Progression-Free Survival as Early Efficacy Endpoint in Resectable Esophageal Cancer Treated With Neoadjuvant Therapy: A Systematic Review

To investigate literature-based evidence regarding progression-free survival (PFS) as an early efficacy endpoint in patients with resectable esophageal or gastroesophageal junction (GEJ) cancer receiving neoadjuvant therapy, this study identified large-scale randomized controlled trials (RCTs) with strict quality control. Twenty-four RCTs involving 7,514 patients were included. Trial-level correlation analysis was conducted to analyze the relationship between PFS hazard ratio (HR) and overall survival (OS) HR, Δ median PFS and Δ median OS. Correlation analysis at the neoadjuvant treatment arm level was performed between 1- to 5-year PFS and 5-year OS, median PFS and median OS. Subgroup analysis was performed in patients treated with standard neoadjuvant chemoradiotherapy (NCRT). The correlation was evaluated using the Pearson correlation coefficient r in weighted linear regression, with weight equal to patient size. In trial-level correlation, PFS were strongly associated with OS HR (r, 0.82 [95% confidence interval (CI), 0.42-0.97]) and Δ median survival (r, 0.83 [95% CI, 0.54-0.96]). In neoadjuvant treatment arms, there was a strong correlation between 1 to 5-year PFS rates and 5-year OS (r, 0.83-0.95), and median PFS and median OS (r, 0.97 [95% CI, 0.85-0.99]). NCRT subgroup analysis demonstrated acceptable consistency. In conclusion, we recommend PFS as an early efficacy endpoint in resected esophageal or GEJ cancer treated with neoadjuvant therapy.

Serum apolipoprotein B to apolipoprotein A-I ratio is an independent predictor of liver metastasis from locally advanced rectal cancer in patients receiving neoadjuvant chemoradiotherapy plus surgery

Background The ratio of serum apolipoprotein B (apoB) to apolipoprotein A-I (apoAI) had been reported as a prognostic factor in colorectal cancer. This retrospective study aimed to assess the implication of apoB-to-apoAI ratio in predicting liver metastasis from rectal cancer (RC). Methods The clinical data of 599 locally advanced RC patients treated with chemoradiotherapy followed by surgery were reviewed. Serum apoAI, apoB and apoB-to-apoAI ratio were analyzed for their correlation with the liver-metastasis-free, other-metastasis-free and overall survivals, together with the pretreatment and postsurgical pathoclinical features of the patients. Univariate and multivariate survival analyses were realized through the Kaplan-Meier approach and Cox model, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for independent predictors. Results Carbohydrate antigen 19 − 9 ≥ 26.3 U/ml, apoB-to-apoAI ratio ≥ 0.63, tumor regression grade 5 − 3, pT4 and pN + stage emerged as independent predictors of poorer liver-metastasis-free survival. The hazard ratios were 1.656 (95% CI, 1.094–2.506), 1.919 (95% CI, 1.174–3.145), 1.686 (95% CI, 1.053–2.703), 1.890 (95% CI, 1.110–3.226) and 2.012 (95% CI, 1.314–2.077), respectively. Except apoB-to-apoAI ratio, the other 4 factors were also independent predictors of poorer other-metastasis-free and overall survivals. And the independent predictors of poorer overall survival also included age ≥ 67 years old, distance to anal verge < 5 cm. Conclusions Serum apoB-to-apoAI ratio could be used as a biomarker for prediction of liver metastasis risk in locally advanced RC.

Predictive Value of the Prognostic Nutritional Index in Neoadjuvant Chemoradiotherapy for Rectal Cancer

Background/Aim: Prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) indicate nutritional status and host immunity. We used immunohistochemistry and apparent diffusion coefficient (ADC) values calculated using diffusion-weighted imaging (DWI) to investigate relationships of these factors with pathological and radiological characteristics in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT). Patients and Methods: We evaluated expression levels of VEGFA, CD8, CD33, and ADC values in tumors pre/post nCRT; and analyzed the relationships between those factors and PNI, NLR in 32 patients. Results: Pretreatment PNI negatively correlated with change in tumor stromal CD8+ T cells and positively correlated with ADC values. Pretreatment NLR and PNI change correlated with recurrence-free survival (RFS). Conclusion: Patients with higher pretreatment PNI had greater changes in ADC values and stromal CD8+ T-cell counts, and those with greater PNI reduction from nCRT had a worse prognosis. Proper nutritional management during nCRT benefits patients and may lead to better prognosis in rectal cancer.

Metabolic and Texture Features of PET/CT Scan to Predict Response in Patients with Locally Advanced Rectal Cancer Treated by Concurrent Neoadjuvant Chemoradiotherapy

Background: Neoadjuvant chemoradiotherapy (nCRT) before surgical resection is the standard treatment for patients with locally advanced rectal cancer (LARC). Radiomics can be used as noninvasive biomarker for response prediction. The purpose of our study was to evaluate the potential of PET/CT texture features to predict the responses of LARC subjects treated with nCRT.Methods: One week prior to nCRT, patients underwent Positron Emission Tomography/Computed Tomography (PET/CT) scan and then received concurrent nCRT. For each patient, intensity, shape and texture-based features were derived from PET/CT images using the IBEX software. The logistic regression classifier was used to identify the responders from non-responders. Results: In this study, 23 patients with LARC were included. The patients’ responses included 5 patients with Grade 0, 7 with Grade 1, 6 with Grade 2, and 5 with Grade 3 according to American Joint Committee on Cancer/College of American Pathologists (AJCC/CAP) pathologic grading. In quantitative texture features analysis, the dissimilarity feature had the highest performance [Area under Curve (AUC) = 0.65] and in metabolic parameters analysis the best performance was for total lesion glycolysis (TLG; AUC= 0.61)Conclusions: In conclusion, performance of quantitative texture features is better than metabolic parameters but their performance should be improved.