the profound tumor-dependent induction of local and systemic immunosuppression, and immune evasion exhibited by these tumors. Therefore, novel approaches must be explored that aim to overcome these stringent barriers. LITT is an emerging treatment for brain tumors that utilizes thermal ablation to kill tumor cells. LITT provides an additional therapeutic benefit by synergizing with ICI and systemic chemotherapies to strengthen the anti-tumor immune response. This synergistic relationship involves transient disruption of the BBB and local augmentation of immune function, culminating in increased CNS drug penetrance and improved anti-tumor immunity. In this review, we will provide an overview of the challenges facing immunotherapy for brain tumors, and discuss how LITT may synergize with the endogenous anti-tumor response to improve the efficacy of ICI.


Subject(s)
Brain Neoplasms , Hyperthermia, Induced , Laser Therapy , Blood-Brain Barrier , Brain Neoplasms/drug therapy , Heating , Humans
8.
Front Immunol ; 12: 777073, 2021.
Article in English | MEDLINE | ID: mdl-34868044

ABSTRACT

Successful cancer immunotherapies rely on a replete and functional immune compartment. Within the immune compartment, T cells are often the effector arm of immune-based strategies due to their potent cytotoxic capabilities. However, many tumors have evolved a variety of mechanisms to evade T cell-mediated killing. Thus, while many T cell-based immunotherapies, such as immune checkpoint inhibition (ICI) and chimeric antigen receptor (CAR) T cells, have achieved considerable success in some solid cancers and hematological malignancies, these therapies often fail in solid tumors due to tumor-imposed T cell dysfunctions. These dysfunctional mechanisms broadly include reduced T cell access into and identification of tumors, as well as an overall immunosuppressive tumor microenvironment that elicits T cell exhaustion. Therefore, novel, rational approaches are necessary to overcome the barriers to T cell function elicited by solid tumors. In this review, we will provide an overview of conventional immunotherapeutic strategies and the various barriers to T cell anti-tumor function encountered in solid tumors that lead to resistance. We will also explore a sampling of emerging strategies specifically aimed to bypass these tumor-imposed boundaries to T cell-based immunotherapies.


Subject(s)
Immunotherapy , Neoplasms/immunology , Neoplasms/therapy , T-Lymphocytes/immunology , Animals , Biomarkers, Tumor , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Disease Management , Disease Susceptibility , Humans , Immunity , Immunotherapy/adverse effects , Immunotherapy/methods , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Neoplasms/diagnosis , Neoplasms/metabolism , Prognosis , T-Lymphocytes/metabolism , Treatment Outcome , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/metabolism
9.
Neurosurg Rev ; 44(3): 1471-1478, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32562019

ABSTRACT

Fusiform aneurysms are less common than saccular aneurysms, but have higher associated mortality and rebleeding rates. Recently, flow diversion has emerged as a possible treatment option. The purpose of this study was to determine the safety and efficacy of the Pipeline Embolization Device (PED) for the treatment of ruptured and unruptured fusiform aneurysms. This was a retrospective analysis of patients with fusiform intracranial aneurysms treated with a PED at a quaternary care center between January 2012 and September 2019. Occlusion rates, neurologic morbidity/mortality, and other clinical variables were analyzed. Twenty-nine patients with 30 fusiform aneurysms were treated with a PED. Sixteen aneurysms (53%) were located in the anterior circulation and 14 aneurysms (47%) were in the posterior circulation. The mean maximal diameter of the aneurysms was 10.1 ± 5.6 mm (range 2.3-25 mm). Angiographic and clinical follow-up were available for 28 aneurysms (93%). The median follow-up was 17.4 months (IQR 4.8 to 28 months) and occlusion rates were graded according to the O'Kelly-Marotta (OKM) scale. Of patients with DSA follow-up, 15 aneurysms (60%) were completely occluded (OKM D) and 19 aneurysms (76%) had a favorable occlusion result (OKM C1-3 and D). The overall complication rate was 26.7% with a neurological morbidity rate of 6.7% and neurological mortality rate of 3.4%. Flow diversion can be an effective treatment for both ruptured and unruptured fusiform aneurysms. Nevertheless, complete occlusion rates are lower than for saccular aneurysms. Therefore, flow diversion should be considered only if other more direct treatment options, such as clipping or stent/coiling are not applicable. Flow diversion should be used cautiously in patients presenting with rupture.


Subject(s)
Blood Vessel Prosthesis , Cerebrovascular Circulation/physiology , Endovascular Procedures/instrumentation , Intracranial Aneurysm/surgery , Self Expandable Metallic Stents , Adolescent , Adult , Aged , Aneurysm/diagnostic imaging , Aneurysm/surgery , Child , Endovascular Procedures/methods , Female , Follow-Up Studies , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/physiopathology , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
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