Reduction of fatal complications from combined modality therapy in Hodgkin's disease.

A total of 464 pathologically staged IA through IIIB Hodgkin's disease patients were evaluated for the risk of developing acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, or a fatal infection after treatment with radiation therapy (RT) alone, initial combined radiation therapy and chemotherapy (CMT), or RT with MOPP administered at relapse. Patients received a standard six cycles of MOPP, and additional maintenance chemotherapy was not administered. Patients receiving total nodal irradiation (TNI) and MOPP chemotherapy have an 11.9% actuarial risk of developing a fatal complication at ten years, as compared to a 0.8% risk for lesser field irradiation and MOPP (P = .005). The risk with RT alone is 0.6%. Patients 40 years of age or older have a greater risk for complications. These data report a low risk for fatal complication with CMT when less than TNI is administered and when maintenance chemotherapy is not used.

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Risk-Adapted, Combined-Modality Therapy With VAMP/COP and Response-Based, Involved-Field Radiation for Unfavorable Pediatric Hodgkin's Disease

Journal of Clinical Oncology ◽

10.1200/jco.2004.02.139 ◽

2004 ◽

Vol 22 (22) ◽

pp. 4541-4550 ◽

Cited By ~ 56

Author(s):

Melissa M. Hudson ◽

Matthew Krasin ◽

Michael P. Link ◽

Sarah S. Donaldson ◽

Catherine Billups ◽

...

Keyword(s):

Radiation Therapy ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Combined Modality Therapy ◽

Alkylating Agents ◽

Stage I ◽

Stage Iii ◽

Combined Modality ◽

Field Radiation ◽

Involved Field

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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Stage I to IIB Hodgkin's disease: the combined experience at Stanford University and the Joint Center for Radiation Therapy.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.7.1041 ◽

1987 ◽

Vol 5 (7) ◽

pp. 1041-1049 ◽

Cited By ~ 53

Author(s):

M J Crnkovich ◽

K Leopold ◽

R T Hoppe ◽

P M Mauch

Keyword(s):

Radiation Therapy ◽

Hodgkin's Disease ◽

Medical Center ◽

Hodgkin’S Disease ◽

Combined Modality Therapy ◽

Entire Group ◽

Stanford University ◽

Night Sweats ◽

Similar Survival ◽

Joint Center

The treatment records of 180 patients with pathological stage (PS) IB to IIB Hodgkin's disease treated at Stanford University Medical Center (SUMC) or the Joint Center for Radiation Therapy (JCRT) were reviewed. Pretreatment characteristics were analyzed to assess their influence on survival and freedom from relapse (FFR). The two most important disease characteristics predictive of relapse were the number and type of B symptoms present and the mediastinal mass ratio (MMR). Patients with both fevers and weight loss had a 7-year survival and FFR of only 57% and 48%, respectively. The poor prognosis in this group was apparent for treatment with either radiation (XRT) alone or combined modality therapy (CMT). Patients with night sweats only had no adverse effect of B symptoms on outcome. Patients with a MMR greater than 1/3 had a 7-year FFR of only 58% after XRT, but 79% after CMT (P = .12). The 7-year survivals for these patients were 85% and 88%, respectively. CMT improved the FFR of the entire group of 180 patients when compared with XRT (7-year FFR 86% and 74%, respectively, P = .02); however, survival in the two treatment groups was similar (88% and 89%). Among patients treated with radiation alone, there was a similar survival and FFR irrespective of whether pelvic irradiation was included in the initial treatment fields.

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Fatal complications from combined modality therapy in Hodgkin's disease: age is not a risk factor.

Journal of Clinical Oncology ◽

10.1200/jco.1986.4.1.114 ◽

1986 ◽

Vol 4 (1) ◽

pp. 114-115

Author(s):

G A Gomez

Keyword(s):

Risk Factor ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Combined Modality Therapy ◽

Combined Modality ◽

Fatal Complications

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Major complications and causes of death in patients treated for Hodgkin's disease.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.10.1624 ◽

1987 ◽

Vol 5 (10) ◽

pp. 1624-1633 ◽

Cited By ~ 45

Author(s):

R E van Rijswijk ◽

J Verbeek ◽

C Haanen ◽

A W Dekker ◽

W A van Daal ◽

...

Keyword(s):

Solid Tumors ◽

Hodgkin's Disease ◽

Causes Of Death ◽

Hodgkin’S Disease ◽

Combined Modality Therapy ◽

Salvage Chemotherapy ◽

Histologic Subtype ◽

Combined Modality ◽

Increased Risk ◽

Actuarial Risk

A total of 340 patients with Hodgkin's disease were evaluated for the occurrence of intercurrent fatalities after treatment with radiotherapy, chemotherapy, combined modality therapy, and salvage chemotherapy. Mean follow-up time was 76.6 months. Causes of death were compared with the expected risk, calculated from mortality statistics of the Netherlands' population. Sixty-seven patients died of progressive Hodgkin's disease, whereas 37 patients died of causes unrelated to advanced disease. Patients showed an increased risk of dying of leukemia and solid tumors (P less than .001), whereas the risk of dying of cardiovascular complications was not increased. The 10-year actuarial risk of dying of leukemia varied between 0% for patients treated with radiotherapy only and 5.7% for those needing salvage chemotherapy. The 10-year risk of dying of solid tumors was 0% for patients treated with chemotherapy and 6.5% for those receiving radiotherapy. Treatment-related fatalities were highest after combined modality therapy (P less than .025); the corresponding 10-year risk was 6.1%. Compared with younger ones, patients greater than or equal to 40 years had an increased risk of dying of causes unrelated to progressive Hodgkin's diseases. The actuarial risk of developing intercurrent fatalities at 10 years was 4.9% in patients less than 40 years, and 34.7% in those greater than or equal to 40 years (P less than .001). Compared with population based statistics, patients successfully treated for Hodgkin's disease still showed an increased risk of dying (P less than .001). Treatment modality, stage, and histologic subtype were not predictors of intercurrent death.

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Combined modality therapy for advanced stage hodgkin's disease: patterns of relapse, prognostic factors and the role of radiation therapy

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/0360-3016(90)90729-4 ◽

1990 ◽

Vol 19 ◽

pp. 164-165

Author(s):

Janice Ryu ◽

Joachim Yahalom ◽

Jane Myers ◽

Jeffrey Gaynor ◽

Bayard Clarkson ◽

...

Keyword(s):

Radiation Therapy ◽

Prognostic Factors ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Combined Modality Therapy ◽

Advanced Stage ◽

Disease Patterns ◽

Combined Modality

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Stage III Hodgkin's disease: improved survival with combined modality therapy as compared with radiation therapy alone.

Journal of Clinical Oncology ◽

10.1200/jco.1985.3.9.1166 ◽

1985 ◽

Vol 3 (9) ◽

pp. 1166-1173 ◽

Cited By ~ 55

Author(s):

P Mauch ◽

T Goffman ◽

D S Rosenthal ◽

G P Canellos ◽

S E Come ◽

...

Keyword(s):

Radiation Therapy ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Combined Modality Therapy ◽

Stage Iii ◽

Stage Iiia ◽

Combined Modality ◽

Splenic Involvement ◽

First Relapse ◽

Survival Differences

This is a retrospective analysis of 120 patients with pathologically stage IIIA and IIIB Hodgkin's disease treated from April 1969 to December 1982. The median follow-up was 108 months. Treatment consisted of radiation therapy (RT) alone in 54 patients and combined radiation therapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy (CMT) in 66 patients. Stage III patients treated with CMT have an improved actuarial 12-year survival as compared with patients treated with RT alone with MOPP reserved for relapse (80% v 64%; P = .026). The 12-year actuarial freedom from first relapse by treatment for stage III patients is 83% and 40%, respectively (P less than .0001). Improved survivals following combined modality therapy are seen for the following subgroups of stage III patients: stage III2, 66% (CMT) v 44% (total nodal irradiation; TNI), P = .04; stage III1, 97% (CMT) v 73% (TNI), P = .05; stage III mixed cellularity or lymphocyte depletion histology, 94% (CMT) v 65% (TNI), P = .007; and stage III extensive splenic involvement, 77% (CMT) v 58% (TNI), P = .02. These survival differences are not seen in patients with nodular sclerosis or lymphocyte predominance histology or in patients with minimal splenic involvement. These data indicate that the initial use of CMT in stage III Hodgkin's disease results in an improved survival as compared with initial treatment with RT with MOPP reserved for relapse. Patients with limited Stage IIIA disease may still be candidates for radiation therapy alone.

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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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