Impact of Different Primary Treatment Strategies on Recurrence-Focused Treatment of Pancreatic Ductal Adenocarcinoma.

Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

Treatment of Recurrence and Post-Recurrence Survival after Different Primary Treatment Strategies for Patients with Pancreatic Cancer

Therapeutic Advances in Pancreatic Cancer

664 Background: We are in the midst of a paradigm shift in the treatment of stage 1 pancreatic ductal adenocarcinoma (PDAC) from surgery first followed by adjuvant therapy (AT) to Neoadjuvant therapy (NAT) first followed by surgery and this is reflected in the current NCCN guidelines as well. Data comparing these two modalities are limited. AIM: To compare long term survival between Surgery + AT and NAT + Surgery in a large National Cancer Database for stage 1 PDAC. Methods: We identified patients with the NCDB with surgically resected AJCC clinical stage 1, 1A, and 1B PDAC between 2004-2016. Patients were stratified into two groups to assess outcomes: AT and NAT. Patients with incomplete survival and sequence of therapy were excluded. Baseline demographic data, 90-Day Mortality, Median survival, and Hazard ratios (HR) for survival was evaluated. Results: 9017 pts with Clinical stage 1, 1A, 1B PDAC between 2004-2016 were identified. Of these 7453 pts had surgery followed by AT; and 1564 pts had NAT followed by surgery. There was a statistically significant difference in age (66.0±9.9 years for AT vs. 64.7±9.78 years for NAT, p < 0.001) but no difference in Charlson Comorbidity Scoring (p = 0.618) or sex (p = 0.073). 90-Day Mortality was 0.35% in the AT group compared to 0.83% in the NAT group (p = < 0.001). Median survival was 28.5 (95% CI 26.5-29.9) months in the NAT group compared to 25.4 (95% CI 24.7-26.1) months in the AT group. With AT as the reference group for survival, there was a HR of 0.904 (95% CI 0.845-0.968, p = 0.003) for NAT. Conclusions: In this retrospective cohort of patients, NAT was associated with increased overall survival. However, NAT was associated with an increased 90 day mortality. A randomized, controlled trial is necessary to further support the superiority of NAT in the management of stage 1 PDAC.

It is unclear whether results from recent trials of resectable pancreatic ductal adenocarcinoma (PDAC) are generalizable to older patients, who are underrepresented. We aimed to evaluate outcomes of surgery and of neoadjuvant and adjuvant therapy in older patients with resectable PDAC. We included patients aged ≥65 years with upfront resectable PDAC from a prospectively maintained pancreatic cancer registry from 2007 to 2016. Patients were stratified into ages 65-75 and 75+ years. Overall survival (OS) was assessed in treatment comparisons: (A) surgery (n = 636) versus nonsurgical (n = 178), (B) neoadjuvant therapy (n = 139) versus upfront surgery (n = 497), and (C) adjuvant therapy (n = 379) versus surgery alone (n = 118). We compared neoadjuvant (n = 139) versus adjuvant therapy (n = 379) in an exploratory analysis. Nine hundred and three patients had a median age of 73.7 (range, 65-96.6) years. Median OS was 26.6 versus 11.9 months (adjusted hazard ratio [HRadj ], 0.4; 95% confidence interval [CI], 0.31-0.52; p < .001) in Comparison A groups, 30.7 versus 25.8 months (HRadj , 0.69; 95% CI, 0.49-0.96; p = .03) in Comparison B groups, and 26.9 versus 17.4 months (HRadj , 0.62; 95% CI, 0.44-0.88; p = .008) in Comparison C groups, respectively. OS benefit in these treatment comparisons was present in age group 75+ with HRadj 0.24 (95% CI, 0.16-0.36; p < .001) in Comparison A and HRadj 0.52 (95% CI, 0.27-1; p = .049) in Comparison B, but not in Comparison C with HRadj 0.68 (95% CI, 0.43-1.08; p = .1). Statistically comparable median OS of patients who received neoadjuvant or adjuvant therapy stratified by age groups was observed. Older patients with resectable PDAC who received surgery, neoadjuvant therapy, or adjuvant therapy appeared to have improved survival outcomes compared with those who did not receive such treatment. Older patients with resectable pancreatic ductal adenocarcinoma (PDAC) in general are underrepresented in large clinical trials and less well studied in terms of the role of surgery, neoadjuvant therapy, and adjuvant therapy. This study collected data on older patients with resectable PDAC from a prospectively maintained single-institutional pancreatic cancer registry of a tertiary referral center from 2007 to 2016. It was found that, with multidisciplinary evaluation, older patients with resectable PDAC who received surgery, neoadjuvant therapy, or adjuvant therapy appeared to have improved survival outcomes compared with those who did not receive such treatment. These results are of substantial importance to practitioners who treat older patients, who are traditionally underrepresented in most clinical trials.

Chemotherapy + PD-1/PD-L1 Blockade Should Be the Preferred Option in the Neoadjuvant Therapy of NSCLC

Multidisciplinary considerations in the treatment of triple-negative breast cancer.

Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger

651 Background: A strengthening consensus exists for neoadjuvant therapy (NAT) in borderline resectable pancreatic adenocarcinoma (PA), but the utilization of NAT in resectable stage I PA remains controversial. Many cancer centers are using NAT for these patients (pts), but others continue to offer upfront surgery and adjuvant therapy (AT). We hypothesized that NAT would improve margin negative resection in clinical stage I resectable PA. Methods: We utilized the IRB approved 2016 national cancer database for pancreas to establish a cohort of stage I PA pts. We divided this subset into pts who underwent NAT vs AT. We compared demographics. Primary endpoint was surgical margins. Results: 10,453pts from 2004 to 2016 had clinical stage I resectable PA: 8483pts (81.1%) AT and 1970pts (18.9%) total or partial NAT. There was a statistical difference in age (64.9 ± 9.9years NAT and 66.2 ± 9.9years AT, p&lt;0.001), but no difference in Charlson comorbidity score (p=0.1693). NAT pts had significantly higher margin negative resection rates (84.5%) than AT pts (79.4%) (p&lt;0.0001). Final pathologic staging was available for 10,237 pts: 8369 (81.8%) AT and 1868 (18.2%) NAT. Significantly fewer pts were upstaged on final pathology to stage II or greater (73.5%) in the NAT group than the AT group (84.1%) (p&lt;0.001). Conclusions: NAT leads to significantly higher margin negative rates for resectable clinical stage I PA than surgery followed by AT. The majority of pts for both groups were upstaged suggesting that we continue to clinically understage the majority of pts. Overall, total or partial NAT for clinical stage I resectable PA provides a better chance for margin negative resection. Further study in the form of a randomized control trial is necessary. [Table: see text]

4157 Background: The use of neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC) has shown clear advantages in locally advanced and borderline resectable disease. The benefit in upfront resectable PDAC is debated. Moreover, in early clinical stages IA/IB, potential benefits including improved R0 resection rate, decreased tumor upstaging, and survival, are not clear. We hypothesize that NAC will be associated with improved outcomes and survival compared to adjuvant therapy in patients with clinical stage IA/IB PDAC. Methods: The National Cancer Database (NCDB) PUFs (2004-2017) were used to perform a retrospective review of patients with clinical stage IA or IB PDAC undergoing surgery. Treatment groups were selected based on timing of chemotherapy. Patients receiving chemotherapy or surgery alone were excluded. Results: We identified 6,613 patients with clinical stage IA or IB PDAC who underwent surgery. The neoadjuvant therapy group (NAT) included 1,533 patients who received neoadjuvant or perioperative chemotherapy, and the adjuvant therapy group (AT) contained 5080 patients who received chemotherapy after surgery. Patients in the NAT had higher rates of T1 and T2 disease and lower rates of T3 pathology compared to the AT (pT1: 18.7% vs 7.8%; pT2: 20.1 vs 18.6%; pT3: 59.3% vs 72.1%, p&lt;0.0001). Additionally, the NAT had significantly higher rates of N0 disease and less N1 pathology (pN0: 54.6% vs 37.5%; pN1: 45.4% vs 62.5%, p&lt;0.0001). The R0 resection rate was higher in the NAT (83.2% vs 62.3%, p=0.0197) and there was less lymphovascular invasion (LVI) compared to the AT (34.8% vs 48.1%, p&lt;0.0001). Using Kaplan Meier estimates, the NAT was associated with improved overall survival (OS) compared to the AT (median OS: 33.4 vs 27.5 months, p&lt;0.0001). On multivariable analysis, R0 resection (HR=0.715, CI: 0.619-0.825, p&lt;0.0001), LVI (HR=1.126, 95% CI: 1.038-1.222, p=0.0043) but not receipt of NAC (HR=0.94, 95% CI: 0.852-1.038, p=0.2229) were independent risk factors for OS. Conclusions: NAC is beneficial in patients with stage IA/IB PDAC undergoing surgical resection as it is associated with improved oncologic outcomes including increased R0 resection rate, decreased tumor upstaging, lymph node metastasis, and LVI. Furthermore, patients receiving NAC were found to have improved survival over those getting adjuvant therapy. Based on these results, we recommend all patients diagnosed with PDAC be considered for NAC prior to surgery. [Table: see text]

Resection is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). Although the outcome of technically resectable PDAC has improved with advances in surgery and adjuvant therapy, the 5-year survival rate remains low at 20% to 40%. More effective therapy is needed. Almost 15 years ago, the National Comprehensive Cancer Network guidelines proposed a resectability classification of PDAC based on preoperative imaging. Since then, treatment strategies for PDAC have been devised based on resectability. The standard of care for resectable PDAC is adjuvant chemotherapy after R0 resection, as shown by the results of pivotal clinical trials. With regard to neoadjuvant treatment, several recent clinical trials comparing neoadjuvant treatment with upfront resection have been conducted on resectable PDAC and borderline resectable PDAC, and the benefits and efficacy of neoadjuvant treatment for pancreatic cancer has become clearer. The significance of neoadjuvant treatment for resectable PDAC remains controversial, but in borderline resectable PDAC the efficacy of neoadjuvant treatment has been further recognised, although the standard of care has not yet been established. Several promising clinical trials for PDAC are ongoing. This review presents previous and ongoing trials of perioperative treatment for resectable and borderline resectable PDAC, focusing on the difference between Asian and Western countries.

Background Adjuvant therapy (AT) and neoadjuvant therapy (NAT) are standard treatments for pancreatic ductal adenocarcinoma (PDAC) depending on the status of the disease. However, whether AT improves survival after NAT and radical resection in all TNM stages remains unclear. Research design and methods We utilized the Surveillance, Epidemiology, and End Results (SEER) database (2010–2019) for PDAC patients who underwent radical surgery and applied Pearson’s chi-square test, multivariate and univariate Cox regression, Kaplan-Meier plot, Log-rank tests, and propensity score matching (PSM) for analysis. Results Given PSM after enrolling 13,868 PDAC patients, significant differences in survival were identified between AT and neoadjuvant therapy plus adjuvant therapy (NATAT) (p = 0.023) as well as between NAT and NATAT (p < 0.001). According to the AJCC 8th TNM stage, a survival advantage associated with NATAT was exclusively observed in stage III and IV disease, except for T4N0M0. Some stage IV patients receiving NATAT exhibited comparable survival to their counterparts without metastasis. Conclusions In this retrospective cohort study, we demonstrated that patients harboring tumors in late TNM stages, including N2 resectable PDAC, might have better survival from NATAT, and that certain patients with M1 disease might still benefit from comprehensive systemic therapy and radical resection.

The systemic immune-inflammation index (SII), calculated using absolute platelet, neutrophil, and lymphocyte counts, has recently emerged as a predictor of survival for patients with pancreatic ductal adenocarcinoma (PDAC) when assessed at diagnosis. Neoadjuvant therapy (NAT) is increasingly used in the treatment of PDAC. However, biomarkers of response are lacking. This study aimed to determine the prognostic significance of SII before and after NAT and its association with the pancreatic tumor biomarker carbohydrate-antigen 19-9 (CA 19-9). This study retrospectively analyzed all PDAC patients treated with NAT before pancreatic resection at a single institution between 2007 and 2017. Pre- and post-NAT lab values were collected to calculate SII. Absolute pre-NAT, post-NAT, and change in SII after NAT were evaluated for their association with clinical outcomes. The study analyzed 419 patients and found no significant correlation between pre-NAT SII and clinical outcomes. Elevated post-NAT SII was an independent, negative predictor of overall survival (OS) when assessed as a continuous variable (hazard ratio [HR], 1.0001; 95% confidence interval [CI] 1.00003-1.00014; p = 0.006). Patients with a post-NAT SII greater than 900 had a shorter median OS (31.9 vs 26.1months; p = 0.050), and a post-NAT SII greater than 900 also was an independent negative predictor of OS (HR, 1.369; 95% CI 1.019-1.838; p = 0.037). An 80% reduction in SII independently predicted a CA 19-9 response after NAT (HR, 4.22; 95% CI 1.209-14.750; p = 0.024). Post-treatment SII may be a useful prognostic marker in PDAC patients receiving NAT.

Prognostic significance of tumor budding in patients with pancreatic invasive ductal carcinoma who received neoadjuvant therapy

BackgroundSurgical and adjuvant management of mucinous cystic neoplasms (MCNs) lacks formal guidelines and data is limited to institutional studies. Factors associated with receipt of adjuvant therapy and any associated impact on survival remain to be clarified. In the absence of other data, guidelines that recommend adjuvant chemotherapy for invasive pancreatic adenocarcinoma have been extrapolated to MCN.Patients and MethodsThe National Cancer Database (2004–2019) was utilized to identify all patients that underwent pancreatic resection for invasive MCNs. Patients that received neoadjuvant therapy or did not undergo lymphadenectomy were excluded. Patient, tumor, and treatment factors associated with survival were assessed.ResultsFor 161 patients with invasive MCN, median overall survival (OS) was 133 months and 45% of patients received adjuvant therapy. Multivariable analysis demonstrated that poorly differentiated tumors [odds ratio (OR) 4.19, 95% confidence interval (CI) 1.47–11.98; p = 0.008] and positive lymph node status (OR 2.67, 95% CI 1.02–6.98; p = 0.042) were independent predictors of receiving adjuvant therapy. Lymph node positivity [hazard ratio (HR) 2.90, 95% CI 1.47–5.73; p = 0.002], positive margins (HR 5.28, 95% CI 2.28–12.27; p < 0.001), and stage III disease (HR 12.46, 95% CI 1.40–111.05; p = 0.024) were associated with worse OS. Receipt of adjuvant systemic therapy was independently associated with decreased risk of mortality in node positive patients (HR 0.23, 95% CI 0.10–0.69; p = 0.002). Survival was not associated with adjuvant therapy in patients with negative lymph nodes or margin negative status.ConclusionIn contrast to pancreatic ductal adenocarcinoma (PDAC), where adjuvant therapy improves OS for every tumor stage, surgery alone for invasive MCN is not associated with improved OS compared with surgery plus adjuvant therapy in node-negative patients. Surgery alone is likely sufficient for a subset of invasive MCN.