Non-viral precision T cell receptor replacement for personalized cell therapy.

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1-3. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRß). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial ( NCT03970382 ). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.

Bile Acid Diarrhea: From Molecular Mechanisms to Clinical Diagnosis and Treatment in the Era of Precision Medicine.

Bile acid diarrhea (BAD) is a multifaceted intestinal disorder involving intricate molecular mechanisms, including farnesoid X receptor (FXR), fibroblast growth factor receptor 4 (FGFR4), and Takeda G protein-coupled receptor 5 (TGR5). Current diagnostic methods encompass bile acid sequestrants (BAS), 48-h fecal bile acid tests, serum 7α-hydroxy-4-cholesten-3-one (C4), fibroblast growth factor 19 (FGF19) testing, and 75Selenium HomotauroCholic acid test (75SeHCAT). Treatment primarily involves BAS and FXR agonists. However, due to the limited sensitivity and specificity of current diagnostic methods, as well as suboptimal treatment efficacy and the presence of side effects, there is an urgent need to establish new diagnostic and treatment methods. While prior literature has summarized various diagnostic and treatment methods and the pathogenesis of BAD, no previous work has linked the two. This review offers a molecular perspective on the clinical diagnosis and treatment of BAD, with a focus on FXR, FGFR4, and TGR5, emphasizing the potential for identifying additional molecular mechanisms as treatment targets and bridging the gap between diagnostic and treatment methods and molecular mechanisms for a novel approach to the clinical management of BAD.

[The precision medicine for the treatment of acute respiratory distress syndrome is based on identification of phenotypes].

The acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome characterized by distinct etiologies and complicated pathobiological mechanism. It is difficult to discriminate patients with unique biological features or individual response to specific therapy by traditional definition and subgrouping. Unfortunately, there are few clinical evidences supporting effective drug therapy to ARDS. The sub-phenotype or endotype of ARDS is related to potential mechanism of the syndrome, and is critical to personalized treatment of ARDS. An appropriate sub-phenotype of ARDS may be defined by data-driven assessment of the available data including clinical features, biological biomarkers and respiratory parameters of the patients. Latent class analysis or machine learning has potential to establish new sub-phenotype of ARDS stably, which is helpful to guide precision medicine approach.

Definitions, phenotypes, and subphenotypes in acute kidney injury-Moving towards precision medicine.

The current definition of acute kidney injury (AKI) is generic and, based only on markers of function, is unsuitable for guiding individualized treatment. AKI is a complex syndrome with multiple presentations and causes. Targeted AKI management will only be possible if different phenotypes and subphenotypes of AKI are recognised, based on causation and related pathophysiology. Molecular signatures to identify subphenotypes are being recognised, as specific biomarkers reveal activated pathways. Assessment of individual clinical risk needs wider dissemination to allow identification of patients at high risk of AKI. New and more timely markers for glomerular filtration rate (GFR) are available. However, AKI diagnosis and classification should not be limited to GFR, but include tubular function and damage. Combining damage and stress biomarkers with functional markers enhances risk prediction, and identifies a population enriched for clinical trials targeting AKI. We review novel developments and aim to encourage implementation of these new techniques into clinical practice as a strategy for individualizing AKI treatment akin to a precision medicine-based approach.

Precision Medicine in Neuropathic Pain.

Neuropathic pain is a common chronic pain condition that is caused by a lesion or disease of the somatosensory nervous system. The multitude of sensory negative and positive sensations and associated comorbidities have a major impact on quality of life of affected patients. Current treatment options often only lead to a partial pain relief or are even completely ineffective. In addition, many clinical trials for the development of new drugs have not met the primary endpoint. Therefore, there is still an unmet clinical need in neuropathic pain syndromes. One reason for this therapeutic dilemma could be the heterogeneity of neuropathic pain with a variety of pathophysiological pain mechanisms that are expressed differently in each patient regardless of the underlying disease etiology. Reclassification of neuropathic pain syndromes therefore focuses on the underlying mechanisms of pain development rather than the disease etiology. A priori stratification of patients based on these individual mechanisms could allow the identification of potential treatment responders and thus realize the concept of a mechanism-based treatment. As no biomarkers for pain mechanisms have been discovered yet, one has to rely on surrogate markers that are thought to be closely related to these mechanisms. In this chapter, we present promising predictive biomarkers, focusing in particular on sensory symptoms and signs assessed by patient-reported outcome measures and sensory testing, and discuss how these tools might be used in clinical trials in the future.

Resiniferatoxin: Nature's Precision Medicine to Silence TRPV1-Positive Afferents.

Resiniferatoxin (RTX) is an ultrapotent capsaicin analog with a unique spectrum of pharmacological actions. The therapeutic window of RTX is broad, allowing for the full desensitization of pain perception and neurogenic inflammation without causing unacceptable side effects. Intravesical RTX was shown to restore continence in a subset of patients with idiopathic and neurogenic detrusor overactivity. RTX can also ablate sensory neurons as a "molecular scalpel" to achieve permanent analgesia. This targeted (intrathecal or epidural) RTX therapy holds great promise in cancer pain management. Intra-articular RTX is undergoing clinical trials to treat moderate-to-severe knee pain in patients with osteoarthritis. Similar targeted approaches may be useful in the management of post-operative pain or pain associated with severe burn injuries. The current state of this field is reviewed, from preclinical studies through veterinary medicine to clinical trials.

The understanding of asthma pathogenesis in the era of precision medicine.

Asthma is a syndrome with extremely diverse clinical phenotypes in which the onset, severity, and response to treatment are defined by the complex interplay of many genetic and environmental factors. Environmental factors epigenetically affect gene expression, and the disease is driven by a multidimensional dynamic network involving RNA and protein molecules derived from gene expression, as well as various metabolic products. In other words, specific pathophysiological mechanisms or endotypes are dynamic networks that arise in response to individual genotypes and the various environmental factors to which individuals have been exposed since before birth, such as diet, infection, air pollution, smoking, antibiotic use, and the bacterial flora of the intestinal tract, skin, and lungs. A key feature of asthma genome scans is their potential to reveal the molecular pathways that lead to pathogenesis. Endotypes that drive the disease have a significant impact on the phenotypes of asthma patients, including their drug responsiveness. Understanding endotypes will lead to not only the implementation of therapies that are tailored to the specific molecular network(s) underlying the patient's condition, but also to the development of therapeutic strategies that target individual endotypes, as well as to precision health, which will enable the prediction of disease onset with high accuracy from an early stage and the implementation of preventive strategies based on endotypes. Understanding of endotypes will pave the way for the practice of precision medicine in asthma care, moving away from 'one-size-fits-all' medicine and population-based prevention approaches that do not take individuals' susceptibility into account.

Precision Medicine Approach for Cardiometabolic Risk Factors in Therapeutic Apheresis.

Lipoprotein apheresis (LA) is currently the most powerful intervention possible to reach a maximal reduction of lipids in patients with familial hypercholesterolemia and lipoprotein(a) hyperlipidemia. Although LA is an invasive method, it has few side effects and the best results in preventing further major cardiovascular events. It has been suggested that the highly significant reduction of cardiovascular complications in patients with severe lipid disorders achieved by LA is mediated not only by the potent reduction of lipid levels but also by the removal of other proinflammatory and proatherogenic factors. Here we performed a comprehensive proteomic analysis of patients on LA treatment using intra-individually a set of differently sized apheresis filters with the INUSpheresis system. This study revealed that proteomic analysis correlates well with routine clinical chemistry in these patients. The method is eminently suited to discover new biomarkers and risk factors for cardiovascular disease in these patients. Different filters achieve reduction and removal of proatherogenic proteins in different quantities. This includes not only apolipoproteins, C-reactive protein, fibrinogen, and plasminogen but also proteins like complement factor B (CFAB), protein AMBP, afamin, and the low affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) among others that have been described as atherosclerosis and metabolic vascular diseases promoting factors. We therefore conclude that future trials should be designed to develop an individualized therapy approach for patients on LA based on their metabolic and vascular risk profile. Furthermore, the power of such cascade filter treatment protocols may improve the prevention of cardiometabolic disease and its complications.

From cryptogenic to ESUS: Toward precision medicine?

Cryptogenic infarctions are infarctions without a defined cause, despite a complete work-up. They differ from infarctions of undetermined causes, which may involve overlapping causes or an incomplete investigation. It is also different from uncommon heritable and non-heritable causes. The term embolic stroke of undetermined source (ESUS) proposed in 2014 is defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources. The major advantage of this definition compared to cryptogenic definition is the proposition of a specific work-up. In a general population, frequent potential sources of embolism in patients with ESUS have been suggested since a long time and include: patent foramen ovale (PFO), covert atrial fibrillation (AF), complex aortic arch atheroma, large vessel atheroma with stenosis<50%, carotid web, atrial cardiomyopathy, thrombophilia associated with cancer. It took almost 30 years to show, in patients under 60 with a cryptogenic stroke and a PFO, that PFO occlusion was superior to medical treatment alone for recurrent stroke. PFO under 60 is therefore no longer a cryptogenic cause of infarction. The concept of cryptogenic stroke and its refinement in ESUS have been fruitful for the identification of PFO associated as a cause. Covert AF can be detected by different techniques but its risk significance for recurrent stroke might be different from the simple electrocardiographic detection of AF. With the development of direct oral anticoagulants (DOAs), randomized studies in patients with ESUS, were run for stroke prevention but no difference was observed between patients treated by DOA compared to aspirin. These studies showed however the heterogeneity of ESUS patients. Further ESUS classification should be considered as a tool to identify homogeneous groups. We propose to further split the ESUS group into different subgroups: ESU-PFO>60-year-old, ESUS-ATH with stenosis<50%, ESUS-AF (covert AF & atrial cardiomyopathy), ESUS-cancer and others. Precision medicine is the ability to make targeted healthcare decisions based on the specific risks of individual patients. One preliminary stage is therefore to identify homogeneous groups suitable in the future for new therapeutic trials and, at the end, for new specific treatments.

Custom Implants in TKA Provide No Substantial Benefit in Terms of Outcome Scores, Reoperation Risk, or Mean Alignment: A Systematic Review.

BACKGROUND: Failure to accurately replicate the native anatomy and biomechanics of the knee has been suggested to contribute to dissatisfaction after TKA. Custom implants promise a personalized surgical approach, with the aim of improving patient satisfaction and pain as well as lowering revision rates. However, some published research on custom TKA implants has found no clinically important improvements in postoperative validated outcomes scores, risks of revision or reoperation, and implant alignment. In the interest of helping to settle this controversy, a systematic review seems warranted. QUESTION/PURPOSE: In this systematic review, we asked whether custom implants result in clinically important improvements over conventional off-the-shelf implants for anatomically uncomplicated primary TKA in terms of (1) validated outcomes scores, (2) the risk of revision or reoperation, and (3) implant alignment. METHODS: The US National Library of Medicine (PubMed/Medline), Embase, Web of Science, and Cochrane Database of Systematic Reviews were systematically searched to identify publications from the past 10 years relevant to this review. Publications that compared the clinical outcome measures, number of revisions and reoperations, and radiological assessment of implant alignment of custom and standard implants with validated endpoints were eligible for inclusion. In the interest of capturing as much potentially relevant information as possible, we applied no requirement for minimum follow-up duration. Clinical outcomes were assessed using patient-reported outcome (PROM) scores including the Knee Society Score (KSS), Forgotten Joint Score, and Knee Injury and Osteoarthritis Outcome Score. The risk for revision or reoperation were evaluated by the number of early and late manipulations, debridement procedures, and replacement of one or more components. Implant alignment was compared using postoperative deviation from the neutral (0°) mechanical axis of the limb and each component and the posterior tibial slope. All qualified studies were retrospective, and all compared custom implants with standard implants. Data on 1510 patients were reviewed (749 with custom implants and 761 with off-the-shelf implants). The mean follow-up time ranged from 12 to 33 months. RESULTS: There was no apparent advantage to custom implants in terms of PROM scores. Of the five studies evaluating clinical outcomes, only one reported better KSS-Function scores at 3 months; two reported no difference, and two found inferior KSS scores. In several studies, custom implants were associated with more frequent reoperations than standard implants. Although in general there were no differences between custom and standard implants in terms of mean coronal plane limb alignment, one of seven studies found that the proportion of patients whose alignment was outside ± 3° from the neutral axis in the coronal plane was lower in the custom group than in the standard group. CONCLUSION: With generally poorer outcomes scores for pain and function, generally higher risks of reoperation and reintervention, and no overall benefit to alignment, custom implants for primary TKA for the general population currently appear to be inferior to standard implants. Whether the slight reduction in the proportion of patients with alignment outliers observed in a minority of studies will result in a substantial reduction in revision risk over time must be addressed by future studies. However, until or unless such a reduction is proven, we recommend against the routine use of custom implants in practice because of increased costs and the risks associated with their novelty. LEVEL OF EVIDENCE: Level III, therapeutic study.

Ovarian Cancer Immunotherapy and Personalized Medicine.

Ovarian cancer response to immunotherapy is limited; however, the evaluation of sensitive/resistant target treatment subpopulations based on stratification by tumor biomarkers may improve the predictiveness of response to immunotherapy. These markers include tumor mutation burden, PD-L1, tumor-infiltrating lymphocytes, homologous recombination deficiency, and neoantigen intratumoral heterogeneity. Future directions in the treatment of ovarian cancer include the utilization of these biomarkers to select ideal candidates. This paper reviews the role of immunotherapy in ovarian cancer as well as novel therapeutics and study designs involving tumor biomarkers that increase the likelihood of success with immunotherapy in ovarian cancer.

A Review of the Mechanisms and Clinical Implications of Precision Cancer Therapy-Related Toxicity: A Primer for the Radiologist.

OBJECTIVE. The purpose of this review is to elucidate the mechanisms, types, and clinical significance of molecular targeted therapy (MTT) and immune checkpoint inhibitors (ICIs) and their related toxicity, emphasizing the radiologic manifestations. CONCLUSION. The related toxicities of MTT and ICIs can have acute, recurrent, chronic, and delayed presentations. These toxicities may serve as markers of response and survival. By understanding the clinical significance of drug toxicities, radiologists can play an important role in personalized cancer therapy.

Bayesian Networks for Risk Prediction Using Real-World Data: A Tool for Precision Medicine.

OBJECTIVE: The fields of medicine and public health are undergoing a data revolution. An increasing availability of data has brought about a growing interest in machine-learning algorithms. Our objective is to present the reader with an introduction to a knowledge representation and machine-learning tool for risk estimation in medical science known as Bayesian networks (BNs). STUDY DESIGN: In this article we review how BNs are compact and intuitive graphical representations of joint probability distributions (JPDs) that can be used to conduct causal reasoning and risk estimation analysis and offer several advantages over regression-based methods. We discuss how BNs represent a different approach to risk estimation in that they are graphical representations of JPDs that take the form of a network representing model random variables and the influences between them, respectively. METHODS: We explore some of the challenges associated with traditional risk prediction methods and then describe BNs, their construction, application, and advantages in risk prediction based on examples in cancer and heart disease. RESULTS: Risk modeling with BNs has advantages over regression-based approaches, and in this article we focus on three that are relevant to health outcomes research: (1) the generation of network structures in which relationships between variables can be easily communicated; (2) their ability to apply Bayes's theorem to conduct individual-level risk estimation; and (3) their easy transformation into decision models. CONCLUSIONS: Bayesian networks represent a powerful and flexible tool for the analysis of health economics and outcomes research data in the era of precision medicine.

[Big Data: Technical improvement, degradation or transformation of the solidarity model?] / Big Data : amélioration technique, dégradation ou transformation du modèle de solidarité ?

Big Data, the production of a massive amount of heterogeneous data, is often presented as a means to ensure the economic survival and sustainability of health systems. According to this perspective, Big Data could help save the spirit of our welfare states based on the principles of risks-sharing and equal access to care for all. According to a second perspective, opposed to the first, Big Data would fuel a process of demutualization, transferring to individuals a growing share of responsibility for managing their health. This article proposes to develop a third approach: Big Data does not induce a loss of solidarity but a transformation of the European model of welfare states. These are the data that are now the objects of the pooling. Individual and collective responsibilities are thus redistributed. However, this model, as new as it is, remains liberal in its inspiration; it basically allows the continuation of political liberalism by other means.

Combining precision radiotherapy with molecular targeting and immunomodulatory agents: a guideline by the American Society for Radiation Oncology.

The practice of radiation oncology is primarily based on precise technical delivery of highly conformal, image-guided external beam radiotherapy or brachytherapy. However, systematic research efforts are being made to facilitate individualised radiation dose prescriptions on the basis of gene-expressssion profiles that reflect the radiosensitivity of tumour and normal tissue. This advance in precision radiotherapy should complement those benefits made in precision cancer medicine that use molecularly targeted agents and immunotherapies. The personalisation of cancer therapy, predicated largely on genomic interrogation, is facilitating the selection of therapies that are directed against driver mutations, aberrant cell signalling, tumour microenvironments, and genetic susceptibilities. With the increasing technical power of radiotherapy to safely increase local tumour control for many solid tumours, it is an opportune time to rigorously explore the potential benefits of combining radiotherapy with molecular targeted agents and immunotherapies to increase cancer survival outcomes. This theme provides the basis and foundation for this American Society for Radiation Oncology guideline on combining radiotherapy with molecular targeting and immunotherapy agents.

Molecular biomarkers in bladder preservation therapy for muscle-invasive bladder cancer.

Although muscle-invasive bladder cancer is commonly treated with radical cystectomy, a standard alternative is bladder preservation therapy, consisting of maximum transurethral bladder tumour resection followed by radiotherapy with concurrent chemotherapy. Although no successfully completed randomised comparisons are available, the two treatment paradigms seem to have similar long-term outcomes; however, clinicopathologic parameters can be insufficient to provide clear guidance in the selection of one treatment over the other. Recent advances in the molecular understanding of bladder cancer have led to the identification of new predictive biomarkers that ultimately might help guide the tailored selection of therapy on the basis of the intrinsic biology of the tumour. In this Review, we discuss the existing evidence for molecular alterations and genomic signatures as prognostic or predictive biomarkers for bladder preservation therapy. If validated in prospective clinical trials, such biomarkers could enable the identification of subgroups of patients who are more likely to benefit from one treatment over another, and guide the use of combination therapies that include other modalities, such as immunotherapy, which might act synergistically with radiotherapy.

New clinical trial designs for establishing drug efficacy and safety in a precision medicine era.

Despite advances in pharmacotherapy, diabetic kidney disease (DKD) remains associated with a high burden of micro- and macrovascular complications often leading to premature mortality. New therapies are highly desirable to mitigate the burden of this disease. However, there are a number of barriers that hamper drug development in DKD. These include, amongst others, the lengthy and complex clinical trials required to prove drug efficacy and safety, inefficiencies in clinical trial conduct, and the high costs associated with these development programs. In this review a number of aspects are discussed, aiming to identify opportunities to transform and innovate drug development for DKD. Many clinical trials in DKD, as well as in other areas, face difficulties in timely and efficient enrolment of participants. To address this issue a network of sites should be created that are continuously recruiting individuals with DKD and collecting crucial information that can be used to understand prognosis and prognostic factors, and more importantly to serve as a pool of participants for recruitment to randomized trials. Second, the current clinical endpoints are late events in the progression of DKD. Endpoints based on lesser declines in estimated glomerular filtration rate (eGFR) or changes in albuminuria can shorten follow-up and/or lead to smaller and cheaper trials. Enrichment by enrolling clinical trial populations based on biomarker profiles is another approach that may facilitate clinical trial efficiency and conduct. Biomarkers can be used to individualize treatment by targeting populations more likely to respond leading to smaller and more efficient trials. Finally, using new trial design such as basket, umbrella or more broadly platform trials to assess a number of therapies simultaneously offers the potential to transform the drug development process in DKD. There are a number of opportunities to transform development approaches for new therapies for DKD. Platform trials along with appropriate biomarker-based enrichment strategies offer the possibility to foster drug development in a precision medicine era.

Functional Outcomes and Accuracy of Patient-Specific Instruments for Total Knee Arthroplasty.

BACKGROUND: Patient-specific instruments (PSIs) were developed to improve mechanical axis alignment for patients undergoing total knee arthroplasty (TKA) as neutral alignment (180°) is a predictor of long-term success. This study examines alignment accuracy and functional outcomes of PSI as compared with standard instruments (SIs). METHODS: We retrospectively reviewed a consecutive series of TKA procedures using PSI. A total of 85 PSI procedures were identified, and these were compared with a matched cohort of 85 TKAs using SI. Intraoperative decision-making, estimated blood loss, efficiency, Knee Society Scores, and postoperative radiographs were evaluated. RESULTS: One hundred and seventy patients with comparable patient demographics were reviewed. Eighty-one percent of the PSI procedures were within target (180 ± 3°) mechanical alignment, while the SI group had 70% of cases within the target plane ( P = .132). Mean target alignment (2.0° PSI vs 2.2° SI, P = .477) was similar between groups. Twenty-seven percent of patients in the PSI group had surgeon-directed intraoperative recuts to improve the perceived coronal alignment. The change in hematocrit was reduced in the PSI group (8.89 vs 7.21, P = .000). Procedure time and total operating room time were equivalent. Knee Society Scores did not differ between groups at 6 months or at 1 year. CONCLUSION: Patient-specific instrumentation decreased change in hematocrit, though coronal alignment and efficiency were equivalent between groups. Surgeons must evaluate cuts intraoperatively to confirm alignment. Functional outcomes are equivalent for PSI and SI groups.

Surgical Endoscopy Versus Endoscopic Surgery for Obesity.

BACKGROUND: Obesity treatment options are of great interest worldwide with major developments in the past 20 years. From general surgery to natural orifice transluminal endoscopic surgery intervention nowadays, obesity surgical therapies have surely developed and are now offering a variety of possibilities. AREAS OF UNCERTAINTY: Although surgery is the only proven approach for weight loss, a joint decision between the physician and patient is required before proceeding to such a procedure. With a lot of options available, the treatment should be individualized because the benefits of surgical intervention must be weighed against the surgical risks. DATA SOURCES: Medline search to locate full-text articles and abstracts with obvious conclusions by using the keywords: obesity, surgical endoscopy, gastric bypass, bariatric surgery, and endoscopic surgery, alone and in various combinations. Additional relevant publications were also searched using the reference lists of the identified articles as a starting point. RESULTS: Laparoscopic Roux-en-Y gastric bypass still is the most effective, less invasive, bariatric surgical intervention, although there are various complications encountered, such as postoperative hemorrhage (1.9%-4.4%), internal hernias, anastomotic strictures (2.9%-23%), marginal ulcerations (1%-16%), fistulas (1.5%-6%), weight gain, and nutritional deficiencies. However, the absence of parietal incisions, less pain, decreased risk of infection, and short hospital stay make room for endoscopic surgery as a possible valid option for obesity for both the doctors' and the patients' perspective. CONCLUSIONS: The current tendency is to promote surgical treatment of obesity to a status of less invasive scars therefore promoting minimally invasive surgical techniques.

Thoracic Complications of Precision Cancer Therapies: A Practical Guide for Radiologists in the New Era of Cancer Care.

Recent advances in understanding the molecular mechanisms of cancer have opened a new era of precision medicine for cancer treatment. Precision cancer therapies target specific molecules that are responsible for cancer development and progression, and they achieve marked treatment benefits in specific cohorts of patients. However, these therapies are also associated with a variety of complications that are often unique to specific groups of anticancer agents. The rapidly increasing use of immune checkpoint inhibitors in the treatment of various advanced malignancies has brought new challenges in diagnosing and monitoring a unique set of toxic effects termed immune-related adverse events. Familiarity with cutting-edge cancer treatment approaches and awareness of the emerging complications from novel therapies are essential for radiologists, who play a key role in the care of patients with cancer. This article provides a comprehensive review of the thoracic complications of precision cancer therapies, describes their imaging features and clinical characteristics, and discusses the role of radiologists in the diagnosis and monitoring of these entities. The authors also address the molecular mechanisms of anticancer agents that relate to thoracic complications and emphasize emerging challenges in novel cancer therapies. This article is designed to serve as a practical reference guide for day-to-day practice for radiologists in the era of precision cancer medicine. ©RSNA, 2017.