Comparison of efficacy and safety of preoperative and postoperative concurrent chemoradiotherapies for stage Ⅲ-Ⅳ A gastric cancer / 中华放射医学与防护杂志

Objective:To compare the efficacy and safety of preoperative and postoperative concurrent chemoradiotherapies in the treatment of stage Ⅲ-Ⅳ A gastric cancer patients who underwent D2 lymphadenectomy with R0 resection. Methods:A retrospective analysis was conducted on the clinical data of patients with stage Ⅲ-Ⅳ A gastric cancer who underwent D2 lymphadenectomy with R0 resection in the Affiliated Cancer Hospital of Zhengzhou University from 2012 to 2019. Among these patients, 25 received preoperative chemoradiotherapy (group A) and 22 received postoperative chemoradiotherapy (group B). The disease-free survival (DFS), overall survival (OS), local recurrence rate, distant metastasis rate, and adverse reactions were compared between both groups. The total dose, single dose, fractions, and duration of radiotherapy for all the patients were 45-50.4 Gy, 1.8-2.0 Gy, 25-28 fractions, and 5-6 weeks, respectively. The target areas were delineated in accordance with the ASTRO and EORTC-ROG guidelines. Results:There was no statistical difference in clinical baseline characteristics between the two groups. The median follow-up was 48 months (3-72 months). The 1-year OS of group A was significantly higher than that of group B (92% vs. 54.5%, χ2= 5.68, P = 0.017). The 3-year OS and DFS of the two groups were 56% vs. 40.9% ( P> 0.05) and 51.4% vs. 31.8% ( P> 0.05), respectively. There was no significant difference in the local recurrence rate between both groups ( P> 0.05), but the distant metastasis rate of group A was significantly lower than that of group B ( χ2= 6.01, P = 0.014). There was no significant difference in digestive side effects and myelosuppression between both groups ( P> 0.05). Conclusions:For patients with stageⅢ-Ⅳ A gastric cancer after D2 lymphadenectomy with R0 resection, the preoperative and postoperative chemoradiotherapies yield similar efficacy and safety. However, compared to postoperative chemoradiotherapy, preoperative chemoradiotherapy improves the 1-year OS and reduces the distant metastasis rate.

Sensitivity of Various Evaluating Modalities for Predicting a Pathologic Complete Response After Preoperative Chemoradiation Therapy for Locally Advanced Rectal Cancer

PURPOSE: We investigated the sensitivity of various evaluating modalities in predicting a pathologic complete response (pCR) after preoperative chemoradiation therapy (PCRT) for locally advanced rectal cancer (LARC). METHODS: From a population of 2,247 LARC patients who underwent PCRT followed by surgery at Asan Medical Center, Seoul, Korea from January 2007 to June 2016, we retrospectively analyzed 313 patients (14.1%) who showed a pCR after surgery. Transrectal ultrasound (TRUS), high-resolution magnetic resonance imaging (MRI), abdominopelvic computed tomography (AP-CT), and endoscopy were performed within 2 weeks prior to surgery. RESULTS: Of the 313 patients analyzed, 256 (81.8%) had a pCR after radical surgery and 57 (18.2%) showed total regression after local excision. Preoperative TRUS, MRI, and AP-CT were performed in 283, 305, and 139 patients, respectively. Among these 3 groups, a prediction of a pCR of the primary tumor was made in 41 (14.5%), 51 (16.7%), and 27 patients (19.4%), respectively, before surgery. A prediction of a clinical N0 stage was made in 204 patients (88.3%) using TRUS, 130 (52.2%) using MRI, and 78 (65.5%) using AP-CT. Of the 211 patients who underwent endoscopy, 87 (41.2%) had a mention of clinical CR in their records. A prediction of a pathologic CR was made for 124 patients (39.6%) through at least one diagnostic modality. CONCLUSION: The various evaluation methods for predicting a pCR after PCRT show a predictive sensitivity of 0.15–0.41 for primary tumors and 0.52–0.88 for lymph nodes. Endoscopy is a relatively superior modality for predicting the pCR of the primary tumor of LARC patients.

What are the most important prognostic factors in patients with residual rectal cancer after preoperative chemoradiotherapy? / 영남의대학술지

BACKGROUND: We aimed to establish robust histoprognostic predictors on residual rectal cancer after preoperative chemoradiotherapy (CRT).METHODS: Analyzing known histoprognostic factors in 146 patients with residual disease allows associations with patient outcome to be evaluated.RESULTS: The median follow-up time was 77.8 months, during which 59 patients (40.4%) experienced recurrence and 41 (28.1%) died of rectal cancer. On univariate analysis, residual tumor size, ypT category, ypN category, ypTNM stage, downstage, tumor regression grade, lymphatic invasion, perineural invasion, venous invasion, and circumferential resection margin (CRM) were significantly associated with recurrence free survival (RFS) or/and cancer-specific survival (CSS) (all p<0.005). On multivariate analysis, higher ypTNM stage and CRM positivity were identified as independent prognostic factors for RFS (ypTNM stage, p=0.024; CRM positivity, p<0.001) and CSS (p=0.022, p=0.017, respectively). Furthermore, CRM positivity was an independent predictor of reduced RFS and CSS, irrespective of subgrouping according to downstage (non-downstage, p<0.001 and p<0.001; downstage, p=0.002 and p=0.002) or lymph node metastasis (non-metastasis, p<0.001 and p=0.001; metastasis, p<0.001 and p<0.001).CONCLUSION: CRM status may be as powerful as ypTNM stage as a prognostic indicator for patient outcome in patients with residual rectal cancer after preoperative CRT.

Analysis of prognostic factors and nomogram for predicting survival for patients with locally resectable esophageal cancer after preoperative chemoradiation therapy / 中华放射肿瘤学杂志

Objective The SEER database was utilized to analyze the prognosis and related factors for patients with locally resectable esophageal cancer undergoing preoperative chemoradiotherapy.A nomogram for predicting survival was established to provide reference for screening patients receiving preoperative chemoradiotherapy.Methods Patients diagnosed with stage T1b-4aN0-3M0(7th version AJCC in 2010) resectable esophageal cancer receiving preoperative chemoradiotherapy between 2010 and 2015 were selected from the SEER database.The survival rate was determined by Kaplan-Meier method.The univariate analysis was performed by log-rank test.The multivariate analysis was conducted by Cox test.The nomogram for survival prediction was established by using R software.The predicting accuracy of the nomogram was evaluated by C-index and calibration curve.Results A total of 1 697 eligible patients were included.Univariate analysis showed that sex,T stage,N stage and tumor differentiation were significantly associated with overall survival (OS) and cancer-specific survival rate (CSS)(all P＜0.001),and age (P=0.027) was significantly correlated with OS.Multivariate analysis demonstrated that age,sex,tumor differentiation and N stage were significantly associated with OS.Sex,tumor differentiation,T stage and N stage were significantly correlated with CSS (all P＜0.05).After the prognostic factors were included into the nomogram,the C-index for 5-year OS and CSS was 0.60 and 0.61.The model for predicting survival of patients with esophageal squamous cell cancer was established by using the same method.The C-index for the OS and CSS was 0.62 and 0.64.Conclusions Sex,clinical stage and tumor differentiation are prognostic factors of CSS in patients with locally resectable esophageal cancer undergoing preoperative chemoradiotherapy followed by surgery.The nomogram established according to the data above can provide certain reference for the selection of preoperative chemoradiotherapy combined with surgery.

Application value of carbon nanoparticle labeled lymph node staining in radical resection of adenocarcinoma of esophagogastric junction with preoperative chemoradiotherapy / 中华消化外科杂志

Objective To explore the application value of carbon nanoparticle labeled lymph node staining in radical resection of adenocarcinoma of esophagogastric junction with preoperative chemoradiotherapy.Methods The retrospective cohort study was conducted.The clinicopathological data of 56 patients with adenocarcinoma of esophagogastric junction who underwent preoperative chemoradiotherapy in the Peking University Cancer Hospital from January 2014 to November 2017 were collected.There were 52 males and 4 females,aged from 22 to 76 years,with an average age of 62 years.Among 56 patients undergoing total gastrectomy and D2 lymphadenectomy,17 using carbon nanoparticle lymph node staining and 39 using traditional lymph node sorting were respectively allocated into observation group and control group.Observation indicators:(1) treatment situations;(2) detection of lymph nodes;(3) perioperative complications;(4) follow-up.Followup using outpatient examination and telephone interview was performed to detect tumor recurrence or metastasis up to May 2019.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was evaluated by the independent sample t test.Measurement data with skewed distribution were represented as M (range),and comparison between groups was evaluated by the Mann-Whitney U test.Count data were described as absolute numbers,and comparison between groups was analyzed using the chi-square test or Fisher exact propability.Comparison of ordinal data was analyzed using the nonparametric rank sum test.Results (1) Treatment situations:patients in both groups were successfully treated with concurrent chemoradiotherapy based on intensity modulated radiotherapy before operation.Radical gastrectomy with D2 lymphadenectomy was successfully performed after chemoradiotherapy,and Roux-en-Y esophagojejunostomy was used to reconstruct the digestive tract during operation.The operation time and volume of intraoperative blood loss were respectively (217± 58)minutes and (112±60)mL in the observation group,and (235±65) minutes and (119±77)mL in the control group,with no statistically significant difference between the two groups (t =1.017,0.341,P＞0.05).(2) Detection of lymph nodes:the average number of harvested lymph nodes,average number of radiation target lymph nodes,and average number of peritarget lymph nodes were respectively 32± 10,21±8,and 7±4 in the observation group,and 22±7,16±5,5±3 in the control group,with statistically significant differences between the two groups (t=4.138,2.881,2.401,P＜0.05).The median number of positive lymph nodes harvested,median number of positive radiation target lymph nodes,and median number of positive peritarget lymph nodes were respectively 0 (range,0-2),0 (range,0-2),and 0 (range,0-0) in the observation group,and 0 (range,0-7),0 (range,0-3),and 0 (range,0-1) in the control group,showing no statistically significant difference between the two groups (Z=1.305,1.101,0.660,P ＞ 0.05).(3) Perioperative complications:6 and 18 patients in the observation group and the control group had complications,respectively,with no statistically significant difference between the two groups (x2=0.570,P＞0.05).Patients with complications were improved after drug treatment and local treatment without second operation.No local or systemic adverse reactions caused by carbon nanoparticles was observed during and after operation in the observation group.(4) Follow-up:56 patients were followed up for 5-65 months,with a median follow-up time of 32 months.There were 14 and 6 patients in the observation group and the control group with tumor recurrence or metastasis,respectively,showing no significant difference between the two groups (x2 =0.002,P＞0.05).Conclusion Carbon nanoparticle labeled lymph node staining in radical resection of adenocarcinoma of esophagogastric junction with preoperative chemoradiotherapy can increase the number of harvested lymph nodes.

Different fractionation schedules of radiotherapy in preoperative concurrent chemoradiotherapy for thoracic esophageal cancer:a clinical study / 中华放射肿瘤学杂志

Objective To investigate the clinical efficacy and safety of preoperative hypofractionated and conventionally-fractionated chemoradiotherapy for thoracic esophageal cancer. Methods A total of 86 patients with thoracic esophageal cancer receiving chemoradiotherpy in Sichuan Cancer Hospital between 2002 and 2011 were enrolled and randomized into the preoperative hypofractionated chemoradiotherapy group ( group A, n=41, 30 Gy in 10 fractions for 2 weeks ) and conventionally-fractionated chemoradiotherapy group ( group B, n=45, 40 Gy in 20 fractions for 4 weeks ) . Surgery was performed at 2-6 weeks after chemoradiotherapy. The probability of patients' survival was estimated by Kaplan-Meier method and analyzed by log-rank test. Results In groups A and B, the pathological downstaging rates were 68％ and 56％( P=0. 270) , the R0 resection rates were 95％ and 89％( P=0. 437) and the pCR rates of 32％ and 24％( P=0. 480).The 1-,3-and 5-year overall survival (OS) rates were 78％ and 69％,44％ and 44％,29％ and 33％(P=0. 114,0. 223,0. 289), and the progression-free survival (PFS) rates were 71％ and 62％,39％ and 38％,24％ and 29％(P=0. 211,0. 689,0. 331), respectively. The incidence rate of chemoradiothery-and surgery-related adverse events did not differ between two groups (P=0. 089-0. 872).The average length of hospital stay, radiotherapy cost and preoperative treatment costs in group A were significantly less compared with those in group B (P=0. 000,0. 000,0. 000). Conclusions Both preoperative hypofractionated and conventionally-fractionated chemoradiotherapy can be used as the regimen of preoperative chemoradiotherapy in patients with resectable thoracic esophageal carcinoma. Compared with conventionally-fractionated chemoradiotherapy, preoperative hypofractionated chemoradiotherapy has shorter treatment cycle, shorter length of hospital stay and lower radiotherapy cost, which is more easily accepted by patients.

A dose-effect analysis of organs at risk during preoperative chemoradiotherapy for gastric cancer / 中华放射肿瘤学杂志

Objective To investigate the clinical and dose-volume factors for damages to organs at risk(OARs)during preoperative chemoradiotherapy for gastric cancer, and to provide a reference for optimization of radiotherapy plans to avoid or reduce damages to OARs.Methods A total of 58 patients with locally advanced gastric adenocarcinoma undergoing neoadjuvant treatment were enrolled as subjects.In those patients,30 received preoperative chemoradiotherapy combined with surgery and adjuvant chemotherapy, while others received preoperative chemotherapy combined with surgery and adjuvant chemotherapy. The preoperative chemotherapy group received 2-3 cycles of xeloxregimen(capecitabine+oxaliplatin)before surgery and 3-4 cycles of xeloxregimen after surgery(a total of 6 cycles). The preoperative chemoradiotherapy group received preoperative radiotherapy(45 Gy in 25 fractions)combined with 2 cycles of concurrent xeloxchemotherapy at 14-21 days after the first cycle of xeloxregimen, as well as 3 cycles of xeloxchemotherapy after surgery. The analyses of clinical and dose-volume factors for damages to OARs were performed based on laboratory indices and clinical symptoms during the treatment. Results In all the patients,the incidence rates of liver injury(LI), renal injury(RI), and duodenum injury(DI)before surgery were 22%,48%,and 33%,respectively;the incidence rates of LI and RI after treatment were 35%and 49%, respectively. After appropriate treatment, neither LI nor DI affected the treatment of gastric cancer. RI healed without any special treatment. Compared with preoperative chemotherapy, preoperative chemoradiotherapy caused higher incidence of LI(P=0.00,0.03).RI was only associated with glomerular filtration rate before radiotherapy(P=0.08,0.13). A V3.5of ≤98.96% for the liver reduced LI, while a D2ccof ≤48 Gy for the duodenum reduced DI. Conclusions Preoperative chemoradiotherapy is safe for treating gastric cancer. Compared with preoperative chemotherapy, preoperative chemoradiotherapy does not increase the risk of RI. However,preoperative chemoradiotherapy tends to increase LI.Further studies are needed to improve the treatment method.

Comparison of efficacy between trimodality and chemoradiation therapy alone in treatment of locally advanced esophageal squamous cell carcinoma / 中华放射医学与防护杂志

Objective To compare the efficacy of trimodality therapy and chemoradiation therapy (CRT) alone in patients with locally advanced resectable esophageal squamous cell carcinoma (SCC).Methods A total of 124 cases with locally advanced resectable esophageal SCC were retrospectively analyzed and classified into 2 groups.Fifty-four cases in trimodality group were treated with surgery and preoperative chemoradiation,while 70 cases in CRT alone group only received radiation and chemotherapy.Local tumor control,3-year survival and treatment-related mortality were assessed.Results The local recurrent rate of the resected patients was 18.5％ in trimodality group and 35.7％ in CRT alone group,respectively(x2 =4.445,P ＜ 0.05).The 3-year progression-free survival (PFS) was 65.3％ (95％ CI 50.7-80.5) in trimodality group and31.9％ (95％CI 19.6-44.2) in CRT alone group (P＜0.05),while the overall survival (OS) 66.3％ (95％ CI43.0-89.6) and 34.4％ (95％ CI 21.1-47.7),respectively(P ＜ 0.05).Treatment-related mortality was 1.9％ in trimodality group and 2.9％ in CRT alone group (P ＞ 0.05).For CRT alone group,the sub-group analysis showed that there was no statistically significant difference in the 3-year OS between patients who received 50-50.4 Gy and those who received the dose over 50.4 Gy (39.9％ 95％ CI 18.5-61.3 vs.31.5％ 95％ CI 14.8-48.2,P ＞0.05).Conclusions Compared with CRT alone,trimodality therapy showed the superior local control,PFS and OS,with similar treatment-related mortality in the treatment of patients with SCC of esophagus.The role of surgery could not be replaced by CRT alone even with the augment of radiation dose.

Comparison of the therapeutic effect of preoperative and postoperative chemoradiotherapy for locally advanced rectal cancer / 重庆医学

Objective To compare the therapeutic effect of preoperative chemoradiotherapy or postoperative adjutant chemoradiotherapy for locally advanced rectal cancer.Methods The clinical data of 76 patients with locally advanced rectal cancer from 2011 to 2016 in Guizhou Provincial People's Hospital were retrospectively analysed.A total of 30 cases received preoperative chemoradiotherapy (group A),5 of them received concurrent chemoradiotherapy combined with bevacizumab target treatment.The other 46 cases (group B) were given post-operative adjutant chemoradiotherapy.Both group A and group B were treated with intensity-modulated radiation therapy (IMRT).The chemoradiotherapy regime was as follows:the median of target volume dose was 50.4 Gy (45.0-55.8 Gy);the median of chemotherapy sessions was 26 times (24-28 times).Capecitabine tablets (825 mg/m2,twice a day) were also given on the date of chemotherapy.The clinical data and follow-up results of all patients were compared between the two groups.Results The five-year disease free survival rates of group A and group B were 66.7％ and 57.7％,respectively;and the five-year overall survival rates of group A and group B were 81.8％ and 73.0％,respectively,no statistically significant difference was found between the two groups (P=0.599,0.489).The anus-preserving rates of patients with tumor below peritoneal reflection in group A and group B were 56.52％ and 25.00％,there was statistically significant difference (P=0.045).In the group A,86.6 ％ patients resulted in down-staging,including 3 cases with complete pathologic response.Conclusion Preoperative chemotherapy could down tumor stage and improve rates of anal preservation and local control without increasing possibility of postoperative complications.Preoperative chemotherapy in combination with bevacizumab target treatment may be more effective in lowering tumor stage.

Genetic variations in MLH3 and MSH2 genes are associated with the sensitivity and prognosis in locally advanced rectal cancer patients receiving preoperative chemoradiotherapy / 中华肿瘤杂志

Objective@#To investigate the associations between genetic variations in DNA mismatch repair genes and sensitivity as well as prognosis to preoperative chemoradiotherapy in patients with locally advanced rectal cancer.@*Methods@#Fourteen haplotype-tagging single nucleotide polymorphisms (htSNPs) of MLH1, MLH3 and MSH2 genes were genotyped by Sequenom MassARRAY method in 146 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. The associations between genotypes and response to capecitabine-based neoadjuvant chemoradiotherapy (nCRT) were measured by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for sex, age, clinical stages and karnofsky performance score (KPS) by unconditional logistic regression model. The survival analyses were performed by the hazard ratios (HRs) and 95% CIs by Cox proportional regression model.@*Results@#Among 146 cases, 64 patients were nCRT responders with a response rate of 43.8%. MLH3 rs175057 C>T and MSH2 rs13019654 G>T loci were associated with the sensitivity to preoperative chemoradiotherapy. Compared with the rs175057 CC genotype, the adjusted OR for patients with CT and TT genotypes was 0.42 (95% CI: 0.19-0.91; P=0.029). Moreover, for rs13019654, the adjusted OR for patients with the GT or TT genotypes was 0.49 (95% CI: 0.24-0.98; P=0.047) than those with GG genotype. The remaining 12 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs3771273, rs4608577, rs4952887, rs6544991, rs6544997, rs10188090 and rs10191478, were not significantly associated with therapeutic response to preoperative chemoradiotherapy. Meanwhile, MLH3 rs175057 C>T locus was also associated with longer overall survival time in locally advanced rectal cancer (HR=0.44, 95% CI: 0.20-0.96, P=0.038), whereas MSH2 rs3771273 T>A, rs10188090 A>G and rs10191478 T>G loci were associated with shorter overall survival time (HR=1.74, 95% CI: 1.06-2.84, P=0.028; HR=1.64, 95% CI: 1.01-2.66, P=0.046; HR=1.71, 95% CI: 1.01-2.91, P=0.047, respectively). The remaining 10 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs4608577, rs4952887, rs6544991, rs6544997 and rs13019654, were not significantly associated with prognosis.@*Conclusions@#Genetic polymorphisms of MLH3 rs175057 and MSH2 rs13019654 loci can predict the nCRT response, while MLH3 rs175057 as well as MSH2 rs3771273, rs10188090 and rs10191478 may predict prognosis in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. Therefore, these SNPs could be used as potential genetic markers in the personalized therapy of rectal cancer.

Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical factors could be valuable for post-operative assessment of pathological complete response.

A randomized controlled trial comparing the efficacy and toxicities between neoadjuvant concomitant boost intensity-modulated radiotherapy (IMRT) and 3-dimensional conformal radiotherapy (3-DCRT) for locally advanced rectal cancer / 中华放射医学与防护杂志

Objective To compare the efficacy and toxicities between preoperative concomitant boost intensity-modulated radiotherapy (IMRT) and 3-dimensional conformal RT (3-DCRT) for locally advanced rectal cancer.Methods A prospective study from May 2010 to May 2015.A total of 130 patients with histologically confirmed,newly diagnosed,locally advanced rectal adenocarcinoma (cT3-T4 and/or cN +) located within 10 cm from the anal verge were included in this study.The patients were divided into IMRT and 3D-CRT groups by random number table method.Sixty-six patients were treated with IMRT,and the other sixty-four patients were treated with 3-DCRT.In the IMRT group,the prescription dose was 1.8 Gy/fraction to 45 Gy to the pelvis and 2.2 Gy/fraction to 55 Gy to the gross tumor volume simultaneously.The 3D-CRT prescription was 45 Gy in 25 fractions to the pelvis.Capecitabine (1 650 mg· m 2 · d-1) was given twice daily from days 1 to 14 and days 22 to 35 during RT in both arms.Total mesorectal excision (TME) was scheduled 6-8 weeks after the completion of chemoradiation.Results There were no significant differences in age,gender,tumor location,pathological differentiation degree and clinical stage between the two groups.Two patients withdrew from the study:one for grade 3 radiation dermatitis in IMRT group and the other for grade 3 fatigue in 3D-CRT.There was no significant difference in hematologic or nonhematologic toxicities between the two groups.No grade 4 or 5 toxicity was observed in either group.Compared with conformal radiotherapy,IMRT did not increase the difficulty of surgery.No significant difference was found in type of surgery or postoperative complications between the two groups.The rate of tumor regression grade (TRG) 4 (pathologic complete response,pCR) was 22.7％ for IMRT and 15.6％ for 3D-CRT,respectively(P ＞ 0.05).The rate of both TRG4 and 3 was 42.4％ for IMRT and 25.0％ for 3D-CRT,respectively (x2 =4.406,P=0.036).Conclusions Neoadjuvant concomitant boost IMRT is feasible and has a higher histopathological regression for patients with locally advanced rectal cancer.Trial registration Chinese clinical trial registry,ChiCTR-IN R-16008004.

Predictive value of imaging evaluation in stage Ⅱ/Ⅲ esophageal carcinoma patients treated with preoperative chemoradiotherapy / 中华放射医学与防护杂志

Objective Retrospectively analyzed the predictive value of imaging evaluation in stage Ⅱ/Ⅲ esophageal carcinoma patients treated with preoperative chemoradiotherapy.Methods A total of 145 stage Ⅱ/Ⅲ esophageal carcinoma pantients were enrolled.We analyzed the overall survival rates of the patients with pathological complete response (pCR) and those without (NpCR),X-film complete response (xCR) and those without (NxCR),RECIST complete response (rCR) and those without (NrCR).And we used Cox model for multivariate analysis.Results The rates of pCR,xCR and rCR were 33.8％,42.8％ and 38.6％ for all patients,respectively.The 1-,3-5-year overall survival rates were 87.8％,79.6％,61.2％ for pCR patients and 75％,40.6％,24.0％ for NpCR patients (x2 =20.215,P ＜0.05),respectively;The 1-,3-5-year overall survival rates were 80.6％,66.1％,51.6％ for xCR patients and 75％,44.6％,25.3％ for NxCR patients(x2 =8.895,P ＜0.05),respectively;The 1-,3-5-year overall survival rates were 83.9％,69.6％,53.6％ for rCR patients and 76.4％,46.1％,25.8％ for NxCR patients(x2 =10.862,P ＜ 0.05),respectively.Multivariate survival analysis using Cox regression model showed that pCR was a positive independent prognostic factor (HR =0.333,95％ CI:0.200-0.554,P ＜ 0.05).Conclusions Short-term imaging evaluation could effectively predict the prognosis of stage Ⅱ/Ⅲ esophageal carcinoma patients treated with preoperative chemoradiotherapy.And pCR was a positive independent prognostic factor.

Clinical Outcomes of Local Excision Following Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the treatment outcomes of local excision following preoperative chemoradiotherapy in patients with locally advanced rectal cancer who have not undergone radical surgery for any reason. MATERIALS AND METHODS: The data of 27 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy followed by local excision were analyzed retrospectively. The primary endpoint was the 5-year relapse-free survival rate, and the secondary endpoint was the pattern of recurrence. RESULTS: The median follow-up time was 81.8 months (range, 28.6 to 138.5 months). The 5-year local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were 88.9%, 81.1%, 77.8%, and 85.0%, respectively. Six (22%) patients developed treatment failure; one (4%) patient had local recurrence only, three (11%) patients had distant recurrence only, and two (7%) patients had both. The 5-year LRFS, DMFS, RFS, and OS for patients with ypT0-1 compared with ypT2-3 were 94.1% vs. 77.8% (p=0.244), 94.1% vs. 55.6% (p=0.016), 88.2% vs. 55.6% (p=0.051), and 94.1% vs. 66.7% (p=0.073), respectively. CONCLUSION: Local excision following preoperative chemoradiotherapy may be an alternative treatment for highly selected patients with locally advanced rectal cancer who have achieved ypT0-1 after preoperative chemoradiotherapy.

Clinical impact of fat clearing technique in nodal staging of rectal cancer after preoperative chemoradiotherapy / 대한외과학회지

PURPOSE: This study was designed to evaluate the efficacy of a fat clearing technique for accurate nodal staging of rectal cancer patients after preoperative chemoradiotherapy (CRT). METHODS: A total of 19 patients with rectal cancer within 10 cm from anal verge were divided into two groups: non-CRT group (n = 10) and CRT group (n = 9). For pathologic assessment, lymph node (LN) harvest was performed using conventional manual dissection followed by a fat clearing technique. RESULTS: A median of 3.0 additional LNs in non-CRT group and 3.8 LNs in CRT group were identified by the fat clearing technique. When subanalysis was performed in patients with fewer than 12 retrieved LNs, a median of 4.0 extra LNs in non-CRT group and 3.5 extra LNs in CRT group were identified after the fat clearing technique. None of additionally identified nodes were metastatic. In both groups, the median size of retrieved LNs following the fat clearing technique was smaller than that obtained by manual dissection (2.0 mm vs. 3.0 mm, P < 0.001). CONCLUSION: The fat clearing technique allowed detection of additional LNs that were missed by the manual method, but these detected LNs were not proven to be metastatic.

Clinical predictive factors of pathologic tumor response after preoperative chemoradiotherapy in rectal cancer

PURPOSE: The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer. MATERIALS AND METHODS: The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used (5-fluorouracil and leucovorin, capecitabine, or tegafur/uracil). Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. RESULTS: Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR. CONCLUSION: Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

The efficacy of neoadjuvant concurrent chemoradiotherapy or radiotherapy alone in patients with locally advanced rectal cancer / 中华放射肿瘤学杂志

Objective To observe the efficacy and safety of preoperative concurrent chemoradiotherapy or radiotherapy alone in patients with T3,T4 or lymph node-positive rectal cancer.Methods 141 rectal cancer patients with locally advanced or node-positive based on imaging from 2000 to 2009 were retrospective analyzed.Ninety-seven patients received preoperative concurrent chemoradiotherapy and 44 received preoperative radiotherapy alone.Two-dimensional or three-dimensional radiation technique and four types of chemotherapy regimens were used.Results The following-up rate was 91.5％.106 patients were followed up for at least 3 years and 68 patients for at least 5 years.The 3-and 5-year overall survival rates were 85.8％ and 65.7％,respectively.The 3-and 5-year local recurrence rates were 9.2％ and 14.1％,respectively.The 3-and 5-year metastasis rates were 33.8％ and 45.8％,respectively.The downstaging rate was up to 59.0％ (82/139) and the rate of sphincter preservation was 65.5％ (91/139).The median disease-free survival in patients treated with preoperative concurrent chemoradiotherapy was superior to radiotherapy alone (51 months vs 31 months,x2 =12.88,P =0.000).The time to metastasis in patients with downstaging was significantly delayed than that in patients without downstaging (60 months vs 29 months,x2 =14.65,P =0.000).Most acute toxicity was grade 1 and grade 2.The incidence of delayed wound healing and anastomotic leakage was very low.Conclusions Preoperative concurrent chemoradiotherapy or radiotherapy alone has excellent tumor downstaging effect and helps in sphincter preservation,with tolerable side effects.

Clinical Significance of Tumor Regression Grade in Rectal Cancer with Preoperative Chemoradiotherapy

PURPOSE: Neoadjuvant chemoradiotherapy applied to the locally advanced rectal cancer reduces local recurrence and improves survival. We assessed tumor regression grade (TRG) and its influence on survival in rectal cancer patients treated with chemoradiotherapy followed by surgical resection. METHODS: We studied 108 patients that were seen at our hospital between August 2004 and December 2008. Patients received preoperative chemoradiotherapy consisting of 5-fluorouracil and leucovorin by continous infusion during the first and fifth week, delivered with concurrent pelvic radiation of 50.4 Gy, followed by radical surgery at 6-8 weeks. The TRG was determined by the amount of fibrosis in the tumor embedding area and was divided into 5 grades based on the relative amount of fibrosis. We analyzed all preoperative clinicopathologic factors, postoperative pathologic stages, TRG and prognosis, retrospectively. RESULTS: Downstaging of rectal cancer through neoadjuvant chemoradiotherapy occurred in 64 (59%) patients. The numbers of total regressions (TRG4), good regressions (TRG3), moderate regressions (TRG2), minor regressions (TRG1), and no regression (TRG0) were 19 (18%), 65 (60%), 17 (16%), 6 (5%), and 1 (1%) respectively. The TRG was inversely correlated with perineural invasion and lymphovascular invasion (P = 0.008, P = 0.032). The local recurrence rate declined as the tumor regression grade increased (P = 0.032). The 19 patients with TRG4 had a better three-year disease free survival than the 89 patients with TRG0-3 (P = 0.034). The 16 patients with pathologic complete remission (pCR) had a better three-year disease free survival than the 92 patients with non-pCR (P = 0.025). CONCLUSION: Higher TRG after preoperative chemoradiotherapy for rectal cancer closely correlates with better survival and low local recurrence. The TRG is considered to be a significant prognostic factor.

Pathologic Complete Remission after Preoperative Chemoradiation for Rectal Cancer: Analysis of Clinicopathologic Characteristics and Oncologic Outcome

PURPOSE: To assess the clinico-pathologic characteristics associated with pathologic complete remission (pCR) after preoperative chemoradiotherapy (PCRT) for rectal cancer and evaluate predictive factors for pCR and prognostic impact of pCR. METHODS: We analyzed 325 patients who underwent PCRT and surgical resection between September 1999 and September 2006. We have treated 319 patients with PCRT for locally advanced rectal cancer and 6 patients for sphincter-saving procedure. Chemotherapy consisted of either of bolus 5-FU (325 mg/m2/d) or capecitabine (1,650 mg/m2/d) for the duration of radiation and after surgery. Radiation therapy was delivered and surgery was performed 4~6 weeks following the completion of PCRT. We compared pCR patients with non-pCR patients according to the clinico-pathologic characteristics and followed up with a median of 32 (range, 12~91) months. RESULTS: The pCR (n=41, 12.6%) and non-pCR (n=284) groups were comparable in age, sex, location of the tumor, chemotherapy regimen, pre-CRT CEA level except pre-CRT clinical stage (12.2% vs. 0.4% in stage I, P= 0.047). There was no significant difference in genetic characteristics between groups. There was no specific predictive factors for pCR except pre-CRT T category (pCR in T2 (5/8, 62.5%) vs. T3 (33/283, 11.7%) or T4 (3/33, 9.1%), P=0.001). The 3-year disease free survival (DFS) was 100% and 83.6% in the pCR and non-pCR group respectively (P=0.012). There were 5 local and 34 systemic recurrences only in non-pCR group. CONCLUSIONS: Rectal cancer patients with pCR after PCRT have an excellent prognosis and are unlikely to fail locally or systemically because of the effect of stage. However there was no specific predictive factor for pCR except preoperative T category.

Results of Preoperative Concurrent Chemoradiotherapy for the Treatment of Rectal Cancer / 대한방사선종양학회지

PURPOSE: The purpose of this study is to evaluate anal sphincter preservation rates, survival rates, and prognostic factors in patients with rectal cancer treated with preoperative chemoradiotherapy. MATERIALS AND METHODS: One hundred fifty patients with pathologic confirmed rectal cancer and treated by preoperative chemoradiotherapy between January 1999 and June 2007. Of the 150 patients, the 82 who completed the scheduled chemoradiotherapy, received definitive surgery at our hospital, and did not have distant metastasis upon initial diagnosis were enrolled in this study. The radiation dose delivered to the whole pelvis ranged from 41.4 to 46.0 Gy (median 44.0 Gy) using daily fractions of 1.8~2.0 Gy at 5 days per week and a boost dose to the primary tumor and high risk area up to a total of 43.2~54 Gy (median 50.4 Gy). Sixty patients (80.5%) received 5-fluorouracil, leucovorin, and cisplatin, while 16 patients (19.5%) were administered 5-fluorouracil and leucovorin every 4 weeks concurrently during radiotherapy. Surgery was performed for 3 to 45 weeks (median 7 weeks) after completion of chemoradiotherapy. RESULTS: The sphincter preservation rates for all patients were 73.2% (60/82). Of the 48 patients whose tumor was located at less than 5 cm away from the anal verge, 31 (64.6%) underwent sphincter-saving surgery. Moreover, of the 34 patients whose tumor was located at greater than or equal to 5 cm away from the anal verge, 29 (85.3%) were able to preserve their anal sphincter. A pathologic complete response was achieved in 14.6% (12/82) of all patients. The downstaging rates were 42.7% (35/82) for the T stage, 75.5% (37/49) for the N stage, and 67.1% (55/82) for the overall stages. The median follow-up period was 38 months (range 11~107 months). The overall 5-year survival, disease-free survival, and locoregional control rates were 67.4%, 58.9% and 84.4%, respectively. The 5-year overall survival rates based on the pathologic stage were 100% for stage 0 (n=12), 59.1% for stage I (n=16), 78.6% for stage II (n=30), 36.9% for stage III (n=23), and one patient with pathologic stage IV was alive for 43 months (p=0.02). The 5-year disease-free survival rates were 77.8% for stage 0, 63.6% for stage I, 58.9% for stage II, 51.1% for stage III, and 0% for stage IV (p55), clinical stage (I+II vs. III), radiotherapy to surgery interval (6 weeks), operation type (sphincter preservation vs. no preservation), pathologic T stage, pathologic N stage, pathologic overall stage (0 vs. I+II vs. III+IV), and pathologic response (complete vs. non-CR), only age and pathologic N stage were significant predictors of overall survival, pathologic overall stage for disease-free survival, and pathologic N stage for locoregional control rates, respectively. Recurrence was observed in 25 patients (local recurrence in 10 patients, distant metastasis in 13 patients, and both in 2 patients). Acute hematologic toxicity (> or =grade 3) during chemoradiotherapy was observed in 2 patients, while skin toxicity was observed in 1 patient. Complications developing within 60 days after surgery and required admission or surgical intervention, were observed in 11 patients: anastomotic leakage in 5 patients, pelvic abscess in 2 patients, and others in 4 patients. CONCLUSION: Preoperative chemoradiotherapy was an effective modality to achieve downstaging and sphincter preservation in rectal cancer cases with a relatively low toxicity. Pathologic N stage was a statistically significant prognostic factor for survival and locoregional control and so, more intensified postoperative adjuvant chemotherapy should be considered in these patients.