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Have We Made Any Progress?
by
Dr. Murray F. Brennan Memorial Sloan Kettering Cancer Center
[Editor’s Note: Dr. Murray Brennan was awarded the "Nobility in Science" award by the Sarcoma Foundation of America in June of this year. He has authored or co-authored more than 800 scientific papers and book chapters, many focusing on sarcoma, and is the author of a book on soft tissue sarcoma. He has designed and conducted prospective clinical trials that have produced significant findings for the management of soft tissue sarcoma and other cancers. He has received honorary degrees or fellowships in over 20 medical associations or universities. In 1995 he was honored with membership in the Institute of Medicine of the National Academy of Sciences and in 2000 with the American College of Surgeons' highest award, The Distinguished Service Award. Among other things, he is a avid cyclist.]
As I look back on the thirty years since I became actively involved in the management of soft-tissue sarcoma, I wonder if the glass is half full or half empty. I am always reminded that it depends on whether you are drinking or pouring! In 1975, when I joined Dr. Steven Rosenberg at the National Cancer Institute, he was just initiating the studies that allowed us to subsequently show that a limb-sparing operation with adjuvant radiation therapy was equivalent to an amputation, both in terms of local recurrence and in terms of survival.
Those pioneering studies done at a time when amputation was the standard approach would hardly be accepted today given the small numbers in the trial groups; but can anyone imagine the thought of a randomized trial between amputation and conservative surgery, knowing what we know now? In 1975 amputation was the standard approach, and greater than 50% of all patients with an extremity sarcoma underwent an amputation, that percentage is now less than 5%!
Yes, we have made enormous progress in the conservation of limbs of patients with soft tissue sarcoma. We have also made extraordinary progress in the understanding of the disease; and ultimately, our ability to eradicate disease will depend on our understanding. The accuracy with which we make the diagnosis of sarcoma, the conservative way by which it can be obtained by needle or core biopsy, the ability to define the natural history, to know at the start what the risks of a subsequent recurrence, or indeed, ultimate metastasis, are all factors that we can clearly define.
As important as our demonstration that amputation was not needed, was the demonstration that not all patients need more than a simple operation and that aggressive and ablative—not only operations—but systemic treatments can now be tailored to the prognosis that justifies the utilization.
One of the frustrations has been our failure to translate some of the progress made in the treatment of metastatic disease in children to that of adults. So on the one hand, while we can now predict those patients with the likelihood of a good outcome or a poor outcome, such that we can prevent those with good outcome from undergoing unnecessary treatment; but we still struggle with the high-risk patient with the aggressive tumor in our ability to eradicate subsequent death from the spread of disease.
The development of a targeted therapy directed at a particular tumor cell abnormality, as is seen in the use of Gleevec (imatinib) for the GI stromal tumor with a c-Kit mutation, is an example of the direction in which much of cancer care will be directed. Such approaches where the target is specific, the administration relatively simple, and the complications minimal is an important milestone in the management of malignancy in general. In addition, we can now predict the likelihood of response to a drug by the specific mutation (“genetic signature”) in the tumor, and demonstrate by such tests as PET scan, response in the tumor before it can be measured by size reduction. While at the present time such treatments are cytostatic (they stop growth), rather than cytotoxic (they do not kill), they make living with cancer a reality, and death from cancer, if not eradicated, at least postponed. The majority of patients who develop a soft tissue sarcoma will now be cured, and will lead a functional life, with only minimal limitation in their functional capacity, both physically and mentally.
Sarcoma suffers, as do other orphan diseases, from the lack of a strong voice to initiate the research studies essential to the development of prevention and cure, so I believe that there has been a great deal of progress, though there is still a lot to be done. There is a great need for all of the support groups, websites, alliances, and foundations, to begin to speak with a united voice, especially in representations to Congress and the NIH.
Great strides have been made in the sensitivity with which we approach patients, looking once again not just to the physical limitation that a malignancy presents, but to the psychological consequences of the presence of malignancy and its treatment. We now see the patient in his or her entirety with all the fears, desires, and frustrations that such a diagnosis brings. We acknowledge the impact of a cancer diagnosis not just on the patient, but on his or her family and friends. While this is true for some, it is not true for all. I am saddened to see the loss of autonomy and the treatment by committee that often leaves the patient isolated and adrift. We need more effort to put the care back into caring for all patients.
V2N4 ESUN Copyright © 2005 Liddy Shriver Sarcoma Initiative.
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