Daniel O Persky1, Hongli Li2, Deborah M Stephens3, Steven I Park4,5, Nancy L Bartlett6, Lode J Swinnen7, Paul M Barr8, Jerome D Winegarden9, Louis S Constine10, Thomas J Fitzgerald11, John P Leonard12, Brad S Kahl6, Michael L LeBlanc2, Joo Y Song13, Richard I Fisher14, Lisa M Rimsza15, Sonali M Smith16, Thomas P Miller1, Jonathan W Friedberg8. 1. Division of Hematology/Oncology, University of Arizona, Tucson, AZ. 2. SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA. 3. Division of Hematology, University of Utah, Salt Lake City, UT. 4. Department of Medicine, Levine Cancer Institute/Atrium Health, Charlotte, NC. 5. University of North Carolina, Chapel Hill, NC. 6. Department of Medicine, Washington University School of Medicine, St. Louis, MO. 7. Division of Medical Oncology, Johns Hopkins Cancer Center, Baltimore, MD. 8. Division of Hematology/Oncology, Wilmot Cancer Institute, University of Rochester, Rochester, NY. 9. IHA Hematology Oncology Consultants/Michigan CRC NCORP, Ann Arbor, MI. 10. Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester, Rochester, NY. 11. Imaging and Radiation Oncology Core, Lincoln, RI. 12. Division of Hematology and Medical Oncology, Weill Cornell Medical Center, New York, NY. 13. Department of Pathology, City of Hope, Duarte, CA. 14. Department of Hematology/Oncology, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA. 15. Department of Pathology, Mayo Clinic, Scottsdale, AZ. 16. Section of Hematology/Oncology, University of Chicago, Chicago, IL.
Abstract
PURPOSE: Diffuse large B-cell lymphoma (DLBCL) presents as a limited-stage disease in 25% to 30% of patients, with better overall survival (OS) than that for advanced-stage disease but with continuous relapse regardless of treatment approach. The preferred treatment is abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and radiation therapy. On the basis of promising results of positron emission tomography (PET)-directed treatment approaches, we designed a National Clinical Trials Network (NCTN) study to improve outcomes and decrease toxicity. METHODS: Patients with nonbulky (< 10 cm) stage I/II untreated DLBCL received 3 cycles of standard R-CHOP therapy and underwent a centrally reviewed interim PET/computed tomography scan (iPET). Those with a negative iPET proceeded with 1 additional cycle of R-CHOP, whereas those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy. RESULTS: Of 158 patients enrolled, 132 were eligible and 128 underwent iPET, which was positive in 14 (11%) of the patients. With a median follow-up of 4.92 years (range, 1.1-7.7 years), only 6 patients progressed and 3 died as a result of lymphoma. Eleven patients died as a result of nonlymphoma causes at a median age of 80 years. The 5-year progression-free survival estimate was 87% (95% CI, 79% to 92%) and the OS estimate was 89% (95% CI, 82% to 94%), with iPET-positive and iPET-negative patients having similar outcomes. CONCLUSION: To our knowledge, S1001 is the largest prospective study in the United States of limited-stage DLBCL in the rituximab era, with the best NCTN results in this disease subset. With PET-directed therapy, 89% of the patients with a negative iPET received R-CHOP × 4, and only 11% had a positive iPET and required radiation, with both groups having excellent outcomes. The trial establishes R-CHOP × 4 alone as the new standard approach to limited-stage disease for the absolute majority of patients.
PURPOSE: Diffuse large B-cell lymphoma (DLBCL) presents as a limited-stage disease in 25% to 30% of patients, with better overall survival (OS) than that for advanced-stage disease but with continuous relapse regardless of treatment approach. The preferred treatment is abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and radiation therapy. On the basis of promising results of positron emission tomography (PET)-directed treatment approaches, we designed a National Clinical Trials Network (NCTN) study to improve outcomes and decrease toxicity. METHODS:Patients with nonbulky (< 10 cm) stage I/II untreated DLBCL received 3 cycles of standard R-CHOP therapy and underwent a centrally reviewed interim PET/computed tomography scan (iPET). Those with a negative iPET proceeded with 1 additional cycle of R-CHOP, whereas those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy. RESULTS: Of 158 patients enrolled, 132 were eligible and 128 underwent iPET, which was positive in 14 (11%) of the patients. With a median follow-up of 4.92 years (range, 1.1-7.7 years), only 6 patients progressed and 3 died as a result of lymphoma. Eleven patientsdied as a result of nonlymphoma causes at a median age of 80 years. The 5-year progression-free survival estimate was 87% (95% CI, 79% to 92%) and the OS estimate was 89% (95% CI, 82% to 94%), with iPET-positive and iPET-negative patients having similar outcomes. CONCLUSION: To our knowledge, S1001 is the largest prospective study in the United States of limited-stage DLBCL in the rituximab era, with the best NCTN results in this disease subset. With PET-directed therapy, 89% of the patients with a negative iPET received R-CHOP × 4, and only 11% had a positive iPET and required radiation, with both groups having excellent outcomes. The trial establishes R-CHOP × 4 alone as the new standard approach to limited-stage disease for the absolute majority of patients.
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Authors: T P Miller; S Dahlberg; J R Cassady; D J Adelstein; C M Spier; T M Grogan; M LeBlanc; S Carlin; E Chase; R I Fisher Journal: N Engl J Med Date: 1998-07-02 Impact factor: 91.245
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