Cancer

A recent Stanford Hospital & Clinics video tells the story of a patient with colorectal cancer whose treatment wound up being much different than he had expected. “You’ll need a colostomy, I’m 100 percent certain,” was what William Mussone was told when he was first diagnosed at a local hospital. But after coming to Stanford for a second opinion, he discovered that physicians here had other ideas on how to manage the disease over its years-long course. Click play to hear his story.

Previously: No day on the beach: A colon cancer survivor’s story

My colleague writes today of the passing of Karl Blume, MD, a major figure in bone marrow transplantation at Stanford. Referred to by colleagues as a deeply valued visionary who had a strong commitment to his patients, Blume directed the Division of Bone Marrow Transplantation from 1987 until 2000 and would later lead Stanford’s effort to attain Cancer Center designation from the National Cancer Institute.

From the obituary:

Blume not only built the bone marrow transplantation program at Stanford from the ground up, but he also shepherded it through a multitude of clinical advances and changes. During his tenure, the process of transplantation evolved from a reliance on whole bone marrow, often from a patient or a patient’s relative, to the use of blood stem cells that can be harvested from the plasma of an unrelated, matched donor. The program grew from about 40 transplants during its first year in 1987 to more than 300 transplants during 2012.

“We’ve seen an incredible evolution of this treatment over time,” said Robert Negrin, MD, current chief of the blood and marrow transplant program. “Karl always brought a sense of commitment to the patients and their experience. He also encouraged discipline in the design of clinical trials, which enabled the field to move forward with rigor and clarity. He excelled in his ability to relate to many different kinds of people and personalities and to bring them together to work toward a common goal in a very effective way.”

In 2003, Blume dedicated himself to achieving National Cancer Institute-designated Cancer Center status for the Stanford Cancer Institute, which would afford greater access to NCI resources, funding and clinical trials. The designation was awarded by the NCI in 2007 after a three-year grant application process.

When I first interviewed Brian Kobilka, MD, winner of the 2012 Nobel Prize for Chemistry in October, I was struck by an off-hand comment about his motivation for his near-obsessive two-decades long research quest to uncover the workings of GPCRs, or G-protein-coupled receptors, which serve as one of the main methods of molecular communication within the body.

The research, which it’s believed will lead to the creation of new drugs for clinical care, was not originally done for this purpose. It was motivated by simple scientific curiosity – the kind that often leads to amazing discoveries that help cure suffering or save lives. Initially, Kobilka just really wanted to know how it worked.

In a story published in today’s Inside Stanford Medicine,  I describe the success of research based on scientific curiosity in leading to clinical care breakthroughs. The story describes the 30-year history of scientific breakthroughs that led to the approval of a new drug called vismodegib that is used to treat inoperable basal cell carcinomas, and how the drug helped save the eyesight of 101-year-old Winnie Bazurto of San Mateo, Calif. It’s a story that begins with a similar motivation – basic scientific interest – and ends with discoveries that help patients in a very practical way. As Jean Tang, MD, PhD, Bazurto’s dermatologist and vismodegib researcher, says in the article:

If a patient only knew the whole story — how the happenstance of science led to their treatment… If they could go back to when this molecular pathway was first discovered in fruit flies, they’d be amazed. It’s not until the dots are connected 30 years later that it begins to make sense.

Stanford’s Matthew Scott, PhD, one of the key players in this basic-science success story, commented to me in an e-mail just how essential it is for future clinical discoveries that basic science continues to be funded. He expressed concern about a current trend toward conservatism in funding that requires much quicker results that lead to treatment options for patients saying, “Current conservatism in funding asks for translational work that gives cures in a few years (which never happens). Far-sighted funding of basic science … pays off big time.”

The vismodegib story illustrates just how essential basic science is to the future of clinical discoveries:

For many of the basic scientists involved in this research, the clinical use of hedgehog-inhibiting drugs to treat patients like Bazurto — while not the original goal of their research — is the ultimate success.

Previously: Why basic research is the venture capital of the biomedical world, Future of medical research is at risk, says Stanford medical school dean and The economic benefits of publicly funded medical research
Photo by Norbert von der Groeben

Fisher, Fleshman, Eshoo, Swayze and Rubin (L-R) at yesterday’s press conference.

In a press conference held at Stanford Hospital & Clinics yesterday, Rep. Anna G. Eshoo (D-Palo Alto) announced the passage of a new law aimed at developing better treatments and potential cures for the deadliest of cancers.

Signed into law by President Obama on January 3, the Recalcitrant Cancer Research Act, requires the National Cancer Institute to examine its current research efforts on cancers with very low survival rates, including pancreatic and lung cancer, and work to develop early detection methods and better treatment options to improve outcomes. The NCI will develop a long-term plan, or scientific framework, for pancreatic and other recalcitrant cancers to gauge its current efforts in the disease and make recommendations on ways to speed progress.

Eshoo was joined by Lisa Niemi Swayze, Patrick Swayze’s widow and chief ambassador of hope for the Pancreatic Cancer Action Network; Stanford oncologist George Fisher, MD, a leading cancer-research advocate who treated Patrick Swayze for pancreatic cancer; and Julie Fleshman, president and CEO of the Pancreatic Cancer Action Network. Eshoo was introduced by Amir Dan Rubin, president & CEO of Stanford Hospital & Clinics.

In her speech, Eshoo explained the signficance of the law:

This is larger than a piece of legislation. This is about hope for families and people across our country. We are here in a place that does the most superb research in the world and to speed up the research and to move these recalcitrant cancers to the top of the list at the NCI is absolutely essential for us to make progress.

Fisher also shared his views as a physician and researcher:

When patients come to me with pancreatic cancer, they come to me with both hope and fear. They fear what they’ve read. They fear the statistics we’ve already heard today. But they hope they can beat the odds and that some cutting edge treatment will give them a better outlook in life, more time, or maybe chance for a cure. We do cure some, but only some. My patients deserve better than that. They deserve better than what I can offer them.

I’m confident that the success that we will achieve in pancreas cancer through this effort will have a tremendous trickledown effect. If we can beat one of the toughest cancers, we’re going to have gains in many other cancers.

Previously: New clues arise in pancreatic cancer from Stanford researchers
Photo by Norbert von der Groeben/Stanford Hospital

Several cancers associated with human papillomavirus (HPV) infection are on the rise in the U.S., but the country’s HPV vaccination rates remain dismally low, according to the just-published Annual Report to the Nation on the Status of Cancer.

This year’s report, which focuses on cancer data from 1975 to 2009, includes lots of good news, such as ongoing declines in the nation’s overall cancer death rate and in the incidence of many kinds of cancer. But the HPV-associated cancers, highlighted in a special section of the report, present a less rosy picture.

When the first HPV vaccine was introduced in 2006, physicians welcomed the opportunity to protect patients against cancers linked to HPV, the most common sexually transmitted infection. But doctors have faced an uphill battle convincing parents to give their kids the vaccine, which is now recommended for all 11- and 12-year-old boys and girls.

“Some parents are under the mistaken impression that ‘if I give my kids the vaccine, I’m giving them license to have sex,’” said Packard Children’s adolescent medicine specialist Sophia Yen, MD, when I asked for her opinion of the reason for low U.S. vaccination rates.

As the new report describes, by 2010, only 32 percent of U.S. girls aged 13 to 17 had received the entire three-dose series of injections. (The vaccine has been recommended for boys only since 2011, so vaccination rates among boys are even lower.) In contrast, more than half of Canadian girls in the same age group have completed the vaccination series, as have more than 70 percent of teen girls in Australia and the U.K.

Meanwhile, in the U.S., the incidence of HPV-associated cancers of the mouth, throat, anus and vulva increased between 2000 and 2009, the new report says. Cervical cancer, which is also associated with HPV, declined over the same period, but still accounts for more than half of HPV-associated cancers in women.

When she’s talking with parents about the HPV vaccine, Yen has some favorite talking points:

• The HPV vaccine is a safe and effective way to protect against many HPV-associated cancers and genital warts.

• HPV vaccination elicits a stronger immune response in younger kids, so it’s best to give children the series of shots at the recommended age of 11 or 12 instead of waiting for them to make their own decision about receiving the vaccine at age 18, as some parents say they want to do.

• If you’re uncomfortable discussing it with your pre-teen, you don’t have to tell your child the vaccination has anything to do with sex.

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A shortage of a cancer drug used to treat Hodgkin lymphoma has been linked to increased cancer relapses among children with this type of lymphoma, or cancer of the lymph glands, according to a report released today in the New England Journal of Medicine.

Chemotherapy drug shortages have been in the news a lot this year, with heart-wrenching reports focusing on families who were told their children’s chemo might become unavailable. So far, most chemotherapy shortages have been resolved in time to give patients the treatment they needed, but the drug shortages continue to threaten the treatment of many pediatric and adult patients.

The finding implies that some pediatric cancer patients [experienced] more acute and long-term side effects than they would have had the mechlorethamide shortage not occurred

The mechlorethamine shortage, which began in 2009 and ended recently, was different. The drug, one of a group of chemotherapy medications typically used to treat Hodgkin lymphoma, was completely unavailable for more than two years. In its absence, doctors had no choice but to substitute a different drug, cyclophosphamide, into the chemo regimens of their patients with Hodgkin lymphoma. This substitution seemed very reasonable because the two drugs are close relatives and work by similar mechanisms.  In fact, cyclophosphamide has been used to treat patients with Hodgkin lymphoma for many years.

Three pediatric cancer researchers, including scientists at St. Jude Children’s Research Hospital, the Dana-Farber Cancer Institute, and Stanford’s Michael Link, MD, analyzed the consequences of the substitution. Initially, they thought the two drugs would work equally well, but they found something quite different.

Using a chemotherapy regimen that included mechlorethamide, 88 percent of patients were cancer-free two years after completing therapy; among patients who received the same regimen but with cyclophosphamide instead of mechlorethamide, only 75 percent were cancer-free two years after therapy ended. The patients who developed relapse required additional, intensive therapies, including bone marrow transplants to treat recurrence. Although doctors gave the best treatments they had available and all patients are still living, the finding implies that some pediatric cancer patients received additional therapy associated with more acute and long-term side effects than they would have had the mechlorethamide shortage not occurred.

From our press release about the findings:

“This is a devastating example of how drug shortages affect patients and why these shortages must be prevented,” said Monika Metzger, MD, an associate member of the St. Jude Department of Oncology and the study’s principal investigator. “Our results demonstrate that, for many chemotherapy drugs, there are no adequate substitute drugs available.”

…

“This puts a face on the problem of drug shortages and shows that the problem is real, not theoretical. This is about a curative therapy that we were unable to administer because the drug we needed was not available,” Link said. “Despite heroic efforts by the drug shortage office of the Food and Drug Administration to solve the shortages of a number of medically necessary drugs, it is clear that patients are still suffering from the unavailability of life-saving drugs. A more systematic solution to the problem is needed.”

Previously: A Q&A on cancer-drug supply shortage; An in-depth look at the even-deeper problem of drug supply and Childhood leukemia patient on methotrexate shortage

From Dec. 24 to Jan. 7, Scope will be on a limited holiday publishing schedule. During that time, it may also take longer than usual for comments to be approved.

About one in four breast-cancer survivors eventually develops lymphedema, a painful inflammatory condition resulting from the blockage of lymphatic vessels that ordinarily drain fluid from the tissues throughout the body. While in the developed world lymphedema most often arises as an unintended consequence of radiation therapy for cancer, there are numerous other causes as well. An estimated 10 million people in the U.S. alone suffer from it.

But by the time the main symptom of lymphedema — swelling of one or more limbs — is detectable, the condition may have gotten such a foothold that it becomes difficult or impossible to reverse, at least given the treatment choices now available.

In a study just published in PLoS ONE, veteran vascular expert Stan Rockson, PhD, and his Stanford colleagues have identified a set of proteins circulating in blood whose levels accurately flag lymphedema’s presence. This could make a difference. As I wrote in my release about this study:

The only known way to diagnose lymphedema now is via physical inspection, and all too often it is misdiagnosed or overlooked altogether. But the biological events underpinning this condition may be present five years or more before symptoms become evident, said Rockson. Moreover, there are no effective drugs for combating lymphedema, just costly, time-consuming and annoying physical therapy, which virtually never completely eliminates the symptoms. While physical therapy can arrest progression and reduce swelling by as much as half, the condition typically remains a long-term problem. “Lymphedema virtually never just goes away on its own,” said Rockson. Indeed, it tends to progress in severity over time, whether it is treated or not.

When I asked Rockson about the findings’ significance, he told me,  “A standardized, accurate bioassay for lymphedema could help to pave the road for future human clinical trials of drugs to treat it.” Monitoring trial subjects at the molecular level with a lymphedema-detecting blood test could provide early evidence regarding whether an experimental treatment was working. Rockson is conducting clinical trials of pharmaceutical agents for lymphedema, and expects to incorporate the new test into those trials.

The upshot: some reason for optimism that a common but relatively neglected condition finally will be amenable to detection and, eventually, treatment with 21^st-century techniques.

Previously: New Stanford registry to track lymphedema in breast cancer patients and New breast cancer finding suggests limiting surgery
Photo by Kalyber

Every two weeks, I call my 99-year-old grandmother in Taiwan on Skype. And every time she repeats the same message before we sign off: “Eat well, sleep well, don’t work too hard.” This is exactly what she used to say to me when I was a child growing up in Taipei. Now, fifty years later and halfway around the world, she repeats the same advice to me as if I were still a little girl.

As much as I respected her, for most of my adult life I considered my grandma’s words a well-intentioned old wives’ tale. I am a woman of science, after all – a molecular epidemiologist who has devoted her life to cutting-edge cancer research. I believe in data, not proverbs.

Of course, it turns out that Grandma was right. I am now aware of abundant data suggesting that eating and sleeping well boost our immune function, minimize harmful inflammatory conditions and regulate hormonal metabolism, thereby lowering our risk for cancer.

Epidemiological studies suggest that consuming whole grains (containing fiber and vitamins), fruits and vegetables (antioxidants, fiber, and specific compounds such as sulforaphane in cruciferous vegetables), tomatoes (lycopene), allium vegetables such as garlic and chives, tofu (isoflavones) and fish (the omega-3-containing varieties) reduces the risk of cancer. Research also suggests that eating foods high in certain chemicals, such as heterocyclic amines found in some grilled foods, increases the risk of cancer.

Although we are still learning about the specific biological mechanisms underlying these epidemiologic findings, ongoing studies, including those at the Stanford Cancer Institute and the affiliated Cancer Prevention Institute of California (CPIC), are revealing the molecular relationships between dietary components and cancer risk.

The value of getting to sleep early (before 11 p.m.) and sleeping well long escaped the attention of scientists. I first became interested in sleep as a risk factor for cancer when epidemiologic studies began to show that rotating-shift workers have a higher risk of endocrine-related malignancies, including breast and prostate cancers.

Over the last seven years, my research group has investigated the association of circadian rhythms, including sleep duration, serum melatonin, and 9 circadian core genes, with prostate cancer risk. During the same period, laboratory studies have shown a link between circadian rhythms and inflammation. The numbers of different immune cells (e.g., “T-cells” or natural killer cells) have been shown to peak during different parts of the sleep/wake cycle. We have found evidence that several risk factors that appear to be related to inflammation – including gallstones, obesity, and diet – are risk factors for cancers of the prostate, gallbladder and liver.

While I and other researchers continue our quest to understand the molecular steps involved in carcinogenesis and design the most effective interventions and medicines for cancer prevention, it is clear that we can behave better to reduce our cancer risk – even without knowing the detailed biological pathways – through a sensible lifestyle. My 99-year-old grandmother, who loves broccoli but doesn’t know anything about DNA methylation, is living proof. And her habits reveal a lot: She rises each day at 5 a.m. and is asleep at 11 p.m.; she eats three small meals daily, at exactly the same time; and she has a cup of coffee (containing phenols) every day at 3 p.m. My grandma believes that having healthy habits improves life, and I now have the data suggesting that they decrease cancer risk and improve life expectancy, as well.

Before I ever studied the role of circadian rhythms in cancer, my grandmother knew that sleeping well was good for her health. So I’m looking forward to my next conversation with my grandma. Perhaps if I listen well, I’ll find another pearl of wisdom that leads to my next research project.

Ann Hsing, PhD, MPH, is director of research for the Cancer Prevention Institute of California (CPIC). Part of the Stanford Cancer Institute, the CPIC conducts population-based research to prevent cancer and reduce its burden where it cannot yet be prevented.

This young football fan is rockin’ a SUNSPORT tattoo (the temporary kind) during a sun-drenched November afternoon at Stanford Stadium. The 27-23 victory over Oregon State was one of seven straight wins on the Cardinal’s dramatic run to the Rose Bowl.

SUNSPORT is a new education and research program to improve sun-protection knowledge and habits among Stanford student-athletes – as well as outdoor athletes and fans of all ages. The SUNSPORT logo tattoo delivers a message: “I’ve got my sunscreen on. Do you?”

A partnership among the Stanford Cancer Institute, the medical school’s Department of Dermatology, Stanford Athletics, and Stanford Hospital & Clinics, SUNSPORT is establishing the most comprehensive sun protection outreach and research program of any university in the country. SUNSPORT research focuses on surveying Stanford’s outdoor athletes to identify attitudes and sun-protection practices in this high-risk population, and program dermatologists also work closely with athletes, coaches and athletic trainers to improve sun safety behaviors.

Going to the Rose Bowl? Post your photos wearing the SUNSPORT logo on the Stanford SUNSPORT Facebook page. Tattoos are available by e-mailing a request with your mailing address to sunsportinfo@stanford.edu.

Photo by Kristin Nord/Stanford Department of Dermatology

Researchers at MIT and Brigham and Women’s Hospital have developed a new device that captures and isolates cancer cells from blood samples for analysis and that could lead to improved methods of patient monitoring. A recent MIT release describes the technology:

Inspired by the tentacles of a jellyfish, the team coated a microfluidic channel with long strands of DNA that grab specific proteins found on the surfaces of leukemia cells as they flow by. Using this strategy, the researchers achieved flow rates 10 times higher than existing devices — fast enough to make the systems practical for clinical use.

Using this technology… doctors could monitor cancer patients to determine whether their treatment is working.

“If you had a rapid test that could tell you whether there are more or less of these cells over time, that would help to monitor the progression of therapy and progression of the disease,” says Jeff Karp, an associate professor of medicine at Harvard Medical School and co-director of the Center for Regenerative Therapeutics at Brigham and Women’s Hospital in Boston.

The above image illustrates how cells traveling through a microfluidic device can be trapped by strands of DNA, which are shown in green.

Previously: Researchers use ultrafast microscopic camera to detect cancer cells in the bloodstream
Photo by Suman Bose and Chong Shen, MIT