Primary tumor control in patients with stage 3/4 unfavorable neuroblastoma treated with tandem double autologous stem cell transplants

OBJECTIVE: To assess the efficacy and toxicity of local radiotherapy in achieving local control in patients with stage 4 or high-risk stage 3 neuroblastoma treated with induction chemotherapy and tandem stem cell transplants. METHODS: Fifty-two children with stage 4 or high-risk stage 3 neuroblastoma were treated on a standardized protocol that included five cycles of induction chemotherapy, surgical resection of the primary tumor when feasible, local radiotherapy, and then consolidation with tandem myeloablative cycles with autologous peripheral blood stem cell rescue. Local radiotherapy (10.5-18 Gy) was administered to patients with gross or microscopic residual disease prior to the myeloablative cycles. Thirty-seven patients received local radiotherapy to the primary tumor or primary tumor bed. Two patients with unknown primaries each received radiotherapy to single, unresectable, bulky metastatic sites. The second of the myeloablative regimens included 12 Gy of total body irradiation. RESULTS: Of the 52 consecutively treated patients analyzed, 44 underwent both transplants, 6 underwent a single transplant, and 2 progressed during induction. Local radiotherapy did not prolong recovery of hematopoiesis following transplants, did not increase peritransplant morbidity, and did not prolong the hospital stay compared with patients who had not received local radiotherapy. Local control was excellent. Of 11 patients with disease recurrence after completion of therapy, 9 failed in bony metastatic sites 3 to 21 months after the completion of therapy, 1 recurred 67 months following therapy in the previously bulky metastatic site that had been irradiated, and 1 had local recurrence concurrent with distant progression 15 months following the second transplant. The three-year event-free survival was 63%, with a median follow-up of 29.5 months. The actuarial probability of local control was 97%. CONCLUSIONS: The use of induction chemotherapy, aggressive multimodality therapy for the primary tumor, followed by tandem myeloablative cycles with stem cell transplant in patients with stage 4 or high risk stage 3 neuroblastoma has resulted in acceptable toxicity, a very low local recurrence risk, and an improvement in survival.     

Radiation therapy in juvenile aggressive fibromatosis]

BACKGROUND: In about one third of patients suffering from a desmoid tumor primary complete resection is not feasible. Furthermore in locally relapsing tumors reoperation alone does not result in cure in many cases. Radiotherapy can be applied in both groups of patients with curative intention. But the indication of radiotherapy is challenging particularly in children and adolescents due to the impending late radiation sequelae such as growth delay, fibrosis and radiation induced secondary malignancy. PATIENTS AND METHOD: The follow up and outcome of five irradiated children/adolescents with desmoid tumors, registered in the German-Cooperative-Soft-Tissue-Sarcoma Study (CWS) was looked at, and the corresponding literature was reviewed. RESULTS: Radiotherapy of gross residual or relapsing tumors resulted in long lasting event free survival in two cases (3/8 years), but in one patient local progression occurred despite irradiation. Postoperative radiotherapy in patients with microscopic residual disease resulted in both, long lasting event free survival (14 years, 1 patient) and in early local relapse (1.5 years, 1 patient). The role of radiotherapy could not be evaluated clearly by the CWS-experience due to the fact that the irradiated patients were treated individually also by chemotherapy and/or tamoxifen. But despite sparse and retrospective data there is evidence in the literature, that radiotherapy is able to control 65-90% of the unresectable desmoid tumors and that the local relapse rate can be reduced by radiotherapy by 10-20% in patients with microscopic residual disease following resection. CONCLUSIONS: Radiotherapy as primary treatment should be given if complete tumor resection is not feasible without mutilation. Radiotherapy can be applied postoperatively if the risk of local relapse seems to be highly life- or function threatening.     

Pleuropulmonary blastoma: a single-institution experience

Pleuropulmonary blastoma (PPB) is a rare primary intrathoracic mesenchymal malignancy that occurs exclusively in early childhood. Twelve patients were diagnosed with PPB (1 type I, 5 type II, and 6 type III) between 1979 and 2009 at our institution. Upfront complete tumor resection was successful in 5 of 6 patients. Six patients had biopsy followed by neoadjuvant chemotherapy, 2 had complete tumor resection, and 2 had microscopic residual disease after surgery. All patients received vincristine, dactinomycin, and cyclophosphamide chemotherapy. Eight received additional chemotherapy with doxorubicin, cisplatin, etoposide, or ifosfamide. Three patients received local irradiation. The 5-year event-free and overall survivals were 33% ± 14% and 42% ± 14%, respectively. Median time to progression was 8 months. Five of 9 patients with gross total resection survived, whereas all 3 with gross residual disease died. Three of 5 survivors did not receive radiation. A high index of suspicion for PPB must be maintained in all patients diagnosed with intrathoracic sarcoma in early childhood. Gross total resection is necessary for cure, and selected patients do not require radiation therapy.     

Complete surgical resection plus chemotherapy prolongs survival in children with stage 4 neuroblastoma

The factors that affect survival in patients with stage 4 neuroblastoma vary. Several prospective and retrospective studies have provided conflicting conclusions regarding the benefit of combining aggressive chemotherapy with complete surgical resection. We analyzed our experience to evaluate the effect of complete surgical resection of the primary tumor on survival when disseminated disease has been controlled by chemotherapy. We retrospectively reviewed the medical records of 44 consecutive children with neuroblastoma treated between 1990 and 2000. Twenty-six children with stage 4 disease were enrolled. Most were treated with surgical resection combined with chemotherapy. The survival rate was compared based on the timing (primary versus delayed until chemotherapy had been given) and results of surgery (complete tumor resection, microscopic residual disease, and gross residual disease). The mean survival (52.8 months) of children with delayed complete surgical resection (CSR) was statistically superior to that of those with microscopic residual (20.8 months, p=0.0111) or gross residual tumor (12.2 months, p=0.0141). In the CSR group, 1-, 2-, 3-, and 5-year survival rates were 88%, 77%, 77%, and 65%, respectively, vs. 80%, 40%, 20%, and 0% in the microscopic residual group. In conclusion, complete resection of the primary tumor with no residual disease was associated with improved survival in children with advanced neuroblastoma whose metastatic disease had been controlled by chemotherapy.     

Combined radiation and chemotherapy for advanced undifferentiated nasopharyngeal carcinoma in children

Five children, 11–16 years of age at diagnosis, with advanced (stage IV) undifferentiated nasopharyngeal carcinoma, are reviewed. All had radiotherapy and chemotherapy, four at first treatment, are disease free in 8 months, 6, 10, and 13 years from diagnosis. One patient who had radiotherapy only as primary treatment and chemotherapy for metastases, died 15 months from diagnosis. One patient who received 60 Gy and chemotherapy according to the BACON protocol had severe early toxicity and severe late sequelae of treatment. Three patients who received chemotherapy according to a modified UICC-2 protocol for nasopharyngeal carcinoma and 50 to 54 Gy to the primary site had only mild early toxicity and mild late effects of treatment. With lower radiation doses, adjusted to the effect of preradiation chemotherapy, complete tumor control was achieved and acute and long-term morbidity reduced. Med. Pediatr. Oncol. 28:366–369, 1997. © 1997 Wiley-Liss, Inc.     

Preliminary results of the multicenter trial GPOH-HD 95 for the treatment of Hodgkin's disease in children and adolescents: analysis and outlook

BACKGROUND: In 5 consecutive pediatric and adolescent Hodgkin's disease trials DAL-HD since 1978 the invasive diagnostic procedures and the radiotherapy have gradually been reduced and chemotherapy modified to minimize toxicity and the risk of late effects. Since 1982 the overall survival increased up to 95%. In this trial the possibility of reducing local radiation doses to 20 Gy in patients with good response to chemotherapy and omitting radiotherapy totally for patients with complete remission after chemotherapy was tested. PATIENTS AND METHODS: Over a period of 6 years, from August 1995 to July 2001, 1018 children and adolescents with Hodgkin's disease from Germany, Austria,Switzerland, the Netherlands, Sweden, Norway and Denmark were enrolled in this trial. The chemotherapy was equivalent to previous trial DAL-HD 90. The treatment group (TG) 1 (stages I and IIA) received 2 cycles OPPA for girls and 2 cycles OEPA for boys, TG2 (stages IIEA, IIB, IIIA) and TG3 (stages IIEB, IIIEA, IIIB, IV) received additional 2 or 4 cycles COPP respectively. In contrast to trial DAL-HD 90 boys in stage IIIB and IIIEB received OPPA instead of OEPA. The initial staging as well as the restaging for evaluating tumor volume reduction after chemotherapy was reviewed by the study center. Radiotherapy was planned accordingly: patients with complete remission after chemotherapy were not irradiated (21.9%); all other patients received local radiotherapy to the initially involved sites, depending on the tu-mor response. Patients with a partial remission of> 75 tumor regression were irradiated with 20 Gy (50AX), partial remission of< 75% with 30 Gy (4.1 %), and residual masses of > 50 ml were boosted up to 35 Gy (20.2 %). RESULTS: 36 tumor progressions and 49 relapses occurred over a period of 7 1/2 years (median followup 3 years, data deadline 12/19/02). Kaplan-Meier-analysis after 5 years showed a probability for event-free survival (pEFS) for all patients of 0.88 and for overall survival (pOS) of 0.97. For the total group the pDFS (disease free survival) was lower in 222 non irradiated patients than in the 758 irradiated patients (0.88 vs. 0.92,p - 0.049). But there was a difference between the individual treatment groups. In TG 1 there was no difference between nonirradiated and irradiated patients (0.97 vs. 0.94) and the non-ir-radiated patients showed a better trend. In TG 2, and in TG 2 and TG 3 combined, the pDFS was significantly worse for non irradiated patients in comparison with the irradiated patients (TG2:0.78 vs. 0.92; TG 2 +3:0.79 vs. 0.91). Compared to former DAL-HD trials the pOS stayed stable despite therapy reduction. CONCLUSIONS: A reduction of radiotherapy to 20 Gy for patients in all stages with good response to chemotherapy is possible without deterioration of the results. The omission of radiotherapy for patients in complete remission after chemotherapy is recommended only for patients in early stages (TG1). In future trials the possibility of a wider selection for chemotherapy alone for this group needs to be evaluated. In intermediate (TG2) and advanced (TG3) stages omission of radiotherapy for patients incomplete remission results in a lower pEFS, but the pOS is not significantly reduced. Only with knowledge of the long term effects of today's therapy we can give a satisfactory answer to the question whether in future trials the primary aim should be pEFS as high as possible due to front-line-therapy or reduction of late effects.     

Radiotherapeutic management of intracranial ependymoma

Ependymomas comprise about 10% of all pediatric brain tumors. The most consistent prognostic factor for cure has been the extent of surgical resection. Radiation therapy is considered the standard adjuvant treatment, although there has been no randomized trial comparing surgery alone to surgery and postoperative radiotherapy. Craniospinal irradiation has been used in the past to treat these tumors; however, current data indicate that the most common pattern of failure is an isolated local relapse. Furthermore, prophylactic spinal irradiation has not been shown to prevent spinal dissemination. For this reason, most radiation oncologists currently employ localized radiotherapy fields. Available data indicate that doses greater than 45-50 Gy are needed and associated with better local control. Preliminary data using hyperfractionated radiotherapy doses of greater than 65 Gy indicate an improvement in progression-free survival for subtotally respected ependymoma. Chemotherapy can be used to delay institution of radiotherapy in children less than 3 years of age. The role of chemotherapy in older children needs to be further defined.     

RADIOTHERAPEUTIC MANAGEMENT OF INTRACRANIAL EPENDYMOMA

Ependymomas comprise about 10% of all pediatric brain tumors. The most consistent prognostic factor for cure has been the extent of surgical resection. Radiation therapy is considered the standard adjuvant treatment, although there has been no randomized trial comparing surgery alone to surgery and postoperative radiotherapy. Craniospinal irradiation has been used in the past to treat these tumors; however, current data indicate that the most common pattern of failure is an isolated local relapse. Furthermore, prophylactic spinal irradiation has not been shown to prevent spinal dissemination. For this reason, most radiation oncologists currently employ localized radiotherapy fields. Available data indicate that doses greater than 45-50 Gy are needed and associated with better local control. Preliminary data using hyperfractionated radiotherapy doses of greater than 65 Gy indicate an improvement in progression-free survival for subtotally respected ependymoma. Chemotherapy can be used to delay institution of radiotherapy in children less than 3 years of age. The role of chemotherapy in older children needs to be further defined.     

Primary chemotherapy and tumor resection in Ewing's sarcoma of the ribs. Report of the French society of paediatric oncology

Fifteen patients with primary Ewing's sarcoma of the ribs were entered into the same protocol: thirteen of them had localized disease while two had metastatic disease. The protocol consisted of (1) initial chemotherapy according to size of tumor: patients with a small tumor were given rwo courses of VAC (vincristine, actinomycine D. cyclophosphamide); patients with a large tumor, pleuraj effusion or metastatic disease were given alternating courses of VAC and VAd (vincristine. adriamycine) until maximum regression of the tumor: (2) local radiotherapy: (3) maintenance chemotherapy with VAC/VAd: (4) complete surgical excision at diagnosis in 4 patients, after primary chemotherapy in 6 patients, after chemotherapy and radiotherapy in 2 patients. Six of the 9 evaluable patients had tumor regression higher than 50% after primary chemotherapy. Fourteen patients achieved complete remission. Six patients with localized disease remained disease-free for a median duration of 50 months. These 6 patients were treated by chemotherapy, complete surgical excision and radiotherapy. The results suggest that aggressive treatment with chemotherapy and surgery improve disease-free survival in patients with Ewing's sarcoma of the ribs. Chemotherapy, Ewing's Sarcoma, Rib, Surgery     

Intrakraniale Keimzelltumoren

Germ cell tumors (GCT) of the central nervous system (CNS) derive from primordial totipotent germ cells, which are capable of embryonic and extraembryonic differentiation. The specific feature of GCTs is their midline appearance in respect to the embryonic migration of germ cells and their ability to produce tumor markers. With an annual incidence of 2.2/10⁶ in children, 50% of tumors occur during adolescence. Medical history depends on tumor site. In germinoma, which predominantly appear in the suprasellar region, the time to diagnosis can be several months to years. Tumors of the pineal region are diagnosed earlier because of the appearance of raised intracranial pressure. About 50% of patients show hormone failure at diagnosis due to pituitary involvement. Approximately 25% of patients present with tumor spread at diagnosis. Treatment is stratified according to histology and stage. In yolk sac tumors, chorioncarcinoma, embryonal carcinoma and localized germinoma, treatment consists of chemotherapy and radiotherapy. Disseminated germinoma receive craniospinal irradiation alone. Surgery plays a role in the resection of residual disease following chemotherapy or irradiation. Initial tumor resection is not beneficial to patients with malignant CNS GCT and leads to increased morbidity. Two thirds of all children and adolescents diagnosed with this disease can be cured.     

Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors

Neuraxis radiation therapy (RT) for primary intracranial tumors is associated with major late effects if administered to very young children. To control residual tumor and to delay RT, we treated eight young children (median age 6.5 months) with primary central nervous system (CNS) tumors using combination chemotherapy: cisplatin, 20 mg/M2/day plus VP-16, 75 mg/M2/day i.v. for 5 days, given q. 3-6 weeks for 8 cycles. The tumors were medulloblastoma (one), malignant ependymoma (two), primitive neuroectodermal tumor PNET (two), malignant glioma (two), astrocytoma (one). Six had measurable disease; three had positive cerebrospinal fluid (CSF) cytopathology. All patients with measurable tumor had initial objective responses (three) complete response [CR], one partial response [PR], two minor response [MR], including cytopathology (three CR of three) and metastatic deposits (two CR of two). One patient relapsed during chemotherapy. Median time to disease progression was 17.5 months; median survival was 34 months. Three patients, none of whom received RT, have prolonged progression-free intervals of 47-67 months to date. Neurodevelopmental progress continued during and after chemotherapy. Chemotherapy toxicity was mild. Median neutrophil nadir was 312/mm3, platelets 72,000. Fever during neutropenia occurred in six of 61 courses. Moderate high-frequency auditory losses were detected in three patients, and mild renal injury (GFR less than 70 ml/min) was detected in two of seven evaluable children. This pilot study demonstrates the apparent efficacy and mild toxicity of 5 day courses of cisplatin plus VP-16, with delayed RT, in young children with CNS neoplasms. A POG treatment protocol that incorporates cisplatin plus VP-16 is evaluating primary chemotherapy with delayed radiotherapy in larger numbers of pediatric brain tumor patients.     

Long-term pulmonary function in children with Hodgkin's disease

We studied the long-term pulmonary function of 25 patients who were at least 5 years post-treatment for Hodgkin's disease. The mean age of the patients was 17 years (range 9.5–25 years) at the time of study. Twenty-one of the patients were male. All patients received six courses of COPP chemotherapy and, in addition, 8 of the 25 patients received radiotherapy to the mediastinum in low or moderate doses (20–30 Gy). One patient had symptoms of bronchiectasia. The chest radiographs of nine patients (36%) showed minimal abnormalities. We divided patients into two groups while evaluating their pulmonary function tests according to whether they received mantle irradiation or not. In patients who received mantle irradiation, pulmonary function tests showed a minimal decrease in FEV₁. The decrease in FEV₁ indicated an obstructive ventilatory defect. We concluded that our treatment protocols for paediatric Hodgkin's disease were curative, well tolerable and might minimize pulmonary functional changes.     

Solitary bone plasmocytoma of the spine in an adolescent

Solitary plasmocytoma (SP) represent only about 5% of plasma cell neoplasia. Most patients have generalized disease, that is, multiple myeloma (MM). Solitary bone plasmocytoma (SBP) is a localized plasma cell tumor and is a very rare disease in young patients. We reported here, a case of SPB in a 14-year-old girl with a 10-year disease-free survival after an aggressive treatment. The relationship of SBP to MM continues to be controversial. Recommendations on the diagnosis and management of SBP in adults, based on a literature search and consensus of expert opinion, were recently published on behalf of the Guidelines Working Group of the United Kingdom Myeloma Forum 1. MRI of the spine is necessary to assess local disease. Radiotherapy with doses of 45-50 Gy is the recommended treatment and gives a high rate of local control (83-96%). Chemotherapy remains controversial in contrast to MM, in which intensive chemotherapy with autologous bone marrow transplantation (ABMT) is widely accepted. At the present time, considering the good prognosis of patients with a normal MRI at diagnosis and a complete disappearance of the M protein after radiotherapy, we believe that ABMT should be reserved for relapse or primary therapeutic failure.     

Central nervous system relapse of rhabdomyosarcoma

1 Purpose

The optimal management of central nervous system (CNS) relapse of rhabdomyosarcoma (RMS) is unclear. We examined diagnosis, management, and outcomes of patients with RMS developing CNS relapse.

2 Methods

Records of 23 patients diagnosed with CNS relapse between 1999 and 2016 were reviewed. Median age at presentation of CNS relapse was 15 years (range, 1–34 years). High‐risk features at initial presentation were as follows: 16 alveolar patients, 13 Stage IV, and 13 with primary tumor in parameningeal locations.

3 Results

CNS relapse occurred at a median 12 months (range, 1–23 months) from diagnosis and most common presenting symptoms were headache (n = 9), nausea/vomiting (n = 8), visual difficulty (n = 5), and none (n = 5). Leptomeningeal metastases were detected in 21 patients while only 2 developed parenchymal metastases without leptomeningeal involvement. Fifteen patients received CNS‐directed radiation therapy (RT), including craniospinal irradiation to a median 36 Gy (range, 18–36 Gy) and/or whole brain radiotherapy to a median 30 Gy (range, 6–41.4 Gy). Three patients received concurrent chemotherapy. Follow‐up magnetic resonance imaging was conducted in 13 patients after RT initiation with 8 demonstrating improvement, 2 with stable disease, and 3 with progression. Twelve patients were tested for reactivity to I‐131‐labeled monoclonal antibody 8H9, and three tested positive and received at least one intra‐Ommaya dose; all three lived >12 months post‐CNS relapse. Twenty‐one patients died of CNS disease and two of metastatic disease at other sites. Median survival post‐CNS relapse was 5 months (range, 0.1–49 months).

4 Conclusions

The prognosis for patients with RMS developing CNS relapse remains poor. Treatment including CNS‐directed RT should be considered and investigation into preventative therapies is warranted.     

Treatment of rhabdomyosarcoma in children with surgery,radiotherapy and chemotherapy

From May, 1970 through December, 1972, Children's Cancer Study Group entered 112 patients on an amended treatment program for rhabdomyosarcoma and undifferentiated sarcoma in children. These patients had Group II disease with residual tumor remaining after surgery, or metastatic disease at onset. Another group consisted of patients who previously had treatment with surgery and radiotherapy and had recurrent disease. Cyclophosphamide was added to a previously used drug regimen which consisted of actinomycin D and vincristine. The drugs were given sequentially in repeated cycles for 18 months. Of 97 evaluable patients, there were 24 with microscopic residual disease, 37 with gross residual disease, 22 with metastatic disease at onset, and 14 patients who were treated with chemotherapy for the first time with recurrent or metastatic disease. All patients have been followed for 3 or more years. Survival in each group was 70.8%, 43.2%, 27.2%, and 28.2%, respectively. Although the number of complete remissions was greater than with two-drug therapy, survival with three-drug therapy was not significantly different than that seen in the earlier study.     

Sparing strategy does not compromise prognosis in pediatric localized synovial sarcoma: experience of the International Society of Pediatric Oncology, Malignant Mesenchymal Tumors (SIOP-MMT) Working Group

Background

The aim of this analysis was to identify if the modified indications of radiotherapy (RT) or radical surgery compromised survival in pediatric synovial sarcoma (SS).

Procedure

Children with non‐metastatic SS, prospectively enrolled in three trials, were analyzed. After primary surgery or biopsy, they received chemotherapy. RT was planned after chemotherapy in patients who had not achieved a complete response (CR). The considered outcome was 5‐year overall survival (OS) and event‐free survival (EFS).

Results

Eighty‐eight patients were identified. Primary tumors were mainly located in limbs (66%). The first‐line therapy for 65 patients was primary resection. Of the 49 patients who had gross tumor resection, 43 received adjuvant chemotherapy, and 8 had RT. All of the 39 patients with macroscopic residual disease received chemotherapy, then only surgery (n = 12) ± RT (n = 22). The 5‐year EFS and OS rates were 68% and 85%, respectively. The TNM stage was a prognostic factor for relapse, whereas primary site of the tumor and TNM stage were prognostic factors for death.

Conclusions

Only 32% of survivors received RT. OS was similar to published data. Omission of RT may be considered in younger children, to limit the potential sequelae in patients with tumors less than 5 cm in size initially submitted to marginal resection. This strategy may also be considered in initially unresected cases, when the tumor is resected at delayed surgery with microscopically free margins, and in patients in complete remission after primary chemotherapy. Pediatr Blood Cancer 2011; 57: 1130–1136. © 2011 Wiley Periodicals, Inc.     

Evolving of therapeutic strategies for CNS‐PNET

Background

A protocol for the intensive treatment of non‐cerebellar PNET (CNS‐PNET) combining chemotherapy and radiotherapy was launched in 2000. Efforts were subsequently made to improve the prognosis and to de‐escalate the treatment for selected patient groups.

Procedure

Twenty‐eight consecutive patients were enrolled for a high‐dose drug schedule (methotrexate, etoposide, cyclophosphamide, and carboplatin ± vincristine), followed by hyperfractionated accelerated CSI (HART‐CSI) at total doses of 31–39 Gy, depending on the patient's age, with two high‐dose thiotepa courses following CSI. After the first 15 patients had been treated, craniospinal irradiation (CSI) was replaced with focal radiotherapy (RT) for selected cases (non‐metastatic and not progressing during induction chemotherapy). Eight of the 28 children received the same chemotherapy but conventionally fractionated focal RT at 54 Gy.

Results

The 5‐year progression‐free survival (PFS), event‐free survival (EFS), and overall survival (OS) rates were 62%, 53%, and 52%, respectively, for the whole series, and 70%, 70%, and 87% for the eight focally irradiated children. Residual disease and metastases were not prognostically significant. In children with residual disease, response to RT was significant (5‐year PFS 59% vs. 20%, P = 0.01), while the total dose of CSI was not. There were three treatment‐related toxic events. Relapses were local in seven cases (including two of the eight focally irradiated patients), and both local and disseminated in 2.

Conclusions

This intensive schedule enabled treatment stratification for the purposes of radiation, thereby sparing some children full‐dose CSI. Local control is the main goal of treatment for CNS‐PNET. Pediatr Blood Cancer 2013;60:2031–2035. © 2013 Wiley Periodicals, Inc.     

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.     

The role of radiotherapy in the treatment of childhood intracranial germinoma: long-term survival and late effects

BACKGROUND: The aim of the present report was to evaluate the role of radiotherapy in the treatment of childhood intracranial germinoma in view of long-term survival and functional outcome. PROCEDURE: Nine children with histologically verified intracranial germinomas treated in Slovenia between 1983 and 1995 were reviewed. The four boys and five girls were 8.8-16.9 years old (median, 11.3 years). Five tumors were suprasellar, three were in the pineal region, and one patient had bifocal disease. Two patients had disseminated tumor. All patients received radiotherapy: six to the tumor bed, one to the whole brain, and two to the whole central nervous axis (CNA). The doses to the tumor bed ranged from 30 to 46 Gy (median, 44 Gy) and to the CNA were 24 and 34.5 Gy. Five patients received neoadjuvant cyclophosphamide and three patients, all with beta-human chorionic gonadotropin secreting tumors, received neoadjuvant cisplatin-based chemotherapy. RESULTS: Six patients are alive 12.8-21.8 years (median, 19 years) from diagnosis. The causes of death in three patients were disseminated disease, toxicity of salvage chemotherapy, and secondary etoposide-induced leukemia. All patients with suprasellar tumors presented with overt endocrinopathy. Results of psychological evaluation were subnormal in one out of five patients tested. Estimate of mental deterioration due to therapy ranged from 0% to 30% (median, 15%). Emotional disorder was registered in four patients and psycho-organic syndrome in three. CONCLUSIONS: Our results on long-term survival and functional outcome confirm the efficacy and relative safety of limited-field and reduced-dose radiotherapy for childhood intracranial germinoma when supplemented with chemotherapy.     

Radiotherapy in Ewing sarcoma: current results of the German Society of Pediatric Oncology studies CESS 81 and CESS 86

In CESS 81 the rate of local recurrences was high particularly in patients with radiation for local control. To improve the safety of local control, in the follow-up study CESS 86 chemotherapy for high risk patients was intensified. The combination of surgery with postoperative radiation was favoured when possible, local control was brought forward from week 18 to week 9, the doses of postoperative radiotherapy was increased from 36 to 46 Gy, and a radiation planning center was established for centralized planning of radiotherapy on the basis of tumor extension at diagnosis. In addition patients with radiation were randomized for conventional fractionation or a scheme of accelerated split course hyperfractionation with simultaneous chemotherapy. Preliminary results of 76 CESS 86 patients (incl. pilot phase), show a lowered rate of local recurrences compared to CESS 81: 6% local recurrences and 15% local recurrences in patients with radiation. With selection of patients with small and chemoresponsive tumors for radiotherapy no longer a disadvantage was seen for patients with radiotherapy concerning the safety of local control.