Locoregional Therapies for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Importance: Several locoregional therapies (LRTs) for nonmetastatic hepatocellular carcinoma (HCC) are available; however, a global comparison of the relative efficacy of each is needed.

Objective: To conduct a systematic review and direct, pairwise meta-analytic comparison of all identified randomized clinical trials evaluating the treatment of nonmetastatic HCC.

Data Sources: A comprehensive search of PubMed and the proceedings of the American Society of Clinical Oncology and American Society for Radiation Oncology annual meetings from January 1, 2010, to November 1, 2023, was performed.

A Phase 1 Trial of Image Guided Risk Volume-Adapted Postprostatectomy Radiation Therapy.

Purpose: This was a phase 1 trial with the primary objective of identifying the most compressed dose schedule (DS) tolerable using risk volume-adapted, hypofractionated, postoperative radiation therapy (PORT) for biochemically recurrent prostate cancer. Secondary endpoints included biochemical progression-free survival and quality of life (QOL).

Methods And Materials: Patients were treated with 1 of 3 isoeffective DSs (DS1: 20 fractions, DS2: 15 fractions, and DS3: 10 fractions) that escalated the dose to the imaging-defined local recurrence (73 Gy equivalent dose in 2Gy fractions) and de-escalated the dose to the remainder of the prostate bed (48 Gy equivalent dose in 2Gy fractions).

Resource requirements to accelerate clinical applications of next-generation sequencing and radiomics: workshop commentary and review.

The National Institutes of Health-US Food and Drug Administration Joint Leadership Council Next-Generation Sequencing and Radiomics Working Group was formed by the National Institutes of Health-Food and Drug Administration Joint Leadership Council to promote the development and validation of innovative next-generation sequencing tests, radiomic tools, and associated data analysis and interpretation enhanced by artificial intelligence and machine learning technologies. A 2-day workshop was held on September 29-30, 2021, to convene members of the scientific community to discuss how to overcome the "ground truth" gap that has frequently been acknowledged as 1 of the limiting factors impeding high-quality research, development, validation, and regulatory science in these fields. This report provides a summary of the resource gaps identified by the working group and attendees, highlights existing resources and the ways they can potentially be employed to accelerate growth in these fields, and presents opportunities to support next-generation sequencing and radiomic tool development and validation using technologies such as artificial intelligence and machine learning.

A Phase 1 Trial of Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer After Brachytherapy.

Purpose: NCT03253744 is a phase 1 trial with the primary objective to identify the maximum tolerated dose (MTD) of salvage stereotactic body radiation therapy (SBRT) in patients with local prostate cancer recurrence after brachytherapy. Additional objectives included biochemical control and imaging response.

Methods And Materials: This trial was initially designed to test 3 therapeutic dose levels (DLs): 40 Gy (DL1), 42.

A Phase 1 Trial of Focal Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer.

Purpose: NCT03253744 was a phase 1 trial to identify the maximum tolerated dose (MTD) of image-guided, focal, salvage stereotactic body radiation therapy (SBRT) for patients with locally radiorecurrent prostate cancer. Additional objectives included biochemical control and imaging response.

Methods And Materials: The trial design included 3 dose levels (DLs): 40 Gy (DL1), 42.

Multiparametric Quantitative Imaging Biomarker as a Multivariate Descriptor of Health: A Roadmap.

Multiparametric quantitative imaging biomarkers (QIBs) offer distinct advantages over single, univariate descriptors because they provide a more complete measure of complex, multidimensional biological systems. In disease, where structural and functional disturbances occur across a multitude of subsystems, multivariate QIBs are needed to measure the extent of system malfunction. This paper, the first Use Case in a series of articles on multiparameter imaging biomarkers, considers multiple QIBs as a multidimensional vector to represent all relevant disease constructs more completely.

Criteria for the translation of radiomics into clinically useful tests.

Computer-extracted tumour characteristics have been incorporated into medical imaging computer-aided diagnosis (CAD) algorithms for decades. With the advent of radiomics, an extension of CAD involving high-throughput computer-extracted quantitative characterization of healthy or pathological structures and processes as captured by medical imaging, interest in such computer-extracted measurements has increased substantially. However, despite the thousands of radiomic studies, the number of settings in which radiomics has been successfully translated into a clinically useful tool or has obtained FDA clearance is comparatively small.

Multiparametric Data-driven Imaging Markers: Guidelines for Development, Application and Reporting of Model Outputs in Radiomics.

This paper is the fifth in a five-part series on statistical methodology for performance assessment of multi-parametric quantitative imaging biomarkers (mpQIBs) for radiomic analysis. Radiomics is the process of extracting visually imperceptible features from radiographic medical images using data-driven algorithms. We refer to the radiomic features as data-driven imaging markers (DIMs), which are quantitative measures discovered under a data-driven framework from images beyond visual recognition but evident as patterns of disease processes irrespective of whether or not ground truth exists for the true value of the DIM.

Multiparametric Quantitative Imaging in Risk Prediction: Recommendations for Data Acquisition, Technical Performance Assessment, and Model Development and Validation.

Combinations of multiple quantitative imaging biomarkers (QIBs) are often able to predict the likelihood of an event of interest such as death or disease recurrence more effectively than single imaging measurements can alone. The development of such multiparametric quantitative imaging and evaluation of its fitness of use differs from the analogous processes for individual QIBs in several key aspects. A computational procedure to combine the QIB values into a model output must be specified.

Multiparametric Quantitative Imaging Biomarkers for Phenotype Classification: A Framework for Development and Validation.

This manuscript is the third in a five-part series related to statistical assessment methodology for technical performance of multi-parametric quantitative imaging biomarkers (mp-QIBs). We outline approaches and statistical methodologies for developing and evaluating a phenotype classification model from a set of multiparametric QIBs. We then describe validation studies of the classifier for precision, diagnostic accuracy, and interchangeability with a comparator classifier.

Early drug development in solid tumours: analysis of National Cancer Institute-sponsored phase 1 trials.

Background: The low expectation of clinical benefit from phase 1 cancer therapeutics trials might negatively affect patient and physician participation, study reimbursement, and slow the progress of oncology research. Advances in cancer drug development, meanwhile, might have favourably improved treatment responses; however, little comprehensive data exist describing the response and toxicity associated with phase 1 trials across solid tumours. The aim of the study is to evaluate the trend of toxicity and response in phase 1 trials for solid tumours over time.

Trends in Grade 5 Toxicity and Response in Phase I Trials in Hematologic Malignancy: 20-Year Experience From the Cancer Therapy Evaluation Program at the National Cancer Institute.

Purpose: Cancer drug development has largely shifted from cytotoxic chemotherapy to targeted treatment in the past two decades. Although previous studies have highlighted improvement in response rates in recent phase I trials, disease-focused reporting is limited.

Methods: We integrated patient-level data for patients with hematologic malignancies who participated in phase I trials sponsored by the National Cancer Institute Cancer Therapy Evaluation Program between January 2000 and May 2019 and estimated the trend of grade 5 toxicity and response by disease subtype over time.

Assigning readers to cases in imaging studies using balanced incomplete block designs.

In many imaging studies, each case is reviewed by human readers and characterized according to one or more features. Often, the inter-reader agreement of the feature indications is of interest in addition to their diagnostic accuracy or association with clinical outcomes. Complete designs in which all participating readers review all cases maximize efficiency and guarantee estimability of agreement metrics for all pairs of readers but often involve a heavy reading burden.

Integrated Multi-Tumor Radio-Genomic Marker of Outcomes in Patients with High Serous Ovarian Carcinoma.

Develop an integrated intra-site and inter-site radiomics-clinical-genomic marker of high grade serous ovarian cancer (HGSOC) outcomes and explore the biological basis of radiomics with respect to molecular signaling pathways and the tumor microenvironment (TME). Seventy-five stage III-IV HGSOC patients from internal ( = 40) and external factors via the Cancer Imaging Archive (TCGA) ( = 35) with pre-operative contrast enhanced CT, attempted primary cytoreduction, at least two disease sites, and molecular analysis performed within TCGA were retrospectively analyzed. An intra-site and inter-site radiomics (cluDiss) measure was combined with clinical-genomic variables (iRCG) and compared against conventional (volume and number of sites) and average radiomics ( = 75) for prognosticating progression-free survival (PFS) and platinum resistance.

Factors Affecting Combination Trial Success (FACTS): Investigator Survey Results on Early-Phase Combination Trials.

Experimental therapeutic oncology agents are often combined to circumvent tumor resistance to individual agents. However, most combination trials fail to demonstrate sufficient safety and efficacy to advance to a later phase. This study collected survey data on phase 1 combination therapy trials identified from ClinicalTrials.

Multiple-response regression analysis links magnetic resonance imaging features to de-regulated protein expression and pathway activity in lower grade glioma.

Background And Purpose: Lower grade gliomas (LGGs), lesions of WHO grades II and III, comprise 10-15% of primary brain tumors. In this study, we aim to carry out a radioproteomic characterization of LGGs using proteomics data from the TCGA and imaging data from the TCIA cohorts, to obtain an association between tumor MRI characteristics and protein measurements. The availability of linked imaging and molecular data permits the assessment of relationships between tumor genomic/proteomic measurements with phenotypic features.

Radiogenomics of High-Grade Serous Ovarian Cancer: Multireader Multi-Institutional Study from the Cancer Genome Atlas Ovarian Cancer Imaging Research Group.

Purpose To evaluate interradiologist agreement on assessments of computed tomography (CT) imaging features of high-grade serous ovarian cancer (HGSOC), to assess their associations with time-to-disease progression (TTP) and HGSOC transcriptomic profiles (Classification of Ovarian Cancer [CLOVAR]), and to develop an imaging-based risk score system to predict TTP and CLOVAR profiles. Materials and Methods This study was a multireader, multi-institutional, institutional review board-approved, HIPAA-compliant retrospective analysis of 92 patients with HGSOC (median age, 61 years) with abdominopelvic CT before primary cytoreductive surgery available through the Cancer Imaging Archive. Eight radiologists from the Cancer Genome Atlas Ovarian Cancer Imaging Research Group developed and independently recorded the following CT features: characteristics of primary ovarian mass(es), presence of definable mesenteric implants and infiltration, presence of other implants, presence and distribution of peritoneal spread, presence and size of pleural effusions and ascites, lymphadenopathy, and distant metastases.

Beyond Correlations, Sensitivities, and Specificities: A Roadmap for Demonstrating Utility of Advanced Imaging in Oncology Treatment and Clinical Trial Design.

Despite the widespread belief that advanced imaging should be very helpful in guiding oncology treatment decision and improving efficiency and success rates in treatment clinical trials, its acceptance has been slow. Part of this is likely attributable to gaps in study design and statistical methodology for these imaging studies. Also, results supporting the performance of the imaging in these roles have largely been insufficient to justify their use within the design of a clinical trial or in treatment decision making.

Beyond Correlations, Sensitivities, and Specificities: Case Examples of the Evaluation of Advanced Imaging in Oncology Clinical Trials and Cancer Treatment.

Although advanced imaging is an important component of oncology clinical trials, there has not been a lot of success in advancing its use from a research perspective. One likely reason is the lack of consensus on the methodology used to study advanced imaging in trials, which results in a disconcerted research effort and produces data that are difficult to collate for use in validating the imaging components being studied. Imaging is used in cancer clinical trials for various indications, and the study design needed to evaluate the imaging in a particular indication will vary.

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development.

RECIST 1.1 - Standardisation and disease-specific adaptations: Perspectives from the RECIST Working Group.

Radiologic imaging of disease sites plays a pivotal role in the management of patients with cancer. Response Evaluation Criteria in Solid Tumours (RECIST), introduced in 2000, and modified in 2009, has become the de facto standard for assessment of response in solid tumours in patients on clinical trials. The RECIST Working Group considers the ability of the global oncology community to implement and adopt updates to RECIST in a timely manner to be critical.

RECIST 1.1-Update and clarification: From the RECIST committee.

The Response Evaluation Criteria in Solid Tumours (RECIST) were developed and published in 2000, based on the original World Health Organisation guidelines first published in 1981. In 2009, revisions were made (RECIST 1.1) incorporating major changes, including a reduction in the number of lesions to be assessed, a new measurement method to classify lymph nodes as pathologic or normal, the clarification of the requirement to confirm a complete response or partial response and new methodologies for more appropriate measurement of disease progression.