Treatment of Hodgkin's disease in children with VAMP (vinblastine, adriamycin, methotrexate, prednisone) and VEPA (vinblastine, etoposide, prednisone, adriamycin)

Treatment of Hodgkin's disease in children should be directed at maximizing cures and minimizing the long-term effects of alkylating agents, anthracyclines, and bleomycin. In this study methotrexate and etoposide were used in the VAMP/VEPA regimens to treat 60 clinically staged pediatric patients with Hodgkin's disease. Twenty-nine patients with stages I-IIA received four courses of VAMP plus low-dose radiotherapy. Thirty-one IIA bulky disease and IIB-IVB patients received four or six courses of VEPA plus low-dose radiotherapy. There were 6 partial remissions after the completion of chemotherapy and all of these patients relapsed, but 4 were successfuly salvaged with ABMT. Two patients have died. The 3.1-year overall survival rate is 97% (100% VAMP, 94% VEPA) and the event-free survival rate is 88% (97% VAMP, 77% VEPA). These results suggest that VAMP is a reasonable treatment for low stages of Hodgkin's disease, but more advanced disease is not adequately treated by VEPA and low-dose radiotherapy.     

Testicular germ cell tumors in prepubertal children

Pediatric testicular germ cell tumors are rare. Fifteen children, all less than 5 years of age, were evaluated and treated during February 1987 to July 1996. The median age was 18 months (range, 4-60 months). All were staged according to the Pediatric Oncology Group/Children's Cancer Study Group staging system. Seven patients had stage III disease. Histologically, 9 patients had pure endodermal sinus tumor, 1 had endodermal sinus tumor with embryonal carcinoma, 1 had embryonal carcinoma alone, 2 had immature teratoma, and 2 had mature teratoma. Six children were kept on surveillance. All others received chemotherapy with cisplatin, bleomycin, and vinblastine. The 10-year actuarial overall survival rate was 86.7%.     

Clinical staging, primary chemotherapy and involved field radiotherapy in childhood Hodgkin's disease

Sixty children with Hodgkin's disease were clinically staged and treated by MOPP primary chemotherapy followed by 40 Gy nodal radiation limited to involved fields. Overall 5-year survival is 93% while relapse-free survival is 86%. Four patients relapsed. These results confirm that laparotomy no longer has a place in routine staging when chemotherapy is given to all patients and that radiotherapy of localized disease (IA and IIA) can be limited to involved fields. On the basis of these results and data of other published series, the French Society of Clinical Oncology and Hopital Saint Louis initiated a new joint national study to minimize the late effects of combined modality therapy without jeopardizing the good survival. Outlines and preliminary results of this study are presented.     

Hodgkin's disease in Indian children: outcome with chemotherapy alone

BACKGROUND: To assess the efficacy of chemotherapy alone, using four cycles of COPP alternating with four cycles of ABVD in all stages of childhood Hodgkin's disease (HD). PROCEDURE: Between January 1991 and February 2001, 148 previously untreated patients were investigated, treated, and analyzed for remission and survival. RESULTS: There were 134 boys and 14 girls with a median age of 8 years, 75% were less than 10 years old. 63.5% had advanced stage disease (IIB-IV). B symptoms were present in 54.4% of cases; bulky mediastinal mass in 18 cases (12.2%); spleen and bone marrow involvement in 22 (14.9%) and four cases (2.7%), respectively. Mixed cellularity (MC) subtype was found in 86.0%. Response to treatment was evaluated in 133 patients: complete remission (CR) was achieved in 121 patients (91.0%), partial remission (PR) in seven (5.3%), progression occurred in two (1.5%), and three (2.3%) died on therapy. Four patients with mediastinal residual disease were given additional involved field radiotherapy. Out of 111 patients analyzable, five (4.5%) have relapsed 6-30 months after completing chemotherapy, and were treated with additional cycles of ABVD and low-dose involved field radiotherapy. The 5-year actuarial overall survival (OS) and event-free survival (EFS) are 91.5 and 87.9%, respectively. Advanced stage, B symptoms, anemia, spleen, and marrow involvement were adverse prognostic factors for survival. CONCLUSIONS: Chemotherapy alone with alternating COPP/ABVD, without additional radiotherapy, provides high rates of durable remission and is an effective therapy in childhood HD, even in case of large mediastinal mass and peripheral or abdominal bulky disease.     

Hodgkin's disease in Turkish children: clinical characteristics and treatment results of 210 patients

Although Hodgkin's disease (HD) is one of the common malignancies in childhood, there is limited information from developing countries in English literature. The aim of this study is to give epidemiologic features and treatment results of 210 previously untreated children with HD from a developing country. Between 1 June 1984 and 31 December 1992, all children seen who were younger than 18 years old with newly diagnosed, untreated, biopsy-proven Hodgkin's disease were included in this study. A clinical staging system was used to determine the dissemination of the disease. While patients with stage I-II disease received canape treatment protocol (three cycles COPP \[cyclophosphamide, vincristine, procarbazine, prednisolone] or ABVD \[doxorubicin, bleomycine, vinblastine, dacarbazine] plus low-dose involved-field radiotherapy), patients with stage III-IV disease were treated by sandwich protocol (six cycles COPP plus low-dose involved-field radiotherapy). A total of 210 patients with a median age of 8 years were eligible for this study. Male to female ratio was 3:1 and 37 (17.6%) were less than 5 years of age. The major histologic subtype was mixed cellularity (69.6%). Overall survival rates were 91.5 and 87.7%, and event-free survival rates were 71.5 and 70.5% at 5 and 10 years, respectively. No secondary malignancy has been observed so far. The prevalance of Hodgkin's disease in young children is higher and the distribution of histologic subtypes is also different from many Western countries. Canape and sandwich treatment protocols could be used safely in clinically staged childhood HD with tolerable toxicity.     

Pediatric hodgkin's disease in costa rica: Twelve years' experience of primary treatment by chemotherapy alone,without staging laparotomy

This is a prospective and nonrandomized study in which 86 children with previously untreated Hodgkin's disease (HD) were clinically staged (CS) and treated with chemotherapy (CT) alone. Fifty-two (CS IA-38, IIA-7, IIB-3, IIIA-4) received six courses of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP). Ten (CS IA with peripheral nodes) received only three courses of CVPP with a reinforcement of C on day 8. Twenty-four (CS IIIB-18, IVA-2, IVB-4) received six courses of CVPP alternating with six courses of epirubicine, bleomycine, and vincristine (EBO). Surgical staging was not performed in any patient. Two patients (CS IIIB) had partial remission and died from progressive disease. Seventy out of 86 children have not relapsed and are in complete remission with a median follow-up of 65 months (range 13-156 months); 14 children relapsed seven to 37 months from diagnosis (median 16 months); one of them (IV B) died of disease. Thirteen are in second and third remission (median 55 months). Actuarial five year survival rates and relapse-free survival rates are 100% and 90% for CS I to IIIA and 81% and 60% for CS 1MB and IV, respectively. As a result of this study, we can conclude that in developing countries most of the children with HD staged by noninvasive diagnostic techniques can be cured with CT alone as primary treatment and thus will not suffer from the late effects of radiotherapy (RT) and the morbidity of laparotomy and splenectomy. RT alone or with other CT combinations should be considered for children who develop relapse of HD. © 1994 Wiley-Liss, Inc.     

TESTICULAR GERM CELL TUMORS IN PREPUBERTAL CHILDREN

Pediatric testicular germ cell tumors are rare. Fifteen children, all less than 5 years of age, were evaluated and treated during February 1987 to July 1996. The median age was 18 months (range, 4-60 months). All were staged according to the Pediatric Oncology Group/Children's Cancer Study Group staging system. Seven patients had stage III disease. Histologically, 9 patients had pure endodermal sinus tumor, 1 had endodermal sinus tumor with embryonal carcinoma, 1 had embryonal carcinoma alone, 2 had immature teratoma, and 2 had mature teratoma. Six children were kept on surveillance. All others received chemotherapy with cisplatin, bleomycin, and vinblastine. The 10-year actuarial overall survival rate was 86.7%.     

Multimodal therapy for the treatment of nonmetastatic Ewing sarcoma of pelvis

The purpose of this study was to evaluate the outcome of patients with Ewing sarcoma (ES) of the pelvis, attempting to identify prognostic factors to select patients for more aggressive treatment. Seventy-seven patients with nonmetastatic ES of the pelvis were treated at Rizzoli Institute between 1979 and 1996. Four different protocols of chemotherapy were used successively. Two protocols consisted of VACAc, and two of VACAc plus ifosfamide and etoposide. Local treatment consisted of surgery in 5 patients, radiotherapy in 60, and surgery followed by radiotherapy in 12. Mean follow-up was 11 years (range 5-25 years). Thirty-three patients remained continuously free of disease; 43 relapsed (24 due to metastases and 19 to local recurrence and metastases); 1 died of treatment-related complications. The 5- and 10-year event-free survival rates were 45% and 44%, respectively, and the 5- and 10-year overall survival rates were 48 and 44. These results are significantly worse than the ones achieved in 329 contemporary patients with extrapelvic lesions treated with the same protocols of chemotherapy (5- and 10-year event-free survival = 46% vs. 64% and 44% vs. 69%). Thus, despite associated chemotherapy, the outcome of ES localized in the pelvis remains poor, and new innovative methods for the treatment of this tumor are needed.     

Management of childhood lymphomas—Hodgkin's disease and non-Hodgkin's lymphomas

Hodgkin's disease can be cured in greater than 70% of the children diagnosed. Overall 5-year survival rates now approach 90% and approximotely 80% for 10-year survival. Combination chemotherapy along with irradiation has decreased the relapse rate in all stages of Hodgkin's disease. Intensive chemotherapy and irradiation therapy is associated with long-term complications including development of second malignant tumors. Optimum therapy is the minimum therapy associated with uncomplicated care. In 80 to 90% of children with non-Hodgkin's lymphoma the disease is widerspread when obvious clinically at diagnosis, and the first site of relapse is commonly the bone marrow or central nervous system (CNS). Combined chemotherapy, irradiation and CNS prophylaxis has resulted in 50% to 80% 3-year, disease-free survival. Patients with mediast'nal or extensive intrabdominal disease have a poor prognosis.     

MOPP therapy in children with Hodgkin's disease

Between 1979 and 1987, 28 children with Hodgkin's disease were treated with MOPP (nitrogen mustard, Oncovin, prednisone, procarbazine) combination chemotherapy without radiotherapy. Twenty-four were staged clinically. Splenectomy was performed in four only. Staging was as follows: nine (32%) in stage I, five (18%) in stage II, nine (32%) in stage III, and five (18%) in stage IV. Histologic types were lymphocytic predominance in five (18%), mixed cellularity in 15 (54%), nodular sclerosis in seven (25%) and lymphocytic depletion in one (4%). All children achieved complete remission. Two in stages III and IV relapsed and were salvaged with additional chemotherapy and radiotherapy. Twenty-six are in continuous relapse-free remission for periods ranging from 2 to 9 years. The relapse-free survival rate of 92% and survival rate of 100% compares favorably with results obtained using combined modality treatment.     

Nonmetastatic thoracic neuroblastomas: a review of 40 cases

From 1982 to 1987, 40 children with non-metastatic thoracic neuroblastoma were treated with the same therapeutic regimen. According to TNM staging, there were 11 CS I, 19 CS II, and 10 CS III. All patients underwent surgery; 30 had primary surgical excision; in 10 whose tumors were deemed unresectable, surgery was delayed until after a trial of chemotherapy. Operation was completed by several courses of chemotherapy in case of microscopic residual disease or regional lymph node involvement; radiotherapy was delivered in case of gross residual disease. Using this therapeutic approach, EFS is 92% with a median follow-up of 40 months. Severe complications were rare and sequellae appear to be related to the disease, i.e., neurologic consequences of cord compression.     

MALIGNANT LYMPHOMAS IN CHILDREN A CLINICO-PATHOLOGIC RETROSPECTIVE STUDY

ABSTRACT. Garwicr, S., Landherg, T. and Åkerman, M. (Departments of Paediatrics, Radiotherapy, Cytodiagnostics and Pathology, University Hospital, Lund, Sweden). Malignant lymphomas in children—A clinico-pathologic retrospective study. I. Hodgkin's Disease. Acta Paediatr Scand, 63: 673, 1974—Data on 23 children with Hodgkin's disease from a 29-year period are given. Sixteen were boys and 7 girls. At microscopic review of the biopsy material the lesions were typed according to Lukes. Three had Lymphocyte predominance, 7 had Nodular sclerosing type, and 13 had Mixed cellularity. Viewed with the limited staging procedures that often had been used, 17 patients had at presentation localized disease (stages 1 or II), 4 had generalized lymph-adenopathy, and 2 had extralymphatic disease. Treatment had been given with radiation therapy or chemotherapy or the two combined. Data on local recurrence after radiotherapy is in line with other reports, indicating that Hodgkin's disease in children responds in the same way to irradiation as in adults. Fifteen of the 23 are still alive mean 69 months after the initial treatment, 6 of them having been followed for at least 8 years. Of 13 patients evaluable for 5-year survival 6 were alive at 5 years. Children with Hodgkin's disease appear to have similar distribution on histologic types, progression of disease and response to treatment as adults. It seems that similar clinical evaluation procedures and similar therapeutic techniques should he used in Hodgkin's disease in children as in adults.     

The role of fast neutron therapy in unresectable pelvic osteosarcoma: preliminary report

Primary osteosarcoma of the pelvic bones represents less than 10% of all osteosarcoma. despite mutilating surgical procedures or high-dose radiotherapy and neoadjuvant chemotherapy, local failures and distant metastases remain common. the 2-year actuarial survival rate is less than 50% and the disease-free survival is under 20% at 2 years. we report 4 cases of pelvic osteosarcoma treated by a combination of chemotherapy, photon beam and neutron beam radiotherapy. after a median follow-up of 24 months, all 4 patients are alive and disease free. © 1994 wiley-liss, inc.     

Improved survival of children with wilms tumor

To analyze changes in the overall survival (OS) rate of children with Wilms tumor treated in a single institute over nearly 30 years. This study included 327 children with a newly diagnosed Wilms tumor. Their median age was 3 years, and the male:female ratio was 1.1. Survival rates were analyzed according to the stage of disease, histopathology, and different treatment regimens used between 1972 and 1999. At diagnosis, 51.1% of patients had advanced stage disease. Ten patients had anaplasia, and; 97% (317 patients) of the tumors had favorable histopathology. The 10-year OS rate was 60.6% for the entire group, but varied according to the years in which the patients were treated, the chemotherapy regimen, and stage of disease. Patients treated during the periods of 1972 to 1979, 1980 to 1989, and 1990 to 1999 had 10-year OS rates of 48.5%, 64.3%, and 72.8%, respectively. The 10-year OS rate in children treated with actinomycin only was 36.7% compared with 48% for children treated with the actinomycin-D+vincristine regimen with a 3-month interval, 67% for the actinomycin-D+vincristine regimen with a 1.5-month interval, 54.5% for the poor-risk regimen (actinomycin-D, vincristine, cyclophosphamide, and adriamycin), and 53.4% for the SIOP-9 protocol. Children with stage I to IV disease had 10-year OS rates of 75%, 77.1%, 54.4%, and 30.4%, respectively. The 10-year OS rates for children with stage III and IV disease increased from 46.4% and 13.4% for patients treated between 1972 to 1979 period to 75% and 54.5% for children treated during 1990 to 1999. The 10-year OS rate for children with Wilms tumor improved as treatment strategies evolved, illustrating that pediatric oncology in Turkey is developing parallel to the Western world.     

Childhood stage IV Hodgkin disease: therapeutic results of the Polish pediatric leukemia/lymphoma study group.

BACKGROUND: The therapeutic management in patients with stage IV Hodgkin disease is still controversial. PROCEDURE: Among 783 children with Hodgkin disease treated from 1971 to 1996, 56 patients (7.3%) were diagnosed with stage IV. The treatment consisted of MVPP or MVPP/B-DOPA chemotherapy combined with involved-field radiotherapy in 50 children. RESULTS: The results of treatment of stage IV patients were compared in the three sequential time periods, during which the therapy was modified. In these periods, the first complete remission was obtained in 67%, 86%, and 90% of children, respectively, and the 10-year event-free survival was 42%, 64%, and 85%, respectively. CONCLUSIONS: Alternate multidrug chemotherapy combined with low-dose involved-field radiotherapy is at present a satisfactory therapeutic method in children with stage IV Hodgkin disease.     

Treatment Results of Hodgkin's Disease in Indian Children

This is a retrospective study of Hodgkin's disease in children less than 15 years of age who were registered at Tata Memorial Hospital in India from January 1985 through December 1990. Clinicopathologic characteristics and response were evaluated in 147 patients and survival was calculated in 187. There were 126 boys and 21 girls (6:1). All patients were treated with combination chemotherapy and involved field radiotherapy. The COPP schedule was given to 108 patients, COPP/ABVD to 33, and ABVD to 6. Ninety-three patients (63%) had stage 1 or II disease and 54 (37%) had stage III or IV disease. B symptoms were observed in 65 patients (56%) and bulky disease in 40 (27%). Histologically, the most common subtype was mixed cellularity, seen in 95 patients (65%). Complete response was observed in 136 (89%), partial response in 6 (4%), and there were 4 treatment-related deaths. Relapse has been observed in 11%. Seven-year actuarial survival was 73% and event-free survival was 64%. Median survival has not yet been reached, with a median follow-up of 36 months.     

Combined treatment strategy in over 200 children with Hodgkin's disease: graduated chemotherapy, involved field irradiation with low dosage and selective splenectomy. A report of the cooperative therapy study DAL-HD-82

It was the aim of the cooperative therapy study HD-82 for children with Hodgkin's disease to reduce chemo- and radiotherapy and to investigate of a strategy for selective splenectomy previously developed in the Hodgkin study HD-78. Between December 1981 and December 1984 207 patients (131 boys and 76 girls) below 16 years of age were enrolled in this study. In 174 out of 207 patients (84.1%) the criteria for selective splenectomy were applied i.e. the spleen was only removed when the splenic surface was nodular or when the lymphnodes at the splenic hilus and/or the pancreatic tail were enlarged. 69 out of 174 patients (39.7%) had a splenectomy. 50 of the removed 69 spleens (72%) showed histological evidence of Hodgkin's disease. These results were comparable to the 36% and 73% predicted from the retrospective analysis in the HD-78 study. According to the stage of Hodgkin's disease three different treatment groups with 2, 4 and 6 cycles of OPPA/COPP were formed (stage I/IIA, IIB/IIIA and IIIB/IV). Radiation therapy was given as involved field irradiation with a total dose of 35, 30 and 25 Gy depending on the extent of the chemotherapy. 203 patients were treated according to the protocol. Until the 30th of November 1985 3 patients died from intercurrent disease during a follow-up period of 11 to 47 months (median 29 months). 5 patients relapsed. The probability for disease-free survival after 3 1/2 years is 96% for the total group and 99%, 96% and 87% for the three treatment groups including 100, 53 and 50 patients in each group respectively. Conclusions: 1. The OPPA/COPP chemotherapy eliminates reliably occult microfoci. 2. The radiation doses in combination with the chemotherapy are sufficient to prevent local recurrences. 3. The decisional model for selective splenectomy has proved to be extremely valuable prospectively.     

Metastatic rhabdomyosarcoma: a retrospective review of patients treated at the hospital for sick children between 1989 and 1999

Children with metastatic rhabdomyosarcoma (RMS) continue to fare poorly (3-year survival 20-30%). Various therapies, including end-intensification with high-dose chemotherapy and stem cell support, have been used in an attempt to improve the outcome of these patients. The authors reviewed their clinical experience over a 10-year period to identify predictors of outcome in these patients. The authors reviewed the clinical characteristics, treatment, and outcome of all patients with metastatic RMS diagnosed and treated at the Hospital for Sick Children between 1989 and 1999. Kaplan-Meier curves were generated to compare survival and failure-free survival of different subgroups of patients. Differences between groups were analyzed using univariate analysis and the log-rank test. Seventeen patients with metastatic RMS were identified. Thirteen patients were treated with standard chemotherapy +/- radiotherapy and four received high-dose end-intensification therapy with stem cell support. The estimated 3-year overall survival (OS) and failure-free survival rates for all patients were 35% (95% CI 13-58) and 29% (95% CI 18-40), respectively. Patients with embryonal histology, metastases confined to the lung, and age younger than 10 years had a 3-year OS of 100%, compared with an OS of 0% for the remaining patients (P < 0.0006). The median follow-up for the five survivors was 5.5 years. The authors have identified a subset of children with metastatic RMS having embryonal histology, age less than 10 years, and only pulmonary metastases who have favorable survival outcomes when treated with chemotherapy with or without stem cell support.     

Survival and late effects in medulloblastoma patients treated with craniospinal irradiation under three years old

Conventional treatment of medulloblastoma has involved surgery to the primary tumour and radiotherapy to the primary tumour and radiotherapy to the primary site and craniospinal axis. However CNS irradiation in a young child may result in significant side effects. Thus new treatment strategies have emerged which include chemotherapy, given in order to delay radiotherapy, to enable radiation dose reduction to the primary site and craniospinal axis, or even to eliminate radiotherapy completely. Such treatments have not yet been adequately evaluated in terms of survival and late effects. We report a retrospective study of 37 patients under the age of 36 months treated with postoperative craniospinal irradiation, in which the radiation dose to the neuroaxis was below conventional dosage. The overall actuarial 10-year survival rate was 44% and the actuarial 10-year relapse free survival rate was 54%. Both radiotherapy and chemotherapy contributed to morbidity and mortality. Four of 16 patients who survived longer than 10 years had no hard neurological signs; all but one patient have required extra support at school. Of nine patients available for work, two have obtained employment but only one has maintained this. No young adults have married. Despite lower doses of radiation, all but 1 survivor has significant spine shortening, and all who reached final height were short. Further work is needed to complete the profile of late effects in this group, which should include the survivors own perceptions of quality of life. It is hoped that multimodality treatment and supportive care can sustain acceptable survival rates but reduce the burden of late effects. Med. Pediatr. Oncol. 28:348–354, 1997. © 1997 Wiley-Liss, Inc.     

Adjuvant chemotherapy with vincristine, doxorubicin, and cyclophosphamide in the treatment of postenucleation high risk retinoblastoma.

PURPOSE: To study risk factors and outcome of children with high risk retinoblastoma who receive postenucleation vincristine, doxorubicin, and cyclophosphamide. PATIENTS AND METHODS: Charts of all patients who received adjuvant chemotherapy for retinoblastoma were reviewed. Thirty-six patients were identified who received chemotherapy for high risk histopathologic features. Histopathology slides of these 36 patients were retrieved and reviewed, and the disease was staged according to the modified St. Jude staging system. The disease was unilateral in 23 patients (64%). There were 9 patients with stage I disease, 18 with stage II, and 9 with stage III. Twenty-four patients (67%) completed 12 of the 12 scheduled chemotherapy cycles, and 11 patients (30%) received 4 to 11 cycles because of relapse, disease progression, or family reasons. A life-threatening complication developed in one patient after the first cycle, and this patient received no further chemotherapy. RESULTS: Five (3 with unilateral and 2 with bilateral disease) of the 36 patients developed distant metastasis and subsequently died. All had massive tumors; three had choroidal and up to surgical margin optic nerve invasion, and two had tumor extending posterior to lamina cribrosa. Six other patients had local relapse or progressive disease. All of these six patients had bilateral disease and failed in the intact eye during (three patients) or after (three patients) chemotherapy. Only two of the six patients were alive with no disease 50 and 102 months from diagnosis. With a median follow-up of 5.6 years, the 5-year and 10-year actuarial overall survival rates were 86% and 74%, respectively. The 5-year survival rates for patients with modified St. Jude stage I, II, and III disease were 100%, 91% (95% confidence interval, 57% to 100%), and 58% (95% confidence interval, 22% to 94%), respectively (P = 0.008). The survival rate was significantly different among patients with optic nerve involvement anterior to lamina cribrosa, posterior to lamina cribrosa, and surgical margin involvement (100%, 55%, and 41%, respectively; P = 0.003). Multivariate analysis showed that only the degree of optic nerve involvement (and therefore, modified St. Jude stage) was predictive of poor outcome. CONCLUSION: Patients with retinoblastoma involving the optic nerve beyond the lamina cribrosa have low survival rate despite local therapy and adjuvant chemotherapy with vincristine, doxorubicin, and cyclophosphamide. Progression of disease in the intact eye of three patients receiving chemotherapy is of concern. Alternative chemotherapeutic agents should be considered for patients with such high risk features.