Yu- Wen

Predictors of pathological complete response to neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma.

BackgroundsIn this study, we evaluated the factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma (ESCC).MethodsPre-nCRT parameters in ESCC patients treated between 1999 and 2006 were analyzed to identify predictors of pCR. All patients received 5-fluorouracil/cisplatin-based chemotherapy and external beam radiation followed by scheduled esophagectomy. Variables were analyzed using univariate and multivariate analyses with pCR as the dependent variable. Estimated pCR rate was calculated with a regression model.ResultsFifty-nine (20.9%) of 282 patients achieved pCR. Univariate analysis identified four patient factors (age, smoking status, drinking history and hypertension), one pre-nCRT parameter (tumor length) as significant predictors of pCR (all P <0.05). On multivariate analysis, tumor length ≤3 cm (favorable, odds ratio (OR): 4.85, P = 0.001), patient age >55 years (favorable, OR: 1.95, P = 0.035), and being a non-smoker (favorable, OR: 3.6, P = 0.003) were independent predictors of pCR. The estimated pCR rates based on a logistic regression including those three predictors were 71%, 35 to approximately 58%, 19 to approximately 38%, and 12% for patients with 3, 2, 1 and 0 predictors, respectively.ConclusionAge, smoking habit and tumor length were important pCR predictors. These factors may be used to predict outcomes for ESCC patients receiving nCRT, to develop risk-adapted treatment strategies, and to select patients who could participate in trials on new therapies.

Correlation Between Tumor Regression Grade and Clinicopathological Parameters in Patients With Squamous Cell Carcinoma of the Esophagus Who Received Neoadjuvant Chemoradiotherapy.

AbstractThe aim of this study was 2-fold: first, to assess the prognostic significance on overall survival (OS) of the 3-point tumor regression grade (TRG) in patients with esophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy (nCRT); second, to investigate the associations of TRG with the clinicopathological characteristics of the study patients.A total of 357 ESCC patients were retrospectively enrolled. The 3-point TRG was determined by assessing the percentage of viable residual tumor cells (VRTC) in the resected specimens as follows: TRG 1, 0% VRTC; TRG 2, 1% to 50% VRTC; and TRG 3, >50% VRTC.A TRG of 1, 2, and 3 was found in 32.2%, 38.9%, and 28.9% of the specimens, respectively. High TRG values were significantly associated with advanced pretreatment clinical stage, longer tumor length, and higher posttreatment tumor depth of invasion (yT), the presence of lymph node metastases (LNM), and lymphovascular invasion. We observed a stepwise decrease in 5-year OS rates with increasing TRG, as follows: 51% for patients with a TRG of 1, 28% for patients with a TRG of 2, and 22% for patients with a TRG of 3 (P < 0.001). TRG and LNM were independent predictors of OS in multivariate analysis. Notably, the prognostic impact of TRG on OS was greater in patients without LNM (P < 0.001) and ypT3 disease (P = 0.021).TRG is independently associated with OS in ESCC patients treated with nCRT. The interrelationships between TRG, LNM, and depth of tumor invasion may improve the prognostic stratification in esophageal cancer.

Factors associated with false-negative endoscopic biopsy results after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.

Abstract The usefulness of endoscopic biopsy following neoadjuvant chemoradiotherapy (nCRT) is limited because of its high false-negative (FN) rates. However, data on the factors associated with FN biopsy results remain scarce. The purpose of this study was to investigate factors associated with FN results on endoscopic biopsies in patients with esophageal squamous cell carcinoma (ESCC) following nCRT. We retrospectively reviewed the records of ESCC patients who were treated at the Chang Gung Memorial Hospital, Taoyuan, Taiwan, between 1999 and 2013. Inclusion criteria were receiving nCRT as first-line treatment before esophagectomy and having been preoperatively submitted to an endoscopic biopsy. Endoscopic findings at the lesion site were classified into 6 distinct categories: stricture, tumor, ulcer, scar, other findings, or normal. Univariate and multivariate analyses were used to identify factors associated with FN biopsy findings. A total of 227 patients were selected, of which 92 (41.9%) had positive biopsy results. Among patients with negative biopsy findings (n = 135), 85 were found to have residual cancer on the resected esophagus. Multivariate analysis identified endoscopic findings as the only independent predictor of FN biopsy results. The negative predictive values were 77.8%, 61.9%, 52.6%, 30.3%, 23.1%, and 20.0% for the normal, scar, other findings, ulcer, stricture, and tumor categories, respectively (P < 0.001). In ESCC patients, the FN rate of endoscopic biopsy after nCRT is associated with the type of residual lesion.

An analysis of factors affecting the accuracy of endoscopic biopsy after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma

PURPOSE The accuracy of endoscopic esophageal biopsy after neoadjuvant chemoradiotherapy (nCRT) remains suboptimal. We retrospectively examined the factors that may affect the diagnostic accuracy of post-nCRT endoscopic biopsy in patients with esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS A total of 213 ESCC patients were enrolled. Biopsy findings were cross-checked against the final pathology outcomes (ypT0 versus non-ypT0) to assess their accuracy. The independent predictors of diagnostic accuracy were identified by multivariate logistic regression analysis. RESULTS Post-nCRT endoscopic biopsy results were diagnostically consistent with the final pathology outcomes in 116 (54.5%) patients. Multivariate logistic regression analysis identified a long time interval between the completion of nCRT and the endoscopic examination as the only factor independently associated with a higher diagnostic accuracy. Receiver operating characteristic curve analysis showed that the optimal cutoff value for the time interval between nCRT completion and endoscopic biopsy was 45 days. The estimated diagnostic accuracies of biopsies performed before and after the optimal cutoff time were 49.1% and 72.9%, respectively. CONCLUSIONS Endoscopic biopsies performed ≥45 days after nCRT are associated with a higher diagnostic accuracy. This time cutoff may serve as a reference to inform the choice of the optimal treatment strategy following nCRT, especially among complete responders in whom surgery withholding is being considered.

Association between the thoroughness of the histopathological examination and survival in patients with esophageal squamous cell carcinoma who achieve pathological complete response after chemoradiotherapy

The College of American Pathologists guidelines recommend examining at least four representative tumor blocks for determining pathological T stage in patients with primarily resected esophageal cancer. Whether the same pathological requirements are adequate in patients undergoing esophagectomy following neoadjuvant chemoradiotherapy (nCRT) remains unclear. We hypothesized that current examination protocols may underestimate the presence of microscopical residual disease after nCRT, potentially leading to under-staging. We retrospectively reviewed the records of patients with esophageal squamous cancer (ESCC) who were diagnosed as having pathological complete response (pCR) following nCRT. The thoroughness of the pathological examination in pCR patients was examined using (i) the number of blocks examined in suspicious tumor area (≤4 vs. >4), and (ii) the block quotient (calculated as the pretreatment tumor length divided by the number of blocks examined in suspicious tumor area). A total of 91 patients were enrolled. The mean number of blocks used to confirm pCR was 4.8 (range: 2-14). The 5-year overall survival (OS) and disease-free survival (DFS) in the entire cohort were 55% and 65%, respectively. Multivariate analyses identified the block quotient as the only independent predictor of OS and DFS. Receiver operating characteristic curve analysis indicated an optimal cutoff value of 1.4 for the block quotient. Among the patients who achieved pCR, the 5-year DFS differed significantly between subjects with a low (≤1.4) or high (>1.4) block quotient (76% vs. 47%, respectively, P = 0.03). The block quotient (calculated by the pretreatment tumor length divided by the number of blocks) - which reflects the meticulousness of the histopathological examination for confirming pCR - is associated with survival in ESCC patients.

Intraoperative computed tomography-guided pulmonary tumour localization: a thoracic surgeon’s learning curve

OBJECTIVES With the increasing availability of hybrid operating rooms, single-stage tumour localization and removal under intraoperative computed tomography (CT) guidance is gaining popularity. The objective of this study was to describe the learning curve for this procedure. METHODS Over a 15-month period, a single team of thoracic surgeons without experience in intraoperative CT-guided lung tumour localization performed a total of 91 procedures in 89 patients. All these procedures were conducted in a hybrid operating room equipped with cone-beam CT and a laser navigation system. The learning curve was analysed using the cumulative sum method (target success rate 90%), whereas the moving average was used as an indicator of localization time. RESULTS The mean lung tumour size on preoperative CT images was 7.81 mm, whereas their mean distance from the pleural surface was 10.16 mm. The localization time (mean 21.19 min) was inversely associated with the surgeons experience (Pearsons r = -0.6601; P < 0.001). The moving average analysis revealed that localization time stabilized after 32 procedures. There were 6 failures; of these, 2 occurred during lesion localization (as a result of needle puncture-related pneumothorax) and 4 during surgery (caused either by wire dislodgement or dye spillage). The cumulative sum analysis revealed that proficiency was achieved after 38 procedures. The mean localization time and success rates before and after procedure 38 were 32.13 min vs 13.34 min (P < 0.001) and 86.8% vs 98.1% (P = 0.078), respectively. CONCLUSIONS The procedural time and success rates of intraoperative CT-guided lung tumour localization were optimized after 38 consecutive procedures.

Lymph node dissection along the recurrent laryngeal nerves in patients with oesophageal cancer who had undergone chemoradiotherapy: is it safe?

OBJECTIVES Upper mediastinal lymph node dissection (LND)-especially along the recurrent laryngeal nerve (RN)-is the most challenging part of oesophageal cancer surgery. We investigated whether thoracoscopic RN LND may be safely performed in patients with oesophageal cancer who had undergone chemoradiotherapy (CRT). METHODS Patients with oesophageal cancer who had undergone thoracoscopic RN LND (n = 103) were divided into 2 groups according to whether they had prior treatment with CRT or not [the CRT group (n = 65) vs the upfront surgery group (n = 38), respectively]. All patients were operated on by a single surgeon. Intergroup comparisons were made in terms of (i) the number of dissected nodes, (ii) rates of RN palsy and (iii) rates of perioperative complications. The learning curve for the RN LND procedure was investigated using the cumulative sum method. RESULTS RN LND after CRT was more technically challenging when performed in the left side. Complete skeletonization of the left RN was achieved only in 66.2% of patients in the CRT group (vs 86.8% in the upfront surgery group; P = 0.022). The rate of postoperative left side RN palsy was significantly higher in the CRT group (26.6%) than in the upfront surgery group (7.9%, P = 0.022), albeit resulting in neither higher pneumonia rates nor longer hospital stays. The cumulative sum analysis revealed a steep learning curve for left RN LND in the CRT group. Unfortunately, an acceptable proficiency (left RN palsy rate: 15%) was not achievable even after treatment in 65 cases. CONCLUSIONS Thoracoscopic RN LND is safe but poses significant challenges in CRT-treated patients.

Development of a nomogram for the prediction of pathological complete response after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma

Nomograms incorporating multiple prognostic factors are useful for individualized estimation of survival in cancer patients. However, nomograms for the prediction of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal cancer are scarce. Here, we describe the development of a nomogram for predicting pCR after nCRT in patients with esophageal squamous cell carcinoma (ESCC). We retrospectively reviewed the records of 392 ESCC patients who underwent nCRT followed by esophagectomy. Seventy percent of the participants (n = 274) were randomly assigned to a training cohort, whereas the remaining 30% were included in a validation cohort (n = 118). Data from the training cohort were subjected to multivariate logistic regression analyses for selecting variables to be included in the nomogram. The performance of the resulting nomogram was internally and externally validated by calculating the bias-corrected concordance statistic (c-statistic) and the area under the receiver operating characteristics curve (AUROC) in the training and validation cohorts, respectively. After surgery, 25.77% of the study patients achieved pCR. The following variables were included in the nomogram: (i) age, (ii) pretreatment tumor length, (iii) history of head and neck cancer, (iv) post-nCRT albumin levels, and (v) post-nCRT endoscopic findings coupled with endoscopic biopsy results. The bias-corrected c-statistic and AUROC of the internal and external validation sets were 0.77 and 0.747, respectively. Our nomogram showed a good performance for predicting pCR after nCRT in ESCC patients.