Scintigraphic and radiographic patterns of skeletal metastases in breast cancer: value of sequential imaging in predicting outcome

Objective To determine whether temporal changes in scintigraphic and bone radiographic findings have prognostic significance in patients with skeletal metastases from breast cancer.Design Clinical information and films were retrospecitvely reviewed in 101 randomly selected patients with skeletal metastases. Images from sequential bone scans and bone radiographs were correlated with survival after detection of the metastases.Results Time to detection of skeletal metastases and the length of time for which patients were classified as radiologically stable after development of skeletal metastases correlated with survival (r=0.843; r=0.821, respectively). Failure to develop a radiographically and scintigraphically stable pattern after treatment was associated with significantly decreased survival compared with the rest of the patients (mean survival 2.1±1.3 years vs 4.3±2.3 years; p<0.001). Scintigraphic regression of metastases was associated with significant survival benefit and longer stabilization of disease compared to all other patterns (mean survival 5.0±2.7 years for regressive disease vs 3.7±1.9 years for stable disease and 2.2±1.3 years for progressive disease; p<0.001).Conclusions Sequential scintigraphic and radiographic imaging is useful in breast cancer patients not only for detection of metastases and monitoring of treatment effect, but also because these studies provide valuable prognostic information.     

The role of bone scintigraphy in osteogenic sarcoma

Hospital records of 27 children with osteogenic sarcoma were reviewed in an effort to define the usefulness of skeletal scintigraphy in the initial evaluation and follow-up of their disease. Serial bone scans as well as plain radiographs, linear tomograms, and computed tomograms were evaluated for evidence of bone or lung metastases. Eighteen patients developed lung metastases and three developed bone metastases. Seven patients demonstrated uptake of tracer in lung metastases, however, the lesions were all easily identifiable by radiographic means. All bone metastases were detected by scintigraphy, in one instance prior to radiographic abnormality. In no cases were bone metastases known to occur in the absence of lung metastases. None of the bone scans performed for routine follow-up pruposes resulted in altered therapy for the patient. We propose that skeletal scintigraphy is useful in the initial metastatic work up of osteogenic sarcoma, and may be helpful in some patients with specific indications during their follow-up, but is less valuable when there is no clinical suspicion for bone metastases.     

Bone metastases in Wilms' tumour.

In a series of 81 patients with a diagnosis of Wilms' tumour seen at the Hospital for Sick Children, Great Ormond Street, between 1960-1972, two patients developed histologically proven bone metastases. In one patient a lump on the head was the presenting symptom of his Wilms' tumour. In the second patient an isolated metastasis developed in the iliac bone 2 3/4 years after complete removal of an encapsulated Wilms' tumour. The bone lesion was outside the previously irradiated volume. Response to treatment was poor and both patients died with further widespread disease. A review of other series confirms the low incidence of bone metastases from Wilms' tumour and the poor prognosis of this complication. This contrasts with a high incidence of pulmonary metastases in which the response to treatment and subsequent survival is good. The value of skeletal surveys and scans in detecting this relatively rare site of metastases from Wilms' tumour is discussed.     

Whole-body MRI using a rolling table platform for the detection of bone metastases

The aim of this study was to compare the results of whole-body MRI using a recently developed rolling table platform with findings of nuclear scintigraphy in patients with bone metastases. Twenty-six patients with known or suspected bone metastases who had undergone radionuclide scintigraphy were examined by MRI. Patients were placed on a rolling table platform with integrated phased-array surface coils [BodySURF (system for unlimited field of view)] capable of pulling the patient through the isocenter of the magnet. Using a five-station approach three different image sets (T1-weighted gradient recalled echo, half-Fourier acquired single-shot turbo spin echo, and short tau inversion recovery) were collected in the coronal plane. In addition, the spine was imaged in the sagittal plane. The MRI findings were compared with the results obtained by scintigraphy. The whole-body MR examination lasting merely 40 min was feasible in all 26 patients. The MRI revealed excellent correlation with scintigraphy regarding metastatic lesions. A total of 60 regions with metastatic lesions were identified on bone scintigraphy. Fifty-three regions were detected on identical locations by MRI. The regions missed by MRI were located mainly in ribs and skull. The MRI could identify additional bone metastases in spine, pelvis, and femur. The MRI screening for bone metastases correlated well with bone scintigraphy. Use of the rolling table platform permits rapid imaging based on three different contrast mechanisms of the entire skeletal system.     

Screening for skeletal metastases of the spine and pelvis: gradient echo opposed-phase MRIcompared with bone scintigraphy

Opposed-phase gradient eho (GRE) MRI at 0.5 T was compared with T1-weighted GRE MRI and bone scintigraphy regarding the detection of malignant bone marrow infiltrates of the spine and pelvis. Seventeen control patients and 41 patients with suspected skeletal metastases were studied with plain and gadolinium-enhanced MRI. In the control group only a vertebral haemangiona showed contrast enhancement, while all metastases (confirmed histologically or by follw-up) were enhancing. Opposed-phase surface coil MRI showed a significantly higher contrast-to-noise ratio of 56 metastases than T1-weighted images. In 28 patients body coil opposed-phased MRI detectedmore metastatic foci of the spine and pelvis than did bone scintigraphy (84 vs 56). No scintigraphically visualised lesion was missed by MRI. In conclusion,body coil gadolinium-enhanced opposed-phase GRE MRI may be applied as a screning method for skeletal metastases of the spine and pelvis at intermediate field strengths. Correspondence to: K. Neumann     

Correlation of prostate-specific antigen and technetium-99m HMDP bone imaging

For an evaluation of the clinical utility of prostate-specific antigen (PSA), 32 prostatic carcinoma patients (ages 54-76) and 13 nonprostatic carcinoma patients (ages 60-70) underwent PSA measurements and bone imaging. At the time of bone imaging, each patient's PSA value was measured by a monoclonal immunoradiometric assay. All 13 nonprostatic carcinoma patients (11 bronchogenic, 1 colon, and 1 urinary bladder) gave normal PSA values, although 6 had metastatic bone disease. The 32 prostatic cancer patients were divided into 2 groups of 16 each; PSA levels in Group 1 were abnormal (greater than or equal to ng/ml): PSA levels in Group 2 were normal (less than 4 ng/ml). In Group 1, bone images of 14 patients showed bone metastases; 6 of the 14 showed progression of metastases in a 6- to 12-month period. Two patients in Group 1 were negative for skeletal metastases. Twelve patients in Group 2 were negative for skeletal metastases; bone imaging in 1 showed regression of skeletal metastases; and 3 patients had unchanged bone lesion(s). The data indicate that PSA measurements may enhance bone imaging interpretation and provide valuable clinical monitoring of prostatic carcinoma. In the case of a patient with positive bone imaging and an unknown primary, PSA measurements may definitively determine if metastases originated from prostatic carcinoma.     

Bony metastases from malignant intra-cranial astrocytoma

Summary Extra-cranial skeletal metastases from primary intra-cranial gliomas are very rare. A case is reported of a patient who developed widespread skeletal deposits fifteen months after the excision of a cystic frontal astrocytoma.     

Bone pain palliation with strontium-89 in breast cancer patients with bone metastases and refractory bone pain

Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency on analgesics were evaluated before and 4, 8 and 12 weeks after⁸⁹Sr administration. Patients received 2 MBq/kg (118–148 MBq) of⁸⁹Sr by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%–66% reduction in white cell count and a 14%–75% reduction in platelet count were detected at 12 weeks after treatment in these patients. We conclude that⁸⁹Sr is effective (47% response rate) for bone pain palliation in patients with bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain.     

Omission of bone scanning according to staging guidelines leads to futile therapy in non-small cell lung cancer

The leading European and American professional societies recommend that bone scans (BS) should be performed in the staging of lung cancer only in those patients with bone pain. This prospective study investigated the sensitivity of conventional skeletal scintigraphy in detecting osseous metastases in patients with lung cancer and addressed the potential consequences of failure to use this method in the work-up of asymptomatic patients. Subsequent to initial diagnosis of non-small cell lung cancer, 100 patients were examined and questioned regarding skeletal complaints. Two specialists in internal medicine decided whether they would recommend a bone scan on the basis of the clinical evaluation. Skeletal scintigraphy was then performed blinded to the findings of history and physical examination. The combined results of magnetic resonance imaging (MRI) of the vertebral column, positron emission tomography (PET) of skeletal bone and the subsequent clinical course served as the gold standard for the identification of osseous metastases. Bone scintigraphy showed an 87% sensitivity in the detection of bone metastases. Failure to perform skeletal scintigraphy in asymptomatic patients reduced the sensitivity of the method, depending on the interpretation of the symptoms, to 19–39%. Without the findings of skeletal scintigraphy and the gold standard methods, 14–22% of patients would have undergone unnecessary surgery or neoadjuvant therapy. On this basis it is concluded that bone scans should not be omitted in asymptomatic patients.     

Radionuclide evaluation of skeletal metastases: Practical considerations

The indications for radionuclide bone scanning to evaluate possible metastatic disease are reviewed. The causes of false-positive and falsenegative interpretations are discussed and illustrated. Since breast cancer leads all malignant tumors in incidence of skeletal metastases found at autopsy, the efficacy of preoperative bone scans in patients with breast cancer is analyzed in detail. A routine preoperative bone scan for patients with Stage I breast cancer produces negligible immediate benefits, but may serve a useful purpose as a baseline to enhance the detection of subtle changes that could represent metastases in a subsequent scan. However, the clinical usefulness of this screening procedure for Stage I disease must be balanced with its cost. Clinical Stage II is a grey area and may include patients with large primary tumors and axillary nodal involvement, implying a greater chance for the occurrence of skeletal metastases and hence a significant yield in bone scans. Patients with clinical Stages III or IV disease have the greatest chance of harboring metastases and should have an extensive diagnostic evaluation including bone scans prior to definitive treatment. Selected radiographs of sites of abnormally increased radionuclide activity and an anteroposterior radiograph of the pelvis should be correlated with the scan to permit a single comprehensive diagnostic impression.Presented at the 11th Annual Meeting and Refresher Course of the International Skeletal Society, Philadelphia, Pennsylvania, USA, September 12–15, 1984     

Skeletal metastases from breast cancer: uptake of 18F-fluoride measured with positron emission tomography in correlation with CT

Objective. To characterise the uptake of ¹⁸F in skeletal metastases from breast cancer using positron emission tomography (PET) and to relate these findings to the appearance on CT. Patients and design. PET with ¹⁸F and CT were performed in five patients with multiple skeletal metastases from breast cancer. The CT characteristics were analysed in areas with high uptake on the PET study. Dynamic PET imaging of the skeletal kinetics of the ¹⁸F-fluoride ion were included. Results. The areas of abnormal high accumulation of ¹⁸F correlated well with the pathological appearance on CT. Lytic as well as sclerotic lesions had markedly higher uptake than normal bone, with a 5–10 times higher transport rate constant for trapping of the tracer in the metastatic lesions than in normal bone. Conclusion. PET with ¹⁸F-fluoride demonstrates very high uptake in lytic and sclerotic breast cancer metastases.     

MR imaging of skeletal metastases from medulloblastoma

The findings of MR imaging in 3 patients with bone metastases from medulloblastoma are reported. The first patient showed focal lesions of low signal intensity on T1-weighted spin echo images at a time when bone scintigraphy was negative for metastases. This patient later developed extensive osteosclerotic lesions visible on plain films. The bone marrow of the second patient showed diffuse low signal intensity on T1-weighted images. After chemotherapy the signal intensity of the bone marrow increased which correlated with a return of normal hematopoietic tissue. A response to chemotherapy was also found on MR imaging and repeat bone marrow biopsies in a third patient. A consistent finding was a low signal intensity on pre-gadolinium images, but the pattern (focal or diffuse abnormal signal intensity) was different in each patient. To our knowledge, this is the first report on MR imaging findings in bone metastases from medulloblastoma.     

Prostate cancer bone metastases confined to the distal left lower limb

Bone metastases from prostate cancer most commonly affect the axial and proximal appendicular skeleton with rare involvement of the distal limbs. We describe a case of multiple bone metastases confined to the left lower limb in a patient with biochemical recurrence of prostate cancer. Following an initial post-operative PSA rise, the patient received a course of salvage radiotherapy to the pelvis, however, the PSA level continued to rise and two consequent staging CT scans were negative for local recurrence and metastatic disease. Subsequent development of left ankle pain and swelling led the patient to present to his General Practitioner, which triggered a series of imaging investigations that revealed isolated left lower limb bone metastases. This case report highlights the need to consider peripheral limb bone metastases in patients with biochemical recurrence of prostate cancer, particularly in the setting of a negative staging CT scan and/or bone pain.     

Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma

OBJECTIVE: The objective was to elucidate clinical and imaging features of skeletal involvement, recurrences, and metastases of extraskeletal myxoid chondrosarcoma. MATERIALS AND METHODS: Included in this series are 4 patients, aged 44 to 65 years, 3 of whom were men and 1 a woman. RESULTS: The primary lesions were in the thigh (n = 3) and the upper arm (n = 1). Three patients with multiple metastases died of the disease, 2 were considered to have local recurrence in the adjacent bone. Skeletal metastases occurred after lung metastases in 2 cases, and before lung metastases in 1 case. Typical imaging findings are well-defined lesions with no sclerotic margin or matrix mineralization. A slow, but persistent growth is noted on the imaging features. CONCLUSION: Although skeletal metastases of chondrosarcoma of bone and soft tissue are rare, myxoid chondrosarcomas, currently classified tumors of uncertain differentiation, rarely metastasize and/or recur in the bones. The imaging features are typically of a localized lesion with cortical disruption or expansion.     

Samarium — 153 EDTMP therapy of disseminated skeletal metastasis

¹⁵³Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of ¹⁵³Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of ¹⁵³Sm-EDTMP in 15 of 19 patients (79%) who could be evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with ¹⁵³Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow 270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of ¹⁵³Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of ¹⁵³Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 1.0% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of ¹⁵³Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed ¹⁵³Sm-EDTMP-induced myclotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients.     

MRI of bone metastases

Some knowledge of MR theory is required to be able to achieve high contrast between bone metastases and normal marrow. Three factors are used in MR to diagnose bone metastases: fat–water distribution, artifacts induced by bone trabeculae, and uptake of contrast medium. Using MR-histological correlations based on specimens of the lumbar spine, and studies of patients, we explain the advantages and limitations of sequences studying fat and water (spin-echo T1, STIR, in- and out-of-phase gradient echo, fat presaturation), bone trabeculae (gradient echo with long TE), and the injection of contrast medium. Received 27 October 1997; Revision received 16 February 1998; Accepted 18 February 1998     

胃癌132例核素骨显像结果分析

目的 探讨胃癌患者骨显像结果与不同临床分期和病理类型的关系,以及胃癌骨转移的特点和规律。方法 回顾性分析132例胃癌患者骨显像结果,从病理、临床分期、骨转移灶数目和分布部位进行讨论和分析。结果 132例患者中骨转移21例,占15.9%,其中多发性骨转移19例,占转移患者90.5%;低分化腺癌及未分化癌、黏液腺癌骨转移率分别为15.2%和20%,Ⅲ、Ⅳ期胃癌骨转移率18.4%和26.6%;骨转移的部位以椎体最常见,其次是肋骨、骨盆。结论 胃癌较少转移至骨,一旦发生骨转移,一般转移病灶范围较广泛,已属肿瘤晚期。对分期晚、分化差胃癌患者应定期进行骨核素显像,以早期发现骨转移。     

Fast spin echo MRI and bone scintigraphy in the detection of skeletal metastases

Standard Spin Echo (SE) magnetic resonance imaging (MRI) is known to be a very sensitive method for the detection of bone metastases and in comparison to skeletal scintigraphy, MRI detects more lesions when field of view includes the area of suspicion. However, only with the introduction of new fast SE sequences, have MRI protocols, for the detection of metastases, become rapid enough to make it a potential screening procedure for metastatic disease. Twenty-one patients with a suspicion of carcinomatous bone metastases were evaluated with both conventional T1 weighted (T1w), T2 weighted (T2w) and fast T2w SE (FSE) sequences (thoraco-lumbar spine and pelvis) and whole body bone scintigraphy. Conventional and fast T2w SE sequences detected the same number of lesions while bone scintigraphy detected only 70% of the lesions seen on MRI. However, more importantly, in 11 of the 21 patients bone scintigraphy detected lesions outside the MR field of view, lying in the ribs, skull, scapulae and extremities and in 4 of them, MRI was negative. Our results suggest first that fast SE MRI can replace conventional SE MRI when looking for carcinomatous bone metastases in the axial skeleton, with the advantage of a four to six times reduced acquisition time for fast T2w sequences. However, the limited field of view still limits the usefulness of MRI and whole body bone scintigraphy remains the screening modality for bone metastases. Fast MRI plays an important complementary role. Correspondence to: G. K. von Schulthess     

Localization of 99mTc-HMDP in hepatic metastases from colonic carcinoma

To evaluate the significance and frequency of skeletal imaging agent localization in hepatic metastases from colonic carcinoma, scintigrams from 54 patients were retrospectively studied. Of 54 patients, 22 had hepatic metastases, and skeletal metastases were present in seven of 54. Six of the seven patients with skeletal metastases had concurrent hepatic deposits. Two patterns of bone agent localization in liver metastases occurred: diffuse and mild (10 patients) and ringlike in appearance (two patients). Twelve of the 22 patients had localization of skeletal imaging agent in hepatic metastases and extensive or large liver lesions. Concurrent serum calcium values for nine of 12 patients were reviewed; none had a high level of serum calcium. Among available plain films and /or CT scans of the abdomen for 21 of the 22 patients, only one patient with extensive colonic metastases had multiple calcifications shown on CT but not seen in plain films. The data indicate a high frequency of hepatic metastases in colon carcinoma (22/54, 40%) and a high frequency of skeletal imaging agent localization in the hepatic colonic metastases (12/22, 54.5%). Once skeletal metastases are observed, there are almost always hepatic metastases present (6/7). There was no relation between elevated serum calcium values and bone agent localization in hepatic deposits. The relation between skeletal imaging agent localization or radiographic calcifications and histopathology of colonic carcinoma was inconclusive. The presence of bone agent localization in a 99mTc hydroxymethylene diphosphonate (HMDP) bone study indicates colonic hepatic metastases that are substantially widespread and/or bulky.     

Paget's disease mimicing skeletal metastases in a patient with coexisting prostatic carcinoma

We present a 93-year-old man with prostatic carcinoma whose ^99mTc-HMDP skeletal images showed multiple areas of abnormally increased radioactivity in the bone and virtual absence of renal activity. These findings were interpreted as representing multiple skeletal metastases. When correlated with concurrent radiographs, the abnormalities were found to be due to Paget's disease. Multiple areas of bone involvement are not rare in Paget's disease. We reemphasize that an abnormal bone scintigram should always be correlated with regional radiographs to rule out conditions other than malignancy.This investigation was supported in part by Biomedical Research Support Grant # RR05374 from the Biomedical Research Support Branch, Division of Research Facilities and Resources, NIH