RESUMO
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.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Metotrexato/uso terapêutico , Prednisona/uso terapêutico , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/uso terapêuticoRESUMO
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.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/radioterapia , Humanos , Masculino , Metotrexato/administração & dosagem , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Prognóstico , Medição de Risco , Resultado do Tratamento , Vimblastina/administração & dosagemRESUMO
OBJECTIVE: To further evaluate the role of chromosomal translocation (15;19) in the presentation of the carcinoma (CA) of the upper aerodigestive tract. STUDY DESIGN AND SETTING: A retrospective study at a tertiary care pediatric medical center. RESULTS: Seven patients with a mean age of 12 years presented with CA of nasopharynx (N = 2), sinonasal region (N = I), parotid gland (N = 2), or larynx (N = 2). Treatments included combinations of surgery (N = 5), chemotherapy (N = 5), and radiation therapy (N = 4). One patient with sinonasal CA and one patient with laryngeal CA had chromosomal translocation (15;19); these patients both died of their disease with a mean survival of 6 months. The 5 patients without translocation (15;19) responded well to treatment and are disease-free with a mean follow-up of 47 months. CONCLUSION: The preliminary results appear to indicate poor prognosis associated with the presentation of chromosomal translocation (15;19) despite aggressive multi-modality treatment. Further investigation is needed to better understand the cause and relationship of the translocation (15;19) and aggressive behavior of these tumors.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Laríngeas/genética , Neoplasias Nasofaríngeas/genética , Neoplasias dos Seios Paranasais/genética , Neoplasias Parotídeas/genética , Translocação Genética/genética , Adolescente , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Criança , Pré-Escolar , Cromossomos Humanos 13-15 , Cromossomos Humanos 19-20 , Feminino , Humanos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/terapia , Masculino , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/terapia , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/terapia , Neoplasias Parotídeas/diagnóstico , Neoplasias Parotídeas/terapia , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: To establish outcome and optimal timing of local control for patients with nonmetastatic Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the chest wall. METHODS: Patients < or =30 years of age with ES/PNET of the chest wall were entered in 2 consecutive protocols. Therapy included multiagent chemotherapy; local control was achieved by resection, radiotherapy, or both. We compared completeness of resection and disease-free survival in patients undergoing initial surgical resection versus those treated with neoadjuvant chemotherapy followed by resection, radiotherapy, or both. Patients with a positive surgical margin received radiotherapy. RESULTS: Ninety-eight (11.3%) of 869 patients had primary tumors of the chest wall. Median follow-up was 3.47 years and 5-year event-free survival was 56% for the chest wall lesions. Ten of 20 (50%) initial resections resulted in negative margins compared with 41 of 53 (77%) negative margins with delayed resections after chemotherapy (P = 0.043). Event-free survival did not differ by timing of surgery (P = 0.69) or type of local control (P = 0.17). Initial chemotherapy decreased the percentage of patients needing radiation therapy. Seventeen of 24 patients (70.8%) with initial surgery received radiotherapy compared with 34 of 71 patients (47.9%) who started with chemotherapy (P = 0.061). If a delayed operation was performed, excluding those patients who received only radiotherapy for local control, only 25 of 62 patients needed radiotherapy (40.3%; P = 0.016). CONCLUSION: The likelihood of complete tumor resection with a negative microscopic margin and consequent avoidance of external beam radiation and its potential complications is increased with neoadjuvant chemotherapy and delayed resection of chest wall ES/PNET.
Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/cirurgia , Tumores Neuroectodérmicos Primitivos/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos/cirurgia , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/cirurgia , Adulto , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/radioterapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Humanos , Tumores Neuroectodérmicos Primitivos/mortalidade , Tumores Neuroectodérmicos Primitivos/radioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Costelas , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/radioterapia , Fatores de TempoRESUMO
The excess risk of second malignancy after Hodgkin disease is an increasing problem. In light of the long-term data, guidelines for follow-up of survivors of Hodgkin disease need to be redefined. In this study we attempt to analyze the long-term risks and temporal trends, identify patient- and treatment-related risk factors, and determine the prognosis of patients who develop a second malignancy after radiation treatment with or without chemotherapy for Hodgkin disease. Among 1319 patients with clinical stage I-IV Hodgkin disease, 181 second malignancies and 18 third malignancies were observed. With a median follow-up of 12 years, the relative risk (RR) and absolute excess risk of second malignancy were 4.6 and 89.3/10 000 person-years. The RR was significantly higher with combined chemotherapy and radiation therapy (6.1) than with radiation therapy alone (4.0, P =.015). The risk increased with increasing radiation field size (P =.03) in patients who received combined modality therapy, and with time after Hodgkin disease. After 15 and 20 years, there was a 2.3% and 4.0% excess risk of second malignancy per person per year. The 5-year survival after development of a second malignancy was 38.1%, with the worst prognosis seen after acute leukemia and lung cancer. The excess risk of second malignancy after Hodgkin disease continues to be increased after 15 to 20 years, and there does not appear to be a plateau. Our analysis suggests that the risk may be reduced with smaller radiation fields, as are used in current trials of abbreviated chemotherapy and limited-field radiation therapy.
Assuntos
Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Segunda Neoplasia Primária/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Terapia Combinada/efeitos adversos , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Doença de Hodgkin/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/mortalidade , Risco , Fatores de Risco , Taxa de SobrevidaRESUMO
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.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia Adjuvante , Criança , Doxorrubicina/administração & dosagem , Esquema de Medicação , Doença de Hodgkin/patologia , Humanos , Metotrexato/administração & dosagem , Estadiamento de Neoplasias , Procarbazina/administração & dosagem , Dosagem Radioterapêutica , Radioterapia Adjuvante/métodos , Fatores de Risco , Falha de Tratamento , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
PURPOSE: To analyze the long-term survival and the pattern and timing of excess mortality in patients with early-stage Hodgkin's disease. PATIENTS AND METHODS: Between 1969 and 1997, 1,080 patients age 50 or younger were treated for clinical stage IA to IIB Hodgkin's disease. Overall survival was determined, and prognostic factors were assessed. Relative risk and absolute excess risk (AR) of mortality were calculated for the entire cohort and by prognostic groups (on the basis of B symptoms, mediastinal status, and number of sites, modified from the European Organization for Research and Treatment of Cancer). RESULTS: The median follow-up was 12 years. The 15- and 20-year Kaplan-Meier survival estimates were 84% and 78%, respectively. Cox proportional hazards models showed that number of involved sites (P =.006), mediastinal status (P =.02), and histology (P =.02) were independent predictors of death from all causes. The AR of mortality in patients with a favorable prognosis increased over time, whereas for those with an unfavorable prognosis, the AR peaked in the first 5 years, predominantly from Hodgkin's disease. The relative risk of mortality from all causes, causes other than Hodgkin's disease, second tumors, and cardiac disease remained significantly elevated more than 20 years after treatment. CONCLUSION: Patients treated for early-stage Hodgkin's disease have a sustained excess mortality risk despite good control of the disease. Treatment reduction efforts in patients with early-stage, favorable-prognosis disease should continue, but for patients with an unfavorable prognosis, modified treatment may not be advisable. The excess mortality noted beyond two decades underscores the importance of long-term follow-up care in patients treated for Hodgkin's disease.