局部进展期直肠癌新辅助放化疗后缓解率的准确性评估

新辅助放化疗是局部进展期直肠癌术前的首选辅助治疗,其使肿瘤降期、降级的作用已得到广泛认可.部分局部进展期直肠癌患者经新辅助放化疗后可达到临床完全缓解(cCR),经术后病理证实为病理完全缓解(pCR).而准确评估缓解率对制定局部进展期直肠癌的后续治疗策略有重要指导作用,本文主要对局部进展期直肠癌缓解率的准确性评估予以综述.     

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.     

结直肠癌肝转移的新辅助治疗进展

目前,新辅助治疗已逐步应用到结直肠癌肝转移的治疗模式中.临床研究表明,新辅助化疗、新辅助放疗和新辅助放化疗可提高结直肠癌肝转移的手术切除率和根治性,对中下段直肠癌可术前降期、提高手术切除率、保肛率和降低复发率.新辅助治疗在结直肠癌肝转移综合治疗中具有较大的临床应用价值.     

直肠癌新辅助放化疗疗效及围手术期并发症的研究进展

新辅助放化疗后行全直肠系膜切除术(TME)是局部进展期直肠癌的标准治疗模式。但在临床工作中,仍有外科医师认为新辅助放化疗会增加手术并发症,影响了手术的实施,这在一定程度上阻碍了新辅助放化疗的推广。近年来,国内外学者应用单纯新辅助化疗替代新辅助放化疗进行了一些尝试,并初步取得与新辅助放化疗一样的R0切除率、降期率,但与新辅助放化疗相比,单纯新辅助化疗并未明显改善病理学完全缓解(pCR)率,也未降低复发率。进一步了解新辅助放化疗的疗效并明确其是否给后期手术切除增加了困难是有非常必要的。临床医师既要关注新辅助放化疗产生的并发症,同时也要重视其在直肠癌治疗中的作用。为寻找更加适合直肠癌患者的治疗方案,本文通过查阅大量相关文献,对目前直肠癌新辅助治疗的常用方法、疗效及围手术期并发症作一综述。     

直肠癌新辅助放化疗的ESMO临床实践指南解读

目前新辅助放化疗已经逐渐变成局部进展期直肠癌的标准治疗手段之一。新辅助放化疗能使肿瘤降期,提高病理缓解率和保肛率,减少局部复发率。欧洲肿瘤内科学会（ European society for medical oncology , ESMO ）针对局部进展期直肠癌新辅助放化疗制定了治疗指南,并作了相关推荐［1］。     

中低位直肠癌的新辅助治疗

提高中低位直肠癌的治疗疗效一直是结直肠外科医生的研究重点。在手术过程引入全直肠系膜切除的概念之后,术前给予放化疗可以进一步提高中低位直肠癌的疗效。通过术前新辅助治疗,可以达到肿瘤降期、提高保肛率、降低术后局部复发率等目的。术前新辅助治疗的适应证、放化疗方案、手术时机等问题已趋于统一,但是如何选择敏感人群进行有效的术前放化疗仍是急需解决的关键问题。     

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.     

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。     

直肠腔内彩色多普勒超声对低位局部进展期直肠癌新辅助放化疗后浸润分期的评估及其影响因素

目的：评价直肠腔内彩色多普勒超声（ERUS）对低位局部进展期直肠癌新辅助放化疗后浸润分期的评估价值及其准确性的影响因素。方法：收集2014年2月至2016年2月我院确诊的Ⅱ、Ⅲ期低位直肠癌患者38例,局部 T3/ T4期,均进行新辅助放化疗。ERUS 评价放疗前后局部病灶改变情况,与病理 T 分期比较,评价 ERUS 新辅助治疗后再分期的准确性,进行准确性影响因素的单因素分析。结果：与新辅助放化疗前比较 ERUS 显示治疗后病灶内部血流分布明显减少（P <0.05）,病灶纵轴最大长度及最大厚度降低（t =2.093, P <0.05;t =6.498,P <0.01）,uT 分期新辅助放化疗后降低（P <0.05）。与术后病理比较,ERUS 在 T1分期准确率为11.11%,T2分期准确率为28.57%,T3分期准确率为27.27%,T4分期准确率为100%。单因素分析显示,复查 ERUS 时间、术后 T 分期及 Wheeler 直肠癌消退分级是 ERUS 对低位直肠癌再分期准确性的影响因素（P =0.043;P =0.004;P =0.017）。结论：ERUS 对 T4再分期准确性较高,在辅助放化疗结束6周后复查ERUS 及消退较差的肿瘤中准确性较高,对低位直肠癌新辅助放化疗后疗效评估有应用价值。     

直肠癌新辅助放化疗疗效预测指标研究进展

 目前新辅助放化疗联合手术逐渐成为局部进展期直肠癌的推荐治疗或标准治疗方案。但直肠癌患者对术前同步放化疗敏感性存在明显差异,部分患者可获得病理完全缓解（pCR）,而部分患者对治疗不敏感,导致肿瘤进展,延误手术时机。因此,对直肠癌患者新辅助治疗敏感性预测指标的相关研究成为热点。本文就局部晚期直肠癌患者新辅助放化疗疗效预测评价指标研究进展作一综述,为临床个体化方案制定提供参考。     

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma

Background

We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC).

Methods

A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013.

Results

Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered.

Conclusions

Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.     

Chemoradiotherapy‐induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse

Cervical cancer therapy is still a major clinical challenge, as patients substantially differ in their response to standard treatments, including chemoradiotherapy (CRT). During cervical carcinogenesis, T‐helper (Th)‐17 cells accumulate in the peripheral blood and tumor tissues of cancer patients and are associated with poor prognosis. In this prospective study, we find increased Th17 frequencies in the blood of patients after chemoradiotherapy and a post‐therapeutic ratio of Th17/CD4⁺ T cells > 8% was associated with early recurrence. Furthermore, Th17 cells promote resistance of cervical cancer cells toward CRT, which was dependent on the AKT signaling pathway. Consistently, patients with high Th17 frequencies in pretherapeutic biopsies exhibit lower response to primary CRT. This work reveals a key role of Th17 cells in CRT resistance and elevated Th17 frequencies in the blood after CRT correspond with early recurrence. Our results may help to explain individual treatment responses of cervical cancer patients and suggest evaluation of Th17 cells as a novel predictive biomarker for chemoradiotherapy responses and as a potential target for immunotherapy in cervical cancer.     

局部晚期非小细胞肺癌的治疗

同步放化疗使局部晚期非小细胞肺癌(NSCLC)的5年生存率由单纯放疗的5%提高到目前的15%左右,是目前标准治疗模式.应用三维适形放疗技术,采用常规分割方式和累及野照射,给予肿瘤较高的剂量,以及同步放化疗后进行巩固化疗显示出更好的疗效;诱导化疗的作用尚不确定;分子靶向药物有较好的应用前景.     

Comparison of intensity‐modulated radiotherapy and 3‐dimensional conformal radiotherapy as adjuvant therapy for gastric cancer

BACKGROUND:

The current study was performed to compare the clinical outcomes and toxicity in patients treated with postoperative chemoradiotherapy for gastric cancer using intensity‐modulated radiotherapy (IMRT) versus 3‐dimensional conformal radiotherapy (3D CRT).

METHODS:

Fifty‐seven patients with gastric or gastroesophageal junction cancer were treated postoperatively: 26 with 3D CRT and 31 with IMRT. Concurrent chemotherapy was capecitabine (n = 31), 5‐fluorouracil (5‐FU) (n = 25), or none (n = 1). The median radiation dose was 45 Gy. Dose volume histogram parameters for kidney and liver were compared between treatment groups.

RESULTS:

The 2‐year overall survival rates for 3D CRT versus IMRT were 51% and 65%, respectively (P = .5). Four locoregional failures occurred each in the 3D CRT (15%) and the IMRT (13%) patients. Grade ≥2 acute gastrointestinal toxicity was found to be similar between the 3D CRT and IMRT patients (61.5% vs 61.2%, respectively) but more treatment breaks were needed (3 vs 0, respectively). The median serum creatinine from before radiotherapy to most recent creatinine was unchanged in the IMRT group (0.80 mg/dL) but increased in the 3D CRT group from 0.80 mg/dL to 1.0 mg/dL (P = .02). The median kidney mean dose was higher in the IMRT versus the 3D CRT group (13.9 Gy vs 11.1 Gy; P = .05). The median kidney V20 was lower for the IMRT versus the 3D CRT group (17.5% vs 22%; P = .17). The median liver mean dose for IMRT and 3D CRT was 13.6 Gy and 18.6 Gy, respectively (P = .19). The median liver V30 was 16.1% and 28%, respectively (P < .001).

CONCLUSIONS:

Adjuvant chemoradiotherapy was well tolerated. IMRT was found to provide sparing to the liver and possibly renal function. Cancer 2010. © 2010 American Cancer Society.     

Discussion of the treatment of esophageal carcinoma,especially in the point of non-surgical treatments, from the viewpoint of medical oncology

Recently,remarkable advances of non-surgical treatments such as endoscopic treatment and chemoradiotherapy (CRT) are made in the treatment of esophageal carcinoma. Endoscopic treatment is recognized a standard for m 1, m 2 esophageal carcinoma, and it's indication is being extended for sm esophageal carcinoma in combination with chemoradiotherapy. In stage I and stage II, treatment result of CRT is comparative with that of surgical resection. In patients with T 4 esophageal carcinoma, it is already accepted that CRT is a standard therapy. This progress of non-surgical treatments contributes to preservation of esophagus in the treatment of esophageal carcinoma. But various problems such as technical problems, complication of CRT and salvage surgery for non-CR or recurrent case also remain. To improve results in treatment of esophageal carcinoma,it is necessary that we make an effort to cooperate with surgeons and radiation oncologists, further.     

新辅助放化疗联合手术与单纯手术治疗局部晚期食管癌的疗效比较

目的探讨新辅助放化疗联合手术治疗局部晚期食管癌较单纯手术治疗能否改善总生存率。方法Ⅱa～Ⅲ期食管癌患者60例,随机分成新辅助放化疗联合手术组及单纯手术治疗组,每组30例。化疗使用PF方案,DDP 75 mg/（m2.d）,d1,5-FU 500 mg/（m2.d）,d1-5持续滴注,第1次化疗与第1次放疗同时实施,每3周1个疗程,放疗期间共2个疗程。放化疗结束后2-4周行食管癌根治术。放疗剂量PTV靶区给予每次2.0 Gy,5次/周,总剂量50 Gy。结果给予新辅助放化疗联合手术组患者必要的对症支持治疗,患者均能够完成同期放化疗。新辅助放化疗联合手术组并发症多于单纯手术组,但两组比较差异无统计学意义。1、2、3年生存率新辅助放化疗联合手术组分别为83.3%、65.3%、42.8%,单纯手术组分别为80.0%、41.6%、25.0%（χ2=3.992,P=0.046）。结论新辅助放化疗联合手术治疗可以改善局部晚期食管癌的总生存率,且不明显增加术后并发症,值得临床推广应用。     

Comparison of Radical Cystectomy and Chemoradiotherapy in Patients with Locally Advanced Bladder Cancer

The aim of this study was to evaluate the clinical outcomes of radical cystectomy (RC) and concurrent chemoradiotherapy (CRT) with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with locally advanced bladder cancer (BC). From December 2000 to February 2012, 72 patients with locally advanced BC (T3-4a, N0 or N+, M0) received either RC or CRT. RC with bilateral pelvic lymph node dissection including the common iliac region as the standard procedure. Patients in the CRT group received one cycle of MVAC followedby radiotherapy with a half dose of MVAC and then two more cycles of MVAC. Standard fractionation at a daily dose of 1.8-2.0 Gy was used, with a median total dose of 50 Gy (range, 45-60 Gy). The 3-year progression-free survival (PFS) rates in the RC and CRT groups were 56.2% and 25.6%, respectively (p=-0.015) and the 3-year overall survival (OS) rates were 63.5% and 48.1% (p=0.272). Multivariate Cox proportional hazards regression analysis with application of a propensity score indicated that RC was a significant predictor of PFS (p=0.033)but not of OS (p=0.291). Among patients with locally advanced BC, PFS was significantly prolonged in the RC group compared with the CRT group. However, RC was not a significant predictor of OS. Although the sample size in this study was small, the results suggest that patient background and postoperative quality of life should be considered when choosing treatment strategy for locally advanced BC.     

Patterns of failure for stage I ampulla of Vater adenocarcinoma: a single institutional experience

Background

Ampullary adenocarcinoma is a rare malignancy associated with a relatively favorable prognosis. Given high survival rates in stage I patients reported in small series with surgery alone, adjuvant chemoradiotherapy (CRT) has traditionally been recommended only for patients with high risk disease. Recent population-based data have demonstrated inferior outcomes to previous series. We examined disease-related outcomes for stage I tumors treated with pancreaticoduodenectomy, with and without CRT.

Methods

All patients with stage I ampullary adenocarcinoma treated from 1976 to 2011 at Duke University were reviewed. Disease-related endpoints including local control (LC), metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.

Results

Forty-four patients were included in this study. Thirty-one patients underwent surgery alone, while 13 also received adjuvant CRT. Five-year LC, MFS, DFS and OS for patients treated with surgery only and surgery with CRT were 56% and 83% (P=0.13), 67% and 83% (P=0.31), 56% and 83% (P=0.13), and 53% and 68% (P=0.09), respectively.

Conclusions

The prognosis for patients diagnosed with stage I ampullary adenocarcinoma may not be as favorable as previously described. Our data suggests a possible benefit of adjuvant CRT delivery.     

Short-term Mortality Associated with Definitive Chemoradiotherapy Versus Radical Cystectomy for Muscle-invasive Bladder Cancer

BackgroundMuscle-invasive bladder cancer (MIBC) may be managed with radical cystectomy (RC) or chemoradiotherapy (CRT). Because patient selection for RC is important to avoid treatment-related mortality, this study addressed a knowledge gap by quantifying short-term mortality with both approaches, as well as predictors thereof.Materials and MethodsThe National Cancer Database was queried (2004-2014) for clinically staged T2-4aN0M0 MIBC that received either CRT or RC. Statistics included cumulative incidence comparisons of 30- and 90-day mortality between patients treated with either CRT or RC and Cox regression to evaluate predictors thereof.ResultsOf 16,658 patients, 15,208 (91.3%) underwent RC and 1450 (8.7%) CRT. Crude rates of post-treatment mortality at 30 days were 2.7% versus 0.6% (P < .001) and at 90 days were 7.5% versus 4.5% (P = .017) for patients treated with RC and CRT, respectively. When stratifying by age, worse 30- and 90-day mortality with RC was observed for patients aged ≥ 76 years.ConclusionsThis study describes 30- and 90-day mortality following RC versus CRT. Both approaches yield statistically similar treatment-related mortality rates in patients ≤ 75 years of age; however, worse post-treatment mortality was observed with use of RC in patients ≥ 76 years of age. These results may be utilized to better inform shared decision-making between patients and providers when weighing both RC and CRT for MIBC.     

Chemoradiotherapy regimens for locoregionally advanced nasopharyngeal carcinoma: A Bayesian network meta-analysis

BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-A) is often the regimen of choice in locoregionally advanced nasopharyngeal carcinoma (NPC). Many alternative regimens have been reported in the literature, however, it is unknown how effective these regimens are compared to each other due to the lack of direct comparisons. Our objective was to perform a network meta-analysis (NMA) to determine the relative survival benefits of these treatments for locoregionally advanced NPC.MethodsWe performed a systematic review following the Cochrane methodology, using MEDLINE, EMBASE and CENTRAL to identify all randomised controlled trials (RCTs) that compared different chemoradiotherapy regimens for locoregionally advanced NPC. Overall survival (OS) was the primary outcome of interest, and hazard ratios (HRs) were extracted using the Parmar method. Bayesian NMAs with random effects were conducted using WinBUGS.ResultsTwenty-five RCTs (5576 patients) were included in this review. All together, these trials compared seven different regimens: radiotherapy (RT), concurrent chemoradiotherapy (CRT), neoadjuvant followed by CRT (N-CRT), CRT-A, RT-A, N-RT and N-RT-A. All regimens that contained CRT performed significantly better than RT. CRT-A did not improve survival compared to CRT alone (0.98; 95% credible regions: 0.71–1.34). For N-CRT versus CRT, the HR was 1.03 (0.69–1.47). When CRT-A was compared against N-CRT, the resulting HR was 0.96 (0.64–1.48).ConclusionsAdjuvant chemotherapy does not appear to improve survival following CRT. The efficacies of CRT, CRT-A and N-CRT all appeared to be similar. Further studies are warranted to determine the value of additional chemotherapy phases in specific patient subgroups.