Chemoradiotherapy for esophageal cancer: current status and perspectives

The optimal role of chemoradiotherapy in the multimodality treatment of esophageal cancer is still controversial. According to a series of clinical trials, definitive chemoradiotherapy is considered the standard of care for patients with medically inoperable or surgically unresectable esophageal cancer. This modality provides survivals comparable to those in Western series of surgery alone and is one of the standards of care even for resectable-stage disease. Recent reports of primary chemoradiotherapy from Japan suggest survival comparable to that of surgery in Japanese patients with stage I disease, but radical surgery is still the standard treatment for T2–3NanyM0 disease in Japan. However, it is clear that this approach has limitations in treatment outcomes. Trimodality therapy, i.e., preoperative chemoradiotherapy followed by surgery, is more favored than surgery alone in clinical practice, particularly in patients with adenocarcinoma, although current data from randomized trials are insufficient to support this approach. To improve the local control rate of chemoradiotherapy, intensification of the radiation dose has been attempted, but this has failed to demonstrate any superiority in terms of local control or survival. The addition of new agents, including molecular targeting agents, to the current standard chemoradiotherapy has shown more promising results and warrants further investigations in future studies. Salvage treatment for patients who do not achieve a complete response (CR) is necessary to improve the overall treatment results. Salvage surgery, as well as endoscopic resection, in selected patients, may provide an improvement in survival. Until high rates of local control can be consistently achieved with chemoradiotherapy alone, these salvage treatments will be an integral component of multimodality treatment for esophageal cancer, and should be active areas for clinical investigations.     

Chemoradiotherapy for uterine cancer: current status and perspectives

The conventional local treatment methods (surgery and radiation) for cervical cancer have reached a plateau in terms of survival benefit and, therefore, in this review, new treatment strategies (combined chemotherapy [CT] and local therapy) to overcome the poor prognosis were examined in high-risk groups. The effectiveness of neoadjuvant chemotherapy (NAC) administered prior to radiotherapy (RT) has not been confirmed for any disease stages. But NAC followed by surgery may improve survival in patients with stage Ib2 compared with surgery alone; and in patients with stage Ib2 to IIB compared with RT alone. Five large randomized clinical trials (RCTs) demonstrated a significant survival benefit for patients treated with concurrent chemoradiotherapy (CCRT), using a cisplatin (CDDP)-based regimen, with a 28%–50% relative reduction in the risk of death. In addition, the results of a metaanalysis of 19 RCTs of CCRT (1981–2000) involving 4580 patients showed that CCRT significantly improved overall survival (OS) hazard ratio ([HR] 0.71; P < 0.0001), as well as progression-free survival (PFS; HR 0.61; P < 0.0001). In line with these results, CCRT is currently recommended as standard therapy for advanced cancer (stage III/IVA) in the United States. However, there remains much controversy and uncertainty regarding the optimal therapeutic approaches, especially for patients with advanced cancer. Additional RCTs should be conducted to find the optimal CT regimen and RT for Japanese patients, considering acute and late complications, as well as differences in pelvic anatomy, total radiation dose, and RT procedures between Japan and other countries. Evidence obtained from such studies should establish the optimal CCRT treatment protocol and define the patient population (disease stage) that the protocol really benefits.     

Chemoradiotherapy as a bladder-preservation approach for muscle-invasive bladder cancer: current status and perspectives

Radical cystectomy has been considered the gold standard for the treatment of muscle-invasive bladder cancer. However, because of disappointing results with radical surgery in terms of survival and decreased quality of life (QOL), bladder-preservation treatment has been introduced as an alternative to radical cystectomy. The primary purpose of the bladder-preservation approach has been to maximize overall cure rates, with the secondary purpose being to preserve the patients bladder. The modalities used to ensure successful bladder preservation include radical transurethral resection (TUR), concurrent cisplatin (CDDP)-based chemotherapy, and radiotherapy. In patients who achieve a complete response (CR) after trimodality therapy, 5-year survival rates of more than 50%, the same as those of radical cystectomy, can be achieved and 70% of this group will retain an intact functional bladder.In this article, bladder-preservation studies using chemoradiotherapy are reviewed.     

Chemoradiotherapy for brain tumors: current status and perspectives

Brain tumors growing in the parenchyma of the brain infiltrate diffusely, and the role of surgery is restricted to maximal tumor-bulk removal. Residual tumor cells beyond the surgical margin are not killed by conventional radiation therapy with 60Gy. Many clinical trials delivering chemotherapy during radiation therapy and after radiation therapy have been performed, but the results remain poor. Here the author reviews the current treatments of gliomas, malignant lymphomas, medulloblastomas, and germ cell tumors, and their results.     

Chemoradiotherapy for pancreatic cancer: current status and perspectives

The poor prognosis of pancreatic cancer is due to both its metastasis-prone and locally resistant nature. To improve therapeutic outcome, a multimodality approach is necessary. Chemoradiotherapy has been regarded as one of the standard treatment options, particularly for locally advanced pancreatic cancer. A number of clinical studies have been undertaken to establish the use of chemoradiotherapy, with or without surgical resection. This review systematically summarizes the current status, controversies, and prospects of postoperative, definitive, and preoperative chemoradiotherapy for pancreatic cancer.     

Small cell lung cancer transformation from EGFR-mutated lung adenocarcinoma: A case report and literatures review

Epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the response of non-small cell lung cancer (NSCLC) with EGFR-mutant patients. However, these patients inevitably come cross acquired resistance to EGFR-TKIs. The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) following treatment with EGFR-TKIs is rare, which leads to resistance to EGFR-TKIs.

The present case concerns a case of a 38-year-old man presenting with cough and dyspnea. Radical resection was performed and confirmed an EGFR exon 21 L858R lung adenocarcinoma. However, the patient suffered pleural metastasis after successful treatment with surgery and adjuvant treatment. So, erlotinib was administered with 18 months. Because of enlarged pleural nodule, repeat biopsy identified an SCLC and chemotherapy was started. However, despite the brief success of chemotherapy, our patient suffered brain metastasis.

Our case emaphsizes both the profile of transformation from NSCLC to SCLC and the importance of repeat biopsy dealing with drug resistance. We also summarize the clinical characteristics, mechanisms, predictors of SCLC transformation, treatment after transformation and other types of transformation to SCLC.     

The surgical management of lung cancer

Since the introduction of the pneumonectomy as a technically feasible strategy for the treatment of lung cancer, surgical resection has played a pivotal role in the management of early stage non-small cell lung carcinoma (NSCLC). In the last two decades, surgical, medical, and radiation oncologists have produced a growing body of evidence to support the combination of neoadjuvant or adjuvant treatments with standard surgical resection, to improve disease-free and overall survival for specific patient subgroups. Furthermore, alternatives to aggressive surgical management have evolved for patients who are medically inoperable due to compromised pulmonary function or other comorbidities. In this review, surgical options and multimodal treatment strategies are discussed, as well as completed and ongoing clinical trials addressing the surgical management of NSCLC.     

Induction Chemoradiotherapy Followed by Surgery for Stage III Non-small Cell Lung Cancer

Twenty-five patients with stage III, non-small cell lung cancerwere treated with cisplatin-based chemotherapy and thoracicradiation therapy followed by surgery. Thirteen patients hadstage IIIA disease and 12, stage IIIB disease. The chemotherapyand radiotherapy were intensively combined with only a few days'interval between them. Radiation therapy delivering a totaldose of 50–70 Gy was started 10 days after the beginningof chemotherapy. A few additional courses of chemotherapy wererepeated until a thoracotomy was performed. All but two surgicallytreatedpatients underwent tumor resection, with 19 lobectomies andfour pneumonectomies. Eighteen patients underwent curative andfive, non-curative resections. Pathological examination of theresected specimen provided accurate intrathoracic information.Six patients (24%) showed a pathologically complete response,with no cancer cells detected in the resected specimens. Severepostoperative complications occurred in five patients (20%),with one death. The disease recurred in five of the 18 patientswho underwent a curative resection. A second primary tumor developedin two other patients. Seventeen patients (68%) are alive, witha median follow-up of 37 months after thoracotomy. The estimatedthree-year survival was 67% for all patients.     

Chemoradiotherapy for head and neck cancer: current status and perspectives

Chemoradiotherapy for head and neck cancer has achieved remarkable progress in the past two decades. This progress has resulted in efforts to redefine the standard of care for patients with this disease. A brief review of the history of current chemoradiotherapy was conducted to clarify the rationale for this approach. An attempt was made to present problems that remain to be solved. The review showed that chemoradiotherapy for head and neck cancer is now becoming a vital treatment option for patients with advanced disease. Currently available and upcoming data are about to clarify important issues regarding proper patient selection, standard procedures, management of toxicities, ultimate cure, and quality of life. This newly developed and promising treatment option has, however, confounding problems to be solved. Meticulous collaboration in an experienced multidisciplinary team is required to address these problems and to spread this approach in daily clinical practice.     

化疗和放射治疗应用时机和顺序与肺癌疗效(附94例局限期小细胞肺癌临床观察)

目的　评价局限期小细胞肺癌应用化疗和放射治疗时机和顺序的重要性。方法　94例局限期小细胞肺癌按化疗和放射治疗使用的时间和顺序随机分为先化疗后放射治疗组( 简称序贯组,46 例) 和化疗、放射治疗交替组(简称交替组,48 例) 。化疗方案用顺铂(Cisplatin,PDD) 依托泊甙(Etoposide,VP16)(EP方案) ,顺铂20 mg/m2 ,1～5 天,依托泊甙100 mg/m2 ,1 ～3 天,每3 ～4 周1疗程,共6 疗程。60Co 放射治疗:每次2 Gy,5 周,50 Gy;交替组在第1 个疗程化疗后第3 天开始,序贯组则在6 个疗程化疗结束后。结果　交替组完全缓解率高于序贯组(66 .7 % 对58.7% ),但差异无显著意义(P> 0.05) 。交替组2 年生存率高于序贯组(43.7 % 对23 .9 %) ,差异有显著意义( P<0 .05) 。结论　交替组疗效优于序贯组,提示尽早放射治疗可提高小细胞肺癌生存率;EP方案可作为与放射治疗交替使用的首选化疗方案     

非小细胞肺癌放化综合治疗的前瞻性随机研究

目的 对比观察非小细胞肺癌单纯放疗和放化综合治疗的疗效。方法 从１９９５年１月 到１９９７年１２月,将符合入组条件的８２例非小细胞肺癌患者随机分为放疗组和化放疗综合治疗组。其中完成治疗计划的有７４例,３５例属单纯放疗组,３９例属化放疗综合治疗组。综合治疗组中２１例为增敏化疗（氟脲嘧啶、顺铂）,在放疗的第１、４周给药;１８例为联合方案化疗,在放疗前、中、后进行,最少两周期,药物为卡铂、顺铂、足叶乙甙     

Evaluation of the Simplified Comorbidity Score (Colinet) as a prognostic indicator for patients with lung cancer: A cancer registry study

Introduction

A Simplified Comorbidity Score (SCS) provided additional prognostic information to the established factors in patients with non-small cell lung cancer lung cancer. We undertook this analysis to test the prognostic value of the SCS in a population-based study.

Patients and methods

Retrospective survey of all Victorians diagnosed with lung cancer in January–June 2003, identified from the Victorian Cancer Registry.

Results

There were 921 patients, with data available for 841 (91.3%). Median age was 72 years (range 30–94) and 63.1% were male. A tissue diagnosis was made for 89.9%, of which 86.6% were non-small cell (NSCLC), and 13.4% small cell carcinoma (SCLC). Comorbidities on which the SCS is based were distributed: cardiovascular 54.6%; respiratory 38.9%; neoplastic 19.9%; renal 4.6%; diabetes 11.7%; alcoholism 5.5%; and tobacco 83.1%.In patients with NSCLC, higher SCS score (>9) was associated with increasing stage, ECOG performance status, male sex, increasing age, tobacco consumption and not receiving treatment. Using Cox regression, survival was analysed by SCS score after adjusting for the effect of age, sex, cell type (NSCLC, SCLC, no histology), ECOG performance status and stage for all patients and then restricted to NSCLC. As a continuous or dichotomous (≤ or >9) variable, SCS was not a significant prognostic factor for all patients or when restricted to NSCLC.

Conclusion

In this retrospective analysis of population based registry patients, SCS did not provide additional prognostic information in patients with lung cancer. ECOG performance status may be a substitute for the effect of comorbidity.     

局部晚期非鳞非小细胞肺癌同步放化疗两种方案比较研究

目的 比较两种方案治疗局部晚期非鳞非小细胞肺癌副反应及近期疗效。方法 回顾2009年3月—2013年1月42例局部晚期非鳞非小细胞肺癌患者,所有患者均接受同步放化疗,A组放疗同步培美曲塞+顺铂化疗,B组放疗同步多西他赛+顺铂化疗,比较A、B两组患者副反应及近期疗效。结果 A组28例患者,B组14例患者,两组副反应比较,血液毒性:白细胞减少、中性粒细胞减少、血色素降低、血小板减少无统计学差异(P＞0.05)。非血液毒性:放射性肺损伤发生率、咳嗽发生率B组明显高于A组,有统计学差异(P＜0.05)。而其他非血液毒性:肝功能损伤、肾功能损伤、发热、呼吸困难、放射性食管炎、乏力、体重下降、消化道反应、皮肤反应均无统计学差异(P＞0.05)。近期疗效:A、B两组有效率分别为75%及71.43%,无统计学差异(P＞0.05)。结论 放疗同步培美曲塞+顺铂化疗与同步多西他塞+顺铂化疗的两组疗效无显著差异,但培美曲塞在治疗局部晚期非鳞非小细胞肺癌副反应方面存在一定优势。     

非小细胞肺癌抗血管生成治疗研究现状

血管生成是指从已有血管网络中生成新生血管的生理过程.在肿瘤微环境中,一个不断增长的肿瘤的动态平衡有利于转向持续促血管生成状态.自人类认识到可以通过抵抗肿瘤血管生成从而抑制肿瘤生长后,抗血管生成药物应运而生并已被应用在多种实体肿瘤中,包括肺癌.本文就肿瘤血管生成以及非小细胞肺癌抗血管生成的研究现状进行综述.     

Current treatment landscape for oligometastatic non-small cell lung cancer

The management of patients with advanced non-small cell lung carcinoma (NSCLC) has undergone major changes in recent years. On the one hand, improved sensitivity of diagnostic tests, both radiological and endoscopic, has altered the way patients are staged. On the other hand, the arrival of new drugs with antitumoral activity, such as targeted therapies or immunotherapy, has changed the prognosis of patients, improving disease control and prolonging survival. Finally, the development of radiotherapy and surgical and interventional radiology techniques means that radical ablative treatments can be performed on metastases in any location in the body. All of these advances have impacted the treatment of patients with advanced lung cancer, especially in a subgroup of these patients in which all of these treatment modalities converge. This poses a challenge for physicians who must decide upon the best treatment strategy for each patient, without solid evidence for one optimal mode of treatment in this patient population. The aim of this article is to review, from a practical and multidisciplinary perspective, published evidence on the management of oligometastatic NSCLC patients. We evaluate the different alternatives for radical ablative treatments, the role of primary tumor resection or radiation, the impact of systemic treatments, and the therapeutic sequence. In short, the present document aims to provide clinicians with a practical guide for the treatment of oligometastatic patients in routine clinical practice.     

晚期非小细胞肺癌免疫治疗现状及未来方向

肺癌仍然是中国发病率和死亡率最高的恶性肿瘤,其中非小细胞肺癌（non-small cell lung cancer,NSCLC）约占80%以上。以靶向程序性死亡[蛋白]-1（programmed death protein-1,PD-1）或程序性死亡[蛋白]配体-1（programmed death ligand-1,PD-L1）的免疫检查点抑制剂（immune checkpoint inhibitor,ICI）为基础的治疗已成为了晚期肺癌的标准治疗手段之一。本综述将对晚期NSCLC免疫治疗的现状予以梳理,探讨现阶段面临的问题与挑战,并思考与展望未来发展方向。     

平消胶囊联合化疗治疗肺癌初步临床疗效分析

目的 观察平消胶囊联合化疗治疗对一线治疗无效的小细胞及非小细胞肺癌的疗效及毒副反应。方法 从2002年5月至2003年3月应用平消胶囊联合其他常用化疗药物组成的联合化疗方案治疗非小细胞肺癌42例，小细胞肺癌11例。结果 总有效率(CR PR)为68．2％，血液毒性：WBC减少为68％，其中Ⅲ度占13．3％，无Ⅳ度反应。PLT减少为59％，其中Ⅲ度占9．1％，无Ⅳ度反应。无严重非血液毒性。结论 本组资料显示平消胶囊与其它化疗药物联合治疗小细胞及非细胞肺癌获得68．2％的疗效并且未有明显的血液及非血液系统毒副反应，是有效、经济和安全的。     

Angiogenesis and antiangiogenic treatment in lung cancer

Angiogenic factors released by cancer cells increase structurally and functionally abnormal tumor micro-vascularization, resulting in metastases and progressive disease. Such diffusible factors bind to specific receptors of endothelial cells and activate the angiogenic signal pathway. Treatments with antiangiogenic monoclonal antibodies (e.g., bevacizumab) or using small molecules with anti-tyrosine kinase activity (e.g., sunitinib, sorafenib, ZD6474, erlotinib, or thalidomide) can block angiogenic signaling, lower blood tumoral irrigation, and improve chemotherapy distribution. Numerous studies have shown that a combination of biotherapy and chemotherapy can improve medical management of patients with advanced or metastatic non-small cell lung carcinomas. Biotherapy combination approaches also yield encouraging results promoting the development of targeted antitumor drugs.