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PHILADELPHIA - In a finding that suggests the potential for practice change that would reduce the use of antibiotics in dermatology, researchers in the Perelman School of Medicine at the University of Pennsylvania have found the diuretic drug spironolactone may be just as effective as antibiotics for the treatment of women's acne. The study, published this month in the Journal of Drugs and Dermatology, found patients who were originally prescribed spironolactone changed to a different drug within one year at almost the same rate as those who were prescribed antibiotics. The prescription change is a proxy for ineffectiveness, since switching is often the result of treatment failure due to lack of efficacy, side effects, cost, or other factors.

Acne is one of the most common diseases in the world. It affects 85 percent of people under the age of 18, but it also regularly impacts adults. More than 50 percent of women in the United States are treated for acne between the ages of 20 and 29, while more than 35 percent are treated between the ages of 30 and 39.

Oral antibiotics are the most common systemic treatment for acne, and when combined with the large patient population, the result is that dermatologists prescribe the highest level of antibiotics per provider among all medical specialties, according to the Centers for Disease Control - a fact that contributes to concerns about increased resistance to antibiotics across all fields of medicine.

"It's clear that a safe alternative to oral antibiotics could have a huge benefit, and our data show spironolactone may be that alternative," said the study's lead author John S. Barbieri, MD, MBA, Dermatology chief resident at Penn. David J. Margolis, MD, PhD, a professor of Dermatology, was the study's senior author.

Spironolactone, marketed under the name aldactone, is currently approved to treat high blood pressure, heart failure, and conditions that cause people to retain fluid. It blocks the effects of male hormones like androgen, meaning it's not an option to treat acne in men. However, those same anti-hormonal effects can help prevent acne outbreaks in women. As a result, some dermatologists use it to treat female acne patients.

Researchers compared data on 6,684 women and girls taking spironolactone to 31,614 who were prescribed antibiotics. Within a year, 14.4 percent of spironolactone patients and 13.4 percent of antibiotic patients had switched to alternative treatments, suggesting each treatment was working at almost the same rate, despite the fact that tetracycline-class antibiotics are prescribed five times as frequently.

"These numbers suggest dermatologists should consider spironolactone first instead of antibiotics when it comes to women with acne," Barbieri said.

In addition to the benefits for antibiotic stewardship, Barbieri pointed to several studies showing long-term oral antibiotic use may be associated with antibiotic resistance, lupus, inflammatory bowel disease, and even colon and breast cancer.

"This indicates spironolactone may have a better safety profile than oral antibiotics, which is another factor that makes it such an appealing option," Barbieri said. He also noted spironolactone is less expensive, which may be relevant to patients with high deductibles or who are uninsured.

Spironolactone is not approved for the treatment of acne by the U.S. Food and Drug Administration despite expert opinion supporting its use, and Barbieri says the findings of this study should be confirmed by a randomized controlled trial that directly compares the two treatment options.

A new study has identified important factors that can improve the transfer of patients from the intensive care unit (ICU) to a general hospital ward, a high-risk transition in which breakdowns in communication, medical errors and adverse events resulting in readmission can occur. The research, published in CMAJ (Canadian Medical Association Journal) includes patient and health care provider perspectives that identify resource availability, communications and institutional culture as key factors to be addressed.

"The transfer of patients from the ICU to a hospital ward is one of the most challenging, high-risk and inefficient transitions of care because the patients are among the sickest in the health care system, they are transitioning from high technological units to less acute environments, and many providers are involved in exchanges of information and responsibility," writes Dr. Jeanna Parsons Leigh, Cumming School of Medicine, University of Calgary, Calgary, Alberta, with coauthors.

The study was conducted in 8 hospitals in 7 cities across Canada. Three broad themes emerged from consultation with patients, families and health care professionals that can hinder or improve, high-quality patient transfers: resource availability, communication and culture.

Suggestions to improve patient transfers from the ICU to ward include

Standardized discharge communication tools to ensure open, continuous communication between patients or families and health care providers

Standardized discharge communication tools for use among health care providers

Multiple forms of communication, including both verbal and written tools, to document transfer and ensure continuity of care

Procedures to manage delays in transferring patients and coordinate care.

The study provides qualitative information on the experiences of patients, families and health care professionals who are involved in this high-risk health care transition.

The authors note that as some participants were interviewed up to two years after the relevant ICU admission, the time elapsed may have affected their recall.

"Patients, family and provider experiences with transfers from intensive care unit to hospital ward: a multi-centre qualitative study" is published June 4, 2018

HOUSTON - Clinical trials show that an immune checkpoint inhibitor shrinks the tumors of nearly half of patients with an incurable, advanced form of a common skin cancer, an international team led by a researcher at The University of Texas MD Anderson Cancer Center reports in the New England Journal of Medicine.

"These results mark a potential paradigm shift in the treatment of patients with advanced cutaneous squamous cell carcinoma, who to date have had very limited results with chemotherapy and targeted therapies," said lead author Michael Migden, M.D., associate professor of Dermatology and of Head and Neck Surgery.

Migden is principal investigator of the international, multicenter phase II registrational clinical trial of cemiplimab, an immune checkpoint inhibitor that works by blocking PD1, a surface receptor on T cells that shuts down immune response to cancer.

Cutaneous squamous cell carcinoma is the second most common skin cancer, with an estimated 1 million new cases diagnosed annually. More than 95 percent of patients are cured by surgery and radiation at the disease's early stages. But for the fraction who progress, there are no systemic therapies approved as a standard of care, the researchers note.

At a median follow-up of 7.9 months, 28 of 59 patients with metastatic disease (47.5 percent) had an objective response to cemiplimab, defined as at least 30 percent tumor shrinkage observed via imaging. Four were complete responses, 24 had partial responses, and 82 percent of responders remain on the drug.

"Patients continue to do well, so median progression-free survival and overall survival have not been reached yet," said Migden, a Mohs surgeon and dermatologic oncologist at MD Anderson. The durable disease control rate of responders plus those with stable disease for at least 105 days was 61 percent. Migden notes that response rates to chemotherapy regimens or targeted therapy against the epidermal growth factor receptor (EGFR) now used against advanced cutaneous squamous cell carcinoma range from 15-25 percent, with many debilitating side effects.

Immunotherapies pose risks of inflammatory side effects that have to be monitored, but otherwise have fewer day-to-day complications than chemotherapy and EGFR inhibitors, Migden said.

Common side effects in the cemiplimab phase II trial were diarrhea, fatigue, nausea, constipation, and rash. Four patients (6.8 percent) had to discontinue treatment. Three patients died of adverse events during the trial, but the deaths were not considered related to treatment.

Median age of patients in the phase II trial was 71, with 33 (55.9 percent) having received prior systemic therapy and 50 (84.7 percent) having received radiotherapy.

In the phase I trial of patients with metastatic or locally advanced but inoperable disease, 13 of 26 (50 percent) had a partial response. At 11 months median follow-up, seven patients remained in response. Two patients (7.7 percent) had to discontinue treatment due to adverse events. Median age was 73.

The U.S. Food and Drug Administration has granted an application for breakthrough therapy status for the drug, providing a faster potential route for FDA approval. Regeneron Pharmaceuticals, Inc., and Sanofi are co-developing cemiplimab.

Cutaneous squamous cell carcinoma develops from genetic damage caused by exposure to UV light. These tumors have a high mutation burden, providing a target-rich environment for immune system attack and this cancer also is strongly associated with immune suppression. Those factors made it a strong candidate for PD1 inhibition, which unleashes the immune system to attack cancer.

The clinical trials are funded by Regeneron and Sanofi.

Cutaneous squamous cell carcinoma is not included in national cancer registries, so the incidence of the disease and its mortality rates are unknown. Estimates or annual diagnoses range from 700,000 to 1 million. One study estimated that between 3,900 and 8,700 people died from this cancer in 2012.

MAYWOOD, IL - A major international study has found that 2.6 percent of infants and children hospitalized for stroke die in the hospital.

Loyola Medicine neurologist José Biller, MD, a nationally known expert on strokes in children, is among the co-authors of the study, published in the journal Pediatrics. First author is Lauren A. Beslow, MD, of the Children's Hospital of Philadelphia.

The retrospective study included 915 infants younger than one month and 2,273 children aged one month to 18 years who were stroke patients at 87 hospitals in 24 countries. The type of stroke examined in the study, called ischemic, is caused by blood clots and is the most common type.

The study found that during their hospitalizations for ischemic stroke, 1.5 percent of the infants and 3.1 percent of the children died, with an overall mortality rate of 2.6 percent.

Researchers classified the causes of death as stroke alone, a combination of an underlying disease and stroke or simply an underlying disease. Nearly two-thirds (65 percent) of hospital deaths with a known cause were related to the stroke and/or subsequent deficits.

Risk factors for dying in the hospital included congenital heart disease and having a severe type of ischemic stroke known as "posterior plus anterior circulation."

Hispanic ethnicity also was associated with higher mortality, but black infants and children were not at higher risk of dying. The reason for the higher Hispanic mortality rate is not known. Future studies "should explore whether ethnic differences in mortality rates are related to disparities in care," researchers wrote.

Also at higher risk of dying were infants and children who did not have seizures. The reason may be that infants who present with seizures might be diagnosed and treated more quickly for their strokes, researchers wrote.

Childhood ischemic strokes affect 1.2 to 2.4 per 100,000 children per year in developed countries. Although deaths from ischemic and other types of stroke appear to have declined, stroke remains among the top 10 causes of death among children in the United States.

Researchers wrote that improved stroke recognition, earlier supportive care, more rapid intervention and neuroprotective treatments "are critical for decreasing mortality after stroke in the pediatric population."

The study is titled, "Mortality After Pediatric Arterial Ischemic Stroke."

Researchers have shed light on how taking aspirin can help to stave off bowel cancer.

Experts found that the painkiller blocks a key process linked to tumour formation.

Regular use of aspirin is known to reduce a person's risk of developing colon cancer but the drug's tumour fighting properties have not been well understood.

Researchers at the University of Edinburgh focused on a structure found inside cells called the nucleolus.

Activation of the nucleolus is known to drive tumour formation and dysfunction has also been linked to Alzheimer's and Parkinson's.

The team at the University's Cancer Research UK Edinburgh Centre tested the effects of aspirin on cells grown in the lab and on tumour biopsies removed from colon cancer patients.

They found that aspirin blocks a key molecule called TIF-IA, which is essential for the nucleolus to function.

Not all colon cancer patients respond to aspirin but the researchers say their findings could help pinpoint those most likely to benefit.

Aspirin has side effects that include internal bleeding and it can cause certain types of stroke. Long term use is not recommended. The researchers say the study paves the way for the development of new, safer therapies that mimic aspirin's effects.

The research, published in Nucleic Acids Research, was funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council. Worldwide Cancer Research, Bowel and Cancer Research and The Rosetrees Trust also supported the work.

Dr Lesley Stark, of the Cancer Research UK Edinburgh Centre at the University of Edinburgh, said: "We are really excited by these findings as they suggest a mechanism by which aspirin may act to prevent multiple diseases. A better understanding of how aspirin blocks TIF-IA and nucleolar activity provides great promise for the development of new treatments and targeted therapy."

The newer high-sensitivity troponin test discovers smaller amounts of heart-specific proteins, troponins, than the older troponin test and thus identifies more myocardial infarction patients than before. A new study from Karolinska Institutet in Sweden published in The Journal of the American College of Cardiology now reports that the risk of a future heart attack is lower in patients diagnosed with the new test.

A blood test that measures the presence of heart-specific proteins called troponins is used by emergency clinics to diagnose myocardial infarction in patients with chest pain. For the past few years a newer laboratory method has been used at most hospitals in Sweden that is ten times more sensitive than the conventional troponin test. The high-sensitivity troponin test can discover heart attacks earlier so that treatment can commence, which is thought to improve the patients' prognosis.

"But there is a lack of larger studies examining whether the high-sensitivity troponin test is of any significance for patients with newly diagnosed myocardial infarction in terms of survival or the risk of another heart attack," says study leader Dr Martin Holzmann, associate professor of epidemiology at Karolinska Institutet's Department of Medicine in Solna and physician at Karolinska University Hospital.

The study included all patients in Sweden who had had their first heart attack between 2009 and 2013. This gave a study population of almost 88,000 patients, 40,000 of whom had been diagnosed using the high-sensitivity troponin test and just over 47,000 using the conventional troponin test.

The researchers found that five per cent more myocardial infarctions were being diagnosed in hospitals that used the high-sensitivity troponin test. A year after the heart attack was registered there was no difference in mortality between the two groups, although the number of new heart attacks was lower in the group that had been diagnosed using the high-sensitivity troponin test.

"This surprised us," says Dr Holzmann. "We didn't think that the more sensitive test would affect the risk of future heart attacks."

The use of coronary angiography and balloon angioplasty was 16 and 13 per cent more common, respectively in the patients diagnosed with the high-sensitivity troponin test. In the USA, where the new test was not approved until 2017, there are fears that the more sensitive methods can entail a large increase in the number of examinations with no benefit to the patients.

"The increase we observed in our study was less than expected, which means that the high-sensitivity troponin test has enabled doctors to single out the patients who benefit from such intervention. We found no differences in medication between the two groups, so the differences in prognosis with fewer new heart attacks could be attributed to the fact that more coronary angiography and balloon dilation procedures have been performed on the right patients," says Dr Holzmann, who also believes that the study supports the idea that the handful of hospitals in Sweden that still do not use the high-sensitivity troponin test should start to do so.

The study was conducted in association with the Sahlgrenska Academy and Uppsala University. Martin Holzmann receives a grant from the Swedish Heart and Lung Foundation. Per-Ola Andersson has received a lecture fee from pharmaceutical companies Roche, Gilead and Janssen and a consultancy fee from AbbVie, CTI Bipharma and Glaxo-Smith-Kline. Kai M. Eggers has received a consultancy fee from pharmaceutical company Abbott Laboratories, AstraZeneca and Fiomi Diagnostics. Martin Holzmann has received a consultancy fee from pharmaceutical companies Actelion and Pfizer. No other potential conflicts of interest have been reported.

The blood vessels of middle-aged men and women adapt differently to regular exercise according to new research being presented today at the British Cardiovascular Society conference in Manchester.

Researchers at Loughborough University examined the effects of regular exercise training on the blood vessels of 12 men and post-menopausal women. Blood pressure and arterial stiffness were assessed before and one hour after a brisk walk.

Their preliminary findings suggest that arterial stiffness, an independent risk factor for heart disease, is higher in women compared with age-matched men. A single bout of brisk walking improved arterial stiffness and blood pressure in both groups, however, arterial stiffness remained higher in women. Interestingly, the improvements in arterial stiffness were related to changes in blood pressure in men only, suggesting possible sex-differences in how the blood vessels adapt and respond to exercise.

Research has shown that regular physical activity helps reduce the stiffening of the arteries, which in turn lowers a person's risk of developing heart or circulatory disease. However, the blood vessels of men and women appear to adapt differently to regular exercise, with post-menopausal women demonstrating less exercise-associated benefits than men.

The researchers are now looking at whether daily folic acid supplements could help postmenopausal women to reduce their risk by relaxing the blood vessels and as such lowering arterial stiffness and reducing strain on the heart.

Jen Craig, the PhD student undertaking the research at Loughborough University under the lead of Dr Emma O'Donnell, said: "Regular physical activity is associated with lower risk of cardiovascular disease. However, regular exercise does not seem to benefit the blood vessels of post-menopausal women as much as it does their male counterparts. If we are to help women to decrease their risk of heart disease we need to consider alternative strategies that may enable these women to maximise their benefits from engaging in regular exercise."

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: "This research adds to our understanding of the relationship between physical activity and heart disease as we get older. If you're more physically active you give yourself the best chance of a heart-healthy retirement. And although post-menopausal women don't see quite the same exercise benefits as men, staying active will still reduce their overall risk of developing heart disease."

Survival results for the CALGB 80303 Trial presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting 2018 demonstrate that esophageal cancer patients shown by PET scan to be non-responders to induction chemotherapy, and were then switched to a new chemotherapy during chemoradiation, showed median overall survival of 27 months. This improves on 18-month median overall survival of previous studies that used the same chemotherapy with non-responders during induction and chemoradiation treatment phases. Patients who were shown by PET to be responders to induction chemotherapy with the regimen FOLFOX and then stayed on FOLFOX during chemoradiation showed 55 percent 4-year survival, the best ever outcome reported for patients with this disease.

"Esophageal cancer patients undergo treatments to shrink tumors before surgery. We wanted to see if PET scan could help us personalize the best pre-operative treatment," says Karyn Goodman, MD, MS, Grohne Chair of Clinical Oncology at University of Colorado Cancer Center, and the national study chair of the CALGB 80303 Trial.

Currently, patients with stage II/III esophageal and gastroesophageal cancers typically receive 5.5 weeks of chemotherapy with radiation (chemoradiation) followed by surgery. Chemoradiation before surgery has been shown to improve survival compared with surgery alone, but the optimal chemotherapy for this patient population remains unknown.

The goal of the CALGB 80303 trial was to determine whether PET scan at baseline and then again after a short course of "induction chemotherapy" prior to chemoradiation could show which patients responded to the prescribed chemotherapy regimen, allowing responders to confidently continue the regimen that was working, while helping non-responders switch to the other chemotherapy regimen during chemoradiation.

In all, 257 U.S. patients with adenocarcinoma of the esophagus or gastroesophageal junction received PET scan at the time of diagnosis and again after six weeks of induction chemotherapy with either FOLFOX or carboplatin/taxol.

"If there was a good response by PET, they continued on the same chemotherapy during chemoradiation. If they had a poor response, they switched over to the alternative chemotherapy agent during chemoradiation," Goodman says.

After six weeks of chemoradiation including the same or the other chemotherapy regimen, patients underwent surgery, and then researchers followed their survival outcomes. Last year at ASCO 2017, Goodman and colleagues reported that changing chemotherapy regimen for non-responders increased the rate of pathologic complete response, meaning, "there were no traces of cancer in the tissue specimen taken at the time of surgery," Goodman says. This year at ASCO, researchers present survival data in this same population.

Overall, median survival remained higher in the group of patients that responded to induction chemotherapy than in the group that did not respond to induction therapy, at 46 months for responders and 27 months for non-responders.

"This makes sense," Goodman says. "Again, these are patients who benefitted from induction chemotherapy, whether with FOLFOX or with carboplatin/taxol. We would expect them to live longer than patients who did not respond."

In fact, it was impossible to accurately determine the median overall survival for patients who responded to FOLFOX during induction and then stayed on FOLFOX during chemoradiation, because more than half of these patients were still alive at the time of data analysis (the 55 percent 4-year survival listed above).

But the major update in outcomes was seen for patients who did not respond to induction treatment, and then switched to the other chemotherapy regimen during chemoradiation.

"Twenty-seven months median overall survival is much better than we have seen in previous studies for patients who do not respond to induction chemotherapy," Goodman says. "We show that using PET scan at baseline and then again after induction chemotherapy can help to determine who should stick with the chemotherapy used during induction and who should switch to the other regimen during chemoradiation."

Bottom Line: Vigorous exercise is associated with reductions in the risk of death among adult survivors of childhood cancer.

Why The Research Is Interesting: In the general population, a healthy lifestyle that includes regular exercise is associated with a reduced risk of death. It is unknown whether that applies to adult survivors of childhood cancer who have an elevated risk of death because of the late effects of cancer treatment.

Who and When: 15,450 adult survivors of cancer diagnosed before age 21 at hospitals in the United States and Canada between 1970 and 1999 and enrolled in the Childhood Cancer Survivor Study

What (Study Measures): Self-reported vigorous exercise in metabolic equivalent task (MET) hours per week (exposures); all cause-mortality (primary outcome)

Study Design: This was an observational study. Researchers were not intervening for purposes of the study and cannot control all the natural differences that could explain the study findings.

Authors: Jessica M. Scott, Ph.D., and Lee W. Jones, Ph.D., of Memorial Sloan Kettering Cancer Center, New York, and coauthors

Results: Vigorous exercise for adult survivors of childhood cancer was associated with reductions in risk of death; in a subset of these survivors, increased exercise (an average of nearly 8 MET-hours per week) over an eight-year period was associated with a lower risk of death compared with maintaining a low level of exercise.

Limitations: Exercise was self-reported by a single item that evaluated only vigorous exercise

Study Conclusions: Our findings indicate that regular vigorous exercise, as well as an increase in exercise, is associated with significant reductions in the risk of mortality in adult survivors of childhood cancer. These findings may be of importance for the large and rapidly growing global population of adult survivors of childhood cancer at substantially higher risk of mortality due to multiple competing risks.

Updated results of the global phase III ALEX trial comparing alectinib with crizotinib as first-line treatment against ALK-positive non-small cell lung cancer show a median progression-free survival (PFS) of 34.8 months in 152 patients treated with alectinib versus 10.9 months in 151 patients treated with crizotinib.

"Think of it like a horse race, only it's not about who crosses the finish line first, but how far the horses can run," says D. Ross Camidge, MD, PhD, the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, director of Thoracic Oncology at the CU School of Medicine, and the study's first author. "In this trial, it's as if half of the people 'riding' crizotinib had exhausted their horses at about 11 months. For patients on alectinib, when this trial first started reporting data last year, more than half were still on their horses, still running. Now enough time has elapsed to estimate the median performance of these alectinib 'horses' more accurately."

Camidge's analogy explains the results above: At 10.9 months half of the cancers treated with crizotinib had restarted their growth, whereas it took 34.8 months for patients on alectinib to reach this same "median progression free survival". Impressively, the PFS was almost identical in patients without brain metastases at the point of diagnosis, demonstrating the drug's success broad overall cancer control.

"When preliminary data were reported last year, estimates were looking to be more like 25 months PFS on alectinib, so this jump to 34.8 months is huge and may surprise people," Camidge says. "In reality, it's just that patients' progression tends to be rather sparse around the time of the 50 percent point, and when that happens the median can jump around a lot."

Additionally, 45 percent of patients treated with crizotinib went on to develop brain metastases while on trial, compared with only 12 percent of patients treated with alectinib. The overall response rate for alectinib was 82.9 percent, compared with 75.5 percent for crizotinib. And alectinib was also associated with fewer overall side effects than crizotinib, with 16 percent of alectinib patients requiring dose reduction and 22 percent requiring dose interruption, compared with 21 and 25 percent of crizotinib patients, respectively.

"In addition to median progression-free survival, another way to describe the duration of a drug's benefit is to compare the risk, over time, that each 'horse' will 'stop running'. We call this a hazard ratio. It's a little harder to understand, but in a comparison trial it's probably the better way to really show the difference. Last year, when the data were presented the risk of progression or death - the 'hazard ratio' - of alectinib was reported as 47 percent of what it was on crizotinib, and now we show that the risk of progression or death for patients on alectinib was even lower, just 43 percent that of patients on crizotinib," says Camidge.

Both drugs target lung cancers in which the gene ALK becomes improperly fused with a partner gene, such as EML4, to code for a protein made from bits of both genes. These ALK fusion proteins have been shown to drive about 4 percent of all lung cancers, resulting in about 12,000 diagnoses of ALK-positive non-small cell lung cancer in the United States every year. Crizotinib earned FDA approval in 2011 to treat advanced ALK-positive lung cancer, and now next-generation ALK inhibitors such as alectinib, which have shown activity post-crizotinib, are replacing or vying to replace crizotinib in many settings.

In Camidge's opinion, these updated data further consolidate alectinib as the standard-of-care for first-line treatment of ALK+ non-small cell lung cancer.

New research presented at this year's Euroanaesthesia congress in Copenhagen, Denmark shows that hypnosedation is a valuable alternative to conventional general anaesthesia.

Hypnosedation is a technique which combines hypnosis, conscious sedation (where drugs are used to make the patient comfortable and relaxed while remaining conscious), and local anaesthesia to block pain. It has previously been shown to decrease the need for medication, reduce adverse effects, and to accelerate postoperative rehabilitation when compared to general anaesthesia in which the patient is rendered unconscious.

This research team led by Dr Aurore Marcou and colleagues from the Institut Curie, Paris, France, say: "By minimising effects of anaesthesia on vital functions while preserving the patients' well-being, it contributes to a sustainable development of anaesthesia."

The authors performed a retrospective study of 150 cancer patients who were treated at the Institut Curie between 2011 and 2017, and whose operations were performed under hypnosis. Procedures were conducted with the usual safety conditions and monitoring in place, however they excluded all premedication or hypnotic drugs. A continuous supply of the opioid remifentanil was given during each operation to keep the patients comfortable, and they were provided with the usual anti-sickness drugs and a painkiller as a preventative measure. Local or locoregional anaesthesia was performed depending on the type and location of surgery, but the patient remained conscious throughout the procedure.

Hypnosedation was used in breast surgeries (including total mastectomies), which represented 90% of the surgeries in this study, and also gynaecological surgeries, colonoscopies, and superficial plastic surgeries (representing 10% between them). The mean duration of procedures was 60 minutes (30 to 160 minutes), and the mean length of stay in the recovery room was 35 minutes. Patients were aged from 18 to 100 years with a mean of 60.5 years, with 22% older than 75 years. Individuals were grouped according to the severity of their condition, with 2% being classified as having severe cardiac, respiratory, or renal failures that seriously questioned the benefit of using traditional general anaesthesia.

The authors found that in 99% of cases, hypnosedation provided comfortable conditions for both the patient and the surgeon operating on them. Patient discomfort happened in just two cases, and in both of these, general anaesthesia was quickly and easily implemented.

The authors conclude that: "Hypnosedation can be proposed as a useful alternative to general anaesthesia in various types of surgeries including major breast surgeries. By minimising effects of anaesthesia, this technique is particularly valuable for vulnerable patients. Hypnosis benefits the patient as well as the caregivers."

The drug crizotinib has activity against a number of genetic targets relevant to non-small cell lung cancer, already earning FDA-approval against ALK- and ROS1-positive lung cancers. Now updated phase 1 clinical trial results presented at the American Association for Clinical Oncology (ASCO) Annual Meeting 2018 show a 40 percent response rate and 6.7-month median progression-free survival from crizotinib in highly MET-amplified non-small cell lung cancer, as well. The study also identifies new criteria to define "highly MET-amplified" cancer, adjusting the number of MET copies down from 5 per chromosome to 4 per chromosome. By lowering the bar for "high MET amplification", the study suggests that crizotinib may benefit more MET-amplified patients than previously thought.

The study comes in the context of continuing work to target MET amplification in cancer. While alterations in the gene MET have been known to cause lung and other cancers, and drugs have been developed to target MET, these drugs have been largely unsuccessful in the clinic.

"It may not be that there is anything wrong with the drugs; it may be that we haven't known exactly who to give these drugs to," says D. Ross Camidge, MD, PhD, the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center and Director of Thoracic Oncology at the CU School of Medicine.

In fact, there are a few kinds of MET alterations that have been shown to cause and/or drive the growth of cancer. One type, called "MET exon 14 skip mutations", exists in about 4 percent of lung cancers and causes especially slow degradation of the MET protein, leading to improper accumulation. Another type, called MET amplification, increases the number of copies of the MET gene itself, which leads to overproduction of the MET protein.

Amplification can happen in two ways - either there can be multiple copies of the chromosome that holds MET, or one chromosome may come to hold additional copies of the MET gene itself. The latter measurement is the focus on the current trial results, with the question being, How many copies of the MET gene on its chromosome are required to make a patient's cancer sensitive to MET inhibition?

In other words, how amplified does MET need to be for crizotinib to be useful?

There is another way to ask this question: At what ratio of MET:Chromosome is MET likely to be the prime or only genetic driver of the cancer? A 2016 study by the CU Cancer Center Lung Cancer Group led by Sinead Noonan, MD, suggested that at a 5:1 ratio or higher of MET-per-chromosome, lung cancer was almost exclusively driven by MET and not by other genetic alterations. (Refer to the linked study for a more detailed description of the science behind measuring MET amplification.)

Earlier analysis of the phase I clinical trial of crizotinib against MET-amplified lung cancer showed that, indeed, patients with MET:Chromosome ratios greater than or equal to 5 were most likely to have a significant response to the drug. However, a few responses did occur in the next highest group. The current ASCO report of the same study both expands the number of patients and defines a new cut-point to more accurately predict who will respond, namely a MET:Chromosome ratio greater than or equal to four.

Results are reported for thirty-seven patients with MET-amplified non-small cell lung cancer treated with crizotinib. Of these patients, 20 were considered to have "high" MET amplification (MET:Chromosome ratio of 4 or more). Of these 20, eight showed objective responses to treatment (40 percent), with a median progression-free survival of 6.7 months. Two of these patients showed a complete response.

"While using either the gene copy number alone or lower MET amplification ratio simply to categorize more patients as 'MET positive' might be attractive, it hasn't helped the field much. Instead, it has led to giving MET inhibitors to patients who go on to receive little benefit, and along with that, a lot of negative trials and disillusionment in the MET field," says Camidge, the study's first author. "Patients who are MET-amplified at a ratio of greater than or equal to four, denoting MET as the primary driver of their cancer, are rare and probably represent only about a half of a percent of all lung cancer patients. But if it were your mom or dad, you'd want to know and to treat it. These results show that crizotinib may be an attractive treatment option for these patients."

SEATTLE - Lifestyle-related cancers, such as lung, colorectal, and skin cancers, have increased globally over the past decade, according to the most comprehensive analysis of cancer-related health outcomes and patterns ever conducted.

"While the increase in lung, colorectal, and skin cancers over the past decade is concerning, the prevention potential is substantial," said Dr. Christina Fitzmaurice, Assistant Professor of Global Health at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, whose organization coordinated the study. "Vital prevention efforts such as tobacco control, dietary interventions, and broader health promotion campaigns need to be scaled up in response to this rise in lifestyle-related cancers."

The study, published today in JAMA Oncology, covers 1990 to 2016; it is part of the Global Burden of Disease (GBD) study, a comprehensive effort to quantify health internationally. Researchers reviewed 29 cancer groups, including lung, breast, prostate, skin, colorectal, pancreatic, stomach, and liver cancers, as well as leukemia and other cancer groups (full list below). The study provides findings by age and sex for 195 countries and territories.

While lifestyle-related cancers saw a universal increase from 2006 to 2016, several cancers from infectious causes - including cervical and stomach cancers - decreased over the same time period.

Study estimates were analyzed using a Socio-demographic Index (SDI) based on rates of education, fertility, and income. SDI is more comprehensive than the historical "developed" versus "developing" nations framework. Countries with high SDI have high levels of income and education and low fertility, whereas low-SDI countries have low levels of income and education and high fertility.

Large disparities in cancer incidence and death persist between high- and low-SDI countries. Researchers found rates of cancer incidence and death remained higher in high-SDI countries in 2016. For example, the odds of developing breast cancer over the course of one's lifetime were the highest - at 1 in 10 women - in high-SDI countries, but only 1 in 50 for women in low-SDI countries.

Conversely, the largest and fastest increase in new cancer cases between 2006 and 2016 occurred in middle-SDI countries. And women in low-SDI countries are nearly four times more likely to develop cervical cancer than women in high-SDI countries, and in 2016, cervical cancer was the most common cause of cancer incidence and death in low-SDI countries.

"Ensuring universal access to health care is a vital prerequisite for early detection and cancer treatment," said Fitzmaurice. "And improving access to advanced diagnostic technologies not commonly available in low-SDI countries is a critical step toward achieving health equity globally."

Additional key findings include:

In 2016, there were 17.2 million cancer cases worldwide, an increase of 28% over the past decade. There were 8.9 million cancer deaths the same year.

While cancer death rates decreased in a majority of countries from 2006 to 2016, incidence rates conversely increased.

Breast cancer was the leading cause of cancer death in women.

Lung cancer was the leading cause of cancer death in men; it was also the leading cause of cancer mortality globally, accounting for nearly 20 percent of all cancer deaths in 2016.

Prostate cancer is one of the most common causes of cancer incidence and death in men, in both high- and low-SDI countries, but especially in sub-Saharan Africa.

NEW CASES PER 100,000 PEOPLE (AGE-ADJUSTED), 2016
"Worst" and "best" countries and global

Tracheal, bronchus, and lung cancer: North Korea (56.9), Kenya (4.2), global (30.2)

Colon and rectum cancer: Netherlands (57.5), The Gambia (4.3), global (25.9)

Breast cancer: Luxembourg (61.8), Niger (5.8), global (24.1)

Non-melanoma skin cancer: Australia (300.4), Bangladesh (0.7), global (23.2)

Prostate cancer: Dominica (113.1), North Korea (2.4), global (22.1)

Stomach cancer: South Korea (44.5), Namibia (2.7), global (17.3)

Liver cancer: Mongolia (108.4), Morocco (1.9), global (14.6)

Other neoplasms: Malawi (39.6), Syria (2.6), global (10.9)

Cervical cancer: Somalia (34.0), Qatar (1.1), global (7.0)

Leukemia: New Zealand (20.3), Zambia (2.0), global (6.8)

Non-Hodgkin lymphoma: Canada (21.2), Kyrgyzstan (1.5), global (6.7)

Bladder cancer: Lebanon (31.1), Nigeria (1.2), global (6.7)

Esophageal cancer: Malawi (25.2), Syria (0.7), global (6.6)

Pancreatic cancer: Czech Republic (12.5), India (2.6), global (6.4)

Uterine cancer: Latvia (23.1), Bangladesh (0.8), global (6.0)

Lip and oral cavity cancer: Pakistan (22.1), Sao Tome and Principe (1.0), global (5.5)

Kidney cancer: Latvia (20.5), Nepal (1.0), global (5.0)

Brain and nervous system cancer: Iceland (20.8), Namibia (1.4), global (4.6)

Malignant skin melanoma: Australia (55.6), Nepal (0.2), global (4.1)

Ovarian cancer: Estonia (9.3), Niger (1.2), global (3.6)

Thyroid cancer: Iceland (18.7), Ghana (0.2), global (3.3)

Gallbladder and biliary tract cancer: Chile (11.5), Uzbekistan (0.6), global (2.8)

Larynx cancer: Cuba (8.8), The Gambia (0.6), global (2.7)

Other pharynx cancer: Hungary (7.3), Palestine (0.2), global (2.4)

Multiple myeloma: Barbados (6.3), Tajikistan (0.4), global (2.1)

Nasopharynx cancer: Malaysia (5.1), Mali (0.1), global (1.3)

Hodgkin lymphoma: Greece (5.3), Syria (0.1), global (1.0)

Testicular cancer: Chile (6.4), Mozambique (0.04), global (0.9)

Mesothelioma: United Kingdom (2.9), Palestine (0.1), global (0.5)

DEATHS PER 100,000 PEOPLE (AGE-ADJUSTED) IN 2016
"Worst," and "best" countries and global

Tracheal, bronchus, and lung cancer: North Korea (61.7), Egypt (4.8), global (25.8)

Colon and rectum cancer: Hungary (31.3), Sri Lanka (5.0), global (12.8)

Stomach cancer: Mongolia (44.0), Maldives (3.2), global (12.6)

Liver cancer: Mongolia (114.7), Morocco (2.0), global (12.1)

Breast cancer: Tonga (24.7), Oman (4.0), global (7.9)

Other neoplasms: Malawi (37.6), Syria (2.6), global (6.4)

Esophageal cancer: Malawi (32.4), Syria (0.8), global (6.2)

Pancreatic cancer: Uruguay (12.8), Bangladesh (2.5), global (6.2)

Prostate cancer: Dominica (54.9), North Korea (1.9), global (6.1)

Leukemia: Syria (15.3), Bangladesh (1.9), global (4.6)

Non-Hodgkin lymphoma: Grenada (11.0), Kyrgyzstan (1.4), global (3.6)

Cervical cancer: Zimbabwe (28.7), Syria (0.6), global (3.5)

Brain and nervous system cancer: Palestine (8.3), Japan (1.2), global (3.2)

Bladder cancer: Malawi (11.8), Albania (0.9), global (2.9)

Lip oral cavity cancer: Kiribati (14.6), Syria (0.6), global (2.6)

Gallbladder and biliary tract cancer: Chile (11.3), Uzbekistan (0.6), global (2.5)

Ovarian cancer: Lithuania (5.9), United Arab Emirates (0.9), global (2.4)

Kidney cancer: Czech Republic (7.1), Bangladesh (0.5), global (2.0)

Other pharynx cancer: India (6.1), Syria (0.2), global (1.7)

Larynx cancer: Cuba (5.3), Japan (0.4), global (1.6)

Multiple myeloma: Dominica (5.9), Tajikistan (0.4), global (1.5)

Uterine cancer: Grenada (5.4), Maldives (0.5), global (1.3)

Malignant skin melanoma: New Zealand (6.6), Bangladesh (0.2), global (0.9)

Nasopharynx cancer: Malaysia (3.7), Chile (0.1), global (0.9)

Non-melanoma skin cancer: Zimbabwe (4.5), Bangladesh (0.2) global (0.8)

Thyroid cancer: Zimbabwe (2.3), Syria (0.2), global (0.6)

Mesothelioma: United Kingdom (2.6), Palestine (0.1), global (0.5)

Hodgkin lymphoma: Afghanistan (2.2), Japan (0.1), global (0.4)

Testicular cancer: Kiribati (1.0), Maldives (0.02), global (0.1)

NEW CANCER CASES PER 100,000 PEOPLE (AGE-ADJUSTED) IN 2016

Highest rates

Australia (743.8)

New Zealand (542.8)

United States (532.9)

Netherlands (477.3)

Luxembourg (455.4)

Iceland (455.0)

Norway (446.1)

United Kingdom (438.6)

Ireland (429.7)

Denmark (421.7)

Lowest rates

Syria (85.0)

Bhutan (86.0)

Algeria (86.7)

Nepal (90.7)

Oman (94.9)

Maldives (101.3)

Sri Lanka (101.6)

Niger (102.3)

Timor-Leste (105.9)

India (106.6)

CANCER DEATHS PER 100,000 PEOPLE (AGE-ADJUSTED) IN 2016

Highest rates

Mongolia (272.1)

Zimbabwe (245.8)

Dominica (203.1)

Hungary (202.7)

Grenada (201.0)

Uruguay (190.6)

Tonga (189.7)

North Korea (188.7)

Saint Vincent and the Grenadines (183.1)

Croatia (180.2)

Lowest rates

Syria (67.4)

Algeria (67.5)

Oman (69.2)

Maldives (72.0)

Sri Lanka (74.7)

Bhutan (78.6)

Uzbekistan (80.6)

Nicaragua (80.9)

Morocco (81.0)

Qatar (81.6)

CHICAGO - A test that analyzes free-floating DNA in the blood may be able to detect early-stage lung cancer, a preliminary report from the ongoing Circulating Cell-Free Genome Atlas (CCGA) study suggests.

The findings, from one of the first studies to explore whether sequencing blood-borne DNA is a feasible approach to the early cancer detection, will be featured in a press briefing today and presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.

"We're excited that the initial results from the CCGA study show it is possible to detect early-stage lung cancer from blood samples using genome sequencing," said lead study author Geoffrey R. Oxnard, MD, of Dana-Farber Cancer Institute. "There is an unmet need globally for early-detection tests for lung cancer that can be easily implemented by health-care systems. These are promising early results and the next steps are to further optimize the assays and validate the results in a larger group of people."

Early diagnosis is key to improving survival rates for lung cancer. A blood test that could be done through a simple blood draw at the doctor's office could potentially have a major impact on survival, but before such a test could be widely used, additional validation in larger data sets and in studies involving people who have not been diagnosed with cancer would be needed, researchers say.

Tests that analyze cell-free DNA in blood, known as "liquid biopsies," are already used to help choose targeted therapies for people already diagnosed with lung cancer. Until recently, there has been limited evidence to indicate that cell-free DNA analysis may be feasible for early detection of the disease.

The CCGA study has enrolled more than 12,000 of the planned 15,000 participants (70 percent with cancer, 30 percent without cancer) across 141 sites in the United States and Canada.

The new report is from the first sub-study from the CCGA, in which three prototype sequencing assays were performed on blood samples from approximately 1,700 participants. Twenty different cancer types of all stages were included in the sub-study (additional early results from the sub-study, including breast, gastrointestinal, gynecologic, blood and other cancers will be presented separately at the 2018 ASCO Annual Meeting).

In this initial analysis, researchers explored the ability of the three assays to detect cancer in 127 people with stage I-IV lung cancer. The assays were designed to detect cancer-defining signals (mutations and other genomic changes) that could be used in an early cancer detection test:

Targeted sequencing to detect non-inherited (somatic) mutations, such as single nucleotide variants and small insertions and/or deletions;

Whole-genome sequencing (WGS) to detect somatic gene copy number changes;

Whole-genome bisulfite sequencing (WGBS) of cell-free DNA to detect epigenetic changes.

At 98 percent specificity, the WGBS assay detected 41 percent of early-stage (stage I-IIIA) lung cancers and 89 percent of late-stage (stage IIIB-IV) lung cancers. The WGS assay was similarly effective, detecting 38 percent of early-stage cancers and 87 percent of late-stage cancers,
whereas the targeted assay detected 51 percent of early-stage cancers and 89 percent of late-stage cancers.

The initial results showed that all three assays could detect lung cancer with a low rate of false positives (in which a test indicates a person has cancer when there is no cancer). Of the 580 samples from people without cancer at the time of enrollment in the sub-study, five (less than 1 percent) had a cancer-like signal across all three assays. Of those five participants, two were subsequently diagnosed with cancer (one with stage III ovarian cancer and one with stage II endometrial cancer) - highlighting the potential for such tests to identify early-stage cancers.

Among participants with lung cancer, the study found that more than 54 percent of the somatic (non-inherited) mutations detected in blood samples were derived from white blood cells and not from tumors. These mutations are likely the result of natural aging processes (so-called clonal hematopoiesis of indeterminate potential, or CHIP) and will need to be taken into account when developing blood tests for early detection of blood cancers, noted Oxnard.

The researchers are verifying these results in an independent group of approximately 1,000 participants from CCGA as part of the same sub-study. Following this, they will continue to optimize the assays, then validate them in an even larger data set from CCGA. With increased sample sizes, machine learning approaches are expected to improve assay performance, Oxnard noted.

Early phase clinical trial results presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting 2018 of 258 patients with IDH1+ acute myeloid leukemia (AML) treated with the IDH1 inhibitor ivosidenib show an overall response rate of 41.9 percent, with median progression free survival of 8.2 months. Twenty-four percent of patients achieved a complete response.

The gene IDH1 is cousin to another AML driver, IDH2, which is targeted by the drug enasidenib, which earned FDA approval in 2017. Though the function of both IDH genes is complex, previous work has shown that mutations in either IDH1 or IDH2 can activate other oncogenes while muting the action of tumor-suppressor genes. Both enasidenib and now ivosidenib seek to disrupt the action of these mutated IDH genes.

The current study takes place in the context of increased understanding of the underlying genetics that drive AML.

"Ten years ago, the first cancer genome was sequenced, and it was from an AML patient," says Daniel A. Pollyea, MD, MS, investigator at the University of Colorado Cancer Center and clinical director of Leukemia Services at the CU School of Medicine. AML has remained a frontrunner in the genetic sequencing of cancer, leading to a robust understanding of the genes the drive the condition.

"We know about 50 or so genes that contribute to AML and now researchers are working to design and test drugs that treat the most common and the most powerful of these genes," says Pollyea, presenting author of the current study at ASCO. CU Cancer Center was one of the early sites to offer the current trial.

The conventional wisdom, Pollyea says, is that attacking AML will depend on developing targeted treatments against many, most, or all of these genetic drivers, and then sequencing patients' tumors to match individual cancers with the drug or drugs that target their specific genetic drivers. (In fact, this strategy encapsulates the philosophy of targeted treatments against cancer, in general.) Parallel to these efforts to match oncogenes with targeted treatments, Pollyea points out that strategies that attack leukemia stem cells also hold promise.

"I think ivosidenib is going to be an important weapon in the arsenal," Pollyea says. "It's a very well tolerated oral therapy for patients who have few options and it will be an important new tool for us to use."