Enhanced IL-15-mediated NK cell activation and proliferation by an ADAM17 function-blocking antibody involves CD16A, CD137, and accessory cells.

BACKGROUND: Natural killer (NK) cells are being extensively studied as a cell therapy for cancer. These cells are activated by recognition of ligands and antigens on tumor cells. Cytokine therapies, such as IL-15, are also broadly used to stimulate endogenous and adoptively transferred NK cells in patients with cancer. These stimuli activate the membrane protease ADAM17, which cleaves various cell-surface receptors on NK cells as a negative feedback loop to limit their cytolytic function. ADAM17 inhibition can enhance IL-15-mediated NK cell proliferation in vitro and in vivo. In this study, we investigated the underlying mechanism of this process. METHODS: Peripheral blood mononuclear cells (PBMCs) or enriched NK cells from human peripheral blood, either unlabeled or labeled with a cell proliferation dye, were cultured for up to 7 days in the presence of rhIL-15±an ADAM17 function-blocking antibody. Different fully human versions of the antibody were generated; Medi-1 (IgG1), Medi-4 (IgG4), Medi-PGLALA, Medi-F(ab')2, and TAB16 (anti-ADAM17 and anti-CD16 bispecific) to modulate CD16A binding. Flow cytometry was used to assess NK cell proliferation and phenotypic markers, immunoblotting to examine CD16A signaling, and IncuCyte-based live cell imaging to measure NK cell antitumor activity. RESULTS: The ADAM17 function-blocking monoclonal antibody (mAb) Medi-1 markedly increased early NK cell activation by IL-15. By using different engineered versions of the antibody, we demonstrate involvement by CD16A, an activating Fcγ receptor and well-described ADAM17 substrate. Hence, Medi-1 when bound to ADAM17 on NK cells is engaged by CD16A and blocks its shedding, inducing and prolonging its signaling. This process did not promote evident NK cell fratricide or dysfunction. Synergistic signaling by Medi-1 and IL-15 enhanced the upregulation of CD137 on CD16A+ NK cells and augmented their proliferation in the presence of PBMC accessory cells or an anti-CD137 agonistic mAb. CONCLUSIONS: Our data reveal for the first time that CD16A and CD137 underpin Medi-1 enhancement of IL-15-driven NK cell activation and proliferation, respectively, with the latter requiring PBMC accessory cells. The use of Medi-1 represents a novel strategy to enhance IL-15-driven NK cell proliferation, and it may be of therapeutic importance by increasing the antitumor activity of NK cells in patients with cancer.

Enhanced IL-15-mediated NK cell activation and proliferation by an ADAM17 function-blocking antibody involves CD16A, CD137, and accessory cells.

Background: NK cells are being extensively studied as a cell therapy for cancer. Their effector functions are induced by the recognition of ligands on tumor cells and by various cytokines. IL-15 is broadly used to stimulate endogenous and adoptively transferred NK cells in cancer patients. These stimuli activate the membrane protease ADAM17, which then cleaves assorted receptors on the surface of NK cells as a negative feedback loop to limit their activation and function. We have shown that ADAM17 inhibition can enhance IL-15-mediated NK cell proliferation in vitro and in vivo . In this study, we investigated the underlying mechanism of this process. Methods: PBMCs or enriched NK cells from human peripheral blood, either unlabeled or labeled with a cell proliferation dye, were cultured for up to 7 days in the presence of rhIL-15 +/- an ADAM17 function-blocking antibody. Different versions of the antibody were generated; Medi-1 (IgG1), Medi-4 (IgG4), Medi-PGLALA, Medi-F(ab') 2 , and TAB16 (anti-ADAM17 and anti-CD16 bispecific) to modulate CD16A engagement on NK cells. Flow cytometry was used to assess NK cell proliferation and phenotypic markers, immunoblotting to examine CD16A signaling, and IncuCyte-based live cell imaging to measure NK cell anti-tumor activity. Results: The ADAM17 function-blocking mAb Medi-1 markedly increased initial NK cell activation by IL-15. Using different engineered versions of the antibody revealed that the activating Fcγ receptor CD16A, a well-described ADAM17 substrate, was critical for enhancing IL-15 stimulation. Hence, Medi-1 bound to ADAM17 on NK cells can be engaged by CD16A and block its shedding, inducing and prolonging its signaling. This process did not promote evident NK cell fratricide, phagocytosis, or dysfunction. Synergistic activity by Medi-1 and IL-15 enhanced the upregulation of CD137 on CD16A + NK cells and augmented their proliferation in the presence of PBMC accessory cells. Conclusions: Our data reveal for the first time that CD16A and CD137 underpin Medi-1 enhancement of IL-15-driven NK cell activation and proliferation, respectively. The use of Medi-1 represents a novel strategy to enhance IL-15-driven NK cell proliferation, and it may be of therapeutic importance by increasing the anti-tumor activity of NK cells in cancer patients. What is already known on this topic: NK cell therapies are being broadly investigated to treat cancer. NK cell stimulation by IL-15 prolongs their survival in cancer patients. Various stimuli including IL-15 activate ADAM17 in NK cells, a membrane protease that regulates the cell surface density of various receptors as a negative feedback mechanism. What this study adds: Treating NK cells with the ADAM17 function-blocking mAb Medi-1 markedly enhanced their activation and proliferation. Our study reveals that the Fc and Fab regions of Medi-1 function synergistically with IL-15 in NK cell activation. Medi-1 treatment augments the upregulation of CD137 by NK cells, which enhances their proliferation in the presence of PBMC accessory cells. How this study might affect research practice or policy: Our study is of translational importance as Medi-1 treatment in combination with IL-15 could potentially augment the proliferation and function of endogenous or adoptively transferred NK cells in cancer patients.

Enhancing Readability of Online Patient-Facing Content: The Role of AI Chatbots in Improving Cancer Information Accessibility.

BACKGROUND: Internet-based health education is increasingly vital in patient care. However, the readability of online information often exceeds the average reading level of the US population, limiting accessibility and comprehension. This study investigates the use of chatbot artificial intelligence to improve the readability of cancer-related patient-facing content. METHODS: We used ChatGPT 4.0 to rewrite content about breast, colon, lung, prostate, and pancreas cancer across 34 websites associated with NCCN Member Institutions. Readability was analyzed using Fry Readability Score, Flesch-Kincaid Grade Level, Gunning Fog Index, and Simple Measure of Gobbledygook. The primary outcome was the mean readability score for the original and artificial intelligence (AI)-generated content. As secondary outcomes, we assessed the accuracy, similarity, and quality using F1 scores, cosine similarity scores, and section 2 of the DISCERN instrument, respectively. RESULTS: The mean readability level across the 34 websites was equivalent to a university freshman level (grade 13±1.5). However, after ChatGPT's intervention, the AI-generated outputs had a mean readability score equivalent to a high school freshman education level (grade 9±0.8). The overall F1 score for the rewritten content was 0.87, the precision score was 0.934, and the recall score was 0.814. Compared with their original counterparts, the AI-rewritten content had a cosine similarity score of 0.915 (95% CI, 0.908-0.922). The improved readability was attributed to simpler words and shorter sentences. The mean DISCERN score of the random sample of AI-generated content was equivalent to "good" (28.5±5), with no significant differences compared with their original counterparts. CONCLUSIONS: Our study demonstrates the potential of AI chatbots to improve the readability of patient-facing content while maintaining content quality. The decrease in requisite literacy after AI revision emphasizes the potential of this technology to reduce health care disparities caused by a mismatch between educational resources available to a patient and their health literacy.

Minimally invasive pancreaticoduodenectomy: A favorable approach for frail patients with pancreatic cancer.

BACKGROUND: Within the past decade, minimally invasive pancreaticoduodenectomy has been increasingly adopted in high-volume cancer centers. Amid broader trends of a growing older population, the numbers of frail patients with cancer are expected to increase. In this study, we compared the postoperative outcomes of open pancreaticoduodenectomy and minimally invasive pancreaticoduodenectomy in frail patients with pancreatic ductal adenocarcinoma. METHODS: Using the pancreatectomy-targeted American College of Surgeons-National Surgical Quality Improvement Program database (2014-2021), we identified pancreaticoduodenectomy cases for pancreatic ductal adenocarcinoma. Patients with a modified frailty index ≥2 were considered frail. We performed 2:1 (open pancreaticoduodenectomy to minimally invasive pancreaticoduodenectomy) optimal pair propensity score matching for both patient- and disease-specific characteristics. We evaluated baseline covariate balance for homogeneity and assessed 30-day postoperative outcomes: complications, discharge destination, major morbidity, and mortality. RESULTS: We identified 3,143 frail patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. Of those, 275 (9%) underwent minimally invasive pancreaticoduodenectomy. Minimally invasive pancreaticoduodenectomy was associated with a lower rate of any complications compared with open pancreaticoduodenectomy (43% vs 54%; P < .001), major morbidity (29% vs 35%; P = .042), and nonhome discharge (12% vs 17%; P = .022). When comparing the 2 minimally invasive pancreaticoduodenectomy approaches, robotic surgery was associated with fewer complications compared with laparoscopy (39% vs 51%; P = .040) and a lower mortality rate (1% vs 4%; P = .041) CONCLUSION: In frail patients with pancreatic cancer, minimally invasive pancreaticoduodenectomy was associated with better postoperative outcomes than open pancreaticoduodenectomy. This study builds on growing literature reporting that, when properly implemented, minimally invasive pancreaticoduodenectomy is associated with more favorable postoperative outcomes. Given the particularly high risk of complication in frail patients, implementing a preoperative frailty assessment can provide valuable insights to inform patient counseling.

Presence of underlying cirrhosis is associated with increased in-hospital mortality and length of stay following pancreatoduodenectomy.

BACKGROUND: Patient- and hospital-level factors associated with outcomes following pancreatoduodenectomy (PD) are well established. However, despite theoretical disruption in hepatopetal flow, the impact of cirrhosis on in-hospital mortality following PD is not well-studied. The objective of this study was to evaluate in-hospital mortality, length of stay (LOS), and post-discharge disposition in patients with cirrhosis undergoing PD. METHODS: A retrospective analysis of the National Inpatient Sample (January 2002-August 2015) was conducted identifying patients undergoing PD. Using previously validated ICD-9-CM codes, patients were stratified into presence and absence of cirrhosis. Factors associated with in-hospital mortality following PD were analyzed adjusting for patient- and hospital-level factors. Following PD were analyzed after adjusting for patient- and hospital-level factors. RESULTS: In 16,344 patients that underwent PD, 203 (1.2 %) patients had underlying cirrhosis prior to resection. Overall in-hospital mortality following PD was significantly worse in the cirrhosis cohort (11.3 % vs. 3.6 %, p < 0.001). Patients with underlying cirrhosis were less likely to be discharged home (73.9 % vs. 83.2 %, p < 0.001) and had a longer median LOS (12.0 vs. 10.0 days, p = 0.001). CONCLUSION: The presence of underlying cirrhosis is associated with increased in-hospital mortality, longer LOS, and decreased likelihood of home discharge following PD. Given the prohibitive risks, PD should not be performed in patients with underlying cirrhosis.

Association of race, demographic and socioeconomic factors with failure to rescue after hepato-pancreato-biliary surgery in the United States.

BACKGROUND: We aimed to describe the association of patient-related factors such as race, socioeconomic status, and insurance on failure to rescue (FTR) after hepato-pancreato-biliary (HPB) surgeries. METHODS: Using the National Inpatient Sample, we analyzed 98,788 elective HPB surgeries between 2004 and 2017. Major and minor complications were identified using ICD9/10 codes. We evaluated mortality rates and FTR (inpatient mortality after major complications). We used multivariate logistic regression analysis to assess racial, socioeconomic, and demographic factors on FTR, adjusting for covariates. RESULTS: Overall, 43 % of patients (n = 42,256) had pancreatic operations, 36% (n = 35,526) had liver surgery, and 21% (n = 21,006) had biliary interventions. The overall major complication rate was 21% (n = 20,640), of which 8% (n = 1655) suffered FTR. Factors independently associated with increased risk for FTR were male sex, older age, higher Charlson Comorbidity Index, Hispanic ethnicity, Asian or other race, lower income quartile, Medicare insurance, and southern region hospitals. CONCLUSIONS: Medicare insurance, male gender, Hispanic ethnicity, and lower income quartile were associated with increased risk for FTR. Efforts should be made to improve the identification and subsequent treatment of complications for those at high risk of FTR.

Intensifying supportive care is associated with improved survival in gastric cancer patients with malignant ascites.

BACKGROUND: Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that preclude receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan. METHODS: We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010 and 2022. We compared overall survival (OS) between patients diagnosed from 2010 to 2018, which will be referred to as the historical control era and patients diagnosed from 2019 to 2022, which will be called the aggressive supportive care era. RESULTS: Fifty-four patients were included in our analysis; 31 patients were treated in the historical control time frame, and 23 patients were treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p < 0.01). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p < 0.01). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median OS for historical control patients was 5.4 months as compared with 10.4 months for patients treated during aggressive supportive care era (p = 0.04). CONCLUSIONS: Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared with historic controls. Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.

Defining Volume Targets for Regionalization of Pancreaticoduodenectomy, Esophagectomy, and Major Lung Resection Centers to Improve Oncologic and Surgical Outcomes.

BACKGROUND: Performance of complex cancer surgeries at high-volume (HV) centers has been shown to reduce operative mortality. However, the case volume threshold that should be used to define HV centers is unknown. In this study, we determined thresholds to define HV pancreaticoduodenectomy, esophagectomy, and major lung resection centers based on clinical parameters. Then, we assessed the association of hospital volume with oncologic outcomes and overall survival. METHODS: We identified adult NCDB patients undergoing pancreaticoduodenectomy, esophagectomy, and major lung resections between 2004 and 2015. Multivariable models with restricted cubic splines were built to predict 5-year overall survival for each surgery group according to average yearly case volume, adjusting for demographic and clinicopathologic factors. The change point procedure was then used to identify volume cut-points for each surgery type. RESULTS: We identified the following thresholds to define HV status: 25 cases/year for pancreaticoduodenectomy; 18 cases/year for esophagectomy; and 54 cases/year for major lung resections. For all surgery types, treatment at a HV center was associated with an increased likelihood of R0 resection and adequate lymph node evaluation. HV centers had significantly decreased 30- and 90-day, postoperative mortality after adjusting for age, sex, race, comorbidities, histology, and stage. An overall survival benefit also was observed for patients undergoing resections at HV centers. CONCLUSIONS: Using novel methodology, our study identified volume thresholds for HV pancreaticoduodenectomy, esophagectomy, and major lung resection centers that were associated with improved oncologic outcomes and overall survival. These definitions of HV centers should be considered when evaluating regionalization of complex cancer care.

Cost Analysis and Financial Implications of a Peritoneal Surface Malignancy Program in the USA.

BACKGROUND: We aimed to describe the financial implications of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in the USA. MATERIALS AND METHODS: We conducted a retrospective cost analysis of 100 CRS/HIPEC procedures to examine the impact of patient and procedural factors on hospital costs and reimbursement. A comparison of surgeons' work relative value units (wRVUs) between CRS/HIPEC and a representative sample of complex surgical oncology procedures was made to assess the physicians' compensation rate. Univariable and multivariable backward logistic regression was used to analyze the association between perioperative variables and high direct cost (HDCs). RESULTS: The median direct cost per CRS/HIPEC procedure was US $44,770. The median hospital reimbursement was US $43,066, while professional reimbursement was US $8608, resulting in a positive contribution margin of US $7493/procedure. However, the contribution margin significantly varied with the payer mix. Privately insured patients had a positive median contribution margin of US $23,033, whereas Medicare-insured patients had a negative contribution margin of US $13,034. Length of stay (LOS) had the most significant association with HDC, and major complications had the most significant association with LOS. Finally, CRS/HIPEC procedures generated a median of 13 wRVU/h, which is significantly lower than the wRVU/h generated by open pancreatoduodenectomies, open gastrectomies, and hepatectomies. However, higher operation complexity and multiple visceral resections help compensate for the relatively low wRVU/h. CONCLUSIONS: CRS/HIPEC is an expensive operation, and prolonged LOS has the most significant impact on the total cost of the procedure. High-quality care is essential to improve patient outcomes and maintain the economic sustainability of the procedure.

Patient outcomes associated with subcutaneous C1INH prophylaxis for hereditary angioedema: a retrospective analysis.

BACKGROUND: Real-world data on subcutaneous C1INH (C1INH[SC]) usage and patient-level impacts on hereditary angioedema (HAE)-related outcomes and quality of life (QoL) are both lacking and challenging to generate using conventional study methodologies. Using a hybrid study design involving patient interviews supplemented by retrospective medical chart data review, we conducted a real-world assessment of the impact of C1INH(SC) prophylaxis on HAE attack patterns, QoL, and on-demand medication use. METHODS: The study was conducted at seven US sites and included 36 adults with HAE who had been treated with C1INH(SC) long-term prophylaxis following ≥ 12 months of on-demand management only. Patients underwent 30-min interviews, facilitated and analyzed by a trained qualitative research specialist. Medical records were reviewed for 12 months before (pre-index) and after (post-index) initiation of C1INH(SC). Using interview data with descriptive terms converted to numerical values, we compared pre- versus post-index attack frequency, severity, and rescue medication usage. RESULTS: Mean (SD) annualized attack frequency per patient decreased 82.0%, from 38.8 (38.8) attacks/year pre-index to 7.0 (15.3) attacks/year (P < 0.001); the median number of attacks decreased by 97.0% (30 pre-index to 1 post-index). For 20 patients, the annualized attack rate after starting C1INH(SC) prophylaxis was ≤ 1 attack/year; 12 of these patients reported 0 attacks. Mean (SD) attack severity (scale: 0 = none/mild to 4 = very severe) decreased from 2.3 (0.7) pre-index to 0.9 (0.9) post-index (P < 0.001). Mean/median rescue medication use decreased by 77.2%/96.3%. Improved QoL was narratively described for many domains. CONCLUSIONS: These real-world findings indicate that long-term prophylaxis with C1INH(SC) markedly improves important factors that contribute to the goal of achieving total disease control and normalization of patients' lives, including fewer and less severe attacks, less rescue medication usage, and improved QoL.

Impact of Neoadjuvant Treatment and Minimally Invasive Surgery on Perioperative Outcomes of Pancreatoduodenectomy: an ACS NSQIP Analysis.

BACKGROUND: There is an increasing use of neoadjuvant treatment (NAT) for pancreatic cancer (PC) followed by minimally invasive pancreatoduodenectomy (MIPD). We evaluate the impact of the surgical approach on 30-day outcomes in PC patients who underwent NAT. METHODS: Patients with PC who had NAT followed by MIPD or open pancreatoduodenectomy (OPD) were identified from a pancreatectomy-targeted dataset (2014-2020) of the National Surgical Quality Improvement Program. Comparisons were made between MIPD and OPD within NAT groups. RESULTS: A total of 5588 patients were analyzed. Of those, 4907 underwent OPD and 476 underwent MIPD. In addition, 3559 patients received neoadjuvant chemotherapy alone and 1830 received neoadjuvant chemoradiation. In the chemotherapy-alone group, the MIPD subgroup had lower rates of any complication (38.2% vs. 45.8%, P = 0.005), but there were no differences in mortality (2.1% for MIPD vs 1.9% for OPD, P=0.8) or serious complication (11.8% for MIPD vs 15% for OPD, P=0.1). On multivariable analysis, MIPD was independently predictive of lower rates of any complication (OR: 0.74, 95% CI 0.6-0.93, P = 0.0009), CR-POPF (OR: 0.58, 95% CI 0.35-0.96, P = 0.04), and shorter LOS (estimate: -1.03, 95% CI -1.73 to -0.32, P = 0.004). In the chemoradiation group, patients undergoing MIPD had higher rates of preoperative diabetes (P < 0.05), but there were no significant differences in any outcomes between the two approaches in this group. CONCLUSION: MIPD is safe and feasible after NAT. Patients having neoadjuvant chemotherapy alone followed by MIPD had lower rates of complications, shorter LOS, and fewer CR-POPFs compared to OPD.

Serum Interleukin 6 Level is Associated With Overall Survival and Treatment Response in Gastric and Gastroesophageal Junction Cancer.

OBJECTIVE: To identify novel prognostic and predictive biomarkers for gastric and gastroesophageal junction (G+GEJ) adenocarcinoma. BACKGROUND: There are few biomarkers to guide treatment for G+GEJ. The systemic inflammatory response of G+GEJ patients is associated with survival. In this study, we evaluated the relationship of circulating serum cytokine levels with overall survival (OS) and pathologic tumor regression grade (TRG) in G+GEJ patients. PATIENTS AND METHODS: We queried the UT Southwestern gastric cancer biobank to identify consecutive patients diagnosed with G+GEJ from 2016 to 2022; these patients had pretreatment serum collected at diagnosis. For patients who received neoadjuvant therapy, an additional serum sample was collected immediately before surgical resection. An unbiased screen of 17 cytokines was measured in a discovery cohort. A multivariable Cox proportional hazards model was used to assess the association of cytokine concentration with OS. Findings were validated in additional patients. In patients who received neoadjuvant therapy, we assessed whether the change in interleukin 6 (IL-6) after therapy was associated with TRG. RESULTS: Sixty-seven patients were included in the discovery cohort, and IL-6 was the only pretreatment cytokine associated with OS; this was validated in 134 other patients (hazard ratio: 1.012 per 1 pg/mL increase, 95% CI: 1.006-1.019, P = 0.0002). Patients in the top tercile of IL-6 level had worse median OS (10.6 months) compared with patients in the intermediate (17.4 months) and bottom tercile (35.8 months, P < 0.0001). Among patients who underwent neoadjuvant therapy (n = 50), an unchanged or decrease in IL-6 level from pretreatment to posttreatment, had a sensitivity and specificity of 80% for predicting complete or near-complete pathologic tumor regression (TRG 0-1). CONCLUSIONS: Pretreatment serum level of IL-6 is a promising prognostic biomarker for G+GEJ patients. Comparing pre and post-neoadjuvant IL-6 levels may predict pathologic response to neoadjuvant therapy.

Factors associated with failure to operate and its impact on survival in early-stage pancreatic cancer.

INTRODUCTION: Curative intent for localized pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) requires surgery, but despite improved perioperative outcomes, surgery remains underutilized. This study analyzed the Texas Cancer Registry (TCR) to identify resectable PDAC patients who underwent curative-intent surgery in Texas between 2004 and 2018. We then evaluated demographic and clinical factors associated with failure to operate and survival (OS). METHODS: We identified patients with localized PDAC or regional lymph node spread between 2004 and 2018 in the TCR. Resection rates were determined and multivariable regression and cox proportional hazards were used to identify factors associated with failure to OS. RESULTS: Of 4274 patients, 22% underwent resection, 57% were not offered surgery, 6% had comorbidities precluding surgery, and 3% refused. Resection rates decreased from 31% in 2004 to 22% in 2018. Increasing age was associated with failure to operate (odds ratio [OR] 2.55; 95% confidence interval [CI] 1.80-3.61; p < 0.0001) while treatment at a Commission on Cancer (CoC) center correlated with reduced failure to operate (OR 0.63; 95% CI 0.50-0.78; p < 0.0001). Resection correlated with survival (HR 0.34; 95% CI 0.31-0.38; p < 0.0001) as did treatment at a National Cancer Institute (NCI)-designated center (hazard ratio 0.79; 95% CI 0.70-0.89; p < 0.0001). CONCLUSIONS: Surgery is underutilized for the treatment of resectable PDAC in Texas with decreasing utilization, annually. Evaluation at CoC was associated with improved resection rates and NCI was associated with increased survival. Expanding access to multidisciplinary care including trained hepato-pancreatico-biliary surgeons may improve outcomes for PDAC patients.

Defining the Price Tag of Complications Following Pancreatic Surgery: A US National Perspective.

INTRODUCTION: Pancreatic surgery tends to have a high rate of postoperative complications due to its complex nature, significantly increasing hospital costs. Our aim was to describe the true association between complications and hospital costs in a national cohort of US patients. METHODS: The National Inpatient Sample was used to conduct a retrospective analysis of elective pancreatic resections performed between 2004 and 2017, categorizing them based on whether patients experienced major complications (MaC), minor complications (MiC), or no complications (NC). Multivariable quantile regression was used to analyze how costs varied at different percentiles of the cost curve. RESULTS: Of 37,893 patients, 45.3%, 28.6%, and 26.1% experienced NC, MiC, and MaC, respectively. Factors associated with MaC were a Charlson Comorbidity Index of ≥4, prolonged length of stay, proximal pancreatectomy, older age, male sex, and surgery performed at hospitals with a small number of beds or at urban nonteaching hospitals (all P < 0.01). Multivariable quantile regression revealed significant variation in MiC and MaC across the cost curve. At the 50th percentile, MiC increased the cost by $3352 compared to NC while MaC almost doubled the cost of the surgery, increasing it by $20,215 (both P < 0.01). The association between complications and cost was even greater at the 95th percentile, increasing the cost by $10,162 and $108,793 for MiC and MaC, respectively (P < 0.01). CONCLUSIONS: MiC and MaC were significantly associated with increased hospital costs. Furthermore, the relationship between MaC and costs was especially apparent at higher percentiles of the cost curve.

Hospital Designations and Their Impact on Guideline-Concordant Care and Survival in Pancreatic Cancer. Do They Matter?

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) requires complex multidisciplinary care. European evidence suggests potential benefit from regionalization, however, data characterizing the ideal setting in the United States are sparse. Our study compares the significance of four hospital designations on guideline-concordant care (GCC) and overall survival (OS). PATIENTS AND METHODS: The Texas Cancer Registry was queried for 17,071 patients with PDAC treated between 2004 and 2015. Clinical data were correlated with hospital designations: NCI designated (NCI), high volume (HV), safety net (SNH), and American College of Surgeons Commission on Cancer accredited (ACS). Univariable (UVA) and multivariable (MVA) logistic regression were used to assess associations with GCC [on the basis of National Comprehensive Cancer Network (NCCN) recommendations]. Cox regression analysis assessed survival. RESULTS: Only 43% of patients received GCC. NCI had the largest associated risk reduction (HR 0.61, CI 0.58-0.65), followed by HV (HR 0.87, CI 0.83-0.90) and ACS (HR 0.91, CI 0.87-0.95). GCC was associated with a survival benefit in the full (HR 0.75, CI 0.69-0.81) and resected cohort (HR 0.74, CI 0.68-0.80). NCI (OR 1.52, CI 1.37-1.70), HV (OR 1.14, CI 1.05-1.23), and SNH (OR 0.78, CI 0.68-0.91) all correlated with receipt of GCC. For resected patients, ACS (OR 0.63, CI 0.50-0.79) and SNH (OR 0.50, CI 0.33-0.75) correlate with GCC. CONCLUSIONS: A total of 43% of patients received GCC. Treatment at NCI and HV correlated with improved GCC and survival. Including GCC as a metric in accreditation standards could impact survival for patients with PDAC.

A Study Design to Harmonize Patient-Reported Outcomes Across Data Sets.

PURPOSE: Using patient-reported outcomes (PROs) provides important insights from the patient's perspective and can be valuable to monitor and manage treatment-related adverse events during cancer treatment. Additionally, the digital administration of PROs (electronic PROs [ePROs]) provides real-time updates to clinical care teams on treatment-related symptoms in-between clinic visits. However, given the variability in the methodology and timing of the data collection, using and harmonizing these data across different systems remains challenging. Identifying data elements to capture and operating procedures for harmonization across ePRO tools will expedite efforts to generate relevant and robust data on use of ePRO data in clinical care. METHODS: Friends of Cancer Research assembled a consortium of project partners from key health care sectors to align on a framework for ePRO data capture across ePRO tools and assessment of the impact of ePRO data capture on patient outcomes. RESULTS: We identified challenges and opportunities to align ePRO data capture across ePRO tools and aligned on key data elements for assessing the impact of ePRO data capture on patient care and outcomes. Ultimately, we proposed a study protocol to leverage ePRO data for symptom and adverse event management to measure real-world effectiveness of ePRO tool implementation on patient care and outcomes. CONCLUSION: This work provides considerations for harmonizing ePRO data sets and a common framework to align across multiple ePRO tools to assess the value of ePROs for improving patient outcomes. Future efforts to interpret evidence and evaluate the impact of ePRO tools on patient outcomes will be aided by improved alignment across studies.