直肠癌的辅助治疗

直肠癌辅助治疗观念的提出是基于手术后局部失败率较高。通过术前、术后的放疗或加化疗来提高保肛率、减少复发、提高生存率是近年研究的焦点，对T3期的病人建议采用术前联合治疗、手术加术后以5-Fu为基础的化疗。术前放疗建议按照常规剂量，放疗后4-8周行手术治疗。术后是否行辅助治疗应取决于病理分期，术后辅助治疗方案的选择建议以5-Fu为基础。加用LV、或Capecitabine、或Oxaliplatin、或CPT-11伴随放疗的临床研究正在进行中。     

189例ⅢA期非小细胞肺癌完全切除术后辅助治疗的疗效分析

背景与目的:ⅢA期非小细胞肺癌(non-small cell lung cancer,NSCIC)完全切除术后的辅助治疗一直是临床研究的热点.本研究目的在于探讨ⅢA期NSCIC完全切除术后辅助放疗或化疗对生存时间的影响.方法:收集1995年1月至2000年1月我院收治的189例ⅢA期NSCIC完全切除术后患者的临床资料,回顾分析术后放疗、化疗对患者生存期的影响.统计分析采用SPSS10统计软件,单因素分析用Kaplan-meier法计算累计生存率,各因素比较用秩和对数检验(log-rank),多因素分析采用COX模型.结果:全组的中位生存时间鳞癌为46.39个月,腺癌为26.81个月,两者比较有统计学意义(P=0.038).其中,鳞癌单纯手术21例,中位生存42.8个月;术后放疗28例,中位生存45.5个月,两者比较无统计学意义(P=0.068).术后化疗19例中位生存52.0个月,与单纯手术比较无统计学意义(P=0.075).腺癌单纯手术41例,中位生存26.7个月;术后放疗43例,中位生存26.6个月,两者比较无统计学意义(P=0.555);术后化疗37例,中位生存37.9个月,与单纯手术比较无统计学意义(P=0.0242).多因素分析结果显示,患者的年龄、性别、治疗方式与生存期均无关;病理学类型是影响患者预后的独立因素.结论:本组资料表明病理类型是影响可完全切除ⅢA期NSCIC术后生存期的主要因素;虽然术后放疗、化疗在统计学上未能显示可延长患者生存期,但化疗有提高患者生存期的趋势.     

The Role of Adjuvant Treatment in Resected T3N0 Rectal Cancer

Since the adoption of total meso-rectal excision as the standard surgical approach for management of locally advanced rectal cancer, there has been a significant reduction in local recurrence. Neoadjuvant combined modality treatment with 5-fluorouracil-based chemotherapy and radiation has further improved local disease control and overall survival. Given the excellent survival obtained with this combined approach in T3N0 rectal cancer, there are concerns about the need for further exposure to chemotherapy with unproven benefit. We review the evidence for adjuvant chemotherapy in this setting and set out clinico-pathologic variables that may be useful for making a decision in favor of offering adjuvant therapy or observation.     

Timing of Adjuvant and Neoadjuvant Therapy in Colorectal Cancers

Surgery remains the only curative therapy for colorectal cancer (CRC); however, several studies have proved that adjuvant chemotherapy improves the curative rate. A growing body of evidence indicates that significant deviations from recommended treatment plans are frequent. Patients may experience delays in the administration of adjuvant chemotherapy that can reduce its survival benefit. To date, few studies have examined factors associated with the timing of adjuvant chemotherapy or have described the effects of delayed therapy on overall survival. In this review, we discuss the extent and predictors of delay in administration of adjuvant chemotherapy as well as the relationship between timing and outcomes in CRC.     

Modeling the Cost-Effectiveness of Adjuvant Osimertinib for Patients with Resected EGFR-mutant Non-Small Cell Lung Cancer

IntroductionThe epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib was recently approved for resected EGFR-mutant stages IB-IIIA non-small cell lung cancer due to improved disease-free survival (DFS) in this population compared with placebo. This study aimed to evaluate the cost-effectiveness (CE) of this strategy.Materials and MethodsWe constructed a Markov model using post-resection health state transitions with digitized DFS data from the ADAURA trial to compare cost and quality-adjusted life years (QALYs) of 3 years of adjuvant osimertinib versus placebo over a 10-year time horizon. An overall survival (OS) benefit of 5% was assumed. Costs and utility values were derived from Medicare reimbursement data and literature. A CE threshold of 3 times the gross domestic product per capita was used. Sensitivity analyses were performed.ResultsThe incremental cost-effectiveness ratio for adjuvant osimertinib was $317 119 per QALY-gained versus placebo. Initial costs of osimertinib are higher in years 1-3. Costs due to progressive disease (PD) are higher in the placebo group through the first 6.5 years. Average pre-PD, post-PD, and total costs were $2388, $379 047, and $502 937, respectively, in the placebo group, and $505 775, $255 638, and $800 697, respectively, in the osimertinib group. Sensitivity analysis of OS gains reaches CE with an hazard ratio (HR) of 0.70-0.75 benefit of osimertinib over placebo. A 50% discount to osimertinib drug cost yielded an ICER of $115 419.ConclusionsThree-years of adjuvant osimertinib is CE if one is willing to pay $317 119 more per QALY-gained. Considerable OS benefit over placebo or other economic interventions will be needed to reach CE.     

Pathological Complete Response After Neoadjuvant Therapy for Rectal Cancer and the Role of Adjuvant Therapy

Both the addition of neoadjuvant chemoradiation therapy and improvements in surgical techniques have improved local control and overall survival for locally advanced rectal cancer patients over the past few decades. The addition of adjuvant chemotherapy has likely improved outcomes as well, though the contribution has been more difficult to quantify. At present, the majority of resected locally advanced rectal cancer patients receive adjuvant chemotherapy, though there is great variability in this practice based on both patient and institution characteristics. Recently, questions have been raised regarding which sub-groups of patients benefit most from adjuvant chemotherapy. As pathologic complete response (pCR) is increasingly found to be a reasonable surrogate for long-term favorable outcomes, some have questioned the need for adjuvant therapy in this select group of patients. Multiple retrospective analyses have shown minimal to no benefit for adjuvant chemotherapy in this group. Indeed, the patients most consistently shown to benefit from adjuvant therapy both in terms of disease free survival (DFS) and overall survival (OS) are those who achieve an intermediate pathologic response to neoadjuvant treatment. Tumors that have high expression of thymidylate synthetase have also shown to benefit from adjuvant therapy. More study is needed into clinical and molecular features that predict patient benefit from adjuvant therapy.     

放射治疗在局部晚期胃肠恶性肿瘤治疗中的地位

摘 要：手术是胃肠肿瘤的主要治疗手段,但局部晚期患者很难通过单纯手术获得疾病根治,需要通过综合治疗来达到治愈肿瘤的目的,以取得治愈率最大化的同时毒性最小化,获得最佳的生活质量。在局部晚期直肠癌的治疗中,放疗的地位比较肯定,已有相关随机研究结果。但在局部晚期胃癌的治疗中,对于放疗的作用,虽然已有一些随机研究提供了一些循证医学依据,但还存在很多不确定因素。     

Adjuvant External Beam and Intraoperative Radiation Therapy in Rectal Cancer

The use of radical surgery has maximized local control, sphincter preservation, and overall survival in patients with rectal cancer. Despite the advances in surgical techniques, local recurrence still remains a problem. Following potentially curative surgery, the incidence of local recurrence inpatients with stages B2,C disease varies from 15% to 65%. There are four major approaches in which radiation therapy (RT) has been used in the adjuvant treatment of rectal cancer. These include postoperative RT ± chemotherapy, preoperative RT ± chemotherapy, both pre-and postoperative RT (sandwich technique), and intraoperative RT in conjunction with preoperative external beam RT. In patients with resectable rectal cancer, adjuvant RT has been shown to decrease the incidence of local recurrence and, in some series, may influence survival rates. In patients with locally advanced, unresectable, or recurrent rectal cancer, the use of preoperative radiation therapy, attempted surgical resection, and intraoperative RT further enhances local control.     

Adjuvant Subcutaneous Interleukin-2 in Patients with Resected Renal Cell Carcinoma: A Pilot Study

BackgroundA pilot study was conducted to investigate the toxicity and tolerance to low-dose subcutaneous interleukin-2 (IL-2) for patients with resected renal cell carcinoma (RCC) at high risk for recurrent disease (TNM stages III and IV resected distant metastases).Patients and MethodsPatients with surgically resected locally advanced (T3-4 or N1-2) or metastatic RCC were randomly assigned to 1 of 4 treatment groups that received different dose levels and schedules of subcutaneous IL-2 as follows: dose level 1, 4 MIU/m² per day, every other week for 24 weeks (n = 10); dose level 2, 8 MIU/m² per day, every other week for 24 weeks (n = 9); dose level 3, 4 MIU/m² per day, weeks 1-4, 9-12, and 17-20 (n = 11); and dose level 4, 8 MIU/m² per day, weeks 1-4, 9-12, and 17-20 (n = 10). Interleukin-2 was administered in 2 daily doses on days 1-5 of each week indicated. A dose level was considered tolerable if no more than 2 patients experienced grade 3/4 toxicity.ResultsForty-one patients were entered in the study and 40 were evaluable for toxicity. Therapy was well tolerated at all dose levels and schedules, with most patients (98%) experiencing mild-to-moderate constitutional symptoms. Grade 3/4 toxicity was seen in 8 patients (20%). Interleukin-2 dose reductions were required in 7 patients, and no patient discontinued therapy secondary to toxicity. Of 39 patients evaluable for efficacy, 31 have experienced relapse (79%), and 15 have died (38%). Median survival was 1.4 years, and the 3-year disease-free survival rate was 33%. Median overall survival has not been reached; however, the 3-year survival rate was 70%. There was no statistically significant difference between any of the treatment arms with respect to disease-free survival or 3-year survival (P > 0.54 and P ≥ 0.09 for all pairwise comparisons), schedules (dose level 1/2 vs. 3/4; P = 0.46 and P = 0.5), or dose of IL-2 administered (dose level 1/3 vs. 2/4; P = 0.99 and P = 0.1).ConclusionSubcutaneous IL-2 was well tolerated for 6 months in patients with surgically resected RCC at high risk of recurrence. Future adjuvant trials in this setting are not likely to include IL-2 in view of the clinical efficacy and favorable toxicity profiles of selected multitargeted kinase inhibitors.     

Postoperative Chemotherapy Use and Outcomes From ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR-Mutated NSCLC

IntroductionAdjuvant chemotherapy is recommended in patients with resected stages II to IIIA (and select IB) NSCLC; however, recurrence rates are high. In the phase 3 ADAURA study (NCT02511106), osimertinib was found to have a clinically meaningful improvement in disease-free survival (DFS) in patients with resected stages IB to IIIA EGFR-mutated (EGFRm) NSCLC. Here, we report prespecified and exploratory analyses of adjuvant chemotherapy use and outcomes from ADAURA.MethodsPatients with resected stages IB to IIIA EGFRm NSCLC were randomized 1:1 to receive osimertinib or placebo for 3 years. Adjuvant chemotherapy before randomization was not mandatory, per physician and patient choice. DFS in the overall population (IB–IIIA), with and without adjuvant chemotherapy, was a prespecified analysis. Exploratory analyses included the following: adjuvant chemotherapy use by patient age, disease stage, and geographic location; DFS by adjuvant chemotherapy use and disease stage.ResultsOverall, 410 of 682 patients (60%) received adjuvant chemotherapy (osimertinib, n = 203; placebo, n = 207) for a median duration of 4.0 cycles. Adjuvant chemotherapy use was more frequent in patients: aged less than 70 years (338 of 509; 66%) versus more than or equal to 70 years (72 of 173; 42%); with stages II to IIIA (352 of 466; 76%) versus stage IB (57 of 216; 26%); and enrolled in Asia (268 of 414; 65%) versus outside of Asia (142 of 268; 53%). A DFS benefit favoring osimertinib versus placebo was observed in patients with (DFS hazard ratio = 0.16, 95% confidence interval: 0.10–0.26) and without adjuvant chemotherapy (hazard ratio = 0.23, 95% confidence interval: 0.13–0.40), regardless of disease stage.ConclusionsThese findings support adjuvant osimertinib as an effective treatment for patients with stages IB to IIIA EGFRm NSCLC after resection, with or without previous adjuvant chemotherapy.     

三维适形放射治疗20例复发性直肠癌

目的 探讨三维适形放射治疗对复发性直肠癌的临床疗效。方法 20例复发性直肠癌患者均采用三维适形放疗，3～4Gy／次，隔日1次，总剂量48～60Cy。结果1、2、3年生存率分别为40％（8／20），15％（3／20），5％（1／20）。结论 三维适形放射治疗可提高复发性直肠癌生存率，改善生存质量。     

新辅助治疗用于老年进展期直肠癌患者的临床研究

[目的]探讨新辅助治疗应用于老年进展期直肠癌的临床意义,并对其临床价值进行评估。[方法]61例老年进展期直肠癌患者,分为研究组33例,接受新辅助治疗后进行手术治疗,对照组28例,直接进行手术治疗。主要观察指标为两组患者的肿瘤切除率、根治性切除率、保肛率、病理学变化、术后并发症情况、随访局部复发率、远处转移率。[结果]研究组肿瘤根治性切除率和保肛率分别为96.97%（32/33）和90.91%（30/33）,明显高于对照组78.57%（22/28）和78.57%（22/28）,差异均具有统计学意义（P〈0.05）;研究组局部复发率和远处转移率分别为9.09%（3/33）和21.21%（7/33）,明显低于对照组17.86%（5/28）和39.29%（11/28）,差异均具有统计学意义（P〈0.05）;研究组术后肿瘤退化分级TRG3为24.24%（8/33）,明显低于对照组39.29%（11/28）,差异均具有统计学意义（P〈0.05）;两组术后吻合口瘘、切口裂开、切口愈合不良、肠黏连等并发症结果比较,差异无统计学意义（P〉0.05）。[结论]新辅助治疗后再手术可以提高老年进展期直肠癌手术切除率,减少直肠癌的转移和复发,改善患者的预后。     

Relation between the Serum E-Selectin Level and the Survival Rate of Patients with Resected Non-small Cell Lung Cancers

E-Selectin is an inducible adhesion molecule, which is expressed on cytokine-activated endothelial cells and is thought to interact with cancer cells to initiate metastases. The relationship between serum E-selectin levels and prognoses in 101 patients with resected non-small cell lung cancers (NSCLCs) was studied, and survival curves were compared in relation to E-selectin levels and expression of two carbohydrate antigens, Sialyl Lewis^x (SLX) and Sialyl Lewis^a (CA19-9), which were immunohistochemically detected in resected specimens in 65 of the 101 cases. The serum Eselectin level on admission was 48.9±25.7 ng/ml (mean±SD, n =101), and the E-selectin-positive rate was 22.7%, being correlated with the progression of T-factor. The high E-selectin group showed a significantly worse survival rate than the normal E-selectin group. Multivariate analysis confirmed the significant prognostic value of E-selectin. The mean postoperative E-selectin level in 52 cases (36.93 ng/ml) was significantly lower than the preoperative E-selectin level (43.57 ng/ml), indicating that certain NSCLCs might induce the expression of E-selectin. In cases expressing carbohydrate antigens (SLX, CA19-9), the high E-selectin group showed a significantly worse survival curve than the normal E-selectin group. On the other hand, there was no significant difference in the survival curve between the high and normal E-selectin groups when carbohydrate antigens were negative. These results suggest that patients who have high serum E-selectin levels, especially with carbohydrate antigen-positive NSCLC, might be expected to have poor prognoses.     

食管癌切除患者术前术后化疗的临床研究

目的　探讨食管癌术前术后化疗的远期疗效。方法　食管癌患者 172例 ,随机分为术前术后化疗A组 ,单一手术B组。A组患者术前 1周连续化疗两次 ,术后第 3、5、7天各化疗 1次 ,出院休息 1～ 2周后口服化疗药物 3个月 ;B组单纯手术治疗。结果　A、B两组 5年生存率分别为 45 9%和 2 8% ,二者差异有显著性意义 (P <0 0 5 ) ;其中Ⅲ期病例的 5年生存率分别为 40 %和 17 9% ,其差异有显著性意义 (P <0 0 5 )。结论　术前术后化疗能显著提高食管癌尤其是Ⅲ期患者的 5年生存率 ,优于单一手术组 ,而且方法简单、安全、实用     

A Follow-up Study of Resected Stomach Cancer Patients with Special Emphasis on the Incidence of Second Primary Cancers

The causes of death in long-term survivors of stomach cancerafter a gastrectomy have been investigated in a follow-up studyof 320 such patients, with special focus on the postoperativedevelopment of a second primary cancer. The five- and 10-yearoverall survival rates of early stomach cancer patients were87.5 and 75.8%, respectively, and of advanced stomach cancerpatients, 44.2 and 37.5%, respectively. A multivariate analysisidentified the patient's age and stage of cancer at the timeof diagnosis as separate prognostic factors for overall survival.During the observation period, 15 (4.7%) patients developeda second primary cancer, so that no significantly elevated riskof developing a second primary cancer was demonstrated. Duringthe same observation period, however, 48 (15%) of the patientsdied of a non-cancerous disease, 12 succumbing to an acute myocardialinfarction and/or heart failure. Given these results, it isfelt that continued follow-up of long-term stomach cancer survivorsshould be pursued to prevent or impede the development of anon-cancerous disease and/or a second primary cancer, so thatthe life of such former patients can be prolonged.     

Comparative Effectiveness of Total Neoadjuvant Therapy Versus Standard Adjuvant Chemotherapy for Locally Advanced Rectal Cancer

IntroductionThe use of total neoadjuvant therapy (TNT) for locally advanced rectal cancer has been increasing in recent years, but the long-term overall survival characteristics of this approach is currently unknown.MethodsWe performed a retrospective study of patients with clinical stage II/III rectal cancer within the National Cancer Database. Patients who received TNT (defined as chemotherapy, followed by CRT, followed by surgery) were propensity score matched to patients who received adjuvant therapy (defined as CRT, followed by surgery, followed by chemotherapy). We compared overall survival (OS) and rates of pathologic complete response (pCR) between the 2 arms.ResultsOf the 4300 patients in our cohort, 3502 (81%) received adjuvant therapy and 798 (19%) received TNT. At baseline, patients who received TNT were more likely to have higher clinical T and N stages (P< .001). The 5-year OS was 77% for both TNT and adjuvant therapy patients (hazard ratio [HR] 1.06, 95% confidence interval [CI], 0.88-1.28, P = .57). After propensity score matching and adjusting for potential confounders, there were no significant differences in OS (HR_adj 1.00, 95% CI, 0.71-1.40, P = .99). After propensity score matching, there were higher pCR rates among TNT patients (16.1%) compared to adjuvant therapy patients (12.0%) (P = .037).ConclusionIn this observational study, we found TNT was not associated with a lower OS compared to standard adjuvant chemotherapy. This finding potentially reassures clinicians choosing TNT as an alternative to adjuvant chemotherapy. However, future prospective data are needed to confirm these findings.