Osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: a retrospective study

OBJECTIVE: Bone metastases are a major cause of morbidity in cancer patients. Treatment includes bisphosphonates, which are also associated with avascular osteonecrosis of the jaw (ONJ). Our aim was to evaluate the correlation between bisphosphonates and ONJ. PATIENTS AND METHODS: Of the 539 patients with bone metastases treated in our department from June 2002 to December 2006 with i.v. bisphosphonates, eight (1.5%) developed ONJ. RESULTS: The eight patients with ONJ had all been given zoledronic acid, and two had also been treated with pamidronic acid. In four of the patients, ONJ was diagnosed during treatment, while in the remaining four it was diagnosed several months after therapy with bisphosphonates had ended. Six of these patients received local noninvasive treatment, of whom five progressed. Two showed apparent autolimitation of the disease. The remaining two patients underwent surgical resection and currently show no signs of relapse. All eight ONJ patients presented with various concomitant risk factors such as paradontopathy, dental extraction, or spontaneous avulsion. CONCLUSIONS: Our results show that ONJ can appear months after interruption of treatment and that a surgical approach can be used in suitable cases. Closer cooperation is needed among specialists to define guidelines for the prevention of ONJ in patients with bone metastases.     

Management of vertebral metastases in prostate cancer: a retrospective analysis in 119 patients

The objectives of this study were to define clinical problems and treatment strategies in vertebral metastases of prostate cancer. The clinical files of 634 patients with prostate cancer seen in a comprehensive cancer center during a 4-year period were retrospectively reviewed. One hundred nineteen patients (18.8%) had 212 significant episodes of osseous spinal metastases. Pain was nearly universal (93%), and motor and bladder impairment occurred in 25% and 3.1% of patients, respectively. Bone scan and magnetic resonance imaging (MRI) were performed in 197 and 64 episodes, respectively. Fifteen episodes of spinal cord compression were treated surgically. Other treatments included hormonal therapy (163 episodes), chemotherapy (70 episodes), and radiation therapy (103 episodes). Osteolytic lesions were observed alone and in combination with osteoblastic pattern in 18% and 26% of episodes, respectively. Bone scan was the most effective screening procedure of vertebral involvement, and MRI effectively showed epidural involvement. Overall treatment led to improvements in pain and motor impairment in 77% and 50% of patients, respectively. However, clinical episodes were recurrent (1.78 episodes per patient; range, 1-8). Median survival after vertebral metastasis episode was 14 months compared with only 4 months after surgery for spinal cord compression. Vertebral metastases strongly alter quality of life in patients with prostate cancer. Pain and neurologic complications are the major problems. Careful early screening with bone scan and MRI may help to define better treatment strategy. However, further prospective studies of clinical management are needed to determine the optimal timing of radiation therapy, medical treatments, and surgery.     

Renal toxicity and osteonecrosis of the jaw in cancer patients treated with bisphosphonates: a long-term retrospective analysis

Background: Bisphosphonates (BPs) are the mainstay of bone-directed therapy for bone metastases from multiple myelomas and a wide range of solid tumours, but some patients experience renal toxicity or osteonecrosis of the jaw (ONJ). Patients and methods: We reviewed data relating to 398 patients treated with intravenous BP for bone metastases, checking their serum creatinine levels throughout the treatment period in order to assess renal function, and seeking any signs and symptoms of ONJ recorded in their medical records. We also analysed other risk factors for renal toxicity and ONJ in patients who developed them. Results: The median treatment period was 14 months (range 1–119); 108 patients received BP for more than 1 year, and 112 for more than 2 years. Sixteen patients (4%) developed renal toxicity after a median of 24 months of BP treatment, eight of them had been treated for more than 2 years. Ten patients (2.5%) were diagnosed as having ONJ after a median of 39 months on BP, only three of them had been treated for less than 2 years. Two patients experienced both ONJ and renal toxicity. Conclusions: The low incidence of ONJ and renal toxicity indicates the safety of BP. However, prevention and early detection are still the “first-line therapy” for decreasing their occurrence further.     

Osteonecrosis of the jaw: dental outcomes in metastatic breast cancer patients treated with bisphosphonates with/without bevacizumab

The etiology, optimal management, and outcome of osteonecrosis of the jaw (ONJ) are not well understood. Because healing after mucosal trauma requires revascularization, theoretically, the combination of bevacizumab (bev) and a bisphosphonate (BP) could affect the time to development of ONJ and/or the response to dental therapy. We reviewed all cases of ONJ in metastatic breast cancer patients treated at our institution with bev+BPs and BPs alone between October 2002 and April 2010. We identified 27 ONJ patients with a median age of 57 years (range, 40 to 68 years). Seven patients received bev+BPs; 20 patients received BPs alone. Patients received intravenous zolendronate (95%), pamidronate (20%), or both (15%). Patients were treated with antibiotics (93%), alveoplasty/debridement (67%), and chlorhexidine scrub (81%). There was no difference in dental treatment between the groups or by the year of diagnosis (before 2007 versus 2007-2010). Complete resolution (CR) was achieved in 24% of all patients; 33% treated with bev+BPs, and 21% treated with BPs alone. Rates of CR improved from 15% to 33% after 2007. The median time to response was 5.6 months (range, 1.3 to 67.5 months). The addition of bev to BPs did not appear to alter the time to development of ONJ (32.6 months versus 34.6 months, respectively). The number of BP treatments administered before the diagnosis of ONJ between bev+BPs and BPs (32 doses versus 36.5 doses) was similar. However, our sample size was too small to characterize the difference statistically. Because dental management of ONJ has not changed over time at our institute, early recognition and screening may account for the improvement in dental outcomes.     

The risk of renal impairment in hormone-refractory prostate cancer patients with bone metastases treated with zoledronic acid

BACKGROUND: Bisphosphonates have been used to treat bone metastases in hormone-refractory prostate cancer (HRPC), but certain agents have been associated with renal toxicity. For this observational study, the authors assessed the risk of renal impairment in patients with HRPC who received zoledronic acid from December 1999 to April 2005. METHODS: A comprehensive medical records review was performed in a major tertiary oncology center (n = 122 patients). The primary outcome of renal impairment was defined as an increase >or=0.5 mg/dL or >or=1.0 mg/dL over baseline creatinine value if the baseline value was <1.4 mg/dL or >or=1.4 mg/dL, respectively. A risk factor analysis was conducted using the Andersen-Gill extension to the Cox proportional hazards model. RESULTS: Renal impairment was observed in 23.8% of patients. The risk of renal impairment increased with an extended duration of zoledronic acid therapy (<6 months, 11.1%; >or=24 months, 26.3%) and previous pamidronate treatment (45.5% vs 19.0% for patients with no prior pamidronate). A significantly greater risk of renal impairment was associated with increasing age at zoledronic acid initiation, prior pamidronate use, and a history of renal disease, hypertension, or smoking (P 相似文献   

Osteonecrosis of the jaw in cancer patients receiving IV bisphosphonates

Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing frequency over the past few years. ONJ is most often identified in patients with cancer who are receiving intravenous bisphosphonate therapy but it has also been diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions. The condition involves exposed bone of the maxilla or mandible. Although it is often associated with a recent dental surgical procedure, spontaneous ONJ can also occur. Patients commonly present with symptoms. Through case reporting and clinical experience, there is a suggestion that the incidence of ONJ in patients with cancer receiving intravenous bisphosphonates ranges between 1% and 10%. Management of ONJ focuses on maximizing oral health, conservative actions with mouth rinses, antibiotics, and avoidance of unnecessary invasive dental procedures. The currently available data on ONJ are reviewed here.     

Anaemia and thrombocytopenia in patients with prostate cancer and bone metastases

Background  

The purpose of this study was to determine the incidence, risk factors and prognostic impact of anaemia and thrombocytopenia in patients with bone metastases (BM) from prostate cancer.     

乳腺癌术后骨转移回顾性分析

目的 分析乳腺癌术后骨转移的临床特征.方法 对407例原发乳腺癌术后发生骨转移的情况进行回顾性分析.结果 50例患者术后发生骨转移.这50例患者中,术后30个月内发生骨转移的病例占54.0%,5年内骨转移发生率为76.0%,发病年龄≤50岁的占60%.病理类型以浸润性导管癌为主的占82.0%.骨转移部位最多发生在脊柱,以胸椎、腰椎为主.其次是骨盆、肋骨、胸骨、颅骨、下肢骨.乳腺癌术后是否出现骨转移在年龄、腋淋巴结转移、孕激素受体(PR)、癌基因CerbB2表达方面无统计学差异(P＞0.05).但在肿瘤病理类型及雌激素受体(ER)表达方面的差异有统计学意义(P＜0.05).结论 乳腺癌术后30个月内为骨转移高发期,骨转移部位以脊柱及骨盆、肋骨、胸骨多见.乳腺癌术后发生骨转移与年龄、腋淋巴结转移、PR、CerbB2表达方面无关,与肿瘤病理类型、ER有关.     

Osteonecrosis of the jaw and bisphosphonate use in breast cancer patients

It is renowned that breast cancer patients suffer from a number of cancer-related skeletal events, while drugs recently added to the practitioners’ quiver, such as aromatase inhibitors, intensify the need to preserve bone mass in this group of patients. Bisphosphonates are potent inhibitors of both normal and pathologic bone resorption. Besides their apoptotic and antiproliferative activity on osteoclasts, bisphosphonates can also exert various effects on macrophages, keratinocytes and fibroblasts. Bisphosphonate-related osteonecrosis of the jaw is a complication that emerged after broad clinical use of bisphosphonates, and which has not yet been adequately described in a clinical trial setting. The purpose of this review is to critically reflect the incidence, etiopathogenesis, prevention and treatment of osteonecrosis of the jaw. Succinct suggestions are provided to ensure clinicians prevent and detect the complications early.     

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to that of bone formation in patients with bone metastases from prostate cancer before and after bisphosphonate treatment. Thirty-nine patients with prostate cancer and bone metastasis, nine patients with prostate cancer without bone metastases, nine patients with benign prostatic hyperplasia and 355 healthy age-matched men were included. Urinary non-isomerized (alpha CTX) and beta isomerized (beta CTX) type I collagen C-telopeptides (CTX) and a new assay for serum CTX were used to assess bone resorption. Bone formation was determined by serum osteocalcin, serum total (T-ALP) and bone (BAP) alkaline phosphatase and serum type I collagen C-terminal propeptide (PICP). Fourteen patients with bone metastases were also evaluated 15 days after a single injection of the bisphosphonate pamidronate (120 mg). Levels of all bone formation and bone resorption markers were significantly (P < 0.006-0.0001) higher in patients with prostate cancer and bone metastasis than in patients with benign prostatic hyperplasia, patients with prostate cancer without bone metastases and healthy controls. In patients with bone metastases the median was increased by 67% for serum osteocalcin, 128% for T-ALP, 138% for BAP, 79% for PICP, 220% for urinary alpha CTX, 149% for urinary beta CTX and 214% for serum CTX. After bisphosphonate treatment all three resorption markers significantly decreased by an average of 65% (P = 0.001), 71% (P = 0.0010) and 61% (P = 0.0015) for urinary alpha CTX, urinary beta CTX and serum CTX, respectively, whereas no significant change was observed for any bone formation markers. Patients with prostate cancer and bone metastases exhibit a marked increase in bone resorption, which decreases within a few days of treatment with pamidronate. These findings suggest that these new resorption markers may be useful for the management of these patients.     

Prolonged control of bone metastases in non-small-cell lung cancer patients treated with gefitinib

We describe two non-small-cell lung cancer (NSCLC) patients in which treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs) gefitinib produced a prolonged control of bone disease. In the first patient, a 48-year-old male with adenocarcinoma (ADC) of the lung and multiple bone metastases, the bone scan became completely negative following treatment with gefitinib for 9 months. The patient remained alive and with no evidence of bone metastases for 20 months, despite two local recurrences that were surgically removed. Similarly, the bone scan of the second patient, a 49-year-old male with ADC of the lung and bone metastases, became negative after 6 months on gefitinib. The molecular mechanisms potentially involved in this phenomenon are discussed.     

Thyroid disorders in patients treated with radiotherapy for head-and-neck cancer: a retrospective analysis of seventy-three patients

PURPOSE: To evaluate the incidence of thyroid disorders and dose distribution to the thyroid in patients treated with radiotherapy for head-and-neck carcinomas. METHODS AND MATERIALS: A retrospective evaluation of data from 73 patients treated for head-and-neck cancers in our department was performed. Thyroid function was evaluated mainly by the measurement of thyrotropin (thyroid stimulating hormone [TSH]). A retrospective analysis of treatment plans was performed for 57 patients. Percentages of thyroid glandular volume absorbing 10, 30, and 50 Gy (V10, V30, and V50 respectively) were considered for statistical analysis. RESULTS: A majority of patients (61%) had a normal thyroid function whereas 19 patients (26%) had hypothyroidism. Mean thyroid volume was 30.39 cc. Point 3 (located at isthmus) absorbed lower doses compared with other points (p < 0.0001). Median values of V10, V30, and V50 were 92% (range, 57-100%), 75% (range, 28.5-100%), and 35% (range, 3-83%) respectively. Gender was associated with toxicity (presence of any kind of thyroid disorders) (p < 0.05), with females displaying higher levels of TSHr (relative TSH = patient's value/maximum value of the laboratory range) (p = 0.0005) and smaller thyroid volume (p = 0.0012) compared with male population. TSHr values were associated with thyroid volume, and the presence of midline shielding block in the anterior field was associated with relative free thyroxine (FT4r = patient's value/maximum value of the laboratory range) values. CONCLUSIONS: Gender and thyroid volume seem to play an important role in the occurrence of thyroid toxicity, but further studies on dose-effect relationship for radiotherapy-induced thyroid toxicity are needed.     

55例肺癌骨转移患者的回顾性分析

目的 探讨晚期肺癌骨转移的临床特征及诊断、治疗方法.方法 回顾性分析55例晚期肺癌骨转移患者的临床资料.结果55例晚期肺癌骨转移患者中,腺癌占70.91%,主要转移部位依次是椎体、肋骨、骨盆、肩胛骨、股骨和颅骨.多发骨转移占76.36%(42/55),孤立性骨转移占23.64%(13/55).诊断方法包括发射单光子计算机断层扫描(ECT)、磁共振成像(MRI)、电子计算机断层扫描(CT)及正电子发射计算机断层扫描(PET-CT)等.治疗主要以唑来膦酸联合止痛药物为主,有19例患者伴随疼痛,其中,15例患者经治疗后缓解.结论晚期肺癌骨转移中腺癌的发生率最高,转移部位以椎体为主.唑来膦酸联合止痛药物可以缓解患者的骨痛,改善患者的生活质量.晚期肺癌患者应常规进行全身骨扫描检查.     

115例前列腺癌骨转移临床特征与预后因素分析

淋巴结转移(χ2 =12.45,P=0.000)的生存率有差异,余各项无差异.Cox模型多因素分析显示骨转移时ALP水平(χ2 =4.08,P=0.020)、诊断原发灶时Gleason评分(χ2 =4.57,P=0.044)和是否有非区域淋巴结转移(χ2 = 3.93,P=0.030)是影响预后的因素.结论 前列腺癌骨转移患者生存期较长,而骨转移时ALP水平、诊断原发灶时Glason评分和是否有非区域淋巴结转移与预后有关.     

Role of bisphosphonates in prostate cancer bone metastases

Bisphosphonate inhibitors of bone resorption have a variety of positive actions against prostate cancer cells in vitro and in preclinical animal models. In patients, they can reduce skeletal-related events and bone pain, as well as reduce the adverse effects of androgen deprivation therapy on skeletal integrity. The preclinical and clinical data to support this are reviewed here. Further clinical trials are required to determine whether bisphosphonates decrease tumor burden or increase patient survival or quality of life, and whether such adjuvant treatments will be cost-effective.     

Tumor control and survival in patients with ten or more brain metastases treated with stereotactic radiosurgery: a retrospective analysis

Journal of Neuro-Oncology - This study aims to identify the neuropsychological tests commonly used for assessment in each neurocognitive domain, and quantify the post-operative changes in...