 |
 |
A new generation of “anti-angiogenesis” drugs, which stop tumors from developing the blood vessels they need to grow, is showing great promise in treating a wide array of lethal cancers. Since Judah Folkman, M.D., discovered the anti-angiogenesis approach more than 30 years ago, treatment advances, along with new ways to optimize treatment delivery, are leading to longer life spans in some patients, while causing far fewer side effects. Clinicians and research scientists are collaborating to find new ways to leverage these powerful medicines with the hope of revolutionizing the treatment of cancer and other illnesses.
At the Massachusetts Eye and Ear Infirmary (MEEI), James W. Rocco, M.D., Ph.D., is among a group of doctors and researchers who are working to bring the potential benefits of next-generation anti-angiogenesis drugs and other effective treatments to patients with head and neck cancers. As part of this work, Dr. Rocco will serve as principal investigator for a proposed Phase II head-and-neck clinical trial at MEEI and the Massachusetts General Hospital (MGH). The study is currently being reviewed by the Institutional Review Board (IRB) and has not yet begun. When it is initiated, Dr. Rocco’s team hopes to enroll as many as 40 patients, with advanced stages of head-and-neck cancer, over a two-year period. The trial will study the overall therapeutic impact of an experimental anti-angiogenesis drug from AstraZeneca – AZD2171 – on patients with recurrent head and neck squamous cell carcinoma. The goal of AZD2171 is to inhibit blood vessel growth in cancer cells, thus preventing cell growth and, hopefully, causing cell death. Early testing of AZD2171 in animal trials and humans with other forms of cancer shows promising results, including significant reductions in tumor size and fewer side effects. Unlike older generation anti-angiogenesis drugs, AZD2717 is easy to administer and can be taken orally at home.
In addition to looking at the long-term therapeutic benefits of AZD2171, researchers will also explore a newly discovered “therapeutic window” when certain changes in the tumor, in response to AZD2171, may allow chemotherapy and radiation to be particularly effective. If doctors can pinpoint when this window opens and initiate treatment at that time, it could lead to improved survival rates in patients with head-and-neck and other cancers. The trial headed by Dr. Rocco will enroll patients with late stage cancers who have not responded to previous therapies. “The implications of this study are exciting and far-reaching for head-and-neck cancer patients,” said Dr. Rocco. “We will initially enroll patients who normally would receive only palliative care to treat pain and other symptoms. We hope that AZD2171 will help these patients and extend their lives. In the future, we hope to administer AZD2171 far earlier, during the therapeutic window, so that results can be greater.” According to the American Academy of Otolaryngology—Head and Neck Surgery, more than 55,000 Americans will develop cancer of the head and neck this year, and nearly 13,000 of them will die from it. Head and neck cancer includes cancer that arises in the head or neck region, e.g., mouth, nose and throat. Most head and neck cancers begin in the cells that line the “mucosal” surfaces in the head and neck area.
Dr. Daniel Deschler, director of the Division of Head & Neck Surgery at MEEI, and assistant professor at Harvard Medical School said, “Head and neck cancer is the sixth most common cancer in the U.S. It affects areas of the body that are so visible to the outside world and necessary for daily functions like speaking and swallowing. The challenge of this cancer, and our commitment to achieving success, is to provide patients not only with a cure, but also with rehabilitation including advanced reconstructive surgery so that people can resume their normal, daily lives.” He continued, “We treat the full spectrum of head-and-neck cancers from early presentation through advanced stages. Yet, as the leading tertiary care center for this region, we see far advanced cancers that are sometimes not amenable to current treatments. The study looking at AZD2171 and the therapeutic window is exciting as it offers the potential to eventually use the drug across the entire spectrum of the disease.”
To better understand AZD2171 and other anti-angiogenesis drugs, it’s important to know about angiogenesis: the creation of tiny new blood vessels. The term comes from the two Greek words: angio, meaning "blood vessel," and genesis, meaning "beginning." Normally, angiogenesis is a healthy process where the growing body creates new blood vessels to feed its cells. Angiogenesis is also important for healing wounds and repairing damaged body tissues.
In a person with cancer, however, this same process creates new, small, immature blood vessels that provide a tumor with its own blood supply and allow it to grow. If doctors can inhibit the ability of blood vessels to invade a tumor, they can eliminate the tumor's ability to access the blood supply as well as disrupt its ability to get its cancerous cells into the body’s blood circulation system.
While anti-angiogenesis drugs like AZD2171 show promise, research shows that they work best when combined with standard treatments like chemotherapy and radiation. Doctors have been perplexed as to why these treatments vary greatly in their effectiveness. “Delivery of these treatments can be hampered by pressure in the tumor caused by the small immature and leaky blood vessels that support it,” said Dr. Rocco. However, new research in rectal cancer patients and in mice indicates that for a short time after some anti-angiogenesis drugs are administered, the blood vessels in the tumor “normalize” – and actually work better than before. This normalization period may allow for more effective delivery of chemotherapy and increase the tumor's response to radiation treatment, thereby improving patient survival.
According to Dr. Rocco, “We believe that for a short period of time after a patient receives AZD2171, the leaky blood vessels to the tumor will normalize and cause pressure within the tumor to drop and blood flow to improve. During this window, which may last only a couple of days, the tumor will become fully perfused and oxygenated, enabling more effective treatment delivery.”
During the trial, researchers will take frequent biopsies and measure pressure and oxygenation in the patients’ tumors. They hope the findings will enable them to "plot out" the window as it opens and closes. Because this therapeutic window involves changes in blood vessels, the research could also have implications for other diseases affected by blood vessels, such as macular degeneration and heart disease.
Dr. Rocco and his team are leveraging work done by Rakesh K. Jain, Ph.D., A. W. Cook professor of Tumor Biology at Harvard Medical School, and director of the Edwin L. Steele Laboratory at MGH. Dr. Jain's research shows that some anti-angiogenesis drugs are able to "prune" immature, inefficient vessels created in the angiogenesis process during tumor development and fortify the remaining vessels. Thus anti-angiogenesis drugs, when judiciously used, may make the tumors' blood vessels more efficient in delivering treatment.
Dr. Rocco is also involved in other projects to advance head-and-neck cancer treatments, including working with Professor Nick Dyson at the MGH Cancer Center to conduct research that could open the door to a new generation of anti-cancer agents by targeting metastasis, the spreading of tumors to other parts of the body that is a major source of treatment failure of all cancers. Additionally, Dr. Rocco is establishing a world-class molecular oncology research laboratory at MEEI in collaboration with the MGH Cancer Center.
Dr. Rocco serves as the director of the Laboratory of Head and Neck Molecular Oncology and the MEEI Head and Neck Tumor Bank. He is supported by the Daniel Miller Chair in Molecular Oncology and is an assistant professor at Harvard Medical School.
The MEEI Head and Neck Oncology Service specializes in the treatment of patients with cancerous and non-cancerous tumors of the head and neck region. The service combines the expert resources of the MEEI and MGH to provide complete care from screening and diagnosis to treatment and follow-up. In addition to funding from the National Institutes of Health and the Flight Attendant Medical Research Institute, Dr. Rocco and his team receive support from the Norman Knight Head and Neck Cancer Research Fund and the Caridad Bolivar Bacardi Cancer Research Fund. If you would like to learn more about supporting MEEI’s head and neck cancer research efforts, please contact the Development Office at 617-573-3345.
Young doctors training to be eye surgeons learn in classrooms. They practice in labs. They observe experienced surgeons. They perform minor steps and eventually more substantial procedures on patients. Only then are they ready to take the lead in a surgery.
While such training is a time honored method of educating surgeons, John Loewenstein, M.D., director of ophthalmology residency training at the Massachusetts Eye and Ear Infirmary, thinks virtual reality can make training even better.
"Currently, residents learn techniques on animal and cadaver eyes. These methods are useful, but they fall short of performing surgery on live patients.
"The difference between a live, human eye and a synthetic, animal or post-mortem one is significant. There is no substitute for actual experience. But virtual reality can create an artificial environment that closely simulates a true human operation and aids in developing better surgeons. The better the surgeon, the better the outcomes for patients."
Dr. Loewenstein is collaborating with a group of educators, physicists, mathematicians and other surgeons to develop a virtual reality simulator for teaching cataract surgery at the Infirmary.
In cataract surgery, doctors use precise instruments while viewing the eye through a surgical microscope to remove a cloudy, gel-like lens (the cataract) from its fragile membrane capsule. Then a replacement lens is maneuvered into place inside the capsule. At each step, surgeons must maneuver their instruments in very carefully to avoid complications, such as tearing the capsule. Each step in the procedure depends on the previous step, so small errors early in the operation can lead to larger problems later.
Today, cataract surgery is performed millions of times a year in the United States alone and complications are rare. This is because cataract surgeons have spent a great deal of time and effort to perfect their techniques. It is crucial that trainees have enough experience to acquire top-notch skills to minimize risks.
"The best learning is experiential," says Dr. Loewenstein. "And, we learn best when we fail - our minds are most receptive at that point.
"Lab work is good as far as it goes, but virtual reality catapults learning to another level. Eye structures in a living patient have a certain look and feel. Some of it is tactile. You get a response from the tissue -- a certain look or a sense of pressure, resistance -- that guides your movements. Cadaver and animal eyes simply do not respond in the same way. The dimensions of the animal eyes are also different than in human eyes. Since the entire operation takes place within a tiny space in the eye, it is critical that the surgeon become accustomed to those specific dimensions.
Visual and tactile feedback are just some of the advantages of a virtual reality system. Residents also have the opportunity to practice as much as they want, taking as much time as they need. Real-time feedback from the system guides them in correcting their technique, especially when they encounter that all-important moment of failure. All this happens in the safety of a computerized system without risk to patients. In addition, students can repeat entire procedures or focus only on the parts they found difficult.
A summary of the procedure can prove useful to teachers like Dr. Loewenstein who oversee training by highlighting where individual residents most need expert guidance. Experienced surgeons can review techniques with residents in virtual reality before moving to the operating arena and a real patient. Dr. Loewenstein notes that even the most experienced surgeons sometimes have trouble verbalizing skills they've acquired over decades, and the simulator can help with that. “Decades of experience in pilot training have demonstrated that a combination of simulator training and flying real airplanes is the fastest route to competence,” says Dr. Loewenstein. “It is time that we applied this to surgical training.”
Experienced surgeons also can make good use of the virtual reality system in cases, for instance, when they are planning an unusual surgery. The system is ideal for rehearsal of uncommon procedures.
With hospitals constantly striving to improve efficiency, a virtual reality training module can help by reducing the need for extra teaching time in operating rooms, which are in high demand and are costly to run.
The Infirmary’s surgical resident training program will expand to 24 students next year. He aims to have the virtual reality system operational within three to five years to help meet the growing need for training these new eye surgeons.
"The number of residents we are training is growing, and we have to find innovative ways to work with limited resources," says Dr. Loewenstein.
Dr. Loewenstein also imagines a virtual reality system being useful in providing routine information on eye structures, outlining common surgeries, assisting in planning surgery, and even offering interactive training videos.
"The possibilities are quite broad," he says. "And the benefits to residents and the hospital in efficiencies of time and cost are clear. But most important is the promise of offering residents the best possible training, which will translate into better patient care."
To find out more about the Cataract Surgery Virtual Reality Program and how you can support the effort, please contact the MEEI Development Office at 617-573-3345.
Like the parent of a teenager, Matt Gardiner, M.D., hears the telephone ring all day long. But these calls aren’t personal calls. Dr. Gardiner is the director of the Emergency Room and the director of Ophthalmology Emergency Services at the Massachusetts Eye and Ear Infirmary (MEEI). “We get phone calls from ER physicians at other hospitals all over New England who don’t have access to ophthalmologists,” he says.
“May we send this patient to you?” is a question Dr. Gardiner hears frequently from physicians at other hospitals. The question is a testament to the quality of care and level of specialization at MEEI, the only hospital in the Commonwealth of Massachusetts that is dedicated to treating eye injuries.
“MEEI is a great place to work because I have access to so many wonderfully talented people. If I need a subspecialty consultation, all I have to do is call one of my colleagues here,” says Dr. Gardiner.
In addition to caring for patients and supervising residents and fellows in the Emergency Room, Dr. Gardiner is also an attending physician in MEEI’s Comprehensive Ophthalmology department. Receiving more than 15,000 patient visits per year, primary care ophthalmologists for this general eye service provide comprehensive eye care, including annual eye exams and management of a variety of eye conditions, such as cataracts and age-related macular degeneration.
Though Dr. Gardiner enjoys his position because it offers him the variety of providing primary care and managing eye emergencies, he emphasizes that it is always important to educate people about preventing eye trauma. “Something as simple as wearing your seatbelt when you drive or wearing safety glasses when you are mowing the lawn could prevent a significant eye injury,” he says.
Massachusetts Eye and Ear Infirmary Pediatric Otologist Dr. Roland Eavey is determined to make young people aware of the unexpected hazards of noise-induced hearing loss, and in a manner that group can understand — via music.
Dr. Eavey and collaborators from the Harvard School of Public Health conducted an unusual web-based survey in collaboration with Music Television (MTV) to determine adolescents’ views on a number of health issues, including hearing loss. The results of the 28-question online survey were published in the April 2005 issue of the journal, Pediatrics. The results of this study received year-long global multi-media coverage, including coverage in Rolling Stone, Forbes, Newsweek, USA Today, on National Public Radio, as well as major television, radio and newspaper coverage in many nations.
“Educating real people is just as important a responsibility for researchers as educating medical colleagues. We were extremely fortunate to be able to team up with MTV for the best possible credibility in the music arena and then to be so favorably covered by the media to carry the message to our audience. The initial step in public health behavior modification is to raise awareness and we exceeded beyond wildest expectations,” notes Eavey.
Of those who responded to the survey, most ranked preventing hearing loss as a low priority, even though the majority of those surveyed said they had experienced hearing loss or ringing in their ears after listening to loud music or going to a club. Short durations of exposure to loud music may not lead to permanent hearing damage, but constant exposure during childhood, such as listening to loud music through MP3 player headphones, could lead to significant hearing loss as an adult. “The danger is that once noise-induced hearing loss occurs, there is no way to reverse it,” warns Dr. Eavey.
The good news is that many respondents said they would be willing to wear earplugs if they knew it could prevent hearing loss while listening to loud music, especially if the advice came from a doctor. Dr. Eavey wants to use this finding to encourage children and adolescents to wear earplugs. He wants to change culture to make wearing earplugs the normal and “cool” thing to do.
“Fortunately, this type of hearing loss is preventable,” says Dr. Eavey. “If we can get children and adolescents to change their behavior early, we can help them avoid unnecessary hearing damage later in life.”
Dr. Eavey recommends the following guidelines to help protect your hearing.
Click here for more information on noise-induced hearing loss from the Massachusetts Eye and Ear Infirmary.
Members of Massachusetts Eye and Ear Infirmary’s (MEEI) inaugural marathon team, Team Eye and Ear, recently ran in the 110th Boston Marathon. Each runner dedicated months of rigorous training and braved the infamous Heartbreak Hill to raise at least $2,500 to help MEEI provide the best possible care to its patients and remain an institution of excellence.
This year’s runners included MEEI physicians and employees, current and former MEEI patients, and others who were roused by the hospital’s mission.
MEEI's marathon team would not have been possible without the generosity of the Boston Marathon's lead sponsor, John Hancock. Also a sponsor of the hospital's Reynolds Society Dinner, John Hancock donated 60 numbers to MEEI for the race. "MEEI has developed an exceptional marathon program and team that is a great success. The institution's history in the Boston community, as well as its reputation of excellence, make it a worthy recipient of this fundraising opportunity," said John Hancock's President and CEO John D. DesPrez III.
If you'd like to join the MEEI marathon team or know someone who would, please contact Special Events and Research Coordinator Courtney Hudson at 617-573-3347 or email Courtney at:courtney_hudson@meei.harvard.edu.
For more than half a century, the Lions Clubs of Massachusetts have tirelessly raised money for eye research with the hope of one day eradicating blindness. Last year they raised more than $1 million and directed a grant of $180,000 to support innovative “seed” projects of physicians and scientists at the Massachusetts Eye and Ear Infirmary (MEEI). In total, MEEI has received nearly $4 million in grants for research and equipment.
Now, thanks to the generosity of long-time MEEI Board member Jim Sullivan and his wife, Margaret, MEEI is giving a little something back and helping the Lions by sponsoring their international convention, which will be held in Boston from June 30 to July 4.
“The Infirmary wants to be helpful because the Lions are a tremendous group and their members are wonderful people. We owe an enormous debt of gratitude to them,” said Joan W. Miller, M.D., MEEI chief of Ophthalmology. “Understanding the special nature of our partnership, Jim and Margaret Sullivan donated the funds to allow MEEI to be the official Lions Club International Convention sponsor. We could have not done it without them!”
The Lions Clubs of Massachusetts are part of the Lions organization, which has 46,000 clubs across 191 countries, comprising 1.3 million Lions in all. Each year the Lions hold an international convention. The 2006 convention was originally planned for New Orleans, but the devastation caused by Hurricane Katrina necessitated a change of venue and Boston was recently selected as the new site for the 2006 Convention. It is anticipated that between 17,000 and 20,000 Lions will come to Boston from all over the United States and the world from June 30 to July 4 to participate.
“MEEI and the Lions have been great partners for many years,” said Chuck Kostro, past international director of the Lions Club International and chairperson of the local convention host committee. “I am glad that we were able to work together on this project.”
Highlights of the convention will be a welcome from Mass. Lion and Boston Mayor Thomas Menino, a keynote speech by the President of Iceland, and an international parade, which will include dignitaries being ferried by Duck Tour boats, throughout Boston. Watch for the MEEI banner at the end of the parade to be carried by our friends at the Mass. Lions and for the MEEI booth in the convention center.
The Massachusetts Eye and Ear Infirmary continues the fight to preserve and restore sight, hearing, voice and balance. Support this important cause by making a tax-deductible gift. There are many ways that you can contribute. Every gift, no matter the size, is important and is deeply appreciated.
 | We comply with the HONcode standard for
health trustworthy information: Verify here. |
|
|
|
