The value of tumor markers in men with metastatic prostate cancer undergoing [177 Lu]Lu-PSMA therapy.
肿瘤标志物在接受 [177 Lu]Lu-PSMA治疗的转移性前列腺癌男性中的价值。
- 作者列表："Yordanova A","Linden P","Hauser S","Feldmann G","Brossart P","Fimmers R","Essler M","Holdenrieder S","Ahmadzadehfar H
BACKGROUND:Currently, prostate-specific membrane antigen-radioligand therapy (PSMA-RLT) is considered a last-line treatment option in advanced castration-resistant prostate cancer. Despite these patients' poor prognosis, accurate estimation of their overall survival (OS) is essential to determine whether benefits exist from the treatment and whether the loss of valuable time and unnecessary side effects can be avoided. The aim of the present study is to evaluate whether various biochemical markers can predict OS in men undergoing PSMA-RLT and whether the changes assessed after PSMA-RLT correlate with the OS. METHODS:The tested tumor markers in this retrospective analysis were alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), prostate-specific antigen (PSA), lactate dehydrogenase (LDH), chromogranin A, and pro-gastrin-releasing peptide (pro-GRP). For the evaluation, we performed blood tests before each PSMA-RLT cycle and during follow-up visits (which were 2-3 months apart). All patients were followed up until their deaths. To test the correlations between the tumor markers and survival, we conducted the logrank tests and the multivariate Cox proportional-hazards regression model. The significance level was set at P < .05. RESULTS:The study included 137 patients who received a total of 487 PSMA-RLT cycles between January 2015 and November 2017. Of the tested biochemical tumor markers, baseline ALP (120 U/L cut-off), LDH (248 U/L cut-off), and PSA (first quartile cut-off) correlated significantly with survival post-PSMA-RLT (P < .001 for ALP and LDH, and P = .007 for PSA). Stable and/or decreased values in most of the initially abnormal parameters were associated with significantly better OS; these parameters were ALP (P = .009), LDH (P = .005), PSA (P < .001), and pro-GRP (P = .013). The BAP and ALP responses also correlated significantly with survival in patients with bone metastases (P = .002 and P < .001, respectively). Furthermore, there was a strong correlation of the kinetic patterns of PSA, ALP, BAP, and LDH with the survival, showing that patients with steadily increasing markers had the shortest OS. CONCLUSION:Along with the established tumor marker PSA, ALP, LDH, BAP, and pro-GRP were correlated with the OS post-PSMA-RLT in the univariate and multivariate analyses.
背景: 目前，前列腺特异性膜抗原放射配体治疗 (PSMA-RLT) 被认为是晚期去势抵抗性前列腺癌的最后一线治疗选择。尽管这些患者预后不良，但准确估计其总生存期 (OS) 对于确定治疗是否获益以及是否可以避免宝贵时间的损失和不必要的副作用至关重要。本研究的目的是评估各种生化标志物是否能预测接受PSMA-RLT的男性的OS，以及PSMA-RLT后评估的变化是否与OS相关。 方法: 回顾性分析检测的肿瘤标志物为碱性磷酸酶 (ALP) 、骨特异性碱性磷酸酶 (BAP) 、前列腺特异性抗原 (PSA) 、乳酸脱氢酶 (LDH) 、嗜铬粒蛋白A和促胃泌素释放肽 (pro-GRP)。为了评价，我们在每个PSMA-RLT周期前和随访访视期间 (间隔 2-3 个月) 进行了血液检查。所有患者均随访至死亡。为了检验肿瘤标志物与生存率之间的相关性，我们进行了logrank检验和多变量Cox比例风险回归模型。显著性水平设定为p <0.05。 结果: 研究纳入了 137 例患者，他们在 2015 年 1 月至 2017 年 11 月期间共接受了 487 个PSMA-RLT周期。在检测的生化肿瘤标志物中，基线ALP (120 u/L临界值) 、LDH (248 u/L临界值) 和PSA (第一四分位数临界值) 与PSMA-RLT后生存显著相关 (p < 。001 为ALP和LDH，且p = 。007 为PSA)。大多数最初异常参数的稳定和/或下降值与显著较好的OS相关; 这些参数为ALP (p =.009) 、LDH (p =.005)，PSA (p <.001) 和pro-GRP (p =.013)。BAP和ALP反应也与骨转移患者的生存率显著相关 (分别为p =.002 和p <.001)。此外，PSA、ALP、BAP和LDH的动力学模式与生存期有很强的相关性，表明标志物稳定增加的患者OS最短。 结论: 在单因素和多因素分析中，ALP、LDH、BAP和pro-GRP与PSMA-RLT后的OS相关。
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.