Neoadjuvant chemotherapy is associated with improved disease-free survival in pancreatic cancer patients undergoing pancreaticoduodenectomy with vascular resection.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NAC) is becoming favored for all pancreatic adenocarcinoma (PDAC). Patients with seemingly resectable disease infrequently still display vascular involvement intraoperatively. Outcomes following NAC versus upfront surgery in patients undergoing pancreaticoduodenectomy (PD) with vascular resection are unknown. METHODS: We performed a retrospective cohort study of PDAC patients who underwent PD with vascular resection between January 1, 2013, to December 31, 2020, within a single academic center. Clinicopathologic characteristics and disease-free survival (DFS) were compared between NAC versus upfront surgery cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. RESULTS: Eighty-one patients who underwent PD with vascular resection for PDAC were included. Forty-six patients (56%) received NAC. The NAC cohort more often had pathologic N0 status (47.8% vs. 8.6%, p < 0.001), had decreased vascular invasion (11% vs. 40%, p = 0.002), and completed chemotherapy (80% vs. 40%, p < 0.01). The NAC cohort demonstrated improved DFS (40.5 vs. 14.3 months, p = 0.007). In multivariable analysis, NAC remained independently associated with increased DFS (HR = 0.48, p = 0.02). CONCLUSIONS: NAC was associated with improved clinicopathologic outcomes and DFS in PD with vascular resection. These findings demonstrate the advantage of NAC in PDAC patients undergoing PD with vascular resection.

Clinical and pathological factors associated with survival in patients with pancreatic cancer who receive adjuvant therapy after neoadjuvant therapy: A retrospective multi-institutional analysis.

BACKGROUND: Neoadjuvant therapy is being increasingly used for patients with pancreatic cancer. The role of adjuvant therapy in these patients is unclear. The purpose of this study was to identify clinical and pathologic characteristics that are associated with longer overall survival in patients with pancreatic cancer who receive adjuvant therapy after neoadjuvant therapy. METHODS: This study was conducted using multi-institutional data. All patients underwent surgery after at least 1 cycle of neoadjuvant therapy for pancreatic cancer. Patients who died within 3 months after surgery and were known to have distant metastasis or macroscopic residual disease were excluded. Mann-Whitney U test, χ2 analysis, Kaplan-Meier plot, and univariate and multivariate Cox regression analysis were performed as statistical analyses. RESULTS: In the present study, 529 patients with resected pancreatic cancer after neoadjuvant therapy were reviewed. For neoadjuvant therapy, 177 (33.5%) patients received neoadjuvant chemotherapy, and 352 (66.5%) patients received neoadjuvant chemoradiotherapy. The median duration of neoadjuvant therapy was 7.0 months (interquartile range, 5.0-8.7). Patients were followed for a median of 23.0 months after surgery. Adjuvant therapy was administered to 297 (56.1%) patients and was not associated with longer overall survival for the entire cohort (24 vs 22 months, P = .31). Interaction analysis showed that adjuvant therapy was associated with longer overall survival in patients who received less than 4 months neoadjuvant therapy (hazard ratio 0.40; 95% confidence interval 0.17-0.95; P = .03) or who had microscopic margin positive surgical resections (hazard ratio 0.56; 95% confidence interval 0.33-0.93; P = .03). CONCLUSION: In this retrospective study, there was a survival benefit associated with adjuvant therapy for patients who received less than 4 months of neoadjuvant therapy or had microscopic positive margins.

Dual antiplatelet management in the perioperative period: updated and expanded systematic review.

BACKGROUND: Antiplatelet agents are central in the management of vascular disease. The use of dual antiplatelet therapy (DAPT) for the management of thromboembolic complications must be weighed against bleeding risk in the perioperative setting. This balance is critical in patients undergoing cardiac or non-cardiac surgery. The management of patients on DAPT for any indication (including stents) is not clear and there is limited evidence to guide decision-making. This review summarizes current evidence since 2015 regarding the occurrence of major adverse events associated with continuing, suspending, or varying DAPT in the perioperative period. METHODS: A research librarian searched PubMed and Cochrane from November 30, 2015 to May 17, 2022, for relevant terms regarding adult patients on DAPT for any reason undergoing surgery, with a perioperative variation in DAPT strategy. Outcomes of interest included the occurrence of major adverse cardiac events, major adverse limb events, all-cause death, major bleeding, and reoperation. We considered withdrawal or discontinuation of DAPT as stopping either aspirin or a P2Y12 inhibitor or both agents; continuation of DAPT indicates that both drugs were given in the specified timeframe. RESULTS: Eighteen observational studies met the inclusion criteria. No RCTs were identified, and no studies were judged to be at low risk of bias. Twelve studies reported on CABG. Withholding DAPT therapy for more than 2 days was associated with less blood loss and a slight trend favoring less transfusion and surgical re-exploration. Among five observational CABG studies, there were no statistically significant differences in patient death across DAPT management strategies. Few studies reported cardiac outcomes. The remaining studies, which were about procedures other than exclusively CABG, demonstrated mixed findings with respect to DAPT strategy, bleeding, and ischemic outcomes. CONCLUSION: The evidence base on the benefits and risks of different perioperative DAPT strategies for patients with stents is extremely limited. The strongest signal, which was still judged as low certainty evidence, is that suspension of DAPT for greater than 2 days prior to CABG surgery is associated with less bleeding, transfusions, and re-explorations. Different DAPT strategies' association with other outcomes of interest, such as MACE, remains uncertain. SYSTEMATIC REVIEW REGISTRATION: A preregistered protocol for this review can be found on the PROSPERO International Prospective Register of systematic reviews ( http://www.crd.york.ac.uk/PROSPERO/ ; registration number: CRD42022371032).

Endoscopic therapies for patients with obesity: a systematic review and meta-analysis.

BACKGROUND: Obesity is a major threat to public health and traditional bariatric surgery continues to have low utilization. Endoscopic treatments for obesity have emerged that offer less risk, but questions remain regarding efficacy, durability, and safety. We compared the efficacy of endoscopic bariatric procedures as compared to other existing treatments. METHODS: A literature search of Embase, Cochrane Central, and Pubmed was conducted from January 1, 2014 to December 7, 2021, including endoscopic bariatric therapies that were FDA or CE approved at the time of search to non-endoscopic treatments. Thirty-seven studies involving 15,639 patients were included. Primary outcomes included % total body weight loss (%TBWL), % excess body weight loss (%EBWL), and adverse events. Secondary outcomes included quality of life data and differences in hemoglobin A1C levels. Strength of clinical trial and observational data were graded according to the Cochrane methods. RESULTS: Intragastric balloons achieved greater %TBWL with a range of 7.6-14.1% compared to 3.3-6.7% with lifestyle modification at 6 months, and 7.5-14.0% compared to 3.1-7.9%, respectively, at 12 months. When endoscopic sleeve gastroplasty (ESG) was compared to laparoscopic sleeve gastrectomy (LSG), ESG had less %TBWL at 4.7-14.4% compared to 18.8-26.5% after LSG at 6 months, and 4.5-18.6% as compared to 28.4-29.3%, respectively, at 12 months. For the AspireAssist, there was greater %TBWL with aspiration therapy compared to lifestyle modification at 12 months, 12.1-18.3% TBWL versus 3.5-5.9% TBWL, respectively. All endoscopic interventions had higher adverse events rates compared to lifestyle modification. CONCLUSION: This review is the first to evaluate various endoscopic bariatric therapies using only RCTs and observational studies for evaluation of weight loss compared with conservative management, lifestyle modification, and bariatric surgery. Endoscopic therapies result in greater weight loss compared to lifestyle modification, but not as much as bariatric surgery. Endoscopic therapies may be beneficial as an alternative to bariatric surgery.

Laparoscopic compared to open approach for distal gastrectomy may reduce pneumonia risk for patients with gastric cancer.

Background: Whether laparoscopic approach to gastrectomy for gastric cancer (GC) reduces the risk of pneumonia remains unknown. In this study, we compared pneumonia outcomes for patients with GC who underwent either laparoscopic gastrectomy (LG) or open gastrectomy (OG). Methods: The ACS NSQIP database was queried to identify patients with GC who underwent LG or OG between Jan 2012 - Dec 2018. Outcomes were compared using regression models. A post-hoc analysis was performed for elderly patients. Results: The study cohort included 2661 patients, 23.4 % undergoing LG. Laparoscopic approach lowered pneumonia risk (OR 0.47, p = .028) and reduced hospital length of stay, (5.3 vs 7.1 days, p < .001). Elderly patients undergoing LG demonstrated similar benefits. Risk factors for pneumonia included advanced age, dyspnea and weight-loss, whereas laparoscopic approach reduced this risk. Conclusions: LG in patients with GC has both statistically and clinically significant advantages over OG with respect to pneumonia. Further studies are needed to validate the relationship between postoperative pneumonia and surgical approach for gastrectomy.

Surgical and Endoscopic Resection of Duodenal Neuroendocrine Tumors Have Similar Disease-Specific Survival Outcome.

BACKGROUND: Duodenal neuroendocrine tumors (dNETs) are rare, and their management is not well-defined. National Comprehensive Cancer Network (NCCN) guidelines recommend surgical resection of large dNETs (> 2 cm) and endoscopic resection of small tumors (< 2 cm). We compared the survival outcomes between surgical and endoscopic resection in various dNET sizes. METHODS: A retrospective cohort study was conducted using patient data from Surveillance, Epidemiology, and End Results Program (SEER) database. Variables analyzed included age, tumor size, grade, stage, and lymph node status. Disease-specific survival (DSS) was compared for endoscopic and surgical groups in dNET size strata: 0-0.5, 0.5-1, 1-2, 2-3, and > 3 cm. Kaplan-Meier and multivariable Cox proportional hazards models were used for survival analysis. RESULTS: The study included 465 patients, with 124 (26.7%) undergoing surgical resection. The average age was 61.9 years, and tumor sizes ranged from 0.1 to 10.5 cm. Endoscopic resection had 40.5% of tumors between 0 and 0.5 cm, while surgery had only 21% (p < 0.001). In the surgical cohort, 79.8% had grade 1 tumors compared to 88.3% in the endoscopy group (P = 0.024). Among surgically resected cases, 48.4% (60 patients) had lymph node involvement. Age, tumor size, grade, and stage did not significantly predict survival after surgical resection. Stratified by tumor size, no difference in DSS was observed between surgery and endoscopy groups. CONCLUSIONS: Endoscopic resection demonstrated similar survival outcomes to surgical resection across dNET sizes in this national analysis. Given the risks and the lack of survival benefits for surgery, endoscopic resection may be beneficial for both small and large tumors. Further studies are warranted to validate the current NCCN guidelines.

Learning Curves in Establishing a New Minimally Invasive Pancreas Program.

INTRODUCTION: Robotic pancreaticoduodenectomy (rPD) is a complex operation with a reported learning curve of 80 cases. Two recent graduates of a formal robotic complex general surgical oncology training program have been performing rPD at our institution since 2016, which had no previous institutional experience with rPD. OBJECTIVE: To evaluate the learning curve associated with developing a new robotic pancreaticoduodenectomy (rPD) program by fellowship trained surgeons with institutional support. METHODS: Sixty patients undergoing rPD from 2016 to 2022 were reviewed for and compared with proficiency benchmarks set by the University of Pittsburg experience. RESULTS: By 30 cases, operative time met the proficiency benchmark of 391 minutes. Additionally, the entire cohort had comparable rates of clinically relevant postoperative pancreatic fistula (6.7% vs 3%, P = .6), 30-day mortality (0% vs 3%, P = .18), major complications (Clavien >2; 23% vs 17%, P = .14), and length of stay (6 vs 7 days, P = .49) when compared to the benchmark. CONCLUSION: Perioperative outcomes were comparable to proficiency benchmarks from initiation of the new rPD program, and operative time reached proficiency benchmark by 30 cases. This data suggests that graduates of formal rPD training programs can safely establish new minimally invasive pancreas programs at sites with no previous institutional rPD experience.

Comparing Quality of Surgical Care Between the US Department of Veterans Affairs and Non-Veterans Affairs Settings: A Systematic Review.

In response to concerns about healthcare access and long wait times within the Veterans Health Administration (VA), Congress passed the Choice Act of 2014 and the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act of 2018 to create a program for patients to receive care in non-VA sites of care, paid by VA. Questions remain about the quality of surgical care between these sites in specific and between VA and non-VA care in general. This review synthesizes recent evidence comparing surgical care between VA and non-VA delivered care across the domains of quality and safety, access, patient experience, and comparative cost/efficiency (2015 to 2021). Eighteen studies met the inclusion criteria. Of 13 studies reporting quality and safety outcomes, 11 reported that quality and safety of VA surgical care were as good as or better than non-VA sites of care. Six studies of access did not have a preponderance of evidence favoring care in either setting. One study of patient experience reported VA care as about equal to non-VA care. All 4 studies of cost/efficiency outcomes favored non-VA care. Based on limited data, these findings suggest that expanding eligibility for veterans to get care in the community may not provide benefits in terms of increasing access to surgical procedures, will not result in better quality, and may result in worse quality of care, but may reduce inpatient length of stay and perhaps cost less.

Gastric outlet obstruction caused by heterotopic pancreas in a patient with alcohol use disorder.

INTRODUCTION AND IMPORTANCE: Heterotopic Pancreas (HP) is defined by the presence of pancreatic tissue in an anatomically distinct location from the main pancreas. While often clinically silent, it may present symptomatically. If located in the gastric antrum, HP may cause gastric outlet obstruction (GOO). The objective of this paper is to present a rare case of HP in the gastric antrum causing GOO. CASE PRESENTATION: Herein, we report a 43-year-old man who presented with abdominal pain and non-bilious emesis in the setting of COVID-19 infection and alcohol consumption. During the initial workup, computed-tomography (CT) was non-specific but demonstrated GOO, concerning for cancer. Cold forceps biopsies taken during esophagogastroduodenoscopy (EGD) confirmed benign HP. Since the patient was symptomatic from gastric outlet compression, he underwent resection via laparoscopic distal gastrectomy and Billroth II gastrojejunostomy. At 1-month postoperative follow-up, the patient recovered uneventfully. We hypothesized that GOO by HP in this case may have been associated with cumulative effects of alcohol consumption and COVID-19 infection on the ectopic tissue. CLINICAL DISCUSSION: HP is rare and difficult to diagnose preoperatively. When located in gastric antrum, HP can cause GOO, mimicking gastric malignancy. Combination of EGD/EUS, biopsy/FNA, and surgical resection are necessary to definitively make the diagnosis. Finally, it is important to consider that heterotopic pancreatitis or structural changes in HP may occur due to classic pancreatic stressors like alcohol and viral infections. CONCLUSION: HP may cause GOO presenting with non-bilious emesis and abdominal pain, mistaken for malignancy on CT imaging.

Higher Numbers of Examined Lymph Nodes Are Associated with Increased Survival in Resected, Treatment-Naïve, Node-Positive Esophageal, Gastric, Pancreatic, and Colon Cancers.

BACKGROUND OR PURPOSE: The role of extended lymphadenectomy as part of resection for lymph node (LN)-positive gastrointestinal (GI) malignancies remains controversial with no clear clinical guidance. The purpose of this retrospective study is to determine whether the number of LNs examined as part of GI malignancy resections affects overall survival (OS) among patients with node-positive esophageal, gastric, pancreatic, and colon cancers. METHODS: Participants with LN-positive GI cancers who were diagnosed between 2004 and 2015 and underwent oncologic resections were selected from National Cancer Database (NCDB). The primary predictor was the number of examined LNs categorized in tertiles. The effect on OS was measured by hazard ratio (HR) derived from multivariate Cox regression analyses. RESULTS: From 2004 to 2015, 1877, 10,086, 18,193, and 102,500 patients with LN-positive esophageal, gastric, pancreatic, and colon adenocarcinomas who did not receive neoadjuvant treatment and underwent oncologic tumor resection were registered in the NCDB. Using multivariate Cox proportional hazard modeling, greater LNs examined in surgically resected LN-positive GI cancers were found to be associated with increased OS for all histologies. This association was the strongest (as compared to the lowest tertile) for gastric cancer (middle tertile: HR = 0.91, 95% CI, 0.86-0.96, p = 0.001; highest tertile: HR = 0.73, 95% CI, 0.69-0.78, p < 0.001), followed by colon (highest tertile: HR = 0.86, 95% CI, 0.84-0.88, p < 0.001), esophageal (highest tertile: HR = 0.83, 95% CI, 0.72-0.95, p = 0.01), and pancreatic (highest tertile: HR = 0.93, 95% CI, 0.89-0.98, p = 0.002) cancers. DISCUSSION AND CONCLUSION: In patients with surgically resected node-positive GI malignancies who did not receive neoadjuvant systemic therapy, a higher number of examined LNs is associated with increased OS. This association is the strongest for gastric cancer, followed by colon, esophageal, and pancreatic cancers respectively.

Robotic versus open pancreaticoduodenectomy in elderly patients: a propensity score-matched analysis.

BACKGROUND: Pancreaticoduodenectomy (PD) is complex procedure with high morbidity in the elderly. This retrospective study aimed to compare post-operative outcomes in patients ≥75 years of age who underwent robot-assisted (RA)PD and open PD. METHODS: We analyzed 2502 patients ≥75 years of age who underwent PD from 2015 to 2018 in the National Surgical Quality Improvement Program (NSQIP) database. RAPD and open PD patients were propensity score matched 1:5 to assess the 30-day outcomes of interest: postoperative complications, length of stay, discharge destination, and readmissions. RESULTS: Of 725 matched patients, 110 underwent RAPD, 615 OPD, and 12 were converted to an open operation. Post-operative outcomes were largely similar between cohorts. RAPD was associated a shorter length of stay (median 8 days, interquartile range [IQR] 6 to 11) than OPD (median 8 days, IQR 7 to 13) (p = 0.003). However, RAPD was associated with more readmissions (28.1% vs. 17.7%; p = 0.02). CONCLUSIONS: RAPD in patients ≥75 years of age appears to be safe and has a similar complication profile to open PD. Randomized or well-designed prospective matched studies are needed to confirm these findings.

Trends in Robot-Assisted Procedures for General Surgery in the Veterans Health Administration.

INTRODUCTION: Implementation of robot-assisted procedures is growing. Utilization within the country's largest healthcare network, the Veterans Health Administration, is unclear. METHODS: A retrospective cohort study using data from the Department of Veterans Affairs Corporate Data Warehouse from January 2015 through December 2019. Trends in robot utilization for cholecystectomy, ventral hernia repair, and inguinal hernia repair were characterized nationally and regionally by Veterans Integrated Services Network. Patients, who underwent laparoscopic repairs for these procedures and open hernia repairs, were included to determine proportion performed robotically. RESULTS: We identified 119,191 patients, of which 5689 (4.77%) received a robotic operation. The proportion of operations performed robotically increased from 1.49% to 10.55% (7.08-fold change; slope, 2.14% per year; 95% confidence interval [0.79%, 3.49%]). Ventral hernia repair had the largest growth in robotic procedures (1.51% to 13.94%; 9.23-fold change; slope, 2.86% per year; 95% confidence interval [1.04%, 4.68%]). Regions with the largest increase in robotic utilization were primarily along the Northeast, Midwest, and West Coast. CONCLUSIONS: Robot utilization in general surgery is increasing at different rates across the United States in the Veterans Health Administration. Future studies should investigate the regional disparities and drivers of this approach.

Robot-Assisted General Surgery Procedures at the Veterans Health Administration: A Comparison of Surgical Techniques.

INTRODUCTION: The use of the robot in general surgery has exploded in the last decade. The Veterans Health Administration presents a unique opportunity to study differences between surgical approaches due to the ability to control for health system and insurance variability. This study compares clinical outcomes between robot-assisted and laparoscopic or open techniques for three general surgery procedures. METHODS: A retrospective observational study using the Veterans Affair Surgical Quality Improvement Program database. Operative time, length of stay, and complications were compared for cholecystectomy (robot-assisted versus laparoscopic), ventral, and inguinal hernia repair (robot-assisted versus laparoscopic or open) from 2015 to 2019. RESULTS: More than 80,000 cases were analyzed (21,652 cholecystectomy, 9214 ventral hernia repairs, and 51,324 inguinal hernia repairs). Median operative time was longer for all robot-assisted approaches as compared to laparoscopic or open techniques with the largest difference seen between open and robot-assisted primary ventral hernia repair (unadjusted difference of 93 min, P < 0.001). Median length of stay was between 1 and 4 d and significantly for robot-assisted ventral hernia repairs (versus open, P < 0.01; versus lap for recurrent hernia, P < 0.05). Specific postoperative outcomes of interest were overall low with few differences between techniques. CONCLUSIONS: While the robotic platform was associated with longer operative time, these findings must be interpreted in the context of a learning curve and indications for use (i.e., use of the robot for technically challenging cases). Our findings suggest that at the Veterans Health Administration, the robot is as safe a platform for common general surgery procedures as traditional approaches. Future studies should focus on patient-centered outcomes including pain and cosmesis.

Disparities in Utilization and Outcomes of Minimally Invasive Techniques for Gastric Cancer Surgery in the United States.

BACKGROUND: This study investigated national implementation patterns and perioperative outcomes of minimally invasive gastrectomy (MIG) in gastric cancer surgery in the United States. METHODS: The National Inpatient Sample (NIS) was queried for patients who underwent elective gastrectomy for gastric cancer from 2008-2018. The MIG versus open gastrectomy approach was correlated with hospital factors, patient characteristics, and complications. RESULTS: There was more than a fivefold increase in MIG from 5.8% in 2008 to 32.9% in 2018 (nptrend < 0.001). Patients undergoing MIG had a lower Elixhauser Comorbidity Index (p = 0.001). On risk adjusted analysis, black patients (AOR = 0.77, p = 0.024) and patients with income below 25th percentile (AOR = 0.80, p = 0.018) were less likely to undergo MIG. When these analyses were limited to minimally invasive capable centers only, these differences were not observed. Hospitals in the upper tertile of gastrectomy case volume, Northeast, and urban teaching centers were more likely to perform MIG. Overall, MIG was associated with a 0.7-day decrease in length of stay, reduced risk adjusted mortality rates (AOR = 0.58, p = 0.05), and a $4,700 increase in total cost. CONCLUSIONS: In this national retrospective study, we observe socioeconomic differences in patients undergoing MIG, which is explained by hospital level factors in MIG utilization. We demonstrate that MIG is associated with a lower mortality compared with open gastrectomy. Establishing MIG as a safe approach to gastric cancers and understanding regional differences in implementation patterns can inform delivery of equitable high-quality health care.

18F-FDG PET/CT Imaging Biomarkers for Early and Late Evaluation of Response to First-Line Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma.

The purpose of this study was to evaluate 18F-FDG PET/CT as an early and late interim imaging biomarker in patients with pancreatic ductal adenocarcinoma who undergo first-line systemic therapy. Methods: This was a prospective, single-center, single-arm, open-label study (IRB12-000770). Patient receiving first-line chemotherapy were planned to undergo baseline 18F-FDG PET/CT, early interim 18F-FDG PET/CT, and late interim 18F-FDG PET/CT. Cutoffs for metabolic and radiographic tumor response assessment as selected and established by receiver-operating-characteristic analysis were applied (modified PERCIST/RECIST1.1). Patients were followed to collect data on further treatments and overall survival. Results: The study population consisted of 28 patients who underwent baseline 18F-FDG PET/CT. Twenty-three of these (82%) underwent early interim 18F-FDG PET/CT, and 21 (75%) underwent late interim 18F-FDG PET/CT. Twenty-three deaths occurred during a median follow-up period of 14 mo (maximum follow-up, 58.3 mo). The median overall survival was 36.2 mo (95% CI, 28 mo to not yet reached [NYR]) in early metabolic responders (6/23 [26%], P = 0.016) and 25.4 mo (95% CI, 19.6 mo-NYR) in early radiographic responders (7/23 [30%], P = 0.16). The median overall survival was 27.4 mo (95% CI, 21.4 mo-NYR) in late metabolic responders (10/21 [48%], P = 0.058) and 58.2 mo (95% CI, 21.4 mo-NYR) in late radiographic responders (7/21 [33%], P = 0.008). Conclusion: 18F-FDG PET may serve as an early interim imaging biomarker (at ∼4 wk) for evaluation of response to first-line chemotherapy in patients with pancreatic ductal adenocarcinoma. Radiographic changes might be sufficient for response evaluation after the completion of first-line chemotherapy.

Correlation of 68Ga-FAPi-46 PET Biodistribution with FAP Expression by Immunohistochemistry in Patients with Solid Cancers: Interim Analysis of a Prospective Translational Exploratory Study.

Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts confer treatment resistance and promote metastasis and immunosuppression. Because FAP is overexpressed in many cancers, radiolabeled molecules targeting FAP are studied for their use as pancancer theranostic agents. This study aimed to establish the spectrum of FAP expression across various cancers by immunohistochemistry and to explore whether 68Ga FAP inhibitor (FAPi)-46 PET biodistribution faithfully reflects FAP expression from resected cancer and non-cancer specimens. Methods: We conducted a FAP expression screening using immunohistochemistry on a pancancer human tissue microarray (141 patients, 14 different types of cancer) and an interim analysis of a prospective exploratory imaging trial in cancer patients. Volunteer patients underwent 1 whole-body 68Ga-FAPi-46 PET/CT scan and, subsequently, surgical resection of their primary tumor or metastasis. 68Ga-FAPi-46 PET SUVmax and SUVmean was correlated with FAP immunohistochemistry score in cancer and tumor-adjacent non-cancer tissues for each patient. Results: FAP was expressed across all 14 cancer types on tissue microarray with variable intensity and frequency, ranging from 25% to 100% (mean, 76.6% ± 25.3%). Strong FAP expression was observed in 50%-100% of cancers of the bile duct, bladder, colon, esophagus, stomach, lung, oropharynx, ovary, and pancreas. Fifteen patients with various cancer types (colorectal [n = 4], head and neck [n = 3], pancreas [n = 2], breast [n = 2], stomach [n = 1], esophagus [n = 2], and uterus [n = 1]) underwent surgery after their 68Ga-FAPi-46 PET/CT scan within a mean interval of 16.1 ± 14.4 d. 68Ga-FAPi-46 SUVs and immunohistochemistry scores were higher in cancer than in tumor-adjacent non-cancer tissue: mean SUVmax 7.7 versus 1.6 (P < 0.001), mean SUVmean 6.2 versus 1.0 (P < 0.001), and mean FAP immunohistochemistry score 2.8 versus 0.9 (P < 0.001). FAP immunohistochemistry scores strongly correlated with 68Ga-FAPi 46 SUVmax and SUVmean: r = 0.781 (95% CI, 0.376-0.936; P < 0.001) and r = 0.783 (95% CI, 0.379-0.936; P < 0.001), respectively. Conclusion: In this interim analysis of a prospective exploratory imaging trial, 68Ga-FAPi-46 PET biodistribution across multiple cancers strongly correlated with FAP tissue expression. These findings support further exploration of FAPi PET as a pancancer imaging biomarker for FAP expression and as a stratification tool for FAP-targeted therapies.

Pathological treatment response has different prognostic implications for pancreatic cancer patients treated with neoadjuvant chemotherapy or chemoradiotherapy.

BACKGROUND: Pathological treatment effect of resected pancreatic adenocarcinoma after neoadjuvant therapy has prognostic implications. The impact for patients who received chemotherapy alone or chemoradiotherapy is not well defined. METHODS: Patients with localized pancreatic adenocarcinoma who had pancreatectomy after neoadjuvant therapy at 3 centers from 2011 to 2017 were retrospectively analyzed. The chemotherapy and chemoradiotherapy groups were evaluated separately. RESULTS: Of 525 patients, 148 received neoadjuvant chemotherapy and 377 received chemoradiotherapy. The chemoradiotherapy group had a better treatment effect (score 0: 10%, score 1: 30%, score 2: 42%, and score 3: 18%) than the chemotherapy group (score 0: 2%, score 1: 8%, score 2: 35%, and score 3: 55%) (P < .001). Median overall survival was similar between the 2 groups (25.8 vs 26.4 months). Median overall survival for score 0/1, 2, or 3 was 72.2, 38.5, and 20.0 months in the chemotherapy group and 37.9, 24.5, and 19.0 months in the chemoradiotherapy group. Score 2 in the chemotherapy group was associated with better overall survival compared to score 3 (adjusted hazard ratio: 0.49, P = .005), whereas only combined score 0/1 reached significance over score 2 for the chemoradiotherapy group (hazard ratio: 0.63, P = .006). CONCLUSION: The prognostic significance of pathological treatment effect for localized pancreatic adenocarcinoma differs for patients receiving neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy.