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Secondary Bone Cancer (bone metastasis)

Secondary bone cancer is where malignant cells have spread to the bones from other parts of the body. This is different to cancer that actually started in the bones (primary bone cancer). Virtually all types of cancer can spread to bone. Bone metastases are particularly common in people with breast, lung or prostate cancer. Bone metastases are usually multiple, they cause pain and can can lead to other symptoms such as hypercalcemia (abnormally high levels of calcium in the blood).

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    MeSH term: Bone Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Miranda J, Viñal D, Pinto Á
Radium 223 for the treatment of metastatic castration-resistant prostate cancer.
Arch Esp Urol. 2019; 72(5):500-507 [PubMed] Related Publications
The treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) has evolved dramatically in the recent years with the approval of several new drugs. Together with other treatment modalities including chemotherapy, hormonal therapy and immunotherapy, radiopharmaceuticals have recently been incorporated to the therapeutic scenario of prostate cancer with the approval of Radium 223 dichloride (Ra-223) for the treatment of mCRPC patients with symptomatic bone metastasis and no visceral metastases. Radiopharmaceuticals have long been used for pain palliation in patients with bone metastases. However, the bone seeking properties and the favourable physical characteristic of alpha emitter radium 223 encouraged the clinical development of the drug, leading to survival advantage in the phase III trial ALSYMPCA. Now the efforts are directed to define the optimal patient selection and drug sequence. In this review, we will provide the best available evidence of mechanism of action, clinical data and future directions of Ra-223 in mCRPC.

Wu G, Xie R, Liu X, et al.
Intravoxel incoherent motion diffusion MR and diffusion kurtosis imaging for discriminating atypical bone metastasis from benign bone lesion.
Br J Radiol. 2019; 92(1100):20190119 [PubMed] Related Publications
OBJECTIVES: To investigate the feasibility of intravoxel incoherent motion (IVIM) diffusion MR and diffusion kurtosis imaging (DKI) in discriminating atypical bone metastasis from benign bone lesion in patients with tumors.
METHODS: Patients with bone lesions in lower extremity suspected of metastases were enrolled in this prospective study. IVIM diffusion MR and DKI were performed before biopsy. Apparent diffusion coefficient (ADC), true diffusion (D), perfusion fraction (f) and perfusion-related pseudodiffusion (D*) were generated with IVIM, while mean kurtosis (MK) and mean diffusion (MD) generated with DKI. Two radiologists blinded to pathology results separately measured these parameters for each lesion through drawing region of interest. Intraclass correlation coefficient was used to determine the inter-reader viability in measurement. The patients with pathology-confirmed metastasis or benign lesion were analyzed. The Mann-Whitney test was used to compare IVIM and DKI parameters between metastasis group and benign lesion group. Receiver operating characteristic curves were constructed to evaluate the ability of discrimination.
RESULTS: Bone lesions from 28 patients (metastasis,
CONCLUSIONS: IVIM and DKI derived parameters distinguish between atypical bone metastasis and benign bone lesion in selected patients with tumors.
ADVANCES IN KNOWLEDGE: Bone metastasis and benign bone lesion differ in water molecular diffusion. Intravoxel incoherent motion derived true diffusion distinguishes between atypical bone metastasis and benign lesion.

Liang W, Wang F, Chen Q, et al.
Targeting cathepsin K diminishes prostate cancer establishment and growth in murine bone.
J Cancer Res Clin Oncol. 2019; 145(8):1999-2012 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The processes of prostate cancer (PCa) invasion and metastasis are facilitated by proteolytic cascade involving multiple proteases, such as matrix metalloproteinases, serine proteases and cysteine proteases including cathepsin K (CatK). CatK is predominantly secreted by osteoclasts and specifically degrades collagen I leading to bone destruction. PCa and breast cancer preferentially metastasize to the bone. Importantly, CatK expression level is greater in PCa bone metastatic sites compared to primary tumor and normal prostate tissues. However, the underlying mechanism of CatK during PCa metastases into the bone remains to be elucidated. We investigated the functional role of CatK during the PCa establishment and growth process in the murine bone.
METHODS: CatK mRNA expression was validated by RT-PCR, protein expression by immunoblotting in PCa LNCaP, C4-2B, and PC3 cells as well as in PCa tissues. Its protein production was measured using ELISA assay. The effect of both knockdowns via siRNA and CatK inhibitor was compared in regard to PCa cell invasion. We further studied the dose-dependent CatK inhibitor effect on conditioned media-induced bone resorption. In setting up an animal model, C4-2B cells were injected into the tibiae of SCID mice. The animals treated with either vehicle or CatK inhibitor for 8 weeks at the time of tumor cell injection (tumor establishment model; protocol I) or 4 weeks after tumor cell injection (tumor progression model; protocol II) were applied to histological and histomorphometric analyses.
RESULTS: We confirmed CatK expression in PCa LNCaP, C4-2B, and PC3 cells as well as in PCa tissues. Furthermore, we observed the inhibitory effects of a selective CatK inhibitor on PCa cell invasion. The CatK inhibitor dose-dependently inhibited PCa-conditioned media-induced bone resorption. Upon injection of C4-2B cells into the tibiae of SCID mice, the selective CatK inhibitor significantly prevented the tumor establishment in protocol I, and reduced the tumor growth in bone in protocol II. It also decreased serum PSA levels in both animal models. The inhibitory effects of the CatK inhibitor were enhanced in combination with zoledronic acid (ZA).
CONCLUSION: The selective CatK inhibitor may prevent the establishment and progression of PCa in bone, thus making it a novel therapeutic approach for advanced PCa.

Janssen SJ, Pereira NRP, Thio QCBS, et al.
Physical function and pain intensity in patients with metastatic bone disease.
J Surg Oncol. 2019; 120(3):376-381 [PubMed] Related Publications
BACKGROUND: Patient reported outcome data in bone metastatic disease are scarce and it would be useful to have normative data and understand what patients are at risk for poor function and more pain.
OBJECTIVES: We aimed to assess what factors are independently associated with physical function and pain intensity in patients with bone metastasis.
METHODS: We included data from 211 patients with bone metastasis who completed a survey (2014-2016) including the PROMIS Physical Function Cancer and PROMIS Pain Intensity questionnaires.
RESULTS: Prostate (P < .001) and thyroid carcinoma (P = .007) were associated with better function and having other disabling conditions (P = 0.035) was associated with worse function. Prostate carcinoma (P = .001) and lymphoma (P = .007) were associated with less pain. There was a moderate correlation between pain and function (P < .001). Function was substantially worse as compared to a US reference population of patients with cancer (P < .001), whereas pain was slightly less compared to the US general population average (P < .001).
CONCLUSIONS: Patients with bone metastasis have a poor physical function. Physical function and pain intensity depend on tumor histology, but also on potentially modifiable factors such as other disabling conditions.
LEVEL OF EVIDENCE: Level III, prognostic study.

von Moos R, Costa L, Gonzalez-Suarez E, et al.
Management of bone health in solid tumours: From bisphosphonates to a monoclonal antibody.
Cancer Treat Rev. 2019; 76:57-67 [PubMed] Related Publications
Patients with solid tumours are at risk of impaired bone health from metastases and cancer therapy-induced bone loss (CTIBL). We review medical management of bone health in patients with solid tumours over the past 30 years, from first-generation bisphosphonates to the receptor activator of nuclear factor κB ligand (RANKL)-targeted monoclonal antibody, denosumab. In the 1980s, first-generation bisphosphonates were shown to reduce the incidence of skeletal-related events (SREs) in patients with breast cancer. Subsequently, more potent second- and third-generation bisphosphonates were developed, particularly zoledronic acid (ZA). Head-to-head studies showed that ZA was significantly more effective than pamidronate for reducing SREs in patients with breast and castrate-resistant prostate cancer (CRPC), becoming the standard of care for more than a decade. The RANKL inhibitor denosumab was licensed in 2010, and head-to-head studies and integrated analyses confirmed its superiority to ZA for preventing SREs, particularly in breast cancer and CRPC. Bisphosphonates and denosumab have also been investigated for prevention of CTIBL in patients receiving hormonal therapy for breast and prostate cancer, and denosumab is licensed in this indication. Despite advances in management of bone health, several issues remain, notably the optimal time to initiate therapy, duration of therapy, and dosing frequency, and how to avoid toxicity, particularly with long-term treatment. In summary, introduction of ZA and denosumab has protected patients with bone metastasis from serious bone complications and improved their quality of life. Ongoing research will hopefully guide the optimal use of these agents to help maintain bone health in patients with solid tumours.

Liao TY, Liaw CC, Tsui KH, Juan YH
Invasion of Adjacent Lumbar Vertebral Body from Renal Pelvis Carcinoma: Associated With Bone Metastasis But Easily Overlooked on Initial CT Scan.
In Vivo. 2019 May-Jun; 33(3):939-943 [PubMed] Free Access to Full Article Related Publications
BACKGROUND/AIM: We hypothesized that regional tumor growth into L1 and L2 vertebral bodies from renal pelvis carcinoma was linked to the development of bone metastases.
MATERIALS AND METHODS: Criteria for the study were: (i) Metastatic renal pelvis carcinoma confirmed via pathology and computed tomographic (CT) scan, (ii) L1 and L2 invasion confirmed from retrospective CT scan review, and (iii) detection of bone metastases using radionuclide images/CT scans.
RESULTS: A total of 71 cases were enrolled in the study. Initial L1 and L2 vertebral body invasion. were detected in 45 (63%) patients. As well as L1 and L2 invasion, 32 (71%) had development of bone metastases. All bone lesions were osteolytic. Initial L1 and L2 invasion (p<0.00001) was associated with the development of bone metastasis.
CONCLUSION: CT scan can help to detect L1 and L2 vertebral body invasion in patients with renal pelvis carcinoma. Early identification and optimal management of such patients is necessary.

Khan M, Garg R, Gui C, et al.
Neuroimaging and Stereotactic Body Radiation Therapy (SBRT) for Spine Metastasis.
Top Magn Reson Imaging. 2019; 28(2):85-96 [PubMed] Related Publications
Historically, management options for spinal metastases include surgery for stabilization and decompression and/or external beam radiation therapy (EBRT). EBRT is palliative in nature, as it lacks accurate targeting such that the prescribed radiation doses must be limited in order to maintain safety. Modern advancement in imaging and radiotherapy technology have facilitated the development of stereotactic body radiation therapy (SBRT), which provides increased targeted precision for radiation delivery to tumors resulting in lower overall toxicity, particularly to regional structures such as the spinal cord and esophagus, while delivering higher, more effective, and radically ablative radiation doses.Over the past decade, SBRT has been increasingly utilized as a method of treating spinal metastases either as the primary modality or following surgical intervention in both de novo and reirradiation setting. Numerous studies suggest that SBRT is associated with an 80% to 90% rate of 1-year local control across clinical scenarios. For example, studies of SBRT as the primary treatment modality suggest long-term local control rate of 80% to 95% for spinal metastases. Similarly, SBRT in the adjuvant setting following surgery is associated with local control rates ranging from 70% to 100%. Furthermore, because SBRT allows for lower dose to the spinal cord, it has also been used in patients who have had prior radiation therapy, with studies showing 66% to 93% local control in this scenario.

Tesfamariam Y, Jakob T, Wöckel A, et al.
Adjuvant bisphosphonates or RANK-ligand inhibitors for patients with breast cancer and bone metastases: A systematic review and network meta-analysis.
Crit Rev Oncol Hematol. 2019; 137:1-8 [PubMed] Related Publications
Bone-modifying agents like bisphosphonates and receptor activator of nuclear factor kappaβ ligand (RANK-L) inhibitors are used as supportive treatments in breast cancer patients with bone metastases to prevent skeletal-related events (SREs). Due to missing head-to-head comparisons, a network meta-analysis was performed to provide a hierarchy of these therapeutic options. Through a systematic literature search, 21 randomized controlled trials (RCTs) that fulfilled the inclusion criteria were identified. To prevent SREs, the ranking through P-scores showed denosumab (RR: 0.62; 95%CI: 0.50-0.76), zoledronic acid (RR: 0.72; 95%CI: 0.61-0.84) and pamidronate (RR: 0.76; 95%CI: 0.67-0.85) to be significantly superior to placebo. Due to insufficient or heterogeneous data, overall survival, quality of life, pain response and adverse events were not able to be analyzed within the network. Although data were sparse on adverse events, the risk of significant adverse events appeared low. The results of this review can therefore be used to formulate clinical studies more precisely in order to standardise and focus on patient-relevant outcomes.

Hirai T, Shinoda Y, Tateishi R, et al.
Early detection of bone metastases of hepatocellular carcinoma reduces bone fracture and paralysis.
Jpn J Clin Oncol. 2019; 49(6):529-536 [PubMed] Related Publications
BACKGROUND: With the improvement in survival of hepatocellular carcinoma patients, extrahepatic metastases have become a more frequent complication. Although pathological fractures or paralysis due to bone metastases deteriorate the quality of life of patients, no treatment guideline for bone metastases has been established. This study aimed to clarify the risk factors for these events and the clinical course of patients with bone metastases.
METHODS: Out of 783 hepatocellular carcinoma patients treated in our institution between 2009 and 2016, 76 patients with bone metastases were enrolled. They were divided into two groups by the trigger of bone metastases detection. One was those diagnosed by surveillance (surveillance group), and the other was those based on symptom presentation (non-surveillance group). We investigated the clinical features, risk factors for fractures or paralysis and prognostic factors for survival after bone metastases.
RESULTS: Baseline characteristics and survival were not significantly different between two groups. Fractures or paralysis occurred in 10 patients (13.2%), and the frequency was significantly higher in the non-surveillance group (20.9%) than the surveillance group (3.0%) in univariate analysis (p = 0.036). The median survival after diagnosis of bone metastases was 11.7 months. Age over 75 years (p = 0.002), hepatitis C-virus etiology (p = 0.007) and Child-Pugh class B/C (p < 0.001) were significantly associated with a shorter survival in multivariate analysis, but fractures or paralysis did not affect the survival.
CONCLUSIONS: Early diagnosis through surveillance for hepatocellular carcinoma bone metastases may prevent fractures or paralysis and lead to a better quality of life for these patients.

Woodhouse L, Watkins J, Navalkissoor S, Gillmore R
Metastatic bone disease from an occult renal primary.
BMJ Case Rep. 2019; 12(4) [PubMed] Related Publications
We report a rare presentation of metastatic renal cell carcinoma (RCC) in a 71-year-old man who presented with persistent shoulder pain. MRI revealed widespread lytic lesions within the bones suggestive of metastatic disease but extensive imaging including CT chest, abdomen and pelvis with contrast and fluorodeoxyglucose-positron emission tomography did not identify a primary cancer. The diagnosis was ultimately made from a targeted bone and subsequently targeted liver biopsy, whereby immunohistochemistry was consistent with metastatic RCC (mRCC). While bone metastases in RCC are very common, it is extremely rare for patients to present with mRCC and no identifiable renal primary.

Cho YJ, Cho YM, Kim SH, et al.
Clinical analysis of patients with skeletal metastasis of lung cancer.
BMC Cancer. 2019; 19(1):303 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Many factors influence bone metastases of lung cancer, and several studies report about survival of skeletal metastasis. However, few studies have focused on identifying the prognostic factors for skeletal metastasis of lung cancer, especially following orthopedic surgery. We conducted a retrospective analysis of the clinical characteristics of skeletal metastasis from lung cancer and discuss the prognostic factors.
METHODS: We performed a medical record review of 202 patients who were diagnosed with skeletal metastasis from lung cancer. Adenocarcinoma was found in 116 patients (57.4%), squamous cell carcinoma in 29 (14.4%), small-cell lung cancer (SCLC) in 37 (18.7%), and large-cell carcinoma and other types of cancer in 20 patients (9.9%). Orthopedic surgery for skeletal metastasis was performed in 41 patients (20.3%).
RESULTS: Lung cancer survival was 12.1 months. After diagnosis of lung cancer, skeletal metastasis was found at a mean of 2.5 months, and skeletal metastasis survival was 9.8 months. Lung cancer survival in patients younger than 60 years was 13.8 months, and lung cancer survival in patients 60 years or older was 10.8 months (p = 0.009). Skeletal metastasis survival in patients younger than 60 years was 11.0 months, and skeletal metastasis survival in patients 60 years or older was 8.8 months (p = 0.002). Mean skeletal metastasis survival with surgery was 12.6 months and without surgery was 9.1 months (p < 0.000). In the multivariate analysis of lung cancer survival, age under 60 years [HR (95% CI) 1.549 (1.122-2.139), p = 0.008], non-small cell lung cancer pathology type [HR (95% CI) 1.711 (1.157-2.532), p = 0.008], chemotherapy for skeletal metastasis [HR (95% CI) 8.064 (3.981-16.332), p < 0.000], and radiation therapy for skeletal metastasis [HR (95% CI) 1.791 (1.170-2.742), p = 0.007] were significant, independent, good prognostic factors. In the multivariate analysis of skeletal metastasis survival, age under 60 years [HR (95% CI) 1.549 (1.124-2.134), p = 0.007], non-small cell lung cancer pathology type [HR (95% CI) 2.045 (1.373-3.047), p < 0.000], chemotherapy for skeletal metastasis [HR (95% CI) 7.121 (3.542-14.317), p < 0.000], and orthopedic surgical treatment for skeletal metastasis [HR (95% CI) 1.710 (1.148-2.547), p = 0.008] were significant, independent, good prognostic factors.
CONCLUSIONS: Patients who survived longer were less than 60 years old, received chemotherapy as treatment for skeletal metastasis, had NSCLC rather than SCLC, and underwent orthopedic surgery for skeletal metastasis.

Kaestner J, Schlodder D, Preussler C, Gruhn B
Supportive mistletoe therapy in a patient with metastasised neuroblastoma.
BMJ Case Rep. 2019; 12(3) [PubMed] Free Access to Full Article Related Publications
Therapies of complementary and alternative medicine (CAM) are used increasingly in paediatric oncology. We present and discuss the influence of supportive mistletoe therapy on factors, such as quality of life, physical ability and performance, and course of disease based on the case of a female patient diagnosed at age 18 with metastasised neuroblastoma, which responded insufficiently to chemotherapy.

Ribeiro B, Silva R, Dias R, Patrício V
Carcinosarcoma of the uterine cervix: a rare pathological finding originating from mesonephric remnants.
BMJ Case Rep. 2019; 12(3) [PubMed] Related Publications
Carcinosarcoma of the uterine cervix is a very rare tumour that has been described in less than 70 cases in the literature. It is less common compared with carcinosarcoma of the uterine corpus and it can have two origins: the Müllerian ducts and the mesonephric duct remnants. The association of mesonephric carcinoma with a sarcomatous component was reported in only 11 cases, including the following. We describe a case of a 64-year-old woman, presenting with vaginal bleeding and a cervical lesion reported as a sarcoma of endometrial stroma in the first biopsy. After exclusion of distant disease, she was submitted to radical surgery and the final histopathological examination showed a carcinosarcoma of the cervix with mesonephric origin.

Kitagawa Y, Ito T, Mizuno Y, et al.
Diagnosis of Bone Metastasis in Patients Without a History of Cancer.
J Nippon Med Sch. 2019; 86(1):22-26 [PubMed] Related Publications
BACKGROUND: Diagnosing bone metastasis in patients without a history of cancer remains challenging. Diagnostic evaluation may be prolonged owing to difficulties in distinguishing between bone metastasis and common orthopedic diseases. We hypothesized that bone metastasis due to occult cancer would be more difficult to diagnose than bone metastasis in patients with a history of cancer. Few studies exist on the difficulty of diagnosing bone metastasis in patients without a history of cancer. Therefore, we reviewed the clinical course of patients with bone metastasis between January 2011 and December 2014.
METHODS: We reviewed patients with bone metastasis to determine the diagnostic rate at first visit, period from symptom-onset to first visit, period from first visit to diagnosis, and presence of severe skeletal-related events at diagnosis, and compared these between 27 patients without a history of cancer (Group A) and 54 patients with a history of cancer (Group B).
RESULTS: The diagnostic rate at first visit was significantly lower (11.5% vs. 52.4%, p=0.00069), the period from first visit to diagnosis was significantly longer (median, 7 weeks vs. 3 weeks, p=0.018), and the presence of severe skeletal-related events at diagnosis was significantly higher (81.4% vs. 50.0%, p=0.05) in patients without a history of cancer compared with those with a history of cancer.
CONCLUSIONS: The results of this study indicate that it is difficult to diagnose bone metastasis in patients without a history of cancer. This must be considered in the early diagnosis of bone metastasis to prevent severe skeletal-related events.

Baranowska A, Baranowski P, Rybarczyk M, et al.
Spinal cord infarction after tumor removal surgery of the thoracic region - a case report.
Pol Merkur Lekarski. 2019; 46(273):142-145 [PubMed] Related Publications
Spinal cord infarction is very rare condition and usually occurs in the thoracic region of the spine. The etiology is often unknown and patophysiology can be diverse. The stroke may occur while performing a surgical procedure, but it is also found in vascular diseases, for example dissecting aneurysms, vasculitis and vascular malformations.
A CASE REPORT: The authors present the case of a 62 year old woman admitted to the Neuroortopedics department due to metastasis of papillary renal carcinoma to the spine. During physical examination no neurological deficits were found. However magnetic resonance imaging revealed pathological tissue covering the left pedicle of the Th9 vertebra, penetrating the spinal canal, and compressing the spinal cord. The patient was qualified to the surgery and underwent tumor removal and transpedicular stabilization of the spine. The operation proceeded on schedule, without complications. After the operation the patient did not have any neurological deficits. In the first 24 hours post-surgery paresis of the lower limbs appeared, which rapidly deepened until the right limb was paralyzed. Due to the lack of improvement after administration of solumedrol, and suspicion of hematoma at the surgical site, the patient was qualified for reoperation. Intraoperatively there was no compression of the spinal cord, nonetheless, after being awaken from surgery, no active movements were found in the left lower limb. Magnetic resonance imaging was performed and revealed spinal cord infarction in its ventral part extending from Th9 to Th12.
CONCLUSIONS: Even in procedures where no surgical complications appeared it should be noted that the rare risk of spinal cord infarction exists.

Lin AJ, Ma S, Markovina S, et al.
Clinical outcomes after isolated pelvic failure in cervical cancer patients treated with definitive radiation.
Gynecol Oncol. 2019; 153(3):530-534 [PubMed] Related Publications
PURPOSE: To describe clinical outcomes in patients with isolated pelvic failures after definitive radiation treatment for cervical cancer.
METHODS AND MATERIALS: Cervical cancer patients with isolated pelvic failure after definitive radiation with brachytherapy boost were identified in a tertiary academic center database from 1997 to 2016. All patients received an FDG-PET scan prior to their initial treatment and at the time of their first recurrence. Isolated failures in the cervix or pelvic nodes were biopsy-proven. Distant failure and overall survival (OS) were censored outcomes.
RESULTS: Isolated pelvic failure was detected in 67(11%) out of 607 consecutive patients treated with external beam pelvic radiation and brachytherapy boost. The median time to isolated pelvic recurrence was 9 months (range 3-198). Median follow-up time for patients alive after isolated pelvic recurrence was 40 months (range 0.6-183). Of these 67 patients, 28(42%) received salvage surgery, 17(25%) received chemotherapy alone, and 22(33%) received neither surgery nor chemotherapy. The median time to distant failure after isolated pelvic failure was 20 months (95% CI 3-37), with no significant difference between patients treated surgically vs. non-surgically. FDG-avid pelvic and para-aortic nodes at initial presentation were associated with worse distant control after isolated pelvic failure (HR = 3.4, 95% CI 1.0-12). Median OS for patients treated with surgery, chemotherapy alone, and neither surgery nor chemotherapy was 29 months (95% CI 16-41), 12 months (95% CI 3-21), and 3 months (95% CI 1-5), respectively.
CONCLUSIONS: Patients who have pelvic and para-aortic nodal disease at initial presentation are at higher risk of failing distantly after isolated pelvic failure, which should be considered when counseling patients on aggressive surgical salvage. Surgical salvage was associated with prolonged survival after isolated pelvic failure.

Qiu Y, Li B, Zhang Y, et al.
ALK-rearranged lung adenocarcinoma patient with development of severe sinus bradycardia after treatment with crizotinib: A case report.
Medicine (Baltimore). 2019; 98(11):e14826 [PubMed] Free Access to Full Article Related Publications
RATIONALE: The anaplastic lymphoma kinase (ALK) rearrangements represent a subtype of nonsmall-cell lung cancer (NSCLC), and targeting ALK has radically changed the treatment of NSCLC. Crizotinib, as an ALK inhibitor, has been used in the treatment of ALK-rearranged NSCLC for several years and some adverse effects should be given attention.
PATIENT CONCERNS: A 64-year-old woman with a no-smoking history visited hospital in November 2016 because of a persistent cough, expectoration, and progressive dysphagia for 2 months.
DIAGNOSES AND INTERVENTIONS: She was diagnosed with primary lung adenocarcinoma, accompanied by pleural and bone metastases. After receiving chemotherapy for nearly 1 year, she showed progressive disease. DNA-sequencing identified an intergenic ALK rearrangement. Surprisingly, RNA-sequencing revealed the EML4-ALK fusion transcript. Subsequently, this patient switched to crizotinib therapy.
OUTCOMES: The patient achieved partial response after 1-month treatment. However, this patient suffered a severe sinus bradycardia after 4 months of treatment. When reducing the dose of crizotinib, the side effect was alleviated and this patient showed stable disease until now.
LESSONS: Given that the severe sinus bradycardia was an unusual adverse effect, physicians should be aware of these side effects when using crizotinib. Moreover, it should be noted that this patient harbored an intergenic ALK rearrangement identified by DNA-sequencing, but EML4-ALK fusion transcript verified by RNA-sequencing. However, the mechanism remains unknown and requires further research.

Gao Z, Wu Z, Lin Y, Zhang P
Percutaneous transforaminal endoscopic decompression in the treatment of spinal metastases: A case report.
Medicine (Baltimore). 2019; 98(11):e14819 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Spinal metastases are always associated with specific pain of back and limbs caused by nerve root compression. Although percutaneous endoscopic lumbar discectomy (PELD) has been widely performed on patients with back and radicular pain originating from lumbar disc herniation, this minimally invasive surgery is rarely used for the treatment of spinal metastases.
PATIENT CONCERNS: A 71-year-old woman with colon cancer and a known L3 vertebral body metastasis presented with significant progressive pain of low back and limbs.
DIAGNOSES: Magnetic resonance imaging (MRI) showed the L3 vertebral body had been involved by osteolytic vertebral metastasis, which extended into spinal canal and compressed the dural sac and nerve root.
INTERVENTIONS: The patient was treated with percutaneous transforaminal endoscopic decompression and palliative resection of metastases was performed twice on both sides, respectively. After the minimally invasive procedure, the decompression of the dural sac and nerve root was ideal.
OUTCOMES: No complications during the procedure were reported. The minimally invasive surgery resulted in prompt and permanent pain relief until the patient died 6 months later.
LESSONS: Percutaneous transforaminal endoscopic decompression could be an appropriate treatment option for the patients who suffer neurologic deficits that result from the spinal metastases.

Sheikhbahaei S, Jones KM, Werner RA, et al.
Ann Nucl Med. 2019; 33(5):351-361 [PubMed] Related Publications
PURPOSE: This meta-analysis aims to establish the diagnostic performance of
METHODS: A systematic search was performed in PubMed/Medline and EMBASE (last Updated, September 28, 2018). Studies with histopathology confirmation and/or clinical/imaging follow-up as reference standard were eligible for inclusion.
RESULTS: A total of 14 studies were included. Twelve studies including 507 patients provided per-patient basis information. The pooled sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristics curve (AUC) of

Zhang C, Mao M, Guo X, et al.
Nomogram based on homogeneous and heterogeneous associated factors for predicting bone metastases in patients with different histological types of lung cancer.
BMC Cancer. 2019; 19(1):238 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The purpose of the present study was to characterize the prevalence, associated factors, and to construct a nomogram for predicting bone metastasis (BM) with different histological types of lung cancer.
PATIENTS AND METHODS: This study was a descriptive study that basing on the invasive lung cancer patients diagnosed between 2010 and 2014 in Surveillance, Epidemiology, and End Results program. A total of 125,652 adult patients were retrieved. Logistic regression analysis was conducted to investigate homogeneous and heterogeneous factors for BM occurrence. Nomogram was constructed to predict the risk for developing BM and the performance was evaluated by the receiver operating characteristics curve (ROC) and the calibration curve. The overall survival of the patients with BM was analyzed using the Kaplan-Meier method and the survival differences were tested by the log-rank test.
RESULTS: A total of 25,645 (20.9%) were reported to have BM, and the prevalence in adenocarcinoma, squamous cell carcinoma, small cell lung cancer (SCLC), large cell lung cancer (LCLC), and non-small cell lung cancer/not otherwise specified lung cancer (NSCLC/NOS) were 24.4, 12.5, 24.7, 19.5 and 19.4%, respectively, with significant difference (P < 0.001). Male gender, more metastatic sites and lymphatic metastasis were positively associated with BM in all lung cancer subtypes. Larger tumor size was positively associated with BM in all the lung cancer subtypes except for NSCLC/NOS. Poorly differentiated histology was positively associated with adenocarcinoma, squamous cell carcinoma and NSCLC/NOS. The calibration curve and ROC curve exhibited good performance for predicting BM. The median survival of the bone metastatic lung cancer patients was 4.00 (95%CI: 3.89-4.11) months. With the increased number of the other metastatic sites (brain, lung and liver metastasis), the survival significantly decreased (p < 0.001).
CONCLUSION: Different lung cancer histological subtypes exhibited distinct prevalence and homogeneity and heterogeneity associated factors for BM. The nomogram has good calibration and discrimination for predicting BM of lung cancer.

Pandey A, Liaukovich M, Joshi K, et al.
Uncommon Presentation of Metastatic Squamous Cell Carcinoma of the Skin and Treatment Challenges.
Am J Case Rep. 2019; 20:294-299 [PubMed] Free Access to Full Article Related Publications
BACKGROUND Squamous cell carcinoma is one of the most common keratinocytic skin cancers, the other being basal cell carcinoma. It is the second most common skin cancer after melanoma. Cutaneous squamous cell carcinoma is mostly a localized disease. The metastatic presentation is rare even in the presence of invasive disease. The metastatic potential depends on the presence of high-risk features at the time of diagnosis. Lung, liver, and bone are the frequent sites of metastasis. Local and locoregional disease undergoes excision with or without adjuvant radiation. However, we lack proper treatment paradigms for this metastatic disease. CASE REPORT We are reporting a case of an elderly female with a history of high-risk localized cutaneous squamous cell carcinoma treated with complete local excision and radiation presenting 5 years later with extensive disease to the lung and liver, abdominal nodes, and spinal fracture. The patient was not a candidate for chemotherapy due to kidney failure. On the basis of ongoing separate trials on different immunotherapies, she was started on nivolumab. CONCLUSIONS Treating metastatic cutaneous squamous cell carcinoma is a challenge considering the absence of phase III trials due to the rarity of this disease. Historically, platinum with or without 5-FU (fluorouracil), bleomycin, doxorubicin, and retinoic acid were used with variable responses. Data on epidermal growth factor receptor (EGFR) inhibitors on EGFR expressing tumors are available. However, even with the most recent reports on immunotherapy in patients with high programmed death-1 expression or high mutation burden, it is difficult to achieve good response.

Wadhwani M, Phuljhele S, Kumar R, Shameer A
Cervical carcinoma leading to orbital apex syndrome and blindness.
BMJ Case Rep. 2019; 12(3) [PubMed] Related Publications
Orbit is an unusual and rare site for metastases from cancer. The most frequent site of a primary malignancy to metastasise to the orbit is the breast, followed by the lung. The malignant mixed mullerian tumour is a rare uterine and cervical carcinoma and accounts for <5% of uterine cancers. It is the primary tumour of the uterus, and de novo involvement of the cervix itself is extremely rare. We report the first case of cervical carcinoma with mixed mullerian aetiology to be associated with orbital metastasis and eventually leading to blindness and death.

Xiang L, Gilkes DM
The Contribution of the Immune System in Bone Metastasis Pathogenesis.
Int J Mol Sci. 2019; 20(4) [PubMed] Free Access to Full Article Related Publications
Bone metastasis is associated with significant morbidity for cancer patients and results in a reduced quality of life. The bone marrow is a fertile soil containing a complex composition of immune cells that may actually provide an immune-privileged niche for disseminated tumor cells to colonize and proliferate. In this unique immune milieu, multiple immune cells including T cells, natural killer cells, macrophages, dendritic cells, myeloid-derived suppressor cells, and neutrophils are involved in the process of bone metastasis. In this review, we will discuss the crosstalk between immune cells in bone microenvironment and their involvement with cancer cell metastasis to the bone. Furthermore, we will highlight the anti-tumoral and pro-tumoral function of each immune cell type that contributes to bone metastasis. We will end with a discussion of current therapeutic strategies aimed at sensitizing immune cells.

Yuda S, Shimizu C, Yoshida M, et al.
Biomarker discordance between primary breast cancer and bone or bone marrow metastases.
Jpn J Clin Oncol. 2019; 49(5):426-430 [PubMed] Related Publications
BACKGROUND: Discordance in biomarker expression between primary and metastatic tumor sites has been reported in several studies; yet, few have examined this feature in bone lesions.
METHODS: We retrospectively enrolled patients with breast cancer metastasis to the bone or bone marrow, excluding cases where samples from both the primary and metastatic lesions were not available. Expression patterns of the estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) and Ki67 were compared in primary tumors and bone or bone marrow lesions.
RESULTS: Forty-six patients with a median age of 52 years (range, 34-72 years) were included in the study. Discordant rates of ER, PgR and HER2 were 20%, 46% and 0%, respectively. Physicians usually determined treatment options considering the results of biomarker re-evaluation. It is unlikely that biomarker discordance was related to prior treatment.
CONCLUSIONS: Biomarker discordance in bone or bone marrow lesions is common in patients with breast cancer. An accurate and thorough analysis of biomarkers and metastatic tumor properties is important for clinical decision-making.

Costa RP, Tripoli V, Princiotta A, et al.
Therapeutic effect of RA223 in the management of breast cancer bone metastases.
Clin Ter. 2019 Jan-Feb; 170(1):e1-e3 [PubMed] Related Publications
Radium 223 dichloride (Ra223) is the only targeted alpha therapy able to extend survival in patients with bone metastases from prostate cancer. Mechanism of action and data currently available focused mainly on osteoblastic metastases from prostate cancer. Phase 1 and 2 trials documented a clinical efficacy also in breast cancer patients with predominately bone disease, highlighting a reduction in alkaline phosphatase and other bone biomarkers. In our institution, a patient with breast cancer affected by osteolytic metastases was treated with off-label use of Ra223. Our patient had a good treatment compliance and up to now she has not been revealed the presence of SSE or hematological complications. Our preliminary experience shows that Ra223 may play a critical role to bone metastates in patients with breast cancer.

Azorín-Vega E, Rojas-Calderón E, Ferro-Flores G, et al.
Assessment of the radiation absorbed dose produced by
Appl Radiat Isot. 2019; 146:66-71 [PubMed] Related Publications
This research aimed to assess the radiation absorbed dose produced by

Mansinho A, Ferreira AR, Casimiro S, et al.
Levels of Circulating Fibroblast Growth Factor 23 (FGF23) and Prognosis in Cancer Patients with Bone Metastases.
Int J Mol Sci. 2019; 20(3) [PubMed] Free Access to Full Article Related Publications
The fibroblast growth factor (FGF) signaling pathway plays a key role in tumorigenesis and is recognized as a potential therapeutic target. In this study, the authors aimed to assess the impact of serum FGF23 levels in the prognosis of patients with cancer and bone metastases from solid tumors. A cohort of 112 patients with cancer and metastatic bone disease were treated with bone-targeted agents (BTA). Serum baseline FGF23 was quantified by ELISA and dichotomized in FGF23

Allocca G, Wang N
Tracking Cancer Cells Colonization in Rodent Bone Using Two-Photon Microscopy.
Methods Mol Biol. 2019; 1914:631-639 [PubMed] Related Publications
Two-photon microscopy has been widely accepted as a powerful tool to provide both qualitative and quantitative information in bone research. This chapter will describe a step-by-step protocol for using two-photon microscopy to track the colonization of cancer cells to bone using frozen bone samples of xenograft mouse models.

Uluçkan Ö
Mouse Models of Melanoma Bone Metastasis.
Methods Mol Biol. 2019; 1914:343-348 [PubMed] Related Publications
Melanomas are aggressive cancers of the skin with high metastatic capacity. Mouse models are necessary to delineate the mechanisms of cancer metastasis and xenograft models can also allow examining the role of the host using different genetically-modified mouse models. In this chapter, I provide a detailed protocol for the preparation and inoculation of tumor cells intra-cardially and intra-tibially to achieve bone metastasis.

Tulotta C, Groenewoud A, Snaar-Jagalska BE, Ottewell P
Animal Models of Breast Cancer Bone Metastasis.
Methods Mol Biol. 2019; 1914:309-330 [PubMed] Related Publications
This chapter is designed to provide a comprehensive overview outlining the different in vivo models available for research into breast cancer bone metastasis. The main focus is to guide the researcher through the methodological processes required to establish and utilize these models within their own laboratory. These detailed methods are designed to enable the acquisition of accurate and meaningful results that can be used for publication and future translation into clinical benefit for women with breast cancer-induced bone metastasis.

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