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Looking at cancer often means taking the long view. Research scientists, oncologists, and patients are all waiting to see what the coronavirus pandemic’s long-term effects might be on cancer detection and treatment, all while trying to navigate daily life made more precarious by the Omicron variant.

Eighteen months ago, as the pandemic’s first wave was tearing through the U.S., Ned Sharpless, director of the National Cancer Institute, sounded the alarm that, based on 10-year modeling, delaying cancer screening and care could turn one public health crisis into another. In a recent conversation, he told STAT knowing whether that prediction will come true may take a long time, but other lessons are being learned despite or because of Covid right now.

“There’s no way a disruption of this scale doesn’t translate into some excess death from cancer in the future,” he said late last week. “Our challenge now is to make that as little as possible.”

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In a conversation 50 years almost to the day from when the National Cancer Act of 1971 launched what became known as the “war on cancer,” Sharpless expressed concern about medical staffing shortages, optimism about new cancer therapies, and empathy for cancer patients who just want to know how to protect themselves from Covid and their doctors who don’t have a guaranteed answer to give them. This interview has been edited and condensed for clarity.

Earlier this year, you were concerned about Covid lockdowns keeping people from screenings or other cancer care. What do you think now?

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This is still playing out. We probably missed on the order of 10 million screening events during 2020 and early 2021, for example. We think that some of those missed screenings are going to be severely delayed if they occur at all. And remember, most cancers are not diagnosed through screening but when a patient goes to a doctor with a symptom, and that kind of cancer diagnosis was down markedly, too. So you have a delayed diagnosis of both screen-detected cancers and screened undetected cancers. That generally means later-stage diagnosis and worse prognosis, and we will see how that plays out.

Any updates?

We redid some of the modeling with the mammography data around breast cancer. And the impact on excess deaths may not be quite as bad as we predicted, but it’s still on the order of 5,000 to 10,000 more deaths over the next 10 years — still quite a significant impact. We remain very worried about this. Mammography is closer to where it was pre-pandemic but not fully recovered yet. And cancer diagnoses are closer to where they were. The same is largely true for clinical trials enrollment, where we are seeing mostly recovery.

What about Omicron?

With these new waves, there’s a big disruption in hospitals and clinics that causes problems, perhaps not on the national scale they did back in April and May of 2020, but now we’re seeing isolated pockets of care disruption, where scheduled surgeries will be canceled and clinical trials enrollment will be canceled. We as a field have to prioritize cancer care to the extent possible. And we really have to get people who miss screenings and missed other health activities to come back in for that care.

When will we know more?

It’s too soon to say if any of this is having a real impact on national statistics, but it’s something we’re going to watch carefully. The most important data are going to be the cancer incidence and mortality data we collect as part of the annual report to the nation every year. And we just saw data for 2018, right? So it’s going to take us a few more years to really see what the pandemic did in terms of incidence and mortality.

We are worried about excess mortality, particularly in younger, otherwise healthy populations. Our fear is that as cancer mortality in the U.S. has been declining annually every year since the 1990s, most recently on the order of two and a half percent or two and a quarter percent or in the individual year, we worry we will see that rate of decline slow, maybe even maybe even stop declining and we’ll see mortality go up for the first time since the 1990s — which would be bad — as a result of pandemic-induced disruptions. I don’t think that’s going to happen, but I think it could happen.

How should cancer patients think about protecting themselves from Covid infection?

We can clearly say that some patients with cancer are at increased risk for infection and an increased risk for bad outcomes if infected, particularly those likely to have significant immunocompromise either because of their cancer or because of the treatment for their cancer. High-dose chemotherapy or drugs like rituximab kill off B cells, the cells that make antibodies. And so by depleting these cells, you make someone more susceptible to coronavirus infection, for example.

We have very good evidence that those patients benefit from vaccination and benefit from boosters, so we strongly encourage those individuals to get three shots now. We also have evidence that these individuals would benefit from taking non-pharmacological interventions that decrease the risk of being infected: staying out of crowds, masking, social distancing, the usual stuff. People who are immunocompromised have to be even more careful.

What would you tell cancer patients who want to know how much protection they have against Covid?

We don’t want to just tell people because you have cancer, you’re at high risk. That’s not useful. A lot of people have cancer. A lot of people are cancer survivors. And so we would like to be able to measure someone’s risk.

Neutralizing antibodies seem to correlate with the risk of future infection, especially after vaccination, and likely also after a convalescent infection as well. So we think antibody levels are one thing that are useful to measure. They are not FDA-authorized for that purpose. I want to be clear: Presently, many, many people are going to their oncologist or their doctor, and they’re having their antibody levels measured using these many available FDA-authorized assays. Those assays are really only authorized to diagnose prior infection.

I was a practicing physician who took care of cancer patients for many years. I know why people do things off label, and I’m not one to criticize that. But I think right now we don’t know if that’s a good idea or not, whether that works in an individual patient and whether you can predict someone’s future risk is currently unknown.

What about T cells?

We don’t think T cells may be as important at preventing infection, but we think they can be very important in preventing severe infection. The T cell component could be particularly important, and that is an open scientific question that we and others are actively studying. The T cell response is much harder to measure.

I get a lot of email about this, so it is not an abstract problem at all for me. My advice in general is, do the things you’re supposed to do: get boosted and practice good social distancing and mask-wearing to avoid the risk of exposure. Many patients are asking me, should they get this T cell assay or should they get their antibodies measured at Quest or LabCorp, which have these commercially available assays? And again, I defer that to their personal physician. But I will say that if a patient has been vaccinated and has a nice antibody response and neutralizing antibody response in particular, that does make you feel a little more relaxed.

What’s happening with clinical trials?

Clearly there was a very significant disruption to clinical trials accrual for the first five or six months of the pandemic. It was just sort of a body blow. We have data that some types of trials haven’t recovered to the same extent: single-institution trials, investigator-initiated trials, non-therapeutic trials — some of these other kinds of trials presumably have been harder to reopen because of staffing issues. Nurses are in short supply now.

What about hospitals?

The staffing shortages are a big problem. Nurses are in short supply, but also respiratory therapists and social workers and certain classes of physicians. Physician burnout was something we were worried about before the pandemic, and certainly the pandemic has only made that worse, so I think that is limiting national capacity to provide care for cancer patients as well.

Any good news?

Despite the sort of hellacious impact of the pandemic, we’ve still been able to really make advances for cancer patients. And I’m hoping that the good news of all these improvements of therapy and diagnosis and prevention will counterbalance the transient negative effects of the pandemic, but we won’t know that for a few more years.

What are some examples?

A really interesting evolving story is how do you use immuno-oncology drugs? We had surgery, chemotherapy, radiation. Now we’ve added immuno-oncology, both checkpoint inhibitors and CAR-T. Although some of those agents were approved as early as 2011, we’re still sort of figuring out how to use them in combination.

And in advanced ovarian cancer, there has been a successful recent trial for PARP inhibitors. We’re used to seeing these very small differences in survival from cancer agents. And here we’re seeing — you could drive a truck through the differences between the old standard of care and the new way of doing things. It’s not for every patient, it’s for patients with molecularly defined subtypes of cancer.

And a notable achievement in novel medicinal chemistry was the first approval this year of an anti-RAS drug. RAS is an oncogene mutated in like 30% of cancer. It’s been the sort of white whale of drug discovery for 40 years in oncology. And we had not been able to effectively drug that target despite lots of effort. Finally, this year, we had the anti-RAS therapy developed. It’s not for all RAS mutations, and it’s still an area where we needed to work. But it is an important milestone for novel drug discovery and novel medicinal chemistry translating into new therapies for patients.

When you look back over the past 50 years and the “war on cancer,” is there anything that compares with Covid and what it means in both cancer research and patient care?

There’s been nothing like Covid in public health history for over 100 years in the United States. It’s probably most reminiscent to me of the HIV epidemic, which had a tremendous impact on medicine and clinical care and a very dramatic impact on the field of oncology. A lot of the early HIV research was done in the cancer field. Bob Gallo, who co-discovered the virus that causes AIDS, was an NCI scientist and Sam Broder, one of the first scientists to find effective therapeutics for HIV, was an NCI scientist.

Not to be too Pollyanna-ish about it, but the HIV epidemic provided tremendous research opportunities. Yes, it was devastating and HIV is still a global tragedy, but we learned a lot of basic science. We learned about T cells and helper T cells and the role of the humoral and innate immune systems. And so things like immuno-oncology and CAR-T cells, all these cancer things we have today, were in part developed because of scientific understanding related to the AIDS epidemic. These disruptive things that really challenge our notions of medicine and care are scientific opportunities that I’m sure we’re going to learn a lot from the coronavirus pandemic as well.

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