-
Journal of Cellular and Molecular... Jul 2023Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are... (Review)
Review
Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life-threatening immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI-pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X-ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI-pneumonitis. Additionally, it is tried to differentiate ICI-pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID-19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help.
PubMed: 37525480
DOI: 10.1111/jcmm.17895 -
Cancers Sep 2023Glioma and glioblastoma multiform (GBM) remain among the most debilitating and life-threatening brain tumors. Despite advances in diagnosing approaches, patient... (Review)
Review
Glioma and glioblastoma multiform (GBM) remain among the most debilitating and life-threatening brain tumors. Despite advances in diagnosing approaches, patient follow-up after treatment (surgery and chemoradiation) is still challenging for differentiation between tumor progression/recurrence, pseudoprogression, and radionecrosis. Radiomics emerges as a promising tool in initial diagnosis, grading, and survival prediction in patients with glioma and can help differentiate these post-treatment scenarios. Preliminary published studies are promising about the role of radiomics in post-treatment glioma/GBM. However, this field faces significant challenges, including a lack of evidence-based solid data, scattering publication, heterogeneity of studies, and small sample sizes. The present review explores radiomics's capabilities in following patients with glioma/GBM status post-treatment and to differentiate tumor progression, recurrence, pseudoprogression, and radionecrosis.
PubMed: 37760399
DOI: 10.3390/cancers15184429 -
Expert Review of Hematology 2023Immune checkpoint inhibitors (ICIs) are widely used for multiple types of malignancies and are considered the fourth pillar in cancer treatment. Anti-programmed death-1... (Review)
Review
INTRODUCTION
Immune checkpoint inhibitors (ICIs) are widely used for multiple types of malignancies and are considered the fourth pillar in cancer treatment. Anti-programmed death-1 (PD-1) antibodies pembrolizumab and nivolumab are approved for relapsed/refractory classical Hodgkin lymphoma. Nonetheless, two phase 2 trials for T-cell lymphoma were terminated because of hyperprogression after a single dose in some patients.
AREAS COVERED
In this review, we summarize available information on the rapid progression of peripheral T-cell lymphoma including adult T-cell leukemia/lymphoma (ATLL).
EXPERT OPINION
In the abovementioned two trials, disease subtypes in patients who experienced hyperprogression were mostly ATLL or angioimmunoblastic T-cell lymphoma. Possible hyperprogression mechanisms induced by PD-1 blockade are the compensatory upregulation of the expression of other checkpoints, altered expression of lymphoma-promoting growth factors, functional blockade of stromal PD-ligand 1 acting as a tumor suppressor, and unique immune environment in indolent ATLL. The differentiation between hyperprogression and pseudoprogression is practically essential. There are no established methods to predict hyperprogression before administration of an ICI. In the future, the progress of novel diagnostic modalities such as positron emission tomography with computed tomography and circulating tumor DNA is expected to facilitate early cancer detection.
Topics: Adult; Humans; Antibodies, Monoclonal; Immune Checkpoint Inhibitors; Lymphoma, T-Cell, Peripheral; Leukemia-Lymphoma, Adult T-Cell; Programmed Cell Death 1 Receptor; Hodgkin Disease; Lymphoma, T-Cell
PubMed: 37191476
DOI: 10.1080/17474086.2023.2215424 -
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 -
Frontiers in Oncology 2023This study aimed to elucidate the relationship between dynamic genomic mutation alteration and pseudoprogression (PsPD)/hyperprogressive disease (HPD) in...
INTRODUCTION
This study aimed to elucidate the relationship between dynamic genomic mutation alteration and pseudoprogression (PsPD)/hyperprogressive disease (HPD) in immunotherapy-treated advanced non-small-cell lung cancer (NSCLC), to provide clinical evidence for identifying and distinguishing between PsPD and HPD.
METHOD
Patients with advanced NSCLC who were treated with anti-PD1 were enrolled. Whole blood was collected at baseline and post image progression. Serum was separated and sequenced using 425-panel next-generation sequencing analysis (NGS).
RESULTS
NGS revealed that not only single gene mutations were associated with PsPD/HPD before treatment, dynamic monitoring of the whole-blood genome mutation spectrum also varied greatly. Mutational burden, allele frequency%, and relative circulating tumor DNA abundance indicated that the fold change after image progression was much higher in the HPD group.
DISCUSSION
The gene mutation profiles of PsPD and HPD not only differed before treatment, but higher genome mutation spectrum post image progression indicated true disease progression in patients with HPD. This suggests that dynamic whole-genome mutation profile monitoring as NGS can distinguish PsPD from HPD more effectively than single gene detection, providing a novel method for guiding clinical immune treatment.
PubMed: 38023206
DOI: 10.3389/fonc.2023.1231094 -
Frontiers in Oncology 2024There is no theory to quantitatively describe the complex tumor ecosystem. At the same time, cancer immunotherapy is considered a revolution in oncology, but the methods...
OBJECTIVES
There is no theory to quantitatively describe the complex tumor ecosystem. At the same time, cancer immunotherapy is considered a revolution in oncology, but the methods used to describe tumors and the criteria used to evaluate efficacy are not keeping pace. The purpose of this study is to establish a new theory for quantitatively describing the tumor ecosystem, innovating the methods of tumor characterization, and establishing new efficacy evaluation criteria for cancer immunotherapy.
METHODS
Based on the mathematization of immune equilibrium theory and the establishment of immunodynamics in a previous study, the method of reverse immunodynamics was used, namely, the immune braking force was regarded as the tumor ecological force and the immune force was regarded as the tumor ecological braking force, and the concept of momentum in physics was applied to the tumor ecosystem to establish a series of tumor ecodynamic equations. These equations were used to solve the fundamental and applied problems of the complex tumor ecosystem.
RESULTS
A series of tumor ecodynamic equations were established. The tumor ecological momentum equations and their component factors could be used to distinguish disease progression, pseudoprogression, and hyperprogression in cancer immunotherapy. On this basis, the adjusted tumor momentum equations were established to achieve the equivalence of tumor activity (including immunosuppressive activity and metabolic activity) and tumor volume, which could be used to calculate individual disease remission rate and establish new efficacy evaluation criteria (ieRECIST) for immunotherapy of solid tumor based on tumor ecodynamics. At the same time, the concept of moving cube-to-force square ratio and its expression were proposed to calculate the area under the curve of tumor ecological braking force of blood required to achieve an individual disease remission rate when the adjusted tumor ecological momentum was known.
CONCLUSIONS
A new theory termed tumor ecodynamics emphasizing both tumor activity and tumor volume is established to solve a series of basic and applied problems in the complex tumor ecosystem. It can be predicted that the future will be the era of cancer immune ecotherapy that targets the entire tumor ecosystem.
PubMed: 38807760
DOI: 10.3389/fonc.2024.1335533 -
Seminars in Liver Disease Nov 2023Immune checkpoint inhibitors (ICIs) have emerged as effective therapeutics for multiple cancers. Nevertheless, as immunotherapeutic approaches are being extensively... (Review)
Review
Immune checkpoint inhibitors (ICIs) have emerged as effective therapeutics for multiple cancers. Nevertheless, as immunotherapeutic approaches are being extensively utilized, substantial hurdles have arisen for clinicians. These include countering ICIs resistance and ensuring precise efficacy assessments of these drugs, especially in the context of hepatocellular carcinoma (HCC). This review attempts to offer a holistic overview of the latest insights into the ICIs resistance mechanisms in HCC, the molecular underpinnings, and immune response. The intent is to inspire the development of efficacious combination strategies. This review also examines the unconventional response patterns, namely pseudoprogression (PsP) and hyperprogression (HPD). The prompt and rigorous evaluation of these treatment efficacies has emerged as a crucial imperative. Multiple clinical, radiological, and biomarker tests have been advanced to meticulously assess tumor response. Despite progress, precise mechanisms of action and predictive biomarkers remain elusive. This necessitates further investigation through prospective cohort studies in the impending future.
Topics: Humans; Carcinoma, Hepatocellular; Immune Checkpoint Inhibitors; Prospective Studies; Liver Neoplasms; Disease Progression
PubMed: 37931901
DOI: 10.1055/s-0043-1776127 -
BMJ Case Reports Jun 2024A man in his 70s with metastatic colorectal cancer presented with worsening clinical symptoms and imaging studies concerning for disease progression. He had received two...
A man in his 70s with metastatic colorectal cancer presented with worsening clinical symptoms and imaging studies concerning for disease progression. He had received two cycles of pembrolizumab, but due to his symptomatic presentation and significant decline in performance status, there was concern for worsening disease. Transitioning to hospice was briefly considered, given his clinical decline and the notable increase in tumour size. Despite the presence of clinical symptoms and radiographic findings, pseudoprogression-defined as an increase in the size(s) of and/or visual appearance of new lesion(s), followed by a response-was also considered as part of the diagnostic possibilities. Consequently, the decision was made to proceed with a third cycle of pembrolizumab. During his subsequent outpatient follow-up, the patient showed significant symptomatic improvement and reported a decrease in his palpable right flank mass. With further immunotherapy, the patient continued to demonstrate symptomatic and radiological improvement.
Topics: Humans; Male; Colorectal Neoplasms; Disease Progression; Antibodies, Monoclonal, Humanized; Aged; Antineoplastic Agents, Immunological; Neoplasm Metastasis
PubMed: 38871645
DOI: 10.1136/bcr-2023-258816 -
Current Opinion in Neurology Dec 2023To provide an updated overview of artificial intelligence (AI) applications in neuro-oncologic imaging and discuss current barriers to wider clinical adoption. (Review)
Review
PURPOSE OF REVIEW
To provide an updated overview of artificial intelligence (AI) applications in neuro-oncologic imaging and discuss current barriers to wider clinical adoption.
RECENT FINDINGS
A wide variety of AI applications in neuro-oncologic imaging have been developed and researched, spanning tasks from pretreatment brain tumor classification and segmentation, preoperative planning, radiogenomics, prognostication and survival prediction, posttreatment surveillance, and differentiating between pseudoprogression and true disease progression. While earlier studies were largely based on data from a single institution, more recent studies have demonstrated that the performance of these algorithms are also effective on external data from other institutions. Nevertheless, most of these algorithms have yet to see widespread clinical adoption, given the lack of prospective studies demonstrating their efficacy and the logistical difficulties involved in clinical implementation.
SUMMARY
While there has been significant progress in AI and neuro-oncologic imaging, clinical utility remains to be demonstrated. The next wave of progress in this area will be driven by prospective studies measuring outcomes relevant to clinical practice and go beyond retrospective studies which primarily aim to demonstrate high performance.
Topics: Humans; Artificial Intelligence; Prospective Studies; Retrospective Studies; Neuroimaging; Brain Neoplasms
PubMed: 37973024
DOI: 10.1097/WCO.0000000000001213 -
Radiotherapy and Oncology : Journal of... Jul 2023The interpretation of new enhancing lesions after radiotherapy for diffuse glioma remains a clinical challenge. We sought to characterize and classify new contrast... (Review)
Review
OBJECTIVE
The interpretation of new enhancing lesions after radiotherapy for diffuse glioma remains a clinical challenge. We sought to characterize and classify new contrast enhancing lesions in a historical multicenter cohort of patients with IDH mutated grade 2 diffuse glioma treated with photon therapy.
METHODS
We reviewed all follow-up MRI's of all patients treated with radiotherapy for histologically confirmed, IDH mutated diffuse grade 2 glioma between 1-1-2007 and 31-12-2018 in two tertiary referral centers. Disease progression (PD) was defined in accordance with the RANO criteria for progressive disease in low grade glioma. Pseudoprogression (psPD) was defined as any transient contrast-enhancing lesion between the end of radiotherapy and PD, or any new contrast-enhancing lesion that remained stable over a period of 12 months in patients who did not exhibit PD.
RESULTS
A total of 860 MRI's of 106 patients were reviewed. psPD was identified in 24 patients (23%) on 76 MRI's. The cumulative incidence of psPD was 13% at 1 year, 22% at 5 years, and 28% at 10 years. The mean of the observed maximal volume of psPD was 2.4 cc. The median Dmin in psPD lesions was 50.1 Gy. The presence of an 1p/19q codeletion was associated with an increased risk of psPD (subhazard ratio 2.34, p = 0.048). psPD was asymptomatic in 83% of patients.
CONCLUSION
The cumulative incidence of psPD in grade 2 diffuse glioma increases over time. Consensus regarding event definition and statistical analysis is needed for comparisons between series investigating psPD.
Topics: Humans; Brain Neoplasms; Glioma; Magnetic Resonance Imaging; Disease Progression; Mutation; Isocitrate Dehydrogenase; Multicenter Studies as Topic
PubMed: 37084885
DOI: 10.1016/j.radonc.2023.109674