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International Journal of Cancer Sep 2023Assessment of treatment response in patients (pts) with leptomeningeal metastases (LM) represents a significant challenge and standardized criteria are needed. In 2017,...
Assessment of treatment response in patients (pts) with leptomeningeal metastases (LM) represents a significant challenge and standardized criteria are needed. In 2017, the RANO LM Working Group proposed a standardized scorecard to evaluate MRI findings (further simplified in 2019). Here, we aim to validate the prognostic impact of response to treatment assessed using this tool in a multicentric cohort of breast cancer (BC) pts. Pts with BC-related LM diagnosed at two institutions between 2005 and 2018 were identified. Baseline and follow-up MRI scans were centrally reviewed and response assessment was evaluated using 2019 revised RANO LM criteria. A total of 142 pts with BC-related LM and available baseline brain MRI imaging were identified; 60 of them had at least one follow-up MRI. In this subgroup, median overall survival (OS) was 15.2 months (95%CI 9.5-21.0). At first re-evaluation, radiological response by RANO criteria was: complete response (CR) in 2 pts (3%), partial response (PR) in 12 (20%), stable disease (SD) in 33 (55%) and progression of disease (PD) in 13 (22%). Median OS was 31.1 months (HR 0.10, 95%CI 0.01-0.78) in pts with CR, 16.1 months (HR 0.41, 95%CI 0.17-0.97) in pts with PR, 17.9 months (HR 0.45, 95%CI 0.22-0.91) in pts with SD and 9.5 months in pts with PD (P = .029). A second blinded evaluation showed a moderate interobserver agreement (K = 0.562). Radiological response according to 2019 RANO criteria is significantly associated with OS in pts with BC-related LM, thus supporting the use of this evaluation tool both in trials and clinical practice.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Magnetic Resonance Imaging; Breast; Retrospective Studies
PubMed: 37243480
DOI: 10.1002/ijc.34571 -
BJR Case Reports Nov 2023Gorham-Stout disease (GSD) is a rare, non-hereditary, bone disease characterised by progressive osteolysis as a result of uncontrolled proliferation of endothelial-lined...
Gorham-Stout disease (GSD) is a rare, non-hereditary, bone disease characterised by progressive osteolysis as a result of uncontrolled proliferation of endothelial-lined vessels replacing normal bone. We present a baby-girl with the classic radiological features of GSD and compatible clinical and histological findings, who developed progressive disease for over 2 years despite propranolol treatment. Propranolol treatment was stopped and sirolimus monotherapy started which resulted in near-complete resolution after 1 year, with no recurrence after discontinuation of treatment. This case not only illustrates the typical features of GSD on a variety of imaging modalities, but is also the first report showing stark contrast in response between propranolol and sirolimus treatment for GSD, highlighting how targeting lymphatic, rather than solely angiomatous, proliferation at the vascular endothelial growth factor-level may be a future direction.
PubMed: 37928714
DOI: 10.1259/bjrcr.20230032 -
Cancer Immunology, Immunotherapy : CII Sep 2023Radiotherapy (XRT), a well-known activator of the inflammasome and immune priming, is in part capable of reversing resistance to anti-PD1 treatment. The NLRP3...
Radiotherapy (XRT), a well-known activator of the inflammasome and immune priming, is in part capable of reversing resistance to anti-PD1 treatment. The NLRP3 inflammasome is a pattern recognition receptor which is activated by both exogenous and endogenous stimuli, leading to a downstream inflammatory response. Although NLRP3 is typically recognized for its role in exacerbating XRT-induced tissue damage, the NLRP3 inflammasome can also yield an effective antitumor response when used in proper dosing and sequencing with XRT. However, whether NLRP3 agonist boosts radiation-induced immune priming and promote abscopal responses in anti-PD1 resistant model is still unknown. Therefore, in this study, we paired intratumoral injection of an NLRP3 agonist with XRT to stimulate the immune system in both wild type (344SQ-P) and anti-PD1 resistant (344SQ-R) murine-implanted lung adenocarcinoma models. We found that the combination of XRT + NLPR3 agonist enhanced the control of implanted lung adenocarcinoma primary as well as secondary tumors in a radiological dose-dependent manner, in which 12Gyx3 fractions of stereotactic XRT was better than 5Gyx3, while 1Gyx2 did not improve the NLRP3 effect. Survival and tumor growth data also showed significant abscopal response with the triple therapy (12Gyx3 + NLRP3 agonist + α-PD1) in both 344SQ-P and 344SQ-R aggressively growing models. Multiple pro-inflammatory cytokines (IL-1b, IL-4, IL-12, IL-17, IFN-γ and GM-CSF) were elevated in the serum of mice treated with XRT + NLRP3 or triple therapy. The Nanostring results showed that NLRP3 agonist is capable of increasing antigen presentation, innate function, and T-cell priming. This study can be of particular importance to treat patients with immunologically-cold solid tumors whom are also refractory to prior checkpoint treatments.
Topics: Mice; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Antigen Presentation; Cytokines; Adenocarcinoma of Lung
PubMed: 37289257
DOI: 10.1007/s00262-023-03471-x -
European Radiology Experimental Feb 2024This review aims to take a journey into the transformative impact of artificial intelligence (AI) on positron emission tomography (PET) imaging. To this scope, a broad... (Review)
Review
This review aims to take a journey into the transformative impact of artificial intelligence (AI) on positron emission tomography (PET) imaging. To this scope, a broad overview of AI applications in the field of nuclear medicine and a thorough exploration of deep learning (DL) implementations in cancer diagnosis and therapy through PET imaging will be presented. We firstly describe the behind-the-scenes use of AI for image generation, including acquisition (event positioning, noise reduction though time-of-flight estimation and scatter correction), reconstruction (data-driven and model-driven approaches), restoration (supervised and unsupervised methods), and motion correction. Thereafter, we outline the integration of AI into clinical practice through the applications to segmentation, detection and classification, quantification, treatment planning, dosimetry, and radiomics/radiogenomics combined to tumour biological characteristics. Thus, this review seeks to showcase the overarching transformation of the field, ultimately leading to tangible improvements in patient treatment and response assessment. Finally, limitations and ethical considerations of the AI application to PET imaging and future directions of multimodal data mining in this discipline will be briefly discussed, including pressing challenges to the adoption of AI in molecular imaging such as the access to and interoperability of huge amount of data as well as the "black-box" problem, contributing to the ongoing dialogue on the transformative potential of AI in nuclear medicine.Relevance statementAI is rapidly revolutionising the world of medicine, including the fields of radiology and nuclear medicine. In the near future, AI will be used to support healthcare professionals. These advances will lead to improvements in diagnosis, in the assessment of response to treatment, in clinical decision making and in patient management.Key points• Applying AI has the potential to enhance the entire PET imaging pipeline.• AI may support several clinical tasks in both PET diagnosis and prognosis.• Interpreting the relationships between imaging and multiomics data will heavily rely on AI.
Topics: Humans; Artificial Intelligence; Deep Learning; Positron-Emission Tomography; Radiology; Power, Psychological
PubMed: 38321340
DOI: 10.1186/s41747-023-00413-1 -
Skeletal Radiology Jan 2024The surgical management of extremity bone and soft tissue sarcomas has evolved significantly over the last 50 years. The introduction and refinement of high-resolution... (Review)
Review
The surgical management of extremity bone and soft tissue sarcomas has evolved significantly over the last 50 years. The introduction and refinement of high-resolution cross-sectional imaging has allowed accurate assessment of anatomy and tumor extent, and in the current era more than 90% of patients can successfully undergo limb-salvage surgery. Advances in imaging have also revolutionized the clinician's ability to assess treatment response, detect metastatic disease, and perform intraoperative surgical navigation. This review summarizes the broad and essential role radiology plays in caring for sarcoma patients from diagnosis to post-treatment surveillance. Present evidence-based imaging paradigms are highlighted along with key future directions.
PubMed: 38233634
DOI: 10.1007/s00256-024-04586-7 -
The Journal of Infectious Diseases Oct 2023Recently developed molecular imaging approaches can be used to visualize specific host responses and pathology in a quest to image infections where few microbe-specific...
Recently developed molecular imaging approaches can be used to visualize specific host responses and pathology in a quest to image infections where few microbe-specific tracers have been developed and in recognition that host responses contribute to morbidity and mortality in their own right. Here we highlight several recent examples of these imaging approaches adapted for imaging infections. The early successes and new avenues described here encompass diverse imaging modalities and leverage diverse aspects of the host response to infection-including inflammation, tissue injury and healing, and key nutrients during host-pathogen interactions. Clearly, these approaches merit further preclinical and clinical study as they are complementary and orthogonal to the pathogen-focused imaging modalities currently under investigation.
Topics: Humans; Inflammation; Host-Pathogen Interactions
PubMed: 37788497
DOI: 10.1093/infdis/jiad313 -
Radiation Oncology (London, England) Sep 2023One of the most important therapeutic interventions for non-small cell lung cancer is radiotherapy. Ionizing radiation (IR) is classified by traditional radiobiology... (Review)
Review
One of the most important therapeutic interventions for non-small cell lung cancer is radiotherapy. Ionizing radiation (IR) is classified by traditional radiobiology principles as a direct cytocidal therapeutic agent against cancer, although there is growing recognition of other antitumor immunological responses induced by this modality. The most effective therapeutic combinations to harness radiation-generated antitumor immunity and enhance treatment results for malignancies resistant to existing radiotherapy regimens could be determined by a more sophisticated understanding of the immunological pathways created by radiation. Innate immune signaling is triggered by the activation of cGAS-STING, and this promotes adaptive immune responses to help fight cancer. This identifies a molecular mechanism radiation can use to trigger antitumor immune responses by bridging the DNA-damaging ability of IR with the activation of CD8 + cytotoxic T cell-mediated killing of tumors. We also discuss radiotherapy-related parameters that affect cGAS-STING signaling, negative consequences of cGAS-STING activation, and intriguing treatment options being tested in conjunction with IR to support immune activation by activating STING-signaling. Improved therapeutic outcomes will result from a better understanding of how IR promotes cGAS-STING signaling in immune-based treatment regimens that maximize radiotherapy's anticancer effectiveness.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; CD8-Positive T-Lymphocytes; Nucleotidyltransferases; Radiation Oncology
PubMed: 37667279
DOI: 10.1186/s13014-023-02335-z -
Journal of Gastrointestinal Oncology Oct 2023Intrahepatic cholangiocarcinoma (ICC) is a rare primary hepatic malignancy. One of the treatment strategies which has shown some promise is transarterial...
BACKGROUND
Intrahepatic cholangiocarcinoma (ICC) is a rare primary hepatic malignancy. One of the treatment strategies which has shown some promise is transarterial radioembolization (TARE). However, data on dose thresholds, arguably the most important aspect of the procedure itself, is still limited. The study aims to evaluate the relationship between dose to tumor and radiologic response in intrahepatic cholangiocarcinoma patients undergoing transarterial radioembolization.
METHODS
Twenty-patients who underwent treatment for 26 tumors were retrospectively reviewed. Radiologic response at 3-month was evaluated and post yttrium-90 bremsstrahlung single photon emission computerized tomography computed tomography was evaluated to determine tumor dose. Other factors such as particle load and activity per particle were evaluated.
RESULTS
The mean tumor dose for those with progressive disease or stable disease, partial response, and complete response (CR) by European Association for the Study of Liver (EASL) criteria for the glass cohort was 294±0, 465.4±292.4 and 951.8±666.5 Gy respectively (P=0.039). A receiver operating characteristic (ROC) curve analysis of tumor dose demonstrated an area under the curve (AUC) of 0.738 (P=0.038) with Youden-index analysis demonstrated a cutoff point of >541.7 Gy (sensitivity: 55.56%; specificity: 92.86%) for the glass cohort. Significantly longer survival was noted in those who achieved a CR [HR: 4.79 (95% CI: 1.41-16.25)] and those treated with glass as compared to resin [HR: 5.02 (95% CI: 1.23-20.55), P=0.025]. Of the 17 treatments in 13 patients which were done concomitantly with chemotherapy 7/17 (41.2%) required a delay in chemotherapy, however all patients reinitiated chemotherapy after a delay.
CONCLUSIONS
There appears to be a relationship between tumor dose and radiologic response, with this study suggesting a target of ≥541.7 Gy being warranted in patients receiving treatment with glass microspheres.
PubMed: 37969824
DOI: 10.21037/jgo-23-210 -
Frontiers in Immunology 2023Immune control of (Mtb) infection is largely influenced by the extensive disease heterogeneity that is typical for tuberculosis (TB). In this study, the peripheral...
BACKGROUND
Immune control of (Mtb) infection is largely influenced by the extensive disease heterogeneity that is typical for tuberculosis (TB). In this study, the peripheral inflammatory immune profile of different sub-groups of pulmonary TB patients was explored based on clinical disease severity, anemia of chronic disease, or the radiological extent of lung disease.
METHODS
Plasma samples were obtained from n=107 patients with active pulmonary TB at the time of diagnosis and after start of standard chemotherapy. A composite clinical TB symptoms score, blood hemoglobin status and chest X-ray imaging were used to sub-group TB patients into 1.) mild and moderate-severe clinical TB, 2.) anemic and non-anemic TB, or 3.) limited and extensive lung involvement. Plasma levels of biomarkers associated with inflammation pathways were assessed using a Bio-Plex Magpix 37-multiplex assay. In parallel, Th1/Th2 cytokines were quantified with a 27-multiplex in matched plasma and cell culture supernatants from whole blood stimulated with -antigens using the QuantiFERON-TB Gold assay.
RESULTS
Clinical TB disease severity correlated with low blood hemoglobin levels and anemia but not with radiological findings in this study cohort. Multiplex protein analyses revealed that distinct clusters of inflammation markers and cytokines separated the different TB disease sub-groups with variable efficacy. Several top-ranked markers overlapped, while other markers were unique with regards to their importance to differentiate the TB disease severity groups. A distinct immune response profile defined by elevated levels of BAFF, LIGHT, sTNF-R1 and 2, IP-10, osteopontin, chitinase-3-like protein 1, and IFNα2 and IL-8, were most effective in separating TB patients with different clinical disease severity and were also promising candidates for treatment monitoring. TB patients with mild disease displayed immune polarization towards mixed Th1/Th2 responses, while pro-inflammatory and B cell stimulating cytokines as well as immunomodulatory mediators predominated in moderate-severe TB disease and anemia of TB.
CONCLUSIONS
Our data demonstrated that clinical disease severity in TB is associated with anemia and distinct inflammatory immune profiles. These results contribute to the understanding of immunopathology in pulmonary TB and define top-ranked inflammatory mediators as biomarkers of disease severity and treatment prognosis.
Topics: Humans; Tuberculosis; Tuberculosis, Pulmonary; Cytokines; Patient Acuity; Biomarkers; Anemia; Hemoglobins; Inflammation
PubMed: 38162636
DOI: 10.3389/fimmu.2023.1296501 -
Chest Jun 2024One of the major challenges in managing allergic bronchopulmonary aspergillosis remains consistent and reproducible assessment of response to treatment. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
One of the major challenges in managing allergic bronchopulmonary aspergillosis remains consistent and reproducible assessment of response to treatment.
RESEARCH QUESTION
What are the most relevant changes in CT scan parameters over time for assessing response to treatment?
STUDY DESIGN AND METHODS
In this ancillary study of a randomized clinical trial (NebuLamB), patients with asthma with available CT scan and without exacerbation during a 4-month allergic bronchopulmonary aspergillosis exacerbation treatment period (corticosteroids and itraconazole) were included. Changed CT scan parameters were assessed by systematic analyses of CT scan findings at initiation and end of treatment. CT scans were assessed by two radiologists anonymized to the clinical data. Radiologic parameters were determined by selecting those showing significant changes over time. Improvement of at least one, without worsening of the others, defined the radiologic response. Agreement between radiologic changes and clinical and immunologic responses was likewise investigated.
RESULTS
Among the 139 originally randomized patients, 132 were included. We identified five CT scan parameters showing significant changes at end of treatment: mucoid impaction extent, mucoid impaction density, centrilobular micronodules, consolidation/ground-glass opacities, and bronchial wall thickening (P < .05). These changes were only weakly associated with one another, except for mucoid impaction extent and density. No agreement was observed between clinical, immunologic, and radiologic responses, assessed as an overall response, or considering each of the parameters (Cohen κ, -0.01 to 0.24).
INTERPRETATION
Changes in extent and density of mucoid impaction, centrilobular micronodules, consolidation/ground-glass opacities, and thickening of the bronchial walls were found to be the most relevant CT scan parameters to assess radiologic response to treatment. A clinical, immunologic, and radiologic multidimensional approach should be adopted to assess outcomes, probably with a composite definition of response to treatment.
TRIAL REGISTRATION
ClinicalTrials.gov; No.: NCT02273661; URL: www.
CLINICALTRIALS
gov).
Topics: Humans; Aspergillosis, Allergic Bronchopulmonary; Male; Female; Tomography, X-Ray Computed; Asthma; Adult; Middle Aged; Itraconazole; Antifungal Agents; Treatment Outcome; Adrenal Cortex Hormones
PubMed: 38387646
DOI: 10.1016/j.chest.2024.02.026