Phase I study of involved-field radiotherapy preceding autologous stem cell transplantation for patients with high-risk lymphoma or Hodgkin's disease

• Published in: International journal of radiation oncology, biology, physics Vol. 59; no. 1; pp. 208 - 218
• Main Authors: Dawson, Laura A, Saito, Naoyuki G, Ratanatharathorn, Voravit, Uberti, Joseph P, Adams, Paul T, Ayash, Lois J, Reynolds, Christopher M, Silver, Samuel M, Schipper, Matthew J, Lichter, Allen S, Eisbruch, Avraham
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2004; Elsevier
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Autologous stem cell transplantation; Biological and medical sciences; Carmustine - administration & dosage; Combined Modality Therapy; Cyclophosphamide - administration & dosage; Etoposide - administration & dosage; Female; Hodgkin Disease - drug therapy; Hodgkin Disease - radiotherapy; Hodgkin Disease - therapy; Hodgkin's disease; Humans; Involved-field radiotherapy; Lymphoma; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - radiotherapy; Lymphoma, Non-Hodgkin - therapy; Male; Medical sciences; Middle Aged; Prospective Studies; Radiation Injuries - classification; Radiotherapy Dosage; Radiotherapy, Conformal - methods; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Recurrence; Statistics as Topic; Stem Cell Transplantation; Technology. Biomaterials. Equipments. Material. Instrumentation; Transplantation, Autologous; Involved-field radiotherapy; Lymphoma; Autologous stem cell transplantation; Hodgkin's disease; Biomedical engineering
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2003.07.004

This Phase I study was designed to evaluate the tolerability of involved-field radiotherapy (IFRT) to areas of persistent disease in patients with high-risk Hodgkin's disease and non-Hodgkin's lymphomas before autologous stem cell transplantation (ASCT). Thirty-one patients with primary refractory or relapsed Hodgkin's disease ( n = 13) and non-Hodgkin's lymphoma ( n = 18) were treated with IFRT followed by high-dose chemotherapy and ASCT. All patients had bulky disease (≥5 cm) and/or an inadequate response to salvage chemotherapy. The IFRT dose was escalated to a maximum of 36 Gy. Dose-limiting toxicity was defined as Grade 3-4 Bearman toxicity (life-threatening/fatal toxicity occurring within 28 days of ASCT). The chemotherapy regimen consisted of cyclophosphamide, etoposide, and carmustine. The delivered dose of IFRT was 20 Gy in 9 patients, 28–30 Gy in 20, and 32–36 Gy in 2 patients to mediastinal ( n = 19) and nonmediastinal ( n = 12) sites. The median interval between IFRT completion and ASCT was 19 days. One patient developed Bearman Grade 3 hepatic toxicity. No other Grade 3 or 4 Bearman toxicity was observed. An increased requirement for i.v. narcotics was observed in patients treated with mediastinal IFRT vs. nonmediastinal IFRT ( p = 0.02). A trend toward increased mucositis severity was seen in patients previously treated with a larger number of chemotherapy agents ( p = 0.09) and in those with a shorter interval between IFRT and ASCT ( p = 0.12). Pulmonary toxicity was more common in patients treated with mediastinal IFRT than in those treated with nonmediastinal IFRT (21% vs. 0%, p = 0.13). The 2-year overall and progression-free survival rate was 70% and 49% for all patients, 84% and 50% for patients with Hodgkin's disease, and 59% and 47% for patients with non-Hodgkin's lymphoma, respectively. The maximal tolerated dose of IFRT was not reached when Grade 3-4 Bearman toxicity was dose limiting. Increased pulmonary toxicity and mucositis severity was seen after mediastinal IFRT compared with nonmediastinal IFRT. Because local control was excellent, higher doses of IFRT are not recommended. The absolute benefit of IFRT in this patient population needs investigation in future studies.