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Reviving old therapy, Israeli doctors unleash lung radiation against COVID-19

Doctors at Sheba Medical Center outside Tel Aviv are set to give lung radiation to coronavirus patients after the Health Ministry approved a 30-person trial, Israel’s first for the experimental therapy.

The coronavirus pandemic has left doctors worldwide struggling with hard-to-treat lung inflammations the likes of which many haven’t seen before.

Sheba doctors believe that targeted radiation on the lungs may slow inflammation there, and prevent or reduce the effects of the pneumonia that causes many coronavirus deaths. Within days, they will start radiation therapy on the first patients.

“Low-dose radiation is extremely effective in reducing the types of inflammatory cells that invade the lungs of coronavirus patients, prevent them from oxygenating the blood, and cause failure of the systems and possibly death, and I’m hopeful that this will save lives,” Zvi Symon, the director of Sheba’s Radiation Oncology Department and the doctor behind the trial, told The Times of Israel.

“These doses won’t kill the virus itself or change the viral replication rate in the body in any way, but we anticipate they will reduce the severe inflammation in the lung that it induces and it’s this inflammation that causes patients to die from inflammatory failure,” he stressed.

“We have already seen that in animal models low-dose radiation has a broad range of anti-inflammatory effects,” Symon added.

He acknowledged that introducing the therapy for COVID-19 was controversial given fears that despite the low dose it could cause cancer, but said he believes the benefits outweigh the risks.

Symon said that the noninvasive procedure could have major benefits for the most frail coronavirus patients, who don’t fare well with intubation and other invasive procedures.

“I believe this intervention is much more mild than an intensive-care intervention, and could really help elderly people who are seen as too frail for intensive care,” he said. “If we assess early on in the disease that they are deteriorating and give radiation therapy, we have a good chance of saving some lives.”

Several hospitals internationally are experimenting with low-dose radiation therapy, known as LDRT, which currently has a range of uses including preparing cancer patients for the transplant of their own bone marrow, and preventing unwanted bone growth in joints after surgeons operate on fractures.

Doctors from Emory University in Atlanta have already published, on a non-peer reviewed repository, a report on a small 10-patient study of lung radiation for coronavirus patients.

They found that the LDRT patients were discharged after 12 days, compared to 20 days for a control group that didn’t get the therapy, and showed significant improvement after three days rather than 12 for the control group.

The Emory team concluded that its “strong efficacy signals” suggest that potential benefits of LDRT should be further explored, and a team of Spanish researchers has shown similar enthusiasm, writing that the therapy “could modify the immune landscape in the affected lung.”

David Macias, of Hospital Universitario San Roque in Gran Canaria, made the claim writing with two colleagues in the journal Clinical and Translational Radiation Oncology. They argued that as a cost-effective, nontoxic treatment that is available in most hospitals, it could prove valuable.

Symon said that he, and the other radiation enthusiasts, arrived at the idea by listening to doctors who were working decades ago.

“At the beginning of this crisis there were several radiation oncologists who are still alive from 50 to 70 years ago, before the era of randomized phase-three clinical trials and widespread antibiotics, when many people with pneumonia died from respiratory failure,” he said. “There was an effort to treat those people with radiation, and there’s literature on 700 people who received radiation when shortness of breath started to look bad.

“There was a high response rate, but [the treatment] fell out of favor when the death rate from pneumonia was reduced due to antibiotics and anti-microbial therapies,” Symon added.

He acknowledged concerns that it could cause patients to develop cancer in the future, but said the risk was relatively small. He also said that as it will be given to consenting people, normally of very advanced age and facing danger to their lives from the coronavirus, it will be a calculated, reasonable risk.

“Regarding the worry about secondary cancer, you are most likely talking about someone who could die within two weeks or be given another 10 years,” he said.

But the question of risk is causing controversy internationally.

Ralph Weichselbaum, chair of the Department of Radiation and Cellular Oncology at the University of Chicago’s medical school, argued that radiation therapy shouldn’t be used or tested in clinical trials, in an article co-authored with academics from Duke; Stanford; and the University of Nevada, Las Vegas.

They wrote in the journal Radiotherapy and Oncology that while the seriousness of the pandemic “has motivated colleagues to propose clinical trials of low dose radiotherapy for COVID-19 pneumonia with the best of intentions, we believe that based on the available data, the potential risks of such trials outweigh the potential benefits.”

They argued that radiation therapy could end up causing cancer for patients in the future, and wrote that the evidence is currently “not sufficient for exposing COVID-19 patients to the risks of radiation exposure in a clinical trial.”

But a group of seven medical experts, from Italy, New Zealand and the US, disagreed, writing in a response: “With thorough informed consent, it is a reasonable late risk for older patients balanced against a potential reduction in COVID-19 related morbidity or mortality within weeks.”

Source: Nathan Jeffay – TOI