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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 -
Advances in Radiation Oncology 2023Pseudoprogression mimicking recurrent glioblastoma remains a diagnostic challenge that may adversely confound or delay appropriate treatment or clinical trial...
PURPOSE
Pseudoprogression mimicking recurrent glioblastoma remains a diagnostic challenge that may adversely confound or delay appropriate treatment or clinical trial enrollment. We sought to build a radiomic classifier to predict pseudoprogression in patients with primary isocitrate dehydrogenase wild type glioblastoma.
METHODS AND MATERIALS
We retrospectively examined a training cohort of 74 patients with isocitrate dehydrogenase wild type glioblastomas with brain magnetic resonance imaging including dynamic contrast enhanced T1 perfusion before resection of an enhancing lesion indeterminate for recurrent tumor or pseudoprogression. A recursive feature elimination random forest classifier was built using nested cross-validation without and with O-methylguanine-DNA methyltransferase status to predict pseudoprogression.
RESULTS
A classifier constructed with cross-validation on the training cohort achieved an area under the receiver operating curve of 81% for predicting pseudoprogression. This was further improved to 89% with the addition of O-methylguanine-DNA methyltransferase status into the classifier.
CONCLUSIONS
Our results suggest that radiomic analysis of contrast T1-weighted images and magnetic resonance imaging perfusion images can assist the prompt diagnosis of pseudoprogression. Validation on external and independent data sets is necessary to verify these advanced analyses, which can be performed on routinely acquired clinical images and may help inform clinical treatment decisions.
PubMed: 36711062
DOI: 10.1016/j.adro.2022.100916 -
Clinical Nuclear Medicine Apr 2023Recognition of pseudoprogression in malignant glioma is one of the major challenges in the Response Assessment in Neuro-Oncology criteria. Somatostatin receptors were...
Recognition of pseudoprogression in malignant glioma is one of the major challenges in the Response Assessment in Neuro-Oncology criteria. Somatostatin receptors were overexpressed on the surface of the most high-grade glioma. The corresponding PET imaging is used for planning radiation and radionuclide therapy. However, the heterogeneity of somatostatin receptors distribution is mainly responsible for the lack of specificity. Here we reported a case of a 35-year-old man with mesenchymal oligodendroglioma operation and radiotherapy 19 months ago. 68 Ga-DOTATATE PET showed intense uptake near the operation region, which has been misinterpreted as tumor recurrence.
Topics: Male; Humans; Adult; Positron Emission Tomography Computed Tomography; Receptors, Somatostatin; Neuroendocrine Tumors; Neoplasm Recurrence, Local; Organometallic Compounds; Glioma
PubMed: 36728314
DOI: 10.1097/RLU.0000000000004511 -
Neuro-oncology Practice Jun 2017Management of glioblastoma is complicated by pseudoprogression, a radiological phenomenon mimicking progression. This retrospective cohort study investigated the...
BACKGROUND
Management of glioblastoma is complicated by pseudoprogression, a radiological phenomenon mimicking progression. This retrospective cohort study investigated the incidence, prognostic implications, and most clinically appropriate definition of pseudoprogression.
METHODS
Consecutive glioblastoma patients treated at the Juravinski Hospital and Cancer Centre, Hamilton, Ontario between 2004 and 2012 with temozolomide chemoradiotherapy and with contrast-enhanced MRI at standard imaging intervals were included. At each imaging interval, patient responses as per the RECIST (Response Evaluation Criteria in Solid Tumors), MacDonald, and RANO (Response Assessment in Neuro-Oncology) criteria were reported. Based on each set of criteria, subjects were classified as having disease response, stable disease, pseudoprogression, or true progression. The primary outcome was overall survival.
RESULTS
The incidence of pseudoprogression among 130 glioblastoma patients treated with chemoradiotherapy was 15%, 19%, and 23% as defined by RANO, MacDonald, and RECIST criteria, respectively. Using the RANO definition, median survival for patients with pseudoprogression was 13.0 months compared with 12.5 months for patients with stable disease (hazard ratio [HR]=0.70; 95% confidence interval [CI], 0.35-1.42). Similarly, using the MacDonald definition, median survival for the pseudoprogression group was 11.8 months compared with 12.0 months for the stable disease group (HR=0.86; 95% CI, 0.47-1.58). Furthermore, disease response compared with stable disease was also similar using the RANO (HR=0.52; 95% CI, 0.20-1.35) and MacDonald (HR=0.51: 95% CI, 0.20-1.31) definitions.
CONCLUSIONS
Of all conventional glioblastoma response criteria, the RANO criteria gave the lowest incidence of pseudoprogression. Regardless of criteria, patients with pseudoprogression did not have statistically significant difference in survival compared with patients with stable disease.
PubMed: 31386017
DOI: 10.1093/nop/npw021 -
Clinical Journal of Gastroenterology Jun 2022A 74-year-old Asian man was referred for numb and painful sensation in the right upper limb. He was diagnosed with lung large cell neuroendocrine carcinoma and started...
A 74-year-old Asian man was referred for numb and painful sensation in the right upper limb. He was diagnosed with lung large cell neuroendocrine carcinoma and started receiving durvalumab therapy as second-line treatment. Sixteen days after the first dose, laboratory examination revealed increased liver enzyme levels and a marked inflammatory response. Contrast-enhanced computed tomography revealed an unenhanced tumor measuring approximately 25 mm in the head of pancreas and dilation of the intra- and extra-hepatic bile ducts. Magnetic resonance cholangiopancreatography confirmed stricture in the lower common bile duct and main pancreatic duct. We suspected acute cholangitis caused by a pancreatic cancer and performed an endoscopic biliary drainage. Two weeks after the procedure, computed tomography revealed significant shrinkage of the tumor. The tumor gradually reduced and pseudoprogression in lung large cell neuroendocrine carcinoma was ultimately diagnosed. Acute cholangitis caused by pseudoprogression resembling pancreatic cancer during immune therapy has not yet been reported. We are mindful that pseudoprogression should be considered as a differential diagnosis if a rapidly developing pancreatic tumor is observed during immunotherapy.
Topics: Aged; Antibodies, Monoclonal; Carcinoma, Neuroendocrine; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis; Humans; Lung; Male; Pancreatic Neoplasms
PubMed: 34984635
DOI: 10.1007/s12328-021-01588-z -
Respirology Case Reports Apr 2023The incidence rate of pseudoprogression during immune checkpoint inhibitor monotherapy for non-small cell lung cancer is reportedly 3.6%-6.9%, while pseudoprogression...
The incidence rate of pseudoprogression during immune checkpoint inhibitor monotherapy for non-small cell lung cancer is reportedly 3.6%-6.9%, while pseudoprogression during chemoimmunotherapy is rare. Reports on pseudoprogression during dual immunotherapy combined with chemotherapy are lacking. Herein, a 55-year-old male with invasive mucinous adenocarcinoma (cT2aN2M1c [OTH, PUL], stage IVB, and programmed death-ligand 1 expression <1%), renal dysfunction, and disseminated intravascular coagulation was treated with carboplatin, solvent-based paclitaxel, nivolumab, and ipilimumab. After treatment initiation, computed tomography (CT) on day 14 showed disease progression. The patient was diagnosed with pseudoprogression because of a lack of symptoms, improved platelet count, and decreased fibrin/fibrinogen degradation product levels. CT on day 36 showed a reduction in the primary lesion size, multiple lung metastases, and mesenteric metastases. Therefore, pseudoprogression should be considered during dual immunotherapy with chemotherapy.
PubMed: 36926450
DOI: 10.1002/rcr2.1122 -
Neurosurgery Dec 2023The pathophysiology of vestibular schwannoma (VS) pseudoprogression after Gamma Knife radiosurgery (GKRS) remains unclear. Radiological features in pretreatment magnetic...
BACKGROUND AND OBJECTIVES
The pathophysiology of vestibular schwannoma (VS) pseudoprogression after Gamma Knife radiosurgery (GKRS) remains unclear. Radiological features in pretreatment magnetic resonance images may help predict VS pseudoprogression. This study used VS radiological features quantified using an automated segmentation algorithm to predict pseudoprogression after GKRS treatment.
METHODS
This is a retrospective study comprising 330 patients with VS who received GKRS. After image preprocessing and T2W/contrast-enhanced T1-weighted image (CET1W) image generation, with fuzzy C-means clustering, VSs were segmented into solid and cystic components and classified as solid and cystic. Relevant radiological features were then extracted. The response to GKRS was classified into "nonpseudoprogression" and "pseudoprogression/fluctuation". The Z test for two proportions was used to compare solid and cystic VS for the likelihood of pseudoprogression/fluctuation. Logistic regression was used to assess the correlation between clinical variables and radiological features and response to GKRS.
RESULTS
The likelihood of pseudoprogression/fluctuation after GKRS was significantly higher for solid VS compared with cystic VS (55% vs 31%, P < .001). For the entire VS cohort, multivariable logistic regression revealed that a lower mean tumor signal intensity (SI) in T2W/CET1W images was associated with pseudoprogression/fluctuation after GKRS ( P = .001). For the solid VS subgroup, a lower mean tumor SI in T2W/CET1W images ( P = .035) was associated with pseudoprogression/fluctuation after GKRS. For the cystic VS subgroup, a lower mean SI of the cystic component in T2W/CET1W images ( P = .040) was associated with pseudoprogression/fluctuation after GKRS.
CONCLUSION
Pseudoprogression is more likely to occur in solid VS compared with cystic VS. Quantitative radiological features in pretreatment magnetic resonance images were associated with pseudoprogression after GKRS. In T2W/CET1W images, solid VS with a lower mean tumor SI and cystic VS with a lower mean SI of cystic component were more likely to have pseudoprogression after GKRS. These radiological features can help predict the likelihood of pseudoprogression after GKRS.
Topics: Humans; Neuroma, Acoustic; Treatment Outcome; Radiosurgery; Retrospective Studies; Radiography
PubMed: 37432016
DOI: 10.1227/neu.0000000000002599 -
Journal of Medical Case Reports Jul 2022Pseudoprogression, the initial apparent worsening of cancer prior to eventual improvement, is a documented feature of immune checkpoint inhibitor administration and...
BACKGROUND
Pseudoprogression, the initial apparent worsening of cancer prior to eventual improvement, is a documented feature of immune checkpoint inhibitor administration and presents a challenge to clinicians distinguishing true progression from pseudoprogression. This phenomenon does not typically occur with traditional cytotoxic chemotherapy. We present a case in which a patient treated with combination carboplatin-pemetrexed plus pembrolizumab experienced transient radiographic worsening of disease with subsequent regression.
CASE PRESENTATION
A 65-year-old never-smoking white male with advanced sarcomatoid non-small cell lung cancer (NSCLC) harboring a MET exon 14 skipping mutation and with PD-L1 tumor proportion score of 80% was initiated on combination chemotherapy plus immune checkpoint inhibitor (ICI) therapy after progression on a MET inhibitor. After two cycles of carboplatin-pemetrexed plus pembrolizumab, repeat imaging suggested disease progression. Following discontinuation of the carboplatin-pemetrexed plus pembrolizumab regimen, the patient reported improved symptoms and energy levels, which were attributed to the waning of treatment-associated toxicities. On the day prior to initiation of the next planned line of therapy, repeat imaging was preformed to provide a baseline for treatment efficacy. Imaging revealed improvement compared to the prior imaging. Chemotherapy with carboplatin-pemetrexed plus pembrolizumab was resumed, with response ongoing 8 months later.
CONCLUSIONS
Pseudoprogression is a documented feature of ICI administration. Pseudoprogression is not typically observed in patients treated with traditional cytotoxic chemotherapy and has not yet been documented in patients treated with combination cytotoxic chemotherapy plus immunotherapy. At this time, there are no reliable means to predict or diagnose these rare events; therefore, more studies should be conducted to understand which patients are predisposed to developing this phenomenon and to increase clinical recognition.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Lung Neoplasms; Male; Pemetrexed
PubMed: 35871685
DOI: 10.1186/s13256-022-03485-6 -
Journal of Neuro-oncology Jan 2020It can be challenging to differentiate pseudoprogression from progression. We assessed the ability of dynamic contrast enhanced T1 MRI (DCE-MRI) perfusion to identify...
PURPOSE
It can be challenging to differentiate pseudoprogression from progression. We assessed the ability of dynamic contrast enhanced T1 MRI (DCE-MRI) perfusion to identify pseudoprogression in melanoma brain metastases.
METHODS
Patients with melanoma brain metastases who underwent immunotherapy and DCE-MRI were identified. Enhancing lesions ≥ 5mm in diameter on DCE-MRI and that were new or increased in size between a week from beginning the treatment, and a month after completing the treatment were included in the analysis. The 90th percentiles of rVp and rKtrans and the presence or absence of hemorrhage were recorded. Histopathology served as the reference standard for pseudoprogression. If not available, pseudoprogression was defined as neurological and radiographic stability or improvement without any new treatment for ≥ 2 months.
RESULTS
Forty-four patients were identified; 64% received ipilimumab monotherapy for a median duration of 9 weeks (range, 1-138). Sixty-four lesions in 44 patients were included in the study. Of these, nine lesions in eight patients were determined to be pseudoprogression and seven lesions were previously irradiated. Forty-four progression lesions and eight pseudoprogression lesions were hemorrhagic. Median lesion volume for pseudoprogression and progression were not significantly different, at 2.3 cm and 3.2 cm, respectively (p = 0.82). The rVp was smaller in pseudoprogression versus progression, at 2.2 and 5.3, respectively (p = 0.02), and remained significant after false discovery rate adjustment (p = 0.04).
CONCLUSIONS
Pseudoprogression exhibited significantly lower rVp on DCE-MRI compared with progression. This knowledge can be useful for managing growing lesions in patients with melanoma brain metastases who are receiving immunotherapy.
Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Disease Progression; Female; Follow-Up Studies; Humans; Immunotherapy; Magnetic Resonance Imaging; Male; Melanoma; Middle Aged; Prognosis; Retrospective Studies; Survival Rate
PubMed: 31873875
DOI: 10.1007/s11060-019-03379-6 -
Clinical Nuclear Medicine Aug 2020After standard treatment of glioblastoma, pseudoprogression versus true progression is a clinical challenge. Indeed, to differentiate these 2 on contrast MRI (cMRI) is...
After standard treatment of glioblastoma, pseudoprogression versus true progression is a clinical challenge. Indeed, to differentiate these 2 on contrast MRI (cMRI) is problematic. In recent time, Ga-prostate-specific membrane antigen-11 (Ga-PSMA) PET/CT has been suggested to have high accuracy in glioblastoma recurrence. We present a case of a 40-year-old man with right frontotemporal glioblastoma underwent surgery and radiotherapy. One month posttreatment cMRI showed a new enhancing lesion in the right hippocampal region, which was also positive on Ga-PSMA-11 PET/CT. On follow-up with conservative management, both cMRI and Ga-PSMA-11 PET/CT showed regression in new lesion, hence suggest pseudoprogression.
Topics: Adult; Brain Neoplasms; Gallium Isotopes; Gallium Radioisotopes; Glioblastoma; Humans; Male; Membrane Glycoproteins; Neoplasm Recurrence, Local; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals
PubMed: 32520501
DOI: 10.1097/RLU.0000000000003121