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EJNMMI Physics Dec 2023The aim was to investigate the feasibility of a shortened dynamic whole-body (dWB) FDG-PET/CT protocol and Patlak imaging using a population-based input function (PBIF),...
Clinical application of a population-based input function (PBIF) for a shortened dynamic whole-body FDG-PET/CT protocol in patients with metastatic melanoma treated by immunotherapy.
BACKGROUND
The aim was to investigate the feasibility of a shortened dynamic whole-body (dWB) FDG-PET/CT protocol and Patlak imaging using a population-based input function (PBIF), instead of an image-derived input function (IDIF) across the 60-min post-injection period, and study its effect on the FDG influx rate (Ki) quantification in patients with metastatic melanoma (MM) undergoing immunotherapy.
METHODS
Thirty-seven patients were enrolled, including a PBIF modeling group (n = 17) and an independent validation cohort (n = 20) of MM from the ongoing prospective IMMUNOPET2 trial. All dWB-PET data were acquired on Vision 600 PET/CT systems. The PBIF was fitted using a Feng's 4-compartments model and scaled to the individual IDIF tail's section within the shortened acquisition time. The area under the curve (AUC) of PBIFs was compared to respective IDIFs AUC within 9 shortened time windows (TW) in terms of linear correlation (R) and Bland-Altman tests. Ki metrics calculated with PBIF vs IDIF on 8 organs with physiological tracer uptake, 44 tumoral lesions of MM and 11 immune-induced inflammatory sites of pseudo-progression disease were also compared (Mann-Whitney test).
RESULTS
The mean ± SD relative AUC bias was calculated at 0.5 ± 3.8% (R = 0.961, AUC = 1.007 × AUC). In terms of optimal use in routine practice and statistical results, the 5th-7th pass (R = 0.999 for both Ki mean and Ki max) and 5th-8th pass (mean ± SD bias = - 4.9 ± 6.5% for Ki mean and - 4.8% ± 5.6% for Ki max) windows were selected. There was no significant difference in Ki values from PBIF vs IDIF for physiological uptakes (p > 0.05) as well as for tumor lesions (mean ± SD Ki IDIF 3.07 ± 3.27 vs Ki PBIF 2.86 ± 2.96 100ml/ml/min, p = 0.586) and for inflammatory sites (mean ± SD Ki IDIF 1.13 ± 0.59 vs Ki PBIF 1.13 ± 0.55 100ml/ml/min, p = 0.98).
CONCLUSION
Our study showed the feasibility of a shortened dWB-PET imaging protocol with a PBIF approach, allowing to reduce acquisition duration from 70 to 20 min with reasonable bias. These findings open perspectives for its clinical use in routine practice such as treatment response assessment in oncology.
PubMed: 38062278
DOI: 10.1186/s40658-023-00601-3 -
Acta Neuropathologica Communications Dec 2023Post-resection radiologic monitoring to identify areas of new or progressive enhancement concerning for cancer recurrence is critical during patients with glioblastoma...
Post-resection radiologic monitoring to identify areas of new or progressive enhancement concerning for cancer recurrence is critical during patients with glioblastoma follow-up. However, treatment-related pseudoprogression presents with similar imaging features but requires different clinical management. While pathologic diagnosis is the gold standard to differentiate true progression and pseudoprogression, the lack of objective clinical standards and admixed histologic presentation creates the needs to (1) validate the accuracy of current approaches and (2) characterize differences between these entities to objectively differentiate true disease. We demonstrated using an online RNAseq repository of recurrent glioblastoma samples that cancer-immune cell activity levels correlate with heterogenous clinical outcomes in patients. Furthermore, nCounter RNA expression analysis of 48 clinical samples taken from second neurosurgical resection supports that pseudoprogression gene expression pathways are dominated with immune activation, whereas progression is predominated with cell cycle activity. Automated image processing and spatial expression analysis however highlight a failure to apply these broad expressional differences in a subset of cases with clinically challenging admixed histology. Encouragingly, applying unsupervised clustering approaches over our segmented histologic images provides novel understanding of morphologically derived differences between progression and pseudoprogression. Spatially derived data further highlighted polarization of myeloid populations that may underscore the tumorgenicity of novel lesions. These findings not only help provide further clarity of potential targets for pathologists to better assist stratification of progression and pseudoprogression, but also highlight the evolution of tumor-immune microenvironment changes which promote tumor recurrence.
Topics: Humans; Glioblastoma; Disease Progression; Brain Neoplasms; Chemoradiotherapy; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Tumor Microenvironment
PubMed: 38049893
DOI: 10.1186/s40478-023-01587-w -
Journal of Neurosurgery Jun 2024The modern management of patients with Koos grade IV vestibular schwannomas (VSs) aims at functional preservation and long-term tumor control. Gross-total resection...
OBJECTIVE
The modern management of patients with Koos grade IV vestibular schwannomas (VSs) aims at functional preservation and long-term tumor control. Gross-total resection (GTR) leads to optimal tumor control but frequently also results in permanent facial nerve (FN) palsy. Subtotal resection (STR) or near-total resection (NTR) followed by a wait-and-scan protocol and second-line radiation therapy (RT) in case of progressive residuals yields excellent tumor control rates with less permanent morbidity.
METHODS
The authors present the results of their prospective cohort of Koos grade IV VS patients who underwent less-than-total resection followed by a wait-and-scan protocol between January 2009 and December 2019 and discuss the latest evidence on this controversial subject. The cohort was followed up with annual clinical and volumetric outcome analyses after standardized MRI.
RESULTS
Forty-eight patients were included in the analysis. The mean extent of resection was 87% (median 91%, range 45%-100%), best fitting into the definition of STR rather than NTR. In 2 cases, the proximal portion of the FN at the brainstem could not be reliably identified and monitored during the initial operation, and a second-stage resection was necessary. At 4.4 years after surgery, 81% (39/48) of the tumor residuals regressed or were stable in size. The percentage of regressive tumor residuals increased over time. Nineteen percent (9/48) of the tumor residuals displayed volumetric progression within a mean time of 35 months (median 36 months, range 14-72 months), resulting in a Kaplan-Meier estimate for progression-free survival of 79% after 4 years; higher postoperative volume showed a linear correlation with higher volumetric progression (factor 1.96, 95% CI 1.67-2.30; p < 0.001). Thirty-four of the 48 (71%) patients continue to undergo a wait-and-scan protocol. Second-line RT was performed in 14 patients (29%) within a mean time of 25 months (median 23 months, range 5-54 months), 12 (86%) of whom responded with post-RT pseudoprogression, resulting in an overall tumor control rate of 96%. At the 4.4-year follow-up from the initial resection, 92% of the patients had a good facial outcome (House-Brackmann [HB] grade I or II), 6% had a fair facial outcome (HB grade III), and 2% had a poor facial outcome (HB grades IV-VI). So far, there has been no need for salvage surgery after RT.
CONCLUSIONS
STR followed by observation and second-line RT in cases of progression leads to good facial outcome and an excellent tumor control rate in the longer term.
Topics: Humans; Neuroma, Acoustic; Male; Female; Middle Aged; Adult; Aged; Prospective Studies; Treatment Outcome; Neurosurgical Procedures; Neoplasm Grading; Young Adult; Follow-Up Studies; Magnetic Resonance Imaging; Cohort Studies
PubMed: 38039537
DOI: 10.3171/2023.9.JNS231316 -
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 -
Magnetic Resonance Imaging Clinics of... Feb 2024Accurate diagnosis and treatment evaluation of patients with gliomas is imperative to make clinical decisions. Multiparametric MR perfusion imaging reveals physiologic... (Review)
Review
Accurate diagnosis and treatment evaluation of patients with gliomas is imperative to make clinical decisions. Multiparametric MR perfusion imaging reveals physiologic features of gliomas that can help classify them according to their histologic and molecular features as well as distinguish them from other neoplastic and nonneoplastic entities. It is also helpful in distinguishing tumor recurrence or progression from radiation necrosis, pseudoprogression, and pseudoresponse, which is difficult with conventional MR imaging. This review provides an update on MR perfusion imaging for the diagnosis and treatment monitoring of patients with gliomas following standard-of-care chemoradiation therapy and other treatment regimens such as immunotherapy.
Topics: Humans; Magnetic Resonance Imaging; Brain Neoplasms; Contrast Media; Glioma; Perfusion Imaging
PubMed: 38007284
DOI: 10.1016/j.mric.2023.07.003 -
Current Opinion in Neurology Dec 2023To provide an updated overview of artificial intelligence (AI) applications in neuro-oncologic imaging and discuss current barriers to wider clinical adoption. (Review)
Review
PURPOSE OF REVIEW
To provide an updated overview of artificial intelligence (AI) applications in neuro-oncologic imaging and discuss current barriers to wider clinical adoption.
RECENT FINDINGS
A wide variety of AI applications in neuro-oncologic imaging have been developed and researched, spanning tasks from pretreatment brain tumor classification and segmentation, preoperative planning, radiogenomics, prognostication and survival prediction, posttreatment surveillance, and differentiating between pseudoprogression and true disease progression. While earlier studies were largely based on data from a single institution, more recent studies have demonstrated that the performance of these algorithms are also effective on external data from other institutions. Nevertheless, most of these algorithms have yet to see widespread clinical adoption, given the lack of prospective studies demonstrating their efficacy and the logistical difficulties involved in clinical implementation.
SUMMARY
While there has been significant progress in AI and neuro-oncologic imaging, clinical utility remains to be demonstrated. The next wave of progress in this area will be driven by prospective studies measuring outcomes relevant to clinical practice and go beyond retrospective studies which primarily aim to demonstrate high performance.
Topics: Humans; Artificial Intelligence; Prospective Studies; Retrospective Studies; Neuroimaging; Brain Neoplasms
PubMed: 37973024
DOI: 10.1097/WCO.0000000000001213 -
Cancers Oct 2023[F]-FDG positron emission tomography with computed tomography (PET/CT) imaging is widely used to enhance the quality of care in patients diagnosed with cancer....
Integrating [F]-Fluorodeoxyglucose Positron Emission Tomography with Computed Tomography with Radiation Therapy and Immunomodulation in Precision Therapy for Solid Tumors.
[F]-FDG positron emission tomography with computed tomography (PET/CT) imaging is widely used to enhance the quality of care in patients diagnosed with cancer. Furthermore, it holds the potential to offer insight into the synergic effect of combining radiation therapy (RT) with immuno-oncological (IO) agents. This is achieved by evaluating treatment responses both at the RT and distant tumor sites, thereby encompassing the phenomenon known as the abscopal effect. In this context, PET/CT can play an important role in establishing timelines for RT/IO administration and monitoring responses, including novel patterns such as hyperprogression, oligoprogression, and pseudoprogression, as well as immune-related adverse events. In this commentary, we explore the incremental value of PET/CT to enhance the combination of RT with IO in precision therapy for solid tumors, by offering supplementary insights to recently released joint guidelines.
PubMed: 37958353
DOI: 10.3390/cancers15215179 -
Neurosurgery Apr 2024Tectal plate gliomas (TPGs) are midbrain tumors that grow slowly and have a benign clinical course. Most TPGs are low-grade astrocytomas, but they can encompass various... (Review)
Review
BACKGROUND AND OBJECTIVES
Tectal plate gliomas (TPGs) are midbrain tumors that grow slowly and have a benign clinical course. Most TPGs are low-grade astrocytomas, but they can encompass various histological tumor types. Gamma Knife radiosurgery (GKRS) is being explored as a potentially safe and effective treatment option for TPGs, although research in this area is limited. This study aims to evaluate GKRS's efficacy and safety in patients with TPG and provide a comprehensive review of existing literature on the topic.
METHODS
This retrospective, single-center study included 48 patients with consecutive TPG who underwent GKRS between September 2005 and June 2022. Patients diagnosed with TPGs based on radiological or tissue-based criteria and who had a minimum follow-up period of 12 months were eligible for inclusion. The primary end points were local control and the absence of GKRS-associated or tumor-associated mortality and morbidity.
RESULTS
During a median follow-up of 28.5 months (range, 12-128), the radiological assessment showed tumor control in all cases, with 16.7% achieving a complete response and 68.8% achieving a partial response. Pseudoprogression occurred in 6.2% of cases, with onset ranging from 3 to 8 months. Clinical outcomes revealed no permanent neurological deterioration, with symptoms improving in 14.6% of patients and remaining stable in the others. One patient in the pseudoprogression group experienced transient Parinaud syndrome. One patient died during follow-up because of unrelated causes. The mean survival time after GKRS was 123.7 months. None of the clinical, radiological, or radiosurgical variables showed a correlation with partial/complete response, clinical improvement, or overall survival.
CONCLUSION
There is limited research available on the management of TPGs, and this study presents the largest patient cohort treated with GKRS, along with a substantial follow-up duration. Despite its limitations, this study demonstrates the efficacy and low-risk profile of GKRS for TPGs.
Topics: Humans; Follow-Up Studies; Radiosurgery; Retrospective Studies; Treatment Outcome; Glioma; Meningeal Neoplasms
PubMed: 37955438
DOI: 10.1227/neu.0000000000002754 -
Current Neurology and Neuroscience... Dec 2023To outline the spectrum of neurotoxicity seen with approved immunotherapies and in pivotal clinical trials including immune checkpoint inhibitors, chimeric antigen... (Review)
Review
PURPOSE OF REVIEW
To outline the spectrum of neurotoxicity seen with approved immunotherapies and in pivotal clinical trials including immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy, vaccine therapy, and oncolytic viruses.
RECENT FINDINGS
There has been an exponential growth in new immunotherapies, which has transformed the landscape of oncology treatment. With more widespread use of cancer immunotherapies, there have also been advances in characterization of its associated neurotoxicity, research into potential underlying mechanisms, and development of management guidelines. Increasingly, there is also mounting interest in long-term neurologic sequelae. Neurologic complications of immunotherapy can impact every aspect of the central and peripheral nervous system. Early recognition and treatment are critical. Expanding indications for immunotherapy to solid and CNS tumors has led to new challenges, such as how to reliably distinguish neurotoxicity from disease progression. Our evolving understanding of immunotherapy neurotoxicity highlights important areas for future research and the need for novel immunomodulatory therapeutics.
Topics: Humans; Immunotherapy, Adoptive; Immunotherapy; Neoplasms
PubMed: 37938472
DOI: 10.1007/s11910-023-01315-w -
BMC Medical Imaging Nov 2023We focused on Differentiated pseudoprogression (PPN) of progression (PN) and the response to radiotherapy (RT) or chemoradiotherapy (CRT) using diffusion and metabolic...
BACKGROUND
We focused on Differentiated pseudoprogression (PPN) of progression (PN) and the response to radiotherapy (RT) or chemoradiotherapy (CRT) using diffusion and metabolic imaging.
METHODS
Seventy-five patients with glioma were included in this prospective study (approved by the Iranian Registry of Clinical Trials (IRCT) (IRCT20230904059352N1) in September 2023). Contrast-enhanced lesion volume (CELV), non-enhanced lesion volume (NELV), necrotic tumor volume (NTV), and quantitative values of apparent diffusion coefficient (ADC) and magnetic resonance spectroscopy (Cho/Cr, Cho/NAA and NAA/Cr) were calculated by a neuroradiologist using a semi-automatic method. All patients were followed at one and six months after CRT.
RESULTS
The results of the study showed statistically significant changes before and six months after RT-CRT for M-CELV in all glioma types (𝑝 < 0.05). In glioma cell types, the changes in M-ADC, M-Cho/Cr, and Cho/NAA indices for PN were incremental and greater for PPN patients. M-NAA/Cr ratio decreased after six months which was significant only on PN for GBM, and Epn (𝑝 < 0.05). A significant difference was observed between diffusion indices, metabolic ratios, and CELV changes after six months in all types (𝑝 < 0.05). None of the patients were suspected PPN one month after treatment. The DWI/ADC indices had higher sensitivity and specificity (98.25% and 96.57%, respectively).
CONCLUSION
The results of the present study showed that ADC values and Cho/Cr and Cho/NAA ratios can be used to differentiate between patients with PPN and PN, although ADC is more sensitive and specific.
Topics: Humans; Prospective Studies; Brain Neoplasms; Iran; Glioma; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Diffusion Magnetic Resonance Imaging; Chemoradiotherapy
PubMed: 37932656
DOI: 10.1186/s12880-023-01135-x