Crizotinib-induced osteitis mimicking bone metastasis in a stage IV ALK-rearranged NSCLC patient: a case report.
- 作者列表："Guisier F","Piton N","Bellefleur M","Delberghe N","Avenel G","Angot E","Vittecoq O","Ould-Slimane M","Morisse-Pradier H","Salaun M","Thiberville L
BACKGROUND:Targeted therapies are a standard of care for first-line treatment of Anaplastic lymphoma kinase (ALK)-rearranged non small cell lung cancer (NSCLC). Giving the rapid pace of drug discovery and development in this area, reporting of adverse effects of ALK inhibitors is crucial. Here, we report a case of osteitis induced by an ALK inhibitor mimicking bone metastasis, a previously undescribed side effect of crizotinib. CASE PRESENTATION:A 31-year-old woman with stage IV ALK-rearranged NSCLC presented with back pain after 3 months of crizotinib treatment. Diagnostic work-up showed osteitis on the 4th and 5th thoracic vertebrae, anterior soft tissue infiltration and epiduritis, without any sign of infection. Spinal cord decompression, histological removal and osteosynthesis were performed. Histologic examination showed necrosis with abundant peripheral neutrophils, no microorganism nor malignant cell. Symptoms and Computarized Tomography-abnormalities rapidly diseappeared after crizotinib withdrawal and did not recur after ceritinib onset. CONCLUSIONS:This is the first report of crizotinib-induced osteitis. Crizotinib differs from other ALK inhibitors as it targets other kinases as well, which may have been responsible for the osteitis. Crizotinib can induce rapidly extensive osteitis, which can mimic tumor progression.
背景: 靶向治疗是间变性淋巴瘤激酶 (ALK) 重排非小细胞肺癌 (NSCLC) 一线治疗的标准治疗。鉴于这一领域药物发现和开发的快速步伐，报告ALK抑制剂的不良反应至关重要。在此，我们报告一例由一种类似骨转移的ALK抑制剂诱导的骨炎，这是一种先前未描述的克唑替尼的副作用。 病例报告: 1 例 31 岁女性IV期ALK重排NSCLC患者，接受克唑替尼治疗 3 个月后出现背痛。诊断性检查显示第 4 、 5 胸椎骨炎，前软组织浸润及腱鞘炎，无感染征象。进行脊髓减压、组织学切除和接骨术。组织学检查示坏死，周围中性粒细胞丰富，无微生物及恶性细胞。症状和计算机断层扫描-crizotinib停药后异常迅速出现，ceritinib发作后不复发。 结论: 这是crizotinib引起的骨炎的首次报道。克唑替尼与其他ALK抑制剂不同，因为它也靶向其他激酶，这可能是骨炎的原因。克唑替尼可诱导迅速广泛的骨炎，可模拟肿瘤进展。
METHODS:OBJECTIVE:Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS: :Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS: :Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION:Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE: :This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.
METHODS:BACKGROUND:National guidelines recommend screening and treatment for cancer-related bone disease and continued monitoring of bone-modifying agents. It is unclear whether a standardized screening tool is utilized to identify eligible patients and ensure appropriate supportive care is implemented. The purpose of this study was to evaluate current prescribing practices and optimize management of bone-modifying agents. METHODS:A retrospective chart review was performed to identify patients who received hormone deprivation therapy or had bone metastases through Hematology/Oncology or Urology clinics from 1 November 2016 to 31 October 2017. The primary endpoints of this study were the incidence of completed baseline dual-energy X-ray absorptiometry (DEXA) scan for patients on hormone deprivation therapy and percent of patients started on a bone-modifying agent for the prevention of skeletal-related events secondary to bone metastasis. Secondary endpoints included percent of patients with dental examinations prior to initiation, adequate calcium and vitamin D supplementation, incidence of osteonecrosis of the jaw or flu-like symptoms and education, and percent of bisphosphonate doses appropriately adjusted based on renal function. RESULTS:A total of 375 patients were assessed for baseline DEXA scans and bone-modifying therapy. Of the 226 patients on hormone deprivation therapy, 111 (49%) patients were appropriately screened with a DEXA scan prior to initiation of hormone deprivation therapy. Among the 149 patients with bone metastases, only 94 (63.1%) patients were started on a bone-modifying agent. CONCLUSIONS:Opportunities have been identified to optimize management of patients with cancer-related bone disease. Implementation of standardized tools may increase the rate of appropriate screening and initiation of bone-modifying therapy when warranted.
METHODS:PURPOSE:Low skeletal muscle mass has been associated with poor prognosis in patients with advanced lung cancer. However, little is known about the relationship between skeletal muscle mass and overall survival in patients with bone metastases from lung cancer. The objective of the present study was to evaluate the prognostic value of low trunk muscle mass in predicting overall survival in these patients. METHODS:The data from 198 patients who were diagnosed with bone metastases from lung cancer from April 2009 to May 2017 were retrospectively reviewed. The areas of the psoas and paravertebral muscles were measured at the level of the third lumbar vertebra on computed tomography scans taken at the time nearest to the diagnosis of bone metastasis. Muscle area was evaluated for male and female cohorts separately using different cutoff points. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival. RESULTS:The overall survival of patients in the lowest quartile for psoas muscle area or paravertebral muscle area was significantly shorter than that of patients above the 25th percentile for muscle area (p < 0.001). Multivariate analyses showed that paravertebral muscle mass (hazard ratio, 1.73; 95% confidence interval, 1.17-2.56; p = 0.006), epidermal growth factor receptor-targeted therapy, and performance status were independent prognostic factors. CONCLUSIONS:Low paravertebral muscle mass was associated with shorter survival, independently of known prognostic factors.