Introduction: Contributions of the Cooperative Groups

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Since its inception, most issues of Seminars in Oncology have focused on specific tumor types or therapies. This issue of Seminars is dedicated to the US national cancer cooperative groups first organized in 1956. The latest group, the American College of Radiology Imaging Network (ACRIN), was formed as recently as 1999. Many of the groups started in the mid 1950s as new agents active against acute lymphocytic leukemia, such as methotrexate and 6-mercaptopurine, were discovered and required testing in the clinic. Interested individuals from various treatment centers came together to cooperate in prospectively designed clinical trials. Following success in designing and conducting multicenter trials in acute leukemia, the clinical research methods and infrastructure that were developed were next applied in studies of the lymphomas and eventually, with the further discovery of other agents, in studies of solid tumors. Today, the US cooperative group program is the largest publicly supported cancer clinical trials network in the world. In 2007 there were more than 28,000 accruals to cooperative group trials and 146 million dollars were allocated to the cooperative group program by the National Cancer Institute (NCI).

The NCI-sponsored oncology cooperative groups have been responsible for many of the advances in cancer treatment and prevention currently in standard practice. These include the identification of new drugs and the development of new treatment regimens, combined modality therapy for diseases such as cancer of the cervix, esophagus, nasopharynx, and others, adjuvant and neoadjuvant therapy for virtually all solid tumors, curative therapy for childhood acute leukemia and Wilms' tumor, and improvements in quality of life and survivorship, not to mention the identification of cytogenetic and molecular markers for risk stratification and prognosis, advances in staging and tumor classification, and the development of tamoxifen, raloxifene, finasteride, and potentially other interventions as effective chemoprevention strategies. The groups also have been able to disprove the utility of popular and toxic therapies such as high-dose chemotherapy and autologous bone marrow transplantation for breast cancer, which could never have been studied by individual centers and would never have been studied by the pharmaceutical industry.

Originally composed of hematologists, medical and pediatric oncologists, and statisticians, other specialists were recruited to the cooperative groups, including gynecologic oncologists, radiation oncologists, surgeons, psychiatrists, nurses, clinical research associates, and laboratory scientists.

In this issue, each NCI-sponsored cooperative group was given the opportunity to highlight their own achievements so we will not attempt to list their accomplishments here. It is safe to say, however, that most therapies that are considered “standard of care” in oncology were either devised by cooperative groups or confirmed by cooperative group studies.

Although advances in cancer therapy have been made by individuals, groups, cancer centers, Specialized Programs of Research Excellence (SPORES), pharmaceutical companies, etc, cooperative groups have been responsible for many of the defining treatments today. Perhaps the biggest contribution has been the development of rigorous clinical research methods, particularly large randomized controlled trials, to compare two or more treatment strategies, along with a standing national infrastructure of high-quality, experienced, and dedicated institutions.

The assembly of large groups of well-characterized patients treated in the same way and followed for life also makes the conduct of correlative studies in pathology, cytogenetics, molecular biology, and quality of life an extraordinary byproduct of such trials. Indeed, some trials are now designed with the correlative science or quality-of-life end point as the major objective. With the increasing use of molecular subtyping to better characterize cancer, multicenter trials will become even more important as “common tumors” become collections of “uncommon tumors.”

It is also safe to say that many cancer investigators have had their careers made or enhanced through participation in cooperative groups. The cooperative groups, through their repositories of patient records and tissue banks, remain a treasure trove for future investigation. If properly nourished and funded, the groups will enhance the outlook for many future patients diagnosed with cancer. Therefore, this issue of Seminars is dedicated to the investigators of the cooperative groups and the many thousands of patients who bravely volunteered to participate in cooperative group trials over the past half century and into the future.