RTOG: Paving the Way for Tomorrow's Patient Care


For more than 30 years, the Radiation Therapy Oncology Group has been a recognized leader for its efforts to increase survival and improve the quality of life for cancer patients. Based in Philadelphia, RTOG is a key clinical research component of the American College of Radiology and serves as a multi-institutional international clinical cooperative group funded primarily by the National Cancer Institute.

Today, more than 250 prominent research institutions in the United States and Canada participate in RTOG studies. More than 40 studies currently are being conducted under RTOG's leadership that involve radiation therapy alone or in conjunction with surgery or chemotherapeutic drugs. There are also studies that examine quality of life issues and their effect on cancer patients.

While RTOG's phase I and phase II studies identify promising new treatment strategies, it is the phase III research that ultimately defines new standards of care for cancer patients. Accordingly, one quarter of RTOG's protocols are phase III studies and account for 70% of the group's patient accrual.

RTOG's research efforts are classified in 3 primary research strategies: (1) evaluate new forms of radiotherapy delivery, (2) test new systemic therapies in conjunction with radiotherapy, and (3) employ translational research tools to identify optimal treatment strategies for specific patient subgroups.

Radiotherapy Delivery

One of RTOG's primary research strategies is to evaluate new forms of radiotherapy delivery, including stereotactic radiotherapy, brachytherapy, 3D conformal radiotherapy (3D CRT), and intensity-modulated radio-therapy (IMRT) in the context of clinical research.

Currently, RTOG has 5 phase III studies that test hypotheses concerning radiotherapy delivery:

  • RTOG 0126 looks to improve survival for men with localized prostate cancer by testing high-dose 3D CRT/IMRT versus standard-dose 3D CRT/IMRT. Jeff M. Michalski, MD, of Washington University in St. Louis, is the principal investigator of this study of 1,520 men.

  • RTOG 0129 will determine whether accelerated fractionation radiotherapy in combination with concurrent chemotherapy can improve the survival results of standard radiotherapy in combination with concurrent chemotherapy for patients with advanced head and neck cancer. ACR Fellow Kian Ang, MD, PhD, of the M. D. Anderson Cancer Center in Houston, is the principal investigator of this study that will enroll 720 patients.

  • RTOG 0214 will evaluate the effectiveness of prophylactic cranial irradiation versus observation in improving survival for non-small cell cancer patients who have been definitively treated with locoregional or systemic therapy. RTOG is the coordinating center for this intergroup study of 1,058 patients. Elizabeth M. Gore, MD, of the Medical College of Wisconsin in Milwaukee, is the principal investigator.

  • RTOG 0232 is testing the hypothesis that the addition of external beam radiation to permanent brachytherapy will improve survival for men with intermediate risk prostate cancer. Bradley R. Prestidge, MD, of the Cancer Therapy and Research Center in San Antonio, is the principal investigator of this study of 1,520 patients.

  • RTOG 0413, a joint study with the National Surgical Adjuvant Breast and Bowel Project, will evaluate the effectiveness of partial breast irradiation compared to whole breast irradiation in providing equivalent local tumor control in the breast following lumpectomy for early stage breast cancer. Julia R. White, MD, of the Medical College of Wisconsin in Milwaukee, is the principal investigator of this study of 3,000 women.

Systemic Therapy Trial

RTOG's second research strategy evaluates new systemic therapies in conjunction with radiotherapy, including chemotherapeutic drugs, hormonal strategies, biologic agents, and new classes of cytostatic and cytotoxic therapies. RTOG currently has 4 protocols testing hypotheses concerning systemic therapy:

  • RTOG 9804 is examining the role of whole breast radiation in preventing or delaying local failure for women with occult, "good risk" duct carcinoma in situ. This is an intergroup study coordinated by RTOG. ACR Fellow Beryl McCormick, MD, of Memorial Sloan-Kettering Cancer Center in New York, is the principal investigator of this study of 1,790 women.

  • RTOG 9811 will assess the benefit of induction chemotherapy prior to concurrent radiotherapy and chemotherapy for patients with cancer of the anal canal. Jaffer Ajani, MD, of M. D. Anderson Cancer Center in Houston, is the principal investigator of this intergroup study coordinated by RTOG that will enroll 650 patients.

  • RTOG 9813 will determine whether administering temozolomide in combination with radiotherapy can improve survival rates obtained with the standard treatment of BCNU and radiotherapy for patients with anaplastic astrocytoma. This RTOG-coordinated intergroup study of 483 patients has Susan M. Chang, MD, of the University of California–San Francisco as the principal investigator.

  • RTOG 0412 will evaluate the survival benefit of concurrent radiotherapy and chemotherapy prior to surgical resection versus preoperative chemotherapy alone for favorable prognosis in patients with stage IIIa (N2) non-small cell lung cancer. Maria Werner-Wasik, MD, of Jefferson Medical College in Philadelphia, is principal investigator of this intergroup study of 574 patients.

Translational Research

RTOG is committed to exploring translational research strategies that identify patient subgroups at risk for failure with existing treatments and identifying new approaches for these patients. RTOG has been developing and expanding its tissue bank since the 1980s and nearly all of the group's phase III protocols have a translational research component as a secondary endpoint. Below are some examples of translational research that is incorporated into current RTOG phase III protocols:

Lung Cancer

With the activation of RTOG 0412, RTOG will embark on its most extensive investigation of the prognostic value of genomic data. As part of the correlative studies for this trial, researchers will evaluate the correlation of the PCR with the disease-free and overall survival rates; investigate the association of DNA damage repair genes (ERCC1 and XRCC1), microtubule-related proteins (TUBB-III and MAP4), and shed tumor DNA with patient responses and outcomes to the platinum/taxane/radiation therapy in this trial; employ MALDI-TOF proteomic analysis of tumor and serum to identify protein profiles associated with response to therapy and prognosis; and evaluate the role of FDG-PET post-therapy in predicting long-term outcome, as well as pathological response both in the tumor and in the mediastinal lymph nodes.

Lung Cancer

RTOG 0235/ACRIN 6668 is a joint study with the American College of Radiology Imaging Network to evaluate the ability of peak standardized uptake value for positron emission tomography with FDG-PET to predict long-term survival for patients with inoperable locally advanced non-small cell lung carcinoma who are treated with definitive chemotherapy and radiotherapy. Mitchell Machtay, MD, of Jefferson Medical College in Philadelphia, is the principal investigator of this study that is expected to enroll 250 patients.

Prostate Cancer

Fresh tissue specimens obtained from men enrolled in the external beam and brachytherapy study, RTOG 0232, will be used to obtain RNA for gene expression analysis to identify genes that predict radiotherapy outcomes or identify patient populations with more aggressive tumor phenotypes.

Anaplastic Astrocytoma

An important goal of RTOG 9813 is a better understanding of the biology of malignant astrocytomas. Grading criteria need to be expanded to include genetic analyses or radiographic characteristics to better distinguish AA from GMB to enhance the credibility of survival obtained in clinical trials. There will be a central pathology review, a central radiographic review, and an evaluation of pathologic specimens to identify molecular predictors of response to chemotherapy and survival, specifically 1p, 10q, 19q, p53 mutations, RB, CDKN2A, and EGFR status, and Ki-67 proliferation index.

Anal Canal Carcinoma

Both pre- and post-treatment biopsies will be obtained from patients enrolled in RTOG 9811 to evaluate the prognostic effects of tumor markers P53 overexpression, human papilloma virus status, and enzyme HAP1.

Head and Neck Cancer

A secondary endpoint of RTOG 0129 is to establish whether EGFR and COX-2 expressions are independent prognostic markers for patients receiving concurrent chemoradiation.

Breast Cancer

A registry of epidemiologic data together with tissue and blood samples for women with DCIS enrolled in RTOG 9804 will be used to identify correlations with local failure.

Copies of RTOG protocols are available on the RTOG Web site at www.rtog.org.

RTOG's Key Areas of Research

The primary areas of research for RTOG's extraordinary lineup of researchers are:

  • Brain tumors
  • Head and neck cancer
  • Lung cancer
  • Cancers of the gastrointestinal system (esophagus, rectum, anal canal, stomach)
  • Genitourinary tract cancers (bladder, prostate)
  • Sarcomas
  • Gynecologic cancer (cervix)
  • Breast cancer