Major research objectives

Abstract

The Radiation Therapy Oncology Group (RTOG) is a multidisciplinary cancer research organization committed to improving the outcome of adults afflicted with malignancies for which new therapeutic approaches to locoregional tumor burden are needed. The Group’s major research efforts are directed against tumors of the brain, upper aerodigestive tract, lung, gastrointestinal system, and genitourinary tract and against soft tissue sarcomas. Focused efforts also continue in research for women with gynecologic or breast cancer. The Group consists of both clinical and laboratory investigators from more than 260 institutions across the United States and Canada and includes in its membership nearly 90% of all National Cancer Institute (NCI)-designated comprehensive and clinical cancer centers. The Group’s objectives include, but are not limited to, the following: (1) improve the survival of patients with those common forms of cancer for which locoregional tumor control is an important determinant of outcome; (2) enhance cancer patients’ quality of life by optimizing structural and functional organ preservation while improving or maintaining survival; and (3) pursue new initiatives in drug development, technology assessment, outcomes methodology, combined modality integration, and translational research to advance the first two objectives. The RTOG believes that these objectives can be realized through the conduct of high-quality clinical and translational research and that such research is uniquely facilitated by the group’s scientific and administrative infrastructure. The major research accomplishments of the current funding period are summarized in each Committee Report. Some examples of these achievements include that the Group has 1.Demonstrated a substantial survival benefit for women with locally advanced carcinoma of the cervix with the addition of concurrent 5-fluorouracil and cisplatin to external beam radiotherapy (RT) and brachytherapy (RTOG 90-01). This trial contributed to the creation of an NCI Clinical Alert, emphasizing the change in the standard of care for such women (1Morris M Eifel P Lu J et al.Pelvic radiation with concurrent chemotherapy versus pelvic and para-aortic radiation for high-risk cervical cancer A randomized RTOG clinical trial.N Engl J Med. 1999; 340: 1137-1143Crossref PubMed Scopus (1931) Google Scholar).2.Demonstrated a survival benefit for patients with locally advanced, unresected non-small cell lung cancer (NSCLC) receiving cisplatin-based chemotherapy concurrently with thoracic RT compared with those receiving these therapies sequentially (RTOG 94-10) (2Curran W Scott C Langer C et al.Phase III comparison of sequential vs. concurrent chemo radiation for patients with unresected stage III non-small cell lung cancer (NSCLC) Initial report of Radiation Therapy Oncology Group (RTOG) 94-10. Proceedings of the American Society for Clinical Oncology (ASCO), New Orleans.J Clin Oncol. 2000; 19: 484aGoogle Scholar). This report has influenced both the standard of care for such patients and the clinical trial design of ongoing and future studies.3.Identified two of the three tested altered fractionation RT regimens as superior to standard RT in achieving locoregional tumor control for patients with unresected, advanced head and neck squamous cell carcinomas (RTOG 90-03) (3Fu K Pajak T Trotti A et al.A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas First report of RTOG 90-03.Int J Radiat Oncol Biol Phys. 2000; 48: 7-16Abstract Full Text Full Text PDF PubMed Scopus (1125) Google Scholar). In the largest Phase III trial ever conducted for this disease, the “concomitant boost” and the hyperfractionated RT arms were sufficiently promising to warrant testing in new combined modality regimens.4.Identified that men with high-grade localized prostate cancer receiving long-term androgen ablation and RT have better overall and disease-free survival outcomes than those receiving short-term androgen ablation and RT (4Hanks G Lu J Machtay M et al.RTOG protocol 92-02 A phase III trial of the use of long term total androgen suppression following neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate. Proceedings of the American Society for Clinical Oncology (ASCO), New Orleans.J Clin Oncol. 2000; 19 (#1284): 327aGoogle Scholar).5.Contributed intellectual and patient accrual leadership to several major intergroup trials managed by other groups, including those that demonstrated a survival benefit to twice-daily vs. once-daily RT with concurrent chemotherapy for patients with limited-stage small cell lung cancer (5Turrisi A.T Kim K Blum R et al.Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide.N Engl J Med. 1999; 340: 265-271Crossref PubMed Scopus (1236) Google Scholar) and that demonstrated a survival advantage to an adjuvant chemo-RT regimen compared with no adjuvant therapy for patients with high-risk gastric cancer (6Macdonald J Smalley S Benedetti J et al.Postoperative combined radiation and chemotherapy improves disease-free survival (DFS) and overall survival (OS) in resected adenocarcinoma of the stomach and GE junction Results of intergroup study INT-0116 (SWOG 9008). Proceedings of the American Society for Clinical Oncology, New Orleans.J Clin Oncol. 2000; 19 (#1): 1aGoogle Scholar). Several intergroup trials that did not confirm the superiority of the investigational arm include an RTOG-led effort in resectable esophageal cancer testing induction chemotherapy (7Kelsen D Ginsberg R Pajak T et al.Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer.N Engl J Med. 1998; 339: 1979-1984Crossref PubMed Scopus (1194) Google Scholar) and other efforts in resected, lymph node-positive NSCLC (8Keller S Adak S Wagner H et al.A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIa non-small cell lung cancer.N Engl J Med. 2000; 343: 1217-1222Crossref PubMed Scopus (447) Google Scholar) and resected, high-risk colon cancer (9Martenson J Willett C Sargent D et al.A phase III study of adjuvant radiation therapy (RT), 5-fluorouracil (5-FU), and levamisole (LEV) vs 5-FU and LEV in selected patients with resected high risk colon cancer Initial results of INT 0130. Proceedings of the American Society for Clinical Oncology, New Orleans.J Clin Oncol. 1999; 18 (#904): 235aGoogle Scholar). Such trials have important implications for defining standard therapy and considering new investigational approaches.6.Completed accrual to major Phase III trials that, when mature, will define the value of (1) stereotactic radiosurgery in the initial treatment of patients with brain metastases (RTOG 95-08) or glioblastoma multiforme (GBM) (RTOG 93-05); (2) concurrent or induction chemotherapy in organ-preserving laryngeal cancer therapy (RTOG 91-11); (3) short-term androgen ablation in addition to RT for men with early-stage prostate cancer (RTOG 94-08); and (4) the role of pelvic RT vs. involved-field RT for men with locally advanced prostate cancer (RTOG 94-13).7.Led an intergroup Phase II trial for primary central nervous lymphoma patients with a methotrexate-based chemo-RT regimen in which the survival results exceeded prior results by more than 100%, thereby defining a new standard therapy for this disease (10Schultz C Scott C DeAngelis L et al.Radiation therapy (RT) alone vs. pre-RT chemotherapy (CTX) for the treatment of primary CNS lymphoma (PCNSL) Aged matched survival analysis of RTOG 83-15 and RTOG 93-10. Proceedings of the American Society for Clinical Oncology, New Orleans.J Clin Oncol. 2000; 19 (#617): 159aGoogle Scholar).8.Defined quality assurance guidelines, institutional review procedures, central quality assurance procedures, electronic data transfer techniques, and clinical research questions in at least nine Phase I, II, or III trials open during the current grant cycle that tested novel image-guided RT approaches.9.Continued hypothesis-based translational research, particularly for patients with head and neck cancer, prostate cancer, and brain tumors, that has identified the relationship of specific tumor markers with therapeutic success or failure. One example is the observation that aneuploidy, but not microvessel density status, is an independent predictor by multivariate analysis of subsequent failure of hormonal ablation and RT regimens (11Hammond E.H Grignon D.J Lu J et al.Multiple tumor marker analysis in a prostate clinical trial population. American Urological Association, Dallas1999Google Scholar). The Group objectives include the following: 1.To improve on the survival outcome and quality of life of North American adults with leading types of cancer by the multi-institutional testing of novel therapeutic approaches, integrating RT with surgical resection and systemic therapy, as appropriate.2.To evaluate novel techniques of RT delivery, including stereotactic RT, brachytherapy, three-dimensional (3D) conformal RT (CRT), intensity-modulated RT, and to determine the value of their integration into multimodality management of common forms of cancer.3.To test the value of new systemic therapies when integrated into multimodality cancer management. These therapies include oral therapies, new hormonal strategies, biologic agents, new classes of cytostatic and cytotoxic therapies, and combinations of these and established systemic therapies.4.To decrease the morbidity of cancer and its therapy and to improve the quality of life by conserving structure and function, without compromising survival, by the testing of new promising multimodality strategies.5.To employ translational research strategies to identify patient subgroups at greatest risk of therapeutic failure with existing strategies and to identify new approaches to such patients. To achieve these objectives, the Group has based its research agenda on addressing three important hypotheses. Although the method by which these hypotheses are tested varies among the Group’s Disease Site Committees, each hypothesis has a role in each Committee’s research agenda. The RTOG has held as axiomatic that optimizing the locoregional management of many malignancies will improve the survival outcome of patients afflicted with these diseases. There are ample retrospective and randomized data to support this concept for patients with cancers of the head and neck region, prostate, breast, and other disease sites. Despite this, many strategies to enhance locoregional tumor control and survival outcome provided by conventional RT have been unsuccessful to date. These strategies include the testing of radiation sensitizers such as misonidazole and etanidazole and hypoxic bioreductive agents such as tirapazamine, the use of many altered fractionation RT regimens alone, and modest escalations in the total RT dose. The Group is pleased to report that evidence from its trials conducted during the current grant cycle and other trials now lend further support to the first portion of this hypothesis. During the current grant cycle, the following RTOG trials have demonstrated that enhancement of locoregional tumor control significantly improved either the overall or the disease-free survival rates: •RTOG 90-03: This four-arm randomized trial for patients with squamous cell carcinoma of the head and neck region demonstrated that disease-free survival rates were better for those patients receiving either “concomitant boost” or hyperfractionated RT than for those receiving standard RT (3Fu K Pajak T Trotti A et al.A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas First report of RTOG 90-03.Int J Radiat Oncol Biol Phys. 2000; 48: 7-16Abstract Full Text Full Text PDF PubMed Scopus (1125) Google Scholar). In addition, a recent European trial demonstrated improved disease-free survival outcomes with an accelerated hyperfractionated regimen (12Bourhis J Lapeyne M Rives M et al.Very accelerated radiotherapy in HNSCC Results of the GORTEC 94-02 randomized trial. Proceedings of the American Society for Clinical Oncology, New Orleans.J Clin Oncol. 2000; 19 (#1627): 412aGoogle Scholar).•RTOG 88-15: This Eastern Cooperative Oncology Group (ECOG)-led intergroup trial for patients with limited stage small cell lung cancer demonstrated a significant survival advantage for patients receiving an accelerated hyperfractionated RT regimen vs. standard RT when delivered concurrently with identical chemotherapy (5Turrisi A.T Kim K Blum R et al.Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide.N Engl J Med. 1999; 340: 265-271Crossref PubMed Scopus (1236) Google Scholar).•RTOG 94-10: Patients with Stage III NSCLC had significantly better survival outcomes when the thoracic RT was delivered on Day 1 (concurrent) rather than Day 50 (sequential) in conjunction with the same chemotherapy regimen (2Curran W Scott C Langer C et al.Phase III comparison of sequential vs. concurrent chemo radiation for patients with unresected stage III non-small cell lung cancer (NSCLC) Initial report of Radiation Therapy Oncology Group (RTOG) 94-10. Proceedings of the American Society for Clinical Oncology (ASCO), New Orleans.J Clin Oncol. 2000; 19: 484aGoogle Scholar). These landmark clinical trials have demonstrated that more aggressive RT approaches can improve the treatment outcome for either RT alone or combined modality strategies. It is important to note that substantial increases in acute toxicity were observed in the investigational arms of all three of these trials, thereby potentially limiting additional improvements in outcome without substantial changes in either treatment delivery and/or toxicity prevention. The strategy of toxicity prevention is being addressed in a number of RTOG trials coordinated between the RTOG Cancer Prevention and Control Committee and the Disease Site Committees, such as RTOG 98-01, in which the putative cytoprotectant amifostine is being tested as a means to reduce esophagitis and pneumonitis among patients being treated with chemo-RT for Stage III NSCLC. The changes in treatment delivery, especially the RT component, has been a critical component of the Group’s work during the current grant cycle and its research strategy for the proposed grant period. The RTOG believes that substantial improvements in tumor control and survival rates compared with those observed using current multimodality cancer therapy will come through improvements in both the diagnostic and the therapeutic realms. Optimizing the delivery of RT requires using advances in both realms, including new tumor imaging modalities and advances in computing hardware and software, RT treatment planning, and RT delivery. In addition, this effort requires multidisciplinary expertise to employ these developments in clinical disease management and to design ethical clinical trials to test such technologies. The RTOG has conducted sufficient preliminary work in the current grant period in these areas to move to “proof of principle” Phase III testing of these developments in the proposed grant period. This prior work has included the following: 1.Completion of a large Phase I/II RT dose-escalation trial for 3D-CRT for men with prostate cancer, in which the RT dose/fractionation schedule for Phase III testing was identified (RTOG 94-06).2.Completion of a Phase I/II 3D-CRT trial for Stage III NSCLC patients followed by the activation of a trial testing the addition of concurrent chemotherapy (RTOG 93-11 and 01-17).3.Activation of Phase I/II testing of both a 3D-CRT trial and a fractionated stereotactic RT trial for malignant glioma patients (RTOG 98-03 and 00-23).4.Activation of a trial testing intensity-modulated RT for patients with oropharyngeal cancer (RTOG 00-22).5.Completion of an image-guided prostate brachytherapy trial and activation of a second trial (RTOG 98-05 and 00-19).6.Completion of accrual to two Phase III trials testing the value of stereotactic radiosurgery (RTOG 93-05 and 95-08).7.Creation of accreditation processes (including electronic data transfer) for accrediting institutions for such trials and creating quality assurance processes for these new modalities. For each of these seven examples, the RTOG was the first multi-institutional organization to conduct such research. Evidence that such novel RT initiatives will reduce treatment-related morbidity is now emerging. The incidence of severe (Grade ≥3) late bladder and rectal complications has been reduced with 3D-CRT, despite dose escalation, in the Phase I/II prostate cancer trial (RTOG 94-06). Furthermore, the correlation of dose and volume of normal tissue irradiation to clinical outcomes can be performed with the database at the 3D Quality Assurance Center and the RTOG. For example, it was suggested that the RT dose delivered to the penile bulb correlates with the potency among men enrolled in that same trial (13Roach M Winter K Michalski J et al.Mean dose of radiation to the bulb of the penis correlates with risk of impotence at 24 months Preliminary analysis of Radiation Therapy Oncology Group (RTOG) phase I/II dose escalation trial 94-06. Proceedings of the American Society for Therapeutic Radiology and Oncology (ASTRO), Boston.Int J Radiat Oncol Biol Phys. 2000; 48 (#2194): 316Abstract Full Text PDF Google Scholar). The RTOG is committed to testing optimized RT in all disease sites for which a significant improvement in outcome could be expected. The Group does not assume that “newer is better” or that the higher RT doses sometimes achievable with newer techniques will invariably improve the outcome. Such expectations, whenever possible, do invite Phase III testing, and the Group is committed to such a strategy. The strategies for Phase I, II, and III testing of these new treatment planning and delivery modalities during the proposed grant period are summarized in the relevant Disease Site Committee, the Medical Physics Committee, and the Image-Guided RT Committee Reports. In addition to an improved therapeutic ratio achievable with optimized RT, it is also expected that another result will be the enhanced tolerance of combined modality approaches, thereby allowing an opportunity, if deemed appropriate, to escalate the intensity of the systemic component of the therapy. The survival benefit derived from the addition of systemic chemotherapy to the locoregional management of many locally advanced malignancies has accounted for substantive progress in clinical cancer research during the past 15 years. The RTOG has led at least four of the pivotal randomized trials demonstrating this advantage, including trials for patients with unresected esophageal cancer (RTOG 85-01) (14Herskovic A Martz K Al-Sarraf M et al.Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus.N Engl J Med. 1992; 326: 1593-1598Crossref PubMed Scopus (1826) Google Scholar), Stage III NSCLC (RTOG 88-08 and 94-10) (2Curran W Scott C Langer C et al.Phase III comparison of sequential vs. concurrent chemo radiation for patients with unresected stage III non-small cell lung cancer (NSCLC) Initial report of Radiation Therapy Oncology Group (RTOG) 94-10. Proceedings of the American Society for Clinical Oncology (ASCO), New Orleans.J Clin Oncol. 2000; 19: 484aGoogle Scholar, 15Sause W.T Scott C Taylor S et al.RTOG 88-08/ECOG 4588 Preliminary results of a phase III trial in regionally advanced unresectable non-small cell lung cancer.J Natl Cancer Inst. 1995; 87: 198-205Crossref PubMed Scopus (683) Google Scholar), and cervical cancer (RTOG 90-01) (1Morris M Eifel P Lu J et al.Pelvic radiation with concurrent chemotherapy versus pelvic and para-aortic radiation for high-risk cervical cancer A randomized RTOG clinical trial.N Engl J Med. 1999; 340: 1137-1143Crossref PubMed Scopus (1931) Google Scholar). Also, the addition of androgen ablation to locoregional therapy for men with locally advanced prostate cancer has improved the outcome for these men. Three of the pivotal randomized trials have been completed by the RTOG (RTOG 86-10, 85-31, and 92-02) (4Hanks G Lu J Machtay M et al.RTOG protocol 92-02 A phase III trial of the use of long term total androgen suppression following neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate. Proceedings of the American Society for Clinical Oncology (ASCO), New Orleans.J Clin Oncol. 2000; 19 (#1284): 327aGoogle Scholar, 16Pilepich M Winter K Byhardt R et al.Androgen ablation adjuvant to definitive radiotherapy in carcinoma of the prostate Year 2000 update of RTOG phase III studies 86-10 and 85-31. Proceedings of the American Society for Therapeutic Radiology and Oncology (ASTRO), Boston.Int J Radiat Oncol Biol Phys. 2000; 48 (#114): 169Abstract Full Text PDF PubMed Google Scholar). Several Phase III RTOG studies have completed or nearly completed accrual with the potential to be such pivotal studies, including studies testing the role of androgen ablation for men with early-stage prostate cancer (RTOG 94-08); the role of chemotherapy for low-grade glioma (RTOG 98-02); the role of chemotherapy in laryngeal preservation therapy (RTOG 91-11) and in the postoperative management of high-risk head and neck cancer (RTOG 95-01); and the role of chemotherapy in early-stage NSCLC (RTOG 96-16 and 00-15). The research questions following these trials will not ask whether systemic therapy adds value to locoregional therapy for eligible patients but will ask how to optimize the integration of systemic and locoregional therapies. Many chemotherapy dose schedules were originally developed for patients receiving only systemic therapy and were then minimally modified to accommodate patients receiving concurrent RT. This strategy may result in a suboptimal combined modality regimen in terms of both antitumor effect and toxicity. The RTOG believes that many conventional chemotherapy regimens used in chemo-RT regimens have a suboptimal therapeutic index and that Phase I testing of new systemic regimens delivered simultaneously with RT may improve such regimens. Such an example will occur in a Phase I trial for patients with Stage III NSCLC (RTOG 00-17), in which weekly schedules of the doublet gemcitabine and carboplatin, as well as gemcitabine and paclitaxel, will be dose escalated in conjunction with concurrent thoracic RT. It is hypothesized that more continuous exposure of the cancer cells to the systemic agents may increase the radio-enhancing properties of these agents, and this hypothesis will encourage further investigations of oral therapies, weekly infusions, or more continuous drug delivery schedules within the group. The RTOG is uniquely positioned to test new agents, new classes of agents, and new drug combinations for their activity and clinically relevant interactions with RT. Such trials have included the testing of the antiangiogenesis agent thalidomide with RT for GBM (RTOG 98-06), the hypoxic bioreductive agent tirapazamine with RT for GBM (RTOG 94-17), the hypoxic cell sensitizer etanidazole with stereotactic radiosurgery (RTOG 95-02), the biologic agent interferon-β with RT for GBM (RTOG 97-10), and the oxygen-mimetic agent RSR-13 with stereotactic radiosurgery (RTOG 99-08). Future trials that are already approved include the testing of the antiangiogenesis agent SU5416 in two sarcoma trials (RTOG 01-20 and 01-21), the antiangiogenesis agent squalamine in a trial for GBM (RTOG 01-15), and the cyclooxygenase-2 inhibitor Vioxx in a GBM patient trial (RTOG 1089). In addition, the group will continue to test existing regimens in the early evaluation of their appropriateness for combined modality inclusion. More detailed research plans involving new agents and classes of agents are summarized in the research plan of each disease site committee. The RTOG Publications Committee has created a formal mechanism by which investigators can propose a new or “secondary” analysis to test a hypothesis not considered in the initial clinical trial design or only possible through combining the resources of several trials. This process has resulted in important observations leading to new clinical research initiatives, new patient stratification and eligibility criteria, and new statistical methods. These include the creation of the widely employed recursive partitioning and analysis classes of malignant glioma and brain metastases patients (17Curran W.J Scott C.B Horton J et al.Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials.J Natl Cancer Inst. 1993; 85: 704-710Crossref PubMed Scopus (1139) Google Scholar, 18Gaspar L Scott C Rotman M et al.Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials.Int J Radiat Oncol Biol Phys. 1997; 37: 745-751Abstract Full Text PDF PubMed Scopus (2065) Google Scholar), the identification of patients with high-risk resected head and neck cancer appropriate for inclusion in a Phase III trial of chemo-RT (RTOG 95-01) (19Cooper J, Berkey B, Marcial V, et al. Validation of the RTOG recursive partitioning analysis for head and neck cancers. International Conference on Head and Neck Cancer, San Francisco. Final Program and Abstract Book. Fifth International Conference on Head and Neck Cancer, Abstract 168, 2000. p. 108.Google Scholar), the application of quality-of-life and quality-adjusted survival methods to combined modality trials for Stage III NSCLC patients (20Movsas B, Scott C, Sause W, et al. A quality-adjusted time without symptoms or toxicity (Q-TWIST) analysis of the Radiation Therapy Oncology Group (RTOG) chemoradiation studies for locally advanced non-small cell lung cancer (LA-NSCLC). American Radium Society Proceedings, April 1–5, 2000. London, England: American Radium Society Proceedings; 2000. p. 31–32.Google Scholar), and the testing of surrogate end points such as the first biochemical failure in prostate cancer (21Lu J Statistical aspects of evaluating treatment and prognostic factors for clinically localized prostate cancer.Semin Urol Oncol. 2000; 18: 83-92PubMed Google Scholar) or the 1-year survival rate in lung cancer trials (22Seiferheld W Scott C Byhardt R et al.The triangular test reduces time to decision in phase II trials of survival Results from the Radiation Therapy Oncology Group (RTOG). Proceedings of the Society for Clinical Trials, Anaheim, CA.Control Clin Trials. 1999; 20: 54sGoogle Scholar) as earlier measures of efficacy than the long-term survival rates. The image and dose-volume database at the 3D Quality Assurance Center contains rich dosimetric information about patients treated in the 3D-CRT trials (RTOG 94-06, 93-11, and 98-03). These data can be correlated to clinical outcomes registered in the RTOG clinical trial and outcomes database to create models of normal tissue complication and tumor control probabilities. A unique feature of the 3D database is its inclusion of patient treatment planning images, allowing retrospective review or modification to answer questions not previously considered. For example, software tools that allowed remote data entry of new normal organ contours by the investigator facilitated the study of impotence caused by RT to the penile bulb (13Roach M Winter K Michalski J et al.Mean dose of radiation to the bulb of the penis correlates with risk of impotence at 24 months Preliminary analysis of Radiation Therapy Oncology Group (RTOG) phase I/II dose escalation trial 94-06. Proceedings of the American Society for Therapeutic Radiology and Oncology (ASTRO), Boston.Int J Radiat Oncol Biol Phys. 2000; 48 (#2194): 316Abstract Full Text PDF Google Scholar). In addition, the RTOG Translational Research Program has created a mechanism for the review of research proposals to use relevant specimens from the RTOG Tissue Bank in conjunction with the associated clinical databases to answer relevant hypothesis-based translational research questions. A favorable review has afforded investigators partial support of these efforts as well, and nine such proposals from a diverse group of researchers were partially funded in 1999 and 2000. A complete list is provided in the Translational Research Program Report, and these efforts include studies correlating Her-2/neu gene overexpression with therapeutic response in pancreatic cancer; CYP3A4 genotype expression and associated clinical characteristics among black men with prostate cancer; and patterns of mutant epidermal growth factor receptor overexpression and outcome in prostate cancer. The RTOG Tissue Bank continues to expand its available specimens and its facility to handle multiple requests (see the Tissue Utilization Committee Report), and the scale of this research will expand during the proposed grant cycle. It is expected that such correlative translational research will identify new prognostic categories of patients not previously considered and potential targets for new therapeutic approaches. The RTOG believes it is positioned to be the premiere cancer research organization to systematically study novel methods of delivering RT and the critical translational research questions underlying such an effort. In addition, the Group is organized to continue its outstanding research in defining new standards for combined modality therapy for patients with advanced malignancies.