Long Bone Metastases Research Articles

Intervention for impending pathological fractures at proximal femur is associated with lower mortality rates in patients with intermediate-to-high risk according to the Katagiri-New score

BackgroundProphylactic intervention for impending pathological fractures (IF) is associated with improved survival in patients with long-bone metastasis. However, information regarding whether the tumor burden and/or physical status are associated with survival benefits of intervention for IF is lacking.MethodsThis multicenter retrospective study investigated 121 patients who underwent surgery for 63 impending and 58 complete metastatic fractures of the proximal femur between 2008 and 2023. After matching for age, sex, body mass index, and Katagiri-New score, 42 patients with IF were compared with 42 patients with complete pathological fractures. The 1-year mortality rate was considered the primary outcome, and was compared and stratified by risk based on the Katagiri-New score. The 1-year mortality rate was evaluated according to the surgical method in the subgroup analysis of patients with IF.ResultsThe 1-year mortality rate was significantly lower in patients with IF with intermediate-to-high risk(p = 0.04), whereas no difference was observed in patients with low-to-high risk. IF was associated with a significantly higher rate of home discharge (p < 0.01) and improved post-operative ambulatory function (p = 0.07). The subgroup analysis of patients with IF revealed no difference in the survival rate between nailing and hemiarthroplasty.ConclusionPatients with intermediate-to-high risk IF based on the Katagiri-New score had a lower mortality rate than those who underwent surgery for pathological fractures. A higher rate of home discharge was observed in patients with IF. Based on the Katagiri-New score, survival benefits can be obtained from prophylactic intervention for IF of the proximal femur in patients with intermediate-to high-risk.

Long bone metastases of renal cell carcinoma imaging features: case report and literature review

Abstract Objectives This article analyzed the imaging features of 18 long bone metastasis (LBM) of renal cell carcinoma (RCC) confirmed by pathology and reviewed the available literature. Case presentation Patients who underwent radiographic examinations at our hospital between January 2015 and December 2021 with pathology-confirmed bone metastases were evaluated. The clinical and radiographs and CT, and MR images features of the patients were analyzed. Eighteen patients with pathology-confirmed LBM from RCC were collected. All the patients had X-ray examinations, 15 had computed tomography (CT), 13 had magnetic resonance (MR) imaging, and six had MR enhancement. The clinical and imaging features of the lesions were analyzed, including morphological and signal intensity characteristics. Ten patients were found with metastases after nephrectomy, and eight patients were admitted to the hospital with skeletal-related events (SREs). Eighteen cases originated from clear cell RCC. Fourteen lesions were located in the epiphysis and four in the diaphysis. The height-to-width ratio of the lesions ranged from 1.11 to 3.41 (mean, 1.84). All lesions showed osteolytic destruction, with 16 lesions showing expansile destruction. Seven lesions demonstrated soap bubble hyperintensity and hypointense separation on T2-weighted images. Six lesions demonstrated a flow-void sign, and six showed marked marginal enhancement. Conclusions The LBM of RCC mainly occurred in the proximal epiphysis and tended to spread along the long bone axis with expansile osteolytic destruction. In some cases, soap bubble hyperintensity, hypointense separation, and the flow-void sign were seen.

Factors Associated with Revision Surgery in Long Bones Metastases

Background. Bones as an organ are one of the most common targets for tumor metastasis. Currently, the number of patients undergoing surgical treatment for metastatic bone lesions is steadily increasing. In most patients, after surgical treatment, the manifestation of clinical symptoms decreases, primarily pain syndrome, which improves their quality of life. However, it should be noted that the number of patients with bone metastases who underwent revision surgery is also increasing. This article retrospectively analyzes the factors leading to revision after surgical treatment of metastases in long bones.&#x0D; The aim of this study was to identify factors leading to revision after surgical treatment of patients with metastases in long bones.&#x0D; Methods. A retrospective medical records analysis of 247 patients who underwent surgical treatment for metastases in long bones on the basis of the P.A. Herzen Moscow Research Institute of Oncology in 20062020 was performed. Of these, 33 patients underwent revision surgery. The median age was 62 years. The localization of the primary tumor was as follows: breast cancer 10 cases, kidney cancer 13, lung cancer 3, prostate cancer 2, rectal cancer 3, liver cancer and Ewings sarcoma with bone metastases 1 case each.&#x0D; Results. The following factors led to revision surgery: mistakes in preoperative diagnosis (3 patients); postoperative infectious complication (6 patients); dislocation of the endoprosthesis (4 patients); continued growth of solitary metastasis after osteosynthesis (5 cases); aseptic instability after intramedullary osteosynthesis (14 patients); traumatic fracture of the endoprosthesis stem (1 patient).&#x0D; Conclusions. Revision after surgical treatment of metastases in long bones, in addition to postoperative complications, lead to mistakes in diagnosis and incorrect choice of surgical treatment method. To reduce the risk of revision surgical interventions, a multidisciplinary approach is needed with the development of surgical treatment tactics in consultation and the use of specialized scales of oncological prognosis.

Stereotactic Body Radiation Therapy for Metastases in Long Bones

To evaluate the cumulative incidence of fracture and local failure and associated risk factors after stereotactic body radiation therapy (SBRT) for long bone metastases. Data from 111 patients with 114 metastases in the femur, humerus, and tibia treated with SBRT in 7 international centers between October 2011 and February 2021 were retrospectively reviewed and analyzed using a competing risk regression model. The median follow-up was 21 months (range, 6-91 months). All but 1 patient had a Karnofsky performance status ≥70. There were 84 femur (73.7%), 26 humerus (22.8%), and 4 tibia (3.5%) metastases from prostate (45 [39.5%]), breast (22 [19.3%]), lung (15 [13.2%]), kidney (13 [11.4%]), and other (19 [16.6%]) malignancies. Oligometastases accounted for 74.8% of metastases and 28.1% were osteolytic. The most common total doses were 30 to 50 Gy in 5 daily fractions (50.9%). Eight fractures (5 in the femur, 2 in the tibia, and 1 in the humerus) were observed with a median time to fracture of 12 months (range, 0.8-33 months). In 6 out of 8 patients, fracture was not associated with local failure. The cumulative incidence of fracture was 3.5%, 6.1%, and 9.8% at 1, 2, and 3 years, respectively. The cumulative incidence of local failure (9/110 metastases with imaging follow-up) was 5.7%, 7.2%, and 13.5% at 1, 2, and 3 years, respectively. On multivariate analysis, extraosseous disease extension was significantly associated with fracture (P=.001; subhazard ratio, 10.8; 95% confidence interval, 2.8-41.9) and local failure (P=.02; subhazard ratio, 7.9; 95% confidence interval, 1.4-44.7). SBRT for metastases in long bones achieved high rates of durable local metastasis control without an increased risk of fracture. Similar to spine SBRT, patients with extraosseous disease extension are at higher risk of local failure and fracture.

Clinical Outcome Differences in the Treatment of Impending Versus Completed Pathological Long-Bone Fractures.

The outcome differences following surgery for an impending versus a completed pathological fracture have not been clearly defined. The purpose of the present study was to assess differences in outcomes following the surgical treatment of impending versus completed pathological fractures in patients with long-bone metastases in terms of (1) 90-day and 1-year survival and (2) intraoperative blood loss, perioperative blood transfusion, anesthesia time, duration of hospitalization, 30-day postoperative systemic complications, and reoperations. We retrospectively performed a matched cohort study utilizing a database of 1,064 patients who had undergone operative treatment for 462 impending and 602 completed metastatic long-bone fractures. After matching on 22 variables, including primary tumor, visceral metastases, and surgical treatment, 270 impending pathological fractures were matched to 270 completed pathological fractures. The primary outcome was assessed with the Cox proportional hazard model. The secondary outcomes were assessed with the McNemar test and the Wilcoxon signed-rank test. The 90-day survival rate did not differ between the groups (HR, 1.13 [95% CI, 0.81 to 1.56]; p = 0.48), but the 1-year survival rate was worse for completed pathological fractures (46% versus 38%) (HR, 1.28 [95% CI, 1.02 to 1.61]; p = 0.03). With regard to secondary outcomes, completed pathological fractures were associated with higher intraoperative estimated blood loss (p = 0.03), a higher rate of perioperative blood transfusions (p = 0.01), longer anesthesia time (p = 0.04), and more reoperations (OR, 2.50 [95% CI, 1.92 to 7.86]; p = 0.03); no differences were found in terms of the rate of 30-day postoperative complications or the duration of hospitalization. Patients undergoing surgery for impending pathological fractures had lower 1-year mortality rates and better secondary outcomes as compared with patients undergoing surgery for completed pathological fractures when accounting for 22 covariates through propensity matching. Patients with an impending pathological fracture appear to benefit from prophylactic stabilization as stabilizing a completed pathological fracture seems to be associated with increased mortality, blood loss, rate of blood transfusions, duration of surgery, and reoperation risk. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

International Validation of the SORG Machine-learning Algorithm for Predicting the Survival of Patients with Extremity Metastases Undergoing Surgical Treatment.

The Skeletal Oncology Research Group machine-learning algorithms (SORG-MLAs) estimate 90-day and 1-year survival in patients with long-bone metastases undergoing surgical treatment and have demonstrated good discriminatory ability on internal validation. However, the performance of a prediction model could potentially vary by race or region, and the SORG-MLA must be externally validated in an Asian cohort. Furthermore, the authors of the original developmental study did not consider the Eastern Cooperative Oncology Group (ECOG) performance status, a survival prognosticator repeatedly validated in other studies, in their algorithms because of missing data. (1) Is the SORG-MLA generalizable to Taiwanese patients for predicting 90-day and 1-year mortality? (2) Is the ECOG score an independent factor associated with 90-day and 1-year mortality while controlling for SORG-MLA predictions? All 356 patients who underwent surgery for long-bone metastases between 2014 and 2019 at one tertiary care center in Taiwan were included. Ninety-eight percent (349 of 356) of patients were of Han Chinese descent. The median (range) patient age was 61 years (25 to 95), 52% (184 of 356) were women, and the median BMI was 23 kg/m2 (13 to 39 kg/m2). The most common primary tumors were lung cancer (33% [116 of 356]) and breast cancer (16% [58 of 356]). Fifty-five percent (195 of 356) of patients presented with a complete pathologic fracture. Intramedullary nailing was the most commonly performed type of surgery (59% [210 of 356]), followed by plate screw fixation (23% [81 of 356]) and endoprosthetic reconstruction (18% [65 of 356]). Six patients were lost to follow-up within 90 days; 30 were lost to follow-up within 1 year. Eighty-five percent (301 of 356) of patients were followed until death or for at least 2 years. Survival was 82% (287 of 350) at 90 days and 49% (159 of 326) at 1 year. The model's performance metrics included discrimination (concordance index [c-index]), calibration (intercept and slope), and Brier score. In general, a c-index of 0.5 indicates random guess and a c-index of 0.8 denotes excellent discrimination. Calibration refers to the agreement between the predicted outcomes and the actual outcomes, with a perfect calibration having an intercept of 0 and a slope of 1. The Brier score of a prediction model must be compared with and ideally should be smaller than the score of the null model. A decision curve analysis was then performed for the 90-day and 1-year prediction models to evaluate their net benefit across a range of different threshold probabilities. A multivariate logistic regression analysis was used to evaluate whether the ECOG score was an independent prognosticator while controlling for the SORG-MLA's predictions. We did not perform retraining/recalibration because we were not trying to update the SORG-MLA algorithm in this study. The SORG-MLA had good discriminatory ability at both timepoints, with a c-index of 0.80 (95% confidence interval 0.74 to 0.86) for 90-day survival prediction and a c-index of 0.84 (95% CI 0.80 to 0.89) for 1-year survival prediction. However, the calibration analysis showed that the SORG-MLAs tended to underestimate Taiwanese patients' survival (90-day survival prediction: calibration intercept 0.78 [95% CI 0.46 to 1.10], calibration slope 0.74 [95% CI 0.53 to 0.96]; 1-year survival prediction: calibration intercept 0.75 [95% CI 0.49 to 1.00], calibration slope 1.22 [95% CI 0.95 to 1.49]). The Brier score of the 90-day and 1-year SORG-MLA prediction models was lower than their respective null model (0.12 versus 0.16 for 90-day prediction; 0.16 versus 0.25 for 1-year prediction), indicating good overall performance of SORG-MLAs at these two timepoints. Decision curve analysis showed SORG-MLAs provided net benefits when threshold probabilities ranged from 0.40 to 0.95 for 90-day survival prediction and from 0.15 to 1.0 for 1-year prediction. The ECOG score was an independent factor associated with 90-day mortality (odds ratio 1.94 [95% CI 1.01 to 3.73]) but not 1-year mortality (OR 1.07 [95% CI 0.53 to 2.17]) after controlling for SORG-MLA predictions for 90-day and 1-year survival, respectively. SORG-MLAs retained good discriminatory ability in Taiwanese patients with long-bone metastases, although their actual survival time was slightly underestimated. More international validation and incremental value studies that address factors such as the ECOG score are warranted to refine the algorithms, which can be freely accessed online at https://sorg-apps.shinyapps.io/extremitymetssurvival/. Level III, therapeutic study.

International Consensus Contouring Recommendations for Stereotactic Body Radiotherapy of Non-Spine Bone Metastases

Despite the increasing use of stereotactic body radiotherapy (SBRT) for non-spine bone metastases (NSBM), there are no established guidelines for clinical target volume (CTV) delineation. The objective of this study was to provide recommendations on CTV delineation based on international expert consensus contours. Eleven cases were contoured by nine international radiation oncologists with demonstrated expertise in NSBM SBRT via publications and/or clinical experience. Cases included metastases in long bones (femur, humerus), pelvic bones (ilium, ischium, acetabulum, pubic symphysis) and thoracic bones (rib, sternum, scapula, clavicle). For each case the gross tumor volume (GTV) was provided on the simulation CT scans, which were accompanied by corresponding MR imaging. Experts then contoured the CTV and completed a clinical survey. Agreement between expert CTV contours was analyzed with simultaneous truth and performance level estimation (STAPLE) using the kappa coefficient and with the Dice similarity coefficient (DSC), and summarized to establish contouring recommendations. All CTV contours were completed for each of the eleven cases. Six experts used a single dose level, while 3 used a two-dose level (high dose and low dose) simultaneous integrated boost (SIB) technique. For the SIB cases, only the high dose CTV was used for contour analysis. There was substantial agreement between expert contours across cases with a mean and median kappa measure of 0.72 and 0.71 (range, 0.61-0.86), respectively. The mean and median DSC values were 0.77 and 0.79 (range, 0.67-0.87), respectively. Consensus CTV contouring recommendations consist of: 1) A ≤5mm intraosseous ± ≤5mm extraosseous margin beyond the GTV; 2) An extraosseous CTV margin should be strongly considered in cases of associated soft tissue disease and/or significant cortical bone disruption; 3) All CTVs should be manually modified to spare uninvolved joint spaces and organs-at-risk while respecting natural anatomical barriers (e.g. peritoneal cavity, pleura). Consensus CTV contouring recommendations for NSBM SBRT were established based on analysis of international expert consensus contours with a high level of agreement. Detailed quantitative margin analysis in three-dimensions is ongoing to define the optimal extent of CTV margins. Until prospective clinical data are available to inform patterns of failure, these recommendations may serve as guiding principles for treating physicians.

High rate of fracture in long-bone metastasis: Proposal for an improved Mirels predictive score

IntroductionPathologic fracture is the most feared complication in long-bone metastasis. Various radiographic tools are available for identifying at-risk patients and guide preventive treatment. The Mirels score is the most frequently studied and widely used, but has been criticized, many patients not being operated on until the actual fracture stage. We therefore conducted a French national multicenter prospective study: (1) to determine the proportion of patients operated on at fracture stage versus preventively; (2) to compare Mirels score between the two; and (3) to identify factors for operation at fracture stage according to Mirels score and other epidemiological, clinical and biological criteria. HypothesisSimple discriminatory items can be identified to as to complete the Mirels score and enhance its predictive capacity. Material and MethodsA non-controlled multicenter prospective study included 245 patients operated on for non-revelatory long-bone metastasis, comparing patients operated on for fracture versus preventively according to body-mass index (BMI), ASA score, Katagiri score items and the 4 Mirels items. ResultsOne hundred and twenty-six patients (51.4%) were operated on at fracture stage: 106 (84.1%) showed high risk on Mirels score (score>8), and 15 (11.9%) moderate risk (score=8). On multivariate analysis, 4 independent factors emerged: in increasing order, advanced age (OR=1.03; 95%CI 1.01–1.06), VAS pain score>6 (OR=1.47; 95%CI 1.02–2.11), WHO grade>2 (OR=2.74; 95%CI 1.22–6.15), and upper-limb location (OR=5.26; 95%CI 2.13–12.84). DiscussionThe present study confirmed that more than half of patients with long-bone metastasis are operated on at actual fracture stage, in agreement with the literature. Several studies highlighted the weakness of the Mirels score as a predictive instrument. Comparison between preventive and fracture-stage surgery showed that upper-limb location, intense pain, advanced age and impaired functional status were associated with fracture-stage surgery, and should be taken into account alongside the original Mirels criteria. This improved scoring instrument remains to be validated in a prospective study. Level of evidenceIV, prospective cohort study without control group.

Preoperative embolization in surgical treatment of long bone metastasis: a systematic literature review.

Surgery of long bone metastases is associated with a significant risk of perioperative blood loss, which may necessitate blood transfusion.Successful embolization (> 70% obliteration of vascularity) can be achieved in 36–75% of cases.The reported rate of embolization-related complications is 0–9%.Three out of six level III evidence studies showed a reduction in perioperative blood loss and/or blood transfusion requirement after preoperative embolization of renal cell carcinoma metastasis in long bones; three out of six studies did not.One level III evidence study did not show a reduction in perioperative blood loss and/or transfusion requirement after preoperative embolization of hepatocellular carcinoma metastases in long bones.There were no studies found that support preoperative embolization of thyroid metastases or other frequent long bone metastases (e.g. mamma carcinoma, lung carcinoma, or prostate carcinoma).The clinical level of evidence of the studies found is low and randomized studies taking into account primary tumour, location of metastases and type of surgery are therefore desired.Cite this article: EFORT Open Rev 2020;5:17-25. DOI: 10.1302/2058-5241.5.190013

Evaluation of Factors Affecting Local Failure of Radiation for Long Bone Metastasis Following Orthopedic Stabilization

For patients with long-bone metastases who undergo orthopedic stabilization followed by radiotherapy (RT), it is unclear what extent of hardware coverage by the radiation field is needed for optimal tumor control. We investigated factors that contribute to tumor recurrence in a long bone after orthopedic stabilization and RT. One hundred one patients with 107 long-bone metastases managed with orthopedic stabilization followed by RT at our institution from 8/2011 to 3/2017 were included. Patients who did not receive RT within 4 months following orthopedic stabilization and those who did not have follow up imaging at least 3 months following completion of RT were excluded. Local failure (LF) was defined as any in-bone recurrence, whether in-field or out-of-field from radiation. Univariate analysis (UVA) assessing relation of various factors to LF was performed for age, time from surgery to RT, tumor histology, biologically effective dose using an alpha/beta of 10 (BED10; < vs ≥ 39Gy), extent of orthopedic hardware included in RT field (whole vs partial), and which bone contained metastasis. LF among patients with whole versus partial hardware coverage by RT was estimated with the Kaplan-Meier (KM) method and compared using the log-rank test. Median follow-up was 12.3 months (range 2.8 - 47.5). Median time to RT was 1.4 months (range 0.2 – 3.9) and median BED10 was 39 (range 14.4 – 59.5). There were 53 bones (49.5%) that received RT to whole hardware, while 54 (50.5%) received partial hardware RT. Long-bone metastases were located in femur (69%), humerus (21%), tibia (8%), radius (1%), and ulna (1%); 56% were right-sided and 44% left-sided. There were 23 local failures (21.5%) with median time to failure 9.6 months (range 2.8 – 27.2). In bones treated to whole hardware there were 9 local failures (17.0%), while there were 14 local failures (25.9%) in bones treated to partial hardware. Among the 14 local failures in partial hardware treatment, 5 failures were out-of-field or marginal (9.3%). On UVA, LF was not associated with age, time from surgery to RT, tumor histology, BED10, extent of orthopedic hardware coverage, or which bone contained metastasis. KM analysis and log-rank testing showed no statistically significant difference (p=0.30) in freedom from local failure for patients with whole versus partial hardware coverage. This analysis did not find a significant association between extent of hardware coverage and LF, indicating that whole hardware coverage may not be required for treatment of bone metastasis following surgical stabilization. Further study is needed to evaluate what factors may play a role in LF among patients receiving radiation for long bone metastasis following orthopedic stabilization.

Preliminary results: use of multi-hole injection nails for intramedullary nailing with simultaneous bone cement injection in long-bone metastasis.

For symptomatic metastasis of the long bones, intramedullary nailing has been the most accepted fixation method. Intramedullary nailing has effective control of pain, perioperative bleeding, and local tumor progression by augmentation with bone cement around the nail. Here, we report the preliminary results of a new surgical implant that allows for simultaneous injection of bone cement while inserting a percutaneous, flexible intramedullary nail. We performed palliative surgeries for long-bone metastasis using a multi-hole injection nail (MIN) with multiple side holes in the distal one third. When the nail tip entered the metastatic cancer lesion, the bone cement injection was started, and continued until the nail was completely seated. Ten patients with advanced cancer underwent palliative surgery using the new implant with simultaneous bone cement injection for humeral (n = 4), femoral (n = 4), and tibial (n = 2) metastases. The mean operative time was 42min (range, 36-52min). The mean length of the injection nail was 23.0cm (range, 18.0-33.0cm), and the mean volume of cement was 28.0ml (range, 14.0-40.0ml). Marked pain palliation (p < 0.001) and functional recovery (p = 0.01) were verified. The mean Musculoskeletal Tumor Society (MSTS) functional score improved significantly from 12.5 at 6weeks preoperatively, to 24.9 postoperatively. No acute postoperative complications, including cement embolism, occurred. This minimally invasive surgical method with MIN could be useful for stabilization of long-bone metastases in patients with advanced cancer.

An Easy-to-Use Prognostic Model for Survival Estimation for Patients with Symptomatic Long Bone Metastases.

A survival estimation for patients with symptomatic long bone metastases (LBM) is crucial to prevent overtreatment and undertreatment. This study analyzed prognostic factors for overall survival and developed a simple, easy-to-use prognostic model. A multicenter retrospective study of 1,520 patients treated for symptomatic LBM between 2000 and 2013 at the radiation therapy and/or orthopaedic departments was performed. Primary tumors were categorized into 3 clinical profiles (favorable, moderate, or unfavorable) according to an existing classification system. Associations between prognostic variables and overall survival were investigated using the Kaplan-Meier method and multivariate Cox regression models. The discriminatory ability of the developed model was assessed with the Harrell C-statistic. The observed and expected survival for each survival category were compared on the basis of an external cohort. Median overall survival was 7.4 months (95% confidence interval [CI], 6.7 to 8.1 months). On the basis of the independent prognostic factors, namely the clinical profile, Karnofsky Performance Score, and presence of visceral and/or brain metastases, 12 prognostic categories were created. The Harrell C-statistic was 0.70. A flowchart was developed to easily stratify patients. Using cutoff points for clinical decision-making, the 12 categories were narrowed down to 4 categories with clinical consequences. Median survival was 21.9 months (95% CI, 18.7 to 25.1 months), 10.5 months (95% CI, 7.9 to 13.1 months), 4.6 months (95% CI, 3.9 to 5.3 months), and 2.2 months (95% CI, 1.8 to 2.6 months) for the 4 categories. This study presents a model to easily stratify patients with symptomatic LBM according to their expected survival. The simplicity and clarity of the model facilitate and encourage its use in the routine care of patients with LBM, to provide the most appropriate treatment for each individual patient. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Cementoplasty for managing painful bone metastases outside the spine

To illustrate the effect of treatment with cementoplasty in patients with painful bone metastases in the extraspinal region. A retrospective study was conducted to review 51 consecutive patients who underwent cementoplasty under CT or fluoroscopic guidance, a total of 65 lesions involving the ilium, ischium, pubis, acetabulum, humeral, femur and tibia. In 5 patients with a high risk of impending fracture in long bones based on Mirels' scoring system, an innovative technique using a cement-filled catheter was applied. The clinical effects were evaluated using the visual analogue scale (VAS) preoperatively and postoperatively. All patients were treated successfully with a satisfying resolution of painful symptoms at 3months' follow-up. Cement leakage was found in 8 lesions without any symptoms. VAS scores decreased from 8.19 ± 1.1 preoperatively to 4.94 ± 1.6 at 3days, 3.41 ± 2.1 at 1month and 3.02 ± 1.9 at 3months postoperatively. There was a significant difference between the mean preoperative baseline score and the mean score at all of the postoperative follow-up points (P < 0.01). Cementoplasty is an effective technique for treating painful bone metastases in extraspinal regions, which is a valuable, minimally invasive, method that allows reduction of pain and improvement of patients' quality of life. • Metastases in long bones may cause pain and subsequent pathological fractures. • Cement-filled catheter resulted in a fixation effect to prevent pathological fractures. • Cementoplasty resulted in significant pain relief in patients with extraspinal metastases.

Encounter of cancer cells with bone. Therapy for bone metastasis from lung cancer

Bone metastasis from lung cancer requires a thorough examination of bones, including axial bones (e.g., spine, pelvis, and proximal femur) . Most patients have multiple bone metastases by the time they are initially diagnosed. In such patients, radiation therapy is often the first choice of treatment. Surgical treatment is indicated for pathological fracture and impending fracture associated with cortical bone invasion in long bone metastasis. Spinal metastasis requires accurate imaging to evaluate the extent of bone metastasis ; surgical treatment is indicated when the spinal cord is compressed. Given reports that bisphosphonates decrease the incidence of pathological fractures, prescribing bisphosphonates at an early stage is likely to be an effective therapeutic strategy for bone metastasis.

Working towards a real cure for patients with small hepatocellular carcinoma

See article on page 46 The natural history of hepatocellular carcinoma (HCC) can follow a very variable course. A majority of them progress without symptoms until the advanced stage. Distant metastases are reported to be uncommon. The rapid progression of this disease (HCC) to death occurs before the clinical presentation of metastases. In addition, the search for distant metastases is futile among patients with advanced HCC, especially when effective treatment is lacking. In a review of seven reports on 1673 HCC patients, lung (44%), portal vein (35%) and portal lymph nodes (27%) were found to be the three leading sites of metastases.1 Bone metastases were only found in 8% of patients. These reports are mostly based on post-mortem series, and bone metastases in long bones could have been missed. Two Italian studies reported 5–7% bone metastases among HCC patients with skeletal pain.2, 3 In a Japanese study of a specific subgroup of 323 patients with resected HCC, 12 (3.7%) developed bone metastasis at 1–36 months of follow-up. The time interval to the development of bone metastasis after resection was closely related to the presence of intrahepatic metastasis and the stage of the HCC at operation.4 In this issue of JGH, Iwata et al. report a prospective study of post-treatment bone metastasis in 202 patients with HCC.5 These patients were assigned to different treatment modalities: surgical resection, TAE (transcatheter arterial embolization), PEIT (percutaneous ethanol injection therapy), PMCT (percutaneous microwave coagulation therapy), chemotherapy or a combination of them. Before treatment, the patients were all carefully staged and found to be free of bone metastasis by the use of a technecium 99 m-methylene diphosphonate bone scan, which has an accuracy of 0.78. During the follow-up period, 21 (10.4%) patients developed bone metastasis after 2–82 months (median 24 months). This prevalence is slightly higher than in previous published data.1-4 The authors offered three explanations for this: (i) longer survival; (ii) a more sensitive bone scan method; and (iii) the treatment itself. Univariate analyses showed that pretreatment characteristics such as multiple tumor, tumor size > 5 cm in diameter, distant metastasis, α-fetoprotein > 100 ng/mL, chemotherapy and insufficient therapeutic effects are risk factors. Among these, tumor size > 5 cm in diameter and insufficient therapeutic effects are independent predisposing factors. The study by Iwata et al. highlights two important points in the management of HCC. Surveillance and early diagnosis of HCC while it is small is important. Chemotherapy, identified as a risk factor, probably reflects more advanced disease among patients who are assigned to this treatment and thus are more likely to develop bone metastasis. Furthermore, the choice of treatment modalities is important in order to aim for a complete ablation of the tumor. This study used surgical resection, TAE, PEIT, PMCT, chemotherapy or combination of these treatments. Unfortunately, the algorithm for treatment choice is not given in the paper. Neither was methodology for the assessment of sufficiency of the therapy explained. The authors postulated that the apparently higher prevalence of post-treatment bone metastasis in this study, compared to other reported prevalences, might be related to an insufficient therapeutic effect. A tumor-necrotic factor is then released and facilitates hematogenic metastasis. It does so by interfering with proper intracellular junction, damaging endothelium and inducing cellular detachment. This encourages the release of viable tumor cells to distant metastatic sites. Apart from bone metastasis, lung metastasis will presumably also be increased. The author has not addressed this aspect. Percutaneous ethanol injection therapy and PMCT are increasingly used for small HCC cases, instead of surgical resection. Tumor cells seeding along percutaneous track or released during instrumentation is likely and subsequently jeopardizes the chance of a cure. To detect micrometastasis, a highly-sensitive method by the identification of mRNA in circulating peripheral blood of hepatocellular carcinoma patients may be an useful too.6 Further studies are needed to gain a better understanding about the mechanism of distant metastasis, so that it can be detected and early treatment can be provided.7

Skeletal metastasis of prostate adenocarcinoma in rats: Morphometric analysis and role of parathyroid hormone‐related protein

BACKGROUND Prostate cancer frequently metastasizes to bone, where it induces osteoblastic lesions. Parathyroid hormone-related protein (PTHrP), a product of normal and neoplastic prostate cells, may promote growth and bone metastasis of certain types of cancer. In this study, we investigated the: 1) pathogenesis and morphology of bone metastases in the MATLyLu rat prostate adenocarcinoma model, and 2) effect of PTHrP overexpression on tumor growth and incidence of bone metastasis. METHODS MATLyLu cells were stably transfected with a PTHrP expression vector or control plasmid. PTHrP expression was determined in vitro by immunoradiometric assay and Northern blot analysis. MATLyLu cells were injected into the left ventricle of Copenhagen rats to induce bone metastases. Histology and radiography were used to quantify the size and number of bone metastases. Serum alkaline phosphatase isoenzyme concentrations and histomorphometric analysis were used to evaluate bone formation and resorption. RESULTS All rats developed osteolytic metastases in long bones and vertebrae. There was no evidence of increased intramedullary bone formation. PTHrP overexpression by MATLyLu cells was not associated with any difference in the incidence of bone metastasis, size of metastatic foci or tumor-cell proliferation. CONCLUSIONS The MATLyLu intracardiac injection model of prostate carcinoma is an aggressive tumor model with a high incidence of osteolytic skeletal metastases, and is not altered by increased PTHrP production by neoplastic prostate epithelial cells. Prostate 39:187–197, 1999. © 1999 Wiley-Liss, Inc.

Skeletal metastasis of prostate adenocarcinoma in rats: morphometric analysis and role of parathyroid hormone-related protein.

Prostate cancer frequently metastasizes to bone, where it induces osteoblastic lesions. Parathyroid hormone-related protein (PTHrP), a product of normal and neoplastic prostate cells, may promote growth and bone metastasis of certain types of cancer. In this study, we investigated the: 1) pathogenesis and morphology of bone metastases in the MATLyLu rat prostate adenocarcinoma model, and 2) effect of PTHrP overexpression on tumor growth and incidence of bone metastasis. MATLyLu cells were stably transfected with a PTHrP expression vector or control plasmid. PTHrP expression was determined in vitro by immunoradiometric assay and Northern blot analysis. MATLyLu cells were injected into the left ventricle of Copenhagen rats to induce bone metastases. Histology and radiography were used to quantify the size and number of bone metastases. Serum alkaline phosphatase isoenzyme concentrations and histomorphometric analysis were used to evaluate bone formation and resorption. All rats developed osteolytic metastases in long bones and vertebrae. There was no evidence of increased intramedullary bone formation. PTHrP overexpression by MATLyLu cells was not associated with any difference in the incidence of bone metastasis, size of metastatic foci or tumor-cell proliferation. The MATLyLu intracardiac injection model of prostate carcinoma is an aggressive tumor model with a high incidence of osteolytic skeletal metastases, and is not altered by increased PTHrP production by neoplastic prostate epithelial cells.

LCC15-MB: a vimentin-positive human breast cancer cell line from a femoral bone metastasis.

The LCC15-MB cell line was established from a femoral bone metastasis that arose in a 29-year-old woman initially diagnosed with an infiltrating ductal mammary adenocarcinoma. The tumor had a relatively high (8%) S-phase fraction and 1/23 positive lymph nodes (LN). Both the primary tumor and LN metastasis were positive for estrogen receptor (ER) and progesterone receptor (PgR), but lacked erbB2 expression. Approximately one year later, the patient presented with a 0.8 cm comedo-type intraductal mammary adenocarcinoma in the left breast that was negative for ER and PgR, but positive for erbB2. Thirty-five months after the initial diagnosis she was treated for acute skeletal metastasis, and stabilized with a hip replacement. At this time, tumor cells were removed from surplus involved bone, inoculated into cell culture, and developed into the LCC 15-MB cell line. The bone metastasis was a poorly differentiated adenocarcinoma lacking ER, PgR, and erbB2, characteristics shared by the LCC15-MB cells, although ER can be re-expressed by treatment of the LCC15-MB cells for 5 days with 75 microM 5-aza-2'-deoxycytidine. The LCC15-MB cell line is tumorigenic when implanted subcutaneously in NCr nu/nu mice and produces long-bone metastases after intracardiac injection. Although the bone metastasis from which the LCC15-MB cell line was derived lacked vimentin (VIM) expression, the original primary tumor and lymph node metastasis were strongly VIM positive, as are LCC15-MB cells in vitro and in nude mice. The karyotype and isozyme profiles of LCC15-MB cells are consistent with its origin from a human female, with most chromosome counts in the hypertriploid range. Thirty-two marker chromosomes are present. These cells provide an in vitro/in vivo model in which to study the inter-relationships between ER, VIM, and bone metastasis in human breast cancer.

Incidence of fracture through metastases in long bones.

A knowledge of the incidence of fractures through metastases of various sizes in long bones is important when considering prophylactic internal fixation. The notes and X-rays of 66 consecutive patients with 100 metastases in long bones were analysed. Fractures are highly unlikely to occur (2.3 per cent) when less than 50 per cent of the cortex is destroyed and most likely to occur (80 per cent) when over 75 per cent of the cortex is destroyed.

SURGERY FOR LONG BONE METASTASES

Australian and New Zealand Journal of SurgeryVolume 40, Issue 3 p. 278-284 SURGERY FOR LONG BONE METASTASES First published: February 1971 https://doi.org/10.1111/j.1445-2197.1971.tb04073.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume40, Issue3February 1971Pages 278-284 RelatedInformation