Involved field radiation therapy for early stage Hodgkin's disease in children.Preliminary results

Purpose To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease. Patients and Methods From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or “B” symptoms and all stage III and IV. Results Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% ± 2.5% and 75.6% ± 4.1%, respectively. Conclusion Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease.

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Faculty Opinions recommendation of Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1095850.554489 ◽

2007 ◽

Author(s):

Nicolas Mounier

Keyword(s):

Hodgkin's Disease ◽

Early Stage ◽

Hodgkin’S Disease ◽

Field Radiation ◽

Involved Field

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Wide-field radiation therapy alone or with chemotherapy for Hodgkin's disease in relapse from combination chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.4.544 ◽

1987 ◽

Vol 5 (4) ◽

pp. 544-549 ◽

Cited By ~ 54

Author(s):

P Mauch ◽

N Tarbell ◽

A Skarin ◽

D Rosenthal ◽

H Weinstein

Keyword(s):

Radiation Therapy ◽

Combination Chemotherapy ◽

Hodgkin's Disease ◽

Early Stage ◽

Hodgkin’S Disease ◽

Wide Field ◽

Additional Chemotherapy ◽

Field Radiation ◽

First Relapse ◽

Therapy Field

Nineteen patients with Hodgkin's disease who relapsed primarily in nodal sites after intensive combination chemotherapy were retreated with wide-field radiation therapy alone or with additional chemotherapy between January 1971 and December 1984. Six patients presented in second relapse and 13 patients in first relapse. Seven patients were treated with combination chemotherapy and radiation therapy and twelve patients were treated with radiation therapy alone. Radiation therapy field sizes and doses were similar to those recommended for early-stage Hodgkin's disease patients treated with radiation therapy alone. The 5-year actuarial freedom from relapse (FFR) and survival following retreatment were 48% and 69%, respectively. Twelve patients are currently disease-free 12 to 172 months following retreatment. Wide-field radiation therapy alone or with additional chemotherapy should be considered for patients with advanced Hodgkin's disease who relapse in nodal sites after initial combination chemotherapy.

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VAMP and Low-Dose, Involved-Field Radiation for Children and Adolescents With Favorable, Early-Stage Hodgkin’s Disease: Results of a Prospective Clinical Trial

Journal of Clinical Oncology ◽

10.1200/jco.2002.12.101 ◽

2002 ◽

Vol 20 (14) ◽

pp. 3081-3087 ◽

Cited By ~ 94

Author(s):

Sarah S. Donaldson ◽

Melissa M. Hudson ◽

Kathleen R. Lamborn ◽

Michael P. Link ◽

Larry Kun ◽

...

Keyword(s):

Hodgkin's Disease ◽

Low Dose ◽

Early Stage ◽

Hodgkin’S Disease ◽

Complete Response ◽

Event Free Survival ◽

Free Survival ◽

Clinical Stages ◽

Field Radiation ◽

Involved Field

PURPOSE: To evaluate outcome and assess toxicity of children and adolescents with early-stage, favorable Hodgkin’s disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and low-dose, involved-field radiation. PATIENTS AND METHODS: One hundred ten patients with clinical stages I and II, favorable (nonbulky) Hodgkin’s disease were treated with four cycles of VAMP chemotherapy and 15 Gy involved-field radiation for those who achieved a complete response, or 25.5 Gy for those who achieved a partial response to two cycles of VAMP. RESULTS: With a median follow-up of 5.6 years (range, 1.1 to 10.4 years), the 5-year survival and event-free survival were 99% (lower confidence limit [CL], 97.4%) and 93% (lower CL, 88.6%), respectively. Factors associated with event-free survival of 100% were complete response to two cycles of VAMP and histology other than nodular sclerosing Hodgkin’s disease (NSHD). No serious early or late toxicity has been observed. Patients presenting with clinical stages I and IIA, nonbulky disease involving fewer than three nodal sites have a projected survival and event-free survival of 100% and 97% (lower CL, 93%), respectively, at 5 years. CONCLUSION: Risk-adapted, combined-modality therapy using only four cycles of VAMP chemotherapy with 15 to 25.5 Gy of involved-field radiation for patients with early-stage/favorable Hodgkin’s disease is highly effective and without demonstrable late effects. These results indicate that pediatric patients with stages I and II favorable Hodgkin’s disease can be cured with limited therapy that does not include an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiation therapy.

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Final Results of a Prospective Clinical Trial With VAMP and Low-Dose Involved-Field Radiation for Children With Low-Risk Hodgkin's Disease

Journal of Clinical Oncology ◽

10.1200/jco.2006.08.4772 ◽

2007 ◽

Vol 25 (3) ◽

pp. 332-337 ◽

Cited By ~ 105

Author(s):

Sarah S. Donaldson ◽

Michael P. Link ◽

Howard J. Weinstein ◽

Shesh N. Rai ◽

Sam Brain ◽

...

Keyword(s):

Radiation Therapy ◽

Hodgkin's Disease ◽

Low Dose ◽

Hodgkin’S Disease ◽

Low Risk ◽

High Dose ◽

Histologic Subtype ◽

Field Radiation ◽

Therapy Field ◽

Involved Field

Purpose To evaluate outcome and assess complications in children and adolescents with low-risk Hodgkin's disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) chemotherapy and low-dose, involved-field radiation therapy (IFRT). Patients and Methods One hundred ten children with low-risk Hodgkin's disease were treated with four cycles of VAMP and 15 Gy IFRT for those who achieved a complete response (CR) or 25.5 Gy for those with a partial response after two cycles of VAMP. Results With median follow-up of 9.6 years (range, 1.7 to 15.0), 5- and 10-year overall survival were 99.1% and 96.1%, respectively, and 5-and 10-year event-free survival (EFS) were 92.7% and 89.4%. Factors contributing to 10-year EFS were: early CR (P = .02), absence of B symptoms (P = .01), lymphocyte predominant histologic subtype (P = .04), and less than three initial sites of disease (P = .02). Organ toxicity has been limited to correctable hypothyroidism in 42% of irradiated patients, and one case of cardiac dysfunction. Seventeen healthy babies have been born to 106 survivors. There have been two malignant tumors: one thyroid cancer within the radiation therapy field and one Ewing's sarcoma outside the radiation therapy field. Conclusion Risk-adapted, combined-modality therapy using VAMP chemotherapy with radiation is effective and well tolerated. Pediatric patients with low-risk Hodgkin's disease can be cured with therapy without an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiotherapy. Thus, these children are expected to retain normal fertility, organ function, and be at low risk of a second malignant tumor.

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