Bone scans with one or two new abnormalities in cancer patients with no known metastases: frequency and serial scintigraphic behavior of benign and malignant lesions

Scintigraphic, radiologic, and clinical follow-up findings were reviewed in cases in which bone scans (n = 301) showed one or two new abnormalities in patients with malignancy but no known metastases. Metastatic disease was confirmed for 25 of 231 scans (11%) with one new abnormality and for 17 of 70 scans (24%) with two new abnormalities. The prevalence of metastases was 0.06 to 0.13 for lesions in all regions of the skeleton, except the sternum (three of six) and the pelvis (10 of 32). On follow-up scans, in the absence of an interval change in therapy, 19 of 21 metastases became more intense, whereas most benign abnormalities either remained unchanged (47%) or resolved (41%). Benign lesions in the ribs, extremities, and pelvis generally resolved within 12-24 months, while most benign skull and spine abnormalities were still apparent after 35-58 months of follow-up.     

Clinical significance and outcome of one or two rib lesions on bone scans in breast cancer patients without known metastases

The presence of one or two rib lesions on bone scans of post-treatment breast cancer patients without known metastases often makes clinical decision making problematic. The aim of this study was to identify skeletal metastasis predictors that might help the management of these patients. We recruited post-treatment breast cancer patients without overt metastases whose bone scans showed (1) one or two rib hot spots, or (2) one rib lesion and a concurrent bone abnormality. Their clinical and serial scintigraphic data were collected, reviewed and evaluated for correlations. After their first abnormal bone scans, 23 patients (11 of the 77 patients initially with one rib lesion (incidence, 14.3%), three of the 27 patients with two rib lesions (incidence, 11.1%), and nine of the 11 patients with one rib lesion plus a concurrent bone abnormality (incidence, 81.8%)) developed multiple bone metastases within 2 years of the initial rib lesions in all but one case. Univariate analyses revealed that a concurrent bone lesion other than the rib, direct tumour invasion to the chest wall or skin, and 10 or more lymph nodes involved were associated with increased risks of bone metastases whereas longer persistence of the rib lesions was associated with a lower risk. Multivariate proportional hazard analyses indicated that patients with a concurrent bone lesion other than the rib (relative risk (RR)=39.65; 95% confidence interval (CI)=8.13-193.28), 10 or more lymph nodes involved (RR=13.49; 95% CI=2.09-86.91), and no radiotherapy (RR=7.59; 95% CI=2.11-27.39) were more likely to have bone metastases, while those with longer persistence of the rib lesions (RR=0.92; 95% CI=0.84-0.98) and longer time interval between surgery and the rib lesion detection (RR=0.96; 95% CI=0.94-0.99) were less likely. We have identified clinical features applicable to risk stratification. High incidence of bone metastases was noted in patients with one rib lesion and a concurrent bone abnormality. Regular follow-up for 2 years after detection of rib lesions is recommended, especially for those with risk factors.     

Early MR demonstration of spinal metastases in patients with normal radiographs and CT and radionuclide bone scans

Forty patients with known primary tumor and progressive back pain, suspected of having spinal metastatic disease, underwent magnetic resonance (MR) examinations of the thoracic and lumbosacral spine. Conventional radiographs and CT scans of the spine were all normal. The radionuclide bone scans were equivocal. In 21 patients focal or diffuse vertebral MR abnormalities were detected. In nine patients the lesions were hypointense on T1 sequence, and the same lesions were demonstrated poorly or not at all on T2 and proton density sequences. In eight other patients the bone marrow metastases presented with strong signal intensity on T2 and were poorly or not at all demonstrated on T1 and proton density sequences. In three patients with multiple myeloma, the signal intensity pattern of the vertebrae was diffusely heterogeneous, with alternating small foci of strong and weak signals (a mosaic-like pattern). Following the MR studies, needle biopsy confirmed the malignancy in the 21 patients who had shown abnormalities. No correlation between the type of primary tumor and the signal intensity of the vertebral metastases was shown. Possibly the mosaic pattern shown in three of the multiple myeloma patients represents a special case.     

Bone pain palliation with strontium-89 in cancer patients with bone metastases.

Strontium-89 is a pure beta-emitting radioisotope, a chemical analogue of calcium, and it is therefore avidly concentrated by areas of high osteoblastic activity. Selective uptake and prolonged retention at sites of increased bone mineral turnover provide precise bone lesions targeting. 89Sr chloride (commercialised as Metastron) is typically administered in a single 150 MBq parenteral dose. Its radioactive emission poses very little radioprotection concerns. Overall, studies show pain relief in up to 80% of patients, of which 10 to 40% became effectively pain free. The mean duration of palliation was 3-4 months. The mechanism of pain relief is controversial ; it is probably, but not only, related to the absorbed dose in the tumour and bone. There is no clear dose-response relationship. The only reported toxicity is temporary myelosuppression. WBC and platelets should be monitored at least on a weekly basis until they return to baseline. It seems that only patients with a reasonably good general condition stand to benefit from this treatment. In conclusion, systemic radionuclide therapy using 89Sr represents a feasible, safe, effective, well tolerated and cost-effective palliative treatment in patients with refractory bone pain.     

Radioiodine whole-body scans, thyroglobulin levels, 99mTc-MIBI scans and computed tomography: results in patients with lung metastases from differentiated thyroid cancer

OBJECTIVES: The correlation between a 131I whole-body scan (WBS), a 99mTc sestamibi (99mTc-MIBI) WBS, a computed tomography (CT) scan and the value of routine follow-up for 131I WBS and thyroglobulin (Tg) levels in patients with lung metastases from differentiated thyroid cancer was assessed. METHOD: Pulmonary metastases were detected in 32 patients out of 583 with differentiated thyroid cancer (DTC) who were admitted to our clinic between 1985 and 2004 (age range, 22-79 years; mean, 58 +/- 19 years; 15 women and 17 men). Pulmonary metastases were diagnosed by considering the 131I WBS, increased Tg levels and/or other positive radiological findings. Papillary carcinoma was diagnosed in 15/32 patients and follicular carcinoma in 13/32. A mixed type found in 4/32 patients was classified histopathologically. A total of 3.7-53.65 GBq (100-1450 mCi) 131I was given to each patient. The duration of follow-up ranged from 36 to 240 months. A 131I WBS, the determination of Tg levels and/or a CT scan were carried out in the assessment of a diagnosis and follow-up of patients with lung metastases. A 99mTc-MIBI WBS was performed on 19 patients who were chosen at random from the 583. RESULTS: Nineteen of 32 patients had lung metastases before they received the first 131I treatment. Six of the 32 had distant-organ metastases other than in the lungs. Four of these six patients had only lung and bone metastases. Pulmonary metastases were observed on the 131I WBS patients 31/32 (96.8%) whereas no pulmonary metastases, were detected on the CT scans in 3/32 patients. The last diagnostic whole-body scan (DWBS) was normal in 13/32 patients. At the first examination, the Tg levels in 27/32 (84.4%) patients were below 30 ng . ml(-1). At the final examination, 20/32 (62.5%) patients had Tg levels higher than 30 ng . ml(-1), while Tg levels were lower than 30 ng . ml(-1) in 12/32 patients. Tg levels decreased in 21/32 and increased in 3/32 patients. The 131I WBS continued to be abnormal in 2/3 patients with increased Tg levels but became normal in one patient whose CT scan still showed macro-nodular lesions. Tg levels did not change significantly in 8/32 patients. The 131I WBS became normal in 5/8 patients, while the CT scans for 4/5 showed micro-nodules. Metastases were detected in 12/19 patients who underwent 99mTc-MIBI whole-body scanning: 18/19 showed metastases on the 131I WBSs and 17/19 on the CT scans. Of the seven patients without a sign of metastasis on the 99mTc-MIBI WBS, one was negative in terms of metastasis on the 131I WBS and one on the CT scan. Fibrosis was observed on the CT scans of 2/32 patients. One patient developed dedifferentiation, as determined by the negative 131I WBS and positive CT scan. CONCLUSION: 131I whole-body scanning and the determination of Tg levels are the most important procedures for the evaluation of lung metastases in differentiated thyroid cancer. Computed tomography is a useful addition to 131I whole-body scanning. MIBI imaging alone may not be enough to detect lung metastases from differentiated thyroid cancer.     

Association between number and sites of new bone scan abnormalities and presence of skeletal metastases in patients with breast cancer

Review of 1,441 bone scans performed on 242 breast cancer patients without known skeletal metastases identified 239 scans with new abnormalities. Findings on 54 of these 239 scans (23%) represented bone metastases. The proportion of scans reflecting metastases, grouped by the number of new abnormalities, was: (1) 20/182 (11%); (2) 9/26 (35%); (3) 4/9 (45%); (4) 1/2 (50%); greater than or equal to 5-20/20 (100%). When metastatic disease presented as a bone scan with 1-4 new abnormalities, the spine was the most common site of involvement (18 of 34 (53%)), followed by the skull (5/34; 15%), extremities and sternum (each 4/34; 12%). Rib lesions were the most common new findings on scans with less than 5 new abnormalities (seen on 76 of 219 scans (35%)) but only infrequently represented metastases (n = 2). Considering as indicative of malignancy only, those bone scans which demonstrated either (a) greater than or equal to 5 new abnormalities, (b) initial radiographic correlation suggestive of metastases, or (c) thoracic spine lesions with normal correlative radiographs, the presence of skeletal metastatic disease could be predicted with a sensitivity of 0.80 and a specificity of 0.94.     

Simulated bone metastases: a case study of two patients with breast cancer

Two case studies are used to discuss topical issues current in follow-up management of patients with early stage breast cancer. These issues include the role of screening and diagnostic bone scintigraphy and patient self-advocacy in clinical management.     

Bone marrow immunoscintigraphy for the detection of skeletal metastases in patients with breast cancer

In this study, we evaluated the efficacy of bone marrow immunoscintigraphy (BMIS) for the detection of skeletal metastases in 23 patients with histologically confirmed breast cancer. All patients underwent whole-body BMIS 3-6 h after the intravenous injection of 0.20-0.33 mg of the intact anti-NCA 95 MAb BW 250/183 labelled with 259-555 MBq 99Tcm and a whole-body 99Tcm-MDP bone scan. In four patients, BMIS SPET of the lumbar spine was also performed. Serum alkaline phosphatase was determined in all patients and the level of human anti-mouse antibody (HAMA) in 16. Final diagnosis was confirmed by radiology and 2 years follow-up. Compared with the 99Tcm-MDP bone scan, BMIS demonstrated better specificity (88% vs 75%) and a better positive predictive value (92% vs 85%). There were no significant differences between BMIS and the bone scan in the detection of skeletal metastases (P > 0.05). In one patient with normal planar BMIS of the lumbar spine, SPET disclosed a metastatic lesion in the bone marrow. The correlation coefficient between BMIS and bone scan and between BMIS and serum alkaline phosphatase was r = 0.688 and r = 0.483 respectively. One patient developed a minor HAMA response after BMIS. Patients with diffuse increased activity of the skull on the bone scan had a significantly higher skull to whole body ratio on BMIS (P < 0.01). Thus BMIS can improve the specificity and positive predictive value of bone scanning in the detection of skeletal metastases, with a low HAMA response. Diffuse increased activity of the skull on bone scans could be explained by bone marrow extension. SPET scanning of the spine may improve the sensitivity of BMIS.     

Percutaneous radio-frequency ablation of liver metastases from breast cancer: initial experience in 24 patients.

PURPOSE: To evaluate the authors' initial experience in a consecutive series of 24 patients with breast cancer liver metastases treated with radio-frequency (RF) ablation. MATERIALS AND METHODS: Twenty-four consecutive patients with 64 metastases measuring 1.0--6.6 cm in diameter (mean, 1.9 cm) underwent ultrasonography-guided percutaneous RF ablation with 18-gauge, internally cooled electrodes. Treatment was performed with the patient under conscious sedation and analgesia or general anesthesia. A single lesion was treated in 16 patients, and multiple lesions were treated in eight patients. Follow-up with serial computed tomography ranged from 4 to 44 months (mean, 10 months; median, 19 months). RESULTS: Complete necrosis was achieved in 59 (92%) of 64 lesions. Among the 59 lesions, complete necrosis required a single treatment session in 58 lesions (92%) and two treatment sessions in one lesion (2%). In 14 (58%) of 24 patients, new metastases developed during follow-up. Ten (71%) of these 14 patients developed new liver metastases. Currently, 10 (63%) of 16 patients whose lesions were initially confined to the liver are free of disease. One patient died of progressive brain metastases. No major complications occurred. Two minor complications were observed. CONCLUSION: On the basis of preliminary study results, percutaneous RF ablation appears to be a simple, safe, and effective treatment for focal liver metastases in selected patients with breast cancer.     

Bone metastases in breast cancer: higher prevalence of osteosclerotic lesions

PURPOSE: It is well known that bone metastases from breast cancer usually show osteolytic changes. We retrospectively analysed the computed tomography (CT) appearance of bone metastases to quantify the distribution of lytic, mixed and sclerotic changes in a series of patients presenting with neoplastic bone involvement from breast cancer. MATERIALS AND METHODS: Between 1996 and 2005, 468 women with a diagnosis of breast cancer were referred to our department for staging or follow-up CT examinations. Staging CT examinations detected systemic metastases in 142/468 patients, 60 of which had bone involvement. Patients with a second primary tumour or bone metabolic disorders were excluded from this retrospective analysis. RESULTS: In patients with bone metastases, CT identified 18 with osteolytic lesions (30%), 32 with osteosclerotic lesions (53.3%) and ten with mixed lesions (16.7%). Analysis of the cases observed for the first time during the 1996-2000 period showed osteolytic lesions in 53.6% (15/28), osteosclerotic lesions in 32.1% (9/28) and mixed lesions in 14.3% (4/28). Results were 9.4% (3/32), 71.9% (23/32) and 18.7% (6/32), respectively, for the same groups in the 2001-2005 period. Histological analysis of all cases included 81.9% of infiltrative ductal carcinoma, 11.2% of infiltrative lobular carcinoma, 3.7% of ductal lobular mixed carcinoma and 3% of medullar carcinoma. We found no statistically significant correlation between histological type of breast cancer and radiological appearance of bone metastasis. A significant difference between patients treated with or without zoledronic acid was observed, with a higher prevalence of osteosclerotic lesions in the former group of patients (p<0.05). CONCLUSIONS: We observed an increasing prevalence of osteosclerotic bone metastasis when comparing the 1996-2000 period with the 2001-2005 period. The significance of these distribution changes is not clear. However, we found a significant correlation of osteosclerotic lesions with zoledronic acid treatment. The advent of third generation bisphosphonates may have changed the CT appearance of bone metastasis from breast cancer.     

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.     

Relevance of image fusion with MRI for the interpretation of I-123 iodo-methyl-tyrosine scans in patients with suspected recurrent or residual brain tumor

PURPOSE: The aim of the study was to investigate the impact of MR/SPECT image fusion on the interpretation of I-123 iodo-methyl-tyrosine (IMT) SPECT examinations in patients with pretreated brain tumors. MATERIAL AND METHODS: In this retrospective study, 45 consecutive patients with suspected recurrent/residual gliomas (n = 41) or cerebral metastases (n = 4) were included. SPECT studies were performed using a triple-head gamma-camera system 10 minutes after injection of 300 to 370 MBq (8.1-10 mCi) I-123 IMT. Concerning MR, T1-, T2-, and FLAIR-weighted sequences as well as contrast-enhanced T1-weighted sequences were acquired by 1.5-T or 3.0-T scanners. For image fusion, the MPI-tool software package was used. SPECT and MR/SPECT fusion images were anonymized and then independently evaluated by 3 observers aware of the clinical data. Tumor localization and extent were evaluated and correlated with histopathology or clinical follow up, including MR imaging. RESULTS: In 10 of 45 (22%) patients, image fusion had a significant impact on the interpretation of scans: 5 suspected SPECT findings were correctly classified as physiological or therapy-related; in another 5 patients, image fusion added relevant clinical information on tumor extent (infiltration of the contralateral hemisphere n = 3, infiltration of the brain stem n = 2). CONCLUSIONS: According to our data, image fusion is crucial for the interpretation of positive I-123 IMT SPECT findings.     

Bone scintigraphy as a new imaging biomarker: the relationship between bone scan index and bone metabolic markers in prostate cancer patients with bone metastases

Objective

A computer-aided diagnosis system for bone scintigraphy with a semiquantitative index from the Bone Scan Index (BSI) has been used to quantify the spread of bone metastases. However, few papers have made clear associations among BSI, bone metabolic markers, and prostate-specific antigen (PSA). This retrospective study aimed to examine these relationships in prostate cancer patients with bone metastases.

Methods

A total of 158 scans from 52 patients (number of median examinations/person 3, range 1–8; median age 71 years, age range 46–86) were included. The intervals between bone scans and blood examinations were 0–16 days (median 0 day). The serum markers of PSA, pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (1-CTP), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase-5b (TRACP-5b) were examined. Subjects were divided into 4 groups according to BSI; Group A: 0 to <2, Group B: 2 to <4, Group C: 4 to <8, and Group D: over 8. BSI, which corresponded to the amount of metastatic lesion, was automatically calculated by BONENAVI^® software (FUJIFILM RI Pharma, Co. Ltd., Tokyo, Japan; Exini Bone, Exini Diagnostics, Sweden).

Results

All bone scans showed high uptake with bone metastases. BSI was correlated significantly with the serum 1-CTP, serum BAP, serum TRACP-5b, logBAP, logTRACP-5b, and logPSA (r = 0.39, 0.66, 0.69, 0.71, 0.62 and 0.41, respectively). BSI did not correlate significantly with the serum PSA. The statistical F value was 11 in the serum 1-CTP, 31 in serum BAP, 29 in logBAP, 19 in serum TRACP-5b, 14 in logTRACP-5b, 3 in serum PSA, and 9 in logPSA by analysis of variance. Comparison by Dunnett’s test showed significantly higher values in Group D for all original bone metabolic markers and the logPSA, Group C for the serum BAP, logBAP, serum TRACP-5b, and logTRACP-5b, and Group B for the logTRACP-5b compared with Group A.

Conclusion

The changes in BSI showed a close relationship with all bone metabolic markers but not with the serum PSA. The BSI is confirmed to reflect the activity and extent of bone metastases, and can be used as an imaging biomarker.     

卵巢癌肝周转移的多层螺旋CT诊断研究

目的研究卵巢癌肝周转移的CT表现特点;并探讨CT诊断肝周转移灶侵犯肝实质的准确性。方法以89例可以进行手术治疗的卵巢癌患者为研究对象,三位影像科医师对其术前CT结果进行回顾性分析,观察并记录是否存在卵巢肝周转移、转移灶特点及转移灶是否侵犯肝实质。以术中观察及病理检验结果作为判断标准,判断CT诊断卵巢癌肝周转移的真实性。结果有36位患者存在肝周转移,转移灶共有58处,其中51处未侵及肝实质,其余的7处侵及肝实质。CT判断卵巢癌患者是否存在肝周转移灶的敏感度和特异度分别是89%、98%;CT诊断转移灶是否侵及肝实质的结果与病理检验的结果无明显统计学差异。结论利用CT检查可准确判断卵巢癌是否存在肝周转移,以及转移灶是否侵及肝实质。有助于临床医师制定正确的诊疗方案。     

Hepatic colorectal cancer metastases: imaging initial steps of formation in mice

PURPOSE: To prospectively use optical imaging to study the cell-specific mechanisms of entrapment and subsequent growth of two human colon cancer cell lines differing in their propensity to form hepatic metastases. MATERIALS AND METHODS: In this Animal Care Committee-approved study, intravital optical imaging was performed in exteriorized livers of three groups of mice after intrasplenic inoculation of human colon cancer cells. Group 1 mice (control group; n=12) received a cell-maintaining solution only. Groups 2 and 3 (n=12 in each) were administered poorly (MIP-101 colon cancer cells) or highly (CX-1 colon cancer cells) metastatic cells. Imaging was performed on postinoculation days 0, 1, 3, and 6 to document sites and mechanisms of tumor cell entrapment and presence and sites of endothelial cell activation and of tumor cell interactions with systemic macrophages and Kupffer cells. Fluorescence intensity of Kupffer cells was compared by using the Mann-Whitney test. Immunohistochemistry served as the reference standard for all in vivo observations. RESULTS: Whereas both MIP-101 and CX-1 colon cancer cells adhered to periportal Kupffer cells, the CX-1 cells resulted in Kupffer cell activation, evidenced in vivo by increased visible peroxidase activity (P<.05). Only CX-1 cells were associated with subsequent downstream endothelial cell activation, evidenced by in vivo expression of E-selectin. By day 6, regression of periportal MIP-101 tumor growth correlated with ingrowth of systemic macrophages, while CX-1 tumor growth, originating in the outflow venous regions, correlated with translobular migration and ingrowth of activated Kupffer cells. Conclusion: Formation of hepatic colon cancer metastases is cancer cell-type specific, with cell lines differing in their mechanisms and intrahepatic locations of initial entrapment and Kupffer cell activation and subsequent growth.