ABSTRACT
Primary hypothyroidism commonly occurs after radiotherapy (RT), and coincides with increased circulating thyroid-stimulating hormone (TSH) levels.We tested therefore the protective effect of suppressing TSH with L-thyroxine during RT for medulloblastoma/PNET and Hodgkin lymphoma (HL) in a prospective cohort study. From1998 to 2001, a total of 37 euthyroid children with medulloblastoma/PNET plus 14 with HL, scheduled for craniospinal irradiation and mediastinum/neck radiotherapy, respectively, underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of craniospinal iiradiation. From 14 days before and up to the end of radiotherapy, patients were administered L-thyroxine checking every 3 days TSH to ensure a value < 0.3 μIU/mL. During follow-up, blood tests and ultrasound were repeated; primary hypothyroidism was considered an increased TSH level greater than normal range. Twenty-two/37 patients with medulloblastoma/PNET and all the 14 patients with HL were alive after a median 231 months from radiotherapy with 7/22 and 8/14 having correctly reached TSH levels < 0.3 μIU/mL and well matched for other variables. Twenty years on, hypothyroidism-free survival rates differed significantly, being 60% ± 15% and 15.6% ± 8.2% in TSH-suppressed vs. not-TSH suppressed patients, respectively (P = 0.001). These findings suggest that hypothyroidism could be durably prevented in two populations at risk of late RT sequelae, but it should be confirmed in a larger cohort.
Subject(s)
Child , Humans , Cerebellar Neoplasms , Hodgkin Disease/radiotherapy , Hypothyroidism/prevention & control , Medulloblastoma/radiotherapy , Prospective Studies , ThyrotropinABSTRACT
O linfoma primário de mama (LPM) é um tumor raro, correspondente a até 0,5% dos cânceres de mama. Apresenta-se o caso de uma paciente do sexo feminino, de 56 anos, que apresentava um nódulo em união dos quadrantes laterais de mama direita, medindo 4,0x3,0 cm, de aparecimento há cerca de dois anos, com aumento progressivo e sem outros sintomas associados. Na axila direita havia sinais clínicos e ultrassonográficos de comprometimento linfonodal. A mamografia identificou três nódulos em mama direita, lobulados e definidos, confirmados à ultrassonografia. O diagnóstico inicial, feito através de punção aspirativa por agulha fina (PAAF) e biópsia por agulha grossa (BAG), foi de um carcinoma ductal invasor de mama. O exame imuno-histoquímico para definição de receptores hormonais, acompanhado de revisão de lâminas, evidenciou um linfoma difuso de grandes células com fenótipo B e CD20 positivo. A paciente foi submetida à quimioterapia com rituximab, vincristina, prednisona e ciclofosmamida (R-CHOP), com resposta clínica completa e, posteriormente, à radioterapia da mama. O tipo mais comum de LPM é o linfoma não Hodgkin difuso de grandes células, que corresponde a aproximadamente 2% de todos os linfomas extranodais. O tratamento do LPM consiste de quimioterapia e radioterapia, estando a cirurgia reservada para casos selecionados.
Subject(s)
Humans , Female , Middle Aged , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Biopsy, Needle , Biopsy, Fine-NeedleABSTRACT
A prevenção de complicações cardiovasculares tardias após radioterapia (RT) para tratamento de um tumor maligno é um desafio. Relatamos o caso de um jovem paciente com linfoma de Hodgkin submetido a tratamento com RT que desenvolveu doença cardíaca isquêmica no seguimento, embora não apresentasse fatores de risco cardiovasculares. Concluímos que pacientes submetidos a RT que apresentam dor torácica deveriam ser criteriosamente avaliados em relação à doença arterial coronariana.
Prevention of late cardiovascular complications after radiation therapy (RT) for treatment of a malignant tumor is challenging. We report the case of a young male patient with Hodgkin's lymphoma treated with RT, who developed ischemic heart disease during follow-up, although he had no cardiovascular risk factors. We conclude that patients undergoing RT who experience chest pain should be fully investigated for coronary artery disease.
Subject(s)
Humans , Male , Young Adult , Coronary Artery Disease/etiology , Coronary Vessels/radiation effects , Hodgkin Disease/radiotherapy , Radiation Injuries/complications , Coronary Artery Disease/surgery , Radiation Injuries/surgeryABSTRACT
OBJETIVO: Comparar o desempenho das sequências T1, T2, STIR e DWIBS (difusão de corpo inteiro com supressão do sinal de fundo) na identificação de sítios caracterizados como acometidos pelo linfoma de Hodgkin nas cadeias linfonodais, órgãos parenquimatosos e medula óssea, e avaliar a concordância entre os examinadores. MATERIAIS E MÉTODOS: Foram estudados 12 pacientes com diagnóstico confirmado de linfoma de Hodgkin. Os pacientes foram encaminhados para o exame de ressonância magnética, sendo realizadas as sequências ponderadas em T1, T2, STIR e DWIBS. RESULTADOS: O número de sítios linfonodais caracterizados como acometidos nas sequências ponderadas em T1 e T2 apresentaram resultados semelhantes (8 sítios), mas inferiores às sequências STIR e DWIBS (11 e 12 sítios, respectivamente). Quanto ao acometimento da medula óssea, observaram-se os mesmos valores para as sequências T1, T2 e DWIBS (17 lesões), superiores ao valor encontrado na sequência STIR (13 lesões). Quando realizada a comparação entre os examinadores, nota-se que há alta concordância entre as quatro sequências. CONCLUSÃO: As sequências STIR e DWIBS detectaram maior número de linfonodos caracterizados como acometidos. Todas as sequências apresentaram resultados semelhantes na avaliação dos órgãos parenquimatosos e medula óssea. Em todas as sequências analisadas houve alta concordância entre os examinadores.
OBJECTIVE: To compare the performance of the T1, T2, STIR and DWIBS (diffusion-weighted whole-body imaging with background body signal suppression) sequences in the staging and follow-up of pediatric patients with Hodgkin's lymphoma in lymph node chains, parenchymal organs and bone marrow, and to evaluate interobserver agreement. MATERIALS AND METHODS: The authors studied 12 patients with confirmed diagnosis of Hodgkin's lymphoma. The patients were referred for whole body magnetic resonance imaging with T1-weighted, T2-weighted, STIR and DWIBS sequences. RESULTS: The number of lymph node sites characterized as affected by the disease on T1- and T2-weighted sequences showed similar results (8 sites for both sequences), but lower than DWIBS and STIR sequences (11 and 12 sites, respectively). The bone marrow involvement by lymphoma showed the same values for the T1-, T2-weighted and DWIBS sequences (17 lesions), higher than the value found on STIR (13 lesions). A high rate of interobserver agreement was observed as the four sequences were analyzed. CONCLUSION: STIR and DWIBS sequences detected the highest number of lymph node sites characterized as affected by the disease. Similar results were demonstrated by all the sequences in the evaluation of parenchymal organs and bone marrow. A high interobserver agreement was observed as the four sequences were analyzed.
Subject(s)
Humans , Male , Female , Child , Adolescent , Carcinoma , Hodgkin Disease/diagnosis , Hodgkin Disease/radiotherapy , Head and Neck Neoplasms , Hodgkin Disease , Leukocyte Count , Brazil , Magnetic Resonance Spectroscopy , Prospective StudiesABSTRACT
To evaluate the outcome of children with Hodgkin's disease over a period of Loyrs from a Single instituhon in Kuwait Sixty-three children with previously untreated Hodgkin's disease, who were diagnosed at the Pediatric Oncology Unit of Kuwait Cancer Control Centre, Shuwaikh, Kuwait from January 1998 to December 2007 were included in the study. All cases were proved by histopathology, and staging was carried out according to the Ann Arbor system. Our series included 37 [59%] males and 26 [41%] females with a median age of 10 years [range 3-15 years]. B symptoms were present in 20 [32%] children. Bulky disease was noted in 28 [44%] children, with stages III in 8 [13%] and IV in 12 [19%] children. Chemotherapy was administered as a primary treatment in 63 children. The median number of chemotherapy cycles given was 6 [range 2-8]. Radiotherapy was used in 40 [63%] children. Grade III hematological toxicity was observed in 23[37%] and grade IV in 14 [22%] children. Hypothyroidism was observed in 20 [32%] children. Fifty-five children achieved a complete remission [87%] and 2 children achieved a partial remission [3%] with an overall response rate of 90%. Three children achieved a progressive disease [5%] and response could not be evaluated in 3 [5%] children. At a median follow-up of 67 months [5.5 years], the overall survival was 91%. With moderate toxicity, combined modality therapy is effective in the treatment of childhood Hodgkin's disease
Subject(s)
Humans , Female , Male , Child, Preschool , Child , Adolescent , Hodgkin Disease/radiotherapy , Hodgkin Disease/mortality , Antineoplastic Agents , Survival Analysis , Treatment OutcomeABSTRACT
Background: Hodgkin lymphoma is a highly curable disease. Aim: To evaluate the clinical characteristics and the treatment results of Hodgkin lymphoma patients of the National Cancer Program in Chile. Patients and methods: Prospective assessment of 682 patients treated in 18 adult cancer centers. Progression free survival (PFS) and overall survival (OS) were calculated. Median follow up was 127, 95, 87, 72 and 50 months for C-MOPP, radiotherapy (RT), C-MOPP/ABV, NOVP and ABVD, respectively. Results: Median age was 37 years (15-84). Nodular sclerosis and mixed cellularity were equally expressed. Advanced stages (III & IV) were present at diagnosis in 61 percent of cases. Age over 40 was an adverse prognostic factor (p <0.001). The rate of PFS at 5 and 10 years for early stages was 73 percent and 66 percent with RT, 80 percent and 74 percent with C-MOPP+RT, 73 percent and 71 percent with C-MOPP/ABV, 59 percent and 59 percent with NOVP+RT, and 81 percent with ABVD+RT, at 5 years, being significantly lower for NOVP (p =0.02). The rate of OS at 5 and 10 years for advanced stages was 82 percent and 70 percent with RT, 82 percent and 76 percent with C-MOPP+RT, 82 percent and 80 percent with C-MOPP/ABV, 68 percent and 60 percent with NOVP, and 85 percent with ABVD at 5 years, also significantly lower for NOVP (p =0.04). For advanced stages, the rate of PFS at 5 and 10 years was 49 percent and 43 percent with C-MOPP, 69 percent and 62 percent with C-MOPP/ABVD or C-MOPP/ABV, and 71 percent at 5 years with ABVD, significantly lower for C-MOPP (p =0.01). The rate of OS at 5 and 10 years was 52 percent and 46 percent with C-MOPP, 70 percent and 63 percent with C-MOPP/ABVD or C-MOPP/ABV and 76 percent with ABVD at 5 years, significantly lower for C-MOPP (p =0.0002). Conclusions: Age over 40 years was an adverse prognostic factor. C-MOPP/ABVD, C-MOPP/ABV and ABVD had comparable results and reached a high tumor control and overall survival in both early...
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , National Health Programs , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Chi-Square Distribution , Chile , Cyclophosphamide/administration & dosage , Dacarbazine/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Follow-Up Studies , Hodgkin Disease/radiotherapy , Mitoxantrone/administration & dosage , Prednisolone/administration & dosage , Prednisone/administration & dosage , Procarbazine/administration & dosage , Prospective Studies , Treatment Outcome , Vinblastine/administration & dosage , Vincristine/administration & dosageABSTRACT
An interesting case was found while audit / computation of previous medical record during last year at Nuclear Institute of Medical Radiotherapy Jamshoro - Pakistan. Case was a young lady who presented with upper third esophageal carcinoma some 14 years, after the patient had external beam radiotherapy by upper mantle field set up for stage I-A Hodgkin's disease. Long latent period, site of the second cancer at the most in-homogenous dose distribution during previous radiotherapy and deviation of age at presentation from standards seem the previous radiotherapy as cause of this second primary cancer. This case report will help to identify the factors / tools responsible for this deadly complication and for improvement in the management profile of such patients
Subject(s)
Humans , Female , Hodgkin Disease/radiotherapy , Hodgkin Disease/mortality , Lymphatic Irradiation , Radiotherapy/adverse effects , Treatment OutcomeABSTRACT
El Linfoma de Hodgkin es una de las neoplasias malignas más comunes en la población joven. Es esencial la correcta estadificación para aplicar la estrategía terapéutica, el estadiaje es condicionado directamente por la diseminación tumoral. Este método de diagnóstico utilizado en Medicina Núclear vence limitaciones de otras técnicas convencionales: Tomografía y Resonancia, que sólo aportan información morfológica, al proporcionar información funcional, metabólica y estructural permite la detención de metástasis a distancia con sensibilidad del 79 por ciento y especificidad del 97 por ciento. Se describe, caso clínico de paciente femenino 32 años, con: Linfoma de Hodgkin EST IIA, que presentó pobre respuesta a quimioterapia inicial, y al ser sometida a la realización de la Tomografía por emisión de positrones, ésta detectó focos activos de neoplasia a nivel de la superficie hepática que en la tomografía habían sido desapercibidos, criterio que condicionó el estadiaje a IVA, hecho que permitió la modificación del plan terapéutico a poliquimioterapia, con la cual se obtuvo mejores resultados.
Subject(s)
Humans , Adult , Female , Hodgkin Disease/pathology , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Neoplasm Metastasis/diagnosis , Neoplasm Metastasis/therapy , Tomography, Emission-Computed/methods , Asthma/etiology , Biopsy/methods , Myopia/ethnologyABSTRACT
Positron emission tomography (PET) with fluorine-18 labeled deoxyglucose (FDG) is useful in the management of lymphomas. In this review, some general concepts of this metabolic test are defined. It has an excellent diagnostic yield in Hodgkin disease as well as in most non Hodgkin lymphomas. Staging, restaging residual mass evaluation and the control of therapy are the main indications for FDG-PET. Images with FDG have a high diagnostic and prognostic value, that is superior to anatomical images and conventional staging techniques. They are also helpful for the assessment of tumor activity in abnormal lymph nodes or large masses that have been treated and reduce their size slowly or show an incomplete resolution. Currently, the resolution of dedicated PET equipments is 6 mm and bigger lesions can easily be detected. The main differences and advantages of FDG versus gallium-67 in lymphoma are also discussed, as well as the initial local experience with the technique in lymphoma patients.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Hodgkin Disease , Lymphoma, Non-Hodgkin , Positron-Emission Tomography , Radiopharmaceuticals , Disease-Free Survival , Gallium Radioisotopes , Hodgkin Disease/pathology , Hodgkin Disease/radiotherapy , Lymphoma, Non-Hodgkin/pathology , Lymphoma, Non-Hodgkin/radiotherapy , Neoplasm Staging , Prognosis , Sensitivity and SpecificityABSTRACT
The proper treatment for early-stage Hodgkin's disease is controversial. The purpose of this study was to evaluate the therapeutic outcomes of various treatment strategies in supradiaphragmatic clinical early-stage Hodgkin's disease. This retrospective study reviewed the medical records of 105 eligible patients [49 stage I, 59 stage II] who were treated at radiotherapy- oncology departments of Qaem and Omid hospitals in Mashhad [Iran] from April 1995 to April 2000. 26 patients had B symptoms and 5 had large mediastinal mass. Treatment of patients consisted of chemotherapy alone [43 cases], radiotherapy alone [46 cases, 40 mantle and 6 Total nodal irradiation] and combined modality [16 cases]. Survival rates were calculated by Kaplan- Meier model. Log-rank test was used to compare the survival profile between groups. The median age of patients was 25 years with a male to female ratio of 1.56: 1. In comparison with radiotherapy only group, Primary chemotherapy and combined modality groups had significantly more cases with unfavorable factors such as B symptoms, Large mediastinal mass, ESR>40 and stage II. For chemotherapy, combined modality and radiotherapy groups the 5-year progression free survival was 72.5%, 82.5% and 56.2% [P<0.05] and the 5-year disease specific survival was 82.9%, 91.6% and 82.5% respectively. Despite having more cases with unfavorable factors, patients who underwent chemotherapy or combined treatment had lower relapse rates compared to radiotherapy only group. However, there was not a significant difference in 5-year disease specific survival rates between these groups
Subject(s)
Humans , Male , Female , Diaphragm/pathology , Hodgkin Disease/radiotherapy , Hodgkin Disease/drug therapy , Retrospective StudiesABSTRACT
Doença cardíaca isquêmica é uma complicação rara e, só recentemente reconhecida, de irradiação mediastínica para tratamento de tumores nesta região. É relatado caso de uma mulher de 51 anos com angina do peito, rapidamente progressiva, em que o achado angiográfico foi representado por lesão suboclusiva ostial de tronco de coronária esquerda. A história pregressa era marcada por uso de radioterapia para tratamento de linfoma Hodgkin mediastínico, com íntima relação com ventrículo direito, ressecado cirurgicamente e tratado em seqüência com irradiação e quimioterapia, dois anos antes. A indução de estenoses coronarianas nesses pacientes pode ser dependente ou não de aterosclerose focal e é mediada, principalmente, por espessamento intimal decorrente de fibrose tissular, sem que haja alteração na camada média e com predileção pelas porções proximais (ostiais) das artérias principais. O reconhecimento desta condição (radioterapia torácica), como fator isolado e independente para doença coronariana, deve ser considerada na programação de medidas para prevenção, detecção e tratamento precoce.
Subject(s)
Humans , Female , Middle Aged , Coronary Disease/etiology , Graft Occlusion, Vascular/etiology , Hodgkin Disease/radiotherapy , Mediastinal Neoplasms/radiotherapy , Radiotherapy/adverse effects , Mammary ArteriesABSTRACT
Nos últimos anos, houve um progresso substancial na abordagem do paciente com doença de Hodgkin. Uma nova classificação histopatológica foi adotada, e fatores prognósticos reprodutíveis foram identificados. Os pacientes são tratados de acordo com o estádio clínico e, no caso de pacientes com doença localizada, também de acordo com os fatores prognósticos. Uma consistente série de estudos em pacientes com doença localizada tornou obsoleta a realização de laparotomia e a abordagem radioterápica isolada. Nos pacientes com doença avançada, o ABVD emergiu como o regime com a melhor relação risco/benefício após uma dura seqüência de comparações com o MOPP e combinações de MOPP e ABVD. Dois regimes inovadores estão em testes, o Stanford V e o BEACOPP. Entretanto, o avanço dos resultados terapêuticos depende da redução da toxicidade nos pacientes de baixo risco e da melhora do controle da doença nos pacientes de alto risco.
Subject(s)
Humans , Hodgkin Disease/diagnosis , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Hodgkin Disease/therapy , Neoplasms, Second Primary/drug therapy , Neoplasms, Second Primary/radiotherapy , PrognosisABSTRACT
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 twenty-four patients with clinical stages I and IIA, favorable [nonbulky] Hodgkin's disease were treated with four cycles of VAMP chemotherapy and 15Gy involved field radiation for those who achieved a complete response, or 25.5Gy for those who achieved a partial response to two cycles of VAMP with a median follow-up of 49 months [range, 74 to 66 months], the overall and event-free survival were 95.8% and 87.5%, respectively. The only factor associated with longer event-free survival was the number of initially involved sites. 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 side-effects. These results indicates that patients with stages I and IIA, non-bulky, and involving less than three Ann Arbor sites can be cured with limited therapy that does not include an alkylating agent bleomycin, etoposide, or high-dose extended-field radiation therapy
Subject(s)
Humans , Male , Female , Vinblastine , Doxorubicin , Methotrexate , Prednisone , Child , Adolescent , Combined Modality Therapy , Treatment Outcome , Hodgkin Disease/radiotherapyABSTRACT
En las últimas décadas se ha producido un incremento en la sobrevida de las enfermedades malignas pediátricas. En la enfermedad de Hodgkin (EH) esta ha alcanzado el 90 por ciento, sin embargo la morbilidad secundaria al tratamiento persiste. Objetivos: determinar la incidencia de enfermedad pulmonar secundaria al tratamiento de la EH en pacientes pediátricos que reciben el protocolo COPP/ABV. Material y métodos: desde el año 1996 gasta el 2000 se diagnosticaron 55 pacientes con diagnóstico de EH que fueron enrolados en este protocolo. Se incluyeron en el estudio 22 pacientes con estudio funcional respiratorio completo. Los pacientes se dividieron en cuatro estadios y estos en A o B de acuerdo a si presentaron síntomas o no al momento del diagnóstico. Las drogas utilizadas fueron Vincristina, Ciclofosfamida. Procarbazina, Prednisona, Doxorrubicina, Bleomicina y Vinblastina. En todos los pacientes se realizaron pruebas de función pulmonar completas. Resultados: se estudiaron 22 pacientes con EH desde el punto de vista respiratorio. Once varones, edad x 12.1 (r6.1 -16.4); 3 pacientes fueron estadio 1.7 estadio II, 2 estadio III y 10 estadio IV. Todos recibieron quimioterapia (QMT) y 13 además radioterapia (RDT). La CVF estubo disminuida en forma significativa en 1/22 luego del 4º ciclo, en 4/22 la DLCO disminuyó más del 20 por ciento, y la CPT presentó caída en 1/22. De los pacientes que recibieron RDT, 10 completaron los estudios funcionales, 6/10 presentaron disminución de la CVF y 4/10 de la DLCO y la CPT. Conclusión: la quimioterapia y la radioterapia producen morbilidad pulmonar. Nosotros creemos necesario monitorear la toxicidad pulmonar mediante pruebas de función pulmonar seriadas en los niños con EH.
Subject(s)
Male , Female , Child , Adolescent , Bleomycin/therapeutic use , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Hodgkin Disease/therapy , Morbidity , Respiratory Function Tests , Prospective StudiesABSTRACT
Destacando a importância da doença de Hodgkin na infância, responsável por cerca de 10 porcento de todos os tumores malignos em Pediatria, o autor resume seu histórico, descreve o comportamento da célula neoplásica na doença, estuda o quadro clínico, diagnóstico, avaliaçäo inicial e estadiamento, a relaçäo do linfoma de Hodgkin com o vírus Epstein-Baar, sua classificaçäo, segundo a OMS, e as formas de tratamento, que incluem radio e quimioterapia, finalizando com um resumo das complicaçöes eventualmente encontradas
Subject(s)
Humans , Child , Reed-Sternberg Cells , Hodgkin Disease/classification , Hodgkin Disease/complications , Hodgkin Disease/history , Hodgkin Disease/pathology , Hodgkin Disease/drug therapy , Hodgkin Disease/radiotherapy , Biopsy , Herpesvirus 4, HumanABSTRACT
Although survival rates have improved dramatically for childhood Hodgkin's disease current treatment entails substantial risks for the late effects such as infertility, second malignancies and cardiopulmonary toxicities. A treatment regimen was chosen with decreased risks of long term sequelae while maintaining efficacy in terms of response and survival. Sixteen children with newly diagnosed and previously untreated Hodgkin's disease were registered and monitored over a two year period. After pretreatment evaluation all patients were treated with six cycles of combination chemotherapy-three of chlorambucil, procarbazine, vinblastine and prednisolone [ChIVPP] and three of adriamycin, bleomycin, vincristine and DTIC [ABVD]. Residual disease was treated with 15-20 Gy of involved-field irradiation. Patients were followed up at six-monthly intervals with physical examination, ECG, chest radiographs, echocardiography and levels of thyroid hormones. After the twelfth birthday patients underwent assessment for levels of gonadotrophins and male patients for testosterone every six months.The observation period now ranges from eleven months to twenty-five months. Fourteen patients are in continued complete remission. One patient died of bilateral severe pneumonia six weeks after the completion of therapy. No long term adverse effects of treatment have been observed so far. In our experience this regimen is well-tolerated and effective and is expected to reduce the risks for late toxicities. A longer follow up duration is, however, required for definitive evaluation