Metachronous Bone Metastasis Research Articles

The map of bone metastasis in nasopharyngeal carcinoma: A real-world study.

The aim of this study was to compare the metastatic patterns of synchronous bone metastasis (SBM) and metachronous bone metastasis (MBM) in nasopharyngeal carcinoma (NPC). This study included bone metastases in NPC patients from 2005 to 2016 in a Chinese hospital. Cohort 1 was collected from 2005 to 2010 for discovery, and Cohort 2 from 2011 to 2016 for validation. The chi-squared test, Wilcoxon rank sum test, and Kaplan-Meier technique were used to compare site, time, and survival between cohorts 1 and 2. Prognostic factors were analyzed using univariate or multivariate Cox regression. Cohort 1 had 112 individuals with SBM and 394 with MBM, and cohort 2 had 328 with SBM and 307 with MBM. The thoracic vertebra was the most frequently affected site of metastasis. Patients with SBM more often had metastasis to the cervical vertebrae compared with patients with MBM (34.5% vs. 22.3%, p < 0.05). Patients with SBM had better overall survival (42.2 months, 95% CI: 33.9-50.7) than patients with MBM (24.9 months, 95% CI: 22.2-28.7). Age at bone metastasis detection, metastasis to other organs, and more bone metastasis locations were associated with worse prognosis. The majority of MBMs occurred at 7 to 18 months after NPC diagnosis. Radiotherapy does not modify the metastatic patterns of NPC bone metastases. Patients with SBM tend to have metastasis to the cervical vertebra, which is close to the nasopharynx. Paying more attention to bone metastases during follow-up in the first 2 years after an NPC diagnosis.

A retrospective study on bone metastasis in dogs with advanced-stage solid cancer.

To review clinical characteristics, treatment, outcome and prognostic factors in dogs with solid cancer-bearing bone metastases. Records were reviewed from dogs with histologically-proven solid cancer and bone metastases. Clinicopathologic variables, bone metastases characteristics and skeletal-related events were recorded. Endpoints were time to bone metastases and survival. Fifty dogs were included, 20 of them with synchronous and 30 of them with metachronous bone metastases. In the latter group, median time to diagnosis of bone metastases was 210 days (range, 30 to 1835). Most common primary cancer locations included mammary gland (n=6), spleen (n=5) and tonsil (n=5). Most common histotypes were carcinoma (n=32) and hemangiosarcoma (n=10). Nineteen dogs had multiple bones involvement, with humeri and vertebrae more commonly affected. Twenty-four dogs received antitumoural therapy, five symptomatic treatment and 21 were not treated. Overall median survival after bone metastases diagnosis was 30 days (range, 11 to 49); 83% of dogs died because of skeletal-related events. Lack of antitumoural therapy was significantly associated with shorter survival (hazard ratio: 2.7; 95% confidence interval: 1.3 to 5.6) and with increased risk of skeletal-related death (hazard ratio: 3.3; 95% confidence interval: 1.4 to 7.4). Dogs with endocrine/neuroendocrine tumours (odds ratio: 8.8; 95% confidence interval: 1.2 to 63.9), without appendicular metastases (odds ratio: 5.1; 95% confidence interval: 1.0 to 25.8), without extra-skeletal metastases (odds ratio: 5.2; 95% confidence interval: 1.1 to 24.5) and receiving antitumoural therapy (odds ratio: 14.8; 95% confidence interval: 1.7 to 131.4) had an increased chance of surviving more than 100 days. Bone metastases in dogs with solid cancers are associated with poor prognosis and a high risk of skeletal-related events. Treatment appears to have an impact on survival.

The homogeneity and heterogeneity of occurrence, characteristics, and prognosis in hepatocellular carcinoma patients with synchronous and metachronous bone metastasis.

Purpose: Based on the one of the largest hepatocellular carcinoma (HCC) population with bone metastasis (BM) from the single center in Tianjin, China, the present study aimed to investigate the risk and survival of synchronous bone metastasis (sBM) and metachronous bone metastasis (mBM) in HCC, and to reveal characteristics and related factors of HCC patients with bone metastasis.Methods: HCC patients with bone metastasis between 2009 and 2017 from Tianjin Medical University Cancer Institute & Hospital, Tianjin, China, were involved. Chi-square test/ Fisher's exact test and Logistic regression were used to estimate the risk factors of bone metastasis in HCC. Kaplan-Meier method was used to estimate the survival of HCC patients, and the Log-rank test was used to analyze the survival of HCC patients. The prognostic factors of HCC patients with BM were identified via Kaplan-Meier method and multivariable COX regression model.Results: Among 4421 HCC patients, 128 patients with BM were identified. Of the 128 patients with BM, 77 patients (60.16%) were with sBM and 51 patients (39.84%) were with mBM. The incidence of sBM in HCC was 1.74% at initial diagnosis. The most common metastatic site of sBM was rib, followed by lumbar, thoracic, and sacral. The median latency time from HCC diagnosis to mBM was six months. The most common site of mBM was thoracic, followed by lumbar, sacral and rib. Alcohol-drinking history (P=0.027), numbers (P=0.023) and size (P=0.008) of intrahepatic tumor, lymph node metastasis (P<0.001), serum ALP (P=0.004) and HGB (P=0.004) level were found to be correlated with the occurrence of BM. The overall survival between non-BM and BM were statistically different (P=0.028).Conclusion: The incidence of sBM in HCC was 1.74% at initial diagnosis. The median latency time from HCC diagnosis to mBM was 6 months. The characteristics between occurrence and prognosis showed significant difference between sBM and mBM. Early identification of high-risk BM population was essential for the improvement of both quality of life and prognosis. The revealed related factors can potentially guide sBM and mBM identification and early diagnosis in HCC.

Clinical features and KRAS mutation in colorectal cancer with bone metastasis

Bone metastasis is known as a poor prognostic factor in colorectal cancer (CRC), but its clinical manifestations and outcomes are uncertain. CRC with bone metastasis was searched from January 2006 to April 2016. Of 11,551 CRC patients, 321 (2.7%) patients had bone metastasis. Bone-only metastasis was found in only 8.7% of patients. Synchronous bone metastasis was present in 147 (45.8%) patients. In patients with metachronous bone metastasis, the median time from CRC diagnosis to bone metastasis (TTB) was 27.2 months. KRAS mutation status was a marginally significant factor affecting TTB (median TTB, KRAS wild-type or mutation: 29 or 25.8 months, respectively, P = 0.068). Skeletal-related events (SREs) were noted in 200 (62.3%) patients. Median overall survival (OS) from diagnosis of bone metastasis was 8.0 months. On multivariate analysis, multi-organ metastasis, peritoneal metastasis, neutrophil-to-lymphocyte ratio (NLR) ≥ 2.7, and alkaline phosphatase (ALP) ≥ 123 were independent factors for OS. Palliative chemotherapy prolonged survival in CRC patients with bone metastasis (HR 0.25, 95% CI 0.2–0.33). In conclusion, bone metastasis of CRC is rare, but it is related to SREs. Most patients have other organ metastasis and survival is 8.0 months. Attention should be paid to bone metastasis in CRC patients.

A rare case of PSA-negative metastasized prostate cancer to the stomach with serum CEA and CA19-9 elevation: a case report

BackgroundMetastatic cancer to the stomach is relatively rare. Prostate-specific antigen (PSA) is a reliable biomarker used in the screening and management of patients with prostate cancer. However, it is difficult to definitively diagnose a PSA-negative metastatic gastric tumor of prostate cancer because the cancer sometimes resembles primary gastric cancer in clinical images. It is also difficult to distinguish metastatic cancer from primary cancer even in the pathological examination of biopsy samples when the lesion is poorly differentiated adenocarcinoma. There is a possibility that the characteristics of the cancer are changed during treatment such as chemotherapy or radiation therapy. Therefore, careful consideration is required for surgical indication.Case presentationA 60-year-old male underwent radical prostatectomy and subsequent radiation therapy for advanced prostate cancer (pT3N1M0) 10 years previously, and hormone therapy was started for metachronous multiple bone metastasis 10 months before. Upper gastrointestinal endoscopy revealed an irregular depressed lesion with a convergence of folds at the greater curvature of the upper gastric body. Biopsy showed poorly differentiated adenocarcinoma that was negative for PSA upon immunohistochemistry. He had high serum carcinoembryonic antigen (CEA) (946.1 ng/ml) and carbohydrate antigen 19-9 (CA19-9) (465.1 U/ml) levels with no elevation of PSA (0.152 ng/ml). The tumor was diagnosed as primary gastric cancer based on the clinical imaging and pathological examination of the biopsy sample including the PSA staining. Based on the diagnosis, laparoscopic proximal gastrectomy with lymphadenectomy was performed. However, pathological examination of the resected specimen revealed poorly differentiated adenocarcinoma that was positive for other prostate markers such as androgen receptor. Thus, the patient was diagnosed with metastasized prostate cancer to the stomach.ConclusionsWe report a case of metastatic gastric cancer of prostate cancer 10 years after radical prostatectomy. In the present case, it was difficult to diagnose a metastatic gastric tumor of prostate cancer preoperatively, because of its resemblance to primary gastric cancer without PSA expression and no serum PSA elevation. Although a rare case entity, it is important to consider the possibility of a metastatic gastric tumor when the surgical indication is determined in cases with another co-existing cancer.

An Italian Retrospective Survey on Bone Metastasis in Melanoma: Impact of Immunotherapy and Radiotherapy on Survival.

BackgroundWe performed a multicenter retrospective observational study to investigate the impact of clinical–pathological features and therapeutic strategies on both the complications and survival of patients with bone metastases (BMs) from malignant melanoma.Patients and MethodsA total of 305 patients with melanoma and radiological evidence of BMs were retrospectively enrolled from 19 Italian centers. All patients received conventional treatments in accordance with each own treating physician’s practice. Both univariate and multivariate models were used to explore the impact of melanoma features, including skeletal-related events (SREs), and different treatments on both overall survival (OS) and time-to-SREs. The chi-squared test evaluated the suitability of several parameters to predict the occurrence of SREs.ResultsEighty-three percent of patients had metachronous BMs. The prevalent (90%) bone metastatic site was the spine, while 45% had involvement of the appendicular skeleton. Forty-seven percent experienced at least one SRE, including palliative radiotherapy (RT) in 37% of cases. No melanoma-associated factor was predictive of the development of SREs, although patients receiving early treatment with bone-targeted agents showed 62% lower risk and delayed time of SRE occurrence. Median OS from the diagnosis of bone metastasis was 10.7 months. The multivariate analysis revealed as independent prognostic factors the number of BMs, number of metastatic organs, baseline lactate dehydrogenase levels, and treatment with targeted therapy or immunotherapy. Subgroup analyses showed the best OS (median = 16.5 months) in the subset of patients receiving both immunotherapy and palliative RT.ConclusionBased on our results, patients undergoing immunotherapy and palliative RT showed an OS benefit suggestive of a possible additive effect. The apparent protective role of bone targeting agent use on SREs observed in our analysis should deserve prospective evaluation.

The Distinction of Clinicopathological Characteristics, Treatment Strategy and Outcome in Colorectal Cancer Patients With Synchronous vs. Metachronous Bone Metastasis.

Background: The impact of the timing of bone metastasis (BM) diagnosis on colorectal cancer (CRC) patients is unclear. Our study aimed to explore the differences in clinicopathological characteristics, treatments and prognosis between synchronous BM (SBM) and metachronous BM (MBM) from CRC.Methods: We retrospectively investigated clinical data of CRC patients with SBM or MBM from 2008 to 2017 at Chinese National Cancer Center. Cancer specific survival (CSS) after BM diagnosis was estimated using the Kaplan-Meier method. The multivariable COX regression model identified the prognostic factors of CSS.Results: Finally, 63 CRC patients with SBM and 138 CRC patients with MBM were identified. Compared to SBM from CRC, MBM significantly was more involving multiple bone lesions (63.0 vs. 7.9%; p < 0.001), and more frequently originated from rectal cancer (60.9 vs. 41.3%; p = 0.033). The therapeutic strategies in SBM and MBM group were contrasted including systemic treatment, bisphosphonates, radiotherapy and metastasectomy for BM. 85.5% of patients in MBM group and 25.4% of patients in SBM group underwent primary tumor resection at initial diagnosis (p < 0.001). The median CSS was 11 months in both SBM and MBM group (p = 0.556), yet MBM patients developed from CRC in early AJCC stage presented obviously longer survival than those from advanced stage. Furthermore, patients could have improved CSS from primary tumor resection while there might be no survival benefit from targeted therapy in both SBM and MBM groups. Bisphosphonates was associated with a better CSS for patients with SBM, while radiotherapy for BM was related to a better CSS for patients with MBM.Conclusion: The CRC patients in SBM and MBM group represented different clinicopathological characteristics and treatment modalities, which affected the prognosis in different ways. Distinct consideration for CRC patients with SBM and MBM in clinical decision making is required.

The prognostic and predictive role of hyponatremia in patients with advanced non-small cell lung cancer (NSCLC) with bone metastases.

Hyponatremia and bone metastasis (BMs) are known as negative prognostic factors in patients affected by metastatic non-small cell lung cancer (NSCLC). Hyponatremia is associated with higher risk of osteoporosis and bone fracture, but no data are available about the relationship between hyponatremia and bone metastasis. This study aims to analyze the prognostic impact of hyponatremia in NSCLC patients with bone metastases. We retrospectively collected data about advanced NSCLC patients. Survival curves were estimated using Kaplan-Meier method, and comparisons were made using chi-square test. Six hundred forty-seven patients were enrolled into the study. BMs were present in 264 patients (41%) at diagnosis, while hyponatremia appeared in 237 (37%) patients during the first-line treatment. Patients without BMs had a median overall survival (mOS) of 15.9months (95% CI 14.1-17.9) versus 11.4months (95% CI 9.4-13.4) for patients with BMs (p = 0.001). Eunatremic patients had a better outcome (mOS 16.3months, 95% CI 14.6-18.0 vs 10.3months, 95% I 7.6-12.8, p = 0.003). Considering the two variables, patients with BMs and hyponatremia had a mOS of 10.1months (95% CI 4.3-15.9), patients with hyponatremia without BMs 11.9months (95% CI 11.4-12.4), while mOS was 13.1months (95% CI 12.0-14.2) for eunatremic patients with BMs versus 17.1months (95% CI 15.2-19.1) in eunatremic patients without BMs (p = 0.0020). Hyponatremic patients developed metachronous BMs significantly earlier (3.73 vs 5.76months, p = 0.0187). Our study showed that hyponatremia is an important prognostic factor and it should be necessarily considered to enhance the management of NSCLC patients with BMs.

ERG alterations and mTOR pathway activation in primary prostate carcinomas developing castration-resistance

IntroductionOne of the most common sites of distant metastasization of prostate cancer is bone, but to date reliable biomarkers able to predict the risk and timing of bone metastasization are still lacking. Patients and methodsSurgically resected paraffin embedded samples from 12 primary prostate cancers that developed metachronous bone metastasis at different time points were studied (six cases within 2 years, six cases after 5 years from surgery). A targeted next-generation DNA and RNA sequencing able to assess simultaneously mutations, copy number alterations and fusion events of multiple genes was used. Immunohistochemistry was used to assess mTOR pathway activation. ResultsRearrangements of ETS family genes, molecular alterations in PTEN and TP53 genes were detected in 10, 6 and 5 cancers, respectively. Nine samples showed TMPRSS2-ERG fusions, which were associated with increased ERG expression at immunohistochemistry. mTOR pathway activation was documented in 6 patients, with a clear trend of prevalence in late-metastatic patients (p = 0.08). ConclusionsA simultaneous next-generation targeted DNA and RNA sequencing is applicable on routine formalin-fixed paraffin-embedded tissues to assess the multigene molecular asset of individual prostate cancers. This approach, coupled with immunohistochemistry for ERG and mTOR pathway proteins, may help to better characterize prostate cancer molecular features with a potential impact on clinical decisions.

Métastase humérale du cancer du rein : prise en charge chirurgicale et revue de la littérature

IntroductionThe humerus is the second most common long bone site of metastatic disease from renal cell carcinomas (RCC) after femur. Surgery has an important role in the treatment of these lesions due to renal cell tumor's resistance to chemotherapy and radiotherapy. The aim of this study is to determinate if prosthetic replacement is an effective and safe solution in treatment of renal cancer. HypothesisProsthetic replacement is an effective and safe solution in treatment of renal humeral metastasis. Material and methodsFifty-six patients affected by RCC bone metastases of the humerus that underwent a surgical reconstruction were reviewed. Thirty-five lesions were localized on proximal third, 12 on the shaft, 9 on distal third. Among proximal 29 were treated with resection and endoprosthetic replacement and 6 with plate and cement. Six diaphyseal lesions were stabilized with intramedullary nailing, 5 with plate and cement and 1 with an intercalary prosthesis. Regarding distal lesions, 7 elbow prostheses and 2 plates and cement were used. ResultsThe average age was 63 years. Metastasis was single in 55% of cases, and in 45% metachronous. A pathologic fracture (PF) occurred in 64% of cases. Only 9% of patients had a mechanical complication, 7% an infection and 5% neurological deficit. A local recurrence occurred in 14% of patients. An implant failure has been observed in 10 patients, 5 for mechanical complications, 2 for infections and 3 for local recurrence; of these 7 were treated with a prosthesis and 3 with plate and cement. The mean value of MSTS score was 64%, 63% and 59% respectively in patients with proximal, diaphyseal and distal humerus metastases. DiscussionSolitary and metachronous bone metastases have a longer survival. Disease-free interval>2 years is another important prognostic factor. Reconstruction with a modular prosthesis is recommended in proximal and distal third. Instead in diaphyseal lesions a closed reduction and fixation with intramedullary locked nailing are preferred. When surgical indications are correctly followed, good oncologic and functional outcomes are obtained, leading to markedly improvement of patients’ quality of life. Retrospective studyLevel of evidence IV.

Humeral metastasis of renal cancer: Surgical options and review of literature.

The humerus is the second most common long bone site of metastatic disease from renal cell carcinomas (RCC) after femur. Surgery has an important role in the treatment of these lesions due to renal cell tumor's resistance to chemotherapy and radiotherapy. Prosthetic replacement is an effective and safe solution in treatment of renal humeral metastasis. Fifty-six patients affected by RCC bone metastases of the humerus that underwent a surgical reconstruction were rewised. Thirty-five lesions were localized on proximal third, 12 on the shaft, 9 on distal third. Among proximal 29 were treated with resection and endoprosthetic replacement and 6 with plate and cement. Six diaphyseal lesions were stabilized with intramedullary nailing, 5 with plate and cement and 1 with an intercalary prosthesis. Regarding distal lesions, 7 elbow prostheses and 2 plates and cement were used. The average age was 63years. Metastasis was single in 55% of cases, and in 45% metachronous. A pathologic fracture (PF) occurred in 64% of cases. Only 9% of patients had a mechanical complication, 7% an infection and 5% neurological deficit. A local recurrence occurred in 14% of patients. An implant failure has been observed in 10 patients, 5 for mechanical complications, 2 for infections and 3 for local recurrence; of these 7 were treated with a prosthesis and 3 with plate and cement. The mean value of MSTS score was 64%, 63% and 59% respectively in patients with proximal, diaphyseal and distal humerus metastases. Solitary and metachronous bone metastases have a longer survival. Disease-free interval>2years is another important prognostic factor. Reconstruction with a modular prosthesis is recommended in proximal and distal third. Instead in diaphyseal lesions a closed reduction and fixation with intramedullary locked nailing are preferred. When surgical indications are correctly followed, good oncologic and functional outcomes are obtained, leading to markedly improvement of patients' quality of life. Level of evidence: IV.

Real-life management and outcome of thyroid carcinoma-related bone metastases: results from a nationwide multicenter experience.

The M.O.S.CA.TI. (Metastases of the Skeleton from CArcinoma of the ThyroId) is a multicenter, retrospective study investigating the real-life outcome and management of bone metastases (BM) in 143 patients (63 M, 80 F; median age 64 years, range 11-87) with differentiated thyroid carcinoma (DTC). Radio-active iodine (RAI) treatment was performed in 131 patients (91.6%), surgical approach and/or external radiotherapy in 68 patients (47.6%), and anti-resorptive bone-active drugs in 32 patients (22.4%; in 31 zoledronate and in one denosumab). At the start of treatment, 24 patients (75.0%) receiving anti-resorptive bone-active drugs had at least one clinical skeletal-related event (SRE) (p < 0.001). One or more clinical SREs (pathological fractures and/or malignant hypercalcemia and/or spinal cord compression) developed in 53 patients (37.1%). Development of SREs was significantly associated with metachronous BM (hazard ratio (HR) 2.04; p = 0.04), localization of BM to cervical spine (HR 3.89; p = 0.01), and lack of avid RAI uptake (HR 2.66; p = 0.02). Thirty-nine patients (27.3%) died in correlation with development of SREs (HR 6.97; p = 0.006) and localization of BM to the hip (HR 3.86; p = 0.02). Moreover, overall mortality was significantly decreased by RAI therapy (HR 0.10; p = 0.02), whereas no significant effects were induced by bone-active drugs (p = 0.36), external radiotherapy (p = 0.54), and surgery (p = 0.43) of BM. SREs are very frequent in BM from DTC and they impact patient survival. In the real life, the use of bone-active drugs is currently limited to zoledronate in patients with pre-existing SREs. In this clinical setting, RAI therapy, but not zoledronate, decreased mortality.

Salvage Radiotherapy for Solitary Metachronous Bone Metastasis in Patients with Breast Cancer.

We assessed the efficacy and toxicity of salvage radiotherapy for solitary metachronous bone metastasis (SMBM) in patients with breast cancer. We retrospectively analyzed 17 patients with SMBM who were treated with salvage radiotherapy. First failure was detected as SMBM in all patients. Salvage radiotherapy using three-dimensional treatment planning was performed at a median total dose of 50 Gy. Median daily dose was 2.0 Gy. Median follow-up was 40 months. Local recurrence of SMBM was noted in only two patients. The 3-year overall survival, progression-free survival, and local control rates were 93%, 51%, and 85%, respectively. Median overall and progression-free survival were 74 and 30 months, respectively. Toxicities were mild, and bone fractures were not observed. Salvage radiotherapy for SMBM was able to achieve higher local control rates without severe toxicity, as well as to provide longer progression-free survival; therefore, this may be an effective modality.

Prognostic Factors and Treatment Outcome of Nasopharyngeal Carcinoma with Bone Metastases

This study was aimed to investigate prognostic factors of nasopharyngeal carcinoma (NPC) patients with bone metastases. A total of 72 NPC patients with bone metastases were treated in Salah Azaiz Cancer Institute between 2000 and 2012. Of the 72 patients, 33 patients had synchronous bone metastasis and 39 had metachronous bone metastasis. The survival rate was calculated by Kaplan-Meier method and compared by log-rank test. The 2- and 5- year survival rates of the 72 patients were 45.4 % and 21.7 %, respectively. The median survival was 23 months (range 2–144 months). Univariate analysis showed that the patients with synchronous bone metastasis had significantly poorer overall survival (OS) than that of the patients with metachronous bone metastasis (14 vs. 28 months, P=0.004). The use of biphosphonate therapy was a prognostic factor of NPC with bone metastasis. Patients with only single bone metastases had better survival. Our study revealed that the time of metastases and the use of biphosphonates were prognostic factors associated with better OS. Curative treatment should be considered for patients with single bone metastasis.

Does the onset of bone metastasis in sunitinib-treated renal cell carcinoma patients impact the overall survival?

To evaluate the impact of bone metastasis (BM) onset toward prognosis in metastatic renal cell carcinoma (mRCC) patients treated with sunitinib. mRCC patients with BM and sunitinib as first targeted therapy between May 2005 and December 2012 were retrospectively analyzed. Patients with synchronous (s) BM or metachronous (m) BM were compared with regard to treatment and outcome [time to clinical progression (TTcP), overall survival (OS), skeletal-related events (SRE)]. Descriptive statistics, Kaplan-Meier estimation of TTcP and OS, Cox regression analyses, and a landmark analysis were administered. BM was identified in 127 mRCC patients; thereof, 82 sunitinib-treated patients were analyzed [sBM n=57 (69.5%), mBM n=25 (30.5%)]. Higher tumor grading (p=0.029), male predominance (p=0.02), and less second-line therapy (p=0.001) were detected in sBM compared to mBM. SRE remained similar between subgroups (p=0.462). TTcP during sunitinib was similar [median sBM 8.1 (95% CI 3.9-12.3) vs. mBM 8.7 (95% CI 2.7-14.8) months, p=0.903]. OS remained significantly inferior in sBM patients compared to mBM [median sBM 21.1 (95% CI 16-26.2) months vs. mBM 38.5 (95% CI 15-62) months, p=0.001], which was confirmed by landmark analyses at 1.5, 3, 6, 9, and 12months. However, OS after occurrence of BM was similar in both groups [median sBM 24.2 (95% CI 17.3-31.1) months vs. mBM 17.2 (95% CI 8.4-26) months, p=0.519]. mBM is associated with an improved OS compared to sBM in mRCC with sunitinib treatment, despite similar efficacy of sunitinib treatment in both groups of patients.

Risk factors for the development of metachronous bone metastasis in colorectal cancer patients after curative resection

ObjectiveMetachronous bone metastasis (MBM) occurs in 6–10% of colorectal cancer (CRC) patients following surgical treatment. The aim of this study is to determine the risk factors affecting the development of MBM in CRC patients following curative resection. MethodClinical and pathological records of 516 CRC patients who underwent curative resection were retrospectively studied. The association between clinicopathological variables and development of MBM was investigated using univariate and multivariate analyses. ResultThe incidence of MBM was 6.0% and the median time of developing MBM was 15 (range, 1–89) months. Univariate analysis identified that lymph node involvement (p = 0.001), tumor stage (p = 0.020) and tumor location (p = 0.015) were significantly correlated with development of MBM. Multivariate analyses showed tumor location (p = 0.039) and lymph node involvement (p = 0.003) were independent risk factors contributing to the occurrence of MBM. ConclusionThis study indicated that tumor location and lymph node involvement were independent risk factors for development of MBM in CRC patients after curative resection.

Late onset of bone metastases as a prognostic parameter in metastatic renal cell cancer (mRCC): A single-center experience in 82 mRCC patients treated with sunitinib.

523 Background: Bone metastasis (BM) is considered a negative prognostic marker in metastatic renal cell carcinoma (mRCC). Here, we address the impact of BM onset on overall survival (OS) in mRCC patients during targeted therapy. Methods: Patients with BM who received sunitinib (SU) as 1st targeted treatment at our center between May 2005 and December 2012 were included in this retrospective analyzes. Treatment was performed according to local standard and patients were followed for survival. Spine surgery, fracture or irradiation were considered skeletal related events (SRE). Results: Out of 128 mRCC patients with BM, 82 patients had SU as 1st line targeted agent. 57 (69.5%) patients suffered from BM at initial diagnosis of mRCC (=synchronous BM [sBM]), while 25 (30.5%) patients developed BM during treatment course (=metachronous BM [mBM]). Baseline characteristics showed different histological gradings for sBM compared to mBM patients (p=0.029) and higher frequency of ≥3 metastatic organ sites prior to SU for sBM patients (sBM: n=40 [70.2%] vs. mBM: n=10 [40%], p=0.016). In Kaplan-Meier analysis, sBM patients showed a reduced mean OS from SU start (sBM 23.5 [95%CI:18.6-28.3] vs. mBM 41.3 [95%CI:31.7-50.9] month, p=0.001), whereas PFS during SU treatment was similar (sBM: 8.1 [95%CI:3.9-12.3] vs. mBM: 8.7 [95CI:2.7-14.8] months, p=0.93). Bisphosphonate treatment and SRE revealed no differences between subgroups (p=0.62), while spinal compression occurred in 6 patients with sBM, but none with mBM (p=0.153). 2nd-line targeted agents were less frequently administered in sBM patients (sBM n=17 vs. mBM: n=10). Multivariate Cox-regression confirmed MSKCC score (OR: 2.6 [95%CI:0.99-7.28], p=0.052), liver metastases (OR: 2.66 [95%CI:1.28-5.51], p=0.009], and sBM [OR: 2.45 [95%CI:1.19-5.08], p=0.016) as independent prognostic parameters for reduced OS after SU start. Conclusions: In our cohort, OS in patients with sBM was significantly reduced compared to mBM patients, despite similar PFS with SU and SRE rate. Despite the lower incidence of subsequent therapies in sBM, a more aggressive biology is likely to be the cause of these findings.

18F-fluorodeoxyglucose positron emission tomography–computed tomography for the evaluation of bone metastasis in patients with gastric cancer

The roles of positron emission tomography and bone scanning in identifying bone metastasis in gastric cancer are unclear. We compared the usefulness of positron emission tomography-computed tomography and scanning in detecting bone metastasis in gastric cancer. Data from 1485 patients diagnosed with gastric cancer who had undergone positron emission tomography-computed tomography and scanning were reviewed. Of 170 enrolled patients who were suspected of bone metastasis in either positron emission tomography or scanning, 81.2% were confirmed to have bone metastasis. The sensitivity, specificity, and accuracy were 93.5%, 25.0%, and 80.6%, respectively, for positron emission tomography and 93.5%, 37.5%, and 82.9%, respectively, for scanning. 87.7% of patients with bone metastasis showed positive findings on two modalities. 15.0% of solitary bone metastases were positive on positron emission tomography only. Positron emission tomography was superior to scanning for the detection of synchronous bone metastasis, but the two modalities were similar for the detection of metachronous bone metastasis. The concordance rate of response assessment after treatment between two modalities was moderate. Positron emission tomography-computed tomography may be more effective for the diagnosis of bone metastasis in the initial staging workup. Conversely, bone scanning and positron emission tomography-computed tomography may be similarly effective for the detection of metachronous bone metastasis.

Cord compression by metachronous bone metastases of gastric cancer treated 4 and 20 years before. Report of two cases

Cord compression by metachronous bone metastases of gastric cancer treated 4 and 20 years before. Report of two cases

Bone Metastases and Skeletal-Related Events in Patients With Malignant Pheochromocytoma and Sympathetic Paraganglioma

Bone metastases (BM) can cause severe pain, spinal cord compression, pathological fractures, and/or hypercalcemia. These skeletal-related events (SREs) may cause immobilization, loss of independence, poor quality of life, and reduced survival. There is limited information on the clinical effects of BM and SREs in patients with malignant pheochromocytoma or sympathetic paraganglioma (PHEO/sPGL). We studied the prevalence and clinical characteristics of BM and SREs in patients with PHEO/sPGL and investigated the risk factors for SRE development. Using a large institutional database, we conducted a retrospective study of 128 patients with malignant PHEO/sPGL at The University of Texas MD Anderson Cancer Center from 1967 through 2011. Of the patients, 91 (71%) had BM, and 57 of these (63%) developed metachronous BM at a median time of 3.4 years (range, 5 months to 23 years) after the primary tumor diagnosis. Metastatic disease was confined exclusively to the skeleton in 26 of 128 (20%) patients. Sufficient information to assess SRE occurrence was available for 67 patients, and 48 of 67 (72%) patients had at least 1 SRE. The median overall survival for the 128 patients was 12 years for patients with only BM, 7.5 years for patients with nonosseous metastases, and 5 years for patients with both BM and nonosseous metastases (log rank test P value = .005). We were unable to identify factors predictive of SRE development, but the occurrence of a first SRE was associated with the development of subsequent SREs in 48% of subjects. In responsive patients, the use of systemic therapy was associated with fewer SREs (P < .0001). BM and SREs are frequent in patients with malignant PHEO/sPGL. SREs often develop shortly after the diagnosis of BM; severe pain is the most frequent SRE. These patients should be followed long-term by a multidisciplinary team to promptly identify the need for medical or surgical intervention.