Interpretation of Tumor Response Grade following Preoperative Therapy for Gastric Cancer: An Overview.

Gastric cancer is among the top five causes of cancer-related death worldwide. Preoperative chemotherapy has been established as an option in patients with locally advanced gastric cancer. However, chemotherapy yields variable results, owing to the cellular and molecular heterogeneity of this disease. Identifying patients who did or did not respond to preoperative therapy can allow clinicians to alter treatment modalities and provide important information related to prognostication. A pathologic response to preoperative therapies, called the Tumor Response Grade (TRG), has been evaluated to quantify treatment response. Multiple systems for TRG have been established. However, the literature has demonstrated inconsistent results for TRG systems and prognosis, possibly due to variability in interpretation of tumor response between systems and interobserver variability. Radiographic responses to preoperative therapies using RECIST 1.1 criteria and endoscopically assessed tumor response have demonstrated association with survival; however, their use in gastric cancer remains challenging given the inability to accurately and consistently identify and measure the tumor, especially in the setting of neoadjuvant therapy, where treatment-related changes can obscure the gastric wall layers. While the response to preoperative therapies with positron emission tomography (PET) has shown promising results in esophageal and esophagogastric junction (EGJ) malignancies, its role in gastric cancer is still under investigation. This review is focused on summarizing the available literature related to evaluating TRG in gastric cancer, as well as providing a brief overview of the use of radiographic and endoscopic methods to assess response to preoperative therapies. Lastly, we outline future directions regarding the use of a universal TRG system to guide care and assist with prognosis.

Comparative Analyses of the Clinicopathologic Features of Short-Term and Long-Term Survivors of Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreatoduodenectomy.

Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15-60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated tumor histology (p = 0.006), more positive lymph nodes (p = 0.04), higher ypN stage (p = 0.002), and higher positive lymph node ratio (p = 0.03). The long-term survivor group had smaller tumor size (p = 0.001), lower ypT stage (p = 0.001), fewer positive lymph nodes (p < 0.001), lower ypN stage (p < 0.001), lower positive lymph node ratio (p < 0.001), lower rate of lymphovascular invasion (p = 0.001) and perineural invasion (p < 0.001), better tumor response grading (p < 0.001), and less frequent recurrence/metastasis (p < 0.001). The ypN stage is an independent predictor of both short-term and long-term survivors by multivariate logistic regression analyses. In addition, tumor differentiation was also an independent predictor for short-term survivors, and tumor response grading and perineural invasion were independent predictors for long-term survivors. Our results may help to plan and select post-operative adjuvant therapy for patients with PDAC who received NAT and pancreatoduodenectomy based on the pathologic data.

Prognosticators for Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Therapy and Pancreatectomy.

Neoadjuvant FOLFIRINOX and gemcitabine/nab-paclitaxel (GemNP) therapies are increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). However, limited data are available on their clinicopathologic prognosticators. We examined the clinicopathologic factors and survival of 213 PDAC patients who received FOLFIRINOX with 71 patients who received GemNP. The FOLFIRINOX group was younger (p < 0.01) and had a higher rate of radiation (p = 0.049), higher rate of borderline resectable and locally advanced disease (p < 0.001), higher rate of Group 1 response (p = 0.045) and lower ypN stage (p = 0.03) than the GemNP group. Within FOLFIRINOX group, radiation was associated with decreased lymph node metastasis (p = 0.01) and lower ypN stage (p = 0.01). The tumor response group, ypT, ypN, LVI and PNI, correlated significantly with both DFS and OS (p < 0.05). Patients with the ypT0/T1a/T1b tumor had better DFS (p = 0.04) and OS (p = 0.03) than those with ypT1c tumor. In multivariate analysis, the tumor response group and ypN were independently prognostic factors for DFS and OS (p < 0.05). Our study demonstrated that the FOLFIRINOX group was younger and had a better pathologic response than the GemNP group and that the tumor response group, ypN, ypT, LVI and PNI, are significant prognostic factors for survival in these patients. Our results also suggest that the tumor size of 1.0 cm is a better cut off for ypT2. Our study highlights the importance of systemic pathologic examination and the reporting of post-treatment pancreatectomies.

Critical issues in pathologic evaluation of pancreatic ductal adenocarcinoma resected after neoadjuvant treatment: a narrative review.

BACKGROUND AND OBJECTIVE: Preoperative neoadjuvant therapy (NAT) is increasingly used in the treatment of patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Because NAT often induces heterogeneous tumor response and extensive fibrosis both in tumor and adjacent pancreatic tissue, pathologic assessment of posttherapy pancreatectomy specimens is challenging. A limited number of studies examined the optimal grossing and sampling methods, tumor response grading (TRG), and the prognostic value of posttherapy tumor (ypT) and lymph node (ypN) stages of treated PDAC patients. In this review, we will provide an overview of the current status and critical issues in pathologic evaluation of PDAC resected after NAT. METHODS: In PubMed, Google Scholar and Web of Science, we reviewed existing English literature (published up to December 2021) highlighting the most recent ones using electronic databases and authors' experience to outline the challenging aspects and new perspectives on pathologic assessment of the treated PDAC. KEY CONTENT AND FINDINGS: The recent recommendations from the Pancreatobiliary Pathology Society (PBPS) provide the much-needed guidelines for systematic and standardized pathologic evaluation and reporting of treated PDAC for optimal patient care. For treated PDAC, tumor size measured by gross and radiology is not reliable. Histologic validation of tumor size on consecutive mapping sections is recommended for accurate ypT stage. A tumor size of 1.0 cm seems to be a better cutoff for ypT2 for treated PDACs. The published data suggested that the MD Anderson Cancer Center (MDA) TRG system is easy to use, has a better interobserver agreement and better correlation with patient prognosis compared to the College of American Pathologists (CAP) and Evans grading systems and may be used as an alternative TRG system for the CAP cancer protocol. CONCLUSIONS: Systemic and standardized grossing and sampling are essential for accurate pathologic evaluation and reporting for optimal care of PDAC patients who received NAT. Future studies on optimal sampling and integration of histopathology with artificial intelligence (AI), molecular and immunohistochemical markers are needed for better and personalized care of treated PDAC patients.

Clinicopathological correlation of radiologic measurement of post-therapy tumor size and tumor volume for pancreatic ductal adenocarcinoma.

OBJECTIVES: Tumor size measurement is critical for accurate tumor staging in patients with pancreatic ductal adenocarcinoma (PDAC). However, accurate tumor size measurement is challenging in patients who received neoadjuvant therapy before resection, due to treatment-induced fibrosis and tumor invasion beyond the grossly identified tumor area. In this study, we evaluated the correlation between the tumor size and tumor volume measured on post-therapy computed tomography (CT) scans and the pathological measurement. Also, we investigated the correlation between these measurements and clinicopathological parameters and survival. MATERIALS AND METHODS: Retrospectively, we evaluated 343 patients with PDAC who received neoadjuvant therapy, followed by pancreaticoduodenectomy and had pre-operative pancreatic protocol CT imaging. We measured the longest tumor diameter (RadL) and the radiological tumor volume (RadV) on the post-therapy CT scan, then we categorized RadL into four radiologic tumor stages (RTS) based on the current AJCC staging (8th edition) protocol and RadV based on the median. Pearson correlation or Spearman's coefficient (δ), T-test and ANOVA was used to test the correlation between the radiological and pathological measurement. Chi-square analysis was used to test the correlation with the tumor pathological response, lymph-node metastasis and margin status and Kaplan-Meier and Cox-proportional hazard for survival analysis. P-value < 0.05 was considered significant. RESULTS: As a continuous variable, RadL showed a positive linear correlation with the post-therapy pathologic tumor size in the overall patient population (Pearson correlation coefficient: 0.72, P < 0.001) and RadV (δ: 0.63, p < 0.0001). However, there was no correlation between RadL and pathologic tumor size in patients with ypT0 and those with pathologic tumor size of ≤1.0 cm. Post-therapy RTS and RadV group correlated with ypT stage, tumor response grades using either CAP or MDA grading system, distance of superior mesenteric artery margin and tumor recurrence/metastasis. CONCLUSION: Although RadL tends to understage ypT in PDAC patients who had no radiologically detectable tumor or small tumors (RTS0 or RTS1), radiologic measurement of post-therapy tumor size may be used as a marker for the pathologic tumor staging and tumor response to neoadjuvant therapy.