Abstract
OBJECTIVE:
Typically, bone metastasis causes osteolytic and osteoblastic lesions resulting from the interactions of tumor cells with osteoclasts and osteoblasts. In addition to these interactions, tumor tissues may grow inside bones and cause mass lesions. In the present study, we aimed to demonstrate the negative impact of a tumor mass in a large cohort of patients with bone metastatic cancer.
METHODS:
Data from 335 patients with bone metastases were retrospectively reviewed. For the analysis, all patients were divided into three subgroups with respect to the type of bone metastasis: osteolytic, osteoblastic, or mixed. The patients were subsequently categorized as having bone metastasis with or without a tumor mass, and statistically significant differences in median survival and 2-year overall survival were observed between these patients (the median survival and 2-year overall survival were respectively 3 months and 16% in patients with a tumor mass and 11 months and 26% in patients without a tumor mass; p<0.001).
RESULTS:
According to multivariate analysis, the presence of bone metastasis with a tumor mass was found to be an independent prognostic factor (p=0.011, hazard ratio: 1.62, 95% confidence interval: 1.11–1.76). Bone metastasis with a tumor mass was more strongly associated with osteolytic lesions, other primary diseases (except for primary breast and prostate cancers), and spinal cord compression.
CONCLUSION:
Bone metastasis with a tumor mass is a strong and independent negative prognostic factor for survival in cancer patients.
Bone metastasis; Bone metastasis with a tumor mass; Prognostic factor; Survival
INTRODUCTION
Bone metastasis is the most frequent complication of cancer, occurring in
up to 70% of patients with breast or prostate cancer and in
approximately 15–30% of patients with carcinoma of the lung, colon,
stomach, bladder, rectum, thyroid, or kidney (11. Coleman RE, Rubens RD. The clinical course of
bone metastases from breast cancer. Br J Cancer.
1987;55(1):61–6, 10.1038/bjc.1987.13
http://dx.doi.org/10.1038/bjc.1987.13...
). Although the exact incidence of bone
metastasis remains unknown, this type of metastasis is an attractive
area of study given its high prevalence in cancer patients.
Bone metastases develop as a result of interactions between tumor cells
and bone cells. Cancer cells can induce various metastatic bone
lesions through different mechanisms that depend on the primary
disease, and two types of metastatic bone lesions have been
described (22. Roodman GD. Mechanisms of bone metastasis. N Engl
J Med. 2004;350(16):1655–64,
10.1056/NEJMra030831
http://dx.doi.org/10.1056/NEJMra030831...
,33. Mundy GR. Metastasis to bone: causes,
consequences and therapeutic opportunities. Nat Rev Cancer.
2002;2(8):584–93, 10.1038/nrc867
http://dx.doi.org/10.1038/nrc867...
). The first is an
osteolytic lesion that progresses with bone resorption as a result
of osteoclast activation; the second is an osteoblastic lesion that
triggers bone formation and osteoblastic cell activation. These two
types of lesions may be present concomitantly in certain patients
(mixed type) following stimulation of the two different types of
bone cells. Alternatively, the tumor itself may grow inside the bone
tissue and destroy the bone directly (44. Käkönen SM, Mundy GR. Mechanisms of osteolytic
bone metastases in breast carcinoma. Cancer.
2003;97(3Suppl):834–9,
10.1002/(ISSN)1097-0142
http://dx.doi.org/10.1002/(ISSN)1097-014...
). These mass lesions may cause an
increase in complications (e.g., spinal cord compression, pathologic
fracture) due to metastasis-related bone destruction and suggest the
presence of a significant tumor burden. Examples of computerized
tomography images of osteolytic lesions, osteoblastic lesions, and
bone metastasis with a tumor mass are shown in Figure 1.
Types of bone metastasis (white arrows). A) Osteolytic metastasis. B) Osteoblastic metastasis. C) Bone metastasis with a tumor mass.
Although the duration of survival varies according to the primary tumor,
bone metastases are usually incurable (55. Coleman RE. Metastatic bone disease: clinical
features, pathophysiology and treatment strategies. Cancer
Treat Rev.2001;27(3):165–76,
10.1053/ctrv.2000.0210
http://dx.doi.org/10.1053/ctrv.2000.0210...
). General treatment procedures for
patients with bone metastasis include bisphosphonate administration,
chemotherapy, and palliative radiation therapy. However, responses
to these treatment modalities are relatively poor, and the patient’s
quality of life is generally impaired. Prognosis may vary among
patients depending on factors such as the primary disease type, age,
the patient’s performance status, the metastatic interval, and the
number of metastatic sites (66. Katagiri H, Takahashi M, Wakai K, Sugiura H,
Kataoka T, Nakanishi K. Prognostic factors and a scoring
system for patients with skeletal metastasis. J Bone Joint
Surg Br. 2005;87(5):698–703,
10.1302/0301-620X.87B5.15185
http://dx.doi.org/10.1302/0301-620X.87B5...
,77. Van der Linder YM, Dijkstra SPDS, Vonk EJA,
Marijnen CAM, Leer JWH. Prediction of survival in patients
with metastases in the spinal column.
Cancer.2005;103(2):320–8,
10.1002/(ISSN)1097-0142
http://dx.doi.org/10.1002/(ISSN)1097-014...
).
Nevertheless, these factors are not particularly helpful with
respect to decision making in routine clinical practice. Moreover,
data on both the prognostic impact of the mechanism type on bone
metastasis and the additional role of tumor masses in these patients
are lacking.
Therefore, we designed a retrospective analysis to evaluate the impact of bone metastasis-related tumor mass on patient survival. We also evaluated differences in the response to radiation therapy, in complications, and in the pain response in our cohort according to the type of metastasis.
MATERIALS AND METHODS
This study was conducted at the Department of Radiation Oncology at Cumhuriyet University Hospital in Sivas, Turkey, in accordance with the principles of the Declaration of Helsinki. A total of 335 cancer patients with bone metastasis who were admitted to the department between 2007 and 2013 were evaluated retrospectively.
All patients were treated with palliative radiotherapy and bisphosphonate. During the treatment period, all patients were examined by a radiation oncologist immediately before and 1 month after radiotherapy. The physical examination findings as well as body weight; Eastern Cooperative Oncology Group (ECOG) performance scores; and histopathological, radiological, and laboratory data (alkaline phosphatase [ALP] and calcium levels) were recorded. The patients’ survival data were obtained from hospital records, and patients lost to follow-up were contacted to obtain information about their condition. Survival was defined as the time between the date of the first detection of bone metastasis and the date of last contact or death.
The cancer type was classified based on the primary site: head and neck,
lung, breast, prostate, gastrointestinal system, genitourinary
system, or other. Prior to palliative radiotherapy, each patient’s
performance status was scored according to the ECOG scoring system
(88. Oken MM, Creech RH, Tormey DC, Horton J, Davis T,
Mc Fadden ET, et al. Toxicity and response criteria of the
Eastern Cooperative Oncology Group. Am J ClinOncol.
1982:5(6):649–55,
10.1097/00000421-198212000-00014
http://dx.doi.org/10.1097/00000421-19821...
). Weight loss was
defined as loss of >10% of body weight in 1 month.
Bone metastasis was revealed by computerized tomography or magnetic resonance imaging and was confirmed by bone scintigraphy and positron emission tomography.
All patients were divided into three subgroups with respect to the type of bone metastasis: osteolytic, osteoblastic, or mixed type. All patients were subsequently recategorized into two groups: bone metastasis with or without a tumor mass.
Pain intensity was evaluated using visual analog scales in 139 (41%) of
the cases (99. Price DD, McGrath PA, Rafii A, Buckingham B. The
validation of visual analogue scales as ratio scale measures
for chronic and experimental pain. Pain. 1981;17(1):45–56,
10.1016/0304-3959(83)90126-4
http://dx.doi.org/10.1016/0304-3959(83)9...
). Patients were
routinely asked to rate their pain intensity by placing a mark on a
10-mm visual analog scale at the start of radiotherapy and at 1
month after radiotherapy. This scaling system was used to evaluate
the intensity of pain only in the radiotherapy-affected region. The
response to radiotherapy was determined by calculating the
difference between the pain intensity on the visual analog scale
before and 1 month after the initiation of radiotherapy.
Statistical Package for Social Sciences (SPSS) for Windows 14.0 (SPSS, Inc., Chicago, IL, USA) was used for the statistical analysis. For descriptive statistics, the mean, standard deviation, frequency, and median were used. Categorical data were compared statistically using the chi-square test or Fisher’s exact test. Survival rates were calculated according to the Kaplan-Meier method. A multivariate analysis (Cox regression analysis) was used to evaluate independent risk factors affecting survival. P-values ≤0.05 were accepted as statistically significant.
RESULTS
The study group comprised 234 (70%) men and 101 (30%) women. The median age at the time of cancer diagnosis was 59 years (range, 21-82 years). The primary disease distribution was as follows: lung cancer in 107 (32%) patients, breast cancer in 64 (19%), prostate cancer in 62 (19%), gastrointestinal system tumors in 40 (12%), genitourinary system tumors in 20 (6%), head and neck tumors in 11 (3%), and tumors in other organs in 31 (9%).
Osteolytic bone metastasis was observed in 99 (30%) patients, whereas 155 (46%) had osteoblastic bone metastasis, and 71 (21%) had mixed-type bone metastasis. Ten (3%) patients had bone metastasis and only a tumor mass, without any other lesions; these 10 patients were excluded when categorizing the patients with respect to the type of bone lesion (i.e., osteolytic, osteoblastic, or mixed). Bone metastasis with a tumor mass was present in 73 (22%) cases. Eleven (3%) patients had a single bone metastatic lesion, and 324 (97%) had two or more lesions. The 11 patients with single bone lesions had no metastases in other organs. The locations and frequencies of bone metastases were as follows: vertebral column metastasis in 283 (84%) patients, pelvic bone metastasis in 246 (73%), long bone metastasis in 189 (56%), costal metastasis in 189 (56%), and skull metastasis in 63 (19%).
Spinal cord compression was observed in 20 patients, or 7% of all patients with vertebral column metastases (N: 283), whereas 49 (15%) patients had pathologic fractures, 26 (8%) had neurological deficits, and 16 (5%) had hypercalcemia. Surgical interventions were performed for pathologic fractures in 19 (39%) patients with pathologic fractures (N: 49).
The types of bone metastasis with respect to primary disease were as follows. Among patients with lung cancer, 42 (39%) had osteolytic lesions, 44 (41%) had osteoblastic lesions, 19 (18%) had mixed lesions, and 2 (2%) had bone metastases with only tumor masses. For patients with breast cancer, 22 (34%), 19 (30%), and 22 (34%) had osteolytic, osteoblastic, and mixed lesions, respectively; 1 (2%) had a bone metastasis with only a tumor mass. Osteolytic, osteoblastic, and mixed lesions developed in 2 (3%), 53 (86%), and 7 (11%), respectively, patients with prostate cancer. Regarding patients with gastrointestinal system tumors, 9 (22%), 18 (45%), and 11 (28%) had osteolytic, osteoblastic, and mixed lesions, respectively, and 2 (5%) showed bone metastases with only tumor masses. Among patients with genitourinary system tumors, 8 (40%), 5 (25%), and 5 (25%) had osteolytic, osteoblastic, and mixed lesions, respectively, with 2 (10%) exhibiting bone metastases with only tumor masses. The incidence of osteolytic, osteoblastic, and mixed lesions was 2 (18%), 5 (46%), and 2 (18%), respectively, for the patients with head and neck tumors; 2 (18%) had bone metastases with only tumor masses.
Bone metastasis with a tumor mass was observed more frequently in patients with osteolytic lesions than in those with other bone lesions. Spinal cord compression was observed more frequently in cases of bone metastasis with a tumor mass compared to cases without a tumor mass; when occurring in the latter, the compression was mostly due to compression fracture, as observed for osteolytic metastases, or to new bone formation, as observed in osteoblastic lesions. However, serum ALP levels were higher in patients without tumor masses. In addition, bone metastases with tumor masses were observed less frequently in patients with primary breast or prostate cancer compared with patients with other primary diseases, such as lung or gastrointestinal system tumors. With respect to pathologic fractures, pain severity, and responses to radiotherapy, no differences were observed between cases of bone metastases with tumor masses and cases of other bone metastases (Table 1).
The median survival duration was 10 months (range, 1-147 months), and the 1- and 2-year survival rates were 46% and 24%, respectively. The median survival duration was 3 months and the 1- and 2-year survival rates were 28% and 16%, respectively, among patients who had bone metastases with tumor masses and 11 months and 50% and 26%, respectively, in patients who had bone metastasis without tumor masses. The survival curves of the patients with or without a tumor mass are shown in Figure 2. Univariate analyses showed that the survival duration after metastasis was affected by the presence of bone metastasis with a tumor mass as well as by gender, weight loss, performance status, serum ALP and calcium levels, primary disease, bone metastasis type, number of bone lesions, the presence of extraosseous metastasis, and the disease-free interval. The prognostic factors that affected survival time after the development of bone metastasis are shown in Table 2.
Multivariate analyses revealed that the presence of bone metastasis with a tumor mass as well as gender, weight loss, primary disease, type of bone metastasis, and serum ALP and calcium levels were independent prognostic factors that affected survival. The independent prognostic factors that affected the duration of survival after the development of bone metastasis are shown in Table 3.
DISCUSSION
The prevalence of bone metastasis is higher in advanced-stage cancers. Patients diagnosed with bone metastasis usually have incurable disease, though the survival duration does vary based on the primary disease. Accordingly, it is very important to determine prognostic factors once a diagnosis of bone metastasis has been made. The present study investigated the prognostic and clinical importance of bone metastasis with a tumor mass and found that this feature was an apparently strong negative prognostic factor for survival. The higher incidence of these metastases in association with osteolytic lesions might have contributed to this result, as the presence of osteolytic lesions was found to be a poor prognostic factor in a multivariate analysis. In addition, growth of the tumor itself inside the bone might indicate a larger tumor burden, which might also contribute to a shorter survival duration. Given the soft tissue component of bone metastasis with a tumor mass, spinal cord compression was observed more frequently in these patients; nonetheless, the presence of these lesions did not increase the pain intensity or affect the response to radiotherapy.
Certain researchers have studied prognostic factors in patients with bone
metastases. In a study of 350 patients with skeletal metastases,
Katagiri et al. (66. Katagiri H, Takahashi M, Wakai K, Sugiura H,
Kataoka T, Nakanishi K. Prognostic factors and a scoring
system for patients with skeletal metastasis. J Bone Joint
Surg Br. 2005;87(5):698–703,
10.1302/0301-620X.87B5.15185
http://dx.doi.org/10.1302/0301-620X.87B5...
) reported
that the patient’s performance status, the primary lesion site, the
presence of multiple skeletal metastases, the presence of visceral
or cerebral metastases, and a history of previous chemotherapy were
important prognostic factors. Van der Linder et al. (77. Van der Linder YM, Dijkstra SPDS, Vonk EJA,
Marijnen CAM, Leer JWH. Prediction of survival in patients
with metastases in the spinal column.
Cancer.2005;103(2):320–8,
10.1002/(ISSN)1097-0142
http://dx.doi.org/10.1002/(ISSN)1097-014...
) reported a median
survival time of 7 months for 342 patients with vertebral
metastases, and Karnofsky stated that the performance score, the
primary tumor type, and absence of visceral metastasis were
significant predictors of survival. In the present study, female
gender, the presence of osteoblastic and/or mixed lesions, and
primary breast or prostate cancer were considered to be good
prognostic predictors. In contrast, the presence of bone metastasis
with a tumor mass as well as male gender, weight loss, primary lung
cancer, the presence of osteolytic lesions, and elevated ALP and
calcium levels were found to be poor prognostic predictors. Poor
performance in a single-variable analysis, a disease-free interval
of <2 years, the presence of extraosseous metastasis, and
multiple bone lesions were also poor prognostic factors.
Circulating metastatic cells in blood become entrapped by the bone marrow
spongiosum. Cancerous bone undergoes secondary lytic or blastic
changes (1010. Rubin P, Brasacchio R, Katz A. Solitary
metastases: illusion versus reality. Semin Radiat Oncol.
2006;16(2):120–30,
10.1016/j.semradonc.2005.12.007
http://dx.doi.org/10.1016/j.semradonc.20...
), and the type of
bone metastasis is determined by these changes. In the literature,
osteolytic lesions have been reported to be more frequent in breast
cancer cases, whereas osteoblastic lesions are observed in cases of
prostate cancer. In the present study, osteoblastic lesions (46%)
were more frequently observed in the overall patient population;
similar to the findings of other studies, osteolytic lesions were
more frequent in patients with breast cancer, with osteoblastic
lesions being more common in patients with prostate cancer. In terms
of the conventional classification of bone metastases, the presence
of a tumor mass was significantly more frequent among osteolytic
lesions (62%). The frequencies of bone metastasis with a tumor mass
were low among patients with breast or prostate cancer and similar
among those with other types of cancer. Specifically, 25–36% of
patients with other types of cancer (non-breast or prostatic) had
bone lesions with tumor masses.
Bone metastases are associated with a particular set of complications,
and the frequency of these complications varies depending on the
features of the metastatic lesions. For example, pathologic
fractures and spinal cord compression are encountered more
frequently with osteolytic lesions, as these lesions cause bone
destruction (22. Roodman GD. Mechanisms of bone metastasis. N Engl
J Med. 2004;350(16):1655–64,
10.1056/NEJMra030831
http://dx.doi.org/10.1056/NEJMra030831...
,1111. Coleman RE. Clinical features of metastatic bone
disease and risk of skeletal morbidity. Clin Cancer Res.
2006;66(12):6243–9,
10.1158/1078-0432.CCR-06-0931
http://dx.doi.org/10.1158/1078-0432.CCR-...
). It is rational to
expect that bone metastases with tumor masses would present more
complications; indeed, spinal cord compression was more frequent
among cases of bone metastasis with a tumor mass in the current
study. However, an elevated serum ALP level was more frequently
observed in cases of bone metastasis without a tumor mass. In terms
of pathologic fractures, serum calcium levels, surgical
intervention, pain severity, and responses to radiotherapy, no
differences were observed between patients with bone metastasis with
a tumor mass and those with other types of bone metastases.
The survival duration in patients with bone metastases varied quite
significantly depending on the primary disease, and it is reported
that the duration is generally longer for patients with breast or
prostate cancer than for those with other types of cancer (11. Coleman RE, Rubens RD. The clinical course of
bone metastases from breast cancer. Br J Cancer.
1987;55(1):61–6, 10.1038/bjc.1987.13
http://dx.doi.org/10.1038/bjc.1987.13...
,77. Van der Linder YM, Dijkstra SPDS, Vonk EJA,
Marijnen CAM, Leer JWH. Prediction of survival in patients
with metastases in the spinal column.
Cancer.2005;103(2):320–8,
10.1002/(ISSN)1097-0142
http://dx.doi.org/10.1002/(ISSN)1097-014...
,66. Katagiri H, Takahashi M, Wakai K, Sugiura H,
Kataoka T, Nakanishi K. Prognostic factors and a scoring
system for patients with skeletal metastasis. J Bone Joint
Surg Br. 2005;87(5):698–703,
10.1302/0301-620X.87B5.15185
http://dx.doi.org/10.1302/0301-620X.87B5...
,1111. Coleman RE. Clinical features of metastatic bone
disease and risk of skeletal morbidity. Clin Cancer Res.
2006;66(12):6243–9,
10.1158/1078-0432.CCR-06-0931
http://dx.doi.org/10.1158/1078-0432.CCR-...
). Ahn et
al. (1212. Ahn SG, Lee HM, Cho SH, Lee SA, Hwang SH, Jeong
J, et al. Prognostic factors for patients with bone-only
metastasis in breast cancer. Yonsei Med J.
2013;54(5):1168–77,
10.3349/ymj.2013.54.5.1168
http://dx.doi.org/10.3349/ymj.2013.54.5....
) reported a median
survival time of 55.2 months among 110 breast cancer patients with
only bone metastases. In contrast, survival durations as short as
5-7 months were reported among patients with lung cancer and bone
metastases (1111. Coleman RE. Clinical features of metastatic bone
disease and risk of skeletal morbidity. Clin Cancer Res.
2006;66(12):6243–9,
10.1158/1078-0432.CCR-06-0931
http://dx.doi.org/10.1158/1078-0432.CCR-...
,1313. Stanley KE. Prognostic factors for survival in
patients with inoperable lung cancer. J Natl Cancer Inst.
1980;65(1):25–32.,1414. Sugiura H, Yamada K, Sugiura T, Hida T,
Mitsudomi T. Predictors of survival in patients with bone
metastasis of lung cancer. Clin Orthop Relat Res.
2008;466(3):729–36,
10.1007/s11999-007-0051-0
http://dx.doi.org/10.1007/s11999-007-005...
). In our study, the longest survival
durations were observed in patients with breast cancer, followed by
those with prostate cancer (median survival durations of 18 months
and 15 months, respectively); conversely, the survival times of
patients with other cancers were relatively short.
Many studies have reported that patients with single bone lesions in the
absence of metastases in other organs have a longer survival
duration relative to those with multiple bone metastases (1515. Hoshi M, Takada J, Leguchi M, Takahashi S,
Nakamura H. Prognostic factors for patients with solitary
bone metastasis. Int J Clin Oncol. 2013;18(1):164–9,
10.1007/s10147-011-0359-3
http://dx.doi.org/10.1007/s10147-011-035...
16. Koizumi M, Yoshimoto M, Kasumi M, Ogata E.
Comparison between solitary and multiple skeletal metastatic
lesions of breast cancer patients. Ann Oncol.
2003;14(8):1234–40, 10.1093/annonc/mdg348
http://dx.doi.org/10.1093/annonc/mdg348...
-1717. Hirano Y, Oda M, Tsunezuka Y, Ishikawa N,
Watanabe G. Long-term survival cases of lung cancer
presented as solitary bone metastasis. Ann Thorac Cardiovasc
Surg. 2005;11(6):401–4.). In a study of 42 patients with
solitary bone metastases, Hoshi et al. (1515. Hoshi M, Takada J, Leguchi M, Takahashi S,
Nakamura H. Prognostic factors for patients with solitary
bone metastasis. Int J Clin Oncol. 2013;18(1):164–9,
10.1007/s10147-011-0359-3
http://dx.doi.org/10.1007/s10147-011-035...
) reported a median survival duration of
30 months and a 1-year survival rate of 76.5%. In the present study,
the 11 patients with single bone lesions had a median survival
duration of 32 months and a 1-year survival rate of 68%. The
survival durations were shorter among the patients with osteolytic
lesions compared with patients with osteoblastic or mixed lesions.
Moreover, patients with bone metastases with tumor masses had
significantly shorter survival durations compared with those with
bone metastases without tumor masses (median survival durations of 3
months and 11 months, respectively; 1-year survival rates of 28% and
50%, respectively).
Two major limitations of the present study were its retrospective design and its heterogeneous study population. We believe that studies of more specific groups would yield more significant results.
The presence of bone metastasis with a tumor mass appeared to be a strong negative prognostic factor and was associated with a higher incidence of spinal cord compression.
REFERENCES
-
1Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer. 1987;55(1):61–6, 10.1038/bjc.1987.13
» http://dx.doi.org/10.1038/bjc.1987.13 -
2Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350(16):1655–64, 10.1056/NEJMra030831
» http://dx.doi.org/10.1056/NEJMra030831 -
3Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2(8):584–93, 10.1038/nrc867
» http://dx.doi.org/10.1038/nrc867 -
4Käkönen SM, Mundy GR. Mechanisms of osteolytic bone metastases in breast carcinoma. Cancer. 2003;97(3Suppl):834–9, 10.1002/(ISSN)1097-0142
» http://dx.doi.org/10.1002/(ISSN)1097-0142 -
5Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev.2001;27(3):165–76, 10.1053/ctrv.2000.0210
» http://dx.doi.org/10.1053/ctrv.2000.0210 -
6Katagiri H, Takahashi M, Wakai K, Sugiura H, Kataoka T, Nakanishi K. Prognostic factors and a scoring system for patients with skeletal metastasis. J Bone Joint Surg Br. 2005;87(5):698–703, 10.1302/0301-620X.87B5.15185
» http://dx.doi.org/10.1302/0301-620X.87B5.15185 -
7Van der Linder YM, Dijkstra SPDS, Vonk EJA, Marijnen CAM, Leer JWH. Prediction of survival in patients with metastases in the spinal column. Cancer.2005;103(2):320–8, 10.1002/(ISSN)1097-0142
» http://dx.doi.org/10.1002/(ISSN)1097-0142 -
8Oken MM, Creech RH, Tormey DC, Horton J, Davis T, Mc Fadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J ClinOncol. 1982:5(6):649–55, 10.1097/00000421-198212000-00014
» http://dx.doi.org/10.1097/00000421-198212000-00014 -
9Price DD, McGrath PA, Rafii A, Buckingham B. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain. 1981;17(1):45–56, 10.1016/0304-3959(83)90126-4
» http://dx.doi.org/10.1016/0304-3959(83)90126-4 -
10Rubin P, Brasacchio R, Katz A. Solitary metastases: illusion versus reality. Semin Radiat Oncol. 2006;16(2):120–30, 10.1016/j.semradonc.2005.12.007
» http://dx.doi.org/10.1016/j.semradonc.2005.12.007 -
11Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;66(12):6243–9, 10.1158/1078-0432.CCR-06-0931
» http://dx.doi.org/10.1158/1078-0432.CCR-06-0931 -
12Ahn SG, Lee HM, Cho SH, Lee SA, Hwang SH, Jeong J, et al. Prognostic factors for patients with bone-only metastasis in breast cancer. Yonsei Med J. 2013;54(5):1168–77, 10.3349/ymj.2013.54.5.1168
» http://dx.doi.org/10.3349/ymj.2013.54.5.1168 -
13Stanley KE. Prognostic factors for survival in patients with inoperable lung cancer. J Natl Cancer Inst. 1980;65(1):25–32.
-
14Sugiura H, Yamada K, Sugiura T, Hida T, Mitsudomi T. Predictors of survival in patients with bone metastasis of lung cancer. Clin Orthop Relat Res. 2008;466(3):729–36, 10.1007/s11999-007-0051-0
» http://dx.doi.org/10.1007/s11999-007-0051-0 -
15Hoshi M, Takada J, Leguchi M, Takahashi S, Nakamura H. Prognostic factors for patients with solitary bone metastasis. Int J Clin Oncol. 2013;18(1):164–9, 10.1007/s10147-011-0359-3
» http://dx.doi.org/10.1007/s10147-011-0359-3 -
16Koizumi M, Yoshimoto M, Kasumi M, Ogata E. Comparison between solitary and multiple skeletal metastatic lesions of breast cancer patients. Ann Oncol. 2003;14(8):1234–40, 10.1093/annonc/mdg348
» http://dx.doi.org/10.1093/annonc/mdg348 -
17Hirano Y, Oda M, Tsunezuka Y, Ishikawa N, Watanabe G. Long-term survival cases of lung cancer presented as solitary bone metastasis. Ann Thorac Cardiovasc Surg. 2005;11(6):401–4.
Publication Dates
-
Publication in this collection
Aug 2015
History
-
Received
6 Feb 2015 -
Reviewed
23 Mar 2015 -
Accepted
31 Mar 2015