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Originally published as JCO Early Release 10.1200/JCO.2005.11.952 on March 14 2005 © 2005 American Society of Clinical Oncology.
Medical and Pediatric Oncology, Not Adult and Pediatric OncologyUniversity of Michigan Medical School, Ann Arbor, MI There are at least three good reasons to study patients with sarcomas; sarcomas can serve as a model of other more common human cancers, important clinically relevant genetic discoveries have been made disproportionately more often in sarcoma than in other tumors (p53, RB, c-kit, pdgfr, etc), and sarcomas affect patients of all ages from the newborn to the elderly.1,2 Despite many newly gained laboratory insights, as with many other cancers, progress in sarcoma is often too slow. Unlike other epithelial cancers, sarcomas are quite uncommon in our population. For every 100,000 Americans, 5,000 will have cancer. Of those 5,000 people, fewer than 30 will have any one of the 70 or more types of sarcomas. Progress is partly slowed in sarcomas because of competition for patient accrual into important clinical trials. Pediatric oncologists have been highly successful in accruing patients to clinical trials. Recently, however, there has been a decline in accrual to pediatric studies, perhaps because of new competition or insufficient funding for clinical trial participation. Pediatric oncologists have made important strides in patients with the Ewing's family of cancers,3-6 osteosarcoma,7-9 and rhabdomyosarcoma,10-13 achieving cure rates from 65% to 75% in patients without metastasis. Many medical oncologists are in awe of the up to 25% cure rate of these diseases, even in the face of metastatic disease. But what about other soft tissue sarcomas? Pediatric oncologists have become comfortable with the phrase "nonrhabdomyosarcoma soft tissue sarcomas."14-16 Medical oncologists giggle snidely at the phrase. Paul Meyers (pediatric oncologist at Memorial Sloan-Kettering Cancer Center, New York, NY) has said it is not adult and pediatric oncologists, but rather medical and pediatric oncologists. The following two articles in this issue are relevant to this point: "Phase II Trial of Neoadjuvant Vincristine, Ifosfamide, and Doxorubicin With Granulocyte Colony-Stimulating Factor Support in Children and Adolescents With Advanced-Stage Nonrhabdomyosarcomatous Soft Tissue Sarcomas: A Pediatric Oncology Group Study" by Pappo et al17 and "Adult-Type Soft Tissue Sarcomas in Pediatric Age: Experience at the Istituto Nazionale Tumori in Milan" by Ferrari et al.18 I must confess that I like the sound of the second title much more than the first, but the fact is that both titles are accurate. The histologies studied do not include the rhabdomyosarcomas; rather, the histologies studied more often occur in the adult age group. Both articles describe sizeable patient populations. The Children’s Oncology Group article describes 39 patients in a prospective trial.17 Patients were accrued over less than a 3-year period; 26 institutions contributed patients to the study, of which 24 enrolled one patient. The Milan study reported retrospectively on a group of 182 patients treated at a single institution over a 25-year period.18 Both studies agree that this population represents 3% to 4% of pediatric cancers and that these cancers are quite heterogeneous in biology and natural history. Both studies agree that synovial sarcoma is the most common histology among the pediatric nonrhabdo soft tissue sarcomas. The Italian group indicates that "most of the experience gained in the treatment of pediatric NRSTS [nonrhabdomyosarcoma soft tissue sarcomas] either derives from managing soft tissue sarcomas in adults or relies on the principles deriving from the management of RMS [rhabdomyosarcomas]." Evidence for the managing principles being derived from rhabdomyosarcoma includes pretreatment evaluation of these patients with bone scans and bone marrow biopsies. Neither of these diagnostic studies is routinely used by medical oncologists who treat soft tissue sarcoma patients.18,19 Similar to medical oncologists, many pediatric oncologists choose to treat patients with anthracycline- and ifosfamide-based chemotherapy regimens.20-23 However, sometimes the experiences of medical oncologists are not considered by pediatric oncologists. Both studies included patients with alveolar soft part sarcoma. Few, if any, medical oncologists would treat patients with alveolar soft part sarcoma with anthracycline and ifosfamide combinations because they are already aware of the futility of such an approach from research in adult patients. Ten years ago, driven by the foresight of Herman Suit (radiation oncologist at Massachusetts General Hospital, Boston, MA), Fred Eilber (surgical oncologist at the University of California at Los Angeles, Los Angeles, CA), Bob Benjamin (medical oncologist at M.D. Anderson Cancer Center, Houston, TX), and others, the Connective Tissue Oncology Society was formed. For the first time, experts in sarcoma were organized into one group from the eight separate medical disciplines involved in diagnosis and treatment. The initial success of this organization became realized to its membership when significant barriers were systematically torn down among the oncologists from Europe and North America. This organization also inspired the development of another group, the Sarcoma Alliance through Research and Collaboration (SARC), which was organized as a clinical trials consortium in the realization that American efforts were sputtering in this field. SARC includes members from 11 institutions, all of which diagnose and treat more than 200 sarcoma patients yearly. Two of the initial trials of SARC were designed at its inception by both pediatric and medical oncology investigators. One such trial is authored by Lee Helman (pediatric oncologist at the National Cancer Institute, Bethesda, MD) and Shreyaskumar Patel (medical oncologist at M.D. Anderson Cancer Center) as a phase II trial of gemcitabine and docetaxel in three cohorts of bone sarcoma patients (osteosarcoma, Ewing's sarcoma, and chondrosarcoma). In part, because at its inception the trial design included considerations from both pediatric and medical oncology, it became attractive to the Children's Oncology Group, which is now participating with the members of SARC in the conduct of this trial. Similarly, a phase III randomized trial in patients with soft tissue sarcoma, which includes patients 10 years of age and older, has nearly completed accrual in less than 2 years. Commonly, in cooperative-group clinical trials, one group writes a protocol and then realizes it doesn't have enough patients to complete the trial efficiently and tries to recruit others to join. For a host of reasons, this approach is unsatisfactory and likely less successful than trials in which all participants agree initially on a common protocol. Uncommon tumors, such as soft tissue sarcomas in children and adolescents, require the full cooperation of pediatric and medical oncologists along with their colleagues in orthopedic oncology, surgical oncology, pediatric surgery, radiation oncology, radiology, and pathology. At cancer centers, these physicians should serve on a single sarcoma tumor board. Such full participation will encourage appropriate, jointly developed clinical trials providing for the best possible treatment plan for the individual patient and leading to important insights and opportunities for clinical research. Children, young adults, and older adults with sarcoma should not be cast aside because we don't cooperate or have sufficient resources. Just as we have begun to develop geriatric oncology, we should also develop adolescent and young adult oncology. The quickest way to do this is with jointly developed clinical trials in this population of patients. Author's Disclosures of Potential Conflicts of Interest The following author or their immediate family members have indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. Consultant/Advisory Role: Laurence H. Baker, Ascentia, Kinisa, Novartis. Honoraria: Laurence H. Baker, Ascentia, Kinisa, Novartis. For a detailed description of these categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section of Information for Contributors found in the front of every issue. REFERENCES
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3. Paulussen M, Ahrens S, Dunst J, et al: Localized Ewing tumor of bone: Final results of the cooperative Ewing's Sarcoma Study CESS 86. J Clin Oncol 19:1818-1829, 2001 4. Nesbit ME Jr, Gehan EA, Burgert EO Jr, et al: Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: A long-term follow-up of the First Intergroup study. J Clin Oncol 8:1664-1674, 1990[Abstract]
5. Grier HE, Krailo MD, Tarbell NJ, et al: Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med 348:694-701, 2003 6. Ginsberg JP, Woo SY, Hicks MJ, et al: Ewing's sarcoma family of tumors: Ewing's sarcoma of bone and soft tissue and the peripheral primitive neuroectodermal tumors, in Pizzo PA, Poplack DG (eds): Principles and Practice of Pediatric Oncology (ed 4). Philadelphia, PA, Lippincott Williams & Wilkins, 2002, 973-1016 7. Link MP, Gebhardt MC, Meyers PA: Osteosarcoma, in Pizzo PA, Poplack DG (eds): Principles and Practice of Pediatric Oncology (ed 4). Philadelphia, PA, Lippincott, Williams & Wilkins, 2002, p 1051 8. Meyers PA, Gorlick R: Osteosarcoma. Pediatr Clin North Am 44:973-989, 1997[CrossRef][Medline] 9. Link MP, Goorin AM, Horowitz M, et al: Adjuvant chemotherapy of high-grade osteosarcoma of the extremity: Updated results of the Multi-Institutional Osteosarcoma Study. Clin Orthop 270:8-14, 1991
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15. Pratt CB, Pappo AS, Gieser P, et al: Role of adjuvant chemotherapy in the treatment of surgically resected non-rhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group study. J Clin Oncol 17:1219-1226, 1999 16. Pappo AS, Rao BN, Jenkins JJ, et al: Metastatic nonrhabdomyosarcomatous soft tissue sarcomas in children and adolescents: The St. Jude Children's Research Hospital experience. Med Pediatr Oncol 33:76-82, 1999[CrossRef][Medline]
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18. Ferrari A, Casanova M, Collini P, et al: Adult-type soft tissue sarcomas in pediatric age: Experience at the Istituto Nazionale Tumori in Milan. J Clin Oncol 23:4039-4047, 2005 19. Staudenherz A, Steiner B, Puig S, et al: Is there a diagnostic role for bone scanning of patients with a high pretest probability for metastatic renal cell carcinoma? Cancer 85:153-155, 1999[CrossRef][Medline] 20. Brown DH, Leakos M: The value of a routine bone scan in a metastatic survey. J Otolaryngol 27:187-189, 1998[Medline]
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23. Van Glabbeke M, van Oosterom AT, Oosterhuis JW, et al: Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: An analysis of 2185 patients treated with anthracycline-containing first-line regimens—A European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol 17:150-157, 1999
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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