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.

The Role of MRI Pancreatic Protocol in Assessing Response to Neoadjuvant Therapy for Patients With Borderline Resectable Pancreatic Cancer

BackgroundBorderline Resectable Pancreatic Cancer (BRPC) remains a unique entity that is difficult to categorize due to variance in definitions and the small number of patients. The ultimate goal is to achieve a free resection (R0) after a favorable response to neoadjuvant therapy that is somewhat difficult to assess by current radiological parameters.AimTo evaluate the role of Magnetic Resonance Imaging (MRI) pancreatic protocol, including Diffusion-Weighted Imaging (DWI), in patients with BRPC receiving neoadjuvant therapy, and further compare it to RECIST criteria and outcome.MethodsHistologically confirmed BRPC patients were prospectively included. DWI-MRI was performed pre- and post-therapy. Clinical characteristics with ensuing operability were recorded and correlated to radiological RECIST/apparent diffusion coefficient (ADC) change, preoperative therapy administrated, surgical resection status, and survival.ResultsOut of 30 BRPC cases, only 11 (36.7%) ultimately underwent pancreaticoduodenectomy. Attaining a stationary or stable disease via ADC/RECIST was achieved in the majority of cases (60%/53.3% respectively). Of the 12 patients (40%) who achieved a regression by ADC, 11 underwent surgery with an R0 status. These surgical cases showed variable RECIST responses (PR=5, SD=4, PD=3). Responders by ADC to neoadjuvant therapy were significantly associated to presenting with abdominal pain (p =0.07), a decline in post-therapy CA19-9 (p<0.001), going through surgery (p<0.001), and even achieving better survival (p<0.001 vs. 0.66).ConclusionDWI-MRI ADC picked up patients most likely to undergo a successful operative procedure better than traditional RECIST criteria. An algorithm incorporating novel radiological advances with CA19-9 deserves further assessment in future studies.

Evaluation of Log Odds of Positive Lymph Nodes in Predicting the Survival of Neoadjuvant Therapy Patients with Non-Small Cell Lung Cancer After Surgery: A SEER Cohort-Based Study

Background log odds of positive lymph nodes (LODDS) is a novel lymph node (LN) descriptor, demonstrating promising prognostic value in many tumors. However, there was limited information on LODDS in non-small cell lung cancer (NSCLC) patients, especially those receiving neoadjuvant therapy followed by lung surgery. Methods A total of 2,059 NSCLC patients who received neoadjuvant therapy and surgery were identified in the Surveillance, Epidemiology, and End Results (SEER) database. We used the X-tile software to calculate the cut-off value of LODDS. Kaplan-Meier survival analysis and receiver operating characteristics (ROC) curve were used to compare the predictive value of the American Joint Committee on Cancer (AJCC) N staging descriptor and LODDS. Univariate and multivariate Cox regression and inverse probability of treatment weighting (IPTW) analyses were conducted to construct the model predicting the prognosis. Results LODDS showed better differentiating ability in survival analysis than N staging descriptor (Log-rank test, P<0.0001 vs. P=0.031). The ROC curve demonstrated that the AUC of LODDS was significantly higher than the N staging descriptor in 1-year, 3-year, and 5-year survival analyses (All P<0.05). Univariate and multivariate Cox regression analysis showed that the LODDS was an independent risk factor for NSCLC patients receiving neoadjuvant therapy followed by surgery, both before and after IPTW (all P<0.001). A clinicopathological model with LODDS, age, gender, T, and radiotherapy could better predict the prognosis. Conclusions Compared with the AJCC N staging descriptor, LODDS exhibits better predictive ability for NSCLC patients receiving neoadjuvant therapy followed by surgery. A multivariate clinicopathological model with LODDS included demonstrates sound performance in predicting the prognosis.

Application of Circulating Tumor Cells and Circulating Free DNA from Peripheral Blood in the Prognosis of Advanced Gastric Cancer

Objective. To explore the application value of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood in the prognosis of advanced gastric cancer (AGC). Here, we measured CTCs and cfDNA quantity for predicting the outcome of patients. Patients and Methods. Forty-five patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and surgical treatment were enrolled in this study. All patients received neoadjuvant chemotherapy with paclitaxel + S-1 + oxaliplatin (PSOX) regimen, and CTCs and cfDNA of the peripheral blood were detected before and after neoadjuvant therapy. Relationships between the number/type of CTC or cfDNA and the efficacy of neoadjuvant chemotherapy were analyzed. Results. Among 45 patients, 43 (95.6%) were positive, and the positive rate of mesenchymal CTC was increased with the increase in the T stage. The proportion of mesenchymal CTC was positively correlated with the N stage ( P < 0.05 ), and the larger N stage will have the higher proportion of mesenchymal CTC. Patients with a small number of mesenchymal CTC before neoadjuvant chemotherapy were more likely to achieve partial response (PR) with neoadjuvant therapy. Patients with positive CA-199 were more likely to achieve PR with neoadjuvant therapy ( P < 0.05 ). Patients in the PR group were more likely to have decreased/unchanged cfDNA concentration after neoadjuvant therapy ( P = 0.119 ). After neoadjuvant therapy (before surgery), the cfDNA concentration was higher and the efficacy of neoadjuvant therapy (SD or PD) was lower ( P = 0.045 ). Conclusions. Peripheral blood CTC, especially interstitial CTC and cfDNA, has a certain value in predicting the efficacy and prognosis of neoadjuvant chemotherapy in advanced gastric cancer.