Life Expectancy After Treatment of Metastatic Bone Disease: An International Trend Analysis.

INTRODUCTION: The decision to treat metastatic bone disease (MBD) surgically depends in part on patient life expectancy. We are unaware of an international analysis of how life expectancy among these patients has changed over time. Therefore, we asked (1) how has the life expectancy for patients treated for MBD changed over time, and (2) which, if any, of the common primary cancer types are associated with longer survival after treatment of MBD? METHODS: We reviewed data collected from 2000 to 2022 in an international MBD database, as well as data used for survival model validation. We included 3,353 adults who underwent surgery and/or radiation. No patients were excluded. Patients were grouped by treatment date into period 1 (2000 to 2009), period 2 (2010 to 2019), and period 3 (2020 to 2022). Cumulative survival was portrayed using Kaplan-Meier curves; log-rank tests were used to determine significance at P < 0.05. Subgroup analyses by primary cancer diagnosis were performed. RESULTS: Median survival in period 2 was longer than in period 1 ( P < 0.001). Median survival (at which point 50% of patients survived) had not been reached for period 3. Median survival was longer in period 2 for all cancer types ( P < 0.001) except thyroid. Only lung cancer reached median survival in period 3, which was longer compared with periods 1 and 2 ( P < 0.001). Slow-growth, moderate-growth, and rapid-growth tumors all demonstrated longer median survival from period 1 to period 2; only rapid-growth tumors reached median survival for period 3, which was longer compared with periods 1 and 2 ( P < 0.001). DISCUSSION: Median duration of survival after treatment of MBD has increased, which was a consistent finding in nearly all cancer types. Longer survival is likely attributable to improvements in both medical and surgical treatments. As life expectancy for patients with MBD increases, surgical methods should be selected with this in mind. LEVEL OF EVIDENCE: VI.

Solitary versus multiple bone metastases in the appendicular skeleton.

Aims: We first sought to compare survival for patients treated surgically for solitary and multiple metastases in the appendicular skeleton, and second, to explore the role of complete and incomplete resection (R0 and R1/R2) in patients with a solitary bony metastasis in the appendicular skeleton. Methods: We conducted a retrospective study on a population-based cohort of all adult patients treated surgically for bony metastases of the appendicular skeleton between January 2014 and December 2019. We excluded patients in whom the status of bone metastases and resection margin was unknown. Patients were followed until the end of the study or to their death. We had no loss to follow-up. We used Kaplan-Meier analysis (with log-rank test) to evaluate patient survival. We identified 506 operations in 459 patients. A total of 120 operations (in 116 patients) were for solitary metastases and 386 (in 345 patients) for multiple metastases. Of the 120 operations, 70 (in 69 patients) had no/an unknown status of visceral metastases (solitary group) and 50 (in 49 patients) had visceral metastases. In the solitary group, 45 operations (in 44 patients) were R0 (resections for cure or complete remission) and 25 (in 25 patients) were R1/R2 (resections leaving microscopic or macroscopic tumour, respectively). The most common types of cancer in the solitary group were kidney (n = 27), lung (n = 25), and breast (n = 20). Results: The one-year patient survival was 47% (95% confidence interval (CI) 38 to 57) for the solitary bony metastases and 34% (95% CI 29 to 39) for multiple bone metastases (p < 0.001). The one-year patient survival was 64% (95% CI 52 to 75) for solitary bony metastases without/with unknown visceral metastases and 23% (95% CI 11 to 36) for solitary bony metastases with visceral metastases (p < 0.001). The one-year patient survival was 75% (95% CI 62 to 89) for a solitary bony metastasis after R0 surgery and 42% (95% CI 22 to 61) for a solitary bony metastasis with R1/R2 surgery (p < 0.001). Conclusion: Our study suggests that the surgical treatment of patients with a solitary bony metastasis to the appendicular skeleton results in better survival than for patients with multiple bony metastases. Furthermore, aggressive treatment of a solitary bony metastasis with R0 surgery may improve patient survival.

Major surgery for metastatic bone disease is not a risk for 30-day mortality: a population-based study from Denmark.

BACKGROUND AND PURPOSE: Surgery for bone metastases in the appendicular skeleton (aBM) is a trade-off between limb function and survival. A previous study from a highly specialized center found that extended surgery is not a risk for 30-day mortality and hypothesized that wide resection and reconstruction might reduce postoperative mortality. The study aimed to investigate whether parameters describing the surgical trauma (blood loss, duration of surgery, and degree of bone resection) pose a risk for 30-day mortality in patients treated with endoprostheses (EPR) or internal fixation (IF) in a population-based cohort. PATIENTS AND METHODS: A population-based cohort having EPR/IF for aBM in the Capital Region of Denmark 2014-2019 was retrospectively assessed. Intraoperative variables and patient demographics were evaluated for association with 30-day mortality by logistic regression analysis. Kaplan-Meier estimate was used to evaluate survival with no loss to follow-up. RESULTS: 437 patients had aBM surgery with EPR/IF. No parameters describing the magnitude of the surgical trauma (blood loss/duration of surgery/degree of bone resection) were associated with mortality. Overall 30-day survival was 85% (95% confidence interval [CI] 81-88). Univariate analysis identified ASA group 3+4, Karnofsky score < 70, fast-growth primary cancer, and visceral and multiple bone metastases as risk factors for 30-day mortality. Male sex (OR 2.8, CI 1.3-6.3), Karnofsky score < 70 (OR 4.2, CI 2.1-8.6), and multiple bone metastases (OR 3.4, CI 1.2-9.9) were independent prognostic factors for 30-day-mortality in multivariate analysis. CONCLUSION: The parameters describing the surgical trauma were not associated with 30-day mortality but, instead, general health status and extent of primary cancer influenced survival post-surgery.

Neuronal Sprouting and Reorganization in Bone Tissue Infiltrated by Human Breast Cancer Cells.

Background: Pain is a common complication for patients with metastatic bone disease. Animal models suggest that the pain, in part, is driven by pathological sprouting and reorganization of the nerve fibers innervating the bone. Here, we investigate how these findings translate to humans. Methods: Bone biopsies were collected from healthy volunteers (n = 7) and patients with breast cancer and metastatic bone disease (permissions H-15000679, S-20180057 and S-20110112). Cancer-infiltrated biopsies were from patients without recent anticancer treatment (n = 10), patients with recent anticancer treatment (n = 10), and patients with joint replacement surgery (n = 9). Adjacent bone sections were stained for (1) protein gene product 9.5 and CD34, and (2) cytokeratin 7 and 19. Histomorphometry was used to estimate the area of bone marrow and tumor burden. Nerve profiles were counted, and the nerve profile density calculated. The location of each nerve profile within 25 µm of a vascular structure and/or cancer cells was determined. Results: Cancer-infiltrated bone tissue demonstrated a significantly higher nerve profile density compared to healthy bone tissue. The percentage of nerve profiles found close to vascular structures was significantly lower in cancer-infiltrated bone tissue. No difference was found in the percentage of nerve profiles located close to cancer between the subgroups of cancer-infiltrated bone tissue. Interestingly, no correlation was found between nerve profile density and tumor burden. Conclusions: Together, the increased nerve profile density and the decreased association of nerve profiles to vasculature strongly suggests that neuronal sprouting and reorganization occurs in human cancer-infiltrated bone tissue.

Preoperative BMD does not influence femoral stem subsidence of uncemented THA when the femoral T-score is > -2.5.

Background and purpose - It is believed that in uncemented primary total hip arthroplasty (THA) the anchorage of the stem is dependent on the level of bone mineral density (BMD) of the femoral bone. This is one of the reasons for the widely accepted agreement that a cemented solution should be selected for people with osteoporosis or age > 75 years. We evaluated whether preoperative BMD of the femur bone is related to femoral stem migration in uncemented THA.Patients and methods - We enrolled 62 patients (mean age 64 years (range 49-74), 34 males) scheduled for an uncemented THA. Before surgery we undertook DEXA scans of the proximal femur including calculation of the T- and Z-scores for the femoral neck. Evaluation of stem migration by radiostereometric analysis (RSA) was performed with 24 months of follow-up. In 56 patients both preoperative DEXA data and RSA data were available with 24 months of follow-up.Results - None of the patients had a T-score below -2.5. We found no statistically significant relationship between preoperative BMD and femoral stem subsidence after 3 or 24 months. When comparing the average femoral stem subsidence between 2 groups with T-score > -1 and T-score ≤ -1, respectively, we found no statistically significant difference after either 3 or 24 months when measured with RSA.Interpretation - In a cohort of people ≤ 75 years of age and with local femur T-score > -2.5 we found no relationship between preoperative BMD and postoperative femoral stem subsidence of a cementless THA.

Long-term results of the Global Modular Replacement System tumor prosthesis for reconstruction after limb-sparing bone resections in orthopedic oncologic conditions: Results from a national cohort.

BACKGROUND AND OBJECTIVES: We investigated implant revision, implant failure, and amputation risk after limb-sparing bone tumor surgery using the Global Modular Replacement System (GMRS) tumor prosthesis in patients suffering from bone sarcomas (BS), giant cell tumors (GCT), or metastatic bone disease (MBD). MATERIAL AND METHODS: A retrospective study of a nationwide consecutive cohort (n = 119, 47 [12-81] years, M/F = 65/54) having limb-sparing surgery and reconstruction using the GMRS tumor prosthesis due to bone tumors (BS/GCT/MBD = 70/8/41) from 2005 to 2013. Anatomical locations were as followed: distal femur (n = 49), proximal femur (n = 41), proximal tibia (n = 26), or total femur (n = 3). Kaplan-Meier survival analysis and competing risk analysis with death as a competing risk were used for statistical analysis. RESULTS: For BS and GCT patients, 5-year patient survival was 72% (95% confidence interval [CI]: 59-85%) and for MBD 33% (95% CI: 19-48%). Thirty-two patients underwent revision surgery (5-year revision incidence 14%; 95% CI: 8-21%). Twelve patients had revision of bone-anchored parts (implant failure) with a 5-year revision incidence 6% (95% CI: 2-10%). Ten amputations were performed due to local relapse (n = 9) or recurrent infections (n = 1) with a 5-year incidence of amputation: 8% (95% CI: 3-13%). CONCLUSIONS: We identified a low risk of revision and amputation when using the GMRS tumor prosthesis for limb-sparing bone tumor.

Patient and implant survival following joint replacement because of metastatic bone disease.

BACKGROUND: Patients suffering from a pathological fracture or painful bony lesion because of metastatic bone disease often benefit from a total joint replacement. However, these are large operations in patients who are often weak. We examined the patient survival and complication rates after total joint replacement as the treatment for bone metastasis or hematological diseases of the extremities. PATIENTS AND METHODS: 130 patients (mean age 64 (30-85) years, 76 females) received 140 joint replacements due to skeletal metastases (n = 114) or hematological disease (n = 16) during the period 2003-2008. 21 replaced joints were located in the upper extremities and 119 in the lower extremities. Clinical and survival data were extracted from patient files and various registers. RESULTS: The probability of patient survival was 51% (95% CI: 42-59) after 6 months, 39% (CI: 31-48) after 12 months, and 29% (CI: 21-37) after 24 months. The following surgical complications were seen (8 of which led to additional surgery): 2-5 hip dislocations (n = 8), deep infection (n = 3), peroneal palsy (n = 2), a shoulder prosthesis penetrating the skin (n = 1), and disassembly of an elbow prosthesis (n = 1). The probability of avoiding all kinds of surgery related to the implanted prosthesis was 94% (CI: 89-99) after 1 year and 92% (CI: 85-98) after 2 years. CONCLUSION: Joint replacement operations because of metastatic bone disease do not appear to have given a poorer rate of patient survival than other types of surgical treatment, and the reoperation rate was low.