Targeting HER 2 and angiogenesis in gastric cancer

Gastric cancer is one of the most commonly diagnosed and the second leading cause of cancer death worldwide. Surgery combined with multimodal therapy remains the only curative therapy. However, local relapse or distant metastases occur in more than 50% of radically resected patients. Due to molecular therapies, targeting HER2 and angiogenesis, major advances in the treatment of gastric cancer could be achieved. Nevertheless, development of resistance to monoclonal antibodies, such as trastuzumab, is arising. Currently a number of promising new therapeutic are under investigation, combining chemotherapy with newly developed agents to overcome cancer resistance. In this review we report current clinical applications of targeted therapies and overview ongoing trials, investigating the use of monoclonal antibodies in (HER2 positive) gastric cancer.     

Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial)

A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m² paclitaxel, 100 mg/m² cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56–70 Gy in 5.5–7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4–72.2%), after 42 months was 56.5% (95% CI, 44.2–68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9–55.0%); after 42 months, 41.3% (95% CI, 29.3–53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials. This trial was initiated and conducted by the German Larynx Organ Preservation Study Group (DeLOS) which was founded as collaboration between head and neck surgeons and radiation oncologists to focus on the role of multimodality treatment in advanced laryngeal and hypopharyngeal cancer in Germany.     

32例初发初治晚期恶性肿瘤合并血小板减少临床分析

目的：探讨初发初治晚期恶性实体瘤合并血小板减少的常见病因及其对化疗的影响。方法：对32例初发初治晚期恶性肿瘤合并血小板减少的病因及化疗后的结果进行回顾性分析。结果：32例引起初发初治晚期恶性实体瘤合并血小板减少的病因：脾功能亢进6例,弥散性血管内凝血5例,骨髓增生减低2例,巨核系成熟障碍3例,免疫性因素14例,肿瘤侵犯骨髓2例;其中30例进行了化疗,PR19例,SD 11例。结论：初发初治晚期恶性实体瘤合并血小板减少,大多数可耐受化疗,并从化疗中获益。     

胆道支架置放结合动脉化疗栓塞治疗恶性梗阻性黄疸

目的 探讨胆道支架置放结合动脉化疗栓塞治疗恶性梗阻性黄疸的疗效。方法 28例恶性梗阻性黄疸患者行经皮穿肝胆道引流术后,采用置放胆道支架（总计33枚）结合动脉化疗栓塞（总计53次）的治疗方法。分别观察血清胆红素下降程度,手术并发症,并随访患者生存期和胆道支架维持通畅时间。结果 28例患者中2例失访,平均生存期为17．7个月,平均支架维持通畅时间为15．3个月。结论 胆道支架置放结合动脉化疗栓塞治疗恶性梗阻性黄疸有较好疗效。     

局限期小细胞肺癌放化疗后疗效与脑转移的关系探讨*

目的：探讨局限期小细胞肺癌（LD-SCLC ）放化疗后疗效与脑转移的关系。方法：回顾性分析天津医科大学肿瘤医院放疗科2009年4 月至2012年4 月间行放化疗的149 例LD-SCLC患者临床资料,放化疗后疗效评价根据RECIST标准分为完全缓解（CR）、部分缓解（PR）、病情稳定（SD）及疾病进展（PD）,客观缓解包括CR和PR。生存分析采用Kaplan-Meier 法并用Log-rank进行检验,χ2检验进行组间比较。结果：全组患者的中位生存时间（OS）为20.0 个月,3 年OS为33.0% 。多因素分析发现,放化疗后疗效（P < 0.001）及是否出现脑转移（P < 0.001）是影响患者OS的重要因素。全组共43例（28.8%）出现脑转移,CR、PR、SD/PD 患者分别有12例（29.3%）、9 例（11.8%）、22例（68.8%）出现脑转移（P = 0.027）。 放化疗后疗效与无脑转移生存率（BMFS）之间差异具有统计学意义（P = 0.005）,CR、PR、SD及PD患者的2 年BMFS分别为79.5% 、71.9% 、45.8% 和49.6% 。进一步分析发现,放化疗后达CR者,行脑预防性放疗（PCI）与未行PCI 患者的生存率亦存在统计学差异（P = 0.007）。 结论：LD-SCLC患者放化疗后达CR者有较好的BMFS和较低的脑转移率,且行脑预防照射者OS亦优于未行脑预防者,建议放化疗后达CR患者,应尽快考虑脑预防放疗。     

Local recurrences in western low rectal cancer patients treated with or without lateral lymph node dissection after neoadjuvant (chemo)radiotherapy: An international multi-centre comparative study

BackgroundIn the West, low rectal cancer patients with abnormal lateral lymph nodes (LLNs) are commonly treated with neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). Additionally, some perform a lateral lymph node dissection (LLND). To date, no comparative data (nCRT vs. nCRT + LLND) are available in Western patients.MethodsAn international multi-centre cohort study was conducted at six centres from the Netherlands, US and Australia. Patients with low rectal cancers from the Netherlands and Australia with abnormal LLNs (≥5 mm short-axis in the obturator, internal iliac, external iliac and/or common iliac basin) who underwent nCRT and TME (LLND-group) were compared to similarly staged patients from the US who underwent a LLND in addition to nCRT and TME (LLND + group).ResultsLLND + patients (n = 44) were younger with higher ASA-classifications and ypN-stages compared to LLND-patients (n = 115). LLND + patients had larger median LLNs short-axes and received more adjuvant chemotherapy (100 vs. 30%; p < 0.0001). Between groups, the local recurrence rate (LRR) was 3% for LLND + vs. 11% for LLND- (p = 0.13). Disease-free survival (DFS, p = 0.94) and overall survival (OS, p = 0.42) were similar. On multivariable analysis, LLND was an independent significant factor for local recurrences (p = 0.01). Sub-analysis of patients who underwent long-course nCRT and had adjuvant chemotherapy (LLND-n = 30, LLND + n = 44) demonstrated a lower LRR for LLND + patients (3% vs. 16% for LLND-; p = 0.04). DFS (p = 0.10) and OS (p = 0.11) were similar between groups.ConclusionA LLND in addition to nCRT may improve loco-regional control in Western patients with low rectal cancer and abnormal LLNs. Larger studies in Western patients are required to evaluate its contribution.     

Oncologic impact of lateral lymph node metastasis at the distal lateral compartment in locally advanced low rectal cancer after neoadjuvant (chemo)radiotherapy

IntroductionThe frequency and oncologic outcomes of lateral lymph node (LLN) metastasis at the most distal lateral compartment (DLC) among clinical stage II-III low rectal cancer patients treated with neoadjuvant (chemo)radiotherapy (nCRT) are poorly understood. The aim was to investigate the oncologic impact of LLN metastasis in the DLC versus the proximal lateral compartment (PLC).Materials and methodsConsecutive patients with low rectal cancer treated with nCRT followed by total mesorectal excision and selective LLN dissection including the DLC were analyzed retrospectively. DLC was defined as the area distal to the infra–piriformis foramen on axial MRI images. Size and location of LLN metastasis on MRI, and survival were retrospectively assessed.ResultsOf the 718 patients, 72 (10.0%) had pathological LLN metastasis. Thirty-two (44.4%) had metastasis in the DLC (DLC group), while 40 (55.6%) had metastasis in the PLC without metastasis in the DLC (PLC group). The proportion of ypN2 category tended to be lower in the DLC group (15.6% vs 35.0%, P = 0.105). The median number of metastatic LLN was similar (1 vs. 1, P = 0.691). The median short-axis size of metastatic LLN was smaller in the DLC group than in the PLC group on pre-treatment (P < 0.001) and re-staging (P = 0.004) MRI. By multivariable analysis, LLN metastasis in the DLC was predictive of better disease-free survival (HR, 0.412; 95% CI, 0.159–0.958, P = 0.039).ConclusionLLN metastasis in the DLC is frequent and has favorable oncologic outcomes after surgical dissection with nCRT.     

bFGF反义硫代寡核苷酸增强人喉鳞癌Hep2细胞的化疗敏感性

目的:研究bFGF反义硫代寡核苷酸增强人喉鳞癌Hep2细胞对多柔比星、氟脲嘧啶及顺铂的敏感性。方法:设计、合成bFGF反义脱氧寡核苷酸(AS),用聚乙烯亚胺(jetPEI)介导bFGF反义脱氧寡核苷酸转染入Hep2细胞;半定量RT- PCR测定bFGF反义硫代寡核苷酸转染后细胞中bFGF mRNA水平;免疫细胞化学法检测Hep2细胞转染前后bEGF的表达水平;FACS分析bFGF反义硫代寡核苷酸诱导细胞的凋亡;MTT法检测bEGF反义硫代寡核苷酸及其与化疗药物联合处理后的细胞增殖。结果:bFGF反义硫代寡核苷酸呈剂量与时间依赖抑制Hep2细胞增殖,最高抑制率为25.5%;被转染细胞bFGF mRNA和蛋白的表达分别降低52.0%和41.1%,细胞凋亡率为20.5%;bFGF反义硫代寡核苷酸协同多柔比星、氟脲嘧啶及顺铂作用Hep2,使3种药物的IC_(50)分别降低75.5%、83.5%及65.4%。结论:bFGF反义硫代寡核苷酸协同化疗药物增强Hep2细胞对化疗药物敏感性,将为人喉鳞癌的生物和化学药物治疗增添新途径。