Advances in postoperative adjuvant therapy for primary liver cancer

Hepatocellular carcinoma (HCC) is a highly heterogeneous, invasive, and conventional chemotherapy-insensitive tumor with unique biological characteristics. The main methods for the radical treatment of HCC are surgical resection or liver transplantation. However, recurrence rates are as high as 50% and 70% at 3 and 5 years after liver resection, respectively, and even in Milan-eligible recipients, the recurrence rate is approximately 20% at 5 years after liver transplantation. Therefore, reducing the postoperative recurrence rate is key to improving the overall outcome of liver cancer. This review discusses the risk factors for recurrence in patients with HCC radical surgical resection and adjuvant treatment options that may reduce the risk of recurrence and improve overall survival, including local adjuvant therapy (e.g., transcatheter arterial chemoembolization), adjuvant systemic therapy (e.g., molecular targeted agents and immunotherapy), and other adjuvant therapies (e.g., antiviral and herbal therapy). Finally, potential research directions that may change the paradigm of adjuvant therapy for HCC are analyzed.     

Advances in adjuvant systemic therapy for non-small-cell lung cancer

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.     

Progress in systemic adjuvant therapy of early-stage breast cancer

Despite major improvements in the treatment of early-stage breast cancer over the past 15 years, many controversies exist surrounding the optimal adjuvant therapies for these patients. Adjuvant chemotherapy has been demonstrated to reduce recurrence and improve mortality, but questions persist as to what is the optimal regimen and how much adjuvant therapy should be administered. Among the adjuvant chemotherapy issues that remain controversial are the role of the taxanes and the optimal number of adjuvant chemotherapy treatment cycles. In the realm of adjuvant endocrine therapy, the early results of the Anastrozole, Tamoxifen and Combination (ATAC) trial have led to confusion as to how best to treat postmenopausal patients with estrogen receptor-positive, early-stage breast cancer. Clinicians are faced with the decision of choosing between tamoxifen and anastrozole. The enthusiasm for so-called targeted therapies, such as trastuzumab, in patients with metastatic disease, is now being carried over into the adjuvant setting. Multiple clinical trials around the world are evaluating the potential benefit of adding trastuzumab to chemotherapy in patients with HER2-positive, early-stage breast cancer. In the United States, clinicians are faced with many decisions on how to optimally treat patients with early-stage breast cancer. Evidence-based treatment guidelines such as those developed by the National Comprehensive Cancer Network (NCCN) provide a useful algorithm for assisting in making treatment decisions. It is hoped that, in the next few years, the results of ongoing clinical trials now underway will lead to further improvements in the outcome of patients with early-stage breast cancer.Presentation made at the ASCO-JSCO Joint Symposium held at Tokyo, Japan, on October 18, 2002.     

胆道恶性肿瘤辅助治疗的研究现状及展望

胆道恶性肿瘤侵袭性强,恶性程度高,预后差。早期根治性切除是目前首选的治疗方法,也是唯一可能获得长期生存的方法。但大多数患者初诊时已为晚期,只有约20%的患者有手术机会。不仅如此,即使行根治性手术,复发率依然极高。为了降低术后复发率,多年来人们一直致力于探索辅助治疗策略,包括放疗、化疗和放化疗结合。但大多数数据来源于Ⅱ期临床试验和回顾性研究,缺乏高质量的数据来证实辅助治疗的效果。近年来随着几项大型随机临床试验的发布以及精准治疗的发展,越来越多的研究聚焦于该领域,结果令人期待。本综述总结并分析了近年来胆道恶性肿瘤辅助治疗领域的研究数据,并探讨了未来的研究方向。     

Risk group criteria for tailoring adjuvant treatment in patients with endometrial cancer: a validation study of the Gynecologic Oncology Group criteria

Objective

The purpose of this study is to validate the Gynecologic Oncology Group (GOG) criteria for adjuvant treatment in a different cohort of patients and to evaluate the simplified risk criteria predicting the prognosis and tailoring adjuvant treatment in patients with surgically staged endometrial cancer.

Methods

We performed a retrospective analysis of 261 consecutive patients with surgically staged endometrial cancer between January 2000 and February 2013. All patients had complete staging procedures and were surgically staged according to the 2009 International Federation of Gynecology and Obstetrics staging system. Clinical and pathologic data were obtained from medical records. We designed the simplified risk criteria for adjuvant treatment according to the risk factors associated with survival. The patients were divided into low and low-intermediate, high-intermediate, and high-risk groups according to the GOG criteria and simplified criteria and their survivals were compared. Receiver-operating characteristic curve analysis was used to evaluate the prognostic significance of both criteria.

Results

Median follow-up time was 48 months (range, 10 to 122 months). According to the GOG criteria, we identified 197 low and low-intermediate risk patients, 20 high-intermediate risk patients, and 44 high-risk patients. There were significant differences in disease-free (p<0.001) and overall survival (p<0.001) among the three groups. Using the simplified risk criteria, we identified 189 low and low-intermediate risk patients, 28 high-intermediate risk patients, and 44 high-risk patients. There were significant differences in disease-free (p<0.001) and overall survival (p<0.001) among the three groups. The performance of the simplified criteria (area under the curve [AUC]=0.829 and 0.916 for disease recurrences and deaths, respectively) was as good as the GOG criteria (AUC=0.836 and 0.921 for disease recurrences and deaths, respectively).

Conclusion

The simplified criteria may be easily applicable and offer useful information for planning strategy of adjuvant treatment in patients with surgically staged endometrial cancer as the GOG criteria.     

Short term safety of coronavirus disease 2019 vaccines in patients with solid tumors receiving systemic therapy

BACKGROUNDThere are currently three coronavirus disease 2019 (COVID-19) vaccines approved by the United States Food and Drug Administration to prevent coronavirus infection. However, robust data are unavailable on the adverse events of the vaccines in patients with solid tumor malignancies undergoing systemic therapies. AIMTo evaluate the safety of COVID-19 vaccines in patients with solid tumors undergoing systemic therapies.METHODSThe study included patients with solid tumors treated in an academic tertiary care center who received COVID-19 vaccination between January 1, 2021 and August 15, 2021, while undergoing systemic therapy. Electronic medical records were accessed to collect information on patient characteristics, systemic therapies, type of vaccine received, and adverse effects associated with the vaccine administration. Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events, version 5.0.RESULTSThe analysis included 210 patients; the median age was 70 years, and 51% of patients were female. The most common chemotherapy, immunotherapy, and targeted therapy administered were taxane-based regimens 14.2% (30/210), anti-programmed death 1 (PD-1) agents 22.8% (48/210), and antiangiogenic agents 7.1% (15/210), respectively. The most common cancers were gastrointestinal 43.8% (92/210), thoracic 30.4% (64/210), and genitourinary 17.6% (37/210). Patients received the following vaccines: 2 doses of BNT162b2 by Pfizer 52% (110/210), 2 doses of mRNA-1273 by Moderna 42% (89/210), and 1 dose of JNJ-78436735 by Johnson & Johnson 5% (11/210). At least 1 AE attributable to the vaccine was observed in 37 patients 17.6% (37/210). The total number of AEs attributable to vaccines was 62: Fifty-three grade 1 and nine grade 2. Most adverse events occurred after the second dose 59.7% (37/62). The most frequent grade 1 AEs included fatigue 17% (9/53), fever 15% (8/53), injection site reaction 13.2% (7/53), and chills 9.4% (5/53). The most frequent grade 2 AEs were fatigue 33.3% (3/9) and generalized weakness 22.2% (2/9). Therapy was delayed by 2 wk because of the AEs possibly related to vaccine administration in 3 patients 1.4% (3/210). CONCLUSIONThe present study demonstrates that the adverse events associated with COVID-19 vaccination are infrequent, mild, and rarely delay treatment in patients with solid tumors receiving systemic therapies.     

Current status of adjuvant therapy for pancreatic cancer

In this article, we review the rationale for and outcomes associated with the use of adjuvant and neoadjuvant therapy for resectable and borderline resectable cancer of the pancreatic head and uncinate process. Localized pancreatic cancer is a systemic disease that requires nonoperative therapies to minimize the local and systemic recurrences that almost invariably occur in the absence of such therapy, even following complete surgical resection. A well-defined role exists for the systemic administration of gemcitabine or 5-fluorouracil in the postoperative setting. Although the survival benefit associated with adjuvant chemoradiation has not been as rigorously defined, its use is supported by extensive historic experience; chemoradiation should be considered particularly for patients at high risk for local recurrence. Delivery of chemotherapy and/or chemoradiation prior to surgery has multiple potential advantages, although the superiority of neoadjuvant therapy over standard postoperative therapy has yet to be demonstrated. Neoadjuvant therapy may be particularly beneficial among patients with borderline resectable cancers. Although the existing literature is confusing, and indeed controversial, available evidence suggests that systemic chemotherapy and/or chemoradiation should be offered to all patients with pancreatic cancer who undergo potentially curative resection. Well-designed prospective trials are needed to define the optimal adjuvant or neoadjuvant therapy strategy for these patients.     

Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience

Introduction

Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy.

实体瘤免疫治疗疗效评价标准

免疫治疗已经成为实体瘤除手术、放疗、化疗、靶向治疗之外的重要治疗手段。然而免疫治疗的作用机制不同于既往的治疗手段,它是通过激活机体的免疫效应而杀伤肿瘤细胞,达到肿瘤负荷的下降及生存期延长的目的。所以传统的世界卫生组织（WHO）疗效评价标准和实体瘤疗效评价标准（RECIST）也就很难对肿瘤免疫治疗的临床疗效进行准确解读,新的免疫疗效评价标准则涵盖了免疫疗效的各种表现形式,正逐渐应用于临床。     

Role of adjuvant chemoradiation therapy in adenocarcinomas of the ampulla of vater

PURPOSE: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. METHODS AND MATERIALS: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). RESULTS: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). CONCLUSIONS: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.     

Meta-analysis for the evaluation of surrogate endpoints in cancer clinical trials

The identification and validation of putative surrogate endpoints in oncology is a great challenge to medical investigators, statisticians, and regulators. A putative surrogate endpoint must be validated at both individual-level and trial-level before it can be used to replace the clinical endpoint in a future clinical trial. Recently, meta-analytic methods for evaluating potential surrogates have become widely accepted in cancer clinical trials. In this review, after addressing multiple complications and general issues surrounding surrogate endpoints, we review various proposed and adopted meta-analytic methodologies pertaining to the application of these methods to oncology clinical trials with different tumor types. In oncology, several applications have successfully identified useful surrogates. For example, disease-free survival and progression-free survival have been validated through meta-analyses as acceptable surrogates for overall survival in adjuvant colon cancer and advanced colorectal cancer, respectively. We also discuss several limitations of surrogate endpoints, including the critical issues that the extrapolation of the validity of a surrogate is always context-dependent and that such extrapolation should be exercised with caution.     

结肠癌术后辅助治疗的研究进展

结肠癌是消化道最常见恶性肿瘤之一。在过去的10年里,结肠癌的辅助治疗取得了巨大进步。虽然外科手术是治疗结肠癌的中流砥柱,但是辅助治疗也是增加结肠癌患者无病生存期和总生存期的一个重要方面。在接受根治性手术后的结肠癌患者中,约1／3的患者伴有区域淋巴结转移,1／4的患者虽不伴有区域淋巴结转移但存在高危复发因素。辅助治疗的作用就是消除微转移肿瘤沉积物,这种微转移沉积物可以增加癌症复发的机会。本文将对辅助化疗疗程、不同临床分期患者如何辅助化疗、老年患者的辅助化疗及国际上普遍存在的争议等方面的进展作一综述。     

实体瘤疗效评价标准简介

随着靶向治疗时代的到来,新的实体瘤评价标准如改良的实体瘤反应评价标准、正电子发射断层扫描反应标准、Choi 标准和免疫相关反应标准相继出现。血清标志物和循环肿瘤细胞等也用于临床反应的评价。这些指标为肿瘤疗效评价提供了有力的工具。     

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.     

Predictive markers in the adjuvant therapy of non-small cell lung cancer

Adjuvant chemotherapy increases the 5-year survival rate of patients with completely resected non-small cell lung cancer (NSCLC) by absolute 5%. Molecular-targeted therapies and predictive biomarkers to select those patients who benefit hold promise to further improve the outcome. Several biomarkers including ERCC1, BRCA1, EGFR, or gene signatures have been characterized in retrospective analyses of adjuvant therapy trials. However, differences in trial design and laboratory tests might have affected the outcome and might explain discordant results. With regard to many biomarkers, laboratory tests for their assessment remain to be standardized. After standardization of these tests and further validation studies, biomarkers might allow individualizing adjuvant treatment in patients with completely resected NSCLC in the future.     

An exploratory survival analysis of anti-angiogenic therapy for recurrent malignant glioma

Recent clinical trial results suggest that anti-angiogenic therapy may be effective against recurrent malignant glioma. Though these treatments prolong progression-free survival, the extent to which they prolong overall survival is unknown. We pooled data from 34 patients treated at a single institution on phase II clinical trials of bevacizumab and cediranib, and we compared these data to 18 patients treated on clinical trials of cytotoxic chemotherapies. In univariate and multivariate analyses, treatment group was a significant predictor of progression-free but not overall survival. Median progression-free survival was 8 vs. 22 weeks in patients treated with cytotoxic as compared to anti-angiogenic therapy (P = 0.01). Median overall survival was nearly identical in the two groups (39 vs. 37 weeks). The results of this exploratory analysis suggest that anti-angiogenic therapy may fail to prolong overall survival in patients with recurrent malignant glioma. If this conclusion proves correct, progression-free survival may be an inappropriate endpoint for phase II trials of anti-angiogenic therapies.     

间充质干细胞介导的肿瘤免疫性基因治疗

肿瘤的主要免疫方式是细胞免疫,是一个包括多种免疫细胞和细胞因子参与的复杂过程。肿瘤发生与转移的重要原因是肿瘤细胞获得逃逸免疫监视的能力,同时,机体免疫系统清除非己成分的能力减弱,导致机体不能有效地产生针对肿瘤的免疫反应。肿瘤免疫治疗的目标是提高肿瘤细胞的免疫原性,加强免疫系统的识别和清除能力。具有免疫活性的