Tag: 7/3/22

Completion Lymph Node Dissection Shows no Benefit in Advanced Melanoma

Melanoma cells. Source: National Cancer Institute.

A review of data, published in Annals of Surgical Oncology, shows that completion lymph node dissection surgery for patients with stage III melanoma confers no benefit. This is especially true given that immunotherapy has shown success in treating metastases.

For years, surgery for patients with stage III melanoma, where the cancer had metastasised into lymph nodes, involved removing them along with the primary tumour. Known as completion lymph node dissection (CLND), the surgery was meant to ensure that no cancer remained after surgery.

More recently, however, cancer surgeons have discovered that CLND has the potential to cause more problems than it solves. In most cases, patients do better on immunotherapy alone than they do when their surgery involves removal of the lymph nodes, due to potential complications from lymph node surgery.

To address this, researchers reviewed their patient data to determine if immunotherapy alone resulted in better outcomes than CLND.

“In the few years prior to immunotherapy being available, some surgical trials were done asking if regional node dissection by itself improves overall survival for the patients,” said Martin McCarter, MD, a professor of surgical oncology at the University of Colorado (CU). “And the answer came back: no, it did not improve survival. That had been the standard forever, because we didn’t have other effective therapies, but once the definitive trials were done, we learned that CLND wasn’t helping, it wasn’t improving survival. Subsequent trials demonstrated that immunotherapy can improve survival in metastatic melanoma.”

For the study, the researchers looked at data on 90 patients who underwent sentinel lymph node biopsy (a procedure to determine if a skin melanoma has spread microscopically) only for stage III melanoma but did not undergo CLND. Of those patients, 56 received immunotherapy and 34 did not. Those who received immunotherapy had better rates of distant metastasis-free survival, meaning their cancer was less likely to come back.

“As treatments for melanoma have evolved, the standard of care may be evolving as well,” Prof McCarter said. “This study took a look at the patients who had a sentinel lymph node biopsy, so we knew the patient had a positive melanoma metastasis to their regional node. Those folks historically used to go on and get the completion lymph node dissection, but recently, people started to forego doing that lymph node dissection, which did not improve survival, and instead moved directly to immunotherapy, which did improve survival in other clinical trials. We proved that this is acceptable, that we’re not causing more harm to patients by doing it, and that those who do go on to get the immunotherapy seem to benefit from it.”

Forgoing CLND is part of a recent movement in cancer treatment known as de-escalation (or de-implementation) — performing only absolutely needed surgery. It’s especially important when it comes to lymph node surgery, Prof McCarter said, as in addition to the usual surgical risks, CLND has a 20% to 30% risk of permanent lymphoedema.

“If you could avoid that complication and not compromise a patient’s survival, that would be beneficial,” McCarter said. “That’s what we guessed was happening outside of definitive clinical trial evidence, and that’s what we were able to show. We know that we often overtreat patients, and this fits in that paradigm of finding ways to de-escalate unnecessary therapies, which has been done in breast cancer and other cancers as well.”

The researchers hope the findings will sway surgeons for whom CLND is still routine, despite the earlier studies showing that the additional surgery was not improving survival.

“Previous clinical trials with the use of adjuvant immunotherapy for melanoma had required a CLND,” Prof McCarter explained. “This study used real-world data from our stage III melanoma patients who were treated with immunotherapy without having a prior CLND.

“It takes years to change people’s practice patterns. I still have conversations with community surgeons who treat melanoma, asking me, ‘Should I be doing these regional node dissections?’ even though this data has been out for five to 10 years now,” Prof McCarter continued. “They’re afraid to give up what they used to do, and they’re afraid that they are doing a disservice to the patients or not giving them the best chance, when in reality, our understanding of cancer biology has evolved. We now have effective immunotherapy, which is overcoming some of the limitations of surgery while improving outcomes.”

Source:  University of Colorado

Taller Adults Have a Greater Colorectal Cancer Risk

Photo by Monstera from Pexels

Taller adults may be more likely than shorter ones to develop colorectal cancer or precancerous colon polyps, according to a new meta-analysis published in Cancer Epidemiology, Biomarkers & Prevention. While the association between taller height and colorectal cancer has been previously investigated, the researchers say those studies offered conflicting results, used inconsistent measures of height and did not include the risk of adenomas.

“This is the largest study of its kind to date. It builds on evidence that taller height is an overlooked risk factor, and should be considered when evaluating and recommending patients for colorectal cancer screenings,” said Associate Professor Gerard Mullin, MD. Greater height is still not proven to be causative, nor is it a great a risk factor as genetics, he and his team cautioned. However, it does add to long-standing evidence linking height to colorectal cancer risk.

“One possible reason for this link is that adult height correlates with body organ size. More active proliferation in organs of taller people could increase the possibility of mutations leading to malignant transformation,” said co-first author Elinor Zhou, MD.

The researchers first identified 47 international, observational studies involving 280 660 cases of colorectal cancer and 14 139 cases of colorectal adenoma. They also included original data from the Johns Hopkins Colon Biofilm study, which recruited 1459 adult patients undergoing outpatient colonoscopies to investigate the relationship between cancer and biofilm on the colon.

Because the definition of tallness differs around the world, the researchers compared the highest versus the lowest height percentile of various study groups. “The findings suggest that, overall, the tallest individuals within the highest percentile of height had a 24% higher risk of developing colorectal cancer than the shortest within the lowest percentile. Every 10-centimeter increase (about 4 inches) in height was found to be associated with a 14% increased risk of developing colorectal cancer and 6% increased odds of having adenomas,” said A/Prof Mullin.

In the US, the average height for men is 175.3cm, and for women it is 162.6 inches. This means men who are 185.4cm and women who are 172.7cm (10cm above the average US height) or taller are at a 14% increased risk of colorectal cancer and a 6% increased risk of adenomas.

The percentage results were adjusted for known risk factors of colorectal cancer, including non-modifiable factors such as age, familial colorectal cancer history and a personal history of chronic inflammatory bowel disease. Though not directly comparable due to differences in measurement scale, tallness may impart an order of magnitude of colorectal cancer risk similar to better-known modifiable factors such as cigarette smoking, moderate alcohol consumption and high processed red meat intake. At present, gastroenterologists focus on genetic and age-related risks for colorectal cancer screenings recommendations.

While colorectal cancer is the third most common cancer in both men and women in the US, fewer people are diagnosed with colorectal cancer each year has dropped overall since the mid-1980s, mainly due to prevention and screening. However, the downward trend is mostly in older adults. Among adults under 50, colorectal cancer deaths have increased 2% per year from 2007 to 2016, an as yet unexplained phenomenon.

“Greater awareness by the public and government will help promote more interest and funding for more research, which ultimately could change guidelines for physicians to consider height as a risk for cancer,” said A/Prof Mullin. “There are well-known modifiable dietary associations for colorectal cancer, such as processed red meats and smoking, but guidelines currently are fixated on family history, and height is clinically neglected when it comes to risk screening.”

Dr Zhou says more research is needed to define particular taller populations at risk for colon cancer. “For instance, tall athletes and individuals with inherited tallness, such as those with Marfan syndrome, could be screened earlier and the impact of height further explored,” she said. “We need more studies before we can definitively say at what height you would need earlier colorectal cancer screening.”

Source: John Hopkins Medicine

Comprehensive Bloodstream Lipid Level Test Can Predict CVD Decades Early

Source: Pixabay CC0

Lipidomics, measuring many different bloodstream lipid levels, can predict the risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD) years in the future, according to a new study in PLOS Biology. Such early prediction through lipidomic profiling may provide the basis for recommending diet and lifestyle interventions before disease develops.

At present, patient history and current risk behaviours are the main predictors for T2D and CVD, along with high- and low-density cholesterol ratios and levels. But there are over one hundred other types of lipids in the blood, which are thought to at least partially reflect aspects of metabolism and homeostasis throughout the body.

Nowadays, it is possible to measure thousands of individual lipids that make up the lipidome. Nuclear magnetic resonance spectrometry (NMR) metabolomics is also being increasingly used in large cohort studies to report on total levels of selected lipid classes, and relative levels of fatty acid saturation.

To find out if detailed lipid profiles could be better predictors, the authors drew on data and blood samples from a longitudinal health study of over 4000 middle-aged participants, first assessed from 1991 to 1994, with follow-up to 2015. Using baseline blood samples, the concentrations of 184 lipids were assessed. During the follow-up period, 13.8% of participants developed T2D, and 22% developed CVD.

The authors performed repeated training and testing on the data to create a risk model. Once the model was developed, individuals were clustered into one of six subgroups based on their lipidomics profile.

Compared to the group averages, the risk for T2D in the highest-risk group was 37%, an increase in risk of 168%. The risk for CVD in the highest-risk group was 40.5%, an increase in risk of 84%. Significant reductions in risk compared to the averages were also seen in the lowest-risk groups. The increased risk for either disease was independent of known genetic risk factors, and independent of the number of years until disease onset.

Rsk could be individually defined decades before disease onset, possibly in time to take steps to avert disease. Lipidomics could be combined with genetics and patient history to provide new insights into the beginnings of the disease. Additionally, new drug candidates could be identified from the lipids  contributing the greatest risk.

“The lipidomic risk, which is derived from only one single mass-spectrometric measurement that is cheap and fast, could extend traditional risk assessment based on clinical assay,” said lead researcher Chris Lauber of Lipotype. “In addition, individual lipids in blood may be the consequences of or contribute to a wide variety of metabolic processes, which may be individually significant as markers of those processes. If that is true, Lauber said, “the lipidome may provide insights much beyond diabetes and cardiovascular disease risk.”

Lauber added: “Strengthening disease prevention is a global joint effort with many facets. We show how lipidomics can expand our toolkit for early detection of individuals at high risk of developing diabetes and cardiovascular diseases.”

Source: EurekAlert!

For Reducing Health Risk Behaviours, Seeing is Believing

Doctor shows an X-ray of a foot
Photo by Tima Miroshnichenko on Pexels

It is said that seeing is believing, and researchers have found that using patients’ own medical imaging such as CT scans may discourage risk-related behaviours more than non-visual information. The meta-analysis, which appears in PLOS Medicine, found that when patients see imaging results about their risk of disease, they may be more likely to reduce risky behaviours.

Modifiable behaviours such as smoking, poor diet and physical inactivity are linked to non-communicable disease. Encouraging behavioural changes can help reduce the global burden of such diseases, which account for two-thirds of deaths around the world. The investigators were interested to see whether the growing use of medical imaging technologies could help.

Gareth Hollands and University of Cambridge colleagues conducted a meta-analysis of 21 randomised controlled trials involving over 9000 adult participants. Participants were either shown visual examples of personalised risk information following an imaging procedure, such as computed tomography, ultrasound, or radiography, in addition to health information or advice, or they received health information or advice with no visual feedback. The trials reported on behaviours such as smoking, medication use and levels of physical activity.

The strongest evidence was for smoking reduction, a healthier diet, increased physical activity, and increased oral hygiene behaviours. Single studies also reported increased skin self-examination and foot care following visualised feedback. Improvement in other behaviours examined were not statistically significant. The authors conclude that the growth of medical imaging technology could be capitalised on to help people modify their lifestyles and reduce disease risk.

Hollands said: “Medical imaging scans are used ever more widely by healthcare professionals. By gathering together the existing research, this study suggests that showing the scan results to patients to highlight the state of their health could motivate them to behave in a healthier way.”

Source: Science Daily

Cohorting an Effective Response for an Emerging Pandemic

Phot by Artem Podrez on Unsplash

During the extenuating circumstances of an emerging pandemic, grouping patients together in one area or facility, a practice known as cohorting, was successful in providing high-quality care and containing infectious patients, according to a new study published in JAMA Open.

The University of Minnesota Medical School researchers reported that cohorting was implemented by M Health Fairview early in the pandemic when there was little known about how to effectively treat patients with COVID.

“This study highlights the academic and clinical expertise of the M Health Fairview system to deliver outstanding medical care to the people of Minnesota,” said Dr Greg Beilman, a critical care surgeon at the U of M Medical School and was a co-lead of the M Health Fairview COVID response team. “In this study we demonstrated our ability to rapidly bring new developments in science to the patient’s bedside and improve outcomes for patients affected by this frequently dire disease.”

Because every person being treated in the cohorts had COVID, frontline healthcare workers quickly gained experience in COVID care. These experienced specialists worked side by side with academic physicians who were translating the latest medical research into new solutions they could apply in real time to patient care. COVID patients had access to leading-edge clinical trials, internal COVID testing capabilities, and innovative technology.

The study found that dedicated COVID units in Minnesota were associated with a 2% overall improvement in in-hospital survival rates when patients were properly matched for severity of illness. Complications associated with COVID were significantly better in this group as was the swift implementation of new care processes by health care providers.

“The opportunity to care for patients at our COVID cohort hospitals was a shining light in a dark time for many of us,” said Dr Andrew Olson, medical intensivist at the U of M Medical School and medical director of COVID hospital medicine at M Health Fairview. “We watched our colleagues develop expertise, conduct research and care for one another while staying healthy in a challenging time.”

The research team hopes the cohorting method could be implemented during other infectious disease outbreaks, like viral pneumonia. The framework helps provide infectious patients the best care during times of rapid learning in scientific research.

“As the pandemic progressed, we had broad availability of personal protective equipment, vaccinations, and more health care workers developed familiarity with treatment of COVID,” said Dr Beilman. “These developments combined with the fact that the incidence of COVID decreased last year – this care model was no longer necessary.”

Researchers plan to further investigate which patients benefit most from care at such facilities, as well as evaluate the experience for those healthcare professionals who work in them.

Source: University of Minnesota Medical School