Severe Late Effects Research Articles

Impact of psychological and cancer-related factors on HRQoL for Korean childhood cancer survivors.

The purposes of this study were (1) to compare health-related quality of life (HRQoL) between Korean childhood cancer survivors and healthy controls and (2) to examine the impact of demographic, diagnosis/treatment, and psychological variables on physical and psychosocial health in survivors. The HRQoL (PedsQL), Self-Concept Inventory, and Child Behavior Checklist were administered to childhood cancer survivors, age/gender-matched healthy counterparts, and their parents. Independent-samples t tests and hierarchical multiple regression analyses were conducted. Compared with healthy controls, childhood cancer survivors reported significantly lower scores across physical and psychosocial HRQoL. For survivors, demographic, diagnosis/treatment, current health status, and psychological variables explained more than 50 % of the variance in both subscales of HRQoL. Especially, self-concept, a psychological variable, explained a significant portion of the variance in physical and psychosocial HRQoL after controlling for cancer-related factors. Several cancer-related factors including time since treatment completion, having a history of allogeneic hematopoietic stem cell transplantation, multiple treatment modalities, and suffering from severe late effects also associated with specific dimension of HRQoL. Childhood cancer survivors do experience lower level of QoL and psychological factors, especially self-concept, should be considered when supporting the well-being of childhood cancer survivors.

Development and validation of a prediction model for tube feeding dependence after curative (chemo-) radiation in head and neck cancer.

BackgroundCurative radiotherapy or chemoradiation for head and neck cancer (HNC) may result in severe acute and late side effects, including tube feeding dependence.The purpose of this prospective cohort study was to develop a prediction model for tube feeding dependence 6 months (TUBEM6) after curative (chemo-) radiotherapy in HNC patients.Patients and MethodsTube feeding dependence was scored prospectively. To develop the multivariable model, a group LASSO analysis was carried out, with TUBEM6 as the primary endpoint (n = 427). The model was then validated in a test cohort (n = 183). The training cohort was divided into three groups based on the risk of TUBEM6 to test whether the model could be extrapolated to later time points (12, 18 and 24 months).ResultsMost important predictors for TUBEM6 were weight loss prior to treatment, advanced T-stage, positive N-stage, bilateral neck irradiation, accelerated radiotherapy and chemoradiation. Model performance was good, with an Area under the Curve of 0.86 in the training cohort and 0.82 in the test cohort. The TUBEM6-based risk groups were significantly associated with tube feeding dependence at later time points (p<0.001).ConclusionWe established an externally validated predictive model for tube feeding dependence after curative radiotherapy or chemoradiation, which can be used to predict TUBEM6.

Long-term Outcome and Late Side Effects in Endometrial Cancer Patients Treated with Surgery and Postoperative Radiation Therapy

We retrospectively reviewed the long-term outcome and late side effects of endometrial cancer (EC) patients treated with different techniques of postoperative radiotherapy (PORT). Between 1999 and 2012, 237 patients with EC were treated with PORT. Two-dimensional external beam radiotherapy (2D-EBRT) was used in 69 patients (30 %), three-dimensional EBRT (3D-EBRT) in 51 (21 %), and intensity-modulated RT (IMRT) with helical Tomotherapy in 47 (20 %). All patients received a vaginal brachytherapy (VB) boost. Seventy patients (29 %) received VB alone. After a median of 68 months (range, 6-154) of follow-up, overall survival was 75 % [95 % confidence interval (CI), 69-81], disease-free survival was 72 % (95% CI, 66-78), cancer-specific survival was 85 % (95 % CI, 80-89), and locoregional control was 86 % (95 % CI, 81-91). The 5-year estimates of grade 3 or more toxicity and second cancer rates were 0 and 7 % (95 % CI, 1-13) for VB alone, 6 % (95 % CI, 1-11) and 0 % for IMRT + VB, 9 % (95 % CI, 1-17) and 5 % (95 % CI, 1-9) for 3D-EBRT + VB, and 22 % (95 % CI, 12-32) and 12 % (95 % CI, 4-20) for 2D-EBRT + VB (P = 0.002 and P = 0.01), respectively. Pelvic EBRT should be tailored to patients with high-risk EC because the severe late toxicity observed might outweigh the benefits. When EBRT is prescribed for EC, IMRT should be considered, because it was associated with a significant reduction of severe late side effects.

Chimioradiothérapie de rattrapage à visée curative de rechutes pelviennes isolées de cancers du col utérin

PurposeEvaluation of the results of salvage radiation therapy with curative intent in the treatment of recurrent cervical carcinoma. Patients and methodsFourteen patients with a recurrence of a cervical cancer were treated in our department between 1982 and 2009. Five patients had a pelvic relapse, four a vaginal relapse and five a pelvic lymph node relapse. Four patients had first a surgical resection of the relapse, which was incomplete in two patients. All patients had pelvic radiotherapy with a median dose of 55Gy in conventional fractionation. Concurrent chemotherapy was administered to 12 patients. A vaginal brachytherapy with a median dose of 20Gy was performed in addition in 3 patients. The median follow-up was 39months. ResultsSafety of radiation therapy was correct with 29% of grade 3 acute or intestinal toxicity. Tumor control was observed in 10 patients (71%). Four patients presented a locoregional tumor progression. At the time of analysis, three patients had died from their cancer. From the date of relapse, the rate of overall survival at 2 and 5year was respectively 84% and 74%. Three patients (21%) had severe late effects. ConclusionIn our experience, chemoradiotherapy can achieve a high rate of remission in patients with isolated pelvic recurrence of cervical cancer. This treatment is feasible only if the patient had not received radiation therapy before or if the relapse is out of the previously irradiated volume.

Extrakranielle stereotaktische Bestrahlung bei Lungenrundherden

Stereotactic body radiotherapy (SBRT) is a method for the highly precise application of percutaneous high dose radiotherapy of extracranial targets in a limited number of treatment fractions. Due to the excellent local control rates, SBRT is now well established in limited stage lung tumours. In medically inoperable patients SBRT is the method of choice, in high-risk patients and patients who refuse resection, the current literature recommends SBRT as a reasonable therapeutic option. An analysis of the SBRT working group of the German Society for Radiation Oncology showed that the treatment results in Germany are well comparable to international data. The limitations of SBRT lie in the treatment of tumours in the direct neighbourhood of so-called "serial" normal tissues, which is due to the risk of severe late effects of high dose radiation. Therefore these patients should be treated by SBRT, if at all, in the context of respective clinical studies.

Irradiation to the young mouse brain impaired white matter growth more in females than in males

Modern therapy cures 80% of all children with brains tumors, but may also cause long-lasting side effects, so called late effects. Radiotherapy is particularly prone to cause severe late effects, such as intellectual impairment. The extent and nature of the resulting cognitive deficits may be influenced by age, treatment and gender, where girls suffer more severe late effects than boys. The reason for this difference between boys and girls is unknown, but very few experimental studies have addressed this issue. Our aim was to investigate the effects of ionizing radiation on the corpus callosum (CC) in both male and female mice. We found that a single dose of 8 Gray (Gy) to the brains of postnatal day 14 mice induced apoptosis in the CC and reduced the number of proliferating cells by one third, as judged by the number of phospho-histone H3 positive cells 6 h after irradiation (IR). BrdU incorporation was reduced (62% and 42% lower in females and males, respectively) and the number of oligodendrocytes (Olig2+ cells) was lower (43% and 21% fewer in females and males, respectively) 4 months after IR, so the lack of developing and differentiated cells was more pronounced in females. The number of microglia was unchanged in females but increased in males at this late time point. The density of microvessel profiles was unchanged by IR. This single, moderate dose of 8 Gy impaired the brain growth to some extent (8.1% and 0.4% lower brain/body weight ratio in females and males, respectively) but the CC growth was even more impaired (31% and 19% smaller in females and males, respectively) 4 months after IR compared with non-irradiated mice. In conclusion, this is the first study to our knowledge demonstrating that IR to the young rodent brain affects white matter development more in females than in males.

Mature Clinical Outcomes of Proton Radiation for Pediatric Low-Grade Gliomas

Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy as definitive treatment. Radiation therapy in the pediatric brain is associated with a variety of late effects. However, increased conformality of radiation therapy to spare as much normal brain tissue from radiation will decrease the incidence and severity of late effects. We report our experience with 36 pediatric patients treated with proton radiation therapy for low-grade gliomas.

Investigating chromosome damage using fluorescent in situ hybridization to identify biomarkers of radiosensitivity in prostate cancer patients

Purpose: In order to evaluate fluorescent in situ hybridization (FISH) as a method for predicting radiosensitivity, this study examined the incidence of translocations, after exposure to in vitro radiation, in both normally responding patients and those exhibiting severe late effects after radiotherapy treatment.Materials and methods: Patients were selected from a randomized trial for intermediate-risk prostate cancer. Of the patients entered on trial with mature follow-up, 3% developed grade 3 late proctitis. Blood samples were taken from this radiosensitive cohort along with matched control patients with no late proctitis. Whole blood samples were exposed to 0 or 4 Gy and cultured according to the recommended methods. Colour junctions were evaluated in the resulting metaphases and scored according to the Protocol for Aberration Identification and Nomenclature Terminology (PAINT) system.Results: Both groups were statistically similar at 0 Gy. After 4 Gy in vitro radiation, the radiosensitive group had significantly higher rates of chromosome damage in the number of colour junctions per cell (p = 0.002), the number of deletions per cell (p = 0.01) and the number of dicentrics per cell (p = 0.005).Conclusions: These results indicate that the analysis of translocations using FISH after in vitro irradiation correlates with clinical response to radiation. This cytogenetic assay should be considered as a potential predictor of radiosensitivity.

The Influence of Developmental Stage on the Relationship Between Severity of Late Effects of Anticancer Therapy and Perceived Quality of Life of Childhood Cancer Survivors

The present study aims to investigate the relationship between severity of late effects and subjective quality of life of childhood cancer survivors in different age brackets. The sample consisted of 147 cancer survivors (70 boys and 77 girls) aged 8 to 18 who were in remission 2 to 5 years. The analyses were carried out separately for younger (8-12 years) and older (13-19 years) age groups. Cancer survivors were asked to complete Minnesota–Minneapolis Quality of Life Instrument (MMQL) as well as other methods of measuring involvement in everyday life activities and parent–child interactions Social And Health Assessment (SAHA) were used. Severity of late effects was assessed on a 4-point scale in accordance with Common Terminology Criteria for Adverse Events v3.0. While severity of late effects correlated positively only with parental warmth in younger age bracket, there were many relationships between severity of late effects and quality of life in older age bracket. The difference between the two age brackets is explained by the fact that adolescents are able to assess the impact of the disease.

Neurological morbidity of surgical resection of pediatric cerebellar astrocytomas

Review of children with low-grade cerebellar astrocytoma (LGCA) prior to 1992 showed a 98% rate of gross total resection (GTR) but a concerning incidence of permanent neurological dysfunction. The purpose of this study was to determine the rate of GTR of LGCA since 1992 and frequency of neurologic injury. Retrospective review of children with LGCA was performed. CT/MR scans were rereviewed to assess extent of resection. Primary outcomes included incidence of GTR and incidence of permanent new neurological deficits. Other outcomes included late effects severity score (LESS), Bloom score for functional status, and educational assessment. Of 50 LGCA, GTR was achieved in 38 (76%) compared to 43 of 44 (98%) prior to 1992 (p < 0.004). Permanent new neurologic deficits from surgery occurred in 16% compared to 18% in the prior era (p = 0.61). For 35 patients operated on by the 2 surgeons in the prior study, 74% had GTR, with permanent neurological deficits in 8.6%. At latest follow-up, all patients were alive, 16% with residual tumor. LESS was two or less (mild or no deficit) in 94%. Bloom score was one or two (no or mild disability) in 90%. Eighty-six percent attended normal school. Less aggressive resection of LGCA in children may reduce postoperative neurologic deficits in the hands of the same surgeons as in the prior study but not overall at our institution. The good long-term outcomes suggest that it may be appropriate to do incomplete resection rather than risk additional neurological deficit.

Carbon-ion radiotherapy for marginal lymph node recurrences of cervical cancer after definitive radiotherapy: a case report

Recurrences of cervical cancer after definitive radiotherapy often occur at common iliac or para-aortic lymph nodes as marginal lymph node recurrences. Patients with these recurrences have a chance of long-term survival by optimal re-treatment with radiotherapy. However, the re-irradiation often overlaps the initial and the secondary radiotherapy fields and can result in increased normal tissue toxicities in the bowels or the stomach. Carbon-ion radiotherapy, a form of particle beam radiotherapy using accelerated carbon ions, offers more conformal and sharp dose distribution than X-ray radiotherapy. Therefore, this approach enables the delivery of high radiation doses to the target while sparing its surrounding normal tissues. Marginal lymph node recurrences in common iliac lymph nodes after radiotherapy were treated successfully by carbon-ion radiotherapy in two patients. These two patients were initially treated with a combination of external beam radiotherapy and intracavitary and interstitial brachytherapy. However, the diseases recurred in the lymph nodes near the border of the initial radiotherapy fields after 22 months and 23 months. Because re-irradiation with X-ray radiotherapy may deliver high doses to a section of the bowels, carbon-ion radiotherapy was selected to treat the lymph node recurrences. A total dose of 48 Gy (RBE) in 12 fractions over 3 weeks was given to the lymph node recurrences, and the tumors disappeared completely with no severe acute toxicities. The two patients showed no evidence of disease for 75 months and 63 months after the initial radiotherapy and for 50 months and 37 months after the carbon-ion radiotherapy, respectively. No severe late adverse effects are observed in these patients. The two presented cases suggest that the highly conformal dose distribution of carbon-ion radiotherapy may be beneficial in the treatment of marginal lymph node recurrences after radiotherapy. In addition, the higher biological effect of carbon-ion radiotherapy and its superior dose distribution may provide more effective tumor control in treatment for re-irradiation of the marginal recurrences in radiation resistant tumors other than cervical cancer.

Increased uptake of social security benefits among long-term survivors of cancer in childhood, adolescence and young adulthood: a Norwegian population-based cohort study

Background:As the number of cancer survivors increases, their health and welfare have come into focus. Thus, long-term medical consequences of cancer at a young age (<25 years), obtained from social security benefit records, were studied.Methods:Standardised incidence ratios (SIRs) of long-term medical consequences for 5-year cancer survivors, born during 1965–1985, were explored by linking population-based registries in Norway.Results:Among the 5-year cancer survivors (4031 individuals), 29.7% received social security benefits. The survivors had an overall 4.4 times (95% confidence interval (95% CI): 4.1–4.6) higher risk of social security benefit uptake than the cancer-free population. Survivors of malignancies of bone and connective tissues (SIR: 10.8; 95% CI: 9.1–12.9), CNS tumours (SIR: 7.7; 95% CI: 6.9–8.6) and malignancies of the haematopoietic system (SIR: 6.1; 95% CI: 5.3–7.0) had the highest risks of social security benefits uptake. The most notified causes of social security benefit uptake were diseases of the nervous system, and injury and poisoning.Conclusion:The uptake of social security benefits among 5-year cancer survivors increased substantially and it may represent a solid outcome measure for the burden of the most severe late effects, especially in countries with comparable social welfare systems.

Editorial: Skull base surgery

In their paper in this issue, Hayhurst et al.1 report a single-institutional retrospective review over a 10-year period of 23 children with tumors of varying types who required skull base surgical approaches. The children ranged from 1 to 15 years of age. Fifty-seven percent of the children had benign histology, and half underwent complete resection of their tumors. At a mean follow-up of 60 months, the authors reported 1 perioperative death and 2 children who died of disease progression. Progression-free survival was 95% at 1 year and 68% at 5 years. Fifty-nine percent of patients required adjuvant therapy. Interestingly, 1 child underwent subtotal resection of a clival chordoma, but did not receive adjuvant therapy and has not shown tumor progression during follow-up. Two children suffered the complication of postoperative CSF leakage followed by meningitis, postmeningitic hydrocephalus, and shunt placement, and are cognitively impaired as a result. This result emphasizes the fact that CSF leakage, the most common complication of skull base surgery in children, can have serious long-term consequences. Alternatively, the authors report that 85% of the children remain in mainstream schooling without the need for special educational assistance. This review, as have others, reminds us that recent technical advances—such as image guidance, better neurophysiological monitoring, endoscope-assisted minimally invasive surgery, and intraoperative imaging—can further reduce morbidity from these operations. The development of dedicated pediatric skull base surgical teams further improves the cosmetic and functional outcomes of these children by avoiding injury to rudimentary teeth, minimizing injury to the developing facial skeleton, and limiting radiation doses to growing basicranial structures. The last 3 columns of Table 2 demonstrate the relative insensitivity of the Late Effects Severity Score (LESS) in rating the functional outcomes of these children. (http://thejns.org/doi/abs/10.3171/2012.10.PEDS12479)

Skull base surgery for tumors in children: long-term clinical and functional outcome

Skull base tumors in children are rare but require complex approaches with potential morbidity to the developing craniofacial skeleton, in addition to tumor-related morbidity. Reports of long-term clinical and functional outcome following skull base approaches in children are scarce. The authors report long-term outcome in children with tumors undergoing multidisciplinary skull base surgery. A retrospective analysis was undertaken of children undergoing surgery at a single institution between 1998 and 2008 for benign and malignant lesions of the anterior, middle, or posterior cranial base. Patients with craniopharyngioma, pituitary tumors, and optic glioma were excluded. Histology, surgical morbidity, length of hospital stay, progression-free survival, and adjuvant therapy were recorded. Functional and cognitive outcome was assessed prospectively using the Late Effects Severity Score (LESS). Twenty-three children ranging in age from 13 months to 15 years underwent skull base approaches for resection of tumors during the study period. The median follow-up duration was 60 months. Tumor types included meningioma, schwannoma, rhabdomyosarcoma, neuroblastoma, angiofibroma, and chordoma. Complete resection was achieved in 12 patients (52%). Thirteen patients (57%) had benign histology. The median hospital stay was 7 days. There were 3 deaths, 1 perioperative and 2 from tumor progression. Two patients had CSF leakage (9%) and 2 developed meningitis. Two children (9%) had residual neurological deficit at last follow-up evaluation. Thirteen (59%) of 22 surviving patients received adjuvant therapy. The majority of the patients remain in mainstream education and 19 of the 20 surviving children have an LESS of 3 or lower. Children tolerate complex skull base procedures well, with minimal surgical-related morbidity as well as good long-term tumor control rates and functional outcomes from maximal safe resection combined with adjuvant treatment when required.

Risk Model and Nomogram for Dysphagia and Xerostomia Prediction in Head and Neck Cancer Patients Treated by Radiotherapy and/or Chemotherapy

In our randomized trial on hyperbaric oxygen (HBO), it was shown that HBO could reduce dysphagia and xerostomia, which are frequently encountered after (chemo-) radiotherapy (RT) and/or surgery for head and neck cancer (HNC). A risk model and nomogram are developed to select those patients who most likely will respond to HBO treatment. A total of 434 HNC patients treated from 2000 to 2008 were analyzed and filled out the EORTC QLQC-30 and H&N35 questionnaires. Age, gender, chemotherapy, T and N stages, site, radiotherapy technique, RT boost, surgery of the primary tumor and neck, bilateral RT, and dose were analyzed in a statistical model. The discriminative value of the model was evaluated based on receiver operating characteristics (ROC), the area under the curve (AUC), sensitivity, specificity, and proportion of correctly classified measures. Significant factors in predicting swallowing problems are age, follow-up duration, tumor site, chemotherapy, surgery of the primary tumor and neck, and dose. For dry mouth, the significant factors are age, gender, tumor site, N stage, chemotherapy, and bilateral irradiation. For dysphagia and xerostomia, the area under the ROC curve is 0.7034 and 0.7224, respectively, with a specificity of 89/77%, sensitivity of 27/58%, and a positive predictive value of 83/67% for dysphagia and xerostomia, respectively. The developed predictive risk model could be used to select patients for costly hyperbaric oxygen treatment to prevent or reduce severe late side effects of HNC treatment. Our model serves as a guideline for the Department of Radiation Oncology to reduce costs by excluding patients not amenable to hyperbaric oxygen protocols. The nomogram presented is a useful tool for clinicians in assessing patient risks when deciding on follow-up strategies (e.g., hyperbaric oxygen treatment) after RT or surgery for HNC.

Stereotactic body radiation therapy in the re-irradiation situation – a review

Although locoregional relapse is frequent after definitive radiotherapy (RT) or multimodal treatments, re-irradiation is only performed in few patients even in palliative settings like e.g. vertebral metastasis. This is most due to concern about potentially severe complications, especially when large volumes are exposed to re-irradiation. With technological advancements in treatment planning the interest in re-irradiation as a local treatment approach has been reinforced. Recently, several studies reported re-irradiation for spinal metastases using SBRT with promising local and symptom control rates and simultaneously low rates of toxicity. These early data consistently indicate that SBRT is a safe and effective treatment modality in this clinical situation, where other treatment alternatives are rare. Similarly, good results have been shown for SBRT in the re-irradiation of head and neck tumors. Despite severe late adverse effects were reported in several studies, especially after single fraction doses >10 Gy, they appear less frequently compared to conventional radiotherapy. Few studies with small patient numbers have been published on SBRT re-irradiation for non-small cell lung cancer (NSCLC). Overall survival (OS) is limited by systemic progression and seems to depend particularly on patient selection. SBRT re-irradiation after primary SBRT should not be practiced in centrally located tumors due to high risk of severe toxicity. Only limited data is available for SBRT re-irradiation of pelvic tumors: feasibility and acceptable toxicity has been described, suggesting SBRT as a complementary treatment modality for local symptom control.

Radiation myelopathy: a case report

Normal tissue injury may lead to severe late side effects after therapeutic use of irradiation. Radiation myelopathy (RM) is an uncommon complication of therapeutic irradiation whenever the spinal cord is included within the radiation treatment field. Several factors such as radiation dose, fractination, linear energy transfer, chemotherapy, modify its occurrence and severity. Herein, we report a 43-year-old male patient with nasopharyngeal cancer who developed RM after concomitant chemoradiotherapy and discussed the literature.

Expression and Regulation of the Endogenous Retrovirus 3 in Hodgkin’s Lymphoma Cells

Human endogenous retroviruses (ERV) are an integral part of our genome. Expression of ERV is usually switched off but reactivation of ERV has been observed in varying human diseases including cancer. Recently, reactivation of ERV associated promoters in Hodgkin’s lymphoma (HL) cells has been described. Despite relatively good prognosis, not all patients with HL can be cured with the established therapy and this therapy is associated with severe late side effects. Therefore, new targets are required for the development of future treatment strategies. Reactivated ERV might represent such target structures. Therefore, we asked which ERV loci are expressed in HL cells. Using DNA microarray analysis, we found no evidence for a general activation of ERV transcription in HL cells. In contrast, we observed down-regulation of ERV3, an ERV with potential tumor suppressor function, in HL cells in comparison to normal blood cells. Interestingly, ERV3 was also differentially expressed in published DNA microarray data from resting versus cycling B cells. Treatment of HL cells with the histone deacetylase inhibitor vorinostat strongly up-regulated ERV3 expression. In addition, we observed up-regulation in HL cells after treatment with hypoxia-mimetic cobalt(II) chloride. Like vorinostat, cobalt(II) chloride inhibited cell growth of HL cells. Our results suggest that cell cycle inhibition of HL cells is accompanied by up-regulation of ERV3.

Obstetric interventions in preterm birth: a literature review and therapeutic update

Prematurity is an important theme that impacts greatly both public and individual health. It is still the highest cause of morbimortality in the perinatal period and its consequences include potentially severe immediate and late effects. Although there are still severe limitations to the early identification of preterm labor as well as in the measures to avoid complications, many advances have been made in terms of assistance to pregnant mothers and neonates, including more widespread neonatal intensive care centers. This review aims to present therapeutic measures that can minimize the consequences of preterm delivery. Whenever indicated, medication for tocolysis, fetus lung maturation, neural protection, and infection prevention must be prescribed, given that any intervention capable of improving fetal prognosis has relevant social, psychological and financial impact on affected families.

Magnetic resonance imaging of the brain in survivors of childhood acute lymphoblastic leukemia

The issue of delayed neurological damage as a result of treatment is becoming increasingly important now that an increased number of children survive treatment for acute lymphoblastic leukemia (ALL). Following modification of the treatment protocols, severe symptomatic late effects are rare, and most adverse effects are detected by sensitive imaging methods such as magnetic resonance imaging (MRI) or by neuropsychological testing. In this study we aimed to determine the prevalence and characteristics of late central nervous system (CNS) damage by MRI and clinical examination in children treated for ALL. A cross-sectional study was carried out at the pediatric oncology unit of Zagazig University, Egypt, and included 25 patients who were consecutively enrolled and treated according to the modified Children’s Cancer Group (CCG) 1991 protocol for standard risk ALL and the modified CCG 1961 protocol for high-risk ALL and who had survived more than 5 years from the diagnosis. All relevant data were collected from patients’ medical records; particularly the data concerning the initial clinical presentation and initial brain imaging. All patients were subjected to thorough history and full physical examination with special emphasis on the neurological system. MRI of the brain was performed for all patients. The mean age of patients was 6.9±3.04 years at diagnosis and was 12.9±3.2 years at the time of study. The patients comprised 14 boys and 11 girls. Abnormal MRI findings were detected in six patients (24%). They were in the form of leukoencephalopathy in two patients (8%), brain atrophy in two patients (8%), old infarct in one patient (4%) and old hemorrhage in one patient (4%). The number of abnormal MRI findings was significantly higher in high-risk patients, patients who had CNS manifestations at diagnosis and patients who had received cranial irradiation. We concluded that cranial irradiation is associated with higher incidence of MRI changes in children treated for ALL. Limitation of cranial irradiation to selected patients contributed to a lower incidence of neurological complications in our study. MRI is a sensitive radiological tool to detect structural changes in children treated for ALL, even in asymptomatic cases.