Cancer in the Family

Posted By SHL Librarian

Presented by: Kerry Kingham, MS, CGC
Genetic Counselor, Cancer Genetics Clinic
Stanford Center for Clinical Informatics
September 30, 2009

Lecture Overview:

Although most cancers are not “inherited,” some families are particularly susceptible to cancer and may benefit from early detection or other risk reduction strategies.

  • The most common inherited cancers include breast, ovarian, and certain kinds of colorectal cancer.
  • A BRCA mutation is linked to a higher risk of developing breast cancer and ovarian cancer, and a higher risk for male breast cancer.
  • Genetic tests can help patients understand their risk of develop cancer and allow them to make educated decisions about screening and preventive measures

Hereditary cancer is the development of cancer due to an inherited gene mutation that has been passed from parent to child. People who have inherited a gene mutation have also inherited an increased risk to develop cancer that is higher than those in the general population.

Inherited cancers begin in the DNA, the body’s cellular blueprint. Each cell contains two sets of chromosomes—one from the father and one from the mother—that replicate each time a cell divides. Genes are segments of DNA carried on the chromosomes that determine specific characteristics. Though the body makes proteins to control mutations before cell division, when certain mutations are part of the original programming, they can lead to cancer.

Although most cancers are not “inherited,” some families are susceptible to cancer and may benefit from early detection or other risk reduction strategies. Specialists in the Stanford Cancer Genetics Clinic can help patients and their families understand the genetic contributions to cancer and develop personalized plans to manage their risk.

“As genetic counselors, we translate the information we find to help families make educated choices,” said Kerry Kingham, MS, CGC, a genetic counselor who explained the process at a presentation sponsored by the Stanford Hospital Health Library. “We provide short-term counseling, offering empathy as we help them to understand the impact of getting tested and their test results. And because we work closely with oncologists, we are able to explain various screening and prevention options.”

Most inherited genetic mutations that cause cancer are autosomal dominant, passed along in the dominant gene. “This means that the person has a 50 percent chance of having the mutated gene passed along—not that 50 percent of these people will get cancer,” said Kingham.

The most common inherited cancers include breast, ovarian, and certain kinds of colorectal cancer. Of the 12 percent of the population who develop breast cancer, the majority (70-80 percent) have sporadic cancer—the kind that develops from environmental factors or other causes. Only about 10 percent have the inherited form of breast cancer. In the 2 percent of the population who develop ovarian cancer, the ratio remains about the same, with about 10-15 percent carrying a genetic mutation.

Women with a BRCA1 gene mutation have a 65 percent chance of developing breast cancer, tend to have early-onset cancer, have a higher risk of developing a second primary breast cancer later on, and are at higher risk for ovarian cancer. The mutation affects about one person in 400 in the general population and about one in 40 in Ashkenazi Jews. A BRCA2 mutation is linked to a higher risk of developing breast cancer and ovarian cancer, and a higher risk for male breast cancer.

Though the BRCA test itself is expensive, Kingham said that insurance usually covers the costs if certain criteria are met. Tests are less expensive for people from the Ashkenazi Jewish population and even less for that group if previous tests have shown that the mutation is already in the family.

Tests are available for two types of inherited colon cancer: hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP). People with HNPCC must undergo early and regular screening since they have a much higher risk of developing the polyps that can lead to colon cancer. People with FAP develop thousands of polyps at a very young age and often need to have their colon removed.

Before being tested, counselors go over an extensive list of criteria, check medical records of relatives, and talk to families as a group to clarify details. They look for certain trends and characteristics, such as the first-degree relatives affected, early-age onset, bilateral tumors, or multiple primary cancers. If a woman tests positive for a mutation, counselors will recommend early screening and discuss options like a prophylactic mastectomy or removing the ovaries.

“We’re in the cancer prevention business,” said Kingham, who interviews several generations of a family whenever possible. “We try to provide a balance between prevention and screening, and we work together to get as accurate information as possible. Our goal is to provide clear options for medical or surgical interventions, and to make sure the patient understands the risk before making a medical decision.”

About the Cancer Genetics Clinic
The Stanford Cancer Genetics Clinic offers testing and counseling for people who are concerned about the risk of inherited cancer. The clinic’s specialists help patients and their families understand the genetic contributions to cancer and develop personalized plans to manage their risk. Services include individualized cancer risk assessments based on medical and family history, detailed discussions of options for genetic testing, and recommendations for preventive screening and treatments.

The clinic provides counseling for several types of inherited cancer, including colon, breast, and ovarian.

For More Information:

Stanford Health Library can do the searching for you. Send us your medical questions.

Cancer Genetics Clinic
http://cancer.stanford.edu/patient_care/services/geneticCounseling/

Stanford Cancer Center
http://cancer.stanford.edu/

Cancer Genetics (National Cancer Institute)
http://www.cancer.gov/cancertopics/prevention-genetics-causes/genetics

Genetic Testing for Breast and Ovarian Cancer Risk (National Cancer Institute)
http://www.nci.nih.gov/cancertopics/Genetic-Testing-for-Breast-and-Ovarian-Cancer-Risk

Ovarian Cancer: Current and Novel Treatment Strategies

Posted By SHL Librarian

Presented by: Oliver Dorigo, MD, PhD
Associate Professor of Gynecologic Oncology
Stanford University Medical Center
August 22, 2013

Watch the video

Ovarian cancer affects about a quarter million women worldwide each year. When detected early on—when still confined to just the ovaries—it is a highly curable disease. However because it has no distinct symptoms, ovarian cancer is usually detected at a late stage. Once it metastasizes, survival rates are about 30 percent after five years. It is the 10th most common cancer in the United States and the fifth most common cause of cancer death.

New understanding of the basic biology of ovarian cancer has led to more accurate diagnosis and specialized treatments that are based on the location of the cancer and its cellular anatomy.

“There are several kinds of cells in the ovaries, and each cell type can generate a different tumor type with different prognosis and response to chemotherapy,” said Oliver Dorigo, MD, PhD, a professor of gynecologic oncology, who spoke at a presentation sponsored by the Stanford Hospital Health Library. “Even within each group there are different subtypes, so not every cancer is treated the same.”

Most ovarian cancer arises from the epithelial cells, which cover the surface of the ovaries. However it can also originate in the germ cells that produce eggs, in the stromal cells that produce hormones, or in the lining of the abdomen (peritoneum).

Though it’s not clear what causes ovarian cancer, at some point a genetic mutation turns normal cells into abnormal cells that grow and multiply out of control. As abnormal cells accumulate, they form a tumor, and cells can spread to nearby tissues and metastasize throughout the body.

Current Treatment Strategies
Treatment usually involves surgery followed by chemotherapy based on a detailed analysis of the genetics, genomics, and pathways of the disease. Scientists are consolidating their research in the Cancer Genome Atlas (TCGA), a National Institutes of Health-sponsored effort to study molecular aspects of human cancer to improve diagnosis, treatment, and prevention. “It’s a database for new knowledge,” said Dr. Dorigo. “The project will be extremely useful for developing future therapies, when we will have a different way to classify cancer based on specific genetic mutations.”

Currently initial treatment usually involves site reduction—an extensive operation to remove both ovaries, fallopian tubes, and the uterus as well as nearby lymph nodes and abdominal tissue known as the omentum, where ovarian cancer often spreads. Surgery involves the use of extremely accurate, minimally invasive robotic surgery techniques that require very small incisions and shorter recovery times.

“The first surgery is of utmost importance because the more cancer disease is removed the better the prognosis,” Dr. Dorigo said.

For almost all ovarian cancer patients, surgery is followed by several cycles of chemotherapy to destroy any remaining cancer cells, usually comprising a combination of a platinum drug and a taxane, such as Taxol. Chemotherapy can be done either intravenously through a vein or directly into the abdomen using intraperitoneal chemotherapy, which increases tumor exposure to the drugs.

Researchers are tracking patients and working with animal models in the laboratory to refine all aspects of chemotherapy, from dosage to timing of treatment to new combinations of drugs.

One recent study showed that intraperitoneal chemotherapy resulted in both longer progression-free survival when the disease does not get worse (an average of 24 months cancer-free compared to 18 months with intravenous chemotherapy) and overall survival (65 months compared to 49 months). Another study looked at modifying the timing of conventional chemotherapy (Taxol) from every three weeks to every week, and found marked improvement in survival rates. “The timing of treatment made a big difference,” said Dr. Dorigo.

Most women who undergo a combination of surgery and chemotherapy do go into remission. However 70 to 90 percent will have a recurrence of disease at some point. One of the biggest challenges in treating ovarian cancer is the development of platinum resistance, a change in the cancer cells’ DNA that makes them unresponsive to chemotherapy. Research is providing new insights into the molecular mechanisms of DNA repair pathways in these cells, and studies are looking adding new treatments to the initial therapy to prolong remission or prevent disease from returning.

Dr. Dorigo said there are a number of factors to consider when a cancer recurs, such as platinum resistance and platinum sensitivity, the extent of recurrence, the women’s tolerance for therapy or another surgery, quality of life, and clinical trials that may be available.

New Approaches
The future of ovarian cancer treatments lies in developing new targets based on how cancer cells grow, such as enzyme inhibitors to block growth factor pathways. Some studies are looking at ways to deprive cancer cells of the nutrients they need to grow and thrive. Tumors create an environment that encourages the growth of new blood vessels to deliver nutrients to the site, a process called angiogenesis. One anti-angiogenesis approach combined conventional chemotherapy with antibodies to stop vessels from growing in patients with advanced stage ovarian cancer.

Recently a promising new study combined an oral drug called pazopanib with conventional chemotherapy, and showed an increase in six-month progression-free survival.

Other research is looking at drugs that override mutations in the BRCA tumor suppressor genes. Mutations in BRCA1 and BRCA2 have been linked to an increased chance of developing ovarian cancer. In one study, a new drug called olaparib used BRCA as a biomarker and showed significant tumor shrinkage in subjects with BRCA mutations.

“These drugs use antitumor inhibitors to slow progression and decrease tumors, and appear to be very promising,” said Dr. Dorigo. “They are using completely different mechanisms than have been targeted prior.”

Another approach involves teaching the immune system to recognize and attack cancer. Tumors are able to block the immune system by using the molecule CD47 as a “don’t-eat-me” signal to immune system cells called macrophages. Early studies have shown that anti-CD47 antibodies can block this signal and allow macrophages to destroy the tumor cells.

“The CD47 trial is meaningful because high CD47 levels are associated with poor survival rates. The research showed impressive control of tumor development, and may be a step toward cancer vaccines and personalized medicine,” Dr. Dorigo said. “However these are still very early studies and it will be a while before they are approved as treatment.”

Dr. Dorigo encouraged women to take part in clinical trials to speed the process of refining scientific insights into new therapies and to gain access to treatment options that are not yet available.

About the Speaker
Oliver Dorigo, MD, PhD, is director and associate professor of the Division of Gynecologic Oncology and the director of the gynecologic clinical care program at the Women’s Cancer Center at Stanford. He is also director of the Mary Lake Polan Gynecologic Oncology Research Laboratory. Dr. Dorigo received his MD from the University of Heidelberg Medical School in Germany. He did a residency in obstetrics and gynecology at the University of Munich, followed by a research fellowship in cancer gene therapy at the Sidney Kimmel Cancer Center in San Diego. He completed his PhD in molecular biology at University of California, Los Angeles, and a clinical fellowship in gynecologic oncology at UCLA/Cedars Sinai Medical Center. Dr. Dorigo was an assistant professor at UCLA until he joined the Stanford faculty in 2013.

For More Information:

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About Dr. Dorigo

Stanford Gynecology Clinic

Department of Obstetrics and Gynecology

Stanford Women’s Cancer Center

Clinical Trials at Stanford

NIH Clinical Trials

New Insights into Breast Cancer Treatment and Survivorship

Posted By SHL Librarian

Moderator: Frederick M. Dirbas, MD
Physician Leader, Stanford Cancer Center’s Breast Disease Management Group
Thursday, October 7, 2010

Each year more than 190,000 American women are diagnosed with breast cancer, the second-most common type of cancer in the United States (skin cancer is first). As research and innovations in technology and treatments enable earlier detection and better care, more people are surviving cancer and living longer after a diagnosis. The National Cancer Institute estimates that 3 million people were living with cancer in the United States in 1971; today that number is close to 12 million.

There are more than 2 million breast cancer survivors today, which is creating a new niche of care because survivorship can lead to new health needs and concerns. Survivors can have heightened risks for long-term side effects from treatments or the disease, and they must deal with psychological issues, sexual concerns, pain, fatigue, and quality of life issues.

Stanford Supportive Care, a program that addresses these concerns by bridging medical care with non-medical healing, and the Stanford Health Library brought together several Stanford specialists to talk about the unique issues of breast cancer survivorship.

“After we treat the disease, we want to help patients live a full and healthy life,” said Frederick M. Dirbas, MD, Physician Leader of the Stanford Cancer Center’s Breast Disease Management Group, who moderated the panel of experts. “It’s important to bring our expertise together for patients, their families, investigators, and clinicians.”

Survivorship: Dealing With Feelings
David Spiegel, MD
Medical Director, Stanford Center for Integrative Medicine

Sadness and grief are normal reactions to a diagnosis of cancer, and for most people these feelings will come and go throughout treatment and afterwards. But as many as 25 percent of cancer patients suffer from depression and go undiagnosed.

“The worst time is when you are told you have cancer,” said Spiegel. “The second worst time is when the treatment is over. You lose your contacts and your routine, but your body reminds you all the time that you are a cancer survivor. It’s a difficult transition at many levels.”

It’s important to develop strategies to adjust to this transition, from health maintenance to social activities and family roles. And an important part of taking care of yourself is to manage your moods. Depression can have a direct effect on quality of life, and can also influence recovery time, pain thresholds, and even life expectancy.

“Cancer has an effect on the brain both in terms of emotion and cognition,” said Spiegel. “There is a relationship between psychological stress and cancer:  Emotional well-being can have a profound effect on health outcomes.”

Studies of cancer survivors have shown that that depression affects 25 percent of cancer survivors, compared to 3 percent of the general population. Depression, fatigue, poor sleeping patterns, and medications also affect memory, concentration, and mental agility-a condition referred to as “chemo brain.” Exercise and sleep can help, as can medication to help restore perspective.

Many cancer survivors benefit from group or individual psychotherapy. “Therapy can create an opportunity for emotional release, to learn new coping skills, and to develop new goals,” Spiegel said. “Dealing with your feelings-even negative ones-can help you covert from feeling damaged to being in a position of coping and even transcendence.”

Advances in Breast Cancer Surgery
Irene Wapnir, MD
Chief, Breast Surgery

How breast cancer is treated depends on the size of the tumor, whether the cancer is invasive or non-invasive, whether lymph nodes are involved, and whether the cancer has spread beyond the breast. There are gradients in each of those factors, however, that can complicate what surgery is most appropriate as well as outcomes.

For example, improved screening from mammograms and breast imaging has led to a 500 percent increase in finding invasive lesions, growths that can vary from normal cells to cancer. The surgical treatment of breast cancer has changed drastically over the years, from mastectomy to lumpectomy to axillary lymph node dissection (ALND).

Twenty years of data has shown outcomes to be almost equal for these surgical modalities, said Wapnir, but which one to use is based on the tumor size or whether the cancer is localized. “A lumpectomy preserves much of the breast but still increases chance of recurrence,” she said. “You have to be aware of how much risk you’re willing to accept.”

Improvements to lumpectomy techniques also make the option available to older and pregnant women as well as women with multiple cancers. Advances in reconstruction are also leading to better cosmetic outcomes.

“We are now in a better place in terms of choices, making the aftermath of surgery less frightening to women,” she said. “We have new procedures to avoid side effects like lymphedema and the ability to modify treatment regimens so we can get insight on what the tumor is like and select the best treatment more quickly and effectively.”

Sexuality and Breast Cancer Survivorship
Leah Millheiser, MD
Clinical Assistant Professor
, Obstetrics and Gynecology
Director, Female Sexual Medicine

Though there is not much data available on female sexuality problems after cancer treatment, it appears to be a significant issue. One large-scale study found that while 80 percent of responders reported a good or satisfying sex life before treatment, 70 percent reported sexual problems after treatment.

“The most common concerns are body image issues and hot flashes,” said Millheiser. “Since early-onset menopause is a result of cancer treatment, there are real physical problems, such as vaginal dryness, pain during intercourse, and vaginal shrinkage. And for younger women, especially, there is the increased emotional distress of dealing with infertility.”

Because estrogen is closely related to cancer, many women are leery of using vaginal estrogen to address dryness and sexual discomfort. But vaginal estrogen is minimally absorbed, unlike systemic estrogen, so many women can use it, Millheiser said. For those who cannot use vaginal estrogen, she advises using a moisturizer or vaginal dilator as soon as there is pain: Waiting will not help the problem and can lead to a cycle of miscommunication with your partner.

She recommends silicone-, water-, or oil-based personal lubricants during intercourse, such as Replens or K-Y Liquibeads, but warns that petroleum-based lubricants can harbor bacteria in the vagina and cause damage to latex condoms. Though there are no FDA-approved treatments to enhance female libido, a neutraceutical called ArginMax and a nonhormonal arousal oil called Zestra appear to increase desire. Studies also show that a Mediterranean diet, one high in fruits, vegetables, fish, and whole grains, may improve sexual function.

“After cancer therapy, women need to become comfortable with their body,” Millheiser said. “They need to use whatever methods work for them-self-exploration, pain medications, sexual lubricants-and they need to go slowly and chose the right timing to learn to relax with their sexuality.”

Breast Cancer and Cardiac Complications
Randall Vagelos, MD
Medical Director, Cardiac Care Unit

The heart can be affected by cancer therapy, especially in conjunction with other lifetime risk factors, such as smoking, high blood pressure, enlarged heart muscle, or other conditions. And many common side effects of treatment, like tightness in the chest, shortness of breath, or fatigue, can also be symptoms of a heart problem.

“It’s important to know the state of the heart before starting any cancer treatment,” said Vagelos. “Many cancer therapies can exacerbate cardiac conditions.”

Radiation can be a risk to heart heath and tends to amplify the effects of other therapies. Common anticancer drugs like anthracycline affect cell turnover and replication, which can cause cardiac damage over time. The long-term use of anthracyclines can lead to cardiomyopathy and congestive heart failure even years after exposure. Tyrosine kinase inhibitors, which can “turn off” certain cell functions, can weaken heart muscle, although its effects reverse as soon as the drug is stopped.

The condition of the heart can be carefully scanned and monitored with noninvasive imaging techniques and other technologies to make sure patients receive optimal benefits from their treatment. Minimizing cardiac toxicity requires knowing pre-existing conditions and risk factors; using medications like ACE inhibitors and B blockers to override risk; and monitoring the heart using imaging, biomarkers, cardiac biopsies, or echocardiograms.

“All medical interventions have some risk, but our challenge is to maintain the balance between risk and benefit,” he said.

Osteoporosis and Bone Health
David Feldman, MD
Professor, Endocrinology

Because estrogen is so intertwined with breast cancer, and the hormone is so crucial in protecting the bones, osteoporosis (loss of bone density) has become a common concern for cancer survivors, said Feldman.

All women dealing with lower estrogen levels-whether from cancer treatment or age-related menopause- should take a bone density scan (DXA) to measure and track osteoporosis. The test results compare your measurements with others your age (Z score) and with a normal young person (T score). FRAX, an online fracture assessment tool, can also allow you to measure your risk for osteoporosis.

To prevent osteoporosis, you need to take 1200-1500 milligrams a day of calcium supplements, maintain a regimen of weight-bearing and strengthening exercises, and be aware of strategies to prevent falls.

Most people do not get enough sun exposure to produce the necessary levels of vitamin D, which helps the body absorb calcium, so take at least 400 International Units per day. Feldman said he expects new guidelines will more than double the recommended dosage of this essential vitamin but suggests getting a blood test to know your starting point so you can track its benefits.

“Everybody should be on calcium and vitamin D,” said Feldman. “Vitamin D supplements are not just for your bones. They also stop cancer cells from dividing, modulate the immune system, and reduce hypertension, and they appear to have potential for other applications. The proof in humans is not quite there yet, but there’s undeniable benefit.”

He also recommends bisphosphonates like Fosamax, Boniva, or Actonel, which are safe and convenient, although bone loss tends to accelerate as soon as you stop taking the drug.

For More Information:

Stanford Health Library can do the searching for you. Send us your medical questions.

Stanford Cancer Center
http://cancer.stanford.edu/breastcancer/

Stanford Health Library
http://healthlibrary.stanford.edu/

Women’s Health @ Stanford
http://womenshealth.stanford.edu/

Stanford Center on Stress and Health
http://stresshealthcenter.stanford.edu/

Stanford Hospital Heart Center
http://stanfordhospital.org/clinicsmedServices/COE/heart/HeartCentersClinics/

Cancer Awareness Series: New Successes in Colorectal Cancer Treatments and Outcomes

Posted By SHL Librarian

Presented by: George Fisher, MD, PhD
Associate Professor, Oncology

Uri Ladabaum, MD, MS
Associate Professor, Gastroenterology

Hanlee Ji, MD, PhD
Assistant Professor, Oncology

Samuel Strober, MD
Professor, Immunology and Rheumatology

March 24, 2011

Lecture Overview:

Colorectal cancer (CRC) is the third most common cancer in the United States and is the country’s second leading cause of cancer death (behind lung cancer)

“We are working to raise awareness of the disease and to celebrate the  successes we have had with colorectal cancer,” said George Fisher, MD, PhD, an associate professor of oncology, who spoke at a presentation sponsored by the Stanford Cancer Center and the Stanford Health Library. “Our strongest advocates are the people who have been touched by the disease who can help us engage others and build a community dedicated to the elimination of colorectal cancer.”

Colorectal cancer can develop from an atypical growth called a polyp. There are two types of polyps: hyperplastic, which have a very small chance of developing into cancer, and adenomatous, the source of nine out of 10 cases of CRC.

At least half the cases could be prevented with regular screening since early detection is crucial to successful treatment. Colorectal cancer’s mortality rate has declined steadily in recent years, aided by a public awareness of the importance of screening for prevention and early detection, as well as significant improvements in treatment.

“Advances are being made, but until we can create screening systems for all people at risk, we will continue to deal with advanced disease. We are improving our therapies and looking for a cure so that colorectal cancer is gone forever. The challenge can be met if we are able to put all the pieces together,” said Dr. Fisher. “That’s the advantage of an academic medical center like Stanford, where we can combine the multidisciplinary expertise of scientists in different specialties together with clinicians working directly patients.”

Patients benefit from teams made up of surgeons, radiologists, gastroenterologists, and radiation oncologists, he said, as well as experts in peripheral specialties like interventional radiology and genetics, who discuss treatment plans for each individual. “This approach is of enormous value because it allows us to provide care that is both seamless and cutting-edge,” he said. Research is integrated into patient care and includes investigations into cancer stem cells, vaccines, and cancer genomics.

Dr. Fisher also advocated for community involvement to support research in pivotal areas, including investigations to:

  • identify biomarkers to aid in early diagnosis and therapy follow-up
  • study the genes involved in colon cancer
  • refine prevention and therapeutic trials
  • educate individuals and families
  • encourage lifestyle changes to eliminate avoidable risk factors like smoking and obesity
  • promote early screening and develop strategies for early diagnosis
  • improve treatments through targeted therapies and genomics

Genetics and Screening
While we do not know the cause of colorectal cancer, it’s most likely related to genetic changes from external influences in our cellular DNA. Risk factors include age (most cases appear in people over age 50), a diet high in red or processed meat, lack of physical activity, obesity, smoking and alcohol use, and health conditions like diabetes.

“Why screen? To find and remove polyps before they can develop into cancer and to identify cancer at an early stage when treatments are most effective,” said Uri Ladabaum, MD, MS, a professor of gastroenterology, who spoke on Screening and the Role of Genetic Evaluation.

The lifetime risk for developing colorectal cancer is one in 18 for men, and one in 20 for women. In most cases, physicians cannot identify a specific risk. In fact, in about 75-85 percent of cases, there is no genetic cause for the disease. Only between 10 and 30 percent of cases are clustered within a family, pointing to a genetic, or hereditary, root.

“When there is a family history of colorectal cancer, the risk is higher based on the number the relatives and the age they had it,” he said. “The younger the age, the greater the risk. But even when older, a first-degree relative (a parent or sibling) can elevate the risk.”

For example, a person with no family history of CRC has a 5 percent chance of developing the disease. The chance is 10 percent for a person with one family member with CRC and three times higher with two family members. Risk is also elevated when a person has an inflammatory bowel disease such as Crohn’s or ulcerative colitis. Irritable bowel is not a risk factor, he said.

Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is a rare inherited condition that increases the risk and early onset of colon cancer. If a parent has the gene mutation for Lynch, each child has a 50 percent greater chance of inheriting the defective gene and an 80 percent chance of developing cancer over their lifetime, said Dr. Ladabaum. However if the gene mutation is identified, colonoscopies can remove polyps before cancer develops and significantly decrease the risk.

Genetic testing for inherited conditions like Lynch syndrome can help identify who is at an elevated risk so screenings can be scheduled more frequently and at a younger age.

“The point of screening is to reduce risk—to find the precursors of cancer and remove them. It’s not just early detection, it’s also prevention,” he said. “We remove the adenomas before symptoms develop, when the condition is most treatable.”

Adults with average risk should start screening at age 50 and repeat the test every 10 years. A person with a relative who developed symptoms after age 60 should start screening at age 40 and return every 10 years; a person with a relative who developed symptoms under age 60 should be screened at age 40, or 10 years before the relative’s onset, and return every five years.

“We’ve progressed from one-size-fits-all screening protocols to the ability to tailor tests for individual risk,” said Dr. Ladabaum. “Intensive screening can dramatically reduce the incidence of CRC and its mortality rate.”

Analyzing Cancer Genomes
Deoxyribonucleic acid (DNA) is the chemical compound that encodes your genetic blueprint—the instructions your cells need to develop and function. A complete set of DNA is called the genome.

Throughout your life, DNA can make mistakes during cell replication. Most of these genetic glitches are harmless, but once in a while a mutation causes damage that pushes a cell to becoming cancerous. Through a process called sequencing, scientists have created vast databases of the genomic mutations found in several cancers, including CRC.

“Through a combination of technology, computational analysis, and DNA  sequencing, we know more about the genetic factors of colorectal cancer than any other cancer,” said Hanlee Ji, MD, an assistant professor of medicine (oncology), who discussed Personalized Colon Cancer Medicine through Analyzing Cancer Genomics.  “There’s a new era in personalized cancer treatment, based on the analysis of the genes in tumor cells.”

DNA sequencing allows scientists to identify mutations, cellular variations, and other genomic anomalies that contribute to cancer development. They can then home in on likely suspects, and these mutations can then be used to identify targets for therapy and to anticipate how a patient will respond.

Dr. Ji predicts that as technology continues to improve, genomic applications will be more fully integrated into a diagnostic setting. Assessing the genome will allow physicians to determine the risk of developing CRC, track the possibility of metastasis, and predict patient response. This process is accelerated at Stanford by the close proximity of scientists to clinicians who are working together in a back-and-forth dynamic called translational medicine.

“It used to take months to deal with the amount of data contained in a cell genome, and now it’s possible to isolate a tumor and potentially sequence an entire cancer genome in weeks,” he said. “There is no comparison as to what we could do and what we can do now. Next-generation gene sequencing will cause a major change in how we look at genomics. Diagnostic solutions will allow personalized medicine to become a reality.”

Vaccine Strategies
“The purpose of cancer vaccines is to elicit a more powerful immunity in the patient,” said Samuel Strober, MD, a professor of immunology and rheumatology. “However, tumor-specific antigens have been hard to find, and many immune agents now in use target healthy cells as well as the cancerous cells.”

Dr. Strober spoke about the challenge of developing ways to attack a tumor without affecting normal cells. One promising option may be the development of a cancer vaccine. Last year the U.S. Food and Drug Administration approved the first anti-cancer vaccine: a patient-specific dendritic-cell vaccine for use against advanced prostate cancer.

There are two fundamental concepts behind vaccines. One is prophylactic—to prevent the disease from occurring. The Human Papillomavirus vaccine (HPV) works by causing the body to make antibodies that recognize and fight the virus cells before they develop. HPV is a cause of cervical cancer and genital warts.

The other type of vaccine is therapeutic— stimulating the immune system response to home in on existing cancer cells.

Current cancer treatments—radiation and chemotherapy—are non-specific: They destroy healthy as well as malignant cells and can cause severe side-effects. Dr. Strober has been looking at ways to harness the immune system to develop precisely targeted therapies that home in on just the tumor cells.

His research involves using T-cells, a type of white blood cell that protects the body from infection by responding to antigens presented to T-cells by dendritic cells. Antigens stimulate the T-cells to produce proteins that can kill or slow the growth of a foreign invader or a tumor.

Dr. Strober’s laboratory has been developing ways to stimulate immunity to tumors in animal models of primary and metastatic tumors that involve three steps:

  • The primary tumor is treated with focused, high doses of radiation to kill the cancer cells. The few cells remaining are made more apparent to the immune system as foreign. The scientists take dendritic cells and insert them into the tumor to activate a T-cell response. The T-cells, which have now been trained to recognize tumor antigens, are collected and stored.
  • Animals are treated with additional irradiation and/or chemotherapy to kill metastatic tumor cells and to promote expansion of T-cells that will be injected.
  • The T-cells are injected into the blood. Because they have been conditioned to recognize the cancer antigen, they go straight to the tumor and destroy remaining tumor cells.

All three steps are required for the system to work, said Dr. Strober. Using all three steps resulted in a cure in eight of 11 animals, and when a second tumor was introduced, the immune system prevented its growth. “The animal was immunized,” he said, “and 80 percent survived more than six months.”

The process showed that advanced tumors can be treated with the three-step strategy, and Dr. Strober and his team are working with clinicians to develop protocols for human clinical trials. “We hope to have trials in place by the end of 2011,” he said.

For More Information:

Stanford Health Library can do the searching for you. Send us your medical questions.

Stanford Cancer Center
http://cancer.stanford.edu

Colorectal Surgery
http://med.stanford.edu/gensurg/patient_care/colorectal.html

Virtual Colonoscopy
http://stanfordhospital.org/clinicsmedServices/medicalServices/imaging/services_ct_virtual.html

National Cancer Institute
http://www.cancer.gov/cancertopics/types/colon-and-rectal

Advancing the Standard of Care for Prostate Cancer

Posted By SHL Librarian

Introduction: Eila Skinner, MD
Chair of the Department of Urology
Stanford University Medical Center
September 6, 2014
Sheraton Hotel, Palo Alto

Watch the video

Prostate cancer tends to be relatively slow-growing, which means that it typically takes a number of years to become large enough to be detected and even longer to spread beyond the prostate. It’s still extremely serious and the second most-common cause of cancer deaths in U.S. men (lung cancer is first). And because the prostate is close to several vital organs, prostate cancer and its treatment can disrupt normal urinary, bowel, and sexual function.

Prostate cancer affects one in six American men, and studies have shown that most men over the age of 70 have some form of the disease. As research and innovations in technology and treatments enable earlier detection and more effective care, more people are surviving cancer and living longer after a diagnosis. But how it is treated and when it is treated remains debated among prostate specialists.

The Stanford Cancer Center, with support from the Canary Foundation and the Early Detection Research Network, recognized September as National Prostate Health Month by bringing together several specialists to discuss the latest screening and treatment advances in prostate cancer.

Active Surveillance for Prostate Cancer
James Brooks, MD
Professor of Urology

Though the accuracy of prostate specific antigen (PSA) tests has been brought into question, PSA remains a powerful detection tool and mortality rates have dropped significantly since PSA screening was introduced. Much of the current controversy falls under how to approach early-stage prostate cancer and who would most benefit from treatment.

While the number of men with prostate cancer has risen, most die of other causes. About one third of men in their 40s show some sign of prostate cancer, and the percentage increases with age. But elevated PSA levels are not necessarily a sign of cancer, and many men with indolent or latent cancer never develop symptoms. The challenge lies in determining who will require treatment and who will not benefit, avoiding unnecessary biopsies or unwanted side effects from treatment.

“There’s a new paradigm for who will need treatment and who can be watched,” Dr. Brooks said. “Not all cancers warrant aggressive treatment. The benefits of treatment do not always outweigh the risks.”

In the past, many clinicians took an approach called “watchful waiting” that tracked changes in a man’s symptoms and introduced treatment after cancer developed. Today, many have adopted an approach of active surveillance, which involves recurring tests and monitoring of progression before introducing therapeutic intervention. The national Prostate Active Surveillance Study (PASS) collected samples from 1,100 men to test for biomarkers associated with aggressive prostate cancer. One-third of the participants have gone on to receive treatment.

New insights into the genetic makeup of cancer and improved technologies are leading to more focused diagnosis and treatment. Trials using targeted microbubbles, which use contrast agents to deliver drugs and genes that are then activated by ultrasound, have shown to home in on prostate cancer cells. An image-guided biopsy system combines a type of magnetic resonance imaging (MRI) with ultrasound pinpoints tumors for precisely targeted procedures.

Surgical Management of Prostate Cancer
Benjamin Chung, MD
Assistant Professor of Urology

New technologies are allowing surgeons to use minimally invasive approaches using robotics to treat prostate cancer. Robotic-assisted laparoscopic prostatectomy (RALP) systems, like DaVinci, use the smallest possible incisions, making surgery less painful with shorter recovery time and decreased blood loss for patients. Cancer outcomes, complications, and safety appear to be comparable to results from open surgery, but surgeon experience with RALP is important for achieving good outcomes.

Because the prostate is small and difficult to reach, robotics offers several advantages for surgeons as well. Robotic surgical systems help to reduce or eliminate any slight hand tremors, provide greatly increased magnification in 3-D, and offer more flexibility and maneuverability than traditional laparoscopic instrumentation. In a RALP procedure, the surgeon sits at a console in the operating room and uses hand controls to directly guide all the movements of the robotic system accurately and precisely.

Dr. Chung stated that all interventions for prostate cancer can lead to side effects, such as urinary incontinence and erectile dysfunction. The possibility of complete urinary incontinence is very unlikely after RALP. The intense magnification of robotic surgery systems provides more detail during vesicourethral anastomosis, the process of suturing a new connection between the bladder and the urethra, and can help identify the intricate network of nerves needed to preserve erectile function after surgery.

Radiation Oncology for Prostate Cancer
Mark Buyyounouski, MD
Associate professor of Radiation Oncology

Improved biological insights and advances in technology have made a great impact on radiation therapy. New tools use lower doses of radiation that can be applied with pinpoint accuracy, targeting the tumor and sparing nearby health tissue. Stanford has been a long-time pioneer in developing and refining the field.

When planning treatment, specialists stage patients by risk and how far the cancer how progressed based on PSA levels. But they also look at the progression of the disease and other factors to individualize care and recommendations. They will look at the biopsy, patterns in the PSA levels, and other secondary factors before deciding on the best approach.

Patients are treated with Volumetric Modulated Arc Therapy (VMAT), a system that focuses radiation in way that minimizes exposure to surrounding healthy tissues, resulting in fewer side effects, and cuts treatment time by delivering a higher and more targeted dose to the cancer site. CT scans or MRIs are used to create maps of the target area, and markers are then embedded for image-guided therapy.

A technique called fractionated radiotherapy uses small doses of radiation over time, which allows normal cells time to recover. Stanford commonly uses hypo-fractionation, which uses higher doses of radiation per day that may shorten overall treatment time without compromising toxicity.

Brachytherapy involves placing devices containing radiation in the prostate gland close to the cancer cells, which kills the cancer cells while causing less damage to healthy tissue nearby. Brachytherapy is commonly combined with VMAT.

Temporary prostate brachytherapy involves placing hollow needles in the prostate where a radioactive source can deliver treatment for several minutes before the needles are removed. Permanent prostate brachytherapy involves placing radioactive seeds in the prostate, where they slowly release radiation. The temporary approach provides short-term exposure in a same-day procedure; this strategy tends to show better PSA control and survival because of its higher doses of radiation.

These therapies may be used in conjunction with androgen deprivation therapy (ADT), which suppresses the hormones that encourage prostate cancer cells to grow. Studies are being planned to assess the outcomes of using brachytherapy alone to determine whether it can reduce treatment.

“When it comes to radiation therapy, more is better. The higher the dose, the better the outcome,” Dr. Buyyounouski said. “The goal is to target the tumor while sparing the adjacent tissue.”

Drug Treatments for Prostate Cancer
Sandy Srinivas, MD
Associate Professor of Medical Oncology

Lowering testosterone levels has been used to treat prostate cancer since the 1940s, but new therapies are being introduced and refined for patients who do not respond to standard treatment. Since 2010, six new drugs have been approved by the FDA. Chemotherapy is primarily used if the cancer has spread outside the prostate, often to the bones. These drugs are designed to prolong life, not simply lower PSA levels.

The most commonly used chemotherapy drug is docetaxel, which interferes with cell division. Because cancer cells divide faster than normal cells, they are more likely than normal cells to be affected by this drug.

Immunotherapy uses a patient’s own cells to stimulate the immune system’s T cells to respond against the cancer. Androgen targeting agents cause testosterone levels to drop, which consequently drops PSA levels as well. Bone targeting drugs (radium 223) treat metastatic cancers in bone by mimicking calcium in areas affected by increased cell activity.

Traditionally chemohormones are used when other treatments have failed. However, studies have shown that drugs approved for late-stage disease help to suppress tumor development when used early on. In one trial, men who received chemotherapy in conjunction with hormone therapy lived 13 months longer than those who received only hormone therapy.

“Used early on, and in new combinations, these drugs show dramatic results. The higher the risk, the greater the benefit,” said Dr. Srinivas. “The goal is identify more new targets so we can develop more new drugs.”

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Latest Advances in Breast Cancer

Posted By SHL Librarian

Introduction: Mark Pegram, MD
Director, Stanford Breast Cancer Oncology Program
October 16, 2014

After skin cancer, breast cancer is the most common cancer diagnosed in women in the United States and the most common invasive cancer in women worldwide. According to the Centers for Disease Control and Prevention, more than 210,000 women in the U.S. are diagnosed each year and close to 40,000 die annually from the disease. Awareness of the disease, along with earlier detection and new scientific insights, has improved breast cancer survival rates dramatically over the past few decades.

The Stanford Women’s Cancer Center recognized October as National Breast Cancer Awareness Month by bringing together several specialists to discuss the latest screening and treatment advances in breast cancer.

Genetic Testing for Hereditary Breast Cancer
Courtney Rowe-Teeter, CGC

Certified Genetics Counselor

Inherited cancers begin in the DNA, the body’s cellular blueprint. Each cell contains two sets of chromosomes—one from the father and one from the mother—that replicate each time a cell divides. Chromosomes package genetic information in the form of genes, the blueprints that tell our bodies how to grow develop and function. Therefore it is always important to assess for a history of breast and other cancers on both sides of the family.

The genes tested in the Stanford hereditary cancer clinic are considered tumor suppressor genes. When working correctly they prevent cells from growing out of control or inhibit tumor development. And individual who inherits a mutation within one of these tumor suppressor genes has a higher lifetime risk to develop cancers associated with those mutated genes..

Most breast cancer diagnoses are sporadic, developing by chance, and are not due to an inherited gene mutation. Only about 5 to 10 percent of breast cancers are thought to be due to a single underlying inherited gene mutation. Inherited mutations in the BRCA1 and BRCA2 genes are the most common cause for hereditary breast cancer; mutations in these genes primarily lead to increased risk for breast, ovarian, prostate, and pancreatic cancer. Recent research has identified more genes that contribute to hereditary breast cancer.

Next-generation sequencing technologies now allow for clinical analysis of multiple genes simultaneously. Panel testing is a more comprehensive—and cost-effective—approach than testing one gene at a time. “The BRCA genes do not work in a vacuum; there are other genes and a cascade process involved,” said genetic counselor, Courtney Rowe-Teeter. “Panel testing allows us to cast a wide net to catch a broader range of gene mutations that could be underlying a history of breast and other cancers.”

Most inherited gene mutations that predispose to cancer development are inherited in an autosomal dominant manner. That means each individual with the mutation has a 50 percent chance of passing it along. When a specific mutation has been identified, targeted testing for that specific mutation becomes available to family members.

The ultimate goal of genetic testing is to identify individuals with an inherited predisposition to cancer so they can be proactive in developing a focused medical management plan with their physicians to allow for early detection and prevention. Genetic counselors are a critical component to the genetic testing process. They help patients and their families understand the genetic contributions to developing cancer, what type of information genetic testing could yield, and in collaboration with physicians create personalized plans to manage their risk regardless of the test result. “We translate the information we find to help women and men make educated choices,” she said.

Breast Surgery: We’ve Come a Long Way
Amanda Wheeler, MD
Clinical Assistant Professor of Surgery

The breast contains milk-producing glands called lobules that are connected to the nipple by ducts. Much of the rest of the breast is composed of fatty tissue which is usually in proportion to the rest of your body. Cancer that begins in the milk duct, known as ductal carcinoma, is the most common; cancer that begins in the lobules is known as lobular carcinoma.

Surgical treatment of breast cancer involves a multidisciplinary team of specialists, from radiologists to microvascular surgeons. How the cancer is treated depends on the size of the tumor, whether the cancer is invasive or non-invasive, whether lymph nodes are involved, and whether the cancer has spread. There are additional elements that also must be factored in to determine the most appropriate surgical approach.

For example, improved screening from mammograms and breast imaging has led to a dramatic increase in early detection and smaller tumor size. “The size of the tumor at diagnosis has decreased over time due to regular screening mammograms,” said Dr. Wheeler. “The smaller a tumor is when first detected, the better the cosmetic results.”

The goal of breast surgery is to remove the tumor which can be made significantly smaller following chemotherapy. Strategies have changed over the years, and today surgeons can spare much of the overlying skin and nipple area for a more normal-appearing mastectomy. Oncoplastic surgery and advances in micro-reconstruction also are leading to better cosmetic outcomes.

“Breast cancer is an emotional diagnosis for women, but the techniques for surgical treatment are greatly improved, especially with early detection,” Dr. Wheeler said.

Reconstructive Surgery: Rebuilding After Breast Cancer
Rahim Nazerali, MD

Clinical Assistant Professor of Plastic and Reconstructive Surgery

For the one in eight American women dealing with the aftereffects of breast cancer treatment, such as a mastectomy or lumpectomy, reconstructive surgery can restore their body’s natural shape and form, and improve self-esteem.

Some women prefer to have breast reconstruction immediately, which has improved aesthetic results but can delay follow-up therapy if complications occur. Others choose to wait after the initial surgical procedure. Research has shown that the more an institution performs a procedure, the better the results are, so be sure to ask your doctor how many reconstructions he or she has done. Additionally, ensure your surgeon is board certified by the American Board of Plastic Surgery and ask about areas of expertise and specialized training. The surgeon should be trained and have expertise in microsurgery to be able to provide you the comprehensive set of options for reconstruction.

The most common breast reconstruction option is implants, which is considered an extremely safe procedure with a rapid recovery time. It requires only a brief surgery but involves a two-step process. The reconstruction first requires tissue expansion, a gradual process that stretches the chest skin and expands tissue to make room for the implant. The expander is then exchanged for a permanent implant made of either silicone or saline. Although nipple sparing procedures are becoming more common, if that is not an option during the mastectomy, local tissue rearrangement and tattooing can create a similar appearing nipple as an outpatient procedure.

Women can also use tissue transplanted from another part of the body, a process called autologous reconstruction. A flap of tissue composed of skin, fat, and sometimes muscle is detached with its blood supply, usually from the abdomen, thighs, or butt. This tissue is then moved to the chest, where it is reattached and formed into the shape of a breast.

Using specialized microsurgery techniques, the vessels are stitched into place. Breast reconstruction using transplanted tissue lasts a lifetime and looks natural. In addition, the patient gets an added bonus of a tummy tuck or butt lift depending on where the tissue was taken, Dr. Nazerali said. However, the procedure can be lengthy, involves specialized surgical expertise, and requires a longer recovery time.

Breast Imaging
Jafi Lipson, MD
Assistant Professor of Radiology

Technological advances have made a great impact on imaging, an essential resource for assessing risk, improving early detection, directing pre-operative localization, and tracking outcomes. It requires special expertise to interpret mammograms, MRIs, and other imaging modalities to help target deep breast tumors and spare nearby healthy tissue. Stanford has been a long-time pioneer in developing and refining the field of radiology.

Every major breast care organization recommends having a mammogram annually starting at age 40, unless the woman is at high risk, in which case screening mammography may start at a younger age. If a screening test result is abnormal, the patient will be called back for additional mammographs and possible diagnostic breast ultrasound. If suspicious findings persist, a minimally invasive breast biopsy will be recommended. Biopsied tissue is sent to the pathology lab for analysis, and the lab’s findings will be correlated with the radiologist’s reading. After diagnosis, some women will undergo a dynamic contrast-enhanced breast MRI, a noninvasive imaging scan that can identify additional sites of disease.

Radiologists also play an important role during surgery, placing a pre-op wire into the tumor to guide the surgeon to the exact location to excise and reviewing a specimen X-ray during the procedure to ensure that the entire tumor is removed. They also provide follow-up surveillance with mammograms during and after treatment.

A new imaging breakthrough called breast tomosynthesis offers a more accurate image compared to standard mammography. Used in conjunction with two-dimensional digital mammography, the technology takes multiple low-dose images and then reconstructs the slices into a three-dimensional image volume. Breast radiologists can see through layers of tissue and examine areas of concern from all angles, which helps to improve breast cancer detection rates and reduce the patient callback rate.

Another promising new breast imaging tool, soon to be tested in clinical trials at Stanford, is called contrast-enhanced digital mammography (CEDM), a detection modality that uses low levels of radiation and an iodine-based contrast agent to visualize vascular tumors. The resulting images compare a regular mammogram and the contrast information. Preliminary studies have shown that CEDM to be a low-cost, well-tolerated option and may approach the diagnostic accuracy of breast MRI.

“We continue to develop and refine patient-centered solutions,” said Dr. Lipson.

Breast Cancer Oncology
Mark Pegram, MD
Director of the Stanford Breast Cancer Oncology Program

Cancer by its very nature is genetically unstable and can mutate rapidly, scrambling chromosomes at a rapid pace. This process makes it hard to treat—the cancer becomes a moving target in terms of treatment options. The situation becomes even more complex because there can be multiple mutations in one tumor, adding yet another level of complexity. There also can be a lack of cellular uniformity in mutation profiles even within the same tumor from the same patient (molecular heterogeneity).

Because breast cancer genes are so complicated and easily altered, early detection and prevention is a real key to treating the disease, he said. There is also a direct link between heterogeneity and drug resistance.

“Most of the complexity [in breast cancer] has already occurred by the time of diagnosis,” said Dr. Pegram, who is co-director of Stanford’s Molecular Therapeutics Program. “Consequently, a theoretical ideal would be to intervene as early as possible in the evolution of a cancer, before the it acquires the ability to spread.”

For example, one recent study found a 98 percent relapse-free survival rate in HER2-positive breast cancer patients (human epidermal growth factor receptor 2) is a protein that, when overexpressed, promotes aggressive cancer growth], who were treated early with taxol plus Herceptin. Herceptin is an antibody that binds to HER2 and prevents just those cells from multiplying.

Other studies at Stanford are looking at therapeutic antibodies that use the body’s natural immune system defense mechanisms to target and destroy cancer cells. In one ongoing study, researchers are employing engineered antibodies (with more potent immune stimulating capabilities) to enhance anti-tumor response. These types of immune-enhancing strategies may hold promise for patients who do not respond to standard treatments.

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Advances in Surgical and Nonsurgical Treatment of Brain Tumors

Posted By SHL Librarian

Presented by: Steven D. Chang, MD
Professor, Neurosurgery
Stanford University Medical Center

October 30, 2014

There is a delicate balance when it comes to treating brain tumors. How do you effectively destroy the cancer cells while avoiding damage to the nearby normal cells? How can you operate on such a complex organ without causing neurological problems?

The answer lies in new tools and technologies that involve less invasive procedures that use computers and robotics, and more refined use of radiologic imaging, said Steven D. Chang, MD, a professor of neurosurgery, who spoke at a presentation sponsored by the Stanford Health Library. The optimal strategy depends on the individual and the type of brain cancer that needs to be treated, and is individualized for each patient.

Glioblastoma, for example, is an extremely aggressive form of brain cancer that affects more than 15,000 people each year. These tumors are highly malignant, and because the cells reproduce quickly patients usually survive only a few months without treatment.

Surgical Procedures
In the past, glioblastoma was treated solely with basic surgical techniques. Today an innovation known as an interoperative MRI scanner (iMRI) allows a surgeon to conduct an imaging scan while the patient is still in the operating room to ensure that all visible cancerous cells have been removed. The OR team can access the MRI images during the procedure without having to move the patient out of the operating room.  This process maximizes the chance of removing as much tumor as possible and improves patient outcome.

The system can be set up in several ways, with the imaging instruments on a sliding mechanism on the ceiling, in an adjacent room, or integrated into the operating room bed. “We can take a picture of the skull to see if we have done the best job possible,” Dr. Chang said. “It’s a powerful tool to have available.”

A recent study of 44 glioblastoma patients found that almost half had a residual tumor after the surgeon thought the procedure was complete. The iMRI allows the surgeon to continue to resect the tumor after the scan for the complete removal of all radiographically visible cancer cells before the skull is closed up.

Another advanced surgical strategy is an awake craniotomy, in which language function directly tested during the procedure by having the patient speak to the surgical team during the tumor resection. This procedure is used when the tumor lies close to the language center of the brain as a way to preserve speech. The patient is sedated without a general anesthesia for initial comfort and then awakened once the brain is exposed.

Since the brain has no pain receptors, there is no discomfort during the actual surgery. The neurosurgeon is able to map the brain’s speech areas as the patient speaks and interacts. If speech is affected during the electrical stimulation and mapping that area of the brain is marked and preserved. This approach is especially useful since many tumors look like normal brain tissue, said Dr. Chang.

Diffusion tensor imaging (DTI) is a type of magnetic resonance imaging that maps the internal structure of the brain. The brain’s neurons are intrinsically interconnected like the branches of a major highway. DTI creates a complex and detailed map of the white matter tracts, which are the internal neurological pathways of the brain. The resulting image shows where the neurons intersect so the surgeon can avoid critical areas.

Dr. Chang showed an image of a tumor that abutted the neurological pathways involved in motor function; DTI enabled the team to plan the surgical approach in a direction that avoided these crucial nerve tracts. In another example, DTI was used to identify and avoid the neural tracks in the back of the brain essential to vision, preserving the patient’s sight.

Another useful technique is a functional MRI (fMRI), which depicts the patterns of activity and creates detailed maps that show which parts of the brain are involved in a particular neurologic process. During the MRI scan, the patient performs a series of tasks, such as speaking, answering questions, and moving the hands to activate the parts of the brain involved in motor, speech reception, and expressive function. The MRI shows the patterns of activation so critical function can be spared while removing the tumor. This powerful tool is especially helpful for patients who have had a previous injury or for those who are bilingual since the site of activity may be moved from its normal location.

Noninvasive Procedures
The CyberKnife is a robotic radiosurgery system that delivers beams of high-dose radiation with extreme accuracy to treat tumors. It combines computerized imaging with radiation therapy from a linear accelerator to precisely deliver radiation in the three-dimensional pattern of a tumor.

This noninvasive technology is used as an outpatient procedure so patients are back to work or school almost immediately. It is also often more cost-effective compared to surgery or traditional radiotherapy and does not interfere with other treatments such as chemotherapy.

“It is extremely precise and can be used to treat inaccessible tumors,” said Dr. Chang. “It can be used as an alternative to conventional surgery or radiation therapy, and in conjunction with these strategies as part of a multimodality treatment plan.”

The CyberKnife, which was invented by Stanford neurosurgeon Dr John Adler, incorporates a robotic delivery system that can deliver images in real time, which means it can accommodate a patient’s movements during treatment. Multiple radiation beams are used, with each beam focused on the target for an accrued impact. Originally designed to treat brain tumors, it is now used for prostate, pancreas, spine, lungs, and liver. More than 7,000 patients have been treated with the two CyberKnifes at Stanford.

This type of radiosurgery is also an important tool for peri-optic tumors, which are difficult to treat because of their location so close to the optic nerve. Studies have shown that vision is preserved—and in some cases improved—after treatment with the CyberKnife. A similar challenge is addressed with acoustic neuromas, which are accessible for surgery but located right alongside the hearing nerve.

Dr. Chang said that these advances are due in large part because Stanford’s experienced neurosurgeons work as a team with specialists in radiology, pathology, oncology, radiation oncology, and other professionals to improve outcomes and quality of life for people with brain cancer.

About the Speaker
Steven D. Chang, MD, is the Robert C. and Jeannette Powell Professor in the Neurosciences, director of the Stanford Neurogenetics Program and the Stanford Neuromolecular Innovation Program, and co-director of the Stanford Cyberknife Program. A noted expert in radiosurgery technology, Dr. Chang is at the forefront of refining new strategies for using radiation to treat brain cancer. He received his MD and completed his internship, residency, and fellowship at Stanford. He is board certified by the American Board of Neurological Surgery.

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