Multimodality therapy in surgically resectable early non-small cell lung cancer

Lung cancer is a global epidemic. Unfortunately only a fraction of patients can undergo curative surgery and in these, only one-third survive five years. The remainder die of locoregional and distant metastatic disease. With advances in chemotherapy for systemic control and radiation therapy for local control, responses and survivals have shown promise in extensive inoperable disease. In order to attempt to extend survival in extensive local but operable disease (Stage IIIa), these treatment modalities were added to the surgical regimen either before (neoadjuvant, induction) or after (adjuvant) surgery. Several small phase III trials substantiated the benefits. Since early lung cancer (Stage I and II) recur in 30% of instances to distant sites as well as regionally, multimodality therapies have recently been encouraged in global trials in an attempt to prolong time to recurrence and survival in this latter group of patients. A review follows:     

Ⅱ~Ⅲ期食管癌根治性切除术后患者预后的影响因素分析

目的 探讨影响Ⅱ~Ⅲ期食管癌根治性切除术后患者预后的因素。方法 回顾性分析 2007年 1月—2010年 12月行食管癌根治性切除术且术后病理分期为Ⅱ~Ⅲ期共 716例患者的临床资料。选择可能影响预后的临床病理资料及术后治疗情况进行单因素和多因素分析。结果 716 例患者 1、3、5 年总生存率分别为 79.85%、58.27%、 49.73%。多因素分析显示：性别、术中粘连程度、术后阳性淋巴结数目、T分期及术后辅助治疗是影响患者总生存时间（OS）的独立预后因素（均 P＜0.05）。对术后辅助治疗方式进行分层分析显示：Ⅱa期（342例）患者术后化疗组 OS优于单纯手术组和术后放疗组（χ2分别为 9.301、4.422,P＜0.05或P＜0.01）;Ⅱb（75例）及Ⅲ期（299例）患者术后放化疗组及术后放疗组 OS均优于单纯手术组（Ⅱb期：χ2分别为 3.926、4.605,P＜0.05;Ⅲ期：χ2分别为 8.504、7.435,P＜0.01）。716例患者 1、3、5年无进展生存率分别为 71.23%、49.32%、38.26%。多因素分析显示：性别、术中粘连程度、TNM分期及术后辅助治疗是影响患者无进展生存时间（PFS）的独立预后因素（均P＜0.05）。对术后辅助治疗方式进行分层分析显示：Ⅱa期患者术后化疗组 PFS优于单纯手术组（χ2=7.481,P＜0.01）;Ⅱb及Ⅲ期患者术后放化疗组 PFS均优于单纯手术组（χ2分别为 6.684、5.741,P＜0.05）。结论 根治术后辅助治疗为影响Ⅱ~Ⅲ期食管癌患者预后的重要因素。Ⅱa期患者可仅行术后化疗,而Ⅱb～Ⅲ期患者接受辅助放疗或放化疗可获得更优预后。     

Treatment of non-localised, non-metastatic rectal cancer

The standard treatment for rectal cancer is surgical removal of the rectum and mesorectum. Is the prognosis for non-metastatic rectal cancer that extends beyond the bowel wall improved by adding radiotherapy and/or chemotherapy to surgery? To answer this question, we conducted a review of the literature using the standard Prescrire methodology. Randomised trials conducted before optimal surgery was developed showed that, compared with surgery alone, postoperative radiotherapy reduced the risk of local recurrence and possibly increased overall survival. In the only randomised trial in which the mesorectum was systematically removed, preoperative radiotherapy had no impact on overall survival but reduced the risk of local recurrence (5% at 10 years, versus 11% without radiation therapy).This result was statistically significant in patients with lymph node involvement. Radiotherapy for rectal cancer carries a risk of faecal incontinence (about 50% of patients), small bowel occlusion, and secondary cancers (about 1 in 15 patients). In patients who receive neither radiotherapy nor chemotherapy before surgery, postoperative chemotherapy based on fluorouracil or the tegafur + uracil combination increases overall survival by about 5% at 5 years, in absolute numbers, but carries a risk of serious adverse effects, including haematological and gastrointestinal disorders. Eight randomised trials suggest that the beneficial effects of post-operative chemotherapy and radiotherapy persist and are additive. However, the same is true for adverse effects. In four randomised trials, adding chemotherapy to preoperative radiotherapy roughly halved the risk of local recurrence. In three randomised trials, preoperative chemoradiotherapy appeared to be slightly more effective than postoperative chemoradiotherapy in terms of recurrence, and to carry a similar or lower risk of serious adverse effects, without improving overall survival. Preoperative chemoradiotherapy carries a risk of unnecessarily exposing between 8% and 18% of patients to adverse effects, as their tumour is found to be less extensive than initially thought. There is no firm evidence that postoperative chemotherapy is beneficial after preoperative radiotherapy. Preoperative treatments do not prevent removal of the anal sphincter. The probable benefits of adjuvant therapies in surgical patients must be weighed, on a case by case basis, against the potential risk of serious adverse effects and complications.     

直肠癌的新辅助治疗

局部晚期直肠癌的治疗已经形成放疗、化疗联合手术切除的多学科综合治疗的模式。NCCN指南推荐的局部晚期直肠癌综合治疗的最佳顺序是新辅助短程放疗或新辅助同步放化疗后接受全直肠系膜切除手术,随后4个月的辅助化疗。新辅助治疗可以使肿瘤降期、降级,达到提高根治性切除率、减少局部复发和增加保肛率的目的。但是随着晚期治疗中更高疗效药物的出现以及对生活质量的重视,个体化治疗成为未来研究的方向。     

甲状腺癌术后复发相关危险因素分析

目的 总结分析甲状腺癌术后复发的相关危险因素.方法 回顾性分析2004年1月至2014年1月行手术治疗的甲状腺癌患者145例临床资料,对其中术后甲状腺癌复发患者的资料与同期其他患者的临床资料进行对比,应用单因素和多因素非条件Logistic回归分析比较两组患者的性别、年龄、自身营养状况、TNM分期、术后是否正规放化疗、是否有淋巴结转移、手术方式、病理类型、术后是否出现并发症与甲状腺癌术后复发的相关强度,分析可能导致甲状腺癌术后复发的危险因素.结果 统计资料分析其中有29例患者术后出现甲状腺癌复发,单因素非条件Logistic回归分析显示:术前TNM分期为Ⅲ～Ⅳ期、术后正规放化疗、有淋巴结转移等危险因素比较差异有统计学意义(P＜ 0.05),年龄、性别、手术方式、病理类型、术后是否出现并发症与甲状腺癌术后复发无相关性(P＞0.05);多因素非条件Logistic回归分析显示:TNM分期中Ⅲ ～ Ⅳ期、术后正规放化疗、有淋巴结转移与甲状腺癌术后复发有显著相关性(P＜0.05);其余因素均无统计学意义.结论 甲状腺癌术后复发的原因复杂,其中与术前肿瘤TNM分期为Ⅲ-Ⅳ期、术后未行放化疗或者放化疗不正规、术前有淋巴结转移等关系密切.与患者的年龄、性别、手术方式、病理类型、术后是否出现并发症等未见明显相关性.     

Synovial sarcoma of carotid space

Synovial sarcomas are malignant tumors of mesenchymal origin, extremely rarely located in the area of the head and neck. Histologically they can be monophasic, biphasic or poorly differentiated with numerous differential diagnostic dilemmas. A 54-year-old male with synovial sarcoma of the carotid space is presented. The patient refused suggested postoperative radiotherapy and, nine months after the primary surgery, local relapse was verified. Following surgical resection of the local relapse, postoperative radiotherapy treatment was utilized. Ten months after the second surgery, secondary deposits in the lungs were radiographically confirmed, and local recurrence was noticed again. Treatment was continued with symptomatic therapy and eleven months later patient died. Synovial sarcomas of the carotid space are extremely rare, with complex surgical approaches and pathohistological differential diagnostic dilemmas. Diagnosis requires determination of the immunophenotype of the tumor cells, whereas therapy requires an aggressive surgical approach and postoperative radiotherapy.     

Combined modality treatments in pancreatic cancer

INTRODUCTION: Of all the carcinomas, pancreatic carcinoma (PC) has the highest mortality rate, with a 1- and 5-year survival rate of 25% and less than 5% respectively. This is regardless of the stage at diagnosis. AREAS COVERED: In this review relevant literature assessing the evidence regarding preoperative and adjuvant chemoradiotherapy (CRT) is discussed. Furthermore, new therapeutic approaches are summarized, while the future direction regarding the multimodality approach to PC is also discussed. EXPERT OPINION: The role of combined-modality therapy for PC is continuously evolving. There have been several recent developments, as well as the completion of major, multi-institutional clinical trials. One of the challenges for the busy clinician is to appreciate the variation in staging, surgical expertise, and application of either definitive CRT or neo-adjuvant CRT for local and/or borderline disease.     

Current chemotherapy options for thymic epithelial neoplasms

Thymomas and thymic carcinoma are rare neoplasms. Surgical resection is the cornerstone of effective therapy. Stage I disease is effectively treated by complete surgical resection. The role of radiation therapy in completely resected stage II disease remains controversial. Adjuvant radiation therapy is useful for local control and may improve survival in patients with incompletely resected tumours. Cisplatin-based chemotherapy regimens play an important role in the treatment of advanced stage III/IV or recurrent disease thymomas, but have proven less effective for thymic carcinoma. Phase II trials of multimodality therapy incorporating neoadjuvant chemotherapy, surgery and postoperative radiation therapy show promise for unresectable disease. This review discusses recent clinical data and the potential role for agents targeting the epidermal growth factor receptor, angiogenesis and apoptotic pathways.     

Current chemotherapy options for thymic epithelial neoplasms

Thymomas and thymic carcinoma are rare neoplasms. Surgical resection is the cornerstone of effective therapy. Stage I disease is effectively treated by complete surgical resection. The role of radiation therapy in completely resected stage II disease remains controversial. Adjuvant radiation therapy is useful for local control and may improve survival in patients with incompletely resected tumours. Cisplatin-based chemotherapy regimens play an important role in the treatment of advanced stage III/IV or recurrent disease thymomas, but have proven less effective for thymic carcinoma. Phase II trials of multimodality therapy incorporating neoadjuvant chemotherapy, surgery and postoperative radiation therapy show promise for unresectable disease. This review discusses recent clinical data and the potential role for agents targeting the epidermal growth factor receptor, angiogenesis and apoptotic pathways.     

The role of induction therapy for resectable non-small cell lung cancer

Lung cancer is the leading cause of cancer death among men and women in the US. Surgical resection is potentially curative; however, even after complete resection many patients experience systemic recurrence and subsequently die of their disease. As a means of reducing the chances of recurrence there has been significant interest in combining chemotherapy with surgical resection. Recently, several large phase III clinical trials have demonstrated a significant survival benefit with adjuvant or postoperative cisplatin-based chemotherapy. Use of preoperative or induction chemotherapy has also been an area of active investigation; however, the trials that have demonstrated a survival benefit were small in size, and there has not been widespread acceptance of this treatment approach. The trials of induction chemoradiotherapy have generally been performed in patients with locally advanced disease, frequently in patients with involvement of the level 2 mediastinal lymph nodes (N2). The results of the recent US Intergroup trial, 0139, which compared induction chemoradiotherapy followed by surgical resection versus nonsurgical therapy with chemoradiotherapy in patients with resectable stage IIIA-N2 disease, revealed equivalent overall survival between the two treatment approaches. The results of an unplanned subset analysis of patients who were treated with lobectomy in the surgical arm have generated significant interest and debate. When the strategy of induction therapy is used, pathological clearance of the mediastinal lymph nodes is a significant prognostic factor for overall survival. Current investigations are attempting to determine the optimal method of assessing this critical prognostic factor. The toxicity, efficacy and proper selection of patients for induction therapy, particularly induction chemoradiotherapy, will be assessed in ongoing and future clinical trials.     

肺癌新辅助放化疗后肺功能变化对手术安全性的影响

目的 观察新辅助放化疗对局部晚期非小细胞肺癌肺功能影响及其对手术安全性的影响.方法 2007年8月至2009年8月收治25例ⅢA～ⅢB期非小细胞肺癌,接受新辅助同期放化疗,评价基线肺功能和新辅助治疗后的肺功能,然后接受手术切除.结果 新辅助放化疗后第1秒用力肺活量(FEV1)占预计值百分比、FEV1/用力肺活量百分比以及肺弥散功能占预计值百分比与治疗前相比均有所降低,差异有统计学意义.只有1例可以手术切除的患者因为肺功能下降而没有接受手术.19例患者接受手术,其中16例患者(84%)完全切除,2例患者(10%)镜下残留,1例患者(5%)出现肉眼残留.没有围术期死亡.结论 新辅助同期放化疗可降低肺癌患者的肺功能,但是经过恰当的选择,对手术安全性的影响有限.

Abstract：

Objective To evaluate the efficacy and surgical risk of neoadjuvant concurrent chemoradiotherapy for local advanced non-small cell lung cancer (NSCLC). Methods Twenty-five stage Ⅲ A/Ⅲ B NSCLC patients received neoadjuvant concurrent chemoradiotherapy and surgery. Pulmonary function tests (PFT) were obtained at baseline and after induction therapy. Results The changes of forced expiratory volume in one second (FEV1),FEV1/forced vital capacity(FVC) and diffusing capacity of lung(DLco) were statistically significant after neoadjuvant chemoradiotherapy. But only one of the 20 eligible patients did not undergo surgery due to PFT reduction after neoajuvant chemoradiotherapy. Nineteen patients underwent resection,including 16(84%),2(10%),1(5%) patients undergoing R0,R1,R2 resection respectively. No mortality ocurred perioperatively. Conclusions neoadjuvant chemoradiotherapy reduces PFT but the impact of Neoaddjuvant chemoradiotherapy on the surgical risk can be limited when patients are properly selected for operation.     

Neoadjuvant chemotherapy in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a systemic illness. More than half of those patients who present with stage I-IIIA disease and are resected will experience distant relapse. Postoperative adjuvant chemotherapy has been evaluated in several randomized trials but the results of these trials have been inconclusive with increased survival reported in few trials. In resectable stage IIIA NSCLC the findings of three randomized trials have indicated that the survival of these patients is better with neoadjuvant chemotherapy plus surgical resection than with resection alone. Phase II trials using preoperative concurrent chemoradiotherapy have been carried out with encouraging results. The majority of patients with stage IIIA NSCLC require multimodality therapy if they are to achieve a 5-year survival. Combined modality treatment in locally advanced NSCLC continues to evolve and is a subject of ongoing research. One focus for present research is to integrate new active agents into the neoadjuvant setting. Another challenge is to find better treatment approaches in earlier stages of disease. Some data suggest that induction chemotherapy in stage I-II is feasible, does not appear to compromise surgery and yields high response rates. A further aim is to use molecular biological markers of malignancy to identify patients at highest risk of metastatic relapse.     

肺大细胞癌54例临床分析

目的：本文旨在研究临床中肺大细胞癌（LCLC）的相关诊断以及通过总结外科手术治疗的一些经验,来进一步探讨其临床与病理特征,并对病患手术后的生存期进行了系统分析。方法回顾性的总结分析了冀中能源峰峰集团有限公司总医院自1982年2月至2010年4月间LCLC病患接受外科手术治疗的54例病患临床资料,其中：9例Ⅰa期,19例Ⅰb期,3例Ⅱa期,5例Ⅱb期,14例Ⅲa期,3例Ⅲb期,1例Ⅳ期。并对其生存率进行系统分析。结果54例LCLC研究资料分析结果表明,1、3、5年生存率分别为74．1％、44．1％、31．6％。预后相对应的影响因素主要为TNM分期。结论LCLC生存率低,预后相对较差、TNM分期也极大地影响着LCLC术后的生存率,而提高LCLC的早期发现率,及时进行手术是改善术后远期疗效的关键问题。。     

Canine malignant mammary gland neoplasms with advanced clinical staging treated with carboplatin and cyclooxygenase inhibitors

Surgery remains the treatment of choice for female dogs with mammary gland tumors. Chemotherapy is not commonly used as an adjuvant therapy. Cyclooxygenase 2 (COX-2) has been related to angiogenesis development in tumors, disease progression and worse prognosis. The aim of this prospective study was to compare overall survival periods of female dogs diagnosed with advanced mammary tumors submitted to different treatment protocols, including surgery, chemotherapy and cyclooxygenase inhibitors. Twenty-nine female dogs were evaluated and treated with four different protocols. The overall survival of patients with low COX-2 scores was longer when compared to patients with high COX-2 scores. Different proposed adjuvant treatments associated with surgery led to a statistically significant longer overall survival when compared to surgical treatment alone. Canine patients presenting malignant mammary gland neoplasms with advanced clinical staging should be submitted to complementary therapeutic medication based on clinical staging and immunophenotypical characteristics of the disease.     

低位直肠癌术后辅助放疗的临床研究

目的:探讨手术后辅助放射治疗对低位直肠癌局部复发的影响.方法:72例低位直肠癌患者,分为单纯手术组和术后放疗组各36例.术后放疗组于术后半个月行三维适形调强放疗方法分割照射治疗,照射总剂量为5 000 cGy.比较两组的局部复发率.结果:随访4年,术后放疗组和单纯手术组肿瘤局部复发率分别为13.3%和30.6%(P＜0.05).结论:对低位直肠癌患者,术后进行辅助放疗有助于降低肿瘤局部复发.     

胆道闭锁Kasai术后辅助治疗研究进展

摘要：胆道闭锁（BA）是累及肝内外胆管的一种进行性疾病，目前广泛采用的治疗策略是行肝门空肠吻合术（Kasai术），但约60%的患儿Kasai术后效果不佳，继而需要行肝移植。虽然患儿本身BA分型、手术方式（腹腔镜或传统开放）、手术时年龄、术时肝脏病变情况均是影响BA患儿Kasai术后生存的因素，但是BA术后的辅助治疗仍有较大的改进空间。近年来对于BA术后应用激素、胆汁酸代谢药物、抗生素、益生菌等的报道较多，为了使BA患儿获得更好的预后，该文章就BA术后辅助治疗的研究进展进行综述，进一步探讨辅助治疗改善BA患儿预后的价值。     

139例肺腺鳞癌的预后因素分析

目的探讨肺腺鳞癌临床病理特点及预后因素。方法对139例肺腺鳞癌患者的临床资料进行回顾性分析。选择性别、年龄、自然病程、病理T分期、病理N分期、病理M分期,病理TMN分期、手术方式、术后放疗、术后辅助化疗等因素进行预后分析。统计分析运用SPSS12.0软件行Log-rank检验和Cox模型多因素分析。结果本组肺腺鳞癌的5年生存率分别为21.6%,手术治疗组的5年生存率为23.6%。Log-rank检验显示、N分期、M分期、病理TMN分期、手术方式、术后放疗及术后化疗对预后有显著影响（P〈0.05）。经Cox多因素分析结果表明仅有病理TMN分期对预后有显著影响;辅助化疗明显改善生存。结论肺腺鳞癌是一种生物学行为恶性程度较高的非小细胞肺癌,单纯外科治疗效果差,需积极联合辅助化疗。     

局部区域晚期鼻咽癌同期放化疗联合辅助化疗不良反应的临床分析

目的探讨局部区域晚期鼻咽癌同期放化疗联合或不联合辅助化疗的治疗毒性及治疗顺应性。方法选取中山大学附属第五医院放疗科2007年6月至2009年12月44例鼻咽非角化型癌（WHO病理分型）,第六版AJCC分期Ⅲ-IVb期（T3-4N1或N2-3M0）的患者入组。将患者随机分为同期放化疗组（对照组）和同期放化疗联合辅助化疗组（试验组）。两组均采用根治性常规分割放疗,放疗期间均同时给予顺铂40mg/m^2,d1,1次/周,连续7次。试验组患者放疗结束后1个月开始辅助化疗,采用顺铂80mg/m^2,d1,5-氟尿嘧啶800mg/m^2d1-5,每四周一个疗程,共三个疗程。结果采用意向性分析,比较两组治疗毒性及顺应性。结果两组病例的性别、年龄、一般状况评分、分期方法及临床分期等均具有可比性。两组36.4%（16/44）患者完成7次同期化疗,81.8%（36/44）患者完成6次同期化疗,90.9%（40/44）患者完成5次同期化疗。试验组72.7%（16/22）患者完成3个疗程辅助化疗。全组放疗期间3级以上急性毒性反应为79.5%（35/44）。辅助化疗期间试验组89.4%（17/19）患者发生3级以上毒性反应。结论局部区域晚期鼻咽癌患者使用同期放化疗联合辅助化疗是NCCN推荐的标准治疗。本研究试验组比对照组治疗毒性大,顺应性差,建议对局部区域晚期鼻咽癌患者进行分层治疗,根据年龄、临床分期、一般状况评分进行分层,改善治疗顺应性。