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Experimental and Therapeutic Medicine Feb 2024Systemic emboli are not uncommon in patients with advanced non-small cell lung cancer. The present study describes a rare case of long-term control in a patient with...
Systemic emboli are not uncommon in patients with advanced non-small cell lung cancer. The present study describes a rare case of long-term control in a patient with lung adenocarcinoma, nonbacterial thrombotic endocarditis and multiple systemic emboli. Briefly, a 56-year-old man was diagnosed with metastatic lung adenocarcinoma and was treated with pembrolizumab, which was discontinued due to the appearance of a pulmonary immune-related adverse event. During the clinical course, the patient developed pseudo-progression of a brain tumor, repeated thromboembolism in multiple organs and a small vegetation attached to the aortic valve. These lesions were controlled with apixaban after heparin therapy for >3 years. Lung cancer was subsequently treated with pemetrexed and bevacizumab; however, this treatment was terminated due to a complete response and the patient's request to discontinue treatment. More than 3 years have passed since the diagnosis of lung adenocarcinoma, and the patient has been followed up at the hospital without signs of cancer recurrence. Although unusual, the patient's course may provide useful suggestions for the treatment of other patients with a similar evolution.
PubMed: 38274345
DOI: 10.3892/etm.2024.12370 -
Journal of Clinical Medicine Jan 2024The use of immune checkpoint inhibitors (ICIs) in combination with tyrosine kinase inhibitors or other ICIs has significantly improved the prognosis for patients with... (Review)
Review
The use of immune checkpoint inhibitors (ICIs) in combination with tyrosine kinase inhibitors or other ICIs has significantly improved the prognosis for patients with mccRCC. This marks a major milestone in the treatment of mccRCC. Nonetheless, most patients will discontinue first-line therapy. In this narrative review, we analyze the different patterns of treatment discontinuation in the four pivotal phase III trials that have shown an improvement in overall survival in mccRCC first-line therapy, starting from 1 January 2017 to 1 June 2023. We highlight the different discontinuation scenarios and their influences on subsequent treatment options, aiming to provide more data to clinicians to navigate a complex decision-making process through a narrative review approach. We have identified several causes for discontinuations for patients treated with ICI-based combinations, such as interruption for drug-related adverse events, ICI treatment completion, treatment discontinuation due to complete response or maximum clinical benefit, or due to progression (pseudoprogression, systemic progression, and oligoprogression); for each case, an extensive analysis of the trials and current medical review has been conducted.
PubMed: 38256441
DOI: 10.3390/jcm13020307 -
Cancers Jan 2024The lack of early detection and a high rate of recurrence/progression after surgery are defined as the most common causes of a very poor prognosis of Gliomas. The... (Review)
Review
The lack of early detection and a high rate of recurrence/progression after surgery are defined as the most common causes of a very poor prognosis of Gliomas. The developments of quantification systems with special regards to artificial intelligence (AI) on medical images (CT, MRI, PET) are under evaluation in the clinical and research context in view of several applications providing different information related to the reconstruction of imaging, the segmentation of tissues acquired, the selection of features, and the proper data analyses. Different approaches of AI have been proposed as the machine and deep learning, which utilize artificial neural networks inspired by neuronal architectures. In addition, new systems have been developed using AI techniques to offer suggestions or make decisions in medical diagnosis, emulating the judgment of radiologist experts. The potential clinical role of AI focuses on the prediction of disease progression in more aggressive forms in gliomas, differential diagnosis (pseudoprogression vs. proper progression), and the follow-up of aggressive gliomas. This narrative Review will focus on the available applications of AI in brain tumor diagnosis, mainly related to malignant gliomas, with particular attention to the postoperative application of MRI and PET imaging, considering the current state of technical approach and the evaluation after treatment (including surgery, radiotherapy/chemotherapy, and prognostic stratification).
PubMed: 38254896
DOI: 10.3390/cancers16020407 -
World Neurosurgery Mar 2024One of the most frequent phenomena in the follow-up of glioblastoma is pseudoprogression, present in up to half of cases. The clinical usefulness of discriminating this...
Glioblastoma Pseudoprogression Discrimination Using Multiparametric Magnetic Resonance Imaging, Principal Component Analysis, and Supervised and Unsupervised Machine Learning.
BACKGROUND
One of the most frequent phenomena in the follow-up of glioblastoma is pseudoprogression, present in up to half of cases. The clinical usefulness of discriminating this phenomenon through magnetic resonance imaging and nuclear medicine has not yet been standardized; in this study, we used machine learning on multiparametric magnetic resonance imaging to explore discriminators of this phenomenon.
METHODS
For the study, 30 patients diagnosed with IDH wild-type glioblastoma operated on at both study centers in 2011-2020 were selected; 15 patients corresponded to early tumor progression and 15 patients to pseudoprogression. Using unsupervised learning, the number of clusters and tumor segmentation was recorded using gap-stat and k-means method, adjusting to voxel adjacency. In a second phase, a class prediction was carried out with a multinomial logistic regression supervised learning method; the outcome variables were the percentage of assignment, class overrepresentation, and degree of voxel adjacency.
RESULTS
Unsupervised learning of the tumor in its diagnosis shows up to 14 well-differentiated tumor areas. In the supervised learning phase, there is a higher percentage of assigned classes (P < 0.01), less overrepresentation of classes (P < 0.01), and greater adjacency (55% vs. 33%) in cases of true tumor progression compared with pseudoprogression.
CONCLUSIONS
True tumor progression preserves the multidimensional characteristics of the basal tumor at the voxel and region of interest level, resulting in a characteristic differential pattern when supervised learning is used.
Topics: Humans; Glioblastoma; Unsupervised Machine Learning; Multiparametric Magnetic Resonance Imaging; Principal Component Analysis; Brain Neoplasms; Magnetic Resonance Imaging; Disease Progression
PubMed: 38253179
DOI: 10.1016/j.wneu.2024.01.074 -
Neuro-oncology Practice Feb 2024
PubMed: 38222056
DOI: 10.1093/nop/npad078 -
Neuro-oncology Practice Feb 2024Differentiating post-radiation MRI changes from progressive disease (PD) in glioblastoma (GBM) patients represents a major challenge. The clinical problem is two-sided;...
BACKGROUND
Differentiating post-radiation MRI changes from progressive disease (PD) in glioblastoma (GBM) patients represents a major challenge. The clinical problem is two-sided; avoid termination of effective therapy in case of pseudoprogression (PsP) and continuation of ineffective therapy in case of PD. We retrospectively assessed the incidence, management, and prognostic impact of PsP and analyzed factors associated with PsP in a GBM patient cohort.
METHODS
Consecutive GBM patients diagnosed in the South-Eastern Norway Health Region from 2015 to 2018 who had received RT and follow-up MRI were included. Tumor, patient, and treatment characteristics were analyzed in relationship to re-evaluated MRI examinations at 3 and 6 months post-radiation using Response Assessment in Neuro-Oncology criteria.
RESULTS
A total of 284 patients were included in the study. PsP incidence 3 and 6 months post-radiation was 19.4% and 7.0%, respectively. In adjusted analyses, methylated - () promoter and the absence of neurological deterioration were associated with PsP at both 3 ( < .001 and = .029, respectively) and 6 months ( = .045 and = .034, respectively) post-radiation. For patients retrospectively assessed as PD 3 months post-radiation, there was no survival benefit of treatment change ( = .838).
CONCLUSIONS
PsP incidence was similar to previous reports. In addition to the previously described correlation of methylated promoter with PsP, we also found that absence of neurological deterioration significantly correlated with PsP. Continuation of temozolomide courses did not seem to compromise survival for patients with PD at 3 months post-radiation; therefore, we recommend continuing adjuvant temozolomide courses in case of inconclusive MRI findings.
PubMed: 38222046
DOI: 10.1093/nop/npad063 -
Neuro-oncology May 2024Radiological progression may originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. We assessed radiological progression in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Radiological progression may originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. We assessed radiological progression in O6-methylguanine-DNA methyltransferase (MGMT) promoter-methylated glioblastoma treated with standard-of-care chemoradiotherapy with or without the integrin inhibitor cilengitide according to the modified response assessment in neuro-oncology (RANO) criteria of 2017.
METHODS
Patients with ≥ 3 follow-up MRIs were included. Preliminary PD was defined as a ≥ 25% increase of the sum of products of perpendicular diameters (SPD) of a new or increasing lesion compared to baseline. PD required a second ≥25% increase of the SPD. Treatment-associated changes require stable or regressing disease after preliminary PD.
RESULTS
Of the 424 evaluable patients, 221 patients (52%) were randomized into the cilengitide and 203 patients (48%) into the control arm. After chemoradiation with or without cilengitide, preliminary PD occurred in 274 patients (65%) during available follow-up, and 88 of these patients (32%) had treatment-associated changes, whereas 67 patients (25%) had PD. The remaining 119 patients (43%) had no further follow-up after preliminary PD. Treatment-associated changes were more common in the cilengitide arm than in the standard-of-care arm (24% vs. 17%; relative risk, 1.3; 95% CI, 1.004-1.795; P = .047). Treatment-associated changes occurred mainly during the first 6 months after RT (54% after 3 months vs. 13% after 6 months).
CONCLUSIONS
With the modified RANO criteria, the rate of treatment-associated changes was low compared to previous studies in MGMT promoter-methylated glioblastoma. This rate was higher after cilengitide compared to standard-of-care treatment. Confirmatory scans, as recommended in the modified RANO criteria, were not always available reflecting current clinical practice.
Topics: Humans; Glioblastoma; Snake Venoms; Brain Neoplasms; DNA Modification Methylases; Chemoradiotherapy; Female; Male; DNA Repair Enzymes; Middle Aged; Promoter Regions, Genetic; DNA Methylation; Aged; Tumor Suppressor Proteins; Adult; Magnetic Resonance Imaging; Follow-Up Studies; Disease Progression; Prognosis; Aged, 80 and over
PubMed: 38219019
DOI: 10.1093/neuonc/noad247 -
Surgical Neurology International 2023The management of vestibular schwannoma has evolved over the past hundred years. In the last decades, surgery has been gradually replaced by radiation therapy as a...
BACKGROUND
The management of vestibular schwannoma has evolved over the past hundred years. In the last decades, surgery has been gradually replaced by radiation therapy as a primary treatment modality, particularly for small tumors, due to the less invasive nature and the compared reported outcomes in tumor control and hearing preservation. However, irradiation sometimes fails to stop tumor growth. In a long-term follow-up after primary fractionated stereotactic radiotherapy, the rate of treatment failure was reported as 3% and needed surgical salvage. For single-fraction modality, Hasegawa . reported salvage treatment after primary Gamma Knife radiosurgery in 8%, where 90% of these underwent surgery and 50% of those who were treated with a second gamma knife surgery required surgical intervention later. An increase in tumor volume by more than 10-20%, tumor growth after three years, and no return to pretreatment volume after transient swelling have been considered as tumor recurrence rather than pseudoprogression, a transient increase in tumor volume after radiotherapy that occurs up to 30% of cases. It has been reported that microsurgery after radiotherapy is more difficult, with most authors reporting a loss of defined arachnoid planes and worse cranial nerve outcomes, especially for hearing and facial nerve function.
CASE DESCRIPTION
A 43-year-old female patient was incidentally (asymptomatic) diagnosed on a magnetic resonance imaging (MRI) scan harboring a left vestibular schwannoma, grade T2 (Hannover classification), in 2015. Neurologic examination was unremarkable, and audiometry testing was normal. She was initially treated with observation. Three years later, in 2018, the lesion had enlarged, becoming a grade T3a and reaching the cistern of the cerebellopontine angle. The tumor was then treated with fractionated stereotactic radiosurgery (5 sessions of 5 Gy). MRI scans in 2019 and 2020 showed slight tumor growth. This enlargement was attributed to a pseudoprogression after radiosurgery, and only observation was advocated. In 2022, 4 years later, after radiosurgery, the tumor was still growing, and the patient began to suffer from hearing loss. A failure treatment was considered, and microsurgery was indicated. The patient was counseled about the risk of functional nerve impairment, and surgical consent was obtained. A retro sigmoid approach was planned. A gross total resection was attempted due to the clear subperineural plane during tumor dissection and because it was the only option that would provide a cure for the patient. The adjacent neurovascular structures were firmly adhered to the tumor capsule, which represented a major challenge for microdissection. The tumor was soft, without significant bleeding. A total resection was achieved, and the facial nerve was anatomically preserved. The patient developed facial paresis (House-Brackmann III) in the immediate postoperative period, which improved at the 6-month follow-up. Hearing loss did not improve. Postoperative MRI showed total resection.
CONCLUSION
Microsurgery after radiotherapy for vestibular schwannoma is challenging in terms of indication, when to indicate, resection target, difficulty in dissection due to local changes, and outcome. Gross total resection may be considered, as it is the only treatment that may provide a cure for the patient. However, the patient should be counseled about the risks.
PubMed: 38213456
DOI: 10.25259/SNI_875_2023 -
Therapeutic Advances in Medical Oncology 2024The microsatellite instability (MSI) phenotype is related to a deficiency of the DNA mismatch repair (dMMR) system and is observed in 5% of metastatic colorectal cancers... (Review)
Review
The microsatellite instability (MSI) phenotype is related to a deficiency of the DNA mismatch repair (dMMR) system and is observed in 5% of metastatic colorectal cancers (mCRCs). MSI/dMMR phenotype testing should be routine for all CRCs regardless of stage. Two complementary techniques with a high concordance (90-97%) allow us to determine the MSI/dMMR status of a tumor: immunohistochemistry and polymerase chain reaction. Since 2020 and the results of the phase III KEYNOTE 177 trial, pembrolizumab [anti-programmed cell death protein 1 (PD1)] is the new standard of care in first-line MSI/dMMR mCRC. To date, no combination of chemtotherapy ± targeted therapy with immune checkpoint inhibitors (ICIs) has been validated in the management of MSI/dMMR mCRC, and it is not known whether this combination would be beneficial. It is also unclear whether dual therapy with two ICIs is more effective than monotherapy. Several phase III trials are ongoing to answer these questions. Despite a high response rate and long-term benefit of a first line by anti-PD1, 30-50% of patients with MSI/dMMR mCRC experience an early or secondary progression. There are currently no validated predictive biomarkers of anti-PD1 ± anti-cytotoxic T lymphocyte antigen-4 resistance in patients with MSI/dMMR mCRC. In case of early progression on ICIs, the first two questions to consider are the possibility of pseudoprogression and the correct diagnosis of MSI/dMMR status. To date, there are no data on the use of adjuvant ICIs for MSI/dMMR resected colon cancers. By contrast, data are accumulating regarding the efficacy of neoadjuvant ICIs, with at least two-thirds of patients in the different trials in pathological complete response, making it possible to envisage 'Watch and wait' strategies in future.
PubMed: 38205076
DOI: 10.1177/17588359231170473 -
Cancers Dec 2023The follow-up of glioma patients after therapeutic intervention remains a challenging topic, as therapy-related changes can emulate true progression in contrast-enhanced... (Review)
Review
F-Fluoroethyl-L Tyrosine Positron Emission Tomography Radiomics in the Differentiation of Treatment-Related Changes from Disease Progression in Patients with Glioblastoma.
The follow-up of glioma patients after therapeutic intervention remains a challenging topic, as therapy-related changes can emulate true progression in contrast-enhanced magnetic resonance imaging. F-fluoroethyl-tyrosine (F-FET) is a radiopharmaceutical that accumulates in glioma cells due to an increased expression of L-amino acid transporters and, contrary to gadolinium, does not depend on blood-brain barrier disruption to reach tumoral cells. It has demonstrated a high diagnostic value in the differentiation of tumoral viability and pseudoprogression or any other therapy-related changes, especially when combining traditional visual analysis with modern radiomics. In this review, we aim to cover the potential role of 18F-FET positron emission tomography in everyday clinical practice when applied to the follow-up of patients after the first therapeutical intervention, early response evaluation, and the differential diagnosis between therapy-related changes and progression.
PubMed: 38201621
DOI: 10.3390/cancers16010195