Olaparib not cost-effective as maintenance therapy for platinum-sensitive, BRCA1/2 germline-mutated metastatic pancreatic cancer.

OBJECTIVE: To assess the cost-effectiveness and budget impact of olaparib as a maintenance therapy in platinum-responsive, metastatic pancreatic cancer patients harboring a germline BRCA1/2 mutation, using the Swiss context as a model. METHODS: Based on data from the POLO trial, published literature and local cost data, we developed a partitioned survival model of olaparib maintenance including full costs for BRCA1/2 germline testing compared to FOLFIRI maintenance chemotherapy and watch-and-wait. We calculated the incremental cost-effectiveness ratio (ICER) for the base case and several scenario analyses and estimated 5-year budget impact. RESULTS: Comparing olaparib with watch-and wait and maintenance chemotherapy resulted in incremental cost-effectiveness ratios of CHF 2,711,716 and CHF 2,217,083 per QALY gained, respectively. The 5-year costs for the olaparib strategy in Switzerland would be CHF 22.4 million, of which CHF 11.4 million would be accounted for by germline BRCA1/2 screening of the potentially eligible population. This would amount to a budget impact of CHF 15.4 million (USD 16.9 million) versus watch-and-wait. CONCLUSIONS: Olaparib is not a cost-effective maintenance treatment option. Companion diagnostics are an equally important cost driver as the drug itself.

Efficient Assessment of Tumor Vascular Shutdown by Photodynamic Therapy on Orthotopic Pancreatic Cancer Using High-Speed Wide-Field Waterproof Galvanometer Scanner Photoacoustic Microscopy.

To identify the vascular alteration by photodynamic therapy (PDT), the utilization of high-resolution, high-speed, and wide-field photoacoustic microscopy (PAM) has gained enormous interest. The rapid changes in vasculature during PDT treatment and monitoring of tumor tissue activation in the orthotopic pancreatic cancer model have received limited attention in previous studies. Here, a fully two-axes waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system was developed for in vivo monitoring of dynamic variations in micro blood vessels due to PDT in an orthotopic pancreatic cancer mouse model. The photosensitizer (PS), Chlorin e6 (Ce6), was utilized to activate antitumor reactions in response to the irradiation of a 660 nm light source. Microvasculatures of angiogenesis tissue were visualized on a 40 mm2 area using the WGS-PAM system at 30 min intervals for 3 h after the PDT treatment. The decline in vascular intensity was observed at 24.5% along with a 32.4% reduction of the vascular density at 3 h post-PDT by the analysis of PAM images. The anti-vascularization effect was also identified with fluorescent imaging. Moreover, Ce6-PDT increased apoptotic and necrotic markers while decreasing vascular endothelial growth factor (VEGF) expression in MIA PaCa-2 and BxPC-3 pancreatic cancer cell lines. The approach of the WGS-PAM system shows the potential to investigate PDT effects on the mechanism of angiographic dynamics with high-resolution wide-field imaging modalities.

Short-term serial circulating tumor DNA assessment predicts therapeutic efficacy for patients with advanced pancreatic cancer.

PURPOSE: We investigated the potential clinical utility of short-term serial KRAS-mutated circulating cell-free tumor DNA (ctDNA) assessment for predicting therapeutic response in patients undergoing first-line chemotherapy for advanced pancreatic cancer. METHODS: We collected 144 blood samples from 18 patients with locally advanced or metastatic cancer that were undergoing initial first-line chemotherapy of gemcitabine plus nab-paclitaxel (GEM plus nab-PTX). Analysis of KRAS-mutated ctDNA was quantified by digital droplet polymerase chain reaction (ddPCR) as mutant allele frequency (MAF). This study investigated pretreatment KRAS-mutated ctDNA status and ctDNA kinetics every few days (days 1, 3, 5 and 7) after initiation of chemotherapy and their potential as predictive indicators. RESULTS: Of the 18 enrolled patients, an increase in KRAS-mutated ctDNA MAF values from day 0-7 after initiation of chemotherapy was significantly associated with disease progression (P < 0.001). Meanwhile, positive pretreatment ctDNA status (MAF ≥ 0.02%) (P = 0.585) and carbohydrate antigen 19-9 (CA19-9) values above the median (P = 0.266) were not associated with disease progression. In univariate analysis, this short-term increase in ctDNA MAF values (day 0-7) was found to be associated with significantly shorter progression free survival (PFS) (hazard ration [HR], 24.234; range, (2.761-212.686); P = 0.0002). CONCLUSION: This short-term ctDNA kinetics assessment may provide predictive information to reflect real-time therapeutic response and lead to effective refinement of regimen in patients with advanced pancreatic cancer undergoing systemic chemotherapy.

Association between social determinants of health and delayed postoperative adjuvant therapy among patients undergoing resection of pancreatic cancer.

BACKGROUND AND OBJECTIVES: Pancreatic cancer (PDAC) requires a multimodality approach. We sought to define the association between social determinants of health (SDOH) and delayed or nonreceipt of adjuvant chemotherapy (aCT) among patients undergoing PDAC resection. METHODS: Data on patients who underwent PDAC resection between 2014 and 2020 were identified from Medicare Standard Analytic Files and merged with the county-level social vulnerability index (SVI). Mediation analysis defined the association between SVI subthemes and aCT receipt. RESULTS: Among 24 078 patients, 47.7% received timely aCT, 17.7% received delayed aCT, and 34.6% did not receive any aCT. High SVI was associated with delay (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.10-1.34) and nonreceipt of aCT (OR 1.30, 95% CI 1.20-1.41) (both p < 0.05). 73.1% of the variation in timely aCT receipt was directly attributable to SVI, whereas 26.9% of the effect was due to indirect mediators including hospital volume (6.4%), length-of-stay (7.9%) and postoperative complications (12.6%). Socioeconomic status (delayed aCT: OR 1.25, 95% CI 1.13-1.38; nonreceipt aCT: OR 1.25, 95% CI 1.15-1.36) and household composition and disability (delayed aCT: OR 1.30, 95% CI 1.17-1.43; nonreceipt aCT: OR 1.19, 95% CI 1.09-1.29) were associated with receipt of aCT (both p < 0.001). CONCLUSIONS: Most of the disparities in receipt of aCT after PDAC surgery are driven by underlying SDOH such as SVI.

Calcium channel blockers are associated with improved survival in pancreatic cancer patients undergoing neoadjuvant chemotherapy and resection.

BACKGROUND: Repurposing existing drugs for use in oncology is more efficient, cost-effective and safe than novel drug discovery. Calcium signalling is increasingly recognised to have a key role in chemoresistance. This study assessed the impact of calcium channel blockers (CCB) in pancreatic cancer. METHODS: Retrospective population study of patients undergoing resection (curative intent) of pancreatic ductal adenocarcinoma (SEER-Medicare, 2007-2017). Cox models were built to assess the impact on overall survival. As laboratory studies suggest a chemosensitising effect, the impact of CCB was assessed separately in patients receiving neoadjuvant chemotherapy. RESULTS: 6,223 patients were included, of whom 660 were prescribed CCB. In total, 591 received neoadjuvant chemotherapy; in this cohort CCB prescription was associated with improved overall survival when adjusting for multiple prognostic factors (aHR = 0.715, 0.514-0.996, P = 0.047). This effect was not observed in patients not receiving neoadjuvant chemotherapy (aHR = 1.082, 0.982-1.191, P = 0.112). CONCLUSION: CCB prescription was associated with improved overall survival in patients receiving neoadjuvant chemotherapy prior to pancreatic cancer resection. The association was specific to the group of patients receiving neoadjuvant chemotherapy, mirroring the chemosensitising effect in laboratory studies. This defines patients receiving neoadjuvant chemotherapy as a target population for prospective clinical trials of CCB in pancreatic cancer.

Unraveling Racial Disparities in Supportive Care Medication Use among End-of-Life Pancreatic Cancer Patients: Focus on Pain Management and Psychiatric Therapies.

BACKGROUND: Supportive care medication use differences may contribute to racial disparities observed in health-related quality of life in patients with pancreatic cancer. METHODS: In this observation study using the Surveillance, Epidemiology, and End Results-Medicare linked database, we sought to examine supportive care medication use disparities in patients with pancreatic cancer from 2005 to 2017 by race and ethnicity. RESULTS: Among 74,309 patients included in the final analysis, racial and ethnic disparities in the use of supportive care medications were identified. After adjustment for confounding factors and compared with non-Hispanic Whites, minorities had significantly less use of opioids [Black: adjusted OR (aOR), 0.84; 95% confidence interval (CI), 0.79-0.88; Asian: aOR, 0.84; 95% CI, 0.79-0.90), and skeletomuscular relaxants (Black: aOR, 0.90; 95% CI, 0.82-0.99; Hispanic: aOR, 0.82; 95% CI, 0.74-0.91; Asian: aOR, 0.59; 95% CI, 0.51-0.68), and increased use of non-opioid analgesics (Hispanic: aOR, 1.16; 95% CI, 1.01-1.14; Asian: aOR, 1.37; 95% CI, 1.26-1.49). Racial and ethnic minorities had less use of antidepressants (Black: aOR, 0.56; 95% CI, 0.53-0.59; Hispanic: aOR, 0.77; 95% CI, 0.73-0.82; Asian: aOR, 0.47; 95% CI, 0.44-0.51), anxiolytics (Black: aOR, 0.78; 95% CI, 0.74-0.82; Hispanic: aOR, 0.66; 95% CI, 0.62-0.71; Asian: aOR, 0.52; 95% CI, 0.48-0.57), and antipsychotics (Hispanic: aOR, 0.90; 95% CI, 0.82-0.99; Asian: aOR, 0.84; 95% CI, 0.74-0.95). CONCLUSIONS: Racial and ethnic disparities in the use of supportive care medications among patients with pancreatic cancer were observed, with the differences unexplained by sociodemographic factors. IMPACT: Future studies should identify strategies to promote equitable use of supportive care medications among racial minorities and explore factors that may influence their use in these populations.

Clinical Impact of Nutrition and Inflammation Assessment Tools in Pancreatic Cancer Treatment.

Perioperative adjuvant treatment and complete resection is the standard treatment for resectable pancreatic cancer and systemic chemotherapy is standard treatment for unresectable pancreatic cancer. To improve the survival of patients with pancreatic cancer, it is necessary to identify promising biomarkers to optimize the treatment. The availability of biomarkers may allow patients to receive a more aggressive or less toxic treatment. Recent studies showed that the inflammatory and nutritional status perioperatively and/or during chemotherapy affect short and long-term oncological outcomes in pancreatic cancer. Introduction of inflammatory and nutritional status evaluation in pancreatic cancer treatment might improve the postoperative surgical complications or chemotherapy-induced adverse events. However, to introduce these various nutritional and inflammation assessment tools in daily clinical practice, it is necessary to understand the characteristics of each nutrition and inflammation assessment tool. This review summarizes the background, current status, and future perspectives of nutrition and inflammation assessment tools in pancreatic cancer treatment.

Preclinical Assessment of ADAM9-Responsive Mesoporous Silica Nanoparticles for the Treatment of Pancreatic Cancer.

Pancreatic adenocarcinoma (PDAC) remains largely refractory to chemotherapeutic treatment regimens and, consequently, has the worst survival rate of all cancers. The low efficacy of current treatments results largely from toxicity-dependent dose limitations and premature cessation of therapy. Recently, targeted delivery approaches that may reduce off-target toxicities have been developed. In this paper, we present a preclinical evaluation of a PDAC-specific drug delivery system based on mesoporous silica nanoparticles (MSNs) functionalized with a protease linker that is specifically cleaved by PDAC cells. Our previous work demonstrated that ADAM9 is a PDAC-enriched protease and that paclitaxel-loaded ADAM9-responsive MSNs effectively kill PDAC cells in vitro. Here, we show that paclitaxel-loaded ADAM9-MSNs result in off-target cytotoxicity in clinically relevant models, which spurred the development of optimized ADAM9-responsive MSNs (OPT-MSNs). We found that these OPT-MSNs still efficiently kill PDAC cells but, as opposed to free paclitaxel, do not induce death in neuronal or bone marrow cells. In line with these in vitro data, paclitaxel-loaded OPT-MSNs showed reduced organ damage and leukopenia in a preclinical PDAC xenograft model. However, no antitumor response was observed upon OPT-MSN administration in vivo. The poor in vivo antitumor activity of OPT-MSNs despite efficient antitumor effects in vitro highlights that although MSN-based tumor-targeting strategies may hold therapeutic potential, clinical translation does not seem as straightforward as anticipated.

Olaparib versus Placebo in Maintenance Treatment of Germline BRCA-Mutated Metastatic Pancreatic Cancer: A Cost-Utility Analysis from the Canadian Public Payer's Perspective.

Pancreatic cancer has an annual incidence of 2/10,000 in Canada, with a one-year mortality rate greater than 80%. In the absence of a cost-effectiveness analysis in Canada, this study's objective was to assess the cost-effectiveness of olaparib versus a placebo in adult patients with deleterious or suspected deleterious BRCA metastatic pancreatic adenocarcinoma, who did not show any progression for at least 16 weeks with first-line platinum-based chemotherapy. A partitioned survival model with a 5-year time horizon was adopted to estimate the costs and effectiveness. All of the costs were extracted from the public payer's available resources, effectiveness data were obtained from the POLO trial, and Canadian studies were used for utility inputs. Probabilistic sensitivity analyses and scenario analyses were performed. The total costs of olaparib and the placebo over five years were CAD 179,477 and CAD 68,569, with overall quality-adjusted life-years (QALYs) of 1.70 and 1.36, respectively. The incremental cost-effectiveness ratio (ICER) of the olaparib group compared with the placebo was CAD 329,517 per QALY. With a commonly cited willingness to pay (WTP) threshold of CAD 50,000 per QALY, the drug does not achieve acceptable cost-effectiveness mainly due to the high price of the medication and insufficient impact on the overall survival of patients with metastatic pancreatic cancer.

Association of County-level Upward Economic Mobility with Stage at Diagnosis and Receipt of Treatment Among Patients Diagnosed with Pancreatic Adenocarcinoma.

OBJECTIVE: Determining the impact of county-level upward economic mobility on stage at diagnosis and receipt of treatment among Medicare beneficiaries with pancreatic adenocarcinoma. SUMMARY BACKGROUND DATA: The extent to which economic mobility contributes to socioeconomic disparities in health outcomes remains largely unknown. METHODS: Pancreatic adenocarcinoma patients diagnosed in 2004-2015 were identified from the SEER-Medicare linked database. Information on countylevel upward economic mobility was obtained from the Opportunity Atlas. Its impact on early-stage diagnosis (stage I or II), as well as receipt of chemotherapy or surgery was analyzed, stratified by patient race/ethnicity. RESULTS: Among 25,233 patients with pancreatic adenocarcinoma, 37.1% (n = 9349) were diagnosed at an early stage; only 16.7% (n = 4218) underwent resection, whereas 31.7% (n = 7996) received chemotherapy. In turn, 10,073 (39.9%) patients received any treatment. Individuals from counties with high upward economic mobility were more likely to be diagnosed at an earlier stage (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07-1.25), as well as to receive surgery (OR 1.58, 95% CI 1.41-1.77) or chemotherapy (OR 1.51, 95% CI 1.39-1.63). White patients and patients who identified as neither White or Black had increased odds of being diagnosed at an early stage (OR 1.12, 95% CI 1.02-1.22 and OR 1.35, 95% CI 1.02-1.80, respectively) and of receiving treatment (OR 1.73, 95% CI 1.59-1.88 and OR 1.49, 95% CI 1.13-1.98, respectively) when they resided in a county of high vs low upward economic mobility. The impact of economic mobility on stage at diagnosis and receipt of treatment was much less pronounced among Black patients (high vs low, OR 1.28, 95% CI 0.96-1.71 and OR 1.30, 95% CI 0.99-1.72, respectively). CONCLUSIONS: Pancreatic adenocarcinoma patients from higher upward mobility areas were more likely to be diagnosed at an earlier stage, as well as to receive surgery or chemotherapy. The impact of county-level upward mobility was less pronounced among Black patients.

Examining the relationship between metformin dose and cancer survival: A SEER-Medicare analysis.

Cancer is a major health problem in the U.S and type 2 diabetes mellitus (T2DM) is known to increase the risk for the development of many cancers. Metformin, a first-line therapy for treating T2DM, is increasingly being used for its anticancer effects; however, the literature is limited on the effect of metformin dose on overall survival in patients with stage IV cancer. Overall survival was defined as the time interval from the date of diagnosis to the last known follow-up or death from any cause. Subjects who were alive on December 31, 2016 were censored. In this cohort study we examined the relationship between metformin dose and overall survival in persons with both T2DM and stage IV lung, breast, colorectal, prostate, or pancreas cancers. We used a retrospective study design with Cox proportional hazards regression analysis of the 2007-2016 of the Surveillance Epidemiology and End Results-Medicare (SEER) dataset. Of the 7,725 patients, 2,981(38.5%) had been prescribed metformin. Patients who used metformin had significantly better overall survival in both unadjusted (Unadjusted HR, 0.73; 95% CI, 0.69-0.76; p < 0.001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; p < 0.001). The overall survival between patients who took metformin with average daily dose ≥ 1000mg or < 1000mg were not statistically significant (aHR, 1.00; 95% CI, 0.93-1.08; p = 0.90). Metformin use regardless of dose is associated with increased overall survival in older adults with stage IV cancer.

The Addition of Chemoradiation to Adjuvant Chemotherapy is Associated With Improved Survival Following Upfront Surgical Resection for Pancreatic Cancer With Nodal Metastases.

BACKGROUND: It is unclear whether the addition of chemoradiation (CRT) to adjuvant chemotherapy (CT) following upfront resection of pancreatic ductal adenocarcinoma (PDAC) provides any benefit. While some studies have suggested a benefit to combined modality therapy (CMT) (adjuvant CT plus CRT), it is not clear if this benefit was related to increased CT usage in patients who received CMT. We sought to clarify the use of CMT in patients who underwent upfront resection of PDAC. METHODS: Patients with non-metastatic PDAC were retrospectively identified from the linked SEER-Medicare database. Those who underwent upfront resection were identified and divided into two cohorts - patients who received adjuvant CT and patients who received adjuvant CMT. Cohorts were compared. Univariate analysis described patient characteristics. Kaplan-Meier and multivariable Cox proportional hazards modeling were used to estimate overall survival (OS). RESULTS: 3555 patients were identified; 856 (24%) received CT and 573 (16%) received CMT. The median number of CT doses was 11 for both groups. Patients who received CMT were younger, diagnosed in the earlier time frame, and had fewer comorbidities. The median OS was 21 months and 18 months for those treated with CMT and CT (P < .0001), respectively, but when stratified by nodal status, the association with improved OS in the CMT cohort was only observed in node-positive patients. On multivariable analysis, receipt of CMT and removal of >15 lymph nodes decreased the risk of death (P < .05). DISCUSSION: Receipt of CMT following upfront resection for PDAC was associated with improved survival, which was confined to node-positive patients. The role of adjuvant CMT in PDAC with nodal metastases warrants further study.

Real-World Cost-Effectiveness of First-Line Gemcitabine Plus Nab-Paclitaxel vs FOLFIRINOX in Patients With Advanced Pancreatic Cancer.

BACKGROUND: There are no randomized control trials (RCTs) comparing gemcitabine and nab-paclitaxel (Gem-Nab) and fluorouracil, folinic acid, irinotecan, oxaliplatin (FOLFIRINOX) for advanced pancreatic cancer (APC). Although it is well known that RCT-based efficacy often does not translate to real-world effectiveness, there is limited literature investigating comparative cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC. We aimed to examine the real-world cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC in Ontario, Canada. METHODS: This study compared patients treated with first-line Gem-Nab or FOLFIRINOX for APC in Ontario from April 2015 to March 2019. Patients were linked to administrative databases. Using propensity scores and a stabilizing weights method, an inverse probability of treatment weighted cohort was developed. Mean survival and total costs were calculated over a 5-year time horizon, adjusted for censoring, and discounted at 1.5%. Incremental cost-effectiveness ratio and net monetary benefit were computed to estimate cost-effectiveness from the public health-care payer's perspective. Sensitivity analysis was conducted using the propensity score matching method. RESULTS: A total of 1988 patients were identified (Gem-Nab: n = 928; FOLFIRINOX: n = 1060). Mean survival was lower for patients in the Gem-Nab than the FOLFIRINOX group (0.98 vs 1.26 life-years; incremental effectiveness = -0.28 life-years [95% confidence interval = -0.47 to -0.13]). Patients in the Gem-Nab group incurred greater mean 5-year total costs (Gem-Nab: $103 884; FOLFIRINOX: $101 518). Key cost contributors include ambulatory cancer care, acute inpatient hospitalization, and systemic therapy drug acquisition. Gem-Nab was dominated by FOLFIRINOX, as it was less effective and more costly. Results from the sensitivity analysis were similar. CONCLUSIONS: Gem-Nab is likely more costly and less effective than FOLFIRINOX and therefore not considered cost-effective at commonly accepted willingness-to-pay thresholds.

Trends in Preoperative Chemotherapy Utilization for Proximal Pancreatic Cancer: Are We Making Progress?

BACKGROUND: While it has been shown that neoadjuvant chemotherapy (NCT) for pancreatic cancer (PDAC) undergoing pancreaticoduodenectomy (PD) is critical for optimal oncologic management, NCT is (A) not universally practiced and (B) the reasons ill-defined. This study investigates national rates, trends, and factors affecting NCT utilization. PATIENTS AND METHODS: Using the National Cancer Database, patients who underwent PD for PDAC between 2006 and 2017 were identified. Changes in chemotherapy sequence over time were identified. For patients diagnosed after 2010, multivariable logistic regression models for factors affecting NCT were created. RESULTS: A total of 128,980 patients were diagnosed and 23,206 underwent surgery. Three thousand five (12.9%) received NCT with a preoperative chemotherapy (NCT + PCT) utilization rate of 7.3% in 2004 that increased to 36.8% in 2017. Factors affecting utilization of preoperative chemotherapy were age (OR 0.972), academic and integrated network institutions (OR 1.916, OR 1.559), institutional case volume (OR 1.007), distance from the hospital (OR 1.002), stage (IB OR 3.108, IIA OR 3.133, IIB OR 3.775, III OR 3.782), grade IV (OR 1.977), and insurance status (private OR 2.371, Medicaid OR 1.811, and Medicare OR 2.191, government OR 2.645). CONCLUSION: Even though more than 3/5 of patients receive no preoperative chemotherapy (NCT + PCT) and nearly 1/5 of patients still receive no chemotherapy at all, utilization of NCT is increasing. Moreover, since this study demonstrates that omission of NCT is associated with modifiable factors such as type of institution and health care disparity, mechanisms (reimbursement, policy) geared to change current national practice patterns may most immediately affect optimal oncologic management.

Intraoperative Pancreatic Neck Margin Assessment During Pancreaticoduodenectomy for Pancreatic Adenocarcinoma in the Era of Neoadjuvant Therapy: A Multi-institutional Analysis from the Central Pancreatic Consortium.

BACKGROUND: Data regarding the survival impact of converting frozen-section (FS):R1 pancreatic neck margins to permanent section (PS):R0 by additional resection (i.e., converted-R0) during upfront pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) are conflicting. The impact of neoadjuvant therapy on this practice and its relationship with overall survival (OS) is incompletely understood. METHODS: We reviewed PDAC patients (80% borderline resectable/locally advanced [BR/LA]) undergoing pancreaticoduodenectomy after neoadjuvant therapy at seven, academic, high-volume centers (2010-2018). Multivariable models examined the association of PS:R0, PS:R1, and converted-R0 margins with OS. RESULTS: Of 272 patients receiving at least 2 (median 4) cycles of neoadjuvant chemotherapy (71% mFOLFIRINOX or gemcitabine/nab-paclitaxel) and undergoing pancreaticoduodenectomy with intraoperative frozen-section assessment of the transected pancreatic neck margin, PS:R0 (n = 220, 80.9%) was observed in a majority of patients; 18 patients (6.6%) had converted-R0 margins following additional resection, whereas 34 patients (12.5%) had persistently positive PS:R1 margins. At a median follow-up of 42 months, PS:R0 resection was associated with improved OS compared with either converted-R0 or PS:R1 resection (median 25 vs. 14 vs. 16 months, respectively; p = 0.023), with no survival difference between the converted-R0 and PS:R1 groups (p = 0.9). On Cox regression, SMA margin positivity (hazard ratio 2.2, p = 0.012), but not neck margin positivity (hazard ratio 1.2, p = 0.65), was associated with worse OS. CONCLUSIONS: In this multi-institutional cohort of predominantly BR/LA PDAC patients undergoing pancreaticoduodenectomy following modern neoadjuvant therapy, pursuing a negative neck margin intraoperatively if the initial margin is positive does not appear to be associated with improved survival.

Real-World Assessment of Cancer Drugs Using Local Data Uploaded to the Systemic Anti-Cancer Therapy Dataset in England.

AIMS: In England, not all cancer drugs are routinely funded; new medicines are first appraised by the National Institute for Health and Care Excellence. Funding can be temporarily given through the Cancer Drugs Fund while further information is collected. The Systemic Anti-Cancer Therapy (SACT) dataset collects information on all patients receiving chemotherapy in England. To date, little has been published, despite concerns that real-world effectiveness of medicines may be inferior to that seen in clinical trials. The aim of the present study was to establish the feasibility of using our local copy of routinely collected SACT data for the evaluation of outcomes, using the data within the context of gastrointestinal cancers. MATERIALS AND METHODS: We used our local SACT dataset submissions from three National Health Service trusts, with a reproducible method of data linkage, to undertake a cohort analysis of treatment duration and overall survival for cetuximab, panitumumab, trifluridine/tipiracil (all three in colorectal cancer), sorafenib (in hepatocellular cancer) and nab-paclitaxel (nanoparticle albumin-bound paclitaxel) with gemcitabine (in pancreatic cancer) for all patients treated from May 2016 to March 2021. RESULTS: In our population, epidermal growth factor receptor inhibitors and trifluridine/tipiracil and sorafenib performed similarly to expected but nab-paclitaxel with gemcitabine in pancreatic cancer seemed to be no better than gemcitabine alone, when given within the current funding arrangements in England. CONCLUSIONS: Our results support the publication of national outcome data. If these results are confirmed on a larger cohort, it would support the reappraisal of certain drugs and provide further evidence to clinicians and patients when deciding the best treatment.

Celiac Plexus Neurolysis Is Associated With Decreased Survival in Patients With Pancreatic Cancer: A Propensity Score Analysis.

OBJECTIVE: The aim of this study was to investigate survival in patients who received celiac plexus neurolysis (CPN) compared with patients who received opioids. METHODS: The Surveillance, Epidemiology and End Results-Medicare database was used to identify patients older than 65 years diagnosed with pancreatic cancer between 2007 and 2015. We used claims data to identify patients with a history of CPN and opioid use within 1 year of diagnosis, and other demographic, clinical, and treatment variables. Kaplan-Meier analyses and inverse propensity-weighted adjusted Cox proportional hazard ratios were used to evaluate survival. RESULTS: We identified 648 patients who underwent CPN (19.0%) compared with 2769 patients who received opioids (81.0%). The median survival and interquartile range for patients who received CPN was 4.0 months (2.0-8.0 months) compared with 7.0 months (3.0-12.0 months) for opioid users (P < 0.0001). After adjusting for confounders and propensity score, the patients who received CPN showed worsened survival (hazard ratio, 1.69; 95% confidence interval, 1.59-1.79). CONCLUSIONS: Pancreatic cancer patients who underwent CPN had decreased survival compared with opioid users. This suggests that opioid sparing methods to reduce pancreatic cancer pain may actually be harmful. Future prospective studies should investigate whether other opioid sparing therapies impact pancreatic cancer survival.

Differences in receipt of multimodality therapy by race, insurance status, and socioeconomic disadvantage in patients with resected pancreatic cancer.

BACKGROUND AND METHODS: Racial and socioeconomic disparities in receipt of adjuvant chemotherapy affect patients with pancreatic cancer. However, differences in receipt of neoadjuvant chemotherapy among patients undergoing resection are not well-understood. A retrospective cross-sectional cohort of patients with resected AJCC Stage I/II pancreatic ductal adenocarcinoma was identified from the National Cancer Database (2014-2017). Outcomes included receipt of neoadjuvant versus adjuvant chemotherapy, or receipt of either, defined as multimodality therapy and were assessed by univariate and multivariate analysis. RESULTS: Of 19 588 patients, 5098 (26%) received neoadjuvant chemotherapy, 9624 (49.1%) received adjuvant chemotherapy only, and 4757 (24.3%) received no chemotherapy. On multivariable analysis, Black patients had lower odds of neoadjuvant chemotherapy compared to White patients (OR: 0.80, 95% CI: 0.67-0.97) but no differences in receipt of multimodality therapy (OR: 0.89, 95% CI: 0.77-1.03). Patients with Medicaid or no insurance, low educational attainment, or low median income had significantly lower odds of receiving neoadjuvant chemotherapy or multimodality therapy. CONCLUSIONS: Racial and socioeconomic disparities persist in receipt of neoadjuvant and multimodality therapy in patients with resected pancreatic adenocarcinoma. DISCUSSION: Policy and interventional implementations are needed to bridge the continued socioeconomic and racial disparity gap in pancreatic cancer care.