Predictors of Survival in Patients With Bone Metastasis of Lung Cancer

Sugiura, Hideshi; Yamada, Kenji; Sugiura, Takahiko; Hida, Toyoaki; Mitsudomi, Tetsuya

doi:10.1007/s11999-007-0051-0

Cited by 232 publications

(217 citation statements)

References 19 publications

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“…There was no significant difference observed in overall survival between the patients with and without SRE at enrollment (16). In a study performed by Sugiura et al (17), the cumulative survival rate following bone metastasis was observed to be 59.9% for 6-month survival, 31.6% for 1-year survival and 11.3% for 2-year survival. The mean survival time was 9.7 months (17).…”

Section: A B Discussionmentioning

confidence: 87%

Effect of synchronous solitary bone metastasectomy and lung cancer resection on non-small cell lung cancer patients

Zhao

Gao

et al. 2016

Oncology Letters

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Abstract. Lung cancer is the most frequent cause of cancer-associated mortality among men and women globally. The skeleton is one of the most common metastatic sites. The majority of patients exhibiting bone metastases are treated using systemic therapy or symptom-based palliative approaches without surgery. The present study attempted to improve the therapeutic effects of synchronous surgeries in resectable non-small cell lung cancer patients exhibiting solitary bone metastasis. A total of 5 patients underwent synchronous lung cancer resections and solitary bone metastasectomies between October 2009 and November 2011 in the Department of Cardiothoracic Surgery, Shanghai Sixth People's Hospital (Shanghai, China). All patients had received fluorodeoxyglucose positron emission tomography-computed tomography or bone scintigraphy to demonstrate the presence of solitary bone metastasis and to exclude the presence of metastases at alternative sites. The patients received standard lung cancer and mediastinal lymph node resections. In addition, bone lesions were assessed by orthopedists and operated on synchronously with standard procedures. Following surgery, all patients were administered standard chemotherapeutic regimens. Perioperative indicators, including time for thoracic drainage, length of hospital stay, incidence of post-operative complications and progression-free survival (PFS) time, were observed. The average time for post-operative drainage was 4.6±1.1 days, and the average length of post-operative hospitalization was 8.8±2.2 days. All procedures were performed safely with no serious complications. The PFS of the patients was 13.2±7.7 months. While 2 patients presenting with spinal metastases succumbed at ~1 year post-surgery, the remaining 3 patients presenting with limb bone metastases survived for >16 months post-surgery, and were alive at the last follow-up. In conclusion, the present study indicated that a synchronous metastasectomy and lung tumor resection is a safe method of treatment. The PFS time and survival results demonstrated that on the rare occasion that a patient exhibits solitary bone metastasis, aggressive surgical treatment may be a potential therapeutic option.

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Section: A B Discussionmentioning

confidence: 87%

Effect of synchronous solitary bone metastasectomy and lung cancer resection on non-small cell lung cancer patients

Zhao

Gao

et al. 2016

Oncology Letters

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“…The onset of bone lesions in A549-luc mice was rapid; lesions were lytic and localized to the femur and spine, similar to those in humans. 2,3 Tumors recapitulated adenocarcinoma morphology with a high proliferation rate and showed osteoclasts along the tumor bone interface with marked trabecular and cortical bone loss. A significant osteoblastic component was not observed in our study, which could be related to the mouse strain, age of mice, or route of A549 cell administration.…”

Section: Discussionmentioning

confidence: 99%

“…These tumors have a high mortality rate and metastasize rapidly, often within months of diagnosis, with 60-70% of patients developing bone metastasis. 2,3 Lesions are predominantly osteolytic, involving vertebrae, rib, pelvis, and femur that lead to significant morbidity from spinal cord compression, pathologic fractures, and intractable pain. Metastasis to bone is associated with a poor prognosis and a mean survival of 9.7 months.…”

mentioning

confidence: 99%

Colony-stimulating factor 1 potentiates lung cancer bone metastasis

Hung¹,

Horn

Woodruff

et al. 2014

Laboratory Investigation

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Colony-stimulating factor 1 (CSF1) is essential for osteoclastogenesis that mediates osteolysis in metastatic tumors. Patients with lung cancer have increased CSF1 in serum and high levels are associated with poor survival. Adenocarcinomas metastasize rapidly and many patients suffer from bone metastasis. Lung cancer stem-like cells sustain tumor growth and potentiate metastasis. The purpose of this study was to determine the role of CSF1 in lung cancer bone metastasis and whether inhibition of CSF1 ameliorates the disease. Human lung adenocarcinoma A549 cells were examined in vitro for CSF1/CSF1R. A549-luc cells were injected intracardiac in NOD/SCID mice and metastasis was assessed. To determine the effect of CSF1 knockdown (KD) in A549 cells on bone metastasis, cells were stably transfected with a retroviral vector containing short-hairpin CSF1 (KD) or empty vector (CT). Results showed that A549 cells express CSF1/CSF1R; CSF1 increased their proliferation and invasion, whereas soluble CSF1R inhibited invasion. Mice injected with A549-luc cells showed osteolytic bone lesions 3.5 weeks after injection and lesions increased over 5 weeks. Tumors recapitulated adenocarcinoma morphology and showed osteoclasts along the tumor/bone interface, trabecular, and cortical bone loss. Analyses of KD cells showed decreased CSF1 protein levels, reduced colony formation in soft agar assay, and decreased fraction of stem-like cells. In CSF1KD mice, the incidence of tumor metastasis was similar to controls, although fewer CSF1KD mice had metastasis in both hind limbs. KD tumors showed reduced CSF1 expression, Ki-67 þ cells, and osteoclasts. Importantly, there was a low incidence of large tumors 40.1 mm 2 in CSF1KD mice compared with control mice (10% vs 62.5%). This study established a lung osteolytic bone metastasis model that resembles human disease and suggests that CSF1 is a key determinant of cancer stem cell survival and tumor growth. Results may lead to novel strategies to inhibit CSF1 in lung cancer and improve management of bone metastasis.Laboratory Investigation (2014) 94, 371-381; doi:10.1038/labinvest.2014.1; published online 27 January 2014 KEYWORDS: bone; cancer; CSF1; lung; metastasis Lung cancer is the leading cause of cancer deaths world wide. 1 The majority of lung cancers are non-small-cell type and, of those, adenocarcinoma is the most common. These tumors have a high mortality rate and metastasize rapidly, often within months of diagnosis, with 60-70% of patients developing bone metastasis. 2,3 Lesions are predominantly osteolytic, involving vertebrae, rib, pelvis, and femur that lead to significant morbidity from spinal cord compression, pathologic fractures, and intractable pain. Metastasis to bone is associated with a poor prognosis and a mean survival of 9.7 months. 2 Colony-stimulating factor 1 (CSF1) is essential for osteoclastogenesis that mediates osteolysis in metastatic tumors to bone. The effect of CSF1 is mediated via the c-fms tyrosine kinase receptor (CSF1R) that is expressed on mononuclear ph...

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“…Recent unpublished data indicate that denosumab treatment was superior to the bisphosphonate zoledronic acid to treat breast cancer bone metastases (Crook and Guise 2009). Small studies and anecdotal evidence suggest that anti-EGFR therapy is beneficial in patients with bone metastases due to lung and breast cancer (Albain et al 2002;von Minckwitz et al 2003;Sugiura et al 2008;Zampa et al 2008). Indeed, anti-EGFR therapy was highly effective in treating bone pain in a phase II study of patients with breast cancer and bone metastases (Albain et al 2002;von Minckwitz et al 2003).…”

Section: Downstream Effectors Of Mmps: Contributions To Osteolysismentioning

confidence: 99%

Breaking down bone: new insight into site-specific mechanisms of breast cancer osteolysis mediated by metalloproteinases: Figure 1.

Guise

2009

Genes Dev.

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Bone metastases are the most common skeletal complication of malignancy. Tumor cells disrupt normal bone remodeling to promote bone destruction and its associated morbidity. In the August 15, 2009, issue of Genes & Development, Lu and colleagues (pp. 1882-1894) propose a novel molecular mechanism by which tumor-produced metalloproteinases release epidermal growth factor (EGF) ligands to activate the central osteoclastogenic pathway receptor activator of NF-kB ligand (RANKL) to promote breast cancer osteolysis. This work has important therapeutic applications that may quickly translate to more effective treatment for bone metastases.Bone metastases are common in breast, prostate, and lung cancer, and are associated with significant morbidity. Unique aspects of the bone microenvironment-such as mineralized bone matrix, which houses immobilized growth factors, bone-destroying osteoclasts, and boneforming osteoblasts-make it a fertile soil for these cancers to grow. Significant insight into the molecular mechanisms responsible for the proclivity of tumors to metastasize and grow in bone has been gleaned in recent years from mouse models and clinical studies. Bone destruction mediated by solid tumor metastases to bone, particularly in breast cancer, is driven by tumor stimulation of osteoclastic bone resorption. Collective evidence supports the notion that effective therapy for bone metastases should target both the tumor and the bone microenvironment. Indeed, bisphosphonate therapy to block osteoclastic bone resorption, used in conjunction with standard anti-cancer treatments, reduces bone pain, pathologic fracture, and hypercalcemia associated with bone metastases from all tumor types. However, regression and cure of bone metastases have yet to be achieved with the current therapeutic armamentarium. Thus, a better understanding of the molecular mechanisms responsible for this devastating skeletal complication of malignancy is required to develop more effective therapy, with the eventual goal of curing and preventing bone metastases. In the August 15, 2009, issue of Genes & Development, Lu et al. (2009) bring the field closer to this goal. They describe an autocrine/paracrine signaling cascade triggered by metalloproteinases-matrix metalloproteinase-1 (MMP-1) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS1)-and cleavage of epidermal growth factor (EGF) ligands to reduce the ratio of osteoblast-produced receptor activator of NF-kB ligand (RANKL) to osteoprotegerin (OPG) to favor osteoclastogenesis and promote breast cancer osteolysis. These studies, described herein, have important implications for new applications of standard cancer therapy that could result in more effective treatment for bone metastases. Bone metastases: clinical features and current therapyCertain solid tumors-such as breast, prostate, and lung cancer-have a propensity to metastasize to bone to cause bone pain, fracture, hypercalcemia, and paralysis. This morbidity is great: Up to 75% of advanced breast and prostate c...

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Predictors of Survival in Patients With Bone Metastasis of Lung Cancer

Cited by 232 publications

References 19 publications

Effect of synchronous solitary bone metastasectomy and lung cancer resection on non-small cell lung cancer patients

Effect of synchronous solitary bone metastasectomy and lung cancer resection on non-small cell lung cancer patients

Colony-stimulating factor 1 potentiates lung cancer bone metastasis

Breaking down bone: new insight into site-specific mechanisms of breast cancer osteolysis mediated by metalloproteinases: Figure 1.

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