Factors associated with work sustainability in patients with bone metastasis.

BACKGROUND: Working while receiving cancer treatment is challenging for patients, with considerable impact on their quality of life (QOL). However, there have been no reports on the factors that prevent employment in patients with bone metastases. This study aimed to investigate the employment status and factors impacting the continued employment of patients with bone metastases. METHODS: We analyzed clinical data from new patients consulting The University of Tokyo Hospital team for bone metastasis treatment between June 2015 and September 2017. Patients who were working at the time of cancer diagnosis (n = 124) completed four QOL questionnaires. Factors associated with work sustainability were identified via univariate analysis and a chi-squared test. Multivariate logistic regression analysis was used for significant variables. Relationships between employment and QOL scales were investigated using the Wilcoxon rank-sum test, with P < .05 considered as statistically significant. RESULTS: Among the 124 patients, only 45 (36.3%) were still working when the questionnaire was administered. Multivariate analysis revealed temporary employment, lytic or mixed bone metastases, and lower limb or acetabular metastasis, as significant factors hindering work sustainability. The QOL scores were high in the continued employment group. However, the relationship between employment status and pain remains unclear. CONCLUSIONS: Lytic or mixed bone metastases and the lower limb and acetabular metastasis were significantly associated with employment resignation. Mobility difficulties may prevent patients with bone metastases from sustaining employment. Collaboration between rehabilitation professionals, oncologists, and workplaces is imperative to address this problem.

End-of-life walking ability in cancer patients with spinal metastases.

BACKGROUND: Even terminal cancer patients desire to walk to the toilet by themselves until the very last day. This study aimed to describe the walking ability of patients with spinal metastases at the end-of-life stage and identify the factors affecting this ability. METHODS: Among 527 patients who first visited our multidisciplinary team for bone metastasis between 2013 and 2016, 56 patients who had spinal metastases with a Spinal Instability Neoplastic Score ≥7 and died during follow-up were included. We collected general clinical data, performance status, Frankel classification, epidural spinal cord compression scale and Spinal Instability Neoplastic Score at the first consultation. Patients' last day of walking and date of death were also examined. Univariate analyses (chi-squared tests) were performed to identify the factors that impacted walking ability 30 and 14 days before patients' death. RESULTS: A total of 56 patients were extracted, and 57.1% (32/56) and 32.7% (16/49) of patients were ambulatory 30 and 14 days before death, respectively. Their performance status (P = 0.0007), Frankel grade (P = 0.012) and epidural spinal cord compression grade (P = 0.006) at the first examination, and administration of bone modifying agents during follow-up period (P = 0.029) were significantly related to walking ability 30 days before death. Among ambulatory patients 30 days before death, those with Spinal Instability Neoplastic Score ≥10 (P = 0.005), especially with high scores of collapse (P = 0.002) and alignment (P = 0.002), were less likely to walk 14 days before death. The walking period in the last month of their life was significantly longer in patients with total Spinal Instability Neoplastic Score 7-9 (P = 0.009) and in patients without collapse (P = 0.040) by the Wilcoxon test. CONCLUSION: The progression of spinal metastasis, especially neurological deficit, at the initial consultation were associated with walking ability 30 days before death, and spinal stability might be crucial for preserving walking ability during the last month. Early diagnosis and implementation of appropriate bone management might be important for the end-of-life walking ability.

Comparison of clinical outcome between surgical treatment and particle beam therapy for pelvic bone sarcomas: A retrospective multicenter study in Japan.

BACKGROUND: Few studies have compared the clinical outcomes of patients with pelvic bone sarcomas treated surgically and those treated with particle beam therapy. This is a multicenter retrospective cohort study which compared the clinical outcomes of patients with pelvic bone sarcoma who underwent surgical treatment and particle beam therapy in Japan. METHODS: A total of 116 patients with pelvic bone sarcoma treated at 19 specialized sarcoma centers in Japan were included in this study. Fifty-seven patients underwent surgery (surgery group), and 59 patients underwent particle beam therapy (particle beam group; carbon-ion radiotherapy: 55 patients, proton: four patients). RESULTS: The median age at primary tumor diagnosis was 52 years in the surgery group and 66 years in the particle beam group (P < 0.001), and the median tumor size was 9 cm in the surgery group and 8 cm in the particle beam group (P = 0.091). Overall survival (OS), local control (LC), and metastasis-free survival (MFS) rates were evaluated using the Kaplan-Meier method and compared among 116 patients with bone sarcoma (surgery group, 57 patients; particle beam group, 59 patients). After propensity score matching, the 3-year OS, LC, and MFS rates were 82.9% (95% confidence interval [CI], 60.5-93.2%), 66.0% (95% CI, 43.3-81.3%), and 78.4% (95% CI, 55.5-90.5%), respectively, in the surgery group and 64.9% (95% CI, 41.7-80.8%), 86.4% (95% CI, 63.3-95.4%), and 62.6% (95% CI, 38.5-79.4%), respectively, in the particle beam group. In chordoma patients, only surgery was significantly correlated with worse LC in the univariate analysis. CONCLUSIONS: The groups had no significant differences in the OS, LC, and MFS rates. Among the patients with chordomas, the 3-year LC rate in the particle beam group was significantly higher than in the surgery group.

Evaluation of Changes in Activities of Daily Living and Quality of Life of Patients with Bone Metastasis Who Underwent Conservative Therapy through Bone Metastasis Cancer Boards.

Background and Objectives: Changes in activities of daily living (ADL) and quality of life (QOL) of patients with bone metastasis who underwent surgical treatment through Bone Metastasis Cancer Boards (BMCBs), a recent multidisciplinary approach for managing bone metastases, have been reported; however, no reports exist on patients who undergo conservative treatment. In this study, we aimed to evaluate these patients' ADL and QOL and examine the factors influencing changes in these parameters. Materials and Methods: We retrospectively reviewed 200 patients with bone metastases who underwent conservative therapy through BMCBs between 2013 and 2021. A reassessment was conducted within 2-8 weeks after the initial assessment. Patients' background and changes in performance status (PS), Barthel Index (BI), EuroQol five-dimension (EQ-5D) scores, and Numerical Rating Scale (NRS) scores were initially assessed. Furthermore, we categorized patients into two groups based on improvements or deteriorations in ADL and QOL and performed comparative analyses. Results: Significant improvements in EQ-5D (0.57 ± 0.02 versus [vs.] 0.64 ± 0.02), NRS max (5.21 ± 0.24 vs. 3.56 ± 0.21), and NRS average (2.98 ± 0.18 vs. 1.85 ± 0.13) scores were observed between the initial assessment and reassessment (all p < 0.001). PS (1.84 ± 0.08 vs. 1.72 ± 0.08) and BI (83.15 ± 1.68 vs. 84.42 ± 1.73) also showed improvements (p = 0.06, and 0.054, respectively). In addition, spinal cord paralysis (odds ratio [OR]: 3.69, p = 0.049; OR: 8.42, p < 0.001), chemotherapy (OR: 0.43, p = 0.02; OR: 0.25, p = 0.007), and NRS average scores (OR: 0.38, p = 0.02; OR: 0.14, p < 0.001) were independent factors associated with ADL and QOL. Conclusions: Patients with bone metastases who underwent conservative treatment through BMCBs exhibited an increase in QOL without a decline in ADL. The presence of spinal cord paralysis, absence of chemotherapy, and poor pain control were associated with a higher risk of deterioration in ADL and QOL.

Systemic inflammation response index (SIRI) as a predictive factor for overall survival in advanced soft tissue sarcoma treated with eribulin.

BACKGROUND: Eribulin is a tubulin and microtubule-targeting drug that has clinical benefit in overall survival (OS) for patients with advanced soft tissue sarcoma. Eribulin's efficacy has been confirmed in several clinical trials, although no clinically useful biomarkers have been identified. We therefore sought to clarify the predictive factor of eribulin treatment, while focusing on systemic inflammation and immune response values. METHODS: This study included 33 advanced STS patients treated with eribulin between March 2016 and September 2019. We evaluated the associations of clinical factors influencing the efficacy of eribulin treatment and systemic inflammatory and immune response, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the systemic inflammation response index (SIRI), and the prognostic nutrition index (PNI), with progression-free survival (PFS) and OS using the Kaplan-Meier method and log-rank test. RESULTS: NLR, LMR, PLR, SIRI, and PNI were unassociated with PFS. Compared with patients with SIRI <1.5, those with an SIRI ≥1.5 had a significantly shorter OS [median OS 15 months (95% confidence interval [CI] 8-not reached) vs. 7 months (95% CI 3-14), P = 0.04]. Moreover, the PFS tended to be shorter for patients with SIRI ≥1.5 who received chemotherapy after eribulin treatment than in those with SIRI >1.5 [median PFS 92.5 days (95% CI 27-204) vs. 133 days (95% CI 36-507), P = 0.08]. CONCLUSIONS: High SIRI values may predict poorer overall survival and the efficacy of subsequent drugs after eribulin treatment among patients with advanced soft tissue sarcoma.

Predictive factors of the 30-day mortality after surgery for spinal metastasis: Analysis of a nationwide database.

BACKGROUND: Surgical procedure for symptomatic spinal metastasis is expected to improve the quality of life. Factors related to short-term perioperative mortality after surgery for spinal metastasis may be different from those related to long-term mortality, which have classically been used to determine the indication for surgery. The purposes of this study were to evaluate factors related to the 30-day mortality after surgery for spinal metastasis and create an integer risk scoring system. METHODS: Using the Diagnosis Procedure Combination database from 2010 to 2016, we extracted data of patients who underwent surgical procedure for spinal metastasis. Multivariable logistic regression analysis was performed to clarify the association between patient backgrounds and the 30-day postoperative mortality. We created a risk scoring system using regression coefficients to estimate the 30-day mortality for each patient. RESULTS: Among 3524 patients, the 30-day mortality was 2.6%. Factors associated with a higher 30-day mortality were male sex (odds ratio, 2.50 [95% confidence interval, 1.45-4.31]), emergency admission (1.80 [1.11-2.92]), rapid growth tumors (3.83 [2.49-5.90]), and non-skeletal metastasis (2.27 [1.42-3.64]). In patients with the maximum risk score of five, the 30-day mortality was 16.2%. CONCLUSIONS: Factors related to the 30-day mortality were male sex, emergency admission, rapid growth tumors, and non-skeletal metastasis. These findings provide spine surgeons and patients knowledge of the potential risk of short-term perioperative mortality and allow them to consider the risk of surgery.

Pretreatment serum C-reactive protein is a significant prognostic factor in patients with soft tissue metastases.

BACKGROUND: Soft tissue metastasis is rarer than bone metastasis. Patients with soft tissue metastasis generally have a dismal prognosis. The treatment for metastatic lesions is sometimes difficult, because the prognostic factors of patients with soft tissue metastasis remain unelucidated. Therefore, this study aimed to identify these prognostic factors. METHODS: Thirty-one patients with soft tissue metastasis were included in the study. We evaluated associations of overall survival with clinical parameters and inflammatory markers using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Twelve patients received surgery for soft tissue metastasis, while radiation therapy was performed in six cases. The median overall survival after the detection of soft tissue metastasis was 11 months. Univariate analysis revealed that detection of soft tissue metastasis after the multidisciplinary treatment (P = 0.01); solitary metastasis (P = 0.0003); and pretreatment C-reactive protein (CRP) level < 0.4 mg/dL (P < 0.0001), white blood cell count < 8500 × 103/µL (P = 0.0003), and neutrophil-to-lymphocyte ratio < 5 (P = 0.02) were significant good prognostic factors. Multivariate analysis revealed that a CRP value < 0.4 mg/dL (P = 0.07) and solitary metastasis (P = 0.09) were possible significant predictors of survival. Furthermore, in case of CRP levels <0.4 mg/dL and metastatic tumor resection, patients had a good prognosis; however, when the CRP levels increased to 0.4 mg/dL and above, patients had a poor prognosis, irrespective of tumor resection. CONCLUSIONS: CRP is potentially useful for determining the indication of radical metastasectomy in soft tissue metastasis.

Bone metastasis of limb segments: Is mesometastasis another poor prognostic factor of cancer patients?

OBJECTIVE: In contrast to acrometastasis, defined as bone metastasis to the hand or foot, the frequency and prognosis of bone metastasis of other limb segments remain unclear. To compare prognosis according to sites of bone metastasis, we defined two new terms in this study: 'mesometastasis' and 'rhizometastasis' as bone metastasis of 'forearm or lower leg' and 'arm or thigh', respectively. METHODS: A total of 539 patients who were registered to the bone metastasis database of The University of Tokyo Hospital from April 2012 to May 2016 were retrospectively surveyed. All patients who were diagnosed to have bone metastases in our hospital are registered to the database. Patients were categorized into four groups according to the most distal site of bone metastases: 'acrometastasis', 'mesometastasis', 'rhizometastasis' and 'body trunk metastasis'. RESULTS: The frequency of rhizometastasis (22.5%) or body trunk metastasis (73.1%) was significantly higher than that of acrometastasis (2.0%) or mesometastasis (2.4%). The median survival time after diagnosis of bone metastases for each group was as follows: 6.5 months in acrometastasis, 4.0 months in mesometastasis, 16 months in rhizometastasis, 17 months in body trunk metastasis and 16 months overall. In survival curve, there was a statistically significant difference between mesometastasis and body trunk metastasis. CONCLUSIONS: Our findings suggest that 'mesometastasis' could be another poor prognostic factor in cancer patients and that patients with mesometastasis should receive appropriate treatments according to their expected prognosis.

Fibrodysplasia ossificans progressiva: Review and research activities in Japan.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic skeletal disorder manifesting progressive heterotopic ossification (HO) and congenital malformation of the great toes. Since 2007, we have conducted research on FOP. Here, we review the findings on FOP published to date, including the results of our research. Epidemiological studies in Japan have indicated that FOP has nearly the same prevalence in Japan as in the rest of the world. Basic research on its pathoetiology has progressed rapidly since the identification of the causal gene in 2006. Clinical and radiological findings have been thoroughly researched, including early radiological signs, and diagnostic criteria were established, designating FOP as an intractable disease in Japan. In patients with FOP, the progression of HO is associated with numerous disabilities, often manifesting in vicious cycles that can lead to early mortality. Through cross-sectional and short-term longitudinal studies, we have explored patient education, quality of life, and activities of daily living among Japanese patients. The management of FOP requires education of patients and caregivers, the use of medications to settle inflammation and flare-ups, instructions to ensure proper oral care, and other compensatory approaches that aid in rehabilitation. An avoidance of medical intervention, which may cause HO to progress, is also important. The advent of new drugs to prevent HO could have clinical benefit.

Early detection of bone metastases of hepatocellular carcinoma reduces bone fracture and paralysis.

BACKGROUND: With the improvement in survival of hepatocellular carcinoma patients, extrahepatic metastases have become a more frequent complication. Although pathological fractures or paralysis due to bone metastases deteriorate the quality of life of patients, no treatment guideline for bone metastases has been established. This study aimed to clarify the risk factors for these events and the clinical course of patients with bone metastases. METHODS: Out of 783 hepatocellular carcinoma patients treated in our institution between 2009 and 2016, 76 patients with bone metastases were enrolled. They were divided into two groups by the trigger of bone metastases detection. One was those diagnosed by surveillance (surveillance group), and the other was those based on symptom presentation (non-surveillance group). We investigated the clinical features, risk factors for fractures or paralysis and prognostic factors for survival after bone metastases. RESULTS: Baseline characteristics and survival were not significantly different between two groups. Fractures or paralysis occurred in 10 patients (13.2%), and the frequency was significantly higher in the non-surveillance group (20.9%) than the surveillance group (3.0%) in univariate analysis (p = 0.036). The median survival after diagnosis of bone metastases was 11.7 months. Age over 75 years (p = 0.002), hepatitis C-virus etiology (p = 0.007) and Child-Pugh class B/C (p < 0.001) were significantly associated with a shorter survival in multivariate analysis, but fractures or paralysis did not affect the survival. CONCLUSIONS: Early diagnosis through surveillance for hepatocellular carcinoma bone metastases may prevent fractures or paralysis and lead to a better quality of life for these patients.

Body composition as a predictor of toxicity after treatment with eribulin for advanced soft tissue sarcoma.

BACKGROUND: Despite the clinical benefits of eribulin on overall survival of advanced soft tissue sarcoma (STS) patients, treatment-related toxicity reduces their QOL. Body composition metrics (BCMs) are associated with poor outcome and drug toxicities in several cancers. This study investigated whether BCMs could predict drug toxicity occurrence in advanced STS patients treated with eribulin. METHODS: This study included 23 advanced STS patients treated with eribulin between March 2016 and April 2018. BCMs were evaluated using a CT scan obtained within 1 month before or after treatment initiation. The relationship of BCMs and other clinical factors was evaluated and CART analysis used to develop classification models for risk groups of drug toxicity. RESULTS: Sixteen patients (69.6%) experienced any grade 3/4 toxicity. Eleven patients (47.8%) developed G4 hematologic toxicity, which was significantly higher in those with low skeletal muscle gauge (SMG) (P = 0.02) and low pretreatment neutrophil count (P = 0.0002). Six patients (26.1%) had grade 3/4 non-hematologic toxicity, and was higher in those with low SMG (P = 0.004), and low serum albumin level (P = 0.02). Five patients with high BMI (P = 0.03) experienced febrile neutropenia (FN) and low pretreatment neutrophil count (P = 0.02). CART analysis classified three risk groups, and area under the receiver operating characteristic curve (AUROCC) was 0.92, 0.88, 0.92 in G4 hematologic AE, G3/4 non-hematologic AE, FN, respectively. CONCLUSIONS: SMG is a significant predictive factor of eribulin drug toxicity in advanced STS patients. Risk classification of drug toxicity through combining predictive factors, could improve the therapeutic strategy used in chemotherapy.

Predictive factors for complications after surgical treatment for schwannomas of the extremities.

BACKGROUND: Schwannomas are well-encapsulated, benign neoplasms, and enucleation is a standard operation procedure. The incidence of neurological complications after surgical treatment for schwannomas of the extremities varies, and there is no consensus concerning predictive factors for complications. The aim of this study was to elucidate predictive factors for complications after surgical treatment of schwannomas that develop in the major nerves of the extremities. METHODS: A total of 139 patients with 141 schwannomas arising in major nerves were retrospectively analyzed. Data regarding preoperative clinical features, the postoperative neurological complications, and clinical course of complications, with a median follow-up period of 2 months (range, 0.5-96), were obtained. Predictive factors for complications were statistically analyzed. RESULTS: Postoperative complications occurred in 49 lesions (34.8%), including 42 with sensory disturbance and 8 with motor weakness. In univariate analysis, older age, tumors originating from the upper extremity, and major motor nerve involvement were associated with a higher complication rate (p = 0.03, p = 0.003, and p = 0.001, respectively). In multivariate analysis, major motor nerve involvement was an independent predictive factor for postoperative complications (p = 0.03). Almost all complications gradually improved, but 6 out of 8 patients with motor weakness did not show full recovery at the final follow-up. CONCLUSIONS: Schwannomas originating from major motor nerves can lead to a higher risk for postoperative complications.

Prediction of the pathological fracture risk during stance and fall-loading configurations for metastases in the proximal femur, using a computed tomography-based finite element method.

BACKGROUND: It is important to assess the fracture risk associated with metastasis in the proximal femur. The study aimed to clarify the effect of tumor location on the risk of pathological fracture of the proximal femur and investigate the fracture risk not only in the stance-loading configuration (SC), but also in the fall-loading configuration (FC) using a computed tomography (CT)-based finite element (FE) method based on a simulated metastatic model. METHODS: The axial CT scans of the proximal femora of non-osteoporotic healthy men (n = 4; age range, 42-48 years) and osteoporotic post-menopausal women (n = 4; age range, 69-78 years) were obtained with a calibration phantom, from which the three-dimensional FE models were constructed. A single 15-mm-diameter spherical void simulating a tumor was created at various locations from the neck to subtrochanteric level. Nonlinear FE analyses were performed. RESULTS: The mean predicted fracture loads without spherical voids in the SC were 7700 N in men and 4370 N in women. With the void at the medial femoral neck and in the region anteromedial to lesser trochanter, the mean predicted fracture load significantly reduced to 51.3% and 59.4% in men and 34.1% and 64.5% in women, respectively. The mean predicted fracture loads without a spherical void in the FC were 2500 N in men and 1862 N in women. With the void at the medial and posterior femoral neck, the predicted fracture load was significantly reduced to 65.7% and 79.7% in men and 48.3% and 65.4% in women, respectively. CONCLUSIONS: These results showed that the risk of pathologic fracture was quite high in both the SC and FC when the lytic lesion existed along the principal compressive trabecular trajectory or posterior neck. Prophylactic intervention should be considered for metastases at these locations.

Neutrophil-to-lymphocyte ratio after pazopanib treatment predicts response in patients with advanced soft-tissue sarcoma.

BACKGROUND: Pazopanib is a multi-tyrosine kinase inhibitor that is used to treat advanced soft-tissue sarcoma, and its efficacy has been confirmed in several clinical trials, although no clinically useful biomarkers have been identified. In other cancers, the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the lymphocyte-to-monocyte ratio (LMR) are associated with chemotherapy response and prognosis. Therefore, we aimed to evaluate the associations of pazopanib response with NLR, PLR, and LMR among patients with advanced soft-tissue sarcoma. METHODS: Data regarding NLR, PLR, and LMR were obtained for 25 patients who received pazopanib for soft-tissue sarcoma. The patients were categorized according to their values for NLR (≥3.8 vs. <3.8), PLR (≥230 vs. <230), and LMR (≥2.4 vs. <2.4), and we evaluated the associations of these markers with progression-free survival and overall survival using Kaplan-Meier curves and Cox proportional models. RESULTS: No significant differences in progression-free survival or overall survival were observed based on the pre-treatment NLR, PLR, and LMR values. However, decreased NLR values after treatment using pazopanib were independently associated with significantly prolonged progression-free survival (hazard ratio: 0.07, p = 0.001) and overall survival (hazard ratio: 0.17, p = 0.0006). CONCLUSIONS: Decreased NLR values after treatment using pazopanib may predict high efficacy and favorable outcomes among patients with advanced soft-tissue sarcoma.

Skeletal-related events and prognosis in urothelial cancer patients with bone metastasis.

BACKGROUND: The aim of the present study was to elucidate the details of bone metastasis (BM) and the resulting skeletal-related events (SREs), and survival and prognostic factors, in urothelial cancer (UC) patients with BM. METHODS: A total of 48 UC patients with BM who were treated at our institution between 1994 and 2013 were enrolled. Details of BM and SREs were investigated. The Kaplan-Meier method was used to estimate survival duration. Relationships between several clinical features and survival were analyzed using the log-rank test and the Cox hazard model. RESULTS: Of the 48 patients, 39 (81.3%) were male, with a median age at diagnosis of BM of 68 years [interquartile range (IQR), 61-75 years]. Frequent metastatic sites included the pelvis (31 patients, 64.6%) and spine (28, 58.3%). SREs occurred in 31 patients (64.6%) at a median duration of 0.9 months (IQR, 0.3-5.4 months) after diagnosis of BM, including radiation therapy (n = 23; 74.2%), spinal cord compression (n = 4; 12.9%), pathological fracture (n = 3; 9.7%) and hypercalcemia (n = 1; 3.2%). Median overall survival periods after diagnosis of BM and SREs were 6.2 and 5.6 months, respectively. On multivariate analysis, factors significantly associated with survival after BM were performance status [hazard ratio (HR) for ≥2 vs. 0-1, 4.94; P = 0.0003], liver metastasis (HR, 4.08; P = 0.0018), chemotherapy after BM (HR, 0.31; P = 0.0018), and use of bone-modifying agents (HR, 0.36; P = 0.0147). CONCLUSIONS: We revealed clinicopathological factors that are predictive of prognosis of UC patients with BM. Although the prognosis is poor, chemotherapy and bone-modifying agents may confer survival benefits.

Multidisciplinary Treatment for Breast Cancer-related Multiple Bone Metastases during Pregnancy Using Bone Metastasis Cancer Boards: A Case Report.

Background: In patients vulnerable to skeletal-related events (SREs), a multidisciplinary approach is required to manage risk and determine the best treatment plan. We have used Bone Metastasis Cancer Boards (BMCBs) to deliver multidisciplinary treatments in our hospital since 2013. Here, we report a case in which we used BMCBs to coordinate multidisciplinary treatment for a pregnant patient with breast cancer and multiple bone metastases. Case: A 41-year-old pregnant woman was admitted to our hospital because low back pain compromised her ability to stand. She was diagnosed with breast cancer-associated multiple bone metastases. Our unit was consulted for rehabilitation therapy, for which we formed a BMCB. The treatment was integrated and performed according to the recommendations of the BMCB. The patient underwent a cesarean section to initiate primary tumor treatment. After evaluating the risk of SREs, we provided her with rehabilitation therapy. Wearing a plastic molded thoracolumbosacral orthosis, she was able to walk with a pick-up walker. The patient continued outpatient chemotherapy and cared for her infant without experiencing any significant adverse events. Discussion: In this case, we formed our BMCB to determine the treatment plan, which we used to support the patient's needs during childbirth and successfully improved her activities of daily living. BMCBs can contribute to preventing SREs and provide effective rehabilitation therapy for patients with bone metastases. We aspire to continually gather experience through our BMCBs and contribute to the establishment of evidence regarding the effectiveness of rehabilitation therapy for patients with bone metastases.

Outcomes of palliative surgery for bone metastasis of metastatic renal cell carcinoma in the era of targeted therapy.

INTRODUCTION: The introduction of tyrosine kinase inhibitors has revolutionized treatment strategies for metastatic renal cell carcinoma (RCC) and has improved survival rates. The number of patients with bone metastases from RCC requiring surgery will increase as survival rates improve. However, there is insufficient evidence to standardize the treatment of bone metastases after the introduction of targeted therapy for metastatic RCC. We aimed to determine the outcomes of palliative surgical treatment of bone metastases in the extremities of patients with metastatic RCC. MATERIALS AND METHODS: We retrospectively reviewed 26 lesions from 17 patients who underwent surgery for extremity and acetabular bone metastases and were treated with targeted therapies for advanced RCC between 2008 and 2020. The median follow-up duration was 19 months (range, 4-76). We assessed the patients' activities of daily living, quality of life, and pain and analyzed their postoperative values relative to preoperative values. Postoperative overall survival (OS), local progression-free survival (LPFS), and the factors affecting them were evaluated using the Kaplan-Meier method and log-rank test. RESULTS: The 5-year OS and LPFS rates were 39.5% and 65.6%, respectively. The factors affecting OS were sex, Katagiri score, visceral metastases, and preoperative targeted therapy, while the factors affecting LPFS were pathologic fractures and surgical technique. CONCLUSION: In this study, the postoperative outcomes of palliative surgery for bone metastases from metastatic RCC were good. We suggest that systemic treatment should be prioritized over local control for advanced bone metastasis in RCC and surgery before pathological fracture should be performed for local control.

Identification and characterization of slow­cycling cells in Ewing sarcoma.

Ewing sarcoma (ES) is an aggressive primary malignant bone tumor that predominantly affects children and young adults. Multimodal treatment approaches have markedly improved the survival of patients with localized ES. However, local recurrence and distant metastasis following curative therapies remain a main concern for patients with ES. Recent studies have suggested that slow­cycling cells (SCCs) are associated with tumor progression, local recurrence and distant metastasis in various types of cancers. According to the results of these studies, it was hypothesized that SCCs may play a critical role in tumor progression, chemoresistance and local/distal recurrence in patients with ES. The present study applied a label­retaining system using carboxyfluorescein diacetate succinimidyl ester (CFSE) to identify and isolate SCCs in ES cell lines. In addition, the properties of SCCs, including sphere formation ability, cell cycle distribution and chemoresistance, in comparison with non­SCCs were investigated. RNA sequencing also revealed several upregulated genes in SCCs as compared with non­SCCs; the identified genes not only inhibited cell cycle progression, but also promoted the malignant properties of SCCs. On the whole, the present study successfully identified SCCs in ES cells through a label­retaining system using CFSE. Moreover, to the best of our knowledge, the present study is the first to describe the characteristic properties of SCCs in ES. The findings of this study, if confirmed, may prove to be useful in elucidating the underlying molecular mechanisms and identifying effective therapeutic targets for ES.

Prediction of pathological fracture in patients with lower limb bone metastasis using computed tomography imaging.

Lower limb pathological fractures caused by bone metastases can severely impair activities of daily living, so recognizing fracture risk is essential. Medial cortical involvement (MCI) in the proximal femur has been demonstrated to affect bone strength in biomechanical studies, but it has not been investigated in real patients. Between 2012 and 2019, 161 bone metastases with computed tomography (CT) images were retrospectively examined. Twenty-nine fractures were observed including 14 metastases with pathological fractures at the first examination, and prophylactic surgery was performed for 50 metastases. We extracted clinicopathological data using CT images, including patient's background, MCI in the proximal femur, site, size, circumferential cortical involvement (CCI), pain, and nature of metastasis. Cox proportional hazard regression analyses were performed, and we created integer scores for predicting fractures. We revealed that MCI, CCI, lytic dominant lesion, and pain were significant factors by univariate analyses. By multivariable analysis, MCI and each 25% CCI were significant and integer score 1 was assigned based on hazard ratio. The full score was four points, with MCI in the proximal femur (one point) and ≥ 75% CCI (three points). With integer score two, sensitivity was 88.9% and specificity was 81.2% for predicting fracture within 60 days. In conclusion, MCI and CCI examined by CT images were the risk factors for pathological fracture. CCI ≥ 50% is a widely known risk factor, but in addition, it may be better to consider surgery if MCI in the proximal femur is observed in metastasis with 25-50% CCI.