A Non-Stanford Mature Experience With Stanford V ± RT Regimen for Locally Extensive and Advanced Hodgkin's Lymphoma (HL)

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Copyright

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Purpose/Objective(s) 

Advanced HL is often treated with either chemotherapy alone, or with brief intensive chemotherapy combined with radiation therapy. The Stanford group reported excellent outcome with the Stanford V dose-intense chemotherapy regimen with radiation therapy, using specific criteria for incorporation of radiation therapy (Horning, JCO 20: 630–637, 2002). An Italian randomized study (Gobbi et al., JCO 23: 9198–9207, 2005) reported markedly inferior results with the Stanford V regimen. The study was however criticized for not stringently following the radiation guidelines specified by the Stanford protocol. We examined whether careful adherence to the Stanford V guidelines for radiotherapy would confirm the original Stanford results.

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Materials/Methods 

From June 1995 to May 2002, 126 patients with either locally extensive or advanced HL were treated with the 12 week-Stanford V chemotherapy regimen followed by 36 Gy involved-field radiotherapy (IFRT) to sites initially ≥5 cm or to macroscopic splenic disease.

Sixty-seven patients (53%) had locally extensive disease, 26 (21%) had stage III and 33 (26%) had stage IV disease. According to the international prognostic score (IPS) for advanced HL, 106 (84%) had 0–3 risk factors and 20 (16%) had 4 or more risk factors. One hundred and eleven (88%) patients received 36 Gy IFRT following chemotherapy. Overall survival (OS), freedom-from-treatment failure (FFTF) and freedom-from-second relapse (FF2R) were determined using the Kaplan-Meier method. Multivariate analysis of prognostic factors was performed using Cox regression analysis.

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Results 

With a median follow-up of 74 months (26–137 months), 114 patients are alive and disease-free with an actuarial 10-year OS of 90%. There were 26 treatment failures (21%) yielding a FFTF of 79% at 10 years. FFTF for advanced stage HL was significantly lower than for early stage disease (71% vs 86%, p = 0.03). The 10-year FFTF for stage IV was significantly lower than for earlier stages (63% vs. 85%, p = 0.002). Patients with IPS ≥ 4 (n = 20) had inferior FFTF (50% vs. 85%; p < 0.00001) compared to those with IPS of 0–3.

Cox regression analysis indicated that IPS ≥ 4 was the most significant independent predictor for worse OS (p < 0.0001). Bone marrow involvement was a significant predictor of decreased FFTF (p < 0.0001).

Twenty-six patients failed Stanford V. Of the 26 failures, 25 underwent high-dose salvage therapy with a FF2R of 58% at 6 years. Twelve patients died (9 of disease, 1 of toxicity with progressive disease, 1 of MDS/leukemia after salvage therapy, 1 of colon cancer with no evidence of HD. Seventeen successful conceptions were reported including 14 female conceptions and a set of twins.

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Conclusions 

Our data confirm that when radiation therapy is administered according to the Stanford guidelines, Stanford V with radiotherapy is highly effective for locally extensive and advanced HL and has a relatively low toxicity profile. This study also shows the relevance of the IPS model in predicting treatment outcome and demonstrates that failures of Stanford V remain highly salvageable with high-dose chemo-radiotherapy followed by autologous stem cell transplantation.