Early-stage Pancreatic Adenocarcinoma Research Articles

An Analysis on the Effect of Income Changes in the Resection of Early-Stage Pancreatic Adenocarcinoma.

The impact of socioeconomic inequalities on cancer care and outcomes has been well recognized and the underlying causes are likely multifactorial. Income is regarded as a cornerstone of socioeconomic status and has been assumed to correlate with access to care. We therefore sought to investigate whether income and changes in income would affect the rate of patients undergoing surgical resection for early-stage pancreatic cancer. Inflation-adjusted income data were obtained from the United States Census Bureau from 2010 to 2019. The cancer data were obtained from the SEER database. Counties present in both data sets were included in the analysis. Patients with stage I or II pancreatic cancer who underwent formal resection were deemed to have undergone appropriate surgical management. Patients were grouped into an early (2010-2014) and late (2015-2019) time period. The final analysis included 23968 patients from 173 counties across 11 states. The resection rate was 45.1% for the entire study and rose from 42.8% to 47.4% from the early to late time periods (P < .001). The median change in income between the two time periods was an increase by $2387. The rate of resection was not dependent on income class or income change in our study population. Our surgical care of pancreatic cancer is improving with more patients undergoing resection. In addition, there are now fewer disparities between patients of lower-income and higher-income groups with respect to receiving surgical intervention. This implies that our access to care has improved over the past decade. This is an encouraging finding with regards to reducing health care disparities.

ASO Visual Abstract: The Impact of Medicaid Expansion on Early Stage Pancreatic Adenocarcinoma at High- versus Low-Volume Facilities.

ASO Visual Abstract: The Impact of Medicaid Expansion on Early Stage Pancreatic Adenocarcinoma at High- versus Low-Volume Facilities.

The Impact of Medicaid Expansion on Early-Stage Pancreatic Adenocarcinoma at High- Versus Low-Volume Facilities.

While Medicaid Expansion (ME) has improved healthcare access, disparities in outcomes after volume-dependent surgical care persist. We sought to characterize the impact of ME on postoperative outcomes among patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC) at high-volume (HVF) versus low-volume (LVF) facilities. Patients who underwent resection for PDAC were identified from the National Cancer Database (NCDB; 2011-2018). HVF was defined as ≥20 resections/year. Patients were divided into pre-and post-ME cohorts, and the primary outcome was textbook oncologic outcomes (TOO). Difference-in-difference (DID) analysis was used to assess changes in TOO achievement among patients living in ME versus non-ME states. Among 33,764 patients who underwent resection of PDAC, 19.1% (n=6461) were treated at HVF. Rates of TOO achievement were higher at HVF (HVF: 45.7% vs. LVF: 32.8%; p<0.001). On multivariable analysis, undergoing surgery at HVF was associated with higher odds of achieving TOO (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.49-1.72) and improved overall survival (OS) [hazard ratio (HR) 0.96, 95% CI 0.92-0.99]. Compared with patients living in non-ME states, individuals living in ME states were more likely to achieve TOO on adjusted DID analysis (5.4%, p=0.041). Although rates of TOO achievement did not improve after ME at HVF (3.7%, p=0.574), ME contributed to markedly higher rates of TOO among patients treated at LVF (6.7%, p=0.022). Although outcomes for PDAC remain volume-dependent, ME has contributed to significant improvement in TOO achievement among patients treated at LVF. These data highlight the impact of ME on reducing disparities in surgical outcomes relative to site of care.

Association between the Environmental Quality Index and Textbook Outcomes Among Medicare Beneficiaries Undergoing Surgery for Early-Stage Pancreatic Adenocarcinoma

BackgroundAccess to high-quality cancer care is affected by environmental exposures and structural inequities. This study sought to investigate the association between the environmental quality index (EQI) and achievement of textbook outcomes (TO) among Medicare beneficiaries over the age of 65 who underwent surgical resection for early-stage pancreatic adenocarcinoma (PDAC). MethodsPatients diagnosed with early-stage PDAC from 2004 to 2015 were identified using the SEER-Medicare database and combined with the US Environmental Protection Agency’s EQI data. High EQI category indicated poor environmental quality, whereas low EQI indicated better environmental conditions. ResultsA total of 5,310 patients were included, of which 45.0% (n = 2,387) patients achieved TO. Median age was 73 years and more than half were female (n = 2,807, 52.9%), married (n = 3,280, 61.8%), and resided in the Western region of the US (n = 2,712, 51.1%). On multivariable analysis, patients residing in moderate and high EQI counties were less likely to achieve a TO (referent: low EQI; moderate EQI: OR 0.66, 95% CI 0.46–0.95; high EQI: OR 0.65, 95% CI 0.45–0.94; p < 0.05). Increasing age (OR 0.98, 95%CI 0.97–0.99), racial minorities (OR 0.73, 95% CI 0.63–0.85), having a Charlson co-morbidity index > 2 (OR 0.54, 95%CI 0.47–0.61) and stage II disease (OR 0.82, 95%CI 0.71–0.96) were also associated with not achieving a TO (all p < 0.001). ConclusionOlder Medicare patients residing in moderate or high EQI counties were less likely to achieve an “optimal” TO after surgery. These results demonstrate that environmental factors may drive post-operative outcomes among patients with PDAC.

Circulating tumor DNA (ctDNA) and disease recurrence in early stage pancreatic cancer.

e16313 Background: Surgical resection with neoadjuvant and/or adjuvant chemotherapy remains to be the cornerstone in treatment for early-stage pancreatic adenocarcinoma. Disease recurrence after curative intent treatment remains to be very common, and early detection of disease recurrence remains challenging. Recent studies explored the role of ctDNA in guiding adjuvant treatment in colon cancer, but its role in pancreatic cancer remains unknown. Methods: Through comprehensive chart review, we identified patients who: 1. Diagnosed with early-stage pancreatic adenocarcinoma; 2. Underwent curative intent surgery at our institution from 2019 to 2021; 3. Have postoperative tissue informed ctDNA results with commercially available assay (Signatera, by Natera Inc). Results: A total of 14 patients, including 7 males and 7 females, were included in the study. Depending on location of tumor, types of surgery included Whipple procedure (N = 13) and distal pancreatectomy (N = 1). The median age at time of surgery was 62 years (Range: 41-83 years). Two patients received neoadjuvant chemotherapy, and 13 patients received adjuvant chemotherapy. Two patients also received adjuvant radiation. A total of 41 ctDNA readings were obtained. The median time from surgery to first ctDNA assay was 2.4 months. First post-op ctDNA was positive in 6 patients, all of whom received adjuvant chemotherapy but still experienced clinical recurrence after a median of 3.7 months. The median overall survival of those ctDNA+ patients was 11.4 months. In the remaining 8 patients, the median progression free survival was 14 months, with clinical recurrence being observed in 4 patients. Median overall survival was not reached at median follow up of 30.5 months (one patient died at 6 months without disease recurrence, and another died at 14 months with progressive disease). In the 4 patients who had clinical recurrence despite initially negative ctDNA, ctDNA turned positive 1 month before clinical recurrence in 1 patient. However, in the other 3 patients, recurrence occurred 3.1, 1.9 and 3.5 months after the most recent negative ctDNA result. Conclusions: Our study demonstrated that positive ctDNA reliably predicts clinical recurrence in early-stage pancreatic cancer after surgery, with a positive predictive value of 100%. Negative result appears to be less reliable. This may be explained by different shedding pattern and test sensitivity. Larger scale study is underway to further evaluate its role in determining prognosis and guiding adjuvant treatment.

Health Disparities in Presentation, Treatment, Genomic Testing, and Outcomes of Pancreatic Cancer in Hispanic and Non-Hispanic Patients

BackgroundThere are few conflicting results regarding the treatment and outcomes of Hispanic patients with pancreatic cancer. This study comprehensively evaluated the differences in baseline characteristics, treatments, genomic testing, and outcomes among Hispanic (H) and Non-Hispanic (NH) patients with early-stage (ES) and late-stage (LS) pancreatic cancer (PC).MethodsThis is a retrospective analysis from 2013 to 2020 of 294 patients with pancreatic ductal adenocarcinoma; data collected included patient demographics, clinical characteristics, treatment regimens, response, germline and somatic genetic testing, and survival outcomes. Excluded those with insufficient data. Univariate comparisons used parametric and nonparametric tests as appropriate to evaluate for differences between H and NH groups. Fisher’s exact tests were performed to evaluate the difference in frequency. Kaplan–Meier and Cox regression analysis assessed the survival.ResultsThe analysis included 198 patients who had a late-stage disease and 96 patients with early-stage disease at the time of diagnosis. Among the early-stage patients, the median age at diagnosis was 60.7 years in the H versus 66.7 years in the NH (p = 0.03). No other differences were observed in baseline characteristics, treatments offered, and median overall survival (NH 25 vs. H 17.7 months, p = 0.28). Performance status, negative surgical margins, and adjuvant therapy were clinically significant and univariable with improved OS (p < 0.05), regardless of ethnicity. Hispanic patients with early pancreatic cancer were noted to be at a greater risk of death with a statistically significant hazard ratio of 3.1 (p = 0.005, 95% CI, 1.39–6.90). Among the late-stage patients, Hispanic patients with ≥ 3 predisposing risk factors for pancreatic cancer were 44% vs. 25% of NH (p = 0.006). No significant differences were noted in baseline characteristic treatments, progression-free, and median overall survivals (NH 10.0 vs. 9.2 months, p = 0.4577). In the late-stage genomic testing, germline testing performed in NH 69.4% vs. H 43.9% (p = 0.003) revealed no difference among groups. For the somatic testing, the pathogenic variants with actionable mutations were 2.5% of NH and 17.6% of H patients (p = 0.03).ConclusionHispanic patients with early-stage pancreatic adenocarcinoma present at a younger age and with more risk factors in the late stage. These patients have significantly lower overall survival compared to their non-Hispanic counterparts. Hispanic patients in our study were 2.9 less likely to receive germline screening and more like to have somatic genetic actionable pathogenic variants. Overall, only a minority of all patients were enrolled in a pancreatic cancer clinical trial or offered genomic testing, highlighting a critical need and missed opportunity in advancing progress and improving outcomes for this disease, mainly in the underrepresented Hispanic population.

ASO Author Reflections: Disparities in NCCN Guideline-Compliant Care for Patients with Early-Stage Pancreatic Adenocarcinoma at Minority-Serving Versus Non-minority-Serving Hospitals.

ASO Author Reflections: Disparities in NCCN Guideline-Compliant Care for Patients with Early-Stage Pancreatic Adenocarcinoma at Minority-Serving Versus Non-minority-Serving Hospitals.

Disparities in NCCN Guideline-Compliant Care for Patients with Early-Stage Pancreatic Adenocarcinoma at Minority-Serving versus Non-Minority-Serving Hospitals.

Racial/ethnic disparities in pancreatic adenocarcinoma (PDAC) outcomes may relate to receipt of National Comprehensive Cancer Network (NCCN) guideline-compliant care. We assessed the association between treatment at minority-serving hospitals (MSH) and receipt of NCCN-compliant care. Patients who underwent resection of early-stage PDAC between 2006 and 2019 were identified from the National Cancer Database (NCDB). MSH was defined as the top decile of facilities treating minority ethnicities (Black and/or Hispanic). Factors associated with receipt of NCCN-compliant care and its impact on overall survival (OS) were assessed. Among 44,873 patients who underwent resection of PDAC, most were treated at non-MSH (n=42,571, 94.9%), while a smaller subset were treated at MSH (n=2302, 5.1%). Patients treated at MSH were more likely to be at a younger median age (MSH 66 years versus non-MSH 67 years), Black or Hispanic (MSH 58.4% versus non-MSH 12.0%), and not insured (MSH 7.8% versus non-MSH 1.6%). While 71.7% (n=31,182) of patients were compliant with NCCN care, guideline-compliant care was lower at MSH (MSH 62.5% versus non-MSH 72.2%). On multivariable analysis, receiving care at MSH was associated with not receiving guideline-compliant care [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.74]. At non-MSH, non-white patients had lower odds of receiving guideline-compliant PDCA care (OR 0.85, 95% CI 0.78-0.91). Failure to comply was associated with worse overall survival (OS) [hazard ratio (HR) 1.50, 95% CI 1.46-1.54, all p<0.001]. Patients with PDAC treated at MSH and minorities treated at non-MSH were less likely to receive NCCN-compliant care. Failure to comply with guideline-based PDAC treatment was associated with worse OS.

An analysis on the effect of income change in the resection of early stage pancreatic adenocarcinoma

An analysis on the effect of income change in the resection of early stage pancreatic adenocarcinoma

Outcomes of Early-Stage Pancreatic Adenocarcinoma Based on Clinical Factors and Genomic Mutations

Outcomes of Early-Stage Pancreatic Adenocarcinoma Based on Clinical Factors and Genomic Mutations

Evolving management of early stage pancreatic adenocarcinoma in older patients

BackgroundDue to the aging population, the number of older patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) will continue to rise. Study designUtilizing the NCDB from 2010 to 2016, patients with early stage, clinically node negative PDAC who were ≥70 years old and had a Whipple were identified. Multivariable logistic regressions were used to determine independent factors for R0 resection and NAT. Cox-proportional-hazards regression analyses examined for the impact of NAT on the risk of death. ResultsOf 5086 patients, 51.7% received upfront surgery + adjuvant therapy (UFS + AT), followed by 29.9% UFS only, and the remainder NAT. NAT significantly improved OS compared to a combined cohort of those that had UFS ± AT. NAT retained its independent survival benefit when compared to only patients that had UFS + AT. ConclusionFor older patients diagnosed with early stage PDAC, NAT was associated with improved R0 resection rates and a significant survival benefit when compared to the current standard of care.

Is Biannual Surveillance for Pancreatic Cancer Sufficient in Individuals With Genetic Syndromes or Familial Pancreatic Cancer?

Individuals with a family history of pancreatic adenocarcinoma (PC) or with a germline mutation in a PC susceptibility gene are at increased risk of developing PC. These high-risk individuals (HRIs) may benefit from PC surveillance. A PC surveillance program was developed to evaluate the detection of premalignant lesions and early-stage PCs using biannual imaging and to determine whether locally advanced or metastatic PCs develop despite biannual surveillance. From January 2013 to April 2020, asymptomatic HRIs were enrolled and followed with alternating MRI and endoscopic ultrasound every 6 months. Of 75 HRIs, 43 (57.3%) had a germline mutation in a PC susceptibility gene and 32 (42.7%) had a familial pancreatic cancer (FPC) pedigree. Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) were identified in 26 individuals (34.7%), but only 2 developed progressive lesions. One patient with Peutz-Jeghers syndrome (PJS) developed locally advanced PC arising from a BD-IPMN. Whole-genome sequencing of this patient's PC and of a second patient with PJS-associated PC from the same kindred revealed biallelic inactivation of STK11 in a KRAS-independent manner. A review of 3,853 patients from 2 PC registries identified an additional patient with PJS-associated PC. All 3 patients with PJS developed advanced PC consistent with the malignant transformation of an underlying BD-IPMN in &lt;6 months. The other surveillance patient with a progressive lesion had FPC and underwent resection of a mixed-type IPMN that harbored polyclonal KRAS mutations. PC surveillance identifies a high prevalence of BD-IPMNs in HRIs. Patients with PJS with BD-IPMNs may be at risk for accelerated malignant transformation.

The Role of Circulating MicroRNAs in Patients with Early-Stage Pancreatic Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is still associated with a high rate of mortality. Only a minority of patients are diagnosed in the early stage. Radical surgery is the only potential curative procedure. However, radicality is reached in 20% of patients operated on. Despite the multidisciplinary approach in resectable tumors, early tumor recurrences are common. Options on how to select optimal candidates for resection remain limited. Nevertheless, accumulating evidence shows an important role of circulating non-coding plasma and serum microRNAs (miRNAs), which physiologically regulate the function of a target protein. miRNAs also play a crucial role in carcinogenesis. In PDAC patients, the expression levels of certain miRNAs vary and may modulate the function of oncogenes or tumor suppressor genes. As they can be detected in a patient’s blood, they have the potential to become promising non-invasive diagnostic and prognostic biomarkers. Moreover, they may also serve as markers of chemoresistance. Thus, miRNAs could be useful for early and accurate diagnosis, prognostic stratification, and individual treatment planning. In this review, we summarize the latest findings on miRNAs in PDAC patients, focusing on their potential use in the early stage of the disease.

P-108 Circulating tumor DNA for early relapse detection and monitoring disease status in patients with early-stage pancreatic adenocarcinoma

Pancreatic adenocarcinoma (PDAC) is one of the most aggressive cancer histologies, as evidenced by high recurrence rate (85%) and poor 5-year overall survival of 9%. Numerous circulating biomarkers have been evaluated for the detection of molecular monitoring and residual disease (MRD) detection in PDAC, however, the application of these techniques has been limited in early-stage PDAC due to poor sensitivity and specificity. Recently, an ultrasensitive, personalized, and tumor-informed ctDNA assay (Signatera TM) has been shown to overcome many of the challenges that have limited the clinical utility of the aforementioned biomarkers, for the first time allowing for reliable MRD detection in PDAC and other histologies.

Impact of Race/Ethnicity and County-Level Vulnerability on Receipt of Surgery Among Older Medicare Beneficiaries With the Diagnosis of Early Pancreatic Cancer.

Patients can experience barriers and disparities to access high-quality cancer care. This study sought to characterize receipt of surgery and chemotherapy among Medicare beneficiaries with a diagnosis of early-stage pancreatic adenocarcinoma cancer (PDAC) relative to race/ethnicity and social vulnerability. The Surveillance, Epidemiology, and End Results(SEER)-Medicare database was used to identify patients with a diagnosis of early-stage (stage 1 or 2) PDAC between 2004 and 2016. Data were merged with the CDC's Social Vulnerability Index (SVI) at the beneficiary's county of residence. Multivariable, mixed-effects logistic regression was used to assess the association of SVI with resection. Among 15,931 older Medicare beneficiaries with early-stage PDAC (median age, 77 years; interquartile range [IQR], 71-82 years), the majority was White (n = 12,737, 80.0 %), whereas a smaller subset was Black or Latino (n = 3194, 20.0 %) A minority of patients was more likely to live in highly vulnerable communities (low SVI: white [90.5 %] vs minority [9.5 %] vs high SVI: white [71.9 %] vs minority [28.1 %]; p < 0.001). Use of resection for early-stage PDAC was lowest among the patients who resided in high-SVI areas (low [38.0 %] vs average [34.3 %] vs high [31.9 %]; p < 0.001). The minority patients were less likely to undergo resection than the White patients (no resection: white [64.1 %] vs minority [70.7 %]; p < 0.001). The median SVI was higher among the patients who underwent resection (57.6; IQR, 36.0-81.0) than among those who did not (60.4; IQR, 41.9-84.3), and increased SVI resulted in a decline in the likelihood of resection (SVI trend: OR, 0.98; 95 % confidence interval [CI], 0.97-1.00), especially among the minority patients. Minority patients from high-SVI counties had markedly lower odds of preoperative chemotherapy than minority patients from a low-SVI neighborhood (OR, 0.62; 95 % CI, 0.52-0.73). Older Medicare beneficiaries with early-stage PDAC residing in counties with higher social vulnerability had lower odds of undergoing pancreatic resection, which was more pronounced among minority versus older White Medicare beneficiaries.

Multi-agent neoadjuvant chemotherapy improves survival in early-stage pancreatic cancer: A National Cancer Database analysis

PurposeTo compare overall survival (OS) in patients who underwent surgery for early-stage pancreatic adenocarcinoma (rPca) based on sequence (NAT, neoadjuvant therapy and/or AT, adjuvant therapy) and type (SA, single-agent or MA, multi-agent) of chemotherapy received. MethodsUsing the National Cancer Database, patients with clinical stage I/II rPca diagnosed between 2010 and 2014 were identified and five comparison matches (1: NAT vs. upfront resection (UR); 2: multi-agent neoadjuvant (MA NAT) vs. single-agent adjuvant therapy (SA AT), single-agent neoadjuvant therapy (SA NAT), multi-agent adjuvant therapy (MA AT); 3: MA NAT vs. MA AT; 4: NAT + AT vs NAT; 5: NAT + AT vs AT) were constructed using minimum distance matching strategy. Median OS (mOS) was analysed using Kaplan-Meier method, log-rank test and Cox proportional hazard model. ResultsA total of 18,470 patients with stage I/II rPca were eligible for analysis. NAT showed a 5 month (mo.) improved OS compared with UR (3271 patients/group, 28.1 vs 23.2 mo. P < 0.0001 hazard ratio [HR]: 0.79). MA-NAT was shown to be superior to other chemotherapy approaches SA AT, SA NAT, and MA AT (1349 patients/group: 30 vs. 25.9 mo., P = 0.0001 [HR: 0.82]). MA NAT showed a survival advantage over MA-AT (1349 patients/group, 30 vs 26.1 mo., P = 0.0008 [HR: 0.86]). The combination of NAT and AT showed a better outcome when compared with NAT alone (1128 patients/group, 31.6 vs 27.4 mo., P = 0.0011 [HR: 0.81]) or AT alone (1128 patients/group, 31.6 vs. 25.2 mo., P < 0.0001 [HR: 0.76]). ConclusionsIn patients with stage I/II rPca, MA NAT showed improved mOS compared to UR and all other chemotherapy sequences except both NAT plus AT. These findings support the use of MA NAT in stage I/II rPca patients and warrant prospective trials evaluating MA NAT and post-resection maintenance therapies.

Facility volume-survival relationship in patients with early-stage pancreatic adenocarcinoma treated with neoadjuvant chemotherapy followed by pancreatoduodenectomy

BackgroundThere is evidence that neoadjuvant therapy is associated with improved survival compared with upfront pancreatectomy for pancreatic adenocarcinoma. Treatment at high-volume pancreatic surgery centers is associated with improved short-term postoperative outcomes compared with low-volume centers. We compared overall survival of patients with early-stage pancreatic adenocarcinoma who received neoadjuvant therapy before resection stratified by facility volume. MethodsPatients with clinical T0 to T2 pancreatic adenocarcinoma who received neoadjuvant therapy before pancreatoduodenectomy were identified in the National Cancer Database (2010–2016). High-volume pancreatic surgery centers performed ≥36 pancreatectomies/year. Patients were matched 1:1 by propensity score. Pathologic outcomes, postoperative outcomes, and overall survival were compared. ResultsBefore matching, 1,449 patients were treated at low-volume centers and 250 at high-volume pancreatic surgery centers. After matching, there were 177 patients per group. High-volume pancreatic surgery centers were more commonly academic/research facilities (99.4% vs 54.0%; P < .001), and patients traveled greater distances (65 vs 13 miles; P < .001). Time from diagnosis to neoadjuvant therapy and surgery was similar. Treatment at high-volume pancreatic surgery centers was associated with shorter duration of stay (7 vs 8 days; P = .003) and lower 90-day mortality rate after pancreatoduodenectomy (0.0% vs 5.0%; P = .01). Patients treated at high-volume pancreatic surgery centers had improved overall survival (36.3 vs 29.4 months; P = .03; hazard ratio 0.73). On subset analysis of academic/research facilities, high-volume pancreatic surgery centers remained associated with shorter duration of stay, lower 90-day mortality, and greater overall survival. ConclusionThe majority of patients treated with neoadjuvant therapy for early-stage pancreatic adenocarcinoma received care at low-volume centers. Treatment at high-volume pancreatic surgery centers was associated with improved overall survival and short-term postoperative outcomes.

Neoadjuvant chemotherapy improves outcomes in resectable pancreatic adenocarcinoma: an updated national cancer database analysis

Presenter: Wade Christopher MD | Providence Saint John's Cancer Institute Background: Systemic chemotherapy has been shown to have a survival benefit for all stages of pancreatic adenocarcinoma. Historically adjuvant chemotherapy (AC) was given for all patients. However, recently there has been a shift towards neoadjuvant chemotherapy (NAC) for both resectable and borderline resectable pancreatic adenocarcinoma. This shift has been driven by the observation that many post-operative patients are unable to undergo treatment with AC secondary to surgical complications. The objective of this study was to compare survival and oncologic outcomes of NAC versus AC for early stage resectable pancreatic cancer. Methods: Patients age 18 years and older with stage I or II pancreatic adenocarcinoma in the 2010-2017 National Cancer Database were identified. Patients were grouped as receiving NAC + surgery compared to those patients who underwent upfront surgery +/- AC. Logistic regression evaluated the oncologic outcomes of positive resection margins and positive lymph nodes after NAC. Kaplan-Meier method followed by Cox proportional-hazards regression with inverse probability weighting (IPTW) using propensity score matching was used to compare overall survival (OS). Results: In 19,415 patients with early stage pancreatic adenocarcinoma who underwent surgery, upfront NAC led to a 13% risk reduction of a positive resection margin when compared to surgery +/- AC (odds ratio [OR]:0.87; 95%CI 0.78-0.97), and a 59% decreased risk of positive lymph nodes at the time of surgery (OR:0.41; 95%CI 0.38-0.45), after controlling for patient clinical and pathological risk factors. The median overall survival for all patients treated with NAC was 2.56 years versus 1.95 years for surgery +/- AC (3 and 5 year OS for NAC patients was 43.14% and 26.44%; 3 and 5 year OS for surgery +/- AC patients was 34.94% and 22.42%) (Log-rank p-value < 0.001). The subgroup of stage I patents had a median OS of 2.69 years with NAC versus 2.20 years for surgery +/- AC (Log-rank p-value < 0.001). The subgroup of stage II patients had a median OS of 2.49 years with NAC versus 1.75 years for surgery +/- AC (Log-rank p-value < 0.001). In the Cox proportional-hazards regression analyses with IPTW using propensity score matching, NAC also had a significant OS benefit for all patients (hazards ratio [HR]:0.80; 95%CI 0.78–0.83), as well as for Stage I (HR:0.89; 95%CI 0.84–0.94) and Stage II patients (HR:0.71; 95%CI 0.68–0.75) individually. The survival benefit of NAC remained when only patients that had both surgery and chemotherapy (HR:0.90; 95%CI 0.86–0.93) were evaluated. However, in this cohort, when stratified by clinical stage, NAC was only associated with an improved OS for stage II patients (HR:0.80; 95%CI 0.76–0.84) with no significant OS benefit from NAC for Stage I patients. Conclusion: NAC appears to confer a survival benefit for patients with early stage pancreatic adenocarcinoma. NAC also decreased the risk of a positive resection margin as well as positive lymph nodes at the time of surgical resection. In stage I patients that were able to receive both surgery and chemotherapy, the timing of chemotherapy did not impact survival.

Early Relapse Detection and Monitoring Disease Status in Patients with Early-stage Pancreatic Adenocarcinoma using Circulating Tumor DNA

Pancreatic ductal adenocarcinoma (PDAC) has one of the most aggressive cancer histologies, with high recurrence (85%) and a 5-year survival rate of 9%. The circulating tumor DNA (ctDNA) is evolving field in setting of management for patients with advanced solid tumors. In this study, our aim was to investigate the potential contributions of ctDNA in early-stage pancreatic adenocarcinoma prognostication as early relapse detection and disease status monitoring and to evaluate the relationship with tumor markers carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9).

The treatment sequence may matter in patients undergoing pancreatoduodenectomy for early stage pancreatic cancer in the era of modern chemotherapy

BackgroundThe aim of this study was to investigate outcomes associated with neoadjuvant chemotherapy in patients undergoing pancreatoduodenectomy for early stage pancreatic adenocarcinoma in the era of modern chemotherapy. MethodsThe National Cancer Database (2010–2016) was queried for patients with clinical stage 0–2 pancreatic adenocarcinoma who underwent pancreatoduodenectomy. Patients who underwent up-front pancreatoduodenectomy were propensity matched to patients who received neoadjuvant chemotherapy. Postoperative outcomes, pathologic outcomes, and overall survival were compared. ResultsA total of 2036 patients were in each group. Neoadjuvant chemotherapy was associated with shorter length of stay, lower 30-day readmission rate, and lower 30 and 90-day mortality rates (all p < 0.05). Neoadjuvant chemotherapy was associated with lower rates of positives nodes and positive resection margins (all p < 0.0001). Neoadjuvant chemotherapy was associated with longer survival (26.8 vs. 22.1months, p < 0.0001). Patients who received neoadjuvant chemotherapy followed by surgery and adjuvant therapy had the longest OS, followed by neoadjuvant + surgery, surgery + adjuvant therapy, and surgery alone (29.8 vs. 25.6 vs. 23.9 vs. 13.1 months; p < 0.0001). ConclusionsNeoadjuvant chemotherapy is associated with improved postoperative outcomes, oncologic outcomes, and overall survival in patients with early stage pancreatic adenocarcinoma. Neoadjuvant chemotherapy should be considered in all patients with early stage pancreatic adenocarcinoma.