Established in 1968, RTOG has carried out more than 470 clinical trials to date, accruing over 650,000 patients from member centres throughout the US, Canada and worldwide. As the only National Cancer Institute (NCI)-sponsored clinical-trial cooperative focused on therapeutic radiation, RTOG investigators have been charged with defining the benefits and limitations of new technologies and treatments that involve radiation therapy - on its own and in combination with surgery and/or chemotherapeutic drugs - as well as investigating the effects on cancer patients and their quality of life.

RTOG researchers also work in conjunction with many of the other clinical-trial groups, both in North America and beyond (see the Clinical Trials Cooperative Group Program). Cooperative groups include, for example, the American College of Radiology Imaging Network, the NCI of Canada Clinical Trials Group, and the European Organization for Research and Treatment of Cancer (EORTC).

The mission of RTOG is fourfold:
• improving the survival outcome and quality of life of adults with cancer, through the conduct of high-quality clinical trials;
• evaluating new forms of radiotherapy delivery, including stereotactic radiotherapy, brachytherapy, 3D conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT);
• testing novel systemic therapies in conjunction with radiotherapy, including chemotherapeutic drugs, hormonal strategies, biological agents, and new classes of cytostatic, cytotoxic and targeted therapies;
• employing translational research strategies in order to identify patient subgroups at risk for failure with existing treatments, and identifying new approaches for these patients.

The patient benefits
RTOG clinical studies have defined national standards of care (in the US) for many disease sites. Most notably, RTOG research on the use of concomitant boost and hyperfractionated radiotherapy has increased survival for patients with cervical cancer, central-nervous-system lymphoma, and head-and-neck cancers. Equally significant, the addition of chemotherapy during radiation has increased the survival of lung-cancer patients, while patients with high-grade prostate cancer now benefit from the combination of radiation and long-term hormone suppression.

Of course, RTOG's research is ongoing. Key studies in progress include: a partial-breast irradiation trial being performed in conjunction with the National Surgical Adjuvant Breast and Bowel Project; several large prostate trials, including one with a hypofractionation arm; a head-and-neck study for advanced unresectable tumours; a dose study of non-small cell lung cancer; and an international trial (in conjunction with the EORTC) of high-dose temozolomide for patients with newly diagnosed glioblastoma.

These multi-institutional trials must meet a stringent set of requirements to ensure that the statistical results are valid. Consistency and accuracy in radiation planning, delivery and reporting are essential. Historically, RTOG has relied on the Radiological Physics Center (RPC) in Houston, TX, which employs both remote and on-site monitoring programmes to confirm that the dose being delivered falls within defined standards.

At the same time, RTOG recognizes the increasing demands of emerging radiotherapy technologies. For example, RTOG played an important role in the creation of the Image-Guided Therapy QA Center (ITC) in 1994. The ITC, sited at Washington University in St Louis, MO, is a member of the Advanced Technology Consortium for Clinical Trials Quality Assurance, a consortium that also includes the RTOG Headquarters Dosimetry Group, the RPC and the Quality Assurance Review Center.

The ITC manages thousands of data sets (images, target and normal-tissue structures, and dose distributions) from patients who have been treated as part of an RTOG clinical trial. These data sets are used in the analysis of specific trial endpoints and employed by researchers testing their hypotheses - for example, the correlation of dose-volume parameters and local control or complications.

RTOG, in conjunction with the ITC and RPC, has developed a comprehensive credentialling process that institutions must pass before placing patients on an RTOG trial. The goals of credentialling include ensuring that the institution has the capabilities required by a specific trial, that it understands the requirements of the specific trial, and also has the ability to transmit the required data using the DICOM communication protocol. (Prior to the wide acceptance of DICOM, there was an RTOG standard for data communication.)

Unfortunately, there are still a limited number of established treatment-delivery systems that cannot be used to treat patients entered onto RTOG trials owing to their inability to communicate treatment plans or treatment delivery data using the DICOM protocol.

Setting the standard
One technical challenge that RTOG is currently tackling involves heterogeneity-corrected dose distributions, calculated using both modern and older algorithms. A case in point is the RTOG 0617 trial - a randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal radiotherapy with concurrent and consolidation carboplatin/paclitaxel, in patients with stage IIIA/IIIB non-small cell lung cancer. The trial requires that 95% of the planning target volume be covered by the heterogeneity-calculated dose distribution.

Institutions that use modern algorithms, such as superposition/convolution, and that have been previously credentialled for IMRT, will be permitted to enter patients on this study after completing a questionnaire. Any institution using older algorithms such as Clarkson or Pencil Beam, however, will first need to irradiate the RPC lung phantom and show that the measured dose distribution meets a defined standard (5% or 5 mm) in comparison with the calculated dose distribution. Only then will it be allowed to enter patients on RTOG 0617. This is the first RTOG protocol to impose this standard, which we believe will eventually benefit the entire radiation oncology community.

Following on from its work helping to define standards for prostate implants and for IMRT and 3D CRT, RTOG is currently developing guidelines for image-guided radiation therapy, dose prescription and treatment delivery standards for extracranial stereotactic protocols, and the incorporation of protons into RTOG trials.

Over the years, ionizing radiation has proven an effective tool for treating many types of cancers in diverse disease sites. However, fundamental questions remain concerning appropriate definition of targets and doses. RTOG has made significant contributions in addressing some of these questions during its 39 years. It has also demonstrated that patients do better when their treatments are of high quality. For example, RTOG research presented at the 2007 American Society of Clinical Oncology annual meeting, held in June in Chicago, IL, showed a correlation between survival and high quality-assurance scores for patients with pancreatic adenocarcinoma.

RTOG, with its research base of more than 280 member institutions, and its database of over 450 completed protocols and approximately 40 active protocols, plays a pivotal role in defining and refining cancer patient management. As a result, the cure rate continues to climb and cancer patients enjoy a higher quality of life than ever before.