Evaluation of two-dimensional total bone uptake (2D-TBU) and bone scan index (BSI) extracted from active bone metastatic burden on the bone scintigraphy in patients with radium-223 treatment.

OBJECTIVE: Radium-223 is a first alpha-emitting radionuclide treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with bone metastases. Although the spread-based bone scan index (BSI) and novel index of the intensity-based two-dimensional total bone uptake (2D-TBU) from bone scintigraphy may provide useful input in radium-223 treatment, they have not been evaluated in detail yet. This study aimed to fill this gap by evaluating BSI and 2D-TBU in patients treated with radium-223. METHODS: Twenty-seven Japanese patients with mCRPC treated with radium-223 were retrospectively analyzed. The patients were evaluated via blood tests and bone scans at baseline and 3 cycles intervals of treatment. BSI and 2D-TBU were analyzed via VSBONE BSI in terms of correlations, response to radium-223 treatment, association with treatment completion, and the Kaplan-Meier survival analysis was performed. RESULTS: Nineteen patients (70.4%) completed six cycles of radium-223 treatment, whereas eight patients (29.6%) did not complete the treatment regimen. A significant difference in baseline BSI and 2D-TBU was observed between these groups of patients. Both BSI and 2D-TBU were highly correlated (r = 0.96, p < 0.001). Univariate analysis showed an association between radium-223 completion in median BSI and 2D-TBU values (p = 0.015) and completion percentage differences (91.7% vs. 45.5%; p = 0.027). The Kaplan-Meier product limit estimator showed that the median overall survival was 25.2 months (95% CI 14.0-33.6 months) in the completion group and 7.5 months (95% CI 3.3-14.2 months) in the without completion group (p < 0.001). The overall survival based on median cutoff levels showed a significant difference in 2D-TBU (p = 0.007), but not in BSI (p = 0.15). CONCLUSIONS: The 2D-TBU may offer advantages over BSI in classifying patients towards radium-223 treatment based on the degree of progression of bone metastases. This study supports the importance of preliminary assessment of bone metastasis status using BSI and 2D-TBU extracted from VSBONE BSI for radium-223 treatment decisions.

Wnt1 induces osteoblastic changes in a well-established osteolytic skeletal metastatic model derived from breast cancer.

BACKGROUND: Osteoblastic skeletal metastasis is frequently observed in prostate cancer. An effective therapy has not been developed due to the unclear molecular mechanism. The Wnt family is involved in various biological phenomena including bone metabolism. There is no direct evidence that the family causes osteoblastic skeletal metastasis. AIMS: The present study aims to evaluate whether overexpressed Wnt induces osteoblastic bone metastasis in a well-established osteolytic bone metastatic model. METHODS AND RESULTS: The breast cancer-derived 5a-D-Luc-ZsGreen cells were transfected with Wnt1, Wnt3A, and Wnt5A expression vectors, producing stably highly expressing cells. These cells were intracardially transplanted in nude mice. Bone metastasis development was confirmed by fluorescence imaging. Hind-limb bones including metastasis were dissected and visualized through micro-CT imaging. After imaging, sections were stained with hematoxylin and eosin (H&E), and immunohistochemically stained with an anti-SATB2 antibody. Luminescent imaging confirmed mice with bone metastases in the hind limbs. Micro-CT imaging found an osteoblastic change only in bone metastasis of mice transplanted with Wnt1-expressing cells. This was confirmed on H&E-stained sections. SATB2 immunostaining showed differentiated osteoblasts were at the site of bone metastases in the diaphysis. SATB2 in the Wnt/ß-catenin pathway activated by overexpressed Wnt1 could induce osteoblastic change. CONCLUSION: Our findings provided direct evidence Wnt1 is involved in osteoblastic bone metastasis development. Our model would be a powerful tool for further elucidating molecular mechanisms underlying the disease and developing effective therapies.

Comparison of skeletal segmentation by deep learning-based and atlas-based segmentation in prostate cancer patients.

OBJECTIVE: We aimed to compare the deep learning-based (VSBONE BSI) and atlas-based (BONENAVI) segmentation accuracy that have been developed to measure the bone scan index based on skeletal segmentation. METHODS: We retrospectively conducted bone scans for 383 patients with prostate cancer. These patients were divided into two groups: 208 patients were injected with 99mTc-hydroxymethylene diphosphonate processed by VSBONE BSI, and 175 patients were injected with 99mTc-methylene diphosphonate processed by BONENAVI. Three observers classified the skeletal segmentations as either a "Match" or "Mismatch" in the following regions: the skull, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, pelvis, sacrum, humerus, rib, sternum, clavicle, scapula, and femur. Segmentation error was defined if two or more observers selected "Mismatch" in the same region. We calculated the segmentation error rate according to each administration group and evaluated the presence of hot spots suspected bone metastases in "Mismatch" regions. Multivariate logistic regression analysis was used to determine the association between segmentation error and variables like age, uptake time, total counts, extent of disease, and gamma cameras. RESULTS: The regions of "Mismatch" were more common in the long tube bones for VSBONE BSI and in the pelvis and axial skeletons for BONENAVI. Segmentation error was observed in 49 cases (23.6%) with VSBONE BSI and 58 cases (33.1%) with BONENAVI. VSBONE BSI tended that "Mismatch" regions contained hot spots suspected of bone metastases in patients with multiple bone metastases and showed that patients with higher extent of disease (odds ratio = 8.34) were associated with segmentation error in multivariate logistic regression analysis. CONCLUSIONS: VSBONE BSI has a potential to be higher segmentation accuracy compared with BONENAVI. However, the segmentation error in VSBONE BSI occurred dependent on bone metastases burden. We need to be careful when evaluating multiple bone metastases using VSBONE BSI.

Phantom and clinical evaluation of bone SPECT/CT image reconstruction with xSPECT algorithm.

BACKGROUND: Two novel methods of image reconstruction, xSPECT Quant (xQ) and xSPECT Bone (xB), that use an ordered subset conjugate gradient minimizer (OSCGM) for SPECT/CT reconstruction have been proposed. The present study compares the performance characteristics of xQ, xB, and conventional Flash3D (F3D) reconstruction using images derived from phantoms and patients. METHODS: A custom-designed body phantom for bone SPECT was scanned using a Symbia Intevo (Siemens Healthineers), and reconstructed xSPECT images were evaluated. The phantom experiments proceeded twice with different activity concentrations and sphere sizes. A phantom with 28-mm spheres containing a 99mTc-background and tumor-to-normal bone ratios (TBR) of 1, 2, 4, and 10 were generated, and convergence property against various TBR was evaluated across 96 iterations. A phantom with four spheres (13-, 17-, 22-, and 28-mm diameters), containing a 99mTc-background at TBR4, was also generated. The full width at half maximum of an imaged spinous process (10 mm), coefficients of variance (CV), contrast-to-noise ratio (CNR), and recovery coefficients (RC) were evaluated after reconstructing images of a spine using Flash 3D (F3D), xQ, and xB. We retrospectively analyzed images from 20 patients with suspected bone metastases (male, n = 13) which were acquired using [99mTc]Tc-(H)MDP SPECT/CT, then CV and standardized uptake values (SUV) at the 4th vertebral body (L4) were compared after xQ and xB reconstruction in a clinical setup. RESULTS: Mean activity concentrations with various TBR converged according to increasing numbers of iterations. The spatial resolution of xB was considerably superior to xQ and F3D, and it approached almost the actual size regardless of the iteration numbers during reconstruction. The CV and RC were better for xQ and xB than for F3D. The CNR peaked at 24 iterations for xQ and 48 iterations for F3D and xB, respectively. The RC between xQ and xB significantly differed at lower numbers of iterations but were almost equivalent at higher numbers of iterations. The reconstructed xQ and xB images of the clinical patients showed a significant difference in the SUVmax and SUVpeak. CONCLUSIONS: The reconstructed xQ and xB images were more accurate than those reconstructed conventionally using F3D. The xB for bone SPECT imaging offered essentially unchanged spatial resolution even when the numbers of iterations did not converge. The xB reconstruction further enhanced SPECT image quality using CT data. Our findings provide important information for understanding the performance characteristics of the novel xQ and xB algorithms.

Evaluation of bone metastasis burden as an imaging biomarker by quantitative single-photon emission computed tomography/computed tomography for assessing prostate cancer with bone metastasis: a phantom and clinical study.

Metabolic bone volume (MBV), standardized uptake value (SUV), and total bone uptake (TBU) are new imaging biomarkers for quantitative bone single-photon emission computed tomography/computed tomography. The purpose of this study was to validate the quantitative accuracy and utility of MBV, SUVmean, and TBU for the assessment of bone metastases in prostate cancer. We used a bone-specific phantom with four hot spheres (φ = 13, 17, 22, 28 mm) filled with different Tc-99 m activities to simulate uptake ratios of 3 and 7, corresponding to normal and metastatic values. We calculated the error ratio (%Error) by comparing MBV, SUVmean, and TBU with true values for various parameters, including bone lesion size, uptake ratio, and SUV cut-off level. Differences for MBV, SUVmean, TBU, and bone scan index (BSI) were calculated to verify their utility in assessing bone metastases. Receiver-operating characteristic curve (ROC) analysis was performed to calculate the area under the curve (AUC) for each biomarker. MBV, SUVmean, and TBU were affected by lesion size, uptake ratio, and SUV cut-off level; however, TBU demonstrated the most stable %Error. The TBU %Error was within 15% in spheres 17 mm or larger when the SUV cut-off level was 7, regardless of the uptake ratio. The ROC analyses revealed the AUCs of BSI (0.977) and TBU (0.968). Additionally, TBU was able to assess bone metastasis when BSI provided false-negative results, but TBU also provided false-positive results by degenerative changes. The synergy between TBU and BSI could potentially improve diagnostic accuracy.

Diagnostic performance of a computer-assisted diagnostic system: sensitivity of BONENAVI for bone scintigraphy in patients with disseminated skeletal metastasis is not so high.

PURPOSE: Bone scintigraphy (BS) of disseminated skeletal metastasis is sometimes misinterpreted as normal. The use of computer-assisted diagnosis (CAD) may resolve this problem. We investigated the performance of a CAD system, BONENAVI, in the diagnosis of disseminated skeletal metastasis. METHODS: Cases of disseminated skeletal metastasis were selected from a BS log. These patients' BSs were analyzed by BONENAVI to obtain an artificial neural network (ANN) and bone scan index (BSI). Clinical features (type of primary cancer, CT type, and BS type) were compared with the BONENAVI (ANN and BSI) results. The BS findings (diffuse increased axial skeleton uptake, inhomogeneity of uptake, proximal extremity contrast, and degree of renal uptake) and ANN or BSI were evaluated. Then, negative ANN patients were presented. RESULTS: Fifty-four patients were diagnosed as having disseminated skeletal metastasis. Regarding the primary cancers, 12 had prostate cancer, 16 gastric cancers, 16 breast cancers, and 10 miscellaneous cancers. Total sensitivity of ANN (≥ 0.5) was 76% (41/54). ANN values correlated with the BS type among clinical features. Diffuse increased axial skeleton uptake was mostly correlated with ANN of the BS findings. CONCLUSION: The BONENAVI CAD system was partially helpful in diagnosing disseminated skeletal metastasis, but the sensitivity of BONENAVI was not sufficient and underestimated the disseminated skeletal metastasis. Further improvement of this CAD system is necessary to improve the detectability of disseminated skeletal metastasis.

Imaging of Hypoxic Tumor: Correlation between Diffusion-weighted MR Imaging and 18F-fluoroazomycin Arabinoside Positron Emission Tomography in Head and Neck Carcinoma.

We investigated the usefulness of diffusion-weighted imaging (DWI) for detecting changes in the structure of hypoxic cells by evaluating the correlation between 18F-fluoroazomycin arabinoside (FAZA) positron emission tomography activity and DWI parameters in head and neck carcinoma. The diffusion coefficient corresponding to the slow compartment of a two-compartment model had a significant positive correlation with FAZA activity (ρ = 0.58, P = 0.016), whereas the diffusional kurtosis from diffusion kurtosis imaging had a significant negative correlation (ρ = -0.62, P = 0.008), which suggests that those DWI parameters might be useful as indicators for changes in cell structure.

Granulomatous Myositis Showing Fluctuating "Leopard-Man" Sign: A Case Report on FDG PET/CT Imaging.

A 57-year-old woman with a history of uterine endometrial carcinoma underwent PET/CT examinations for initial staging and posttreatment survey. Multiple patchy accumulations were noted in the muscles, particularly in both thighs. These accumulations resolved spontaneously 6 months after the follow-up examination. However, 3.5 years after the surgery, the multiple patchy accumulations reappeared in the muscle of the upper and lower extremities showing an increase in signal intensity from previous examination. A biopsy of the right thigh revealed epithelioid cell granuloma without necrosis. We therefore consider that this case might be "idiopathic" granulomatous myositis.

Altered lymphatic drainage patterns in re-operative sentinel lymph node biopsy for ipsilateral breast tumor recurrence.

BACKGROUND: This study aimed to evaluate the impact of previous local treatment on lymphatic drainage patterns in ipsilateral breast tumor recurrence (IBTR) based on our data on re-operative sentinel lymph node biopsy (re-SLNB) for IBTR. METHODS: Between April 2005 and December 2016, re-SLNB using lymphoscintigraphy with Tc-99 m phytate was performed in 136 patients with cN0 IBTR. Patients were categorized into two groups: the AX group included 55 patients with previous axillary lymph node dissection; the non-AX group included 69 patients with previous SLNB and 12 patients with no axillary surgery. The whole breast irradiation (RT) after initial surgery had performed in 17 patients in the AX group and 27 patients in the non-AX group. RESULTS: Lymphatic drainage was visualized in 80% of the AX group and 95% of the non-AX group (P < 0.01). The visualization rate of lymphatic drainage was associated with the number of removed lymph nodes in prior surgery. In the non-AX group, lymphatic drainage was visualized in 96% of patients without RT and 93% with RT. Lymphatic drainage was observed at the ipsilateral axilla in 98% of patients without RT and in 64% with RT (P < 0.0001). Aberrant drainage was significantly more common in patients with RT than without RT (60% vs. 19%, P < 0.001); it was observed mostly to the contralateral axilla (52% vs. 2%, P < 0.0001). In the AX group, patients with previous RT showed decreased lymphatic drainage to the ipsilateral axilla compared to those without RT (29% vs. 63%, P < 0.05) and increased aberrant drainage to the contralateral axilla (64% vs. 5%, P < 0.0001). CONCLUSION: Lymphatic drainage patterns altered in re-SLNB in patients with IBTR and previous ALND and RT were associated with alterations in lymphatic drainage patterns.

A novel biomarker, active whole skeletal total lesion glycolysis (WS-TLG), as a quantitative method to measure bone metastatic activity in breast cancer patients.

OBJECTIVE: There is no good response evaluation method for skeletal metastasis. We aimed to develop a novel quantitative method to evaluate the response of skeletal metastasis, especially lytic lesions, for treatment. METHODS: A method to measure active bone metastatic burden quantitatively using F-18 fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) in breast cancer patients, whole skeletal total lesion glycolysis (WS-TLG), a summation of each skeletal lesion's TLG, was developed. To identify active bone lesions, a tentative cutoff value was decided using FDG-PET/CT in 85 breast cancer patients without skeletal metastasis and 35 with skeletal metastasis by changing the cutoff value. Then, the WS-TLG method was evaluated by comparing to PET Response Criteria in Solid Tumor (PERCIST) or European Organization for Research and Treatment of Cancer (EORTC) criteria for only bone in 15 breast cancer patients with skeletal metastasis who were treated. RESULTS: A cutoff value of the standardized uptake value (SUV) = 4.0 gave 91% (77/85) specificity and 97% (34/35) sensitivity. We decided on SUV = 4.0 as a tentative cutoff value. Skeletal metastases of lytic and mixed types showed higher WS-TLG values than those of blastic or intertrabecular types, although statistical significance was not tested. All 15 patients showed agreement with PERCIST or EORTC in the therapeutic bone response. CONCLUSION: This quantitative WS-TLG method appears to be a good biomarker to evaluate skeletal metastasis in breast cancer patients, especially lytic or mixed types. Further clinical studies are warranted to assess the clinical values of this new WS-TLG method.

A case report on 111In chloride bone marrow scintigraphy in management of adrenal myelolipoma.

RATIONALE: Adrenal myelolipoma is a benign hormone-inactive tumor composed of hematopoietic tissue and mature adipose tissue. Because this tumor tends to be rich in fat, in many cases it can be diagnosed based on computed tomography (CT) or magnetic resonance imaging (MRI) findings alone. However, in the presence of much necrosis, calcification and hematopoietic tissue and/or the absence of much fat, and in cases with tumor apoplexy, this tumor becomes difficult to differentiate from other tumors. In such cases, a bone marrow scan may be informative as a non-invasive imaging diagnostic method for preoperative diagnosis of the tumor and determination of the method for the surgical treatment. We herein report a case of huge adrenal myelolipoma with the non-adipose portion identified using an Indium chloride (InCl3) bone marrow scan. PATIENT CONCERNS: A 69-year-old woman was referred to our hospital because of a left peritoneal mass detected on a medical checkup. Abdominal CT revealed a mass measuring 14.3 cm in diameter located between the left kidney and the left adrenal gland, which showed coexistence of fat and soft tissue densities. DIAGNOSES: A bone marrow scan is a nuclear medicine examination to assess hematopoietic activity. To avoid excessive resection of the tumor, we thought that a bone marrow scan could be applied for differentiation between myelolipoma and retroperitoneal liposarcoma by evaluating the hematopoietic activity of the tumor. Tumor enucleation was performed, and pathological examination showed a diagnosis of adrenal myelolipoma. INTERVENTION: The patient was treated with laparoscopic enucleation. OUTCOMES: No metastatic recurrence was found during 8 months of follow-up. LESSONS: Diagnosis of myelolipoma by CT and MRI becomes difficult in the presence of a high volume of hematopoietic tissue. In such cases, a bone marrow scan may be informative as a non-invasive imaging diagnostic method for preoperative diagnosis of the tumor and determination of the method of surgical treatment.

Comparison between single photon emission computed tomography with computed tomography and planar scintigraphy in sentinel node biopsy in breast cancer patients.

OBJECTIVE: Radio-guided sentinel node (SN) biopsy is a standard method used in the treatment of early breast cancer. Single photon emission computed tomography with computed tomography (SPECT/CT) has been commonly used for SN detection. SPECT/CT adds precise anatomical information of SN sites, and it is reported that more SNs may be detectable on SPECT/CT than on planar imaging. We here investigate which breast cancer patients have benefited from SPECT/CT over planar imaging. METHODS: A total of 273 breast cancer patients including 80 with ipsilateral breast tumor relapse (IBTR) underwent both multiple-view planar imaging and SPECT/CT for SN detection. The number of SNs, the patients who had benefitted from SPECT/CT, and the SN procedure failure rate were compared between SPECT/CT and planar imaging. Factors influencing the visualization of para-sternal and ipsilateral level II, III nodes, and contralateral axillary nodes were also analyzed using logistic regression analysis. RESULTS: The number of hot spots did not differ between SPECT/CT and multiple-view planar imaging. Eight contaminated patients and 52 patients with visualized extra-level I axillary nodes benefited from identifying precise anatomical sites. Even though radioactive nodes could be harvested in most (192/193) of the non-IBTR patients (7/8 in non-SN visible patients), no radioactive nodes could be found during surgery in 11 of 80 IBTR patients. Axillary surgery (dissection) increased the visualization of para-sternal and level II, III axillary nodes, and previous irradiation increased the visualization of contralateral axillary nodes. CONCLUSION: Multiple-view planar imaging was equivalent to SPECT/CT for depicting hot nodes for radio-guided SN detection in breast cancer. SPECT/CT was useful when precise anatomical information was necessary, especially regarding sentinel lymph nodes other than ipsilateral axilla. Logistic regression analysis revealed that axillary surgery (dissection) increased the visualization of para-sternal and level II, III axillary nodes, and the only relevant factor influencing visualization of contralateral axillary SNs was previous radiation to the breast.

Efficacy Evaluation of Combination Treatment Using Gemcitabine and Radioimmunotherapy with 90Y-Labeled Fully Human Anti-CD147 Monoclonal Antibody 059-053 in a BxPC-3 Xenograft Mouse Model of Refractory Pancreatic Cancer.

The poor prognosis of pancreatic cancer requires the development of more effective therapy. CD147 expresses in pancreatic cancer with high incidence and has a crucial role in invasion and metastasis. We developed a fully human monoclonal antibody (059-053) with high affinity for CD147. Here we evaluated the efficacy of combined treatment using radioimmunotherapy (RIT) with 90Y-labeled 059-053 and gemcitabine in a BxPC-3 xenograft mouse model. Expression of CD147 and matrix metalloproteinase-2 (MMP2) in BxPC-3 tumors was evaluated. In vitro and in vivo properties of 059-053 were evaluated using 111In-labeled 059-053 and a pancreatic cancer model BxPC-3. Tumor volume and body weight were periodically measured in mice receiving gemcitabine, RIT, and both RIT and gemcitabine (one cycle and two cycles). High expression of CD147 and MMP2 was observed in BxPC-3 tumors and suppressed by 059-053 injection. Radiolabeled 059-053 bound specifically to BxPC-3 cells and accumulated highly in BxPC-3 tumors but low in major organs. Combined treatment using RIT with gemcitabine (one cycle) significantly suppressed tumor growth and prolonged survival with tolerable toxicity. The two-cycle regimen had the highest anti-tumor effect, but was not tolerable. Combined treatment with 90Y-labeled 059-053 and gemcitabine is a promising therapeutic option for pancreatic cancer.

[Administration Accuracy of Automated Infusion Device for PET Using Improved Disposable Kit].

PURPOSE: The AI-300 automated infusion device (Sumitomo Heavy Industries, Ltd., Tokyo, Japan) is subject to administration error as a function of smaller volumes of 18F-FDG dispensed via a three-way cock supplied with a disposable kit. The present study aimed to validate the administration accuracy of the AI-300 using an improved disposable kit for quantitative positron emission tomography (PET) assessment. METHODS: We determined administration accuracy between the improved and previous disposable kits by measuring variations in dispensed volumes and radioactive concentrations of 18F-FDG according to the criteria of the Japanese Society of Nuclear Medicine. A reference value was generated by measuring radioactivity using a standard dose calibrator. RESULTS: The values obtained using the previous kit deviated from the reference values by a maximum of -10.6%, and the deviation depended on dispensed volumes of 18F-FDG<0.25 mL. In contrast, the values were relatively stable when using the improved kit with dispensed 18F-FDG volumes < 0.25 mL. Variations in radioactive concentrations were relatively stable using the improved kit, whereas that of the previous kit was slightly unstable at high radioactive concentrations. CONCLUSION: The administration accuracy of the AI-300 using the previous kit varied considerably according to smaller dispensed volumes, but the improved kit might alleviate this problem. The present results indicated that the improved disposal kit should be immediately implemented to eliminate uncertainty surrounding quantitative PET findings.

Metastasizing pleomorphic adenoma in the multiple organs: A case report on FDG-PET/CT imaging.

RATIONALE: Pleomorphic adenoma, the most common tumor of the salivary glands, is usually benign. It is well known, however, that pleomorphic adenomas occasionally undergo malignant transformation to carcinoma ex pleomorphic adenoma and can metastasize. More rarely pleomorphic adenomas can metastasize without histological malignant transformation. We herein report an unusual case of pleomorphic adenoma with multiple metastases comprehensively demonstrated on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). PATIENT CONCERNS: A 63-year-old woman was referred to our hospital because of urine occult blood and lung nodules detected on a health checkup. She had a history of resection of a pleomorphic adenoma in the parotid gland at the age of 40 years and tumor recurrence at the age of 53 years. CT scan and magnetic resonance imaging revealed bilateral renal tumors, multiple pulmonary nodules, and an osteolytic lesion in the first lumbar vertebra. DIAGNOSES: Ultrasonography-guided percutaneous biopsy of the right renal tumor revealed a myxoid epithelial tumor that was consistent with metastasis of the pleomorphic adenoma from the parotid gland. INTERVENTIONS: The patient was carefully observed with regular imaging examinations. OUTCOMES: The multiple lesions gradually progressed, and FDG-PET/CT subsequently revealed additional metastases in the liver and perineum. LESSONS: Metastases of pleomorphic adenomas may occur years after the initial disease in association with local recurrences. Careful observation with whole-body imaging such as FDG-PET/CT is necessary.

Sequential Sentinel Node Scintigraphy With Planar and SPECT/CT Images Revealed Contralateral Drainage From Ipsilateral Breast Tumor Relapse in a Patient With Bilateral Breast Cancer.

Radio-guided sentinel node (SN) biopsy is routinely performed in patients with early breast cancer. However, repeated SN scintigraphy in ipsilateral breast tumor relapse (IBTR) often shows extra-axillary drainage, including contralateral axilla. A patient diagnosed with bilateral breast cancer, of which one was IBTR, was studied by sequential radio-guided SN mapping, radiocolloid injection to an IBTR breast and scanning, and then radiocolloid injection to the other breast and scanning. This revealed the lymphatic flow from the IBTR breast to the contralateral axilla. Sequential method may help to depict contralateral axillary lymphatic flow from an IBTR breast in patients with bilateral breast cancer.

Impending Atypical Femoral Fracture in a Patient of Breast Cancer With Bone Metastases Receiving Long-term Denosumab.

Atypical femoral fractures (AFFs) occur in both osteoporosis patients and cancer patients who receive long-term bisphosphonate treatment. Denosumab offers an alternative approach for the treatment of bone metastases. We describe a 59-year-old woman with a history of breast carcinoma and bone metastasis who was prescribed denosumab for 4 years. The patient had no history of any prior bisphosphonate use. Bone scintigraphy showed an abnormal uptake in the right femur, which was confirmed as an impending AFF or atypical femoral stress reaction. In oncological patients receiving long-term denosumab, AFF should be included as a differential diagnosis for focal femoral findings.

Evaluation of bone metastatic burden by bone SPECT/CT in metastatic prostate cancer patients: defining threshold value for total bone uptake and assessment in radium-223 treated patients.

OBJECTIVES: To establish a new three-dimensional quantitative evaluation method for bone metastasis, we applied bone single photon emission tomography with computed tomography (SPECT/CT). The total bone uptake (TBU), which measures active bone metastatic burden, was calculated as the sum of [mean uptake obtained as standardized uptake value (SUV) above a cut-off level] × (the volume of the lesion) in the trunk using bone SPECT/CT. We studied the threshold value and utility of TBU in prostate cancer patients treated with radium-223 (Ra-223) therapy. METHODS: To establish the threshold value of TBU, we compared bone metastatic and non-metastatic regions in 61 prostate cancer patients with bone metastasis and 69 without. Five fixed sites in each patient were selected as evaluation points and divided into bone metastatic and non-metastatic sites. Sensitivity and specificity analysis was applied to establish the threshold level. Using the obtained threshold value, we then calculated the TBU in nine prostate cancer patients who received Ra-223 therapy, and compared the results with the bone scan index (BSI) by BONENAVI® and visual evaluation of bone scintigraphy. RESULTS: Uptake was significantly lower in non-metastatic sites in patients with bone metastasis than in patients without metastasis. Sensitivity and specificity analysis revealed SUV = 7.0 as the threshold level. There was a discrepancy between TBU and BSI change in two of the nine patients, in whom TBU change correlated with visual judgement, but BSI change did not. In two patients, BSI was nearly 0 throughout the course, but the TBU was positive and changed, although the change was not large. These results suggest that TBU may be more accurate and sensitive than BSI for quantitative evaluation of active bone metastatic burden. CONCLUSION: We established a threshold value (SUV > 7.0) for three-dimensional TBU for evaluating active bone metastatic burden in prostate cancer patients using bone SPECT/CT. Despite the small number of patients, we expect the change in TBU could be more accurate and sensitive than the change in BSI among patients who received Ra-223.

Japanese Expert Panel Meeting on the Management of Prostate Cancer with Bone Metastases.

INTRODUCTION: The incidence of prostate cancer in Japan continues to increase, necessitating the continued development of effective therapies and strategies. Recent advances in treatments have improved the prognosis of metastatic disease and highlighted the importance of treating bone metastases to reduce the incidence of skeletal complications and improve patients' quality of life. With the increasing number of treatment options that have become available, including bone-targeted therapy with the alpha emitter radium-223 dichloride (Ra-223), Japanese clinicians are faced with making difficult decisions on the choice of optimal treatment strategy. In such situations, guidance based on expert opinions can be beneficial. METHODS: A panel meeting of 27 Japanese experts in the management of prostate cancer was held to share opinions and to establish consensus recommendations on key clinical questions. Panelists were asked to vote on more than 40 questions pertinent to prostate cancer, and the answers helped guide a comprehensive discussion. RESULTS: The panel reached a consensus on key topics related to the optimal treatment strategy for Ra-223 therapy, namely, that patients with symptomatic, metastatic castration-resistant prostate cancer (CRPC) would benefit most from the use of this agent and that this treatment therapy should be provided before chemotherapy. Other topics that achieved consensus included: monitoring for osteoporosis and providing treatment if necessary during androgen deprivation therapy; performing magnetic resonance imaging in the presence of discrepancies in bone scintigram and computed tomography scans; monitoring alkaline phosphatase during CRPC treatment; using osteoclast-targeting in patients with CRPC with bone metastases; and using osteoclast-targeted agents combined with Ra-223. CONCLUSION: These consensus recommendations and the updated information which became available subsequent to the panel meeting included here provide useful information for clinicians to aid in designing optimal treatment strategies for their patients. FUNDING: Bayer Yakuhin Ltd.