LUNG CANCER

LUNG CANCER

Lung cancer is usually diagnosed in advanced stages with majority of patients already presenting metastatic disease. Only 20 % of NSCLC patients have early stage disease at the time of diagnosis, thus being potentially resectable. The current gold standard is lobectomy with hilar and mediastinal lymph-node sampling or dissection. Curative stereotactic body radiotherapy (SABR) should be offered to patients with stage I NSCLC who have clinical comorbidities or are at very high surgery-related risk, and those who refuse to undergo surgical procedure. Post-operative platinum-based chemotherapy is recommended for all patients with stage II and III surgically resected disease. For patients with locally advanced stage NSCLS, there are different recommended options, including

  • Surgery followed by adjuvant chemotherapy
  • Neoadjuvant chemotherapy followed by surgery
  • Neoadjuvant chemo-radiation followed by surgery

Eligibility for pre-operative or post-operative platinum-doublets with or without radiotherapy should be evaluated in the context of an experienced multidisciplinary team.

The diagnostic evaluation initially focuses on careful physical examination and patient’s history, to identify new symptoms or a significant change in the common respiratory symptoms.

In clinical trials, all patients with suspected lung cancer will undergo a non-invasive chest imaging, including X-rays, CT-scan, and if needed positron emission tomography (PET) with fluorodeoxyglucose (FDG).

Conventional contrast-enhanced chest CT-scan is considered the best exam to detect lung cancer, as it provides detailed information on anatomic location, margins, invasion of surrounding structures or chest wall, and mediastinal lymph nodes involvement.

Use of imaging presents a great opportunity for selecting the right patients and enriching the trial.

IAG offers multiple imaging technique solutions, which are utilized in clinical trials both, while scanning patients for inclusion in the clinical studies, and while assessing the efficacy of ongoing treatments.

  • CT Imaging – Computed Tomography (CT) scan of the chest area is the keystone of lung cancer imaging based on which further management options are decided.
  • SPECT imaging – A single-photon emission computed tomography (SPECT) renders tomographic imaging, which could be a more accurate method for regional valuation by diagnosing radioactivity in all pulmonary lobes, avoiding spatial overlapping.
  • ctDNA testing – Without the risks inherent to biopsy, ctDNA can be attained over time permitting for some serial assessments. Numerous clinical studies have furthermore suggested that ctDNA can be used to identify the occurrence of minimal residual disease (MRD) post-surgical resection in various cancer types, especially lung cancer.
  • EGFR/ALK/ROS/BRAF testing – For targeted therapies, with Mechanism of actions targeting multiple mutations in non-small-cell lung cancer (NSCLC) patients, EGFR/ALK/ROS/BRAF testing imaging techniques are useful to assess the patients for eligibility in the trial as well to assess the treatment efficacy.
  • MRI and ECG – MRI and ECG scans are typically utilized to assess the organ functions, before including patients in the Lung cancer clinical trials.

At IAG, we design and implement protocols for thoracic CT images, assess the need for breath hold and use of intravenous contrast. We support image reconstruction, quality control and reading.

To optimise nodule detection, normally all baseline CTs are read by experienced thoracic radiologists; sometimes located in the local trial centres or at a central site. All discrepancies and adjudication is done by IAG’s imaging specialists.  It is common to ask the readers to identify and record all lung nodules greater than a certain size and diameter. We deploy volumetric measures whenever possible. Our measurements include the volume and maximum intensity projections (MIPs) to aid the detection.

MRI exams are done in addition to CT  when we are trying to assess the drug efficacy in a specific way, such as 1) resolution of the tumour invasion into the chest wall and the mediastinal structures (pancoast tumour); 2) impact on the solid and vascular hilar masses; 3) impact on the diaphragmatic abnormalities or when following-up mediastinal lymphoma.

MR exams are susceptible to motion artefacts such as breathing and require specific software to process. Recently, new applications, such as whole-body MR (WBMR) imaging are being deployed to assess metastatic disease. Diffusion weighted imaging (DWI) is used to assess changes in the tumour cellularity and the integrity of the cellular membrane. The DWI sequence is made susceptible to the differences in water mobility. The motion of water molecules is more restricted in tissues with a high cellular density associated with numerous intact cell membranes (e.g. tumour tissue). This technique can be applied for tumour detection and tumour characterisation and for the monitoring of response to treatment.

PET/CT is a combined imaging technique: CT giving anatomical information and PET giving metabolic information to detect lesions initially not seen on CT and to assess more precise localisation of lesions, delineate them from their surrounding structures and provide more accurate characterisation of a lesion as benign or malignant.

Reach out to our expert team, as you are designing and planning your trial.

About IAG, Image Analysis Group

IAG, Image Analysis Group is a strategic partner to bio-pharmaceutical companies developing new treatments to improve patients’ lives. Our dynamic Strategy, Trial Solutions and Bio-Partnering divisions work closely to meet critical needs of biotechnology companies: funding, clinical development, and monetization of their assets. We fuse decades of therapeutic insights, risk-sharing business model and agile culture to accelerate novel drug development. IAG broadly leverages its core imaging expertise, proprietary technology platform DYNAMIKA and capabilities to support an objective early go no/ go decision and drive excellence for tomorrow’s innovative therapeutic agents with speed.

Contact our expert team: imaging.experts @ ia-grp.com

 

 

READ NEXT CASE STUDY >
Experience: Scoring Systems
  • RECIST1.1
  • iRECIST
Experience: Imaging
  • CT
  • PET/CT
  • MRI
  • DWI
  • WBMRI
  • PET
Publications

Since 2007, over 2000 articles were published to cover scientific discoveries, technology break-throughs and special cases. We list here some critically important papers and abstracts.

Testimonials

Combining our technologies and business advisory services with promising life science companies has yielded spectacular results over the past five years. As a trusted partner to many biotech and pharma companies, IAG’s team is proud to share your words and quotes.

Decision Making in Surveillance of High-Grade Gliomas Using Perfusion MRI as Adjunct to Conventional MRI and Artificial Intelligence.

Copyright © 2019 by American Society of Clinical Oncology
Journal of Clinical Oncology. 2019 May;37(15)_suppl doi: 10.1200/JCO.2019.37.15_suppl.2054

Abstract

BACKGROUND:
Surveillance of High-Grade Gliomas (HGGs) remains a major challenge in clinical neurooncology. Histopathological validation is not an option during the course of disease and imaging surveillance suffers from ambiguous features of both disease progression and treatment related changes. This study aimed to differentiate between Pseudoprogression (PsP) and Progressive Disease (PD) using an artificial intelligence (support vector machine – SVM) classification algorithm.
METHODS:
Two groups of patients with histologically proven HGGs were analysed, a group with a single time point DSC perfusion MRI (45 patients) and a group with multiple time point DSC perfusion MRI (19 patients). Both groups included conventional MRI studies prior and after each perfusion MRI. This study design aimed to replicate decision making in clinical practice including multiple previous studies for each patient. SVM training was performed with all available MRI studies for each group and classification was based on different feature datasets from a single or multiple (subtracted features) time points. Classification accuracy comparisons were performed by calculating prediction error rates for different feature datasets and different time point analyses.
RESULTS:
Our results indicate that the addition of multiple time point perfusion MRI combined with structural (conventional with gadolinium-enhanced sequences) MRI features results in optimal classification performance (median error rate: 0.016, lowest value dispersion). Subtracted feature datasets improved classification performance, more prominently when the final and first perfusion studies were included in the analysis. On the contrary, in the single time point group analysis, structural feature-based classification performed best (median error rate: 0.012).
CONCLUSIONS:
Validation of our results with a larger patient cohort may have significant clinical importance in optimising imaging surveillance and clinical decision making for patients with HGG.

Multi-Parametric MRI as Supplement to mRANO Criteria for Response Assessment to MDNA55 in Adults with Recurrent or Progressive Glioblastoma.

Copyright © 2019 by American Society of Clinical Oncology
Journal of Clinical Oncology. 2019 May;37(15)_suppl doi: 10.1200/JCO.2019.37.15_suppl.e13559

Abstract

BACKGROUND:
Modified response assessment in neuro-oncology (mRANO) criteria are widely used in GBM but seem insufficient to capture Pseudoprogression (PsP), which occurs due to extensive inflammatory infiltration, increased vascular permeability, tumor necrosis and edema. mRANO criteria recommend volumetric response evaluation using contrast-enhanced T1 subtraction maps for identifying PsP. Our approach incorporates multi-parametric MRI biomarkers to unravel the true PsP from recurrence or distinguish Pseudo Response (PsR) – following anti-VEGF agents – from delayed (immuno)response.
METHODS:
Multiple time-points MRI (18-24h after convection-enhance delivery of the anti-IL4-R agent MDNA55, then at 30-day intervals) was utilized to determine response. Multi-parametric MRI biomarkers analyzed included (1) 3D-FLAIR-T2-based tumor volume assessment reflecting edema, necrosis and tumor infiltration; (2) 3D-gadolinium-enhanced-based tumor volume estimation reflecting active tumor infiltration, neo-angiogenesis and disrupted blood brain barrier; (3) Dynamic susceptibility contrast-based relative cerebral blood volume (rCBV) measurements for estimation of the vascular tumour properties; and (4) Diffusion weighted imaging – Apparent diffusion coefficient measurements that assess interstitial edema, tumor cellularity and ischemic injury.
RESULTS:
We demonstrate similar imaging phenotypes on conventional FLAIR-T2- and enhanced T1- MR images among different disease states (PsP vs true progression, PsR vs and immuno-response) and describe the perfusion and diffusion MRI biomarkers that improve response staging including PsP masking true progression, PsP masking clinical response, early progression with delayed response, and differentiation between true and PsR. The results are compared with the mRANO-based assessments for concurrence.
CONCLUSIONS:
Incorporating multi-parametric MRI measurements to determine the complex underlying tissue processes enables a better assessment of PsP, PsR and delayed tumour response, and can supplement mRANO-based response assessments in GBM patients undergoing novel immunotherapies.

Early Response Assessment Through Multiparametric MRI Based Endpoints In A Phase II Multicenter Study Evaluating the Efficacy of DPX-Survivac, Intermittent Low Dose Cyclophosphamide (CPA) and Pembrolizumab Combination Study in Subjects with Solid Tumors.

Copyright © 2019 by American Society of Clinical Oncology
Journal of Clinical Oncology. 2019 May;37(15)_suppl doi: 10.1200/JCO.2019.37.15_suppl.e14245

Abstract

BACKGROUND:
Accurate assessment of tumor response to immunotherapy is challenged by pseudoprogression that mimics true progression. Conventional imaging and RECIST assessment do not adequately distinguish between them given their inability to account for changes in the tumor microenvironment. DPX-Survivac is a novel T cell activating therapy that triggers immune responses against tumors expressing survivin and is being studied in this trial in combination with CPA and pembrolizumab in several solid tumors. Multiparametric MRI approaches – dynamic contrast-enhanced MRI and diffusion-weighted imaging MRI are useful for accurate assessment of structural, perfusion and vascular assessment of the lesion and may identify pseudoprogression and compare to the RECIST-based assessment.
METHODS:
The study will enroll up to 226 evaluable subjects in 5 different cohorts: ovarian cancer, HCC, NSCLC, bladder cancer and MSI-H cancer. These subjects will undergo initial imaging 28 days prior to treatment, to be assessed based on RECIST 1.1, and a pre-treatment tumor biopsy for quantitation of survivin and PD-L1 expression and MSI analyses. Treatment for 35 cycles or until disease progression. All patients will have CT images for RECIST 1.1 and iRECIST assessment. A subset of subjects will undergo mpMRI to calculate advanced imaging biomarkers.
RESULTS:
MRI, clinical and patient-reported outcomes will be analyzed.
CONCLUSIONS:
This study will provide important evidence on the utility of mpMRI + CT-based assessment of response to immunotherapy and use it as an adjunct to the CT-based RECIST criteria by providing insight on how tumor lesions are impacted by treatment.

Radiomics in Clinical Trials – The Rationale, Current Practices, and Future Considerations

Radiomics involves deep quantitative analysis of radiological images for structural and/or functional information. – It is a phenomic assessment of disease to understand lesion microstructure, microenvironment and molecular/cellular function. – In oncology, it helps us accurately classify, stratify and prognosticate tumors based on if, how and when they transform, infiltrate, involute or metastasize, – Utilizing radiomics in clinical trials is exploratory, and not an established end-point. – Integrating radiomics in an imaging-based clinical trials involves a streamlined workflow to handle large datasets, robust platforms to accommodate machine learning calculations, and seamless incorporation of derived insights into outcomes matrix.

LIVER CANCER

LIVER CANCER

Liver imaging in patients with a history of known or suspected malignancy is important because the liver is a common site of metastatic spread, especially tumours from the colon, lung, pancreas and stomach, and in patients with chronic liver disease who are at risk for developing hepatocellular carcinoma.

The goal of liver imaging in oncologic patients includes liver tumour detection and characterisation.

Liver biopsy is a standard procedure for diagnosing and staging non-alcoholic fatty-liver disease. However, biopsy has a number of disadvantages, including sampling error, intra- and inter-rater variability and poor patient acceptance due to potential complications. Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide.

Quantitative imaging is a promising approach for evaluating normal biological or pathogenic processes, as well as response to treatment and intervention without the need for invasive procedures. The field of hepatic MRI is relatively new compared with other organ systems as the complexity of hepatic imaging, including the dual blood supply of the portal vein and hepatic vessels, makes tracer imaging particularly challenging.

HCC commonly develops in the setting of concomitant or previous cirrhotic nodules or hepatic fibrosis, which can complicate classification of suspicious lesions using conventional imaging techniques alone. Depending on the imaging technique used (MRI, CT, US), various quantitative biomarkers can be extracted.

Proton Density Fat Fraction (PDFF)

Chemical-shift imaging is used to separate the liver signal into its fat and water parts.  PDFF is the fraction of MRI-visible protons attributable to fat divided by all protons in the liver attributable to fat and water. This technique acquires GREs  at appropriately spaced echo times. To increase examination accuracy, a low flip angle is used for minimizing T1 bias, along with multiple echoes for correcting T2* effects.

A standard MRI scanner of major manufactures will allow to reproducibly image patients and interpret images. The diagnostic accuracy of MRI-PDFF was validated by several studies, including Idilman et al and Bannas et al, which showed that MRI-based PDFF assessments closely correlated with histology acquired from liver biopsy.

MR Spectroscopy 

MR Spectroscopy, similarly to liver biopsy, is collected from a single region positioned in the liver parenchyma and directly measures the differences in water and fat peaks on a resonance frequency domain. Clearly, the quantification is done only within a particular region which limits the comprehensive understanding of the liver disease. Currently, MRS is not available on all MR scanners, which confines its routine adoption for clinical trials and clinical practice.

MR Electrography 

MR elastography uses a modified phase-contrast pulse sequence to visualize rapidly propagating mechanical shear waves. It is available in MRI scanners by major manufactures and can be acquired simultaneously with  other MRI sequences.  The best known application of MRE is in quantification of hepatic fibrosis.

Dynamic Contract Enhanced MRI

Currently, the use of DCE-MRI in both primary hepatic tumors and metastatic lesions are being investigated, as well as non-oncologic disease processes including hepatocellular fibrosis, cirrhosis, acute liver failure, and post-liver transplant rejection. DCE-MRI and tracer parameters can help differentiate regenerative, benign nodules from more concerning lesions. Sahani et al. reported models that differentiated blood flow and blood volume found differences in moderately or poorly differentiated HCCs. General concepts of differing microvascular structure and selection of appropriate anti-angiogenic therapies are important to maximize treatment response. DCE-MRI may assist in assessment of tumor response even before RECIST criteria can apply; early changes during therapy as demonstrated by perfusion parameters are not often seen on morphologic methods of imaging. Our upcoming publication will detail this further.

Our experience in liver imaging and quantitative biomarkers suggests that while there are multiple challenges in implementing MRI-PDFF, MRS, MRE, DCE-MRI in clinical trials, these techniques are reliable and noninvasive tools to assess hepatic steatosis, fibrosis and microvascular structure.In lights of sophisticated therapeutic developments and high treatment standards, we anticipate that in the next few years  multiparametric MR imaging will become more of a standard, enabling better diagnosis and faster assessments of the treatment response.

References

  • Sommer, W. H. et al. Contrast agents as a biological marker in magnetic resonance imaging of the liver: conventional and new approaches. Abdom. Imaging 37, 164–79 (2012).Eisenhauer, E. A. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer45, 228–247. (2009)
  • Yang, X. & Knopp, M. V. Quantifying tumor vascular heterogeneity with dynamic contrast-enhanced magnetic resonance imaging: a review. J Biomed Biotechnol2011, 732848 (2011).
  • Li, S. P. & Padhani, A. R. Tumor response assessments with diffusion and perfusion MRI. J. Magn. Reson. Imaging35, 745–63 (2012).
  • Sourbron, S. P. & Buckley, D. L. Classic models for dynamic contrast-enhanced MRI. NMR Biomed.26(8), 1004–27 (2013).
  • Hylton, N. Dynamic contrast-enhanced magnetic resonance imaging as an imaging biomarker. J. Clin. Oncol.24, 3293–8 (2006).
  • Ferl, G. Z. & Port, R. E. Quantification of antiangiogenic and antivascular drug activity by kinetic analysis of DCE-MRI data. Clin. Pharmacol. Ther.92, 118–24 (2012).
  • Knopp, M., Giesel, F., Marcos, H., von Tengg-Kobligk, H. & Choyke, P. Dynamic contrast-enhanced magnetic resonance imaging in oncology. Top Magn Resnon Imaging12, 301–8. (2001).
  • Padhani, A. & Husband, J. Dynamic contrast-enhanced MRI studies in oncology with an emphasis on quantification, validation and human studies. Clin Radiol56, 607–20 (2001).
  • Padhani, A. Dynamic contrast-enhanced MRI in clinical oncology: current status and future directions. J Magn Reson Imaging16, 407–22 (2002).
  • Tofts, P. Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging7, 91–101 (1997).
  • Barral, J. et al. A robust methodology for in vivo T1 mapping. Magn Reson Med64, 1057–67 (2010).
  •  DCE MRI Technical Committee. DCE MRI Quantification Profile, Quantitative Imaging Biomarkers Alliance. Version 1.0. Publicly Reviewed Version. Available from: RSNA.ORG/QIBA
  • O’Connor, J., Jackson, A., Parker, G., Roberts, C. & Jayson, G. Dynamic contrast-enhanced MRI in clinical trials of antivascular therapies. Nat Rev Clin Oncol9, 167–77 (2012).
  • Boesen, M. et al. Automatic Computer Aided Quantification Of Synovitis In Rheumatoid Arthritis Using Dynamic MRI And The Impact Of Movement Correction On Signal To Noise Ratio (SNR) And Region Of Interest (ROI) Analysis [abstract]. Arthritis Rheum60, 773 (2009).
  • Kubassova, O. et al. in Med. Image Comput. Comput. Interv. – MICCAI. Lect. Notes Comput. Sci. Vol. 4792 261–269 (2007).
READ NEXT CASE STUDY >
Experience: Scoring Systems
  • LI-RADS
  • RECIST1.1
  • iRECIST
Experience: Imaging
  • US
  • CT
  • MRI
  • PET
Publications

Since 2007, over 2000 articles were published to cover scientific discoveries, technology break-throughs and special cases. We list here some critically important papers and abstracts.

Testimonials

Combining our technologies and business advisory services with promising life science companies has yielded spectacular results over the past five years. As a trusted partner to many biotech and pharma companies, IAG’s team is proud to share your words and quotes.

PROSTATE CANCER

PROSTATE CANCER

Prostate cancer is a disease wherein malignant (cancer) cells form in the tissues of the prostate. This is the second most common cancer diagnosed in men3. Worldwide, prostate cancer is the fourth leading cause of death. At an early stage, prostate cancer may be asymptomatic and often has an indolent course that may only need active surveillance. Most of the prostate cancer cases tend to grow slowly and are low-grade with comparatively limited aggressiveness and low risk.

IAG offers multiple imaging solutions in Prostate cancer, which are currently utilized by the companies in conducting clinical trials, either while scanning patients for inclusion or while assesing the disease progression and efficacy of treatments.

  • Positron Emission Tomography (PET) and MRI – PET/MRI compares the benefits of the metabolic imaging of PET and soft-tissue contrast resolution of MRI. Both these modalities have shown parallel performance in prostate cancer lesion diagnosing by using 18F-choline and 11C as radiotracers.

 

  • Multiparametric-MRI (mpMRI) – multiparametric-MRI (mpMRI) is a recommended MRI technique in prostate cancer (PCa), that comprises high-resolution T2-weighted (T2W) images to understand prostate anatomy and two functional MRI techniques, as well as diffusion-weighted imaging (DWI) to demonstrate dynamic contrast-enhanced MRI (DCE-MRI) and cell density that illustrates vascularity.

 

  • Bone scan – If prostate cancer spreads to multiple body parts, bones are the first to be impacted. A bone scan can be proven helpful in such cases to demonstrate if the cancer spread has reached the bones.

 

  • Computed tomography (CT) scan – CT scan helps identify the prostate cancer spread into the nearby lymph nodes and also in cases of recurrence i.e. if it is multiplying into other structures or organs in the patient’s pelvis.

 

  • PSMA PET – At present, Prostate-specific membrane antigen (PSMA) is considered one of the most efficacious targets for therapy and imaging in the field of nuclear medicine. PSMA is considered to be an outstanding theragnostic agent that delivers the possibility to identify prostate cancer lesions with the help of PET/CT imaging, and later to irradiate metastatic sites with personalized doses by using high-energy alpha or beta particle emitters (radioligand therapy [RLT]).

 

  • Digital Rectal Examination (DRE) – It is an essential test for the early diagnosis of prostate cancer and is done as part of an annual physical checkup in prostate cancer. Some recent clinical studies show that the combination of PSA and DRE testing is very effective and helpful in the early diagnosis of prostate cancer than each procedure individually.

 

New-generation diagnostic aids and treatments are evolving and becoming available at a rapid rate that can prove to be very helpful to enhance prognosis in patients with prostate cancer.

IAG, Image Analysis Group offers multiple Prostate Cancer imaging solutions, which are useful while conducting Prostate Cancer clinical trials and which are based on the novel biomarkers emerging in measuring the disease prevalence and disease progression.

 

We will recommend the optimal imaging and help selecting the trial endpoints. Once the trial is designed, IAG’s team will select and train the sites, assist with imaging data collection and review.

Reach out to our expert team, as you are designing and planning your trial.

About IAG, Image Analysis Group

IAG, Image Analysis Group is a strategic partner to bio-pharmaceutical companies developing new treatments to improve patients’ lives. Our dynamic Strategy, Trial Solutions and Bio-Partnering divisions work closely to meet critical needs of biotechnology companies: funding, clinical development, and monetization of their assets. We fuse decades of therapeutic insights, risk-sharing business model and agile culture to accelerate novel drug development. IAG broadly leverages its core imaging expertise, proprietary technology platform DYNAMIKA and capabilities to support an objective early go no/ go decision and drive excellence for tomorrow’s innovative therapeutic agents with speed.

Contact our expert team: imaging.experts @ ia-grp.com

READ NEXT CASE STUDY >
Experience: Scoring Systems
  • RECIST 1.1 /iRECIST
  • PECIST
  • PET-based Standard Uptake Value (SUV)
  • Volumetric Assessment
  • mpMRI
  • PIRADS
Experience: Imaging
  • CT
  • MRI
  • Perfusion imaging (DCE-MRI, DSC)
  • Diffusion imaging (ADC, DWI, DTI)
  • Multiparametric MRI (mpMRI)
  • PET/CT
  • Multiparametric ultrasound (mpUS)
Publications

Since 2007, over 2000 articles were published to cover scientific discoveries, technology break-throughs and special cases. We list here some critically important papers and abstracts.

Testimonials

Combining our technologies and business advisory services with promising life science companies has yielded spectacular results over the past five years. As a trusted partner to many biotech and pharma companies, IAG’s team is proud to share your words and quotes.