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Radiotherapy and Oncology : Journal of... Nov 2017To retrospectively assess the feasibility and safety of a sequential proton boost following conventional chemoradiation in high-grade glioma (HGG).
PURPOSE
To retrospectively assess the feasibility and safety of a sequential proton boost following conventional chemoradiation in high-grade glioma (HGG).
METHOD AND MATERIALS
Sixty-six consecutive patients with HGG were treated with 50.0 Gy photons (50.0-50.4 Gy) in 2.0 Gy (1.8-2.0 Gy) fractions, followed by a proton boost with 10 Gy equivalent (Gy(RBE)) in 2.0 Gy(RBE) fractions. Patients were matched one to one with 66 patients with HGG undergoing conventional radiation therapy (RT) with 60.0 Gy photons (59.4-60.0 Gy) in 2.0 Gy fractions (1.8-2.0 Gy). Matching criteria were age, WHO grade, Karnofsky's performance status, PTV size, temozolomide therapy (each p > 0.1). The study assessed progression-free survival (PFS), overall survival (OS), acute treatment-related toxicity (CTCAE v.4.03) and pseudoprogression (RANO criteria).
RESULTS
Median PFS and OS were similar in both treatment groups (bimodality RT, PFS: 8.8 months [2-32 months], OS 19.1 months [4-41 months]; photon-only RT, PFS: 7.2 months [2-39 months], 20.9 months [3-53 months]; p = 0.430 and p = 0.125). The median PTV of the proton boost was significantly smaller than the photon plan PTVs (each p < 0.001). Acute toxicity was mild. Toxicity ≥grade 2 was observed in 6 patients (9%) receiving bimodality RT and 9 patients (14%) receiving photon-only RT. Two types of severe adverse events (CTCAE grade 3) occurred solely in the photon-only group: severe increase in intracranial pressure (5%); and generalized seizures (3%). Pseudoprogression was rare, occurring on average 6 weeks after radiotherapy, and was balanced in both treatment groups (n = 4 each; 8%).
CONCLUSION
Delivering a proton boost to significantly smaller target volumes when compared to photon-only plans, yielded comparable progression and survival rates at lower CTCAE grade 3 acute toxicity rates. Pseudoprogression occurred rarely and evenly distributed in both treatment groups. Thus, bimodality RT was at least equivalent regarding outcome and potentially superior with respect to toxicity in patients with HGG.
SUMMARY
Treating patients with HGG with 50.0 Gy photons in 2.0 Gy fractions, followed by a proton boost with 10 Gy(RBE) in 2.0 Gy(RBE) fractions, is safe and feasible. Severe radiation-induced acute toxicity and pseudoprogression were rare in both treatment groups. Therefore, in this clinical setting, combined proton radiotherapy might be beneficial in terms of further risk reduction for treatment-related side effects. Interestingly, treatment volume reduction using a proton boost led to comparable survival and progression rates with decreased severe treatment-related toxicity compared to conventional photon radiotherapy.
Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy, Adjuvant; Dacarbazine; Disease Progression; Disease-Free Survival; Glioma; Humans; Male; Middle Aged; Neoplasm Grading; Proton Therapy; Retrospective Studies; Temozolomide; Young Adult
PubMed: 29050959
DOI: 10.1016/j.radonc.2017.09.040 -
Cancer Biology & Medicine Nov 2019As immunotherapy has gained increasing interest as a new foundation for cancer therapy, some atypical response patterns, such as pseudoprogression and hyperprogression,...
As immunotherapy has gained increasing interest as a new foundation for cancer therapy, some atypical response patterns, such as pseudoprogression and hyperprogression, have garnered the attention of physicians. Pseudoprogression is a phenomenon in which an initial increase in tumor size is observed or new lesions appear, followed by a decrease in tumor burden; this phenomenon can benefit patients receiving immunotherapy but often leads to premature discontinuation of treatment owing to the false judgment of progression. Accurately recognizing pseudoprogression is also a challenge for physicians. Because of the extensive attention on pseudoprogression, significant progress has been made. Some new criteria for immunotherapy, such as irRC, iRECIST and imRECIST, were proposed to accurately evaluate the response to immunotherapy. Many new detection indexes, such as ctDNA and IL-8, have also been used to identify pseudoprogression. In this review, the definition, evaluation criteria, mechanism, monitoring, management and prognosis of pseudoprogression are summarized, and diagnostic and treatment processes for patients with progression but with a suspicion of pseudoprogression are proposed; these processes could be helpful for physicians in clinical practice and enhances the understanding of pseudoprogression.
PubMed: 31908886
DOI: 10.20892/j.issn.2095-3941.2019.0144 -
Korean Journal of Radiology Aug 2021Immunotherapy is an effective treatment option for gynecological malignancies. Radiologists dealing with gynecological patients undergoing treatment with immune... (Review)
Review
Immunotherapy is an effective treatment option for gynecological malignancies. Radiologists dealing with gynecological patients undergoing treatment with immune checkpoint inhibitors should be aware of unconventional immune-related imaging features for the evaluation of tumor response and immune-related adverse events. In this paper, immune checkpoint inhibitors used for gynecological malignancies and their mechanisms of action are briefly presented. In the second part, patterns of pseudoprogression are illustrated, and different forms of immune-related adverse events are discussed.
Topics: Diagnostic Imaging; Female; Genital Neoplasms, Female; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Radiologists
PubMed: 34047505
DOI: 10.3348/kjr.2020.1299 -
Journal of Cancer Research and... 2023Systemic therapy in lung cancer is mainstay of treatment as most patients present in advanced stages, with rising importance of new immunotherapy agents.
BACKGROUND
Systemic therapy in lung cancer is mainstay of treatment as most patients present in advanced stages, with rising importance of new immunotherapy agents.
PURPOSE
To compare the RECIST 1.1 and the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECISTs) criteria for response assessment in lung cancer patients on immunotherapy. To find the incidence of pseudoprogression and associated imaging patterns.
MATERIAL AND METHODS
Retrospective study in 28 patients treated with immunotherapy for advanced metastatic NSCLC. End points were progression-free survival (PFS) and overall survival (OS). Response assessments were separately tabulated according to RECIST 1.1 and iRECIST and classified into dichotomous groups of responders and nonresponders. Agreement in assessments between RECIST 1.0 and iRECIST examined using Cohen kappa (κ) coefficient with 95% confidence intervals. Kaplan-Meier survival analysis was done for PFS and OS. Differences between RECIST 1.1 and iRECIST for both responder and nonresponder were evaluated by the log rank test, Breslow (Generalized Wilcoxon) test, and Tarone-Ware test.
RESULTS
Incidence of pseudoprogression was 7% (2/28). The RECIST1.1 and iRECIST were in disagreement in two patients. The agreement between RECIST and iRECIST was almost perfect. The PFS and the OS are significantly longer in duration for responders in comparison to nonresponders for both RECIST and iRECIST and the difference between two assessment criteria is not significant.
CONCLUSION
Although iRECIST aims to monitor treatment more precisely than conventional response criteria, this must be weighed against how infrequent pseudoprogression is and the cost of this therapy, both financially and in the potential delay in changing to a more effective treatment.
Topics: Humans; Lung Neoplasms; Response Evaluation Criteria in Solid Tumors; Nivolumab; Retrospective Studies; Carcinoma, Non-Small-Cell Lung; Treatment Outcome
PubMed: 37787285
DOI: 10.4103/jcrt.jcrt_1456_21 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2023Stereotactic radiosurgery is one of the main treatments for vestibular schwannomas (VS). Their feature is frequent post-radiation pseudoprogression. This may be due to...
INTRODUCTION
Stereotactic radiosurgery is one of the main treatments for vestibular schwannomas (VS). Their feature is frequent post-radiation pseudoprogression. This may be due to hormonal status of patients.
OBJECTIVE
To analyze expression of progesterone and estrogen receptors in women and men with VS.
MATERIAL AND METHODS
Immunohistochemical analysis of expression of progesterone (PR) and estrogen receptors (ER) after biopsy was performed in 240 patients with VS between 2018 and 2021. ER/PR expression was assessed in men (=120) and women (=120) in 3 age subgroups: young age (18-44 years), middle age (45-59 years) and old age (60-79 years). Each subgroup included 40 patients. Statistical analysis was performed using the Mann-Whitney test and MedCalc software.
RESULTS
ER expression is not typical for VS (men - 1 (0.01%), women - 3 (2.5%)). At the same time, PR expression was found in 29 (24.2%) men and 21 (17.5%) women. We found no significant difference in expression of ER and PR between men and women. However, variability in PR expression was revealed, i.e. predominance of this indicator in young women (=0.0463) and middle-aged men (=0.0110). Expression of PR was similar in elderly patients (=0.2382).
CONCLUSION
The established incidence of PR expression may be one of the probable causes affecting development and duration of VS pseudoprogression after radiosurgery without clear relationship between sex and age. Further prospective research is needed to predict the risks of pseudoprogression.
Topics: Middle Aged; Male; Aged; Humans; Female; Adolescent; Young Adult; Adult; Receptors, Progesterone; Receptors, Estrogen; Progesterone; Neuroma, Acoustic; Estrogens; Breast Neoplasms
PubMed: 36763552
DOI: 10.17116/neiro20238701144 -
NMR in Biomedicine Jul 2022Pseudoprogression (PsP) refers to treatment-related clinico-radiologic changes mimicking true progression (TP) that occurs in patients with glioblastoma (GBM),... (Review)
Review
Pseudoprogression (PsP) refers to treatment-related clinico-radiologic changes mimicking true progression (TP) that occurs in patients with glioblastoma (GBM), predominantly within the first 6 months after the completion of surgery and concurrent chemoradiation therapy (CCRT) with temozolomide. Accurate differentiation of TP from PsP is essential for making informed decisions on appropriate therapeutic intervention as well as for prognostication of these patients. Conventional neuroimaging findings are often equivocal in distinguishing between TP and PsP and present a considerable diagnostic dilemma to oncologists and radiologists. These challenges have emphasized the need for developing alternative imaging techniques that may aid in the accurate diagnosis of TP and PsP. In this review, we encapsulate the current state of knowledge in the clinical applications of commonly used metabolic and physiologic magnetic resonance (MR) imaging techniques such as diffusion and perfusion imaging and proton spectroscopy in distinguishing TP from PsP. We also showcase the potential of promising imaging techniques, such as amide proton transfer and amino acid-based positron emission tomography, in providing useful information about the treatment response. Additionally, we highlight the role of "radiomics", which is an emerging field of radiology that has the potential to change the way in which advanced MR techniques are utilized in assessing treatment response in GBM patients. Finally, we present our institutional experiences and discuss future perspectives on the role of multiparametric MR imaging in identifying PsP in GBM patients treated with "standard-of-care" CCRT as well as novel/targeted therapies.
Topics: Brain Neoplasms; Disease Progression; Glioblastoma; Humans; Magnetic Resonance Imaging; Protons
PubMed: 35233862
DOI: 10.1002/nbm.4719 -
Pediatric Radiology Dec 2018Assessing tumor response is a large part of everyday clinical work in neuroradiology. However in the setting of tumor treatment, distinguishing tumor progression from... (Review)
Review
Assessing tumor response is a large part of everyday clinical work in neuroradiology. However in the setting of tumor treatment, distinguishing tumor progression from treatment-related changes is difficult on conventional MRI sequences. This is made even more challenging in children where mainstay advanced imaging techniques that are often used to decipher progression versus treatment-related changes have technical limitations. In this review, we highlight the challenges in pediatric neuro-oncologic tumor assessment with discussion of pseudophenomenon including pseudoresponse and pseudoprogression. Additionally, we discuss the advanced imaging techniques often employed in neuroradiology to distinguish between pseudophenomenon and true progressive disease.
Topics: Brain Neoplasms; Child; Contrast Media; Diagnosis, Differential; Disease Progression; Humans; Magnetic Resonance Imaging; Neuroimaging; Phenotype
PubMed: 30215111
DOI: 10.1007/s00247-018-4232-7 -
Acta Neurochirurgica Apr 2021Radiosurgery is a well-established treatment for vestibular schwannomas (VSs), but it is often difficult to identify which tumors will respond to treatment. We sought to...
BACKGROUND
Radiosurgery is a well-established treatment for vestibular schwannomas (VSs), but it is often difficult to identify which tumors will respond to treatment. We sought to determine whether pretreatment or posttreatment tumor apparent diffusion coefficient (ADC) values could predict tumor control in patients undergoing Gamma Knife radiosurgery (GKRS) and whether these values could differentiate between cases of pseudoprogression and cases of true progression in the early posttreatment period.
METHODS
We retrospectively identified patients who underwent GKRS for solid VSs between June 2008 and November 2016 and who had a minimum follow-up of 36 months. Pretreatment and posttreatment minimum, mean, and maximum ADC values were measured for the whole tumor volume and were compared between patients with tumor control and those with tumor progression. In patients with early posttreatment tumor enlargement, ADC values were compared between patients with pseudoprogression and those with true progression.
RESULTS
Of the 44 study patients, 34 (77.3%) demonstrated tumor control at final follow-up. Patients with tumor control had higher pretreatment minimum (1.35 vs 1.09; p = 0.008), mean (1.80 vs 1.45; p = 0.004), and maximum (2.41 vs 1.91; p = 0.011) ADC values than patients with tumor progression. ADC values did not differ between patients with pseudoprogression and those with true progression at early posttreatment follow-up.
CONCLUSIONS
ADC values may be helpful in predicting response to GKRS in patients with solid VSs but cannot predict which tumors will undergo pseudoprogression. Patients with higher pretreatment ADC values may be more likely to demonstrate posttreatment tumor control.
Topics: Adult; Aged; Diffusion Magnetic Resonance Imaging; Female; Humans; Male; Middle Aged; Neuroma, Acoustic; Radiosurgery; Tumor Burden
PubMed: 33532869
DOI: 10.1007/s00701-021-04738-x -
Neuromolecular Medicine Jun 2022Glioblastoma is the most common primary malignant brain tumor and one of the most aggressive tumors across all cancer types with remarkable resistance to any treatment.... (Review)
Review
Glioblastoma is the most common primary malignant brain tumor and one of the most aggressive tumors across all cancer types with remarkable resistance to any treatment. While immunotherapy has shown a robust clinical benefit in systemic cancers, its benefit is still under investigation in brain cancers. The broader use of immunotherapy in clinical trials for glioblastoma has highlighted the challenges of traditional methods of monitoring progression via imaging. Development of new guidelines, advanced imaging techniques, and immune profiling have emerged to counter premature diagnoses of progressive disease. However, these approaches do not provide a timely diagnosis and are costly and time consuming. Surgery is currently the standard of care for diagnosis of pseudoprogression in cases where MRI is equivocal. However, it is invasive, risky, and disruptive to patient's lives and their oncological treatment. With its increased vascularity, glioblastoma is continually shedding tumor components into the vasculature including tumor cells, genetic material, and extracellular vesicles. These elements can be isolated from routine blood draws and provide a real-time non-invasive indicator of tumor progression. Liquid biopsy therefore presents as an attractive alternative to current methods to guide treatment. While the initial evaluation of liquid biopsy for brain tumors via identification of mutations in the plasma was disappointing, novel technologies and use of alternatives to plasma cell-free DNA analytes provide promise for an effective liquid biopsy approach in brain tumors. This review aims to summarize developments in the use of liquid biopsy to monitor glioblastoma, especially in the context of immunotherapy.
Topics: Biomarkers, Tumor; Brain Neoplasms; Glioblastoma; Humans; Immunotherapy; Liquid Biopsy; Magnetic Resonance Imaging
PubMed: 34297308
DOI: 10.1007/s12017-021-08677-9 -
Cancer Immunology, Immunotherapy : CII Mar 2022Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we...
BACKGROUND
Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment.
METHODS
This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes.
RESULTS
The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4CD25CD127FoxP3 Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4CD25CD127FoxP3 Treg cells and PD-1CD4CD25CD127FoxP3 Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively).
CONCLUSION
Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.
Topics: Aged; Aged, 80 and over; B7-H1 Antigen; Biomarkers; Female; Humans; Immune Checkpoint Inhibitors; Immunophenotyping; Lung Neoplasms; Lymphocyte Count; Male; Middle Aged; Molecular Targeted Therapy; Prognosis; Programmed Cell Death 1 Receptor; T-Lymphocytes, Regulatory; Treatment Outcome
PubMed: 34278517
DOI: 10.1007/s00262-021-03018-y