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Background Limited data from small series have suggested that brain metastases from biliary tract cancers (BrM-BTC) affect ≤2% of patients with BTC. We sought to review our experience with patients with BrM-BTC and to identify associations of tumor-related molecular alterations with outcomes. Materials and Methods A retrospective review of patients with BTC seen at a tertiary referral center from 2005 to 2021 was performed; patients with BrM-BTC were identified, and clinical and molecular data were collected. Results Twenty-one of 823 patients with BTC (2.6%) developed BrM. For patients with BrM-BTC, median follow-up time was 27.9 months after primary BTC diagnosis and 3.1 months after BrM diagnosis. Median time from primary diagnosis to diagnosis of BrM was 14.4 [range, 1.1-66.0] months. Median overall survival (OS) from primary diagnosis was 31.5 [2.9-99.8] months and median OS from BrM diagnosis was 4.2 [0.2-33.8] months. Patients who underwent BrM-directed therapy trended toward longer OS following BrM diagnosis than patients receiving supportive care only (median 6.5 vs 0.8 months, P = .060). The BrM-BTC cohort was enriched for BRAF (30%), PIK3CA (25%), and GNAS (20%) mutations. patients with BrM-BTC with BRAF mutations trended toward longer OS following BrM diagnosis (median 13.1 vs 4.2 months, P = .131). Conclusion This is the largest series of patients with BrM-BTC to date and provides molecular characterization of this rare subgroup of patients with BTC. Patients with BrM-BTC may be more likely to have BRAF mutations. With advances in targeted therapy for patients with BTC with actionable mutations, continued examination of shifting patterns of failure, with emphasis on BrM, is warranted.

The value of individual variable contributions to post-hepatectomy length of stay (LOS) are difficult to quantify within bundled care pathways.Poisson regression and marginal effects models for prolonged post-hepatectomy LOS (25% median) included Kawaguchi-Gayet (KG) complexity, perioperative variables, and pathways (minimally-invasive = MIS; low-intermediate-risk = KGI/II; high-risk = KGIII; combination).Median LOS was 2, 4, 5, and 5 days for MIS, KGI/II, KGIII and combination pathways (N = 978). Poisson regression identified age, intraoperative fluids, delayed diet tolerance, and combination cases as associated with increased LOS (p 0.01). Marginal effects analysis demonstrated the following added probability of longer LOS: each year of age 0.03x, 250 mL intraoperative fluids 0.06x, each operative hour 0.2x, additional day before diet tolerance 0.4x, combination cases 0.7x. MIS was associated with 1.2x increased probability of shorter LOS.Optimizing intraoperative fluids, operative time, and postoperative diet, while favoring MIS approach when feasible, may maximize effects of post-hepatectomy care pathways to reduce LOS.

Background Enhanced Recovery After Surgery (ERAS) has been widely applied in liver surgery since the publication of the first ERAS guidelines in 2016. The aim of the present article was to update the ERAS guidelines in liver surgery using a modified Delphi method based on a systematic review of the literature. Methods A systematic literature review was performed using MEDLINE/PubMed, Embase, and the Cochrane Library. A modified Delphi method including 15 international experts was used. Consensus was judged to be reached when >80% of the experts agreed on the recommended items. Recommendations were based on the Grading of Recommendations, Assessment, Development and Evaluations system. Results A total of 7541 manuscripts were screened, and 240 articles were finally included. Twenty-five recommendation items were elaborated. All of them obtained consensus (>80% agreement) after 3 Delphi rounds. Nine items (36%) had a high level of evidence and 16 (64%) a strong recommendation grade. Compared to the first ERAS guidelines published, 3 novel items were introduced: prehabilitation in high-risk patients, preoperative biliary drainage in cholestatic liver, and preoperative smoking and alcohol cessation at least 4 weeks before hepatectomy. Conclusions These guidelines based on the best available evidence allow standardization of the perioperative management of patients undergoing liver surgery. Specific studies on hepatectomy in cirrhotic patients following an ERAS program are still needed.

Dye design can influence the ability of fluorescently labeled imaging agents to generate tumor contrast and has become an area of significant interest in the field of fluorescence-guided surgery (FGS). Here, we show that the charge-balanced near-infrared fluorescent (NIRF) dye FNIR-Tag enhances the imaging properties of a fluorescently labeled somatostatin analogue.

Identification of circulating tumor DNA (ctDNA) following curative intent therapies is a surrogate for microscopic residual disease for patients with metastatic colorectal cancer (mCRC). Preclinically, in micrometastatic microsatellite stable (MSS) colorectal cancer, increased TGFβ signaling results in exclusion of antitumor cytotoxic T cells from the tumor microenvironment. Bintrafusp alfa (BA) is a bifunctional fusion protein composed of the extracellular domain of the TGFβRII receptor (“TGFβ trap”) and anti-PD-L1 antibody. Patients with liver-limited, MSS mCRC and with detected ctDNA after complete resection of all known tumors and standard-of-care therapy were treated with 1,200 mg of BA intravenously every 14 days for six doses. The primary endpoint was ctDNA clearance. Radiographic characteristics at recurrence were compared using independent t tests to historical data from a similar cohort of patients with liver-limited mCRC who underwent observation. Only 4 of 15 planned patients received BA before the study was stopped early for loss of equipoise. There was no grade ≥3 adverse event. None of the patients cleared ctDNA. All patients developed radiographic recurrence by the first planned restaging. Although not detectable at prior to treatment, TGFβ3 was found in circulation in all patients at cycle 2 day 1. Compared with a historical cohort, patients administered BA developed more metastases (15 vs. 2, P = 0.005) and greater tumor volumes (9 cm vs. 2 cm, P = 0.05). Treatment with BA in patients with ctDNA-detected, liver-limited mCRC did not clear ctDNA and was associated with large-volume recurrence, highlighting the potential context-specific complexity of dual TGFβ and PD-L1 inhibition. Significance: Use of ctDNA to identify patients with micrometastatic disease for therapeutic intervention is feasible. Treatment with BA in patients with liver-limited mCRC and with detectable ctDNA after resection generated rapid progression. Approaches targeting TGFβ signaling must consider its pathway complexity in future immunotherapy combination strategies.

As minimally invasive surgery (MIS) approaches to biliary tract cancers become more commonplace, understanding the adequacy of their oncologic performance is key.The National Cancer Database 2010-2016 was queried for patients who underwent hepatectomy for intrahepatic cholangiocarcinoma (IHC) and T1b or more advanced gallbladder cancer (GBC). Patients were grouped by approach: open (OA), laparoscopic (LA), and robotic (RA). Margin status, rate of lymph node (LN) dissection, and yield of LN dissection were evaluated.This cohort of 8612 patients, including 4034 patients with IHC (OA: 3281, LA: 675, RA: 78) and 4578 patients with GBC (OA: 1893, LA: 2588, RA: 97), MIS was used 40% of the time. R0 resection was achieved in 82% OA, 84% LA, and 91% RA, p = 0.004. Rate of LN dissection was 53% (OA: 60%, LA: 42%, RA: 51%, p 0.001). Among patients who underwent lymphadenectomy, 6 + LN were retrieved less commonly with a LA (OA: 27%, LA: 20%, and RA: 30%, p 0.001). High-volume MIS hepatectomy centers were more likely to perform a lymphadenectomy (odds ratio [OR]: 1.41) and a sampling of 6 + LN (OR: 1.18).Regardless of approach, lymphadenectomy is underperformed nationwide for biliary tract tumors, particularly with LA. As the use of MIS grows for the treatment of biliary tract cancers, scrutiny of oncologic outcomes is required.

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Identification of circulating tumor DNA (ctDNA) following curative intent therapies is a surrogate for microscopic residual disease for patients with metastatic colorectal cancer (mCRC). Preclinically, in micrometastatic microsatellite stable (MSS) colorectal cancer, increased TGFβ signaling results in exclusion of antitumor cytotoxic T cells from the tumor microenvironment. Bintrafusp alfa (BA) is a bifunctional fusion protein composed of the extracellular domain of the TGFβRII receptor (“TGFβ trap”) and anti-PD-L1 antibody. Patients with liver-limited, MSS mCRC and with detected ctDNA after complete resection of all known tumors and standard-of-care therapy were treated with 1,200 mg of BA intravenously every 14 days for six doses. The primary endpoint was ctDNA clearance. Radiographic characteristics at recurrence were compared using independent t tests to historical data from a similar cohort of patients with liver-limited mCRC who underwent observation. Only 4 of 15 planned patients received BA before the study was stopped early for loss of equipoise. There was no grade ≥3 adverse event. None of the patients cleared ctDNA. All patients developed radiographic recurrence by the first planned restaging. Although not detectable at prior to treatment, TGFβ3 was found in circulation in all patients at cycle 2 day 1. Compared with a historical cohort, patients administered BA developed more metastases (15 vs. 2, P = 0.005) and greater tumor volumes (9 cm vs. 2 cm, P = 0.05). Treatment with BA in patients with ctDNA-detected, liver-limited mCRC did not clear ctDNA and was associated with large-volume recurrence, highlighting the potential context-specific complexity of dual TGFβ and PD-L1 inhibition.Significance:Use of ctDNA to identify patients with micrometastatic disease for therapeutic intervention is feasible. Treatment with BA in patients with liver-limited mCRC and with detectable ctDNA after resection generated rapid progression. Approaches targeting TGFβ signaling must consider its pathway complexity in future immunotherapy combination strategies.

Purpose:Clinically available intraoperative imaging tools to assist surgeons in identifying occult lesions are limited and partially responsible for the high rate of disease recurrence in patients with neuroendocrine tumors (NET). Using the established clinical efficacy of radiolabeled somatostatin analogs as a model, we demonstrate the ability of a fluorescent somatostatin analog to selectively target tumors that overexpress somatostatin receptor subtype-2 (SSTR2) and demonstrate utility for fluorescence-guided surgery (FGS).Experimental Design:A multimodality chelator (MMC) was used as a “radioactive linker” to synthesize the fluorescently labeled somatostatin analog, 67/68Ga-MMC(IR800)-TOC. In vivo studies were performed to determine the pharmacokinetic profile, optimal imaging time point, and specificity for SSTR2-expressing tissues. Meso- and microscopic imaging of resected tissues and frozen sections were also performed to further assess specific binding, and binding to human NETs was examined using surgical biospecimens from patients with pancreatic NETs.Results:Direct labeling with 67Ga/68Ga provided quantitative biodistribution analysis that was in agreement with fluorescence data. Receptor-mediated uptake was observed in vivo and ex vivo at the macro-, meso-, and microscopic scales. Surgical biospecimens from patients with pancreatic NETs also displayed receptor-specific agent binding, allowing clear delineation of tumor boundaries that matched pathology findings.Conclusions:The radioactive utility of the MMC allowed us to validate the binding properties of a novel FGS agent that could have a broad impact on cancer outcomes by equipping surgeons with real-time intraoperative imaging capabilities.

Supplementary figures and tables. "Clean" version.

BACKGROUND We evaluated the associations of surgical margin status and somatic mutations with the incidence of local recurrence (LR) and oncologic outcomes in patients undergoing R0-intent (microscopically negative margin) resection of colorectal liver metastases (CLM). METHODS Patients with CLM who underwent initial R0-intent resection and analysis of tumor tissue using next-generation sequencing during 2001-2018 were analyzed. Recurrences were classified as LR (at the resection margin), other intrahepatic recurrence, or extrahepatic recurrence. Predictors and survival effect of LR were evaluated using univariate and multivariate analysis. RESULTS Of 552 patients analyzed, 415 (75%) had R0 resection (margin width ≥ 1.0 mm), and 38 (7%) had LR. LR incidence was not affected by surgical margin width. RAS/TP53 co-mutation was associated with increased risk of intrahepatic recurrence (67% vs. 49%; p 8 cycles of preoperative chemotherapy (HR, 1.98; p = 0.033), tumor viability ≥ 50% (HR, 1.55; p = 0.007), RAS/TP53 co-mutation (HR, 1.69; p = 0.001), and SMAD4 mutation (HR, 2.44; p

To evaluate the association between staging concordance, treatment sequencing, and response to neoadjuvant therapy (NAT) on the survival of patients with pancreatic ductal adenocarcinoma (PDAC).NAT is increasingly utilized in the management of patients with PDAC, but it is unclear whether its benefit is contingent on tumor down-staging.This was a cohort study of stage I-III PDAC patients in the National Cancer Database (2006-2015) treated with upfront resection or NAT followed by surgery. We determined staging concordance using patients' clinical and pathological staging data. For NAT patients, we used Bayesian analysis to ascertain staging concordance accounting for down-staging.Among 16,597 patients treated at 979 hospitals, 13,982 had an upfront resection and 2,615 NAT followed by surgery. Overall survival (OS) at 5-years ranged from 26.0% (95% CI 24.9%-27.1%) among cT1-2N0 patients to 18.6% (17.9%-19.2%) among cT1-3N+ ones. Patients with cT3-4 or cN+ tumors had improved OS after NAT compared to upfront surgery (all p0.001), while there was no difference among patients with cT1-2N0 (P = 0.16) disease. Relative to accurately staged cT1-2-3N+ or cT4 patients treated with upfront surgery, NAT was associated with a lower risk of death [HR 0.46 (0.37-0.57) for N+; HR 0.56 (0.40-0.77) for T4 disease], even among those without tumor down-staging [HR 0.81 (0.73-0.90) for N+; HR 0.48 (0.39-0.60) for T4].NAT is associated with improved survival for PDAC, particularly for patients with more advanced disease and regardless of down-staging. Consideration should be given to recommending NAT for all PDAC patients.

The past 20 years have seen advances in colorectal cancer management. We sought to determine whether survival in patients undergoing resection of colorectal liver metastases (CLM) has improved in association with three landmark advances: introduction of irinotecan- and/or oxaliplatin-containing regimens, molecular targeted therapy, and multigene alteration testing. Patients undergoing CLM resection during 1998–2014 were identified and grouped by resection year. The influence of alterations in RAS, TP53, and SMAD4 was evaluated and validated in an external cohort including patients with unresectable metastatic colorectal cancer. Of 1961 patients, 1599 met the inclusion criteria. Irinotecan- and/or oxaliplatin-containing regimens and molecular targeted therapy were used for more than 50% of patients starting in 2001 and starting in 2006, respectively, so patients were grouped as undergoing resection during 1998–2000, 2001–2005, or 2006–2014. Liver resectability indications expanded over time. The 5-year overall survival (OS) rate was significantly better in 2006–2014, vs. 2001–2005 (56.5% vs. 44.1%, P

Socioeconomic- and demographic-based disparities exist in the treatment of pancreatic adenocarcinoma (PDAC). Medicaid expansion (ME) may have an impact on these disparities. Analyses of patients with PDAC from the National Cancer Database (NCDB) were performed to examine the impact of ME on access to treatment and outcomes. Patients with non-metastatic PDAC diagnosed between 2006 and 2016 were identified. Multiple logistic regression analyses were performed to evaluate factors associated with curative-intent surgical resection, multimodal therapy, treatment at a high-volume facility (HVF), and survival. The study identified 41,876 patients who met the criteria. Medicaid expansion was independently associated with curative-intent resection (odds ratio [OR] 1.54; 95 % confidence interval [CI] 1.43–1.67; p < 0.001). In a multivariable analysis, ME was independently associated with multimodal therapy (OR 1.60; 95 % CI 1.44–1.76; p < 0.001) and treatment at an HVF (OR 1.57; 95 % CI 1.42–1.74; p < 0.001). Medicaid expansion was independently associated with improved 30-day mortality (OR 0.49; 95 % CI 0.34–0.79) and 90-day mortality (OR 0.48 95 % CI 0.35–0.59). Cox regression analysis demonstrated that after adjustment for other variables, ME status was associated with improved overall survival (hazard ratio [HR], 0.82; 95 % CI 0.73–0.90; p < 0.001). Medicaid expansion is associated with increased use of care processes that improve outcomes in PDAC, operative outcomes, and overall survival. The study data suggest that ME has helped to improve disparities in PDAC in ME states.

Hepatocellular carcinoma (HCC) commonly affects patients with cirrhosis. Patients with early-stage disease may be treated with surgery, liver transplantation, and locoregional therapy (e.g., thermal ablation and chemoembolization). The treatment efficacy of thermal ablation can be limited by factors such as proximity to adjacent vessels, which may create a heat sink effect. The heat sink effect can be mitigated by intravascular balloon occlusion. Our case report demonstrates the utility of balloon occlusion during thermal ablation of HCC adjacent to the right hepatic vein complicated by hepatic vein thrombosis.

Background Adequate lymphadenectomy (AL) during surgical resection and delivery of multimodality therapy (MMT) are considered important for optimizing oncologic outcomes in patients with locally advanced gastric cancer. Both neoadjuvant and adjuvant approaches to MMT delivery are considered acceptable treatment strategies. Our goal was to evaluate the association between MMT treatment approach, hospital practice patterns, and survival and to explore whether AL and MMT might represent measures of quality for locally advanced gastric cancer. Methods A national cohort study of 5433 patients with locally advanced gastric cancer (≥cT2 and/or cN+) treated at 987 hospitals within the National Cancer Database (2006-2015). Patients were categorized as receiving a neoadjuvant therapy (NT) or adjuvant therapy (AT) approach. Patients were also categorized based on receipt of AL (≥15 nodes) and MMT (surgery with any preoperative, perioperative, or postoperative AT). Hospitals were stratified based on the predominant treatment approach and the proportion of patients that achieved performance benchmarks (AL ≥ 80%; MMT ≥ 75%). Multivariable Cox shared frailty modeling was used to evaluate the association with the overall risk of death. Results Overall, 54.5% of patients were treated with an AT and 45.6% with an NT approach. Relative to surgery alone, receipt of MMT by either approach was associated with decreased risk of death (NT-hazard ratio [HR]: 0.75, 95% confidence interval: [0.65-0.86]; AT-HR: 0.80 [0.71-0.90]). Relative to care at mixed pattern hospitals, care at predominantly AT hospitals was associated with an increased risk of death (HR: 1.28 [1.12-1.47]). Relative to patients whose care achieved no quality measures, AL (HR: 0.75, [0.67-0.82]) and MMT (HR: 0.68 [0.60-0.76]) were each associated with a reduced risk of death. Receipt of both measures was associated with an even greater reduction (HR: 0.47 [0.40-0.56]). Hospital performance on AL, MMT, or both measures was not associated with the risk of death. Conclusion Because over half of patients are treated with surgery first (many having surgery alone) and care at hospitals favoring a surgery first approach is associated with worse outcomes, quality improvement (QI) efforts should focus on increasing the use of NT strategies. Furthermore, delivery of AL and MMT together may represent an actionable, generalizable target for gastric cancer QI efforts because it improves survival and is unrelated to the context in which care is provided.

The expansion of robotic surgery requires identifying factors of competent robotic bedside assisting. Surgical trainees desire more robotic console time, and we hypothesized that protocolized robotic surgery bedside training could equip Advanced Practice Providers (APPs) to meet this growing need. No standardized precedent exists for training APPs.We designed a pilot study consisting of didactic and clinical skills. APPs completed didactic tests followed by proctored clinical skills checklists intraoperatively. Operating surgeons scored trainees with 10-point Likert scale (5 not confident,5 = confident). APPs scoring5 advanced to a solo practicum. Competence was defined as: didactic test score75Of 10 APP trainees, 5 passed on initial attempt. After individualized development plans, 4 passed retesting. Differences in trainee factors were not statistically significant, but the probability of passing the practicum was50% if more than four checklists were needed.Clinical experience, not didactic knowledge, determines the probability of intraoperative competence. Increasing clinical proctoring did not result in higher probability of competence. Early identification of APPs needing individualized improvement increases the proportion of competent APPs.

While surgery is a mainstay of curative-intent treatment for patients with intrahepatic cholangiocarcinoma (IHC), the role of neoadjuvant therapy (NT) has not been well-established. We sought to describe trends in NT utilization, characterize associated factors, and evaluate association with overall survival (OS). Retrospective cohort study of 4456 surgically resected IHC patients within National Cancer Data Base (2006–2016). NT included chemotherapy alone and/or (chemo)radiation. Descriptive statistics used to describe the cohort. Multivariable hierarchical logistic regression models were used to examine factors associated with NT administration. Analyses conducted comparing OS among upfront surgery patients and NT patients using propensity matching using nearest-neighbor methodology and adjustment using inverse probability of treatment weighting (IPTW). Association between NT and risk of death evaluated using multivariable Cox shared frailty modeling. Utilization of NT did not significantly increase over time (11%-2006 to 16%-2016, trend test p = 0.07) but did increase among patients with clinical nodal involvement (cN+, 13% to 36%, p = 0.002). Factors associated with NT use include cN+ disease (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.31–2.15) and advanced clinical T stage: T2 (OR 1.65, 95% CI 1.33–2.06); T3 (OR 1.51, 95% CI 1.13–2.02). After propensity matching, NT associated with a 23% decreased risk of death relative to upfront surgery (hazard ratio [HR] 0.77, 95% CI 0.61–0.97). Findings were similar after IPTW (HR 0.83, 95% CI 0.78–0.88). NT is increasingly used for the management of IHC patients with characteristics indicating aggressive tumor biology and is associated with decreased risk of death. These data suggest need for prospective studies of NT in management of patients with potentially resectable IHC.

Background Serologic and anthropometric measures are commonly used as surrogate markers of nutritional status in clinical practice. In 2012, leading dietetic organizations published a standard definition of malnutrition based on clinical characteristics. We hypothesize that surrogate markers underrecognize clinical malnutrition and do not accurately identify patients at risk for adverse outcomes. Methods A single-institution cohort study of elective surgical inpatients from August 2015 to November 2017. Nutritional assessment was completed by trained registered dietitians using leading dietetic guidelines. Multivariable logistic regression was used to determine the association between malnutrition and perioperative outcomes. Results Among 953 elective surgical admissions, 456 underwent full clinical nutritional assessment. Of these, 202 (44.3%) met malnutrition criteria. In addition, 20.3% of patients with clinical malnutrition were underweight ( Conclusion In this cohort of elective surgical patients, traditional markers failed to identify malnutrition in a substantial portion of patients who met clinical malnutrition criteria. Clinical malnutrition assessment is effective in identifying patients who may be at risk for suboptimal outcomes. Surgeons should implement clinical nutritional assessment and factor that information into their preoperative evaluation and management of elective surgical patients.

Neoadjuvant therapy (NAT) is increasingly being used in the management of patients with resectable pancreatic ductal adenocarcinoma (PDAC); however, there is a lack of evidence regarding the benefit among these patients. The aim of this study was to evaluate overall survival (OS) in PDAC patients with resectable disease treated with NAT or upfront resection through instrumental variable (IV) analysis. A national cohort study of resectable PDAC patients in the National Cancer Data Base (2007–2015) treated with either upfront surgery or resection after NAT. Using multivariable modeling and IV methods, OS was compared between those treated with NAT and upfront resection. The IV was hospital-level NAT utilization in the most recent year prior to treatment. The cohort included 16,666 patients (14,012 upfront resection; 2654 NAT) treated at 779 hospitals. Among those treated with upfront resection, 59.9% received any adjuvant therapy. NAT patients had higher median (27.9 months, 95% confidence interval [CI] 26.2–29.1) and 5-year OS (24.1%, 95% CI 21.9–26.3%) compared with those treated with upfront surgery (median 21.2 months, 95% CI 20.7–21.6; 5-year survival 20.9%, 95% CI 20.1–21.7%). After multivariable modeling, NAT was associated with an approximately 20% decrease in the risk of death (hazard ratio [HR] 0.78, 95% CI 0.73–0.84), and this effect was magnified in the IV analysis (HR 0.61, 95% CI 0.47–0.79). In patients with resectable PDAC, NAT is associated with improved survival relative to upfront resection. Given the benefits of multimodality therapy and the challenges in receiving adjuvant therapy, consideration should be given to treating all PDAC patients with NAT.

Background Decisions about multimodality treatment for upper gastrointestinal malignancies are largely predicted on clinical staging information. However, hospital-level accuracy of clinical staging is currently unknown. Methods A national cohort study of patients with adenocarcinoma of the esophagus, stomach, or pancreas in the NCDB (2006-2015) who were treated with upfront resection. Hospital-level staging accuracy (ascertained by comparing clinical stage to pathologic stage) was calculated. Within hospital correlation of staging accuracy across disease sites was evaluated using risk and reliability adjustment. Results Overall, 1246 hospitals were evaluated. Median hospital T-staging accuracy was 77.5%, 73.7%, and 60.8% for esophageal, gastric, and pancreatic cancer, respectively. Median hospital N-staging accuracy was 80.2%, 72.9%, and 61.8%, respectively. For T-stage, over-staging was most frequently observed in esophageal patients (11.2%) while under-staging was most frequent in pancreatic patients (36.1%). For N-stage, over-staging was infrequent for all three, while under-staging was most common in pancreatic patients (37.4%). Correlation across disease sites was weak for both T- (best observed, r = .34) and N-stages (r = .30). When high volume hospitals were evaluated, correlation improved but accuracy rates were similar. Conclusions Despite the importance of clinical staging in multimodality treatment planning, hospitals inaccurately stage 20-40% of patients, with low correlation across disease sites.

The management of localized hepatocellular carcinoma (HCC) is complex and requires multidisciplinary consideration. In times of crisis when resources are limited and the health of patients might be compromised, as is the case with COVID-19, a strategic approach that takes into account tumor characteristics, patient factors, and available treatment options can optimize patient outcomes while balancing resource utilization. Herein, we detail our group's management strategy for patients with localized HCC during the global pandemic that carefully considers individual patient needs and those of the institutional workforce, the local healthcare system, and the greater patient community we serve.

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, governmental agencies, state medical boards, and healthcare organizations have called for restricting “elective” operations to mitigate the risk of transmission of the virus amongst patients and healthcare providers and to preserve essential resources for potential regional surges of COVID patients. While the fear of delaying surgical care for many of our patients is deeply challenging for us as cancer care providers, we must balance our personal commitment to providing timely and appropriate oncologic care to our cancer patients with our societal responsibility to protect our patients (including those on whom we are operating), co-workers, trainees, families, and community, from undue risks of contracting and propagating COVID-19. Herein, we present guidelines for surgical decision-making and case prioritization developed among all adult disease specialties in the MD Anderson Cancer Center Departments of Surgical Oncology and Breast Surgical Oncology in Houston, Texas.

Objective To summarize the multi-specialty strategy and initial guidelines of a Case Review Committee in triaging oncologic surgery procedures in a large Comprehensive Cancer Center and to outline current steps moving forward after the initial wave. Summary of background data The impetus for strategic rescheduling of operations is multifactorial and includes our societal responsibility to minimize COVID-19 exposure risk and propagation among patients, the healthcare workforce, and our community at large. Strategic rescheduling is also driven by the need to preserve limited resources. As many states have already or are considering to re-open and relax stay-at-home orders, there remains a continued need for careful surgical scheduling because we must face the reality that we will need to co-exist with COVID-19 for months, if not years. Methods The quality officers, chairs, and leadership of the 9 surgical departments in our Division of Surgery provide specialty-specific approaches to appropriately triage patients. Results We present the strategic approach for surgical rescheduling during and immediately after the COVID-19 first wave for the 9 departments in the Division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, Texas. Conclusions Cancer surgeons should continue to use their oncologic knowledge to determine the window of opportunity for each surgical procedure, based on tumor biology, preoperative treatment sequencing, and response to systemic therapy, to safely guide patients through this cautious recovery phase.

Neoadjuvant therapy (NAT) improves survival among patients with locally advanced gastric cancer (GC), but it remains unclear whether its benefit is contingent on treatment response.This is a national cohort study of stage Ib-III GC patients in the National Cancer Data Base (2006-2015) treated with upfront resection or NAT followed by surgery. Bayesian analysis was used for NAT patients to ascertain staging concordance and to account for down-staging. We used multivariable Cox regression to evaluate the association between staging concordance, treatment, response to NAT, and survival.The cohort included 13 340 patients treated at 1124 hospitals. Staging concordance ranged from 86.1% for cT3-4N+ to 34.7% for cT2N0 patients. Relative to accurately staged patients treated with upfront surgery, NAT was associated with a decreased risk of death if there was disease down-staging among those with cT1-2N+ (hazard ratio [HR]: 0.43 [0.30-0.61]), cT3-4N0 (HR: 0.69 [0.54-0.88]), and cT3-4N+ (HR: 0.51 [0.48-0.58]) tumors, and in the absence of down-staging among cT3-4N+ patients (HR: 0.83 [0.74-0.92]). Conversely, NAT without down-staging increased the risk of death among those with intermediate-stage disease.NAT is associated with improved survival for GC, but it seems to be contingent on treatment response among patients with intermediate-stage disease.

Single-institution studies have shown the oncologic benefit of ablative liver radiotherapy (A-RT) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, adoption of A-RT across the United States and its associated outcomes are unknown.We queried the National Cancer Data Base for nonsurgically managed patients with ICC diagnosed between 2004 and 2018. Patients were labeled A-RT for receipt of biologically effective doses (BEDOf 27,571 patients, the most common treatments were chemotherapy without liver RT (45%), no chemotherapy or liver RT (42%), and liver RT ± chemotherapy (13%). Use of liver RT remained constant over time. Of 1112 patients receiving liver RT with known doses, RT was 73% Conv-RT (median BEDAlthough A-RT has been increasingly used, use of liver RT as a whole in the United States remained constant despite growing evidence supporting its use, suggesting continued unmet need. A-RT is associated with longer survival versus Conv-RT.Bile duct cancer is a rare, deadly disease that often presents at advanced stages. Single-institution retrospective studies have demonstrated that use of high-dose radiotherapy may be associated with longer survival, but larger studies have not been conducted. We used a large, national cancer registry of patients diagnosed between 2004 and 2018 to show that liver radiotherapy use remains low in the United States, despite growing evidence that patients who receive it live longer. Furthermore, we showed that patients who received high-dose radiotherapy lived longer than those who received lower doses. Greater awareness of the benefits of liver radiotherapy is needed to improve patient outcomes.

Circulating tumor DNA (ctDNA) is a promising biomarker for patients undergoing hepatectomy for colorectal liver metastases (CLM). We hypothesized that post-hepatectomy ctDNA detection would identify patients at highest risk for early recurrence of CLM.Patients with CLM who underwent curative-intent hepatectomy with ctDNA analysis within 180 days postoperatively (1/2013 and 6/2020) were included. Tissue somatic mutations and ctDNA analyses were performed by next-generation sequencing panels. Survival analyses determined factors associated with clinical recurrence 1 year or earlier after hepatectomy. Patients with primary tumors in situ and without 1-year follow-up were excluded. Median follow-up was 28.3 months.Of 105 patients, 32 (30%) were ctDNA positive (ctDNA+) after curative-intent hepatectomy. Compared with ctDNA-negative patients, ctDNA+ patients had multiple CLM (84% vs 55%, p = 0.002) and co-mutated RAS/TP53 (47% vs 23%, p = 0.018). Multiple CLM (odds ration (OR), 5.43; p = 0.005) and co-mutated RAS/TP53 (OR, 3.30; p = 0.019) were independently associated with post-hepatectomy ctDNA. Although perioperative carcinoembryonic antigen levels were not prognostic, postoperative ctDNA+ (hazard ratio (HR), 2.04; p = 0.011) and extrahepatic disease (HR, 2.45, p = 0.004) were independently associated with worse recurrence-free survival. After adjusting for extrahepatic disease, preoperative chemotherapy, multiple CLM, tumor viability of 50% or greater, and co-mutated RAS/TP53, ctDNA+ within 180 days was the only independent risk factor for recurrence 1 year or earlier after hepatectomy (94% vs 49%; HR, 11.8; p = 0.003).Postoperative ctDNA detection is associated with early recurrence 1 year or earlier after curative-intent hepatectomy for CLM, and RAS/TP53 co-mutations result in a more than 3-fold increased risk for postoperative ctDNA positivity. This highlights the complementary effect of tumor tissue and circulating mutational profiling for patients with CLM.

Molecular imaging is an emerging non-invasive method to qualitatively and quantitively visualize and characterize biological processes. Among the imaging modalities, PET/SPECT and near-infrared (NIR) imaging provide synergistic properties that result in deep tissue penetration and up to cell-level resolution. Dual-modal PET/SPECT-NIR agents are commonly combined with a targeting ligand (e.g., antibody or small molecule) to engage biomolecules overexpressed in cancer, thereby enabling selective multimodal visualization of primary and metastatic tumors. The use of such agents for (i) preoperative patient selection and surgical planning and (ii) intraoperative FGS could improve surgical workflow and patient outcomes. However, the development of targeted dual-modal agents is a chemical challenge and a topic of ongoing research. In this review, we define key design considerations of targeted dual-modal imaging from a topological perspective, list targeted dual-modal probes disclosed in the last decade, review recent progress in the field of NIR fluorescent probe development, and highlight future directions in this rapidly developing field.