Thea Bechmann Hovgaard

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.Cite this article: Bone Joint J 2023;105-B(11):1206–1215.

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.

Background: Population-based studies of patients with bone metastases in the appendicular skeleton (aBM) requiring surgery for complete or impending fracture are rare. In this epidemiologically-based observational study we created a large population-based cohort of patients treated for aBM, aiming to: (1) monitor possible time-related changes of the incidence of surgical treatment of aBM-lesions, (2) examine differences in the population and care of patients treated at different treatment centers and (3) examine if findings from a previous pilot study regarding absence of a suitable biopsy of the lesions representing debut of cancer or a relapse has improved the awareness of aBM and hereby increased the focus on regular tumor biopsies and follow-up imaging of cancer patients. Methods: We examined a population-based cohort consisting of all patients treated for aBM 2014–2019. Procedures were performed at five secondary surgical centers (SSC) or one tertiary referral Musculoskeletal Tumor Center (MTC). Patients were followed until end of study (30 September 2021) or death. No patients were lost to follow-up. Results: Four-hundred-fifty-seven patients (493 primary aBM-lesions, 482 procedures) were included. Annual incidence of aBM-surgery was 46 aBM-lesions/million. MTC-patients had a significant better preoperative status than SSC-patients considering factors known for survival. Patients with complete fracture experienced longer surgical delay when treated at MTC compared to SSC: 4 (1–9) and 1 (1–3) days (p < 0.001), respectively. Overall survival for the entire cohort was 37% and 11% at 1 and 5 years (MTC and SSC 1 and 5 year respectively: 44% and 15% vs. 29% and 5%, p < 0.001). In patients with debut or relapse of cancer, 8% and 9% had insufficient biopsies, and 21% and 12% had no biopsy, respectively. Comparison showed no change over time. Conclusions: The current study highlights the low awareness on treating aBM at SSC and emphasizes the importance of caution in interpretation of studies not representing an entire population, thus introducing selection bias.

Sarcoma is a rare type of cancer. The incidence increases with age and elderly patients may have comorbidity that affects the prognosis. The aim of this study was to describe the type and prevalence of comorbidity in a nationwide population-based study in Denmark from 2000–2013 and to analyse the impact of the different comorbidities on mortality. The Danish Sarcoma Registry is a national clinical database containing all patients with sarcoma in the extremities or trunk wall from 2000 and onwards. By linking data to other registries, we were able to get patient information on an individual level including date and cause of death as well as the comorbidity type up to 10 years prior to the sarcoma diagnosis. Based on diseases in the Charlson Comorbidity Index, we pooled the patients into six categories: no comorbidity, cardiopulmonary disease, gastrointestinal disease, neurovascular disease, malignant neoplasms, and miscellaneous (diabetes, renal and connective tissue diseases). 2167 patients were included. The prevalence of comorbidity was 20%. For patients with localized disease, comorbidity increased the disease-specific mortality significantly (HR 1.70 (95% CI 1.36–2.13)). For patients with metastatic disease at the time of diagnosis, comorbidity did not affect the disease-specific mortality (HR 1.05 (95% CI 0.78–1.42)). The presence of another cancer diagnosis within 10 years prior to the sarcoma diagnosis was the only significant independent prognostic factor of disease-specific mortality with an increase of 66% in mortality rate compared to patients with no comorbidity (HR 1,66 (95% CI 1.22–2.25)). Comorbidity is a strong independent prognostic factor of mortality in patients with localized disease. This study emphasizes the need for optimizing the general health of comorbid patients in order to achieve a survival benefit from treatment of patients with localized disease, as this is potentially modifiable.

Background: Improvements in medical treatment for cancer have increased survival of cancer patients. We hypothesize that improvement in cancer treatment is reflected in increased survival after surgical intervention for metastatic bone disease (MBD) and that subsequent revision surgery does not pose a risk for survival. Methods: We identified a retrospective consecutive cohort who received bone resection and reconstruction (BRR) with implants (including total joint replacements (with or without wide resection) or bone reconstruction with an intercalary spacer or revisions procedures for failed implants with BBR technique) due to MBD from 2003 to 2008 (early cohort) and 2009 to 2013 (late cohort) at a tertiary referral center. We registered epidemiological data, type of implant (primary or a revision implant), patient survival (Kaplan–Meier), implant survival (competing risk analysis) and complications to surgery. Results: Three hundred and eleven procedures were performed in 291 patients (289 primary BRR (270 patients, early cohort n = 130 late cohort n = 140) and 22 revision BRR (21 patients)). Overall survival was 44% (95% confidence intervals (95% CI): 39–50) and 32% (95% CI: 27–38) after 1 and 2 years. No difference in survival between the early and late cohort was found (p = .458), or between primary and revision BRR (p = .465). Time from diagnosis of cancer to surgery was shorter in the early cohort (p < .001). The cumulative incidence of failure of implant was 2% (95% CI: 0–3%) at 1 year and 3% (95% CI: 1–6%) at 2 years. One year cumulative implant failure for revision implants was 5% (95% CI: 0–13%) at 1 and 2 years. The risk of failure was not statistical significant between primary and revision implant (p = .293) in competing risk analysis. Discussion: We were not able to identify an increased survival after surgery for MBD over time, however, we found an increased interval from diagnosis to surgery for MBD. This study suggests that revision surgery for MBD does not pose a risk for survival.

Background/objectives: Evaluation of our surveillance program for soft tissue sarcomas (STS) and borderline tumors (BT) for identification of local recurrence and lung metastases the first 2 years postoperatively. Methods: We retrospectively assessed the medical files of all patients (n = 232) with STS and BT of the extremities and trunk wall who underwent surgery from 2010 to 2013. Two-hundred-and-thirty-two patients were included in the local recurrence study and 116 patients in the lung metastasis study. We extracted information on how local recurrence and lung metastases were detected. Kaplan–Meier survival analysis and 2 × 2-contingency table with Chi-square test were used. Local recurrence and lung metastases were analyzed separately. Results: Twenty-five of 232 patients experienced local recurrence and 19 of 116 patients experienced lung metastases. Compared to clinical examination, local imaging led to a larger amount of local recurrence suspicions (37/560 vs. 8/706). Suspicions occurring on local imaging were more accurate than on clinical examination (17/37 vs. 0/8 affirmed). Local imaging identified a larger amount of local recurrence than clinical examination (17/560 vs. 0/706). Thirty-three patients suspected local recurrence themselves, 8 were affirmed. Compared to x-ray, computerized tomography (CT) led to a larger amount of lung metastasis suspicions (22/284 vs. 6/276). Suspicions occurring on CT seemed more accurate than on x-ray (15/22 vs. 2/6 affirmed). CT found a larger amount of lung metastases than x-ray (15/284 vs. 2/276). Three patients suspected lung metastases themselves, 1 was affirmed. Conclusion: Bi-annual local imaging and CT the first 2 years after surgery of STS detect local recurrence and lung metastases better than clinical examination and x-ray. Clinical examination and x-ray between these examinations is unnecessary. Patients’ own suspicion of local recurrence and lung metastases is still important.

BACKGROUND AND OBJECTIVE:Prediction of survival in patients having surgery for metastatic bone disease in the extremities (MBDex) has been of interest in more than two decades. Hitherto no consensus on the value of biochemical variables has been achieved. Our purpose was (1) to investigate if standard biochemical variables have independent prognostic value for survival after surgery for MBDex and (2) to identify optimal prognostic cut off values for survival of biochemical variables.METHODS:In a consecutive cohort of 270 patients having surgery for MBDex, we measured preoperative biochemical variables: hemoglobin, alkaline phosphatase, C‐reactive protein and absolute, neutrophil and lymphocyte count. ROC curve analyses were performed to identify optimal cut off levels. Independent prognostic factors for variables were addressed with multiple Cox regression analyses.RESULTS:Optimal cut off levels were identified as: hemoglobin 7.45 mmol/L, absolute lymphocyte count 8.5 × 10⁹/L, neutrophil 5.68 × 10⁹/L, lymphocyte 1.37 × 10⁹/L, C‐reactive protein 22.5 mg/L, and alkaline phosphatase 129 U/L. Regression analyses found alkaline phosphatase (HR 2.49) and neutrophil count (HR 2.49) to be independent prognostic factors.CONCLUSIONS:We found neutrophil count and alkaline phosphatase to be independent prognostic variables in predicting survival in patients after surgery for MBDex.

Estimating patient survival has hitherto been the main focus when treating metastatic bone disease (MBD) in the appendicular skeleton. This has been done in an attempt to allocate the patient to a surgical procedure that outlives them. No questions have been addressed as to whether the extent of the surgery and thus the surgical trauma reduces survival in this patient group.We wanted to evaluate if perioperative parameters such as blood loss, extent of bone resection, and duration of surgery were risk factors for 30-day mortality in patients having surgery due to MBD in the appendicular skeleton.We retrospectively identified 270 consecutive patients who underwent joint replacement surgery or intercalary spacing for skeletal metastases in the appendicular skeleton from January 1, 2003 to December 31, 2013. We collected intraoperative (duration of surgery, extent of bone resection, and blood loss), demographic (age, gender, American Society of Anesthesiologist score [ASA score], and Karnofsky score), and disease-specific (primary cancer) variables. An association with 30-day mortality was addressed using univariate and multivariable analyses and calculation of odds ratio (OR).All patients were included in the analysis. ASA score 3 + 4 (OR 4.16 [95% confidence interval, CI, 1.80-10.85], P = 0.002) and Karnofsky performance status below 70 (OR 7.34 [95% CI 3.16-19.20], P < 0.001) were associated with increased 30-day mortality in univariate analysis. This did not change in multivariable analysis. No parameters describing the extent of the surgical trauma were found to be associated with 30-day mortality.The 30-day mortality in patients undergoing surgery for MBD is highly dependent on the general health status of the patients as measured by the ASA score and the Karnofsky performance status. The extent of surgery, measured as duration of surgery, blood loss, and degree of bone resection were not associated with 30-day mortality.

Background. Compared to conventional hip arthroplasty, endoprosthetic reconstruction after tumor resection is associated with a substantially increased risk of periprosthetic joint infection (PJI), with reported rates of around 10% in a recent systematic review. The optimal duration of antibiotic prophylaxis for this patient population remains unknown.Material and Methods. To establish the infection rate associated with prolonged antibiotic prophylaxis in our department, we performed a retrospective review of all adult patients who underwent endoprosthetic reconstruction of the proximal femur after tumor resection for metastatic bone disease during a 4-year period from 2010 to 2013(n=105patients).Results. Intravenous antibiotic prophylaxis was administrated for an extended duration of a mean of 7.4 days. The overall infection rate was 3.6% (4/111 implants), infection free survival was 96% at 2 years, and the risk of amputation associated with infection was 25% (1/4 patients).Discussion. Preemptive eradication of bacterial contamination may be of value in certain clinical situations, where the risk level and consequences of implant-associated infection are unacceptable. Our findings suggest that extended postoperative antibiotic prophylaxis may reduce the risk of PJI in patients undergoing tumor resection and endoprosthetic replacement for metastatic bone disease associated impending or de facto pathologic fractures of the proximal femur.