Multi-cancer early detection (MCED) tests are blood-based tests designed to screen for signals of multiple cancers. There is growing interest and investment in examining the potential benefits and applications of MCED tests. If MCED tests are shown to have clinical utility, it is important to ensure that all people-regardless of their demographic or socioeconomic background-equitably benefit from these tests. Unfortunately, with health care innovation, such considerations are often ignored until after inequities emerge. We urge for-profit companies, scientists, clinicians, payers, and government agencies to prioritize equity now-when MCEDs are still being developed and researched. In an effort to avoid creating and exacerbating cancer inequities, we propose 9 equity considerations for MCEDs.

Emerging blood-based multicancer early-detection (MCED) tests may redefine cancer screening, reduce mortality, and address health disparities if their benefit is demonstrated. U.S. payers\' coverage policies will impact MCED test adoption and access; thus, their perspectives must be understood. We examined views, coverage barriers, and evidentiary needs for MCED from 19 private payers collectively covering 150 000 000 enrollees. Most saw an MCED test\'s potential merit for cancers without current screening (84%), but fewer saw its merit for cancers with existing screening (37%). The largest coverage barriers were inclusion of cancers without demonstrated benefits of early diagnosis (73%), a high false-negative rate (53%), and lack of care protocols for MCED-detected but unconfirmed cancers (53%). The majority (58%) would not require mortality evidence and would accept surrogate endpoints. Most payers (64%) would accept rigorous real-world evidence in the absence of a large randomized controlled trial. The majority (74%) did not expect MCED to reduce disparities due to potential harm from overtreatment resulting from an MCED and barriers to downstream care. Payers\' perspectives and evidentiary needs may inform MCED test developers, researchers producing evidence, and health systems framing MCED screening programs. Private payers should be stakeholders of a national MCED policy and equity agenda.

OBJECTIVE: Blood-based multi-cancer early detection (MCED) tests are now commercially available. However, there are currently no consensus guidelines available for head and neck cancer (HNC) providers to direct work up or surveillance for patients with a positive MCED test. We seek to describe cases of patients with positive MCED tests suggesting HNC and provide insights for their evaluation.
METHODS: Retrospective chart review of patients referred to Otolaryngology with an MCED result suggesting HNC. Patients enrolled in prospective MCED clinical trials were excluded. Cancer diagnoses were confirmed via frozen-section pathology.
RESULTS: Five patients were included (mean age: 69.2 years, range 50-87; 4 male) with MCED-identified-high-risk for HNC or lymphoma. Only patient was symptomatic. After physical exam and follow-up head and neck imaging, circulating tumor HPV DNA testing, two patients were diagnosed with p16 + oropharyngeal squamous cell carcinomas and underwent appropriate therapy. A third patient had no evidence of head and neck cancer but was diagnosed with sarcoma of the thigh. The remaining two patients had no evidence of malignancy after in-depth workup.
CONCLUSIONS: In this retrospective study, 2 of 5 patients referred to Otolaryngology with a positive MCED result were diagnosed with HPV + oropharyngeal squamous cell carcinoma. We recommend that positive HNC MCED work up include thorough head and neck examination with flexible laryngoscopy and focused CT or MRI imaging. Given the potential for inaccurate MCED tissue of origin classification, PET/CT may be useful in specific situations. For a patient with no cancer identified, development of clear guidelines is warranted.

The new generation of cancer early detection tests holds remarkable promise for revolutionizing and changing the paradigm of cancer early detection. Dozens of cancer early detection tests are being developed and evaluated. Some are already commercialized and available for use, most as a complement to and not in place of existing recommended cancer screening tests. This review evaluates existing single- and multi-cancer early detection tests (MCEDs), discussing their performance characteristics including sensitivity, specificity, positive and negative predictive values, and accuracy. It also critically looks at the potential harms that could result from these tests, including false positive and negative results, the risk of overdiagnosis and overtreatment, psychological and economic harms, and the risk of widening cancer inequities. We also review the large-scale, population-based studies that are being launched in the United States and United Kingdom to determine the impact of MCEDs on clinically relevant outcomes and implications for current practice.

Electrochemical additive manufacturing is an advanced microfabrication technology capable of producing features of almost unlimited geometrical complexity. A unique combination of the capacity to process conductive materials, design freedom, and micro- to nanoscale resolution offered by these electrochemical techniques promises tremendous opportunities for a multitude of future applications spanning microelectronics, sensing, robotics, and energy storage. This review aims to equip readers with the basic principles of electrochemical 3D printing at the small length scale. By describing the basic principles of electrochemical additive manufacturing technology and using the recent advances in the field, this beginner\'s guide illustrates how controlling the fundamental phenomena that underpin the print process can be used to vary dimensions, morphology, and microstructure of printed structures.

Cancer remains a leading cause of death worldwide, partly owing to late detection which entails limited and often ineffective therapeutic options. Most cancers lack validated screening procedures, and the ones available disclose several drawbacks, leading to low patient compliance and unnecessary workups, adding up the costs to healthcare systems. Hence, there is a great need for innovative, accurate, and minimally invasive tools for early cancer detection. In recent years, multi-cancer early detection (MCED) tests emerged as a promising screening tool, combining molecular analysis of tumor-related markers present in body fluids with artificial intelligence to simultaneously detect a variety of cancers and further discriminate the underlying cancer type. Herein, we aim to provide a highlight of the variety of strategies currently under development concerning MCED, as well as the major factors which are preventing clinical implementation. Although MCED tests depict great potential for clinical application, large-scale clinical validation studies are still lacking.

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approaches. The WG methylation feature best predicts cancer signal origin. WG methylation is the most promising technology for MCED and informs development of a targeted methylation MCED test.

Multicancer early detection panels have recently become available to patients with a provider\'s prescription and an out-of-pocket fee. Beyond theoretical modeling, little is known about how these assays will impact primary care practices despite a high likelihood that primary care providers (PCPs) will be ordering these tests with some frequency. In particular, there are concerns about patient counseling, costs, frequency of testing, patient anxiety, and subsequent testing for a positive result. This review aims to appraise the current literature and provide a framework that PCPs can use to discuss these tests with patients and streamline their ordering, interpretation, and overall use into everyday practice.