CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in ...cancer immunotherapy needs to be elucidated.
Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3 mg/kg every 2 weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient's withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR + PR + SD), and survival (PFS and OS).
A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8%, 4 PR + 20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction ≥ 20% over the baseline was significantly associated with DCR (CEA, p = 0.021; CYFRA21-1, p < 0.001), PFS (CEA, p = 0.028; CYFRA21-1, p < 0.001) and OS (CEA, p = 0.026; CYFRA21-1, p = 0.019). Multivariate analysis confirmed the ability of CYFRA21-1 reduction ≥ 20% to predict DCR (p = 0.002) and PFS (p < 0.001).
The reduction in serum level of CYFRA21-1 or CEA might be a reliable biomarker to predict immunotherapy efficacy in NSCLC patients. NSE was not significant for monitoring the efficacy of nivolumab.
Converting forest lands into bioenergy agriculture could accelerate climate change by emitting carbon stored in forests, while converting food agriculture lands into bioenergy agriculture could ...threaten food security. Both problems are potentially avoided by using abandoned agriculture lands for bioenergy agriculture. Here we show the global potential for bioenergy on abandoned agriculture lands to be less than 8% of current primary energy demand, based on historical land use data, satellite-derived land cover data, and global ecosystem modeling. The estimated global area of abandoned agriculture is 385−472 million hectares, or 66−110% of the areas reported in previous preliminary assessments. The area-weighted mean production of above-ground biomass is 4.3 tons ha−1 y−1, in contrast to estimates of up to 10 tons ha−1 y−1 in previous assessments. The energy content of potential biomass grown on 100% of abandoned agriculture lands is less than 10% of primary energy demand for most nations in North America, Europe, and Asia, but it represents many times the energy demand in some African nations where grasslands are relatively productive and current energy demand is low.
The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI remains challenging. Artificial ...intelligence (AI) approaches allow exploitation of high-dimension oncological data in research and development of precision immuno-oncology.
We conducted a systematic literature review of peer-reviewed original articles studying the ICI efficacy prediction in cancer patients across five data modalities: genomics (including genomics, transcriptomics, and epigenomics), radiomics, digital pathology (pathomics), and real-world and multimodality data.
A total of 90 studies were included in this systematic review, with 80% published in 2021-2022. Among them, 37 studies included genomic, 20 radiomic, 8 pathomic, 20 real-world, and 5 multimodal data. Standard machine learning (ML) methods were used in 72% of studies, deep learning (DL) methods in 22%, and both in 6%. The most frequently studied cancer type was non-small-cell lung cancer (36%), followed by melanoma (16%), while 25% included pan-cancer studies. No prospective study design incorporated AI-based methodologies from the outset; rather, all implemented AI as a post hoc analysis. Novel biomarkers for ICI in radiomics and pathomics were identified using AI approaches, and molecular biomarkers have expanded past genomics into transcriptomics and epigenomics. Finally, complex algorithms and new types of AI-based markers, such as meta-biomarkers, are emerging by integrating multimodal/multi-omics data.
AI-based methods have expanded the horizon for biomarker discovery, demonstrating the power of integrating multimodal data from existing datasets to discover new meta-biomarkers. While most of the included studies showed promise for AI-based prediction of benefit from immunotherapy, none provided high-level evidence for immediate practice change. A priori planned prospective trial designs are needed to cover all lifecycle steps of these software biomarkers, from development and validation to integration into clinical practice.
To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy.
Baseline clinical ...prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis.
NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 P < 0.001, hazard ratio (HR) 2.04, pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis.
We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.
•Immunotherapy/chemoimmunotherapy combinations are currently not superior to immunotherapy alone for high PD-L1 aNSCLC.•NLR with a cut-off of 4 was validated as an independent prognostic factor for immunotherapy in high PD-L1 aNSCLC.•The addition of either PD-L1 ≥ 80% or LDH < 252 U/l to NLR < 4 did not result in better prognostic stratification.•The LIPS-3 is a validated 3-class prognostic classification based on the NLR, ECOG PS and pretreatment steroids.•The LIPS-3 is a routinely assessable adjuvant prognostic tool for high PD-L1 aNSCLC patients.
Malignant mesothelioma (MM) is an aggressive tumor, mainly derived from the pleura, which is predominantly associated with exposure to asbestos fibers. The prognosis of MM patients is particularly ...severe, with a median survival of approximately 9–12 months and latency between exposure and diagnosis ranging from 20–50 years (median 30 years). Emerging evidence has demonstrated that tumor aggressiveness is associated with genome and gene expression abnormalities; therefore, several studies have recently focused on the role of microRNAs (miRNAs) in MM tumorigenesis. miRNAs are small non-protein coding single-stranded RNAs (17–22 nucleotides) involved in numerous cellular processes that negatively regulate gene expression by modulating the expression of downstream target genes. miRNAs are often deregulated in cancer; in particular, the differential miRNA expression profiles of MM cells compared to unaffected mesothelial cells have suggested potential roles of miRNAs as either oncogenes or tumor suppressor genes in MM oncogenesis. In this review, the mechanism of MM carcinogenesis was evaluated through the analysis of the published miRNA expression data. The roles of miRNAs as diagnostic biomarkers and prognostic factors for potential therapeutic strategies will be presented and discussed.
Purpose
Immune checkpoint inhibitors (ICPIs) disrupting PD-1/PD-L1 axis have revolutionized the management of advanced non-small cell lung cancer (NSCLC). Some studies identified the development of ...endocrine toxicity as predictor of better survival in cancer patients treated with ICPIs. The aim of study was to evaluate survival and new onset of immune-related endocrine adverse events (irAEs) in patients treated with nivolumab for advanced NSCLC.
Methods
In a prospective study, 73 patients with previously treated advanced NSCLC received nivolumab in monotherapy. Blood samples were collected at each cycle to monitor thyroid autoimmunity, thyroid, adrenal and somatotroph axes, while thyroid morphology was evaluated by ultrasonography.
Results
An impaired thyroid function was recorded in 23.4% of patients (
n
= 15). Eight patients developed asymptomatic transient thyrotoxicosis (ATT) evolving to hypothyroidism in 50% of cases. In addition, seven patients developed overt hypothyroidism without ATT and with negative autoantibodies. Patients who developed hypothyroidism proved to have better overall survival (OS) as compared with non-developers at both univariate (
p
= 0.021) and multivariate analyses (
p
= 0.023). The survival curve of patients with reduced IGF-I at baseline, or displaying its reduction during the follow-up, showed significantly reduced median survival compared to patients with normal/high IGF-I levels (
p
= 0.031).
Conclusions
Thyroid function abnormalities are the major irAEs in patients treated with nivolumab, and hypothyroidism onset is associated with prolonged survival. Our findings indicate that the development of hypothyroidism is a positive predictive biomarker of nivolumab antitumor efficacy in patients with NSCLC. Low IGF-I levels could represent a negative prognostic factor during nivolumab therapy.
VeriStrat is a blood-based proteomic test with predictive and prognostic significance in second-line treatments for non-small cell lung cancer (NSCLC). This trial was designed to investigate the role ...of VeriStrat in first-line treatment of advanced NSCLC with standard chemotherapy. Here we present the results for 76 non-squamous patients treated with a combination of carboplatin or cisplatin with pemetrexed.
The test-assigned classifications of VeriStrat Good or VeriStrat Poor to samples collected at baseline. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and objective response. Exploratory analyses of end points separately in carboplatin/pemetrexed and cisplatin/pemetrexed subgroups were also conducted.
Patients classified as VeriStrat Good had longer PFS and OS than VeriStrat Poor: 6.5 vs 1.6 months and 10.8 vs 3.4 months, respectively; the corresponding hazard ratios (HRs) were 0.36 (P<0.0001) and 0.26 (P<0.0001); they were also more likely to achieve objective response. Prognostic significance of VeriStrat was confirmed in multivariate analysis. Significant differences in OS and PFS between Veristrat classifications were also found when treatment subgroups were analysed separately.
The trial demonstrated clinical utility of VeriStrat as a prognostic test for standard first-line chemotherapy of non-squamous advanced NSCLC.
A large number of people in the world need to use a wheelchair because of different disabilities. Driving a wheelchair requires complex physical and cognitive abilities which need to be trained. ...Virtual training helps users acquire driving skills in a safe environment. The aim of this paper is to describe and technically validate simulation models for both manual (MW) and powered wheelchairs (PW) based on immersive virtual reality CAVE (VR). As VR system, the Gait Real-time Analysis Interactive Lab (GRAIL) was used, a CAVE equipped with a motion platform with two degrees of freedom and an optoelectronic motion capture system. A real wheelchair was positioned onto the motion platform with rear wheels free to turn in MW modality, and a commercial joystick was installed on an armrest to simulate the PW modality. Passive markers were used to track the wheel rotation, the joystick and the user hand motion. Custom D-flow applications were developed to manage virtual scene response to user actions. Overground tests, based on single wheel rotation, were performed to verify the simulation model reliability. Quantitative results demonstrated that the MW simulator kinematics was consistent with a real wheelchair overground in the absence of wheel slip and inertia (median error for MW 0.40 °, no systematic bias
p
= 0.943, high correlation rho > 0.999,
p
< 0.01). The proposed solution is flexible and adaptable to different wheelchairs, joysticks and optoelectronic systems. The main limitation is the absence of force feedback. Nevertheless, it is a reliable prototype that can be used to validate new virtual scenarios as well as for wheelchair training. The next steps include the system validation with real end users and assessment of the simulator effectiveness as a training tool.
Ricciuti B, Genova C, Crinò L, Libra M, Leonardi GC.Onco Targets Ther. 2019;12:3171-3179. Lucio Crinò has advised that affiliation 3 is incorrect. Thecorrect affiliation 3 should be as ...follows:Department of Medical Oncology, Istituto ScientificoRomagnolo per lo Studio e la Cura dei Tumori (IRSTIRCCS), Meldola, Italy.Read the original article
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