Tumour response interpretation with new tumour response criteria vs the World Health Organisation criteria in patients with bone-only metastatic breast cancer

Background:

We compared the utility of a new response classification (MDA; based on computed tomography (CT), magnetic resonance imaging (MRI), plain radiography (XR), and skeletal scintigraphy (SS)) and the World Health Organisation response classification (WHO; based on XR and SS) in stratifying breast cancer patients with bone-only metastases with respect to progression-free survival (PFS), overall survival (OS), and clinical response.

Methods:

We retrospectively reviewed 41 patients with bone-only metastatic breast cancer and assigned responses according to the MDA and WHO criteria. We analysed whether the MDA or WHO response classifications correlated with PFS and OS.

Results:

With the MDA criteria, there were significant differences in PFS between patients classified as responders and those classified as nonresponders (P=0.025), but with the WHO criteria, there were not. Neither criteria distinguished responders from nonresponders in terms of OS. MDA response criteria correlated better than WHO response criteria with clinical response assessment.

Conclusions:

The MDA classification is superior to the WHO classification in differentiating between responders and nonresponders among breast cancer patients with bone-only metastases. Application of the MDA classification may allow bone lesions to be considered measurable disease. Prospective study is needed to test the MDA classification among patients with bone metastasis.     

68例首诊伴单纯骨转移鼻咽癌患者预后分析

目的 探讨首诊伴单纯骨转移鼻咽癌患者的预后影响因素。方法 选取1997—2015年汕头大学医学院附属肿瘤医院收治的68例首诊伴单纯骨转移鼻咽癌患者,49接受放化疗。Kanplan-Meier法计算OS率,Logrank法单因素预后分析,Cox模型多因素预后分析。结果 中位随访时间为95.3个月,1、2、3、5年OS率分别为53%、38%、21%、15%,中位OS期13.4个月。单因素分析结果显示脊柱转移、骨转移数目、疗前LDH水平、原发病灶放疗技术、放疗剂量、原发病灶近期疗效均是影响OS期因素(P=0.02、0.01、0.00、0.02、0.02、0.01),多因素分析显示骨转移数目≤3个、原发病灶放疗剂量>65 Gy、IMRT技术是影响OS期的因素(P=0.03、0.02、0.04)。结论 对于骨转移数目≤3个的首诊伴单纯骨转移鼻咽癌患者,应予以积极治疗,包括采用IMRT技术、原发病灶放疗剂量>65 Gy,以争取原发病灶的近期疗效达到CR,临床意义重大。     

Bone Metastases as the Only Metastatic Site in Patients With Urothelial Carcinoma: Focus on a Special Patient Population

Background

Patients with exclusive bone metastatic spread from urothelial carcinoma (UC) throughout their disease course represent a rare subgroup with unique clinical features. These patients deserved special consideration in a retrospective multicenter study.

CXCR7-mediated progression of osteosarcoma in the lungs

Background:

Osteosarcoma (OS) is the most frequent primary malignant bone tumour in children and adolescents with a high propensity for lung metastasis. Chemokines and chemokine receptors have been described to have an important role in many malignancies including OS. The aim of this study was to investigate the expression of CXCR7 receptor in OS tissues and its role in the progression of the disease in the lungs.

Methods:

Immunohistochemistry was used to study CXCR7 expression in primary tumours and metastatic tissues from patients with OS. Its contribution to tumour expansion in the lungs has been also assessed using animal models and synthetic-specific CXCR7 ligands.

Results:

CXCR7 was expressed on human primary bone tumours and on lung metastases. Its expression was predominantly located on tumour-associated blood vessels. Mice challenged with OS cells and systematically treated with synthetic CXCR7 ligands presented a significant reduction of lung nodules compared with untreated mice.

Conclusion:

This study shows that CXCR7 has a critical role in OS progression in the lungs, where are expressed CXCR7 ligands, especially CXCL12. Moreover, we highlight that synthetic CXCR7 ligands could represent a powerful therapeutic tool to impede lung OS progression.     

Effect of M1a and M1b Category in Metastatic Colorectal Cancer

Background.

In 2009, the American Joint Committee on Cancer version 7 staging system introduced the M1 subclassifications M1a (single metastatic site) and M1b (peritoneal or multiple metastatic sites). The study objectives were to evaluate the prognostic effect of site of metastasis and M1a/b category among patients with newly diagnosed colorectal cancer and synchronous metastasis.

Patients and Methods.

Patients with newly diagnosed pathologic or clinical category M1 colorectal cancer referred to the British Columbia Cancer Agency between 1999 and 2007 were included. Demographic, tumor, treatment, and outcome data were prospectively collected, and prognostic factors were identified. Univariate Cox models were used to assess the prognostic impact of individual sites of metastasis and to determine the effect of M1a/b category on overall survival (OS).

Results.

Among 2,049 eligible patients, 70% had M1a and 30% M1b category disease. The most common sites of common single sites of metastasis included liver (56%), lung (5.3%), and peritoneum (3.6%). Metastasis to a single organ or site, including peritoneum, was associated with improved OS compared with multiple sites of metastasis. In multivariate analysis, M1b category conferred inferior survival and hazard ratio (HR) 1.38 (95% confidence interval [CI]: 1.22, 1.55), along with age >70 and Eastern Cooperative Oncology Group performance status of 3–4. Resection of primary tumor was associated with improved survival, HR 0.46 (95% CI: 0.41, 0.52). Results were similar in subgroup analysis of patients undergoing resection of their primary tumor when histology, tumor, and node category were included.

Conclusion.

The results lend support to the introduction of M1a/b colorectal cancer categories. Consideration may be given to classifying patients with solitary peritoneal metastasis only as M1a rather than M1b category. Further refinement of category M1a to reflect resectability of metastasis at initial diagnosis may improve prognostication.     

A clinical case of the penile metastasis from the rectal carcinoma

Background

Penile metastases are rare and usually secondary to genitourinary and colorectal cancer.

Case report

We present a case of a 77-year-old man with penile metastasis who was operated for rectal carcinoma. He was referred to our clinic for penile ulcerous lesion, semierectile penis and voiding dysfunction. Imaging studies showed nodular lesion at glans penis and multiple bone metastases. He did not respond to chemoradiotherapy and he had bad prognosis.

Conclusions

Imaging methods and biopsy may help to clarify the diagnosis but the treatment modalities are insufficient in these patients.     

Predictive value of miR-9 as a potential biomarker for nasopharyngeal carcinoma metastasis

Background:

Nasopharyngeal carcinoma (NPC) has a distinctive geographic distribution and is characterised by its strong tendency of metastasis. We aimed to examine the microRNA (miRNA) expression profiles in plasma samples of NPC patients to explore their clinical significance in disease development and progression.

Methods:

This study was divided into four steps: (1) confirmation of differentially expressed miRNAs using microarray analysis and quantitative PCR validation; (2) comparison of plasma miR-9 levels during NPC progression; (3) evaluation of the predictive performance of plasma miR-9 as a biomarker for NPC metastasis; and (4) comparison of plasma miR-9 levels between pre- and post-treatment samples.

Results:

Plasma microarray profiling identified 33 differentially expressed miRNAs between NPC patients and healthy volunteers. The significantly declined level of miR-9 in NPC patients was confirmed through two-stage validation. The low level of plasma miR-9 was significantly correlated with worse lymphatic invasion and advanced TNM stage. The plasma miR-9 could distinguish locoregional from metastatic NPC cases with a high sensitivity and specificity. Furthermore, the plasma miR-9 level was significantly elevated in post-treatment plasma compared with those pre-treatment samples.

Conclusion:

Our study reports that plasma miR-9 may serve as a useful biomarker to predict NPC metastasis and to monitor tumour dynamics.     

Experiences of pretreatment laparoscopic surgical staging in patients with locally advanced cervical cancer: results of a prospective study

Objective

To prospectively evaluate the feasibility, safety, and survival of laparoscopic surgical staging in patients with locally advanced cervical cancer.

Methods

From Oct 2001 to Jul 2006, a total of 83 consecutive patients were eligible for inclusion and underwent laparoscopic surgical staging.

Results

Three patients with intraoperative great vessel injury and 1 patient in whom the colpotomizer was unable to be inserted were excluded. Laparoscopic surgical staging was feasible in 95.2% (79/83). Immediate postoperative complications were noted in 12 (15.2%) patients. Prolonged complications directly related to operative procedures numbered 2 (2.5%), and were trocar site metastases. The mean time from surgery to the start of radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) was 11 (5-35) days. All patients tolerated the treatment well and completed scheduled RT or CCRT without disruption of treatment and additional admission. The rate of modification of the radiation field after surgical staging was 8.9% (7/79). Five-year progression-free survival and overall survival (OS) rates were 79% and 89%, respectively. The OS of patients with microscopic lymph node metastases, which were fully resected, were comparable to those of patients without lymph node metastasis. However, the OS of patients with macroscopic lymph node metastases that were fully resected were poorer compared with those of patients without lymph node metastasis.

Conclusion

Pretreatment laparoscopic surgical staging is a feasible and safe treatment modality. However the survival benefit of debulking lymph nodes or full lymph node dissection is not clear.     

Risk of death from cardiovascular disease following breast cancer: a systematic review

Purpose

To analyze the prognostic influence of metastatic pattern (MP) compared with other biologic and clinical factors in stage IV breast cancer at initial diagnosis (BCID) and evaluate factors associated with specific sites of metastases (SSM).

Methods

We evaluated women with stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2013. MP was categorized as bone-only, visceral, bone and visceral (BV), and other. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with SSM.

Results

We included 9143 patients. Bone represented 37.5% of patients, visceral 21.9%, BV 28.8%, and other 11.9%. Median OS by MP was as follows: bone 38 months, visceral 21 months, BV 19 months, and other 33 months (P < 0.0001). Univariate analysis showed that higher number of metastatic sites had worse prognosis. In multivariate analysis, older age (hazard ratio 1.9), black race (hazard ratio 1.17), grade 3/4 tumors (hazard ratio 1.6), triple-negative (hazard ratio 2.24), BV MP (hazard ratio 2.07), and unmarried patients (hazard ratio 1.25) had significantly shorter OS. As compared with HR+/HER2? tumors, triple-negative and HR?/HER2+ had higher odds of brain, liver, lung, and other metastases. HR+/HER2+ had higher odds of liver metastases. All three subtypes had lower odds of bone metastases.

Conclusions

There were substantial differences in OS according to MP. Tumor subtypes have a clear influence among other factors on SSM. We identified several prognostic factors that could guide therapy selection in treatment naïve patients.

     

Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis?

Purpose

Aim of this study was to investigate for the presence of existing prognostic factors in patients with bone metastases (BMs) from RCC since bone represents an unfavorable site of metastasis for renal cell carcinoma (mRCC).

Materials and methods

Data of patients with BMs from RCC were retrospectively collected. Age, sex, ECOG-Performance Status (PS), MSKCC group, tumor histology, presence of concomitant metastases to other sites, time from nephrectomy to bone metastases (TTBM, classified into three groups: <1 year, between 1 and 5 years and >5 years) and time from BMs to skeletal-related event (SRE) were included in the Cox analysis to investigate their prognostic relevance.

Results

470 patients were enrolled in this analysis. In 19 patients (4%),bone was the only metastatic site; 277 patients had concomitant metastases in other sites. Median time to BMs was 16 months (range 0 − 44y) with Median OS of 17 months. Number of metastatic sites (including bone, p = 0.01), concomitant metastases, high Fuhrman grade (p < 0.001) and non-clear cell histology (p = 0.013) were significantly associated with poor prognosis. Patients with TTBM >5 years had longer OS (22 months) compared to patients with TTBM <1 year (13 months) or between 1 and 5 years (19 months) from nephrectomy (p < 0.001), no difference was found between these two last groups (p = 0.18). At multivariate analysis, ECOG-PS, MSKCC group and concomitant lung or lymph node metastases were independent predictors of OS in patients with BMs.

Conclusions

Our study suggest that age, ECOG-PS, histology, MSKCC score, TTBM and the presence of concomitant metastases should be considered in order to optimize the management of RCC patients with BMs.     

Retrospective analysis of results of treatment for nasopharyngeal carcinoma in Macao

Background： Nasopharyngeal carcinoma （NPC） is a common malignancy in Southeast Asia, however, a full consensus has not yet been reached as to the value of comprehensive treatment for NPC. This study was designed to evaluate the epidemiological characteristics of NPC and their prognostic value, as well as the long-term efficacy of NPC treatment. Patients and methods： A total of 248 patients, with different stages of NPC, were included in this study. Results： The 5-year overall survival （OS） rates for patients in stages I, II, lII and IV were 90.48%, 76.71%, 76.89% and 33.87%, respectively （P=0.000）, while the respective 5-year progression-free survival （PFS） rates were 85.15%, 72.36%, 63.88% and 26.26% （P=0.000）. The respective 5-year OS rates, according to stage, for the group that received radiotherapy combined with chemotherapy and for the group that received radiotherapy only were as follows： stages I and II, 81.67% and 79.59% （P=0.753）; stage III, 79.91% and 70.38% （P=0.143）; stage IV,, 35.22% and 0% （P=0.000）. The respective 5-year PFS rates in these groups were as follows： stages I and II, 75.83% and 74.98% （P=0.814）; stage III, 74.08% and 42.25% （P=0.027）; stage IV,, 27.31% and 0% （P=0.000）. Conclusions： Clinical staging appears to be the most important prognostic factor for NPC. As the stage number increases, both the 5-year OS and PFS significantly decrease. Adding chemotherapy to radiotherapy was not advantageous for patients with stage I or II NPC, however the addition of chemotherapy to radiotherapy significantly improved OS and PFS in patients with stage IV NPC. The addition of chemotherapy improved PFS, but not OS in patients with stage III NPC.     

Response in bone turnover markers during therapy predicts overall survival in patients with metastatic prostate cancer: analysis of three clinical trials

Background:

The bone-forming metastases of prostate cancer result from complex stromal–epithelial interactions within the tumour microenvironment. Autocrine–paracrine signalling pathways between prostate cancer epithelial cells, osteoblasts, and osteoclasts stimulate aberrant bone remodelling, and the activity of these three cell populations can be quantitatively measured using prostate-specific antigen (PSA), bone-specific alkaline phosphatase (BAP) and urine N-telopeptide (uNTx), respectively. The purpose of the present study was to test the hypothesis that serial measurements of BAP and uNTx during therapy would facilitate monitoring of disease activity and predict the overall survival (OS) in patients with metastatic prostate cancer receiving therapy.

Methods:

Radionuclide bone scan, PSA, BAP, and uNTx data were retrospectively analysed from three clinical trials in patients with metastatic prostate cancer conducted at our institution. Qualitative changes in bone scans and quantitative changes in PSA, BAP, and uNTx concentrations during therapy were correlated with OS.

Results:

Baseline levels of BAP, but not PSA, were prognostic for OS in both androgen-dependent and castrate-resistant disease. A reduction in PSA, BAP, uNTx, or BAP/uNTx on therapy was predictive of improved OS in both patient groups. Conversely, an increase in PSA, or BAP on therapy was predictive of worse OS in both patient groups. Baseline number of lesions and response on bone scan during therapy were neither prognostic nor predictive of OS in either patient group.

Conclusion:

These observations support the concept that serial measurements of bone turnover metabolites during therapy function as clinically informative predictive biomarkers in patients with advanced prostate cancer and skeletal metastases. PSA measurements and bone scans remain essential to monitor the overall disease activity and determine the anatomic distribution of skeletal metastases.     

Metastatic pattern of uterine leiomyosarcoma: retrospective analysis of the predictors and outcome in 113 patients

Objective

To describe metastatic pattern of uterine leiomyosarcomas (ULMS) and correlate it with clinical and histopathologic parameters.

Methods

We included 113 women (mean age, 53 years; range, 29 to 72 years) with histopathology-confirmed ULMS from 2000 to 2012. Distribution of metastases was noted from imaging by two radiologists in consensus. Predictors of development of metastases were analyzed with univariate and multivariate analysis. Impact of various clinical and histopathologic parameters on survival was compared using Log-rank test and Cox proportional hazard regression model.

Results

Distant metastases were seen in 81.4% (92/113) of the patients after median interval of 7 months (interquartile range, 1 to 21). Lung was most common site of metastases (74%) followed by peritoneum (41%), bones (33%), and liver (27%). Local tumor recurrence was noted in 57 patients (50%), 51 of whom had distant metastases. Statistically significant correlation was noted between local recurrence and peritoneal metastases (p<0.001) and between lung and other common sites of hematogeneous metastases (p<0.05). Age, serosal involvement, local recurrence, and the International Federation of Gynecology and Obstetrics (FIGO) stage were predictive factors for metastases. At the time of reporting, 65% (74/113) of the patients have died; median survival was 45 months. Stage, local recurrence, and age were poor prognostic factors.

Conclusion

ULMS metastasizes most frequently to lung, peritoneum, bone, and liver. Local recurrence was associated with peritoneal spread and lung metastases with other sites of hematogeneous metastases. Age, FIGO stage and local recurrence predicted metastatic disease and advanced stage, older age and local recurrence predicted poor outcome.     

Clinical impact of post-progression survival on overall survival in patients with limited-stage disease small cell lung cancer after first-line chemoradiotherapy

Background

The effects of first-line chemoradiotherapy on overall survival (OS) may be confounded by subsequent lines of therapy in patients with limited-stage disease small cell lung cancer (LD-SCLC). Therefore, we aimed to determine the relationships between progression-free survival (PFS), post-progression survival (PPS) and OS after first-line chemoradiotherapy in LD-SCLC patients.

Patients and methods.

We retrospectively analyzed 71 LD-SCLC patients with performance status (PS) 0–2 who received first-line chemoradiotherapy and had disease recurrence between September 2002 and March 2013 at Shizuoka Cancer Center (Shizuoka, Japan). We determined the correlation between PFS and OS and between PPS and OS at the individual level. In addition, we performed univariate and multivariate analyses to identify significant prognostic factors of PPS.

Results

OS is more strongly correlated with PPS (Spearman’s r = 0.86, R² = 0.72, p < 0.05) than PFS (Spearman’s r = 0.46, R² = 0.38, p < 0.05). In addition, the response to second-line treatments, the presence of distant metastases at recurrence and the number of additional regimens after first-line chemoradiotherapy were significant independent prognostic factors for PPS.

Conclusions

PPS has more impact on OS than PFS in recurrent LD-SCLC patients with good PS at beginning of the treatment. Moreover, treatments administered after first-line chemoradiotherapy may affect their OS. However, larger multicenter studies are needed to validate these findings.     

Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer

Objective

Evaluation of the impact of sequential chemoradiotherapy in high risk endometrial cancer (EC).

Methods

Two hundred fifty-four women with stage IB grade 3, II and III EC (2009 FIGO staging), were included in this retrospective study.

Results

Stage I, II, and III was 24%, 28.7%, and 47.3%, respectively. Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty-five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%) chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and 91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040; overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS, p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015) and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (≤65 years) and sequential chemoradiotherapy were statistically related to the prognosis.

Conclusion

Sequential chemoradiotherapy improves survival rates in high risk EC compared with chemotherapy or radiotherapy alone, in particular in stage III.     

Combining plasma Epstein-Barr virus DNA and nodal maximal standard uptake values of 18F-fluoro-2-deoxy-D-glucose positron emission tomography improved prognostic stratification to predict distant metastasis for locoregionally advanced nasopharyngeal carcinoma

Background

This study aimed to evaluate the value of combining the nodal maximal standard uptake values (SUVmax) of ¹⁸ F-fluoro-2-deoxy-D-glucose positron emission tomography with Epstein-Barr virus DNA(EBV DNA) levels to predict distant metastasis for nasopharyngeal carcinoma (NPC) patients

Patients and Methods

Eight hundred seventy-four patients with stage III-IVa-b NPC were evaluated for the effects of combining SUVmax and EBV DNA levels on distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS).

Results

The optimal cutoff value was 6,220 copies/mL for EBV DNA and 7.5 for SUVmax-N. Patients with lower EBV DNA levels or SUVmax-N had a significantly better 3-year DMFS, DFS, and OS. Patients were divided into four groups based on EBV DNA and SUVmax-N, as follows: low EBV DNA and low SUVmax-N (LL), low EBV DNA and high SUVmax-N (LH), high EBV DNA and low SUVmax-N (HL), and high EBV DNA and high SUVmax-N (HH). There were significant differences between the four mentioned groups in 3-year DMFS: 95.7%, 92.2%, 92.3%, and 80.1%, respectively (P^trend < 0.001). When looking at the disease stage, the 3-year DMFS in group LL, LH, HL, HH were 94.2%, 92.9%, 95.0%, and 81.1%, respectively, in stage III patients (P^trend < 0.001) and 92.7%, 87.2%, 86.3%, and 77.0% in stage IVa–b patients (P^trend = 0.026).

Conclusion

Pretreatment EBV DNA and SUVmax of neck lymph nodes were independent prognostic factors for distant metastasis in NPC patients. Combining EBV DNA and SUVmax-N led to an improved risk stratification for distant metastasis in advanced-stage disease.     

Propensity score matching analysis of cisplatin-based concurrent chemotherapy in low risk nasopharyngeal carcinoma in the intensity-modulated radiotherapy era

Background

Patients with stage II nasopharyngeal carcinoma were reported to benefit from adding cisplatin-based concurrent chemotherapy to two-dimensional conventional radiotherapy. But this benefit becomes uncertain in the intensity-modulated radiotherapy (IMRT) era, owing to its significant advantage.

Methods

We enrolled 661 low risk (T1N1M0, T2N0-1M0 or T3N0M0, the 2010 UICC/AJCC staging system) patients who underwent IMRT with or without concurrent chemotherapy. Particularly, patients with IMRT alone or IMRT plus cisplatin-based concurrent chemotherapy were equally matched using propensity-score matching method. Overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression.

Results

Among 661 patients, IMRT alone achieved parallel OS (P = 0.379), DMFS (P = 0.169) and LRFS (P = 0.849) to IMRT plus concurrent chemotherapy. In the propensity-matched cohort of 482 patients, similar survival were observed between both arms (4-years OS 97.4% vs 96.1%, P = 0.134; DMFS 96.5% vs 95.1%, P = 0.763; LRFS 93.8% vs 91.5%, P = 0.715). In multivariate analysis, cisplatin-based concurrent chemotherapy did not lower the risk of death, distant metastasis or locoregional relapse. And this association remained unchanged in subgroups by age, sex, histology and stage.

Conclusions

In this study, low risk nasopharyngeal carcinoma patients who underwent IMRT could not benefit from cisplatin-based concurrent chemotherapy.     

The role of Fluorine-18-Fluorodeoxyglucose positron emission tomography in staging and restaging of patients with osteosarcoma

Background

The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with Fluorine-18-Fluorodeoxyglucose (FDG) in patients with osteosarcoma (OS).

Methods

A comprehensive literature search of published studies through October 10^th, 2012 in PubMed/MEDLINE, Embase and Scopus databases regarding whole-body FDG-PET and FDG-PET/CT in patients with OS was performed.

Results

We identified 13 studies including 289 patients with OS. With regard to the staging and restaging of OS, the diagnostic performance of FDG-PET and PET/CT seem to be high; FDG-PET and PET/CT seem to be superior to bone scintigraphy and conventional imaging methods in detecting bone metastases; conversely, spiral CT seems to be superior to FDG-PET in detecting pulmonary metastases from OS

Conclusions

Metabolic imaging may provide additional information in the evaluation of OS patients. The combination of FDG-PET or FDG-PET/CT with conventional imaging methods seems to be a valuable tool in the staging and restaging of OS and may have a relevant impact on the treatment planning.     

Primary breast cancer stem-like cells metastasise to bone,switch phenotype and acquire a bone tropism signature

Background:

Bone metastases represent a common and severe complication in breast cancer, and the involvement of cancer stem cells (CSCs) in the promotion of bone metastasis is currently under discussion. Here, we used a human-in-mice model to study bone metastasis formation due to primary breast CSCs-like colonisation.

Methods:

Primary CD44⁺CD24⁻ breast CSCs-like were transduced by a luciferase-lentiviral vector and injected through subcutaneous and intracardiac (IC) routes in non-obese/severe-combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The CSCs-like localisation was monitored by in vivo luciferase imaging. Bone metastatic CSCs-like were analysed through immunohistochemistry and flow cytometry, and gene expression analyses were performed by microarray techniques.

Results:

Breast CSCs-like colonised the human-implanted bone, resulting in bone remodelling. Bone metastatic lesions were histologically apparent by tumour cell expression of epithelial markers and vimentin. The bone-isolated CSCs-like were CD44⁻CD24⁺ and showed tumorigenic abilities after injection in secondary mice. CD44⁻CD24⁺ CSCs-like displayed a distinct bone tropism signature that was enriched in genes that discriminate bone metastases of breast cancer from metastases at other organs.

Conclusion:

Breast CSCs-like promote bone metastasis and display a CSCs-like bone tropism signature. This signature has clinical prognostic relevance, because it efficiently discriminates osteotropic breast cancers from tumour metastases at other sites.