Optimizing PSMA scintigraphy for resource limited settings - a retrospective comparative study.

BACKGROUND: PSMA PET/CT is the most sensitive molecular imaging modality for prostate cancer (PCa), yet much of the developing world has little or no access to PET/CT. [99mTc]Tc-PSMA scintigraphy (PS) is a cheaper and more accessible gamma camera-based alternative. However, many resource-constrained departments have only a single camera without tomographic or hybrid imaging functionality, and camera time is frequently in high demand. Simplifying imaging protocols by limiting the field of view (FOV) and omitting SPECT/CT or even SPECT may provide a partial solution. The aim was thus to determine the adequacy of PS planar-only and/or SPECT-only imaging protocols with a limited FOV. METHODS: The scans of 95 patients with histologically proven PCa who underwent PS with full-body planar and multi-FOV SPECT/CT were reviewed. The detection rates for uptake in the prostate gland/bed and in metastases were compared on planar, SPECT, and SPECT/CT. The agreement between modalities was calculated for the detection of metastases and for staging. The impact of imaging a limited FOV was determined. RESULTS: Pathological prostatic uptake was seen in all cases on SPECT/CT (excluding two post-prostatectomy patients), 90.3% of cases on SPECT, and 15.1% on planar images (p < 0.001). Eleven (11.7%) patients had seminal vesicle involvement on SPECT/CT, which was undetectable/indistinguishable on planar images and SPECT. The agreement between modalities was moderate to good (κ = 0.41 to 0.61) for the detection of nodal metastases, with detection rates that did not differ significantly (SPECT/CT = 11.6%, SPECT = 8.4%, planar = 5.3%). Detection rates for bone metastases were 14.7% (SPECT/CT) and 11.6% (SPECT and planar). Agreement between modalities for the detection of bone metastases was good (κ = 0.73 to 0.77). Three (3.1%) patients had visceral metastases on SPECT/CT, two of which were detected on SPECT and planar. There was good agreement between modalities for the TNM staging of patients (κ = 0.70 to 0.88). No metastatic lesions were missed on the limited FOV images. CONCLUSION: When PS scintigraphy is performed, SPECT/CT is recommended. However, the lack of SPECT/CT capabilities should not preclude the use of PS in the presence of limited resources, as both planar and SPECT imaging are adequate and will correctly stage most PCa patients. Furthermore, time-based optimisations are achievable by limiting the FOV to exclude the distal lower limbs.

Metastasis patterns and prognosis in young gastric cancer patients: A propensity score­matched SEER database analysis.

BACKGROUND: Whether young patients with metastatic gastric cancer (GC) had distinct metastasis patterns and survival outcomes from older patients remains controversial. The aim of the present study was to explore the metastasis patterns and prognostic factors in young patients and evaluate the survival outcome in comparison to their older counterparts. MATERIALS AND METHODS: We identified patients with metastatic GC in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015. The patients were divided into two groups based on age at diagnosis: younger (≤40 years old) and older (>40 years old). We employed the chi-squared test to compare the clinicopathological characteristics between the two age groups. Furthermore, we conducted survival analyses using Kaplan-Meier and Cox regression analyses. To balance disparities in baseline characteristics, we employed propensity score matching (PSM). RESULTS: We identified 5,580 metastatic GC patients from the SEER database, with 237 (4.2%) classified as younger and 5343 (95.8%) as older patients. A total of 237 pairs of patients were generated after adjustment by PSM. Patients in the younger group exhibited a higher proportion of bone-only metastases and a lower proportion of liver-only metastases compared with patients in the older group. Multivariate Cox regression analysis demonstrated that youth was an independent protective factor for overall survival (OS) before and after PSM, but not for gastric cancer-specific survival (GCSS). Among the younger group, patients with liver-only metastasis demonstrated the best prognosis, whereas patients with lung-only metastasis exhibited significantly worse survival outcomes compared with liver-only metastases, even comparable to that of bone metastasis. CONCLUSIONS: Compared with the older group, the metastatic GC patients in the younger group exhibited more aggressive tumors but better prognoses. The metastasis pattern and its effect on the prognosis of GC varied by age group.

Reclassified the phenotypes of cancer types and construct a nomogram for predicting bone metastasis risk: A pan-cancer analysis.

BACKGROUND: Numerous of models have been developed to predict the bone metastasis (BM) risk; however, due to the variety of cancer types, it is difficult for clinicians to use these models efficiently. We aimed to perform the pan-cancer analysis to create the cancer classification system for BM, and construct the nomogram for predicting the BM risk. METHODS: Cancer patients diagnosed between 2010 and 2018 in the Surveillance, Epidemiology, and End Results (SEER) database were included. Unsupervised hierarchical clustering analysis was performed to create the BM prevalence-based cancer classification system (BM-CCS). Multivariable logistic regression was applied to investigate the possible associated factors for BM and construct a nomogram for BM risk prediction. The patients diagnosed between 2017 and 2018 were selected for validating the performance of the BM-CCS and the nomogram, respectively. RESULTS: A total of 50 cancer types with 2,438,680 patients were included in the construction model. Unsupervised hierarchical clustering analysis classified the 50 cancer types into three main phenotypes, namely, categories A, B, and C. The pooled BM prevalence in category A (17.7%; 95% CI: 17.5%-17.8%) was significantly higher than that in category B (5.0%; 95% CI: 4.5%-5.6%), and category C (1.2%; 95% CI: 1.1%-1.4%) (p < 0.001). Advanced age, male gender, race, poorly differentiated grade, higher T, N stage, and brain, lung, liver metastasis were significantly associated with BM risk, but the results were not consistent across all cancers. Based on these factors and BM-CCS, we constructed a nomogram for predicting the BM risk. The nomogram showed good calibration and discrimination ability (AUC in validation cohort = 88%,95% CI: 87.4%-88.5%; AUC in construction cohort = 86.9%,95% CI: 86.8%-87.1%). The decision curve analysis also demonstrated the clinical usefulness. CONCLUSION: The classification system and prediction nomogram may guide the cancer management and individualized BM screening, thus allocating the medical resources to cancer patients. Moreover, it may also have important implications for studying the etiology of BM.

Treatment of bone metastases from solid tumors with bone-modifying agents: a web survey of Italian oncologists investigating patterns of practice drug prescription and prevention of side effects.

PURPOSE: Optimal use of bone-modifying agents (BMAs) in patients with bone metastases from solid tumors is uncertain in some aspects: the drug choice; the planned treatment duration and long-term therapy; the prevention and management of possible side effects, including renal toxicity, hypocalcaemia, and medication-related osteonecrosis of the jaw (MRONJ). METHODS: Italian oncologists were invited to fulfil a 24-question web survey about prescription of BMAs for bone metastases of breast cancer, prostate cancer, and other solid tumors. Prevention and management of side effects were also investigated. RESULTS: Answers of 191 oncologists were collected. BMAs are usually prescribed at the time of diagnosis of bone metastases by 87.0% (breast cancer) and 76.1% (solid tumors except breast and prostate cancers) of oncologists; the decision is more articulated for prostate cancer (endocrine-sensitive versus castration-resistant). The creatinine level (32.3%), the availability of patient venous access (15.8%), and the type of primary neoplasm (13.6%) are the most reported factors involved in choice between bisphosphonates and denosumab. Zoledronic acid every 3 months was considered as a valid alternative to monthly administration by 94% of Italian oncologists. Oncologists reported a good confidence with measures aimed to prevent MRONJ, whereas uncertainness about prevention and management of hypocalcemia was registered. CONCLUSION: Italian oncologists showed a high attitude in prescribing bisphosphonates or denosumab at the time of diagnosis of bone metastases, with a large application of preventive measures of side effects. Further studies are needed to investigate some controversial aspects, such as optimal drug treatment duration and long-term drug schedules.

Prognostic factors and real-life applicability of prognostic models for patients with bone metastases of carcinoma.

OBJECTIVE: This study aimed to investigate the factors affecting the survival of patients with bone carcinoma metastases and assess the clinical applicability of existing prognostic models. METHODS: We retrospectively evaluated 247 patients who presented to our hospital between 2011 and 2021 diagnosed with bone carcinoma metastasis. Demographic data, general health status, primary diagnoses, laboratory and radiological findings, pathological fracture status, treatment methods, and survival times of the patients were recorded, and the effects of these variables on survival time were evaluated. Previously developed Katagiri, Janssen, 2013-Spring, PathFX, and SORG prognostic models were applied, and the predictive performances of these models were evaluated by comparing the predicted survival time with the actual survival time of our patients. RESULTS: After the multivariate analysis, the following factors were shown to be significantly associated with the survival time of patients: blood hemoglobin and leukocyte levels, lactate dehydrogenase concentration, prognostic nutritional index, body mass index, performance status, medium and fast-growing groups of primary tumors, presence of extraspinal and visceral or brain metastases, and pathological fractures. According to receiver operating characteristics and Brier scores, SORG had the overall highest performance scores, while the Janssen nomogram had the lowest. CONCLUSION: Our report showed that all prognostic models were clinically applicable, but their performances varied. Among them, the SORG predictive model had the best performance scores overall and is the model the authors suggested for survival prediction among patients with carcinoma bone metastases. LEVEL OF EVIDENCE: Level IV, Prognostic Study.

Automated Detection and Segmentation of Bone Metastases on Spine MRI Using U-Net: A Multicenter Study.

OBJECTIVE: To develop and evaluate a deep learning model for automated segmentation and detection of bone metastasis on spinal MRI. MATERIALS AND METHODS: We included whole spine MRI scans of adult patients with bone metastasis: 662 MRI series from 302 patients (63.5 ± 11.5 years; male:female, 151:151) from three study centers obtained between January 2015 and August 2021 for training and internal testing (random split into 536 and 126 series, respectively) and 49 MRI series from 20 patients (65.9 ± 11.5 years; male:female, 11:9) from another center obtained between January 2018 and August 2020 for external testing. Three sagittal MRI sequences, including non-contrast T1-weighted image (T1), contrast-enhanced T1-weighted Dixon fat-only image (FO), and contrast-enhanced fat-suppressed T1-weighted image (CE), were used. Seven models trained using the 2D and 3D U-Nets were developed with different combinations (T1, FO, CE, T1 + FO, T1 + CE, FO + CE, and T1 + FO + CE). The segmentation performance was evaluated using Dice coefficient, pixel-wise recall, and pixel-wise precision. The detection performance was analyzed using per-lesion sensitivity and a free-response receiver operating characteristic curve. The performance of the model was compared with that of five radiologists using the external test set. RESULTS: The 2D U-Net T1 + CE model exhibited superior segmentation performance in the external test compared to the other models, with a Dice coefficient of 0.699 and pixel-wise recall of 0.653. The T1 + CE model achieved per-lesion sensitivities of 0.828 (497/600) and 0.857 (150/175) for metastases in the internal and external tests, respectively. The radiologists demonstrated a mean per-lesion sensitivity of 0.746 and a mean per-lesion positive predictive value of 0.701 in the external test. CONCLUSION: The deep learning models proposed for automated segmentation and detection of bone metastases on spinal MRI demonstrated high diagnostic performance.

Epiberberine inhibits bone metastatic breast cancer-induced osteolysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The anti-tumor related diseases of Coptidis Rhizoma (Huanglian) were correlated with its traditional use of removing damp-heat, clearing internal fire, and counteracting toxicity. In the recent years, Coptidis Rhizoma and its components have drawn extensive attention toward their anti-tumor related diseases. Besides, Coptidis Rhizoma is traditionally used as an anti-inflammatory herb. Epiberberine (EPI) is a significant alkaloid isolated from Coptidis Rhizoma, and exhibits multiple pharmacological activities including anti-inflammatory. However, the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis has not been demonstrated clearly. AIM OF THE STUDY: Bone metastatic breast cancer can lead to osteolysis via inflammatory factors-induced osteoclast differentiation and function. In this study, we try to analyze the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis. METHODS: To evaluate whether epiberberine could suppress bone metastatic breast cancer-induced osteolytic damage, healthy female Balb/c mice were intratibially injected with murine triple-negative breast cancer 4T1 cells. Then, we examined the inhibitory effect and underlying mechanism of epiberberine on breast cancer-induced osteoclastogenesis in vitro. Xenograft assay was used to study the effect of epiberberine on breast cancer cells in vivo. Moreover, we also studied the inhibitory effects and underlying mechanisms of epiberberine on RANKL-induced osteoclast differentiation and function in vitro. RESULTS: The results show that epiberberine displayed potential therapeutic effects on breast cancer-induced osteolytic damage. Besides, our results show that epiberberine inhibited breast cancer cells-induced osteoclast differentiation and function by inhibiting secreted inflammatory cytokines such as IL-8. Importantly, we found that epiberberine directly inhibited RANKL-induced differentiation and function of osteoclast without cytotoxicity. Mechanistically, epiberberine inhibited RANKL-induced osteoclastogensis via Akt/c-Fos signaling pathway. Furthermore, epiberberine combined with docetaxel effectively protected against bone loss induced by metastatic breast cancer cells. CONCLUSIONS: Our findings suggested that epiberberine may be a promising natural compound for treating bone metastatic breast cancer-induced osteolytic damage by inhibiting IL-8 and is worthy of further exploration in preclinical and clinical trials.

Detection of HER2 expression using 99mTc-NM-02 nanobody in patients with breast cancer: a non-randomized, non-blinded clinical trial.

BACKGROUND: 99mTc radiolabeled nanobody NM-02 (99mTc-NM-02) is a novel single photon emission computed tomography (SPECT) probe with a high affinity and specificity for human epidermal growth factor receptor 2 (HER2). In this study, a clinical imaging trial was conducted to investigate the relationship between 99mTc-NM-02 uptake and HER2 expression in patients with breast cancer. METHODS: Thirty patients with pathologically confirmed breast cancer were recruited and imaged with both 99mTc-NM-02 SPECT/computed tomography (CT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT. According to the treatment conditions before recruitment, patients were divided into two groups, the newly diagnosed group (n = 24) and the treated group (n = 6). The maximal standard uptake value (SUVmax) of 18F-FDG and SUVmax and mean SUV (SUVmean) of 99mTc-NM-02 in the lesions were determined to analyze the relationship with HER2 expression. RESULTS: No meaningful relationship was observed between 18F-FDG uptake and HER2 expression in 30 patients with breast cancer. 99mTc-NM-02 uptake was positively correlated with HER2 expression in the newly diagnosed group, but no correlation was observed in the treated group. 99mTc-NM-02 uptake in HER2-positive lesions was lower in those with effective HER2-targeted therapy compared with the newly diagnosed group. 99mTc-NM-02 SPECT/CT detected brain and bone metastases of breast cancer with a different imaging pattern from 18F-FDG PET/CT. 99mTc-NM-02 showed no non-specific uptake in inflamed tissues and revealed intra- and intertumoral HER2 heterogeneity by SPECT/CT imaging in 9 of the 30 patients with breast cancer. CONCLUSIONS: 99mTc-NM-02 SPECT/CT has the potential for visualizing whole-body HER2 overexpression in untreated patients, making it a promising method for HER2 assessment in patients with breast cancer. TRIAL REGISTRATION: NCT04674722, Date of registration: December 19, 2020.

Recurrent severe hypocalcemia following chemotherapy regimen changes in advanced breast cancer: two case reports.

BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements. CASE REPORT: We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases. Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole + lapatinib, trastuzumab emtansine, and lapatinib + capecitabine. CONCLUSIONS: We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes.

The RANKL inhibitor denosumab in combination with dual checkpoint inhibition is associated with increased CXCL-13 serum concentrations.

BACKGROUND: Recent evidence suggests additional immunomodulatory properties of RANKL inhibition possibly boosting the clinical efficacy of immune checkpoint inhibitors (ICI). METHODS: We conducted a prospective, multicentre clinical trial in unresectable stage IV melanoma patients with bone metastases who received denosumab in parallel with dual ICI (BONEMET) and performed comprehensive immune monitoring at baseline and 4, 12, and 24 weeks after initiation of therapy. Secondary endpoints included tolerability and efficacy. For comparison, biospecimens from melanoma patients treated with dual ICI without denosumab were analyzed accordingly and served as retrospective reference cohort. RESULTS: In both the BONEMET (n = 16) and the reference cohort (n = 18) serum levels of 17 cytokines, including IFNγ were significantly increased after 4 weeks of treatment. Patients who received ICI and denosumab showed a significantly higher increase in serum CXCL-13 and a significant decrease in VEGFc compared with the reference cohort. While no changes in T cell composition were observed at 4 weeks, patients in the BONEMET cohort showed a significant decrease in the peripheral naïve T-cell population and an increase in CD8+ effector cells after 12 weeks. Treatment-related adverse events occurred with comparable frequency (93.8% in the BONEMET cohort versus 83.3% in the reference cohort). 7/16 patients in the BONEMET cohort and 8/18 patients in the reference cohort achieved disease control. CONCLUSION: Denosumab in combination with dual ICI modulates cytokine expression and T-cell composition in peripheral blood. The upregulation of CXCL-13, a key factor for initiating tertiary lymphoid structures, strengthens the hypothesis that denosumab indeed boost immunological effects.

Clinical effectiveness of combined whole body hyperthermia and external beam radiation therapy (EBRT) versus EBRT alone in patients with painful bony metastases: A phase III clinical trial study.

PURPOSE: To evaluate the response rate, pain relief duration, and time it took for pain to decline or resolve after radiation therapy (RT) with or without fever-range Whole Body Hyperthermia (WBH) in bony metastatic patients with mainly primary tumor of prostate and breast cancer leading to bone pain. MATERIALS & METHODS: Bony metastatic patients with pain score ≥4 on the Brief Pain Inventory (BPI) underwent RT of 30 Gy in 10 fractions in combination with WBH with nursing care under medical supervision versus RT-alone. WBH application time was 3-4 h in three fractions with at least 48-h intervals. All patients were stratified primary site, breast or prostate cancer vs others, BPI score, and exclusion criteria. The primary endpoint was complete response (CR) (BPI equal to zero with no increase of analgesics) within two months of follow-up. RESULTS: Based on this study, the RT-alone group showed the worst pain. The study was terminated after the enrollment of a total of 61 patients, 5 years after the first enrollment (April 2016 to February 2021). Finally, the CR rate in RT + WBH revealed the most significant difference with RT-alone, 47.4% versus 5.3% respectively within 2 months post-treatment (P-value <0.05). The time of complete pain relief was 10 days for RT + WBH, while the endpoint was not reached during the RT-alone arm. Pain progression or stable disease was observed in half of the patients in RT-alone group within 4 weeks after treatment. However, this score was near zero in RT + WBHT patients in two months post-treatment. CONCLUSIONS: WBH plus RT showed significant increases in pain relief and shorter response time in comparison with RT-alone for patients with bone metastatic lesions.

68 Ga-DOTA-Ibandronic Acid PET/CT in a Patient With Chemotherapy-Induced Salivary Gland Hypofunction.

ABSTRACT: DOTA-ibandronic acid (IBA) is a novel precursor targeting bone metastasis. It can be radiolabeled with 68 Ga for the diagnosis of bone metastases. However, extraosseous lesions can also show increased DOTA-IBA uptake. We report the 68 Ga-DOTA-IBA PET/CT findings in a case with cholangiocarcinoma with multiple bone metastases. 68 Ga-DOTA-IBA PET/CT revealed increased uptake of DOTA-IBA in bone metastases. Besides, symmetrical and diffuse increased DOTA-IBA uptake in bilateral salivary glands was observed. 99m TcO 4- salivary gland scintigraphy showed impaired salivary gland function.

Analysis of Factors Influencing Bone Metastasis in Prostate Cancer and Diagnostic Value of Serum PSA, CysC and D-D.

OBJECTIVE: This study aims to analyse factors influencing bone metastasis in prostate cancer and the diagnostic value of serum prostate-specific antigen (PSA), and D-dimer (D-D) combined with cystatin C (CysC) in bone metastasis of prostate cancer. METHODS: Data of 116 patients with prostate cancer admitted to our hospital were retrospectively analysed. They were divided into two groups: Bone metastasis group (46 cases) and non-bone metastasis group (70 cases). Univariate and multivariate logistic regression analyses were used to determine factors influencing bone metastasis in prostate cancer. The values of serum PSA, D-D and CysC were identified using a receiver operating characteristic diagnostic curve. RESULTS: Of the 116 patients, 46 had bone metastases and 70 had non-bone metastases. Among 46 patients with bone metastasis, 8 cases (17.39%) had single bone metastasis and 38 cases (82.61%) had multiple bone metastasis. Based on the univariate analysis, bone metastasis was associated with increases in Gleason score, clinical stage, lymph node metastasis, systemic inflammatory response index, fibrinogen to albumin ratio and alkaline phosphatase and fibrinogen levels. The Gleason score was higher than 8 points, the clinical stages ranged from T3 to T4 and the serum levels of PSA, D-D and CysC were higher in the bone metastasis group (p < 0.05). The combined value of serum PSA, D-D and CysC in the diagnosis of bone metastasis in prostate cancer was higher than the three indicators alone. CONCLUSIONS: Lymph node metastasis in T3-T4 clinical stages with Gleason score >8 was a risk factor for bone metastasis in prostate cancer (all p < 0.05). The risk of bone metastasis in patients with prostate cancer increases with increasing Gleason clinical stage and the occurrence of lymph node metastasis. Serum PSA, D-D and CysC have certain diagnostic value in the diagnosis of bone metastasis, and their combination has the highest value.

Natural history of bone-only metastasis in renal cell carcinoma.

BACKGROUND: Bone metastasis (BM) is considered a poor prognostic factor of renal cell carcinoma (RCC). Confusion exists regarding how to deal with RCC patients with bone-only metastasis. PATIENTS AND METHODS: The clinical data of consecutive RCC patients with bone-only metastasis at Peking University Cancer Hospital between 2006 and 2018 were retrospectively collected and analyzed. RESULTS: Fifty-four eligible patients were screened from an RCC database of 1,878 metastatic patients. After a median follow-up of 43.6 m, 61.1% of the patients were presented with progression of prior BM or new BM. The progression-free survival (PFS) and overall survival (OS) was 16.2 m (95%CI: 11.4-21.0) and 65.2 m, respectively. For the 30 patients with oligo-metastasis (≤3 loci) and 24 ones with multiple-metastasis (>3 loci), the median OS was not reached and 42.0m (95%CI: 12.7-71.2) with statistical difference (P < 0.001). In the oligo-metastasis group, the median PFS of the 15 patients treated with local therapy and of the 13 patients treated with systemic therapy was 14.2 m (95%CI: 5.3-23.3) and 18.0 m (95%CI:15.4-20.6), respectively. In the multiple-metastasis group, the median PFS and OS of the 18 patients treated with systemic therapy was 16.6 m (95%CI: 7.5-25.7) and 63.9 m (95%CI: 21.8-106.0), respectively. Univariate analysis and multivariate analysis showed that the number of metastatic sites (oligo/multiple) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score, RCC pathological subtype were significantly associated with prognosis (P < 0.05). CONCLUSION: RCC patients with bone-only metastases have a favorable prognosis. The number of metastatic sites, IMDC, RCC pathological subtype could serve as survival predictors, which might provide clue of treatment modality.

Verification of image quality improvement of low-count bone scintigraphy using deep learning.

To improve image quality for low-count bone scintigraphy using deep learning and evaluate their clinical applicability. Six hundred patients (training, 500; validation, 50; evaluation, 50) were included in this study. Low-count original images (75%, 50%, 25%, 10%, and 5% counts) were generated from reference images (100% counts) using Poisson resampling. Output (DL-filtered) images were obtained after training with U-Net using reference images as teacher data. Gaussian-filtered images were generated for comparison. Peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) to the reference image were calculated to determine image quality. Artificial neural network (ANN) value, bone scan index (BSI), and number of hotspots (Hs) were computed using BONENAVI analysis to assess diagnostic performance. Accuracy of bone metastasis detection and area under the curve (AUC) were calculated. PSNR and SSIM for DL-filtered images were highest in all count percentages. BONENAVI analysis values for DL-filtered images did not differ significantly, regardless of the presence or absence of bone metastases. BONENAVI analysis values for original and Gaussian-filtered images differed significantly at ≦25% counts in patients without bone metastases. In patients with bone metastases, BSI and Hs for original and Gaussian-filtered images differed significantly at ≦10% counts, whereas ANN values did not. The accuracy of bone metastasis detection was highest for DL-filtered images in all count percentages; the AUC did not differ significantly. The deep learning method improved image quality and bone metastasis detection accuracy for low-count bone scintigraphy, suggesting its clinical applicability.

From breast cancer cell homing to the onset of early bone metastasis: The role of bone (re)modeling in early lesion formation.

Breast cancer often metastasizes to bone, causing osteolytic lesions. Structural and biophysical changes are rarely studied yet are hypothesized to influence metastasis. We developed a mouse model of early bone metastasis and multimodal imaging to quantify cancer cell homing, bone (re)modeling, and onset of metastasis. Using tissue clearing and three-dimensional (3D) light sheet fluorescence microscopy, we located enhanced green fluorescent protein-positive cancer cells and small clusters in intact bones and quantified their size and spatial distribution. We detected early bone lesions using in vivo microcomputed tomography (microCT)-based time-lapse morphometry and revealed altered bone (re)modeling in the absence of detectable lesions. With a new microCT image analysis tool, we tracked the growth of early lesions over time. We showed that cancer cells home in all bone compartments, while osteolytic lesions are only detected in the metaphysis, a region of high (re)modeling. Our study suggests that higher rates of (re)modeling act as a driver of lesion formation during early metastasis.

Pretreatment level of serum sialic acid predicts both qualitative and quantitative bone metastases of prostate cancer.

Background: Recently, serum sialic acid (SA) has emerged as a distinct prognostic marker for prostate cancer (PCa) and bone metastases, warranting differential treatment and prognosis for low-volume (LVD) and high-volume disease (HVD). In clinical settings, evaluating bone metastases can prove advantageous. Objectives: We aimed to establish the correlation between SA and both bone metastasis and HVD in newly diagnosed PCa patients. Methods: We conducted a retrospective analysis of 1202 patients who received a new diagnosis of PCa between November 2014 and February 2021. We compared pretreatment SA levels across multiple groups and investigated the associations between SA levels and the clinical parameters of patients. Additionally, we compared the differences between HVD and LVD. We utilized several statistical methods, including the non-parametric Mann-Whitney U test, Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression. Results: The results indicate that SA may serve as a predictor of bone metastasis in patients with HVD. ROC curve analysis revealed a cut-off value of 56.15 mg/dL with an area under the curve of 0.767 (95% CI: 0.703-0.832, P < 0.001) for bone metastasis versus without bone metastasis and a cut-off value of 65.80 mg/dL with an area under the curve of 0.766 (95% CI: 0.644-0.888, P = 0.003) for HVD versus LVD. Notably, PCa patients with bone metastases exhibited significantly higher SA levels than those without bone metastases, and HVD patients had higher SA levels than LVD patients. In comparison to the non-metastatic and LVD cohorts, the cohort with HVD exhibited higher levels of alkaline phosphatase (AKP) (median, 122.00 U/L), fibrinogen (FIB) (median, 3.63 g/L), and prostate-specific antigen (PSA) (median, 215.70 ng/mL), as well as higher Gleason scores (> 7). Multivariate logistic regression analysis demonstrated that an SA level of > 56.15 mg/dL was independently associated with the presence of bone metastases in PCa patients (OR = 2.966, P = 0.018), while an SA level of > 65.80 mg/dL was independently associated with HVD (OR = 1.194, P = 0.048). Conclusion: The pretreatment serum SA level is positively correlated with the presence of bone metastases.

Magnetic resonance-guided focused ultrasound versus percutaneous thermal ablation in local control of bone oligometastases: a systematic review and meta-analysis.

BACKGROUND: The percutaneous thermal ablation techniques (pTA) are radiofrequency ablation, cryoablation, and microwave ablation, suitable for the treatment of bone oligometastases. Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive ablation technique. OBJECTIVES: To compare the effectiveness and safety of MRgFUS and pTA for treating bone oligometastases and their complications. METHODS: Studies were selected with a PICO/PRISMA protocol: pTA or MRgFUS in patients with bone oligometastases; non-exclusive curative treatment. Exclusion criteria were: primary bone tumor; concurrent radiation therapy; palliative therapy; and absence of imaging at follow-up. PubMed, BioMed Central, and Scopus were searched. The modified Newcastle-Ottawa Scale assessed articles quality. For each treatment (pTA and MRgFUS), we conducted two separate random-effects meta-analyses to estimate the pooled effectiveness and safety. The effectiveness was assessed by combining the proportions of treated lesions achieving local tumor control (LTC); the safety by combining the complications rates of treated patients. Meta-regression analyses were performed to identify any outcome predictor. RESULTS: A total of 24 articles were included. Pooled LTC rate for MRgFUS was 84% (N = 7, 95% CI 66-97%, I2 = 74.7%) compared to 65% of pTA (N = 17, 95% CI 51-78%, I2 = 89.3%). Pooled complications rate was similar, respectively, 13% (95% CI 1-32%, I2 = 81.0%) for MRgFUS and 12% (95% CI 8-18%, I2 = 39.9%) for pTA, but major complications were recorded with pTA only. The meta-regression analyses, including technique type, study design, tumor, and follow-up, found no significant predictors. DISCUSSION: The effectiveness and safety of the two techniques were found comparable, even though MRgFUS is a noninvasive treatment that did not cause any major complication. Limited data availability on MRgFUS and the lack of direct comparisons with pTA may affect these findings. CONCLUSIONS: MRgFUS can be a valid, safe, and noninvasive treatment for bone oligometastases. Direct comparison studies are needed to confirm its promising benefits.

Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis.

Importance: Conventional external beam radiotherapy (cEBRT) and stereotactic body radiotherapy (SBRT) are commonly used treatment options for relieving metastatic bone pain. The effectiveness of SBRT compared with cEBRT in pain relief has been a subject of debate, and conflicting results have been reported. Objective: To compare the effectiveness associated with SBRT vs cEBRT for relieving metastatic bone pain. Data Sources: A structured search was performed in the PubMed, Embase, and Cochrane databases on June 5, 2023. Additionally, results were added from a new randomized clinical trial (RCT) and additional unpublished data from an already published RCT. Study Selection: Comparative studies reporting pain response after SBRT vs cEBRT in patients with painful bone metastases. Data Extraction and Synthesis: Two independent reviewers extracted data from eligible studies. Data were extracted for the intention-to-treat (ITT) and per-protocol (PP) populations. The study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Overall and complete pain response at 1, 3, and 6 months after radiotherapy, according to the study's definition. Relative risk ratios (RRs) with 95% CIs were calculated for each study. A random-effects model using a restricted maximum likelihood estimator was applied for meta-analysis. Results: There were 18 studies with 1685 patients included in the systematic review and 8 RCTs with 1090 patients were included in the meta-analysis. In 7 RCTs, overall pain response was defined according to the International Consensus on Palliative Radiotherapy Endpoints in clinical trials (ICPRE). The complete pain response was reported in 6 RCTs, all defined according to the ICPRE. The ITT meta-analyses showed that the overall pain response rates did not differ between cEBRT and SBRT at 1 (RR, 1.14; 95% CI, 0.99-1.30), 3 (RR, 1.19; 95% CI, 0.96-1.47), or 6 (RR, 1.22; 95% CI, 0.96-1.54) months. However, SBRT was associated with a higher complete pain response at 1 (RR, 1.43; 95% CI, 1.02-2.01), 3 (RR, 1.80; 95% CI, 1.16-2.78), and 6 (RR, 2.47; 95% CI, 1.24-4.91) months after radiotherapy. The PP meta-analyses showed comparable results. Conclusions and Relevance: In this systematic review and meta-analysis, patients with painful bone metastases experienced similar overall pain response after SBRT compared with cEBRT. More patients had complete pain alleviation after SBRT, suggesting that selected subgroups will benefit from SBRT.

Efficacy, Safety, and Population Pharmacokinetics of MW032 Compared With Denosumab for Solid Tumor-Related Bone Metastases: A Randomized, Double-Blind, Phase 3 Equivalence Trial.

Importance: The bioequivalence of denosumab biosimilar has yet to be studied in a 53-week, multicenter, large-scale, and head-to-head trial. A clinically effective biosimilar may help increase access to denosumab in patients with solid tumor-related bone metastases. Objectives: To establish the biosimilarity of MW032 to denosumab in patients with solid tumor-related bone metastases based on a large-scale head-to-head study. Design, Setting, and Participants: In this 53-week, randomized, double-blind, phase 3 equivalence trial, patients with solid tumors with bone metastasis were recruited from 46 clinical sites in China. Overall, 856 patients were screened and 708 eligible patients were randomly allocated to receive either MW032 or denosumab. Interventions: Patients were randomly assigned (1:1) to receive MW032 or reference denosumab subcutaneously every 4 weeks until week 49. Main Outcomes and Measures: The primary end point was percentage change from baseline to week 13 of natural logarithmic transformed urinary N-telopeptide/creatinine ratio (uNTx/uCr). Results: Among the 701 evaluable patients (350 in the MW032 group and 351 in the denosumab group), the mean (range) age was 56.1 (22.0-86.0) years and 460 patients were women (65.6%). The mean change of uNTx/uCr from baseline to week 13 was -72.0% (95% CI, -73.5% to -70.4%) in the MW032 group and -72.7% (95% CI, -74.2% to -71.2%) in the denosumab group. These percent changes corresponded to mean logarithmic ratios of -1.27 and -1.30, or a difference of 0.02. The 90% CI for the difference (-0.04 to 0.09) was within the equivalence margin (-0.13 to 0.13); the mean changes of uNTx/uCr and bone-specific alkaline phosphatase (s-BALP) at each time point were also similar during 53 weeks. The differences of uNTx/uCr change were 0.015 (95% CI, -0.06 to 0.09), -0.02 (95% CI, -0.09 to 0.06), -0.05 (95% CI, -0.13 to 0.03) and 0.001 (95% CI, -0.10 to 0.10) at weeks 5, 25, 37, and 53, respectively. The differences of s-BALP change were -0.006 (95% CI, 0.06 to 0.05), 0.00 (95% CI, -0.07 to 0.07), -0.085 (95% CI, -0.18 to 0.01), -0.09 (95% CI, -0.20 to 0.02), and -0.13 (95% CI, -0.27 to 0.004) at weeks 5, 13, 25, 37 and 53, respectively. No significant differences were observed in the incidence of skeletal-related events (-1.4%; 95% CI, -5.8% to 3.0%) or time to first on-study skeletal-related events (unadjusted HR, 0.86; P = .53; multiplicity adjusted HR, 0.87; P = .55) in the 2 groups. Conclusions and Relevance: MW032 and denosumab were biosimilar in efficacy, population pharmacokinetics, and safety profile. Availability of denosumab biosimilars may broaden the access to denosumab and reduce the drug burden for patients with advanced tumors. Trial Registration: ClinicalTrials.gov Identifier: NCT04812509.