Neuroblastoma.

OBJECTIVE: Due to the poor results achieved on combination chemotherapy and the unproven cost-effectiveness value of myeloablative therapy, the question has been raised; should patients with stage IV neuroblastoma be actively treated? The aim of the current study is to analyze retrospectively treatment results of 43 children with neuroblastoma with special stress on the rate and duration of remission in children with disseminated neuroblastoma. METHODS: Treatment of children with neuroblastoma consisted of surgical removal of the tumor, if possible, followed by chemotherapy for unresectable residual tumor including metastases. Second look surgery was performed to resect residual masses rendered resectable on chemotherapy in the absence of distal metastases. The chemotherapy protocol used in the current study consisted of alternating combination chemotherapy regimens containing, Cyclophosphamide, Vincristine and Doxorubicin, alternating with Cis-platinum and Etoposide. RESULTS: The male to female ratio was 2:1 with a median age of 2.1 years. The abdomen was the primary site of involvement encountered in 32 patients (74%). According to the childrens cancer study group (CCSG) staging system, only 6 patients (14%) had localized tumors (stages I and II). Two patients (5%) were found to have stage IV. Stage III was documented in 5 patients (12%). The majority of patients (70%) had disseminated disease at presentation. The bone marrow was the most common site of metastatic deposit, encountered in 23 patients out of the 30 with stage IV disease (77%). Out of the 12 evaluable non-stage IV patients, only one patient (8%) showed treatment failure. Assessment of response by the end of the 6th month from the date of diagnosis revealed that out of the 27 evaluable patients with stage IV, 4 patients achieved complete remission, 7 patients achieved very good partial remission, 8 patients achieved partial remission and 4 patients achieved mixed response. Three patients showed progressive disease on chemotherapy. Twenty-one patients (78%) were symptom-free and were conducting normal life. Assessment of response to treatment by the end of the 12th month from diagnosis revealed that 6 patients (2 complete remissions, 1 very good partial response, 3 partial responses) were maintaining their remission. Out of the 19 patients showing complete or partial remission at early assessment, 4 patients maintained their remission for more than 18 months. Two (one was in complete remission and the other was in partial response) of them progressed in areas of previous involvement after 20 and 21 months. The other 2 patients (one was in complete remission and the other was in partial response) showed disease progression in areas not previously affected by disease at presentation after 23 and 42 months. CONCLUSION: Results of treatment by multiagent chemotherapy regimens used in the current study show that children with neuroblastoma, even those with advanced stages, should receive the benefit of intensive multimodal therapy, even those with partial response to initial therapy. These patients may experience reasonable symptom-free and sometimes, disease-free survival.

Differentiated thyroid carcinoma referred for radioiodine therapy.

OBJECTIVE: The current work was conducted to study the disease status and treatment results of patients with differentiated thyroid carcinoma referred for radioactive iodine therapy. METHODS: Retrospective review of 78 patients with differentiated thyroid carcinoma referred for radioiodine therapy in the Nuclear Medicine Unit, King Abdulaziz Hospital and Oncology Center, Jeddah, Kingdom of Saudi Arabia. Analysis of the clinicopathologic characteristics, age correlation to different risk factors, treatment protocol and results were performed. RESULTS: Seventy seven percent were female and the female to male ratio was 3.5:1. The age of patients ranged between 13-63 years with a median age of 36 years. Cervical lymph node involvement was detected in 22 patients (25%). Papillary carcinoma was encountered in 78 patients (90%) and follicular carcinoma in 9 patients (10%). Analysis of the clinicopathologic characteristics showed no statistically significant difference between patients in the different age groups except for extrathyroid extension and lymph node involvement. Patients older than 45 years had a statistically significant lower incidence of nodal involvement and higher incidence of extra thyroid extension (P<0.02). In the current study we used a high dose method (Radioiodine-131 dose 75-100mCi) for thyroid remnant ablation after thyroidectomy (total or near total) in 67 patients. An Iodine 131 dose of 150 mCi was used in 12 patients with radioiodine-avid cervical lymph nodes and in 3 patients with gross residual tumor. In 4 patients with distant metastases an Iodine 131 dose of 200 mCi was used. For the whole study group the 5 year overall survival and disease-free survival was 96% and 88%. CONCLUSION: The current study, as with many other retrospective studies, concluded that despite the fact that differentiated thyroid carcinoma is among the most curable cancers, some patients are still at high risk for recurrent disease and associated mortality.

Fever and granulocytopenia in children with acute lymphoblastic leukemia under induction therapy.

OBJECTIVE: Infection is one of the most serious complications of cancer therapy. The rationale of using broad spectrum antibiotics prophylactically has led to a great change in the causative organisms. The aim of the present study is to review retrospectively the type and sequence of infectious complications among Saudi children with acute lymphoblastic leukemia. METHODS: A total of 233 febrile episodes were observed in 137 children with acute lymphoblastic leukemia under induction therapy using modified BFM protocol were studied. RESULTS: Profound neutropenia (Absolute Neutrophil count < 100/mm3) was encountered in 72 episodes (31%). Clinical signs and symptoms suggestive of infection were evident in 39% of the neutropenic episodes. The respiratory system was the most frequently affected site encountered in 17% of the episodes. Microbiologically documented infection was recorded in 59% (n=137) of the fever and granulocytopenia episodes. In 96 episodes (41%), there was neither clinical nor microbiological evidence of infection fever of unknown origin. Out of the 932 cultures, positive isolates were detected in 346 cultures (37%). Gram positive cocci were the most frequently organisms (54%) followed by gram negative bacilli (39%). In the current study, 7 patients (3%) died because of direct or indirect consequences of infection. CONCLUSION: The current study stresses the importance of frequent reviewing of the type, frequency, severity and outcome of infection complications over years to detect changing epidemiological patterns.

Hepatic dysfunction in children with acute lymphoblastic leukemia in remission: relation to hepatitis infection.

BACKGROUND: Viral hepatitis is a cause of hepatic dysfunction in children with ALL in remission during maintenance therapy is debated. The aims of the current study were (1) to explore the incidence of hepatic dysfunction in a group of children (Egyptian and Saudi) with ALL under maintenance therapy, (2) to study the prevalence of hepatitis B (HBV) and/or C (HCV) infection and their contributions to chronic liver disease that might be induced by maintenance therapy. PROCEDURE: The current study included 105 children with ALL (54 Egyptian and 51 Saudi). All eligible patients had been on maintenance therapy for at least 12 months and all had serial assessments of liver function. These included determination of total bilirubin, AST, ALT, and alkaline phosphatase. Markers for HBV and HCV including HBsAg, anti-HBC, and anti-HCV and for some patients HCV RNA by PCR were studied. Percutaneous liver biopsy was performed for a group of children. RESULTS: The prevalence of hepatitis infection (HBV and/or HCV) among Egyptian children was found to be high (43/54-80%). Only five Saudi children had evidence of exposure to HBV (5/51-9.8%), P<0.0001. During the period of study, 22 Egyptian patients vs. four Saudi patients (41 vs. 7.8%, P<0.0001) experienced at least one episode of elevation of liver enzymes, three times the upper limit of normal or more. Twenty-six of the 48 patients (54%) with HBV and/or HCV infection had episodes of elevated liver enzymes, while there was no occurrence among the patients negative for HBV and HCV. In patients with HBV infection, the presence of HBsAg was strongly associated (100%) with elevated liver enzymes. Histopathologic examination of liver biopsies obtained from 35 patients revealed that all five patients negative for HBV and HCV had normal liver biopsies in spite of being under maintenance therapy. CONCLUSION: In children undergoing treatment for ALL, elevations in liver enzymes may be primarily due to hepatitis viruses. However, maintenance therapy using known hepatotoxic drugs, may have additive deleterious effects. Liver enzymes are normalized in affected patients when maintenance therapy is temporarily suspended.

Neuroblastoma: A clinical review.

OBJECTIVE: Due to the poor results achieved on combination chemotherapy and the unproven cost-effectiveness value of myeloablative therapy, the question has been raised; should patients with stage IV neuroblastoma be actively treated? The aim of the current study is to analyze retrospectively treatment results of 43 children with neuroblastoma with special stress on the rate and duration of remission in children with disseminated neuroblastoma. METHODS: Treatment of children with neuroblastoma consisted of surgical removal of the tumor, if possible, followed by chemotherapy for unresectable residual tumor including metastases. Second look surgery was performed to resect residual masses rendered resectable on chemotherapy in the absence of distal metastases. The chemotherapy protocol used in the current study consisted of alternating combination chemotherapy regimens containing, Cyclophosphamide, Vincristine and Doxorubicin, alternating with Cis-platinum and Etoposide. RESULTS: The male to female ratio was 2:1 with a median age of 2.1 years. The abdomen was the primary site of involvement encountered in 32 patients (74%). According to the childrens cancer study group (CCSG) staging system, only 6 patients (14%) had localized tumors (stages I and II). Two patients (5%) were found to have stage IV. Stage III was documented in 5 patients (12%). The majority of patients (70%) had disseminated disease at presentation. The bone marrow was the most common site of metastatic deposit, encountered in 23 patients out of the 30 with stage IV disease (77%). Out of the 12 evaluable non-stage IV patients, only one patient (8%) showed treatment failure. Assessment of response by the end of the 6th month from the date of diagnosis revealed that out of the 27 evaluable patients with stage IV, 4 patients achieved complete remission, 7 patients achieved very good partial remission, 8 patients achieved partial remission and 4 patients achieved mixed response. Three patients showed progressive disease on chemotherapy. Twenty-one patients (78%) were symptom-free and were conducting normal life. Assessment of response to treatment by the end of the 12th month from diagnosis revealed that 6 patients (2 complete remissions, 1 very good partial response, 3 partial responses) were maintaining their remission. Out of the 19 patients showing complete or partial remission at early assessment, 4 patients maintained their remission for more than 18 months. Two (one was in complete remission and the other was in partial response) of them progressed in areas of previous involvement after 20 and 21 months. The other 2 patients (one was in complete remission and the other was in partial response) showed disease progression in areas not previously affected by disease at presentation after 23 and 42 months. CONCLUSION: Results of treatment by multiagent chemotherapy regimens used in the current study show that children with neuroblastoma, even those with advanced stages, should receive the benefit of intensive multimodal therapy, even those with partial response to initial therapy. These patients may experience reasonable symptom-free and sometimes, disease-free survival.

Radiation therapy for malignant astrocytomas in adults.

High grade (or malignant) astrocytomas remain a formidable therapeutic challenge. The main prognostic factors are patient age, patient performance status, tumor grade, the extent of surgical resection and the presence of fits. These factors could help to identify different groups of patients and should be an advantage in deciding on treatment strategies. Modern imaging techniques provide a more precise idea of tumor volume. The study of tumor recurrence shows that they occur in the immediate vicinity of the primary site. Surgery aside, radiotherapy remains the most important treatment modality. Currently, its standards concerning optimal dose and target volume appear to be accepted overall. There is no doubt that a dose-response relation exists; however, doses exceeding 60 Gy increase morbidity. Therefore 60 Gy is the dose most often cited in the literature. Furthermore, as whole brain irradiation does not decrease the risk of recurrence, a focal irradiation including a defined mean volume is generally used today. Radiosensitizers and heavy particles have not fulfilled their initial promise. Brachytherapy remains an interesting alternative for a limited number of patients. Nevertheless, it seems to increase recurrence at a distance from the primary site and to lead to severe focal lesions. Interstitial thermoradiotherapy may minimize local doses and thus help avoid serious local necrosis. Amongst the other therapeutic alternatives, intravenous chemotherapy using nitrosoureas provides a certain but modest benefit. Other administration modalities are currently undergoing evaluation. These include intra-arterial chemotherapy or high dose chemotherapy with auto-bone marrow transplantation. The interest of this latter is concerned mainly with anaplastic astrocytomas. Finally, among the future alternatives, gene therapy appears to hold the most promise. Intensive therapies, combined modality treatments, with the recent help of biological innovations, should be proposed to favorable groups of patients.

Impact of nutritional supplementation on treatment delay and morbidity in patients with head and neck tumors treated with irradiation.

Twenty-three patients with head and neck cancer were randomly allocated, regardless of pretreatment nutrition status, to receive either radiotherapy alone (12 patients) or radiotherapy plus nutritional oral supplementation (11 patients) with high-protein nutritional powder of balanced nutrient content (Ensure). Nutrition status was assessed subjectively and objectively for all patients before and at weekly intervals during the course of irradiation. All patients who received nutritional supplementation experienced an increase in body weight and in triceps skin-fold thickness, whereas 58% of the other group had weight loss (p = 0.001). Irradiation had to be suspended in 5 of the 12 patients who received no nutritional support because of severe mucosal reaction and/or poor performance status. All patients who received nutritional supplementation during radiotherapy had their course of irradiation without interruption.