Prognostic factors in patients with skeletal‑related events at non‑small‑cell lung cancer diagnosis

  • Authors:
    • Hiroyuki Tominaga
    • Takao Setoguchi
    • Hirofumi Shimada
    • Satoshi Nagano
    • Hiromi Sasaki
    • Yasuhiro Ishidou
    • Masami Sato
    • Keiko Mizuno
    • Hiromasa Inoue
    • Setsuro Komiya
  • View Affiliations

  • Published online on: August 25, 2017     https://doi.org/10.3892/mco.2017.1394
  • Pages: 897-902
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The aim of the present study was to detect prognostic factors in patients with skeletal‑related events (SREs) and bone metastasis at the time of non‑small‑cell lung cancer (NSCLC) diagnosis. A total of 85 NSCLC patients were retrospectively enrolled, 47 (55.2%) of whom presented with SREs at the time of NSCLC diagnosis. Multivariate logistic regression analysis identified squamous cell carcinoma as a risk factor for SRE. Kaplan‑Meier analysis demonstrated that there was no difference in the overall survival between the SRE and no SRE groups. Cox hazard model revealed that a higher Eastern Cooperative Oncology Group (ECOG) performance status (PS) score was a risk factor for poor prognosis, while surgery for bone metastasis and molecular‑targeted therapy were factors for better prognosis in patients with SREs at the time of NSCLC diagnosis. Multivariate analysis revealed that a higher ECOG PS score and metastasis to the adrenal gland were risk factors for poor prognosis, while surgery for bone metastasis and molecular‑targeted therapy were factors for better prognosis. Thus, while surgical treatment and molecular‑targeted therapy appear to improve the prognosis of patients with bone metastasis at the time of NSCLC diagnosis, those with a higher ECOG PS score and adrenal metastasis may benefit more from radiotherapy or supportive care.

Introduction

Lung cancer is the leading cause of cancer-related mortality in Japan as well as worldwide (1). Non-small-cell lung cancer NSCLC is the third most common cause of bone metastases following breast and prostate cancer (2). It has been reported that 84.8% of patients exhibit multiple skeletal metastases at the time of NSCLC diagnosis, which cause complications including bone pain, pathological fractures, spinal cord compression and dysmotility (3). There are differences in the prognosis of NSCLC patients with and without bone metastases (4,5). In addition, 54.3% of patients experience skeletal-related events (SREs) at the time of NSCLC diagnosis (3). SREs include radiotherapy, pathological fractures, spinal cord compression, orthopedic surgery and hypercalcemia. SREs affect not only the prognosis but also the activities of daily living (6). However, to the best of our knowledge, there are currently no reports evaluating the risk factors for SREs at NSCLC diagnosis. The aim of the present study was to examine the risk factors for SREs and overall survival in patients with SREs or bone metastases at the time of NSCLC diagnosis.

Patients and methods

Patients

A total of 1,072 NSCLC patients who were treated at Kagoshima University Hospital between 2006 and 2013 were retrospectively identified, and 85 patients with bone metastases at the time of NSCLC diagnosis, whose histopathological diagnosis of NSCLC was available, were enrolled in the present study. All deaths were due to NSCLC or cancer-related complications. The presence of bone metastasis was diagnosed by physicians, radiologists and orthopedic surgeons. Bone metastases were detected by X-ray, computed tomography (CT) scans, magnetic resonance imaging (MRI) of the skeleton, or positron emission tomography (PET)-CT. In all the cases, diagnosis was confirmed by pathological examination. All the patients who received molecular-targeted therapy had epidermal growth factor receptor (EGFR) mutations. Pathological fractures, spinal cord compression and hypercalcemia were defined as SREs, as were radiotherapy and orthopedic surgery that were performed for bone metastases at the time of NSCLC diagnosis. Improvements in the primary tumor were defined as partial or complete response according to the Response Evaluation Criteria In Solid Tumors guidelines (7). Improvements in bone metastases were defined as reduced tumor size on CT scan. When the Mirel's score was >8 points, surgical treatment for long bone metastases was undertaken (8). In one case with a Tokuhashi score of 1, surgery for spinal metastasis was undertaken according to the patient's request.

The local Ethics Committee of Kagoshima University reviewed and approved the present study, and access to the database was approved by the Research Ethics Committee at the Kagoshima University (trial registration no. 438; name of registry: ‘Evaluation of utility of imaging analysis of metastatic bone tumor’; URL of registry: http://www.orthop-kagoshima-u.com/; date of registration: 02/05/2014). All the patients provided written informed consent for their records to be used in this study.

Statistical analysis

Kaplan-Meier analysis was used to evaluate prognosis. Multiple logistic regression analysis was used to evaluate the risk factors for SREs. The Cox proportional hazards model was used to examine the risk factors for survival. All statistical analyses were performed using BellCurve for Excel (Social Survey Research Information Co., Ltd. Tokyo, Japan). P-values of <0.05 were considered to indicate statistically significant differences.

Results

Squamous cell carcinoma is a risk factor for SREs

The median patient age was 66.0 years (range, 55.0–72.0 years), and 52 of the 85 patients were male (61.2%). The median follow-up period from NSCLC diagnosis was 7 months (range, 4.9–9.1 months). The histopathological diagnosis of NSCLC was adenocarcinoma (n=55), squamous cell carcinoma (n=16), and other types of NSCLC (n=14). A total of 73 patients (85.9%) were affected by multiple bone metastases at the time of NSCLC diagnosis. The most common site of bone metastases was the spine (n=70), followed by the pelvis (n=46), sacrum (n=31) and extremities (n=26) (Table I). A total of 47 patients (55.2%) were affected by SREs at the time of NSCLC diagnosis. The most frequent SREs were radiotherapy (87.2%) followed by spinal cord compression (31.9%), pathological fracture (21.3%), surgery (14.9%), and hypercalcemia (8.5%) (Table II). Univariate analysis revealed that a higher ECOG PS score (9) and squamous cell carcinoma were risk factors for SREs at the time of NSCLC diagnosis. Multivariate logistic regression analysis revealed that squamous cell carcinoma was a risk factor for SREs at the time of NSCLC diagnosis (Table III). The incidence rate of SREs in squamous cell carcinoma and adenocarcinoma was 87.5% (14/16) and 47.3% (26/55), respectively. The Fisher's exact test also revealed that the incidence rate of SREs was significantly higher in squamous cell carcinoma compared with that in adenocarcinoma patients at the time of NSCLC diagnosis (Table IV).

Table I.

Non-small-cell lung cancer patients with bone metastases (n=85).

Table I.

Non-small-cell lung cancer patients with bone metastases (n=85).

CharacteristicsValues
Male sex, no. (%)52 (61.2)
Age (years), median (range)66.0 (55.0–72.0)
ECOG PS, median (range)2 (1–2)
BMI (kg/m2), median (range)20.3 (18.2–22.8)
Days on treatment after diagnosis, median (range)15.0 (6.0–24.0)
Brinkmann index, median (range)200 (0–840)
Adenocarcinoma, no. (%)55 (64.7)
Squamous cell carcinoma, no. (%)16 (18.8)
Spine metastasis, no. (%)70 (82.4)
Cervical metastasis, no. (%)25 (29.4)
Thoracic metastasis, no. (%)50 (58.8)
Lumbar metastasis, no. (%)43 (50.6)
Sacral metastasis, no. (%)31 (36.5)
Pelvic metastasis, no. (%)46 (54.1)
Bone of extremities metastasis, no. (%)26 (30.6)
Multiple bone metastasis, no. (%)73 (85.9)
Single bone metastasis, no. (%)12 (14.1)
Brain metastasis, no. (%)32 (37.6)
Adrenal gland metastasis, no. (%)18 (21.2)
Liver metastasis, no. (%)18 (21.2)
Lymph node metastasis, no. (%)72 (84.7)
SREs, no. (%)47 (55.3)
Spinal complaint, no (%)15 (17.6)
Hypercalcemia, no. (%)4 (4.7)
Fracture, no. (%)10 (11.8)
Operation for bone metastasis, no. (%)7 (8.2)
Radiotherapy, no. (%)41 (48.2)
Molecular-targeted therapy, no. (%)18 (21.2)
Chemotherapy, no. (%)43 (50.6)
Bisphosphonates, no. (%)22 (25.9)

[i] ECOG PS, Eastern Cooperative Oncology Group performance status; BMI, body mass index; SREs, skeletal-related events.

Table II.

SREs at the time of NSCLC diagnosis.

Table II.

SREs at the time of NSCLC diagnosis.

SREsNo. (%)
Total47 (55.2)
Radiotherapy41 (87.2)
Spinal cord compression15 (31.9)
Pathological fracture10 (21.3)
Hypercalcemia4 (8.5)
Surgery  7 (14.9)

[i] SREs, skeletal-related events; NSCLC, non-small-cell lung cancer.

Table III.

Risk factors for SREs at the time of NSCLC diagnosis.

Table III.

Risk factors for SREs at the time of NSCLC diagnosis.

Univariate analysisMultivariate analysis


FactorsMedian (range)HR (95% CI)P-valueHR (95% CI)P-value
Age, years66 (55–73)1.00 (0.97–1.04)0.93(−)
Male sex280.85 (0.36–2.07)0.74(−)
BMI20.3 (18.2–21.6)0.94 (0.83–1.06)0.29(−)
Smoking281.07 (0.45–2.55)0.88(−)
Number of bone metastases4 (2–7)1.02 (0.92–1.13)0.72(−)
Spine metastasis412.12 (0.68–6.61)0.203.11 (0.74–13.09)0.12
Cervical metastasis141.04 (0.41–2.66)0.93(−)
Thoracic metastasis270.88 (0.34–2.10)0.77(−)
Lumbar metastasis230.86 (0.37–2.03)0.73(−)
Sacral metastasis170.47 (0.40–2.36)0.95(−)
Pelvic metastasis281.64 (0.69–3.88)0.26(−)
Thigh metastasis141.59 (0.59–4.32)0.361.46 (0.52–4.16)0.47
Rib metastasis200.54 (0.23–1.28)0.16(−)
Humerus metastasis72.04 (0.49–8.50)0.33(−)
Brain metastasis140.92 (0.36–2.32)0.86(−)
Liver metastasis60.65 (0.20–2.12)0.47(−)
Adrenal gland metastasis161.049 (0.35–3.14)0.932(−)
Lymph node metastasis400.32 (0.06–1.63)0.17(−)
PS score2 (1–3)1.67 (1.08–2.60)0.0211.40 (0.88–2.24)0.16
Squamous cell carcinoma147.64 (1.61–36.16)0.019.41 (1.65–53.81)0.012
Adenocarcinoma260.38 (0.15–0.99)0.04(−)
Molecular-targeted therapy181.35 (0.47–3.92)0.58(−)

[i] Bold print indicates statistical significance. HR, hazard ratio; CI, confidence interval; SREs, skeletal-related events; NSCLC, non-small-cell lung cancer; BMI, body mass index; PS, performance status.

Table IV.

Association between SREs and pathological diagnosis of NSCLC.

Table IV.

Association between SREs and pathological diagnosis of NSCLC.

Type of NSCLCSREs at the time of NSCLC diagnosisNo SREs at the time of NSCLC diagnosis
Squamous cell carcinoma142
Adenocarcinoma2629

[i] Fisher's exact test (P<0.01). SREs, skeletal-related events; NSCLC, non-small-cell lung cancer.

Survival rates of patients with bone metastasis at the time of NSCLC diagnosis

The median survival after diagnosis of NSCLC and bone metastasis was 7.0 months. The 1-, 2-, 3- and 5-year survival rates of patients with bone metastasis at the time of NSCLC diagnosis were 38.8, 23.5, 12.9 and 3.5%, respectively (Fig. 1).

Prognostic factors for patients with bone metastasis at the time of NSCLC diagnosis

The Cox proportional hazards model was used to evaluate the prognostic factors for patients with bone metastasis at the time of NSCLC diagnosis. Univariate analysis revealed that older age, male sex, higher ECOG PS score, and presence of adrenal gland and liver metastasis, were risk factors for poor prognosis, whereas molecular-targeted therapy, chemotherapy and improvement of bone metastasis on CT were factors for better prognosis (Table V). Multivariate analysis revealed that higher ECOG PS score and metastasis to the adrenal gland were risk factors for poor prognosis, while surgery for bone metastasis and molecular-targeted therapy were factors for better prognosis (Table V). In addition, Kaplan-Meier analysis revealed that adenocarcinoma with molecular-targeted therapy had a better prognosis compared with squamous cell carcinoma and adenocarcinoma without molecular-targeted therapy (Fig. 2).

Table V.

Risk factors of poor prognosis for patients with bone metastasis at the time of NSCLC diagnosis: Cox proportional hazards model for survival.

Table V.

Risk factors of poor prognosis for patients with bone metastasis at the time of NSCLC diagnosis: Cox proportional hazards model for survival.

Univariate analysisMultivariate analysis


FactorsHR (95% CI)P-valueHR (95% CI)P-value
Age1.03 (1.01–1.06)0.006(−)
Male sex2.00 (1.24–3.24)0.005(−)
ECOG PS1.34 (1.07–1.68)0.011.46 (1.16–1.84)   0.002
BMI1.02 (0.96–1.09)0.51(−)
Smoking1.41 (0.89–2.25)0.14(−)
Adenocarcinoma0.71 (0.45–1.14)0.16(−)
Squamous cell carcinoma1.13 (0.64–2.00)0.67(−)
Number of bone metastasis1.04 (0.99–1.09)0.12(−)
Only bone metastasis0.68 (0.31–1.49)0.33(−)
Brain metastasis0.68 (0.45–1.13)0.13(−)
Adrenal gland metastasis3.02 (1.66–5.48) <0.0012.34 (1.27–4.31) <0.001
Liver metastasis2.80 (1.49–5.24)0.001(−)
Lymph node metastasis1.43 (0.68–2.99)0.34(−)
SREs0.84 (0.53–1.33)0.46(−)
Spinal complaint1.09 (0.63–1.96)0.76(−)
Hypercalcemia0.56 (0.17–1.79)0.32(−)
Fracture1.10 (0.55–2.21)0.79(−)
Radiotherapy0.81 (0.52–1.28)0.37(−)
Operation for bone metastasis0.40 (0.16–1.02)0.050.35 (0.13–0.97)0.04
Molecular-targeted therapy0.38 (0.21–0.69)   0.0020.37 (0.20–0.70)   0.002
Bisphosphonates0.77 (0.45–1.31)0.34(−)
Chemotherapy0.40 (0.25–0.64) <0.0010.66 (0.39–1.01)0.11
Improvement of bone metastasis0.29 (0.09–0.92)0.036(−)
Improvement of primary lesion0.56 (0.30–1.04)0.065(−)

[i] Bold print indicates statistical significance. HR, hazard ratio; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; BMI, body mass index; SREs, skeletal-related events.

Prognostic factors for patients with SREs at the time of NSCLC diagnosis

Kaplan-Meier analysis revealed that there was no difference in the overall survival between the SRE and no SRE groups (Fig. 3). Cox hazard model analysis was performed using four factors that were found to be significant for the prognosis of patients with bone metastasis at the time of NSCLC diagnosis. The Cox hazard model demonstrated that a higher ECOG PS score was a risk factor for poor prognosis, while surgery for bone metastasis and molecular-targeted therapy were factors for better prognosis (Table VI).

Table VI.

Risk factors of poor prognosis with SREs at the time of NSCLC (n=47) Cox proportional hazards model for survival.

Table VI.

Risk factors of poor prognosis with SREs at the time of NSCLC (n=47) Cox proportional hazards model for survival.

Univariate analysisMultivariate analysis


FactorsHR (95% CI)P-valueHR (95% CI)P-value
ECOG PS1.49 (1.10–2.00)   0.011.77 (1.30–2.42) <0.001
Adrenal gland metastasis3.11 (1.39–6.97) <0.012.01 (0.87–4.62)0.10
Surgery for bone metastasis0.39 (0.15–1.03)   0.060.23 (0.08–0.69)0.01
Molecular-targeted therapy0.47 (0.22–0.99)   0.040.32 (0.14–0.72)0.01

[i] Bold print indicates statistical significance. SREs, skeletal-related events; NSCLC, non-small-cell lung cancer; HR, hazard ratio; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status.

Discussion

The overall prognosis of NSCLC for a substantial portion of patients remains poor, as the majority of patients have metastasis at the time of NSCLC diagnosis. Although several risk factors affect overall survival in NSCLC (1015), it remains unclear which risk factors crucially affect SREs. It was hypothesized that examination of the risk factors for patients with SREs and bone metastasis at the time of NSCLC diagnosis would provide a more accurate prediction of prognosis and more suitable therapeutic strategies for these patient groups. Squamous cell carcinoma was found to be an independent risk factor for SREs at the time of NSCLC diagnosis. It has been reported that the frequency of distant metastases is higher in adenocarcinoma (3,16,17); there are discrepancies between those findings and the findings of the present study. It was also observed that the incidence rate of SREs was significantly higher in squamous cell carcinoma compared with that in adenocarcinoma patients at the time of NSCLC diagnosis. These findings suggest that bone metastasis of squamous cell carcinoma causes the development of SREs earlier compared with adenocarcinoma. The development of bone metastasis is a multistage process involving penetration of cancer cells from the surrounding tissue, invasion into the lymphatic or vascular circulation, transportation to the bone, proliferation in the bone tissue and bone destruction (18,19). Our findings suggest that bone metastasis from squamous cell carcinoma may destroy bone tissue more quickly compared with that from adenocarcinoma. Osteoclast cells in close proximity to bone metastases by squamous cell carcinoma were strongly activated for bone resorption (20), which supports this hypothesis.

Although SREs are reported to reduce quality of life, physical function, emotional happiness and overall survival (2123), the present results revealed no difference in overall survival between the SRE and no SRE groups. Multivariate analysis revealed that a higher ECOG PS score was a risk factor for poor prognosis in patients with SREs at the time of NSCLC diagnosis, while surgery for bone metastasis and molecular-targeted therapy were factors for better prognosis. These findings indicated that radical cure may be considered for patients with SREs at the time of NSCLC diagnosis.

Multivariate analysis revealed that a higher ECOG PS score was a risk factor for poor prognosis, while molecular-targeted therapy was a factor for better prognosis in patients with bone metastasis at the time of NSCLC diagnosis. These findings are consistent with previous reports (4,24). Kaplan-Meier analysis revealed that adenocarcinoma with molecular-targeted therapy had a better prognosis compared with squamous carcinoma and adenocarcinoma without molecular-targeted therapy. All the cases treated with molecular-targeted therapy had adenocarcinoma with EGFR mutations. Adenocarcinoma with and without mutations may be categorized into different subgroups of NSCLC for prognosis research.

In addition, surgery for bone metastasis was found to be a factor for better prognosis. In accordance with our findings, several reports demonstrated that a surgical approach to metastatic NSCLC may improve prognosis (2527). There is a possibility that surgery was performed only on patients who were expected to have better prognosis. Nonetheless, our multivariate analysis included several critical explanatory variables for prognosis, including ECOG PS, number of bone metastases, visceral metastasis, SREs, chemotherapy, and molecular-targeted therapy. The inclusion of these critical prognostic factors in the multivariate analysis excludes a significant deviation in the indication for surgery by prediction of overall survival.

The multivariate analysis revealed that metastasis to the adrenal gland was a risk factor for poor prognosis. The adrenal gland is a major site of NSCLC metastases (15%) (28). Adrenal metastases of NSCLC usually exhibit hematogenous spread to other sites. In accordance with our findings, it has been reported that NSCLC metastasizing to the adrenal glands is incurable (29,30).

There were several limitations to the present study: Data collection was retrospective. Furthermore, although the majority of cases with bone metastasis should be referred to the Department of Orthopaedic Surgery of Kagoshima University Hospital, as this is the only university hospital that undertakes orthopedic surgery and therapeutic radiology, several cases were referred to other hospitals in the area.

Several prognostic factors for SREs and bone metastasis patients at the time of NSCLC diagnosis were identified. While surgical treatment and molecular-targeted therapy improve the prognosis of patients with SREs or bone metastasis at the time of NSCLC diagnosis, patients with higher ECOG PS score and adrenal metastasis may benefit more from radiotherapy or best supportive care.

Acknowledgements

The authors would like to thank Ms. Ayano Komure and Ms. Kana Maeda for their excellent assistance. We would also like to thank Edanz Editing Japan (Fukuoka, Japan) for providing medical editing services.

Glossary

Abbreviations

Abbreviations:

NSCLC

non-small-cell lung cancer

SREs

skeletal-related events

CT

computed tomography

MRI

magnetic resonance imaging

PET

positron emission tomography

References

1 

Zeng X, Li J, Peng L, Wang Y, Tan C, Chen G, Wan X, Lu Q and Yi L: Economic outcomes of maintenance gefitinib for locally advanced/metastatic non-small-cell lung cancer with unknown EGFR mutations: A semi-Markov model analysis. PLoS One. 9:e888812014. View Article : Google Scholar : PubMed/NCBI

2 

Rosen LS, Gordon D, Tchekmedyian NS, Yanagihara R, Hirsh V, Krzakowski M, Pawlicki M, De Souza P, Zheng M, Urbanowitz G, et al: Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: A randomized, Phase III, double-blind, placebo-controlled trial. Cancer. 100:2613–2621. 2004. View Article : Google Scholar : PubMed/NCBI

3 

He YF, Luo HQ, Wang W, Chen J, Yao YW, Cai SB, He J, Yan Y, Wu SS, Hu XX, et al: Clinical features and prognosis-associated factors of non-small cell lung cancer exhibiting symptoms of bone metastasis at the time of diagnosis. Oncol Lett. 9:2706–2712. 2015.PubMed/NCBI

4 

Ulas A, Bilici A, Durnali A, Tokluoglu S, Akinci S, Silay K, Oksuzoglu B and Alkis N: Risk factors for skeletal-related events (SREs) and factors affecting SRE-free survival for nonsmall cell lung cancer patients with bone metastases. Tumour Biol. 37:1131–1140. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Santini D, Barni S, Intagliata S, Falcone A, Ferraù F, Galetta D, Moscetti L, La Verde N, Ibrahim T, Petrelli F, et al: Natural history of non-small-cell lung cancer with bone metastases. Sci Rep. 5:186702015. View Article : Google Scholar : PubMed/NCBI

6 

Shimada H, Setoguchi T, Yokouchi M, Sasaki H, Ishidou Y, Kawamura I, Abematsu M, Nagano S and Komiya S: Metastatic bone tumors: Analysis of factors affecting prognosis and efficacy of CT and F-FDG PET-CT in identifying primary lesions. Mol Clin Oncol. 2:875–881. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Mirels H: Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. 1989. Clin Orthop Relat Res. (415 Suppl):S4–S13. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET and Carbone PP: Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 5:649–655. 1982. View Article : Google Scholar : PubMed/NCBI

9 

Wu M, Zhao J, Song SW, Zhuo M, Wang X, Bai H, Wang S, Yang L, An T, Zhang Y, et al: EGFR mutations are associated with prognosis but not with the response to front-line chemotherapy in the Chinese patients with advanced non-small cell lung cancer. Lung Cancer. 67:343–347. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Aggarwal C and Langer CJ: Older age, poor performance status and major comorbidities: How to treat high-risk patients with advanced nonsmall cell lung cancer. Curr Opin Oncol. 24:130–136. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Leprieur Giroux E, Lavole A, Ruppert AM, Gounant V, Wislez M, Cadranel J and Milleron B: Factors associated with long-term survival of patients with advanced non-small cell lung cancer. Respirology. 17:134–142. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Kalikaki A, Koutsopoulos A, Hatzidaki D, Trypaki M, Kontopodis E, Stathopoulos E, Mavroudis D, Georgoulias V and Voutsina A: Clinical outcome of patients with non-small cell lung cancer receiving front-line chemotherapy according to EGFR and K-RAS mutation status. Lung Cancer. 69:110–115. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Leung EY, Scott HR and McMillan DC: Clinical utility of the pretreatment glasgow prognostic score in patients with advanced inoperable non-small cell lung cancer. J Thorac Oncol. 7:655–662. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Eberhardt WE, de Marinis F, et al: Prognostic factors in patients with advanced non-small cell lung cancer: Data from the phase III FLEX study. Lung Cancer. 77:376–382. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Zhang Y, Jin B, Shao M, Dong Y, Lou Y, Huang A and Han B: Monitoring of carcinoembryonic antigen levels is predictive of EGFR mutations and efficacy of EGFR-TKI in patients with lung adenocarcinoma. Tumour Biol. 35:4921–4928. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Duan JC, An TT, Wu MN, Yang L, Bai H, Wang ZJ, Wang YY, Zhuo ML, Zhao J, Wang SH and Wang J: Correlation between the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors and EGFR mutations in advanced squamous cell lung cancer. Zhonghua Jie He He Hu Xi Za Zhi. 35:323–328. 2012.(In Chinese). PubMed/NCBI

17 

Stetler-Stevenson WG: Type IV collagenases in tumor invasion and metastasis. Cancer Metastasis Rev. 9:289–303. 1990. View Article : Google Scholar : PubMed/NCBI

18 

Mundy GR: Mechanisms of bone metastasis. Cancer. 80 (8 Suppl):S1546–S1556. 1997. View Article : Google Scholar

19 

Tomita A, Kasaoka T, Inui T, Toyoshima M, Nishiyama H, Saiki H, Iguchi H and Nakajima M: Human breast adenocarcinoma (MDA-231) and human lung squamous cell carcinoma (Hara) do not have the ability to cause bone resorption by themselves during the establishment of bone metastasis. Clin Exp Metastasis. 25:437–444. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Coleman RE: Metastatic bone disease: Clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 27:165–176. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Coleman RE: Bisphosphonates: Clinical experience. Oncologist. 9 Suppl 4:S14–S27. 2004. View Article : Google Scholar

22 

Cetin K, Christiansen CF, Jacobsen JB, Nørgaard M and Sørensen HT: Bone metastasis, skeletal-related events, and mortality in lung cancer patients: A Danish population-based cohort study. Lung Cancer. 86:247–254. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Bae HM, Lee SH, Kim TM, Kim DW, Yang SC, Wu HG, Kim YW and Heo DS: Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis. Lung Cancer. 77:572–577. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Plones T, Osei-Agyemang T, Krohn A and Passlick B: Surgical treatment of extrapulmonary oligometastatic non-small cell lung cancer. Indian J Surg. 77 Suppl 2:S216–S220. 2015. View Article : Google Scholar

25 

Chen YJ, Chang GC, Chen HT, Yang TY, Kuo BI, Hsu HC, Yang HW and Lee TS: Surgical results of metastatic spinal cord compression secondary to non-small cell lung cancer. Spine (Phila Pa 1976). 32:E413–E418. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Lei M, Liu Y, Tang C, Yang S, Liu S and Zhou S: Prediction of survival prognosis after surgery in patients with symptomatic metastatic spinal cord compression from non-small cell lung cancer. BMC Cancer. 15:8532015. View Article : Google Scholar : PubMed/NCBI

27 

Niu FY, Zhou Q, Yang JJ, Zhong WZ, Chen ZH, Deng W, He YY, Chen HJ, Zeng Z, Ke EE, et al: Distribution and prognosis of uncommon metastases from non-small cell lung cancer. BMC Cancer. 16:1492016. View Article : Google Scholar : PubMed/NCBI

28 

Urschel JD, Finley RK and Takita H: Long-term survival after bilateral adrenalectomy for metastatic lung cancer: A case report. Chest. 112:848–850. 1997. View Article : Google Scholar : PubMed/NCBI

29 

Karolyi P: Do adrenal metastases from lung cancer develop by lymphogenous or hematogenous route? J Surg Oncol. 43:154–156. 1990. View Article : Google Scholar : PubMed/NCBI

30 

Chadeyras JB, Mazel C and Grunenwald D: Vertebral en bloc resection for lung cancer: Twelve years' experience. Ann Chir. 131:616–622. 2006.(In French). View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

November-2017
Volume 7 Issue 5

Print ISSN: 2049-9450
Online ISSN:2049-9469

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Tominaga H, Setoguchi T, Shimada H, Nagano S, Sasaki H, Ishidou Y, Sato M, Mizuno K, Inoue H, Komiya S, Komiya S, et al: Prognostic factors in patients with skeletal‑related events at non‑small‑cell lung cancer diagnosis. Mol Clin Oncol 7: 897-902, 2017
APA
Tominaga, H., Setoguchi, T., Shimada, H., Nagano, S., Sasaki, H., Ishidou, Y. ... Komiya, S. (2017). Prognostic factors in patients with skeletal‑related events at non‑small‑cell lung cancer diagnosis. Molecular and Clinical Oncology, 7, 897-902. https://doi.org/10.3892/mco.2017.1394
MLA
Tominaga, H., Setoguchi, T., Shimada, H., Nagano, S., Sasaki, H., Ishidou, Y., Sato, M., Mizuno, K., Inoue, H., Komiya, S."Prognostic factors in patients with skeletal‑related events at non‑small‑cell lung cancer diagnosis". Molecular and Clinical Oncology 7.5 (2017): 897-902.
Chicago
Tominaga, H., Setoguchi, T., Shimada, H., Nagano, S., Sasaki, H., Ishidou, Y., Sato, M., Mizuno, K., Inoue, H., Komiya, S."Prognostic factors in patients with skeletal‑related events at non‑small‑cell lung cancer diagnosis". Molecular and Clinical Oncology 7, no. 5 (2017): 897-902. https://doi.org/10.3892/mco.2017.1394