氯喹在Ⅳ期胶质母细胞瘤同步放化疗中的应用研究

目的 探讨氯喹(CQ)在Ⅳ期胶质母细胞瘤(GBM)术后同步放化疗(CCRT)中应用的最大耐受剂量(MTD)、药代动力学及对总生存期(OS)的影响。方法 采用简单随机分组法将36例Ⅳ期GBM患者分为试验组(n=18)和对照组(n=18)。对照组患者术后接受替莫唑胺(TMZ)联合放疗的CCRT,试验组患者在对照组的基础上联合CQ治疗。试验组CQ试验包括：采用贝叶斯最优区间(BOIN)设计并确定MTD和采用液相色谱-串联质谱法计算药代动力学参数。比较试验组中不同表皮生长因子受体(EGFR)表达情况患者的临床特征及生存情况,比较试验组和对照组患者的临床特征及生存情况。结果 按照BOIN设计将试验组18例患者平均分为3组,每日CQ剂量分别为100、200、300 mg,最终确定200 mg为MTD。200 mg CQ组患者药代动力学主要参数：达峰时间(t_max)为0.41(0.12～0.85)h,末端消除半衰期(t_1/2)为(1.73±0.54)h,消除速率常数(λ_Z)为(0.37±0.05)。试验组中EGFR(+、++、+++)...     

肿瘤电场治疗同步放化疗方案治疗新诊断胶质母细胞瘤的安全性评估

目的 评价肿瘤电场治疗同步放化疗方案用于治疗新诊断胶质母细胞瘤患者的安全性。方法 回顾性分析南京医科大学第一附属医院神经外科自2022年2月至2022年11月收治的23例新诊断胶质母细胞瘤患者的临床资料。所有患者皆采取肿瘤电场治疗同步放化疗方案。按照常见不良事件通用术语5.0版标准(CTCAE 5.0)和肿瘤电场治疗相关皮肤不良反应(dAE)分级标准记录不良事件。治疗依从性通过Optume Nove TTF-200A治疗设备的使用数据进行评估,以每日肿瘤电场治疗使用时间的百分比计算。结果 23例新诊断胶质母细胞瘤患者每日治疗中位时长为20.0 h,治疗依从性中位值为83.3%,dAE发生率为60.8%,主要为1级(56.5%)和2级(4.3%),无3～4级dAE。dAE主要表现为接触性皮炎、水泡、皮损等。21.7%(5/23)患者出现1～2级放化疗相关血液学不良反应,未发生严重血液系统疾病和重度电解质紊乱。结论 新诊断胶质母细胞瘤术后采取肿瘤电场治疗同步放化疗方案是安全可靠的。     

热疗联合同步放化疗治疗局部晚期宫颈癌的临床观察

目的探讨内生场热疗联合同步放化疗治疗晚期宫颈癌的疗效、不良反应以及对免疫功能的影响。方法选取60例中晚期宫颈癌患者,随机分为对照组和试验组,对照组患者给予同步放化疗;试验组患者在对照组的基础上给予内生场热疗,2次/周,共治疗8次,观察疗效、不良反应及免疫功能。结果 60例患者均完成治疗,对照组患者总有效率(CR+PR)为60.0%,试验组患者总有效率(CP+PR)为86.7%,两组差异有统计学意义(P<0.05);2年总生存率(OS)差异有统计学意义。不良反应主要为胃肠道反应和骨髓抑制,患者均可以耐受,其中试验组患者皮下脂肪硬结2例(6.67%),经常规治疗后痊愈。两组患者严重不良反应比较,差异无统计学意义(P>0.05)。试验组患者T淋巴细胞免疫功能及NK细胞免疫功能较对照组改善,差异有统计学意义(P<0.05)。结论内生场热疗联合同步放化疗能提高局部晚期宫颈癌的局部控制率,延长生存时间,改善患者免疫功能,不良反应轻,患者耐受性良好。     

局部热疗联合同步放化疗治疗Ⅲb期宫颈癌的近期疗效

目的:观察局部热疗联合同步放化疗治疗Ⅲb期宫颈癌的近期临床疗效及不良反应。方法:60例Ⅲb期宫颈癌患者,随机分为局部热疗结合同步放化疗组(治疗组)和同步放化疗组(对照组)。对照组进行根治性放射治疗,放疗第1天开始行化疗,顺铂40mg/m2,静脉滴注,每周1次,化疗6个周期。试验组:放化疗方法同对照组,于化疗当天行盆腔局部热疗,热疗每次60分钟,每周2次,共12次。于热疗后1h内行放射治疗。结果:两组外照射结束时局部肿瘤消退情况、近期疗效比较,差异有统计学意义(P<0．05)。两组不良反应比较,差异无统计学意义(P>0．05)。结论:深部热疗加同步放化疗可以提高患者近期疗效,且无严重的并发症,是Ⅲb期宫颈癌治疗中的一种安全有效的模式。     

同步放化疗联合热疗与同步放化疗治疗局部晚期宫颈癌的有效性和安全性比较

目的:比较后程密集热疗联合放化疗对比单独放化疗在局部晚期宫颈癌治疗中的安全性和有效性。方法:本研究收集了自2012年3月至2019年7月经我院治疗的局部晚期宫颈癌患者62例。其中32例患者接受了标准放化疗联合后程密集盆腔深部热疗,剩余30例患者接受了标准放化疗。两组放化疗方案一致:盆腔外照射（50 Gy/25 f）＋腔内放疗（A点剂量30 Gy／5 f）+同期紫杉醇联合铂类（TP）方案全身化疗。主要研究终点是完全缓解率和5年局部无复发生存率。次要研究终点是客观缓解率、5年无病生存率、5年总生存率和安全性。结果:统计学检查显示两组患者的基线特征是平衡的。研究结果显示热放化疗组的客观缓解率、5年无病生存率和5年总生存率均优于单独放化疗组（93.8% vs 90.0%,P=0.588;62.1% vs 47.4%,P=0.212;71.9% vs 58.8%,P=0.316）,尽管没有达到统计学差异。然而,热放化疗组的完全缓解率显著优于标准放化疗组（78.1% vs 53.3%,P=0.039）。热放化疗组的5年局部无进展生存率也显著高于标准放化疗组（72.9% vs 51.2%,P=0.048）。至于毒副反应,患者能够很好地耐受热放化疗。而且,相比单独放化疗,热放化疗有减轻中性粒细胞缺乏,恶心和乏力等毒副作用的趋势,且未增加额外的急性或者晚期毒副反应。结论:后程密集热疗联合同步放化疗对比单独同步放化疗显著提高了局部晚期宫颈癌患者的完全缓解率和5年局部无复发生存率。     

同期放化疗联合深部热疗治疗食管癌

目的：探讨同期放化疗联合深部热疗治疗食管癌的疗效和毒副反应。方法108例中晚期食管癌患者采用随机数字表法分为2组,每组54例。对照组仅予以同期放化疗方案,观察组采用同期放化疗联合深部热疗方案。比较2组患者近期疗效、远期疗效、复发及转移情况,并比较观察两者的毒副反应发生情况。结果观察组总有效率为889%,高于对照组的741%（P ＜005）;2组患者在3 a 随访中的复发率比较差异无统计学意义（167% vs 204%,P ＞005）;观察组末次随访时生存率为704%,高于对照组的482%（P ＜005）;观察组的转移率为185%,低于对照组的352%（P ＜005）;观察组治疗后恶心呕吐、骨髓抑制、放射性食管炎的发生率分别为426%、519%和463%,均低于对照组的704%、722%和667%（P 均＜005）。结论同期放化疗联合深部热疗方案用于食管癌患者的治疗中,可有效延长其生存期、降低复发及转移风险,且给药方案比较安全,值得临床推广。     

联合MORC2-IDH1检测对胶质母细胞瘤放化疗患者分子分型价值

目的 研究MORC2在胶质母细胞瘤组织中的表达及其联合IDH1突变状态对放化疗疗效的预测作用及分子分型价值。方法 应用免疫组化检测45例胶质母细胞瘤组织中MORC2表达水平,分析其与患者临床特征及放化疗预后间关系。通过胶质瘤转录组数据库进一步联合分析MORC2转录水平及IDH1突变状态对胶质母细胞瘤患者放化疗预后意义。结果 胶质母细胞瘤患者中MORC2蛋白高表达率为76%,且与放化疗预后总生存及无复发生存呈负相关(HR=2.928,95%CI为1.582~5.418,P=0.002;HR=2.204,95%CI为1.186~4.095,P=0.022)。联合IDH1突变状态、MORC2转录水平可将胶质母细胞瘤术后接受放化疗患者分为3个亚型,其中IDH1突变型(IDH1^mt)伴MORC2低表达(MORC2^low)者预后最好,中位生存期为22个月(95%CI为13.98~30.02),而IDH1野生型(IDH1^wt)伴MORC2高表达(MORC2^high)者预后最差,中位生存期为5.63个月(95%CI为3.92~7.34)(HR=4.15,95%CI为1.606~10.720,P=0.002)。在IDH1^wt中MORC2^high比MORC2^low预后更差,提示IDH1^wt/MORC2^high胶质母细胞瘤组织具有更强的DNA损伤修复能力,对放化疗治疗更抗拒。结论 MORC2^high可作为胶质母细胞瘤患者潜在的放化疗预后不良的指标,联合IDH1突变状态及MORC2表达水平可建立一种新的分子分型,为分层治疗提供依据。     

脑胶质母细胞瘤放化疗疗效观察

目的观察并比较脑胶质母细胞瘤放疗加化疗与不加化疗的疗效。方法试验组28例患者放射治疗20～40Gy后,加用化疗药洛莫司汀(CCNU)或卡莫司汀(BCNU);对照组28例单纯放射治疗20～40Gy,不加化疗药。结果经随访,试验组和对照组1,3,5年生存率分别为57.1%,22.5%,15.0%和17.9%,7.1%,3.6%,中位生存期分别为29.7±7.0个月和9.7±3.5个月,P＜0.001,差异有极显著性。显示试验组疗效优于对照组。结论脑瘤放疗20～40Gy后,血脑屏障开放,是化疗最佳时机,这期间加化疗,可显著提高生存率。     

微波深部热疗加同步放化疗治疗中晚期宫颈癌的临床效果

目的:评价微波深部热疗在中晚期巨块型宫颈癌治疗中的疗效及安全性。方法:将经放化疗和放化热疗治疗的100例Ⅱb-Ⅲb期、肿瘤直径大于4cm的巨块型宫颈癌患者各50例,分为对照组和实验组。对照组放化疗:外照射均采用6MV-X加速器调强放射治疗+192铱高剂量率后装腔内照射,同步顺铂40mg/m2,静点,每周1次,与外照射同步结束。实验组:放化疗与对照组相同,另加局部体外热疗,温度为(40±1)℃,60分/次,2次/周,共10次。治疗结束后1个月复查相关检查,进行疗效评价。结果:实验组达到CR者92%(46/50),对照组达到CR者仅78%(39/50),肿瘤缩小率实验组明显高于对照组,差异有统计学意义(χ2=4.201, P＜0.039)。结论:深部热疗联合同步放化疗是治疗中晚期宫颈癌、特别是巨块型宫颈癌的一种安全有效的方法,具有临床推广价值。     

免疫治疗联合放化疗治疗胶质母细胞瘤的研究进展

目前胶质母细胞瘤（glioblastoma,GBM）的标准治疗方法仍然是在最大安全程度的手术切除基础上辅以放化疗,但其5年生存率仍＜10%。免疫治疗如树突状细胞(dendritic cell,DC)疫苗、表皮生长因子受体突变体(EGFRvIII)疫苗、热休克蛋白（heat shock proteins,HSPs）疫苗等在临床试验中已经取得了巨大成就,临床III期试验也证明了免疫治疗与放化疗有协同作用。细胞毒性电离辐射是一种引起促炎信号级联免疫活化辅助细胞死亡的治疗方法,借此可以利用免疫治疗抗肿瘤。肿瘤免疫治疗的发展,使得免疫治疗可能成为继手术、放化疗后GBM治疗的另一个有效方法。寻找新的免疫治疗方法是未来GBM治疗的主要研究方向。本文就目前GBM的治疗策略及困境和放化疗联合免疫检查点抑制剂、DC疫苗以及EGFRvIII疫苗等免疫治疗研究进展作一综述。     

Clinical outcomes of mild hyperthermia for locally advanced rectal cancer treated with preoperative radiochemotherapy

Purpose: The aim of this report was to determine the impact of hyperthermia (HT) on preoperative radiochemotherapy for locally advanced rectal cancer.

Materials and methods: Between 1996 and 2007, 235 patients with locally advanced rectal cancer were treated with concurrent preoperative radiochemotherapy with or without HT. The total dose of radiotherapy was 39.6?Gy for 109 patients (group A) and 45?Gy for 126 patients (group B). Two or three cycles of chemotherapy were administered. Hyperthermia was given immediately after radiotherapy.

Results: In the HT subgroup of group A, more patients achieved down-staging of T stage when compared to the non-HT subgroup (57.9% versus 38%, p?=?0.047). For the cN+ subgroup of all patients, the number of patients with ypN+ were significantly less in the HT subgroup (25% versus 50%, p?=?0.022). In group A, HT appeared to reduce distant metastasis, increase disease-free survival, and improve overall survival.

Conclusions: HT seemed to increase the response of both primary tumour and lymph nodes to preoperative radiochemotherapy in patients with locally advanced rectal cancer. The relationship between increased response by HT and survival should be confirmed by a large prospective randomised trial.     

Racial/ethnic differences in survival among elderly patients with a primary glioblastoma

Background Few studies have assessed racial/ethnic differences in survival after primary glioblastoma diagnosis. We investigate these differences, incorporating information on White, Hispanics and Asians, as well as White, non-Hispanics and Blacks, among elderly individuals with a primary glioblastoma utilizing the population-based Surveillance, Epidemiology and End Results (SEER) Program-Medicare linked database. Methods A total of 1,530 individuals diagnosed > = 66 years of age from 6/1/91 to 12/31/99 in the SEER data were linked with Medicare information from 1/1/91 to 12/31/01. All individuals had Medicare Parts A and B and were non-HMO for 6 months before and 12 months after diagnosis to gather pre-diagnosis co-morbidities and post-diagnosis first course of treatment. Survival differences by race/ethnicity and by race/ethnicity stratified by treatment type and/or median household income were examined using Kaplan–Meier and multivariable Cox proportional hazards models. Results Significant racial/ethnic differences existed between White, non-Hispanics and Blacks in marital status, income and SEER registry region for the entire US. In analysis limited to the West region, significant racial/ethnic differences existed for income only. Overall there were no differences in survival between White, non-Hispanics and Blacks, however, in analysis limited to the West region, Asians had a lower risk of death compared to White, non-Hispanics [HR = 0.67, 95% CI (0.43, 1.03)]. Asians who had multiple treatments also had a lower risk of death compared to White, non-Hispanics [HR = 0.65, 95% CI (0.41, 1.01)]. Conclusions Racial/ethnic differences in survival after primary glioblastoma diagnosis exist and may be partially explained by racial/ethnic differences in treatment and income. Dr Barnholtz-Sloan has now moved to a new institution, but this study was performed while she was at the H. Lee Moffitt Cancer Center and Research Institute     

Long-term local control and survival after preoperative radiochemotherapy in combination with deep regional hyperthermia in locally advanced rectal cancer

Purpose: The aim of this study was to evaluate the impact of deep regional hyperthermia on long-term local control and survival in locally advanced non-metastatic rectal cancer. Methods: In total 103 patients with locally advanced non-metastatic rectal cancer were treated preoperatively with either neoadjuvant radiochemotherapy alone (n?=?43) or the same treatment with additional deep regional hyperthermia (n?=?60). The two groups were compared with respect to local control, overall survival (OS), disease-free survival (DFS), and distant metastases-free survival (DMFS). Results: Patients receiving additional hyperthermia had excellent long-term local control with a 5-year Kaplan-Meier estimate of 98% compared with 87% in the radiochemotherapy only group (p?=?0.09). Five-year rates for OS (88% versus 76%, p?=?0.08), DFS (77% versus 73%, p?=?n.s.) and DMFS (75% versus 77%, p?=?n.s.) were not statistically different between the two groups. Conclusion: Radiochemotherapy combined with hyperthermia results in excellent long-term local control.     

同期放化疗联合深部热疗治疗胸段食管癌的临床观察

目的:探讨同期放化疗联合深部热疗治疗胸段食管癌的近期疗效、远期疗效和不良反应。方法:90例胸段食管癌患者随机分为放化疗联合热疗组（联合组）、同期放化疗组（放化疗组）和单纯放疗组（放疗组）,各30例,分别给予不同的治疗方法,观察和比较三组的近期疗效、远期疗效和不良反应。结果:联合组的临床有效率和临床获益率优于放化疗组和放疗组,差异有统计学意义（P<0.05）。联合组和放化疗组的总体生存率优于放疗组,而远处转移率低于放疗组（P<0.05）。联合组与同期放化疗组的骨髓抑制、放射性食管炎、恶性呕吐和肝肾功能损害的发生率均高于放疗组（P<0.05）;但联合组与同期放化疗组比较,差异无统计学意义（P>0.05）。结论:同期放化疗联合深部热疗治疗胸段食管癌的近期疗效优于同步放化疗和单纯放疗,但在提高患者的生存率和降低放化疗的不良反应等方面无明显优势,具有一定的临床使用价值。     

External validation of a rectal cancer outcome prediction model with a cohort of patients treated with preoperative radiochemotherapy and deep regional hyperthermia

Purpose: To validate a nomogram for the prediction of treatment outcomes after preoperative radiochemotherapy and surgery for locally advanced rectal cancer with a cohort of patients treated with additional deep regional hyperthermia.

Patients and methods: A total of 86 patients were treated with preoperative radiochemotherapy and deep regional hyperthermia at our institution. For every patient, the 5-year probability for death, distant metastases and local failure based on a previously published nomogram were calculated and patients were divided into three risk groups.

Results: Low-lying and clinically lymph node positive tumours were more frequent in the validation cohort. Five-year Kaplan–Meier estimates for overall survival (OS), distant metastases-free survival (DMFS) and local control (LC) were 87.3%, 79.9%, 95.8% (observed) and 75.5%, 71%, 90% (predicted), respectively. Discrimination between low- and high-risk groups was at a significant level for all endpoints. The c-index was 0.81 (OS), 0.67 (DMFS) and 0.92 (LC), respectively.

Conclusions: The nomogram showed reasonable performance when deep regional hyperthermia is incorporated into preoperative therapy. The higher than predicted rates seen for OS and DMFS in particular in the high-risk groups warrant further prospective validation and subsequent investigation of the underlying mechanisms.     

微波热疗联合放化疗治疗进展期胃癌的临床疗效初步观察

目的:初步观察微波热疗联合调强放疗(IMRT)及化疗治疗进展期胃癌的临床疗效。方法:选取不能手术或拒绝手术,经胃镜病理及影像学证实为局部晚期的近端或远端胃癌患者40例。IMRT总剂量为46～56 Gy(中位数50 Gy),1.8～2.0 Gy/次,5次/周;同步热疗温度42～44℃,45 min/次,2次/周;同步化疗...     

Impact of PARP-1 and DNA-PK expression on survival in patients with glioblastoma multiforme

Purpose

To analyze, whether higher tumor levels of DNA repair enzymes contribute to worse treatment results of glioblastoma multiforme (GBM) patients after postoperative radiotherapy.

Materials and methods

Thirty four patients with GBM received postoperative radiotherapy. Tumor sections were examined for poly-ADP ribose polymerase-1 (PARP-1) and DNA protein kinase (DNA-PK) expression. Immunohistochemical staining intensities of PARP-1 and DNA-PK were determined (score 0-3) and expression levels were correlated with patients overall survival.

Results

Median survival time of the whole study group was 10.0 months (95% CI 8.1-11.9). Median survival of patients with high and low (?median and <median) tumor PARP-1 levels were 10.0 months (95% CI 7.9-12.1) and 12.0 months (95% CI 8.3-15.7), respectively (p = 0.93). In contrast, median survival of patients with high and low tumor DNA-PK levels were 9.0 months (95% CI 7.2-10.8) and 13.0 months (95% CI 10.7-15.3), respectively (p = 0.02). In multivariate analysis, DNA-PK expression emerged as a significant independent predictor for overall survival (HR 3.9, 95% CI 1.5-10.7, p = 0.01).

Conclusion

This hypothesis generating study showed that high tumor levels of DNA-PK correlate with poor survival of GBM patients. Further studies are needed to confirm these results and to clarify whether DNA-PK inhibitors might have a potential to radiosensitize GBM and improve the treatment outcome of this devastating disease.     

Optimal management of elderly patients with glioblastoma

Median age at diagnosis in patients with glioblastoma (GB) is slowly increasing with an aging population in Western countries, and was 64 years in 2006. The number of patients age 65 and older with GB will double in 2030 compared with 2000. Survival in this older cohort of patients is significantly less than seen in younger patients. This may in part be related to more aggressive biology of tumor, reduced use of standard management approaches, increased toxicity of available therapies, and increased presence of comorbidities in this older patient population. Limited data do support the use of more extensive resection in these patients. Randomized data support the use of post-operative radiotherapy (RT) versus supportive care, but do not demonstrate a benefit for the use of the standard 6 weeks course of RT over hypofractionated RT given over 3 weeks. Preliminary data of randomized studies raise the possibility of temozolomide alone as an option for these patients. The use of 6 weeks of RT with concurrent and adjuvant temozolomide has been associated with reasonably good survival in several uncontrolled small series of selected older patients; however, this better outcome may be related to the selection of better prognosis patients rather than the specific therapy utilized. The current National Cancer Institute of Canada (NCIC) and European Organization for Research and Treatment of Cancer (EORTC) CE.6/26062/22061 randomized study of short course RT with or without concurrent and adjuvant temozolomide will help determine the optimal therapy for this older cohort with currently available therapies.     

Results of postoperative radiochemotherapy of the patients with resectable gastroesophageal junction adenocarcinoma in Slovenia

Background.

Although the incidence of adenocarcinomas of the gastroesophageal junction (GEJ) is sharply rising in the Western world, there are still some disagreements about the staging and the treatment of this disease. The aim of this retrospective study was to analyse the effectiveness and safety of postoperative radiochemotherapy in patients with a GEJ adenocarcinoma treated at the Institute of Oncology Ljubljana.

Patients and methods.

Seventy patients with GEJ adenocarcinoma, who were treated with postoperative radiochemotherapy between January 2005 and June 2010, were included in the study. The treatment consisted of 6 cycles of chemotherapy with 5-FU and cisplatin and concomitant radiotherapy with the total dose of 45 Gy.

Results.

Twenty-six patients (37.1%) completed the treatment according to the protocol. The median follow-up time was 17.7 months (range: 3.3–64 months). Acute toxicity grade 3 or more, such as stomatitis, dysphagia, nausea or vomiting, and infection, occurred in 2.9%, 34.3%, 38.6% and 41.5% of patients, respectively. At 3 years locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) were 78.2%, 25.3%, 35.8%, and 33.9%, respectively. In the multivariate analysis of survival, splenectomy and level of Ca 19-9 >20 kU/L before the adjuvant treatment were identified as independent prognostic factors for lower DFS, DSS and OS. Age <60 years, higher number of involved lymph nodes and advanced disease stage were identified as independent prognostic factors for lower DSS and OS.

Conclusions.

In patients with GEJ adenocarcinoma who first underwent surgery, postoperative radiochemotherapy is feasible, but we must be aware of a high risk of acute toxic side effects.     

Overall survival prediction in glioblastoma multiforme patients from volumetric,shape and texture features using machine learning

Glioblastoma multiforme (GBM) are aggressive brain tumors, which lead to poor overall survival (OS) of patients. OS prediction of GBM patients provides useful information for surgical and treatment planning. Radiomics research attempts at predicting disease prognosis, thus providing beneficial information for personalized treatment from a variety of imaging features extracted from multiple MR images. In this study, MR image derived texture features, tumor shape and volumetric features, and patient age were obtained for 163 patients. OS group prediction was performed for both 2-class (short and long) and 3-class (short, medium and long) survival groups. Support vector machine classification based recursive feature elimination method was used to perform feature selection. The performance of the classification model was assessed using 5-fold cross-validation. The 2-class and 3-class OS group prediction accuracy obtained were 98.7% and 88.95% respectively. The shape features used in this work have been evaluated for OS prediction of GBM patients for the first time. The feature selection and prediction scheme implemented in this study yielded high accuracy for both 2-class and 3-class OS group predictions. This study was performed using routinely acquired MR images for GBM patients, thus making the translation of this work into a clinical setup convenient.