诱导化疗联合三维适形放疗治疗48例局部晚期非小细胞肺癌

[目的]评价诱导化疗加三维适形放射治疗（3DCRT）治疗局部晚期非小细胞肺癌（NSCLC）的疗效及毒副反应。[方法]经病理学或细胞学确诊的78例局部晚期NSCLC患者随机分为单纯3DCRT治疗组（RT组，30例）和诱导化疗与3DCRT联合治疗组（CMT组，48例）。CMT组在3DCRT治疗前给予2～4个周期以铂类药物为主的静脉化疗。[结果]全组中位生存期12．5个月，CMT组中位生存期15个月，RT组中位生存期10个月（P=0．453）。1年生存率CMT组为70．8％，RT组为43．3％（P=0．016）：2年生存率CMT组为37．5％，RT组为26．6％（P=0．323）。两组毒副反应相似，化疗的毒副反应患者能耐受。[结论]诱导化疗加三维适形放疗治疗晚期NSCLC可延长生存期，但并不增加放射副反应。     

诱导化疗加三维适形放疗治疗局部晚期非小细胞肺癌疗效分析

目的评价诱导化疗加三维适形放疗(3DCRT)治疗局部晚期非小细胞肺癌(NSCLC)的疗效及并发症。方法92例局部晚期NSCLC患者随机分为单纯3DCRT组(RT组50例)和诱导化疗与3DCRT联合组(CMT组42例)。CMT组在3DCRT治疗前给以2—4个疗程铂类为主的化疗。结果全组中位总生存期15个月，RT组中位总生存期12个月，CMT组18个月(P=0．014)。1年生存率RT组为48．6％，CMT组为71．2％(P=0．004)，2年生存率RT组为20．8％，CMT组为37．6％(P=0．041)。两组毒副反应相似，患者均能耐受。结论诱导化疗加三维适形放疗治疗晚期NSCLC可延长生存期，但并不增加放射副反应。     

诱导化疗联合三维适形放射治疗对局部晚期非小细胞肺癌治疗的临床研究

目的:评价诱导化疗加三维适形放射治疗(3DCRT)治疗局部晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效及并发症。方法:经病理细胞学确诊的35例局部晚期NSCLC患者,采用在3DCRT治疗前给予2~4个周期多西他赛75mg/(m2·d),21d为1个周期的化疗。结果:中位总生存期18个月,1年生存率为71·4%,2年生存率为37·1%。毒副反应患者能耐受。结论:诱导化疗加三维适形放疗治疗晚期NSCLC可延长生存期,但并不增加放射不良反应。     

三维适形放射治疗同步泰素治疗晚期食管癌

[目的]探讨局部晚期及术后复发性食管癌三维适形放射治疗（3DCRT）同步泰素化疗的临床疗效。[方法]36例局部晚期和术后复发性食管癌采用3DCRT结合泰素化疗（综合组）17例，单独应用3DCRT（对照组）19例。[结果]综合组和对照组疼痛缓解率分别为88.2％和78．9％，有效（CR＋PR）率分别为88．2％和84.2％，两组均无显著性差异（P〉0．05）。综合组1年、2年生存率分别为87．5％、62．5％．高于对照组（79％、28．7％）．但无显著性差异（P=-0．056），2年局部控制率分别为35．29％和21．05％．无显著性差异（P=0．06）。远处转移率分别为35．2％和63．1％，有显著性差异（P=0．045）。毒副反应方面两组相似（P〉0．05）。[结论]局部晚期和术后复发性食管癌临床上行三维适形放射治疗配合化疗可明显降低远处转移率及提高患者的近期生存率。     

健脾益气中药联合化疗治疗晚期大肠癌47例

[目的]比较健脾益气中药联合化疗与单纯化疗治疗晚期大肠癌的临床疗效。[方法]47例晚期大肠癌患者随机分为治疗组（中药加化疗）和对照组（单纯化疗）,观察临床疗效、生活质量、毒副反应及生存期。[结果]治疗组生活质量改善和毒副反应情况明显优于对照组（P〈0．05）;两组临床疗效及1、2、3年生存率和中位生存期比较差异无统计学意义（P〉0．05）。[结论]健脾益气中药联合化疗可改善晚期大肠癌患者的生活质量、减少化疗药物的毒副反应。     

培美曲塞一线治疗13例老年PS评分差的晚期非小细胞肺癌

[目的]探讨培美曲塞单药治疗老年PS评分差、晚期NSCLC患者的疗效以及毒副反应。[方法]经病理学或细胞学确诊PS评分差、晚期NSCLC患者13例，接受培美曲塞500mg／m^2方案治疗，第1d静脉滴注，每21d重复，至少2个周期以上。[结果]13例全部可评价疗效，PR3例．SD6例，PD4例，总有效率为23．1％（3／13），疾病控制率69．2％，中位无进展生存期4．0个月，中位生存期6．1个月，1年生存率23．1％（3／13），4例功能状态评分好转，3例体重增加，4例止痛药用量减少。主要毒副反应为粒细胞下降、贫血和胃肠道反应。[结论]培美曲塞单药对老年PS评分差、晚期NSCLC患者有一定的疗效，且毒副反应轻，耐受性好，可改善患者生活质量。     

GP方案联合益气化痰汤治疗晚期非小细胞肺癌64例

[目的]评价益气化痰汤联合吉西他滨加顺铂方案治疗晚期非小细胞肺癌（NSCLC）的近期疗效及毒副反应。[方法]64例晚期NSCLC患者随机分为单纯化疗组和联合化疗组,两组的化疗方案均采用GP方案,每21d为1个周期：而联合化疗组加服益气化痰汤（主要药物：黄芪、党参、白术、茯苓、陈皮、神曲、厚朴、生意苡、川 贝、石见穿、葶苈子、桑白皮、白花蛇舌草等）。3个周期后评价疗效和毒副反应。[结果]两组均无CR者,联合治疗组有效率46．88％,单纯化疗组有效率40．0％（P〈0．05）．两组毒副反应均可耐受。联合化疗组在改善症状、延长生存期方面较有优势。[结论]益气化痰汤联合GP方案治疗晚期NSCLC可获得较好疗效．减轻毒副反应。     

注射用薏苡仁油在晚期非小细胞肺癌化疗中的作用

[目的]探讨注射用薏苡仁油（康莱特）在晚期非小细胞肺癌（NSCLC）患者化疗中的作用。[方法]126例接受紫杉醇联合顺铂方案化疗的晚期NSCLC患者随机分为治疗组和对照组．各63例．治疗组在化疗期间每日给予注射用薏苡仁油200ml辅助治疗,对照组为单纯化疗组。比较两组患者的血象及临床症状改变情况,并观察两组患者的治疗有效率、中位生存期及1年生存率。[结果]治疗组和对照组的治疗有效率分别为42．9％和33.3％,中位生存期和1年生存率分别为10．6个月和8.2个月、45．1％和33．6％（P〈0．05）。治疗组Ⅲ／Ⅳ度白细胞下降比例为19．0％,较对照组（33．3％）明显降低（P〈0．05）。[结论]注射用薏苡仁油在晚期NSCLC化疗中作为支持治疗有明显的协同增效作用,可改善晚期患者的生存质量,延长生存时间。     

紫杉醇脂质体周疗法治疗37例老年晚期非小细胞肺癌

[目的]评价周剂量紫杉醇脂质体单药治疗晚期老年非小细胞肺癌（NSCLC）的疗效和安全性。[方法]37例年龄≥70岁的晚期NSCLC患者接受紫杉醇脂质体75mg／m^2静脉滴注，d1.8,每3周重复。2周期后进行疗效评价。观察近期疗效和毒副反应，治疗前、治疗后1月、治疗后2月的生活质量（QOL），以及1、2年的生存率。[结果]36例可评价的患者临床控制率为50．0％，完全缓解率为2．8％，部分缓解率为22．2％，总有效率为25．0％，中位生存期8．5月．毒副反应轻微。治疗前、治疗后1个月、治疗后2个月的QOL分值无显著性差异（P〉0．05）。1年生存率和2年的生存率分别为36．1％和16．7％。[结论]周剂量紫杉醇脂质体单药治疗晚期老年NSCLC安全有效，毒副反应可以接受，不影响生活质量。     

三维适形放疗结合奥沙利铂为主的化疗治疗晚期直肠癌

目的 探讨三维适形放疗（3DCRT）结合奥沙利铂为主化疗治疗局部晚期和术后复发直肠癌的临床疗效。方法 66例局部晚期和术后复发直肠癌均在常规放疗44Gy后进入3DCRT，采用3DCRT结合奥沙利铂、氟尿嘧啶、亚叶酸钙同步化疗（综合组）34例，单独应用3DCRT（对照组）32例。综合组同步放化疗结束3～4周后，再巩固化疗2～3个周期。结果 综合组和对照组疼痛缓解率分别为97％和84％（P〉0．05）；有效率（CR＋PR）分别为91％和84％（P〉0．05）；2年局部控制率与局部无进展率之和分别为71％和66％（P〉0．05）；2年生存率分别为65％和38％（P〈0．01）；2年远处转移率分别为35％和63％（P〈0．01）。在毒副反应方面两个组相似（P〉0．05）。结论 三维适形放疗结合奥沙利铂为主化疗治疗局部晚期和术后复发直肠癌可明显减少远处转移率和提高2年生存率，且毒副反应可以耐受。     

放化疗联合脑转移瘤放疗治疗非小细胞肺癌脑转移的临床疗效分析

目的 分析化疗同期胸部三维放疗联合脑转移瘤放疗治疗非小细胞肺癌（non-small cell lung cancer,NSCLC）单纯脑转移的疗效及影响预后的因素。方法 回顾性分析52例单纯脑转移且脑转移瘤及原发肿瘤均接受放疗的NSCLC患者的临床资料,Kaplan-Meier法计算生存率并行log-rank 检验,Cox回归模型行多因素预后分析。结果 全组患者中位随访时间为13.5个月（4～49个月）,中位生存期为13.0个月（95% CI：11.2～14.8）,1年、2年、3年生存率分别为53.8%、13.5%和3.8%。胸部原发肿瘤体积＜118 cm³组和≥118 cm³组的中位生存期分别为14.0个月（95% CI：11.6～16.4）和12.0个月（95%  CI：10.7～13.3）,1年生存率分别为66.7%和42.9%,2年生存率分别为20.8%和0,3年生存率分别为8.3%和0,两组总生存率比较差异有统计学意义（χ²=5.648,P=0.017）。胸部原发肿瘤放疗剂量（dose to PTV,DTPTV）≥66 Gy组和DTPTV＜66 Gy组的中位生存期分别为13.0个月（95%  CI：10.8～15.2）和14.0个月（95%  CI：10.8～17.2）,两组比较差异无统计学意义（χ²=0.064,P=0.80）。多因素预后分析显示,原发肿瘤体积是影响总生存率的独立预后因素。结论 化疗同期胸部三维放疗联合脑转移瘤放疗治疗NSCLC单纯脑转移取得较好疗效,原发肿瘤体积较小的患者生存获益更大。     

Paraneoplastic syndromes associated with lung cancer

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau’s syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.     

Lack of toxicity in a patient with germline TP53 mutation treated with radiotherapy

Li–Fraumeni syndrome is an autosomal dominant disorder characterized by germline TP53 mutation and increased susceptibility to cancer. Despite certain in vitro findings and a theoretical rationale for patients with TP53 mutation to be more radiosensitive and more prone to developing radiotherapy (rt)–induced secondary malignancies, corresponding clinical data remain elusive. Here, we report the case of a woman with TP53 mutation who was treated with adjuvant pelvic rt for stage ib uterine leiomyosarcoma in 2000, with radioactive iodine for papillary thyroid cancer in 2001, and with palliative rt to the humerus in 2010 for metastatic uterine leiomyosarcoma. She has not developed any acute or late rt-related toxicity, nor any secondary malignancies, since her first rt treatment. The literature review describes the potential risks and benefits of using irradiation in patients with TP53 mutation.     

Gallbladder carcinoma in a pregnant patient with Crohn's disease complicated with gallbladder involvement

Primary gallbladder (GB) carcinoma and Crohn’s disease (CD) of the GB are individually rare. We present a case of a pregnant woman with CD found to have GB involvement and primary GB carcinoma. A 34-year-old female at 6 wk gestation with a 21 year history of CD of uncertain extent presented with 3 mo of diarrhea, urgency and abdominal pain. During work-up, she was found to have elevated transaminases and an abnormal alkaline phosphatase. Imaging revealed two gallbladder polyps both greater than 1 cm in size. Resection and histological evaluation was consistent with Crohn’s involvement of the GB, poorly differentiated adenocarcinoma of the GB with invasion through the muscularis propria and matted lymph nodes in the porta hepatis positive for metastatic carcinoma (stage pT2N1). Six cases of CD involving the GB, two cases of primary GB carcinoma in CD, and ten cases of cholangiocarcinoma in pregnancy have been published. This is the only case that describes all three factors. Common features in CD of the GB include acute cholecystitis, ileal involvement, and presence independent of active intestinal disease. Common features in CD patients with GB malignancy include younger age of detection, a long history of CD, extensive colonic and ileal involvement of disease, the absence of cholelithiasis, and pre-existing gallbladder disease (primary sclerosing cholangitis and gallbladder polyps). Pregnancy is specific to this case. The role of CD in the development of GB malignancy is not well understood nor is the contribution of pregnancy to the spread of disease. Chronic inflammation and immunosuppression compounded by hormonal influence is implicated.     

Alternating irinotecan with oxaliplatin combined with UFT plus leucovorin (SCOUT) in metastatic colorectal cancer

Tegafur-uracil (UFT) plus leucovorin (LV, folinic acid) with alternating irinotecan and oxaliplatin were effective and well tolerated in patients with metastatic colorectal cancer (mCRC) in a phase I study. This study expanded the maximum tolerated dose group. Patients aged >or=18 years had histologically confirmed, inoperable, previously untreated, measurable mCRC. Patients received irinotecan 180 mg m(-2) on day 1, oxaliplatin 100 mg m(-2) on day 15 and UFT 250 mg m(-2) plus LV 90 mg on days 1-21 every 28 days. The phase I/II study comprised 45 patients, 29 at the maximum tolerated dose (MTD). The response rate in 38 evaluable patients was 63% (95% confidence interval (CI): 49-80). Median time to progression and overall survival were 8.7 months (95% CI: 7.9-10.4) and 16.8 months (95% CI: 9.6-25.3), respectively. In the MTD group, one patient had grade 3 leucopenia; one had grade 3 neutropaenia; three had grade 3 diarrhoea; and one had grade 3 neurotoxicity. No hand-foot syndrome grade >1 was seen. In total, 67% of eligible patients received second-line therapy. UFT plus LV with alternating irinotecan and oxaliplatin is an efficacious first-line treatment for mCRC, with minimal neurotoxicity and hand-foot syndrome.     

A dose-escalation study of indisulam in combination with capecitabine (Xeloda) in patients with solid tumours

This dose escalation study was designed to determine the recommended dose of the multi-targeted cell cycle inhibitor indisulam in combination with capecitabine in patients with solid tumours and to evaluate the pharmacokinetics of the combination. Thirty-five patients were treated with indisulam on day 1 of each 21-day cycle. Capecitabine was administered two times daily (BID) on days 1-14. Plasma concentrations of indisulam, capecitabine and its three metabolites were determined for pharmacokinetic analysis. The main dose-limiting toxicity was myelosuppression. Hand/foot syndrome and stomatitis were the major non-haematological toxicities. The recommended dose was initially established at indisulam 700 mg m(-2) and capecitabine 1250 mg m(-2) BID. However, during cycle 2 the recommended dose was poorly tolerated in three patients. A dose of indisulam 500 mg m(-2) and capecitabine 1250 mg m(-2) BID proved to be safe at cycle 1 and 2 in nine additional patients. Indisulam pharmacokinetics during cycle 1 were consistent with pharmacokinetic data from phase I mono-therapy studies. However, exposure to indisulam was remarkably increased at cycle 2 due to a drug-drug interaction between capecitabine and indisulam. Partial response was confirmed in two patients, one with colon carcinoma and the other with pancreatic carcinoma. Seventeen patients had stable disease. Indisulam (700 mg m(-2)) in combination with capecitabine (1250 mg m(-2) BID) was well tolerated during the first cycle. A dose of indisulam 500 mg m(-2) and capecitabine 1250 mg m(-2) BID was considered safe in multiple treatment cycles. The higher incidence of toxicities observed during cycle 2 can be explained by a time-dependent pharmacokinetic drug-drug interaction.     

Targeting the endothelin axis with atrasentan, in combination with IFN-alpha, in metastatic renal cell carcinoma

Background:

The endothelin system is involved in tumour growth. Atrasentan, a selective endothelin-A-receptor antagonist, blocks endothelin signalling. This phase I trial studied combining treatment of interferon-alpha (IFN-α) with atrasentan in renal cell carcinoma (RCC).

Patients and methods:

This study evaluated the safety and tolerance of IFN-α (9MU subcutaneously (s.c.) three times a week) in combination with atrasentan (2.5, 5 and 10 mg orally once daily) in untreated metastatic RCC. Cohort 10 mg was extended to obtain insights in efficacy and pharmacodynamics.

Results:

Observed toxicities mainly consisted of known IFN-like toxicities (anorexia, chills, fever, fatigue and nausea), and of nasal congestion (associated to atrasentan). None of these toxicities were considered dose limiting. Cohort 10 mg was extended up to 32 patients; in a subset of patients treated according to the protocol (n=27), median overall survival (OS) was 17.3 months. One patient (3.1%) showed a partial response lasting 14.3 months. In an exploratory analysis, we observed that in the subset of patients with declining vascular endothelial growth factor (VEGF) levels (in combination with rising Endothelin-1 levels), median OS was 22.2 months compared with 2.2 months in patients with increasing VEGF levels.

Conclusion:

Combination treatment of IFN-α 9MU-α s.c. three times a week and atrasentan 10 mg once daily is tolerated. Clinical activity, especially OS, and biomarkers in our view warrant further studies targeting the endothelin axis.     

胃肠道恶性肿瘤患者围术期营养治疗

目前胃肠道恶性肿瘤发病率逐年上升,其营养风险和营养不良也更为普遍,虽然营养不良与不良临床结局相关,但是营养治疗在国内实行的仍不理想,尤其是在围术期,患者经常存在营养不良,导致术后感染、切口愈合延迟等并发症,增加病死率,严重影响术后恢复。因此,营养治疗在胃肠道恶性肿瘤围术期中显得尤为重要。随着加速康复外科的发展,对围术期营养的管理更加精细化,尤其是胃肠道恶性肿瘤患者,应针对不同患者制定个体化营养治疗,维持围术期良好的营养状态,改善患者营养状况,维持机体有效的代谢和免疫功能,提高患者对手术的耐受性,减小应激,从而减少并发症,加速患者的康复,改善预后。本文主要从胃肠道恶性肿瘤患者的营养状况及影响、术前营养风险筛查及评估、术前术后营养治疗及营养制剂的选择几方面进行综述,以说明胃肠道恶性肿瘤围术期的营养治疗是肿瘤治疗的关键因素之一。     

Cyclooxygenase inhibitors use is associated with reduced risk of esophageal adenocarcinoma in patients with Barrett's esophagus: a meta-analysis

Background:

Esophageal adenocarcinoma (EAC) has high mortality and is increasing in incidence. Barrett''s esophagus (BE) increases the risk for EAC. Studies have reported inconsistent findings on the association between use of cyclooxygenase (COX) inhibitors and the risk of neoplastic progression in BE patients. Therefore, we performed a meta-analysis to investigate this association.

Methods:

A meta-analysis was undertaken among a total of 9 observational studies using fixed- and random-effects models, comprising 5446 participants; 605 had EAC or high-grade dysplasia (HGD).

Results:

Overall, COX inhibitors use was associated with a reduced risk of EAC/HGD among BE patients (relative risk (RR)=0.64, 95% confidence interval (CI)=0.53–0.77). Aspirin use also reduced the risk of EAC/HGD (RR=0.63, 95% CI=0.43–0.94), as well as non-aspirin COX inhibitors (RR=0.50, 95% CI=0.32–0.78). The chemopreventive effect seemed to be independent of duration response.

Conclusions:

Cyclooxygenase inhibitors use is associated with a reduced risk of developing EAC in patients with BE. Both low-dose aspirin and non-aspirin COX inhibitors are associated with a reduced risk of neoplasia. More well-designed randomised controlled trials are needed to increase our understanding of the chemopreventive effect of COX inhibitors.     

癌痛患者的代谢特征与营养治疗对策

癌性疼痛（癌痛）是指肿瘤、肿瘤相关症状或抗肿瘤治疗所致的疼痛,其发生发展与机体营养代谢情况密切相关。 癌痛可从饮食摄入、神经内分泌系统、社会心理等途径影响机体的营养代谢;反过来,机体多种营养物质如维生素类、镁 元素及咖啡因、姜黄素、辣椒素、多不饱和脂肪酸（polyunsaturated fatty acid,PUFA）等的变化亦会通过多种机制对癌 痛产生一定影响 ;另外,肿瘤细胞的异常代谢,如谷氨酸和甲醛含量的增加参与了癌痛的发生发展过程,其中,谷氨酸含量 的升高主要由于肿瘤细胞内氧化 - 还原系统失衡和谷氨酰胺（glutamine, Gln）代谢水平增高所致,进而通过介导瞬时受体电 位阳离子通道亚家族 V 成员 1（transient receptor potential cation channel subfamily V member 1,TRPV1）促使伤害性信号持续性 传导。本文主要对癌痛与营养代谢之间的相互影响以及肿瘤代谢产物引发癌痛的相关机制进行综述,并提出了针对癌痛患者 的营养治疗对策。