Chemotherapy used to shrink a tumor before surgery, called neoadjuvant chemotherapy, is becoming more common in many cancers, including stage II and III rectal cancer. However, the chemotherapy regimens FOLFOX and CapeOx used in this setting come with significant side effects, to the degree that many patients are unable to complete the recommended schedule. A University of Colorado Cancer Center study presented at the 2020 Gastrointestinal Cancers Symposium shows they may not have to: A small study of 48 patients with locally advanced rectal cancer receiving neoadjuvant chemotherapy, found that patients receiving lower-than-recommended doses in fact saw their tumors shrink more than patients receiving the full dose.

"I think we need bigger studies to explore less intensive therapy - maybe lower doses, maybe a shorter course of treatment - to see what is the optimal dosing prior to surgery," says Ashley E. Glode, PharmD, assistant professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences, and the study's first author.

In some cancers, a tumor may be entwined with nearby organs and blood vessels to the point that surgery is not initially an option. Most patients with locally advanced rectal cancer are surgical candidates, but chemotherapy used to shrink a tumor prior to surgery has been associated with more successful surgeries and a lower rate of cancer recurrence. As a high-volume center for the treatment of these cancers, University of Colorado Cancer Center oncologists including Christopher Lieu, MD, noticed that patients who were unable to complete the recommended course of neoadjuvant chemotherapy seemed to have similar or even better outcomes than patients receiving the full dose, prompting the current study.

"We do all sorts of supportive care options to help keep patients on these therapies at the recommended, high doses. But based on our observations and on this early study, we're starting to talk about having less hesitancy to drop the drug or at least decrease the dosing," says Lieu, who is CU Cancer Center's interim associate director for clinical research.

Of the 48 patients included in the study, only 12.5 percent were able to tolerate the full dose of chemotherapy. Due to side effects, zero of six patients taking the regimen CapeOx completed the recommended dose.

Proton therapy leads to significantly lower risk of side effects severe enough to lead to unplanned hospitalizations for cancer patients when compared with traditional radiation, while cure rates between the two groups are almost identical. The findings come from an expanded analysis of the largest review of its kind, performed by researchers in the Perelman School of Medicine at the University of Pennsylvania, to evaluate whether or not patients undergoing radiation therapy at the same time as chemotherapy experienced serious adverse events within 90 days. Researchers found proton therapy reduces the relative risk of these side effects by two-thirds.

"This is exciting because it shows that proton therapy offers a way for us to reduce the serious side effects of chemo-radiation and improve patient health and wellbeing without sacrificing the effectiveness of the therapy," said the study's lead author Brian Baumann, MD, an adjunct assistant professor of Radiation Oncology at Penn and an assistant professor of Radiation Oncology at Washington University School of Medicine in St. Louis.

Proton therapy has a few key differences from traditional photon radiation. Photon radiation typically uses multiple x-ray beams to deliver radiation to the tumor target but unavoidably deposits radiation in the normal tissues beyond the target, potentially damaging those tissues as the beam exits the body. Proton therapy is an FDA-approved alternative radiation treatment that directs positively charged protons at the tumor. They deposit the bulk of the radiation dose to the target with almost no residual radiation delivered beyond the target, reducing damage to surrounding healthy tissue and potentially reducing side effects.

For this study, researchers evaluated side effects including pain or difficulty swallowing, difficulty breathing, nausea, or diarrhea, among others. Researchers focused on grade-three effects or higher, defined as side effects severe enough for patients to be hospitalized. They evaluated data on 1,483 cancer patients receiving radiation and chemotherapy at the same time. Of these, 391 patients received proton therapy, while 1,092 underwent photon treatment. All patients had non-metastatic cancer and were undergoing treatment intended to be curative. Patients with brain cancer, head and neck cancer, lung cancer, gastrointestinal cancer, and gynecologic cancer treated with concurrent chemo-radiation were included.
​
The primary outcome was whether or not patients experienced adverse side effects that were grade-three or higher within 90 days of treatment. In the proton group, only 11.5 percent of patients (45) did, compared to 27.6 percent of patients (301) in the photon group. A weighted analysis of both patient groups, which controlled for other factors that may have led to differences between the patient groups, found that the relative risk of a severe toxicity was two-thirds lower for proton patients compared to photon patients.

What if a metal that's already used to repair broken bones, straighten teeth and keep arteries from clogging could also be used to stop your cancer from spreading? New findings published in Nature Biomedical Engineering from scientists at Fred Hutchinson Cancer Research Center show for the first time that a piece of small, thin metal mesh loaded with cancer-fighting immune cells shrinks tumors in preclinical models of ovarian cancer.

"Cell therapies to fight cancer have had great success in blood cancers but haven't worked well with solid tumors," said lead author Dr. Matthias Stephan, a faculty member in the Fred Hutch Clinical Research Division. "Our findings take a significant step toward making cell therapies effective against solid tumors by showing that a thin metal mesh loaded with T cells engineered to fight ovarian cancer cleared tumors in 70% of the treated mice."

Solid tumors, including cancers of the breast, ovary and pancreas, have a variety of tactics to hide from and fight back against cancer-killing immune cells like CAR (chimeric antigen receptor) T cells. Simply injecting anti-cancer cells has not worked; they don't reach the tumor or if they do reach the cancerous cells, they tire out in trying to kill them and are then shed from the body.

Stephan designs materials that are safe in the body and can carry cancer-fighting cells to tumors. "In addition to minimizing side effects in patients, our ultimate goal is to make T-cell therapies faster and cheaper to make, and easier to deliver to patients." he said.

In a step toward that goal, Stephan's latest study loaded CAR T cells targeting ovarian cancer onto a porous, mesh-like metal film and then placed the film on tumors.

"This is not just a passive delivery device," Stephan said. "It's a release platform that triggers an expansion of CAR T cells that can overcome defenses that tumors make against the immune cells."

The researchers used thin, nearly translucent metal films made by Monarch Biosciences (MonarchBio), which helped fund the project. The films are 10 micrometers thick, which is 1 millionth of a meter, or about seven times thinner than the average width of a human hair. Made of nickel titanium, the film can safely be implanted within the body and is used in other medical devices.
​
Viewed under a powerful microscope, the film has minuscule spaces that can be configured into different patterns. The spaces can be filled with drugs or other liquids and then implanted in the body, where the liquids ooze out and find their targets.

During spaceflight, astronauts experience similar physical stress as cancer patients undergoing treatments such as chemotherapy, immunotherapy, and targeted therapy. In a commentary published November 14 in the journal Cell, researchers suggest that by mimicking a NASA astronaut's schedule of exercising before, during, and after a mission, cancer patients could reduce the long-term impact their treatments often have on their bodies.
​
"It was surprising when we looked at similarities between astronauts during spaceflight and cancer patients during treatment. Both have a decrease in muscle mass, and they have bone demineralization and changes in heart function," says senior author Jessica Scott, an exercise physiology researcher at the Memorial Sloan Kettering Cancer Center's Exercise Oncology Service. The similarities also extend to brain function: "Astronauts may get something called space fog, where they have trouble focusing or get a little forgetful. That's very similar to what some cancer patients experience, which is called chemo brain."

Despite similar symptoms, astronauts and cancer patients often receive very different advice on how to take care of their bodies. Astronauts are required to exercise prior to their mission while physicians monitor their cardiorespiratory fitness and other systems to develop a baseline level. The astronauts are then required to exercise during their mission utilizing special equipment made for working out in space. When they return to Earth, physicians continue to monitor the astronauts until their cardiorespiratory fitness and other systems return to their pre-mission baseline levels.

"That's completely backwards to how it is on Earth, where cancer patients may still be advised to rest in preparation for and during treatment and may have to ask permission to exercise from their physicians," says Scott.

But Scott and her team of researchers suggest that basic exercise such as walking on a treadmill could benefit cancer patients in the long term. Like astronauts preparing for spaceflight, cancer patients that are monitored using similar tests such as cardiorespiratory fitness could develop their own baseline levels prior to receiving treatment. Exercising during and after treatment could then potentially reduce the negative side effects of treatments such as heart problems.

With the advent of new therapies, cancer patients are surviving longer than ever before -- but the incidence of side-effect chemotherapy-induced cardiomyopathy (CHIC), or weakness of the heart muscle, is increasing. Research published in JAMA has shown that treating CHIC with commercially available cardiac resynchronization therapy (CRT) delivered through a surgically implanted defibrillator or pacemaker can significantly improve patient outcomes.
​
"Chemotherapies are systemic toxins," said lead author Jagmeet P. Singh, MD, DPhil, associate chief of cardiology at Massachusetts General Hospital (MGH). "Patients take them to kill the cancer cells but they can also affect different organs and tissues in the body."

Anthracyclines and other drugs used to treat breast cancer and lymphomas are particularly likely to have a negative effect on the heart muscle and result in reduced heart function in approximately 9 percent of patients treated with them. Sometimes, along with the negative effect on the heart muscle, the chemotherapy may also impact the electrical system in the heart, resulting in an abnormal contraction pattern. When contractions in the heart's right and left sides aren't synchronized, said Singh, "the heart begins to progressively fail because it becomes less and less efficient."

While using cardiac resynchronization therapy is "pretty standard therapy for conventional patients with reduced heart function and abnormal electrical activation within the heart," according to Singh, to his knowledge their use in former cancer patients has never before been evaluated in a systematic way. "It's an orphaned cohort of patients. Nobody knows who they 'belong' to -- oncologists, cardiologists, internists?" Added to that, he said, CHIC is associated with decreased quality of life and poor clinical outcomes and is rarely treated aggressively. "There may be some unconscious physician bias because the prognosis isn't good to start with," he added.

Hypertension with ibrutinib more common than previously reported; this study is first to show association between cancer drug-related hypertension and other heart problems.

Over half of the people prescribed the targeted blood cancer-fighting drug ibrutinib developed new or worsened high blood pressure within six months of starting the medication, according to a new study published online today in Blood. The analysis is also the first to tie ibrutinib-related hypertension to a heightened risk of heart problems, particularly atrial fibrillation. Moreover, the association of ibrutinib with cardiovascular complications remained regardless of the prescribed dose.

“This study provides a more clear picture of the extent of hypertension development among patients taking ibrutinib, while allowing us to tease out what ibrutinib-related hypertension means in the long run for other cardiovascular events and survival,” said Daniel Addison, MD, of the Ohio State University Comprehensive Cancer Center Cancer Control Research Program, and the study’s senior author. “Overall, both the magnitude and level of hypertension that developed was higher than previously thought and appears to portend a higher risk of other cardiac events.”

In fact, after controlling for traditional risk factors, people treated with ibrutinib who developed new or worsened hypertension were more than twice as likely to develop other heart problems, including arrhythmias, compared with people who did not develop hypertension while taking the cancer drug. The good news: Addison and his team found that the initiation of blood pressure-lowering medications among ibrutinib patients with new or worsened high blood pressure was associated with a 60 percent reduction in major adverse cardiovascular events.

New estimates suggest strategies to reduce the risk of cardiovascular disease are needed for the growing population of cancer survivors. In one of the largest studies of its kind, the research team, led by the London School of Hygiene & Tropical Medicine, analysed the medical records of more than 630,000 people in the UK, including over 100,000 survivors of a range of cancers.

They found raised risks of blood clots forming in the veins among survivors of most cancers, ranging from approximately a two- to ten-fold increase in risk for different cancer sites. Risks decreased over time but were still elevated for more than five years after the cancer diagnosis. Survivors of half of the 20 cancers studied also faced increased risks of heart muscle damage, known as cardiomyopathy, and heart failure.

For example, survivors of blood, oesophagus, lung, kidney and ovarian cancers were more than one and a half times more likely to experience cardiomyopathy or heart failure than people with no prior cancer.
An increased risk of coronary artery disease and stroke was found in some cancer survivors, including those with prior blood cancers.

The researchers stress that for many people the overall risks will still be low, particularly for younger cancer survivors, but say the findings highlight the need for new strategies to prevent and manage heart and circulation problems in cancer survivors, including a need to raise awareness among GPs of the raised risks.

While the researchers could not definitively identify the causes of the increased risks, the team's analysis suggests that exposure to cancer treatments such as chemotherapy is likely to play a key role.

Lead author Helen Strongman from the London School of Hygiene & Tropical Medicine said: "Over recent decades cancer treatment and management have improved substantially, resulting in a large and growing population of long-term cancer survivors. Around half of those diagnosed with cancer in developed countries are now expected to survive for more than 10 years. However, there are concerns that there may be increased long-term risks of cardiovascular disease following cancer diagnosis, driven by treatment side-effect effects and the potential impact of the cancer itself."

While previous studies have demonstrated the short- to medium-term increased risk of cardiovascular disease from some specific cancer treatments, there have been limited data on the overall and long-term differences in cardiovascular risk between cancer survivors and those who have never had cancer.
​
To address this, the team brought together anonymised data from primary care, hospitals, cancer registries, and death certificates, to quantify the absolute and relative risks of a comprehensive range of cardiovascular diseases in survivors of the 20 most common adult cancers compared with cancer-free general population controls. The research also accounted for other risk factors for cardiovascular disease, such as older age, smoking and body mass index.

Many of the deadliest or most common cancers get the least amount of nonprofit research funding, according to a new Northwestern Medicine study that examined the distribution of nonprofit research funding in 2015 across cancer types.

Colon, endometrial, liver and bile duct, cervical, ovarian, pancreatic and lung cancers were all poorly funded compared to how common they are and how many deaths they cause, the study found. In contrast, breast cancer, leukemia, lymphoma and pediatric cancers were all well-funded, respective to their impact on society.

The study is the first to compare nonprofit funding distribution in the United States across cancer types. It will be published  in the Journal of the National Comprehensive Cancer Network.

"The goal of this study is not to divert funds away from cancers that are well-supported, but rather expand funding for other cancers that aren't getting enough support currently," said corresponding author Dr. Suneel Kamath, who was the chief fellow in the department of hematology and oncology at Northwestern University Feinberg School of Medicine when he conducted the study. "These are all deadly and life-altering diseases that deserve our attention and support."

Cancer-related nonprofit organizations play an important role in funding medical research, supporting the education of patients and their families and influencing health policy. Underfunding of these common cancers could negatively impact research, drug development and the number of FDA drug approvals for poorly funded cancers.
​
"Well-funded patient advocacy organizations should be applauded for their successes," said co-author Dr. Sheetal Kircher, assistant professor of hematology and oncology at Feinberg and a Northwestern Medicine oncologist. "We hope to bring awareness to the organizations with less relative funding so we can collaborate to improve funding and outcomes for all patients with cancer."

Researchers at the University of Sussex have identified how differences in the genetic sequence of the two main strains of the cancer-associated Epstein-Barr virus (EBV) can alter the way the virus behaves when it infects white blood cells.

When EBV enters white blood cells it drives them to grow rapidly and continuously, making them 'immortal'. In some cases this can lead to the development of lymphoma, a type of blood cancer.
There are two main strains of the virus worldwide and although they can both cause cancer, in the laboratory, one strain (type 1) is able to drive white blood cells to become immortal better than the other (type 2).
​
While scientists already knew that the different properties of the two strains were caused by a protein called EBNA2, which is produced by EBV, until now they didn't know how it could cause the viruses to act so differently.