Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: A Pairwise and Network Meta-Analysis of Pathological Complete Response.

We performed a pairwise and network meta-analysis to compare pathological complete response (pCR) among neoadjuvant chemotherapy in patients with triple-negative breast cancer. We searched PubMed for randomized clinical trials between January 1, 2000 and December 1, 2020. Abstracts from meetings were also searched. A frequentist random-effect model was applied to compare pCR and toxicities. The P-score was used to rank treatment effects. Nineteen trials with 16 treatments and 7794 patients were included. On the basis of SoC, the addition of carboplatin (OR = 1.82, 95% CI, 1.24 to 2.68, P < .01) and the addition of checkpoint inhibitors (OR = 1.69, 95% CI, 1.23 to 2.32, P < .01) increased pCR in pairwise meta-analysis; compared with paclitaxel, nab-paclitaxel did not improve pCR rates (OR = 1.81, 95% CI, .80 to 4.12, P = .16). The anthracycline-sparing regimen led to similar pCR compared with the anthracycline-containing regimen (OR = 1.50, 95% CI, .82 to 2.76, P = .19). In network meta-analysis, the addition of carboplatin plus a PD-1 inhibitor (pembrolizumab), carboplatin plus bevacizumab, and carboplatin plus veliparib ranked as the top three treatments for achieving pCR, with corresponding P-scores of .91, .84, and .72, respectively. Among patients with homologous recombination deficiency, the addition of carboplatin (OR = 1.31, 95% CI, .69 to 2.50, P = .41) or carboplatin plus PARP inhibitors (OR = 1.19, 95% CI, .58 to 2.47, P = .63) did not increase pCR. For triple-negative breast cancer, combining carboplatin with taxane-anthracycline-containing neoadjuvant chemotherapy could be the standard of care, and the combination containing checkpoint inhibitor is promising. However, their role in long-term oncologic outcome remains to be determined.

Development and validation of a radiomics-based model to predict local progression-free survival after chemo-radiotherapy in patients with esophageal squamous cell cancer.

PURPOSE: To develop a nomogram model for predicting local progress-free survival (LPFS) in esophageal squamous cell carcinoma (ESCC) patients treated with concurrent chemo-radiotherapy (CCRT). METHODS: We collected the clinical data of ESCC patients treated with CCRT in our hospital. Eligible patients were randomly divided into training cohort and validation cohort. The least absolute shrinkage and selection operator (LASSO) with COX regression was performed to select optimal radiomic features to calculate Rad-score for predicting LPFS in the training cohort. The univariate and multivariate analyses were performed to identify the predictive clinical factors for developing a nomogram model. The C-index was used to assess the performance of the predictive model and calibration curve was used to evaluate the accuracy. RESULTS: A total of 221 ESCC patients were included in our study, with 155 patients in training cohort and 66 patients in validation cohort. Seventeen radiomic features were selected by LASSO COX regression analysis to calculate Rad-score for predicting LPFS. The patients with a Rad-score ≥ 0.1411 had high risk of local recurrence, and those with a Rad-score < 0.1411 had low risk of local recurrence. Multivariate analysis showed that N stage, CR status and Rad-score were independent predictive factors for LPFS. A nomogram model was built based on the result of multivariate analysis. The C-index of the nomogram was 0.745 (95% CI 0.7700-0.790) in training cohort and 0.723(95% CI 0.654-0.791) in validation cohort. The 3-year LPFS rate predicted by the nomogram model was highly consistent with the actual 3-year LPFS rate both in the training cohort and the validation cohort. CONCLUSION: We developed and validated a prediction model based on radiomic features and clinical factors, which can be used to predict LPFS of patients after CCRT. This model is conducive to identifying the patients with ESCC benefited more from CCRT.

Prognostic Significance of Baseline Neutrophil Count and Lactate Dehydrogenase Level in Patients With Esophageal Squamous Cell Cancer Treated With Radiotherapy.

Background: This present study aimed to explore the prognostic value of pretreatment neutrophil and lactate dehydrogenase (LDH) and to develop a prognostic risk scoring model to predict prognosis in esophageal squamous cell cancer (ESCC) patients treated with definitive radiotherapy. Methods: Retrospectively collected data of patients who received definitive radiotherapy for ESCC at Shantou Central Hospital between January 2009 and December 2015 were included for the analysis. The association between the level of LDH and neutrophil and clinicopathological characteristics were analyzed. We performed univariate and multivariate analyses to identify the prognostic predictors for patients with ESCC. Based on the results, we also developed a prognostic risk scoring model and assessed its predictive ability in the subgroups. Results: A total of 567 patients who received definitive radiotherapy for ESCC were included in the present study. The optimal cutoff values were 4.5 × 109/L, 3.25, and 220 U/L for neutrophil, neutrophil-to-lymphocyte ratio (NLR), and LDH, respectively. A high level of LDH was significantly associated with advanced N stage (p = 0.031), and neutrophil count was significantly associated with gender (p = 0.001), T stage (p < 0.001), N stage (p = 0.019), clinical stage (p < 0.001), and NLR (p < 0.001). Multivariate survival analysis identified gender (p = 0.006), T stage (p < 0.001), N stage (p = 0.008), treatment modality (p < 0.001), LDH level (p = 0.012), and neutrophil count (p = 0.038) as independent prognostic factors for overall survival. Furthermore, a new prognostic risk scoring (PRS) model based on six prognostic factors was developed, in which the patients were divided into three groups with distinct prognosis (χ2 = 67.94, p < 0.0001). Conclusions: Elevated baseline LDH level and neutrophil count predicted poor prognosis for ESCC patients treated with definitive radiotherapy. A PRS model comprised of LDH, neutrophil count, and other prognostic factors would help identify the patients who would benefit the most from definitive radiotherapy.

Impact of sex on the prognosis of patients with esophageal squamous cell cancer underwent definitive radiotherapy: a propensity score-matched analysis.

BACKGROUND: The impact of sex on prognosis of patients with esophageal squamous cell cancer (ESCC) who underwent definitive radiotherapy remained unclear. The present study aimed to determine the impact of sex on the prognosis of patients with ESCC underwent definitive radiotherapy. METHODS: Between January 2009 and December 2015, patients with ESCC underwent definitive radiotherapy in Shantou Central Hospital were included in this study. The Progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. The PFS and OS were compared between female and male patients. The Cox regression model was used to identify prognostic factors. Propensity score-matched analysis was performed to balance baseline characteristics between female and male patients. RESULTS: A total of 683 ESCC patients treated with definitive radiotherapy were included, with 497 male and 186 female patients. In the whole cohort, female patients had a significantly longer median PFS (14.0 months vs 10.6 months, P = 0.0001, HR = 0.688, 95% CI, 0.567-0.836) and OS (20.8 months vs 15.9 months, P = 0.0005, HR = 0.702, 95% CI, 0.575-0.857). In the matched cohort, female patients still had a significantly longer median PFS (13.5 months vs 11.6 months) and OS (19.6 months vs 16.1 months). Multivariate analysis showed that sex was an independent prognostic factor for PFS (HR = 0.746, 95% CI, 0.611-0.910, P = 0.004) and OS (HR = 0.755, 95% CI, 0.615-0.926, P = 0.007). CONCLUSIONS: This present study indicated that sex was an independent prognostic factor in Chinese patients with ESCC underwent definitive radiotherapy, with better survival outcome for women than men. Efforts should be made to investigate the underlying biological mechanism.

First-line checkpoint inhibitors for wild-type advanced non-small-cell cancer: a pair-wise and network meta-analysis.

AIM: To estimate efficacy of checkpoint inhibitors and rank treatment effects in non-small-cell lung cancer. MATERIALS & METHODS: Prospective randomized trials were included. p-score was used to rank treatment effects. RESULTS: A total of nine trials were identified, involving 5504 patients and three checkpoint inhibitors. Pembrolizumab plus chemotherapy had the highest p-score of 0.95 among all the treatments, and was superior to pembrolizumab alone (hazard ratio: 0.87; 95% CI: 0.79-0.95). Combination therapy had more grade 3-5 adverse events; but toxicity-related discontinuation and treatment-related death did not increase. CONCLUSION: Pembrolizumab plus chemotherapy was likely to be the most effective treatment for patients with wild-type advanced NSCLC.

Definitive chemoradiation therapy or surgery for clinical T1-3N0-1M0 thoracic esophageal squamous cell carcinoma: A propensity score matching analysis.

BACKGROUND: To compare overall survival in patients with clinical T1-3N0-1 thoracic esophageal squamous cell carcinoma treated with surgery or definitive chemoradiation therapy (CRT). METHODS: We used propensity-score matching to derive 1:1 cohorts of surgery versus definitive CRT. Statistical analysis was performed using χ2 or Fisher's exact tests. Survival functions were estimated using Kaplan-Meier survival plots, and survival distributions were compared using log-rank tests. Cox proportional hazards modeling was used to analyze the factors affecting overall survival. RESULTS: A total of 334 patients treated with surgery and 252 treated with definitive CRT were included. 129 (38.6%) of 334 patients had recurrence after surgery versus 118 (46.8%) of 252 after definitive CRT. Before matching, the median overall survival were 39.5 months (95% CI, 28.8-50.2) and 23.5 months (95% CI, 18.5-28.5) (P < 0.001) in the surgery and definitive CRT group, respectively. After matching (112 patients in each treatment group), median overall survival was 43.6 months (95% CI, 28.1-59.1) with surgery versus 19.3 months (95% CI, 14.4-24.2) with CRT (P < 0.001). CONCLUSIONS: In this retrospective analysis, surgery was associated with better overall survival compared with definitive CRT.

Preoperative Administration of Olive Oil Reduces Chylothorax After Minimally Invasive Esophagectomy.

BACKGROUND: Chylothorax after esophagectomy is uncommon but potentially fatal. We performed a retrospective study to assess the effect of olive oil administered orally before surgery on reducing chylothorax in patients who underwent minimal invasive esophagectomy. METHODS: Between May 2013 and December 2016, patients with esophageal squamous cell cancer who underwent minimal invasive esophagectomy were screened. Patients in the investigational group were preoperatively administered olive oil orally 8 hours before surgery, and patients in the control arm received no olive oil. We used a propensity score matching model to derive 1:1 cohorts. Statistical analysis was performed by using the t test or χ2 or Fisher's exact test. RESULTS: The propensity score matching model finally selected 384 of 425 patients, with 192 patients in each group. The patient characteristics were balanced. Oral olive oil was well tolerated. The thoracic duct identification rate was higher in the investigational group (100% versus 45.31%, χ2 = 141.78, p < 0.01). The investigational group was associated with a reduced incidence of ligation (7.81% versus 18.22%, χ2 = 8.03, p = 0.003). The incidence of chylothorax was significantly reduced in the investigational group compared with that of the control group (0% versus 3.12%, χ2 = 4.23, p = 0.03). CONCLUSIONS: Preoperative administration of olive oil is a simple and safe method to minimize chylothorax complicating minimal invasive esophagectomy.

Effect of consolidation chemotherapy following definitive chemoradiotherapy in patients with esophageal squamous cell cancer.

Definitive chemoradiotherapy (dCRT) is a treatment option for patients with localized esophageal squamous cell carcinoma (ESCC). We investigated consolidation chemotherapy (CCT) in patients with ESCC who attained clinical complete response after dCRT. Between January 2009 and December 2012, medical records of ESCC patients treated with dCRT were retrospectively reviewed, and those who attained CCR were identified. Progression-free survival and overall survival rates were estimated by the Kaplan-Meier method. The Cox regression model was used to determine prognostic factors. Of the 522 patients treated with dCRT, 209 patients achieved CCR, with 67 receiving consolidation chemotherapy (the CCT group) and 142 receiving dCRT alone (the control group). CCT did not prolong progression-free survival (33.0 vs 18.0 months, P = 0.07, HR = 0.70, 95% CI, 0.48-1.04); however, CCT improved the median overall survival (53.4 vs 27.0 months, P = 0.04, HR = 0.67, 95% CI, 0.44-0.99) compared with dCRT alone. CCT remained a favorable prognostic factor for overall survival in a multivariate analysis (HR = 0.59, P = 0.02); however, a propensity score analysis failed to show an additional overall survival benefit with CCT. In the present analysis, CCT did not improve progression-free survival but may have extended overall survival in ESCC patients who achieved complete clinical response after dCRT.

[Anatomy of mesoesophagus in esophagectomy with minimally invasive three-fields lymphadenectomy].

OBJECTIVE: To explore the anatomic features of mesoesophagus in combined thoracoscopic and laparoscopic esophagectomy with three-fields lymphadenectomy. METHODS: Clinical data of 67 patients undergoing thoracoscopic and laparoscopic esophagectomy with three-fields lymphadenectomy from July 2011 to September 2012 were analyzed retrospectively. All the patients underwent three-fields lymphadenectomy. Proper surgical planes were selected according to anatomy of mesoesophagus. Thoracoscopic surgical space was bounded on azygotic vein and divided into upper and low esophageal triangle. Pancreas was the key anatomical mark for laparoscopic gastric dissection, and peripancreatic space was the natural laparoscopic surgical plane. Prevertebral fascia was bottom surface of neck dissection and carotid sheath was the boundary of two sides. RESULTS: The median operative time was 251.6 min (range, 220 to 320 min). The median operative blood loss was 105.6 ml (range, 40 to 320 ml). The median number of lymph nodes dissected was 29.1 (range, 13 to 46, totally 1949). There was no perioperative death. Sixty-six patients were followed up with a mean follow-up time of 8.2 months (range, 2 to 14 months). Postoperative complications included reflux esophagitis in 10 and anastomotic stenosis in 3 cases. CONCLUSION: It is safe and more radical for minimally invasive esophagectomy that overall concept of minimally invasive anatomy of mesoesophagus is applied to identify the anatomic plane and landmark during operation.