Immunotherapy for Cancer

The latest approval of a cancer drug by the US Food and Drug Administration (FDA) changes the paradigm of cancer treatment — the new indication specifies a genetic defect without any mention of tumor types. It allows the drug to be used in any cancer that harbors the specified genetic defect, wherever the tumor appears in the body.

What: Historically, the US Food and Drug Administration (FDA) has approved cancer treatments based on where in the body the cancer started — for example, prostate or breast cancers. For the first time, the FDA approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.

Details: The new approval is for the immunotherapy pembrolizumab (Keytruda, Merck & Co), which is already approved for use in several different tumor types, including melanoma and lung cancer. But this latest approval covers the use of pembrolizumab in tumors that have microsatellite instability-high (MSI-H) or are mismatch repair deficient (dMMR). These defects are found most commonly in colorectal, endometrial, and gastrointestinal cancers but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland, and other places, the agency notes.

Microsatellite instability & immunotherapy: It’s not just colorectal cancer: The results from that trial showed that patients with colorectal cancer with normal DNA repair (microsatellite stable) had zero response to pembrolizumab, whereas those with MSI and deficient DNA repair had a 50% response rate, she said. In addition, about 20% had stable disease. This is much higher than has been seen with immunotherapy in other tumor types, where fewer than 20% patients respond. But the trial also included patients with any solid tumor and MSI, and these patients also showed the 50% response rate and 20% stable disease results.

Downsides: Common side effects of pembrolizumab include fatigue, itchiness, diarrhea, decreased appetite, rash, fever, cough, dyspnea, musculoskeletal pain, constipation, and nausea. The drugs can also cause serious immune-mediated side effects, including lung, liver, kidney, or colon inflammation, endocrine problems.

Action point: All patients with advanced cancer who have had at least one standard therapy should be tested to see if their tumor harbors these genetic defects.

I’m Dr. Michael Hunter.

http://www.medscape.com/viewarticle/880537

Can We Sort Cancer Cells with Sound Waves?

What You Need to Know: Researchers from MIT, Pennsylvania State University, and Carnegie Mellon University have devised a new way to separate cells by exposing them to sound waves as they flow through a tiny channel. Their device, about the size of a dime, could be used to detect the extremely rare tumor cells that circulate in cancer patients’ blood, helping doctors predict whether a tumor is going to spread. Separating cells with sound offers a gentler alternative to existing cell-sorting technologies, which require tagging the cells with chemicals or exposing them to stronger mechanical forces that may damage them.

“Acoustic pressure is very mild and much smaller in terms of forces and disturbance to the cell. This is a most gentle way to separate cells, and there’s no artificial labeling necessary,” says Ming Dao, a principal research scientist in MIT’s Department of Materials Science and Engineering and one of the senior authors of the paper, which appears this week in the Proceedings of the National Academy of Sciences.’

How They Do It: To sort cells using sound waves, scientists have previously built microfluidic devices with two acoustic transducers, which produce sound waves on either side of a microchannel. When the two waves meet, they combine to form a standing wave (a wave that remains in constant position). This wave produces a pressure node, or line of low pressure, running parallel to the direction of cell flow. Cells that encounter this node are pushed to the side of the channel; the distance of cell movement depends on their size and other properties such as compressibility.

However, these existing devices are inefficient: Because there is only one pressure node, cells can be pushed aside only short distances.
The new device overcomes that obstacle by tilting the sound waves so they run across the microchannel at an angle — meaning that each cell encounters several pressure nodes as it flows through the channel. Each time it encounters a node, the pressure guides the cell a little further off center, making it easier to capture cells of different sizes by the time they reach the end of the channel.

This simple modification dramatically boosts the efficiency of such devices, says Taher Saif, a professor of mechanical science and engineering at the University of Illinois at Urbana-Champaign. “That is just enough to make cells of different sizes and properties separate from each other without causing any damage or harm to them,” says Saif, who was not involved in this work.

My Take: Circulating tumor cells in clinical settings are very rare: A 1-milliliter sample of blood may contain only a few tumor cells. If we can detect these rare circulating tumor cells, we may be able to study their biology and determine whether the patient is at a high risk for the cancer taking hold in organs such as the liver, lungs, bones, or brain. While not ready for clinical use, this method is a move in the direction of better detecting circulating tumor cells in the body. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Can a simple handshake predict cancer survival rates? Yes.

Doctor and patient meeting handshake greeting

New acquaintances are often judged by their handshake. Research has now recognized the simple squeeze as an important diagnostic tool in assessing strength and quality of life among critical care patients.

In a study published in the journal, Support Care Cancer, Concordia professor Robert Kilgour and his colleagues at the McGill (Montreal, Canada) Nutrition and Performance Laboratory confirmed a link between handgrip strength and survival rates.

The test was simple: 203 patients fighting advanced-stage cancers squeezed a device known as a dynamometer with their dominant hand. The instrument then measured peak grip strength.

Because it requires minimal equipment, this method of evaluation is both portable and practical, says Kilgour: “This measure is one of several to categorize patients according to the severity of their disease. It can help determine interventions they may need, whether clinical, nutritional or functional.”

While other diagnostic tests rely on a patient’s self-reporting or examine related factors such as decreased body weight,the handgrip test directly focuses on body strength. Its precision allows doctors to better assess a patient’s decline. Clinicians typically classify patients by percentiles; those in the bottom 10th percentile are in the most serious condition, while those in the 25th are somewhat stronger. In most cases, slowing a patient’s decline and maintaining a decent quality of life can be a significant accomplishment.

Kilgour and his colleagues believe the grip test may help all categories of patients, especially those in the 25th percentile. At this stage, even modest interventions, like starting exercise or a diet change, can yield results, boosting both the physical and mental health of patients.

My Take: Seems logical, at least for those with advanced cancer. I hope to never see you as a patient with cancer, but if I do, please don’t crush my hand too much! I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: R. D. Kilgour, A. Vigano, B. Trutschnigg, E. Lucar, M. Borod, J. A. Morais. Handgrip strength predicts survival and is associated with markers of clinical and functional outcomes in advanced cancer patients. Supportive Care in Cancer, 2013; 21 (12): 3261 DOI: 10.1007/s00520-013-1894-4


Steroids Help With Fatigue Linked to Advanced Cancer

Close-up of a businesswoman resting her head on her hand

Take-Home Pearl: Dexamethasone (steroid) can significantly improve cancer-related fatigue among those with advanced cancer. It also improves lack of appetite, but not psychological distress.

Background: Fatigue is the most common cancer-related symptoms among those with advanced disease. While there is data to support the use of steroids, only about 1/3 oncologists prescribe steroids.

Study Design: Prospective, randomized double-blind, placebo-controlled multi-institutional study. 132 patients with advanced cancer had at least 3 symptoms in the prior 24 hours (pain, fatigue, nausea with lack of appetite or with significant weight loss, sleep disturbance, depression). All had hemoglobin levels of at least 9, neutrophils at least 750, and a life expectancy of at least 4 weeks.

  • Randomization: Dexamethasone 4 mg twice daily for 14 days or placebo.

Results: Compared with placebo, dexamethasone produces a rapid and significant improvement in cancer-related fatigue and quality of life, with no significant increase in adverse events among patients with advanced cancer.

My Take: Steroids typically provide only temporary relief. Thus, we don’t fully understand their use for chronic fatigue. Long-term steroid use is not without toxicity. Still, this study provides more incentive to use steroids for short-term pain relief among those with a limited life expectancy. I’m Dr. Michael Hunter.

Reference: Yennurajalingam S et al. J Clinical Oncology 2013;31 (September 1): 3076-3082.