Bone metastases from breast cancer: associations between morphologic CT patterns and glycolytic activity on PET and bone scintigraphy as well as explorative search for influential factors

Background

This study aimed to compare the detection of bone metastases from breast cancer on F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and bone scintigraphy (BS). An explorative search for factors influencing the sensitivity or uptake of BS and FDG-PET was also performed.

Methods

Eighty-eight patients with bone metastases from breast cancer were eligible for this study. Histological confirmation of bone metastases was obtained in 31 patients. The bone metastases were visually classified into four types based on their computed tomography (CT) appearance: osteoblastic, osteolytic, mixed, and negative. The sensitivity of BS and FDG-PET were obtained regarding CT type, adjuvant therapy, and the primary tumor characteristics. The FDG maximum standardized uptake value (SUV_max) was analyzed.

Results

The sensitivities of the three modalities (CT, BS, and FDG-PET) were 77, 89, and 94%, respectively. The sensitivity of FDG-PET for the osteoblastic type (69%) was significantly lower than that for the other types (P < 0.001), and the sensitivity of BS for the negative type (70%) was significantly lower than that for the others. Regarding tumor characteristics, the sensitivity of FDG-PET significantly differed between nuclear grade (NG)1 and NG2–3 (P = 0.032). The SUV_max of the osteoblastic type was significantly lower than that of the other types (P = 0.009). The SUV_max of NG1 was also significantly lower than that of NG2–3 (P = 0.011). No significant difference in FDG uptake (SUV_max) was detected between different histological types.

Conclusion

Although FDG-PET is superior to BS for the detection of bone metastases from breast cancer, this technique has limitations in depicting osteoblastic bone metastases and NG1.

     

FDG-PET and CT patterns of bone metastases and their relationship to previously administered anti-cancer therapy

Purpose To assess ¹⁸F-fluorodeoxyglucose (FDG) uptake in bone metastases in patients with and without previous treatment, and compare positive positron emission tomography (PET) with osteolytic or osteoblastic changes on computed tomography (CT).Methods One hundred and thirty-one FDG-PET/CT studies were reviewed for bone metastases. A total of 294 lesions were found in 76 patients, 81 in untreated patients and 213 in previously treated patients. PET was assessed for abnormal FDG uptake localised by PET/CT to the skeleton. CT was evaluated for bone metastases and for blastic or lytic pattern. The relationship between the presence and pattern of bone metastases on PET and CT, and prior treatment was statistically analysed using the chi-square test.Results PET identified 174 (59%) metastases, while CT detected 280 (95%). FDG-avid metastases included 74/81 (91%) untreated and 100/213 (47%) treated lesions (p<0.001). On CT there were 76/81 (94%) untreated and 204/213 (96%) treated metastases (p NS). In untreated patients, 85% of lesions were seen on both PET and CT (26 blastic, 43 lytic). In treated patients, 53% of lesions were seen only on CT (95 blastic, 18 lytic). Of the osteoblastic metastases, 65/174 (37%) were PET positive and 98/120 (82%), PET negative (p<0.001).Conclusion The results of the present study indicate that when imaging bone metastases, prior treatment can alter the relationship between PET and CT findings. Most untreated bone metastases are PET positive and lytic on CT, while in previously treated patients most lesions are PET negative and blastic on CT. PET and CT therefore appear to be complementary in the assessment of bone metastases.     

PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study

The aim of this study was to evaluate the use of [¹⁸F]fluorothymidine (FLT) as a positron emission tomography (PET) tracer for the diagnosis of breast cancer. To this end, 12 patients with 14 primary breast cancer lesions (T2–T4) were studied by FLT-PET. For comparison, [¹⁸F]fluorodeoxyglucose (FDG) PET scans were performed in six patients. Thirteen of the 14 primary tumours demonstrated focally increased FLT uptake (SUV_mean=3.4±1.1). Seven out of eight patients with histologically proven axillary lymph node metastases showed focally increased FLT uptake in the corresponding areas (SUV_mean=2.4±1.2). The lowest SUV (mean =0.7) was observed in one of two inflammatory cancers. The contrast between primary tumours or metastases and surrounding tissue was high in most cases. In direct comparison to FDG-PET, the SUVs of primary tumours (5/6) and axillary lymph node metastases (3/4) were lower in FLT-PET (SUV_FLT: 3.2 vs SUV_FDG: 4.7 in primary tumours and SUV_FLT: 2.9 vs SUV_FDG: 4.6 in lymph node metastases). Since FLT uptake in surrounding breast tissue was also lower, tumour contrast was comparable to that with FDG. It is of note that normal FLT uptake was very low in the mediastinum, resulting in a higher tumour-to-mediastinum ratio as compared to FDG (P=0.03). FLT-PET is suitable for the diagnosis of primary breast cancer and locoregional metastases. High image contrast may facilitate the detection of small foci, especially in the mediastinum.     

Comparison of18FDG-PET with99mTc-HMDP scntigraphy for the detection of bone metastases in patients with breast cancer

OBJECTIVE: Bone is one of the most common sites of metastasis in breast cancer patients. Although bone scintigraphy is widely used to detect metastatic breast cancer, the usefulness of 18FDG-PET for detecting bone metastasis has not been clearly evaluated. The purpose of this study was to compare the diagnostic accuracy of 18FDG-PET with bone scintigraphy in detecting bone metastasis in breast cancer patients. METHODS: Forty-four women aged 35 to 81 years (mean, 56 years) with breast cancer were examined in this study. Both 18FDG-PET and bone scintigraphy were performed for each patient with 0-69 day intervals (mean, 11.5 days). The results of each image interpretation were compared retrospectively. Whole-body bones were classified into 9 anatomical regions. Metastases were confirmed at 45/187 regions in 14 patients by bone biopsy or clinical follow-up including other imaging techniques for a period of at least 6 months afterwards. RESULTS: On a region basis, the sensitivity, specificity, and accuracy of 18FDG-PET were 84%, 99% and 95%, respectively. Although these results were comparable to those of bone scintigraphy, the combination of 18FDG-PET and bone scintigraphy improved the sensitivity (98%) and accuracy (97%) of detection. False negative lesions of bone scintigraphy were mostly bone marrow metastases and those of 18FDG-PET were mostly osteoblastic metastases. 18FDG-PET was superior to bone scintigraphy in the detection of osteolytic lesions (92% vs. 73%), but inferior in the detection of osteoblastic lesions (74% vs. 95%). CONCLUSIONS: This study shows that 18FDG-PET tends to be superior to bone scintigraphy in the detection of osteolytic lesions, but inferior in the detection of osteoblastic lesions. 18FDG-PET should play a complementary role in detecting bone metastasis with bone scintigraphy.     

Utility of quantitative FDG-PET/CT for the detection of bone marrow involvement in follicular lymphoma: a histopathological correlation study

Objective

To determine the value of visual and quantitative ¹⁸?F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) for the detection of bone marrow involvement in follicular lymphoma, using direct histopathological examination at the right posterior iliac crest as reference standard.

Materials and methods

This retrospective study included 22 patients with newly diagnosed follicular lymphoma who had undergone FDG-PET/CT before BMB of the right posterior iliac crest. FDG-PET/CT images were visually evaluated for bone marrow involvement in the right posterior iliac crest. Volumes of interest were placed in the right posterior iliac crest to calculate the 3D partial volume corrected mean standardized uptake value (cSUV_mean), maximum standardized uptake value (SUV_max) and peak standardized uptake value (SUV_peak).

Results

Sensitivity and specificity of visual FDG-PET/CT analysis for the detection of bone marrow involvement in the right posterior iliac crest were 0.0 % (95 % confidence interval (CI): 0–32.4 %) and 100 % (95 % CI: 78.5–100 %), respectively. Areas under the receiver-operating characteristic curve of cSUV_mean, SUV_max and SUV_peak for the detection of bone marrow involvement in the right posterior iliac crest were 0.85 (95 % CI: 0.63–0.96), 0.89 (95 % CI: 0.68–0.98) and 0.87 (95 % CI: 0.65–0.97), respectively. Optimal cutoff values for cSUV_mean, SUV_max and SUV_peak were 1.3, 2.1 and 1.7, and yielded sensitivity and specificity combinations of 75.0 % and 85.7 %, 87.5 % and 85.7 % and 87.5 % and 85.7 %, respectively.

Conclusion

This histopathological correlation study shows that, unlike visual interpretation of FDG-PET/CT images, quantitative FDG-PET/CT analysis may be beneficial in diagnosing bone marrow involvement by follicular lymphoma.     

Detection of bone metastases in breast cancer by positron emission tomography

Positron emission tomography (PET) is able to demonstrate changes in the metabolism of malignant tumors and metastases before they become visible on anatomical imaging. The skeleton is the most common site of distant metastases of breast cancer. There is convincing evidence that FDG-PET is more sensitive in detecting osteolytic metastases than bone scintigraphy, whereas bone scintigraphy is more sensitive in detecting osteoblastic metastases. Because both types of metastases can occur in breast cancer, bone scintigraphy and FDG-PET should be considered as complementary and can currently be regarded as standard of care for staging in breast cancer patients, whereas the decision to use F-18 fluoride PET should be made individually for each patient, depending on the expected change of therapy management.     

Influences of point-spread function and time-of-flight reconstructions on standardized uptake value of lymph node metastases in FDG-PET

Purpose

The purpose of this study was to investigate the effects of point-spread function (PSF) and time-of-flight (TOF) on the standardized uptake value (SUV) of lymph node metastasis in FDG-PET/CT.

Materials and methods

This study evaluated 41 lymph node metastases in 15 patients who had undergone ¹⁸F-FDG PET/CT. The lesion diameters were 2.5 cm or less. The mean short-axis diameter of the lymph nodes was 10.5 ± 3.7 mm (range 4.6–22.8 mm). The PET data were reconstructed with baseline OSEM algorithm, with OSEM + PSF, with OSEM + TOF and with OSEM + PSF + TOF. A semi-quantitative analysis was performed using the maximum and mean SUV of lymph node metastases (SUV_max and SUV_mean) and mean SUV of normal lung tissue (SUV_lung). We also evaluated image quality using the signal-to-noise ratio in the liver (SNR_liver).

Results

Both PSF and TOF increased the SUV of lymph node metastases. The combination of PSF and TOF increased the SUV_max by 43.3% and the SUV_mean by 31.6% compared with conventional OSEM. By contrast, the SUV_lung was not influenced by PSF and TOF. TOF significantly improved the SNR_liver.

Conclusion

PSF and TOF both increased the SUV of lymph node metastases. Although PSF and TOF are considered to improve small-lesion detectability, it is important to be aware that PSF and TOF influence the accuracy of quantitative measurements.     

Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using 18F-FDG PET/CT and 99mTc-HDP Bone Scintigraphy: Characteristics of Soft Tissue Formation

Purpose

Bone metastasis from hepatocellular carcinoma (HCC) can present with soft tissue formation, resulting in oncologic emergency. Contrast-enhanced FDG PET/CT and bone scintigraphy were compared to evaluate characteristics of bone metastases with or without soft tissue formation from HCC.

Methods

Of 4,151 patients with HCC, 263 patients had bone metastases. Eighty-five patients with bone metastasis from HCC underwent contrast-enhanced FDG PET/CT. Fifty-four of the enrolled subjects had recent ^99mTc-HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value (SUV_max) was used for the quantitative analysis. Confirmation of bone metastasis was based on histopathology, combined imaging modalities, or serial follow-up studies.

Results

Forty-seven patients (55%) presented with soft tissue formation, while the remaining 38 patients presented without soft tissue formation. Frequent sites of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage (14%). The soft-tissue-formation group had more frequent bone pain (77 vs. 37%, p < 0.0001), higher SUV_max (6.02 vs. 3.52, p < 0.007), and higher incidence of photon defect in bone scintigraphy (75 vs. 0%) compared to the non-soft-tissue-formation group. FDG PET/CT had higher detection rate for bone metastasis than bone scintigraphy both in lesion-based analysis (98 vs. 53%, p = 0.0015) and in patient-based analysis (100 vs. 80%, p < 0 .001).

Conclusions

Bone metastasis from HCC showed a high incidence of soft tissue formation requiring emergency treatment. Although the characteristic findings for soft tissue formation such as photon defect in bone scintigraphy are helpful in detection, overall detectability of bone metastasis is higher in FDG PET/CT. Contrast-enhanced PET/CT will be useful in finding and delineating soft-tissue-forming bone metastasis from HCC.     

Hybrid [F]-FDG PET/MRI including non-Gaussian diffusion-weighted imaging (DWI): Preliminary results in non-small cell lung cancer (NSCLC)

Purpose

To assess the feasibility of non-Gaussian DWI as part of a FDG-PET/MRI protocol in patients with histologically proven non-small cell lung cancer.

Material and methods

15 consecutive patients with histologically proven NSCLC (mean age 61 ± 11 years) were included in this study and underwent whole-body FDG-PET/MRI following whole-body FDG-PET/CT. As part of the whole-body FDG-PET/MRI protocol, an EPI-sequence with 5 b-values (0, 100, 500, 1000 and 2000 s/mm²) was acquired for DWI of the thorax during free-breathing. Volume of interest (VOI) measurements were performed to determine the maximum and mean standardized uptake value (SUV_max; SUV_mean). A region of interest (ROI) was manually drawn around the tumor on b = 0 images and then transferred to the corresponding parameter maps to assess ADC_mono, D_app and K_app. To assess the goodness of the mathematical fit R² was calculated for monoexponential and non-Gaussian analysis. Spearman's correlation coefficients were calculated to compare SUV values and diffusion coefficients. A Student's t-test was performed to compare the monoexponential and non-Gaussian diffusion fitting (R²).

Results

T staging was equal between FDG-PET/CT and FDG-PET/MRI in 12 of 15 patients. For NSCLC, mean ADC_mono was 2.11 ± 1.24 × 10⁻³ mm²/s, D_app was 2.46 ± 1.29 × 10⁻³ mm²/s and mean K_app was 0.70 ± 0.21. The non-Gaussian diffusion analysis (R² = 0.98) provided a significantly better mathematical fitting to the DWI signal decay than the monoexponetial analysis (R² = 0.96) (p < 0.001). SUV_max and SUV_mean of NSCLC was 13.5 ± 7.6 and 7.9 ± 4.3 for FDG-PET/MRI. ADC_mono as well as D_app exhibited a significant inverse correlation with the SUV_max (ADC_mono: R = −0.67; p < 0.01; D_app: R = −0.69; p < 0.01) as well as with SUV_mean assessed by FDG-PET/MRI (ADC_mono: R = −0.66; p < 0.01; D_app: R = −0.69; p < 0.01). Furthermore, K_app exhibited a significant correlation with SUV_max (R = 0.72; p < 0.05) and SUV_mean as assessed by FDG-PET/MRI (R = 0.71; p < 0.005).

Conclusion

Simultaneous PET and non-Gaussian diffusion acquisitions are feasible. Non-Gaussian diffusion parameters show a good correlation with SUV and might provide additional information beyond monoexponential ADC, especially as non-Gaussian diffusion exhibits better mathematical fitting to the decay of the diffusion signal than monoexponential DWI.     

The appearance of breast cancer metastases on dry bone: Implications for forensic anthropology

Breast carcinoma is a major cause of morbidity and mortality in women. The study of bone pathologies presents considerable potential in anthropology, paleopathology, forensic science and medicine. In this paper, we present and discuss metastatic lesions found in the skeletons of known individuals from the CAL Milano Cemetery Skeletal Collection, clinically diagnosed with breast cancer during life. Fourteen skeletons from a contemporary and identified collection were macroscopically studied and metastases were identified by comparison with clinical literature. As a result, bone metastases were observed in 43% of the study sample. They were located most commonly on the ribs (28.1%), pelvic girdle (19.8%), vertebrae (15.6%), skull (15.6%), scapulae (10.2%) as well as proximal segment of the femora (8.4%) and humeri (2.4%) respectively, favoring sites of high vascularization. The majority of the lesions were osteolytic, although osteoblastic and mixed metastases did occur. Osteolytic metastases appear as coalescent porosity or round to oval perforating lesions on bones with denticulated margins and pitted surrounding bone, whereas osteoblastic metastases thickened the existing trabecula (spongiosclerosis). Mixed metastases were perforating lytic lesions exposing the osteoblastic activity in the underlying trabecular bone. These results, consistent with the data from the literature, strengthen the diagnostic criteria for metastases and illustrate the aspect of bone metastases in breast carcinoma.     

Prognostic value of FDG-PET and DWI in breast cancer

Objective

To investigate the prognostic value of preoperative FDG-PET/CT and diffusion weighted imaging (DWI) in patients with breast cancer.

Methods

A total of 73 patients with newly diagnosed invasive breast cancer who had undergone preoperative whole-body FDG-PET/CT and 3-Tesla breast MRI including DWI followed by surgery were identified. Effects of primary tumor PET parameters [maximum standardized uptake value (SUV_max), mean SUV (SUV_mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] and DWI parameters [mean apparent diffusion coefficient (ADC_mean) and minimum ADC (ADC_min)] including clinicopathologic factors on disease-free survival (DFS) were retrospectively evaluated using the log-rank and Cox methods.

Results

After a median overall follow-up of 32.3 months in all patients, 6 (8.2%) of the 73 patients had recurrence. Receiver operating characteristic curve analysis and log-rank tests showed that patients with a high primary tumor SUV_max (≥?3.60), MTV (≥?3.15), and TLG (≥?16.0) had a significantly lower DFS rate than those with a low SUV_max (<?3.60), MTV (<?3.15), and TLG (<?16.0), respectively (p?=?0.0054, p?=?0.0054, and p?<?0.0001, respectively). SUV_mean, ADC_mean, and ADC_min were not significantly associated with recurrence. Univariate analysis showed that SUV_max (p?=?0.0054), MTV (p?=?0.0054), TLG (p?<?0.0001), tumor size (p?=?0.0083), estrogen receptor negativity (p?=?0.046), progesterone receptor negativity (p?=?0.0023), human epidermal growth factor receptor 2 positivity (p?=?0.043), and the presence of axillary lymph node metastasis (p?=?0.0037) were also significantly associated with recurrence. However, in multivariate analysis, none of them were an independent factor.

Conclusions

The preoperative SUV_max, MTV, and TLG of primary breast cancer are prognostic factors for recurrence, whereas ADC values are not.

     

Positron emission tomography and bone metastases

The use of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the evaluation and management of patients with malignancy continues to increase. However, its role in the identification of bone metastases is far from clear. FDG has the advantage of demonstrating all metastatic sites, and in the skeleton it is assumed that its uptake is directly into tumor cells. It is probable that for breast and lung carcinoma, FDG-PET has similar sensitivity, although poorer specificity, when compared with the isotope bone scan, although there is conflicting evidence, with several articles suggesting that it is less sensitive than conventional imaging in breast cancer. There is convincing evidence that for prostate cancer, FDG-PET is less sensitive than the bone scan and this may be tumor specific. There is very little data relating to lymphoma, but FDG-PET seems to perform better than the bone scan. There is an increasing body of evidence relating to the valuable role of FDG-PET in myeloma, where it is clearly better than the bone scan, presumably because FDG is identifying marrow-based disease at an early stage. There are, however, several other important variables that should be considered. The morphology of the metastasis itself appears to be relevant. At least in breast cancer, different patterns of FDG uptake have been shown in sclerotic, lytic, or lesions with a mixed pattern, Furthermore, the precise localization of a metastasis in the skeleton may be important with regard to the extent of the metabolic response induced. Previous treatment is highly relevant and it has been found that although the majority of untreated bone metastases are positive on PET scans and have a lytic pattern on computed tomography (CT), after treatment, incongruent CT-positive/PET-negative lesions are significantly more prevalent and generally are blastic, which presumably reflects a direct effect of treatment. Finally, the aggressiveness of the tumor itself may be relevant. The most important question, however, is irrespective of whether a lesion is seen on x-ray, CT, or bone scan and irrespective of lytic of blastic morphology: if the FDG-PET study is negative, what is the clinical relevance of that lesion?     

FDG-PET and CT characterization of adrenal lesions in cancer patients

Purpose Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) may differentiate benign from malignant adrenal lesions. In this study, standardized uptake values (SUVs), visual interpretation, and computed tomography (CT) data were correlated with the final diagnosis to determine the contribution of adrenal FDG-PET in patients with known non-adrenal cancer.Methods Ninety-two patients with adrenal lesions on CT underwent FDG-PET. Eighty adrenals in 74 patients met the inclusion criteria (PET scan within 4 weeks of CT plus >1 year of follow-up after PET scan with repeat CT or biopsy for final diagnosis). CT was considered positive for metastases (CT+) based on two of the following three criteria: >4 cm, Hounsfield units (HU) >30, and delayed contrast enhancement. Lesions with <2 cm, with HU <20, and showing no enhancement were considered benign (CT–). Remaining lesions were considered indeterminate (CT-Ind). Visually, adrenal uptake exceeding liver uptake was considered PET positive (PET+). Diagnosis of metastases was based on biopsy or interval CT growth (unchanged >1 year=benign). SUV_max and SUV_avg were calculated from a 4×4 pixel region of interest drawn from CT, PET, and fused images. A receiver operator curve (ROC) determined the SUV with the best sensitivity and specificity.Results Overall, PET was 93% sensitive and 96% specific for metastases. A SUV_max of 3.4 was 95% sensitive and 86% specific. A SUV_avg of 3.1 was 95% sensitive and 90% specific. There was no significant difference between visual interpretation and SUV (SUV_max or SUV_avg). Among CT+ and CT– lesions, PET was 100% sensitive and 96% specific; CT was 86% sensitive and 100% specific. In the CT-Ind group, PET was 88% sensitive and 96% specific.Conclusion PET accurately characterized adrenal lesions. Visual interpretation was as accurate as SUV. FDG-PET was most useful in the 52.5% of cancer patients with inconclusive adrenal lesions on CT.     

A meta-analysis of <Superscript>18</Superscript>FDG-PET,MRI and bone scintigraphy for diagnosis of bone metastases in patients with breast cancer

Objective  

To perform a meta-analysis comparing the diagnostic value of ¹⁸FDG-PET, MRI, and bone scintigraphy (BS) in detecting bone metastases in patients with breast cancer.     

Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures

The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) with conventional staging techniques. The differentiation between malignant and benign lesions and the detection of multifocal disease, axillary and internal lymph node involvement, and distant metastases were evaluated. One hundred and seventeen female patients were prospectively examined using FDG-PET and conventional staging methods such as chest X-ray, ultrasonography of the breast and liver, mammography and bone scintigraphy. All patients were examined on a modern full-ring PET scanner. Histopathological analysis of resected specimens was employed as the reference method. The readers of FDG-PET were blinded to the results of the other imaging methods and to the site of the breast tumour. The sensitivity and specificity of FDG-PET in detecting malignant breast lesions were 93% and 75% respectively. FDG-PET was twofold more sensitive (sensitivity 63%, specificity 95%) in detecting multifocal lesions than the combination of mammography and ultrasonography (sensitivity 32%, specificity 93%). Sensitivity and specificity of FDG-PET in detecting axillary lymph node metastases were 79% and 92% (41% and 96% for clinical evaluation). FDG-PET correctly indicated distant metastases in seven patients. False-positive or false-negative findings were not encountered with FDG-PET. Chest X-ray was false-negative in three of five patients with lung metastases. Bone scintigraphy was false-positive in four patients. Three patients were upstaged since FDG-PET detected distant metastases missed with the standard staging procedure. It is concluded that, compared with the imaging methods currently employed for initial staging, FDG-PET is as accurate in interpreting the primary tumour and more accurate in screening for lymph node metastases and distant metastases. Due to a false-negative rate of 20% in detecting axillary lymph node metastases, FDG-PET cannot replace histological evaluation of axillary status.     

FDG-avid sclerotic bone metastases in breast cancer patients: a PET/CT case series

Distant metastases from breast cancer most frequently occur in the skeleton. Although 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), with or without computed tomography (CT), is superior to bone scintigraphy for the detection of osteolytic bone metastases, it has been reported that sclerotic bone metastases frequently show no or only a low degree of FDG uptake on PET and PET/CT. Since both lytic and sclerotic metastases can occur in breast cancer patients, bone scintigraphy may remain of additional value in these patients. In this case series, we describe four breast cancer patients in whom FDG PET/CT has clearly visualized sclerotic bone metastases because of increased FDG uptake. Not so much the type of metastasis (sclerotic or lytic), but possibly the characteristics of the primary tumor or treatments prior to the FDG PET/CT scan might influence the degree of FDG uptake of bone metastases. The ability to detect sclerotic bone metastases based on increased FDG uptake supports the use of FDG PET/CT as a staging procedure in breast cancer patients, but knowledge of factors determining the visibility of bone metastases with FDG PET/CT is crucial.     

Osteoblastic response as a healing reaction to chemotherapy mimicking progressive disease in patients with small cell lung cancer

The osteoblastic response (OR) phenomenon as a healing reaction during effective chemotherapy—defined by the appearance of new osteoblastic bone lesions while disease response in other tumor sites was well documented—has previously been described for breast and prostate cancer. The purpose of this study was to investigate this phenomenon that could erroneously be interpreted as progressive disease in patients with small cell lung cancer (SCLC) and to establish guidelines for interpretation of follow-up computed tomography (CT) examinations in this situation. Twenty-four patients with newly diagnosed SCLC and bone metastases were retrospectively included in this study. The characteristics of bone lesions in CT examinations were correlated with bone scintigraphy and magnetic resonance imaging, if available. In target lesions the CT density quantified in Hounsfield units (HU) was evaluated at baseline and during follow-up. New osteoblastic lesions occurred during follow-up in 17 of 24 patients. OR was proven in 4 patients and considered most likely in 11 patients; mean density increase in target lesions was 153 HU. The study indicates that osteoblastic response as a healing reaction seems to occur in the majority of patients with SCLC and bone metastases and should not be misinterpreted as progressive disease.     

Prospective evaluation of [<Superscript>11</Superscript>C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer

Purpose

The aim of this study was to prospectively evaluate the value of [¹¹C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients.

Methods

Thirty-two patients were referred for [¹¹C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [¹¹C] Choline uptake (SUV_max, SUV_mean), CT derived Houndsfield units (HU_max, HU_mean), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUV_max, SUV_mean, HU_max, HU_mean, and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUV_max and SUV_mean (early and late) and changes of PSA_early and PSA_late were evaluated. Prognostic value of initial SUV_max and SUV_mean was assessed. Statistical analyses were performed using SPSS.

Results

In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUV_max and SUV_mean were statistically significantly higher in nPD (applying clinical criteria).

Conclusion

There is no significant correlation between change in choline uptake in [¹¹C] Choline PET/CT and clinically routinely used objective response assessment during the early and late course of docetaxel chemotherapy. Therefore, [¹¹C] Choline PET/CT seems to be of limited use in therapy response assessment in standardized first-line chemotherapy in mCRPC patients.

     

Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. Received 14 April and in revised form 5 July 1997     

Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures

The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) with conventional staging techniques. The differentiation between malignant and benign lesions and the detection of multifocal disease, axillary and internal lymph node involvement, and distant metastases were evaluated. One hundred and seventeen female patients were prospectively examined using FDG-PET and conventional staging methods such as chest X-ray, ultrasonography of the breast and liver, mammography and bone scintigraphy. All patients were examined on a modern full-ring PET scanner. Histopathological analysis of resected specimens was employed as the reference method. The readers of FDG-PET were blinded to the results of the other imaging methods and to the site of the breast tumour. The sensitivity and specificity of FDG-PET in detecting malignant breast lesions were 93% and 75% respectively. FDG-PET was twofold more sensitive (sensitivity 63%, specificity 95%) in detecting multifocal lesions than the combination of mammography and ultrasonography (sensitivity 32%, specificity 93%). Sensitivity and specificity of FDG-PET in detecting axillary lymph node metastases were 79% and 92% (41% and 96% for clinical evaluation). FDG-PET correctly indicated distant metastases in seven patients. False-positive or false-negative findings were not encountered with FDG-PET. Chest X-ray was false-negative in three of five patients with lung metastases. Bone scintigraphy was false-positive in four patients. Three patients were upstaged since FDG-PET detected distant metastases missed with the standard staging procedure. It is concluded that, compared with the imaging methods currently employed for initial staging, FDG-PET is as accurate in interpreting the primary tumour and more accurate in screening for lymph node metastases and distant metastases. Due to a false-negative rate of 20% in detecting axillary lymph node metastases, FDG-PET cannot replace histological evaluation of axillary status.