Stage I/II Hodgkin’s Disease: Comparison of Outcomes of Patients with Bulky Mediastinal Disease Versus Other Risk Factors; the Stanford V Experience.
Authors: Advani Ranjana H. , Hoppe Richard T. , Rosenberg Saul A. , Horning Sandra J. 
Published: April 2020

Abstract
At Stanford, stage I/II Hodgkin’s Disease (HD) with a mediastinal mass ratio ≥ 1/3 (MMR ≥ 1/3) is considered unfavorable (U) and is treated like advanced disease. However, in contrast to the German Hodgkin Study Group (GHSG) or the European Organization for Research and Treatment of Cancer (EORTC), stage I/IIA disease without MMR ≥ 1/3 but with other risk factors such as ≥ 3 nodal sites, ESR ≥ 50 and extra-nodal involvement are not considered unfavorable nor used in risk stratification. The purpose of this study is to evaluate and compare the outcomes of patients (pt) treated uniformly at Stanford with early stage disease considered to be unfavorable due to MMR ≥ 1/3 to those with other adverse factors as defined by the GHSG or the EORTC. In this retrospective analysis we identified from our lymphoma database pt with stage I/II HD with a MMR ≥ 1/3 or stage I/IIA without MMR ≥ 1/3 but with 1 or more risk factors (≥ 3 nodal sites, ESR ≥50, extra-nodal involvement) with a minimum follow-up of 2 years. Pt with MMR ≥ 1/3 were treated with 12 weeks of Stanford V chemotherapy + 36 Gy radiotherapy (RT) to sites of disease ≥5 cm (SV–12 + 36 Gy). Stage I/IIA pt without MMR ≥ 1/3 but with other risk factors were treated on our early stage protocols with 8 weeks of Stanford V chemotherapy + 20 or 30 Gy RT to involved sites (SV–8 + 20/30 Gy IFRT). 120 pt were identified: 56 pt with Stage I/II and MMR ≥ 1/3 treated with SV–12 + 36 Gy and 64 stage I/IIA pt without MMR ≥1/3 but with risk factors treated with SV–8 + 20 Gy (n=16) or SV–8 + 30 Gy (n=48). The estimated freedom from progression (FFP) and overall survival (OS) are shown below.
Treatment was unsuccessful in eleven pt (SV–12 + 36 Gy, n=5 and SV–8 + 20–30, Gy n=6). Relapse was limited to the RT field in 3 pt and combined with distant disease in another 6 pt. Secondary therapy was successful in 2 of the 5 pt with SV–12 + Gy and in 5 of six pt after SV–8 + 20/30 Gy IFRT. Fertility appears to be preserved with twenty-five live births/pregnancies reported. Six second cancers have been reported (2 breast, 2 skin, 1 cervix and 1 post transplant AML). Both the breast cancers occurred in females &gt; 35 ys at diagnosis. In our series, abbreviated chemo-radiotherapy as delivered in SV–8 + 20/30 Gy IFRT to pt with stage I/IIA HD without MMR ≥ 1/3 but with risk factors as identified by the GHSG and EORTC has excellent outcomes comparable to those of the GHSG (HD11) and EORTC (HD9U) which use more intensive treatments. Stage I/II MMR ≥ 1/3 pt treated with SV–12 + 36 Gy also enjoyed excellent FFP and OS but second-line treatment was less successful in this group. These results have implications for balancing the risks and benefits of highly successful treatment strategies.
Outcome Risk Factor (RF) n % 10 y FFP {95 % CI} % 10 y OS {95 % CI} Stage I/II with MMR &gt; 1/3 56 90.6 {83, 99} 89 {80, 98} Stage I/II A (No MMR &gt; 1/3) but other RF 64 90.4 {83, 98} 97 {92, 100}