Lymph node ratio is an independent prognostic factor in patients with rectal cancer treated with preoperative chemoradiotherapy and curative resection

Purpose

To evaluate the prognostic effect of lymph node ratio (LNR) in patients with locally advanced rectal cancer who were treated with curative resection after preoperative chemoradiotherapy (CRT).

Methods

Between October 2001 and December 2007, 519 patients who had undergone curative resection of primary rectal cancer after preoperative CRT were enrolled. Of these, 154 patients were positive for lymph node (LN) metastasis and were divided into three groups according to the LNR (≤0.15 [n = 80], 0.16–0.3 [n = 44], >0.3 [n = 30]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS).

Results

LNR (≤0.15, 0.16–0.3, and >0.3) was significantly associated with 5-year OS (90.3%, 75.1%, and 45.1%; p < 0.001) and DFS (66.7%, 55.8%, and 21.9%; p < 0.001) rates. In a multivariate analysis, LNR (≤0.15, 0.16–0.3, and >0.3) was a significant independent prognostic factor for OS (hazard ratios [HRs], 1, 3.609, and 8.197; p < 0.001) and DFS (HRs, 1, 1.699, and 3.960; p < 0.001). LNR had a prognostic impact on OS and DFS in patients with <12 harvested LNs, as well as in those with ≥12 harvested LNs (p < 0.05).

Conclusion

LNR was a significant independent prognostic predictor for OS and DFS in patients with locally advanced rectal cancer who were treated with curative resection after preoperative CRT.     

Prognostic impact of at least 12 lymph nodes after neoadjuvant therapy in rectal cancer: A meta-analysis

BACKGROUNDThe number of dissected lymph nodes (LNs) in rectal cancer after neoadjuvant therapy has a controversial effect on the prognosis.AIMTo investigate the prognostic impact of the number of LN dissected in rectal cancer patients after neoadjuvant therapy.METHODSWe performed a systematic review and searched PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and Cochrane Library from January 1, 2000 until January 1, 2020. Two reviewers examined all the publications independently and extracted the relevant data. Articles were eligible for inclusion if they compared the number of LNs in rectal cancer specimens resected after neoadjuvant treatment (LNs ≥ 12 vs LNs < 12). The primary endpoints were the overall survival (OS) and disease-free survival (DFS).RESULTSNine articles were included in the meta-analyses. Statistical analysis revealed a statistically significant difference in OS [hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.66-0.88, I² = 12.2%, P = 0.336], DFS (HR = 0.76, 95%CI: 0.63-0.92, I² = 68.4%, P = 0.013), and distant recurrence (DR) (HR = 0.63, 95%CI: 0.48-0.93, I² = 30.5%, P = 0.237) between the LNs ≥ 12 and LNs < 12 groups, but local recurrence (HR = 0.67, 95%CI: 0.38-1.16, I² = 0%, P = 0.348) showed no statistical difference. Moreover, subgroup analysis of LN negative patients revealed a statistically significant difference in DFS (HR = 0.67, 95%CI: 0.52-0.88, I² = 0%, P = 0.565) between the LNs ≥ 12 and LNs < 12 groups.CONCLUSIONAlthough neoadjuvant therapy reduces LN production in rectal cancer, our data indicate that dissecting at least 12 LNs after neoadjuvant therapy may improve the patients’ OS, DFS, and DR.     

局部进展期直肠癌术前“三明治”式neoCRTⅡ期临床研究中期疗效分析

目的 探讨局部进展期直肠癌术前“三明治”式新辅助放化疗的Ⅱ期临床研究的良好近期疗效能否转化为中远期生存获益。 方法 2012年间 45例局部进展期直肠癌患者给予术前“三明治”式新辅助放化疗。采用XELOX方案化疗,放疗采用VMAT技术,GTV 50 Gy分25次、CTV 45~46 Gy分25次。放疗结束 6~8周后遵循TME切除。应用Kaplan-Meier计算生存率并Logrank检验和单因素分析。 结果 中位随访时间为46.7个月,无 1例LR,3年DM率为18%,3年OS、DFS率分别为96%、84%。单因素分析提示神经束受侵、病理N₁-N₂(病理Ⅲ期)、治疗前CA-199是影响DM的因素(P=0.000、0.000、0.013)。 结论 局部进展期直肠癌术前“三明治”式新辅助放化疗获得的显著近期疗效可转化为中期生存获益,但需要进一步Ⅲ期临床研究加以证实。     

术前同步放化疗后yp0-Ⅰ期直肠癌预后分析

目的 探讨局部晚期直肠癌术前同步放化疗后yp0-Ⅰ期的预后及影响因素。方法 ２００８-２０１３ 年纳入研究８７ 例局部晚期直肠癌术前同步放化疗后ｙｐ０-Ⅰ期患者,均接受术前同步放化疗后４～８ 周进行ＴＭＥ。放疗给予全盆腔外照射４５.０～５０.４ Ｇｙ,同步给予单药卡培他滨或卡培他滨联合奥沙利铂化疗。采用Ｋａｐｌａｎ?Ｍｅｉｅｒ 法计算ＬＲＦＳ、ＤＭＦＳ、ＤＦＳ 和ＯＳ 并Ｌｏｇｒａｎｋ 检验和单因素预后分析,Ｃｏｘ 模型多因素预后分析。结果　术前同步放化疗与手术间隔中位时间为５１ ｄ。ＴＭＥ 术后共４５％接受了术后辅助化疗。３ 年ＬＲＦＳ、ＤＭＦＳ、ＤＦＳ 和ＯＳ 分别为９８％、９３％、９３％和９６％。多因素分析发现基于疗前临床分期和术后病理分期的降期深度评分与ＤＭＦＳ、ＤＦＳ 相关（Ｐ ＝ ０.０２０、０.００５）。降期深度评分５ 分为界值,预测３ 年ＤＦＳ 的ＲＯＣ 的ＡＵＣ 值为０.８０３。结论　术前同步放化疗后ｙｐ０-Ⅰ期直肠癌的长期生存结果较好。降期深度评分可以预测预后     

The Prognostic Significance of the Lymph Node Ratio in Axillary Lymph Node Positive Breast Cancer

Purpose

This study evaluated the prognostic impact of the lymph node ratio (LNR; i.e., the ratio of positive to dissected lymph nodes) on recurrence and survival in breast cancer patients with positive axillary lymph nodes (LNs).

Methods

The study cohort was comprised of 330 breast cancer patients with positive axillary nodes who received postoperative radiotherapy between 1987 and 2004. Ten-year Kaplan-Meier locoregional failure, distant metastasis, disease-free survival (DFS) and disease-specific survival (DSS) rates were compared using Kaplan-Meier curves. The prognostic significance of the LNR was evaluated by multivariate analysis.

Results

Median follow-up was 7.5 years. By minimum p-value approach, 0.25 and 0.55 were the cutoff values of LNR at which most significant difference in DFS and DSS was observed. The DFS and DSS rates correlated significantly with tumor size, pN classification, LNR, histologic grade, lymphovascular invasion, the status of estrogen receptor and progesterone receptor. The LNR based classification yielded a statistically larger separation of the DFS curves than pN classification. In multivariate analysis, histologic grade and pN classification were significant prognostic factors for DFS and DSS. However, when the LNR was included as a covariate in the model, the LNR was highly significant (p<0.0001), and pN classification was not statistically significant (p>0.05).

Conclusion

The LNR predicts recurrence and survival more accurately than pN classification in our study. The pN classification and LNR should be considered together in risk estimates for axillary LNs positive breast cancer patients.     

Prognostic Value of Lymph Node Ratios in Node Positive Rectal Cancer Treated with Preoperative Chemoradiation

Background: To investigate the impact of the lymph node ratio (LNR) on the prognosis of patients with locallyadvanced rectal cancer undergoing pre-operative chemoradiation. Methods: Clinicopathologic and follow up dataof 128 patients with stage III rectal cancer who underwent curative resection from 1996 to 2007 were reviewed.The patients were divided into two groups according to the lymph node ratio: LNR ≤0.2 (n=28), and >0.2 (n=100).Kaplan-Meier and the Cox proportional hazard regression models were used to evaluate the prognostic effectsaccording to LNR. Results: Median numbers of lymph nodes examined and lymph nodes involved by tumourwere 10.3 (range 2-28) and 5.8 (range 1-25), respectively, and the median LNR was 0.5 (range, 0-1.6). The 5-yearsurvival rate significantly differed by LNR (≤0.2, 69%; >0.2, 19%; Log-rank p value < 0.001). LNR was alsoa significant prognostic factor of survival adjusted for age, sex, post-operative chemotherapy, total number ofexamined lymph nodes, metastasis and local recurrence (≤0.2, HR=1; >0.2, HR=4.8, 95%CI=2.1-11.1) and asignificant predictor of local recurrence and distant metastasis during follow-up independently of total number ofexamined lymph node. Conclusions: Total number of examined lymph nodes and LNR were significant prognosticfactors for survival in patients with stage III rectal cancer undergoing pre-operative chemoradiotherapy.     

Trimodality therapy of esophagectomy plus neoadjuvant chemoradiotherapy improves the survival of clinical stage II/III esophageal squamous cell carcinoma patients

The prognosis of advanced esophageal cancer patients is poor. Trimodality therapy of surgical resection plus neoadjuvant chemoradiotherapy (CRT) has been developed to improve survival through locoregional control, leading to prevention of micrometastasis. We investigated whether or not neoadjuvant CRT led to survival benefits in TNM stage?II/III esophageal cancer patients. We retrospectively reviewed 62 patients with stage II or III esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant CRT. All patients received esophagectomy 4-7 weeks after CRT consisting of 40?Gy irradiation and chemotherapy (5-FU, 500?mg/m2/day, days 1-5 and cisplatin, 10-20?mg/body, days 1-5). Clinical response and survival rates were analyzed using Kaplan-Meier methods, with p<0.05 considered as significant. The clinical effect rate of CRT for both primary tumors and metastatic nodes was 82.3%. Operative and hospital mortality rates were 1.65 and 6.5%, respectively. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 52.6 and 49.2%, respectively. A significant difference was noted between stages?II and III for both OS and DFS. The 5-year OS rates were 64.2% for stage II, 33.1% for stage III (T4 and non-T4) and 46.9% for stage III (non-T4 only) patients. The depth of tumor invasion (T3 vs. T4), resectability (R0 vs. R1, R2), lymph node metastasis (positive vs. negative), and the effect of CRT were proven to be independent prognostic factors for univariate analysis, with resectability and the effect of CRT for multivariate analysis. These data suggest that CRT in stage II/III (non-T4) ESCC patient contributed to tumor shrinkage, leading to higher resectability and longer survival. Neoadjuvant CRT appears to be a promising option for these patients.     

局部晚期食管鳞癌新辅助放化疗联合手术治疗的临床疗效分析

目的 探讨新辅助放化疗联合手术治疗局部晚期食管鳞癌的临床疗效,并分析临床完全缓解率(cCR)与病理完全缓解率(pCR)的关系。方法 回顾性选取2001—2013年局部晚期胸段食管鳞癌患者 158例,全组均采用术前同期放化疗联合手术方式,化疗采用以铂类为基础化疗方案,放疗剂量为40 Gy,2.0 Gy/次,5 次/周。Kaplan-Meier法计算OS和DFS,Logrank法检验并单因素预后分析,Cox模型多因素预后分析。结果 全组患者的pCR率为41.1%。新辅助放化疗后 44例cCR患者中 32例(73%)达pCR,114例非cCR患者中 33例(28.9%)达pCR (P=0.000)。cCR预测pCR的敏感性、特异性分别为49.2%、87.1%,阳性、阴性预测值分别为72.7%、71.1%。3年总样本数为 53例。全组 3年OS、DFS分别为53.9%、48.6%,cCR的显著高于非cCR的(P=0.012、P=0.026),pCR的显著高于非pCR的(P=0.000、0.000)。多因素分析显示放化疗后病理反应和化疗方案是影响OS的因素。最常见≥3级急性不良反应为白细胞减少(34.2%)。结论 新辅助放化疗联合手术治疗局部晚期食管鳞癌可获得较高pCR率且不良反应可耐受,放化疗后cCR率与pCR率、OS密切相关。     

局部晚期胃癌根治术后放化疗患者复发模式及预后因素分析

目的:分析局部晚期胃癌根治术后(>D 1术)放化疗,影响预后的因素和患者的复发模式,探讨术后辅助放疗的价值。 方法:选取2008—2020年在苏州大学附属第二医院接受术后辅助放化疗的171例胃癌病例进行回顾性分析。用 Kaplan- Meier法计算复发率和生存率, ...     

Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO-04 randomized phase 3 rectal cancer trial

Peripheral blood leukocytosis and neutrophilia reflect cancer inflammation and have been proposed as prognostic immunological biomarkers in various malignancies. However, previous studies were limited by their retrospective nature and small patient numbers. Baseline peripheral blood leukocytes, neutrophils, hemoglobin, platelets, lactate dehydrogenase and carcinoembryonic antigen (CEA) were correlated with clinicopathologic characteristics, and clinical outcome in 1236 patients with rectal cancer treated with 5-FU-based preoperative chemoradiotherapy (CRT) alone or with oxaliplatin followed by surgery and adjuvant chemotherapy within the CAO/ARO/AIO-04 randomized phase 3 trial. Multivariable analyses were performed using Cox regression models. After a median follow-up of 50 months, baseline leukocytosis remained an independent adverse prognostic factor for disease-free survival (DFS; HR 1.457; 95% CI 1.163–1.825; p = 0.001), distant metastasis (HR 1.696; 95% CI 1.266–2.273; p < 0.001) and overall survival (OS; HR 1.716; 95% CI 1.264–2.329; p = 0.001) in multivariable analysis. Similar significant findings were observed for neutrophilia and high CEA levels. Conversely, treatment-induced leukopenia correlated with favorable DFS (p = 0.037), distant metastasis (p = 0.028) and OS (p = 0.012). Intriguingly, addition of oxaliplatin to 5-FU CRT resulted in a significant DFS improvement only in patients with neutrophilia and leukocytosis (p = 0.028 and p = 0.002). Our findings have important clinical implications and provide high-level evidence on the adverse prognostic role of leukocytes and neutrophils, and the impact of chemotherapy in the context of these biomarkers. These data could help guide patient stratification and should be further validated within prospective studies.     

Prognosis Impact of the Lymph Node Ratio in Patients with Colon Adenocarcinoma: a Single-Centre Experience

Purpose

Recently, the positive lymph node ratio (LNR) is considered a new prognostic parameter on survival and time to progression for patients with colon cancer. The aim of this study was to determine the prognostic impact of the LNR as an independent factor for overall survival (OS) and disease-free survival (DFS) in patients with colon cancer regardless of their clinical stage.

Methods

We retrospectively identified 85 consecutive patients diagnosed with colon adenocarcinoma treated in our centre during 2010. We categorized patients according to a LNR cutoff of 0.25. Three-year OS and DFS were determined according to the Kaplan–Meier method. A Cox proportional model was used to assess the influence of other prognostic variables on each outcome.

Results

After median follow-up of 34.8 months, neither median OS nor DFS has been reached by any of the subgroups. Nevertheless, patients with a LNR?≥?0.25 exhibited a higher risk of death (hazard ratio, 3.10; 95 % confidence interval (CI), 1.38–7.01; log-rank test: p?=?0.006) and a shorter interval without progression (hazard ratio, 6.59; 95 % CI, 1.96–22.15; log-rank test: p?=?0.002.) than patients with LNR?<?0.25. After adjusting for prespecifed variables, the impact of a LNR?≥?0.25 was independently associated with OS (hazard ratio, 2.8; 95 % CI, 1.01–7.73; p?=?0.04) and DFS (hazard ratio, 7.07; 95 % CI, 1.23–40.45; p?=?0.03).

Conclusions

LNR was independently associated with OS and DFS in patients with colon adenocarcinoma regardless of its clinical stage.     

保乳术后放疗对乳腺癌局部淋巴结转移患者预后的影响

  目的  探讨术后放疗(post-mastectomy radiation therapy, PMRT)对局部淋巴结阳性行保乳手术的乳腺癌患者预后的影响, 针对不同的pN分期以及淋巴结转移率(lymph node ratio, LNR)提出更具针对性的术后放疗方案。  方法  回顾性分析天津医科大学肿瘤医院1998年2月至2007年3月152例行保乳手术并有局部淋巴结转移的原发浸润性乳腺癌患者的临床病理资料, 比较LNR和pN分期对患者预后的指导意义, 并在LNR基础上, 根据PMRT与否比较无病生存期(disease-free survival, DFS)和总生存期(overall survival, OS)。  结果  152例患者被分为pN1(114例)、pN2(23例)、pN3(15例), 其中LNR < 0.21为114例, 位于0.21~0.65为26例, >0.65为12例。单因素分析显示淋巴结切检总数、pN、LNR、雌激素受体(estrogen receptor, ER)状态、孕激素受体(progesterone receptor, PR)状态、放疗与否均与DFS、OS具有相关性(P < 0.05), 诊断年龄和化疗方案仅与OS具有相关性(P < 0.05)。多因素分析显示, LNR、PMRT依然是DFS、OS的独立预测指标(P < 0.05), 而pN差异无统计学意义(P>0.05);分组分析时仅在LNR < 0.21术后放疗对预后的影响差异有统计学意义。  结论  LNR作为一个独立预测指标, 可用于评价行保留乳房手术治疗发生淋巴结转移的乳腺癌患者的预后。针对不同的LNR分级, 需要进一步细化PMRT的适应症。      

Stepwise neoadjuvant chemoradiotherapy in the management of mid-low locally advanced rectal cancer

BackgroundThis study aimed to compare the treatment response, complications and prognosis in mid-low locally advanced rectal cancer (LARC) patients who underwent stepwise neoadjuvant chemoradiotherapy (SCRT) or traditional neoadjuvant chemoradiotherapy (CRT).MethodsThe medical records of patients with mid-low rectal cancer who underwent SCRT or CRT were retrospectively analyzed. Differences in the treatment response, pathologic complete response (pCR), R0 resection, local recurrence, anastomotic leakage, presacral infection, anal preservation, defunctioning stoma, treatment-emergent adverse events (TEAEs), overall survival (OS) and disease-free survival (DFS) between patients who underwent SCRT and CRT were compared.ResultsA total of 430 medical records were investigated, including 194 patients in the SCRT group and 236 patients in the CRT group. There was no significant difference in the rates of treatment response, pCR, R0 resection, local recurrence, anastomotic leakage, presacral infection, anal preservation or TEAEs between the two groups. However, the rate of defunctioning stoma in the SCRT group was significantly lower than that in the CRT group (20.1% vs. 44.1%, respectively, P < 0.01). Moreover, the median OS time of the SCRT and CRT groups was 44.0 and 50.5 months, respectively (P = 0.17). The median DFS time of the SCRT and CRT groups was 41.0 and 46.8 months, respectively (P = 0.32).ConclusionCompared with the CRT group, the SCRT group had a similar treatment response, local control and long-term prognosis, and more importantly, a portion of the patients in the SCRT group were exempted from excessive radiation.     

Association between pathologic response in metastatic lymph nodes after preoperative chemoradiotherapy and risk of distant metastases in rectal cancer: An analysis of outcomes in a randomized trial

PURPOSE: To compare 5 x 5 Gy preoperative radiotherapy with immediate surgery vs. preoperative chemoradiotherapy (50.4 Gy, 5-fluorouracil, leucovorin) with delayed surgery in a randomized trial for cT3-T4 low-lying rectal cancer. Despite the downstaging effect of chemoradiotherapy, similar long-term outcomes were observed in both groups. METHODS: The Cox model was used to evaluate the prognostic value of ypTN ("yp" denotes that pathologic classification was performed after initial multimodality therapy) categories and the surgical margin status in 291 patients. RESULTS: Disease-free survival (DFS) (hazard ratio [HR] 1.05, 95% confidence interval [CI], 0.73-1.51), distant metastases (HR, 1.17; 95% CI, 0.77-1.78), and local control (HR, 1.45; 95% CI, 0.74-2.84) were similar in both arms. The ypN status was the only independent prognostic factor for DFS (p < 0.001). An interaction (p = 0.016) between N stage and the assigned treatment was demonstrated. For ypN-negative patients, DFS was similar in both arms (HR, 0.83, 95% CI, 0.47-1.48); however, for ypN-positive patients, DFS was worse in the chemoradiotherapy arm (HR, 1.73; 95% CI, 1.07-2.77). The 4-year (median follow-up) DFS rate in N-positive patients was 51% in the 5 x 5-Gy arm vs. 25% in the chemoradiotherapy arm. The corresponding 4-year rates for the incidence of local recurrence and distant metastases were 14% vs. 27% (HR, 1.95; 95% CI, 0.78-4.86) and 38% vs. 68% (HR, 2.05; 95% CI, 1.21-3.48). CONCLUSION: N-positive disease after chemoradiotherapy indicates radiochemoresistance. N-positive disease after 5 x 5 Gy RT includes both radiosensitive and radioresistant tumors, because the interval between radiotherapy and surgery was too short for radiosensitive cancer to undergo necrosis. Thus, the greater risk of distant metastases recorded in the chemoradiotherapy arm suggests that radiochemoresistance of nodal metastases from rectal cancer is associated with a high potential for developing distant metastases.     

Lack of any Prognostic Value of Body Mass Index for Patients Undergoing Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

Background: The relationship between body mass index(BMI) and outcomes after chemoradiotherapy(CRT)has not been systematically addressed. The purpose of this study was to evaluate the effect of BMI on survivalin patients with esophageal squamous cell carcinoma (ESCC). Materials and Methods: Sixty ESCC caseswere retrospectively reviewed in this study. Patient overall survival(OS) and disease-free survival (DFS) werecompared between two groups (BMI<24.00 kg/m2 and BMI≥24.00 kg/m2). Results: There were 41 patients in thelow/normal BMI group (BMI<24.00 kg/m2) and 19 in the high BMI group (BMI≥24.00 kg/m2). No significantdifferences were observed in patient characteristics between these. We found no difference in 2-year OS and DFSassociated with BMI (p=0.763 for OS; p=0.818 for DFS) using the Kaplan-Meier method. Univariate analysisrevealed that higher clinical stage was prognostic for worse 2-year OS and DFS, metastasis for 2-year OS, lymphnode status for 2-year DFS, while age, gender, smoking, drinking, tumor location and BMI were not prognostic.There were no differences in the 2-year OS (hazard ratio=1.117; p=0.789) and DFS(hazard ratio=1.161; p=0.708)between BMI groups in multivariate analysis, whereas we found statistical differences in the 2-year OS and DFSassociated with clinical stage, gender and tumor infiltration (p<0.04), independent of age, smoking, drinking,tumor location, the status of lymph node metastases and BMI. Conclusions: BMI was not associated with survivalin patients with ESCC treated with CRT as primary therapy. BMI should not be considered a prognostic factorfor patients undergoing CRT for ESCC.     

新辅助治疗评分预测临床Ⅲ期中低位直肠癌预后研究

目的 探讨临床Ⅲ期中低位直肠癌经术前同步放化疗后降期以及新辅助治疗评分(NAR)对预后的影响。方法 分析2006—2014年间本中心收治的经盆腔核磁或腹盆CT确诊的cⅢ期中低位直肠癌195例患者,术前放疗42.0~50.4 Gy (中位数50 Gy,93.8%患者放疗剂量≥50 Gy),卡培他滨±奥沙利铂同步化疗于同步放化疗后4—15周(中位数7周) TME手术(R0切除)。分析患者降期(yp0—Ⅱ期)及NAR评分(根据cT、ypT/N分期计算)对预后影响,应用Kaplan-Meier法计算3年DFS并Logrank法检验。结果 全组患者中位随访44个月(6.7~125.5个月),3年DFS为76.8%。术前同步放化疗后降期显著影响3年DFS (92.2%∶56.8%,P=0.000)。全组患者中位NAR评分15.0分(0~65.0分),其中评分低者3年DFS优于评分高者[≤15.0分(90.1%)∶>15.0分(57.0%),P=0.001];在降期患者中低NAR评分仍可获得更好的预后[≤8.4分(95.1%)∶>8.4分(87.5%),P=0.022]。结论 cⅢ期中低位直肠癌经术前同步放化疗后降期者预后相对较好,NAR评分可有效预测患者预后。     

Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes.

PURPOSE: Colorectal cancer is the second leading cause of cancer deaths in the United States, with poor survival predicted by regional lymph node (LN) metastasis. The impact of LN ratio (LNR) on survival is unknown in this disease. PATIENTS AND METHODS: We analyzed data from Intergroup trial 0089 of adjuvant chemotherapy for stage II and III patients with colon cancer, in which all patients received fluorouracil-based therapy. Survival was similar for all arms of the study, allowing us to evaluate all patients together. End points included overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Multivariate analyses were performed on all patients and on groups according to LNR quartiles (LNR: < 0.05, 0.05 to 0.19, 0.2 to 0.39, and 0.4 to 1.0). Covariates included in the models were age, sex, tumor stage, grade, histology, number of positive LNs, number of LNs removed, and LNR. RESULTS: The median age was 63.7 years, and the median number of LNs removed was 11. In the multivariate analysis, LNR was a significant factor for OS, DFS, and CSS in patients with 10 to 15 LN and more than 15 LN removed but not for patients with less than 10 LN removed. Using quartiles, LNR maintained its significance for all three end points when patients were grouped by node status. CONCLUSION: After curative resection for colorectal cancer, the LNR is an important prognostic factor and should be used in stratification schemes for future clinical trials investigating adjuvant treatments.     

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。     

Tumor infiltrating lymphocytes (TILs) before and after neoadjuvant chemoradiotherapy and its clinical utility for rectal cancer

Backgrounds: Radiotherapy (RT) and chemotherapy (CT) can potentiate systemic antitumor immune effect. However, immunomodulation during RT or CT and their clinical implications in rectal cancer have not been thoroughly investigated. Methods: We investigated alterations in the densities of tumor infiltrating lymphocytes (TILs) during chemoradiation and their clinical utilities in patients with rectal cancer. We analyzed 136 rectal cancer patients who underwent neoadjuvant RT, CT or chemoradiotherapy (CRT), followed by radical resection retrospectively. Pretreatment biopsy specimens and posttreatment resected specimens of all patients were immunostained for CD3 and CD8. The predictive value of TILs to neoadjuvant treatment and prognosis were examined. Results: Densities of CD3+ and CD8+TILs in posttreatment specimens after RT, CT or CRT were all significantly higher than those in pretreatment specimens. There were no significant differences between each two of these three groups. High pretreatment CD3+ and CD8+TILs were associated with good response (TRG ≥ 3) after neoadjuvant treatments (P = 0.033 and 0.021). High CD3+TILs and CD8+TILs in pretreatment biopsy specimens were significantly associated with favorable disease free survival (DFS) (P = 0.010 and P = 0.022) and overall survival (OS) (P = 0.019 and P = 0.003). Conclusions: We may, thus, conclude that chemoradiation can enhance local immune response by increased TILs. High TILs densities before treatment are associated with good response to neoadjuvant chemoradiotherapy and a favorable prognosis.     

Molecular prognostic factors in rectal cancer treated by preoperative chemoradiotherapy

The present study evaluated the expression of p53, pRb, hMLH1 and MDM2 prior to preoperative chemoradiotherapy (CRT) in patients with rectal cancer, and attempted to determine any correlation with treatment outcome. Forty-five patients with available pretreatment biopsy tissues and who received preoperative CRT were enrolled in this study. Preoperative CRT consisted of a median 50.4 Gy and 2 cycles of concurrent administration of 5-fluorouracil + leucovorin. Surgery was performed approximately seven weeks after CRT. Protein expression in formalin-fixed paraffin-embedded biopsy specimens was assessed by immunohistochemistry. A positive expression of p53, pRb, hMLH1 and MDM2 was found in 40, 46.7, 40 and 66.7% of the tissue specimens, respectively. The 5-year overall (OS), disease-free (DFS) and locoregional recurrence-free survival (LRFS) rates for patients included in the study were 71.3, 66.1 and 60.9%, respectively. p53 expression presented a significantly different OS (positive vs. negative, 45.8 vs. 86.2%; p=0.02). However, the expression of pRb, hMLH1 and MDM2 was not significant for OS. The expression of p53 was a borderline significant prognostic factor for DFS and for LRFS. Age, p53 and MDM2 expression were significant factors in the multivariate analysis performed for OS with 12 covariates, including 8 clinicopathological parameters and 4 proteins. No significant factor affected DFS or LRFS in the multivariate analysis. We suggest that the expression of p53 is a potential marker of survival. Determinations of this protein expression may be useful for selecting candidates from rectal cancer patients for more tailored treatment.