局部进展期直肠癌新辅助治疗研究进展

直肠癌是常见的消化道恶性肿瘤，手术难度大，术后并发症较为常见，局部复发率较高，尤其以局部进展期直肠癌(LARC)的治疗效果差。随着多学科综合治疗理念在恶性肿瘤诊疗过程中受到重视，局部进展期直肠癌患者的预后也在术前新辅助治疗的应用下得以改善。因新辅助放化疗能有效降低术后局部复发率，新辅助放化疗联合全直肠系膜切除术(TME)已成为局部进展期直肠癌国际公认的治疗模式，临床医生也逐渐重视该疾病的术前治疗。为探求更佳的直肠癌患者的综合治疗方案，通过阅读国内外相关文献，就直肠癌新辅助治疗的现状与研究进展进行综述。     

同步新辅助放化疗联合全直肠系膜切除术治疗中低位局部进展期直肠癌的临床研究

目的:探讨同步新辅助放化疗联合全直肠系膜切除术(total mesorectal excision,TME)治疗中低位局部进展期直肠癌的疗效及安全性。方法:2009年9月-2011年2月30例中低位局部进展期直肠癌患者[Ⅱ期(T3-4N0M0)14例,Ⅲ期(T1-4N1-2M0)16例]接受了术前同步新辅助放化疗(术前放疗总剂量为45～50Gy,1.8Gy/次;化疗方案为FOLFOX4,化疗2个周期)。同步新辅助放化疗结束后4～6周行手术治疗,遵循TME原则。结果:全部患者均完成同步新辅助放化疗,CR5例、PR18例、SD7例,有23例(76.7%)患者的临床TNM分期下降。同步新辅助放化疗结束后4～6周,除1例CR患者拒绝手术外,29例患者均行手术治疗,其中23例行低位或超低位前切除术(Dixon术),6例行腹会阴联合切除术(Miles术),保肛率为80.0%(24/30)。无一例发生围手术期死亡,术后并发症的总发生率为20.7%(6/29)。结论:同步新辅助放化疗联合TME治疗中低位局部进展期直肠癌安全而有效,可以降低肿瘤分期、提高肿瘤切除率和保肛率,改善患者的生活质量。     

辅助化疗对ypⅠ期直肠癌患者术后生存的影响

[目的]比较Ⅰ期直肠癌与新辅助治疗后降期为ypT1-2N0M0的cT3-4或N+的直肠癌患者5年总生存率的差异.[方法]回顾分析105例直肠癌根治术后病理分期为T1～2N0M0的直肠癌患者的临床病理资料及随访资料.按患者是否行新辅助治疗和辅助化疗分为3组.单纯手术组(A组):未经术前新辅助治疗,pT1～2N0M0的早期直肠癌患者(29例).新辅助降期化疗组(B1组):初始诊断为cT3-4或N+,术前行新辅助治疗后降期为ypT1-2N0M0,且术后行辅助化疗的直肠癌患者(54例).新辅助降期非化疗组(B2组):初始诊断为cT3～4或N+,术前行新辅助治疗后降期为ypT1～2N0M0,且术后未行辅助化疗的直肠癌患者(22例).对3组生存情况进行分析.[结果]新辅助治疗后降期为T1～2N0M0的直肠癌患者(B1+B2组)术后5年生存率为94.0％.单纯手术组(A组)患者术后5年生存率为91.0％,新辅助降期化疗组(B1组)为88.9％,新辅助降期非化疗组(B2组)为90.9％.单因素分析提示3组预后差异无统计学意义(P＞0.05).[结论]新辅助治疗后降期为T1-2N0M0的直肠癌患者无论是否行术后化疗都可获得与Ⅰ期直肠癌患者相同的预后.新辅助治疗后降期为T1～2N0M0直肠癌患者术后化疗并未能提高患者5年总生存率.     

局部中晚期直肠癌术前放疗应用进展

直肠癌是常见恶性肿瘤,近年来在我国的发病率有迅速上升的趋势。随着直肠全系膜切除术(total mesorectal excision,TME)作为直肠癌手术金标准在临床上广泛开展,局部复发率已从20年前约25%降低至5%~10%以下^[1-2]。但局部中晚期(Ⅱ~Ⅲ期,TNM分期为T₃~T₄期或N(+)M₀期)直肠癌术后远处转移率及死亡率仍然较高,为了进一步提高局控率及长期生存率,多学科综合治疗已成共识。2008版国立综合癌症网(national comprehensive cancer network,NCCN)指南推荐术前新辅助同期放化疗联合TME手术为Ⅱ~Ⅲ期直肠癌的标准治疗方案。现将术前放疗在可手术切除局部中晚期直肠癌新辅助治疗中应用的最新进展综述如下。     

局部进展期结直肠癌新辅助免疫治疗临床研究及应用进展

局部进展期结直肠癌术后高复发风险使得患者长期生存面临挑战。免疫检查点抑制剂的出现使得许多恶性肿瘤的治疗发生了革命性的转变。目前,免疫检查点抑制剂已被批准用于不可切除的结直肠癌晚期的一线治疗,但其在新辅助治疗中的疗效和安全性的描述尚不多见。早期的临床试验已经初步证实了新辅助免疫治疗在局部进展期结直肠癌患者中的临床益处,进一步高质量的临床试验正在开展。本文就免疫检查点抑制剂在局部进展期结直肠癌新辅助治疗中的相关临床研究和应用进展进行梳理和总结,以期为结直肠癌新辅助免疫治疗的发展提供一定的参考。     

直肠癌新辅助放化疗后等待观察策略疗效分析

目的:比较局部进展期直肠癌新辅助治疗后临床完全缓解(cCR)的患者等待观察(W&W)与直肠癌全系膜切除术(TME)后病理完全缓解(pCR)患者的疗效。方法:回顾性队列研究,收集2014—2019年中国医学科学院肿瘤医院收治的新辅助放化疗Ⅱ-Ⅲ期直肠癌患者,纳入标准为完成新辅助治疗后规律随访≥1年且达到cCR者(W&W组...     

Caspase-1 p20水平预测局部进展期直肠癌新辅助放疗敏感性的临床意义

目的 探讨含半胱氨酸的天冬氨酸蛋白水解酶1(Caspase-1)活化物Caspase-1 p20水平与局部进展期直肠癌新辅助放疗敏感性的关系,评价Caspase-1 p20水平预测术前新辅助放疗效果的价值。方法 收集本院2017年9月至2020年12月接受新辅助放化疗联合手术治疗的直肠癌患者55例,免疫组化法检测术后标本中的Caspase-1 p20水平,根据肿瘤退缩分级(TRG)评价新辅助放疗敏感性,分析Caspase-1 p20水平变化与临床病理特征和放疗敏感性的关系。结果 55例患者放疗敏感(TRG0+TRG1) 26例、放疗抵抗(TRG2+TRG3) 29例,Caspase-1 p20在30例肿瘤组织中呈低水平、25例呈高水平。直肠癌组织的Caspase-1 p20水平与放疗敏感性、新辅助放化疗的术后病理T分期和肿瘤直径有关(P<0.05)。Caspase-1 p20高水平者的肿瘤退缩差、对放疗抵抗,相关性分析证实Caspase-1 p20水平与TRG分级呈正相关(r²=0.44)。多因素分析示,Caspase-1 p20水平是放疗抵抗的独立风险因素...     

直肠癌新辅助放化疗

根治性手术结合术后放、化疗一度被作为国际公认的Ⅱ及Ⅲ期直肠癌的标准疗法。近年,新辅助放化疗逐渐得到广泛的关注。大量研究表明,与术后放化疗相比,新辅助放化疗结合根治性手术的多模式联合治疗在降低直肠癌的局部复发率、延长生存时间等方面均显示出更好的效果,特别是在提高保肛率方面具有突出的优势。目前认为,新辅助放化疗适用于局部进展期(T3~4)或有系膜内淋巴结转移的低位直肠癌患者(Ⅱ~Ⅲ期)。随着先进的诊断技术、更优化的放疗模式,以及更多有效的药物及新配伍方案的引入,对直肠癌患者采取个体化的术前新辅助治疗,将使直肠癌的治疗效果得到进一步提高。     

新辅助同步放化疗联合TME及术后辅助化疗对中低位局部进展期直肠癌的疗效研究

目的探讨新辅助同步放化疗联合全直肠系膜切除（TME）加术后辅助化疗三联疗法治疗中低位局部进展期直肠癌的疗效及安全性.方法选择局部进展期中低位直肠癌Ⅱ、Ⅲ期（T2N＋M0,T3-4N0-2M0期）65例,术前放疗总剂量50～54Gy,术前采用Xelox方案化疗3个疗程,放化疗结束后6～8周根据TME原则行直肠癌根治术.术后采用Forfox4方案辅助化疗6个疗程.结果65例均完成新辅助同步放化疗、手术治疗及术后辅助化疗.其中48例行Dix-on’s手术,17例行mile’s手术,保肛率73.85%,术后并发症发生率23.08%,其中伤口感染延期愈合6例,吻合口瘘4例,吻合口狭窄5例,手术后病理完全缓解（pCR）11例,占16.92%.结论新辅助放化疗＋TME手术治疗＋术后辅助化疗三联疗法治疗中低位进展期直肠癌安全有效,可以降低肿瘤分期,减少局部复发及远处转移,中远期疗效好.     

局部进展期直肠癌术前腹股沟淋巴结灌注化疗的前瞻性随机对照研究

目的探讨术前腹股沟淋巴结灌注化疗在局部进展期直肠癌治疗中的安全性和有效性。方法对100例局部进展期直肠癌患者随机分组行前瞻性对照研究,治疗组50例行术前腹股沟淋巴结灌注化疗,化疗后7~10天行直肠癌根治术,对照组50例不做术前新辅助化疗,直接行根治术。随访观察治疗效果。结果所有患者均安全度过围手术期,无严重并发症,治疗组的淋巴结转移度显著低于对照组(P0.01),术后生存率优于对照组,差异有统计学意义(P0.05)。结论局部进展期直肠癌行术前腹股沟淋巴结灌注化疗安全可行,效果好,是一种较好的新辅助治疗方法。     

Should we favour the use of 5 × 5 preoperative radiation in rectal cancer

The management of patients with “locally advanced rectal cancer” (LARC) is evolving from the original aim of reducing local recurrence. Current practice recognises the importance of surgical technique, high-quality preoperative imaging, and integration of neoadjuvant systemic chemotherapy. Contemporary protocols focus on improving survival and avoiding radical surgery with organ preservation strategies. Both short course preoperative radiotherapy (SCPRT) with immediate surgery and long-course chemoradiation (LCCRT) are standard neoadjuvant strategies, both demonstrating similar efficacy in preventing local recurrence, distant metastases and improving disease-free survival (DFS). SCPRT is highly cost-effective with high compliance rates, hence is gaining traction in Europe and East Asia, partly because of inherent flexibility in timing and the ability to add neoadjuvant systemic chemotherapy as there is a delay to surgery. SCPRT is currently not being exploited to its full extent – particularly in the USA where uptake is approximately 1% of neoadjuvant treatments for rectal cancer. We analyse the use of induction, concurrent and consolidation chemotherapy with SCPRT in a total neoadjuvant therapy (TNT) approach.     

Advances in organ preserving strategies in rectal cancer patients

Treatment of rectal cancer patients has been subjected to change over the past thirty years. Total mesorectal excision is considered the cornerstone of rectal cancer treatment, but is also associated with significant morbidity resulting in an impaired quality of life. The addition of neoadjuvant chemoradiotherapy to surgery has shown to improve survival and local control and may lead to a partial or even complete response (CR). This raises questions regarding the necessity for subsequent radical surgery. After careful patient selection local excision and wait-and-see approaches are explored, aiming to improve quality of life without compromising oncological outcome. A multimodality diagnostic approach for optimal staging is crucial in determining the appropriate neoadjuvant treatment regimen. Adequate endoscopic restaging of rectal tumours after multimodality treatment will aid in selecting patients who are eligible for an organ preserving approach. The role and accuracy of imaging in the detection of the primary tumour, residual rectal cancer or local recurrence seems vital. Alternative neoadjuvant regimens are currently explored to increase the rate of clinical CRs, which may support organ preserving approaches. This review aims to generate insight into the advances in diagnostics and treatment modalities in all stages of rectal cancer and will highlight future studies that may support further implementation of organ preservation treatment in rectal cancer.     

Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study

IntroductionThe addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics.MethodsAll LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics.ResultsOf 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013).ConclusionTreatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics.     

局部进展期直肠癌新辅助治疗策略研究进展

局部进展期直肠癌(LARC)的治疗极具挑战性,仅凭手术切除难以达到满意疗效,近年来LARC诊治倾向于多学科协作(MDT)模式,依托其出现的新辅助治疗策略是LARC诊治的里程碑式进展.目前,LARC首选疗法为新辅助放化疗联合全直肠系膜切除术.本文围绕LARC新辅助治疗主要方案作一综述,以期为临床诊疗提供参考.     

靶向治疗联合新辅助放化疗在局部进展期直肠癌中的应用

目前新辅助放化疗联合全直肠系膜切除术（TME）是局部进展期直肠癌（LARC）的标准治疗模式.靶向药物在LARC新辅助治疗中耐受性及安全性良好,但与常规新辅助放化疗相比较,病理完全缓解（pCR）率并无提高,仍需大样本随机对照研究证实其在LARC新辅助治疗中的作用.     

中低位局部进展期直肠癌器官保留热点问题

局部进展期直肠癌标准治疗为新辅助放化疗后全直肠系膜切除术。临床上部分患者在新辅助治疗后可以达到临床完全缓解或者近临床完全缓解。对于该类患者，很多研究机构采取等待观察策略或者局部切除来代替传统的全直肠系膜切除术。临床上将该种代替治疗手段称之为器官保留。而器官保留自从诞生之日起，争论不断。作者就器官保留中的热点问题做一述评。     

Swing of the pendulum: Optimizing functional outcomes in larynx cancer

For years, total laryngectomy was the only treatment option for patients with intermediate to advanced laryngeal cancer. Over the past two decades, great progress has been made in the management of this disease, with multimodality approaches aimed at laryngeal preservation reshaping the treatment landscape. In the era of chemoradiation, greater focus and attention are now directed toward functional laryngeal preservation—not simply “organ preservation.” The continued development and integration of new treatment approaches, including organ preservation surgery (eg, transoral minimally invasive surgery of the head and neck, supracricoid partial laryngectomy), intensity-modulated radiotherapy, and targeted molecular therapies, offer the potential to improve clinical outcomes, function, and quality of life. Incorporation of these new approaches advances the concept of personalized medicine, with treatment strategies tailored to the circumstances and future of each patient.     

局部晚期直肠癌新辅助放化疗联合免疫治疗的研究进展

对于局部晚期(T3-4/N+M0)直肠癌, 新辅助放化疗联合全直肠系膜切除术的标准治疗模式可以明显减少局部复发、增加肿瘤退缩, 但是远处转移没有得到改善。放疗和免疫治疗相辅相成, 两者联合具有良好的理论基础。近年来, 局部晚期直肠癌新辅助放化疗联合免疫治疗的相关临床试验逐渐展开, 在微卫星不稳定(MSI-H)和微卫星稳定(MSS)患者中均进一步提高肿瘤退缩程度和病理性完全缓解率, 增加器官保留概率, 为"等待观察"策略提供更多可能。新辅助放化疗联合免疫治疗未来仍需要更多的大型临床试验进行验证, 期待能带来更好的生存获益。     

NPS与局部晚期直肠癌新辅助放化疗疗效及预后相关性初步分析

目的 分析Naples预后评分(NPS)与局部晚期直肠癌(LARC)新辅助治疗疗效相关性及其预测预后价值。方法 回顾性分析2015-2020年136例LARC患者资料,搜集并计算新辅助治疗前血清白蛋白、总胆固醇、中性粒细胞与淋巴细胞比值和淋巴细胞与单核细胞比值,根据NPS法则对入组患者进行评分分级。采用Kaplan-Meier法计算生存率,Cox模型多因素预后分析。结果 NPS与LARC新辅助治疗后肿瘤退缩程度及术后pCR无相关性(P=0.192、0.163)。Cox多因素分析显示NPS是LARC的总生存(OS)及无瘤生存(DFS)的独立危险因素(P=0.017、0.003),且分层分析提示评分越低者预后较好;此外,肿瘤大小也是OS的独立危险因素,肿瘤大小与N分期也是DFS的独立危险因素。结论 NPS与LARC新辅助放化疗后肿瘤退缩及pCR无相关性,但能作为LARC治疗长期预后的有效预测指标。     

The effect of neoadjuvant short-course radiotherapy and delayed surgery versus chemoradiation on postoperative outcomes in locally advanced rectal cancer patients – A propensity score matched nationwide audit-based study

ObjectiveTo investigate differences in postoperative outcomes between short-course radiotherapy and delayed surgery (SCRT-delay) and chemoradiation (CRT) in patients with locally advanced rectal cancer (LARC).BackgroundPrevious trials suggest that SCRT-delay could serve as an adequate neoadjuvant treatment for LARC. Therefore, in frail LARC patients SCRT-delay is recommended as an alternative to CRT. However, data on postoperative outcomes after SCRT-delay in comparison to CRT is scarce.MethodsThis was an observational study with data from the Dutch ColoRectal Audit (DCRA). LARC patients who underwent surgery (2014–2017) after an interval of ≥6 weeks were included. Missing values were replaced by multiple imputation. Propensity score matching (PSM), using age, Charlson Comorbidity Index, cT-stage and surgical procedure, was applied to create comparable groups. Differences in postoperative outcomes were analyzed using Chi-square test for categorical variables, independent sample t-test for continuous variables and Mann-Whitney U test for non-parametric data.Results2926 patients were included. In total, 288 patients received SCRT-delay and 2638 patients underwent CRT. Patients in the SCRT-delay group were older and had more comorbidities. Also, ICU-admissions and permanent colostomies were more common, as well as pulmonic, cardiologic, infectious and neurologic complications. After PSM, both groups comprised 246 patients with equivalent age, comorbidities and tumor stage. There were no differences in postoperative complications.ConclusionPostoperative complications were not increased in LARC patients undergoing SCRT-delay as neoadjuvant treatment. Regarding treatment-related complications, SCRT-delay is a safe alternative neoadjuvant treatment option for frail LARC patients.