Early (mucosal) gastric cancer with synchronous osteosclerotic bone metastases: a case report

ANAGNOSTOPOULOS G., SAKORAFAS G.H., KOSTOPOULOS P., MARGANTINIS G., TSIAKOS S. & PAVLAKIS G. (2010) European Journal of Cancer Care
Early (mucosal) gastric cancer with synchronous osteosclerotic bone metastases: a case report Early gastric cancer (EGC) is defined as an adenocarcinoma confined to the gastric mucosa or submucosa, regardless of the presence of lymph node metastases. Early gastric cancer carries an excellent prognosis, with a 5‐year survival rate at least 85% in most series. However, there are rare cases where distant metastases exist. Bone metastases are rare in gastric cancer; osteoblastic bone metastases are even rarer. We report a patient with EGC (mucosal) and synchronous osteosclerotic bone metastasis. To our knowledge, this is the first reported case of submucosal EGC with synchronous bone metastases. The patient was operated and he received adjuvant chemotherapy and radiotherapy. He died 18 months after gastric surgery from generalized disease.     

Massive endoprosthetic replacement for bone metastases resulting from renal cell carcinoma: Factors influencing patient survival

Background

Surgery remains the main treatment of bone metastases due to renal cell carcinoma (RCC). We reviewed 135 patients treated with resection and endoprosthetic replacement (EPR) and examined clinico-pathological factors predicting survival.

Methods

Surgical and oncological outcomes were examined using a prospectively maintained database between 1976 and 2012. Survival rates were calculated by Kaplan–Meier method. Multivariate analyses were performed to investigate factors predictive of increased survival.

Results

At diagnosis, 81 patients had synchronous RCC and bone metastases and the remaining developed metachronous metastases after primary treatment for RCC. The majority were solitary tumours (75%) and 77% had ≥ one concurrent visceral metastases. The median age at surgery was 61 years old (IQR 53–69). The median follow-up was 20 months (IQR 10–43) and the overall survival was 72% at one-year. This declined to 45% and 28% at three and five-years, respectively. After adjustments for prognostic factors, there was an increased risk of death in patients with multiple skeletal metastases (HR = 2), ≥one visceral metastases (HR = 3) and local recurrence (HR = 3) (all p ≤ 0.01). Ten patients required revision (7%) and the risk of revision was 4% at one-year and remained low at 8% from two years postoperatively.

Conclusion

Patients with solitary bone lesions and no visceral metastases should be considered for bone resection and EPR. As survival beyond one-year can be expected in a majority of patients and the risk of further surgery after EPR is low, patients with multiple skeletal metastases and visceral metastases should also be considered.     

Single and multiple metachronous osteosarcoma tumors after therapy

BACKGROUND: The objective of the current study was to determine the incidence, clinical and pathologic characteristics, and outcome of patients with conventional osteosarcoma who developed metachronous tumors after treatment for the primary tumor and prevention of pulmonary metastases. METHODS: The medical records of 270 pediatric patients (younger than age 18 years) were reviewed. The prevention and absence of pulmonary metastases was confirmed by chest radiographs and computerized scans of the lungs. Radionuclide bone scans were used to confirm the absence of skeletal metastases. RESULTS: Eleven patients with metachronous tumors were identified. Index primary tumors involved the femur (n = 8), the tibia (n = 2), and the radius (n = 1). Single metachronous tumors developed in the femur (n = 6), in the humerus (n = 1), and multifocal in multiple bones (n = 4). Two patients later developed second metachronous tumors. The interval between identification of the primary tumor to development of the single metachronous tumors varied from 11 months to 78 months and from 12 months to 42 months for synchronous multifocal tumors. Metachronous tumors were treated with single-agent cisplatin or ifosfamide. Only 1 patient experienced > 90% tumor necrosis. Pulmonary metastases were not detected in 10 of 11 patients at the time metachronous tumors were discovered. In the 11th patient, synchronous pulmonary metastasis with the metachronous tumor was noted. Three patients had a prior history of bilateral retinoblastoma. The Li-Fraumeni syndrome may have been present in another patient. Six patients died. Five patients have survived for 20+ to 50+ months after the appearance, treatment, and resection of metachronous tumors. CONCLUSIONS: With improvement in the cure rate, metachronous osteosarcoma should be recognized as an important sequela in long-term survivors. The etiology of this disease is unknown. Speculation rests on a skeletal multicentric origin, which includes an inherited predisposition to develop osteosarcoma in retinoblastoma and in the Li-Fraumeni syndrome. Meticulous follow-up is required to permit early detection and successful therapeutic intervention.     

A case of osteonecrosis of the jaw in a breast cancer patient with bone metastases receiving long-term treatment with bisphosphonates

Bisphosphonates (BPs) are often used for the treatment of several diseases such as osteoporosis, cancer-associated hypercalcemia, and osteolytic bone metastasis. Recently, there have been reports of osteonecrosis of the jaw (ONJ) in cancer patients whose treatment regimens include BPs. In this case report, we describe complications and treatment of ONJ in a breast cancer patient with bone metastases who received long-term treatment with BPs. A 70-year-old woman underwent modified radical mastectomy on her left breast cancer and received oral 5-fluorouracil derivatives for 2 years in another hospital. Eleven years after the surgery, she came to our hospital complaining of spinalgia and was diagnosed with recurrent breast cancer with multiple metastases to the stomach, liver, multiple lymph nodes, and spine. After surgery for spine metastases, she was given a combination therapy of trastuzumab (initial bolus: 170 mg/body, followed by two or more cycles of 85 mg/body) every week, docetaxel (100 mg/body) every 3 weeks, and BPs (90 mg/body) every 4 weeks. About 1 year and 4 months later, she complained of pain in her right maxilla; biopsy revealed ONJ. Medical oncologists need to recognize ONJ as a serious side effect of BP treatment; dentists and oral and maxillofacial surgeons need to thoroughly consult patients regarding the administration of BPs and have them make an informed consent.     

Prognostic value of disease-free interval in colorectal cancer: Is it time?

BackgroundPrevious studies have outlined that the onset of synchronous colorectal cancer (CRC) metastases is associated with poor overall survival (OS) compared to patients with metachronous disease. The aim of this study was to evaluate the association of disease-free interval with newly diagnosed CRC scheduled for primary tumor resection.MethodsPatients who underwent primary CRC resection over an 18-year period were identified from a prospective database at a tertiary-care hospital. In this observational study, the cohort was stratified for the onset of metastases, i.e. synchronous, early-onset and late-onset metachronous disease. The OS was compared using Kaplan-Meier estimators and stratified Cox hazard regression analysis.ResultsOf 360 patients, 204 (57%) had synchronous, 61 (17%) had early metachronous, and 95 (26%) had late metachronous metastases, respectively. The onset of synchronous metastases was not associated with worse OS compared to early and late metachronous disease. ASA level > II (P = 0.011), right-sided compared to left-sided cancer (P = 0.032) or rectal cancer (P < 0.001), and high-grade tumors (P = 0.022) were identified as independent predictors of poor OS, whereas the only favorable prognostic factor was surgical resection of metastases (P = 0.047). Additionally, ASA level < III (P = 0.003) and low-grade tumors (P = 0.032) were found to predict resection of metastases.ConclusionIndividual patients' and tumor characteristics rather than the timing of metastases are associated with OS in newly diagnosed CRC. These data support curative treatment strategies even in patients with synchronous metastases.     

Histomorphometric analysis of sclerotic bone metastases from prostatic carcinoma special reference to osteomalacia

Transiliac undecalcified bone biopsy specimens were taken after tetracycline double labeling from 14 patients with radiologic evidence of osteosclerotic metastases from prostatic carcinoma. The histomorphometric analysis showed an increased trabecular bone volume in all patients, and in seven morphologic and dynamic evidence of osteomalacia (Group 1). The seven other patients demonstrated an extension of apposition surfaces without evidence of osteomalacia (Group 2). Group 1 was different from Group 2 in terms of a greater increase in serum alkaline phosphatase and a lower urinary calcium. In four Group 1 patients, a second bone sample taken after two to six months of treatment with vitamin D and calcium provided evidence of improving osteomalacia. The high incidence of osteomalacia in osteosclerotic metastases of prostatic origin appears to be the result of the increase in bone formation induced by prostatic cells, and the unability to satisfy the high calcium demand for new bone.     

Tumor-derived platelet-derived growth factor-BB plays a critical role in osteosclerotic bone metastasis in an animal model of human breast cancer

Breast cancer produces a variety of growth factors to promote its behavior at primary and secondary sites in autocrine/paracrine manners. However, the role of these growth factors in the colonization of cancer cells in bone, which is one of the most common metastatic sites, is poorly understood. To study this, we established an in vivo model in which the MCF-7 human breast cancer cells caused predominant osteosclerotic bone metastases 20-25 weeks after inoculation into the left cardiac ventricle in female nude mice. To make this model more time efficient, we overexpressed the oncogene Neu, which is associated with aggressive behavior in human breast cancers, in MCF-7 cells (MCF-7/Neu). MCF-7/Neu cells grew without estrogen and developed osteosclerotic bone metastases in 10-12 weeks in animals. Of note, MCF-7/Neu-bearing mice showed substantial plasma levels of human platelet-derived growth factor-BB (hPDGF-BB; 855 +/- 347 pg/ml; mean +/- SE, n = 5), indicating hPDGF-BB production by inoculated MCF-7/Neu cells. MCF-7/Neu cells in culture also produced large amounts of hPDGF-BB. Conditioned medium harvested from MCF-7/Neu cells stimulated osteoblastic bone formation in organ cultures of neonatal mouse calvariae, and a neutralizing antibody to hPDGF-BB blocked the osteoblastic bone formation. Stable transfection of the hPDGF-B AS in MCF-7/Neu cells reduced hPDGF-BB production in culture. Mice bearing these MCF-7/Neu cells with antisense showed reduced bone metastases with decreased plasma hPDGF-BB levels (54 +/- 20 and 35 +/- 21 in two different antisense and 696 +/- 312 pg/ml in empty vector; mean +/- SE; n = 5). Introduction of hPDGF-B cDNA in the MDA-MB-231 human breast cancer cells, which consistently formed osteolytic bone metastases, induced osteosclerotic lesions in the osteolytic bone metastases. In conclusion, we show that MCF-7 cells cause osteosclerotic bone metastases and that Neu enhances this capacity of MCF-7 cells. Our data suggest that MCF-7/Neu-derived hPDGF-BB plays a causative role in the development of osteosclerotic bone metastases in this model.     

Survival of breast cancer patients with synchronous or metachronous central nervous system metastases

BackgroundCentral nervous system (CNS) metastases represent a devastating complication for advanced breast cancer patients. This observational study examines the influence of patient, tumour and treatment characteristics on overall survival after synchronous or metachronous CNS metastases.MethodsInformation on 992 breast cancer patients with CNS metastases (whose primary tumour was diagnosed between 2004 and 2010) was retrieved from the Netherlands Cancer Registry (NCR). Overall survival was calculated from the date of CNS metastatic diagnosis, and the impact of prognostic factors on survival was assessed using univariate and multivariate extended Cox-regression models.ResultsWe identified 165 patients with synchronous and 827 patients with metachronous CNS metastases. The majority of patients (88%) presented with brain metastases only, 12% had leptomeningeal metastases. Overall median survival was 5.0 months. Non-triple-negative breast cancer and systemic therapy were associated with improved survival in both groups. In patients with synchronous CNS metastases, surgery for the primary tumour and the metastases also improved survival. In patients with metachronous metastases, younger age (<50 years), lower initial tumour stage (I), ductal carcinoma, a prolonged time interval until diagnosis of CNS metastasis (>1 year), and absence of extracranial metastases were associated with improved survival. Metastasectomy and radiation therapy did not provide benefit beyond the first six months.ConclusionsNo difference in survival was established between synchronous and metachronous CNS metastases. Triple-negative disease is prognostically unfavourable in both groups, while those receiving treatment have a better outcome. Metastasectomy and radiotherapy improve survival within the first six months, and additional benefit may be derived from systemic therapy.     

Metachronous peritoneal carcinomatosis after curative treatment of colorectal cancer

Introduction

Population-based data on metachronous peritoneal carcinomatosis (PC) after curative resection of colorectal origin are scarce. The aim of this study was to investigate the incidence of and risk factors for developing metachronous PC from colorectal cancer as well as survival since diagnosis of PC.

Methods

Data on metachronous metastases were collected between 2010 and 2011 for all patients diagnosed with M0 colorectal cancer between 2003 and 2008 in the Dutch Eindhoven Cancer Registry. Median follow-up was 5.0 years. Survival was defined as time from metastases diagnosis to death.

Results

Of the 5671 colorectal cancer patients, 1042 (18%) were diagnosed with metachronous metastases of whom 197 (19%) developed metachronous PC. The peritoneal surface was the only site of metastasis in 81 (41%) patients while 116 (59%) patients were diagnosed with both PC and metastases elsewhere. Median survival after diagnosis of PC was 6 months compared to 15 months for patients with distant metastases in other organs. Patients with an advanced primary tumour stage, positive lymph nodes at initial diagnosis, primary mucinous adenocarcinoma, positive resection margin and a primary tumour located in the colon were at increased risk of developing metachronous PC.

Conclusion

Of the colorectal cancer patients who developed metachronous metastases, approximately one fifth is diagnosed with PC. Prognosis of these patients is poor with a median survival of 6 months after diagnosis. Identifying patients at high risk for developing metachronous PC is important as it may contribute to more accurate patient information, tailor-made follow-up schemes, and more adequate treatment.     

Surgery for metachronous metastasis of soft tissue sarcoma – A magnitude of benefit analysis using propensity score methods

IntroductionMetastasectomy is hypothesised to improve OS in metastatic STS, but evidence in favour of this approach derives from non-controlled single-arm cohorts affected by selection bias. The objective was to quantify the effect of metastasectomy vs. non-surgical management on overall survival (OS) in patients with metachronous metastases from extremity- and trunk soft tissue sarcoma (STS).Materials and methodsFrom a population of 1578 STS patients, 135 patients who underwent surgery for localised STS at two European centres between 1998 and 2015 and developed metachronous STS metastases were included. Propensity score analyses with inverse-probability-of-treatment-weights (IPTW) and landmark analyses were performed to control for selection and immortal time bias, respectively.ResultsOS was significantly longer in the 68 patients undergoing metastasectomy than in the 67 patients who were treated non-invasively for their metastasis (10-year OS: 23% vs. 4%; hazard ratio (HR) = 0.34, 95% CI: 0.22–0.53, p < 0.0001). This association prevailed after IPTW-weighting of the data to control for the higher prevalence of favourable prognostic factors in the surgery group (adjusted 10-year OS: 17% vs. 3%, log-rank p < 0.0001; HR = 0.33, 95% CI: 0.20–0.52, p < 0.0001). Five-year OS estimates were 27.8% in patients who had and 14.5% in patients who had not undergone metastasectomy within the first 3 months after diagnosis of a metastasis (p < 0.0001).ConclusionIn this observational bi-centre study, metastasectomy was associated with prolonged survival in patients with metachronous STS metastases. In the absence of randomized studies, our results indicate that metastasectomy should be considered as an important treatment option for metachronous STS metastases.     

Gamma knife radiosurgery for metastatic brain tumors from thyroid cancer

Objective We report our experience using gamma knife radiosurgery (GKR) for brain metastasis from thyroid cancer, which is extremely rare. Methods Between 1995 and 2007, 9 patients with 26 metastatic brain tumor(s) from thyroid cancer underwent GKR. The mean patient age was 58 years (range: 10–78). Seven patients had metastases from papillary thyroid cancer, and two from medullary thyroid cancer. Five patients had solitary tumors, and four patients had multiple metastases. Three patients who had multiple metastases also underwent whole brain radiation therapy (WBRT). The mean tumor volume was 2.4 cc (range: 0.03–14.0). A median margin dose of 18.0 Gy (range: 12–20) was delivered to the tumor margin. Results Tumor control was obtained in 25 out of 26 tumors (96%). The median progression-free period after GKR was 12 months (range: 4–53). The overall median survival after GKR was 33 months (range: 5–54). There were no procedure-related complications and six patients are still living 5–54 months after GKR. Conclusions Radiosurgery is an effective and minimally invasive strategy for management of brain metastases form thyroid cancer.     

Dukes'C 期结直肠癌异时性肝转移相关因素分析*

目的:探讨影响结直肠癌异时性肝转移的临床病理相关因素。方法:收集2003年1 月～2006年12月的所有Dukes'C期手术患者的临床病理及随访资料。选择性别、年龄、肿瘤大小、组织学类型、肠壁浸润程度、血清CEA 水平等因素作为研究对象。采用非条件Logistic回归单因素分析,对有统计学意义的变量进行非条件Logistic回归多因素分析。结果:随访170 例Dukes'C期患者36例（21.2%）出现异时性肝转移,其中26例（72.2%）发生于术后2 年内,32例（88.9%）发生于术后3 年内。单因素分析示肠壁浸润层次、组织学类型和血清CEA 是异时性肝转移的相关因素。性别、年龄、肿瘤大小、分化程度等与肝转移无相关性。多因素分析显示肿瘤浸润程度、血清CEA 水平是异时性肝转移的独立危险因素,组织学类型是独立保护性因素。结论:肿瘤浸润程度、组织学类型和血清CEA 是异时性肝转移的独立相关因素。结直肠癌根治术后2～3 年内密切随访,特别是术前CEA 值高于正常,肿瘤浸润达浆膜或浆膜外的Dukes'C期患者,早期发现异时性肝转移显得尤为必要。      

A case of breast cancer with multiple bone metastases demonstrating complete remission with high-dose toremifene therapy

We report a 64-year-old woman who underwent mastectomy for stage II (T2N1M0) advanced breast cancer, in whom multiple spine metastases developed 18 months postoperatively. She received 6 cycles of CA (cyclophosphamide 500 mg/m2, ADM 50 mg/m2 3 wq) therapy and oral tamoxifen (20 mg/body) administration for adjuvant therapy. The multiple bone metastases of the spine were revealed by technetium bone scan. The level of serum tumor marker CA15-3 increased two times over the normal range 18 months after surgery. She also developed osteoporosis a few years later, so we selected high-dose toremifene administration (120 mg/body) as a second-line therapy. No adverse effects have occurred and bone metastases disappeared. Moreover, the tumor marker was also normalized 6 months after toremifene therapy started. It was shown that high-dose treatment of toremifene was useful for recurrent breast cancer with bone metastasis.     

A specific KRAS codon 13 mutation is an independent predictor for colorectal cancer metachronous distant metastases

Background: In colorectal cancer, there are significant differences between synchronous and metachronous distant metastases. However in recent studies, synchronous and metachronous metastases were always lumped together, neglecting their clinical and molecular differences. The mechanism of the latency of metachronous metastases is still unclear. We conducted this study to reveal the relationship between EGFR pathways and metachronous metastases, and try to find efficient predictors. Methods: PCRs and pyrosequencing were used to detect KRAS, BRAF, PIK3CA and PTEN mutations in primary tumor tissues in a total of 281 patients from 2002 to 2008. Patients were identified into three groups: no-metastases group, synchronous-metastases group and metachronous-metastases group. Clinical and survival data were collected from a prospective database. Results: KRAS codon 13 mutation was an independent predictor only for metachronous distant metastases (OR = 11.857, P < 0.001), but not for synchronous metastases. Male gender (OR = 2.233, P = 0.024), primary tumor located at rectum (OR = 0.404, P = 0.041), and primary pN2 stage (OR = 3.361, P = 0.01) were also independent predictors for metachronous distant metastases. Different SNPs in KRAS worked significantly different in determining synchronous or metachronous metastases. BRAF mutation (Univariate, OR = 11.5, P = 0.039) and > 200 ng/ml preoperative CEA (Univariate, OR = 41, P = 0.011) potentially predicted metastases within 6 months after primary tumor resection. After metachronous metastases, radical resection (HR = 0.280, P = 0.002) was the most important protective factor for long-term survival. Conclusion: There were significant clinical and molecular differences between synchronous and metachronous metastases. As an independent predictor, KRAS codon 13 mutation might be the key to explain the mechanism of colorectal cancer metachronous distant metastases. Together with clinical characteristics, it could aid in the early detection of metachronous metastases.     

Incidence and prognostic significance of receptor discordance between primary breast cancer and paired bone metastases

ER, PgR and HER-2 status are the cornerstones of choosing systemic therapy for breast cancer, but can change during the disease course. Guidelines recommended the biopsy of the metastatic tumor to reassess receptor status. Bone is the most frequent metastatic site of breast cancer but remained technically difficult to biopsy. Our study aimed to evaluate the incidence and prognostic significance of receptor discordance between primary breast cancer and paired bone metastases. One hundred and fifty-five breast cancer patients were diagnosed with pathology-confirmed bone metastasis at Fudan University Shanghai Cancer Center. Ninety-three patients with receptor status available on both primary tumor and bone metastases were included in our study. ER, PgR and HER-2 status converted from positive to negative in 10.8% (10/93), 28.0% (26/93) and 8.6% (8/93) of the patients, while ER, PgR and HER-2 status converted from negative to positive in 3.2% (3/93), 4.3% (4/93) and 1.1% (1/93) of the patients, respectively. 40.4% (17/42) of the HER2-0 tumors converted to HER2-low, which enabled them to receive the treatment of new antibody-drug conjugates (ADCs). Prior endocrine and anti-HER2 therapy were the independent risk factors for receptor conversion. Loss of HR expression in bone metastases was significantly associated with worse first-line PFS (adjusted hazard ratio = 3.271, P-value = .039) and OS (adjusted hazard ratio = 6.09, P-value = .011). In conclusion, our study confirmed that patients may experience receptor conversion between primary breast cancer and bone metastases, possibly influenced by prior treatments, which significantly influenced prognosis. The rebiopsy of bone metastases in patients with primary HER2-0 tumors may benefit from the new ADC drugs.     

A patient with multiple bone metastases from gastric cancer after an 8-year disease-free interval following gastrectomy

We present a patient with multiple bone metastases who was treated successfully using only TS-1. Metastasis was diagnosed 8 years after distal gastrectomy for early gastric cancer in a woman now 61 years old. Surgery was performed on February 13, 1995. The primary tumor was located in the midportion of the gastric body, and had invaded the submucosa with metastasis to lymph nodes in the area of the lesser curvature and the left gastric artery. She was discharged from our hospital 41 days after surgery. After the 8 years of follow-up, elevation of alkaline phosphatase (ALP: 1,029 IU/l) was noted. Bone scintigraphy disclosed scattered areas of uptake in systemic bones. The biopsy specimen from the pubic bone contained metastatic adenocarcinoma, and the bone lesions were diagnosed as multiple bone metastases from gastric cancer. Chemotherapy was started with oral administration of TS-1 alone at 80 mg/day for 2 weeks, followed by 2 weeks of rest. The patient did not experience any side effects, and treatment was repeated on an outpatient basis. At 4 month after initiation of therapy, decreases in ALP and number of foci of abnormal bone uptake in scintigrams were noted. She has survived for an additional 16 months after starting TS-1, without major complications.     

The presence of tumor cells in bone marrow at the time of first recurrence of breast cancer

The occurrence of bone marrow carcinosis was investigated in 380 patients at the time of first recurrence of breast cancer. Results were related to results from radiographic bone survey, 99mTc MDP bone scintigraphy, clinical examination and serum alkaline phosphatase and serum calcium levels. Eighty-seven patients (23%) had tumor cells in the bone marrow. X-rays showed metastases in 78% of the patients with and in 16% of the patients without bone marrow carcinosis. The diagnostic efficiency of x-rays with bone marrow biopsy as the key diagnostic factor was 83%, and it was superior to that of other investigation methods. Bone tissue biopsies were positive alone in 15 patients (17%) and marrow aspirations were positive alone in seven patients (8%). Imprint preparations were positive alone in 7% of the patients and bone tissue biopsy in 5% of the patients. Heavy tumor infiltration (greater than or equal to 50%) of the bone marrow was associated with the occurrence of numerous regions of radiographically involved bone lesions and with histopathologic evidence of bone destruction. Furthermore, pronounced bone formation and marrow fibrosis were more commonly seen in patients with osteosclerotic bone metastases than in patients with osteolytic bone metastases. This study provides evidence that the primary soil of metastatic bone disease in human breast cancer is the bone marrow and that radiographic evidence of bone metastases is a result of an invasion and destruction of the bone tissue matrix by tumor cells from the marrow cavity.     

Bone marrow biopsies in patients with undifferentiated carcinoma of the nasopharyngeal type

Bone marrow involvement was found in 21 of 56 patients with undifferentiated carcinoma of the nasopharyngeal type UCNT whose nasopharyngeal and bone marrow biopsies were available. Radiotherapy and chemotherapy (cisplatin, 5-fluorouracil and bleomycin) were given because of distant metastases. The microscopic aspects of bone invasion were investigated and were classified into three subtypes osteolytic, osteosclerotic and mixed type. The UCNT patients population was 10 years younger than that studied previously. Both the extent of the primary tumor (T) and cervical lymph node status (N) exerted an influence on the probability of metastases developing. Chemotherapy given to patients must be improved because UCNT with bone metastases is a disease with a poor prognosis.     

Effect of oral clodronate on bone mass,bone turnover and subsequent metastases in women with primary breast cancer

Breast cancer treatments have been associated with accelerated bone loss and increased osteoporosis risk. In a subgroup analysis of a randomised, double-blind, placebo-controlled study, we compared the changes in spine and total hip bone mineral density (BMD) and biochemical markers of bone turnover in women with primary breast cancer who had received standard therapy plus either oral clodronate 1600 mg/d (n = 419) or placebo (n = 432) for 2 years. After 2 years, spine BMD was 1.92% higher in patients who received clodronate instead of placebo (P < 0.0001) and total hip BMD was 1.29% higher (P = 0.002 versus placebo). Patients who received clodronate had a median 26% reduction in levels of serum N-terminal pro-peptide of type I procollagen (PINP) – a marker of bone turnover – after 2 years of therapy. This compares with a median 5% increase in patients who received placebo (P < 0.0001). Effects on BMD, but not biochemical markers, persisted for up to 3 years post-treatment. Early changes in PINP were associated with changes in BMD and the likelihood of developing bone metastases. This study shows the use of oral clodronate during primary breast cancer treatment is associated with reduced bone turnover and protection against bone metastases.     

Palliative percutaneous stabilization of lower extremity for bone metastasis using flexible nails and bone cement

ObjectivePercutaneous stabilization (PS; percutaneous flexible nailing and intramedullary bone cement injection) was performed at lower extremity long bones in patients with multiple bone metastases with short life expectancy to get mechanical stability and local tumor control. We evaluated the usefulness of PS by clinical status, F-18-FDG PET-CT and bone scintigraphy (BS).MethodsPatients comprised 15 patients (total 20 sites) who had undergone PS for the metastatic bone tumors of lower extremity long bones (femur and tibia). After percutaneous flexible nailing, bone cement was injected (mean amount = 15.5 ± 6.4 ml). Patients' clinical status was evaluated by visual analog scale (VAS). Qualitative assessment of PET-CT and BS was categorized by improved, stable and aggravated states of PS lesion. Quantitative assessment of PET-CT was performed by maximum and mean standardized uptake value (SUVmax and SUVmean).ResultsPS was performed in all of the patients without complication, and showed significant pain improvement of VAS (7.2 ± 0.2 vs. 2.8 ± 0.3, P < 0.001). PS lesion showed improved state in 65% (13/20) and stable state in 35% (7/20). However, naive bony metastatic lesion showed mostly aggravated state in 90% (19/20) in the same patients, which was significantly different compared with PS lesion (P < 0.001). In PS lesion, SUVmax (10.1 ± 6.9 vs. 7.1 ± 5.2, P = 0.008) and SUVmean (6.2 ± 4.8 vs. 4.6 ± 3.7, P = 0.008) showed significantly decreased uptake after PS.ConclusionBy PS in lower extremity long bones, patients can reduce regional pain, and has the possibility of local tumor control. PS can be performed for lower extremity bone metastasis in poor general condition to perform conventional intramedullary nailing.