Impact of chemotherapy-induced necrosis on event-free and overall survival after preoperative MAP chemotherapy in patients with primary high-grade localized osteosarcoma.
- 作者列表："Tsuda Y","Tsoi K","Parry MC","Stevenson JD","Fujiwara T","Sumathi V","Jeys LM
AIMS:To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. METHODS:Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson's correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. RESULTS:OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. CONCLUSION:Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795-803.
目的: 评估高级别局限性骨肉瘤患者术前化疗的组织学反应与无事件生存期 (EFS) 或总生存期 (OS) 之间的相关性。 方法: 在 1997 年至 625 年间接受原发性高级别骨肉瘤治疗的 2016 例年龄 ≤ 40 岁的患者中，纳入 232 例诊断时无临床可检出转移灶，术前接受大剂量甲氨蝶呤、阿霉素和顺铂 (MAP) 化疗和手术治疗的患者。使用Cox模型和Pearson相关系数 (r) 评估切除标本中化疗诱导的坏死与EFS或OS的相关性。应用时间依赖性受试者工作特征分析确定化疗诱导坏死对EFS和OS的最佳临界值。 结果: 5 年时OS为 74% (95% 置信区间 (CI) 67 ~ 79)。中位化疗诱导的坏死为 85% (四分位距 (IQR) 50% ~ 97%)。在多变量Cox模型中，化疗诱导的坏死与EFS和OS显著相关 (风险比 (HR) = 0.99 (95% CI 0.98 ~ 0.99); p < 0.001 和HR = 0.98 (分别为 95% CI 0.97 ~ 0.99; p <0.001)。化疗引起的坏死与 5 年EFS和 5 年OS呈正相关 (分别为r = 0.91; p < 0.001 和r = 0.85; p <0.001)。化疗诱导的坏死对 5 年EFS和 5 年OS的最佳临界值分别为 85% 和 72%。 结论: 高级别局部骨肉瘤患者MAP化疗后化疗引起的肿瘤坏死与EFS和OS呈正相关。在我们的分析中，MAP化疗诱导的EFS和OS坏死的最佳临界值低于常用的 90%，建议需要通过更大的国际合作研究重新评估最佳临界值。引用本文: 骨关节J 2020;102-B(6):795-803。
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.