Reoperation after surgery for bone metastasis of renal cell carcinoma.

BACKGROUND AND OBJECTIVE: The prognosis of metastatic renal cell carcinoma (RCC) has markedly improved with the advent of molecular targeted therapies and immune checkpoint inhibitors. However, the therapeutic response in patients with bone metastasis remains low; therefore, surgery still plays a significant role in treatment of bone metastasis. It is important to maintain quality of life for patients with bone metastasis from RCC and avoid reoperation after surgery for bone metastasis. Therefore, we investigated the risk factors for reoperation after surgery in patients with bone metastasis from RCC. METHODS: We retrospectively studied 103 bones of 97 patients who underwent surgery for bone metastasis of RCC from 2001 to 2023 at our institutions. RESULTS: Reoperation was performed in 10 (9.7%) of 103 bones. There was no correlation between reoperation-free survival and any of the following variables: preoperative and postoperative radiotherapy, site of bone metastasis, indication for surgery (solitary bone metastasis or impending or pathologic fractures), surgical method (intramedullary nailing fixation, curettage, or en bloc resection), preoperative embolization, or survival. CONCLUSION: The risk of reoperation for bone metastasis of RCC does not appear to be based on the surgical method.

Is perioperative chemotherapy effective in patients with localized myxoid liposarcoma?

BACKGROUND: This study aimed to compare the local recurrence, distant metastasis and disease-specific survival rates of patients with localized myxoid liposarcoma in the surgery and adjuvant chemotherapy group versus the surgery alone group. METHODS: A total of 456 patients in the Japanese National Bone and Soft Tissue Tumour Registry database who had localized myxoid liposarcoma and underwent surgery and adjuvant chemotherapy or surgery alone between 2001 and 2019 were included in this retrospective study. The study adjusted for background differences between patients who underwent surgery and adjuvant chemotherapy (n = 228) or surgery alone (n = 228) using propensity score matching. RESULTS: Univariate analysis showed no significant difference in local recurrence rate between the two groups (5-year local recurrence-free survival: 98.6% [95% confidence interval: 95.9-99.6] vs. 94.0% [95% confidence interval: 89.7-96.6], P = 0.052). Univariate analysis showed no difference in the incidence of distant metastases between the two groups (5-year distant metastasis-free survival: 80.5% [95% confidence interval: 73.9-85.8] vs. 75.1% [95% confidence interval: 67.7-81.2], P = 0.508). Univariate analysis showed no difference in disease-specific survival between the two groups (5-year disease-specific survival: 92.6% [95% confidence interval: 86.1-96.2] vs. 93.2% [95% confidence interval: 87.6-96.4], P = 0.804). In the high-risk group (n = 203) with high-grade tumours and tumour size ≥10 cm, there were no significant differences in the local recurrence, distant metastasis and disease-specific survival rates between the surgery and adjuvant chemotherapy group and the surgery alone group. CONCLUSION: The effect of adjuvant chemotherapy on localized myxoid liposarcoma appears to be limited.

Malawer type I/V proximal humerus reconstruction after tumor resection: a systematic review.

BACKGROUND: Several reconstruction methods exist for Malawer type I/V proximal humerus reconstruction after bone tumor resection; however, no consensus has been reached regarding the preferred methods. METHODS: We conducted a literature search on various types of proximal humerus oncologic reconstruction methods. We collected data on postoperative functional outcomes assessed based on Musculoskeletal Tumor Society (MSTS) scores, 5-year reconstruction survival rates, and complications. We calculated each reconstruction's weighted mean based on the sample size and standard errors. Complications were categorized based on the Henderson classification. Based on these integrated data, our primary objective is to propose an optimal strategy for proximal humerus reconstruction after bone tumor resection. RESULTS: We examined various reconstruction techniques, including modular prosthesis (752 patients in 21 articles), osteoarticular allograft (142 patients in 6 articles), allograft prosthesis composites (APCs) (236 patients in 12 articles), reverse shoulder total arthroplasty (141 patients in 10 articles), composite reverse shoulder total arthroplasty (33 patients in 4 articles), claviculo-pro-humero (CPH) technique (51 patients in 6 articles), and cement spacer (207 patients in 4 articles). Weighted mean MSTS scores were: modular prosthesis (73.8%), osteoarticular allograft (74.4%), APCs (79.2%), reverse shoulder total arthroplasty (77.0%), composite reverse shoulder total arthroplasty (76.1%), CPH technique (75.1%), and cement spacer (69.1%). Weighted 5-year reconstruction survival rates were modular prosthesis (85.4%), osteoarticular allograft (67.6%), APCs (85.2%), reverse shoulder total arthroplasty (84.1%), and cement spacer (88.0%). Reconstruction survival data was unavailable for composite reverse shoulder total arthroplasty and CPH technique. Major complications included shoulder joint instability: modular prosthesis (26.2%), osteoarticular allograft (41.5%), APCs (33.9%), reverse shoulder total arthroplasty (17%), composite reverse shoulder total arthroplasty (6.1%), CPH technique (2.0%), and cement spacer (8.7%). Aseptic loosening of the prosthesis occurred: modular prosthesis (3.9%) and reverse shoulder total arthroplasty (5.7%). Allograft fracture was observed in 54.9% of patients with osteoarticular allograft. CONCLUSION: The complication profiles differed among reconstruction methods. Weighted mean MSTS scores exceeded 70% in all methods except cement spacer, and the 5-year reconstruction survival rate surpassed 80% for all methods except osteoarticular allograft. Proximal humerus reconstruction after bone tumor resection should consider potential complications and patients' individual factors.

Response rate specific to bone metastasis of various cancers for immune checkpoint inhibitors: a systematic review.

PURPOSE: Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with cancer, such as melanoma, renal cell carcinoma, head and neck cancer, non-small cell lung cancer (NSCLC), and urothelial carcinoma. The extension of life expectancy has led to an increased incidence of bone metastases (BM) among patients with cancer. BM result in skeletal-related events, including severe pain, pathological fractures, and nerve palsy. Surgery is typically required for the treatment of BM in patients with an impending fracture; however, it may be avoided in those who respond to ICIs. We systematically reviewed studies analyzing BM responses to treatment with ICIs. METHODS: This study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement and registered in the UMIN Clinical Trials Registry (ID: UMIN000053707). Studies reporting response rates based on the Response Evaluation Criteria in Solid Tumors (RECIST) or the MD Anderson Cancer Center (MDA) criteria specific for BM in patients treated with ICIs were included; reports of fewer than five cases and review articles were excluded. Studies involving humans, published in English and Japanese, were searched. The PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Ultimately, nine studies were analyzed. The Risk of Bias Assessment tool for Non-randomized Studies was used to assess the quality of studies. RESULTS: Based on the MDA criteria, complete response (CR) or partial response (PR) was observed in 44-78% and 62% patients treated with ICIs plus denosumab for NSCLC and melanoma, respectively. According to the RECIST, CR or PR was recorded in 5% and 7-28% of patients treated with ICIs for renal cell carcinoma and urothelial carcinoma, respectively. CONCLUSION: Although response rates to ICIs for BM are poor, patients treated with ICI plus denosumab for bone metastases with impending fractures from NSCLC and melanoma are likely to avoid surgery to prevent fractures.

Giant cell tumor of bone with secondary aneurysmal bone cyst does not have a higher risk of local recurrence.

BACKGROUND: Fluid-fluid levels (FFLs) is found in 10%-16% of giant cell tumor of bone (GCTB), and the presence of FFLs raises the suspicion of GCTB with secondary aneurysmal bone cyst (ABC), which can lead to increased intraoperative bleeding and, blurring the operative field, be associated with a risk of local recurrence. The first objective of this study is to determine whether secondary ABC is associated with a higher risk of local recurrence after curettage in patients with GCTB of the extremities. The second objective of this study is to investigate the sensitivity, specificity, positive predictive value, and negative predictive value of the presence of FFLs detected on magnetic resonance imaging (MRI) to diagnose secondary ABC associated with GCTB. METHODS: Two hundred and eighty patients with GCTB of the extremities who underwent curettage at the authors' institutions between 1980 and 2021 were included in this study. RESULTS: Secondary ABC was found in 36 of 280 patients (12.9%) and local recurrence occurred in 66 of 280 patients (23.6%). Multivariate analysis showed no significant correlation between secondary ABC and local recurrence (hazard ratio [HR]: 1.87 (95% confidence interval [CI]: 1.00-3.53]; p = 0.051). Preoperative MRI revealed FFLs in 13 of 82 patients (15.9%). Sensitivity, specificity, positive predictive value, and negative predictive value of FFLs detected on preoperative MRI to diagnose secondary ABC were 36.8%, 90.5%, 53.8%, and 82.6%, respectively. CONCLUSION: The results of this study showed that secondary ABC does not increase the risk of local recurrence after curettage in patients with GCTB of the extremities. Although rare, FFLs were present in patients with GCTB and half of those with FFLs detected on preoperative MRI had secondary ABC.

Comparison of pre-operative and post-operative radiotherapy in patients with localized myxoid liposarcoma.

BACKGROUND: Myxoid liposarcoma is more radiosensitive than other soft tissue sarcomas, and radiotherapy has been reported to reduce tumour size. This study was performed to compare the rates of local recurrence, survival and wound complications between pre- and post-operative radiotherapy for localized myxoid liposarcoma. METHODS: From the Japanese Nationwide Bone and Soft Tissue Tumor Registry database, 200 patients with localized myxoid liposarcoma who received pre- (range, 30-56 Gy) or post-operative (range, 45-70 Gy) radiotherapy and surgery were included in this retrospective study. Propensity score matching was used to adjust for background differences between patients who received pre- and post-operative radiotherapy. RESULTS: Local recurrence occurred in five (5.0%) and nine (9.0%) patients in the pre- and post-operative radiotherapy groups, respectively (both n = 100). The median follow-up time from diagnosis was 40.5 months (IQR, 26.3-74). Univariate analysis showed a similar risk of local recurrence between the pre- and post-operative radiotherapy groups (5-year local recurrence-free survival 94.9% [95% CI 87.0-98.1] vs. 89.0% [95% CI 79.6-94.3]; P = 0.167). Disease-specific survival was similar between the pre- and post-operative radiotherapy groups (5-year disease-specific survival 88.1% [95% CI 75.5-94.6] vs. 88.4% [95% CI 77.3-94.5]; P = 0.900). The incidence of wound complications was similar between the pre- and post-operative radiotherapy groups (7.0% vs. 12.0%; P = 0.228). CONCLUSIONS: There was no difference in local recurrence, survival or incidence of wound complications between pre- and post-operative radiotherapy for localized myxoid liposarcoma. Therefore, pre-operative radiotherapy for myxoid liposarcoma provides clinical results equivalent to post-operative radiotherapy.

Influences of comorbidities on perioperative rehabilitation in patients with gastrointestinal cancers: a retrospective study.

BACKGROUND: Older patients are more likely to have comorbidities than younger patients, and multiple comorbidities are associated with mortality in patients with cancer. Therefore, we hypothesized that a functional comorbidity index could predict the therapeutic effects of rehabilitation. OBJECTIVES: In this study, we investigate whether the comorbidities influenced the execution and therapeutic effects of rehabilitation. METHODS: A consecutive cohort of 48 patients with gastrointestinal cancer who underwent surgery between January 1 and November 30, 2020, was analyzed. Charlson Comorbidity Index (CCI) scores were calculated based on data derived from medical records. The primary outcomes were ambulation status, duration (days) from the start of postoperative rehabilitation, and length of hospital stay. We investigated the relationship between CCI scores and primary outcomes. RESULTS: The CCI did not correlate with the duration of rehabilitation or the length of hospital stay. Subsequently, patients with functional recovery problems were evaluated, and we identified the conditions that were not included in the list using CCI scores. Most conditions are associated with surgical complications. Furthermore, using the Clavien-Dindo classification (CDC), we assessed the clinical features of the severity of complications. We found that the length of stay and the duration to start rehabilitation were significantly longer in the patients with higher severity of surgical complications (CDC≧III) than in those with lower severity (CDC≦II). CONCLUSIONS: Treatment-related conditions may significantly impact the perioperative period more than the original comorbidities. In addition to original comorbidities, events related to surgical complications should be assessed to determine the therapeutic effects of rehabilitation in patients with gastrointestinal cancer.

Outcome of re-operation for local recurrence following pre-operative denosumab administration and curettage for giant cell tumour of bone with difficult joint preservation.

PURPOSE: Denosumab enables joint-sparing surgery (curettage) and surgical downstaging in patients with giant cell tumour of bone (GCTB), where joint preservation is not possible. However, denosumab treatment causes osteosclerosis of the lesion, making it difficult to curet the lesion, leaving the tumour behind, and increasing the local recurrence rate. We performed a three-centre retrospective study to investigate the postoperative local re-recurrence rate, joint preservation status, and functional outcomes of locally recurrent lesions after preoperative denosumab treatment and curettage in patients with difficult joint preservation. METHODS: We included 38 of 142 patients with primary GCTB of the extremities who underwent preoperative denosumab and curettage between 2009 and 2021 with local recurrence. Preoperative denosumab was indicated in patients with minimal residual periarticular and subchondral bones, large extraosseous lesions (Campanacci stage 3), and pathological fractures that made joint preservation difficult. RESULTS: Local re-recurrence occurred in 6 (15.8%) of the 38 patients. In 29 patients who underwent re-curettage, local re-recurrence occurred in six patients (20.7%); however, in nine patients who underwent en bloc resection, no local re-recurrence was observed. The joint preservation rate was 63.2% (24 of 38 patients), with a median Musculoskeletal Tumor Society score of 28 (interquartile range: 26.8-29.0). The median follow-up period after surgery for local recurrence was 63.5 months (interquartile range: 42.5-82.4). CONCLUSION: Since the local re-recurrence rate after re-curettage for local recurrence was low, and the joint preservation rate and affected limb function were good, preoperative denosumab administration may be considered in patients who require downstaging to maintain good limb function (joint preservation).

Marginal resection for patients with atypical lipomatous tumours of the extremities and trunk wall: a systematic review and meta-analysis.

BACKGROUND: This systematic review assessed and compared the efficacy of marginal resection to wide resection in patients with atypical lipomatous tumours (ALT) by evaluating the local recurrence rates, overall survival and adverse event rates. METHODS: We evaluated studies published between 1 January 1990 and 31 January 2019. The risks of bias in the selected studies were analyzed using the Cochrane Collaboration Risk of Bias Tool. The quality of the evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: Three case-control studies and three case series studies were identified. A meta-analysis was performed of six studies to evaluate the local recurrence rate after resection. Comparison of marginal and wide resections showed that the local recurrence rate was not significantly higher in the marginal resection group (14.2 and 1.4%, odds ratio: 2.88, 95% confidence interval 0.99-8.33, P = 0.05). We observed no difference in overall survival. In one study, the rates of adverse events were 14.7% in the marginal resection group and 45.4% in the wide treatment group (odds ratio, 0.32; 95% confidence interval 0.11-80.91, P < 0.05). CONCLUSIONS: In our analyses, five of six studies reported no recurrence for wide resection, compared to three to seven recurrences in the marginal resection group. One study reported only one case of recurrence for wide resection. Because ALT has a relatively good prognosis, the use of marginal resection is acceptable to preserve musculoskeletal function.

Effect of adjuvant chemotherapy on periosteal osteosarcoma: a systematic review.

BACKGROUND AND OBJECTIVE: The effects of adjuvant chemotherapy on periosteal osteosarcoma are controversial. Therefore, we conducted a systematic review of studies comparing mortality, local recurrence, distant metastasis and secondary malignancy incidence among patients who underwent surgery and (neo-) adjuvant chemotherapy or surgery alone for periosteal osteosarcoma without distant metastases at diagnosis. METHODS: Of the 210 studies identified in the search, 13 were included in this study, involving 291 patients with periosteal osteosarcoma in total. RESULTS: The mortality rates in the surgery and (neo-) adjuvant chemotherapy and surgery alone groups were 11.3% (8/71) and 16.3% (16/98), respectively. The overall pooled odds ratio was 0.89 (P = 0.800). The local recurrence rate in the surgery and (neo-) adjuvant chemotherapy group was 12.1% (8/66), while that in the surgery alone group was 17.6% (13/74). The overall pooled odds ratio was 1.31 (P = 0.601). The distant metastasis rate in the surgery and (neo-) adjuvant chemotherapy group was 15.2% (10/66) and that in the surgery alone group was 10.8% (8/74). The overall pooled odds ratio was 1.51 (P = 0.444). The incidence of secondary malignancy in the surgery and (neo-) adjuvant chemotherapy group was 7.6% (9/118) and that in the surgery alone group was 2.7% (2/74). The overall pooled odds ratio was 2.29 (P = 0.187). CONCLUSIONS: Adjuvant chemotherapy did not appear to improve the prognosis of patients with periosteal osteosarcoma. No association was found between the use of adjuvant chemotherapy and development of secondary malignancies.

Dedifferentiation in low-grade osteosarcoma: a Japanese Musculoskeletal Oncology Group (JMOG) study.

BACKGROUND: Low-grade osteosarcomas, namely parosteal osteosarcoma (POS) and low-grade central osteosarcoma (LGCOS), occasionally dedifferentiate into high-grade malignancy, referred to as dedifferentiation in low-grade osteosarcoma (DLOS). This study aimed to elucidate the clinicopathologic features of DLOS, which are poorly described to date due to the extreme rarity of the disease. METHODS: A total of 33 patients with DLOS were included. Clinical characteristics, including the diagnostic accuracy of tumor biopsy, multimodal treatments, and clinical course, were retrospectively reviewed. Univariate analysis was performed to identify prognostic factors associated with overall survival (OS) and metastasis-free survival (MFS). RESULTS: The tumor subtypes comprised 10 cases (30.3%) of LGCOS and 23 cases (69.7%) of POS. The timing of dedifferentiation was synchronous in 25 (75.8%) and metachronous in 8 (24.2%) patients. The rates of preoperative diagnosis of DLOS were 40.0% and 65.4% for core needle biopsy and incisional biopsy, respectively. All patients underwent surgery and 25 patients received perioperative chemotherapy. Of the 13 patients who received neoadjuvant chemotherapy, 11 exhibited a poor histological response. The 5-year OS and MFS rates were 88.1% and 77.7%, respectively. Univariate analysis revealed that local recurrence was associated with poor OS (P < 0.01) and MFS (P < 0.01). Perioperative chemotherapy did not affect OS or MFS. CONCLUSIONS: The diagnostic accuracy of tumor biopsy for DLOS was lower than that for bone sarcomas, as reported previously. In contrast to conventional osteosarcomas with high chemosensitivity, both histological responses and survival analysis revealed low efficacy of chemotherapy for DLOS.

Risk factors of fracture following curettage for bone giant cell tumors of the extremities.

BACKGROUND: Following curettage of giant cell tumor of bone (GCTB), it is common to fill the cavity with polymethylmethacrylate (PMMA) bone cement, bone allograft, or artificial bone to maintain bone strength; however, there is a 2-14% risk of postoperative fractures. We conducted this retrospective study to clarify the risk factors for fractures after curettage for GCTB of the extremities. METHODS: This study included 284 patients with GCTBs of the extremities who underwent curettage at our institutions between 1980 and 2018 after excluding patients whose cavities were not filled with anything or who had additional plate fixation. The tumor cavity was filled with PMMA bone cement alone (n = 124), PMMA bone cement and bone allograft (n = 81), bone allograft alone (n = 63), or hydroxyapatite graft alone (n = 16). RESULTS: Fractures after curettage occurred in 10 (3.5%) patients, and the median time from the curettage to fracture was 3.5 months (interquartile range [IQR], 1.8-8.3 months). The median postoperative follow-up period was 86.5 months (IQR, 50.3-118.8 months). On univariate analysis, patients who had GCTB of the proximal or distal femur (1-year fracture-free survival, 92.5%; 95% confidence interval [CI]: 85.8-96.2) presented a higher risk for postoperative fracture than those who had GCTB at another site (100%; p = 0.0005). Patients with a pathological fracture at presentation (1-year fracture-free survival, 88.2%; 95% CI: 63.2-97.0) presented a higher risk for postoperative fracture than those without a pathological fracture at presentation (97.8%; 95% CI: 95.1-99.0; p = 0.048). Patients who received bone grafting (1-year fracture-free survival, 99.4%; 95% CI: 95.7-99.9) had a lower risk of postoperative fracture than those who did not receive bone grafting (94.4%; 95% CI: 88.7-97.3; p = 0.003). CONCLUSIONS: For GCTBs of the femur, especially those with pathological fracture at presentation, bone grafting after curettage is recommended to reduce the risk of postoperative fracture. Additional plate fixation should be considered when curettage and cement filling without bone grafting are performed in patients with GCTB of the femur. This should be specially performed for those patients with a pathological fracture at presentation.

Soft-tissue reconstruction after soft-tissue sarcoma resection: the clinical outcomes of 24 patients.

PURPOSE: Pedicle or free-flap reconstruction is important in surgical sarcoma management. Free flaps are indicated only when pedicle flaps are considered inadequate; however, they are associated with a higher risk of flap failure, longer surgical times, and technical difficulty. To determine the skin defect size that can be covered by a pedicle flap, we investigated the clinical outcomes and complications of reconstruction using pedicle flaps vs. free flaps after sarcoma resection. METHODS: We retrospectively studied the medical records of 24 patients with soft-tissue sarcomas who underwent reconstruction using a pedicle (n = 20) or free flap (n = 4) following wide tumour resection. RESULTS: All skin defects of the knee, lower leg, and ankle were reconstructed using a pedicle flap. Skin defects of the knee, lower leg, and ankle were covered by up to 525 cm2, 325 cm2, and 234 cm2, respectively. The amount of blood loss was significantly greater in the free-flap group than in the pedicle flap group (p = 0.011). Surgical time was significantly shorter in the pedicle flap group than in the free-flap group (p = 0.006). Total necrosis was observed in one (25%) patient in the free-flap group; no case of total necrosis was observed in the pedicle flap group. CONCLUSION: Less blood loss, shorter surgical time, and lower risk of total flap necrosis are notable advantages of pedicle flaps over free flaps. Most skin defects, even large ones, of the lower extremities following sarcoma resection can be covered using a single pedicle flap or multiple pedicle flaps.

Clinical questions on rehabilitation in cancer patients with skeletal metastasis: a content analysis of the multidisciplinary tumor board records.

PURPOSE: Cancer rehabilitation addresses the functional needs of patients who have various impairments. Disease control is a critical oncological consideration, while physical intervention increased weights of importance in several situations. To identify the clinical status that necessitates active physical intervention in cancer patients with skeletal metastasis, we performed a content analysis in the multidisciplinary tumor board (MDTB) records. METHODS: From January 2017 to September 2019, the MDTB discussed 168 consecutive patients with skeletal metastasis. We reviewed the MDTB records and asked responsible physicians to frame clinical questions. Based on these data, we identified the predictor valuables with the association to rehabilitation-related clinical questions using univariate and multivariate analyses. Moreover, we investigated a predictor of the change in Barthel index (BI) scores using univariate analyses. RESULTS: Rehabilitation-related questions arose more frequently in older patients (p = 0.011), in patients with slow-growth vs. rapid-growth tumor (p = 0.002), and in patients with skeletal-related events (p = 0.001) at MDTB. The tumor growth speed was associated with the change in BI scores, as slower-growth tumors had the benefit of BI gains (p = 0.017). CONCLUSIONS: Regarding rehabilitation in patients with skeletal metastasis, we should pay attention to three parameters: occurrence of skeletal events, patient age, and growth speed of tumors. Rehabilitation-related questions may reflect patients' functional needs that occur more frequently in patients with pathological fractures or neurological symptoms, older patients, and patients with slow-growth tumors.

What's new in musculoskeletal oncology.

We reviewed the recent literature related to primary musculoskeletal tumors and metastatic bone tumors. With regard to primary bone tumors, computer navigation systems and three-dimensional-printed prostheses seem to be new treatment options, especially in challenging anatomical locations, such as the sacrum and pelvis. Regarding the treatment of giant cell tumor of bone, recent studies have suggested that denosumab administration is related to a higher local recurrence rate following curettage, but a lower local recurrence rate following en bloc resection. In addition, there was no difference in the local recurrence rate at five years after surgery between short-term and long-term denosumab therapy. With regard to soft tissue tumors, percutaneous cryoablation appears to be a new treatment option for extra-abdominal desmoid tumors, with encouraging results. Regarding soft tissue sarcomas, a negative surgical margin of < 1 mm is sufficient to control local recurrence. Pexidartinib seems to be a promising systemic therapy for the treatment of tenosynovial giant cell tumors for which surgery is not expected to improve the function of the affected limb. Finally, the life expectancy of patients is the most important factor in determining the optimal surgical procedure for patients with impending or pathological fractures of the long bone due to metastatic bone tumors. Elevated C-reactive protein level was found to be an independent poor prognostic factor at 1 year after surgery for long bone metastases.

Upfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors.

BACKGROUND: This study compared the clinical and functional outcomes of patients initially treated with observation or medical treatment with those of patients treated with local treatment (surgery alone or surgery with adjuvant radiotherapy) to confirm whether observation or medical treatment is an appropriate first-line management approach for patients with desmoid tumors. METHODS: We retrospectively reviewed the medical records of 99 patients with histologically confirmed primary desmoid tumors treated between 1978 and 2018. The median follow-up period was 57 months. We evaluated event-free survival, defined as the time interval from the date of initial diagnosis to the date of specific change in treatment strategy or recurrence or the last follow-up. RESULTS: An event (specific change in treatment strategy or recurrence) occurred in 28 patients (28.3%). No significant difference in event-free survival was found between the first-line observation/medical treatment and local treatment groups (p = 0.509). The median Musculoskeletal Tumor Society score of the patients treated with first-line local treatment was 29 (interquartile range [IQR], 23-30), whereas that of the patients managed with first-line observation or medical treatment was 21 (IQR, 19-29.5). First-line observation or medical treatment was more frequently chosen for larger tumors (p = 0.045). In the patients treated with local treatment, local recurrence was not related to the surgical margin (p = 0.976). CONCLUSION: Upfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors.

Intralesional nerve-sparing surgery versus non-surgical treatment for giant cell tumor of the sacrum.

BACKGROUND: There is no standard treatment for giant cell tumors of the sacrum. We compared the outcomes and complications in patients with sacral giant cell tumors who underwent intralesional nerve-sparing surgery with or without (neo-) adjuvant therapies versus those who underwent non-surgical treatment (denosumab therapy and/or embolization). METHODS: We retrospectively investigated 15 cases of sacral giant cell tumors treated at two institutions between 2005 and 2020. Nine patients underwent intralesional nerve-sparing surgery with or without (neo-) adjuvant therapies, and six patients received non-surgical treatment. The mean follow-up period was 85 months for the surgical group (range, 25-154 months) and 59 months (range, 17-94 months) for the non-surgical group. RESULTS: The local recurrence rate was 44% in the surgical group, and the tumor progression rate was 0% in the non-surgical group. There were two surgery-related complications (infection and bladder laceration) and three denosumab-related complications (apical granuloma of the tooth, stress fracture of the sacroiliac joint, and osteonecrosis of the jaw). In the surgical group, the mean modified Biagini score (bowel, bladder, and motor function) was 0.9; in the non-surgical group, it was 0.5. None of the 11 female patients became pregnant or delivered a baby after developing a sacral giant cell tumor. CONCLUSIONS: The cure rate of intralesional nerve-sparing surgery is over 50%. Non-surgical treatment has a similar risk of complications to intralesional nerve-sparing surgery and has better functional outcomes than intralesional nerve-sparing surgery, but patients must remain on therapy over time. Based on our results, the decision on the choice of treatment for sacral giant cell tumors could be discussed between the surgeon and the patient based on the tumor size and location.

What's new in the management of metastatic bone disease.

Metastatic bone disease is a common complication of malignant tumours. As cancer treatment improves the overall survival of patients, the number of patients with bone metastases is expected to increase. The treatments for bone metastases include surgery, radiotherapy, and bone-modifying agents, with patients with a short expected prognosis requiring less invasive treatment. Patients with metastatic bone disease show greatly varying primary tumour histology, metastases sites and numbers, and comorbidities. Therefore, randomised clinical trials are indispensable to compare treatments for these patients. This editorial reviews recent findings on the diagnosis and prognosis prediction and discusses the current treatment of patients with metastatic bone disease.

Is Treatment with Denosumab Associated with Local Recurrence in Patients with Giant Cell Tumor of Bone Treated with Curettage? A Systematic Review.

BACKGROUND: Denosumab, a monoclonal antibody that binds to receptor activation of nuclear factor-kappa ß ligand (RANKL), has been used as a drug to treat aggressive giant cell tumors of bone. It is unclear whether preoperative denosumab therapy is associated with the local recurrence risk in patients with giant cell tumors of bone treated with curettage. Early evidence suggests that denosumab treatment is associated with a reduction in local recurrence, but other studies have questioned that premise. Curettage after a short course of denosumab (3 to 4 months) has been recommended, especially for large, aggressive giant cell tumors in which complete curettage is difficult to achieve. No randomized studies have documented the benefit of this approach, and some investigators have reported higher local recurrence after denosumab treatment. Due to this confusion, we performed a systematic analysis of existing reports to attempt to answer this question and determine whether the appropriate preoperative denosumab therapy duration could be established. QUESTIONS/PURPOSES: (1) Is the use of preoperative denosumab associated with local recurrence risk in patients with giant cell tumors of bone treated with curettage compared with those treated with curettage alone? (2) Is the preoperative denosumab therapy duration associated with local recurrence after curettage? METHODS: We searched the PubMed, EMBASE, and CENTRAL databases on April 26, 2019 and included both randomized and non-randomized studies that compared local recurrence between patients who had giant cell tumors of bone and were treated with curettage after preoperative denosumab and patients treated with curettage alone. Two authors independently screened the studies. There were no randomized studies dealing with denosumab in giant cell tumors of bone, and generally, denosumab was used for more aggressive tumors. We assessed the quality of the included studies using the Risk of Bias Assessment tool for Non-randomized Studies, with a moderate overall risk of bias. We registered our protocol in PROSPERO (registration number CRD42019133288). We selected seven eligible studies involving 619 patients for the final analysis. RESULTS: The proportion of patients with local recurrence ranged from 20% to 100% in the curettage with preoperative denosumab group and ranged from 0% to 50% in the curettage-alone group. The odds ratio of local recurrence ranged from 1.07 to 37.80 in no more than 6 months of preoperative denosumab duration group and ranged from 0.60 to 28.33 in more than 6 months of preoperative denosumab duration group. CONCLUSIONS: The available evidence for the benefit of denosumab in more aggressive giant cell tumors is inconclusive, and denosumab treatment may even be associated with an increase in the proportion of patients experiencing local recurrence. Because there are no randomized studies and the existing studies are of poor quality due to indication bias (the most aggressive Campanacci 3 lesions or those where even a resection would be difficult and result in morbidity are generally the patients who are treated with denosumab), the evidence to suggest a disadvantage is weak. Denosumab treatment should be viewed with caution until more definitive, randomized studies documenting a benefit (or not) have been conducted. Furthermore, we could not find evidence to suggest an appropriate length of preoperative denosumab before curettage.

Impairment-driven cancer rehabilitation in patients with neoplastic spinal cord compression using minimally invasive spine stabilization.

BACKGROUND: Neoplastic spinal cord compression is a cause of severe disability in cancer patients. To prevent irreversible paraplegia, a structured strategy is required to address the various impairments present in cancer patients. In this study, we aimed to identify the status where rehabilitation with minimally invasive spine stabilization (MISt) effectively improves ADL. METHODS: We retrospectively reviewed 27 consecutive patients with neoplastic spinal compression who were treated with MISt. We classified the impairments of patients through our multidisciplinary tumor board based on spine-specific factors, skeletal instability, and tumor growth. The neurological deficits, progress of pathological fracture, incidence of vertebral collapse, and postoperative implant failure were examined. Changes of the Barthel index (BI) scores before and after surgery were investigated throughout the clinical courses. RESULTS: The average duration to ambulation was 7.19 ± 11 days, and we observed no collapse or progression of paralysis except in four cases of complete motor paraplegia before the surgery. Neurological deficiency was improved to or maintained at Frankel's grade E in 16 patients, remained unchanged in 6 patients (in grades B, C, D), and worsened in 5 patients. BI score comparisons before and after surgery in all patients showed statistically significant increments (p < 0.05). On further analysis, we noted good functional prognosis in patients capable of ambulation within 7 days (p < 0.05) and in patients who could survive longer than 3 months after the surgery (p < 0.05). CONCLUSIONS: In various cancer patients with neoplastic spinal cord compression, skeletal instability as the primary impairment is a good indication for MISt, as the patients showed early ambulation with improved BI scores.