Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Stage III Non-Small Cell Lung Cancer.

Purpose: NRG-RTOG0617 demonstrated a detrimental effect of uniform high-dose radiation in stage III non-small cell lung cancer. NRG-RTOG1106/ECOG-ACRIN6697 (ClinicalTrials.gov identifier: NCT01507428), a randomized phase II trial, studied whether midtreatment F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can guide individualized/adaptive dose-intensified radiotherapy (RT) to improve and predict outcomes in patients with this disease.

Intricacies of Human-AI Interaction in Dynamic Decision-Making for Precision Oncology: A Case Study in Response-Adaptive Radiotherapy.

Background: Adaptive treatment strategies that can dynamically react to individual cancer progression can provide effective personalized care. Longitudinal multi-omics information, paired with an artificially intelligent clinical decision support system (AI-CDSS) can assist clinicians in determining optimal therapeutic options and treatment adaptations. However, AI-CDSS is not perfectly accurate, as such, clinicians' over/under reliance on AI may lead to unintended consequences, ultimately failing to develop optimal strategies.

Is Apparent Diffusion Coefficient Established as an Imaging Biomarker for Stereotactic Body Radiation Therapy Assessment in Hepatocellular Carcinoma?

In this article, as part of this special issue on biomarkers of early response, we review currently available reports regarding magnetic resonance imaging apparent diffusion coefficient (ADC) changes in hepatocellular carcinoma (HCC) in response to stereotactic body radiation therapy. We compare diffusion image acquisition, ADC analysis, methods for HCC response assessment, and statistical methods for prediction of local tumor progression by ADC metrics. We discuss the pros and cons of these studies.

A clinical decision support system for AI-assisted decision-making in response-adaptive radiotherapy (ARCliDS).

Involvement of many variables, uncertainty in treatment response, and inter-patient heterogeneity challenge objective decision-making in dynamic treatment regime (DTR) in oncology. Advanced machine learning analytics in conjunction with information-rich dense multi-omics data have the ability to overcome such challenges. We have developed a comprehensive artificial intelligence (AI)-based optimal decision-making framework for assisting oncologists in DTR.

Deep learning prediction of post-SBRT liver function changes and NTCP modeling in hepatocellular carcinoma based on DGAE-MRI.

Background: Stereotactic body radiation therapy (SBRT) produces excellent local control for patients with hepatocellular carcinoma (HCC). However, the risk of toxicity for normal liver tissue is still a limiting factor. Normal tissue complication probability (NTCP) models have been proposed to estimate the toxicity with the assumption of uniform liver function distribution, which is not optimal.

A human-in-the-loop based Bayesian network approach to improve imbalanced radiation outcomes prediction for hepatocellular cancer patients with stereotactic body radiotherapy.

Background: Imbalanced outcome is one of common characteristics of oncology datasets. Current machine learning approaches have limitation in learning from such datasets. Here, we propose to resolve this problem by utilizing a human-in-the-loop (HITL) approach, which we hypothesize will also lead to more accurate and explainable outcome prediction models.

Artificial Intelligence for Outcome Modeling in Radiotherapy.

Outcome modeling plays an important role in personalizing radiotherapy and finds applications in specialized areas such as adaptive radiotherapy. Conventional outcome models that are based on a simplified understanding of radiobiological effects or empirical fitting often only consider dosimetric information. However, it is recognized that response to radiotherapy is multi-factorial and involves a complex interaction of radiation therapy, patient and treatment factors, and the tumor microenvironment.

Current status and future developments in predicting outcomes in radiation oncology.

Advancements in data-driven technologies and the inclusion of information-rich multiomics features have significantly improved the performance of outcomes modeling in radiation oncology. For this current trend to be sustainable, challenges related to robust data modeling such as small sample size, low size to feature ratio, noisy data, as well as issues related to algorithmic modeling such as complexity, uncertainty, and interpretability, need to be mitigated if not resolved. Emerging computational technologies and new paradigms such as federated learning, human-in-the-loop, quantum computing, and novel interpretability methods show great potential in overcoming these challenges and bridging the gap towards precision outcome modeling in radiotherapy.

Precision radiotherapy via information integration of expert human knowledge and AI recommendation to optimize clinical decision making.

In the precision medicine era, there is a growing need for precision radiotherapy where the planned radiation dose needs to be optimally determined by considering a myriad of patient-specific information in order to ensure treatment efficacy. Existing artificial-intelligence (AI) methods can recommend radiation dose prescriptions within the scope of this available information. However, treating physicians may not fully entrust the AI's recommended prescriptions due to known limitations or at instances when the AI recommendation may go beyond physicians' current knowledge.

Improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven Bayesian network analysis.

Grade 2 and higher radiation pneumonitis (RP2) is a potentially fatal toxicity that limits efficacy of radiation therapy (RT). We wished to identify a combined biomarker signature of circulating miRNAs and cytokines which, along with radiobiological and clinical parameters, may better predict a targetable RP2 pathway. In a prospective clinical trial of response-adapted RT for patients (n = 39) with locally advanced non-small cell lung cancer, we analyzed patients' plasma, collected pre- and during RT, for microRNAs (miRNAs) and cytokines using array and multiplex enzyme linked immunosorbent assay (ELISA), respectively.

Dynamic stochastic deep learning approaches for predicting geometric changes in head and neck cancer.

Modern radiotherapy stands to benefit from the ability to efficiently adapt plans during treatment in response to setup and geometric variations such as those caused by internal organ deformation or tumor shrinkage. A promising strategy is to develop a framework, which given an initial state defined by patient-attributes, can predict future states based on pre-learned patterns from a well-defined patient population.Here, we investigate the feasibility of predicting patient anatomical changes, defined as a joint state of volume and daily setup changes, across a fractionated treatment schedule using two approaches.

A situational awareness Bayesian network approach for accurate and credible personalized adaptive radiotherapy outcomes prediction in lung cancer patients.

Purpose: A situational awareness Bayesian network (SA-BN) approach is developed to improve physicians' trust in the prediction of radiation outcomes and evaluate its performance for personalized adaptive radiotherapy (pART).

Methods: 118 non-small-cell lung cancer patients with their biophysical features were employed for discovery (n = 68) and validation (n = 50) of radiation outcomes prediction modeling. Patients' important characteristics identified by radiation experts to predict individual's tumor local control (LC) or radiation pneumonitis with grade ≥ 2 (RP2) were incorporated as expert knowledge (EK).

A Bayesian dose-finding design for outcomes evaluated with uncertainty.

Introduction: In some phase I trial settings, there is uncertainty in assessing whether a given patient meets the criteria for dose-limiting toxicity.

Methods: We present a design which accommodates dose-limiting toxicity outcomes that are assessed with uncertainty for some patients. Our approach could be utilized in many available phase I trial designs, but we focus on the continual reassessment method due to its popularity.

Investigating the SPECT Dose-Function Metrics Associated With Radiation-Induced Lung Toxicity Risk in Patients With Non-small Cell Lung Cancer Undergoing Radiation Therapy.

Purpose: Dose to normal lung has commonly been linked with radiation-induced lung toxicity (RILT) risk, but incorporating functional lung metrics in treatment planning may help further optimize dose delivery and reduce RILT incidence. The purpose of this study was to investigate the impact of the dose delivered to functional lung regions by analyzing perfusion (Q), ventilation (V), and combined V/Q single-photon-emission computed tomography (SPECT) dose-function metrics with regard to RILT risk in patients with non-small cell lung cancer (NSCLC) patients who received radiation therapy (RT).

Methods And Materials: SPECT images acquired from 88 patients with locally advanced NSCLC before undergoing conventionally fractionated RT were retrospectively analyzed.

A deep survival interpretable radiomics model of hepatocellular carcinoma patients.

This work aims to identify a new radiomics signature using imaging phenotypes and clinical variables for risk prediction of overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT). 167 patients were retrospectively analyzed with repeated nested cross-validation to mitigate overfitting issues. 56 radiomic features were extracted from pre-treatment contrast-enhanced (CE) CT images.

Integrating Multiomics Information in Deep Learning Architectures for Joint Actuarial Outcome Prediction in Non-Small Cell Lung Cancer Patients After Radiation Therapy.

Purpose: Novel actuarial deep learning neural network (ADNN) architectures are proposed for joint prediction of radiation therapy outcomes-radiation pneumonitis (RP) and local control (LC)-in stage III non-small cell lung cancer (NSCLC) patients. Unlike normal tissue complication probability/tumor control probability models that use dosimetric information solely, our proposed models consider complex interactions among multiomics information including positron emission tomography (PET) radiomics, cytokines, and miRNAs. Additional time-to-event information is also used in the actuarial prediction.

TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy.

Introduction: Radiation therapy for the management of intrahepatic malignancies can adversely affect liver function. Liver damage has been associated with increased levels of inflammatory cytokines, including tumor necrosis factor alpha (TNFα). We hypothesized that an inflammatory state, characterized by increased soluble TNFα receptor (sTNFR1), mediates sensitivity of the liver to radiation.

Individualized Adaptive Radiation Therapy Allows for Safe Treatment of Hepatocellular Carcinoma in Patients With Child-Turcotte-Pugh B Liver Disease.

Purpose: Previous reports of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) suggest unacceptably high rates of toxicity in patients with Child-Turcotte-Pugh (CTP) B liver disease. We hypothesized that an individualized adaptive treatment approach based on midtreatment liver function would maintain good local control while limiting toxicity in this population.

Methods And Materials: Patients with CTP-B liver disease and HCC were treated on prospective trials of individualized adaptive SBRT between 2006 and 2018.

Central Airway Toxicity After High Dose Radiation: A Combined Analysis of Prospective Clinical Trials for Non-Small Cell Lung Cancer.

Purpose: To study the dosimetric risk factors for radiation-induced proximal bronchial tree (PBT) toxicity in patients treated with radiation therapy for non-small cell lung cancer (NSCLC).

Methods And Materials: Patients with medically inoperable or unresectable NSCLC treated with conventionally fractionated 3-dimensional conformal radiation therapy (3DCRT) in prospective clinical trials were eligible for this study. Proximal bronchial tree (PBT) and PBT wall were contoured consistently per RTOG 1106 OAR-Atlas.

Introduction to machine and deep learning for medical physicists.

Recent years have witnessed tremendous growth in the application of machine learning (ML) and deep learning (DL) techniques in medical physics. Embracing the current big data era, medical physicists equipped with these state-of-the-art tools should be able to solve pressing problems in modern radiation oncology. Here, a review of the basic aspects involved in ML/DL model building, including data processing, model training, and validation for medical physics applications is presented and discussed.

Artificial Intelligence: reshaping the practice of radiological sciences in the 21st century.

Advances in computing hardware and software platforms have led to the recent resurgence in artificial intelligence (AI) touching almost every aspect of our daily lives by its capability for automating complex tasks or providing superior predictive analytics. AI applications are currently spanning many diverse fields from economics to entertainment, to manufacturing, as well as medicine. Since modern AI's inception decades ago, practitioners in radiological sciences have been pioneering its development and implementation in medicine, particularly in areas related to diagnostic imaging and therapy.

Quantum-inspired algorithm for radiotherapy planning optimization.

Purpose: Modern inverse radiotherapy treatment planning requires nonconvex, large-scale optimizations that must be solved within a clinically feasible timeframe. We have developed and tested a quantum-inspired, stochastic algorithm for intensity-modulated radiotherapy (IMRT): quantum tunnel annealing (QTA). By modeling the likelihood probability of accepting a higher energy solution after a particle tunneling through a potential energy barrier, QTA features an additional degree of freedom (the barrier width, w) not shared by traditional stochastic optimization methods such as Simulated Annealing (SA).

Balancing accuracy and interpretability of machine learning approaches for radiation treatment outcomes modeling.

Radiation outcomes prediction (ROP) plays an important role in personalized prescription and adaptive radiotherapy. A clinical decision may not only depend on an accurate radiation outcomes' prediction, but also needs to be made based on an informed understanding of the relationship among patients' characteristics, radiation response and treatment plans. As more patients' biophysical information become available, machine learning (ML) techniques will have a great potential for improving ROP.