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Corticosteroids, which are commonly prescribed to alleviate cancer-related symptoms in patients with non–small cell lung cancer (NSCLC) treated with immunotherapy, may be the reason certain immunotherapies fail in treating the disease, according to new research published by Polyakov et al in Cancer Research Communications.

The study results showed that high doses of steroids, when given before and/or during immune checkpoint inhibitor therapy, caused patients’ tumors to shrink less than those of patients not on steroids. Those patients also did not live as long. 

“Steroids were the biggest predictor of why certain immunotherapies may not be effective, even when considering multiple other factors such as stage and progression of the disease,” said Keck Medicine of USC oncologist and immunologist Fumito Ito, MD, PhD, lead author of the research. 

Additionally, researchers believe they have found the mechanism behind why steroids and some immunotherapies may not mix.  

“Our findings reveal that steroids stop the body’s natural cancer-fighting cells, T cells, from maturing. This makes them unable to attack the cancer as vigorously as they usually would, leading to worse outcomes for patients,” explained Dr. Ito, who is also a member and co-leader of the translational and clinical sciences research program at USC Norris Comprehensive Cancer Center. “While other research has indicated steroids may negatively impact immunotherapy’s efficacy, we are one of the first [groups] to pinpoint a probable cause and effect.”  

Dr. Ito and his colleagues also discovered that steroids blocked circulating biomarkers in the body. “Without the presence of circulating biomarkers to inform our decisions, oncologists cannot treat the cancer as effectively and patients may miss out on the best treatment for their cancer,” he noted.  

The study examined the effect of steroids on immune checkpoint inhibitors, which are often used to treat NSCLC. Steroids are often prescribed to alleviate symptoms of the cancer or treatments given for a variety of reasons, such as fatigue and vomiting, or more serious side effects like brain swelling and lung inflammation. Steroids suppress the immune system, which reduces the inflammation that can cause these conditions. 

Study Methodology

The researchers retrospectively studied the medical records of 277 patients with stage II to IV NSCLC who were treated with immune checkpoint inhibitors alone or in combination with other therapies. They compared outcomes (tumor shrinkage and survival rate) between patients who were prescribed steroids and those who were not at three centers. They analyzed up to 8 years of data to determine that steroids were the sole factor impeding the effectiveness of the immunotherapy.  

They also determined that the T cells of significant numbers of patients on steroids were not fully matured and launched a preclinical study using mice to observe the effects of steroids on immune checkpoint inhibitor therapy in real time. This mouse model study led to the discovery that steroids given before or during immunotherapy inhibit T cells from fully maturing.  

The Future of Steroid Use in NSCLC

While this new research indicates steroids can interfere with immune checkpoint inhibitor efficacy, the authors acknowledged that for some patients with NSCLC, steroids may be necessary to manage their cancer-related symptoms.  

“We know that steroids will continue to play an important role in lung cancer care, but it is important to understand their potential limitations,” said Dr. Ito. “Each patient should talk to their oncologist to make sure they have the best possible care plan tailored to their specific needs.”  

The investigators hope this research will lead to more studies examining the effect of steroids on immunotherapy, so oncologists can make fully informed decisions that will best benefit their patients.  

Disclosures: The study was supported with grants from the National Cancer Institute as well as the Department of Defense Lung Cancer Research Program and the Uehara Memorial Foundation. For full disclosures of the study authors, visit aacrjournals.org/cancerrescommun.

Automated surgery could be trialled on humans within a decade, say researchers, after an AI-trained robot armed with tools to cut, clip and grab soft tissue successfully removed pig gall bladders without human help.

The robot surgeons were schooled on video footage of human medics conducting operations using organs taken from dead pigs. In an apparent research breakthrough, eight operations were conducted on pig organs with a 100% success rate by a team led by experts at Johns Hopkins University in Baltimore in the US.

The Royal College of Surgeons in the UK called it “an exciting development that shows great promise”, while John McGrath, a leading expert on robotic surgery in the UK, called the results “impressive” and “novel” and said it “takes us further into the world of autonomy”.

It opens up the possibility of replicating, en masse, the skills of the best surgeons in the world.

The technology allowing robots to handle complex soft tissues such as gallbladders, which release bile to aid digestion, is rooted in the same type of computerised neural networks that underpin widely used artificial intelligence tools such as Chat GPT or Google Gemini.

The surgical robots were slightly slower than human doctors but they were less jerky and plotted shorter trajectories between tasks. The robots were also able to repeatedly correct mistakes as they went along, asked for different tools and adapted to anatomical variation, according to a peer-reviewed paper published in the journal Science Robotics.

The authors from Johns Hopkins, Stanford and Columbia universities called it “a milestone toward clinical deployment of autonomous surgical systems”.

Almost all the 70,000 robotic procedures carried out annually in the NHS in England were fully controlled under human instruction, with only bone-cutting for hip and knee operations semi-autonomous, McGrath said. Last month the health secretary, Wes Streeting, said increasing robotic surgery was at the heart of a 10-year plan to reform the NHS and cut waiting lists. Within a decade, the NHS has said, nine in 10 of all keyhole surgeries will be carried out with robot assistance, up from one in five today.

In the Johns Hopkins trial, the robots took just over five minutes to carry out the operation, which required 17 steps including cutting the gallbladder away from its connection to the liver, applying six clips in a specific order and removing the organ. The robots on average corrected course without any human help six times in each operation.

“We were able to perform a surgical procedure with a really high level of autonomy,” said Axel Krieger, assistant professor of mechanical engineering at Johns Hopkins. “In prior work, we were able to do some surgical tasks like suturing. What we’ve done here is really a full procedure. We have done this on eight gallbladders, where the robot was able to perform precisely the clipping and cutting step of gallbladder removal without any human intervention.

“So I think it’s a really big landmark study that such a difficult soft tissue surgery is possible to do autonomously.”

McGrath, who chairs NHS England’s robotics steering committee, said autonomous surgery, while still years away, could one day lead to a human surgeon overseeing several autonomous robotic operations at the same time, carrying out simple procedures such as hernia operations or gall bladder removals more rapidly, with greater precision than humans and with less damage to surrounding bodily structures.

But he cautioned that autonomous surgery remained a long way from being clinically deployable, because tests on dead pig organs do not test the robots’ capacity to react to a patient moving and breathing, blood running in the field of operation, an inadvertent injury, smoke from cauterisation or fluid on the camera lens.

Nuha Yassin, who leads on robotic surgery at the Royal College of Surgeons of England, said: “The next step must involve a careful exploration of the nuances within this rapidly evolving field to assess how these findings can be safely and effectively translated into a human pilot. Only then can this approach move toward, becoming a sustainable model for the future.”

She said training, education and patient safety must remain at the forefront.

High and rising levels of tetracycline resistance globally will likely limit the ability of doxycycline post-exposure prophylaxis (doxyPEP) to prevent gonorrhea infections, according to a study published today in JAC-Antimicrobial Resistance.

In a systematic review and meta-analysis, researchers from the University of Melbourne examined data from 67 studies of tetracycline resistance in Neisseria gonorrhoeae, the bacterium that causes gonorrhea, covering 51 countries and 80,645 isolates. Overall, the median tetracycline resistance was 54.2% (range, 4% to 100%), with the highest resistance observed in East Asia and the Pacific (82.1%; range, 18% to 100%) and sub-Saharan Africa (81.6%; range, 44% to 100%). The lowest tetracycline resistance levels were reported in North America (26.5%; range, 4% to 78%). For other regions, median resistance ranged from 38.9% to 61.6%.

Among the 80,645 isolates studied, 91.4% were collected from 2010 through 2013, and the rest from 1996 through 2009. The largest increases in tetracycline resistance between the two reporting periods were seen in South Asia (a 3.8-fold increase) and North America (a 4.1-fold increase). 

Only 11 studies (16%) provided tetracycline resistance data specifically from men who have sex with men (MSM), who are considered a high-risk group for gonorrhea, and only 6 (9%) included women. 

Limited role in gonorrhea control

Although randomized clinical trials have found that doxyPEP, which involves taking a dose of doxycycline within 72 hours of unprotected sex, is highly effective at reducing the incidence of chlamydia and syphilis in high-risk groups (MSM and transgender women), effectiveness against gonorrhea has been more modest. The study authors say these data suggest it may be unreliable for preventing incident gonorrhea infections.

“While tetracyclines are not used to treat N. gonorrhoeae globally, our finding suggests doxyPEP would have a very limited role in N. gonorrhoeae control when used to reduce incidence of other STIs such as chlamydia and syphilis, and as such, doxyPEP policies should make clear statements to prescribers and users regarding this,” they wrote. 

The authors add that countries implementing doxyPEP should ensure surveillance systems are in place to monitor resistance in N gonorrhoeae.