JNeurooncol. Author manuscript; available in PMC 2016 Mar 7.
Published in final edited form as:
J Neurooncol. 2015 May; 123(1): 141–150.
Published online 2015 Apr 18. doi: 10.1007/s11060-015-1774-5
PMCID: PMC4780341
NIHMSID: NIHMS762551
PMID: 25894594
Abstract
Pseudoprogression (psPD) refers to an increase in size or appearance of new areas of MRI contrast enhancement soon after completing chemoradiation, timely diagnosis of which has been a challenge. Given that tissue sampling of the MRI changes would be expected to accurately distinguish psPD from true progression when MRI changes are first seen, we examined the utility of surgery in diagnosing psPD and influencing patient outcome. We retrospectively reviewed data from adults with GBM who had MRI changes suggestive of progression within 3 months of chemoRT; of these, 34 underwent surgical resection. Three subsets–tumor, psPD or mixed-were identified based on histology and immunohistochemistry in the surgical group and by imaging characteristics in the nonsurgical group. A cohort of patients with stable disease post-chemoRT served as control. PFS and OS were determined using the Kaplan–Meier method and log rank analysis. Concordance for psPD between radiological interpretation and subsequent histological diagnosis was seen in only 32 % of cases (11/34) 95 %CI 19–49 %. A large proportion of patients had a histologically “mixed” pattern with tumor and treatment effect. No significant differences in PFS or OS were seen among the three subtypes. Surgical sampling and histologic review of MRI changes after chemoRT may not serve as a gold standard to distinguish psPD from true progression in GBM patients. Refinement of the histological criteria, careful intraoperative selection of regions of interest and advanced imaging modalities are needed for early differentiation of PsPD from progression to guide clinical management.
Keywords: Pseudoprogression, Glioblastoma, Glioma, Radiation, Chemotherapy, Surgery
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780341/
Characterization of pseudoprogression in patients with glioblastoma: is histology the gold standard?
How to differentiate pseudoprogression from true progression in cancer patients treated with immunotherapy
Abstract
Immunotherapy has achieved unprecedented clinical efficacy in patients with various types of advanced tumors; however, some patients experience delayed tumor shrinkage following an increase in tumor burden after such a therapeutic method. This phenomenon is called pseudoprogression and can lead to premature cessation of efficacious immunotherapeutic agents. Consequently, we summarized the available data on methods to differentiate pseudoprogression from true progression in patients who have been treated with immunotherapy including biomarkers, medical imaging techniques and biopsy. We also introduce hyperprogression and special pseudoprogression for improved evaluation of immunotherapy.
Keywords: Immunotherapy, psuedoprogression, ctDNA, PET, biopsy, hyperprogression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726978/
Immunotherapy has achieved unprecedented clinical efficacy in patients with various types of advanced tumors; however, some patients experience delayed tumor shrinkage following an increase in tumor burden after such a therapeutic method. This phenomenon is called pseudoprogression and can lead to premature cessation of efficacious immunotherapeutic agents. Consequently, we summarized the available data on methods to differentiate pseudoprogression from true progression in patients who have been treated with immunotherapy including biomarkers, medical imaging techniques and biopsy. We also introduce hyperprogression and special pseudoprogression for improved evaluation of immunotherapy.
Keywords: Immunotherapy, psuedoprogression, ctDNA, PET, biopsy, hyperprogression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726978/
Debbie
Association Between Circulating Tumor DNA and Pseudoprogression in Patients With Metastatic Melanoma Treated With ..
Association Between Circulating Tumor DNA and Pseudoprogression in Patients With Metastatic Melanoma Treated With Anti-Programmed Cell Death 1 Antibodies
Abstract
Importance: Longitudinal circulating tumor DNA (ctDNA) has been shown to predict response and survival in patients with metastatic melanoma treated with anti-programmed cell death 1 (PD-1) antibodies. Pseudoprogression, defined as radiologic finding of disease progression prior to response, has been a challenge to clinicians.
Objective: To establish whether ctDNA at baseline and up to week 12 of treatment can differentiate between the radiologic findings of pseudoprogression and true progression in patients with metastatic melanoma.
Design, setting, and participants: This explorative biomarker study examined circulating BRAF and NRAS mutations in a cohort of 125 patients with melanoma receiving PD-1 antibodies alone or in combination with ipilimumab between July 3, 2014, and May 24, 2016. Pseudoprogression was defined retrospectively as radiologic progression not confirmed as progressive disease at the next radiologic assessment. Plasma samples of ctDNA at baseline and while receiving treatment were taken for analysis prospectively over the first 12 weeks of treatment. Favorable ctDNA profile (undetectable ctDNA at baseline or detectable ctDNA at baseline followed by >10-fold decrease) and unfavorable ctDNA profile (detectable ctDNA at baseline that remained stable or increased) were correlated with response and prognosis.
Main outcomes and measures: Early differentiation of pseudoprogression from true progression using longitudinal ctDNA profile.
Results: According to guidelines by Response Evaluation Criteria in Solid Tumors (RECIST), progressive disease occurred in 29 of the 125 patients (23.2%). Of the 29 patients, 17 (59%) were 65 years or younger, 18 (62%) were men, 9 (31%) had pseudoprogression, and 20 (69%) had true progression. Of the 9 patients (7%) with confirmed pseudoprogression, all patients had a favorable ctDNA profile. At a median follow-up of 110 weeks, 7 of 9 patients (78%) were alive. All but 2 patients with true progression had an unfavorable ctDNA profile. Sensitivity of ctDNA for predicting pseudoprogression was 90% (95% CI, 68%-99%) and specificity was 100% (95% CI, 60%-100%). The 1-year survival for patients with RECIST-defined progressive disease and favorable ctDNA was 82% vs 39% for unfavorable ctDNA (hazard ratio [HR], 4.8; 95% CI, 1.6-14.3; P = .02). Overall survival was longer in patients with a partial response (54 of 125 patients [43%]) compared with patients with progressive disease and a favorable ctDNA profile (11 of 125 patients [9%]; HR, 0.09; 95% CI, 0.01-0.80; P < .01).
Conclusions and relevance: The results demonstrate that ctDNA profiles can accurately differentiate pseudoprogression from true progression of disease in patients with melanoma treated with PD-1 antibodies. Results of this blood test performed at regular intervals during systemic treatment reflect tumor biology and have potential as a powerful biomarker to predict long-term response and survival.
Conflict of interest statement
Conflict of Interest Disclosures: Drs Long, Kefford, and Carlino reported appointments to advisory boards for Merck (maker of pembrolizumab) and Bristol-Myers Squibb (maker of nivolumab and ipilimumab).
https://www.ncbi.nlm.nih.gov/m/pubmed/29423503/
Abstract
Importance: Longitudinal circulating tumor DNA (ctDNA) has been shown to predict response and survival in patients with metastatic melanoma treated with anti-programmed cell death 1 (PD-1) antibodies. Pseudoprogression, defined as radiologic finding of disease progression prior to response, has been a challenge to clinicians.
Objective: To establish whether ctDNA at baseline and up to week 12 of treatment can differentiate between the radiologic findings of pseudoprogression and true progression in patients with metastatic melanoma.
Design, setting, and participants: This explorative biomarker study examined circulating BRAF and NRAS mutations in a cohort of 125 patients with melanoma receiving PD-1 antibodies alone or in combination with ipilimumab between July 3, 2014, and May 24, 2016. Pseudoprogression was defined retrospectively as radiologic progression not confirmed as progressive disease at the next radiologic assessment. Plasma samples of ctDNA at baseline and while receiving treatment were taken for analysis prospectively over the first 12 weeks of treatment. Favorable ctDNA profile (undetectable ctDNA at baseline or detectable ctDNA at baseline followed by >10-fold decrease) and unfavorable ctDNA profile (detectable ctDNA at baseline that remained stable or increased) were correlated with response and prognosis.
Main outcomes and measures: Early differentiation of pseudoprogression from true progression using longitudinal ctDNA profile.
Results: According to guidelines by Response Evaluation Criteria in Solid Tumors (RECIST), progressive disease occurred in 29 of the 125 patients (23.2%). Of the 29 patients, 17 (59%) were 65 years or younger, 18 (62%) were men, 9 (31%) had pseudoprogression, and 20 (69%) had true progression. Of the 9 patients (7%) with confirmed pseudoprogression, all patients had a favorable ctDNA profile. At a median follow-up of 110 weeks, 7 of 9 patients (78%) were alive. All but 2 patients with true progression had an unfavorable ctDNA profile. Sensitivity of ctDNA for predicting pseudoprogression was 90% (95% CI, 68%-99%) and specificity was 100% (95% CI, 60%-100%). The 1-year survival for patients with RECIST-defined progressive disease and favorable ctDNA was 82% vs 39% for unfavorable ctDNA (hazard ratio [HR], 4.8; 95% CI, 1.6-14.3; P = .02). Overall survival was longer in patients with a partial response (54 of 125 patients [43%]) compared with patients with progressive disease and a favorable ctDNA profile (11 of 125 patients [9%]; HR, 0.09; 95% CI, 0.01-0.80; P < .01).
Conclusions and relevance: The results demonstrate that ctDNA profiles can accurately differentiate pseudoprogression from true progression of disease in patients with melanoma treated with PD-1 antibodies. Results of this blood test performed at regular intervals during systemic treatment reflect tumor biology and have potential as a powerful biomarker to predict long-term response and survival.
Conflict of interest statement
Conflict of Interest Disclosures: Drs Long, Kefford, and Carlino reported appointments to advisory boards for Merck (maker of pembrolizumab) and Bristol-Myers Squibb (maker of nivolumab and ipilimumab).
https://www.ncbi.nlm.nih.gov/m/pubmed/29423503/
Debbie