A LOOK AT BONE SARCOMAS PAST AND PRESENT
Richard Gorlick, M.D.
Associate Professor of Pediatrics and Molecular Pharmacology
Director, Sarcoma Research Laboratory
Albert Einstein College of Medicine
Chief, Section of Hematology/Oncology
Department of Pediatrics
The Children’s Hospital at Montefiore
The major sarcomas that afflict children and young adults are soft tissue tumors, such as rhabdomyosarcoma and synovial sarcoma, and bone tumors, predominantly osteosarcoma and the Ewing sarcoma family tumors. Before chemotherapy was discovered in the 1950-1960s, the only treatment available for patients with soft tissue or bone sarcomas was surgery. Virtually all patients with bone sarcomas— even in cases where the disease appeared to be localized to an extremity and prone to surgical amputation—died after a short period of time because of metastatic lung disease.
Statistically, when combined with surgery and/or radiation therapy, the use of chemotherapy soon after it was identified could cure 30-40% of patients with bone sarcomas. Over the next several decades, intensification of chemotherapy use improved the outcomes for the majority of patients with bone sarcomas such that some 60-70% with localized disease were effectively cured of their cancers. During the same period, advances in surgery resulted in new limb preserving procedures which could be performed instead of amputation for a majority of patients. Improvements in radiation therapy also led to more focused therapy, which spared surrounding normal tissue and resulted in reduced short- and long-term complications.
Unfortunately, since the early 1990s no major additional improvement in the treatment and outcome of bone cancer patients has been achieved. For a subset of patients—such as those with metastatic disease—the predicted outcome remains poor. Patients with localized disease that relapse also have a very low cure probability. Intensification and other changes in the current chemotherapy treatments have simply not resulted in improved cure rates. This suggests that minimum benefit can be obtained by manipulating current treatment approaches. New treatment approaches are clearly needed. The Albert Einstein College of Medicine and other centers are conducting research to increase the understanding of the basic biology of bone sarcomas. The researchers also are exploring the bases of chemotherapy sensitivity and resistance, as well as developing model systems for testing the effectiveness of bone sarcoma treatment agents.
Now underway are programs that trace the step-by-step cellular development of a sarcoma. The goal is to inhibit the formation of the sarcoma by use of a drug or other therapeutic approach. Other studies at Einstein seek to understand why chemotherapy routinely used in bone sarcoma treatment works on some tumors but not others. In addition to helping guide drug development, this information could also be used to develop assays that potentially could tailor chemotherapy to an individual patient’s tumors sensitivity. Other research involves development of a model system for bone sarcomas to test a new agent’s effectiveness prior to clinical trials.
At the Children’s Hospital at Montefiore, a range of sarcomas are treated by a multi-disciplinary team of specialists—medical/ pediatric oncologists, radiation oncologists, pathologists, diagnostic radiologists and surgeons. For patients with a high probability of cure, standard treatment approaches or cooperative group protocols are used to treat patients in a manner appropriate for each specific tumor type and stage. For those patients who are not likely to benefit from standard treatment approaches or for those with relapsed sarcomas, the medical team employs novel treatments. Several clinical trials are, in fact, underway and others are in development. Some of the more promising drugs include novel antifolates and new biological agents that inhibit signal transduction pathways.
Another area of advanced therapeutics involves administering chemotherapy as an inhalation rather than intravenously or orally. This provides the advantage of achieving the highest drug concentration in the lungs, which is the most frequent site of metastases and, theoretically, the target area for maximum therapeutic benefit. The lower drug concentrations in the blood stream also should decrease the systemic side effects of chemotherapy. With more research and support and hope, the coming years will deliver breakthroughs and novel treatments that can be used in tandem with standard chemotherapy, surgery and/or radiation protocols to improve outcomes for patients afflicted with bone sarcomas.