Category: Cancer

Categories : CancerTags :

Pre-op Immune Checkpoint Inhibition in Lung Cancer

On By ModernMedia

According to a prospective multicenter trial, one fifth of patients with operable early-stage non-small cell lung cancer (NSCLC) had major pathologic responses (MPR) and over 40% had pathologic downstaging after neoadjuvant atezolizumab.

Out of 144 patients, 30 achieved MPR (defined as ≤10% viable tumour cells), 10 of whom had pathologic complete response (pCR), while 66 experienced downstaging and upstaging occurred in 29. 

Jay M Lee, MD, of the David Geffen School of Medicine at the University of California Los Angeles, explained: “The LCMC (Lung Cancer Mutation Consortium)3 study successfully met its primary endpoint of achieving major pathologic response in 21% of patients, and a pathologic complete response rate of 7%. Neoadjuvant atezolizumab monotherapy was well tolerated, with no new safety signals, and resection was performed with low perioperative morbidity and mortality, usually within a narrow protocol window, with a short time frame from completion of atezolizumab and with a corresponding high R0, or complete resection rate.”

Some 90% of patients were still alive at 18 months, and 80% were disease-free and alive. The findings indicate that neoadjuvant therapy with an immune checkpoint inhibitor (ICI) is possible thought it does make surgery harder, said invited discussant Shinichi Toyooka, MD, of Okayama University Hospital. Similar outcomes were seen in patients with stage I-II versus stage III disease, although survival data is currently lacking, requiring follow-up to find out if single-agent ICI is sufficient for all patients with operable NSCLC.

“I think single ICI can be used for early-stage disease and poor performance status,” said Toyooka. “On the other hand, a combination of ICI and chemotherapy is suitable for advanced-but-resectable cases.”

Minimally invasive surgery (robotic or VATS) was successful in 86 patients, and 15 others required conversion to thoracotomy. Lee said 79% of patients underwent lobectomy, and 3% had segmentectomy or wedge procedures. R0 (clear surgical margins) status was achieved in 92% of the 159 patients who went to surgery.

The trial included 181 patients with newly diagnosed, resectable stage Ib-IIIa and selected IIIb (T4 because of mediastinal invasion) NSCLC and no targetable mutations, of which 159 underwent surgery. 15 patients were later found to have EGFR/ALK-positive disease and excluded from analysis. Patients had radiographic staging before and after two cycles of atezolizumab and then underwent surgery within 30 to 50 days after finishing neoadjuvant therapy.

Minimally invasive surgery (robotic or VATS) was successful in 86 patients, and 15 others required conversion to thoracotomy; 79% of patients underwent lobectomy, and 3% had segmentectomy or wedge procedures. R0 (clear surgical margins) status was achieved in 92% of the 159 patients who went to surgery.

Source:MedPage Today

Presentation reference: Lee JM, et al “Surgical and clinical outcomes with neoadjuvant atezolizumab in resectable stage Ib-IIIb NSCLC: LCMC3 trial primary analysis” WCLC 2020; Abstract PS01-05.

Categories : Cancer GeneticsTags :

New Method to Pick up Mutations Behind Colorectal Cancer Risks

On By ModernMedia

University of Michigan researchers have developed a method to detect mutations which give rise to colorectal cancer.

Colorectal cancer is the third most common cancer type, and the second most common cause of cancer-related deaths in the United States. Although most cases occur sporadically, some 5 to 10% of cases are hereditary, the most common cause of which is Lynch syndrome. Lynch syndrome results in an 80% increase in the lifetime risk of developing colorectal cancer. Those with a family history of colorectal cancer are advised to start screening before age 45. However, genetic testing for cancer risk does not always provide useful information for those with family history.  

To address this, a new method of genetic testing was developed by Jacob Kitzman, PhD, of the Department of Human Genetics at Michigan Medicine plus together with other colleagues. Since mutations are rare in the human population, determining which one is responsible is difficult, and simply studying one in the lab is too time consuming to be practical.
With deep mutational scanning, the researchers measured the effect of MSH2 mutations, which is one major cause of Lynch syndrome

They deleted the normal copy of MSH2 from human cells with CRISPR-Cas, replacing it with a library of every possible mutation in the MSH2 gene. Each cell in the mix then carried a unique MSH2 mutation. Chemotherapy then killed off only the cells that had a functional variant of MSH2.

The counterintuitive idea, noted Kitzman, is that the surviving cells do not have functioning MSH2—which have mutations that are most likely to cause disease.

“We were basically trying to sit down and make the mutations we could so they could serve as a reference for ones that are newly seen or are amongst the thousands of variants of unknown significance identified in people from clinical testing,” says Kitzman. “Until now, geneticists could not be sure whether these are benign or pathogenic.”

It is hoped that with other patient-specific information, some of these variants could be reclassified, and those individuals advised to undergo more intense screening.

Kitzman said: “One of the next areas that will need some focus in the field of human genetics is to create these sorts of maps for many different genes where there is a clinical connection, so we can be more predictive when variants are found in an individual.”

Source: Medical Xpress

Journal information: Xiaoyan Jia et al, Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk, The American Journal of Human Genetics (2020). DOI: 10.1016/j.ajhg.2020.12.003

Categories : Cancer Diet and NutritionTags :

Breast Cancer in Mice Inhibited by Restricted Feeding Times

On By ModernMedia

Restricting calorie intake to an eight-hour window coinciding with physical activity reduced breast cancer risk in female mouse models.

Researchers from University of California San Diego School of Medicine, Moores Cancer Center and Veterans Affairs San Diego Healthcare System (VASDSH) found that the restricted feeding times, which are kind of circadian rhythm-linked intermittent fasting, enhanced metabolic health and tumour circadian rhythms in female mice with obesity-driven postmenopausal breast cancer. Breast cancer is the second most common cancer in US women, after skin cancer.

“Previous research has shown that obesity increases the risk of a variety of cancers by negatively affecting how the body reacts to insulin levels and changing circadian rhythms,” explained senior author Nicholas Webster, PhD. professor at UC San Diego School of Medicine and senior research career scientist at VASDSH. “We were able to increase insulin sensitivity, reduce hyperinsulinemia, restore circadian rhythms and reduce tumor growth by simply modifying when and for how long mice had access to food.”

Female mouse models mimicking postmenopausal hormone conditions were used to investigate if time-restricted feeding of obese mice affected the tumour growth and development, and reduced metastasis to the lungs. The mice were split into three groups, one with constant access to food, one with access for eight hours at night when they have the greatest activity, and the last was fed an unrestricted low-fat diet.

Obesity and menopause disrupt the circadian rhythm, with increased risk of insulin resistance and thereby chronic diseases such as cancer. A number of cancers are known to be associated with insulin resistance, such as breast cancer and pancreatic cancer. High insulin levels in obese mice drive tumour growth. Artificially increasing insulin levels has been shown to accelerate tumour growth whilst lowering them is similar to the effect of limiting eating.
Manasi Das, PhD, postdoctoral fellow in the Webster lab and first author, said: “Time-restricted eating has a positive effect on metabolic health and does not trigger the hunger and irritability that is associated with long-term fasting or calorie restriction. Through its beneficial metabolic effects, time-restricted eating may also provide an inexpensive, easy to adopt, but effective strategy to prevent and inhibit breast cancer without requiring a change in diet or physical activity.”

Webster believes that time-restricting eating warrants further investigations as it may present a way to reduce breast cancer risk, or that of cancer in general.

“The increase in risk of breast cancer is particularly high in women who are overweight and have been through menopause. For this reason, doctors may advise women to adopt weight loss strategies to prevent tumor growth,” said Das. “Our data suggests that a person may benefit from simply timing their meals differently to prevent breast cancer rather than changing what they eat.”

Source: Medical Xpress

Journal information: Manasi Das et al. Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models, Nature Communications (2021). DOI: 10.1038/s41467-020-20743-7

Categories : Ageing CancerTags :

Aspirin Protects against Colorectal Cancer

On By ModernMedia

Aspirin is known to reduce the risk of colorectal cancer in middle-aged adults and up until age 70, but has some risky side effects, such as colorectal bleeding. 

It was not known at what stage it was still worth it to start taking aspirin. Indeed, the recent Aspirin in Reducing Events in the Elderly (ASPREE) trial reported that participants taking a daily dose of aspirin (100mg) after the age of 70 for five years had a 30% increased risk of cancer mortality.
It is also currently recommended by the US Preventive Services Task Force that people aged 50-59 years with specific cardiovascular risk profiles take aspirin for its protective effect against heart disease.

To answer the question of whether aspirin was beneficial or harmful after age 70, Andrew T Chan MD, MPH, a gastroenterologist and chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital (MGH), led a team of researchers that analysed a pair of large cohort studies.These were The Nurses’ Health Study (January 1980 – June 2014) and the Health Professionals Follow-up Study (January 1986 – January 2014), giving them a total of 94 500 participants over 35 years.

Their findings showed that aspirin could indeed protect adults over 70 from colorectal cancer – with the caveat that the protection only applied if they started taking aspirin before the age of 70.”There is considerable evidence that aspirin can prevent colorectal cancer in adults between 50 and 70 years old,” commented Chan. “But it has not been clear whether the effect is similar in older adults.”

The researchers concluded that their results “strongly suggest that there is a potential biological difference in the effect of aspirin at older ages which requires further research.”

Source: News-Medical.Net

Categories : CancerTags :

Alcohol Linked to A High Proportion of Cancers

On By ModernMedia

A new study shows that cancer is attributable to a significant proportion of cancer cases across the United States.

It is well known that alcohol is linked to cancers, but the state-level data shows for first time the impact of different levels of alcohol consumption and its cancer effects. This is also concerning for South Africa as the country has high rates of alcohol use, consuming 5 billion litres of alcohol annually, around 9 to 10 litres of pure alcohol for each individual (and likely more if sorghum beer is counted).

From data spanning 2013 to 2016, the percentage of cancer cases that are linked to alcohol ranged from a high of 6.7% in Delaware to a low of 2.9% in Utah. Following this pattern, Delaware also had the highest proportion of alcohol-related cancer deaths (4.5%) and Utah had the lowest (1.9%).
Farhad Islami, MD, PhD, and a team at the American Cancer Society, said: “This information is important for prioritising state-level cancer prevention and control efforts to reduce alcohol consumption and the burden of alcohol-related cancers.”

Alcohol use was more tightly linked to certain cancers: the proportion of oral cavity/pharyngeal cancer cases attributable to alcohol ranged from 36% in Utah to 62.5% in Delaware and was over 45% in all but five US states.

The majority of cases and deaths from the examined cancer types were found more in men, reflecting men’s higher consumption of alcohol.

Overall, alcohol was attributable to 8% of all cancer cases and 3.2% of cancer deaths. The American Cancer Society’s guideline for Diet and Physical Activity for Cancer Prevention states that it is best to abstain from alcohol entirely, and if not to limit drinks to 2 per day for men and 1 per day for women.

Source: Science Daily

Journal information: Ann Goding Sauer, Stacey A. Fedewa, Priti Bandi, Adair K. Minihan, Michal Stoklosa, Jeffrey Drope, Susan M. Gapstur, Ahmedin Jemal, Farhad Islami. Proportion of cancer cases and deaths attributable to alcohol consumption by US state, 2013-2016. Cancer Epidemiology, 2021; 71: 101893 DOI: 10.1016/j.canep.2021.101893

Categories : Addiction CancerTags :

Nearly a Fifth of Cancer Patients on Opioids Misuse Them

On By ModernMedia

A new report reveals that 19% of cancer patients receiving opioids are misusing them, referred to a nonmedical opioid use (NMOU) behaviour. 

Opioid addiction remains a persistent and serious problem in the United States, and is growing elsewhere in the world, with some 16 million individuals worldwide suffering from opioid misuse disorder.
The study,  led by Sriram Yennurajalingam, MD, MS, of MD Anderson Cancer Center in Houston, included 1554 patients at a supportive care clinic for a comprehensive cancer centre. Of those engaging in NMOU behaviour, the most common (29%) was an early request for a refill, followed by self-directed dose escalation (15%), co-using illicit or non-prescribed drugs (13%), and impaired daily function due to opioids (11%).

Independent risk factors that increased the risk of NMOU behaviour included being single or divorced, as well as pain levels, opioid risk screening score, and morphine equivalent daily dose.

In their recommendations, Yennurajalingam and co-authors wrote: “Based on these findings, a universal screening, setting limits on opioid use by limiting supply, more intense follow-up with an interdisciplinary team to provide optimal use of medications for pain and symptom management, and the provision of counseling and support to patients and their family members may help prevent the development of these NMOU behaviors.”

Source: MedPage Today

Journal information: Yennurajalingam S, et al. Frequency of and factors associated with nonmedical opioid use behavior among patients with cancer receiving opioids for cancer pain, JAMA Oncol 2020; DOI: 10.1001/jamaoncol.2020.6789.

Categories : CancerTags :

Opioid Use Linked to Pancreatic Cancer Risk

On By ModernMedia

New research has shown that the use and misuse of the highly addictive opioid class of medications may pose an additional threat – pancreatic cancer. 

In the United States, opioid misuse has spiralled into one of the biggest healthcare epidemics facing the country. Of 70 000 deaths from substance abuse in the country in 2017, 68% involved opioids. Among patients prescribed opioids for chronic pain, 29% are misusing them and 12% have developed an opioid misuse disorder. Rates of pancreatic cancer are also on the increase in the US. In West Central Asia, opium use recently been linked to pancreatic cancer.Using Centres for Disease Control (CDC) data, the study’s researchers controlled for confounding variables, took opioid death rates as a surrogate for proscription and misuse, and compared it to incidences of pancreatic cancer. 

Analysing the dataset, they found that opioid use was associated with pancreatic cancer rates, with the opioid use rates predicting the pancreatic cancer trends years later.Faraz Bishehsari, MD, Ph.D., the corresponding author of the study, said: “Our mechanistic studies could provide further insights on the pathways that opioid could potentially impact progression of cancer.”

In order to confirm the findings, there is a need for sizeable population-based studies or longitudinal datasets that reliably track long-term outcomes in opioid users. Once these findings are confirmed by population-based studies, these will have an impact in considering alternative pain management methods in patients.Adding credence to this link is a recent post-hoc analysis of advanced cancer patients that showed patients receiving regular opioid antagonists had a significantly improved survival rate over placebo.

Source: Medical Xpress

Journal information: Usman Barlass et al. Opioid use as a potential risk factor for pancreatic cancer in the United States: An analysis of state and national level databases, PLOS ONE (2021). DOI: 10.1371/journal.pone.0244285

Categories : Cancer Lab Tests and ImagingTags :

New Multi-cancer Blood Test Offered by NHS

On By ModernMedia

A new blood test developed by the California-based Grail company tests for DNA methylation, and is supposedly able to screen for over 50 cancer types this way.

The NHS is to offer the test to 165 000 people from the middle of next year, with 140 000 screened through their medical records and the remaining 25 000 through referrals from suspected symptoms. It is hoped that widespread screening and early detection will drastically improve cancer survival rates, consequently easing pressure on healthcare services.

Lawrence Young, a professor of molecular oncology, at Warwick University, said the Galleri test was one of several novel blood tests being developed to spot cancer early on. “A publication from the Circulating Cell-free Genome Atlas consortium examining the Galleri test in 6 689 participants has generated very encouraging results in more than 50 different cancers at different stages of development.”

However, there was disagreement from some cancer experts regarding Galleri’s  potential effectiveness. Paul Pharoah, a professor of cancer epidemiology, at Cambridge University, said that it was premature for the NHS to embrace an unproven test. He said, “The Galleri blood test is a test that might be able to detect cancer in the blood in individuals with early cancer, though the evidence that it does this effectively is weak,” Pharoah said. According to him, only a single published paper on the tests was available, wherein they detected a mere 25% of early-stage cancers and under half of late-stage cases.

Source: The Guardian

Categories : CancerTags :

Ovarian Cancer Risk not Raised by Fertility Treatments

On By ModernMedia

Existing research has thus far indicated that women who used assisted reproduction technologies (ART) were at greater risk for ovarian cancer and non-malignant borderline ovarian tumours resulting from overstimulation of the ovaries.

The tumours were proposed to be caused by excess sex hormones and disruption of ovarian tissue from multiple punctures. A pair of meta-analyses in 2013 indicated that women who used reproductive technologies were at increased risk of ovarian cancer, but no causative link was established; infertility itself could have caused the increased risk.

Researchers in the Netherlands used a database of 30 625 women who received ovarian stimulation for ART between 1983 and 2001 and 9 988 women who were infertile but did not use ART. These were linked to the Netherlands Cancer Registry and the Dutch Pathology Registry to check for invasive and borderline ovarian cancers.

Though there was an increase in ovarian cancer in women who had received ART, the increase was due to women who had received ART but not been able to fall pregnant: not having had a pregnancy has shown to be a risk factor for ovarian cancer.

Source: Medical Xpress