Cancer mortality continues steady decline, driven by progress against lung cancer

Medical report (stock image).

The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported. The news comes from Cancer Statistics, 2020, the latest edition of the American Cancer Society's annual report on cancer rates and trends.

The steady 26-year decline in overall cancer mortality is driven by long-term drops in death rates for the four major cancers -- lung, colorectal, breast, and prostate, although recent trends are mixed. The pace of mortality reductions for lung cancer -- the leading cause of cancer death -- accelerated in recent years (from 2% per year to 4% overall) spurring the record one-year drop in overall cancer mortality. In contrast, progress slowed for colorectal, breast, and prostate cancers. The article appears early online in CA: A Cancer Journal for Clinicians, and is accompanied by a consumer version, Cancer Facts & Figures 2020.

Overall cancer death rates dropped by an average of 1.5% per year during the most recent decade of data (2008-2017), continuing a trend that began in the early 1990s and resulting in the 29% drop in cancer mortality in that time. The drop translates to approximately 2.9 million fewer cancer deaths than would have occurred had mortality rates remained at their peak. Continuing declines in cancer mortality contrast with a stable trend for all other causes of death combined, reflecting a slowing decline for heart disease, stabilizing rates for cerebrovascular disease, and an increasing trend for accidents and Alzheimer disease.

Lung cancer death rates have dropped by 51% (since 1990) in men and by 26% (since 2002) in women, with the most rapid progress in recent years. For example, reductions in mortality accelerated from 3% per year during 2008-2013 to 5% per year during 2013-2017 in men and from 2% to almost 4% in women. However, lung cancer still accounts for almost one-quarter of all cancer deaths, more than breast, prostate, and colorectal cancers combined.

The most rapid declines in mortality occurred for melanoma of the skin, on the heels of breakthrough treatments approved in 2011 that pushed one-year survival for patients diagnosed with metastatic disease from 42% during 2008-2010 to 55% during 2013-2015. This progress is likewise reflected in the overall melanoma death rate, which dropped by 7% per year during 2013-2017 in people ages 20 to 64, compared to declines during 2006-2010 (prior to FDA approval of ipilimumab and vemurafenib) of 2%-3% per year in those ages 20 to 49 and 1% per year in those ages 50 to 64. Even more striking are the mortality declines of 5% to 6% in individuals 65 and older, among whom rates were previously increasing.

"The news this year is mixed," said Rebecca Siegel, MPH, lead author of the report. "The exciting gains in reducing mortality for melanoma and lung cancer are tempered by slowing progress for colorectal, breast, and prostate cancers, which are amenable to early detection. It's a reminder that increasing our investment in the equitable application of existing cancer control interventions, as well as basic and clinical research to further advance treatment, would undoubtedly accelerate progress against cancer."

Highlights from the report:

• The death rate for breast cancer dropped by 40% from 1989 to 2017.
• The death rate for prostate cancer dropped by 52% from 1993 to 2017.
• The death rate for colorectal cancer dropped by 53% from 1980 to 2017 among males and by 57% from 1969 to 2017 among females.
• Decades-long rapid increases in liver cancer mortality appear to be abating in both men and women.
• Cervical cancer, which is almost completely preventable, caused ten premature deaths per week in women ages 20-39 in 2017.

Other highlights:

• In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States.*
• Progress for hematopoietic and lymphoid malignancies (leukemias and lymphomas) has been especially rapid due to improvements in treatment protocols, including the development of targeted therapies. The 5-year relative survival rate for chronic myeloid leukemia increased from 22% in the mid-1970s to 70% for those diagnosed during 2009 through 2015, and most patients treated with tyrosine kinase inhibitors now experience nearly normal life expectancy.
• The overall cancer incidence rate in men declined rapidly from 2007 to 2014, but stabilized through 2016, reflecting slowing declines for colorectal cancer and stabilizing rates for prostate cancer.
• The overall cancer incidence rate in women has remained generally stable over the past few decades because lung cancer declines have been offset by a tapering decline for colorectal cancer and increasing or stable rates for other common cancers in women.
• The slight rise in breast cancer incidence rates (by approximately 0.3% per year) since 2004 has been attributed at least in part to continued declines in the fertility rate and increased obesity, factors that may also contribute to increasing incidence for uterine cancer (1.3% per year from 2007-2016).
• Lung cancer incidence continues to decline twice as fast in men as in women, reflecting historical differences in tobacco uptake and cessation.
• In contrast, colorectal cancer incidence patterns are generally similar in men and women, with the rapid declines noted during the 2000s in the wake of widespread colonoscopy uptake appearing to taper in more recent years.
• Incidence continues to increase for cancers of the kidney, pancreas, liver, and oral cavity and pharynx (among non-Hispanic whites) and melanoma of the skin. Liver cancer is increasing most rapidly, by 2% to 3% annually during 2007 through 2016, although the pace has slowed from previous years.
• The 5-year relative survival rate for all cancers combined diagnosed during 2009 through 2015 was 67% overall, 68% in whites, and 62% in blacks.
• Cancer survival has improved since the mid-1970s for all of the most common cancers except cervical and uterine cancers. Stagnant survival rates for these cancers largely reflect a lack of major treatment advances for patients with recurrent and metastatic disease.

"The accelerated drops in lung cancer mortality as well as in melanoma that we're seeing are likely due at least in part to advances in cancer treatment over the past decade, such as immunotherapy," said William G. Cance, M.D., chief medical and scientific officer for the American Cancer Society. "They are a profound reminder of how rapidly this area of research is expanding, and now leading to real hope for cancer patients."

Note:

*Estimates should not be compared year-to year. They are based on computer models of cancer trends and population and may vary considerably. Cancer trends should be based on age-adjusted cancer incidence and death rates (expressed as the number of cancer deaths per 100,000 people).

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Materials provided by American Cancer Society. Note: Content may be edited for style and length.

New findings could lead to improved vaccinations against sexually transmitted infections

New findings could lead to improved vaccinations against sexually transmitted infections

In a study published today in the Nature Communications, researchers from King's College London have shown how skin vaccination can generate protective CD8 T-cells that are recruited to the genital tissues and could be used as a vaccination strategy for sexually transmitted infections (STIs).

One of the challenges in developing vaccines for STIs, such as HIV or herpes simplex virus, is understanding how to attract specialised immune cells, called CD8 T-cells, to take up residence in the part of the body where the virus first enters. These cells need to be in place, armed and ready to provide an immediate protective immune defence, rather than waiting for immune cells in the blood to enter the tissues which takes time.

Before this study, it was thought that vaccines ideally needed to be delivered directly to the body surface (e.g. female genital tissue) where the infection might start, so that the immune system can generate these CD8 T-cells, travel back to the vaccination site and eliminate any future virus that is encountered. However, delivering vaccines directly to the female genital tissue is neither patient friendly nor efficient.

Now the team from King's have found that their vaccination strategy marshals a platoon of immune cells, called innate lymphoid cells (ILC1) and monocytes, in the genital tissues to work together and release chemicals (chemokines) to send out a call to the CD8 T-cells generated by the vaccine to troop into the genital tissue.

This research builds on the team's earlier work to develop skin vaccination techniques using a dissolvable 'microneedle' vaccine patch that once placed against the skin dissolves and releases the vaccine without requiring a hypodermic needle injection and generates immune responses.

Lead author, Professor Linda Klavinskis from King's College London said: "This study highlights how specialised groups of 'innate' immune cells in distant tissues can be harnessed to attract protective CD8 T-cells, arming the body's frontline tissues from infection.

"We now need to confirm these results with other types of vaccines from the one used in the study to see if a common pathway is triggered by skin vaccination. If proven, this could have a significant impact in improving the effectiveness of vaccines against sexually transmitted infections."

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Materials provided by King's College London. Note: Content may be edited for style and length.

By targeting flu-enabling protein, antibody may protect against wide-ranging strains

Influenza virus illustration

A nationwide team of researchers has found an antibody that protects mice against a wide range of potentially lethal influenza viruses, advancing efforts to design of a universal vaccine that could either treat or protect people against all strains of the virus.

The study, which Scripps Research conducted jointly with Washington University School of Medicine in St. Louis and Icahn School of Medicine at Mount Sinai in New York, points to a new approach to tackle severe cases of the flu, including pandemics. The research is published in the Oct. 25 issue of Science.

Scripps Research's Ian Wilson, DPhil, one of three senior co-authors, says the antibody at the center of the study binds to a protein called neuraminidase, which is essential for the flu virus to replicate in the body.

The protein, located on the surface of the virus, enables infected host cells to release the virus so it can spread to other cells. Tamiflu, the most widely used drug for severe flu infection, works by inactivating neuraminidase. However, many forms of neuraminidase exist, depending on the flu strain, and such drugs aren't always effective -- particularly as resistance to the drugs is developing.

"There are many strains of influenza virus that circulate so every year we have to design and produce a new vaccine to match the most common strains of that year," says co-senior author Ali Ellebedy, PhD, an assistant professor of pathology and immunology at Washington University. "Now imagine if we could have one vaccine that protected against all influenza strains, including human, swine and other highly lethal avian influenza viruses. This antibody could be the key to design of a truly universal vaccine."

Ellebedy discovered the antibody -- an immune molecule that recognizes and attaches to a foreign molecule -- in blood taken from a patient hospitalized with flu at Barnes-Jewish Hospital in St. Louis in the winter of 2017.

Ellebedy was working on a study analyzing the immune response to flu infection in humans in collaboration with the Washington University Emergency Care and Research Core, which was sending him blood samples from consenting flu patients. He quickly noticed that a particular blood sample was unusual: In addition to containing antibodies against hemagglutinin, the major protein on the surface of the virus, it contained other antibodies that were clearly targeting something else.

"At the time we were just starting, and I was setting up my lab so we didn't have the tools to look at what else the antibodies could be targeting," says Ellebedy, an assistant professor of medicine and of molecular microbiology.

He sent three of the antibodies to co-senior author Florian Krammer, PhD, a microbiology professor at the Icahn School of Medicine at Mount Sinai. An expert on neuraminidase, Krammer tested the antibodies against his extensive library of neuraminidase proteins. At least one of the three antibodies blocked neuraminidase activity in all known types of neuraminidase in flu viruses, representing a variety of human and nonhuman strains.

"The breadth of the antibodies really came as a surprise to us," says Krammer. "Typically, anti-neuraminidase antibodies can be broad within a subtype, like H1N1, but an antibody with potent activity across subtypes was unheard of. At first, we did not believe our results. Especially the ability of the antibodies to cross between influenza A and influenza B viruses is just mind-boggling. It is amazing what the human immune system is capable of if presented with the right antigens."

To find out whether the antibodies could be used to treat severe cases of flu, Krammer and colleagues tested them in mice that were given a lethal dose of influenza virus. All three antibodies were effective against many strains, and one antibody, called "1G01," protected against all 12 strains tested, which included all three groups of human flu virus as well as avian and other nonhuman strains.

"All the mice survived, even if they were given the antibody 72 hours after infection," Ellebedy says. "They definitely got sick and lost weight, but we still saved them. It was remarkable. It made us think that you might be able to use this antibody in an intensive care scenario when you have someone sick with flu and it's too late to use Tamiflu."

Tamiflu must be administered within 24 hours of symptoms. A drug that could be used later would help many people diagnosed after the Tamiflu window has closed. But before the researchers could even think of designing such a drug based on the antibody, they needed to understand how it was interfering with neuraminidase.

They turned to Scripps Research's Wilson, known globally for his work as a structural biologist. Wilson is Chair of the Institute's Department of Integrative Structural and Computational Biology, and has made numerous seminal findings that have shaped efforts to develop universal vaccines for flu and other complex viruses such as HIV.

Wilson and Xueyong Zhu, PhD, a staff scientist in Wilson's lab, mapped the structures of the antibodies while they were bound to neuraminidase. They found that the antibodies each had a loop that slid inside the active site of neuraminidase like a stick between gears. The loops prevented neuraminidase from releasing new virus particles from the surface of cells, thereby breaking the cycle of viral production in host cells.

"We were surprised at how these antibodies managed to insert a single loop into the conserved active site without contacting the surrounding hypervariable regions, thereby achieving much greater breadth against the neuraminidase of different influenza viruses than we have seen before," Wilson says.

The structures showed that the antibodies provide such broad protection because they target the conserved residues in the active site of the neuraminidase protein. That site stays much the same across distantly related flu strains because even minor changes could abolish the protein's ability to do its job, thereby preventing the virus from replicating.

The researchers are working on developing new and improved treatments and vaccines for influenza based on antibody 1G01.

"Neuraminidase has been ignored as a vaccine candidate for a long time," Ellebedy says. "These antibodies tell us that it should not have been overlooked. Now that we know what a broadly protective antibody to the neuraminidase looks like, we have an alternative approach to start designing novel vaccines that induce antibodies like this. And that could be really important if we are going to figure out how to design a truly universal vaccine."

The study was supported by the grants from the National Institute of Allergy and Infectious Diseases (R01 AI117287, R21 AI139813, U01 AI141990) and the National Institutes of Health (R56 AI117675).

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Materials provided by Scripps Research Institute. Note: Content may be edited for style and length.