Prognostic value and clinicopathological correlation of the tumor regression grade in neoadjuvant chemotherapy for gastric adenocarcinoma: a retrospective cohort study

BackgroundNeoadjuvant chemotherapy (NACT) and radical gastrectomy are the gold standard treatments for resectable advanced gastric cancer (GC). However, the prognostic value of the pathological tumor regression grade (TRG) of NACT remains controversial. This retrospective study aimed to investigate the correlation between the TRG after NACT and clinicopathological features as well as its prognostic value in advanced GC.MethodsIn total, 551 patients with GC who received NACT combined with surgical resection at the Zhejiang Cancer Hospital from April 2004 to December 2019 were included. The demographic characteristics, treatment response, tumor characteristics, treatment regimens, and survival data were reviewed from the medical records of all patients. The Chi-square test was used to analyze the correlation between TRG and clinicopathological factors. Kaplan-Meier univariate analysis and Cox regression multivariate analysis were used to determine the independent risk factors affecting the prognosis of GC patients.ResultsAmong the 551 patients with advanced GC who accepted NACT treatment, 14 were determined to be in TRG 0, 98 in TRG 1, 257 in TRG 2, and 182 in TRG 3. Also, TRG was significantly correlated with the cT stage (P=0.015), ypT stage (P<0.001), ypN stage (P<0.001), ypTNM stage (P<0.001), vascular tumor thrombus (P<0.001), Borrmann classification (P=0.042), and lymph node ratio (LNR) (P<0.001). Furthermore, patients who had a good pathological response to NACT had a better prognosis, with a 3-year overall survival (OS) of 70.9% versus 48.8% in patients who had a poor pathological response. We also found that TRG (P=0.042, HR =1.65) was an independent prognostic factor affecting the OS of GC patients.ConclusionsTRG plays a significant role in the prognostic value in neoadjuvant chemotherapy for gastric adenocarcinoma. Patients with higher cT stage, higher levels of pre-CA199 and pre-CA125 may have worse pathological response.     

Pathological complete response following docetaxel-based neoadjuvant chemotherapy for locally advanced gastric adenocarcinoma

Locally advanced gastric adenocarcinoma has a poor outcome. Neoadjuvant treatment is being tested in locally advanced non-resectable tumours and in those resectable tumours with a high risk of recurrence. Efforts to identify prognostic factors and more active and less toxic preoperative regimens are being searched for. We report the case of a patient achieving a complete histopathological complete response following docetaxel-based neoadjuvant chemotherapy.     

Impact of neoadjuvant chemotherapy on nodal regression and survival in oesophageal adenocarcinoma

BackgroundThe prognostic value of lymph node regression (LNR) following neoadjuvant chemotherapy (nCT) for oesophageal and gastro-oeosphageal adenocarcinoma remains unclear. This study aimed to characterise the long-term survival outcomes of LNR in patients having resectional surgery after nCT.MethodsThis study included patients undergoing oesophagectomy or extended total gastrectomy for oesophageal and junctional tumours (Siewert types 1,2,3) at the Queen Elizabeth Hospital Birmingham from 2012 to 2018. Lymph nodes retrieved at surgery were examined for evidence of a response to chemotherapy. Patients were classified as lymph node-negative (either negative nodes with no evidence of previous tumour involvement or negative with evidence of complete regression) or positive with either partial or no response.ResultsThis study identified 183 patients who received nCT, of which 71% (130/183) had positive lymph nodes. Of these 130 patients, 44% (57/130) had a lymph node response and 56% (73/130) did not. The remaining 53 patients (29.0%) had negative lymph nodes with no evidence of tumour. Lymph node responders had a significant survival benefit compared to patients without lymph node response, but shorter than those with negative lymph nodes (median: 27 vs 18 vs NR months, p < 0·001). On multivariable analysis, lymph node responders had an improved overall (Hazard ratio (HR): 0.86, 95% CI: 0.80–0.92, p < 0.001) and recurrence-free (HR: 0.90, 95% CI: 0.82–0.98, p = 0.030) survival.ConclusionLymph node regression is an important prognostic factor, warranting closer evaluation over primary tumour response to help with planning further adjuvant therapy in these patients.     

Response to neoadjuvant chemotherapy and effects of tumor regression in gastric cancer

AIMS: Aim of this study is the evaluation of the effects induced by neoadjuvant chemotherapy (NACT) and its impact on survival on a series of locally advanced gastric carcinomas. METHODS: Downstaging was assessed comparing pre-treatment clinical and laparoscopic staging with post-operative pathologic staging on 30 consecutive patients who completed a 3-year follow-up. Tumor downstaging and the grade of pathologic response were included in a statistical correlation between tumor regression induced by NACT and 3-year survival. RESULTS: In this series tumor downstaging was obtained in 13 out of 30 patients. After the completion of 3-year follow-up, overall survival was >37.5months with an overall survival rate of 56.7%; this figure reached up to 70.8% in those cases who benefited from a R0-resection (24/30 patients: R0-resection rate 80.0%). CONCLUSIONS: In this study the 3-year survival for locally advanced gastric cancer treated by NACT prior to "D2" surgical resection, compares favourably with historical series treated by surgery alone. Patients who obtained T-downstaging and subsequently benefited from a R0-resection had a definitely better chance of cure, according to a complete 3-year follow-up.     

直肠腺癌75例新辅助放化疗肿瘤退缩分级相关临床病理因素分析

目的 通过评估直肠腺癌患者对新辅助放化疗的反应率,旨在探讨新辅助放化疗后组织学消退的预测因素.方法 回顾性分析2015-06-01-2018-05-31郑州大学附属肿瘤医院接受新辅助放化疗,并行手术治疗的75例局部进展期直肠腺癌患者的临床病理资料,KRAS、NRAS和BRAF基因通过等位基因特异性PCR或Sanger测...     

Optimal timing of surgery following breast cancer neoadjuvant chemotherapy: A systematic review and meta-analysis

BackgroundAdministration of chemotherapy before breast surgery has the potential to reduce the risk of distant recurrence by targeting micrometastasis as well as allowing a more minimalistic approach to surgical intervention. We performed a systematic review to determine the optimum timing of surgery post breast cancer neoadjuvant chemotherapy (NACT).MethodsThe primary outcome was to determine whether the timing of surgery post NACT impacted overall survival (OS) and disease-free survival (DFS). We compared patient outcomes between those who had surgery within 8 weeks of completion of NACT to those that had surgery after 8 weeks. An outcome comparison between <4 weeks and 4–8 weeks was also performed. Secondary outcome included complete pathological response (pCR) post NACT. A meta-analysis was performed using the Mantel-Haenszel method.ResultsFive studies, including 8794 patients were eligible for inclusion. Patients that had surgery within 8 weeks of completion of NACT had a statistically significant improved OS(OR 0.47, 95% c. i 0.34–0.65) and DFS(OR 0.71 (95% c. i 0.52–0.98, P = 0.04). There were no survival advantages associated with having surgery less than 4 weeks post completion of NACT (OR 0.78, 95% c. i 0.46–1.33, P = 0.37). There was no difference in pCR rate between those that had surgery <4 weeks and 4–8 weeks (OR 1.01, 95% c. i 0.80–1.28, P = 0.93).ConclusionThis meta-analysis shows that the optimum timing of surgery post completion of NACT is 4–8 weeks as it is associated with increased OS and DFS.     

Clinical effectiveness of neoadjuvant chemotherapy in advanced gastric cancer: An updated meta-analysis of randomized controlled trials

Aims

To assess the efficacy and safety of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (AGC).

Methods

By searching electronic databases (PubMed, Embase, Cochrane Library) and ASCO proceedings from 1990 to 2012, all randomized controlled trials (RCTs) which compared the effect of NAC-combined surgery versus surgery alone in AGC were included. All calculations and statistical tests were performed using RevMan 5.0 software.

Results

12 RCTs with a total of 1820 patients were included. All patients had locally advanced but resectable gastric cancer and received NAC. NAC can slightly improve the survival rate (OR = 1.32, 95% confidence interval (CI): 1.07–1.64, P = 0.01), with little or no significant benefits in subgroup analyses between either different population or regimens. NAC can significantly improve the 3-year progression-free survival (PFS) (OR: 1.85, 95% CI: 1.39–2.46, p < 0.0001), tumor down-staging rate (OR: 1.71, 95% CI: 1.26, 2.33, p = 0.0006) and R0 resection rate (OR: 1.38, 95% CI: 1.08–1.78, P = 0.01) of patients with AGC. There was no difference between the two arms, in terms of relapse rates (OR: 1.03, 95% CI: 0.60–1.78, p = 0.92), operative complications (OR: 1.20, 95% CI: 0.90–1.58, p = 0.21), perioperative mortality (OR: 1.14, 95% CI: 0.64–2.05, p = 0.65) and grade 3/4 adverse effects: gastrointestinal problem (OR: 0.57, 95% CI: 0.25–1.30, p = 0.18), leukopenia (OR: 0.88, 95% CI: 0.41–1.91, p = 0.75), thrombocytopenia (OR: 1.27, 95% CI: 0.27–5.93, p = 0.76).

Conclusion

NAC is effective and safe. However, further prospective multi-national and multi-center RCTs are still needed in order to investigate the long-term oncological and functional outcomes to define the clinical benefits of NAC and the most effective strategies for AGC.     

胃癌新辅助化疗疗效的系统评价——Meta分析

背景与目的:自1989年首次报道新辅助化疗在胃癌治疗中的应用以来,新辅助化疗作为胃癌综合治疗的一种方法已得到越来越多的关注,但其在胃癌治疗的价值仍有争议。本研究拟对全世界中、英文相关随机对照试验研究的结果进行Meta分析,以对胃癌新辅助化疗的疗效进行评价。方法:采用Cochrane系统评价方法,检索Cochrane图书馆临床对照试验库、PubMed、Embase、中国生物医学文献数据库(Chinese Biomedical Literature Database,CBM)、中文科技期刊全文数据库(Chinese Scientific Journal Full-text Database,CSJD)、中国期刊全文数据库(Chinese Journal Full-text Database,CJFD)等数据库,并辅以手工检索和其它检索。由2名评价者独立评价并交叉核对纳入研究的质量,对同质研究采用RevMan4.2.10软件进行Meta分析。结果:共5个随机对照试验838例患者纳入研究,其中2个随机对照研究来自日本,另3个分别来自荷兰、英国和中国;包括新辅助化疗组373例患者,手术组465例患者。5个研究均报道采用了随机方法,David使用了盲法,Yutaka对分配隐藏方案进行了描述。Meta分析结果:新辅助化疗组与单纯手术组的手术切除率、治愈率、1年生存率和5年生存率差异均无统计学意义,其OR值和95%CI分别为1.09(0.67,1.77)、1.25(0.85,1.84)、1.61(0.90,2.90)、1.13(0.83,1.53)。结论:进展期胃癌新辅助化疗的疗效并不优于单纯手术,在没有取得新辅助化疗治疗胃癌有效的临床证据之前,不宜将此治疗方法作为胃癌的临床常规治疗。     

The predictive value of histological tumor regression grading (TRG) for therapeutic evaluation in locally advanced esophageal carcinoma treated with neoadjuvant chemotherapy

Response criteria remain controversial in therapeutic evaluation for locally advanced esophageal carcinoma treated with neoadjuvant chemotherapy.We aimed to identify the predictive value of tumor regression grading(TRG) in tumor response and prognosis.Fifty-two patients who underwent neoadjuvant chemotherapy followed by esophagectomy and radical 2-field lymphadenectomy between June 2007 and June 2011 were included in this study.All tissue specimens were reassessed according to the TRG scale.Potential prognostic factors,including clinicopathologic factors,were evaluated.Survival curves were generated by using the Kaplan-Meier method and compared with the log-rank test.Prognostic factors were determined with multivariate analysis by using the Cox regression model.Our results showed that of 52 cases,43(83%) were squamous cell carcinoma and 9(17%) were adenocarcinoma.TRG was correlated with pathologic T(P = 0.006) and N(P < 0.001) categories.Median overall survival for the entire cohort was 33 months.The 1-and 2-year overall survival rates were 71% and 44%,respectively.Univariate survival analysis results showed that favorable prognostic factors were histological subtype(P = 0.003),pathologic T category(P = 0.026),pathologic N category(P < 0.001),and TRG G0(P = 0.041).Multivariate analyses identified pathologic N category(P < 0.001) as a significant independent prognostic parameter.Our results indicate that histomorphologic TRG can be considered as an alternative option to predict the therapeutic efficacy and prognostic factor for patients with locally advanced esophageal carcinoma treated by neoadjuvant chemotherapy.     

Multimodality management of resectable gastric cancer: A review

Adenocarcinoma of the stomach carries a poor prognosis and is the second most common cause of cancer death worldwide. It is recommended that surgical resection with a D1 or a modified D2 gastrectomy (with at least 15 lymph nodes removed for examination) be performed in the United States, though D2 lymphadenectomies should be performed at experienced centers. A D2 lymphadenectomy is the recommended procedure in Asia. Although surgical resection is considered the definitive treatment, rates of recurrences are high, necessitating the need for neoadjuvant or adjuvant therapy. This review article aims to outline and summarize some of the pivotal trials that have defined optimal treatment options for non-metastatic non-cardia gastric cancer. Some of the most notable trials include the INT-0116 trial, which established a benefit in concurrent chemoradiation and adjuvant chemotherapy. This was again confirmed in the ARTIST trial, especially in patients with nodal involvement. Later, the Medical Research Council Adjuvant Gastric Infusional Chemotherapy trial provided evidence for the use of perioperative chemotherapy. Targeted agents such as ramucirumab and trastuzumab are also being investigated for use in locally advanced gastric cancers after demonstrating a benefit in the metastatic setting. Given the poor response rate of this difficult disease to various treatment modalities, numerous studies are currently ongoing in an attempt to define a more effective therapy, some of which are briefly introduced in this review as well.     

Blast from the past: Perioperative use of the Maruyama computer program for prediction of lymph node involvement in the surgical treatment of gastric cancer following neoadjuvant chemotherapy

BackgroundSurgical quality assurance is a key element of gastric cancer treatment. The Maruyama Computer Program (MCP) allows to predict lymph node involvement in stations no. 1–16. The aim of the current study was to evaluate the accuracy of the MCP predictions in GC patients treated with neoadjuvant chemotherapy (nCTH) followed by gastrectomy with adequate lymphadenectomy.Methods101 patients who underwent preoperative nCTH followed by D2 gastrectomy with curative intent were analysed. The response to nCTH was measured using the tumour regression grade system.ResultsTest sensitivity, specificity, PPV, NPV and accuracy of the MCP were 92%, 33%, 41%, 89%, and 53%, respectively. In patients with response to nCTH, number of false positive (FP) results was significantly higher than in patients who did not respond to nCTH both in the N1 (56.3% vs 28.9%, p < 0.0001) and in the N2 (59% vs 41%, p < 0.0001) trier. The risk for FP results was 6 times higher in N1 (OR = 6.50, 95%CI: 3.91–10.82,; p < 0.0001) and N2 (OR = 5.84, 95%CI: 2.85–11.96; p < 0.0001) triers. In patients with intestinal type GC, the risk for FP results was 4 times higher than in other histologic types of GC in both N1 (OR = 4.23, 95%CI: 2.58–6.95; p < 0.0001) and N2 (OR = 4.23, 95%CI: 2.02–9.62; p = 0.0002) triers.ConclusionsMCP predictions in the GC patients treated with nCTH have low specificity due to significantly high number of FP results. Noticeably low accuracy level of predictions indicate a need for new prediction models, based on Laurén classification, since it may provide some information on expected regression grade.     

Perioperative chemotherapy for resectable gastroesophageal cancer: A single-center experience

Backgrounds

Multimodal treatment for locally advanced gastric cancer has been reported to improve disease-free survival when compared to surgery alone. We aimed to clarify the efficacy and safety of perioperative chemotherapy for locally advanced gastric cancer patients treated in daily clinical practice.

Methods

Patients diagnosed with locally advanced gastric cancer were treated with perioperative chemotherapy and surgery. The primary end point was the complete resection (R0) rate. Secondary end points were disease-free survival (DFS), overall survival (OS), toxicity, radiological response rate, pathological response rate and downstaging rate. We also looked for prognostic and predictive factors for DFS, OS, pathological complete response and the R0 rate.

Results

Forty patients were found eligible for this retrospective analysis. At diagnosis, 52.5% of patients were classified as stage II and 47.5% were stage III. Forty percent of patients completed three preoperative cycles and three postoperative cycles. A tolerable toxicity related to chemotherapy was found. Thirty-nine patients underwent surgery: 80% reached a complete resection (R0), down-staging was detected in 57.5% and 17.5% had a pathologically complete response. The median time of disease-free survival was 34.05 months (95%CI 25.6–42.4), and the median time of overall survival was 39.01 months (95%CI 30.8–47.1). We found that the presence of comorbidities were independent predictive factors for the pathologic response, while the chemotherapy schedule and the clinical response could independently predict a complete resection.

Conclusions

Our results support that perioperative chemotherapy for locally advanced gastric cancer can be safely delivered in daily clinical practice, obtaining an improvement of the pathologic response and the complete resection of gastric cancer.     

系统免疫炎症指数与接受新辅助化疗胰腺导管腺癌患者预后的关系

目的 探讨新辅助化疗后系统免疫炎症指数（systemic immune-inflammation index,SII）对胰腺导管腺癌（pancreatic ductal adenocarcinoma,PDAC）预后评估的价值。方法 回顾性分析2013年1月至2016年12月在盘锦辽油宝石花医院行胰腺切除术的PDAC患者的临床资料。新辅助化疗后检测SII,依据ROC曲线确定SII最佳临界值（885）分为SII＞885组（n=37）和SII≤885组（n=58）,采用Cox回归评估SII与PDAC患者术后生存的关系。结果 SII与肿瘤大小、胆道引流、术前CA19-9水平有关（P<0.05）。SII≤885组的3年生存率高于SII＞885（43.1% vs 18.9%,P=0.015）。多因素Cox回归显示,肿瘤大小>3 cm（HR=1.367,95%CI：1.227～2.215,P=0.031）、CA19-9>37 IU/mL（HR=1.292,95%CI：1.132～1.931,P=0.011）及SII＞885（HR=1.451,95%CI：1.327～2.431,P=0.021）是影响PDAC患者术后生存的独立危险因素。结论 新辅助化疗后SII高的PDAC患者预后较差且SII＞885提示PDAC患者预后不良。     

胃差分化腺癌根治术后辅助化疗的临床研究

目的:观察和比较HELF方案和HELF/HPLF交替方案对胃差分化腺癌(低分化腺癌、粘液腺癌、印戒细胞癌)根治术后患者无病生存期(DFS)、总生存期(OS)的影响。方法:经组织学证实为低分化腺癌、粘液腺癌及印戒细胞癌的Ⅱ~Ⅲ期胃癌根治术后患者,随机分配至A组(单独HELF方案化疗)或B组(HELF/HPLF方案交替化疗),术后3~5周开始化疗,化疗4~6周期。结果:共入组80例患者,72例可按要求随访及评价不良反应,A组、B组各36例。全组患者共随访7~98月,A组与B组中位随访期差异无统计学意义(30月vs.33月,P=0.383)。A组患者的DFS为4~97月(中位值20月),B组为5~98月(中位值39月),两组差异有统计学意义(P=0.025)。A组的OS为10~97月(中位值28月),B组为7~98月(中位值48月),以B组生存时间更长(P=0.042)。主要不良反应为骨髓抑制及消化道反应,多为Ⅰ~Ⅱ度。结论:HELF方案与HPLF方案交替用于差分化胃腺癌根治术后的辅助治疗,在推迟肿瘤复发转移及延长生存期方面可能优于单用HELF方案。