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Cancer Gene Therapy Aug 2020With the advent of immunotherapy as an integral component of multidisciplinary solid tumor treatment, we are confronted by an unfamiliar and novel pattern of... (Review)
Review
With the advent of immunotherapy as an integral component of multidisciplinary solid tumor treatment, we are confronted by an unfamiliar and novel pattern of radiographic responses to treatment. Enlargement of tumors or even new lesions may not represent progression, but rather reflect what will ultimately evolve into a clinically beneficial response. In addition, the kinetics of radiographic changes in response to immunotherapy treatments may be distinct from what has been observed with cytotoxic chemotherapy and radiation. The phenomenon of pseudoprogression has been documented in patients receiving immunotherapeutic agents, such as checkpoint inhibitors and cellular therapies. Currently, there are no clinical response guidelines that adequately account for pseudoprogression and solid tumor responses to immunotherapy in general. Even so, response criteria have evolved to account for the radiographic manifestations of novel therapies. The evolution of World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST), along with the emergence of immune-related response criteria (irRC) and the immune Response Evaluation Criteria in Solid Tumors (iRECIST) reflect the need for new frameworks. This review evaluates the relationship between pseudoprogression, clinical outcomes, and our current understanding of the biology of pseudoprogression. To achieve our goal, we discuss unusual response patterns in patients receiving immunotherapy. We seek to develop a deeper understanding of radiographic responses to immunotherapy such that clinical benefit is not underappreciated in individual patients and during clinical investigation.
Topics: Disease Progression; Humans; Immunotherapy; Neoplasms; Response Evaluation Criteria in Solid Tumors
PubMed: 31822814
DOI: 10.1038/s41417-019-0155-1 -
Canadian Journal of Neuroscience Nursing 2015Glioblastoma Multiforme (GBM) is the most common primary brain malignancy in humans and has a limited survival (median of 14.6 months). The goal of treatment is... (Review)
Review
Glioblastoma Multiforme (GBM) is the most common primary brain malignancy in humans and has a limited survival (median of 14.6 months). The goal of treatment is supportive rather than curative. Patients with a GBM struggle with uncertainty related to the illness trajectory. This uncertainty is compounded when possible progression is noted on imaging. Pseudoprogression (PsP) is an early treatment-related effect where there are apparent imaging changes suggesting progression, which then improve or stabilize through time. This paper provides a review of the literature on PsP in patients with high-grade gliomas. Insights in the patient and family experience of PsP will be informed by Mishel's Uncertainty in Illness Theory, research on patients' and families' neuro-oncology experience, and the author's nursing practice. Nursing implications will be proposed.
Topics: Attitude of Health Personnel; Attitude to Health; Brain Neoplasms; Disease Progression; Female; Glioblastoma; Humans; Male; Nursing Staff; Oncology Nursing; Patients; Uncertainty
PubMed: 26647493
DOI: No ID Found -
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 -
American Society of Clinical Oncology... May 2018Patterns of response and progression to immunotherapy may differ from those observed with drugs such as chemotherapy and molecularly targeted agents. Specifically, some... (Review)
Review
Patterns of response and progression to immunotherapy may differ from those observed with drugs such as chemotherapy and molecularly targeted agents. Specifically, some patients experience a response after progression that is retrospectively named pseudoprogression. This phenomenon of pseudoprogression, first reported in patients with melanoma who were treated with ipilimumab, has led to the development of immune-specific related response criteria, such as irRC (immune-related response criteria), irRECIST (immune-related RECIST), and iRECIST (immunotherapy RECIST) that allow continued treatment beyond progression. However, the rate of pseudoprogression has never exceeded 10% of patients across tumor types. Conversely, rapid progressions after immunotherapy, called hyperprogressions, were reported by three different teams in 9% to 29% of patients treated with immunotherapy. Because of the absence of control arms in these studies, it remains to be determined whether these rapid progressions reflect a detrimental effect of immunotherapy in these patients. Finally, preliminary data suggest that immunotherapy might also affect response to subsequent standard therapies. In total, given the rarity of pseudoprogressions across tumor types and the recent description of hyperprogressions, classic RECIST remains a reasonable and rational method to assess response to immunotherapy. Continuation of treatment beyond progression should be proposed only in carefully selected patients whose clinical conditions have improved and who have not experienced severe toxicities. Although there is an urgent need to identify predictive biomarkers of efficacy to immunotherapy, there is an equally urgent need to identify predictive factors of progression or possibly hyperprogression.
Topics: Biomarkers, Tumor; Disease Management; Disease Progression; Humans; Immunotherapy; Molecular Targeted Therapy; Neoplasms; Prognosis; Treatment Outcome
PubMed: 30231380
DOI: 10.1200/EDBK_200643 -
Journal of Oncology 2021Accurately and quickly differentiating true progression from pseudoprogression in glioma patients is still a challenge. This study aims to explore if dynamic... (Review)
Review
Accurately and quickly differentiating true progression from pseudoprogression in glioma patients is still a challenge. This study aims to explore if dynamic susceptibility contrast- (DSC-) MRI can improve the evaluation of glioma progression. We enrolled 65 glioma patients with suspected gadolinium-enhancing lesion. Longitudinal MRI follow-up (mean 590 days, range: 210-2670 days) or re-operation ( = 3) was used to confirm true progression ( = 51) and pseudoprogression ( = 14). We assessed the diagnostic performance of each MRI variable and the different combinations. Our results showed that the relative cerebral blood volume (rCBV) in the true progression group (1.094, 95%CI: 1.135-1.636) was significantly higher than that of the pseudoprogression group (0.541 ± 0.154) ( < 0.001). Among the 18 patients who had serial DSC-MRI, the rCBV of the progression group (0.480, 95%CI: 0.173-0.810) differed significantly from pseudoprogression (-0.083, 95%CI: -1.138-0.620) group (=0.015). With an rCBV threshold of 0.743, the sensitivity and specificity for discriminating true progression from pseudoprogression were 76.5% and 92.9%, respectively. The Cho/Cr and Cho/NAA ratios of the true progression group (2.520, 95%CI: 2.331-2.773; 2.414 ± 0.665, respectively) were higher than those of the pseudoprogression group (1.719 ± 0.664; 1.499 ± 0.500, respectively) ((=0.001), ( < 0.001), respectively). The areas under ROC curve (AUCs) of enhancement pattern, MRS, and DSC-MRI for the differentiation were 0.782, 0.881, and 0.912, respectively. Interestingly, when combined enhancement pattern, MRS, and DSC-MRI variables, the AUC was 0.965 and achieved sensitivity 90.2% and specificity 100.0%. Our results suggest that DSC-MRI can significantly improve the diagnostic performance for identifying glioma progression. DSC-MRI combined with conventional MRI may promptly distinguish true gliomas progression from pseudoprogression when the suspected gadolinium-enhancing lesion was found, without the need for a long-term follow-up.
PubMed: 33628239
DOI: 10.1155/2021/1696387 -
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 -
Neuroimaging Clinics of North America Feb 2015The current treatment of glioblastoma patients based on surgery, radiation, and chemotherapy has achieved modest improvement in progression-free survival. In this... (Review)
Review
The current treatment of glioblastoma patients based on surgery, radiation, and chemotherapy has achieved modest improvement in progression-free survival. In this direction, personalized treatment is the next achievement for better patient management and increased overall survival. Genetic characterization of high-grade gliomas by MR imaging is the goal in neuroimaging. The main genetic alterations described in these neoplasms, implications in patient treatment, and prognosis are reviewed. MR imaging features and novel techniques are correlated with the main genetic aspects of such tumors. Posttreatment phenomena, such as pseudoprogression and pseudoresponse, are analyzed in association with the genetic expression of these tumors.
Topics: Brain; Brain Neoplasms; Genomics; Glioblastoma; Humans; Magnetic Resonance Imaging; Neuroimaging
PubMed: 25476517
DOI: 10.1016/j.nic.2014.09.011 -
Journal of Thoracic Disease Feb 2018Immunotherapy agents in metastatic non-small cell lung cancer (NSCLC) can result in improved quality of life and survival when compared with platinum-based chemotherapy.... (Review)
Review
Immunotherapy agents in metastatic non-small cell lung cancer (NSCLC) can result in improved quality of life and survival when compared with platinum-based chemotherapy. Novel response patterns such as pseudoprogression and hyperprogression, however, have been described and pose a challenge to treating physicians. Predictors of hyperprogressive disease (HPD) have not yet been identified. Evaluation and management by a multidisciplinary team involving medical and radiation oncologists, thoracic radiologists, and proceduralists is necessary to identify this subset of patients in a timely manner. Repeat biopsy distinguishes HPD from pseudoprogression and may eventually elucidate predictive biomarkers. We describe the epidemiology of these two phenomena, their diagnostic criteria, and their relevance for interventional pulmonologists.
PubMed: 29607190
DOI: 10.21037/jtd.2018.01.79 -
Biomedicines Jan 2022Glioblastoma is the most frequent malignant primitive brain tumor in adults. The treatment includes surgery, radiotherapy, and chemotherapy. During follow-up, combined... (Review)
Review
BACKGROUND
Glioblastoma is the most frequent malignant primitive brain tumor in adults. The treatment includes surgery, radiotherapy, and chemotherapy. During follow-up, combined chemoradiotherapy can induce treatment-related changes mimicking tumor progression on medical imaging, such as pseudoprogression (PsP). Differentiating PsP from true progression (TP) remains a challenge for radiologists and oncologists, who need to promptly start a second-line treatment in the case of TP. Advanced magnetic resonance imaging (MRI) techniques such as diffusion-weighted imaging, perfusion MRI, and proton magnetic resonance spectroscopic imaging are more efficient than conventional MRI in differentiating PsP from TP. None of these techniques are fully effective, but current advances in computer science and the advent of artificial intelligence are opening up new possibilities in the imaging field with radiomics (i.e., extraction of a large number of quantitative MRI features describing tumor density, texture, and geometry). These features are used to build predictive models for diagnosis, prognosis, and therapeutic response.
METHOD
Out of 7350 records for MR spectroscopy, GBM, glioma, recurrence, diffusion, perfusion, pseudoprogression, radiomics, and advanced imaging, we screened 574 papers. A total of 228 were eligible, and we analyzed 72 of them, in order to establish the role of each imaging modality and the usefulness and limitations of radiomics analysis.
PubMed: 35203493
DOI: 10.3390/biomedicines10020285 -
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