Circumferential Extent Of Tumor Research Articles

Nomogram for predicting pathological complete response and tumor downstaging in patients with locally advanced rectal cancer on the basis of a randomized clinical trial.

BackgroundPreoperative fluoropyrimidine with radiotherapy was regarded as the standard of care for locally advanced rectal cancer (LARC). The model for predicting pCR in LARC patients was based on standard treatment only. This study aimed to establish a nomogram with pretherapeutic parameters and different neoadjuvant regimens for predicting pathologic complete response (pCR) and tumor downstaging or good response (ypT0-2N0M0) after receiving neoadjuvant treatment in patients with LARC based on a randomized clinical trial.MethodsBetween January 2011 and February 2015, 309 patients with rectal cancer were enrolled from a prospective randomized study (NCT01211210). All pretreatment clinical parameters were collected to build a nomogram for predicting pCR and tumor downstaging. The model was subjected to bootstrap internal validation. The predictive performance of the model was assessed with concordance index (C-index) and calibration plots.ResultsOf the 309 patients, 53 (17.2%) achieved pCR and 132 (42.7%) patients were classified as tumor downstaging with ypT0-2N0M0. Based on the logistic-regression analysis and clinical consideration, tumor length (P = 0.005), tumor circumferential extent (P = 0.036), distance from the anal verge (P = 0.019), and neoadjuvant treatment regimen (P < 0.001) showed independent association with pCR following neoadjuvant treatment. The tumor length (P = 0.015), tumor circumferential extent (P = 0.001), distance from the anal verge (P = 0.032), clinical T category (P = 0.012), and neoadjuvant treatment regimen (P = 0.001) were significantly associated with good tumor downstaging (ypT0-2N0M0). Nomograms were developed to predict the probability of pCR and tumor downstaging with a C-index of 0.802 (95% confidential interval [CI], 0.736–0.867) and 0.730 (95% CI, 0.672–0.784). Internal validation revealed good performance of the calibration plots.ConclusionsThe nomogram provided individual prediction responses to different preoperative treatment for patients with rectal cancer. This model might help physicians in selecting an optimized treatment, but warrants further external validation.

Serial ctDNA analysis as a real-time indicator of neoadjuvant chemoradiotherapy in rectal cancer.

3569 Background: Neoadjuvant chemoradiotherapy (nCRT) is nowadays the standard of care for the locally advanced rectal cancer (LARC). However, there is no effective method to predict patients’ possible benefits from nCRT and monitor the response to it. Methods: Patients with locally advanced middle and low rectal cancer of stage cT3-4N0M0 or cTanyN+M0 were enrolled from August 2017 to July 2018. All patients received nCRT with long-term radiation plus fluorouracil based chemotherapy, followed by the radical surgery. Serial plasma samples were collected pre-nCRT, during nCRT, and preoperatively (8 weeks after the completion of nCRT). Somatic mutations were detected with next-generation sequencing using a 1021-gene panel with peripheral blood lymphocyte DNA as a germline control. Results: This prospective cohort study enrolled 61 patients with rectal cancer. The pathological complete response (pCR) rate and the downstage rate was 31% (19/61) and 80% (49/61), respectively. ctDNA was detectable in 77% (47/61), 18% (11/61) and 13% (8/61) of blood samples obtained pre-nCRT, during nCRT and preoperatively, respectively. No significant association was observed between pre-nCRT ctDNA status with any clinicopathological factors, including age, gender, differentiation or tumor circumferential extent. Among the 8 patients with detectable ctDNA preoperatively, pathological tumor regression grade (TRG) of CAP 2-3 were observed and hepatic metastasis was found in 4 patients within 2 months. For patients with undetectable pre-operative ctDNA, a higher proportion archived pathological downstaging (85% vs 50%). The correlation between preoperative ctDNA status and achievement of pathological downstage was independent of age, gender or differentiation (p = 0.02). In addition, preoperative ctDNA positivity was associated with the persistently involved lymph node (p = 0.02). However, neither pre-nCRT nor during-nCRT ctDNA status was associated with pathological downstaging or persistently lymph node involvement. Conclusions: Detectable ctDNA after the completion of nCRT is a predicator of unsatisfactory curative effect of patients with LARC, which might indicate novel treatment intensification studies. Clinical trial information: NCT03042000.

Predictors of sensitivity to preoperative chemoradiotherapy of rectal adenocarcinoma.

The purpose of the study was to identify predictive factors of tumor response to preoperative chemoradiotherapy for rectal adenocarcinoma. Ninety-eight patients with nonmetastatic rectal adenocarcinoma received preoperative concurrent chemoradiotherapy and underwent mesorectal excision. After treatment, tumor response according to tumor regression grade were evaluated. The correlation of clinicopathologic factors to tumor response was analyzed. The results from a univariate analysis indicated that pretreatment carcinoembryonic antigen level ≤3.0 ng/ml (P = 0.002), non-fixed tumor (P = 0.001), and tumor circumferential extent ≤50% (P = 0.001) were associated significantly with a good tumor response. They also indicated that pretreatment positive lymph nodes (P = 0.032) were associated significantly with a poor tumor response. In multivariate analysis, the results indicated that pretreatment carcinoembryonic antigen level (hazard ratio, 2.930; P = 0.003), tumor mobility (hazard ratio, 2.651; P = 0.002) and circumferential extent of tumor (hazard ratio, 2.394; P = 0.019) independently predicted a good pathologic response rate. Pretreatment positive lymph nodes were not significantly associated with a good response (hazard ratio, 0.361; P = 0.191). Pretreatment carcinoembryonic antigen level, tumor mobility and circumferential extent of tumor may be helpful in predicting responsiveness in rectal adenocarcinoma to preoperative chemoradiotherapy, although the results should be confirmed in larger, more homogeneous studies.

A nomogram predicting pathological complete response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer: implications for organ preservation strategies.

PurposeTo determine predictors of pathological complete response (pCR) in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), and develop a predictive nomogram.MethodsA total of 522 locally advanced rectal cancer patients undergoing nCRT and curative resection between 2008 and 2014 were included. Uni- and multivariate analysis was performed to identify predictors of pCR. A nomogram was developed and validated by internal (n=425) and external validation (n=97).ResultsWith a median follow-up of 55 months, pCR was associated with better 5-year overall and disease-free survival, distant control, but similar local control. Logistic regression showed that post-CRT distance from the anal verge (OR =0.840, P = 0.022), post-CRT tumor size (OR = 0.565, P = 0.003), post-CRT circumferential extent of tumor (OR = 0.021, P < 0.001), pre-CRT CEA level (OR = 2.004, P = 0.033), and post-CRT CEA level (OR = 3.767, P = 0.038) were independently associated with pCR. A nomogram was developed with a C-index of 0.81 and 0.75 on internal and external validation, respectively.ConclusionpCR was associated with better long-term outcome. A nomogram was successfully developed to predict pCR. It could support decision-making in organ preservation strategies.

Refractory strictures despite steroid injection after esophageal endoscopic resection.

Background: Although steroid injection prevents stricture after esophageal endoscopic submucosal dissection (ESD), some patients require repeated sessions of endoscopic balloon dilation (EBD). We investigated the risk for refractory stricture despite the administration of steroid injections to prevent stricture in patients undergoing esophageal ESD. Refractory stricture was defined as the requirement for more than three sessions of EBD to resolve the stricture. In addition, the safety of steroid injections was assessed based on the rate of complications. Patients and methods: We analyzed data from 127 consecutive patients who underwent esophageal ESD and had mucosal defects with a circumferential extent greater than three-quarters of the esophagus. To prevent stricture, steroid injection was performed. EBD was performed whenever a patient had symptoms of dysphagia. Results: The percentage of patients with a tumor circumferential extent greater than 75 % was significantly higher in those with refractory stricture than in those without stricture (P = 0.001). Multivariate analysis adjusted for age, sex, history of radiation therapy, tumor location, and tumor diameter showed that a tumor circumferential extent greater than 75 % was an independent risk factor for refractory stricture (adjusted odds ratio [OR] 5.49 [95 %CI 1.91 – 15.84], P = 0.002). Major adverse events occurred in 3 patients (2.4 %): perforation during EBD in 2 patients and delayed perforation after EBD in 1 patient. The patient with delayed perforation underwent esophagectomy because of mediastinitis. Conclusions: A tumor circumferential extent greater than 75 % is an independent risk factor for refractory stricture despite steroid injections. The development of more extensive interventions is warranted to prevent refractory stricture.

Nomogram basing pre-treatment parameters predicting early response for locally advanced rectal cancer with neoadjuvant chemotherapy alone: a subgroup efficacy analysis of FOWARC study.

ObjectiveTo develop an accurate model with pre-treatment parameters to predict tumor regression and down-staging in locally advanced rectal cancer patients, basing the cohort of preoperative chemotherapy alone in FOWARC study.Patients and MethodsFrom Jan 2011 to Feb 2015, complete data was available for 137 out of 165 patients who received preoperative chemotherapy alone. All pre-treatment clinical parameters were collected. Tumor regression grade (TRG) 0-1 was defined as good regression, and pathological TNM stage (ypTNM) 0-I after neoadjuvant treatment was defined as good down-staging. Nomogram was established to predict tumor regression and down-staging. The predictive performance of the model was assessed with concordance index and calibration plots.ResultsOf the 137 patients, 10 had TRG 0 (complete regression); 32 patients, TRG 1; and 95 patients, TRG 2 and 3 (poor regression); 56 (40.9%) patients were classified as good down-staging with ypTNM stage 0-I. The predictive nomograms were developed to predict the probability of TRG 0-1 and good down-staging with a C-index of 0.72 (95% CI: 0.604-0.797) and 0.76 (95% CI: 0.681-0.844). Calibration plots showed good statistical performance on internal validation. Predictive factors in the models included tumor length, tumor circumferential extent, age, and ApoA1.ConclusionsThe model based on available clinical parameters could accurately predict early efficacy with neoadjuvant mFOLFOX6 chemotherapy alone, which might help in patient selection for optimized treatment.

Predictive factors associated with pathologic complete response after neoadjuvant chemoradiotherapy in rectal cancer

To explore predictive factors associated with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy for rectal cancer. Clinicopathological data of 163 patients with locally advanced rectal cancer who were treated with neoadjuvant chemoradiotherapy followed by radical surgical resection from January 2007 to May 2013 were analyzed retrospectively. Univariate analysis and multivariate logistic regression analysis were performed to analyze associated factors of pCR, including age, gender, body mass index (BMI), diabetes, anemia, tumor diameter, distance of the tumor from the anal verge, circumferential extent of the tumor, tumor pathological types, tumor differentiation, pre-chemoradiotherapy T stage, pre-chemoradiotherapy N stage, pre-chemoradiotherapy CEA level, pre-chemoradiotherapy CA199 level, per-operation CEA level, pre-operation CA199 level, radiation dose, chemotherapy modality, time interval from completion of chemoradiotherapy to surgery, etc. Twenty-nine patients(17.8%) achieved pCR after neoadjuvant chemoradiotherapy for rectal cancer. Univariate analysis showed circumferential extent of tumor(≥1/2 cycle)(P=0.018), tumor pathological types(adenocarcinoma)(P=0.036), tumor differentiation (moderate or high)(P=0.021) and pre-chemoradiotherapy CEA level(≤2.5 μg/L)(P=0.007) were significantly correlated with pCR after neoadjuvant chemoradiotherapy for rectal cancer. Logistic regression revealed that circumferential extent of tumor (≥1/2 cycle)(OR=2.901, P=0.020) and pre-chemoradiotherapy CEA level (≤2.5 μg/L)(OR=2.775, P=0.022) were independent predictive factors of pCR after neoadjuvant chemoradiotherapy for rectal cancer. Patients with circumferential extent of tumor ≤1/2 and pre-chemoradiotherapy CEA level ≤2.5 μg/L are more likely to achieve pCR after neoadjuvant chemoradiotherapy for rectal cancer, and these two indices can be used to predict pCR after neoadjuvant chemoradiotherapy for rectal cancer.

Predictors of Sensitivity to Preoperative Chemoradiotherapy of Rectal Adenocarcinoma

The purpose of the study was to identify predictive factors of tumor response to preoperative chemoradiotherapy for rectal adenocarcinoma. Ninety-eight patients with nonmetastatic rectal adenocarcinoma received preoperative concurrent chemoradiotherapy and underwent mesorectal excision. After treatment, tumor response according to tumor regression grade were evaluated. The correlation of clinicopathologic factors to tumor response was analyzed. The results from a univariate analysis indicated that pretreatment carcinoembryonic antigen level ≤3.0 ng/ml (P = 0.002), non-fixed tumor (P = 0.001), and tumor circumferential extent ≤50% (P = 0.001) were associated significantly with a good tumor response. They also indicated that pretreatment positive lymph nodes (P = 0.032) were associated significantly with a poor tumor response. In multivariate analysis, the results indicated that pretreatment carcinoembryonic antigen level (hazard ratio, 2.930; P = 0.003), tumor mobility (hazard ratio, 2.651; P = 0.002) and circumferential extent of tumor (hazard ratio, 2.394; P = 0.019) independently predicted a good pathologic response rate. Pretreatment positive lymph nodes were not significantly associated with a good response (hazard ratio, 0.361; P = 0.191). Pretreatment carcinoembryonic antigen level, tumor mobility and circumferential extent of tumor may be helpful in predicting responsiveness in rectal adenocarcinoma to preoperative chemoradiotherapy, although the results should be confirmed in larger, more homogeneous studies.

Importance of the Circumferential Extent of Tumors and Clinical Lymph Node Status as Prognostic Factors after Preoperative Chemoradiotherapy and Surgery in Patients with Rectal Cancer

To evaluate the clinical factors that influence pathological and clinical outcomes after preoperative concurrent chemoradiotherapy in patients with rectal cancer. Between 1999 and 2004, 121 patients with cT3-4 or node-positive rectal cancer received preoperative chemoradiotherapy and surgery. Preoperative radiation therapy with 45 Gy was delivered. Fluorouracil-based chemotherapy was administered to most of the patients. Pathological complete remission was 14.3% after preoperative chemoradiotherapy. More than 60% tumor circumferential extent was an independent adverse factor for complete remission (P = 0.011, HR 4.643, 95% CI 1.415-15.231). Local recurrence developed in 9.9% of the cases. Serum CEA level > 5 ng/ml (P = 0.057, HR 3.022, 95% CI 0.967-9.441) and > 60% circumferential extent of tumor (P = 0.064, HR 4.232, 95% CI 0.918-19.531) were marginal adverse factors for local recurrence. Five-year disease-free survival and overall survival were 72.2% and 86.6%, respectively. Disease-free survival was poor for patients with the lymph nodes > or = 1 cm in diameter (P = 0.028), cN2 stage disease (P = 0.047) and > 60% circumferential extent of tumor (P = 0.058). Multivariate analysis for disease-free survival showed that the lymph node size > or = 1 cm was an adverse factor (P = 0.019, HR 2.380, 95% CI 1.115-4.906). Patients with > 60% circumferential extent of tumor and cN2 stage had a more unfavorable survival than the other patients (disease-free survival, P = 0.018; overall survival, P = 0.015). Patients with > 60% circumferential extent of tumor and/or lymph node > or = 1 cm also had an unfavorable survival (disease-free survival, P = 0.016; overall survival, P = 0.049). In rectal cancer, circumferential extent of tumor and clinical lymph node status were important factors for preoperative chemoradiotherapy and surgery. A further prospective study is needed to confirm and expand these findings.

Lymph node metastasis and its risk factors in T1-2 staging invasive rectal carcinoma

To investigate the lymph node metastasis and its risk factors in T1-2 staging invasive rectal carcinoma. The data of 1116 patients with rectal cancer treated with total mesorectal excision (TME) technique from January 2000 to April 2009 was analyzed retrospectively. The clinicopathological factors analyzed included gender, age, primary symptom type, number of symptoms, duration of symptom, synchronous polyps, preoperative serum carcino-embryonic antigen level, preoperative serum CA19-9 level, the distance of tumor from the anal verge, tumor size, tumor morphological type, tumor circumferential extent, tumor differentiation and tumor T staging. Statistical analysis was performed by using Logistic regression analysis and Chi-square test. A total of 1116 patients were enrolled, and 358 cases (32.1%) were classified as with T1-2 staging tumor. Two cases (5.6%, 2/36) in patients with a T1 staging tumor were found with lymph node metastasis, and 75 cases (23.3%, 75/322) in patients with a T2 staging tumor, respectively. Compared with patients with T3-4 staging tumor, lymph node metastasis rate of the patients with T1-2 staging tumor was significantly lower [21.5% (77/358) vs. 51.6% (391/758), P < 0.05]. Only the tumor T staging was found as the independent risk factor for the lymph node metastasis in patients with T1-2 staging tumor on multivariate Logistic regression analysis (odds ratio: 5.162; 95%CI: 1.212 to 21.991; P = 0.026). A substantial proportion of T1-2 staging rectal cancers harbor metastatic lymph nodes and the clinicopathological features except for T staging fail to predict the lymph node metastasis. Further research is warranted to identify the risk factors and guide the clinical practice in patient with T1-2 staging tumor.

Clinical Factors Predicting Pathologic Response after Preoperative Concurrent Chemoradiation for Rectal Cancer

Clinical Factors Predicting Pathologic Response after Preoperative Concurrent Chemoradiation for Rectal Cancer

Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer

The objective of this study was to identify predictive factors for pathologic complete response and tumor downstaging after preoperative chemoradiation for rectal cancer. Between 1989 and 2004, 562 patients with nonmetastatic rectal adenocarcinoma received preoperative chemoradiation and underwent mesorectal excision. The median radiation dose was 45 Gray (Gy) (range, 19.8-58.6 Gy), 77% of patients received concurrent infusional 5-fluorouracil, 20% of patients received concurrent capecitabine, and 3% of patients received other regimens. Nineteen percent of patients achieved a pathologic complete response (CR), whereas 20% of patients had only microscopic residual disease at surgery, and 61% of patients had macroscopic residual disease at surgery. Downstaging of the tumor stage occurred in 57% of patients. The results from a univariate analysis indicated that tumor circumferential extent>60% (P=.033) and pretreatment carcinoembryonic antigen (CEA) level>2.5 ng/mL (P=.015) were associated significantly with lower pathologic CR rates. The univariate analysis also indicated that tumor circumferential extent>60% (P=.001), pretreatment CEA level>2.5 ng/mL (P=.006), and distance from the anal verge>5 cm (P=.035) were associated significantly with lower downstaging rates. The results from a multivariate logistic regression analysis indicated that greater circumferential extent of tumor (odds ratio [OR], 0.43; P=.033) independently predicted a lower pathologic CR rate. The multivariate logistic regression analysis also indicated that greater circumferential extent of tumor (OR, 0.49; P=.020) and greater distance from the anal verge (OR, 0.46; P=.010) independently predicted a lower downstaging rate. Circumferential extent of tumor, CEA level, and distance from the anal verge predicted for the pathologic response to preoperative chemoradiation for patients with rectal cancer. Therefore, these factors may be used to predict outcomes for patients, to develop risk-adapted treatment strategies, and to target patients who participate in trials of newer therapies.

Clinical and Pathologic Predictors of Locoregional Recurrence, Distant Metastasis, and Overall Survival in Patients Treated With Chemoradiation and Mesorectal Excision for Rectal Cancer

To identify predictive factors for locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) in patients treated with chemoradiation and surgery for rectal cancer. Between 1989 and 2001, 470 patients with rectal cancer were treated with preoperative (89%) or postoperative (11%) chemoradiation and mesorectal excision. Median radiation dose was 45 Gy; 97% received concurrent infusional 5-fluorouracil, and 65% received adjuvant chemotherapy. Median follow-up interval was 5.7 years. The 5-year rates of freedom from LR, freedom from DM, and OS were 90%, 79%, and 80%, respectively. On univariate analysis, significant predictors of LR were female sex, clinical T stage, pathologic T and N stages, and positive radial margin. Significant univariate predictors of DM were circumferential extent of tumor, tumor immobility, lymphovascular invasion, perineural involvement, and pathologic T and N stages. Significant univariate predictors of lower OS were age, circumferential extent of tumor, shorter distance from anal verge, tumor size, tumor immobility, anal canal involvement, lymphovascular invasion, perineural involvement, positive radial margin, and pathologic T and N stages. On Cox multivariate analysis, female sex and pathologic T and N stages independently predicted for LR; pathologic T and N stages independently predicted for DM; and age, circumferential extent of tumor, positive radial margin, and pathologic T and N stages independently predicted for lower OS. Pathologic T and N stages significantly predicted for all 3 end points (LR, DM and OS) on multivariate analysis. Investigations of more aggressive adjuvant chemotherapy appear warranted for pathologic stage T3/T4 or N1/2 rectal cancer.

Clinical and pathologic predictors of locoregional recurrence (LR), distant metastasis (DM) and overall survival (OS) in patients treated with chemoradiation and mesorectal excision for locally advanced rectal cancer

3597 Background: Our goal was to identify predictive factors for LR, DM and OS in patients treated with chemoradiation and surgery for rectal cancer. Methods: Between 1989 and 2001, 470 patients with rectal cancer and no evidence of distant metastasis were treated with pre-operative (89%) or post-operative (11%) chemoradiation. Clinical T stage was ≤ T2 in 7%, T3 in 78%, T4 in 8% and unknown in 6%. Clinical nodal stage was N0 in 30%, N1–2 in 53% and unknown in 16%. Median radiation dose was 45 Gy (range 19.8–58.6 Gy), 97% received concurrent infusional 5-FU, and 65% received adjuvant chemotherapy. Median follow-up was 5.7 years (range 0.3–14.3 years). Results: The 5-year LR-free survival, DM-free survival and OS were 90%, 79% and 80% respectively. On univariate analysis, significant predictors of LR were gender, clinical T and N stage, and pathologic T and N stage. Significant univariate predictors of DM were circumferential extent of tumor, tumor mobility, lymphovascular invasion, perineural involvement, and pathologic T and N stage. Significant univariate predictors of OS were age, circumferential extent of tumor, distance from anal verge, tumor size, tumor mobility, anal canal involvement, lymphovascular invasion, perineural involvement, and pathologic T and N stage. On Cox multivariate analysis, pathologic T stage (HR 1.7, p=0.004) and pathologic N stage (HR 1.9, p=0.002) independently predicted for LR, and pathologic T stage independently predicted for DM (HR 2.1, p=0.001) and OS (HR 2.0, p=0.001). Conclusions: Pathologic T and N stage were the only independent predictors of LR, and pathologic T stage was the only independent predictor of DM and OS. Investigations of more aggressive adjuvant chemotherapy appear warranted in patients with pathologic stage T3/ T4 or N1/2. No significant financial relationships to disclose.

A randomized study of a coaxial fiber versus a naked fiber for endoscopic Nd:YAG laser therapy of esophageal and rectal tumors

The aim of the study was to determine whether the number of Nd:YAG laser sessions necessary to produce the maximal endoscopic effect was different with the noncontact method using the coaxial fiber than with the contact method using the naked fiber inserted into the tumor. Over a 6-month period, 40 consecutive patients were treated for esophageal and rectal cancers or for benign tumors too large to be removed with a diathermy snare. All of the patients who were offered this treatment had been assessed as unsuitable for surgery and radiotherapy. Twenty patients were randomly assigned to the coaxial fiber group and 20 patients to the naked fiber group. Before treatment, patients in the two groups were not different with respect to age, sex, kind of tumor, contraindication for surgery and radiotherapy, luminal patency, and tumor circumferential extent. At the end of the treatment, the endoscopic score, the transit score, and the evolution of rectal hemorrhage and mucous secretions were not different between the two groups. The number of treatments required to achieve the maximal endoscopic benefit was 6.7 +/- 4.9 (range, 2 to 20) (median = 5) in the coaxial fiber group and 3.4 +/- 1 (range, 2 to 5) (median = 3) in the naked fiber group (p = 0.01). Treatment tolerance and complications were not different between the two groups, but the financial cost related to the fiber was lower in the naked fiber group than in the coaxial fiber group. Therefore, we recommend the contact method using the naked fiber inserted into the tumor in endoscopic Nd:YAG laser therapy for gastrointestinal tumors.