Histologic Response and Toxicity following Interval-Compressed Four-Drug Therapy Given Preoperatively in Children and Young Adults with Osteosarcoma: A Retrospective Study.
- 作者列表："Kang JM","Ju HY","Joo J","Sung JY","Park SY","Kim JH","Kang HG","Kwon M","Park M","Park HJ","Park BK
OBJECTIVES:The histologic response to chemotherapy is an important prognostic factor in osteosarcoma. Thus, we attempted to develop an effective neoadjuvant regimen to achieve an improvement in histologic response. METHODS:Twenty-nine patients with a high-grade osteosarcoma received 2 courses of neoadjuvant chemotherapy non-randomly with either the MAP regimen (methotrexate 12 g/m2, cisplatin 120 mg/m2, and doxorubicin 75 mg/m2) or MAPI regimen (MAP plus ifosfamide 9 g/m2). We applied interval compression to MAPI by shortening the preoperative period to be aligned with that of MAP. Adjuvant chemotherapy was tailored according to the necrosis rate of resected tumor specimens. Necrosis rate, toxicity, and survival outcome were compared retrospectively between the 2 groups. RESULTS:The median interval between the beginning of neoadjuvant chemotherapy and surgery was 97.0 days in the MAPI group (17 patients) and 90.5 days in the MAP group (12 patients; p = 0.19). The good histologic response (>90% of necrosis) was observed in 71% of MAPI and in 42% of MAP (p = 0.12). Major toxicities of grade 3 or worse were not different between the 2 groups. The probability of 5-year progression-free survival and overall survival of the MAPI group were 74 and 83%, and those in the MAP group were 50 and 75%, showing no difference. CONCLUSIONS:Interval-compressed MAPI therapy given in a similar duration of the preoperative phase to that of conventional MAP therapy showed a marginal trend toward a better histologic response without a significant increase in major toxicities. Regarding the proportion of good histologic response, 71% is one of the highest values ever reported in the literature. The results warrant further testing in a prospective way in a larger cohort.
目的: 骨肉瘤对化疗的组织学反应是一个重要的预后因素。因此，我们试图开发一种有效的新辅助治疗方案，以实现组织学反应的改善。 方法: 29 例高级别骨肉瘤患者接受非随机 2 个疗程的新辅助化疗方案 (甲氨蝶呤 12g/m2，顺铂 120 mg/m2，和阿霉素 75 mg/m2) 或MAPI方案 (MAP加异环磷酰胺 9g/m2)。我们通过缩短术前周期与MAP对齐，对MAPI应用间隔压缩。根据切除肿瘤标本的坏死率量身定制辅助化疗。回顾性比较 2 组的坏死率、毒性和生存结局。 结果: MAPI组 (17 例) 新辅助化疗开始至手术的中位间隔时间为 97.0 天，MAP组 (12 例) 为 90.5 天 (p = 0.19)。90% 的MAPI和 71% 的MAP观察到良好的组织学反应 (> 42% 的坏死) (p = 0.12)。3 级或更严重的主要毒性在 2 组之间没有差异。MAPI组的 5 年无进展生存期和总生存期的概率为 74 和 83%，MAP组为 50 和 75%，显示无差异。 结论: 在与常规MAP治疗相似的术前阶段给予的间隔压缩MAPI治疗显示出更好的组织学反应的边缘趋势，而主要毒性没有显著增加。关于组织学反应良好的比例，71% 是文献报道的最高值之一。结果需要在更大的队列中以前瞻性的方式进行进一步的测试。
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.