Monika L. Metzger1,2, Amy L. Billett3, Alison M. Friedmann4, Matthew J. Krasin5, Howard J. Weinstein4, Eric C. Larsen6, Karen J. Marcus7, Chen Li8, Zhaohua Lu8, Sarah S. Donaldson9, Michael P. Link10, Melissa M. Hudson1,2
1Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN,2University of Tennessee Health Sciences Center, Memphis, TN,3Pediatric Oncology Children's Hospital Boston, Dana-Farber Cancer Institute, Boston, MA,4Pediatric Hematology-Oncology, Massachusetts General Hospital, Boston, MA,5Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN,6Pediatric Hematology-Oncology, Children's Medical Center, Maine, ME,7Division of Radiation Oncology, Children‘s Hospital Boston Dana-Farber Cancer Institute, Boston, MA,8Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN,9Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA,10Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
Purpose: To evaluate the efficacy of 12 weeks of Stanford V chemotherapy (prednisone, vinblastine, doxorubicin, nitrogen mustard, etoposide, vincristine, and bleomycin) without routine growth factor support plus response-adapted low-dose, conformal radiotherapy (CRT) in children and adolescents with unfavorable or intermediate risk Hodgkin lymphoma (HL) respectively.
Patients and methods: Multi-institutional (St. Jude Children's Research Hospital, Stanford University, Children's Hospital Boston, Massachusetts General Hospital and Maine Children's Hospital) clinical trial. One hundred ninety-three patients with clinical stages IB (n = 1), IIA (n = 47), IIB (n = 38), IIIB (n = 17), IVA (n = 26), and IVB (n = 49) HL were treated with 12 weeks of Stanford V chemotherapy and low dose CRT between August 2002 and October 2010. Involved nodal sites in complete remission (CR, defined as > 75% shrinkage of the original tumor and PET negative) after 8 weeks of Stanford V received 15 Gy RT; those sites that achieved only partial response received 25.5 Gy RT after completion of all 12 weeks of chemotherapy. CRT fields were individually tailored for both the high-risk group (IIB, IIIB and IV) and the intermediate-risk group (IB, IIA with > 2 nodal sites, mediastinal bulk or extranodal extension or IIIA) to avoid excess organ and tissue exposure.
Results: With a median follow-up of 8.8 years, the 5-year overall and event-free survival (EFS) are 97% (SE = 1%) and 84% (SE = 3%) respectively for the entire cohort – 5-year EFS of 81% for the unfavorable risk and 92% for the intermediate risk group (P = 0.12). Most common toxicities were grade 3 hematologic with 308 episodes of neutropenia in 142 patients (74%) and 123 episodes of anemia in 77 patients (40%); Fever and neutropenia occurred 23 times in 20 patients (10%).
Conclusion: Risk-adapted, combined-modality therapy using 12 weeks of Stanford V chemotherapy plus CRT is well tolerated in in children and adolescents with manageable acute toxicities. Overall survival is comparable to other more intense chemotherapy regimens. Future high-risk front-line therapies may consider a Stanford V backbone with targeted intensification and further modification of the CRT.