Friday, March 06, 2020

Combined biopsy more likely to detect aggressive prostate cancers than standard biopsy alone

Using a combination of magnetic resonance imaging (MRI) to target and sample suspicious prostate tissue along with a standard prostate biopsy is significantly more likely to detect the most aggressive prostate cancers than standard biopsy alone.

This finding, published today in the New England Journal of Medicine, could allow a higher percentage of prostate cancer patients to avoid unnecessary treatment for slow-growing prostate cancers that are not likely to spread.

The new study was conducted by National Cancer Institute (NCI) researchers including one who is now at the University of Maryland School of Medicine (UMSOM).

    This study demonstrated that using a combination of both types of biopsies leads to more detection of prostate cancers and is less likely to miss aggressive cancers that can spread and kill."

    This is an important finding that will be practice-changing as we see more cancer centers adopting both types of biopsy methods. Those of us who have already adopted this cutting-edge technology can now give physicians and patients alike the confidence that their prostate cancer diagnosis is accurate and that hard-to- diagnose aggressive cancers are not being missed."
 

About one in nine men will be diagnosed with prostate cancer during his lifetime, according to the American Cancer Society.

Most men diagnosed with prostate cancer do not die from it, and many have milder forms of the disease that do not require immediate treatment but can instead be carefully monitored, called active surveillance, to make sure the tumor is not growing or becoming more aggressive.

Traditional biopsies, that use ultrasound imaging to locate the gland and randomly remove 12 core tissues samples, have been known to miss aggressive cancers, however, so doctors have not felt comfortable relying on them for treatment guidance for fear of under-treating patients with deadly tumors.

As a result, many men with milder forms of the disease have been over-treated with surgery or radiation which often leads to side effects such as impotence and incontinence.


In a targeted biopsy, MRIs of the suspected cancer are fused with real-time ultrasound images, creating a map of the prostate that enables doctors to pinpoint and test suspicious areas.

"With greater confidence in our ability to make an accurate diagnosis, we are better able to use more conservative approaches, such as active surveillance, to manage patients sparing them adverse side effects," says Dr. Siddiqui, who is also Director of Urologic Oncology and Robotic Surgery at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC).

The NCI-designated comprehensive cancer center offers MRI-targeted biopsy, with expanded treatment options, including focal therapy to surgically remove only the tumor, sparing the prostate.

For the study, Dr. Siddiqui and his colleagues evaluated 2,103 men who all had both traditional biopsies using ultrasound and targeted biopsies guided by MRIs to check for prostate cancer.

They then examined the prostate glands of 404 of these patients who were diagnosed with prostate cancer and had their gland surgically removed; they found that aggressive cancers went undetected in 16.8 percent of the standard biopsies compared to 8.8 percent of MRI-targeted biopsies; when the two biopsy methods were combined, only 3.5 percent of aggressive cancers were missed.

"These findings suggest that combined biopsy provides improved diagnostic accuracy over either systemic or MRI-targeted biopsy alone and better predicts the result of final histopathological analysis," the researchers wrote in the study.

The NCI conducted the study with data collected from June 2007 to January 2019. In 2015, the same group of researchers published a study in JAMA that found that 30 percent more high-risk prostate cancers were diagnosed with MRI-targeted biopsy than with the traditional approach.

In addition, 17 percent fewer low-risk cancers were diagnosed with the MRI-targeted biopsy, compared to the standard method. Dr. Siddiqui was the first author of the JAMA article. It led to large cancer institutions, such as UMGCCC, adopting both biopsy methods as the standard of care.


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Thursday, November 14, 2019

Two strains of one bacterium combine to cause deadly flesh-eating infection

A new study used genetic analysis to reveal how two different strains of a single species of flesh-eating bacteria worked in concert to become more dangerous than either one strain alone. The work suggests that other difficult-to-treat infections may be polymicrobial and treating only one organism in a polymicrobial infection could be the cause of many secondary infections and chronic infections that resist treatment. The results of the study were published in the Journal Proceedings of the National ,Academy of Sciences, 2019.

In recent years, scientists have found that serious infections that progress rapidly and resist treatment are often caused by multiple microbes interacting with one another. Very little is known about these so-called polymicrobial infections, but traditional diagnostic methods often misidentify them as monomicrobial, or single-microbe, infections.

"This research provides clear evidence that a very severe infection considered to be caused by a single species of a naturally occurring bacterium actually had two strains," said Rita Colwell, a Distinguished University Professor in the University of Maryland Institute for Advanced Computer Studies and a co-author of the study.

"One of the strains produces a toxin that breaks down muscle tissue and allows the other strain to migrate into the blood system and infect the organs." The original infection -cultured from a patient who developed the severe flesh-eating disease known as necrotising fasciitis- was diagnosed as a monomicrobial disease. Traditional diagnostics could only determine that the infection was caused by a single species of bacteria called Aeromonas hydrophila.

But the disease baffled clinicians when it rapidly turned deadly, requiring a quadruple amputation to save the patient's life. Through genetic analysis of the culture, Colwell and her team discovered important differences among the individual bacterial cultures that could not be detected through standard diagnostic methods.

The ability to identify the agents involved in polymicrobial infections, whether they are different species or variant strains of a single species, can significantly improve treatment outcomes for infected patients.

"When we treat with a given antibiotic, we're clearing an organism out of the body," Colwell said. "But if there's another organism that's participating in the infection and that's also pathogenic, then any antibiotic treatment that doesn't also target that organism may just be clearing ground for it to grow like crazy."

Treating only one organism in a polymicrobial infection could be the cause of many secondary infections and chronic infections that resist treatment. According to Colwell, a mixture of antibiotics or therapeutic drugs may be necessary to treat polymicrobial infections. Routinely using the genomic approach that was developed in this study to analyze infections could result in more effective targeted treatments for diseases caused by polymicrobial infection.

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Monday, September 30, 2019

Immunotherapy drugs when combined prevent melanoma progression

In a new trial, researchers have discovered that a combination of 2 immunotherapy drugs-ipilimumab and nivolumab- is capable of reversing or preventing the progression of advanced melanoma for 5 years or more in every 2 patients.

Just 10 years ago, only 1 in 20 patients with advanced melanoma would survive for 5 years- with many living for just 6-9 months.


The results of the trial,  represent the longest phase 3 trial follow-up for checkpoint inhibitor combination therapy.


In the past, metastatic melanoma was regarded as untreatable. Oncologists considered melanoma different to other cancers-- it couldn't be treated once it had spread. This is the first time we can say that the chances of being a long-term survivor of advanced melanoma are now over 50%, said one of the researcher.


Researchers incorporated 945 patients with advanced melanoma randomised into 3 groups- 314 patients received the ' double-hit' of nivolumab + ipilimumab; 316 patients received nivolumab + a placebo; and 315 patients received ipilimumab + placebo.


Each nivolumab arm was compared to ipilimumab by itself, and was administered until the disease progressed or until any side-effects became unacceptable.


The 5 year overall survival rate for the combination of nivolumab + ipilimumab was 52 %, with 74 % of those patients treatment-free after 5 years. The overall survival for nivolumab was 44 % and 26% for ipilimumab.


The Prof. explained, by giving these drugs together you're effectively taking 2 brakes off the immune system rather than one so that the immune system is able to recognise tumours it wasn't previously recognising and react to that and destroy them.


Importantly, for those patients who stopped treatment because of side-effects such as fatigue, skin rashes and diarrhea, the outcome was just as good as it was for those who were on the combination for longer.


One of the key points about immunotherapies is that the immune system can be re-educated even with a short duration of treatment. This is in contrast to other treatments like chemotherapy which can require a full course to be as effective.


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