Upfront Surgery In Patients Research Articles

Estimating Recurrence after Upfront Surgery in Patients with Resectable Pancreatic Ductal Adenocarcinoma by Using Pancreatic CT: Development and Validation of a Risk Score

Background No preoperative model is available for predicting postsurgical prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC). Purpose To develop and validate a preoperative risk scoring system using clinical and CT variables to predict recurrence-free survival (RFS) after upfront surgery in patients with resectable PDAC. Materials and Methods In this retrospective study, consecutive patients with resectable PDAC underwent upfront surgery from January 2014 to December 2015 (development set) and from January 2016 to January 2017 (test set). In the development set, multivariable Cox proportional hazard modeling with bootstrapping was used to select clinical and CT variables associated with RFS and to construct a risk scoring system. The discrimination capability of the risk score was assessed by using the Harrell C-index and compared with that of pathologic American Joint Committee on Cancer tumor stage. The risk score was validated in the test set. Results A total of 395 patients were evaluated, including 262 patients (mean age ± standard deviation, 64 years ± 10; 155 men) in the development set and 133 (mean age, 64 years ± 9; 79 men) in the test set. Five independent variables predicted risk of recurrence or death: tumor size (hazard ratio [HR], 1.23; 95% confidence interval [CI]: 1.05, 1.44; P = .009), hypodense tumor in the portal venous phase (HR, 1.66; 95% CI: 1.01, 2.73; P = .04), tumor necrosis (HR, 2.04; 95% CI: 1.38, 3.03; P < .001), peripancreatic tumor infiltration (HR, 1.50; 95% CI: 1.07, 2.11; P = .02), and suspicious metastatic lymph nodes (HR, 1.94; 95% CI: 1.38, 2.72; P < .001). In the test set, the risk score showed good discrimination capability (C-index of 0.68; 95% CI: 0.63, 0.74) and outperformed the pathologic tumor stage (C-index of 0.60; 95% CI: 0.55, 0.66; P = .03). Patients were categorized into favorable, intermediate, and poor prognosis groups with 1-year RFS of 0.87, 0.58, and 0.26, respectively. Conclusion The presented preoperative risk score can predict recurrence-free survival after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Pandharipande and Anderson in this issue.

Long-term outcomes of upfront surgery in patients with resectable pathological N2 non-small-cell lung cancer.

Although the standard treatment for pathological N2 (pN2) non-small-cell lung cancer (NSCLC) patients is definitive chemoradiation, surgery can be beneficial for resectable pN2 disease. Herein, we report the long-term clinical outcomes of upfront surgery followed by adjuvant treatment for selected patients with resectable pN2 disease. We performed a retrospective analysis of clinical outcomes for patients with pN2 disease who underwent surgery as the first-line therapy. Multivariable Cox regression analysis was used to identify the significant factors for overall survival (OS) and recurrence-free survival. From 2004 to 2015, a total of 706 patients with pN2 NSCLC underwent complete anatomical resection at our institution. The patients' clinical N stages were cN0, 308 (43.6%); cN1, 123 (17.4%) and cN2, 275 (39.0%). Adjuvant chemotherapy, radiotherapy and chemoradiotherapy were administered to 169 (23.9%), 115 (17.4%) and 299 patients (42.4%), respectively. With a median follow-up of 40 months, the respective median time and 5-year rate of OS were 52 months and 44.7%. According to subdivided pN2 descriptors, the median OS time was 80, 53 and 37 months for patients with pN2a1, pN2a2 and pN2b, respectively. Adjuvant chemotherapy was a significant prognostic factor for both OS [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.28-0.52; P < 0.001] and recurrence-free survival (HR 0.42, 95% CI 0.30-0.58; P < 0.001). Upfront surgery followed by adjuvant therapy for resectable N2 disease showed favourable outcomes compared to those reported in previous studies. Adjuvant chemotherapy is essential to improve the prognosis for patients undergoing upfront surgery for N2 disease.

First-line chemotherapy versus chemoradiation for resectable distal esophageal adenocarcinoma.

331 Background: Multiple randomized controlled trials have shown that both neoadjuvant chemotherapy (CT) and chemoradiation (CRT) convey survival benefit as compared to upfront surgery in patients with esophageal adenocarcinoma. However, international practice remains variable. Therefore, the present study compares the outcomes of first-line CT to CRT for patients with adenocarcinoma arising from the distal esophagus. Methods: Patients with clinical stage T2-T3, N0-N+ esophageal adenocarcinoma originating from the distal esophagus who received first-line CT or CRT were identified from the National Cancer Data Base (2006-2014). Propensity-score were created for the odds of receiving CRT. Patients were matched 1:1 based on propensity score. Subset analysis was performed in patients who underwent esophagectomy. Pathological complete response was defined as ypT0N0M0. Results: In total, 709 and 8,877 patients who received first-line CT and CRT were identified, respectively. CT was associated with stage cT2 (27.2% vs. 23.3%; p = 0.017), and treatment at a high-volume center (27.2% vs. 20.2%; p &lt; 0.001). After matching, resection rates were comparable for patients who received first-line CT and CRT (62.2% vs. 63.7%; p = 0.545). However, median overall survival was slightly lower for patients who receive CT compared to CRT (23.7 vs. 28.4 months; p = 0.044). Among patients who underwent esophagectomy, time to surgery (135 vs. 134 days; p = 0.689) and median overall survival (37.0 vs. 40.5 months; p = 0.630) was similar between matched cohorts. However, complete response (15.8% vs. 25.8%; p &lt; 0.001) and negative margin (94.3% vs. 88.9%; p = 0.004) rates were significantly lower after CT compared to CRT. Conclusions: In patients with esophageal adenocarcinoma, first-line CRT results in significantly higher pathological complete response rates, negative resection margins rates, and improved survival. These findings suggest that first-line CRT is preferable over CT when tolerated in patients with esophageal adenocarcinoma.

Short-term Outcomes After Upfront Chemotherapy Followed by Curative Surgery in Metastatic Colon Cancer: A Comparison With Upfront Surgery Patients

PurposeUpfront systemic chemotherapy with target agents has been recommended for patients with stage IV colon cancer. Some with partial response are considered for curative resection. There is high risk of developing postoperative complications following upfront systemic chemotherapy. We aimed to evaluate short-term perioperative outcomes of curative surgery after upfront chemotherapy in comparison with upfront surgery in patients with metastatic colon cancer.MethodsBetween January 2010 and October 2015, 146 patients (80 in the surgery first group, 66 in the upfront chemotherapy group) who underwent surgical resection before or after systemic chemotherapy for metastatic colon cancer were included in the present study. All decisions for treatment were made through a multidisciplinary team. Postoperative clinical outcomes and complications were analyzed to compare the groups.ResultsThere was no difference between the 2 groups in terms of postoperative clinical outcomes. Overall complication rates were not different between the groups (surgery first group: 46.3% vs. upfront chemotherapy group: 60.6%; P = 0.084). When classified according to the Clavien-Dindo method, there was no difference between the 2 groups in terms of major complications (grade 3 or more) (surgery first group: 18.9% vs. upfront chemotherapy group: 27.5%; P = 0.374).ConclusionThere was no significant increase in major postoperative complications in metastatic colon cancer patients who received upfront chemotherapy followed by curative surgery. Careful patient selection and treatment planning are important.

P2.04-19 Neoadjuvant Chemotherapy Is Associated with Immunogenic Cell Death and Increased T Cell Infiltration in Early-Stage NSCLC

Recent success using immune checkpoint blockade (ICB) in the metastatic setting has raised the need to understand the immune microenvironment (IME) in early-stage disease. Moreover, pre-clinical evidence suggests that cytotoxic agents can modulate this IME. A recent study conducted by our group showed that non-small cell lung cancer (NSCLC) patients who received neoadjuvant chemotherapy followed by surgery (NCT), as compared to patients who received upfront surgery (US), had higher densities of CD3+ lymphocytes and CD68+ tumor-associated macrophages (TAMs). CD3+CD4+ lymphocytes and TAMs also correlated with better clinical outcomes. In this study, we explored the relationships between NCT and the IME by harvesting tumor samples of multiple surgical NSCLC cohorts. The PROSPECT microarray database was queried in NCT (n=45) and US (n=200) patients to investigate differentially expressed genes related to immunogenic cell death (ICD), susceptibility to CD8+ T cell and NK cell cytotoxicity, priming of antigen presenting cells, immunosuppressive enzymes and intra-tumoral cytokines. Available data from the ImmunogenomiC prOfiling of NSCLC (ICON) and other surgical NSCLC cohorts was evaluated to determine: 1) differential immune profiling using FACS (NCT=17; US=39) and multiplex IHC imaging (NCT=10; US=72); 2) plasma circulating cytokines (NCT=18; US=73); 3) tumor mutational burden (TMB) (NCT=40; US=61). Participants who received NCT or US were excluded according to these criteria: 1) concurrent treatment in addition to NCT; 2) sarcomatoid and small cell histologies; 3) clinical or pathological TNM Stage 4 disease; 4) synchronous malignancies other than lung. PROSPECT NCT patients expressed increased damage-associated molecular pattern (DAMP) genes (HSPA2, HSPA4, HSPE1, and S100A2; p<0.05) and T cell-related chemotaxis and antigen presentation genes (CXCR7, CD1A; p<0.05). Concordantly, the ICON cohort FACS results showed that NCT patients display increases in: 1) infiltration of CD8+ T cells (p=0.004); 2) proliferating Ki67+CD8+ T cells (p=0.02); 3) tissue resident memory CD8+CD103+ (p=0.02) and CD4+CD103+ non-Treg cells (p=0.01). Trends from the ICON multiplex IHC also highlighted increases in CD8+ T cells (p=0.09), CD20+ cells (p=0.08), as well as PD-L1+ malignant cells (p=0.08) and PD-L1+ TAMs (p=0.08) in NCT patients, the latter finding being supported by increased circulating MCP-1 (p=0.03). TMB was similar between NCT and US groups (p=0.912). Our data provides the first evidence of ICD (i.e., increased DAMP gene expression) following NCT in human early-stage NSCLC. Furthermore, our data highlights the association of NCT with a favorable IME (i.e., increased T cell infiltration), supporting the rationale of NCT and ICB combinations in localized NSCLC.

Survival benefit of neoadjuvant therapy in patients with non-metastatic pancreatic ductal adenocarcinoma: A propensity matching and intention-to-treat analysis.

Conclusive evidence in favor of neoadjuvant therapy for those with non-metastatic pancreatic ductal adenocarcinoma (PDAC) is still lacking. The objective of this study was to evaluate the survival benefit of neoadjuvant therapy vs upfront surgery for patients with non-metastatic PDAC. The study involved 565 patients undergoing neoadjuvant therapy or upfront surgery as the primary treatment for PDAC. Propensity score matching was performed between the neoadjuvant therapy group (NAT group) and the upfront surgery group (UFS group) using 20 clinical variables at diagnosis. Overall survival and surgical pathology were compared between the two treatment groups on an intent-to-treat basis. In the matched cohort, the NAT group (n = 91) had a longer median overall survival than the UFS group (n = 91) (23.1 months vs 18.5 months, P = .043). The rate of patients undergoing surgical resection was lower in the NAT group (58% vs 80%, P = .001). Regarding surgical pathology, the NAT group had smaller tumor size (2.8 cm vs 4.0 cm, P = .001), lower incidence of positive surgical margins (8% vs 30%, P < .002), and less lymph node metastasis (45% vs 78%, P < .001). The strategy of neoadjuvant therapy before surgical resection appears to offer pathologic effect and survival benefit for the patients presenting with non-metastatic PDAC.

Network meta-analysis comparing neoadjuvant chemoradiation, neoadjuvant chemotherapy and upfront surgery in patients with resectable, borderline resectable, and locally advanced pancreatic ductal adenocarcinoma

PurposeNeoadjuvant chemoradiation or chemotherapy has improved the treatment efficacy of patients with resectable, borderline resectable, and locally advanced pancreatic ductal adenocarcinoma (PDAC). Due to the optimal regimen remains inconclusive, we aimed to compare these treatments in terms of margin negative (R0) resection rate and overall survival (OS) with Bayesian analysis.Patients and methodsWe reviewed literature titles and abstracts comparing three treatment strategies (neoadjuvant chemoradiation, neoadjuvant chemotherapy, and upfront surgery) in PubMed, Embase, Cochrane Library, the American Society of Clinical Oncology and ClinicalTrials.gov database from 2009 to 2018 to estimate relative odds ratios (ORs) for margin negative (R0) resection rate and hazard ratios (HRs) for overall survival (OS) in all include trials.ResultsA total of 14 literatures with 1056 patients were enrolled in this Bayesian analysis. In the pairwise meta-analysis from limited head-to-head studies, compared with neoadjuvant chemotherapy, neoadjuvant chemoradiation showed superior OS significantly (HR 0.8, 95% CI 0.60–0.99, p < 0.001) and there was no significant difference in R0 resection rate (OR 1.02, 95%CI 0.45–2.33, I2 = 34.6%). However, in the network meta-analysis from all enrolled clinical trials, neoadjuvant chemoradiation showed significantly higher R0 resection rate over upfront surgery (HR 0.15, 95% CrI 0.02–0.56), whereas neoadjuvant chemotherapy did not provide better efficacy in R0 resection over upfront surgery (HR 0.42, 95% CrI 0.02–4.41). For R0 resection rate, neoadjuvant chemoradiation has the highest probability of ranking one compared with neoadjuvant chemotherapy or upfront surgery (79% vs 21% vs 0%). For OS, neoadjuvant chemotherapy has the highest probability of ranking one compared with neoadjuvant chemoradiation or upfront surgery (98% vs 0% vs 2%). Neoadjuvant chemotherapy was associated with higher rates of postoperative complications (rank worst: 84%), followed by neoadjuvant chemoradiotherapy (13%) and upfront surgery (3%).ConclusionsDifferent neoadjuvant treatment was selected based on various purposes, whether increasing R0 resection rate or not. Future clinical trials comparing neoadjuvant chemoradiation with neoadjuvant chemotherapy are warranted to confirm our results.

Optimal indication criteria for neoadjuvant chemotherapy in patients with resectable colorectal liver metastases

BackgroundThere are no optimal indication criteria for neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastases (CLM). The aim of this study was to prospectively assess the survival benefit of selective NAC administration in this patient population based on tumor characteristics.MethodsBorderline resectable CLM (BR-CLM) were defined as four or more liver metastases, CLM larger than 5 cm, or CLM with concomitant resectable extrahepatic metastases. From 2010 to 2015, NAC was administered to BR-CLM patients. Upfront surgery without NAC was performed to patients having clearly resectable CLM (less than 3 lesions, smaller than 5 cm, and no extrahepatic metastases: CR-US group). Survival outcomes of the two groups were assessed.ResultsThe BR-NAC group comprised 73 patients and the CR-US group 172. All patients in the BR-NAC group underwent subsequent resection, as none showed disease progression or chemotherapy-associated liver damage. The 3- and 5-year overall survival rates of the CR-US group were 83.0% and 74.0%, while patients in the BR-NAC group had comparable 3-year and 5-year overall survivals (80.5% and 66.6%, P = 0.397).ConclusionDefining BR-CLM based on tumor characteristics optimizes patient selection for NAC. Favorable overall survival can be achieved by upfront surgery in patients with clearly resectable CLM and by NAC in patients with BR-CLM.

Neoadjuvant chemotherapy followed by surgery versus upfront surgery in patients with borderline resectable and locally advanced unresectable pancreatic adenocarcinoma.

312 Background: Although neoadjuvant chemotherapy (NACT) has been widely investigated, the magnitude of the clinical benefit and the potential risk of NACT followed by surgery compared with upfront surgery remains unclear for patients with locally advanced pancreatic cancer (LAPC). Methods: This retrospective, prospective cohort-based analysis included 135 patients who underwent NACT followed by surgery and 359 patients who received upfront surgery for LAPC between October 2005 and April 2017. Disease-free survival (DFS) and overall survival (OS) from surgery were compared between the two groups. Results: There were no significant differences in gender (male, 53% vs 56%) and age (median 60 vs 61 years) between the NACT followed by surgery group and upfront surgery group. As NACT, gemcitabine-based regimens and FOLFIRINOX were used in 69 (51%) and 66 (49%) patients, respectively. The NACT followed by surgery group showed significantly less advanced T stage (T3–4, 93% vs 99%, p = 0.001) and N stage (N+, 49% vs 71%, p &lt; 0.001) than the upfront surgery group. NACT followed by surgery was significantly associated with better OS (median, 25.4 [18.6–32.2] vs 17.1 [15.5–18.7] months, p = 0.001) and DFS (median, 9.0 [95% CI, 6.8–11.2] vs 7.1 [6.4–7.8] months, p = 0.005) than upfront surgery. These results were consistent in the multivariate analysis for OS (adjusted hazard ratio [aHR], 0.73 [95% CI, 0.56–0.96], p = 0.02) and DFS (aHR, 0.72 [95% CI, 0.56–0.93], p = 0.01). There was no difference in length of hospital stay (median 13 vs 17 days, p = 0.14) for surgery between the two groups, and the NACT followed by surgery group showed a significantly lower incidence of postoperative complication than the upfront surgery group (38% vs 27%, p = 0.03). Conclusions: The present study revealed that NACT followed by surgery may provide survival benefit compared with upfront surgery in LAPC without causing significant safety issues.

Validity of upfront surgery for patients with unsuspected lymph node metastasis in esophageal cancer: a propensity scoring matching study

Validity of upfront surgery for patients with unsuspected lymph node metastasis in esophageal cancer: a propensity scoring matching study

Diagnostic Performance of Computed Tomography in Predicting a Positive Circumferential Resection Margin for Resectable and Borderline Resectable Pancreatic Head Cancer

Introduction: To measure the diagnostic performance of computed tomography (CT) for the circumferential resection margin (CRM) status in patients with resectable and borderline resectable pancreatic head cancer. Method: We included 75 patients (37 females, mean age, 71 ± 11 years) who had a resectable and borderline resectable pancreatic head cancer and underwent upfront surgery. For the analysis, the CRM was subdivided into superior mesenteric artery (SMA), superior mesenteric vein/portal vein (SMV/PV) and posterior margins. Three abdominal radiologists retrospectively reviewed the preoperative CT images and evaluated CT resection margin status. The reference standard for the CRM status was pathologically made. A positive resection margin was defined as the presence of tumor cells within 1 mm of the CRM. The diagnostic performance of CT was measured for the overall CRM (per-patient analysis) and each of resection margin (per-margin analysis). We pooled the data across the radiologists using the generalized linear mixed model. Result: Thirty-eight patients were pathologically confirmed to have involved CRM. In per-patient analysis, the pooled sensitivity and specificity was 13.7% and 98.1%, respectively. In per-margin analysis, the pooled sensitivity and specificity for SMA margin was 12.4% and 98.1%, respectively; for posterior margin, 10.3% and 99.4%, respectively; for SMV/PV, 26.9% and 96.3%, respectively. Conclusion: Very low sensitivity and high specificity of CT in predicting a positive CRM suggests that CT has poor performance to select patients who would benefit from neoadjuvant therapy rather than upfront surgery in patients with resectable and borderline resectable pancreatic head cancer.

Upfront surgery in patients with clinical skip N2 lung cancer based on results of modern radiological examinations.

Direct lymphatic drainage from a primary tumor to the right paratracheal or aortic window lymph nodes is often noted in pN2 disease. This multi-institutional retrospective study investigated the outcomes of upfront surgery in patients with clinical skip N2 disease (N2 disease without N1 disease) and a tumor in the right upper lobe or left upper segment based on results of modern radiological examinations, including positron emission tomography (PET). We identified 143 patients with cN2 disease who underwent upfront surgery in 12 institutions under the Thoracic Surgery Study Group of Osaka University between January 2006 and December 2013. Among 143 patients, 94 who underwent PET were analyzed. We classified these patients into Group A (n=39; clinical skip N2 disease and a tumor in the right upper lobe or left upper segment) and Group B (n=55; other). The median follow-up was 56.5 months. Among the 94 patients, 50 (53.2%) had skip N2 disease and 65 (69.1%) had a tumor in the right upper lobe or left upper segment. The 5-year overall survival (OS) rates of the 94 patients with cN2 disease was 47.9%. The 5-year OS rates for the cN2pN0/1 (n=22) and cN2pN2 (n=70) groups were 74.9% and 41.2%, respectively (P=0.034). The univariate analysis of OS revealed no significant differences in age, sex, histology, carcinoembryonic antigen (CEA) level, tumor size, PET findings, and number of metastatic lymph nodes when these parameters were dichotomized. A significantly better 5-year OS rate was observed in Group A than in Group B (64.0% vs. 37.0%; P=0.039). The multivariate analysis of OS revealed that Group A was a significantly prognostic factor (P=0.030). Patients with cN2 disease in Group A had a more favorable prognosis. Upfront surgery may be a treatment option for such selected patients with non-small lung cancer in the specific group.

Validity of upfront surgery for patients with unsuspected lymph node metastasis in esophageal cancer: a propensity scoring matching study

BackgroundAlthough neoadjuvant therapy followed by esophagectomy is well-established as being superior to upfront esophagectomy when locoregional lymph node (LN) metastasis is present in esophageal cancer, upfront esophagectomy without neoadjuvant therapy may be performed in patients with LN metastasis due to unreliable preoperative evaluations. However, outcomes in this setting remain unclear. The purpose of the present study was to clarify whether upfront esophagectomy without neoadjuvant therapy in patients with unsuspected lymph node metastasis in esophageal cancer is appropriate.MethodsWe included 215 squamous cell esophageal cancer patients who met the study criteria. Inclusion criteria included complete (R0) and curative surgery cases, intra-thoracic esophageal cancer, preoperative biopsy-proven squamous cell carcinoma, and cases without LN metastasis (WL, cN0 and pN0) or with unsuspected LN metastasis (UL, cN0 and pN1). Exclusion criteria were palliation or salvage cases, other uncured previous or current primary cancers, complete remission cases, and operative mortalities (defined as patients who died during hospitalization or within one month after surgery). We compared 5-year disease- free survival (DFS) between WL and UL. In addition, we investigated the influence of neoadjuvant therapy in UL. To overcome heterogeneity in baseline characteristics between the groups, a propensity matched-analysis based on propensity scores was then carried out to create a cohort of WL with clinical characteristics similar to those in UL.ResultsThe incidence of UL among preoperative N0 patients was 25.6% and the incidence of UL cases who did not receive neoadjuvant therapy was 47.2%. All subjects were stratified into either WL (160 patients) or UL (55 patients). Twenty nine of 55 patients in UL received neoadjuvant therapy before esophagectomy and all patients with LN metastasis received adjuvant therapy after esophagectomy. There was no significant difference in DFS between WL and UL (p = 0.242). Furthermore, there were no significant differences in DFS between cases that received and did not receive neoadjuvant therapy (p = 0.769).ConclusionsUpfront surgery without neoadjuvant therapy in UL is appropriate for patients who can tolerate adjuvant therapy.

Neoadjuvant FOLFIRINOX for patients with borderline resectable or locally advanced pancreatic cancer: Results of a decision analysis.

4117 Background: With the advent of more effective therapies for metastatic pancreatic ductal adenocarcinoma (PDAC), efforts to incorporate these agents, such as FOLFIRINOX, into the neoadjuvant setting are increasing. However, the efficacy and cost-effectiveness of using neoadjuvant FOLFIRINOX for patients with borderline resectable or locally advanced PDAC are unknown. We performed a decision analysis to assess the value of neoadjuvant FOLFIRINOX versus upfront surgery and adjuvant therapy. Methods: We developed a mathematical simulation model to evaluate the efficacy and cost-effectiveness of neoadjuvant FOLFIRINOX compared to upfront surgery and adjuvant therapy. We used published and institutional data as inputs to inform model development. Model outcomes included overall and disease-free survival, net benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. We used deterministic and probabilistic sensitivity analyses to explore the uncertainty of model assumptions. Results: Model estimated median overall survival (29 vs 23 months) and disease-free survival (14 vs 13 months) were better for neoadjuvant strategy compared with upfront surgery. Neoadjuvant strategy resulted in an additional 0.68 life-years gained, or 0.57 QALYs, at a cost of $59,000/QALY gained. Sensitivity analysis found that cancer recurrence rates affected model results the most. Our findings were otherwise robust with respect to changes in other model parameters, including chemotherapy toxicity, surgical complications and cancer mortality. Probabilistic sensitivity analyses showed that neoadjuvant strategy was cost-effective 80% of the time with a willingness-to-pay threshold of $100,000/QALY. Conclusions: Our model results demonstrate that neoadjuvant strategy is preferable to upfront surgery for patients with borderline resectable or locally advanced PDAC from both an efficacy and cost-effectiveness standpoint. Additional clinical data are needed to further define the long-term effectiveness of neoadjuvant FOLFIRINOX to confirm our results.

Surgically Managed Clinical Stage IIIA–Clinical N2 Lung Cancer in The Society of Thoracic Surgeons Database

The role of surgical resection in patients with clinical stage IIIA-N2 positive (cIIIA-N2) lung cancer is controversial, partly because of the variability in short- and long-term outcomes. The objective of this study was to characterize the management of cIIIA-N2 lung cancer in The Society of Thoracic Surgeons General Thoracic Surgery Database (STS-GTSD). The STS-GTSD was queried for patients who underwent operations for cIIIA-N2 lung cancer between 2002 and 2012. A subset of patients aged older than 65 years was linked to Medicare data. Identified were 3,319 surgically managed, cIIIA-N2 patients, including 1,784 (54%) treated with upfront resection (treatment naïve upfront surgery group, and 1,535 (46%) with induction therapy. A positron emission tomography scan was documented in 93% of patients, and 51% of patients were coded in STS-GTSD as having undergone invasive mediastinal staging. Nodal overstaging (cN2→pN0/N1) was observed in 43% of upfront surgery patients. Lobectomy was performed in 69% of patients and pneumonectomy in 11%. Operative mortality was similar between patients treated with upfront surgery (1.9%) and induction therapy (2.5%, p= .2583). The unadjusted Kaplan-Meier estimate of 5-year survival of cIII-N2 patients treated with induction therapy then resection was 35%. STS surgeons achieve excellent short- and long-term results treating predominantly lobectomy-amenable cIIIA-N2 lung cancer. However, prevalent overstaging and abstention from induction therapy suggest "overcoding" of false positives on imaging or variable compliance with current guidelines for cIIIA-N2 lung cancer. Efforts are needed to improve clinical stage determination and guideline compliance in the GTSD for this cohort.

Upfront surgery, neoadjuvant, and definitive chemoradiation for clinical T2N0 esophageal adenocarcinoma: A propensity score matched analysis from the National Cancer Database analysis.

103 Background: To compare overall survival (OS) of T2N0 esophageal adenocarcinomas treated with either upfront surgery (US), neoadjuvant chemoradiation (NCR), or definitive chemoradiation (DCR) from the National Cancer Database (NCDB). Methods: The NCDB was accessed to identify patients with T2N0 esophageal adenocarcinoma treated between 2004-2013 with either US, NCR, or DCR. NCR and DCR patients were included if they were treated with a radiation dose between 45-50.4 Gy and received chemotherapy. Propensity score matching (PSM) was performed against age and tumor length. Results: After PSM, 446 patients (US 98; NCR 203; DCR 145) were included in the analysis. There was no difference in age, tumor length, and grade. Clinical staging in US patients was accurate pathologically in 32.6% of patients. Median and 5 year OS for US, NCR, and DCR patients was 42.5 months and 40%, 48.5 months and 48%, and 22.9 months and 20%, respectively (p&lt;0.001). There was no difference in OS based on response to NCR compared to US. NCR was associated with improved OS in patients with tumors &gt;3 cm compared to US (median OS 43.8 versus 36.4 months; p=0.01). There was a trend toward improved OS with NCR in high grade tumors compared to US. UVA and MVA of OS revealed that DCR was associated with worse survival. Conclusions: Clinical staging for T2N0 esophageal adenocarcinoma continues to remain highly inaccurate. There was no difference in OS between US and NCR, however, improved OS was seen in NCR patients with tumors &gt;3 cm.

The Comparative-Effectiveness of Neoadjuvant Therapy vs Upfront Surgery in Patients with Early-Stage Esophageal Cancer

Abdelsattar, Zaid MD; Reddy, Rishindra M. MD, FACS; Nasir, Basil S. MB, BCH; Lin, Jules MD, FACS; Shen, K. R. MD, FACS; Hendren, Samantha MD, MPH, FACS; Wong, Sandra L. MD, FACS Author Information

Pathologic Major Response After FOLFIRINOX is Prognostic for Patients Secondary Resected for Borderline or Locally Advanced Pancreatic Adenocarcinoma: An AGEO-FRENCH, Prospective, Multicentric Cohort.

In view of increased response rates and survivals in patients with metastatic pancreatic adenocarcinoma (PAC) with FOLFIRINOX, many centers proposed this regimen as induction chemotherapy for borderline (BR) or locally advanced (LA) PAC. The aim of this study was to assess surgical and oncological outcomes of patients who underwent resection after induction FOLFIRINOX therapy. We prospectively identified surgical consecutive BR or LA PAC patients after induction FOLFIRINOX in 20 observational French centers between November 2010 and December 2013. Two independent experts retrospectively evaluated initial CT scan for central review. Eighty patients were included, 47 had BR and 33 had LA PAC. Median number of FOLFIRINOX cycles was 6 (range 1-30) and 65 % of patients received chemoradiation. The 30-day-mortality, major complications, and symptomatic pancreatic fistula rates were 2.5, 22.5, and 4 %, respectively. R0 resection was achieved in 84 %. After a median follow-up of 38.2 months since diagnosis, disease-free survival (DFS) was 17.16 months. The overall survival rates at 12 and 24 months were 92 and 81 %, respectively. A 26 % (n = 21) pathologic major response (pMR) rate was reached. In univariate and multivariate analysis, pMR was a prognostic factor for DFS (hazard ratio 0.33; P = 0.01 and hazard ratio 0.38; P = 0.035). Resection after induction FOLFIRINOX is safe and associated with similar or better outcomes as upfront surgery in patients with PAC. A pMR was observed in 26 % of cases and was prognostic of DFS. This therapeutic design should be investigated in prospective studies.

884PD - Next Generation Sequencing of Brca1/2 in High Grade Ovarian Tumors Expands Brca Defects Beyond Germline Mutations

ABSTRACT Aim: Germline BRCA1/2 mutation screening is critical in ovarian cancer patients to identify a subset of women who might benefit from PARP inhibitors. A recent clinical study suggests that women with either germline or somatic BRCA1/2 mutations may benefit from PARP inhibitors1. Tumor mutation screening could expand the number of ovarian cancer patients that might consider PARP inhibitor treatment2. Methods: Previously untreated high grade epithelial ovarian cancer patients were prospectively enrolled between January 2011 and December 2013 in accordance with IRB protocol. Patients were offered germline and tumor BRCA1/2 mutation screening. Germline mutation screening was performed on DNA from blood via custom amplicon assay and next generation sequencing. DNA from FFPE tumor samples was sequenced using custom hybridization enrichment and next generation sequencing. Variants and large rearrangements were identified and classified according to established criteria. Results: 263 patients were enrolled and germline testing was completed. Germline mutation analysis revealed 39 deleterious mutations (15% mutation rate, 25 BRCA1 and 14 BRCA2 mutations). Somatic tumor analysis has been completed for 88 patients receiving upfront surgical treatment (out of 123 total upfront surgery patients). 14 (16%) had germline deleterious mutations and all 14 mutations were independently identified in the tumor, giving 100% concordance between the assays. An additional 8 (9%) deleterious somatic mutations were identified, representing an overall BRCA1/2 mutation rate of 25%. One somatic BRCA2 mutation was observed in a patient with a previously identified germline BRCA2 mutation. Conclusions: Data from this prospective cohort support previously reported frequencies of BRCA1/2 deleterious mutations in high grade epithelial ovarian tumors2. Next generation sequencing assays on blood and tumor DNA were 100% concordant. Tumor sequencing identified additional BRCA1/2 defects. Further molecular profiling and clinical follow-up is ongoing to evaluate outcomes in these subgroups of ovarian cancer patients with BRCA1/2 defects.

Dramatic Survival Benefit Related to R0 Resection of Pancreatic Adenocarcinoma in Patients With Tumor ≤25 mm in Size and ≤1 Involved Lymph Nodes

OBJECTIVES:To evaluate i) the relative importance of R0 resection, tumor size and peripancreatic lymph node (LN) status are significant determinants of survival benefit following upfront surgery for pancreatic adenocarcinoma (PaCa), ii) whether R0 resection confers survival benefit in all patients or a patient subset with certain favorable prognostic factors.METHODS:Retrospective analysis of patients (2001–2010) who underwent planned potentially curative surgical resection without neoadjuvant therapy for PaCa.RESULTS:Among 154 patients, median survival following R0 (n=105) and R1 resections was 26.8 and 17.7 months, respectively (P=0.010). Tumor size and LN status were significant determinants of survival following R0 resection. There were no differences in survival based on tumor size and LN in patients with R1 resection. Median survival was 17.7 months following R1 resection and was 70.9 months (P<0.001) and 22.2 months (P=0.44) in patients with tumor ≤25 mm in size and ≤1 involved LN and in the remaining patients in the cohort respectively following R0 resection.CONCLUSIONS:R0 resection is associated with dramatic survival benefit over R1 resection in a subset of patients with tumor size ≤25 mm and ≤1 involved LN. These findings underscore the importance of R0 resection and careful patient selection for upfront surgery in patients with PaCa.