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Monday, June 4, 2018

AI Detects Polyps Better Than Colonoscopists


High-performing colonoscopists can identify 20% more polyps with artificial intelligence (AI) than without, a new study indicates.
Some gastroenterologists have expressed concern, worrying that they will be put out of work, “but I don’t see that happening,” said William Karnes, MD, from UC Irvine Health in California.
“I see what we’re doing with AI as primarily a way to make the colonoscopists’s job easier, giving more time to our patients and less time to paperwork,” he explained.
When Karnes and his colleagues applied a video-based machine-learning model to about 4100 images with polyps and 4500 without, the accuracy rate for polyp detection was 96%, he reported here at Digestive Disease Week 2018.
Four colonoscopists with career adenoma detection rates of at least 50% then examined the videos with and without the AI video overlay.
The researchers hope that the use of AI will ultimately lead to fewer cases of interval colorectal cancer, because 50% to 80% are the result of missed polyps.
“This was basically a feasibility study to try to mimic what happens during a colonoscopy, using some deidentified videos from older studies, to see whether AI enhanced our ability to see polyps,” Karnes told Medscape Medical News.
“When I saw the first overlay on video, I thought, ‘this is so cool’,” he told Medscape Medical News. “I was actually blown away.”
The 8641 images used in the study were considered diverse and balanced, and included all portions of the colon plus random features, such as debris and diverticuli. The machine-learning model, which incorporated a so-called convolutional neural network, operated at a processing speed exceeding that required for live video.
Using the AI polyp detection technique, the four colonoscopists were tasked with identifying all polyps in nine colonoscopy videos. Karnes, who has performed more than 20,000 colonoscopies, was the only one of the four to review machine-learning-overlaid videos, and he determined the uniqueness of each polyp and the confidence level — low to high — of true polyp presence.
This limitation could create potential bias, he acknowledged, but it will be remedied in upcoming clinical trials.
I was actually blown away.
Karnes compared the AI overlay video with a video stream brought into a small gaming computer. Before sending the video to the monitor, an algorithm assessed each frame to determine if a polyp was present and, if so, placed a box around the polyp.
“So we’re seeing, in real time, the original video along with a little green box if a polyp is present,” he explained.

High Performance

No unique polyps were missed with the machine-learning model. In fact, with the machine-overlaid videos, the number of unique polyps detected increased from 36 to 45. Confidence was high for three of the additional nine polyps detected, and low for six.
The AI model produced a false-positive rate of only 7%, and a negative predictive value of 99.5%, Karnes reported. This means that gastroenterologists using this technology might not have to wait for pathology results.
“When combined with accurate optical pathology, AI may eventually bring us to real-time measures of adenoma detection rate,” he said.
The technology, when used by gastroenterologists during colonoscopy, will likely prompt more careful inspection and the detection of additional polyps, Karnes noted. Multiple centers are already lined up to conduct primarily randomized clinical trials on the technique, he said, and data are expected to accrue quickly thereafter.
AI is already being used in other facets of colonoscopy. It can assess the thoroughness of bowel prep, for example, and monitor when the scope is placed inside and removed from the colon.
After conversations with practicing gastroenterologists, Karnes said he believes most will be “very eager” to try this technique.
AI approaches to polyp detection are “what’s going to happen,” said Daniel Stonewall Anderson, MD, from Kaiser Permanente in San Diego, who is president of the California Colorectal Cancer Coalition. However, he noted, the results “seem very, very early.”
“The AI looking at the images will eventually help us,” he told Medscape Medical News. “It is interesting that removing these tiny polyps that would never mean anything [in terms of cancer development] would come to mean something because they’re an index of quality. It means we’re looking well.”
Karnes is a cofounder of DocBot, a spinoff of this study that might eventually lead to profits for the University of California, Irvine. Anderson has disclosed no relevant financial relationships.
Digestive Disease Week (DDW) 2018: Presentation 133. Presented June 2, 2018.

Siemens Healthineers says FDA clears Biograph Vision PET/CT system


The FDA has cleared the Biograph Vision, a new positron emission tomography/computed tomography system from Siemens Healthineers that “delivers a new level of precision in PET/CT imaging.”

#ASCO18: Merck Keytruda ‘alone bests chemo’ in advanced lung cancer


Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab (Keytruda) had a greater median survival than patients treated with standard chemotherapy, even if the former had low levels of PD-L1, researchers reported here.
Depending on the percentage of PD-L1 expression in the tumor, survival was between 4 and 8 months longer for patients treated with immunotherapy alone versus those treated with chemotherapy, according to Gilberto Lopes, MD, MBA, of the Sylvester Comprehensive Cancer Center at the University of Miami, and colleagues.
The benefit in overall survival (OS) was accomplished without an increase in adverse events (62.7% with pembrolizumab vs 89.9% with chemo), Lopes said at a press conference at American Society of Clinical Oncology (ASCO) annual meeting.
Serious adverse events were seen in 17.8% of the patients on pembrolizumab and in 41% of patients on chemotherapy, he added.
“Given the overall efficacy and safety profile, pembrolizumab monotherapy is a standard-of-care first-line therapy for PD-L1 expressing, locally advanced or metastatic, squamous or nonsquamous non-small-cell lung cancer,” Lopes said.
Pembrolizumab currently has FDA approval for NSCLC patients with a PD-L1 level of ≥50% based on results of the phase III KEYNOTE-024 trial. Lopes suggested the current study’s findings would expand the population of patients with NSCLC who could be treated with immunotherapy, rather than chemotherapy, in the first-line setting.
The patient population for the KEYNOTE-042 trial consisted of those with previously untreated advanced/metastatic NSCLC, without sensitizing EGFR or ALK alterations, and a PD-L1 tumor proportion score (TPS) ≥1%.
ASCO expert John Heymach, MD, of the MD Anderson Cancer Center in Houston, said the study results are part of “a new era in treatment” and that immunotherapy is pushing the use of chemotherapy to the back burner for many cancer patients. He said about 75% of NSCLC patients with advanced disease would be eligible to receive pembrolizumab, or other target agents, in lieu of chemotherapy as a first-line treatment.
“Immunotherapy with pembrolizumab alone benefits a much larger number of patients than we had previously thought,” Heymach said. “This is yet another promising result with immunotherapy in lung cancer that brings new momentum to the treatment of this notoriously difficult disease.”
Eligible patients were randomized 1:1 to ≤35 cycles of pembrolizumab 200 mg Q3W, or investigator’s choice of ≤6 cycles of paclitaxel plus carboplatin or pemetrexed plus carboplatin with optional pemetrexed maintenance in nonsquamous disease only.
Randomization was stratified by region (east Asia vs non-east Asia), ECOG performance status (0 vs 1), histology (squamous vs nonsquamous), and TPS (≥50% vs 1-49%).
Lopes said that 299 patients with PD-L1 expression of ≥50% who were assigned pembrolizumab achieved a median OS of 20.0 months versus median OS of 12.2 months for 300 patients who received chemotherapy (hazard ratio 0.69, P=0.003).
Of the 413 patients who had a PD-L1 expression of ≥20% treated with pembrolizumab, the median OS was 17.7 months versus median OS 13 months for the 405 patients assigned to chemotherapy (P=0.002).
The 637 patients who had a PD-L1 level of ≥1% who were assigned to receive pembrolizumab achieved a median OS of 16.7 months compared with a median OS 12.1 months for 637 patients assigned to receive placebo (P=0.0018).
“These data confirm and potentially extend the role of [pembrolizumab] monotherapy as a standard first-line treatment for PD-L1–expressing advanced/metastatic NSCLC,” the authors concluded, adding that the external data monitoring committee recommended continuing the trial to evaluate progression-free survival.
The trial was supported by Merck. Some co-authors are company employees.
Lopes disclosed relevant relationships with Merck Sharp & Dohme, EMD Serono, and AstraZeneca. Co-authors disclosed multiple relevant relationships with industry.
Heymach disclosed relevant relationships with Abbvie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Genentech, Medivation, Novartis, OncoMed, Synta, Bio-Tree and Cardinal Spine.

Gilead-licensed experimental therapy reported eliminating woman’s cancer


Researchers at the U.S. National Cancer Institute grew copies of rare cells custom-made by the immune system from inside tumors and infused them back into a 49-year-old woman whose cancerous tumors were growing despite seven types of chemotherapy and hormonal therapy, reported Bloomberg. The experimental immune cell therapy, which has since been licensed to Gilead Sciences, left the woman cancer-free and also shrank hard-to-treat tumors in six other patients with colon and cervical cancers, according to a report about the study, the results of which were published Monday in the scientific journal Nature Medicine. In late morning trading, Gilead shares are up 1.6% to $69.42

Supreme Court throws out illegal immigrant teen abortion ruling


The U.S. Supreme Court on Monday threw out a lower court ruling that let a pregnant illegal immigrant minor held in federal immigration custody to obtain an abortion last year at age 17 over the objections of President Donald Trump’s administration.
The action by the justices provided a legal victory to Trump’s administration even though the teenager already has had the abortion because it eliminated a precedent at the federal appeals court level that could have applied in similar circumstances in which detained minors sought abortions.
In the unsigned opinion with no dissents, the justices threw out the appeals court decision on the grounds that the dispute became moot once the unnamed teenager had the abortion.
The justices, however, declined to take up the administration’s request for disciplinary action against the American Civil Liberties Union lawyers who represented the girl, who underwent an abortion in Texas last October. The administration had accused the ACLU lawyers of misleading the Justice Department over when she would have the abortion.
The court also allowed litigation to continue in lower courts concerning other detained immigrants in detention in a similar situation.
The high court said that it takes misconduct allegations against lawyers seriously but said “not all communication breakdowns constitute misconduct.”
The ACLU, which has filed a range of lawsuits against the administration, sued in Washington in October, seeking a decision on obtaining abortions that would be binding in any future cases that arise.
A 1973 Supreme Court ruling legalized abortion nationwide. One of the issues raised by the case is whether illegal immigrant women have the same right to an abortion as American citizens and legal residents.
The girl at the center of the legal fight had an abortion on Oct. 25, the day after a U.S. appeals court ruled against the Trump administration’s objections.
The Justice Department has said it was preparing to appeal that ruling to the Supreme Court when it learned she had already had the abortion early that morning.
While the case was pending at the Supreme Court, litigation continued in lower courts.
On March 30, a federal judge in Washington issued an injunction that prevents the administration from impeding access to abortion by detained immigrant minors. U.S. District Judge Tanya Chutkan also certified a class action of similar minors to challenge the administration’s policy.

#ASCO18: CarThera has promising prelim Ph. 1/2a data on recurrent glioblastoma


Preliminary data from the first clinical trial of the company’s intracranial ultrasound implant, SonoCloud®, show a good safety profile and promising trends in overall survival 
Carthera, a French company that designs and develops innovative ultrasound-based medical devices to treat brain disorders, today announced the preliminary data of its Phase I/IIa clinical trial (NCT02253212) on ultrasound induced blood-brain barrier (BBB) opening. Dr. Ahmed Idbaih, principal investigator and neuro-oncologist at AP-HP hospital in Paris, presented preliminary data from a trial involving 21 patients with recurrent glioblastoma (GBM), who were treated monthly with the SonoCloud device prior to carboplatin chemotherapy. The presentation took place at the McCormick Place Convention Center in Chicago, Illinois on June 2 during a session on Central Nervous System Tumors at the American Society of Clinical Oncology (ASCO).
The BBB prevents the passage of most drugs from the blood to the brain and may be responsible for the limited efficacy of current chemotherapies in GBM patients. To tackle this problem, Pr. Alexandre Carpentier, a French neurosurgeon at AP-HP and founder of CarThera, developed SonoCloud, a low-intensity pulsed ultrasound device that temporarily increases the permeability of the BBB and enhances the delivery of therapeutic molecules to the brain.
“Our mission is to improve the prognosis of patients with brain diseases by increasing the permeability of cerebral blood vessels to allow therapeutic molecules such as antibodies, pathway inhibitors, chemotherapies or enzymes to reach effective concentrations in the brain,” said Frederic Sottilini, CEO of CarThera.
In preliminary analysis of the data from 21 GBM patients who received 65 SonoCloud treatments, the investigators observed a good safety profile and trends in improvement of Progression Free and Overall Survival. OS was increased from 8.5 to 12.9 months in patients who had SonoCloud-induced BBB opening. The full abstract #2016 titled ‘Safety and preliminary efficacy data from a phase I study of an implantable low intensity pulsed ultrasound (LIPU) device for disrupting the blood-brain barrier (BBB) in patients treated by chemotherapy for recurrent glioblastoma (GBM)‘ is available on abstracts.asco.org.
“We are excited to share promising preliminary data from our clinical trial at the ASCO annual meeting attended by more than 32,000 oncology professionals from around the world,” said Dr. Idbaih. “The sonication of larger volumes of brain in recurrent GBM will be investigated in a future trial and may further enhance the observed effectiveness of this new treatment modality.”
“Preliminary efficacy results presented by Dr. Idbaih at the annual ASCO meeting demonstrate the proof of concept of our first-in-class solution to enhance delivery of therapeutic agents in the brain. The increase in survival observed in GBM patients paves the way for the combination of the SonoCloud device with different agents for treating various brain disorders, such as cancers and neurodegenerative diseases,” said Frederic Sottilini.
According to the company’s estimates, each year 250,000 patients worldwide are diagnosed with brain tumors. The SonoCloud could benefit these patients as well as millions more with debilitating brain disorders.

#ASCO18: Novocure Has Phase 3 Pivotal Trial Design in Recurrent Ovarian Cancer


 NovoCure (NASDAQ: NVCR) will present today for the first time the design of its phase 3 pivotal trial of Tumor Treating Fields combined with paclitaxel in patients with recurrent, platinum-resistant ovarian cancer at the American Society of Clinical Oncology (ASCO) Annual Meeting 2018 in Chicago. Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and causing affected cancer cells to die.
INNOVATE-3, a prospective, open-label study, will include 540 patients with recurrent, platinum-resistant ovarian cancer. Patients will be randomized to receive either weekly paclitaxel alone or weekly paclitaxel in combination with Tumor Treating Fields tuned to 200 kHz until progression. The primary endpoint is overall survival. Secondary endpoints include progression free survival, objective response rate, severity and frequency of adverse events, time to undisputable deterioration in health-related quality of life or death, and quality of life. Patients must be 18 years or older, and have an epithelial histology of ovarian/primary peritoneal or fallopian tube carcinoma at diagnosis, an Eastern Cooperative Oncology Group (ECOG) score of 0-1, and evaluable disease in the abdominal/pelvic region. Patients may have had a maximum of two prior lines of systemic therapy following diagnosis of platinum-resistance. Patients who have participated in prior clinical trials may be included.
The trial design for INNOVATE-3 was based on the promising results of Novocure’s phase 2 pilot trial in recurrent ovarian cancer, which examined Tumor Treating Fields in combination with standard of care chemotherapy. This trial was a single-arm, open-label, historically-controlled, multi-center study, designed to test the feasibility, safety and preliminary efficacy of Tumor Treating Fields in combination with weekly paclitaxel. The paclitaxel control arm from the bevacizumab phase 3 FDA registration trial was used as a historical control in this trial.
A total of 30 patients were enrolled with a minimum follow-up of six months. Safety results suggested that Tumor Treating Fields in combination with weekly paclitaxel may be tolerable and safe as first-line treatment for patients with recurrent ovarian cancer. Median progression free survival in the Tumor Treating Fields-treated group was 8.9 months (compared to 3.9 months in the paclitaxel-alone historical control) and median overall survival was not yet reached. Median one-year survival was 61 percent. Efficacy results based on the 30 evaluable patients suggested more than doubling of the progression free survival and an improvement in overall survival among patients who received Tumor Treating Fields therapy with paclitaxel compared to paclitaxel alone.
“After having a recurrence, women with ovarian cancer experience a median overall survival of only 13 to 14 months,” said Dr. Eilon Kirson, Novocure’s Chief Science Officer and Head of Research and Development. “Our preclinical research has demonstrated synergistic effects between Tumor Treating Fields and taxane-based chemotherapies. We are excited to present the trial design for INNOVATE-3 at the ASCO Annual Meeting and are eager to make this trial available to patients who are in need of better outcomes.”