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Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention

Science

Cancers diagnosed early are often more responsive to treatment. Blood tests that detect molecular markers of cancer have successfully identified individuals already known to have the disease. Lennon et al. conducted an exploratory study that more closely reflects the way in which such blood tests would be used in the future. They evaluated the feasibility and safety of incorporating a multicancer blood test into the routine clinical care of 10,000 women with no history of cancer. Over a 12-month period, the blood test detected 26 cancers of different types. A combination of the blood test and positron emission tomography–computed tomography (PET-CT) imaging led to surgical removal of nine of these cancers. Use of the blood test did not result in a large number of futile follow-up procedures. Science , this issue p. [eabb9601][1] ### INTRODUCTION The goal of earlier cancer detection is to identify the disease at a stage when it can be effectively treated, thereby offering the patient a better chance of long-term survival. Adherence to screening modalities known to decrease cancer mortality such as colonoscopy, mammography, low-dose computed tomography, and Pap smears varies widely. Moreover, the majority of cancer types are diagnosed only when symptoms occur. Multicancer blood tests offer the exciting possibility of detecting many cancer types at a relatively early stage and in a minimally invasive manner. ### RATIONALE Evaluation of the feasibility and safety of multicancer blood testing requires prospective interventional studies. We designed such a study to answer four critical questions: (i) Can a multicancer blood test detect cancers not previously detected by other means? (ii) Can a positive test result lead to surgical intervention with curative intent? (iii) Can testing be incorporated into routine clinical care and not discourage patients from undergoing recommended screening tests such as mammography? (iv) Can testing be performed safely, without incurring a large number of unnecessary, invasive follow-up tests? ### RESULTS We evaluated a blood test that detects DNA mutations and protein biomarkers of cancer in a prospective, interventional study of 10,006 women who were 65 to 75 years old and who had no prior history of cancer. Positive blood tests were followed by diagnostic positron emission tomography–computed tomography (PET-CT), which served to independently confirm and precisely localize the site and extent of disease if present. The study design incorporated several features to maximize the safety of testing to the participants. Of the 10,006 enrollees, 9911 (99.1%) could be assessed with respect to the four questions posed above. (i) Detection: Of 96 cancers incident during the study period, 26 were first detected by blood testing and 24 additional cancers by conventional screening. Fifteen of the 26 patients in whom cancer was first detected by blood testing underwent PET-CT imaging, and 11 patients developed signs or symptoms of cancer after the blood test that led to imaging procedures other than PET-CT. The specificity and positive predictive value (PPV) of blood testing alone were 98.9% and 19.4%, respectively, and combined with PET-CT, the specificity and PPV increased to 99.6% and 28.3%. The blood test first detected 14 of 45 cancers (31%) in seven organs for which no standard-of-care screening test is available. (ii) Intervention: Of the 26 cancers first detected by blood testing, 17 (65%) had localized or regional disease. Of the 15 participants with positive blood tests as well as positive PET-CT scans, 9 (60%) underwent surgery with curative intent. (iii) Incorporation into clinical care: Blood testing could be combined with conventional screening, leading to detection of more than half of the total incident cancers observed during the study period. Blood testing did not deter participants from undergoing mammography, and surveys revealed that 99% of participants would join a similar, subsequent study if offered. (iv) Safety: 99% of participants did not require any follow-up of blood testing results, and only 0.22% underwent an unnecessary invasive diagnostic procedure as a result of a false-positive blood test. ### CONCLUSION A minimally invasive blood test in combination with PET-CT can safely detect and precisely localize several types of cancers in individuals not previously known to have cancer, in some cases enabling treatment with intent to cure. Further studies will be required to assess the clinical utility, risk-benefit ratio, and cost-effectiveness of such testing. ![Figure][2] Overview of cancers detected by blood testing. Twenty-six cancers (blue dots) in 10 organs were first detected by blood testing. The blue dots with the red halo represent 12 of the 26 cancers that were surgically treated with intent to cure. Nine of these 12 were detected by the combination of the blood test and PET-CT, with the remaining three identified by the blood test combined with another imaging modality. Cancer treatments are often more successful when the disease is detected early. We evaluated the feasibility and safety of multicancer blood testing coupled with positron emission tomography–computed tomography (PET-CT) imaging to detect cancer in a prospective, interventional study of 10,006 women not previously known to have cancer. Positive blood tests were independently confirmed by a diagnostic PET-CT, which also localized the cancer. Twenty-six cancers were detected by blood testing. Of these, 15 underwent PET-CT imaging and nine (60%) were surgically excised. Twenty-four additional cancers were detected by standard-of-care screening and 46 by neither approach. One percent of participants underwent PET-CT imaging based on false-positive blood tests, and 0.22% underwent a futile invasive diagnostic procedure. These data demonstrate that multicancer blood testing combined with PET-CT can be safely incorporated into routine clinical care, in some cases leading to surgery with intent to cure. [1]: /lookup/doi/10.1126/science.abb9601 [2]: pending:yes


Measuring the performance of a Classification problem

#artificialintelligence

It is often convenient to combine precision and recall into a single metric called the F1 score, in particular, if you need a simple way to compare two classifiers. The F1 score is the harmonic mean of precision and recall. The F1 score favors classifiers that have similar precision and recall. This is not always what you want: in some contexts, you mostly care about precision, and in other contexts, you really care about the recall. For example, if you trained a classifier to detect videos that are safe for kids, you would probably prefer a classifier that rejects many good videos (low recall) but keeps only safe ones (high precision), rather than a classifier that has a much higher recall but lets a few really bad videos show up in your product (in such cases, you may even want to add a human pipeline to check the classifier's video selection). On the other hand, suppose you train a classifier to detect shoplifters on surveillance images: it is probably fine if your classifier has only 30% precision as long as it has 99% recall (sure, the security guards will get a few false alerts, but almost all shoplifters will get caught).


A machine learning approach to automatic detection of irregularity in skin lesion border using dermoscopic images

#artificialintelligence

Skin lesion border irregularity is considered an important clinical feature for the early diagnosis of melanoma, representing the B feature in the ABCD rule. In this article we propose an automated approach for skin lesion border irregularity detection. The approach involves extracting the skin lesion from the image, detecting the skin lesion border, measuring the border irregularity, training a Convolutional Neural Network and Gaussian naive Bayes ensemble, to the automatic detection of border irregularity, which results in an objective decision on whether the skin lesion border is considered regular or irregular. The approach achieves outstanding results, obtaining an accuracy, sensitivity, specificity, and F-score of 93.6%, 100%, 92.5% and 96.1%, respectively.


Arena and the disappearing art of bootstrapping startups

ZDNet

Silicon Valley headlines often report on the size of venture capital raised by a startup -- the bigger the funding, the bigger the story. But this is a poor way to understand the startup community. Startup success isn't determined by how much you raise; it's about how much you keep. Arena.im is a great example. It recently raised a seed round of $2.3 million -- a tiny amount by local standards.


Data Science questions for interview prep (Machine Learning Concepts) -Part I

#artificialintelligence

I recently finished watching this Machine Learning playlist (StatQuest by Josh Starmer) on Youtube and thought of summarizing each concept into a Q/A. As I prepare for more data science interviews, I thought it would be a good exercise to make sure that I am communicating my thoughts clearly and concisely during an interview. Let me know in the comments, if I am not doing a good job in explaining any of the concepts. NOTE: This article is not aimed for teaching a concept to beginners. It assumes that the reader has sufficient background in data science concepts.


Abolish the #TechToPrisonPipeline

#artificialintelligence

The authors of the Harrisburg University study make explicit their desire to provide "a significant advantage for law enforcement agencies and other intelligence agencies to prevent crime" as a co-author and former NYPD police officer outlined in the original press release.[38] At a time when the legitimacy of the carceral state, and policing in particular, is being challenged on fundamental grounds in the United States, there is high demand in law enforcement for research of this nature, research which erases historical violence and manufactures fear through the so-called prediction of criminality. Publishers and funding agencies serve a crucial role in feeding this ravenous maw by providing platforms and incentives for such research. The circulation of this work by a major publisher like Springer would represent a significant step towards the legitimation and application of repeatedly debunked, socially harmful research in the real world. To reiterate our demands, the review committee must publicly rescind the offer for publication of this specific study, along with an explanation of the criteria used to evaluate it. Springer must issue a statement condemning the use of criminal justice statistics to predict criminality and acknowledging their role in incentivizing such harmful scholarship in the past. Finally, all publishers must refrain from publishing similar studies in the future.


14 Popular Evaluation Metrics in Machine Learning

#artificialintelligence

The evaluation metric is used to measure the performance of a machine learning model. A correct choice of an evaluation metric is very essential for a model. This article will cover all the metrics used in classification and regression machine learning models. For a classification machine learning algorithm, the output of the model can be a target class label or probability score. The different evaluation metric is used for these two approaches.


Coronavirus: How air passengers can stay safe

BBC News

Thermal-imaging cameras and swab tests for coronavirus are not "clinically valuable" in airports, according to a panel of aviation health experts. About one in every three infectious people would be missed, they say. Air systems and low humidity on planes already reduces virus spread through the cabin. But passengers should wear face coverings at all times, board and disembark one row at a time and be seated apart from others if possible. And those seated at the back should be the first on and last off.


A coronavirus mystery: How many people in L.A. actually have COVID-19?

Los Angeles Times

One of the most pressing questions public health officials are trying to answer about the coronavirus is how many people actually have been infected by it. Have a relatively significant portion of Californians been infected with the virus but survived without much problem? Or has the virus touched only a tiny sliver of California, suggesting the chances of serious illness are greater if you're infected? In April, controversial studies out of Stanford University and USC suggested the coronavirus has circulated much more widely than previously thought in Silicon Valley and Los Angeles County. Almost immediately, there have been questions from other epidemiologists around the country about whether those estimates were too high.


Serology assays to manage COVID-19

Science

In late 2019, China reported a cluster of atypical pneumonia cases of unknown etiology in Wuhan. The causative agent was identified as a new betacoronavirus, called severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), that causes coronavirus disease 2019 (COVID-19) (1). The virus rapidly spread across the globe and caused a pandemic. Sequencing of the viral genome allowed for the development of nucleic acid–based tests that have since been widely used for the diagnosis of acute (current) SARS-CoV-2 infections (2). Development of serological assays, which measure the antibody responses induced by SARS-CoV-2 infection (past but not current infections), took longer.