Postoperative adjuvant chemoradiation in completely resected locally advanced gastric cancer

BACKGROUND: The 5-year survival of patients with completely resected node-positive gastric cancer ranges from 15% to 25%. We explored the feasibility of a chemoradiation regime consisting of concomitant hyperfractionated radiotherapy and 5-fluorouracil protracted venous infusion (5-FU PVI). MATERIALS AND METHODS: Forty patients received a total or partial gastrectomy operation and D2 nodal resection for Stage III gastric cancer; they were then irradiated by linac with 6-15-MV photons. The target included the gastric bed, the anastomosis, stumps, and regional nodes. A total dose of 55 Gy was given in 50 fractions using 1.1 Gy b.i.d. All patients received a concomitant 200 mg/m2/day 5-FU PVI. Patients were examined during the follow-up period as programmed. Toxicity was recorded according to RTOG criteria. RESULTS: After a median follow-up of 75.6 months (range: 22-136 months), 24 (60%) patients had died, and 16 (40%) were alive and free of disease. The 5-year actuarial incidence of relapse was 39%, 22%, and 2% for distant metastases, out-field peritoneal seeding, and in-field local regional recurrences, respectively. The 5-year actuarial cause-specific survival was 43%. Three patients survived more than 11 years. Acute > or = Grade 3 toxicity consisted of hematologic (22.5%) and gastrointestinal toxicity (nausea and vomiting 22.5%, diarrhea 2.8%, and abdominal pain 2.6%). No late toxicity was observed. CONCLUSION: This regime of concomitant 5-FU PVI and hyperfractionated radiotherapy was well tolerated and resulted in successful locoregional control and satisfactory survival.     

Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer

Background.

To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ) cancer treated at a single institution.

Patients and methods.

Between 1/2004 and 6/2012, 90 patients with locoregionally advanced GEJ or unresectable gastric cancer were treated with preoperative radiochemotherapy at the Institute of Oncology Ljubljana. Planned treatment schedule consisted of induction chemotherapy with 5-fluorouracil and cisplatin, followed by concomitant radiochemotherapy four weeks later. Three-dimensional conformal external beam radiotherapy was delivered by dual energy (6 and 15 MV) linear accelerator in 25 daily fractions of 1.8 Gy in 5 weeks with two additional cycles of chemotherapy repeated every 28 days. Surgery was performed 4–6 weeks after completing radiochemotherapy. Following the surgery, multidisciplinary advisory team reassessed patients for the need of adjuvant chemotherapy. The primary endpoints were histopathological R0 resection rate and pathological response rate. The secondary endpoints were toxicity of preoperative radiochemotherapy and survival.

Results.

Treatment with preoperative radiochemotherapy was completed according to the protocol in 84 of 90 patients (93.3%). Twenty patients (22.2%) did not undergo the surgery because of the disease progression, serious comorbidity, poor performance status or still unresectable tumour. In 13 patients (14.4%) only exploration was performed because the tumour was assessed as unresectable or diffuse peritoneal carcinomatosis was established. Fifty-seven patients (63.4%) underwent surgery with the aim of complete removal of the tumour. Radical resection was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). In this group of patients (n = 57), pathological complete response of tumour was achieved in five patients (5.6% of all treated patients or 8.8% of all operated patients). Down-staging was recorded in 49 patients (86%), in one patient (1.8%) the stage after radiochemotherapy was unchanged while in seven patients (12.3%) the pathological stage was higher than clinical, mainly due to higher pN stage. No death was recorded during preoperative radiochemotherapy. Most grade 3 and 4 toxicities were due to vomiting, nausea and bone marrow suppression (granulocytopenia). Twenty-six (45.6%) patients died due to GEJ or gastric carcinoma, one died because of septic shock following the surgery and a reason for two deaths was unknown. Twenty-eight patients (49.1%) were disease free at the time of analysis, while 29 patients (50.9%) developed the recurrence, mostly as distant metastases. At two years, locoregional control, disease-free survival, disease-specific survival and overall survival were 82.9%, 43.9%, 56.9% and 53.9%, respectively.

Conclusions.

Preoperative radiochemotherapy was feasible in our group of patients and had acceptable toxicity. Majority of patients achieved down-staging, allowing greater proportion of radical resections (R0), which are essential for patients’ cure.     

Adjuvant chemoradiation versus chemotherapy in completely resected advanced gastric cancer with D2 nodal dissection

Aim: Adjuvant chemoradiation has become a standard of care in the USA. We evaluated the efficacy and toxicity of adjuvant chemoradiation versus chemotherapy in completely resected locally advanced gastric cancer. Methods: Patients with stage IIIA, IIIB and IV (without metastasis) gastric cancer were treated with chemoradiation and 5‐fluorouracil/cisplatin (FP) (arm A) or FP (arm B). Arm A consisted of one cycle of FP followed by 4500 cGY to radiation field with capecitabine. One month after completion of radiotherapy, patients received three additional cycles of FP every 3 weeks. Arm B consisted of six cycles of FP. Results: A total of 61 patients were enrolled, of whom 31 were placed in arm A and 30 in arm B. The median follow‐up duration was 77.2 months (range 24–92.8 months). We did not find any difference in 3‐year disease‐free survival between arm A and B (80.0 vs 75.2%, respectively; P = 0.887). There was no significant difference between the arms in 5‐year disease‐free survival (76.7 vs 59.1%, respectively; P = 0.222) or overall survival (70.1 vs 70.0%, respectively; P = 0.814). Seven patients (22.6%) relapsed in arm A and 12 patients (40%) relapsed in arm B. Grade 3/4 neutropenia occurred in 48.5% of patients in arm A and 22.9% in arm B. Grade 3 nausea or vomiting occurred in 6% in arm A and 14.6% in arm B. Conclusion: We could not make any conclusion about the benefit of adding radiation to adjuvant chemotherapy.     

Adjuvant therapy in completely resected non-small-cell lung cancer

Less than 20% to 25% of patients with non-small-cell lung cancer (NSCLC) present with stage I or II disease and are best treated by surgical resection. Long-term survival in early NSCLC remains poor. The 5-year survival rate of patients who undergo complete surgical resection is only 40% to 50%. The majority of relapses after surgery are distant metastases; the risk of a local recurrence after complete resection is less than 10%. Postoperative treatments, including chemotherapy, radiotherapy, or both modalities together, have been evaluated widely, but unfortunately none of these treatments have demonstrated any significant impact on survival. Data regarding large-scale adjuvant chemotherapy trials that were closed for accrual almost 4 to 5 years ago will be fully available before the end of the year. It is hoped that a specific meta-analysis will be performed on the basis of these data.     

Adjuvant chemotherapy in completely resected non-small-cell lung cancer.

Surgery alone has long been the standard treatment for patients with operable non-small-cell lung cancer (NSCLC). However, despite complete resection, 5-year survival rates have been disappointing, with about 50% of patients eventually suffering relapse and death from disease. Randomized trials conducted in the 1980s hinted at a survival benefit for postoperative cisplatin-based regimens, but they were underpowered. A meta-analysis published in 1995 found a nonsignificant 13% reduction in the risk of death associated with cisplatin-based chemotherapy, with an increase of survival of 5% at 5 years. This led to renewed interest in adjuvant chemotherapy in resected NSCLC. Thousands of patients have been included in a new generation of randomized trials in the last 10 years. Most of these recent studies have now been reported and several have demonstrated a clear survival advantage for patients treated with platin-based adjuvant therapy. These results also suggest a greater benefit with modern two-drug regimens. In view of the most recent data, postoperative platin-based chemotherapy can now be considered the standard of care for completely resected NSCLC patients with good performance status.     

Concurrent radiochemotherapy in the treatment of locally advanced non-small cell lung cancer

Current evidence suggests that concurrent RT/CHT is the standard of treatment in patients with locally advanced, inoperable NSCLC. This treatment approach, however, bears risk of increased toxicity and, therefore, must be carefully balanced regarding the choice of patients suitable for such an intervention. Newer RT technologies, third-generation CHT drugs, and widely used radioprotectors represent the current framework for numerous clinical studies that ultimately will help optimize the treatment of this disease.     

局部晚期直肠癌的术前同步放射治疗和化疗

目的 观察１５例局部晚期直肠癌术前放射治疗和化疗（术前放化组）后外科手术的结果，以同期２７例直肠癌术前放射治疗加手术治疗作为对照组，分析其疗效及毒副反应。方法 １５例局部晚期直肠癌予术前放射治疗（ＤＴ４０～４６Ｇｙ，２０～２３次，４～５周完成）加同步化疗（氟尿嘧啶加甲酰甲氢叶酸钙静脉滴注和脱氧氟尿苷口服），对照组为同期２７例局部晚期直肠癌，予术前放射治疗，ＤＴ４０～５０Ｇｙ，２０～２５次，４～５周     

局部进展期胃癌根治术后同期放化疗与单纯化疗的临床比较

目的 比较局部进展期胃癌根治术后同期放化疗(RCT)与单纯化疗(CT)的疗效和不良反应。 方法 83例患者随机分为RCT组(43例)和CT组(40例)。RCT组采用三维适形放疗45 Gy同期口服卡培他滨化疗(1600mg/m²),放疗结束2周后继续用FOLFOX4方案巩固化疗 4~6周期。CT组采用FOLFOX4方案化疗 6~8周期。Kaplan Meier 法计算生存率等并 Logrank 检验。结果 随访率为96%,RCT和CT组随访时间满2、3年者分别为37、12例和31、10例。RCT组和CT组1、2、3年局部控制率分别为100%、97%、94%和95%、87%、73%(χ²=4.54,P=0.033),生存率分别为98%、86%、81%和93%、80%、64%(χ²=3.96,P=0.047)。RCT组和CT组治疗期间≥3级白细胞下降发生率分别为23%和15%(χ²=0.93, P=0.630), ≥3级胃肠道反应发生率分别为16%和10%(χ²=0.95,P=0.624)。结论 局部进展期胃癌根治术后RCT比CT可提高患者局部控制率和生存率,不良反应可耐受。     

局部进展期胃癌术前化疗与术前放化疗的对比研究

背景与目的：术前化疗和术前放化疗都是胃癌治疗指南推荐的针对局部进展期胃癌患者的治疗方法。然而,由于缺乏对比性的研究证据,两者的优劣性不详。本研究将对比术前放化疗与术前化疗在临床疗效及毒性反应之间的差异。方法：2007年6月—2012年10月期间,30例局部进展期胃癌患者入组一项术前化疗的Ⅱ期临床试验,采用EOF（表柔比星+奥沙利铂+氟尿嘧啶）方案进行3~4个周期的术前化疗,对于能手术的患者予以手术,术后给于2~3个周期的EOF方案化疗。2012年4月—2014年8月,40例局部晚期胃癌患者入组一项术前放化疗的Ⅱ期临床试验,患者接受1个周期的SOX［替吉奥（S-1）+奥沙利铂］方案化疗,继续行同步放化疗,再进行1个周期的SOX方案化疗,对于能手术的患者予以手术,术后给于4个周期的SOX方案化疗。比较两项临床试验患者的临床病理特点、术前治疗的效果、R0手术切除率、预后及不良反应。结果：术前化疗临床试验定义为化疗组,有30例胃癌患者入组,且完成了所有的术前化疗,都可评估。术前放化疗临床试验定义为放化疗组,有40例胃癌患者入组,其中36例（90%）患者可评估。两组间的基线参数,如性别、年龄、美国东部肿瘤协作组（Eastern Cooperative Oncology Group,ECOG）评分、临床T分期、临床N分期及肿瘤部位,差异无统计学意义。化疗组的临床有效率（CR+PR）为30%（9/30）,放化疗组的临床有效率（CR+PR）为41.7%,两者间的差异无统计学意义（P>0.05）。化疗组与放化疗组间的R0手术切除率差异无统计学意义（46.7% vs 66.7%）。放化疗组的病理有效率高于化疗组,且差异有统计学意义（50.0% vs 23.3%）。术前放化疗组的毒性反应较化疗组明显。放化疗组的3年总生存率为41%,高于化疗组的20% （P=0.009）。结论：放化疗组的病理有效率及3年总生存率高于化疗组。急性毒性反应也较化疗组明显,但无严重的毒性反应。     

Neoadjuvant radiochemotherapy for locally advanced gastric cancer: a phase I-II study.

BACKGROUND: To study in a phase I-II trial the maximum tolerated dose, the toxicity, and the tolerance of adding radiotherapy to systemic chemotherapy administered preoperatively in patients with locoregionally advanced gastric adenocarcinoma. PATIENTS AND METHODS: Patients with adenocarcinoma of the stomach (T(3)(-)(4)N(any) or T(any)N+), performance status 相似文献   

Adjuvant treatment in resected lung cancer

There have been many attempts to develop effective postoperative adjuvant therapy in patients with resected lung cancer. Metastatic disease is the commonest site of first recurrence. In squamous cell carcinoma local failure is another major problem and in adenocarcinoma brain metastases are frequent. There is evidence to suggest that radiotherapy can prevent local recurrence but does not appear to impact on survival. Response rates to chemotherapy alone and chemo-radiotherapy with prolongation of disease-free survival have been encouraging in locally advanced (resected stage II, III) disease when treated postoperatively. Results of clinical trials using immunotherapy or chemotherapy in early stage disease have been disappointing. Several prospective randomized studies by the Lung Cancer Study Group were undertaken to assess the merits of various adjuvant treatments and are presented.     

局部进展期胃癌的诊治

胃癌发病率在男性恶性肿瘤中仅次于肺癌占第二位,在女性恶性肿瘤中居第四位,而局部进展期胃癌占胃癌中大多数,提高其诊治水平是提高胃癌5年生存率的关键。近年来有关局部进展期胃癌的基础及临床研究均取得了一定的成果,现就局部进展期胃癌的诊断及治疗进展作一综述。     

局部进展期胃癌的综合治疗

局部进展期胃癌由于局部区域复发率高,影响治疗的疗效.胃癌根治术后的辅助性放化疗可进一步提高疗效,对于接受D2手术的患者,术后同步放化疗仍可能提高生存率.无论术前放疗还是术前化疗都可以提高局部进展期胃癌的切除率,降低局部复发率,并延长生存期,是目前局部进展期胃癌的研究方向.     

Neoadjuvant radiochemotherapy for locally advanced gastric cancer: long-term results of a phase I trial

PURPOSE: To assess the long-term results of radiation therapy (RT) when added preoperatively to systemic chemotherapy in patients with locally advanced gastric cancer. METHODS AND MATERIALS: Patients presenting with T3-4 or N+ gastric cancer received two cycles of cisplatin 100 mg/m2 d1, 5FU 800 mg/m2 d1-4, and Leucovorin 60 mg twice daily d1-4; one cycle before and one concomitantly with hyperfractionated RT (median dose, 38.4; range, 31.2-45.6 Gy). All patients underwent a total or subtotal gastrectomy with D2 lymph node resection. RESULTS: Nineteen patients were accrued and 18 completed the neoadjuvant therapeutic program. All patients were subsequently operated and no fatality occurred. At a mean follow-up of 8 years for the surviving patients, no severe late toxicity was observed. The 5-year locoregional control, disease-free, and overall survival were of 85%, 41%, and 35%, respectively. The peritoneum was the most frequent site of relapse. Among long terms survivors, no severe (Radiation Therapy Oncology Group Grade 3-4) late complication was reported. CONCLUSIONS: The present neoadjuvant treatment does not seem to increase the operative risk, nor the late side effects. The encouraging locoregional control rate suggests that the neoadjuvant approach should be considered for future trials in locally advanced gastric cancer. Also, the frequency of peritoneal recurrence stresses the need for a more efficient systemic or intraperitoneal treatment.     

局部进展期胃癌围手术期治疗研究进展

对于初始不可切除的局部进展期胃癌患者,东西方治疗方法不尽相同,以手术为基础的多学科综合诊疗是目前的基本治疗策略。在西方国家,围手术期化疗或术后辅助放化疗是首选治疗方式;而亚洲胃D2切除术后辅助化疗是标准治疗方案,近年来,亚洲也在积极开展关于胃癌围手术期治疗的研究,虽然围手术期化疗的疗效已得到保障,但是否联合放疗、是否联合靶向治疗或免疫治疗仍未有统一标准,如何优化治疗模式和疗效预测仍是急需解决的问题。本文综述了局部进展期胃癌围手术期治疗的研究现状,并对其存在的问题及未来的发展前景进行了展望。     

微波热疗联合放化疗治疗进展期胃癌的临床疗效初步观察

目的:初步观察微波热疗联合调强放疗(IMRT)及化疗治疗进展期胃癌的临床疗效。方法:选取不能手术或拒绝手术,经胃镜病理及影像学证实为局部晚期的近端或远端胃癌患者40例。IMRT总剂量为46～56 Gy(中位数50 Gy),1.8～2.0 Gy/次,5次/周;同步热疗温度42～44℃,45 min/次,2次/周;同步化疗...     

新辅助化疗在局部晚期胃癌治疗中的应用

背景与目的：由于临床上治疗局部晚期胃癌的效果仍较差,近几年来,新辅助化疗在局部晚期胃癌治疗中的作用又成为热点.本研究探讨FOLFOX改良新辅助化学方案治疗局部晚期胃癌的疗效及毒副作用.方法：2002年12月-2006年12月,有39例局部晚期胃癌患者入组本次临床研究.入组患者接受的新辅助化疗方案：奥沙利铂（Oxa）145 mg/m2,第1天,静滴2 h,继而亚叶酸钙（CF）500 mg及氟尿嘧啶（5-FU）3.5 g/m2分别置入微量泵内持续滴注5 d,每隔2周为一个周期,共2个周期.观察新辅助化疗后肿瘤原发病灶的缓解情况,并观察毒副反应.结果：所有接受新辅助化疗后的患者临床有效率（CR＋PR）为62.0%（24/39）,SD 11例（28.2%）,PD 4例（10.3%）,39例患者均进行了手术,3例无法手术切除,手术切除率为92.3%（36/39）.毒副反应主要为白细胞减少症、腹泻、恶心、呕吐、脱发、口腔炎.结论：以FOLFOX改良新辅助化疗方案在局部晚期胃癌的治疗中近期疗效显著,耐受性良好.