Use of Diagnostic Laparoscopy and Peritoneal Washings for Pancreatic Cancer.

Pancreatic adenocarcinoma is an aggressive malignancy that often presents with advanced disease. Accurate staging is essential for treatment planning and shared decision-making with patients. Staging laparoscopy is a minimally invasive procedure that can detect radiographically occult metastatic disease. Its routine use with the collection of peritoneal washings in patients with pancreatic cancer remains controversial. We, herein, review the current literature concerning staging laparoscopy and peritoneal washings in patients with pancreatic cancer.

Implementation of Hepatic Artery Infusion Pump Therapy: Real-World Single-Center Experience.

BACKGROUND AND OBJECTIVES: Hepatic artery infusion pump (HAIP) therapy is an available option at highly specialized centers to treat unresectable liver tumors (e.g., colorectal liver metastases [CRLM]). This study describes the safety and outcomes of HAIP program implementation at an academic-based cancer center. METHODS: Patients who underwent HAIP placement (2021-2023) were included. Categorical and continuous variables were compared using Chi-square and Kruska-Wallis tests, respectively. Survival and variables associated with survival were calculated using the Kaplan-Meier method and Cox proportional hazards model, respectively. RESULTS: Of the 26 HAIP procedures for unresectable CRLM, four were done as adjuvant therapy. Median duration of HAIP therapy was 9.2 months and four patients subsequently underwent hepatectomy. Complication rate was 37.5%, with biliary complication rate of 23.1%. Median overall survival (OS) from date of diagnosis was 55.2 months. Concurrent primary tumor resection was associated with inferior OS (p = 0.030). Multivariable regression did not identify independent predictors of OS. Progression-free survival from time of HAIP placement was 7.8 months. CONCLUSIONS: HAIP placement was technically successful in most patients with an acceptable complication rate. Survival outcomes were comparable with those described in the literature for HAIP therapy in combination with systemic therapy. The significant difference in outcomes for those with concurrent colectomy warrants further investigation.

Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts Treatment Response and Outcomes.

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059-0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (n = 36). We established an association of MUC5AC expression with treatment response and outcomes.

Trends in the Use of Observation for Small Nonfunctional Pancreatic Neuroendocrine Tumors.

This study assesses nationwide trends in the use of observation for pancreatic neuroendocrine tumors 2 cm or smaller and to evaluate factors associated with resection.

Association of county-level provider density with hepatobiliary cancer incidence and mortality.

BACKGROUND: Access to healthcare providers is a key factor in reducing cancer incidence and mortality, underscoring the significance of provider density as a crucial metric of health quality. We sought to characterize the association of provider density on hepatobiliary cancer population-level incidence and mortality. STUDY DESIGN: County-level hepatobiliary cancer incidence and mortality data from 2016 to 2020 and provider data from 2016 to 2018 were obtained from the CDC and Area Health Resource File. Multivariable logistic regression was utilized to evaluate the relationship between provider density and hepatobiliary cancer incidence and mortality. RESULTS: Among 1359 counties, 851 (62.6%) and 508 (37.4%) counties were categorized as urban and rural, respectively. The median number of providers in any given county was 104 (IQR: 44-306), while provider density was 120.1 (IQR: 86.7-172.2) per 100,000 population; median household income was $51,928 (IQR: $45,050-$61,655). Low provider-density counties were more likely to have a greater proportion of residents over 65 years of age (52.7% vs. 49.6%) who were uninsured (17.4% vs. 13.2%) versus higher provider-density counties (p < 0.05). Moreover, all-stage incidence, late-stage incidence, and mortality rates were higher in counties with low provider density. On multivariable analysis, moderate, and high provider density were associated with lower odds of all-stage incidence, late-stage incidence, and mortality. CONCLUSION: Higher county-level provider density was associated with lower hepatobiliary cancer-related incidence and mortality. Efforts to increase access to healthcare providers may improve healthcare equity as well as long-term cancer outcomes.

Patterns of Locoregional Pancreatic Cancer Recurrence After Total Neoadjuvant Therapy and Implications on Optimal Neoadjuvant Radiation Treatment Volumes.

PURPOSE: To generate a map of local recurrences after neoadjuvant chemotherapy and radiation (total neoadjuvant therapy or TNT) followed by surgical resection for pancreatic ductal adenocarcinoma (PDAC). Such recurrence patterns will serve to inform radiation treatment planning volumes that should be given in the neoadjuvant setting. METHODS: Locoregional recurrences following TNT followed by surgery treated between 2009-2022 were radiologically identified. Recurrences were individually segmented using MIM software and complied in a single base scan. All contour compilations were used to create a threshold contour encompassing 80% of recurrences among all patients, head only, and body/tail only. The distance between organs at risk and the threshold contour were measured to design an optimal clinical target volume (CTV) contour for patients treated with TNT. Recurrence patterns were also compared to existing adjuvant guidelines to assess coverage. RESULTS: A database of 484 patients managed with TNT for PDAC was queried. While locoregional recurrences were rare in this cohort, we identified eighty patients with either isolated locoregional or simultaneous local and distant recurrences. Patients with diagnostic imaging at the time of recurrence were identified. The majority of recurrences were partially in the field of published contouring guidelines or volumetric expansions off of vessels, and volumetric coverage was low for all. Common areas of recurrence include the aortico-diaphragmatic junction, retro-pancreatic duodenal nodal basin, and the region to the right of the superior mesenteric artery. A novel set of proposed neoadjuvant contours was designed to cover the central-most 80% of recurrences. CONCLUSIONS: This is the largest collection of local/regional PDAC recurrences from a cohort of patients treated exclusively with TNT. Patterns of local/regional recurrence using TNT in PDAC vary significantly from those patients with PDAC treated with a surgery-first approach. Novel contouring guidelines presented herein can help to ensure optimal coverage of high risk regions and avoid reliance on the current adjuvant guidelines to guide treatment planning.

Gender-Based Variations in Medicare Reimbursements Among Different Surgical Subspecialties.

Importance: Gender inequities and limited representation are an obstacle to surgical workforce diversification. There has been limited examination of gender-based disparities in billing practices among surgeons. Objective: To evaluate variations in practice metrics and billing practices among female and male surgeons and identify factors associated with gender disparities in Medicare reimbursements. Design, Setting, and Participants: This retrospective cross-sectional study used publicly available Medicare Fee-for-Service Provider Utilization and Payment data from January to December 31, 2021, to identify demographics, annual services provided, and financial payments and charges for general surgeons, surgical oncologists, and colorectal surgeons. Data were analyzed from November 2023 to February 2024. Exposure: The primary exposure of interest was surgeon gender (ie, female or male). Main Outcomes and Measures: The annual total submitted charges and payments submitted in 2021 by female and male surgeons were assessed. Additionally, the total number and types of services provided each year and the number of beneficiaries treated were examined. Multivariable linear regression models were used to evaluate the association of surgeon gender with payments, number of services, and beneficiaries. Results: A total of 20 549 general surgeons (5036 [24.5%] female; 15 513 [75.5%] male), 1065 surgical oncologists (450 [42.3%] female; 615 [57.7%] male), and 1601 colorectal surgeons (432 [27.0%] female; 1169 [73.0%] male) were included. Across all surgical subspecialties, female surgeons billed fewer mean (SE) Medicare charges (general surgeons: 30.1% difference; $224 934.80 [$3846.97] vs $321 868.50 [$3933.57]; surgical oncologists: 27.5% difference; $277 901.70 [$22 857.37] vs $382 882.90 [$19 566.06]; colorectal surgeons: 21.7% difference; $274 091.70 [$10 468.48] vs $350 146.10 [$8741.66]; all P < .001) and received significantly lower mean (SE) reimbursements (general surgeons: 29.0% difference; $51 787.61 [$917.91] vs $72 903.12 [$890.35]; surgical oncologists: 23.6% difference; $57 945.18 [$3853.28] vs $75 778.22 [$2622.75]; colorectal surgeons: 24.5% difference; $63 117.01 [$2248.10] vs $83 598.53 [$1934.77]; all P < .001). On multivariable analysis, a reimbursement gap remained across all 3 surgical subspecialties (general surgeons: -$14 963.46 [95% CI, -$18 822.27 to -$11 104.64] [P < .001]; surgical oncologists: -$8354.69 [95% CI, -$15 018.12 to -$1691.25] [P = .01]; colorectal surgeons: -$4346.73 [95% CI, -$7660.15 to -$1033.32] [P = .01]). Conclusions and Relevance: In this cross-sectional study, there was considerable gender-based variation in practice patterns and reimbursement among different surgical subspecialties serving the Medicare population. Differences in mean payment per service were associated with variations in billing and coding strategies among female and male surgeons.

Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards.

PURPOSE: To update the American Society of Clinical Oncology (ASCO)-Oncology Nursing Society (ONS) standards for antineoplastic therapy administration safety in adult and pediatric oncology and highlight current standards for antineoplastic therapy for adult and pediatric populations with various routes of administration and location. METHODS: ASCO and ONS convened a multidisciplinary Expert Panel with representation of multiple organizations to conduct literature reviews and add to the standards as needed. The evidence base was combined with the opinion of the ASCO-ONS Expert Panel to develop antineoplastic safety standards and guidance. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: The standards presented here include clarification and expansion of existing standards to include home administration and other changes in processes of ordering, preparing, and administering antineoplastic therapy; the advent of immune effector cellular therapy; the importance of social determinants of health; fertility preservation; and pregnancy avoidance. In addition, the standards have added a fourth verification. STANDARDS: Standards are provided for which health care organizations and those involved in all aspects of patient care can safely deliver antineoplastic therapy, increase the quality of care, and reduce medical errors.

Postoperative Outcomes Among Patients Undergoing Cancer Surgery: United States versus International Medical Graduates.

OBJECTIVE: We sought to characterize postoperative outcomes among patients who underwent an oncologic operation relative to whether the treating surgeon was an international medical graduate (IMG) versus a United States medical graduate (USMG). BACKGROUND: IMGs comprise approximately one quarter of the physician workforce in the United States. METHODS: The 100% Medicare Standard Analytic Files were utilized to extract data on patients with breast, lung, hepato-pancreato-biliary (HPB), and colorectal cancer who underwent surgical resection between 2014 and 2020. Entropy balancing and multivariable regression analysis were performed to evaluate the association between postoperative outcomes among USMG and IMG surgeons. RESULTS: Among 285,930 beneficiaries, 242,914 (85.0%) and 43,016 (15.0%) underwent surgery by a USMG or IMG surgeon, respectively. Overall, 129,576 (45.3%) individuals were male, and 168,848 (59.1%) patients had a Charlson Comorbidity Index score >2. Notably, IMG surgeons were more likely to care for racial/ethnic minority patients (14.7% vs 12.5%) and individuals with a high social vulnerability index (33.3% vs 32.1%) (all P <0.001). On multivariable analysis after entropy balancing, patients treated by an IMG surgeon were less likely to experience adverse postoperative outcomes, including 90-day readmission [odds ratio (OR) 0.89, 95% CI: 0.80-0.99] and index complications (OR: 0.84, 95% CI: 0.74-0.95) versus USMG surgeons (all P <0.05). Patients treated by IMG versus USMG surgeons had no difference in likelihood to achieve a textbook outcome (OR: 1.10, 95% CI: 0.99-1.21; P =0.077). CONCLUSIONS: Postoperative outcomes among patients treated by IMG surgeons were roughly equivalent to those of USMG surgeons. In addition, IMG surgeons were more likely to care for patients with multiple comorbidities and individuals from vulnerable communities.

Association between quality metric adherence and overall survival among patients undergoing resection of pancreatic ductal adenocarcinoma.

BACKGROUND: Process-based quality metrics are important for improving long-term outcomes after surgical resection. We sought to develop a practical surgical quality score for patients diagnosed with pancreatic ductal adenocarcinoma undergoing curative-intent resection. METHODS: Patients who underwent surgical resection for pancreatic ductal adenocarcinoma between 2010 and 2017 were identified using the National Cancer Database. Five surgical quality metrics were defined: minimally invasive approach, adequate lymphadenectomy, negative surgical margins, receipt of adjuvant therapy, and no prolonged hospitalization. Log-rank test and multivariable Cox regression analysis were used to determine the association of quality metrics with overall survival. RESULTS: A total of 38,228 patients underwent curative-intent resection for pancreatic ductal adenocarcinoma. Median age at diagnosis was 68 years (interquartile range = 61-75), and roughly half the cohort was male (n = 19,562; 51.2%). Quality metrics were achieved on a varied basis: minimally invasive approach (n = 5,701; 14.9%), adequate lymphadenectomy (n = 27,122; 80.0%), negative surgical margin (n = 29,248; 76.5%), receipt of adjuvant therapy (n = 26,006; 68.0%), and absence of prolonged hospitalization (n = 26,470; 69.2%). An integer-based surgical quality score from 0 (no quality metrics) to 16 (all quality metrics) was calculated. Patients with higher scores had progressively better overall survival. Median overall survival differed substantially among the score categories (score = 0-4 points, 8.7 [8.0-9.6] months; 5-8 points, 17.5 [16.9-18.2] months; 9-12 points, 22.1 [21.6-22.8] months; and 13-16 points, 30.8 [30.2-31.3] months; P < .001). On multivariable analysis, risk-adjusted mortality hazards decreased in a stepwise manner with higher scores (0-4 points: reference; 5-8 points: multivariable adjusted hazard ratio = 0.60; 95% CI, 0.57-0.63; 9-12 points: adjusted hazard ratio = 0.49; 95% CI, 0.47-0.52; 13-16 points: and adjusted hazard ratio = 0.37; 95% CI, 0.34-0.40; all P < .001). CONCLUSION: Adherence to quality metrics may be associated with improved overall survival. Efforts aimed at increasing compliance with quality metric measures may help optimize long-term outcomes among patients undergoing surgical resection for pancreatic ductal adenocarcinoma.

Textbook oncologic outcomes among patients undergoing laparoscopic, robotic and open surgery for intrahepatic and perihilar cholangiocarcinoma.

BACKGROUND: Textbook oncologic outcome (TOO) serves as a composite, oncologic metric for surgical quality of care. We sought to evaluate variations in TOO among patients undergoing laparoscopic, robotic, and open surgery for intrahepatic (iCCA) and perihilar (pCCA) cholangiocarcinoma. METHODS: Patients who underwent liver resection for iCCA and pCCA between 2010 and 2018 were identified from the National Cancer Database. Entropy balancing was performed for covariate balancing and multivariable regression was used to evaluate the association between surgical approach and TOO. RESULTS: Among 5434 patients who underwent hepatic resection between 2010 and 2018, 3888 (71.6%) had iCCA, and 1546 (28.4%) had pCCA. TOO was achieved in 11.7% (n = 454), and 18.8% (n = 291) of patients with iCCA and pCCA, respectively. There was a difference in achievement of TOO relative to operative approach among patients with iCCA (robotic: 6.2% vs. laparoscopic: 8.1% vs. open: 12.5%; p = 0.002). After entropy balancing, patients with iCCA undergoing laparoscopic surgery had 32% reduced odds of achieving TOO (Ref: open surgery; laparoscopic, OR 0.68, 95%CI 0.49-0.93; p = 0.016; robotic, OR 0.69, 95%CI 0.34-1.39; p = 0.298). CONCLUSIONS: Usage of composite oncologic measures such as TOO may allow for a holistic assessment of different approaches to hepatic resection among patients with CCA.

Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards.

PURPOSE: To update the ASCO-Oncology Nursing Society (ONS) standards for antineoplastic therapy administration safety in adult and pediatric oncology and highlight current standards for antineoplastic therapy for adult and pediatric populations with various routes of administration and location. METHODS: ASCO and ONS convened a multidisciplinary Expert Panel with representation of multiple organizations to conduct literature reviews and add to the standards as needed. The evidence base was combined with the opinion of the ASCO-ONS Expert Panel to develop antineoplastic safety standards and guidance. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: The standards presented here include clarification and expansion of existing standards to include home administration and other changes in processes of ordering, preparing, and administering antineoplastic therapy; the advent of immune effector cellular therapy; the importance of social determinants of health; fertility preservation; and pregnancy avoidance. In addition, the standards have added a fourth verification. STANDARDS: Standards are provided for which health care organizations and those involved in all aspects of patient care can safely deliver antineoplastic therapy, increase the quality of care, and reduce medical errors.Additional information is available at www.asco.org/standards and www.ons.org/onf.

Long-term Health Outcomes of New Persistent Opioid Use After Gastrointestinal Cancer Surgery.

BACKGROUND: New persistent opioid use (NPOU) after surgery has been identified as a common complication. This study sought to assess the long-term health outcomes among patients who experienced NPOU after gastrointestinal (GI) cancer surgery. METHODS: Patients who underwent surgery for hepato-pancreato-biliary and colorectal cancer between 2007 and 2019 were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Mixed-effect multivariable logistic regression and Cox proportional hazard models were used to estimate the risk of mortality and hospital visits related to falls, respiratory events, or pain symptoms. RESULTS: Among 15,456 patients who underwent GI cancer surgery, 967(6.6%) experienced NPOU. Notably, the patients at risk for the development of NPOU were those with a history of substance abuse (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.14-1.84), moderate social vulnerability (OR, 1.26; 95% CI, 1.06-1.50), an advanced disease stage (OR, 4.42; 95% CI, 3.51-5.82), or perioperative opioid use (OR, 3.07; 95% CI, 2.59-3.63. After control for competing risk factors, patients who experienced NPOU were more likely to visit a hospital for falls, respiratory events, or pain symptoms (OR, 1.45, 95% CI 1.18-1.78). Moreover, patients who experienced NPOU had a greater risk of death at 1 year (hazard ratio [HR], 2.15; 95% CI, 1.74-2.66). CONCLUSION: Approximately 1 in 15 patients experienced NPOU after GI cancer surgery. NPOU was associated with an increased risk of subsequent hospital visits and higher mortality. Targeted interventions for individuals at higher risk for NPOU after surgery should be used to help mitigate the harmful effects of NPOU.

Impact of early primary care physician follow-up on hospital readmission following gastrointestinal cancer surgery.

BACKGROUND: We sought to examine the association between primary care physician (PCP) follow-up on readmission following gastrointestinal (GI) cancer surgery. METHODS: Patients who underwent surgery for GI cancer were identified using the Surveillance, Epidemiology and End Results (SEER) database. Multivariable regression was performed to examine the association between early PCP follow-up and hospital readmission. RESULTS: Among 60 957 patients who underwent GI cancer surgery, 19 661 (32.7%) visited a PCP within 30-days after discharge. Of note, patients who visited PCP were less likely to be readmitted within 90 days (PCP visit: 17.4% vs. no PCP visit: 28.2%; p < 0.001). Median postsurgical expenditures were lower among patients who visited a PCP (PCP visit: $4116 [IQR: $670-$13 860] vs. no PCP visit: $6700 [IQR: $870-$21 301]; p < 0.001). On multivariable analysis, PCP follow-up was associated with lower odds of 90-day readmission (OR: 0.52, 95% CI: 0.50-0.55) (both p < 0.001). Moreover, patients who followed up with a PCP had lower risk of death at 90-days (HR: 0.50, 95% CI: 0.40-0.51; p < 0.001). CONCLUSION: PCP follow-up was associated with a reduced risk of readmission and mortality following GI cancer surgery. Care coordination across in-hospital and community-based health platforms is critical to achieve optimal outcomes for patients.

Healthcare utilization and expenditures among patients with venous thromboembolism following gastrointestinal cancer surgery.

BACKGROUND: We sought to assess healthcare utilization and expenditures among patients who developed venous thromboembolism (VTE) after gastrointestinal cancer surgery. METHODS: Patients who underwent surgery for esophageal, gastric, hepatic, biliary duct, pancreatic, and colorectal cancer between 2013 and 2020 were identified using the MarketScan database. Entropy balancing was performed to obtain a cohort that was well balanced relative to different clinical covariates. Generalized linear models were used to compare 1-year postdischarge costs among patients who did and did not develop a postoperative VTE. RESULTS: Among 20,253 individuals in the analytical cohort (esophagus [n = 518 {2.6%}], stomach [n = 970 {4.8%}], liver [n = 608 {3.0%}], bile duct [n = 294 {1.5%}], pancreas [n = 1511 {7.5%}], colon [n = 12,222 {60.3%}], and rectum [n = 4130 {20.4%}]), 894 (4.4%) developed VTE. Overall, most patients were male (n = 10,656 [52.6%]), aged between 55 and 64 years (n = 10,372 [51.2%]), and were employed full time (n = 11,408 [56.3%]). On multivariable analysis, VTE was associated with higher inpatient (mean difference [MD], $17,547; 95% CI, $15,141-$19,952), outpatient (MD, $8769; 95% CI, $7045-$10,491), and pharmacy (MD, $2811; 95% CI, $2509-$3113) expenditures (all P < .001). Furthermore, patients who developed VTE had higher out-of-pocket costs for inpatient (MD, $159; 95% CI, $66-$253) and pharmacy (MD, $122; 95% CI, $109-$136) services (all P < .001). CONCLUSION: Among privately insured patients aged <65 years, VTE was associated with increased healthcare utilization and expenditures during the first year after discharge.

Association of preoperative cholangitis with outcomes and expenditures among patients undergoing pancreaticoduodenectomy.

BACKGROUND: This study aimed to characterize the association of preoperative acute cholangitis (PAC) with surgical outcomes and healthcare costs. METHODS: Patients who underwent pancreaticoduodenectomy (PD) between 2013 and 2021 were identified using 100% Medicare Standard Analytic Files. PAC was defined as the occurrence of at least 1 episode of acute cholangitis within the year preceding surgery. Multivariable regression analyses were used to compare postoperative outcomes and costs relative to PAC. RESULTS: Among 23,455 Medicare beneficiaries who underwent PD, 2,217 patients (9.5%) had at least 1 episode of PAC. Most patients (n = 14,729 [62.8%]) underwent PD for a malignant indication. On multivariable analyses, PAC was associated with elevated odds of surgical site infection (odds ratio [OR], 1.14; 95% CI, 1.01-1.29), sepsis (OR, 1.17; 95% CI, 1.01-1.37), extended length of stay (OR, 1.13; 95% CI, 1.01-1.26), and readmission within 90 days (OR, 1.14; 95% CI, 1.04-1.26). Patients with a history of PAC before PD had a reduced likelihood of achieving a postoperative textbook outcome (OR, 0.83; 95% CI, 0.75-0.92) along with 87.8% and 18.4% higher associated preoperative and postoperative healthcare costs, respectively (all P < .001). Overall costs increased substantially among patients with more than 1 PAC episode ($59,893 [95% CI, $57,827-$61,959] for no episode vs $77,922 [95% CI, $73,854-$81,990] for 1 episode vs $101,205 [95% CI, $94,871-$107,539] for multiple episodes). CONCLUSION: Approximately 1 in 10 patients undergoing PD experienced an antecedent PAC episode, which was associated with adverse surgical outcomes and greater healthcare expenditures.

Chemotherapy-free treatment targeting fusions and driver mutations in KRAS wild-type pancreatic ductal adenocarcinoma, a case series.

Background: KRAS wild-type (WT) pancreatic ductal adenocarcinoma (PDAC) represents a distinct entity with unique biology. The therapeutic impact of matched targeted therapy in these patients in a real-world setting, to date, is less established. Objectives: The aim of our study was to review our institutional database to identify the prevalence of actionable genomic alterations in patients with KRAS-WT tumors and to evaluate the therapeutic impact of matched targeted therapy in these patients. Design: We reviewed electronic medical records of patients with KRAS-WT PDAC and advanced disease (n = 14) who underwent clinical-grade tissue ± liquid next-generation sequencing (315-648 genes for tissue) between years 2015 and 2021. Methods: Demographic and disease characteristics were summarized using descriptive parameters. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: Of 236 PDAC patients, 14 had advanced/metastatic disease with KRAS-WT tumors. Median age at diagnosis was 66 years. There was a high frequency of potentially actionable genomic alterations, including three (21%) with BRAF alterations, two (14%) with fusions [RET-PCM1 and FGFR2-POC1B (N = 1 each)]; and one with a druggable EGFR (EGFR E746_A755delISERD) variant; two other patients had an STK11 and a MUTYH alteration. Five patients were treated with matched targeted therapy, with three having durable benefit: (i) erlotinib for EGFR-altered tumor, followed by osimertinib/capmatinib when MET amplification emerged (first-line therapy); (ii) pralsetinib for RET fusion (fifth line); and (iii) dabrafenib/trametinib for BRAF N486_P490del (third line). Duration of time on chemotherapy-free matched targeted therapy for these patients was 17+, 11, and 18+ months, respectively. Conclusion: Sustained therapeutic benefit can be achieved in a real-world setting in a subset of patients with advanced/metastatic KRAS-WT PDAC treated with chemotherapy-free matched targeted agents. Prospective studies are warranted.