Ⅲ＋Ⅳ期非小细胞肺癌调强放疗剂量学参数预测有症状放射性肺炎的临床研究

目的：探讨接受调强放疗（intensity modulated radiotherapy,IMRT）的Ⅲ、Ⅳ期非小细胞肺癌（non－small－cell lung cancer,NSCLC）患者正常肺组织剂量－体积参数对有症状放射性肺炎（≥2级,radiation pneu-monitis,RP）的预测作用。方法：回顾性分析53例接受调强放疗的Ⅲ、Ⅳ期NSCLC患者临床资料,记录剂量－体积参数V5、V20、平均肺剂量（MLD）及≥2级RP发生率。肺损伤评估根据CTCAE4．0标准。单因素及多因素分析各个剂量学参数与≥2级RP之间的关系,并采用ROC曲线分析各剂量参数的敏感性、特异性对预测≥2级RP的价值。结果：53例患者中2级RP发生率为9．43％（5／53）,3级RP发生率为5．66％（3／53）,4级RP发生率为3．77％（2／53）,≥2级RP总发生率为18．87％（10／53）。经Spearman等级相关分析,V5、V20、MLD均与≥2级RP的发生相关（r＝0．485、0．404、0．404,P＝0．000、0．003、0．003）。单因素分析发现V5、V20、MLD与≥2级RP的发生有相关性（t＝－4．588、－2．433、－2．845,P＝0．000、0．019、0．006）。经单因素分析中有意义的参数,再次进行多因素分析显示：V5是≥2级RP发生的独立影响因素（P＝0．03）。经ROC曲线分析,V5预测≥2级RP有统计学意义（P＜0．05）,其曲线下面积为0．862,敏感性和特异性分别为1．00、0．442。当V5临界值为43．65％时≥2级RP发生率分别为7．14％、32％。结论：剂量－体积参数V5、V20、MLD与≥2级RP相关,其中V5是独立预测因素。     

Ⅲ+Ⅳ期非小细胞肺癌三维适形或调强放疗中复合指标预测放射性肺炎前瞻性临床研究

目的 探讨非小细胞肺癌三维适形或调强放疗正常肺V5和V10联合V20评价放射性肺炎(RP)的意义.方法 采用三维适形或调强后程加速超分割放疗经病理或细胞学证实初治非小细胞肺癌患者90例,其中Ⅲa期6例、Ⅲb期29例、Ⅳ期55例.放疗剂量61～80 Gy,中位数70 Gy.由剂量体积直方图计算全肺V5、V10、V20、V30、平均肺剂量(MLD),对侧肺V5、V10及同侧肺V30.用CTC3.0标准评估肺损伤.结果 90例患者中发生RP为1级29例、2级23例、3级5例、4级1例、5级1例.全肺V5、V10、V20、对侧肺V10、大体肿瘤体积(GTV)、计划靶体积、射野数目与≥1级RP相关(χ2=2.04、2.05、2.01、4.62、6.50、5.61、5.61,P=0.044、0.043、0.047、0.030、0.010、0.020、0.020),全肺V5、V10、V20和V30、MLD与≥2级RP相关(χ2=2.05、2.20、2.96、4.96、5.20,P=0.040、0.030、0.000、0.030、0.020).多因素分析显示GTV与≥1级RP发生相关(χ2=4.06,P=0.044),V20与≥2级RP发生相关(χ2=9.61,P=0.002).全肺V5、V10、V20的中位数分别为66%、48%、31%.V20>31%时≥2级RP概率增加,V20>31%+V10>48%+V5>66%时≥2级RP概率增加,V20>31%+V5>66%时≥2级RP概率增加;V20>31%时V10>48%与<48%比较RP概率相似,V20≤31%时V5>66%与<66%、V10>48%与<48%比较RP概率也相似.性别、年龄、临床分期、病理类型、治疗方式、KPS与≥1、2级RP无关.结论 肺V5、V10联合V20评价放射性肺炎的发生可能提高预测放射性肺炎的能力.     

肺癌、纵隔肿瘤及食管癌放疗后放射性肺炎发生因素的对比研究

 目的　对肺癌（肺靶区）与纵隔肿瘤及食管癌（纵隔靶区）三维适形放疗中放射性肺炎（RP）发生的影响因素及剂量体积直方图（DVH）参数进行对比研究。方法　回顾性分析接受放射治疗的肺癌、纵隔肿瘤及食管癌患者83例的临床资料,采用χ2 检验对临床因素（性别、年龄、肿瘤部位、分期、化疗）与RP发生的相关性进行分析;分别对两靶区的DVH参数与RP的发生进行相关性分析;用t检验对肺靶区与纵隔靶区DVH参数进行比较。结果　≥2级 RP 发生率为36.5 %（31／81）。各临床因素与≥2级RP发生无关（χ2 值分别为0.377、0.215、0.018、0.717、0.215,均P＞0.05）。两靶区的DVH参数中,V5、V10、V20、V30、全肺平均剂量（MLD）与RP的发生均具有明显相关性。两靶区发生RP的患者V5[（50.9±17.8）%、（69.9±20.4）%]（t＝2.745,P＜0.05）、V10[（38.6±15.2）%、（53.5±18.8）%]（t＝2.434,P＜0.05）差异均有统计学意义,而V20（t＝0.388,P＞0.05）、V30（t＝0.005,P＞0.05）及MLD（t＝0.138,P＞0.05）差异均无统计学意义。两靶区未发生RP患者的DVH参数t检验后得到类似结果。结论　在肺靶区、纵隔靶区的放疗中,RP的发生与DVH参数密切相关,尤其是V20、V30及MLD对RP的发生有重要的影响。     

肺癌三维适形及调强放疗诱导肺损伤与剂量体积直方图参数的相关性

目的 探讨肺癌三维适形放疗（3D-CRT）和调强放疗（IMRT）诱导肺损伤（RILI）与剂量体积直方图（DVH）参数的关系及两种放疗计划的差异。方法 151例肺癌患者分别接受3D-CRT（n=90）和IMRT（n=61）,均给予根治性放疗剂量,采用传统分割照射（1.8～2.0Gy／次,1次／天,5次／周）,中位剂量60.0Gy。比较两组发生RILI的差异,并分析两组发生≥2级RILI与DVH参数的关系。结果 3D-CRT组≥2级RILI发生率为17.8％,略低于IMRT组的24.6％;≥3级RILI发生率为8.9％,略高于IMRT组的3.3％,差异无统计学意义（P＞0.05）。单因素分析显示,3D-CRT组V20可增加≥2级RILI的发生风险（OR=3.780,P=0.030）;IMRT组V5、V10、V13、V20和平均照射剂量均可增加≥2级RILI的发生风险（OR：3.575～6.286,P：0.003～0.045）。多因素分析显示V20是RILI的独立危险因素。结论 3D-CRT和IMRT对肺癌患者≥2级RILI的发生率影响不明显,但RILI的发生风险均与V20相关。     

Ⅲ+Ⅳ期非小细胞肺癌三维适形放疗正常肺V_5、V_(10)预测放射性肺损伤前瞻性临床研究

目的 探讨非小细胞肺癌三维适形放疗正常肺低剂量体积对放射性肺损伤的预测作用.方法 采用三维适形后程加速超分割放疗经病理或细胞学证实的非小细胞肺癌患者100例.Ⅲ期14例,Ⅲb期36例,Ⅳ期50例.鳞癌49例,腺癌48例,腺鳞癌3例.初治79例、术后复发8例,术后残留12例,术后辅助1例.单纯放疗9例,放化疗91例.放疗剂量60～80 Gy,60～69 Gy 24例,≥70 Gy76例.化疗方案采用紫杉类+铂类一线方案.用剂量体积直方图计算正常肺V_5、V_(10)、V_(20)、V_(30)和平均肺剂量(MLD).肺损伤评估根据CTC 3.0标准.结果 全组V_5为37%～98%,中位值65%;V_(10)为27%～78%,中位值47.5%;V_(20)为17%～54%,中位值31%;V_(30)为9%～31%,中位值24%.100例患者中发生放射性肺炎(RP)1级34例,2级27例,3级8例,4级1例,5级1例.75例患者中发生放射性肺纤维化1级46例,2级14例,3级2例.V_5、V_(10)、V_(20)、MLD与≥1级RP相关,V_(5)、V_(20)、V_(30)、MLD与≥2级RP相关,V_5与≥3级RP相关.V_(5)、V_(20)、V_(30)、分别>65%、31%、24%时发生≥2级RP概率增加,V_(5)、V_(20)分别>65%、31%时发生≥3级RP概率增加,V_(20)>31%时发生≥1级RP概率增加.大体肿瘤体积、计划靶体积与≥1级RP、≥2级放射性肺纤维化相关.性别、年龄、临床分期、处方剂量、照射野数目与各级放射性肺损伤无关.结论 剂量体积参数V_(5)、V_(10)与RP发生相关,可能成为放射肺损伤有效的预测因子.     

非小细胞肺癌吉西他滨诱导化疗+放疗后放射性肺炎危险因素及剂量学分析

目的 对非小细胞肺癌(NSCLC)吉西他滨化疗后急性放射性肺炎(ARP)的发生情况进行总结,阐明吉西他滨诱导化疗后发生急性放射性肺炎的高危因素及剂量学限制。方法 回顾性分析2010-2017年间浙江省肿瘤医院放疗科收治的接受吉西他滨化疗+胸部放疗的NSCLC患者191例,收集患者的基本信息、放化疗情况以及ARP情况。Logistic法单因素和多因素分析影响ARP发生的因素。结果 共49例患者发生≥2级ARP,占25.7%。单因素分析显示吉西他滨累积剂量≥9.0g发生ARP概率是<9.0g的3.45倍(P=0.015),放疗剂量≥50Gy与ARP发生有关(P=0.008),放化疗间隔时间在10周内ARP发生风险增加7.69倍(P=0.047);双肺V5Gy、V20Gy、V30Gy和平均肺剂量(MLD)均能有效预测ARP发生(P≤0.001)。多因素分析仅有放疗剂量(P=0.044)和V5Gy(P=0.02)是ARP发生的预测因素。结论 对于接受吉西他滨化疗的NSCLC患者来说,吉西他滨累积剂量、化放疗间隔时间以及放疗剂量均与ARP的发生有关,同时应当限制双肺V5Gy、V20Gy、V30Gy和MLD,以减少ARP的发生。     

血浆中TNF-α、IL-6、ACE水平及DVH参数与放射性肺炎发生的相关性研究

背景与目的:随着放射治疗的广泛应用,放射性肺炎(radiation pneumonitis,RP)也日益明显地表现出来,严重时甚至会加速患者的死亡,成为胸部肿瘤放射治疗的剂量限制因素.本研究旨在探讨血浆中TNF-α、IL-6、ACE水平及DVH参数与RP发生的相关性,评价其在预测RP中的价值.方法:123例胸部肿瘤患者按常规给予三维适形放射治疗或调强放射治疗.放射治疗前及照射45～50 Gy时采用酶联免疫吸附法(ELISA)检测血浆中TNF-α、IL-6及ACE的含量.RP的评价依照RTOG急性RP分级标准,观察终点为出现Ⅱ级以及以上RP.DVH参数包括平均肺剂量(MLD)和V10、V20、V30(Vx指照射总剂量高于xGy的肺体积占全肺总体积的百分数).结果:123例接受三维适行或调强放疗的胸部肿瘤患者中有18例患者发生了RP,其中Ⅱ级16例,Ⅲ级2例.血浆中TNF-α、IL-6、ACE水平在放疗前中位数分别为66.3 pg/mL、32.1 pg/mL、19 ng/mL,照射45～50 Gy时中位数分别为125.5 pg/mL、109.3 pg/mL、3.0 ng/mL,差异均有统计学意义(P均为0.000).放疗前后血浆中TNF-α、IL-6、ACE水平变化在未发生RP组与发生RP组间无明显差别.V10、V20、V30、MLD在未发生RP组与发生RP组间差异有统计学意义(P分别为0.011,0.029,0.009,0.006).将上述指标与RP的发生作多因素分析,未发现其中与RP发生有关的独立预测因素.结论:照射45～50 Gy后血浆中TNF-α、IL-6、ACE水平均较放疗前有明显变化,但与RP的发生无明显相关性.V10、V20、V30、MLD、是否合并化疗均与RP的发生有关.上述指标中未发现与RP有关的独立预测因素.     

107例NSCLC患者放疗后≥2级放射性肺炎预测模型的建立和分析

目的 探讨非小细胞肺癌三维适形放疗后放射性肺炎发生的相关因素并建立数学预测模型.方法 收集行三维适形放疗的非小细胞肺癌患者107例.全组患者均为根治性放疗,剂量采用常规放疗,分割方式为2Gy/f,处方剂量60 ～78 Gy,中位剂量66 Gy.不同组别患者放射性肺炎的发生情况单因素分析采用x2检验.Logis-tic回归分析筛选影响放射性肺炎发生的独立预后因素.受试者工作特征(receiver operating characteristic,ROC)曲线分析评价其临床诊断性能.结果 本组患者放射性肺炎发生率为62.6％,≥2级放射性肺炎的发生率为38.3％,其中2级23例(21.5％),3级14例(13.1％),4级4例(3.7％).单因素分析结果显示,放射性肺炎的发生在慢性阻塞性肺疾病、T分期、射野数目、临床靶区(clinical target volume,CTV)的体积、CTV的平均剂量、计划靶区(planning target volume,PTV)体积、PTV的平均剂量、双肺体积和双肺Dmean、V5、V10、V15、V20、V25、V30、V35、V40方面差异均具有统计学意义(均P＜0.05).多因素分析显示,T分期、双肺Dmean、V20、V40为影响≥2级放射性肺炎发生的独立因素(均P＜0.05).在此基础之上,建立放射性肺炎的预测模型为Y=ex/(1+ex),其中x=-5.797-0.986×T分期+1.193×肺平均剂量+1.259 × V20+ 1.329×V40.结论 T分期、双肺Dmean、V20和V40为影响接受三维适形放疗的非小细胞肺癌患者发生≥2级放射性肺炎发生的独立因素,建立的数学预测模型对这类患者≥2级放射性肺炎的发生有较好的预测价值.     

肺低剂量区体积预测胸中下段食管癌放射性肺炎的价值

目的 明确肺低剂量区体积在预测接受放射治疗的胸中下段食管癌患者出现急性放射性肺炎（radiation pneumonitis, RP）的价值。方法 对205例接受放射治疗并符合入组条件的胸中下段食管癌患者发生RP的情况进行分析,对患者临床资料和治疗计划等指标进行单因素及多因素分析,评价肺低剂量区体积指标的价值。结果 全组患者出现≥2级RP的患者为60例占29.27%（60/205）,其中2级48例（23.41%）,3级10例（4.88%）,4级2例（0.98%）。单因素分析结果显示食管癌病变X 线长度、GTV最大横径、GTV长度、射野数、肺MLD、GTV体积、PTV体积、肺V5、肺V10和肺V15均影响患者≥2级RP的发生。多因素分析结果显示射野数、肺MLD及肺V5为患者≥2级RP发生的独立预测影响因素。ROC曲线分析结果显示本组患者肺V5取值为51.17%为预测放射性肺炎的效能值。结论 肺低剂量区体积V5为接受放疗的胸中下段食管癌患者发生≥2级RP的重要预测因素,建议在以后制定胸中下段食管癌的放射治疗计划时应该予以重视,取值应≤51.17%。     

老年食管癌患者三维适形放疗后发生放射性肺炎与剂量体积参数的相关性

目的 分析剂量体积参数与老年食管癌患者三维适形放疗后发生≥2级放射性肺炎的相关性。方法 收集并分析250例来自不同医疗中心、接受三维适形放疗的老年食管癌患者资料,对患者临床特征行χ2检验,对剂量体积参数等因素行Logistic单因素及多因素分析,确定与发生≥2级放射性肺炎的独立相关因素,并通过ROC曲线分析独立相关因素的最佳分界值。 结果 （1）三维适形放疗后共20%的老年食管癌患者发生了≥2级放射性肺炎,单因素分析提示双肺V5、V10、V20、V30及肺平均剂量（MLD）是≥2级放射性肺炎的相关因素;（2）多因素分析提示双肺V5、V20是≥2级放射性肺炎的独立相关因素;（3）ROC曲线提示控制放射性肺炎发生的最佳分界值为V5＜53.9%,V20＜23.2%。结论 双肺V5和V20是老年食管癌患者三维适形放疗后发生≥2级放射性肺炎的独立相关因素。     

拓扑替康联合环磷酰胺治疗儿童神经母细胞瘤

目的观察评价拓扑替康联合环磷酰胺治疗神经母细胞瘤的疗效和毒性.方法14例神经母细胞瘤患儿,应用拓扑替康联合环磷酰胺联合静脉用药.大剂量应用环磷酰胺[70mg/(kg·d)×2 d]和拓扑替康[2mg/(m2·d)×3 d].其中12例治疗2～13个周期,进行疗效和不良反应评价.结果12例患者中,进展3例,稳定及缓解9例,总有效率为75%.不良反应主要为骨髓抑制和消化道反应,但对症治疗后,无相关性死亡.结论拓扑替康联合环磷酰胺治疗儿童神经母细胞瘤安全有效.     

宫颈癌患者中联合检测血清VEGF及SccAg的意义

目的：寻找较为敏感的肿瘤标志物指导制定正确的治疗方案及预测预后。方法：1999年7月至2001年1月，本院妇科住院治疗的宫颈鳞癌37例，用ELISA法测定血清中VEGF值，MEIA法测定血清中SccAg值。用X^2检验，t检验，方差分析及多元线性回归分析行统计处理。以子宫肌瘤26例作为对照。结果：宫颈癌治疗前血清VEGF明显高于良性的子宫平滑肌瘤血清值（P＜0．01）；深肌层浸润及晚期未术病例其血清VEGF及SccAg值均较浅肌层浸润者高（P＜0．01）；宫颈癌Ⅰ－Ⅱ期血清VEGF值明显低于Ⅲ－Ⅳ期者（P＜0．01），术中无残留者明显低于术中有残留者（P＜0．01），淋巴结无转移者明显低于有转移者（P＜0．01），治疗后无复发者（半年内）明显低于有复发者（P＜0．01）。对于血清SccAg而言，其在宫颈癌中表达的阳性率为67．56％。临床I－II期血清SccAg值明显低于Ⅲ－Ⅳ期者（P＜0．01），淋巴结无转移者明显低于有转移者（P＜0．01）。而治疗后有无复发、术中有无残留对其的影响不显著（P＞0．05）。结论：VEGF与SccAg可作为宫颈癌预后判断及宫颈癌术后是否要补充外照射的参考指标。     

Risk of Treatment-related Mortality with Sorafenib in Patients with Cancer

Background: Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growthfactor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis todetermine the overall risk of FAEs associated with sorafenib. Methods: Databases, including PubMed, Embaseand Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetingswere searched to identify relevant studies. Eligible studies included randomized controlled trials evaluatingsorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95%confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed accordingto tumor type and therapy regimen. Results: 13 trials recruiting 5,546 patients were included in our analysis.The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenibhad a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen.A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99;P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs werehemorrhage (8.6%) and thrombus or embolism (4.9%). Conclusions: It is important for health care practitionersto be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.     

美罗华联合化疗治疗B细胞非霍奇金淋巴瘤25例

目的本研究旨在观察美罗华联合化疗治疗B细胞非霍奇金淋巴瘤的疗效和毒副反应。方法我科从2003年8月至2007年2月共有25例经病理确诊的CD20阳性B细胞型非霍奇金淋巴瘤患者接受美罗华联合化疗，中位疗程数为4（2～6）。化疗方案包括CHOP、ProMACE／cytaBOM、FMD、FC、COP、COPP、DVAE。结果25例中完全缓解（CR）16例（64．0％）；部分缓解（PR）8例（32．0％）；总有效（OR）率为96．0％。治疗后随访期3～44个月，中位缓解期32个月，4例存活3个月以上，1例因肿瘤晚期进展死亡，其余20例存活8个月以上（80％），最长已存活45个月。主要毒副反应为骨髓抑制，22例出现白细胞减少，其中Ⅲ～Ⅳ度6例；其它毒副反应包括Ⅰ～Ⅱ度恶心呕吐、轻度脱发和肝功能受损等。美罗华输注相关毒副反应主要有Ⅰ～Ⅱ度寒战和发热、皮疹、诱发哮喘、间质性肺炎、低免疫球蛋白血症等，经对症治疗后均得到缓解。结论美罗华联合化疗治疗B细胞非霍奇金淋巴瘤具有良好的临床疗效且毒副反应较小。     

Adjuvant chemotherapy with anthracyclines in comparison with the standard combination of CMF in breast cancer with high risk of relapse

The effectiveness of adjuvant therapy with adriablastin and doxorubicin for breast cancer has been compared to that of standard CMF. During 1985-1990, the study included 349 patients with T1-2N2M0 and T3N0-2M0 tumors; mean age--46 yrs; mean follow-up--96.7 months. Overall survival rate in the doxorubicin group was 73%, CMF--62%; relapse-free survival--62.1 and 55%, respectively. The absolute difference in overall survival rates (11%) proved barely significant (p = 0.056). However, the difference in overall survival (p < 0.05) after anthracyclines and CMF in patients with tumors T1-2N2M0 and T3N1M0 was significant and in favor of the former. As far as frequency and degree of side-effects is concerned, their patterns were practically identical in both groups, except for the significantly higher frequency of cardiotoxity and complete alopecia in doxorubicin therapy. Cardiotoxic complication rate was significantly reduced from 13.8 to 3.9% by cardioxane treatment.     

Phase I Study of Topotecan in Combination with Concurrent Radiotherapy in Adults with Glioblastoma

A phase I study was performed to determine the maximum tolerated dose and the recommended dose of continuous intravenous infusion of topotecan in combination with radiotherapy (RT) in patients with previously untreated glioblastoma multiforme (GBM). Twenty patients with histologically proven GBM and 1 with rhabdoid tumor were enrolled. After surgery or stereotactic biopsy, patients received cranial RT (60 Gy/30 fractions/40 days) and 3 cycles of topotecan as continuous infusion (CIV) from day 1 to 5 on weeks 1, 3, and 5 during RT. The dose of topotecan was escalated from 0.6 to 1.0 mg/m2/day. Four dose levels were tested. One grade 4 thrombocytopenia was seen at level 1 (topotecan dose 0.6 mg/m2/day; 6 patients). No dose-limiting toxicity was seen at level 2 (0.8 mg/m2/day; 3 patients) or an intermediate level of 2 bis (0.9 mg/m2/day; 6 patients). Six patients were included at level 3 (1.0 mg/m2/day), 4 of whom experienced dose-limiting toxicities, including 3 episodes of grade 4 thrombocytopenia, 1 platelet transfusion, 1 febrile neutropenia, and 1 grade 4 neutropenia of more than 7 days. Eighty percent of patients with GBM were alive at 12 months. The dose-limiting toxicity of topotecan administered as CIV for 5 days every 2 weeks is hematological. The maximum tolerated dose is 1.0 mg/m2/day and the recommended dose is 0.9 mg/m2/day. A phase II trial using the recommended dose of topotecan is ongoing.     

Prophylaxis of Pneumocystis carinii pneumonia with atovaquone in children with leukemia

BACKGROUND: Despite extensive studies of atovaquone in human immunodeficiency virus (HIV)-infected patients, there is little information about its efficacy as a prophylactic agent for Pneumocystis carinii pneumonia (PCP) in pediatric patients with cancer. Therefore, a retrospective analysis was conducted to determine the incidence of PCP in pediatric patients who received prophylactic atovaquone during treatment for acute leukemia. METHODS: We reviewed the medical records of all patients treated at our institution for acute lymphoblastic leukemia or acute myeloid leukemia between 1994 and 2004. Only patients who were intolerant of trimethoprim-sulfamethoxazole (TMP-SMZ) and received atovaquone prophylaxis were included in the analysis. RESULTS: Eighty-six patients were unable to tolerate TMP-SMZ and received daily atovaquone for PCP prophylaxis. PCP was not diagnosed in any patient who received atovaquone prophylaxis: the upper limit of the 95% confidence interval (CI) was 1.74 per 100 person-years. CONCLUSIONS: Atovaquone is an efficacious alternative for PCP prophylaxis in pediatric patients who have leukemia and are intolerant of TMP-SMZ.     

Temozolomide in combination with fotemustine in patients with metastatic melanoma

Purpose  Temozolomide and fotemustine are both active drugs for treating metastatic melanoma. The present study was designed to assess the efficacy and safety of combination therapy with temozolomide + fotemustine in patients with metastatic melanoma. Methods  Forty patients (median age 50.5 and 22 males) with pathologically confirmed, unresectable, AJCO stage IV melanoma were enrolled into the study. The primary endpoints were tumor response and safety. Patients received oral temozolomide 125 mg/m² on days 1–7 and intravenous fotemustine 80 mg/m² on day 3 every 3 weeks. Results  Fourteen (35%) patients achieved an objective response, including 3 (7.5%) complete and 11 (27.5%) partial responses. Median overall survival time was 6.7 months and 6-month survival rate was 57.4%. Myelosupression, particularly thrombocytopenia, was the primary toxicity. Conclusion  The regimen, temozolomide combined with fotemustine, is an active and moderately safe first-line chemotherapy regimen with acceptable and easily manageable toxicities in patients with metastatic melanoma.     

Analysis of dermatologic events in patients with cancer treated with lapatinib

Purpose Dermatologic events (DEs) in patients with cancer treated with lapatinib, a small-molecule dual tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR [ErbB1]) and HER2 (ErbB2), were characterized. Patients and methods Nine clinical trials of metastatic cancer were included in this analysis. Lapatinib was administered at doses ranging from 1000 to 1500 mg/day as monotherapy (n = 928) or in combination with paclitaxel or capecitabine (n = 491). Patients not treated with lapatinib comprised the control group. Dermatologic events included hand-foot syndrome, rash, hair disorder, dry skin, pruritus/urticaria, skin disorder, skin infection, and nail disorder; DEs were characterized based on type, time to onset, severity, duration, and required interventions. Results Fifty-eight percent of patients treated with lapatinib monotherapy, 74% treated with lapatinib plus paclitaxel or capecitabine, and 53% in the control group developed DEs. Among patients receiving lapatinib monotherapy, 55% experienced grade 1/2 DEs, 3% had grade 3 DEs, and no grade 4 DEs were observed. The most common DE was rash (43%); all other events occurred in ≤8% of patients. Most DEs developed between days 1 and 14 of starting treatment, with a median duration of 29 days. Three percent of DEs led to lapatinib dose reduction, 7% resulted in dose interruption, and 1% led to drug discontinuation. Conclusions Most DEs in lapatinib-treated patients present early, are mild to moderate in severity, and infrequently require dose modification or treatment interruption. Lapatinib-associated DEs appear to differ clinically from those associated with EGFR TKIs in both frequency and severity.     

应用额瓣整复老年颊癌患者术后缺损

目的 应用简便、快捷、安全的方法修复老年颊癌术后组织缺损，恢复口腔功能。方法 对5例老年颊粘膜癌患者施行根治性切除术后，同期行全额瓣带蒂移植。其中4例额瓣经颧弓下进入口腔，修复翼下颌皱襞、磨牙后区和颊粘膜；1例经颧弓外侧转移折叠，修复面颊部沿穿性缺损。结果 5例额瓣均完全成活，形态及功能良好。前额部皮片全部成活，但游移度稍差，术后1年以上皮片色泽接近正常。随访9个月-2年半无复发和转移。结论 额瓣适合于老年口腔癌术后组织缺损的修复，尤其是面积较大的颊癌或面颊洞穿性缺损。