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Background Weight changes during neoadjuvant chemotherapy (NAC) for pancreatic cancer (PDAC) are not well studied. We hypothesized that weight loss may predict poor outcomes. Methods Weight change from NAC initiation to pancreatectomy was grouped: gain (≥5%), stable, and loss (≥5%). Pathologic, postoperative, and survival outcomes were compared. Results 95 patients were included: 31.6% lost weight, 58.9% maintained weight, and 9.5% gained weight. There were no differences in chemotherapeutic regimens. Median recurrence-free survival (RFS) and overall survival (OS) were similar between patients with stable weight and those who lost weight (RFS: 9.6vs14.0months; OS: 25.8vs26.7months). Among those who gained weight, RFS (29.5months) and OS (38.4months) were greater relative to the other weight categories. On multivariable regression, weight gain was associated with improved RFS compared to loss (HR = 0.16). Conclusion Most patients maintain or lose weight during NAC, and weight loss does not predict poor outcomes. Weight gain may predict improved RFS.

Pancreatic ductal adenocarcinoma (PDAC) has the worst survival of common cancers, partly because there are no reliable early detection tests. Unintentional weight loss (≥ 5% decrease from baseline) has been linked to PDAC, but the frequency and severity of weight loss using objective measures, and its relationship to prognosis, have not been well characterized. We identified 390 patients with PDAC (all stages) and two or more prediagnosis weights in the electronic medical record. Percentage weight loss in the 365 and 180 days preceding diagnosis was calculated. Results were compared with raw weights of age- and sex-matched non-cancer controls (n = 780). Odds ratios for PDAC were calculated using conditional logistic regression. Cox proportional hazards models were used for survival. Within 1 year of diagnosis, more PDAC patients lost ≥ 5% weight relative to controls (74.9% vs. 11.2%; p

Overall survival (OS) has increased in recent adjuvant clinical trials of pancreatic ductal adenocarcinoma (PDAC). Although oncologists have taken notice, the root causes have not been fully examined. All phase 3 adjuvant PDAC clinical trials were screened (n = 13), and eight trials (2007–2019) that met a study requirement of having a gemcitabine monotherapy arm to serve as a uniform comparative anchor across trials were identified. Patient enrollment eligibility criteria were compared across trials and categorized as tumor- or patient-related factors. Disease-free survival (DFS) and OS in the gemcitabine-only and non-gemcitabine arms were plotted and compared over time using linear regression. In the non-gemcitabine arms, OS increased over time, but the slope did not achieve statistical significance (p = 0.0815). Interestingly, OS improved for patients receiving only gemcitabine (slope, 1.99 months; p = 0.0018), whereas DFS remained constant (p = 0.897). Carbohydrate antigen (CA) 19-9 values and pathologic profiles of tumors were only marginally different across all cohorts. Recent adjuvant trials had stricter inclusion criteria (i.e., more patients were excluded for medical reasons; linear regression, p = 0.010). Survival for patients with resected PDAC has roughly doubled in phase 3 adjuvant trials during the past decade. Improved outcomes likely are attributable to improved adjuvant therapeutic regimens, but also reflect healthier patients enrolled in the more recent trials.

Background While adjuvant chemotherapy benefits patients with pancreatic ductal adenocarcinoma (PDAC), the importance of the time to initiation of adjuvant therapy remains unclear. Aim This study seeks to better understand whether the timing of postoperative chemotherapy initiation affects long‐term outcomes in PDAC. Methods and Results A systematic literature search was performed in Medline, Embase, and Cochrane Library in March 2020. Studies focused on the association between the timing of adjuvant therapy on long‐term outcomes in resected PDAC patients were included. The impact of early and delayed therapy as defined by the respective studies was evaluated using forest plot analysis. Overall survival (OS) and disease‐free survival (DFS) served as primary endpoints. Out of 3099 published articles, 10 retrospective studies met inclusion criteria. Combined, these studies included clinical data of 13 344 patients. The cut off used to define “early” and “delayed” treatment groups varied in the included studies ranging from 3 to 12 weeks. Due to this heterogeneity, a sub‐group analysis of three time cut offs was performed: 3 to 5 weeks, 6 to 8 weeks, and 9 to 12 weeks. There was a significant decrease in OS and DFS when adjuvant therapy was delayed by 3 to 5 weeks after surgery (OS, pooled hazard ratio [HR] = 1.86, 95% confidence interval [CI] = 1.25‐2.78; DFS, pooled HR = 1.62, 95% CI = 1.12‐2.34). However, due to small sample size and limited studies in this subgroup analysis, the results may be indeterminate. There was no significant decrease in OS with delayed initiation of adjuvant therapy by 6 to 8 weeks and 9 to 12 weeks. Similarly, delay in adjuvant therapy beyond 3‐5 weeks. Conclusions There was no conclusive evidence suggesting improved survival in patients starting treatment at various time cut offs. Studies investigating the extreme ends of the time‐to‐treatment spectrum may prove more informative.

Background Neoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer. Methods Based on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010–2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0). Results Of 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson–Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET. Conclusions Although the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-021-10459-3.

Background: Immunotherapy (IT) has led to improved survival in several common cancers but success in pancreatic ductal adenocarcinoma (PDAC) has been limited. We analyzed if combination IT–chemotherapy (IT-CT) is associated with improved survival compared with chemotherapy alone (CT) in patients with metastatic PDAC. Methods: The National Cancer Database (2004–2016) was queried for patients who were diagnosed with metastatic PDAC. Patients were categorized by treatment group: CT only and IT-CT. Patients were excluded if they received radiation or a surgical procedure. The primary outcome was overall survival. Results: A total of 59,289 patients were identified, of whom 58,947 (99.4%) received CT and 342 (0.6%) received IT-CT. The IT-CT group was younger, had fewer comorbidities, and was more often treated at an academic center. The utilization of multiagent CT was similar between the groups. Median survival of patients treated with IT-CT was longer than CT alone (7.9 months vs. 6.3 months, p = 0.005). On multivariable analysis, receipt of IT-CT was associated with a survival advantage as compared with CT (hazard ratio = 0.86, 95% confidence intervals 0.76–0.97) when adjusting for demographics and type of CT regimen. Conclusion: In patients with metastatic PDAC, it appears that combination IT-CT may perhaps be associated with a survival advantage compared with CT alone.

Background Immune checkpoint inhibitors (ICI) and targeted therapies (TT) have improved the survival outcomes in patients with advanced melanoma. However, less is known about their impact on Asian patients with melanoma. In this study, we hypothesize that patients of Asian ancestry would have improved survival for advanced melanoma since the introduction of ICI and TT in 2011. Methods Asian patients with melanoma were identified in the National Cancer Database (NCDB) from 2004–2016. Patient, tumor, and treatment characteristics were compared for populations treated before and after 2011 using Chi-square analyses. Overall survival (OS) was analyzed using Kaplan-Meier estimates. Results 1,411 Asian patients with melanoma were identified. Overall, 21% were melanoma in situ, and 79% were invasive melanomas. 62% of patients did not have a documented histologic subtype. The most common reported histologies were superficial spreading (14%) and acral lentiginous (10%) melanomas. Primary locations included 41% lower extremity, 17% upper extremity, and 11% head and neck. The age at diagnosis has increased during the study period - 38% over 60 years old in 2004, to 54% in 2016 (P Conclusions Asian patients with melanoma are receiving diagnoses at older ages. Despite decreases in OS for all Asian patients with melanoma, advanced stage IV of the diseases have improved outcomes for the group treated in the era of ICI and TT. Further investigation is warranted to understand the treatment, patient, and tumor characteristics that predict response in this demographic of patients.

Background Neoadjuvant therapy is increasingly utilized in the management of pancreatic adenocarcinoma. The type of neoadjuvant therapy and its effect on pathologic response remains understudied. Methods A retrospective review was performed on patients who underwent neoadjuvant therapy followed by pancreatectomy. Multivariable regressions were used to determine associations between neoadjuvant therapy regimens and pathologic response. Results Seventy-five patients with pathologic responses available for review received FOLFIRINOX (61%) or gemcitabine with nab-paclitaxel (39%). Demographics, histologic differentiation, and utilization of chemoradiation were similar between the groups. Multivariable logistic regression demonstrated that chemoradiation was associated with an increased likelihood of a complete or near-complete pathologic response and a decreased rate of lymphovascular invasion and lymph node positivity. Neither chemotherapy regimen nor number of cycles administered were associated with pathologic response. Conclusions Neoadjuvant chemoradiation may be associated with complete or near-complete pathologic response regardless of chemotherapy regimen in pancreatic cancer patients.

Non-functional neuroendocrine tumors of the pancreas (NF-pNETs) are uncommon. Consensus guidelines have conflicting recommendations. We performed a nationwide analysis of patterns in management and outcomes based on facility type and tumor size.The National Cancer Database (2004-2016) was queried for patients with localized NF-pNETs (1 cm, 1-2 cm,2 cm) stratified by facility type. Management decisions, operative outcomes, and survival were compared.A total of 7170 patients were included in the analysis (1 cm = 916; 1-2 cm = 2180;2 cm = 4074). Most patients were treated at academic facilities (62.8%). Over 67% of patients with tumors1 cm underwent resection, independent of facility type (p = 0.443). There was no association between facility type and operative vs non-operative management of patients with NF-pNETs 1-2 cm in size. Patients treated at academic facilities were more likely to undergo resection for tumors2 cm compared to other facility types. Resection was associated with improved survival among patients with tumors 1-2 cm (HR = 0.43,p 0.001) and2 cm (HR = 0.32,p 0.001), but not1 cm (HR = 0.64,p = 0.054), as compared to non-operative management.There is heterogeneity in management of NF-pNETs across facility types. Treatment at academic facilities appears to be associated with higher resection rates for tumors2 cm. There appears to be an independent association between operative management and improved survival for tumors ≥1 cm in size.

e13054 Background: Conflicting data exist regarding benefit of surgery of the primary site for stage IV breast cancer, in which systemic therapy is standard of care and patient characteristics may bias treatment decisions. Metastatic triple negative breast cancer (TNBC) is an aggressive subtype with limited therapy options and poor prognosis. Our aim was to assess whether surgery for the primary tumor in stage IV TNBC provides a survival advantage over systemic therapy alone. Methods: The National Cancer Database was queried for patients with de-novo stage IV TNBC who received systemic therapy alone or systemic therapy and surgery of the primary breast site 2004-2016. Patients receiving surgery for metastatic tumor sites or with incomplete follow up data were excluded. 1:1 propensity matching was performed for demographics, comorbidities, clinical T and N stage, and metastatic sites to minimize confounding factors. Survival outcomes were analyzed using a stratified log-rank test and Cox proportional hazard regression analysis. Results: Of 2989 patients, 782 (26.21%) underwent surgery plus systemic therapy and 2207 (73.84%) were treated with systemic therapy alone. The majority of all patients were aged 51-70 with low co-morbidity, and treated in metropolitan areas. Patients treated at academic facilities (OR = 0.67, p = 0.025), with multiple metastatic sites (OR = 0.59, p < 0.001), or advanced clinical N stage (OR = 0.55, p < 0.001) were less likely to undergo surgery. Of those who completed surgery, 58% had unilateral mastectomy, and 63% had axillary lymph node dissection. Propensity matching identified 507 ‘paired’ patients with similar characteristics in the surgery and systemic therapy alone groups. After multivariable adjustment, surgery was associated with superior overall survival compared with systemic therapy alone (HR 0.73, P < 0.001). Older age (HR = 1.47, p < 0.001), greater comorbidity (HR = 1.28, p < 0.001) and multiple metastatic sites (HR = 1.53, p < 0.001) significantly decreased overall survival in the matched cohort. Median survival was shortest in the systemic therapy alone group (12.8 months, 95% CI 11.3-14.5) and longest in those undergoing systemic therapy plus simple mastectomy (18 months, 95% CI 14.3-21.2), though approximately 4 months of median survival was added for all patients undergoing any surgery vs. systemic therapy alone (p = 0.0001). Conclusions: In stage IV TNBC, surgical resection of the primary tumor site in addition to systemic therapy may provide a survival benefit in selected patients. Though in this retrospective study the sequence of treatment was unknown, surgery could be considered for low disease burden as in other malignancies with oligometastatic disease. Additional research is needed to determine if these findings persist in prospective studies and for other hormone-receptor subtypes.

408 Background: Multi-agent chemotherapy (CT) with or without radiotherapy (RT) is the standard of care for non-metastatic Type B locally advanced pancreatic cancer (LAPC). Irreversible electroporation (IRE) has been described as a treatment modality in patients with LAPC but published postoperative morbidity and mortality rates are high for a non-curative procedure. There have been few studies that have compared directly IRE with standard of care CT ± RT. We performed a meta-analysis of the available literature to compare the outcomes between these treatment groups in LAPC. Methods: A systematic literature search was performed in Medline, Embase, and the Cochrane Library in September 2020. Studies that focused on comparing outcomes between IRE and CT ± RT for LAPC were selected for further study. The impact of IRE versus CT ± RT was evaluated using forest plot analysis. Overall survival (OS) and progression free survival (PFS) served as the primary endpoints. As a secondary objective, short term morbidity and mortality data in both groups was evaluated. Results: Our search yielded 326 papers. After excluding duplicates, 3 studies met inclusion criteria. All were retrospective. Combined, these studies included clinical data on 3,862 patients. The meta-analysis indicated that patients with LAPC who underwent IRE had better OS (HR = 0.46, 95% CI: 0.28-0.74) and PFS (HR = 0.38, 95% CI: 0.24-0.60) compared to patients who received CT ± RT. Due to incomplete morbidity, 30-, and 90- day mortality information reported in the included studies, further analysis was not performed for the same. Conclusions: There is a striking paucity of studies comparing IRE with the standard of care treatment approaches for LAPC. Our meta-analysis reveals that IRE has been associated with longer OS and PFS compared to CT ± RT. However, these studies are limited by retrospective study design, heterogeneity of population and chemotherapy regimens, and incomplete morbidity data, precluding any conclusions. Until higher quality, comparative retrospective studies, or more importantly, prospective studies with standardized indications are conducted, IRE should be used with caution and remains experimental in the treatment of PDAC.

416 Background: Over the last decade, various landmark trials have demonstrated the impact of multi-agent chemotherapy in the treatment of PDAC. However, the impact in the ‘real world’ has been less clear. The ACCORD trial (2011) was a phase III trial comparing combination chemotherapy (FOLFIRINOX) and single agent (gemcitabine) for advanced disease. The MPACT trial introduced another beneficial regimen (nab-paclitaxel and gemcitabine) in 2013. Subsequently, multi-agent chemotherapy became standard of care for medically appropriate patients. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with PDAC between 1998 and 2017. The cohort was divided into two groups: 1998-2011 (pre-ACCORD) and 2012-2017 (post-ACCORD). We analyzed all patients with metastatic PDAC for overall survival and compared results in the two groups using Kaplan Meier analysis and multivariate Cox proportional hazards models. An interrupted time series analysis was also used to compare the temporal trends in 2-year survival between 1998 and 2017. Results: A total of 47,134 patients were diagnosed with PDAC between 1998 and 2017. Nearly two-third of patients (26,438; 57%) had distant disease. On univariate survival analysis, there was a significant increased overall survival probability in the 2012-17 group compared to the 1998-2011 group (p