Coronary-artery calcium (CAC) measured automatically on radiotherapy-planning CT scans in women being treated for breast cancer may be used to spot those at increased risk for cardiovascular disease, researchers say.
"We've shown that we can use routine radiotherapy CT scans to indicate which breast cancer patients are most likely to develop cardiovascular disease," said Dr. Helena M. Verkooijen of University Medical Center Utrecht in the Netherlands.
"Now we need to do more research to find out what can be done to help minimize this risk, for instance whether patients' cardiovascular health should be monitored or treated," she told Reuters Health by email.
Cardiovascular disease (CVD) is common in women with breast cancer and in older patients competes with breast cancer as the leading cause of death, Dr. Verkooijen and colleagues note in JAMA Oncology.
CAC on CT scans is an independent risk factor for CVD, they add, but CAC scoring "is usually performed manually and can be tedious and time consuming." However, the team has developed a deep-learning calcium-scoring algorithm for automated CAC scoring on dedicated cardiac CT scans.
To examine the utility of this information, the researchers studied data on close to 16,000 patients with breast cancer who received radiotherapy between 2005 and 2016. Their mean age at CT scan was 59 years.
CAC scores were used to classify CVD evidence in patients via Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). Overall, 70% of patients had no CAC. Scores of 1 to 10 were seen in 10%, 11 to 100 in 11.5%, 101 to 400 in 5.2%, and greater than 400 in 3.1%.
Over a median follow-up of 51.2 months, CVD events occurred in 5.2% in patients with no CAC and in 28.2% in those with CAC scores higher than 400.
Compared with patients without CAC, the adjusted risk of fatal and nonfatal CVD was 1.1, 1.8, 2.1 and 3.4 higher in patients with a CAC score of 1 to 10, 11 to 100, 101 to 400, and greater than 400, respectively.
Coronary-artery calcium was particularly strongly associated with coronary-artery disease in those with the highest scores (HR, 7.8). The association between CAC and CVD was strongest in patients treated with anthracyclines and those who received a radiation boost.
"Timely and accurate identification of high-risk patients might allow mitigation of cardiovascular risk, including management of CVD risk factors and switching to less cardiotoxic treatment regimens," the researchers say.
Dr. Sherry-Ann Brown, director of Cardio-Oncology at the Medical College of Wisconsin, in Milwaukee, told Reuters Health by email that "according to this cohort study, CAC scoring on radiotherapy-preparation CT scans can be used as a quick and low-cost method to classify patients with breast cancer who are at a higher risk of CVD, enabling CVD risk-reduction measures to be implemented."
"This," she added, "is something we have wanted to see and study for a long time, as we recognize more and more the potential value of synergistic screening in cardiology and medical and radiation oncology. Combining cardiovascular risk screening with treatment planning for breast cancer can enhance and optimize multidisciplinary preventive care and management for individuals with cancer."
Dr. Brown was not involved in the study.
SOURCE: https://bit.ly/3hpjpdc JAMA Oncology online May 6, 2021.
In an unprecedentedpublic rebuke, the FDA accused CytoDyn of trying to cherry pick data from two failed studies of leronlimab in COVID-19 patients to claim the drug is effective.
Back in March, a phase 3 clinical trial of CytoDyn’s leronlimab failed on the primary goal of reducing symptoms and all secondary goals, including one that questioned whether the therapy could reduce mortality. But the company instead focused its data release on a subgroup of 62 mechanically ventilated, critically ill COVID-19 patients, claiming that the drug spurred a 24% reduction in all-cause mortality and a six-day reduction in hospitalization, among other trial wins.
CytoDyn then issued a second press release after performing an “age adjustment” analysis that claimed to show leronlimab reduced mortality in older patients.
Now, the FDA has broken its usual vow of silence on disclosing information on unapproved products to say that CytoDyn’s reshaping of the data is erroneous.
“It has become clear that the data currently available do not support the clinical benefit of leronlimab for the treatment of COVID-19,” the FDA said. “None of these analyses met statistical significance when using established and reliable analytical methods that correct for multiple comparisons.”
Shares of CytoDyn plummeted when the FDA released its statement just before the market closed. The stock lost 76 cents in value, dropping more than 27% to $2.04 at market close.
The FDA is not the only one to have noticed CytoDyn’s missteps. According to the company’s most recent 10-Q, a stockholder has filed a class action lawsuit alleging that CytoDyn made false and misleading statements about the viability of leronlimab in treating COVID-19. A second, similar suit was filed in April.
The U.S. regulatory authority went on to explain how clinical trials actually work: a prespecified endpoint is selected, the trial is conducted and if the goal is not met, the trial is considered a failure. Any so-called “subgroup” analysis following a failed trial are considered by the FDA to be exploratory and can be used only to inform the design of future trials.
“Focusing on only the most favorable of many subgroup analyses, even if the sub-groups are pre-specified, can lead to overestimating the evidence of benefit, because regardless of a drug’s true efficacy, some analyses are likely to appear favorable by chance when a large number of analyses are conducted,” the FDA said.
After two clinical trial readouts, the FDA has therefore found its answer on leronlimab: “With the conclusion of both the CD10 and CD12 clinical trials, it has become clear that the data currently available do not support the clinical benefit of leronlimab for the treatment of COVID-19.”
In the CD10 trial, the FDA said the data appeared to show that patients recovered from COVID-19 regardless of whether they received leronlimab or placebo. As for the larger CD12 trial, the agency said the drug failed to show any effect on the primary endpoint when compared with placebo.
The FDA said the unusual statement was released because of “significant public interest” in the drug.
A request for comment to CytoDyn went unreturned as of publication.
As recently as last week, CytoDyn signed a deal to pursue an emergency authorization and compassionate use program for leronlimab in India. Another deal to start two clinical trials in Brazil was announced on May 7.
The FDA said the subgroup analyses could be used to form the basis of future trials, and pledged to work with CytoDyn should the company wish to move forward with new research in COVID-19.
Outside of COVID-19, CytoDyn is trialing leronlimab in everything but the kitchen sink including HIV, 22 different solid tumor cancers, autoimmune diseases such as psoriasis and Crohn’s disease, graft versus host disease and nonalcoholic fatty liver disease.
ImmunityBio Inc (NASDAQ: IBRX) has received FDA authorization to conduct a Phase 1 study to evaluate the m-ceNK platform combined with Anktiva (N-803) in locally advanced/metastatic solid tumors.
Cryopreserved m-ceNK cells combined with Anktiva will be tested in this QUILT 3.076 Phase 1 study designed to evaluate the safety in subjects.
The study consists of two cohorts, and there will be 10 participants in each cohort. Cohort 1 includes participants with newly diagnosed high-risk solid tumors who have not received prior treatment.
Cohort 2 includes participants with relapsed/refractory solid tumors who have progressive disease after receiving more than two prior therapies.
Cases of unusual thrombosis and thrombocytopenia after administration of the ChAdOx1 nCoV‐19 vaccine (AstraZeneca) have been reported. The term vaccine‐induced prothrombotic immune thrombocytopenia (VIPIT) was coined to reflect this new phenomenon. In vitro experiments with VIPIT patient sera indicated that high dose intravenous immunoglobulins (IVIG) competitively inhibit the platelet activating properties of ChAdOx1 nCoV‐19 vaccine induced antibodies. Here, we report a case of a 62‐year‐old woman, who had received this vaccine and developed VIPIT. She visited the emergency ward because of petechiae and hematomas. In the laboratory work‐up, thrombocytopenia, low fibrinogen, elevated D‐dimer, and positivity in the platelet factor 4/heparin‐enzyme‐immunoassay were present. Signs and symptoms of thrombosis were absent. Upon immediate therapy with non‐heparin anticoagulation, high dose IVIG, and prednisolone laboratory parameters steadily improved and the patient was discharged from hospital without thrombotic complications. We conclude that early initiation of VIPIT treatment results in a swift response without thrombotic complications.
Taiwan Semiconductor Manufacturing Co Ltd (TSMC) said on Monday that from May 19 it will start to operate in separate teams to minimise the risk of COVID-19 infections, after a spike in domestic cases in Taiwan.
The island has recorded more than 700 infections in the past week, a shock for residents used to Taiwan’s relative safety, and the government has tightened curbs in the capital Taipei to try and prevent the numbers rising further.
TSMC, the world’s largest contract chip-maker, said it had tightened its own rules in respond to the government’s raised warning level.
“TSMC’s primary consideration is epidemic safety protection and the company is monitoring the pandemic development closely to make rolling updates,” it said in a statement.
All non-essential vendors will be restricted from entering TSMC facilities and staff and vendors must avoid moving across its main production sites in Hsinchu, Taichung and Tainan, it added.
People should avoid face-to-face meetings, and if they must be held only essential personnel should attend with the number of attendees restricted to 50% of meeting room capacity, the company said.
Training courses should be conducted online, or cancelled, and company recreational facilities will be closed, it added.
Taiwan is a major producer of semiconductors and central to global efforts to resolve a chip shortage that have shuttered some car plants around the world and are now starting to affect consumer electronics.
EMA’s human medicines committee (CHMP) has recommended a change to the approved storage conditions of Comirnaty, the COVID-19 vaccine developed by BioNTech and Pfizer, that will facilitate the handling of the vaccine in vaccination centres across the European Union (EU).
This change extends the approved storage period of the unopened thawed vial at 2-8°C (i.e. in a normal fridge after taking out of deep-freeze conditions) from five days to one month (31 days). The change was approved following assessment of additional stability study data submitted to EMA by the marketing authorisation holder. Increased flexibility in the storage and handling of the vaccine is expected to have a significant impact on planning and logistics of vaccine roll-out in EU Member States.
The changes described will be included in the publicly available information on Comirnaty and will be implemented by the marketing authorisation holder in updated product labelling. Users are reminded to always refer to the label and package leaflet of the supplied product for the correct storage information.
EMA is in continuous dialogue with the marketing authorisation holders of COVID-19 vaccines as they seek to make manufacturing improvements to enhance vaccine distribution in the EU.
Doubts are mounting about the efficacy of Russia’s Sputnik vaccine. Drug regulators in the Czech Republic and Brazil have withheld approval and counterparts in Slovakia have also expressed doubts.
FILE - The exterior of the European Medicines Agency is seen in Amsterdam, Netherlands, Dec. 18, 2020.
European Union regulators are still assessing Sputnik for its effectiveness and safety but a former executive director of the European Medicines Agency, EMA, told the Politico.eu news site that objections raised about Sputnik by Brazil’s regulatory authority, Anvisa, would likely be taken seriously by their counterparts in Brussels.
“It's a very mature authority,” said Rasi, who added that its flagging of quality and safety issues are worrisome. Anvisa announced on April 28 that it was withholding approval because of “flaws in product development” which deviate from the quality standards recommended by the World Health Organization (WHO).
The authority also noted “an absence or insufficiency of quality control, safety and efficacy data.” It raised concerns also with the vaccine’s efficacy for people “with low immunity and respiratory problems, among other health problems.” The Slovak medicines authority has also expressed worries about quality control and insufficient data. Irena Storová, head of SÚKL, told Slovakia’s Radiožurnál recently that the regulator received “only a fraction of the documentation that is submitted by default for the registration or assessment of a drug or medicine.”
FILE - A scientist works inside a laboratory of the Gamaleya Research Institute of Epidemiology and Microbiology during the testing of a coronavirus vaccine, in Moscow, Russia, Aug. 6, 2020. (Russian Direct Investment Fund / Handout via Reuters)
Sputnik was the first coronavirus vaccine to be registered, albeit only by the Russians and not by an authoritative international regulator. Funded by the state and developed by the Gamaleya Research Institute in Moscow, the rapid Russian approval last year in August of the vaccine, which was named for the satellite from half a century ago, was met with skepticism in the broader international scientific community.
Experts expressed their disapproval of Russian authorities for approving distribution before the completion of trials, suggesting the rapidity of authorization was done so as to be able to tout Russian scientific prowess.
Doubts about the vaccine's efficacy dissipated somewhat last year within the Western scientific community due to a study by Russian scientists published by the authoritative British medical journal The Lancet, which suggested the vaccine has a 91.6% efficacy rate against COVID-19, the illness caused by the coronavirus.
Geopolitical motives
Nonetheless, some Central European and Baltic governments have been trading barbs with the Kremlin for what they see as a “Sputnik diplomatic offensive” designed to foment political splits in the Western alliance.
FILE - Workers take care of the shipment of Russia's Sputnik V vaccine at the airport in Caracas, Venezuela, March 29, 2021.
Officials in Kyiv and Warsaw identify geopolitical motives behind Russia’s touting of the vaccine, especially in light of what they say has been a Russian disinformation campaign casting doubt on Western-developed vaccines. Russian officials say politics is behind Western skepticism of Sputnik.
Lithuania's prime minister has labeled the vaccine “another hybrid weapon” for the Kremlin to wield to try to "divide and rule" Europe. Ingrida Šimonytė says altruism isn’t what motivates the aggressive marketing by Russia of Sputnik. “Sputnik comes packed with many layers of propaganda and even not-hidden ambition to divide the EU countries and their partners in the South and in the East,” she said earlier this year.
Facing shortfalls for Western vaccines amid the EU’s contentious rollout, other European states, though, started to buy Sputnik with Hungary first up followed by Serbia. Austria struck a deal and officials in Berlin and in several German regions expressed enthusiasm for the Russian vaccine. But with a boost in supplies of Western vaccines, appetite for Sputnik has dissipated and last week Germany’s Bild newspaper reported that the deal to sell the Sputnik V vaccine to Germany is dead.
Meanwhile, outside Europe, the Russian vaccine has been bought by more than 50 countries including Argentina, Mexico, and Turkey. India, where the pandemic has spiraled out of control, has signed a deal for nearly 400 million doses.
Growing doubts
But scientific doubts about Sputnik remerged last week when The Lancet published a paper by a team of scientists drawn from Europe, the U.S. and Russia questioning the 2020 study of the vaccine the medical journal published and flagging significant discrepancies in the data from the phase two and three trials conducted by the Gamaleya Research Institute, the vaccine’s developer.
“Restricted access to data hampers trust in research,” the scientists said in last week’s study. “Access to data underpinning study findings is imperative to check and confirm the findings claimed. It is even more serious if there are apparent errors and numerical inconsistencies in the statistics and results presented,” they said. The team included Enrico Bucci of Temple University in the U.S., Gowri Gopalakrishna from Amsterdam University and Raffaele Calogero from the University of Turin.
In reply, scientists from the Gamaleya Research Institute say data discrepancies occurred because of typing errors and they point to the approval of Sputnik by 51 countries showing they have been “fully transparent and comply with all regulatory requirements.”
FILE - Russian President Vladimir Putin chairs a video conference meeting with members of the Security Council at the Novo-Ogaryovo state residence outside Moscow, Russia, May 14, 2021. (Sputnik/Sergey Ilyin/Kremlin via Reuters)
Russian President Vladimir Putin on Thursday during a video conference praised Russia's vaccine, saying it as “reliable as a Kalashnikov assault rifle.”
Sputnik isn’t the only non-Western vaccine prompting reservations. Despite approval by WHO of China’s Sinopharm, some scientific researchers have expressed worries about the lack of data on that vaccine’s efficacy, too, and likewise with Sinovac, another Chinese vaccine.
FILE - Health officials guard Zimbabwe’s donation of 200,000 Sinopharm COVID-19 vaccine doses, which arrived at Mugabe International Airport in Harare on Feb. 15, 2021. The vaccines were a donation by Beijing. (Columbus Mavhunga/VOA)
According to researchers outside China, Sinovac’s efficacy rate is around 50%, and Sinopharm’s 79%, much lower than that of the rates for U.S.-developed vaccines like Moderna and Pfizer, both of which are above 90%.
