Adjuvant radiochemotherapy in the treatment of completely resected, locally advanced gastric cancer

PURPOSE: To analyze the efficacy and toxicity of adjuvant whole abdomen irradiation (WAI) and concomitant chemotherapy in the treatment of completely resected, high-risk gastric cancer. METHODS AND MATERIALS: Between October 1990 and September 1997, 52 patients with completely resected gastric cancer, with lymph node and/or serosal involvement, were treated. Ages were 16-78 (median, 53.5) years. Treatment was either total- or sub-total gastrectomy, followed by WAI, 2100 cGy/21 fractions plus a 2400 cGy/16 fractions boost to the tumor bed. Chemotherapy consisted of either 5-fluorouracil (5-FU) 450-500 mg/m(2) i.v. for 5 days first and 5th week or 200-300 mg/m(2) continuous infusion during irradiation. No further chemotherapy was given. RESULTS: With a minimum follow-up of 30 months and a median follow-up of 43.5 months, 25 of the 52 patients have died. Overall 5-year survival rate is 54%. Three patients sustained Grade 3-5 complications. Two patients with Grade 5 complications (malabsorption syndrome) died 31 and 56 months after the beginning of the treatment, respectively, with no evidence of recurrent tumor. For patients with involvement of the lymph nodes alone (n = 19) the 5-year survival was 69%, which was significantly better than the 36% 5-year survival observed for those patients with both serosal and lymph node involvement (n = 26, p = 0.004). CONCLUSION: Adjuvant radiochemotherapy, WAI, and concomitant 5-FU, is a feasible and a fairly well-tolerated treatment for patients with locally advanced (involvement of the lymph nodes or serosa) gastric carcinoma who undergo complete resection. The 54% overall 5-year survival compares favorably with the survival reported after surgery alone for those patients.     

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.     

早期非小细胞肺癌完全切除术后的辅助治疗

外科手术切除是早期非小细胞肺癌的标准治疗方式,文献报道外科可以提供给早期肺癌病人最佳的治愈率。然而,标准的肺叶切除或全肺切除及纵隔淋巴结清扫后IA期病人的5年生存率为68.5%,IB期为66.6%,许多病人死于癌转移[1]。而肺段切除则较多发生局部复发     

Postoperative adjuvant therapy for completely resected early-stage non-small cell lung cancer

Consensus on adjuvant therapy for completely resected non-small cell lung cancer until 2002 was as follows. (1) There was no significant impact of postoperative adjuvant chemotherapy based on meta-analysis and previous clinical trials. (2) Confirmatory studies are necessary in large-scale prospective clinical trials. However, recent mega trials have introduced epoch-making changes for postoperative adjuvant chemotherapy in clinical practice since ASCO 2003. The effectiveness of UFT in N0 patients was confirmed. Patients with completely resected stage I non-small cell lung cancer, especially T2N0 adenocarcinoma, will benefit from adjuvant chemotherapy with UFT. The results of the International Adjuvant Lung Trial (IALT) have confirmed the meta-analysis in 1995. Also, both the JBR10 and Cancer and Leukemia Group B (CALGB) 9633 studies have also confirmed positive IALT results of the benefit for postoperative platinum-based chemotherapy in completely resected non-small cell lung cancer. Adjuvant chemotherapy for pathological stage IB to II, completely resected non-small cell lung cancer is standard care based on clinical trials. UFT showed the strongest evidence for IB in Japan. Platinum doublet chemotherapy with third-generation anticancer agents is also recommended. Adjuvant chemotherapy should be offered as standard care to patients after completely resected early stage non-small cell lung cancer. However, there is no evidence of the feasibility and efficacy for adjuvant chemotherapy with the platinum-based regimen in Japan. Careful management should be necessary in such treatment.The ASCO-JSCO Joint Symposium was held in Kyoto, Japan, on October 29, 2004.     

A case of curatively resected locally advanced pancreatic cancer after chemoradiation therapy

A 68-year-old man admitted for pancreatic tumor detected by US was found by computed tomography(CT)to have locally advanced pancreatic cancer invading the portal vein and neural plexus of the superior mesenteric artery without distant metastasis. We conducted preoperative chemoradiation therapy containing S-1 and hyperfractionated accelerated radiation therapy (50 Gy). Reevaluation of CT after chemoradiation therapy showed that the primary tumor reduced 52% without distant metastasis. Based on these findings, we conducted subtotal stomach-preserving pancreaticoduodenectomy with portal vein resection. Pathological examination revealed moderately-differentiated adenocarcinoma. Extensive fibrosis with a small amount of cancer cells was observed in the marginal area of the tumor. The portal vein was surrounded with extensive fibrosis and free from cancer cells. Extrapancreatic nerve plexus invasion and lymph node metastasis were not observed. There were no residual cancer cells (R0). The postoperative course was uneventful, and adjuvant chemotherapy (S-1) was started. The patient remains well without recurrence 12 months after surgery.     

Role of post-operative chemoradiation in resected gastric cancer

The curative management of gastric adenocarcinoma depends upon complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are at least 70%-80%. There is continued debate over whether more extensive lymph node dissection (D2) improves survival when compared to less extensive operations. Until recently, attempts at preventing recurrence have employed adjuvant chemotherapy and have been ineffective. A large U.S. Intergroup study (INT-0116) demonstrated that combined chemoradiation following complete gastric resection improves median time to relapse (30 vs. 19 months, P < 0.0001) and overall survival (35 vs. 28 months, P = 0.01). The improvements in disease-free and overall survival resulting from post-operative chemoradiation have defined a new standard of care. An update of the results of INT-0116 analysis performed in 2004 with 7 years median follow-up, not only confirms the benefits from post-operative chemoradiation but also shows that chemoradiation does not produce significant long-term toxicity. The recent publication of the first large adequately powered III neoadjuvant chemotherapy trial suggested this technique might down-stage tumors and increase resectability. Future advances in the therapy of resectable gastric cancer may come from studies of pre-operative neoadjuvant chemoradiation and the application of targeted therapies such as growth receptor antagonists and anti-angiogenesis agents.     

Role of adjuvant radiotherapy in completely resected non-small-cell lung cancer

Most long-term survivors of non-small-cell lung cancer (NSCLC) are patients who have had a completely resected tumour. However, this is only achievable in about 30% of the patients. Even in this highly selected group of patients, there is still a high risk of both local and distant failure. Adjuvant treatments such as chemotherapy (CT) and radiotherapy (RT) have therefore been evaluated in order to improve their outcome. In patients with stage II and III, administration of adjuvant platinum-based chemotherapy is now considered the standard of care, based on level 1 evidence. The role of postoperative radiation therapy (PORT) remains controversial. In the PORT meta-analysis published in 1998, the conclusions were that if PORT was detrimental to patients with stage I and II completely resected NSCLC, the role of PORT in the treatment of tumours with N2 involvement was unclear and further research was warranted. Thus at present, after complete resection, adjuvant radiotherapy should not be administered in patients with early lung cancer. Recent retrospective and non-randomised studies, as well as subgroup analyses of recent randomised trials evaluating adjuvant chemotherapy, provide evidence of the possible benefit of PORT in patients with mediastinal nodal involvement. The role of PORT needs to be evaluated also for patients with proven N2 disease who undergo neoadjuvant chemotherapy followed by surgery. The risk of local recurrence for N2 patients varies between 20% and 60%. Based on currently available data, PORT should be discussed for fit patients with completely resected NSCLC with N2 nodal involvement, preferably after completion of adjuvant chemotherapy or after surgery if patients have had preoperative chemotherapy. There is a need for new randomised evidence to reassess PORT using modern three-dimensional conformal radiation technique, with attention to normal organ sparing, particularly lung and heart, to reduce the possible over-added toxicity. Quality assurance of radiotherapy as well as quality of surgery – and most particularly nodal exploration modality – should both be monitored. A new large multi-institutional randomised trial Lung ART evaluating PORT in this patient population is needed and is now under way.     

Neoadjuvant chemoradiation therapy for locally advanced rectal cancer

Not only the improvement of overall survival, but also the control of local recurrence, a unique type of recurrence, is an important issue in the treatment of advanced local rectal cancer. Total mesorectal excision is internationally accepted to be a standard procedure that lowers the rate of local recurrence. In 1999, the National Institutes of Health in the United States recommended "resection plus postoperative chemoradiotherapy" as the standard treatment for pathological stage II and III rectal cancer. In Japan, however, few large clinical trials of adjuvant radiotherapy have been performed because the rate of local recurrence in patients undergoing surgery alone is lower than that in Western countries. Multicenter, randomized, controlled studies with total mesorectal excision as a control are ongoing in Japan, and the results are awaited. We describe the current status of adjuvant chemoradiotherapy for advanced local rectal cancer in Japan and other countries, along with a review of the literature.     

可切除食管癌术前与术后放化疗对比Meta分析

目的 食管癌患者就诊时大多属中晚期,单纯手术疗效不佳,需结合放化疗提高疗效,但手术与放化疗治疗顺序备受争议.本研究通过对比中晚期可切除食管癌术前与术后放化疗2种治疗模式的疗效及安全性,探寻治疗食管癌的有效治疗模式,为指导临床实践提供理论依据.方法 计算机检索The Cochrane Library、Embase、PubMed、Web of Science、CBM和CNKI,同时辅佐其他检索途径,检索2016-10前所有关于对比食管癌术前放化疗与术后放化疗的临床研究.随机对照研究(randomized controlled trial,RCT)采用Cochrane质量评价标准评价文献质量,非随机对照研究采用纽斯卡尔-渥太华量表(newcastle-ottawa scale,NOS)质量评价标准评价文献质量,统计学分析采用Review Manager 5.3软件.本Meta分析遵循系统综述与荟萃分析优先报告条目(PRISMA)规范.结果 共纳入1个RCT和5个非随机对照研究,Meta分析结果显示,1年生存率(OR=1.24,95％CI:0.96～1.61,P=0.09)、3年生存率(OR=1.25,95％CI:1.00～1.55,P=0.05)、5年生存率(OR=1.39,95％CI:0.93～2.06,P=0.11)和术后并发症发生率(OR=1.45,95％CI:0.81～2.60,P=0.21)差异均无统计学意义.亚组分析显示,国内人群1年生存率(OR=1.30,95％CI:0.48～3.58,P=0.61)、国外人群1年生存率(OR=1.37,95％CI:0.79～2.38,P=0.26)、国内人群3年生存率(OR=1.16,95％CI:0.90～1.49,P=0.25)和国外人群3年生存率(OR=1.55,95％CI:1.00～2.41,P=0.05)差异均无统计学意义.结论 中晚期可切除食管癌术前放化疗与术后放化疗疗效及安全性相似.临床上可酌情考虑后决定手术与放化疗治疗顺序,但仍有待大量多中心、前瞻性随机对照临床实验证实.     

Update of adjuvant chemotherapy for resected gastric cancer

Gastric cancer is the second cause of cancer that is related to death and the fourth most common cancer, worldwide. Complete resection of cancer is the only curative treatment for gastric cancer. However, even if complete resection is possible, recurrence is frequently observed in Gastric patients. Therefore, adjuvant treatment modality for resectable gastric cancer is needed to increase the survival of patients. This study wants to describe the role of adjuvant chemotherapy for resectable gastric cancer, with updated data of recent studies. Several meta-analysis studies demonstrated a benefit of adjuvant chemotherapy for resectable gastric cancer. Due to the heterogeneity of the population and regimens, there is no consensus regarding the adjuvant chemotherapy. Recently published, well designed phase III studies demonstrated the statistically significance of adjuvant chemotherapy for the resectable gastric cancer, with the extended lymph node dissection. Further phase III trials, to determine the best regimen and schedule of adjuvant chemotherapy, was suggested to use the fluoropyrimidine based regimen as control group.     

Definitive chemoradiation in the management of locally advanced esophageal cancer

A significant number of patients diagnosed with esophageal cancer will present with locally advanced disease. The appropriate management of these patients continues to be a matter of significant debate. Over the past 2 decades, concurrent chemoradiation has been widely recognized as a viable option for a majority of these patients. Although there have been no randomized trials comparing definitive chemoradiation with surgical resection, there is little doubt that nonoperative therapy offers comparative opportunity for cure with less intendent morbidity and mortality. The broad applicability of this treatment option has led investigators to study methods of maximizing the therapeutic gain associated with the combination of external beam radiation and systemic chemotherapy. The long-term survival results have compared favorably with surgical series, thus leading to clinical trials designed to define the role of surgery in future management strategies. The early evaluation of these recent trials fails to identify any significant advantage associated with the routine use of surgery for most patients. Recent advances in drug development in conjunction with the identification of specific molecular targets has provided new opportunities to improve on the outcomes achieved with standard chemoradiation combinations.     

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer

PURPOSE: Capecitabine (Xeloda) is a new orally administered fluoropyrimidine carbamate that was rationally designed to exert its effect by tumor-selective activation. We attempted to evaluate the efficacy and toxicity of preoperative chemoradiation using capecitabine in locally advanced rectal cancer. METHODS AND MATERIALS: Between July 1999 and March 2001, 45 patients with locally advanced rectal cancer (cT3/T4 or N+) were treated with preoperative chemoradiation. Radiation of 45 Gy/25 fractions was delivered to the pelvis, followed by a 5.4 Gy/3 fractions boost to the primary tumor. Chemotherapy was administered concurrent with radiotherapy and consisted of 2 cycles of 14-day oral capecitabine (1650 mg/m(2)/day) and leucovorin (20 mg/m(2)/day), each of which was followed by a 7-day rest period. Surgery was performed 6 weeks after the completion of chemoradiation. RESULTS: Thirty-eight patients received definitive surgery. Primary tumor and node downstaging occurred in 63% and 90% of patients, respectively. The overall downstaging rate, including both primary tumor and nodes, was 84%. A pathologic complete response was achieved in 31% of patients. Twenty-one patients had tumors located initially 5 cm or less from the anal verge; among the 18 treated with surgery, 72% received sphincter-preserving surgery. No Grade 3 or 4 hematologic toxicities developed. Other Grade 3 toxicities were as follows: hand-foot syndrome (7%), fatigue (4%), diarrhea (4%), and radiation dermatitis (2%). CONCLUSION: These preliminary results suggest that preoperative chemoradiation with capecitabine is a safe, well-tolerated, and effective neoadjuvant treatment modality for locally advanced rectal cancer. In addition, this preoperative treatment has a considerable downstaging effect on the tumor and can increase the possibility of sphincter preservation in distal rectal cancer.     

Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer

Background Despite curative resection, 50%–90% of gastric cancer patients die of disease relapse. Although some clinical trials have indicated that chemotherapy and immunochemotherapy may be effective modalities, more recent studies have not been able to define the standard treatment for advanced gastric cancer. The present study evaluated the effect of adjuvant immunochemotherapy with the use of BCG (bacille Calmette-Guérin) and FAM (5-fluorouracil, adriamycin, mitomycin C) chemotherapy on the survival of patients with locally advanced resectable gastric cancer.Methods A total of 156 patients with stage III or IV gastric cancer who had undergone curative resection were randomly assigned to three treatment groups: BCG + FAM (immunochemotherapy), FAM (chemotherapy), and control (surgery only). Treatment was continued for 2 years or until death. Further postsurgical follow up was carried on for up to 10 years.Results Overall 10-year survival was 47.1% for the immunochemotherapy group (P < 0.037 vs FAM and P < 0.0006 vs control), 30% for the chemotherapy group (vs control, NS), and 15.2% for the control group. In patients with pT2/T3 primary tumors, 10-year survival was 55.3% for BCG + FAM vs 28.2% for FAM (P < 0.01) and 14.6% for the control group (P < 0.00018). BCG + FAM signifi-cantly improved the survival of patients with intestinal-type but not diffuse-type cancer. Immunochemotherapy was well tolerated.Conclusion This study, based on a limited number of patients, indicates that adjuvant immunochemotherapy (BCG + FAM) may prolong the survival of gastric cancer patients after curative gastrectomy; in particular, in patients with pT2/T3 tumors and intestinal-type primary tumors. There was no survival benefit from FAM adjuvant chemotherapy.     

Postoperative adjuvant chemotherapy and pelvic radiotherapy for resected rectal cancer

Conclusions Although postoperative pelvic radiotherapy reduces the incidence of locoregional recurrence in patients with resected rectal cancer, this does not result in any improvement in disease-free or overall survival. These results are consistent with the findings of NSABP R-01, in which postoperative radiotherapy without chemotherapy failed to affect disease-free or overall survival.     

Adjuvant chemoradiation for resected gastric cancer: a 10-year experience

Background  

The Intergroup 0116 study demonstrated that concurrent chemoradiation improved overall survival (OS) in resected gastric cancer. However, there are few reports focusing on late toxicity and factors governing prognosis. This study aimed to determine these two important aspects for employing this regimen.     

Improved survival with adjuvant chemotherapy in locally advanced rectal cancer patients treated with preoperative chemoradiation regardless of pathologic response

ObjectiveThe aim of this study is to examine the effect of postoperative chemotherapy on survival in patients with stage II or III rectal adenocarcinoma who undergo neoadjuvant chemoradiation (CRT) and surgical resection.MethodsA retrospective review of the National Cancer Database (NCDB) from 2006 to 2013 was performed. Cases were analyzed based on pathologic complete response (pCR) status and use of adjuvant therapy. The Kaplan-Meier method was used to estimate overall survival probabilities.Results23,045 cases were identified, of which 5832 (25.31%) achieved pCR. In the pCR group, 1513 (25.9%) received adjuvant chemotherapy, and in the non-pCR group, 5966 (34.7%) received adjuvant therapy. In the pCR group, five-year survival probability was 87% (95% CI 84%–89%) with adjuvant therapy and 81% (95% CI 79%–82%) without adjuvant therapy. In the non-pCR group, five-year survival probability was 78% (95% CI 76%–79%) with adjuvant therapy and 70% (95% CI 69%–71%) without adjuvant therapy. In the non-pCR and node-negative subgroup (ypN-), five-year survival probability was 86% (95% CI 84%–88%) with adjuvant therapy and 76% (95% CI 74%–77%) without adjuvant therapy. In the non-pCR and node-positive subgroup (ypN+), five-year survival probability was 67% (95% CI 65%–70%) with adjuvant therapy and 60% (95% CI 58%–63%) without adjuvant therapy.ConclusionsAdjuvant chemotherapy in stage II or III rectal adenocarcinoma is associated with increased five-year survival probability regardless of pCR status. We observed similar survival outcomes among non-pCR ypN- treated with adjuvant chemotherapy compared with patients achieving pCR treated with adjuvant chemotherapy.