Does revision of resection margins based on frozen section improve overall survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma? A meta-analysis

Background

Margin status is the main surgical determinant of long-term outcome in pancreatic cancer. Intraoperative frozen section (IOFS) detects microscopic positive margins at a stage when margin revision is possible. The aim of this study was to determine if IOFS driven-revision of pancreatic resection margin(s) improves overall survival (OS) in pancreatic cancer.

How well does pathologic stage predict survival for esophageal adenocarcinoma after neoadjuvant therapy?

Background

Cancer staging systems are designed to predict survival and stratify patients. The 7^th edition of the American Joint Commission on Cancer (AJCC7) staging system for esophageal cancer was modeled using survival data on patients who underwent esophagectomy without induction or adjuvant therapy. In the United States, the standard of care for patients with locally advanced tumors often includes neoadjuvant therapy. The prognostic value of the pathologic stage for these patients is unknown.

Methods

Data from the Surveillance Epidemiology and End Results (SEER) were used to identify 1,243 patients with adenocarcinoma of the esophagus who underwent surgery after neoadjuvant therapy from 1988-2009. Included in the analysis were pathologically-staged, non-metastatic patients who had radiation as part of their neoadjuvant therapy. The AJCC7 staging system and an alternate system were modeled using Kaplan-Meier survival methods. The two systems were compared using log-rank chi-squared statistics, with large chi-squared values indicating accuracy in survival prediction.

Results

The AJCC staging system was able to predict survival for patients who had neoadjuvant therapy (P<0.001, chi-squared =81.8); however, there was little distinction between stage subgroups. Patients with neoadjuvant radiotherapy had improved survival for pathologic stage II and III disease. An alternative, simpler staging system was better able to stratify patients with neoadjuvant therapy (P<0.001, chi-squared =100.5).

Conclusions

The current AJCC staging system is able to predict survival in esophageal adenocarcinoma patients undergoing neoadjuvant therapy, however, there is less distinction among stage subgroups. An alternative, simpler stage grouping may better stratify patients receiving neoadjuvant therapy.     

Does gemcitabine-based combination therapy improve the prognosis of unresectable pancreatic cancer?

AIM: To assess whether gemcitabine-based combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone.METHODS: A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy in locally advanced or metastatic pancreatic cancer. Inclusion was limited to high-quality randomized clinical trials.RESULTS: Twenty-six studies were included in the present analysis, with a total of 8808 patients recruited. The studies were divided into four subgroups based on the different kinds of cytotoxic agents, including platinum, fluoropyrimidine, camptothecin and targeted agents. Patients treated with gemcitabine monotherapy had significantly lower objective response rate [risk ratio (RR), 0.72; 95% confidence interval (CI): 0.63-0.83; P < 0.001], and lower 1-year overall survival (RR, 0.90; 95%CI: 0.82-0.99; P = 0.04). Gemcitabine monotherapy caused fewer complications, including fewer grade 3-4 toxicities: including vomiting (RR, 0.75; 95%CI: 0.62-0.89; P = 0.001), diarrhea (RR, 0.66; 95%CI: 0.49-0.89; P = 0.006), neutropenia (RR, 0.88; 95%CI: 0.72-1.06; P = 0.18), anemia (RR, 0.96; 95%CI: 0.82-1.12; P = 0.60), and thrombocytopenia (RR, 0.76; 95%CI: 0.60-0.97; P = 0.03) compared with gemcitabine combination therapies.CONCLUSION: Gemcitabine combination therapy provides a modest improvement of survival, but is associated with more toxicity compared with gemcitabine monotherapy.     

Does the surgical waiting list affect pathological and survival outcome in resectable pancreatic ductal adenocarcinoma?

Background

High-volume centers have to deal with long surgical waiting-lists leading to a potential delay in treatment. This study assessed whether a longer time from diagnosis to surgery worsened pathological and survival outcomes in resectable pancreatic ductal adenocarcinoma (PDAC).

Disease-free survival is not a surrogate endpoint for overall survival in adjuvant trials of pancreatic cancer: a systematic review of randomized trials

Background

Adjuvant chemotherapy (CT) is the standard of care for patients with resected pancreatic cancer (PC). Overall survival (OS) has traditionally represented the primary endpoint in randomized trials assessing adjuvant therapies for PC. The aim of this study was to assess if disease-free survival (DFS) was an adequate surrogate endpoint for OS in randomized trials of adjuvant therapy in PC.

Who to treat with adjuvant therapy in Dukes B/stage II colorectal cancer? The need for high quality pathology

OBJECTIVE: To identify by routine pathology which Dukes B colorectal cancer patients may benefit from chemotherapy. METHOD: Retrospective study of the five year survival of colorectal cancer patients for whom colorectal pathology minimum datasets had been collected between 1997 and 2000 in the Yorkshire region of the UK. The study population consisted of 1625 Dukes B and 480 Dukes C patients who possessed one positive node treated between 1997 and 2000. The predictive ability of the Petersen prognostic model was investigated and survival of Dukes B patients with potentially high risk pathological features was compared to that of Dukes C patients with one positive node. RESULTS: Only 23.3% of patients had all the pathological variables required for the application of Petersen's index reported. The index offered a statistically significant survival difference of 24.3% and 30.3% between high and low risk colon (p<0.01) and rectal cancer patients (p<0.01). The size of these effects was smaller than predicted by the original model. Survival of Dukes B patients with any of the high risk pathological factors or low nodal yields was lower than that of Dukes C patients who possessed one positive node. CONCLUSION: Petersen's index discriminated between high and low risk Dukes B colorectal tumours, but inadequate pathological reporting diminished its ability to identify all high risk patients. The survival of patients with any high risk feature was lower than the threshold for adjuvant therapy of one lymph node positive Dukes C colorectal cancer. Chemotherapy may benefit patients with such features. Improving the quality of pathological reporting is vital if high risk patients are to be reliably identified.     

Evaluation of the significance of adjuvant chemotherapy in patients with stage ⅠA pancreatic ductal adenocarcinoma

BackgroundAlthough adjuvant chemotherapy is considered a standard treatment for resected pancreatic ductal adenocarcinoma (PDAC), its utility in stage ⅠA patients is unclear. We aimed to investigate the recurrence rate, surgical outcome, prognostic factors, effectiveness of adjuvant chemotherapy, and determination of groups in whom adjuvant chemotherapy is effective in patients with stage ⅠA PDAC.MethodsWe retrospectively analyzed 73 patients who underwent pancreatectomy and were pathologically diagnosed with stage ⅠA PDAC between 2000 and 2018. We evaluated the relation between clinicopathological factors, recurrence rates, and outcomes such as the recurrence-free and disease-specific survival rates (RFS and DSS, respectively).ResultsThe 5-year RFS and DSS rates were 52% and 58%, respectively. In multivariate analysis, a platelet-to-lymphocyte ratio (PLR) ≥ 170, prognostic nutrition index (PNI) < 47.5, and pathological grade 2 or 3 constituted risk factors for a shorter DSS (hazard ratios: 4.7, 4.6, and 4.1, respectively). Patients with 0–1 of these risk factors (low-risk group; n = 47) had significantly higher 5-year DSS rates than those with 2–3 risk factors (high-risk group; n = 26) (80% vs. 23%; P < 0.001). Patients in the low-risk group showed similar 5-year RFS rates regardless of whether they received or not adjuvant chemotherapy (75% vs 70%, respectively; P = 0.49). Contrarily, high-risk patients who underwent adjuvant chemotherapy had higher 5-year RFS rates than those who did not receive adjuvant chemotherapy (32% vs 0%; P = 0.045).ConclusionsIn stage IA PDAC, adjuvant chemotherapy seems to be effective only in a subgroup of high-risk patients.     

The utilization and impact of adjuvant therapy following neoadjuvant therapy and resection of pancreatic adenocarcinoma: does more really matter?

BackgroundAlthough neoadjuvant therapy is increasingly administered to patients with pancreatic ductal adenocarcinoma (PDAC), the impact of additional adjuvant therapy (AT) following resection is not well defined.MethodsThe National Cancer Database (NCDB) was queried for patients who received neoadjuvant therapy followed by R0 or R1 resection for PDAC. Factors influencing survival, including the receipt of AT were evaluated.ResultsOf patients receiving neoadjuvant therapy and resection 680 (33.8%) received AT and 1331 (66.2%) did not. For R0 resected patients (n = 1800), lymphovascular invasion (HR 1.24, p = 0.034) and increasing N classification (N1: HR 1.27, p = 0.019; N2: HR 1.51, p = 0.004) were associated with increased risk of death while AT was not associated with improved overall survival (OS) (HR 0.88, p = 0.179). Following R1 resection (n = 211), AT was associated with reduced risk of death (HR 0.57, p = 0.038). Within propensity matched cohorts, median OS for patients receiving and not receiving AT was 32.1 and 30.0 months after R0 resection (p = 0.184), and 23.6 and 20.5 months after R1 resection (p = 0.005).ConclusionThis analysis demonstrated that AT did not yield OS benefit for patients who had neoadjuvant therapy and R0 resection and a statistically significant, although relatively short, improvement in OS for patients who underwent R1 resection.     

Impact of spatio-temporal recurrence pattern on overall survival for invasive intraductal papillary mucinous neoplasia – A comparison with pancreatic ductal adenocarcinoma

BackgroundResections for intraductal papillary mucinous neoplasia (IPMN) have increased dramatically during the last decade. Recurrence pattern and impact of adjuvant chemotherapy for solid pancreatic ductal adenocarcinoma (PDAC) is well known, but not for invasive IPMN (inv-IPMN).ObjectivesTo elucidate the impact of spatio-temporal recurrence pattern and adjuvant chemotherapy on overall survival for inv-IPMN compared with PDAC.MethodsWe conducted a retrospective single-center observational study of consecutive patients ≥18 years of age who underwent resection for inv-IPMN or PDAC at Karolinska University Hospital, between 2009 and 2018. Different initial recurrence sites and time frames as well as predictors for death were assessed with multivariable Cox and logistic regressions. Survival analyses were performed using the Kaplan-Meier model and log rank test.ResultsOf 396 resected patients, 92 were inv-IPMN and 304 PDAC. Both recurrence rate and death rate within three-years were lower for inv-IPMN compared to PDAC (p = 0.006 and p = 0.007 respectively). Across the whole cohort, the most common recurrence patterns were multi-site (25%), single-site liver (21%) and single-site locoregional (10%) recurrence. The most prominent predictors for death in multivariable Cox regression, especially if occurred within the first year, were multi-site (HR 17.0), single-site peritoneal (HR 13.6) and single-site liver (HR 13.1) recurrence. These predictors were less common in inv-IPMN compared to PDAC (p = 0.007). The effect of adjuvant chemotherapy was similar in the two groups.ConclusionResected inv-IPMN exhibits a less aggressive recurrence pattern than PDAC that translates into a more favorable overall survival.     

Preoperative cognitive function predicts survival in?patients with resectable pancreatic ductal adenocarcinoma

Background

The purpose of this prospective study was to evaluate whether pre-surgery health-related quality of life (HRQoL) and subjectively rated symptom scores are prognostic factors for survival in patients with resectable pancreatic ductal adenocarcinoma (PDAC).

Methods

Patients undergoing pancreatic resection for PDAC completed the Edmonton Symptom Assessment System (ESAS) and the EORTC QLQ-C30 and QLQ-PAN26 questionnaires preoperatively. Patient, tumor and treatment characteristics, recurrence and survival were registered.

Results

Sixty-six consecutive patients underwent R0/R1 resection for PDAC. Baseline ESAS and EORTC questionnaire compliance was 44/66 (67%) with no statistically significant differences between compliers (n = 44) and non-compliers (n = 22) when comparing clinicopathological parameters and survival. Univariable analyses showed that three symptoms (nausea, dry mouth, cognitive function) and two clinicopathological factors (CA 19-9 > 400 U/ml, lymph node ratio > 0.1) were significantly associated with shorter survival (p < 0.05). In multivariable analysis, cognitive function was the only independent predictor for survival: hazard ratio = 0.35 (95%CI 0.13–0.93) for high vs low cognitive function. Median survival times for patients with high and low cognitive function were 21 and 10 months, respectively (p < 0.001).

Conclusion

Presurgery cognitive function is a significant independent predictor of survival in patients with resectable PDAC. Thus, presurgery patient reported outcomes may provide as strong prognostic information as clinicopathological factors.     

Early liver metastases after “failure” of adjuvant chemotherapy for stage III colorectal cancer: is there a role for additional adjuvant therapy?

BackgroundThe utility of adjuvant chemotherapy after resection of colorectal liver metastasis (CLM) in patients with rapid recurrence after adjuvant chemotherapy for their primary tumor is unclear. The aim of this study was to evaluate the oncologic benefit of adjuvant hepatic arterial plus systemic chemotherapy (HAIC + Sys) in patients with early CLM.MethodsA retrospective analysis of patients with early CLM (≤12 months of adjuvant chemotherapy for primary tumor) who received either HAIC + Sys, adjuvant systemic chemotherapy alone (Sys), or active surveillance (Surgery alone) following resection of CLM was performed. Recurrence and survival were compared between treatment groups using Kaplan–Meier methods and Cox proportional hazards models.ResultsOf 239 patients undergoing resection of early CLM, 79 (33.1%) received HAIC + Sys, 77 (32.2%) received Sys, and 83 (34.7%) had Surgery alone. HAIC + Sys was independently associated with reduced risk of RFS events (adjusted hazard ratio [HRadj]: 0.64, 95%CI:0.44–0.94, p = 0.022) and all-cause mortality (HRadj: 0.54, 95%CI:0.36–0.81, p = 0.003) compared to Surgery alone patients. Largest tumor >5 cm (HRadj: 2.03, 95%CI: 1.41–2.93, p < 0.001) and right-sided colon tumors (HRadj: 1.93, 95%CI: 1.29–2.89, p = 0.002) were independently associated with worse OS.ConclusionAdjuvant HAIC + Sys after resection of early CLM that occur after chemotherapy for node-positive primary is associated with improved outcomes.     

Does adjuvant steroid therapy post-Kasai portoenterostomy improve the outcome of biliary atresia? A systematic review and meta-analysis

BACKGROUND:The role of adjuvant steroid therapy in the postoperative management of patients with biliary atresia (BA) is unclear.OBJECTIVE:To systematically review the literature and perform a meta-analysis to determine the efficacy of adjuvant steroid therapy post-Kasai portoenterostomy (KP) on BA outcome.METHODS:A systematic review and meta-analysis of randomized trials and/or observational studies that examined the role of steroids on BA outcomes published between January 1969 and June 2010 was conducted. Studies were identified using the Medline, PubMed, EMBASE and Cochrane databases.RESULTS:Sixteen observational studies and one randomized controlled trial (RCT) were found. Four of the 16 observational studies (160 participants) and the RCT (73 participants) met the entry criteria and were eligible to be included in the analysis. There was no statistically significant difference in the effect of steroids either on normalizing serum bilirubin levels at six months (pooled OR 1.48 [95% CI 0.67 to 3.28]) or in delaying the need for early liver transplantation (within the first year post-KP (pooled OR 0.59 [95% CI 0.21 to 1.72]).CONCLUSION:The present meta-analysis did not find a significant effect of steroid over standard therapy, either in normalizing serum bilirubin levels at six months or at delaying the need for early liver transplantation post-KP. RCT studies of sufficient size and comprehensive design using high-dose steroids are needed to determine the effectiveness of steroids on the short and intermediate post-KP outcomes for BA patients.