“…Vice versa, the correlation between IL-6 and TRAC5b was weaker, possibly because IL-6 serum levels are strongly affected by the presence of systemic inflammation that is associated with high IL-6 circulating levels (Tanaka et al, 2014). On this regard, it is noteworthy that we recently found that C-reactive protein, a wellknown marker of inflammation, highly significantly correlates with a poor prognosis rather than with BM (Errani et al, 2021), as also demonstrated in sarcomas (Nakamura et al, 2017). In conclusion, we cannot directly demonstrate that the circulating IL-8 is derived from acid-stressed cells of the OB lineage in BM patients.…”
Bone metastasis (BM) is a dismal complication of cancer that frequently occurs in patients with advanced carcinomas and that often manifests as an osteolytic lesion. In bone, tumor cells promote an imbalance in bone remodeling via the release of growth factors that, directly or indirectly, stimulate osteoclast resorption activity. However, carcinoma cells are also characterized by an altered metabolism responsible for a decrease of extracellular pH, which, in turn, directly intensifies osteoclast bone erosion. Here, we speculated that tumor-derived acidosis causes the osteoblast–osteoclast uncoupling in BM by modulating the pro-osteoclastogenic phenotype of osteoblasts. According to our results, a low pH recruits osteoclast precursors and promotes their differentiation through the secretome of acid-stressed osteoblasts that includes pro-osteoclastogenic factors and inflammatory mediators, such as RANKL, M-CSF, TNF, IL-6, and, above the others, IL-8. The treatment with the anti-IL-6R antibody tocilizumab or with an anti-IL-8 antibody reverted this effect. Finally, in a series of BM patients, circulating levels of the osteolytic marker TRACP5b significantly correlated with IL-8. Our findings brought out that tumor-derived acidosis promotes excessive osteolysis at least in part by inducing an inflammatory phenotype in osteoblasts, and these results strengthen the use of anti-IL-6 or anti-IL-8 strategies to treat osteolysis in BM.
“…Vice versa, the correlation between IL-6 and TRAC5b was weaker, possibly because IL-6 serum levels are strongly affected by the presence of systemic inflammation that is associated with high IL-6 circulating levels (Tanaka et al, 2014). On this regard, it is noteworthy that we recently found that C-reactive protein, a wellknown marker of inflammation, highly significantly correlates with a poor prognosis rather than with BM (Errani et al, 2021), as also demonstrated in sarcomas (Nakamura et al, 2017). In conclusion, we cannot directly demonstrate that the circulating IL-8 is derived from acid-stressed cells of the OB lineage in BM patients.…”
Bone metastasis (BM) is a dismal complication of cancer that frequently occurs in patients with advanced carcinomas and that often manifests as an osteolytic lesion. In bone, tumor cells promote an imbalance in bone remodeling via the release of growth factors that, directly or indirectly, stimulate osteoclast resorption activity. However, carcinoma cells are also characterized by an altered metabolism responsible for a decrease of extracellular pH, which, in turn, directly intensifies osteoclast bone erosion. Here, we speculated that tumor-derived acidosis causes the osteoblast–osteoclast uncoupling in BM by modulating the pro-osteoclastogenic phenotype of osteoblasts. According to our results, a low pH recruits osteoclast precursors and promotes their differentiation through the secretome of acid-stressed osteoblasts that includes pro-osteoclastogenic factors and inflammatory mediators, such as RANKL, M-CSF, TNF, IL-6, and, above the others, IL-8. The treatment with the anti-IL-6R antibody tocilizumab or with an anti-IL-8 antibody reverted this effect. Finally, in a series of BM patients, circulating levels of the osteolytic marker TRACP5b significantly correlated with IL-8. Our findings brought out that tumor-derived acidosis promotes excessive osteolysis at least in part by inducing an inflammatory phenotype in osteoblasts, and these results strengthen the use of anti-IL-6 or anti-IL-8 strategies to treat osteolysis in BM.
“…Table 3 summarizes the prognosis prediction model created by machine learning [ 9 , 10 , 11 , 12 , 13 , 14 , 19 , 20 , 21 , 22 , 23 ]. Errani et al analyzed 159 patients with bone metastases in the extremities who underwent surgery [ 24 ] and reported that pathological CRP (≥1.0 mg/dL) and primary tumor diagnosis were significant negative prognostic factors at 12-month survival. Breast, kidney, prostate, and thyroid cancers were classified as good prognosis, while lung, unknown primary, liver, colorectal, bladder, pancreas, gastric, esophagus, testicle, tonsil cancers, sarcoma, and melanoma were classified as poor prognosis.…”
Section: Prognosismentioning
confidence: 99%
“…Breast, kidney, prostate, and thyroid cancers were classified as good prognosis, while lung, unknown primary, liver, colorectal, bladder, pancreas, gastric, esophagus, testicle, tonsil cancers, sarcoma, and melanoma were classified as poor prognosis. The probability of survival at 12 months was 89% for group A: good prognosis primary tumor and physiological CRP; 57% for group B: bad prognosis primary tumor and physiological CRP or good prognosis primary tumor and pathological CRP; and 13% for group C: bad prognosis primary tumor and pathological CRP [ 24 ].…”
The number of patients with bone metastasis increases as medical management and surgery improve the overall survival of patients with cancer. Bone metastasis can cause skeletal complications, including bone pain, pathological fractures, spinal cord or nerve root compression, and hypercalcemia. Before initiation of treatment for bone metastasis, it is important to exclude primary bone malignancy, which would require a completely different therapeutic approach. It is essential to select surgical methods considering the patient’s prognosis, quality of life, postoperative function, and risk of postoperative complications. Therefore, bone metastasis treatment requires a multidisciplinary team approach, including radiologists, oncologists, and orthopedic surgeons. Recently, many novel palliative treatment options have emerged for bone metastases, such as stereotactic body radiation therapy, radiopharmaceuticals, vertebroplasty, minimally invasive spine stabilization with percutaneous pedicle screws, acetabuloplasty, embolization, thermal ablation techniques, electrochemotherapy, and high-intensity focused ultrasound. These techniques are beneficial for patients who may not benefit from surgery or radiotherapy.
“…A recent study showed that pathological C-reactive protein and a tumor with an unfavorable diagnosis were poor prognostic factors for 1-year survival in patients undergoing surgery for long bone metastases. Based on these results, patients were divided into three different prognostic groups: (A) good prognosis primary tumor and physiological C-reactive protein with 1-year survival rate of 89 %; (B) poor prognosis primary tumor and physiological C-reactive protein or good prognosis primary tumor and pathological C-reactive protein with 1-year survival rate of 57 %; (C) poor prognosis primary tumor and pathological C-reactive protein with 1-year survival rate of 13 % [ 58 ]. Orthopedic surgeons may use these prognostic factors to determine how to operate on very fragile patients with bone metastases.…”
Section: Main Textmentioning
confidence: 99%
“…Following these studies, we suggest a treatment algorithm for bone metastases of the extremities (Fig. 3 ) [ 56 – 58 ]. Fig.…”
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.
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