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Cancers Apr 2021Monitoring treatment response in metastatic breast cancer currently consists mainly of radiological and clinical assessments. These methods have high inter-observer... (Review)
Review
Monitoring treatment response in metastatic breast cancer currently consists mainly of radiological and clinical assessments. These methods have high inter-observer variation, suboptimal sensitivity to determine response to treatment and give little insight into the biological characteristics of the tumor. Assessing circulating tumor DNA (ctDNA) over time could be employed to address these limitations. Several ways to quantify and characterize ctDNA exist, based on somatic mutations, copy number variations, methylation, and global circulating cell-free DNA (cfDNA) fragment sizes and concentrations. These methods are being explored and technically validated, but to date none of these methods are applied clinically. We systematically reviewed the literature on the use of quantitative ctDNA measurements over time to monitor response to systemic therapy in patients with metastatic breast cancer. Cochrane, Embase, PubMed and Google Scholar databases were searched to find studies focusing on the use of cfDNA to longitudinally monitor treatment response in advanced breast cancer patients until October 2020. This resulted in a total of 33 studies which met the inclusion criteria. These studies were heterogeneous in (pre-)processing procedures, applied techniques and design. An association between ctDNA and treatment response was found in most of the included studies, independent of the applied assay. To implement ctDNA-based response monitoring into daily clinical practice for metastatic breast cancer patients, sample (pre-) processing procedures need to be standardized and large prospectively collected sample cohorts with well annotated clinical follow-up are required to establish its clinical validity.
PubMed: 33920135
DOI: 10.3390/cancers13081811 -
Cancers Mar 2022The aims of this systematic review were to (1) assess the utility of PSMA-PET and choline-PET in the assessment of response to systemic and local therapy, and to (2)... (Review)
Review
The aims of this systematic review were to (1) assess the utility of PSMA-PET and choline-PET in the assessment of response to systemic and local therapy, and to (2) determine the value of both tracers for the prediction of response to therapy and survival outcomes in prostate cancer. We performed a systematic literature search in PubMed/Scopus/Google Scholar/Cochrane/EMBASE databases (between January 2010 and October 2021) accordingly. The quality of the included studies was evaluated following the "Quality Assessment of Prognostic Accuracy Studies" tool (QUAPAS-2). We selected 40 articles: 23 articles discussed the use of PET imaging with [Ga]PSMA-11 (16 articles/1123 patients) or [C]/[F]Choline (7 articles/356 patients) for the prediction of response to radiotherapy (RT) and survival outcomes. Seven articles (three with [Ga]PSMA-11, three with [C]Choline, one with [F]Choline) assessed the role of PET imaging in the evaluation of response to docetaxel (as neoadjuvant therapy in one study, as first-line therapy in five studies, and as a palliative regimen in one study). Seven papers with radiolabeled [F]Choline PET/CT ( = 121 patients) and three with [Ga]PSMA-11 PET ( = 87 patients) were selected before and after enzalutamide/abiraterone acetate. Finally, [F]Choline and [Ga]PSMA-11 PET/CT as gatekeepers for the treatment of metastatic prostate cancer with Radium-223 were assessed in three papers. In conclusion, in patients undergoing RT, radiolabeled choline and [Ga]PSMA-11 have an important prognostic role. In the case of systemic therapies, the role of such new-generation imaging techniques is still controversial without sufficient data, thus requiring additional in this scenario.
PubMed: 35406542
DOI: 10.3390/cancers14071770 -
Cancers Mar 2021Radiomics may increase the diagnostic accuracy of medical imaging for localized and metastatic RCC (mRCC). A systematic review and meta-analysis was performed. Doing so,... (Review)
Review
Radiomics may increase the diagnostic accuracy of medical imaging for localized and metastatic RCC (mRCC). A systematic review and meta-analysis was performed. Doing so, we comprehensively searched literature databases until May 2020. Studies investigating the diagnostic value of radiomics in differentiation of localized renal tumors and assessment of treatment response to ST in mRCC were included and assessed with respect to their quality using the radiomics quality score (RQS). A total of 113 out of 1098 identified studies met the criteria and were included in qualitative synthesis. Median RQS of all studies was 13.9% (5.0 points, IQR 0.25-7.0 points), and RQS increased over time. Thirty studies were included into the quantitative synthesis: For distinguishing angiomyolipoma, oncocytoma or unspecified benign tumors from RCC, the random effects model showed a log odds ratio (OR) of 2.89 (95%-CI 2.40-3.39, < 0.001), 3.08 (95%-CI 2.09-4.06, < 0.001) and 3.57 (95%-CI 2.69-4.45, < 0.001), respectively. For the general discrimination of benign tumors from RCC log OR was 3.17 (95%-CI 2.73-3.62, < 0.001). Inhomogeneity of the available studies assessing treatment response in mRCC prevented any meaningful meta-analysis. The application of radiomics seems promising for discrimination of renal tumor dignity. Shared data and open science may assist in improving reproducibility of future studies.
PubMed: 33802699
DOI: 10.3390/cancers13061348 -
Journal of Cachexia, Sarcopenia and... Oct 2021Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta-analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2-51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32-1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88-4.41) for psoas muscle index (PMI), 1.41 (0.87-2.28) for skeletal muscle density (SMD), and 1.43 (1.23-1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08-3.21) for PMI, 1.27 (0.94-1.71) for SMD, and 1.38 (1.11-1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34-0.80 for ORR and OR = 0.45, 95% CI = 0.30-0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15-2.05) for PMI and 0.78 (0.56-1.09) for SMI. The oncologic outcomes associated with melanoma and non-small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26-3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19-2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51-2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre-therapeutically, the presence of sarcopenia should be assessed in clinical practice.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Progression-Free Survival; Sarcopenia
PubMed: 34337889
DOI: 10.1002/jcsm.12755 -
Diagnostic and Interventional Imaging 2020The purpose of this study was to perform a systematic review of current literature describing the efficacy and technical outcomes of transarterial liver therapies using... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The purpose of this study was to perform a systematic review of current literature describing the efficacy and technical outcomes of transarterial liver therapies using automated feeder detection (AFD) software.
MATERIALS AND METHODS
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A structured search was performed in the PubMed, SCOPUS, and Embase databases of patients undergoing locoregional therapy of liver tumors utilizing AFD software. Demographic data, procedure data (including radiometrics) and tumor response rate were recorded. Where available, performance of AFD was compared to conventional digital subtraction angiography (DSA) and cone-beam CT (CBCT) without AFD.
RESULTS
A total of 14 full-text manuscripts met inclusion criteria, comprising 1042 tumors in 604 patients (305 men, 156 women; mean age, 68.6±6.0 [SD] years), including 537 patients with hepatocellular carcinoma, 8 with metastases from neuroendocrine tumors, and 59 patients without reported etiology. Reported sensitivity of AFD ranged between 86% and 98.5%, compared to DSA alone (38% - 64%) or DSA in combination with CBCT (69% - 81%). Three studies reported tumor response by modified response evaluation criteria in solid tumors (mRECIST) guidelines, with complete response in the range of 60% - 69%.
CONCLUSION
AFD is a promising new technology for the identification of intrahepatic and extrahepatic tumor-feeding arteries and should be considered a useful adjunct to conventional DSA and CBCT in the treatment of liver tumors.
Topics: Aged; Angiography, Digital Subtraction; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cone-Beam Computed Tomography; Female; Humans; Liver Neoplasms; Male; Middle Aged; Software
PubMed: 32035822
DOI: 10.1016/j.diii.2020.01.011 -
Bioengineering (Basel, Switzerland) Jan 2023Exercise capacity is limited by environmental heat stress because thermoregulatory systems are altered and cannot prevent the elevation of body temperature due to a... (Review)
Review
Is the Cooling Vest an Ergogenic Tool for Physically Active Individuals? Assessment of Perceptual Response, Thermo-Physiological Behavior, and Sports Performance: A Systematic Review and Meta-Analysis.
Exercise capacity is limited by environmental heat stress because thermoregulatory systems are altered and cannot prevent the elevation of body temperature due to a complex interplay of physiological, physical, and perceptual alterations. Cooling is an effective strategy to attenuate the temperature rise. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the PEDro scale for assessing methodological quality, we systematically reviewed studies indexed in Medline, Web of Science, EMBASE, Science Direct, Sportdiscus, and Scopus, to evaluate the effects of the cooling vest (CVs) on perceptual response, physiological behavior, and sports performance in adult physical activity practitioners under heat stress conditions. Among the 711 studies identified in the search, 10 studies for the systematic review and eight for the meta-analysis met the inclusion and exclusion criteria. Overall, the use of CVs showed improvements in certain sports performance indicators, being significant ( < 0.05) in test time and substantial in peak power that could be influenced directly by the significant reduction ( < 0.05) in skin temperature and indirectly by the significant improvement ( < 0.05) in thermal and exertional perceptual responses, without the involvement of core temperature. In conclusion, the use of CVs is a cooling technique that influences perceptual response, thermo-physiological behavior, and sports performance. However, further studies are needed to elucidate the relevance of its application to CVs.
PubMed: 36829626
DOI: 10.3390/bioengineering10020132 -
NeuroImage. Clinical 2023Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and (es)ketamine are used to treat major depressive disorder... (Review)
Review
Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and (es)ketamine are used to treat major depressive disorder (MDD). These different types of medication may involve common neural pathways related to glutamatergic and GABAergic neurotransmitter systems, both of which have been implicated in MDD pathology. We conducted a systematic review of pharmacological proton Magnetic Resonance Spectroscopy (H-MRS) studies in healthy volunteers and individuals with MDD to explore the potential impact of these medications on glutamatergic and GABAergic systems. We searched PubMed, Web of Science and Embase and included randomized controlled trials or cohort studies, which assessed the effects of SSRIs, SNRIs, or (es)ketamine on glutamate, glutamine, Glx or GABA using single-voxel H-MRS or Magnetic Resonance Spectroscopic Imaging (MRSI). Additionally, studies were included when they used a field strength > 1.5 T, and when a comparison of metabolite levels between antidepressant treatment and placebo or baseline with post-medication metabolite levels was done. We excluded animal studies, duplicate publications, or articles with H-MRS data already described in another included article. Twenty-nine studies were included in this review. Fifteen studies investigated the effect of administration or treatment with SSRIs or SNRIs, and fourteen studies investigated the effect of (es)ketamine on glutamatergic and GABAergic metabolite levels. Studies on SSRIs and SNRIs were highly variable, generally underpowered, and yielded no consistent findings across brain regions or specific populations. Although studies on (es)ketamine were also highly variable, some demonstrated an increase in glutamate levels in the anterior cingulate cortex in a time-dependent manner after administration. Our findings highlight the need for standardized study and acquisition protocols. Additionally, measuring metabolites dynamically over time or combining H-MRS with whole brain functional imaging techniques could provide valuable insights into the effects of these medications on glutamate and GABAergic neurometabolism.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Depressive Disorder, Major; Serotonin and Noradrenaline Reuptake Inhibitors; Ketamine; Antidepressive Agents; Glutamic Acid
PubMed: 37812859
DOI: 10.1016/j.nicl.2023.103517 -
Diagnostics (Basel, Switzerland) Apr 2021Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in... (Review)
Review
Concordance between Response Assessment Using Prostate-Specific Membrane Antigen PET and Serum Prostate-Specific Antigen Levels after Systemic Treatment in Patients with Metastatic Castration Resistant Prostate Cancer: A Systematic Review and Meta-Analysis.
Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and serum prostate-specific antigen (PSA) level after systemic treatment and the association between PSMA PET and overall survival in metastatic CRPC patients. PubMed, Embase, and Cochrane library databases were searched until August 2020. Studies that reported the concordance between PSMA PET and PSA response were included. PSMA PET and PSA response evaluation were dichotomized into response vs. non-response to construct two-by-two contingency tables; an ≥30% increase in PSMA PET according to PET Response Criteria in Solid Tumors 1.0 and as an increase in serum PSA level of ≥25% as per Prostate Cancer Working Group 3 guidelines were defined as non-response. The percent agreement rates were pooled using random-effect model. Ten studies (268 patients) were included. The concordance rates ranged 0.50-0.84 with a pooled proportion of 0.73 (95% confidence interval 0.67-0.79). Patients were treated with Lu-PSMA therapy in five, chemotherapy in three, Ra in one, and more than one type in one study. Various PET parameters were used: the most widely evaluated was PSMA tumor volume (PSMA-TV). Similar proportions were found across different therapeutic agents, PET response parameters, and regarding directionality of discordance (PSA response/PSMA non-response vs. PSMA response/PSA non-response). Two studies reported that a decrease in PSMA-TV was associated with better overall survival. PSMA PET and PSA response assessments were discordant in nearly a fourth of metastatic CRPC patients. Further studies are warranted to establish the clinical meaning of this discordance and define appropriate management for such clinical situation.
PubMed: 33917006
DOI: 10.3390/diagnostics11040663 -
Frontiers in Immunology 2022CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense... (Meta-Analysis)
Meta-Analysis
CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). Of these, 6.4% experienced complete response, 10.4% partial response, and 26.1% stable disease for a 16.7% objective response rate (ORR), 42.8% disease control rate, and 4.8-month median duration of response. ORR was significantly higher for hematologic cancers (25.3%) than solid cancers (9.1%, p=0.042). Comparing by mechanism, seven CD47 monoclonal antibodies (mAbs) and six selective SIRPα blockers were given alone or combined with checkpoint inhibitors, targeted therapy, and/or chemotherapy. In solid cancers, selective SIRPα blockade showed a higher ORR (16.2%) than anti-CD47 mAbs (2.8%, p=0.079), which was significant for combination therapies (ORR 28.3% vs 3.0%, respectively, p=0.010). Responses were seen in head and neck, colorectal, endometrial, ovarian, hepatocellular, non-small cell lung, and HER2+gastroesophageal cancers. Dose-limiting toxicity (DLT) was seen in 3.3% of patients (5.4% anti-CD47 mAbs, 1.4% selective SIRPα blockers; p=0.01). The frequency of treatment-related adverse events (TRAEs) ≥grade 3 was 18.0%, similar between the two groups (p=0.082), and mostly laboratory abnormalities. For anti-CD47 mAbs, the most common toxicities included grade 1-2 fatigue (27.2%), headache (21.0%), and anemia (20.5%). For selective SIRPα blockers, these included grade 1-2 infusion reaction (23.1%) and fatigue (15.8%). Anti-CD47 mAbs were significantly more likely than selective SIRPα blockers to cause grade 1-2 fever, chills, nausea/vomiting, headache, and anemia. In conclusion, combination therapies using selective SIRPα blockade had higher response rates in solid tumors than anti-CD47 mAb combinations. Hematologic changes were the main TRAEs, and selective SIRPα blockers seemed to have a better grade 1-2 toxicity profile. Treatment was well-tolerated with minimal DLTs.
Topics: Humans; Protein Binding; Antibodies, Monoclonal; Fatigue; Headache; Neoplasms; CD47 Antigen
PubMed: 36439116
DOI: 10.3389/fimmu.2022.1027235 -
Cancers Oct 2023Intensity-modulated radiotherapy (IMRT), an advanced RT technique, is a considerable treatment option for hepatocellular carcinoma (HCC). However, the distinguishing... (Review)
Review
Intensity-modulated radiotherapy (IMRT), an advanced RT technique, is a considerable treatment option for hepatocellular carcinoma (HCC). However, the distinguishing features of IMRT for HCC have not yet been clearly defined. A systematic review was performed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The PubMed/MedLine, Embase, Cochrane Library, Web of Science, and KoreaMed were used to screen eligible studies focusing on treatment outcomes after IMRT for HCC until 18 April 2023. A total of 1755 HCC patients receiving IMRT among 29 studies from 2009 to 2023 were selected for the meta-analysis. The median proportion of Barcelona Clinic Liver Cancer stage C was 100% (range: 38-100%). Nineteen studies used combined treatment. Pooled rates of response and 1-year local control were 58% (95% confidence interval [CI], 50-65%) and 84% (95% CI, 70-94%), respectively. The median overall survival (OS) was 13 months (range: 5-45 months), and pooled 1- and 3-year OS rates were 59% (95% CI, 52-66%), and 23% (95% CI, 14-33%), respectively. Pooled rates of classic radiation-induced liver disease (RILD), nonclassic RILD, and hepatic toxicity ≥ grade 3 were 2%, 4%, and 4%, respectively. Although most patients had advanced-stage HCC and combined treatment was commonly used, IMRT for HCC showed similar survival to existing RT modalities and relatively low severe toxicity.
PubMed: 37894281
DOI: 10.3390/cancers15204914