Second Cancers After Treatment with Stanford V Regimen in Eastern Cooperative Oncology Group (ECOG) Pilot Study E1492 At a Median Follow up of 17 Years

The Stanford V regimen is a combined modality approach for treatment of Hodgkin lymphoma (HL). E1492, an ECOG pilot study, consisted of 12 weeks of Stanford V chemotherapy followed by 36 Gy radiation therapy (RT) to sites > 5 cm or macroscropic splenic disease at diagnosis. Efficacy results were reported previously (Horning et al. J Clin Onc 18, 2000). The study now has a median follow up of 17 years and patients have been followed for overall survival (OS) and development of second cancers.

47 eligible patients with stage bulky mediastinal (mass > one third of the maximum intrathoracic diameter) stage I-II or stage III-IV HL were enrolled between March 1992 and February 1995. Patients were followed every 3 months during the first year off therapy, every 6 months during years 2–5 and annually thereafter. The ECOG database was reviewed for OS and reported second cancers. Patient characteristics at baseline, type of second cancer and time to development of second cancer were assessed. RT summary forms were reviewed for patients with second cancers.

41 patients were treated with combined modality therapy and 6 with chemotherapy alone. The median age was 32 years (range 20–56 years). The 5 and 10 year OS are 96%, and 89% respectively. Seven second cancers were reported, as shown in the Table. The cumulative incidence for second cancers accounting for death as a competing risk is 0.02 (95% CI, 0–0.06) at 5 years, 0.07 (95% CI, 0–0.14) at 10 years, and 0.15 (95% CI, 0.04–0.27) at 15 years. Complete details of the exact location, histologic subtype and subsequent management of second cancers were not available for review.

Five of the 7 cancers [2 skin, 1 prostate, 2 acute myeloid leukemia (AML)] were not radiation-related. One patient developed AML after primary therapy as reported in the initial publication. A second patient developed AML 5 years after salvage therapy followed by autologous stem cell transplant for relapsed HL. It is likely the 2 cases of breast cancer were treatment related.

Within the caveats of a retrospective analysis from a small cooperative group phase 2 trial, the mature 10 year OS of 89% and low frequency of secondary cancers are encouraging in comparison to historic treatment with combined modality treatment. Longer follow up of other Stanford V regimen data sets (i.e. United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244 and the Eastern Cooperative Oncology Group E2496) are required to confirm these findings.

No relevant conflicts of interest to declare.