Total neoadjuvant therapy: Fact,fantasy, or fallacy?

Colorectal cancer is the second leading cause of cancer death in the United States for men and women, with an estimated 146,000 new cases per year - a staggering 53,000 patients die each year. Rectal cancer comprises a third of these patients, with a 5-year survival rate of 67%. Management of locally advanced rectal cancer in the U.S. had remained stagnant for more than a decade, with most of these patients being treated with long-course chemoradiotherapy, surgery, followed by adjuvant chemotherapy; adjuvant chemotherapy being administered despite lacking a high level of evidence. Over the past few years, with rectal cancer death rates exceeding 30% from metastatic disease, growing interest focused on the attributes of induction chemotherapy to eradicate minimal residual disease and purportedly increase survival. This led to the development of total neoadjuvant therapy (TNT). We now have high-quality data from randomized prospective trials to review the facts, fantasies, and fallacies of TNT.     

Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Recent Advances and Ongoing Challenges

Locally advanced rectal cancer has a rising global incidence. Over the last 4 decades, advances first in surgery and later in radiotherapy and chemoradiotherapy have improved outcomes, particularly with regard to local recurrence. Unfortunately, distant metastases remain a significant problem. In clinical trials of patients with stage II and III disease, distant relapse occurs in 25% to 30% of patients regardless of the treatment approach. Recent phase 3 trials have therefore focused on intensification of systemic therapy for localized disease, with an aim of reducing the distant relapse rate. Early results of trials of total neoadjuvant therapy with combination systemic therapy provided in the neoadjuvant setting are promising; for the first time, a significant improvement in the rate of distant relapse has been noted. Longer-term follow-up is eagerly awaited. On the other hand, trimodal therapy with chemotherapy, radiotherapy, and surgery is toxic. Several trials are currently assessing the feasibility of a watch-and-wait approach, omitting surgery in those with complete response to neoadjuvant treatment, in an attempt to reduce the burden of treatment on patients. The future for rectal cancer patients is likely to be highly personalized, with more intense approaches for high-risk patients and omission of unnecessary therapy for those whose disease responds well to initial treatment. Biomarkers such as circulating tumor DNA will help to more accurately stratify patients into risk groups. Improvements in survival and quality of life are expected as the results of ongoing research become available throughout the next decade.     

Outcomes after neoadjuvant or adjuvant chemotherapy for cT2-4N0-1 non–small cell lung cancer: A propensity-matched analysis

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

Neoadjuvant Therapy with Drug Arglabin for Breast Cancer with Expression of H-Ras Oncoproteins

Backgrounds: In breast cancer, blocking of Ras signaling and inhibition of H-Ras is quite promising. H-Ras may become a target for farnesyl transferase inhibitors, and in combination with other immunohistochemical factors it will contribute to the progression of a breast tumor. Purpose: The aim of this study was to evaluate the effectiveness of neoadjuvant therapy for breast cancer with the inclusion of farnesyl transferase inhibitor, arglabin interfering with the expression and concentration of H-Ras oncoproteins. Methods: Depending on the presence of H-Ras oncoproteins after Western-blot hybridization, the patients were divided a negative and positive expression of H-Ras groups. Results: Correlation analysis of methods used for determining the expression ability and concentration of H-Ras oncoproteins (immunohistochemistry and Western-blot analysis) demonstrated substantial statistical relationship Rs=0.71, p=0.03. The H-Ras oncoproteins were absent in patients receiving either “Arglabin” or standard AC regimen. However, in the AC + Arglabin group, there was a varying degrees of positive concentration of H-Ras oncoproteins (Kruskal-Wallis=6.92; p=0.03). Conclusion: These results indicate that Arglabin attenuates H-Ras oncoproteins expression which is a promising therapeutic target for breast cancer.     

Does neoadjuvant therapy for pancreatic head adenocarcinoma increase postoperative morbidity? A systematic review of the literature with meta-analysis

Neoadjuvant treatment (NT) for pancreatic head cancer may allow some patients to undergo curative resection, but its impact on postoperative complications remains unclear. A systematic review and meta-analysis were performed to compare overall postoperative morbidity, pancreatic fistula, and mortality between patients who underwent upfront surgery and those who underwent neoadjuvant therapy first. Forty-five studies with 3359 patients were included. No significant differences in morbidity and mortality rates associated with NT for pancreatic head cancer were detected in this study.     

乳腺癌新辅助化疗后腋窝淋巴结转移综合预测模型的建立

目的:建立乳腺癌新辅助化疗后淋巴结转移的综合预测模型，评估新辅助化疗后淋巴结转移情况，指导临床手术方案选择。方法:回顾分析2015年1月至2018年12月143例乳腺癌新辅助化疗患者的临床、病理及影像资料，并根据术后淋巴结病理分为转移组与无转移组。采用χ2/t检验对两组指标进行单因素分析；将P<0.05的指标纳入多因素Logistic回归分析。用多因素分析有统计学意义(P<0.05)的指标构建乳腺癌新辅助化疗后淋巴结转移综合预测模型的列线图，并应用受试者工作特征（receiver operation characteristic,ROC)曲线评价此模型的性能。结果:单因素分析表明化疗方案、化疗前淋巴结穿刺病理、术前查体、术前彩超、术前CT/MRI、RECIST分级对腋窝淋巴结转移有预测作用；多因素分析表明，化疗前淋巴结穿刺病理、术前彩超、RECIST分级是新辅助化疗后腋窝淋巴结转移的独立预测因素。乳腺癌新辅助化疗后淋巴结转移的预测模型的曲线下面积为0.785，特异度为85.4%，敏感度为59.8%。结论:乳腺癌新辅助化疗后淋巴结转移的综合预测模型对腋窝淋巴结有较好的预测能力，可为选择合适的手术方式提供临床指导。