Role of Gallium-67 in management of paediatric solid tumours

ABSTRACT. Gallium-67 citrate (Ga67) has been advocated for the evaluation of cancer in infants and children. Its role in patient management is not well defined. Over a 2-year period, 136 Ga67 whole body scans were performed on 79 infants and children with cancer. Abnormal scans were found in 39 children with solid tumours before the commencement of therapy. Nineteen children on therapy at the time of the scan had normal studies and were clinically disease free. Seventeen children showed Ga67 avid recurrence of disease after treatment. Four of 5 children with leukaemia who had scans for the detection of infection showed an inflammatory focus on scan and directed appropriate management. Two children with a prostatic rhabdomyosarcoma did not accumulate gallium in the primary tumour before treatment. Whole body Ga67 scans should be performed prior to treatment in all children with solid tumours. If the tumour is Ga67 avid then serial scans are indicated to assess response to therapy, to detect recurrence and/or infective complications of the disease.     

Comparison between x-ray and bone scan detection of bone metastases in patients with rhabdomyosarcoma

A comparison of radiographic and 99mTechnetium methyldiphosphonate scintigraphic evaluations for extent of skeletal disease was made retrospectively in 17 pediatric patients with Group III and IV rhabdomyosarcoma. Thirteen children had evidence of skeletal metastases. Of these, four exhibited multiple sites of blastic as well as lytic skeletal involvement on x-rays that were not detected by bone scans: two at the time of initial diagnosis, and two at relapse in children with prior radiotherapy to involved bones. In three additional patients a greater extent of bony disease was evident on x-rays than on bone scan. Neither the pathology of the tumor, lytic versus blastic quality of the bone lesion, nor lesion size per se was found to correlate with the failure to detect them on the bone scan. Although bone scans have greater sensitivity than x-rays for the detection of metastatic bone involvement in several adult and pediatric neoplasms, in the case of rhabdomyosarcoma, the radiographic exam appears to be a more sensitive indicator in some patients and should be considered an essential study in the evaluation of skeletal involvement by this tumor.     

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

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

Occult trauma mimicking metastases on bone scans in pediatric oncology patients

Background. Tracer-avid osseous lesions are usually considered to represent metastases in pediatric oncology patients. However, sites of minor, clinically occult, skeletal trauma may be mistaken for osseous metastases. Objective. The objective of this study was to review our experience with skeletal scintigraphy in pediatric oncology patients to determine specificity for metastatic disease. Materials and methods. We reviewed 164 bone scans performed on 96 consecutive patients (ages 5 months to 23 years) at presentation with malignancy or during chemotherapy. Tumors included osteosarcoma (13), Ewing sarcoma (11), lymphoma (19), neuroblastoma (12), brain tumors (16), rhabdomyosarcoma (10), renal tumors (5), and miscellaneous neoplasms (10). Scintigraphic abnormalities were considered metastatic based on radiographic findings, subsequent tumor progression, or multiplicity of lesions. Lesions were considered benign when spontaneous resolution occurred without change in therapy or radiographs demonstrated a traumatic or other benign lesion. Results. Of the 96 patients, 51 had normal studies or showed only the primary lesion. Of the 45 patients with abnormal scintigraphy, 16 (35 %) had metastases and 29 (65 %) had one or more focal benign lesions. These lesions included abnormalities due to stress/trauma (25), benign neoplasm (2), infection (3), disuse (6), surgery (10) and artifacts (4). Conclusion. The majority of scintigraphic abnormalities have nonmalignant etiologies, most commonly stress reaction and trauma. In patients without known extraosseous metastases, one or two skeletal lesions should not be assumed to represent metastatic disease. Received: 11 December 1995 Accepted: 28 June 1996     

Improved detection of metastatic Ewing's sarcoma with the use of bone marrow scintigraphy

Prognosis in Ewing's sarcoma is inversely related to the extent of the disease at the time of presentation. The most common sites of metastases are the lungs and skeleton. Bone marrow metastases may be present but clinically silent. We report the use of Technetium (Tc)-99m bone marrow scintigraphy to detect sites of marrow involvement by metastatic Ewing's sarcoma. This method of evaluation allowed identification of sites of involvement by Ewing's sarcoma that were not available by any other method of evaluation. In several instances, information provided by this method was pivotal in the management of these patients. Based on this small series of patients, bone marrow scintigraphy appears to be a sensitive modality in the detection of metastatic disease in patients with Ewing's sarcoma. Better understanding of the role of bone marrow scanning and its correlation with other diagnostic procedures in Ewing's sarcoma will require further study.     

Meta-iodobenzylguanidine scintigraphy in neuroblastoma--a comparison with conventional X-ray and ultrasound

To evaluate the accuracy of meta-iodobenzylguanidine (MIBG) imaging in comparison with bone X-ray and ultrasound, 15 patients with histologically verified neuroblastoma were investigated using 123- or 131MIBG scintigraphy. 123MIBG and 131MIBG are used as the abbreviations for 123-iodine-labeled-MIBG and 131-iodine-labeled-MIBG, respectively. Either 7.4 MBq 131MIBG (n = 4) or 111-185 MBq 123MIBG (n = 11) was applied, and scans were performed 24 and 48 h PI. Anatomical orientation was provided in selected cases by single-photon emission CT or scintigraphy of other organs. X-ray procedures or ultrasound depicted 27 neuroblastoma manifestations (primary tumors and metastatic deposits); 24 of these (89%) were identified by MIBG scintigraphy. Of 42 primary neuroblastomas and metastatic deposits, 27 (64%) were detected by corresponding bone X-ray or ultrasound. The 15 neuroblastoma lesions depicted solely by MIBG scans were mainly (80%) situated in the skeletal system. Because of the pronounced physiological MIBG uptake by liver tissue, detection of intrahepatic or perihepatic tumor involvement is difficult. MIBG scintigraphy is a safe and noninvasive means of locating a wide range of neuroblastoma lesions. Its main diagnostic advantage in comparison with bone X-ray lies in the detection of bone marrow infiltration.     

More aggressive bone marrow screening in retinoblastoma patients is not indicated: the memorial Sloan-Kettering cancer center experience

BACKGROUND: Bone marrow involvement in retinoblastoma patients is rare in the more industrialized nations. The purpose of the current study was to determine the frequency of bone marrow involvement in our series of retinoblastoma patients and to investigate whether the use of four bone marrow aspirates (BMA) and two bone marrow biopsies (BMB) has greater sensitivity for the detection of metastatic disease compared to what has been previously reported. METHODS: Retrospective analysis of the charts of 54 patients with retinoblastoma was performed. We performed 265 BMA, 134 BMB (4 aspirates and 2 biopsies per evaluation), and 67 lumbar punctures (LPs) in 54 patients with retinoblastoma. RESULTS: There were no patients found with bone marrow or cerebrospinal fluid (CSF) involvement at the time of the initial diagnosis. Although no patient died of distant metastases, two patients developed metastatic disease at recurrence, involving the bone marrow and other sites. For these two patients all four aspirates and two biopsies were positive for disease at the time of recurrence. CONCLUSIONS: Despite the use of four BMA and two BMB (as opposed to one bone marrow aspirate that is routinely performed in other centers), the detection of patients with metastatic disease was similar to what has been previously reported. Based on these data more aggressive evaluation of the bone marrow in retinoblastoma patients with clinically limited disease using four aspirates and two biopsies cannot be supported.     

Whole-body MRI of paediatric malignant tumours: comparison with conventional oncological imaging methods

Purpose: To evaluate the usefulness of whole-body (WB) MRI for detecting metastases from paediatric malignant tumours in comparison with conventional oncological imaging methods. Materials and methods: Using a 1.5-T system, a coronal short tau inversion recovery (STIR) sequence was obtained in all patients. In addition, sagittal fat-suppressed T2-weighted, sagittal STIR, or coronal fat-suppressed pre-contrast and post-contrast T1-weighted sequences were performed. Patients who underwent WB MRI and conventional oncological imaging within 15 days were enrolled in the study. In total, 58 bone scintigraphies, 26 iodine-123 (¹²³I) meta-iodo-benzylguanidine (MIBG) scintigraphies, and 48 CT scans were available for comparison in 36 patients (median age 3.5 years; 21 boys, 15 girls) who underwent 82 WB MRI examinations. Skeletal and extraskeletal metastases were evaluated for a variety of tumour types. Results: Concordance rate of WB MRI between two readers was 74%. In detecting metastases, WB MRI had higher sensitivity (99%) and PPV (94%) than bone scintigraphy (26 and 76%, respectively). In detecting skeletal metastases, WB MRI revealed higher sensitivity (100%) than ¹²³I-MIBG scintigraphy (25%) and CT (10%). In contrast, WB MRI showed lower PPV in detecting skeletal and extraskeletal metastases (8 and 57%, respectively) than ¹²³I-MIBG scintigraphy (100%), and lower sensitivity (60%) in detecting extraskeletal metastases than CT (100%). In 2 of 11 untreated patients, tumour staging was upgraded from stage 3 to 4 according to WB MRI findings. In 3 patients, WB MRI revealed early treatment responses (<1 year) of skeletal metastases. Conclusions: WB MRI can substitute for bone scintigraphy in detecting skeletal metastases of paediatric malignant tumours, and it is useful in evaluating initial tumour staging and early treatment responses. However, it still has only a complementary role in detecting extraskeletal metastases.     

Complementary use of radiological skeletal survey and bone scintigraphy in detection of bony injuries in suspected child abuse.

AIM: To compare the effectiveness of radiological skeletal survey and bone scintigraphy for the detection of bony injuries in cases of suspected child abuse. METHODS: All cases with a discharge diagnosis of child abuse that presented to the Royal Children's Hospital between 1989 and 1998 were retrieved, and those children that had undergone both skeletal survey and bone scintigraphy (radioisotope bone scan) within a 48 hour period were included in this study. Both examinations followed rigid departmental protocols and protocols remained identical throughout the timeframe of the study. The reports of the skeletal surveys and bone scans were retrospectively reviewed by a paediatric radiology fellow and consultant paediatric radiologist. RESULTS: The total number of bony injuries identified was 124 in 30 children. Of these, 64 were identified on bone scan and 77 on skeletal survey. Rib fractures represented 60/124 (48%) of the bony injuries and were present in 16/30 children (53%), of which 62.5% had multiple rib fractures. Excluding rib fractures, there were 64 (52%) bony injuries, of which 33% were seen on both imaging modalities, 44% were seen on skeletal survey only, and 25% were seen on bone scans alone. Metaphyseal lesions typical of child abuse were present in 20 cases (31%) on skeletal survey; only 35% of these were identified on bone scan. Six children (20%) had normal skeletal surveys, with abnormalities shown on bone scan. There were three children (10%) with normal bone scans who were shown to have injuries radiographically. CONCLUSIONS: Skeletal survey and bone scintigraphy are complementary studies in the evaluation of non-accidental injury, and should both be performed in cases of suspected child abuse.     

Complementary use of radiological skeletal survey and bone scintigraphy in detection of bony injuries in suspected child abuse

Aim: To compare the effectiveness of radiological skeletal survey and bone scintigraphy for the detection of bony injuries in cases of suspected child abuse. Methods: All cases with a discharge diagnosis of child abuse that presented to the Royal Children''s Hospital between 1989 and 1998 were retrieved, and those children that had undergone both skeletal survey and bone scintigraphy (radioisotope bone scan) within a 48 hour period were included in this study. Both examinations followed rigid departmental protocols and protocols remained identical throughout the timeframe of the study. The reports of the skeletal surveys and bone scans were retrospectively reviewed by a paediatric radiology fellow and consultant paediatric radiologist. Results: The total number of bony injuries identified was 124 in 30 children. Of these, 64 were identified on bone scan and 77 on skeletal survey. Rib fractures represented 60/124 (48%) of the bony injuries and were present in 16/30 children (53%), of which 62.5% had multiple rib fractures. Excluding rib fractures, there were 64 (52%) bony injuries, of which 33% were seen on both imaging modalities, 44% were seen on skeletal survey only, and 25% were seen on bone scans alone. Metaphyseal lesions typical of child abuse were present in 20 cases (31%) on skeletal survey; only 35% of these were identified on bone scan. Six children (20%) had normal skeletal surveys, with abnormalities shown on bone scan. There were three children (10%) with normal bone scans who were shown to have injuries radiographically. Conclusions: Skeletal survey and bone scintigraphy are complementary studies in the evaluation of non-accidental injury, and should both be performed in cases of suspected child abuse.     

Whole-body MR imaging with the use of parallel imaging for detection of skeletal metastases in pediatric patients with small-cell neoplasms: comparison with skeletal scintigraphy and FDG PET/CT

BACKGROUND: In pediatric patients with small-cell tumors, there is an increasing demand for accurate and early detection of skeletal, especially bone marrow, metastases as new treatment protocols are introduced. Whole-body MR imaging (WB-MR) and (18)F-fluorodeoxyglucose PET/CT (FDG PET/CT) are new promising imaging methods that can detect metastases before osteoblastic host response occurs, which is the basis for detection of metastases by skeletal scintigraphy (SSC). OBJECTIVE: To assess the ability of WB-MR to detect marrow metastases in children with small-cell neoplasms and compare its performance with that of FDG PET/CT and SSC. MATERIALS AND METHODS: During a 16-month period, 26 children and adolescents with histopathologically proven small-cell neoplasms underwent WB-MR, FDG PET/CT and Tc-phosphonate-based SSC in a random order within a 25-day period. Metastases were localized in relation to eight regions of the body. RESULTS: WB-MR revealed metastases in 39 out of a total of 208 regions in 26 patients (sensitivity 97.5%, specificity 99.4%, positive predictive value 97.5%, negative predictive value 99.4%), SSC in 12 regions (sensitivity 30%, specificity 99.4%, PPV 92.3%, NPV 85.6%) and FDG PET/CT in 36 regions (sensitivity 90.0%, specificity 100%, PPV 100%, NPV 97.7%). Both WB-MR and FDG PET/CT showed excellent agreement (kappa) with the final diagnosis (96.9% and 93.6% respectively), whereas SSC showed only moderate agreement (39.6%). CONCLUSION: Our results suggest that WB-MR and FDG PET/CT studies are robust imaging modalities for screening for skeletal metastases, and are far more accurate than SSC. The lack of radiation is an additional advantage of WB-MR, especially in the pediatric population.     

Meta-Iodobenzylguanidine Scintigraphy in Neuroblastoma–a Comparison with Conventional X-Ray and Ultrasound

To evaluate the accuracy of meta-iodobenzylguanidine (MIBG) imaging in comparison with bone X-ray and ultrasound, 15 patients with histologically verified neuroblastoma were investigated using¹²³- or ¹³¹MIBG scintigraphy. ¹²³MIBG and ¹³¹MIBG are used as the abbreviations for 123-iodine-labeled-MIBG and 131-wdine-labeled-MIBG, respectively. Either 7.4 MBq ¹³¹MIBG (n = 4) or 111-185 MBq ^{123 >}MIBG (n = 11) was applied, and scans were performed 24 and 48 h PI. Anatomical orientation was provided in selected cases by single-photon emission CT or scintigraphy of other organs. X-ray procedures or ultrasound depicted 27 neuroblastoma manifestations (primary tumors and metastatic deposits); 24 of these (89 %) were identified by MIBG scintigraphy. Of 42 primary neuroblastomas and metastatic deposits, 27 (64%) were detected by corresponding bone X-ray or ultrasound. The 15 neuroblastoma lesions depicted solely by MIBG scans were mainly (80%) situated in the skeletal system. Because of the pronounced physiological MIBG uptake by liver tissue, detection of intrahepatic or perihepatic tumor involvement is difficult. MIBG scintigraphy is a safe and noninvasive means of locating a wide range of neuroblastoma lesions. Its main diagnostic advantage in comparison with bone X-ray lies in the detection of bone marrow infiltration.     

Allogeneic stem cell transplantation in a patient with relapsed Ewing sarcoma

Ewing sarcoma (ES) can express tumor antigens which can be recognized by T cells, making allogeneic stem cell transplant (SCT) a potential option for those patients with refractory disease. A 6-year old with multifocal ES developed a recurrence of pulmonary metastases and underwent an allogeneic bone marrow transplant from her human leukocyte antigen (HLA) 10/10 matched mother. During a taper of her immunosuppression, she developed grade 1 skin and oral graft versus host disease (GVHD). CT scans performed 9 months post-transplant revealed a marked decrease in the size of her pulmonary lesions compared to scans 2 months post-transplant. This case highlights the possibility of treating patients with refractory metastatic ES with allogeneic SCT.     

The value of sodium pertechnetate Tc99m scans in the diagnosis of Meckel's diverticulum

A retrospective study was conducted of our experience with sodium pertechnetate Tc99m scans for diagnosing suspected Meckel's diverticula. Seventy-seven cases scanned between 1979 and 1994 were reviewed. Eighty per cent of the group presented with bleeding per rectum, 12% with pain, and 6.5% with anaemia. Ten scans were positive with 7 true-positive and 3 false-positive. Of the 67 negative scans, 3 were false-negatives. There were six Meckel's diverticuli and four duplication cysts between the true-positive and false-negative groups. All presented with major gastrointestinal (GI) bleeding and gastric mucosa was identified on histology. The three false-positive cases had inappropriate laparotomies on the basis of scan results. The test sensitivity was 70% with a specificity of 95%, giving an overall accuracy of 92%. The Meckel's scan is a useful investigation for GI bleeding in children. Surgical intervention should be guided by the full clinical picture and the scan, rather than the scan result alone.     

Radionuclide bone scan in neuroblastoma

A comparison of radionuclide bone scans with other methods of monitoring disease status was undertaken in a series of 51 children with neuroblastoma. The radionuclide bone scan was more accurate than either conventional radiographic studies or physical examination in localizing the primary tumor. When the extent of bony metastatic disease was evaluated, the bone scan and radiographic skeletal surveys were generally both positive, but the bone scan tended to show evidence of greater metastatic disease than radiographs.     

Gallium-67 scintigraphy in children with chronic granulomatous disease

Gallium-67 has been extensively used to diagnose and localize adult and pediatric inflammatory, infectious and malignant disease. Its mechanism of localizing in pathologic foci, although the subject of numerous studies both in vitro and in vivo, has not been clearly understood yet. The presence of normal polymorphonuclear leukocytes has been reported to be important in the accumulation of the tracer in inflammatory sites. We reviewed our experience with Gallium scintigraphy in three children with chronic granulomatous disease, an entity characterized by defective neutrophils and recurrent infection. Radiogallium was found to localize in inflammation in these patients. Hematologic disorders with specific structural or biochemical defects in their polymorphonuclear leukocytes may provide important information as to how these cells contribute to the accumulation of Gallium-67 in inflammation.     

Bone metastases in Wilms' tumor in relation to histologic grading (author's transl)

86 patients with Wilms' tumor were treated in Heidelberg between 1951 and 1980. Using the histopathologic grading according to Hardwick and Stowens the sarcomatous tumor type has an unfavorable prognosis. All the patients in stage III to V developed metastases. In contrast to other types of Wilms' tumor these sarcomatous tumors do metastasize to bones, not primarily to the lung. Boys up to 5 years are mostly affected by the tumor. These were "cold" lesions in bone scan using different radionuclides on skeletal osteolytic metastases, which is limiting the application of scans to detect bone metastases in Wilms' tumor. A more aggressive chemotherapy should be given to improve prognosis of the sarcomatous type of Wilms' tumor.     

Late events in pediatric patients with Ewing sarcoma/primitive neuroectodermal tumor of bone: the Dana-Farber Cancer Institute/Children's Hospital experience

The outcome for 82 pediatric patients with Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) of bone is reported; the patients were treated at the Dana-Farber Cancer Institute (DFCI) and Children's Hospital (CH) in Boston, MA (USA) from 1971-1988. The charts of all patients with ES/PNET of bone treated during this period were reviewed for disease status, therapy, sites of relapse, information on second malignancies, and survival status. Eighty-two patients with ES/PNET of bone treated at DFCI/CH were identified. The 10-year event-free survival (EFS) rates were 12% (95% confidence interval [CI] 0, 27%) and 38% (95% CI 26, 51%) for patients with and without metastases, respectively (P = 0.002); the overall survival (OS) rates were 17% (95% CI 1, 33%) and 48% (95% CI 35, 61%) for patients with and without metastases (P = 0.001). Median follow-up for surviving patients is 10.2 years. Primary site in the pelvis also was associated with a poor outcome for patients with no metastatic disease (P = 0.006 OS, P = 0.03 EFS). Thirty-one patients survived in first remission at least 5 years from diagnosis, and of these, five experienced relapse of original disease, and five experienced secondary malignancies. Pediatric patients treated for ES/PNET of bone remain at risk for life-threatening events into the second decade of follow-up. After 5 years, the risk of second malignant neoplasm is at least as high as the risk of late relapse. Prolonged follow-up of patients with ES and PNET of bone is indicated.     

Gastric and small bowel Crohn's disease assessed with leukocytes-Tc99m scintigraphy

We reviewed 312 ^99mTc leukocyte ^99mTc-WBC studies to evaluate the sensitivity and specificity of ^99mTc-WBC for identifying small-bowel and gastric inflammation in children with Crohn's disease. The ^99mTc-WBC scans were interpreted blindly and compared to the results of colonoscopy with biopsies and surgical specimens. In 46 children, total colonoscopy was done within a few days of a ^99mTc- WBC scan and in 13 others surgical specimens were available. Of the 37 children in whom the terminal ileum was visualized endoscopically (24) or surgically (13), the WBC-Tc^99m scan showed a similar degree of inflammation in 33. The sensitivity of ^99mTc-WBC scanning was 91% and the specificity 96%. The scans allowed evaluation of inflammation in the terminal ileum in 22 children in whom the endoscopist did not cannulate it; the scans were abnormal in 10 of these 22 children. In the children with no ileoscopy the results of the ^99mTc-WBC scan were consistent with the laboratory values, the gastroenterologist's clinical assessment, and long-term clinical follow-up. Finally, the scans of 46 controls did not reveal any false-positive findings in the terminal ileum. Five children with gastritis documented by gastroscopy had normal ^99mTc-WBC scans and upper gastrointestinal barium studies. This study demonstrates in a large number of normal and abnormal children with different pre-test probabilities of having inflammatory bowel disease that scintigraphy is reliable in identifying small-bowel inflammation. Accepted: 2 December 1998