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Case Reports in Oncology 2021Immune checkpoint inhibitors (ICI) have drastically changed the landscape of metastatic melanoma management, thus significantly improving survival. Clinically, assessing...
Immune checkpoint inhibitors (ICI) have drastically changed the landscape of metastatic melanoma management, thus significantly improving survival. Clinically, assessing treatment response may be challenging in a portion of cases due to a massive influx of immune cells into the tumor microenvironment, causing a transient increase in the target lesion size. This phenomenon, coined pseudoprogression, can occur in 5-10% of metastatic patients, and it is commonly followed by a tumor regression. Its incidence, however, may be underestimated, given its ephemeral nature and often being documented in visceral metastatic lesions, which are only assessed by imaging scans every 2-3 months. More recently, ICI has been studied in the neoadjuvant setting, yielding durable pathological responses in patients with cutaneous melanoma. Here, we report a case of a large retroauricular melanoma mass with regional lymph node involvement treated with ipilimumab and nivolumab combination therapy that developed pseudoprogression. Initially documented as an increase in size along with inflammatory features, followed by a dramatic clinical improvement. A complete regression was pathologically documented after 3 months and the patient remains disease-free for 14 months after treatment initiation. In conclusion, we document a pseudoprogression case during neoadjuvant ICI treatment and raise the question of whether the incidence of this phenomenon is higher when observed in superficial lesions, which can be assessed by routine physical exam.
PubMed: 34248554
DOI: 10.1159/000516036 -
American Society of Clinical Oncology... Jan 2019Atypical patterns of response to immunotherapy have been observed, including the abscopal effect and pseudoprogression. Although both are infrequent in head and neck... (Review)
Review
Atypical patterns of response to immunotherapy have been observed, including the abscopal effect and pseudoprogression. Although both are infrequent in head and neck squamous cell carcinoma, the synergism between radiation and checkpoint blockade therapy has generated excitement for exploitation of the abscopal effect. However, robust abscopal tumor regression observed in preclinical models has not translated to clinical experience. The optimal sequencing of radiotherapy with immunotherapy and dosage of radiation to target lesions to elicit this effect is being explored in clinical trials. Predictive markers of efficacy must be studied further to identify patients who may benefit from an abscopal effect and continued checkpoint inhibitor blockade beyond initial signs of radiologic progression. Given the rarity of pseudoprogression in head and neck squamous cell carcinoma, patients should be carefully selected to continue on immunotherapy, despite early radiologic signs of progression, given the risk of aggressive true progression and clinical deterioration that may result in missed opportunities for alternate treatments.
Topics: Animals; Clinical Trials as Topic; Disease Progression; Drug Evaluation, Preclinical; Head and Neck Neoplasms; Humans; Immunotherapy; Radiotherapy; Treatment Outcome
PubMed: 31099687
DOI: 10.1200/EDBK_238339 -
Advanced Biosystems Dec 2020Liquid biopsy for the detection and monitoring of central nervous system tumors is of significant clinical interest. At initial diagnosis, the majority of patients with... (Review)
Review
Liquid biopsy for the detection and monitoring of central nervous system tumors is of significant clinical interest. At initial diagnosis, the majority of patients with central nervous system tumors undergo magnetic resonance imaging (MRI), followed by invasive brain biopsy to determine the molecular diagnosis of the WHO 2016 classification paradigm. Despite the importance of MRI for long-term treatment monitoring, in the majority of patients who receive chemoradiation therapy for glioblastoma, it can be challenging to distinguish between radiation treatment effects including pseudoprogression, radiation necrosis, and recurrent/progressive disease based on imaging alone. Tissue biopsy-based monitoring is high risk and not always feasible. However, distinguishing these entities is of critical importance for the management of patients and can significantly affect survival. Liquid biopsy strategies including circulating tumor cells, circulating free DNA, and extracellular vesicles have the potential to afford significant useful molecular information at both the stage of diagnosis and monitoring for these tumors. Here, current liquid biopsy-based approaches in the context of tumor monitoring to differentiate progressive disease from pseudoprogression and radiation necrosis are reviewed.
Topics: Biomarkers, Tumor; Brain; Brain Neoplasms; Circulating Tumor DNA; Disease Progression; Extracellular Vesicles; Glioblastoma; Humans; Liquid Biopsy; Necrosis; Neoplastic Cells, Circulating; Radiation Injuries; Radiotherapy
PubMed: 32484293
DOI: 10.1002/adbi.202000029 -
Journal of Clinical Oncology : Official... Oct 2016
Topics: Brain Neoplasms; Disease Progression; Glioblastoma; Humans; Magnetic Resonance Imaging
PubMed: 27458299
DOI: 10.1200/JCO.2016.67.6759 -
Wiener Medizinische Wochenschrift (1946) Jan 2011This methodological paper on magnetic resonance tomography imaging recalls the assessment criteria on therapy response of Glioblastoma multiforme as defined by David... (Comparative Study)
Comparative Study Review
This methodological paper on magnetic resonance tomography imaging recalls the assessment criteria on therapy response of Glioblastoma multiforme as defined by David Macdonald in 1990 that have remained State of the Art since their first publication. It defines the terms "pseudoprogression", "radiation induced necrosis" and "pseudoresponse". These phenomena are seen increasingly since the introduction of radiochemotherapy with Temozolomide as treatment standard in glioblastoma and since the use of antiangiogenetic therapy in malignant gliomas. Therefore, the assessment criteria have been recently updated with the newly proposed "RANO criteria (Response assessment in Neuro-Oncology)". Furthermore, the potential of additional information to conventional MR by MR perfusion, MR diffusion and MR spectroscopy is briefly discussed.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Alkylating; Bevacizumab; Brain; Brain Neoplasms; Combined Modality Therapy; Cranial Irradiation; Dacarbazine; Diagnosis, Differential; Diagnostic Imaging; Diffusion Magnetic Resonance Imaging; Disease Progression; Glioblastoma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Positron-Emission Tomography; Radiation Injuries; Sensitivity and Specificity; Temozolomide; Tumor Burden
PubMed: 21312094
DOI: 10.1007/s10354-010-0860-8 -
Frontiers in Immunology 2021The inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led to significant survival benefits in patients with various metastatic cancers....
BACKGROUND
The inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led to significant survival benefits in patients with various metastatic cancers. Concurrently, an increasing number of neurological immune related adverse events (IRAE) has been observed. In this retrospective analysis, we examine the ICI-induced incidence of cerebral pseudoprogression and propose a classification system.
METHODS
We screened our hospital information system to identify patients with any in-house ICI treatment for any tumor disease during the years 2007-2019. All patients with cerebral MR imaging (cMRI) of sufficient diagnostic quality were included. cMRIs were retrospectively analyzed according to immunotherapy response assessment for neuro-oncology (iRANO) criteria.
RESULTS
We identified 12 cases of cerebral pseudoprogression in 123 patients treated with ICIs and sufficient MRI. These patients were receiving ICI therapy for lung cancer (n=5), malignant melanoma (n=4), glioblastoma (n=1), hepatocellular carcinoma (n=1) or lymphoma (n=1) when cerebral pseudoprogression was detected. Median time from the start of ICI treatment to pseudoprogression was 5 months. All but one patient developed neurological symptoms. Three different patterns of cerebral pseudoprogression could be distinguished: new or increasing contrast-enhancing lesions, new or increasing T2 predominant lesions and cerebral vasculitis type pattern.
CONCLUSION
Cerebral pseudoprogression followed three distinct patterns and was detectable in 3.2% of all patients during ICI treatment and in 9.75% of the patients with sufficient brain imaging follow up. The fact that all but one of the affected patients developed neurological symptoms, which would be classified as progressive disease according to iRANO criteria, mandates vigilance in the diagnosis and treatment of ICI-induced cerebral lesions.
Topics: Adult; Aged; Brain; Brain Neoplasms; Female; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Retrospective Studies
PubMed: 35046955
DOI: 10.3389/fimmu.2021.798811 -
Journal of the National Comprehensive... Feb 2023Immune checkpoint inhibitor (ICI) treatment in patients with microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) tumors holds promise in reshaping...
BACKGROUND
Immune checkpoint inhibitor (ICI) treatment in patients with microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) tumors holds promise in reshaping organ preservation in rectal cancer. However, the benefits are accompanied by distinctive patterns of response, introducing a dilemma in the response evaluation for clinical decision-making.
PATIENTS AND METHODS
Patients with locally advanced rectal cancer with MSI-H/dMMR tumors receiving neoadjuvant ICI (nICI) treatment (n=13) and matched patients receiving neoadjuvant chemoradiotherapy (nCRT; n=13) were included to compare clinical response and histopathologic features.
RESULTS
Among the 13 patients receiving nICI treatment, in the final radiologic evaluation prior to surgery (at a median of 103 days after initiation of therapy), progressive disease (n=3), stable disease (n=1), partial response (n=7), and complete response (n=2) were observed. However, these patients were later confirmed as having pathologic complete response, resulting in pseudoprogression and pseudoresidue with incidences of 23.1% (n=3) and 76.9% (n=10), respectively, whereas no pseudoprogression was found in the 13 patients receiving nCRT. We further revealed the histopathologic basis underlying the pseudoprogression and pseudoresidue by discovering the distinctive immune-related regression features after nICI treatment, including fibrogenesis, dense lymphocytes, and plasma cell infiltration.
CONCLUSIONS
Pseudoprogression and pseudoresidue were unique and prevalent response patterns in MSI-H/dMMR rectal cancer after nICI treatment. Our findings highlight the importance of developing specific strategies for response evaluation in neoadjuvant immunotherapy to identify patients with a good response in whom sphincter/organ-preserving or watch-and-wait strategies may be considered.
Topics: Humans; Immune Checkpoint Inhibitors; Neoadjuvant Therapy; Rectal Neoplasms; Colorectal Neoplasms; Microsatellite Instability; DNA Mismatch Repair
PubMed: 36791752
DOI: 10.6004/jnccn.2022.7071 -
Journal of Clinical Oncology : Official... Sep 2008
Topics: Central Nervous System Neoplasms; Disease Progression; Glioblastoma; Humans
PubMed: 18779626
DOI: 10.1200/JCO.2008.18.4440 -
Zhongguo Fei Ai Za Zhi = Chinese... Apr 2024The advent of immune checkpoint inhibitors (ICIs) has greatly improved the prognosis of advanced lung cancer patients, but can lead to pseudoprogression (PsP), which... (Review)
Review
The advent of immune checkpoint inhibitors (ICIs) has greatly improved the prognosis of advanced lung cancer patients, but can lead to pseudoprogression (PsP), which complicates clinical evaluation and management. PsP is manifested as temporary enlargement of the tumour or the appearance of new lesions, etc., and improvement in imaging occurs with continued treatment, mostly without worsening of clinical symptoms. Currently, there are still difficulties in the early diagnosis of PsP, and its occurrence mechanism is not yet clear, lacking good predictive factors and related biomarkers. This article reviews the current research status of PsP of ICIs in non-small cell lung cancer in order to provide helpful clinical strategies for oncologists using these drugs. .
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Disease Progression
PubMed: 38769834
DOI: 10.3779/j.issn.1009-3419.2024.101.10 -
Radiologia 2019Immunotherapy is a new treatment in advanced lung cancer that works by modulating the immune response against malignant cells. One aspect that is challenging for...
OBJECTIVES
Immunotherapy is a new treatment in advanced lung cancer that works by modulating the immune response against malignant cells. One aspect that is challenging for radiologists in the evaluation of the response to immunotherapy is the phenomenon of pseudoprogression, in which the infiltration of inflammatory cells causes lesions to increase in size or new lesions to appear and then decrease in size or disappear. Pseudoprogression actually represents a response to treatment. We aimed to determine the frequency of pseudoprogression in patients with advanced stages of lung cancer treated with nivolumab.
PATIENTS AND METHODS
We included 56 patients with advanced stages of lung cancer treated with nivolumab as a second-line or later treatment. We analyzed CT studies done while patients were undergoing nivolumab treatment. Tumor pseudoprogression was defined as an increase in the size of lesions or appearance of new lesions followed by a decrease in size or disappearance of these lesions on follow-up CT studies 4 to 8 weeks later. We did a descriptive analysis.
RESULTS
In 15 patients, it was impossible to evaluate possible pseudoprogression because a second CT study was unavailable due to change of treatment or death. Tumor pseudoprogression was observed in 5 (12.2%) of the 41 patients, in most cases within 12 weeks of treatment initiation (in the fourth cycle). A second episode of pseudoprogression occurred in 2 (40%) of the 5 patients with an initial episode; the second episode occurred more than 12 weeks after treatment initiation.
CONCLUSION
Tumor pseudoprogression occurred in 12.2% of patients with advanced stage lung cancer treated with nivolumab. An increase in lesion size or the appearance of new lesions must be assessed over time to avoid mistaking pseudoprogression for true progression of disease.
Topics: Aged; Antineoplastic Agents, Immunological; Carcinoma, Non-Small-Cell Lung; Disease Progression; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nivolumab; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 31300214
DOI: 10.1016/j.rx.2019.05.004