Evaluation of new sclerotic bone metastases in breast cancer patients during treatment.

PURPOSE: According to the World Health Organization (WHO) criteria for response of bone metastases to therapy, new lesions indicate progressive disease. We intended to prove that a new sclerotic lesion on conventional radiography may also be a sign of a positive therapeutic response in a previously undetectable lytic metastasis. MATERIAL AND METHODS: In a previous placebo-controlled clinical trial of clodronate (Ostac) therapy, 139 breast cancer patients with bone metastases underwent both conventional radiography and bone scan every 6 months for 2 years with 99mTc before and during clodronate treatment. WHO criteria were applied for therapy response evaluation. RESULTS: In 24 patients, 52 new sclerotic lesions observed during therapy were selected for re-evaluation of conventional radiographs and bone scans. In 8 of the 24 patients, 17 of 52 new sclerotic lesions (33%) had showed positive uptake on previous bone scans. These lesions were possibly misinterpreted as new when applying WHO criteria. CONCLUSION: For better assessment of new sclerotic lesions during treatment, more sensitive techniques, e.g. bone scan, are needed as a complement to conventional radiography.

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.

Overview on human breast cancer with focus on prognostic and predictive factors with special attention on the tumour suppressor gene p53.

A long list of potential prognostic markers has been analysed for breast cancer, some of them will be reviewed in this article. The lymph node status is still the best prognostic marker. The lymph node status combined with information on tumour size, receptor- and proliferation status of the tumour should be analysed as standard for all breast cancer patients. Prognostic information for breast cancer patients has also been described for the membrane protein c-erbB2, the protease cathepsin D, plasminogen activators and inhibitors, certain oncogenes and tumour suppressor genes. Some of these factors also give potential additional information on the response to different oncological therapies, and are better denoted predictive factors. In this overview we shortly describe the above mentioned prognostic factors with major focus on the tumour suppressor gene p53 and its prognostic value and potential predictive value.

Outcome after limited posterior surgery for thoracic and lumbar spine metastases.

The efficacy of 'limited posterior surgery' for metastases in the thoracic and lumbar spine was studied prospectively in 51 patients (32 men and 19 women, mean age 64 years). The most common primary tumors were prostate, breast, and renal carcinoma, 37 patients had metastases in the thoracic spine and 14 in the lumbar spine. Indications for surgery were severe pain or neurologic deficit. Of the 46 patients with neurologic symptoms, 25 were unable to walk. Surgery was confined to direct or indirect decompression and stabilization with a pedicle screw fixator over few segments as possible. Pain, as well as a variety of functional performance parameters and residential status were registered preoperatively and after surgery at 3, 6, 9, and 12 months, and at 6-monthly intervals thereafter. Pain was rated by the patient on a Visual Analog Scale, and functional performance was assessed with the Eastern Co-operative Oncology Group (ECOG) Performance Status Scale. We had no perioperative neurologic deterioration or death. Nineteen of the 25 nonambulatory patients regained their walking ability. Postoperative pain relief was significant and lasting over time. Nearly half of the patients attained improvement in functional performance. The median survival was 8 months. Older age and intact postoperative walking ability were positive factors for survival.

Pathoanatomical and radiographic findings in spinal breast cancer metastases.

Spine specimens infested with breast cancer metastases, ranging from localized seed of small tumor deposits to massive invasion and vertebral collapse, were frozen in situ, removed, examined with both conventional radiography and high resolution computed tomography (CT), and then studied in great detail by serial cryoplaning. The majority of metastases in the total of 53.5 vertebrae were lytic, and most were in close contact with the vertebral wall or the endplates. Depressions and defects of the endplates were associated with compensatory expansion of the intervertebral discs. Although lytic lesions abutting endplate defects had the radiological appearance of metastases, all contained herniated disc material rather than tumor. Only four of the 29 grossly destroyed and collapsed vertebrae showed extrusion of the posterior vertebral wall into the spinal canal. Tumor growth in the epidural space was rare. There were no macroscopical reactive changes of the osseoligamentous or neurovascular spinal elements to the metastases, but abnormalities of the posterior elements (kissing spines, facet joint subluxation, and pars interarticularis failure) were common.

Detection of breast cancer metastases in the cervical spine.

Thirty women with breast cancer and indications of possible cervical spine metastases underwent skeletal scintigraphy, conventional radiography, MR imaging and CT. By combining all examinations a diagnosis was settled in each patient and the different imaging techniques were compared. For all of the 26 patients with metastases in the cervical spine the correct diagnosis was found with MR imaging and CT. Both modalities also revealed paravertebral tumour growth, MR (n = 8) more than CT (n = 3). The sensitivity of skeletal scintigraphy in detecting metastases in the cervical spine was rather low, but as these examinations cover the whole body they are still convenient screening procedures, and combined with conventional radiography of selected areas are probably sufficient in many cases. Supplementary examinations with CT or MR would be valuable in patients with equivocal findings at screening for metastases or with clinical indications of metastases that remain unexplained after scintigraphy and radiography.

MR imaging with histopathological correlation in vertebral metastases of breast cancer.

In 5 patients with advanced breast cancer and spinal metastases MR imaging of the spine was performed before and/or after death. T1-, proton density-, and T2-weighted and "phase contrast" images were obtained in the sagittal plane. Autopsies included histopathologic examination of whole sagittal sections of the vertebral body. The relative signal intensities on the different MR sequences of various tissues identified histologically were evaluated. "Phase contrast" images combined with T1-weighted images were highly sensitive in detecting metastases. All metastatic tumours over 3 mm in size were found with MR imaging. Vertebrae containing connective tissue and reactive bone marrow had an MR appearance similar to that of metastases even though no metastases were found histopathologically.

Diagnostic methods in planning palliation of spinal metastases.

In a prospective study of 30 patients with newly diagnosed spinal metastases the benefit of different imaging techniques in planning palliation was studied. Magnetic resonance imaging (MRI) was compared to scintigraphy, conventional radiography and computerized tomography (CT), prior to radiotherapy or surgery. In the first comparison, a total of 159 pathologic lesions could be evaluated. MRI was superior in the detection of suspect metastases compared to conventional radiography and scintigraphy (P less than 0.0001 and p less than 0.01, respectively). MRI also gave useful information about adjacent soft tissue components, vessels, nerves and spinal cord compression, i.e. useful information when planning stabilizing surgery. Both MRI and CT were sensitive and specific methods but when comparing 120 pathologic lesions the detection rate of MRI was significantly higher than that of CT (p less than 0.01). In conclusion, scintigraphy and conventional radiography are adequate enough if palliative radiotherapy is planned. When considering surgery MRI is advocated preoperatively for defining operability.