Cancer in Children: Clinical Management, 5th Edition

Chapter 6. Radiotherapy in paediatric oncology

Andreas Schuck

General comments


Adequate treatment of malignant disease in children and adolescents can only be provided by an experienced interdisciplinary team including paediatric oncologists, paediatric surgeons, and a radiation oncologist with expertise in the treatment of young patients. Furthermore, there must be close cooperation with diagnostic disciplines (radiology, nuclear medicine, pathology). Paediatric patients with malignant disease should be treated according to national or international protocols for the specific disease. With the introduction of multimodal therapy in the 1970s, considerable improvement was achieved in the treatment of children and adolescents. These results can only be obtained and improved, or achieved with less toxic treatments, if all patients are included in the relevant collaborative protocols. The protocol committees of individual trials usually consist of specialists in each involved medical discipline. The radiation oncologist has two main tasks: recommendation of indications for the use of radiotherapy, radiation doses and fractionation, target volume definitions, and the timing of radiotherapy, and provision of expert advice regarding the treatment of individual patients.

Effect on the tumour and side effects

In most malignant disease in childhood and adolescence, the chance of cure is highest with the primary treatment. In most tumours, relapse is associated with a poor prognosis. This is why the primary treatment of many tumours frequently involves aggressive treatment approaches that may be associated with severe acute and chronic toxicity. Therapy is given in a vulnerable period when patients are growing and developing; this is particularly relevant to the use of radiotherapy. Furthermore, since cure rates have been higher in the last two decades, more patients are developing therapy-associated long-term effects. Decisions regarding the indications for and the extent of radiotherapy involve balancing the expected effect on the tumour against the potential long-term effects of the treatment. This is why age-adapted recommendations are frequently given for very young patients. However, except in prospective clinical trials, the intensity of therapy should not be reduced.

Treatment with sedation or narcosis

Patients who are less than 3 years old generally require deep sedation or anaesthesia to allow a reproducible treatment set-up. This is not usually necessary in older patients. The techniques used for sedation and anaesthesia vary from center to center. It is essential that an experienced anaesthetist monitors the patient during and after treatment.

Malignant tumours

Soft tissue sarcoma

Sarcomas originating from soft tissues form a very heterogenous group of tumours. The most frequent subtype is rhabdomyosarcoma (RMS). Of these chemosensitive tumours, embryonal RMS is generally associated with a favourable prognosis whereas alveolar RMS has a higher relapse rate. Other chemosensitive soft tissue sarcomas include extraosseous Ewing tumours, synovial sarcoma, and undifferentiated sarcoma. There are other soft tissue sarcomas with moderate or no chemosensitivity (non-RMS-like tumours) such as liposarcoma, fibrosarcoma, and malignant rhabdoid tumour. Because of the many histologies and tumour sites, radiotherapy is a complex issue in these diseases and no patient should be treated outside a national or international protocol.


Risk-adapted chemotherapy is administered in all paediatric patients with RMS. Initial surgical resection is performed if surgery can be complete and not mutilating. In all other cases, delayed surgery is planned after biopsy and the initial courses of chemotherapy.

Local control and survival are improved in all patients with alveolar RMS who receive radiotherapy irrespective of the extent of the initial or delayed surgery, even in patients with initial complete resection.1 Local relapses are associated with a very poor outcome.

In embryonal RMS, radiotherapy also increases local control after initial or delayed surgery. If no radiotherapy is given, these patients will have a fair chance of cure after local relapse and radiotherapy as salvage treatment.2 Therefore the decision to use radiotherapy in patients with favourable RMS histology is a balance between improved local control with the use of radiotherapy on the one hand and avoiding radiotherapy with a higher risk that intensive salvage therapy will be necessary on the other hand. The best cure rates have been achieved in the Intergroup Rhabdomyosarcoma Trials (IRS) in the USA with extensive use of radiotherapy.3 Therefore, as a rule, radiotherapy should be performed in patients with favourable histology who have not had an initial complete resection (IRS groups II and III). In small children with embryonal RMS and in particularly sensitive sites that are associated with a favourable course of the disease (e.g. vaginal RMS), radiotherapy can be omitted when patients are in complete remission following chemotherapy.

Depending on the extent of surgery, histology, and response to chemotherapy, 32–50 Gy are used. In the ICG and CWS trials, hyperfractionated accelerated radiotherapy was given at a dose of 1.6 Gy twice daily. Conventional fractionation was used in the SIOP and IRS groups. The planning target volume is defined as the initial extent of the tumour on MRI plus 2 cm. Areas contaminated during surgery, surgical scars, and drainage sites must be included in the radiation fields. If possible, total coverage of the circumference of extremities should be avoided in order to reduce the risk of lymphoedema.

Extraosseous Ewing tumours, synovial sarcoma, and undifferentiated sarcoma

Radiotherapy is crucial in these types of tumour. It is indicated when initial surgery has not been complete even when further surgery can be performed. Furthermore, radiotherapy may also be given in completely resected tumours with unfavourable characteristics (i.e. >5cm diameter). Radiotherapy is applied as the only local therapy modality when surgery is not possible. Radiation doses range between 45 and 55 Gy and an additional boost can be given if surgery is not possible. The target volume is defined as the pre-therapeutic tumour extent plus a margin of at least 2 cm.

Non-RMS-like tumours:

Because of the many histological subtypes with differing tumour biology in this group, very limited data are available concerning the role of radiotherapy. It is usually indicated when surgery is incomplete. Furthermore, radiotherapy may also be given in completely resected tumours with unfavourable characteristics (i.e. >5 cm diameter). Radiation doses range between 45 and 60 Gy.

Ewing tumour

The Ewing tumour family consists of Ewing sarcoma, atypical Ewing sarcoma, and primitive neuroectodermal tumours (PNETs). The most frequent tumour sites are the pelvis and the femur. The treatment of Ewing tumours consists of polychemotherapy, surgery, and radiotherapy. Local therapy is performed following biopsy and initial chemotherapy. No randomized trials comparing definitive radiotherapy with definitive surgery have been performed to date. Therefore the superiority of surgery over radiotherapy has not been proved. However, in prospective non-randomized trials, the best local control was achieved when a wide tumour resection was performed. Radiotherapy following or preceding surgery is recommended when only marginal or intralesional resections are possible or in patients who have a poor histological response to initial chemotherapy.4 Preoperative radiotherapy may be particularly useful when it facilitates function-preserving surgery. Radiotherapy is always necessary for inoperable tumours (e.g. vertebral primaries). Surgical debulking does not improve treatment results and should not be performed. Radiation doses range from 50 to 60 Gy for definitive radiotherapy and from 45 to 55 Gy for preor postoperative radiotherapy. Patients treated with a radiation dose ≤40 Gy experience a high local failure rate.5 In the CESS 86 and EICESS 92 trials, there was no difference in local control and event-free survival between conventional fractionation or a hyperfractionated split course with 1.6 Gy twice daily and a treatment break of about 10 days after 22.4 Gy. Therefore the fractionation seems to be of little or no importance for tumour control.

The planning target volume is defined as the initial tumour extent on MRI with an additional longitudinal margin of 5 cm and lateral margins of 2 cm in long bones. If doses >45 Gy are used, a shrinking field technique is applied. In some patients with an axial tumour site, 5-cm safety margins cannot be used, but a minimum 2-cm safety margin around the initial tumour extent must be allowed. Surgically contaminated areas with scars and drainage sites must be included in the radiation fields. If possible, total coverage of the circumference of extremities should be avoided in order to reduce the risk of lymphoedema.

Good treatment results in patients with lung metastases have been achieved using wholelung irradiation.6 Survival in patients who had complete clinical remission in the lung and received an additional 15–20 Gy external beam radiotherapy to both lungs was improved compared with patients who received chemotherapy only. In the ongoing EURO-EWING 99 trial, whole-lung irradiation is randomized against high-dose chemotherapy for these patients.

Patients with initial bone metastases should receive radiotherapy not only at the primary tumour site but also at metastatic bone sites if there are not too many of these. For multiple bone metastases, an individual decision has to be made as to whether only the largest lesions are treated, whether residual metastases shown by functional imaging (positron emission tomography scan after chemotherapy) are treated, or whether radiotherapy is unlikely to improve the outcome.


Osteosarcoma is the most frequent bone tumour in childhood. It usually develops in the epiphyseal region of long bones. The treatment of choice is polychemotherapy and surgical resection of the primary tumour and metastases. Radical surgery is essential for a good prognosis. This tumour has been considered to be radioresistant, and therefore radiotherapy has no role in the treatment of osteosarcoma to date. However, experimental data have shown that the radiosensitivity is equivalent to those of other human tumour cell lines. Furthermore, cure has been reported for patients with inoperable tumours and patients who refused surgery after radiation doses ranging from 50 to 70 Gy. Therefore radiotherapy is indicated for residual tumours with no option for follow-up surgery, for inoperable tumours, and in the palliative treatment of bone metastases. There have also been reports of benefit from adjuvant wholelung irradiation in patients with initial lung metastases.

2.4 Central nervous system tumours

Central nervous system (CNS) tumours have very different histologies and malignancies. They represent 20 per cent of all malignant diseases in childhood and adolescence and are the largest group of solid tumours.


Medulloblastoma, which is a PNET located in the posterior fossa, is the most frequent brain tumour in children. Tumour dissemination in the cerebrospinal fluid (CSF) is common. Therefore complete tumour resection followed by craniospinal radiotherapy is the treatment of choice. Improved results may be obtained for patients without metastases by the additional use of chemotherapy. In patients SPAN <4 years, results with surgery and chemotherapy alone for resectable localized tumours are favourable. In this age group, it is justifiable to withhold radiotherapy after complete resection until there is a relapse, therefore avoiding radiationassociated side effects.

In the past, craniospinal irradiation was given with conventional fractionation to a dose of 36 Gy. The posterior fossa was then boosted to a dose of 54 Gy. Single institutional experiences with 24 Gy craniospinal irradiation and a boost to the posterior fossa of up to 54 Gy in conjunction with systemic therapy have shown comparable results.8 In the ongoing German HIT 2000 trial, the use of hyperfractionation with 1.0 Gy twice daily up to a cumulative dose of 68 Gy in patients with completely resected tumours is being tested with regard to tumour control and late effects. In patients with localized disease, delaying radiotherapy after surgery in favour of chemotherapy was disadvantageous in the randomized HIT-91 trial. Therefore postoperative radiotherapy should be started as soon as possible. In patients with spinal metastases, the use of chemotherapy after surgery and before radiotherapy was beneficial.

Careful planning of radiotherapy is necessary. It is important that craniospinal irradiation should include the entire compartment of the CSF from the brain down to the cauda equina without gap or overlap. Boost radiation to the posterior fossa must be planned in three dimensions, based on CT and MRI with a three-dimensional conformal approach.

Supratentorial PNET

Treatment is similar to that of infratentorial PNET (medulloblastoma). Craniospinal axis irradiation is followed by a boost to the primary tumour site.

Intracranial germ cell tumours

There are two treatment alternatives for patients with pure germinomas. Craniospinal irradiation with 24–30 Gy can be given followed by a tumour boost to a total dose of 45 Gy. Comparable results have been obtained using systemic therapy combined with involved field radiotherapy to the primary tumour site only.9

Patients with secreting germ cell tumours receive chemotherapy followed by involved field radiotherapy to the primary tumour site at a dose of 54 Gy. Craniospinal radiotherapy is only performed when there has been positive CSF cytology.


Ependymomas develop in the ependyma or lining of the ventricles and the cerebral aqueduct. In two-thirds of cases they are located in the posterior fossa and frequently infiltrate into the cervical spine. In anaplastic tumours arising infratentorially, the risk of CSF dissemination is about 10 per cent. The treatment of choice in malignant ependymoma is complete resection followed by local therapy of at least 54 Gy. No clear benefit has been shown for the use of craniospinal irradiation.10 Complete tumour resection is essential. Patients who have an incomplete resection have a poor prognosis despite the use of radiotherapy and systemic therapy.

Low-grade glioma

Low-grade gliomas comprise a number of different histologies. The treatment of choice is complete resection. In patients who show no progression after surgery, a wait-and-see policy is followed. When clinical symptoms develop or imaging shows progression, local radiotherapy is given to a dose of 45–55 Gy. External beam therapy is also given when complete tumour resection is not possible and the patient remains symptomatic following biopsy or incomplete resection. In small children, chemotherapy is given first. Delayed radiotherapy is performed when systemic therapy fails.

High-grade glioma

Fortunately, high-grade gliomas are rare in children and adolescents. As in adults, these tumours are characterized by aggressive local growth. The treatment of choice is tumour excision followed by local radiotherapy to 54–60 Gy depending on the age of the patient. So far the additional use of chemotherapy has not improved the results.


These histologically benign tumours arise in the suprasellar region. Infiltrating local growth is possible, so that vision and hormone production may be affected. Since aggressive resection is associated with a high risk, subtotal resection followed by local radiotherapy at 50–54 Gy is recommended. Inyoung children (<5 years old), the radiation dose can be reduced to 45 Gy. The 10-year survival rate with limited surgery and postoperative radiotherapy is 80–95 per cent.11


Neuroblastoma is a disease of early childhood. About 60 per cent of the patients present with initial metastases. Children aged <1 year with dissemination to the skin, liver, and bone marrow have a different prognosis. These tumours are frequently radio- and chemosensitive. Furthermore, spontaneous remission may occur. Therefore a wait-and-see strategy may be appropriate in these patients with favourable prognostic factors.

Although neuroblastomas are radiosensitive, the influence of local radiation on survival is not well defined. Therefore the use of external beam therapy in primary treatment differs in the various ongoing trials. It is used either when there is residual tumour following chemotherapy, [131I]mIBG therapy, and second-look surgery or when patients present with advanced local disease irrespective of response. The radiation dose is 36–40 Gy. The planning target volume consists of the (residual) tumour plus a safety margin of 2 cm. Radiotherapy is also useful in palliative treatment.


Nephroblastomas arise mostly in young children; 80 per cent of the patients are <5 years of age. The primary treatment consists of surgery or initial chemotherapy followed by surgery.12 The subsequent treatment depends on histology and on lymph node and resection status. Radiotherapy is given for stage II disease and greater. Nephroblastoma is a radiosensitive tumour and doses range from 10 to 30 Gy. The target volume is defined according to tumour extent at diagnosis, the topography of the tumour at surgery, and whether there was tumour spillage during surgery. Radiotherapy to both lungs is performed in selected patients with lung metastases.

Hodgkin disease

As in adults, early tumour stages can be cured with extended field radiotherapy alone. Because of radiation-associated side effects, use of chemotherapy has become general and radiation dose and fields have reduced. No radiotherapy was given to patients treated in the German HD 95 trial when there was a complete remission following chemotherapy. Overall, there was an increased relapse rate with this approach. Patients in complete remission without the use of radiotherapy had a higher relapse rate than those who had residual disease following chemotherapy and who received radiotherapy. Subsequently, it was recommended that radiotherapy should be used for all patients except those in early stage IA, IB and IIA without further risk factors who were in complete remission following chemotherapy. Radiotherapy is essential for patients with a higher stage of disease or known risk factors and in patients with residual disease following chemotherapy. The doses used range from 20 to 35 Gy depending on response to systemic therapy and residual tumour size. The tolerance doses of organs at risk must be considered in treatment planning. Extended field radiotherapy is no longer considered appropriate. Treatment is only given to the lymph node sites initially involved. The incidence of secondary tumours is considerable. The relative risk 15 years after treatment is 15 per cent. The risk of developing second solid tumours increases with time after treatment.7


Leukaemias are the most frequent malignant diseases of childhood. However, the majority of patients can be cured with aggressive systemic therapy.

Historically, the introduction of prophylactic CNS treatment, initially with craniospinal radiation and later with whole-brain radiation alone, resulted in a dramatic reduction of CNS relapses and disease-related mortality. Because of concerns about long-term effects of cranial radiotherapy, mainly neurocognitive effects, its application has been restricted to patients with high-risk acute lymphoblastic leukaemia (ALL), T-ALL, or initial CNS involvement. In all other patients with ALL, CNS prophylaxis is performed with intrathecal and intravenous methotrexate. The radiation dose is usually 12 Gy for prophylactic treatment and 18 Gy for CNS disease.

In acute myelogenous leukaemia (AML), most trials have not shown a benefit using cranial radiotherapy. However, in the German AML-BFM 87 trial, a reduction in bone marrow relapses was observed for patients who received cranial radiotherapy.13 In the AML-BFM 98 trial, patients were randomized between cranial prophylactic treatment with 12 Gy and 18 Gy.

When there is mediastinal involvement, response to chemotherapy must be evaluated; if residual tumour remains, mediastinal radiation may be given. In most cases with ALL and infiltration of the testes, systemic therapy is adequate. When there is residual tumour, radiotherapy must be considered. Radiation treatment of involved testes is recommended in patients with AML. The doses range from 10 to 24 Gy.

For patients with high-risk ALL or relapse, an allogenic bone marrow or stem cell transplantation is performed. Conditioning is frequently performed with total body irradiation, usually with 12 Gy in six fractions over a period of 3 days. The dose to the lung is reduced to 8 Gy, and some centers reduce the dose given to the kidneys in children to lower the rate of radiation nephropathy.

Radiation-associated toxicity in children and adolescents

Acute side effects are defined as toxicities occuring within 90 days of the start of radiotherapy. They depend on the radiation site, the total dose, the fractionation, the size of treated area, and whether other modalities (surgery, chemotherapy) are given as well. Typical acute side effects in children do not differ from those in adults. They include skin reactions, mucositis, enteritis, epilation, myelosuppression, etc. Most acute side effects are reversible and can be handled with adequate supportive care.

Chronic side effects are defined as reactions occurring or persisting more than 90 days after the start of radiotherapy. Again, they depend on field size and site, total dose, and fractionation, as well as whether further treatment modalities are used. Long-term radiogenic effects are usually irreversible and are more severe the younger the patients are at the time of treatment.

Bone and soft tissue

Radiotherapy results in growth deficits due to damage to chondroblasts. Clinically, a dose of 10–20 Gy results in growth inhibition. Doses above 20 Gy can stop further growth. The extent of the growth deficit depends on the age of the patient at the time of treatment and how much an epiphysis contributes to total growth of the part of the body or the limb. In radiation planning it is essential either to include the growth plate fully in the radiation field or to exclude it entirely if that is possible. A dose gradient through the growth plate results in asymmetric growth and functional deficits. For the same reasons, vertebral bodies should either be fully included in or spared from the treatment.

Hypoplasia in soft tissues can occur after a dose >20 Gy. In addition to a reduction in volume of the muscles and subcutaneous tissue, fibrosis can occur after higher doses, resulting in limitation of movement.


Hormonal deficits and impairment of fertility depend on the radiation dose and probably on the age of the patient. Spermatogenesis is very radiosensitive. After a dose of 15 cGy, reversible reduction in the sperm count can occur in adults. Permanent sterilization has been observed after fractionated doses of 1–2 Gy. The application of small fractionated doses is more toxic than a single dose. The dose that results in damage to the germinal epithelia in children is unknown. Shalet et al14 observed oligospermia or azoospermia in adulthood in eight of ten patients given testicular doses of 2.7–9.8 Gy during treatment for nephroblastoma in childhood. Young patients with ALL treated with doses of 12 Gy to the testicles and chemotherapy all showed azoospermia after puberty.

Leydig cells are more radioresistant. Normal testosterone levels are observed after 20 Gy of fractionated radiotherapy in adults. Leydig cells in children may be more radiosensitive.


Ionizing radiation results in a reduction in the number of small follicles, inhibition of maturation of the follicle, cortical fibrosis, and capsular atrophy. Inhibition of follicular maturation results in infertility and amenorrhoea. Permanent sterility may be seen in adult women who receive a dose >8 Gy during fractionated radiotherapy. Usually, there is no permanent change in the cell cycle after doses <1.5 Gy. Stillmann et al15 evaluated 25 women who received doses of 12–50 Gy to both ovaries when they were <17 years old. Seventeen (68 per cent) of them developed hormonal deficits.

An oophoropexy should be performed in girls who are to receive radiotherapy to the pelvis. The ovaries must be marked with clips to allow identification on radiographic images and therefore facilitate function-conserving radiotherapy.


Females who received abdominal radiotherapy and are pregnant are at higher risk for intrauterine death or a child with a low birth weight. The aetiology is not known. Probably it is due to changes in the uterus and pelvis rather than damage to the germinal epithelia. The number of congenital handicaps in live-borns whose father or mother have undergone previous radio- and/or chemotherapy is not increased.16 There are no clinical data showing that offsping are at higher risk of teratogenesis, although there is an increased incidence of malignancies due to hereditary syndromes.

Central nervous system

The development of the brain is very marked within the first 3 years of life. By the age of 6 years, brain development is almost complete. Therefore radiation-associated side effects are particularly evident in very young children.

Neurocognitive deficits

Neurocognitive deficits have been described after CNS prophylaxis in children with leukaemia. In the past, radiation doses of 18–24 Gy were used. In recent protocols, a dose of 12 Gy is usually given to high-risk patients. There are a large number of retrospective trials evaluating neurocognitive effects in these patients. In the one randomized trial reported,17 49 patients were randomized to receive either intrathecal methotrexate and 18 Gy radiotherapy or both intravenous and intrathecal methotrexate. The median follow-up was about 6 years. Patients were evaluated before and after treatment. There was a statistically significant reduction of the full-scale IQ and the verbal IQ for both the chemotherapy only and the chemotherapy plus radiotherapy groups. The total reduction in IQ was <5 per cent in both groups, and the average IQ was within the normal range. Therefore there is a small reduction in intelligence following CNS prophylactic treatment. It is not clear whether chemotherapy is less toxic than radiotherapy. So far there are no data evaluating patients who have received a dose of 12 Gy.

A dramatic deterioration of IQ can be observed for children <6 years of age treated with craniospinal radiation at higher doses (i.e. for medulloblastoma). The longer the follow-up, the more pronounced these deficits become. Usually, there are no major impairments in older patients.

Thus it is clear that radiation-induced neurocognitive deficits exist after local treatment of brain tumours, but they are difficult to distinguish from tumouror surgery-related effects.

Cerebral necrosis and myelopathy

The incidence of radiation-induced necrosis in the brain following doses of 50–60 Gy ranges from 0.1 to 5 per cent. The incidence may be influenced by the use of concomitant chemo-therapy.

There is partially contradictory data concerning the risk of developing myelopathy. In adults, the application of 55 Gy is probably associated with a risk of 5 per cent after 5 years. The incidence is influenced by the fractionation schedule and probably by the length of the treated cord segment. It is possible that children have a slightly higher sensitivity.

Endocrine system

The secretion of growth hormone is impaired after a dose of >18 Gy to the hypothalamus/ hypophysis. The higher the dose, the earlier the deficit is manifest. Further deficits of the hypothalamic–hypophyseal axis (in ACTH, thyrotrophin-releasing hormone, gonadotrophins, and hyperprolactaemia) are observed after doses >40 Gy.

There is a risk of hypothyroidism after doses >20 Gy to the thyroid. In paediatric patients treated for Hodgkin disease at a dose of 30–45 Gy, the rate of hypothyroidism after 5 years has been reported to be as high as 50 per cent.18


Pneumonitis following radiotherapy is a subacute side effect that occurs 1–4 months after treatment. Spontaneous remission is possible but progression to lung fibrosis may occur. When radiotherapy is given to more than a quarter of the lung or at a dose >15 Gy, the incidence of pneumonitis increases. Chemotherapy, particularly with actinomycin D, bleomycin, or busulfan, can sensitize the lung tissue to radiation. Long-term effects can develop after treatment of very young children because of insufficient formation of alveoli.


In the past, with the use of high radiation doses for patients with Hodgkin disaese and with coverage of large parts of the heart, acute pericarditis and cardiomyopathy were observed. Today, these are very rare events following radiotherapy alone. Cardiomyopathy occurs mainly with the combined use of anthracyclines. The incidence is dependent on the cumulative dose of anthracycline.

An increased incidence of coronary heart disease has been observed following radiotherapy to the mediastinum. Again, most of the retrospective data come from patients who were treated with high doses. No increase in coronary heart disease is expected following treatment with 25 Gy and conventional fractionation. In an analysis of 635 children with Hodgkin disease, 12 patients died from heart disease; seven of these patients had myocardial infarction. Fatal cardiac events were only observed in patients treated with 42–45 Gy.19


The radiation tolerance of the liver depends on the volume irradiated, the concomitant use of chemotherapy, and the age of the patient. Without the use of chemotherapy, there is a significant risk of radiation-associated hepatopathy at a dose of 30 Gy given to the entire organ with conventional fractionation. With the combined use of chemotherapy and radiotherapy, doses >15 Gy are generally avoided. In the German nephroblastoma trial, changes in liver function were observed in 35 per cent of patients following radiotherapy to the entire liver at doses of 15–30 Gy and concomitant adminstration of actinomycin D and vincristine. Most of these changes were reversible.20


There is a significant risk of damage when a dose >25 Gy with conventional fractionation is given to both kidneys. In children, renal damage can occur at a lower dose, particularly if chemotherapy is also used. The risk of nephropathy is reduced if doses to the kidneys are maintained <20 Gy. A temporary increase in blood pressure and urea has been observed after radiotherapy with large fields to the entire abdomen at a dose of 12 Gy.21 Increased vulnerability of the kidneys after total body irradiation has also been observed in children. In patients with ALL and neuroblastoma surviving for >6 months, fractionated radiotherapy of 12–14 Gy resulted in a nephropathy rate of 41 per cent.


There are several important issues in radiotherapy in paediatric oncology that should be considered in the future.

It is essential that radiation-associated toxicities, particularly long-term effects, are studied in the setting of combined treatment modalities in conjuction with surgery and chemotherapy. This will not only allow evaluation of the individual risk for a single patient but provide essential information for the design of future trials.

In tumour entities with good outcome, such as Hodgkin disease, less toxic treatment regimes with reduced radiation doses or smaller planning target volumes can be evaluated in controlled clinical trials. In tumours with a less favourable outcome, such as medulloblastoma, intensification of treatment including radiotherapy must be evaluated in clinical trials to find out whether this results in improved outcome with acceptable toxicities.

The use of modern radiation techniques including three-dimensional treatment planning, intensity modulated radiotherapy, stereotactic radiotherapy, and proton therapy may improve the therapeutic ratio and help to reduce toxicity and increase the antitumour effect.

No patient with a tumour of childhood should be treated outside a national or international clinical trial. The formation of international collaborative groups for single tumour types must be encouraged to allow randomized studies concerning different issues of therapy. Otherwise no real progress can be expected. Furthermore, the treatment must be performed at an experienced center to ensure expertise in the special demands of radiotherapy in paediatric oncology.


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