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1.
J Cancer Res Clin Oncol ; 150(6): 329, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38922374

ABSTRACT

PURPOSE: In this study, we aimed to evaluate the potential of routine blood markers, serum tumour markers and their combination in predicting RECIST-defined progression in patients with stage IV non-small cell lung cancer (NSCLC) undergoing treatment with immune checkpoint inhibitors. METHODS: We employed time-varying statistical models and machine learning classifiers in a Monte Carlo cross-validation approach to investigate the association between RECIST-defined progression and blood markers, serum tumour markers and their combination, in a retrospective cohort of 164 patients with NSCLC. RESULTS: The performance of the routine blood markers in the prediction of progression free survival was moderate. Serum tumour markers and their combination with routine blood markers generally improved performance compared to routine blood markers alone. Elevated levels of C-reactive protein (CRP) and alkaline phosphatase (ALP) ranked as the top predictive routine blood markers, and CYFRA 21.1 was consistently among the most predictive serum tumour markers. Using these classifiers to predict overall survival yielded moderate to high performance, even when cases of death-defined progression were excluded. Performance varied across the treatment journey. CONCLUSION: Routine blood tests, especially when combined with serum tumour markers, show moderate predictive value  of RECIST-defined progression in NSCLC patients receiving immune checkpoint inhibitors. The relationship between overall survival and RECIST-defined progression may be influenced by confounding factors.


Subject(s)
Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung , Disease Progression , Immune Checkpoint Inhibitors , Immunotherapy , Lung Neoplasms , Response Evaluation Criteria in Solid Tumors , Humans , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/blood , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Lung Neoplasms/mortality , Biomarkers, Tumor/blood , Male , Retrospective Studies , Female , Middle Aged , Aged , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Adult , Aged, 80 and over , Prognosis
2.
Eur J Radiol Open ; 12: 100562, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38660370

ABSTRACT

Background: The Response Evaluation Criteria in Solid Tumors (RECIST) aims to provide a standardized approach to assess treatment response in solid tumors. However, discrepancies in the selection of measurable and target lesions among radiologists using these criteria pose a significant limitation to their reproducibility and accuracy. This study aimed to understand the factors contributing to this variability. Methods: Machine learning models were used to replicate, in parallel, the selection process of measurable and target lesions by two radiologists in a cohort of 40 patients from an internal pan-cancer dataset. The models were trained on lesion characteristics such as size, shape, texture, rank, and proximity to other lesions. Ablation experiments were conducted to evaluate the impact of lesion diameter, volume, and rank on the selection process. Results: The models successfully reproduced the selection of measurable lesions, relying primarily on size-related features. Similarly, the models reproduced target lesion selection, relying mostly on lesion rank. Beyond these features, the importance placed by different radiologists on different visual characteristics can vary, specifically when choosing target lesions. Worth noting that substantial variability was still observed between radiologists in both measurable and target lesion selection. Conclusions: Despite the successful replication of lesion selection, our results still revealed significant inter-radiologist disagreement. This underscores the necessity for more precise guidelines to standardize lesion selection processes and minimize reliance on individual interpretation and experience as a means to bridge existing ambiguities.

3.
Comput Biol Med ; 174: 108389, 2024 May.
Article in English | MEDLINE | ID: mdl-38593640

ABSTRACT

PURPOSE: To evaluate the potential of synthetic radiomic data generation in addressing data scarcity in radiomics/radiogenomics models. METHODS: This study was conducted on a retrospectively collected cohort of 386 colorectal cancer patients (n = 2570 lesions) for whom matched contrast-enhanced CT images and gene TP53 mutational status were available. The full cohort data was divided into a training cohort (n = 2055 lesions) and an independent and fixed test set (n = 515 lesions). Differently sized training sets were subsampled from the training cohort to measure the impact of sample size on model performance and assess the added value of synthetic radiomic augmentation at different sizes. Five different tabular synthetic data generation models were used to generate synthetic radiomic data based on "real-world" radiomics data extracted from this cohort. The quality and reproducibility of the generated synthetic radiomic data were assessed. Synthetic radiomics were then combined with "real-world" radiomic training data to evaluate their impact on the predictive model's performance. RESULTS: A prediction model was generated using only "real-world" radiomic data, revealing the impact of data scarcity in this particular data set through a lack of predictive performance at low training sample numbers (n = 200, 400, 1000 lesions with average AUC = 0.52, 0.53, and 0.56 respectively, compared to 0.64 when using 2055 training lesions). Synthetic tabular data generation models created reproducible synthetic radiomic data with properties highly similar to "real-world" data (for n = 1000 lesions, average Chi-square = 0.932, average basic statistical correlation = 0.844). The integration of synthetic radiomic data consistently enhanced the performance of predictive models trained with small sample size sets (AUC enhanced by 9.6%, 11.3%, and 16.7% for models trained on n_samples = 200, 400, and 1000 lesions, respectively). In contrast, synthetic data generated from randomised/noisy radiomic data failed to enhance predictive performance underlining the requirement of true signal data to do so. CONCLUSION: Synthetic radiomic data, when combined with real radiomics, could enhance the performance of predictive models. Tabular synthetic data generation might help to overcome limitations in medical AI stemming from data scarcity.


Subject(s)
Colorectal Neoplasms , Tomography, X-Ray Computed , Humans , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/genetics , Female , Male , Tomography, X-Ray Computed/methods , Retrospective Studies , Middle Aged , Aged , Genomics , Tumor Suppressor Protein p53/genetics , Radiomics
4.
J Thorac Imaging ; 39(3): 165-172, 2024 May 01.
Article in English | MEDLINE | ID: mdl-37905941

ABSTRACT

PURPOSE: Pleural plaques (PPs) are morphologic manifestations of long-term asbestos exposure. The relationship between PP and lung function is not well understood, whereas the time-consuming nature of PP delineation to obtain volume impedes research. To automate the laborious task of delineation, we aimed to develop automatic artificial intelligence (AI)-driven segmentation of PP. Moreover, we aimed to explore the relationship between pleural plaque volume (PPV) and pulmonary function tests. MATERIALS AND METHODS: Radiologists manually delineated PPs retrospectively in computed tomography (CT) images of patients with occupational exposure to asbestos (May 2014 to November 2019). We trained an AI model with a no-new-UNet architecture. The Dice Similarity Coefficient quantified the overlap between AI and radiologists. The Spearman correlation coefficient ( r ) was used for the correlation between PPV and pulmonary function test metrics. When recorded, these were vital capacity (VC), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO). RESULTS: We trained the AI system on 422 CT scans in 5 folds, each time with a different fold (n = 84 to 85) as a test set. On these independent test sets combined, the correlation between the predicted volumes and the ground truth was r = 0.90, and the median overlap was 0.71 Dice Similarity Coefficient. We found weak to moderate correlations with PPV for VC (n = 80, r = -0.40) and FVC (n = 82, r = -0.38), but no correlation for DLCO (n = 84, r = -0.09). When the cohort was split on the median PPV, we observed statistically significantly lower VC ( P = 0.001) and FVC ( P = 0.04) values for the higher PPV patients, but not for DLCO ( P = 0.19). CONCLUSION: We successfully developed an AI algorithm to automatically segment PP in CT images to enable fast volume extraction. Moreover, we have observed that PPV is associated with loss in VC and FVC.

5.
Cancers (Basel) ; 15(23)2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38067353

ABSTRACT

For patients with colorectal cancer liver metastases (CRLM), the genetic mutation status is important in treatment selection and prognostication for survival outcomes. This study aims to investigate the relationship between radiomics imaging features and the genetic mutation status (KRAS mutation versus no mutation) in a large multicenter dataset of patients with CRLM and validate these findings in an external dataset. Patients with initially unresectable CRLM treated with systemic therapy of the randomized controlled CAIRO5 trial (NCT02162563) were included. All CRLM were semi-automatically segmented in pre-treatment CT scans and radiomics features were calculated from these segmentations. Additionally, data from the Netherlands Cancer Institute (NKI) were used for external validation. A total of 255 patients from the CAIRO5 trial were included. Random Forest, Gradient Boosting, Gradient Boosting + LightGBM, and Ensemble machine-learning classifiers showed AUC scores of 0.77 (95%CI 0.62-0.92), 0.77 (95%CI 0.64-0.90), 0.72 (95%CI 0.57-0.87), and 0.86 (95%CI 0.76-0.95) in the internal test set. Validation of the models on the external dataset with 129 patients resulted in AUC scores of 0.47-0.56. Machine-learning models incorporating CT imaging features could identify the genetic mutation status in patients with CRLM with a good accuracy in the internal test set. However, in the external validation set, the models performed poorly. External validation of machine-learning models is crucial for the assessment of clinical applicability and should be mandatory in all future studies in the field of radiomics.

6.
Invest Radiol ; 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37921780

ABSTRACT

OBJECTIVES: Response Evaluation Criteria in Solid Tumors (RECIST) is grounded on the assumption that target lesion selection is objective and representative of the change in total tumor burden (TTB) during therapy. A computer simulation model was designed to challenge this assumption, focusing on a particular aspect of subjectivity: target lesion selection. MATERIALS AND METHODS: Disagreement among readers and the disagreement between individual reader measurements and TTB were analyzed as a function of the total number of lesions, affected organs, and lesion growth. RESULTS: Disagreement rises when the number of lesions increases, when lesions are concentrated on a few organs, and when lesion growth borders the thresholds of progressive disease and partial response. There is an intrinsic methodological error in the estimation of TTB via RECIST 1.1, which depends on the number of lesions and their distributions. For example, for a fixed number of lesions at 5 and 15, distributed over a maximum of 4 organs, the error rates are observed to be 7.8% and 17.3%, respectively. CONCLUSIONS: Our results demonstrate that RECIST can deliver an accurate estimate of TTB in localized disease, but fails in cases of distal metastases and multiple organ involvement. This is worsened by the "selection of the largest lesions," which introduces a bias that makes it hardly possible to perform an accurate estimate of the TTB. Including more (if not all) lesions in the quantitative analysis of tumor burden is desirable.

7.
BJR Open ; 5(1): 20230019, 2023.
Article in English | MEDLINE | ID: mdl-37953866

ABSTRACT

Magnetic resonance imaging (MRI) plays a significant role in the routine imaging workflow, providing both anatomical and functional information. 19F MRI is an evolving imaging modality where instead of 1H, 19F nuclei are excited. As the signal from endogenous 19F in the body is negligible, exogenous 19F signals obtained by 19F radiofrequency coils are exceptionally specific. Highly fluorinated agents targeting particular biological processes (i.e., the presence of immune cells) have been visualised using 19F MRI, highlighting its potential for non-invasive and longitudinal molecular imaging. This article aims to provide both a broad overview of the various applications of 19F MRI, with cancer imaging as a focus, as well as a practical guide to 19F imaging. We will discuss the essential elements of a 19F system and address common pitfalls during acquisition. Last but not least, we will highlight future perspectives that will enhance the role of this modality. While not an exhaustive exploration of all 19F literature, we endeavour to encapsulate the broad themes of the field and introduce the world of 19F molecular imaging to newcomers. 19F MRI bridges several domains, imaging, physics, chemistry, and biology, necessitating multidisciplinary teams to be able to harness this technology effectively. As further technical developments allow for greater sensitivity, we envision that 19F MRI can help unlock insight into biological processes non-invasively and longitudinally.

8.
Cancers (Basel) ; 15(20)2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37894447

ABSTRACT

Magnetic resonance imaging (MRI) is an indispensable, routine technique that provides morphological and functional imaging sequences. MRI can potentially capture tumor biology and allow for longitudinal evaluation of head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis evaluates the ability of MRI to predict tumor biology in primary HNSCC. Studies were screened, selected, and assessed for quality using appropriate tools according to the PRISMA criteria. Fifty-eight articles were analyzed, examining the relationship between (functional) MRI parameters and biological features and genetics. Most studies focused on HPV status associations, revealing that HPV-positive tumors consistently exhibited lower ADCmean (SMD: 0.82; p < 0.001) and ADCminimum (SMD: 0.56; p < 0.001) values. On average, lower ADCmean values are associated with high Ki-67 levels, linking this diffusion restriction to high cellularity. Several perfusion parameters of the vascular compartment were significantly associated with HIF-1α. Analysis of other biological factors (VEGF, EGFR, tumor cell count, p53, and MVD) yielded inconclusive results. Larger datasets with homogenous acquisition are required to develop and test radiomic-based prediction models capable of capturing different aspects of the underlying tumor biology. Overall, our study shows that rapid and non-invasive characterization of tumor biology via MRI is feasible and could enhance clinical outcome predictions and personalized patient management for HNSCC.

9.
Insights Imaging ; 14(1): 133, 2023 Jul 21.
Article in English | MEDLINE | ID: mdl-37477715

ABSTRACT

BACKGROUND: Tumour hypoxia is a negative predictive and prognostic biomarker in colorectal cancer typically assessed by invasive sampling methods, which suffer from many shortcomings. This retrospective proof-of-principle study explores the potential of MRI-derived imaging markers in predicting tumour hypoxia non-invasively in patients with colorectal liver metastases (CLM). METHODS: A single-centre cohort of 146 CLMs from 112 patients were segmented on preoperative T2-weighted (T2W) images and diffusion-weighted imaging (DWI). HIF-1 alpha immunohistochemical staining index (high/low) was used as a reference standard. Radiomic features were extracted, and machine learning approaches were implemented to predict the degree of histopathological tumour hypoxia. RESULTS: Radiomic signatures from DWI b200 (AUC = 0.79, 95% CI 0.61-0.93, p = 0.002) and ADC (AUC = 0.72, 95% CI 0.50-0.90, p = 0.019) were significantly predictive of tumour hypoxia. Morphological T2W TE75 (AUC = 0.64, 95% CI 0.42-0.82, p = 0.092) and functional DWI b0 (AUC = 0.66, 95% CI 0.46-0.84, p = 0.069) and b800 (AUC = 0.64, 95% CI 0.44-0.82, p = 0.071) images also provided predictive information. T2W TE300 (AUC = 0.57, 95% CI 0.33-0.78, p = 0.312) and b = 10 (AUC = 0.53, 95% CI 0.33-0.74, p = 0.415) images were not predictive of tumour hypoxia. CONCLUSIONS: T2W and DWI sequences encode information predictive of tumour hypoxia. Prospective multicentre studies could help develop and validate robust non-invasive hypoxia-detection algorithms. CRITICAL RELEVANCE STATEMENT: Hypoxia is a negative prognostic biomarker in colorectal cancer. Hypoxia is usually assessed by invasive sampling methods. This proof-of-principle retrospective study explores the role of AI-based MRI-derived imaging biomarkers in non-invasively predicting tumour hypoxia in patients with colorectal liver metastases (CLM).

10.
Eur Radiol ; 33(5): 3557-3565, 2023 May.
Article in English | MEDLINE | ID: mdl-36567379

ABSTRACT

OBJECTIVES: In many countries, workers who developed asbestosis due to their occupation are eligible for government support. Based on the results of clinical examination, a team of pulmonologists determine the eligibility of patients to these programs. In this Dutch cohort study, we aim to demonstrate the potential role of an artificial intelligence (AI)-based system for automated, standardized, and cost-effective evaluation of applications for asbestosis patients. METHODS: A dataset of n = 523 suspected asbestosis cases/applications from across the Netherlands was retrospectively collected. Each case/application was reviewed, and based on the criteria, a panel of three pulmonologists would determine eligibility for government support. An AI system is proposed, which uses thoracic CT images as input, and predicts the assessment of the clinical panel. Alongside imaging, we evaluated the added value of lung function parameters. RESULTS: The proposed AI algorithm reached an AUC of 0.87 (p < 0.001) in the prediction of accepted versus rejected applications. Diffusion capacity (DLCO) also showed comparable predictive value (AUC = 0.85, p < 0.001), with little correlation between the two parameters (r-squared = 0.22, p < 0.001). The combination of the imaging AI score and DLCO achieved superior performance (AUC = 0.95, p < 0.001). Interobserver variability between pulmonologists on the panel was estimated at alpha = 0.65 (Krippendorff's alpha). CONCLUSION: We developed an AI system to support the clinical decision-making process for the application to the government support for asbestosis. A multicenter prospective validation study is currently ongoing to examine the added value and reliability of this system alongside the clinic panel. KEY POINTS: • Artificial intelligence can detect imaging patterns of asbestosis in CT scans in a cohort of patients applying for state aid. • Combining the AI prediction with the diffusing lung function parameter reaches the highest diagnostic performance. • Specific cases with fibrosis but no asbestosis were correctly classified, suggesting robustness of the AI system, which is currently under prospective validation.


Subject(s)
Artificial Intelligence , Asbestosis , Humans , Retrospective Studies , Cohort Studies , Reproducibility of Results , Asbestosis/diagnosis
11.
Abdom Radiol (NY) ; 47(8): 2739-2746, 2022 08.
Article in English | MEDLINE | ID: mdl-35661244

ABSTRACT

PURPOSE: To assess the role of radiomics in detection of high-risk (pT3-4) colon cancer and develop a combined model that combines both radiomics and CT staging of colon cancer. METHODS: We included 292 colon cancer patients who underwent pre-operative CT and primary surgical resection within 2 months. Three-dimensional segmentations and CT staging of primary colon tumors were done. From each 3D segmentation of colon tumor, radiomic features were automatically extracted. Logistic regression analysis was performed to identify associations between radiomic features and high-risk (pT3-4) colon tumors. A combined model that integrated both radiomics and CT staging was developed and their diagnostic performance was compared with that of conventional CT staging. Tenfold cross-validation was used to validate the performance of the model and CT staging. RESULTS: The model that combined radiomic features and CT staging demonstrated a significantly better performance in detection of high-risk colon tumors in training set (AUC = 0.799, 95% CI: 0.720-0.839 for combined model and AUC = 0.697, 95% CI = 0.538-0.756 for CT staging only, p < 0.001 for difference). Cross-validation results also demonstrated significantly better detection performance of combined model (AUC = 0.727, 95% Confidence Interval (CI): 0.621-0.777 for combined model and AUC = 0.628, 95% CI = 0.558-0.689 for CT staging only, Boot CI = 0.099). CONCLUSION: CT radiomic features of primary colon cancer, combined with CT staging, can improve the detection of high-risk colon cancer patients.


Subject(s)
Colonic Neoplasms , Tomography, X-Ray Computed , Colonic Neoplasms/diagnostic imaging , Humans , Radiologists , Retrospective Studies , Tomography, X-Ray Computed/methods
13.
Front Oncol ; 11: 637804, 2021.
Article in English | MEDLINE | ID: mdl-33889546

ABSTRACT

Background: Immune checkpoint inhibitor efficacy in advanced cancer patients remains difficult to predict. Imaging is the only technique available that can non-invasively provide whole body information of a patient's response to treatment. We hypothesize that quantitative whole-body prognostic information can be extracted by leveraging artificial intelligence (AI) for treatment monitoring, superior and complementary to the current response evaluation methods. Methods: To test this, a cohort of 74 stage-IV urothelial cancer patients (37 in the discovery set, 37 in the independent test, 1087 CTs), who received anti-PD1 or anti-PDL1 were retrospectively collected. We designed an AI system [named prognostic AI-monitor (PAM)] able to identify morphological changes in chest and abdominal CT scans acquired during follow-up, and link them to survival. Results: Our findings showed significant performance of PAM in the independent test set to predict 1-year overall survival from the date of image acquisition, with an average area under the curve (AUC) of 0.73 (p < 0.001) for abdominal imaging, and 0.67 AUC (p < 0.001) for chest imaging. Subanalysis revealed higher accuracy of abdominal imaging around and in the first 6 months of treatment, reaching an AUC of 0.82 (p < 0.001). Similar accuracy was found by chest imaging, 5-11 months after start of treatment. Univariate comparison with current monitoring methods (laboratory results and radiological assessments) revealed higher or similar prognostic performance. In multivariate analysis, PAM remained significant against all other methods (p < 0.001), suggesting its complementary value in current clinical settings. Conclusions: Our study demonstrates that a comprehensive AI-based method such as PAM, can provide prognostic information in advanced urothelial cancer patients receiving immunotherapy, leveraging morphological changes not only in tumor lesions, but also tumor spread, and side-effects. Further investigations should focus beyond anatomical imaging. Prospective studies are warranted to test and validate our findings.

14.
Front Oncol ; 11: 609054, 2021.
Article in English | MEDLINE | ID: mdl-33738253

ABSTRACT

BACKGROUND: Checkpoint inhibitors provided sustained clinical benefit to metastatic lung cancer patients. Nonetheless, prognostic markers in metastatic settings are still under research. Imaging offers distinctive advantages, providing whole-body information non-invasively, while routinely available in most clinics. We hypothesized that more prognostic information can be extracted by employing artificial intelligence (AI) for treatment monitoring, superior to 2D tumor growth criteria. METHODS: A cohort of 152 stage-IV non-small-cell lung cancer patients (NSCLC) (73 discovery, 79 test, 903CTs), who received nivolumab were retrospectively collected. We trained a neural network to identify morphological changes on chest CT acquired during patients' follow-ups. A classifier was employed to link imaging features learned by the network with overall survival. RESULTS: Our results showed significant performance in the independent test set to predict 1-year overall survival from the date of image acquisition, with an average area under the curve (AUC) of 0.69 (p < 0.01), up to AUC 0.75 (p < 0.01) in the first 3 to 5 months of treatment, and 0.67 AUC (p = 0.01) for durable clinical benefit (6 months progression-free survival). We found the AI-derived survival score to be independent of clinical, radiological, PDL1, and histopathological factors. Visual analysis of AI-generated prognostic heatmaps revealed relative prognostic importance of morphological nodal changes in the mediastinum, supraclavicular, and hilar regions, lung and bone metastases, as well as pleural effusions, atelectasis, and consolidations. CONCLUSIONS: Our results demonstrate that deep learning can quantify tumor- and non-tumor-related morphological changes important for prognostication on serial imaging. Further investigation should focus on the implementation of this technique beyond thoracic imaging.

15.
Crit Rev Oncol Hematol ; 160: 103309, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33757836

ABSTRACT

Soft tissue sarcomas (STS) represent a broad family of rare tumours for which surgery with radiotherapy represents first-line treatment. Recently, neoadjuvant chemo-radiotherapy has been increasingly used in high-risk patients in an effort to reduce surgical morbidity and improve clinical outcomes. An adequate understanding of the efficacy of neoadjuvant therapies would optimise patient care, allowing a tailored approach. Although response evaluation criteria in solid tumours (RECIST) is the most common imaging method to assess tumour response, Choi criteria and functional and molecular imaging (DWI, DCE-MRI and 18F-FDG-PET) seem to outperform it in the discrimination between responders and non-responders. Moreover, the radiologic-pathology correlation of treatment-related changes remains poorly understood. In this review, we provide an overview of the imaging assessment of tumour response in STS undergoing neoadjuvant treatment, including conventional imaging (CT, MRI, PET) and advanced imaging analysis. Future directions will be presented to shed light on potential advances in pre-surgical imaging assessments that have clinical implications for sarcoma patients.


Subject(s)
Sarcoma , Soft Tissue Neoplasms , Fluorodeoxyglucose F18 , Humans , Neoadjuvant Therapy , Positron-Emission Tomography , Radiopharmaceuticals , Sarcoma/diagnostic imaging , Sarcoma/therapy , Treatment Outcome
16.
Abdom Radiol (NY) ; 44(6): 1960-1984, 2019 06.
Article in English | MEDLINE | ID: mdl-31049614

ABSTRACT

From diagnostics to prognosis to response prediction, new applications for radiomics are rapidly being developed. One of the fastest evolving branches involves linking imaging phenotypes to the tumor genetic profile, a field commonly referred to as "radiogenomics." In this review, a general outline of radiogenomic literature concerning prominent mutations across different tumor sites will be provided. The field of radiogenomics originates from image processing techniques developed decades ago; however, many technical and clinical challenges still need to be addressed. Nevertheless, increasingly accurate and robust radiogenomic models are being presented and the future appears to be bright.


Subject(s)
Genomics/trends , Medical Oncology/trends , Precision Medicine/methods , Radiology/trends , Biomarkers, Tumor , Humans , Phenotype
17.
Cancer Immunol Immunother ; 68(3): 503-515, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30652208

ABSTRACT

For the treatment of metastatic renal cell cancer several strategies are used among which the mTOR inhibitor everolimus. As mTOR plays an important role in the immune system, e.g., by controlling the expression of the transcription factor FoxP3 thereby regulating regulatory T cells (Tregs), it plays a key role in the balance between tolerance and inflammation. Previous reports showed stimulatory effects of mTOR inhibition on the expansion of Tregs, an effect that can be considered detrimental in terms of cancer control. Since metronomic cyclophosphamide (CTX) was shown to selectively deplete Tregs, a phase 1 clinical trial was conducted to comprehensively investigate the immune-modulating effects of several dosages and schedules of CTX in combination with the standard dose of everolimus, with the explicit aim to achieve selective Treg depletion. Our data show that 50 mg of CTX once daily and continuously administered, in combination with the standard dose of 10 mg everolimus once daily, not only results in depletion of Tregs, but also leads to a reduction in MDSC, a sustained level of the CD8+ T-cell population accompanied by an increased effector to suppressor ratio, and reversal of negative effects on three peripheral blood DC subsets. These positive effects on the immune response may contribute to improved survival, and therefore this combination therapy is further evaluated in a phase II clinical trial.


Subject(s)
CD8-Positive T-Lymphocytes/drug effects , Carcinoma, Renal Cell/immunology , Cyclophosphamide/pharmacology , Everolimus/pharmacology , Kidney Neoplasms/immunology , T-Lymphocytes, Regulatory/drug effects , B7-2 Antigen/analysis , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Killer Cells, Natural/immunology , Lymphocyte Activation , Myeloid-Derived Suppressor Cells/drug effects , Myeloid-Derived Suppressor Cells/immunology , Neoplasm Metastasis , T-Lymphocytes, Regulatory/immunology
18.
Insights Imaging ; 9(6): 911-914, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30421396

ABSTRACT

Medical imaging is a vital part of the clinical decision-making process, especially in an oncological setting. Radiology has experienced a great wave of change, and the advent of quantitative imaging has provided a unique opportunity to analyse patient images objectively. Leveraging radiomics and deep learning, there is increased potential for synergy between physicians and computer networks-via computer-aided diagnosis (CAD), computer-aided prediction of response (CARP), and computer-aided biological profiling (CABP). The ongoing digitalization of other specialties further opens the door for even greater multidisciplinary integration. We envision the development of an integrated system composed of an aggregation of sub-systems interoperating with the aim of achieving an overarching functionality (in this case' better CAD, CARP, and CABP). This will require close multidisciplinary cooperation among the clinicians, biomedical scientists, and (bio)engineers as well as an administrative framework where the departments will operate not in isolation but in successful harmony. KEY POINTS: • The advent of quantitative imaging provides a unique opportunity to analyse patient images objectively. • Radiomics and deep learning allow for a more detailed overview of the tumour (i.e., CAD, CARP, and CABP) from many different perspectives. • As it currently stands, different medical disciplines have developed different stratification methods, primarily based on their own field-often to the exclusion of other departments. • The digitalization of other specialties further opens the door for multidisciplinary integration. • The long-term vision for precision medicine should focus on the development of integration strategies, wherein data derived from the patients themselves (via multiple disciplines) can be used to guide clinical decisions.

19.
Avicenna J Med ; 5(4): 117-22, 2015.
Article in English | MEDLINE | ID: mdl-26629466

ABSTRACT

BACKGROUND: Surgical site infection (SSI) is considered one of the most serious complications in total joint arthroplasty (TJA). This study seeks to analyze the predictive value of preoperative and postoperative nutritional biomarkers for SSI in elective TJA. METHODOLOGY: Nutritional markers were gathered retrospectively utilizing patient's records from the orthopedics department at Benghazi Medical Center (BMC). The sample spanned cases admitted during the 20-month period between January 2012 and August 2013 and had undergone either elective total hip replacement or total knee replacement. The collected lab results included a complete blood count, total lymphocyte count (TLC), and serum albumin (S. alb.) levels. The patients were then divided into two groups based on the occurrence of an SSI. RESULTS: A total of 135 total knee (81.5%, n = 110/135) and total hip (18.5%, n = 25/135) replacements were performed at BMC during the study period. Among these cases, 57% (n = 78/135) had patient records suitable for statistical analysis. The average preoperative TLC was 2.422 ×10(3) cells/mm(3) (range = 0.8-4.7 ×10(3) cells/mm(3)) whereas that number dropped after the surgery to 1.694 ×10(3) cells/mm(3) (range = 0.6-3.8 ×10(3) cells/mm(3)). S. alb. levels showed a mean of 3.973 g/dl (range = 2.9-4.7 g/dl) preoperatively and 3.145 g/dl (range = 1.0-4.1 g/dl) postoperatively. The majority of TJA patients did not suffer any complication (67.4%, n = 91/135) while eight cases (5.9%) suffered from a superficial SSI. CONCLUSION: Preoperative S. alb. was identified as the only significant predictor for SSI (P = 0.011). Being a preventable cause of postoperative morbidity, it is recommended that the nutritional status (especially preoperative S. alb.) of TJA patients be used as a screening agent and appropriate measures be taken to avoid SSI.

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