Proton beam radiation therapy, a very precise type of radiation treatment, may be an effective treatment for advanced adenoid cystic carcinoma that has spread to the cranial base, according to a study from the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (MGH). In the November issue of Archives of Otolaryngology – Head and Neck Surgery, the research team describes results from 11 years of using proton therapy to treat this tumor, which can be dangerous when it spreads into the complex structures at the base of the skull.
"We are very encouraged by our results, in which local tumor control of advanced adenoid cystic carcinoma of the cranial base compared very favorably with results reported from traditional radiation therapy," says Annie Chan, MD, MGH Radiation Oncology, who led the study.
Frequently originating in the salivary glands, adenoid cystic carcinoma is an indolent but aggressive tumor that is usually treated surgically if diagnosed at an early stage. However, when it originates in or spreads into the cranial base – a complex area involving the cranial nerves, the eyes and critical brain structures – it is impossible to remove the tumor safely. Traditional radiation therapy has had limited success in controlling the tumors' growth, largely because the sensitive adjacent structures sharply limit the ability to deliver a strong enough dose.
Proton therapy takes advantage of an inherent quality of the positively charged atomic particles. As they travel through tissues, protons release most of their energy in a concentrated burst near the end of their range, which allows the power of the proton beam to be focused extremely precisely and spares surrounding structures. The MGH has used proton therapy to treat a variety of benign and malignant conditions since 1961 and in 2001 opened the Burr Proton Therapy Center, at the time the second hospital-based center in the world. Currently, proton therapy is offered in 25 centers worldwide, five of which are in the U.S.
The current study reports on a group of patients with very locally advanced adenoid cystic carcinoma involving the cranial base who were treated with high-dose proton beam therapy during the years 1991 through 2002. The majority of the patients could not undergo surgery, as the tumors were very advanced and involved critical structures in the brain or the cranial base. Patients were treated with high-dose proton beam radiation therapy, with treatment plans individually designed to target their specific tumors.
With proton beam treatment, only 9 percent of patients had local recurrence of their tumors, while with traditional radiation tumors recur locally more than 70 percent of the time. With tumors controlled locally in most patients, cancer that did recur was in the form of distant metastasis. However, more than half the patients remained free of recurrence through the end of the study period, up to eight years after surgery. Although blindness is a common side effect of traditional radiation to this area, none of the patients developed blindness with the proton beam treatment.
While the results of this study – the first known report of the use of proton beam therapy to treat this tumor – are better than trials of other types of radiation treatment, the researchers note that conducting the kind of randomized trial required to confirm a treatment's superiority would be difficult for such a rare tumor. However, multi-institutional prospective studies could further study the use of proton beam therapy to treat this rare and aggressive malignancy.
"We are now investigating whether combining proton beam radiation therapy with chemotherapy could further improve the outcome for these patients," says Chan, an assistant professor of Radiation Oncology at Harvard Medical School. The study was supported by the National Institutes of Health.
The study's first author was Pascal Pommier, MD, formerly of MGH Radiation Oncology and now at the Anticancer Center in Lyon, France. Additional co-authors are Jay Loeffler, MD, Nobert Liebsch, MD, PhD, Fred Barker II, MD, Judy Adams, CMD, and Vrishali Lopes of the MGH; Daniel Deschler, MD, and Derrick Lin, MD, Massachusetts Eye and Ear Infirmary; James McIntyre, MD, now at North Shore Medical Center; and Mark Varvares, MD, now at St. Louis University School of Medicine.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, transplantation biology and photomedicine. MGH and Brigham and Women's Hospital are founding members of Partners HealthCare System, a Boston-based integrated health care delivery system.
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