-
Medicine Jul 2023Radiotherapy (RT) is an essential treatment for patients with high-grade gliomas. however, a consensus on the target area of RT has not yet been achieved. In this study,... (Observational Study)
Observational Study
Radiotherapy (RT) is an essential treatment for patients with high-grade gliomas. however, a consensus on the target area of RT has not yet been achieved. In this study, we aimed to analyze progression-free survival (PFS), recurrence patterns, and toxicity in patients who received reduced volume intensity-modulated radiotherapy with simultaneous integrated boost (rvSIB-IMRT). In addition, we attempted to identify prognostic factors for recurrence. Twenty patients with high-grade gliomas who received rvSIB-IMRT between July 2011 and December 2021 were retrospectively analyzed. For rvSIB-IMRT, clinical target volume 1/2 was set at a 5 to 10 mm margin on each gross tumor volume (GTV) 1 (resection cavity and enhanced lesion) and GTV2 (high-signal lesion of T2/fluid-attenuated inversion recovery). RT doses were prescribed to 60 Gy/30 fractions (fxs) for planning target volume (PTV)1 and 51 to 54 Gy/30 fxs for PTV2. The median PFS and overall survival of the total cohorts were 10.6 and 13.6 months, respectively. Among the 12 relapsed patients, central, in-field, and marginal recurrences were identified in 8 (66.7%), 2 (16.7%), and 1 patient (8.3%), respectively. Distant recurrence was identified in 3 patients. Gross total resection (GTR) and high Ki-67 index (>27.4%), and subventricular involvement (SVI) were identified as significant factors for PFS in the multivariate analysis. During the follow up, 4 patients showed pseudoprogression and 1 patient showed radiation necrosis. The rvSIB-IMRT for high-grade gliomas resulted in comparable PFS and tolerable toxicity. Most recurrences were central/in-field (10 cases of 12, 83.4%). GTR, high Ki-67 index (>27.4%), and SVI were significant factors for recurrence.
Topics: Humans; Radiotherapy, Intensity-Modulated; Radiotherapy Dosage; Retrospective Studies; Ki-67 Antigen; Radiotherapy Planning, Computer-Assisted; Glioma; Recurrence
PubMed: 37443476
DOI: 10.1097/MD.0000000000033955 -
The Oncologist Sep 2023Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB.
METHODS
Patients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months. A standard 3 + 3 Durvalumab dose de-escalation design was used. Longitudinal lymphocytes count, cytokines analyses on plasma samples, and magnetic resonance imaging (MRI) were collected.
RESULTS
Six patients were included. One dose limiting toxicity, an immune-related grade 3 vestibular neuritis related to Durvalumab, was reported. Median progression-free interval (PFI) and overall survival (OS) were 2.3 and 16.7 months, respectively. Multi-modal deep learning-based analysis including MRI, cytokines, and lymphocytes/neutrophil ratio isolated the patients presenting pseudoprogression, the longest PFI and those with the longest OS, but statistical significance cannot be established considering phase I data only.
CONCLUSION
Combination of hFSRT and Durvalumab in recurrent GB was well tolerated in this phase I study. These encouraging results led to an ongoing randomized phase II. (ClinicalTrials.gov Identifier: NCT02866747).
Topics: Humans; Glioblastoma; Treatment Outcome; Re-Irradiation; Brain Neoplasms; Neoplasm Recurrence, Local; Radiosurgery; Cytokines
PubMed: 37196069
DOI: 10.1093/oncolo/oyad095 -
Neuro-oncology Nov 2023Glioblastoma (GB) is incurable at present without established treatment options for recurrent disease. In this phase I first-in-human clinical trial we investigated...
BACKGROUND
Glioblastoma (GB) is incurable at present without established treatment options for recurrent disease. In this phase I first-in-human clinical trial we investigated safety and feasibility of adoptive transfer of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2, which is expressed at elevated levels by a subset of glioblastomas.
METHODS
Nine patients with recurrent HER2-positive GB were treated with single doses of 1 × 107, 3 × 107, or 1 × 108 irradiated CAR-NK cells injected into the margins of the surgical cavity during relapse surgery. Imaging at baseline and follow-up, peripheral blood lymphocyte phenotyping and analyses of the immune architecture by multiplex immunohistochemistry and spatial digital profiling were performed.
RESULTS
There were no dose-limiting toxicities, and none of the patients developed a cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Five patients showed stable disease after relapse surgery and CAR-NK injection that lasted 7 to 37 weeks. Four patients had progressive disease. Pseudoprogression was found at injection sites in 2 patients, suggestive of a treatment-induced immune response. For all patients, median progression-free survival was 7 weeks, and median overall survival was 31 weeks. Furthermore, the level of CD8+ T-cell infiltration in recurrent tumor tissue prior to CAR-NK cell injection positively correlated with time to progression.
CONCLUSIONS
Intracranial injection of HER2-targeted CAR-NK cells is feasible and safe in patients with recurrent GB. 1 × 108 NK-92/5.28.z cells was determined as the maximum feasible dose for a subsequent expansion cohort with repetitive local injections of CAR-NK cells.
Topics: Humans; Receptors, Chimeric Antigen; Glioblastoma; Neoplasm Recurrence, Local; Killer Cells, Natural; Recurrence; Immunotherapy, Adoptive
PubMed: 37148198
DOI: 10.1093/neuonc/noad087 -
The British Journal of Radiology Aug 2023Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths in both sexes combined. Recent years have seen major advances in the diagnostic... (Review)
Review
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths in both sexes combined. Recent years have seen major advances in the diagnostic and treatment options for patients with non-small-cell lung cancer (NSCLC), including the routine use of 2-deoxy-2[F]-fluoro-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) in staging and response evaluation, minimally invasive endoscopic biopsy, targeted radiotherapy, minimally invasive surgery, and molecular and immunotherapies. In this review, the central roles of CT and F-FDG PET/CT in staging and response in both NSCLC and malignant pleural mesothelioma (MPM) are critically assessed. The Tumour Node Metastases (TNM-8) staging systems for NSCLC and MPM are presented with critical appraisal of the strengths and pitfalls of imaging. Overviews of the Response Evaluation Criteria in Solid Tumours (RECIST 1.1) for NSCLC and the modified RECIST criteria for MPM are provided, together with discussion of the benefits and limitations of these anatomical-based tools. Metabolic response assessment (not evaluated by RECIST 1.1) will be explored. We introduce the Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST 1.0) to include its advantages and challenges. The limitations of both anatomical and metabolic assessment criteria when applied to NSCLC treated with immunotherapy and the important concept of pseudoprogression are addressed with reference to immune RECIST (iRECIST). Separate consideration is given to the diagnosis and follow up of solitary pulmonary nodules with reference to the British Thoracic Society guidelines and Fleischner guidelines and use of the Brock (CT-based) and Herder (addition of F-FDG PET/CT) models for assessing malignant potential. We discuss how these models inform decisions by the multidisciplinary team, including referral of suspicious nodules for non-surgical management in patients unsuitable for surgery. We briefly outline current lung screening systems being used in the UK, Europe and North America. Emerging roles for MRI in lung cancer imaging are reviewed. The use of whole-body MRI in diagnosing and staging NSCLC is discussed with reference to the recent multicentre trial. The potential use of diffusion-weighted MRI to distinguish tumour from radiotherapy-induced lung toxicity is discussed. We briefly summarise the new PET-CT radiotracers being developed to evaluate specific aspects of cancer biology, other than glucose uptake. Finally, we describe how CT, MRI and F-FDG PET/CT are moving from primarily diagnostic tools for lung cancer towards having utility in prognostication and personalised medicine with the agency of artificial intelligence.
Topics: Male; Female; Humans; Lung Neoplasms; Positron Emission Tomography Computed Tomography; Carcinoma, Non-Small-Cell Lung; Fluorodeoxyglucose F18; Artificial Intelligence; Radiopharmaceuticals; Positron-Emission Tomography; Magnetic Resonance Imaging; Neoplasm Staging
PubMed: 37097296
DOI: 10.1259/bjr.20220339 -
Journal of Neurosurgery Sep 2023Management of patients with glioblastoma (GBM) is complex and involves implementing standard therapies including resection, radiation therapy, and chemotherapy, as well... (Review)
Review
Management of patients with glioblastoma (GBM) is complex and involves implementing standard therapies including resection, radiation therapy, and chemotherapy, as well as novel immunotherapies and targeted small-molecule inhibitors through clinical trials and precision medicine approaches. As treatments have advanced, the radiological and clinical assessment of patients with GBM has become even more challenging and nuanced. Advances in spatial resolution and both anatomical and physiological information that can be derived from MRI have greatly improved the noninvasive assessment of GBM before, during, and after therapy. Identification of pseudoprogression (PsP), defined as changes concerning for tumor progression that are, in fact, transient and related to treatment response, is critical for successful patient management. These temporary changes can produce new clinical symptoms due to mass effect and edema. Differentiating this entity from true tumor progression is a major decision point in the patient's management and prognosis. Providers may choose to start an alternative therapy, transition to a clinical trial, consider repeat resection, or continue with the current therapy in hopes of resolution. In this review, the authors describe the invasive and noninvasive techniques neurosurgeons need to be aware of to identify PsP and facilitate surgical decision-making.
Topics: Humans; Glioblastoma; Neurosurgeons; Brain Neoplasms; Disease Progression; Magnetic Resonance Imaging
PubMed: 36790010
DOI: 10.3171/2022.12.JNS222173