Curative-intent Resection Research Articles

ASO Author Reflections: Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer

ASO Author Reflections: Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer

Advantage of Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer.

Lymph node metastasis (LNM) is among the most important predictors of poor prognosis after surgery for gallbladder cancer (GBC). Traditionally, staging has been based on the raw count of LNM, with a high risk of understaging patients who undergo inadequate lymph node dissection (LND). The log odds of metastatic lymph nodes (LODDS) may represent an alternative staging approach to stratify patients more accurately after resection of GBC. In this cross-sectional study, patients who underwent curative-intent surgery with LND for GBC were identified from an international database. Two predictive models were built and compared, each integrating a different lymph nodes status indicator [i.e., American Joint Committee on Cancer (AJCC) and LODDS]. Among 199 patients, the median number of lymph nodes examined was 5 [interquartile range (IQR): 3.0, 8.0]; most patients had T1 (n = 26, 13.1%) or T2 (n = 97, 48.7%) disease, and a subset had LNM (n = 87, 44.0%). Multivariable Cox analysis demonstrated LODDS was an independent predictor of overall survival [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.5-2.3; p < 0.001]. The LODDS model demonstrated better performance compared with a traditional model that utilized the AJCC N category [concordance (C) index: 0.814 versus 0.763; p < 0.001]. Patients classified as high- versus low-risk based on LODDS had much worse overall survival (OS) (4.9% versus 83.7%, respectively; p < 0.001). The LODDS model performance remained high even among patients with inadequateLND (< 6 LN) (C index: 0.87). An online calculator was developed ( https://catalano-giovanni.shinyapps.io/LoddsGBC/ ). A novel prognostic model based on LODDS may overcome the inherent limitations of the current AJCC staging system, reducing understaging among patients with fewer than six total lymph nodes evaluated.

OGC SO34 - Textbook Outcome in Gastric Cancer Elective Surgery: A multicentre analysis

Abstract Background Textbook outcome (TO) is a composite measure of surgical outcomes that, when collectively achieved, depict the optimal result for the patient. Multidimensional parameters, like TO offer a in depth picture of hospital performance, by combining multiple indicators. While an increasing number of studies are evaluating TO in cancer, its application for gastric cancer is still a recent advance. Since surgical reality differs worldwide, a common language is essential when setting outcome goals. This study aims to assess TO accomplishment in several hospital typologies that offer curative-intent resections for gastric cancer. Method A prospective observational multi-institutional audit and 90 day follow-up included data from 138 institutions, in 47 countries. This is a preliminary analysis with focus on TO. Adult patients who underwent elective gastric cancer resection with curative intent, between April 1st and September 30th, 2022, were included. Textbook Outcome (TO) was achieved when all the following seven criteria were met: complete resection (R0), more than 15 lymph nodes sampled, discharge before 21 days, no mortality, no severe morbidity (Clavien–Dindo over 2), no reintervention and no readmission within 90 days post-operative. Results A total of 380 collaborators submitted data on 1538 patients. The mean age was 64.2 years and 58.5% were males. A total of 734 (48%) from the included 1538 patients, achieved TO. “No reintervention in 90 days” was registered in 92% of patients. “No morbidity in 90 days” was observed in 71%. “More than 15 lymph nodes sampled" was achieved in only 79%. The 90-day morbidity and mortality rates were 38.2% (n=587) and 2.9% (n=45), respectively. Conclusion This study demonstrates that achieving Textbook Outcome in gastric cancer resection is seldom attainable. A significant variability across the different outcome parameters within the participating centres was expected. The high rates of mortality-free and reintervention-free outcomes express an effective postoperative care. The lower rates of adequate lymph node sampling and morbidity-free outcomes indicate areas for improvement. Further research should focus on standardizing protocols and improving specific surgical practices to enhance overall TO rates in gastric cancer patients, among the hospital typologies and geographic locations, included in this study.

Impact of Socioeconomic Deprivation on Care Quality and Surgical Outcomes for Early-Stage Non-Small Cell Lung Cancer in United States Veterans

Background: Socioeconomic deprivation has been associated with higher lung cancer risk and mortality in non-Veteran populations. However, the impact of socioeconomic deprivation on outcomes for non-small cell lung cancer (NSCLC) in an integrated and equal-access healthcare system, such as the Veterans Health Administration (VHA), remains unclear. Hence, we investigated the impact of area-level socioeconomic deprivation on access to care and postoperative outcomes for early-stage NSCLC in United States Veterans. Methods: We conducted a retrospective cohort study of patients with clinical stage I NSCLC receiving surgical treatment in the VHA between 1 October 2006 and 30 September 2016. A total of 9704 Veterans were included in the study and assigned an area deprivation index (ADI) score, a measure of socioeconomic deprivation incorporating multiple poverty, education, housing, and employment indicators. We used multivariable analyses to evaluate the relationship between ADI and postoperative outcomes as well as adherence to guideline-concordant care quality measures (QMs) for stage I NSCLC in the preoperative (positron emission tomography [PET] imaging, appropriate smoking management, pulmonary function testing [PFT], and timely surgery [≤12 weeks after diagnosis]) and postoperative periods (appropriate surveillance imaging, smoking management, and oncology referral). Results: Compared to Veterans with low socioeconomic deprivation (ADI ≤ 50), those residing in areas with high socioeconomic deprivation (ADI &gt; 75) were less likely to have timely surgery (multivariable-adjusted odds ratio [aOR] 0.832, 95% confidence interval [CI] 0.732–0.945) and receive PET imaging (aOR 0.592, 95% CI 0.502–0.698) and PFT (aOR 0.816, 95% CI 0.694–0.959) prior to surgery. In the postoperative period, Veterans with high socioeconomic deprivation had an increased risk of 30-day readmission (aOR 1.380, 95% CI 1.103–1.726) and decreased odds of meeting all postoperative care QMs (aOR 0.856, 95% CI 0.750–0.978) compared to those with low socioeconomic deprivation. There was no association between ADI and overall survival (adjusted hazard ratio [aHR] 0.984, 95% CI 0.911–1.062) or cumulative incidence of cancer recurrence (aHR 1.047, 95% CI 0.930–1.179). Conclusions: Our results suggest that Veterans with high socioeconomic deprivation have suboptimal adherence to care QMs for stage I NSCLC yet do not have inferior long-term outcomes after curative-intent resection. Collectively, these findings demonstrate the efficacy of an integrated, equal-access healthcare system in mitigating disparities in lung cancer survival that are frequently present in other populations. Future VHA policies should continue to target increasing adherence to QMs and reducing postoperative readmission for socioeconomically disadvantaged Veterans with early-stage NSCLC.

Classifying histopathological growth patterns for resected colorectal liver metastasis with a deep learning analysis.

Histopathological growth patterns are one of the strongest prognostic factors in patients with resected colorectal liver metastases. Development of an efficient, objective and ideally automated histopathological growth pattern scoring method can substantially help the implementation of histopathological growth pattern assessment in daily practice and research. This study aimed to develop and validate a deep-learning algorithm, namely neural image compression, to distinguish desmoplastic from non-desmoplastic histopathological growth patterns of colorectal liver metastases based on digital haematoxylin and eosin-stained slides. The algorithm was developed using digitalized whole-slide images obtained in a single-centre (Erasmus MC Cancer Institute, the Netherlands) cohort of patients who underwent first curative intent resection for colorectal liver metastases between January 2000 and February 2019. External validation was performed on whole-slide images of patients resected between October 2004 and December 2017 in another institution (Radboud University Medical Center, the Netherlands). The outcomes of interest were the automated classification of dichotomous hepatic growth patterns, distinguishing between desmoplastic hepatic growth pattern and non-desmoplatic growth pattern by a deep-learning model; secondary outcome was the correlation of these classifications with overall survival in the histopathology manual-assessed histopathological growth pattern and those assessed using neural image compression. Nine hundred and thirty-two patients, corresponding to 3.641 whole-slide images, were reviewed to develop the algorithm and 870 whole-slide images were used for external validation. Median follow-up for the development and the validation cohorts was 43 and 29 months respectively. The neural image compression approach achieved significant discriminatory power to classify 100% desmoplastic histopathological growth pattern with an area under the curve of 0.93 in the development cohort and 0.95 upon external validation. Both the histopathology manual-scored histopathological growth pattern and neural image compression-classified histopathological growth pattern achieved a similar multivariable hazard ratio for desmoplastic versus non-desmoplastic growth pattern in the development cohort (histopathology manual score: 0.63 versus neural image compression: 0.64) and in the validation cohort (histopathology manual score: 0.40 versus neural image compression: 0.48). The neural image compression approach is suitable for pathology-based classification tasks of colorectal liver metastases.

Preoperative identification of early extrahepatic recurrence after hepatectomy for colorectal liver metastases: A machine learning approach.

Machine learning (ML) may provide novel insights into data patterns and improve model prediction accuracy. The current study sought to develop and validate an ML model to predict early extra-hepatic recurrence (EEHR) among patients undergoing resection of colorectal liver metastasis (CRLM). Patients with CRLM who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. An eXtreme gradient boosting (XGBoost) model was developed to estimate the risk of EEHR, defined as extrahepatic recurrence within 12months after hepatectomy, using clinicopathological factors. The relative importance of factors was determined using Shapley additive explanations (SHAP) values. Among 1410 patients undergoing curative-intent resection, 131 (9.3%) patients experienced EEHR. Median OS among patients with and without EEHR was 35.4months (interquartile range [IQR] 29.9-46.7) versus 120.5months (IQR 97.2-134.0), respectively (p<0.001). The ML predictive model had c-index values of 0.77 (95% CI, 0.72-0.81) and 0.77 (95% CI, 0.73-0.80) in the entire dataset and the validation data set with bootstrapping resamples, respectively. The SHAP algorithm demonstrated that T and N primary tumor categories, as well as tumor burden score were the three most important predictors of EEHR. An easy-to-use risk calculator for EEHR was developed and made available online at: https://junkawashima.shinyapps.io/EEHR/. An easy-to-use online calculator was developed using ML to help clinicians predict the chance of EEHR after curative-intent resection for CRLM. This tool may help clinicians in decision-making related to treatment strategies for patients with CRLM.

Relationships between tumor CD147 expression, tumor-infiltrating lymphocytes, and oncostatin M in hepatocellular carcinoma.

In hepatocellular carcinoma (HCC), CD147 expression contributes to tumor malignancy; however, its relationship with the tumor-immune microenvironment (TIME) remains unclear. This study aimed to elucidate the clinicopathological characteristics associated with CD147 expression in HCC and investigate its association with the TIME, specifically its association with tumor-infiltrating lymphocytes (TILs) and oncostatin M (OSM). Using 397 HCC specimens from patients undergoing curative-intent resection, we assessed CD147 expression in tumor cells and quantified OSM-positive cells and various TILs (CD8+, CD4+, FOXP3+, and CD20+ cells) in the TIME. Using tissue microarrays, these assessments were performed through immunohistochemical analysis. We investigated the associations between CD147 expression status, the density of OSM-positive cells, and the densities of various TILs. High CD147 expression, found in 332 specimens (83.6%), was associated with advanced clinical stage (P = 0.029), fibrosis (P = 0.036), and higher densities of FOXP3+ cells (P = 0.0039), CD4+ cells (P = 0.0012), and OSM-positive cells (P = 0.0017). In CD147-high tumors, OSM-positive cell density was associated with all assessed TIL subsets (CD8+, CD4+, FOXP3+, and CD20+ cells; all Ps < 0.001), whereas in CD147-low tumors, OSM-positive cell density was associated only with FOXP3+ cells (P = 0.0004). In HCC, CD147 expression is associated with an immunosuppressive TIME, characterized by increased FOXP3+ regulatory T cells and a correlation with OSM-positive cells. These results elucidate the potential mechanisms through which CD147 facilitates tumor-immune evasion, suggesting the CD147 - OSM axis as a promising target for therapeutic intervention in HCC.

Preoperative Glycosylated Hemoglobin A1C Impacts Long-Term Outcomes Following Curative-Intent Resection of Nonfunctional Gastroenteropancreatic Neuroendocrine Tumors.

To investigate the impact of preoperative glycosylated hemoglobin A1C (HbA1c) among patients following curative-intent resection of nonfunctional gastroentropancreatic neuroendocrine tumors (GEP-NETs). Patients who underwent curative-intent resection for GEP-NETs from 2000 to 2020 were identified from the US Neuroendocrine Tumor Study Group (US-NETSG). Preoperative blood HbA1c levels were defined as high HbA1c (≥ 6.5%) versus low HbA1c group (< 6.5%). Impact of HbA1c level on postoperative short-term and long-term overall (OS) were investigated. A total of 130 patients with HbA1c < 6.5% and 60 patients with HbA1c ≥ 6.5% were included. Patients with HbA1c ≥ 6.5% had higher proportion of comorbidities, such as hypertension, obesity, anemia, and lower preoperative albumin levels versus patients with HbA1c < 6.5% (all p < 0.05). In addition, high level of preoperative HbA1c was associated with increased incidence of wound and infectious complications, as well as decreased long-term OS (median OS: high Hb1Ac 89.8 months vs. low Hb1Ac not reached, HR 3.487, p = 0.004) among patients with nonfunctional GEP-NETs, as well as among the subset of pancreatic NET patients (median OS: high Hb1Ac 74.3 months vs. low Hb1Ac not reached, p = 0.004), and patients with normal fasting blood glucose (< 140 mg/dL) (median OS: high Hb1Ac 75.4 months vs. low Hb1Ac not reached, p = 0.001). Hb1Ac might have value as a screening tool to identify high-risk patients following surgical resection of nonfunctional GEP-NETs for consideration of more strict postoperative surveillance and treatment of elevated Hb1Ac level.

Feasibility of ctDNA in detecting minimal residual disease and predicting recurrence for colorectal cancer liver metastases.

Approximately 50% of patients diagnosed with colorectal cancer develop colorectal cancer liver metastases (CRLM). Although curative intent liver resection provides 5-year survival of 40-50%, up to 70% of patients develop recurrence of CRLM. Detection of minimal residual disease (MRD) is essential for timely, optimized treatment. This study evaluated the feasibility and utility of using circulating tumor DNA (ctDNA) to identify MRD and predict disease recurrence. Patients with CRLM that underwent liver resection and had known KRAS or PIK3CA mutations were retrospectively identified. Serial blood samples were collected every 3 months following surgery for disease surveillance. ctDNA was isolated from the samples and analyzed with digital PCR (dPCR). KRAS and PIK3CA mutations were identified by dPCR in 29 patients over 115 timepoints. In patients with detectable ctDNA at time of liver resection, 81% (13/16) developed disease recurrence, while 46% (6/13) of the patients with undetectable ctDNA recurred (p=0.064). Presence of ctDNA was detected in 27.6% (8/29) of the initial postoperative samples. Radiologic recurrence was later diagnosed in 100% (8/8) of these patients, while 52% (11/21) who had undetectable ctDNA postoperatively recurred (p=0.026). Detectable ctDNA postoperatively was associated with a shorter disease-free survival (DFS) of 9 months vs 13 months in patients who had undetectable ctDNA (HR 2.95, 95% CI 1.16-7.49; p=0.02). Liquid biopsy using dPCR can identify low levels of ctDNA, enabling early detection of disease recurrence. Additionally, the presence of ctDNA postoperatively was predictive of recurrence. This study corroborates current literature and provides rational for moving toward a clinical trial using ctDNA and dPCR to detect MRD after CRLM resection.

Proteogenomic Characterization of Early Intrahepatic Recurrence after Curative-Intent Treatment of Colorectal Liver Metastases.

Clinical and pathological factors are insufficient to accurately identify patients at risk of early recurrence after curative-intent treatment of colorectal liver metastases (CRLM). This study aimed to identify candidate prognostic proteogenomic biomarkers for early intrahepatic recurrence after curative-intent resection of CRLM. Patients diagnosed with intrahepatic recurrence within 6 months of liver resection were categorized as the "early recurrence" group, while those who achieved a recurrence-free status for 10 years were designated as "durable remission". Comprehensive genomic and proteomic profiling of fresh frozen samples from these prognostically distinct groups was performed using the TruSight Oncology 500 assay and label-free data-dependent acquisition liquid chromatography-mass spectrometry. Genetic alterations were identified in 117 of the 523 profiled genes in patients with early recurrence. The most common somatic mutations linked to early recurrence were TP53 (88%), APC (71%), KRAS (38%), and SMAD4 (21%). SMAD4 alterations were absent in samples from patients with a durable remission. Calponin-2, versican core protein, glutathione peroxidase 3, fibulin-5, and amyloid-β precursor protein were upregulated more than 2-fold in early recurrence. Exploratory analysis of these proteogenomic biomarkers suggests that SMAD4, calponin-2, and glutathione peroxidase 3 may have the potential to predict early recurrence, enabling improved prognostication and precision oncology in CRLM.

Prognostic utility of the modified albumin-bilirubin score among patients undergoing curative-intent surgery for gallbladder cancer

BackgroundGallbladder cancer (GBC) has been associated with high rates of recurrence and dismal prognosis even after curative-intent resection. The prognostic utility of the modified albumin-bilirubin (mALBI) score among individuals undergoing curative-intent resection for GBC has not been determined. MethodsPatients who underwent radical resection for GBC between 2000 and 2022 were identified from an international, multi-institutional database. Preoperative albumin and bilirubin levels were used to calculate the mALBI score. The relationship among mALBI score, overall survival (OS), and recurrence-free survival (RFS) was examined. ResultsAmong 269 patients who underwent radical resection for GBC, 161 (59.9%) had mALBI grade 1, 48 (17.8%) had grade 2a, 47 (17.5%) had grade 2b, and 13 (4.8%) had mALBI grade 3. After surgery, compared with patients with a low mALBI grade (grade 1/2a), individuals with a high mALBI grade (grade 2b/3) had worse 5-year OS (54.4% vs 19.2%, respectively; P < .001) and RFS (42.0% vs 17.8%, respectively; P < .001). On multivariable analysis, after controlling for relevant clinicopathologic variables, individuals with a high mALBI score remained independently associated with higher risks of death and recurrence (OS: hazard ratio [HR], 2.38 [95% CI, 1.50–3.79]; RFS: HR, 2.12 [95% CI 1.41–3.20]) versus patients with a low mALBI score after curative-intent resection for GBC. Of note, mALBI score was associated with incrementally worse survival within T2, T3, and N+ categories, whereas classic American Joint Committee on Cancer subclassifications failed to distinguish patients with long-term survival. ConclusionThe mALBI score presents a simple, objective measure of hepatic functional reserve and may be a useful prognostic tool for patients undergoing curative-intent resection for GBC.

Patterns of recurrence after curative intent hepatic resection for colorectal liver metastasis

BackgroundImproved surgical techniques and more intensive systemic therapy have increased the number of patients with oligometastatic colorectal cancer eligible for resection, but a significant percentage of these cases will ultimately recur. Furthermore, distinct recurrence patterns have been associated with different outcomes. MethodsData for 195 patients who underwent curative-intent colorectal liver metastasis (CRLM) resection between 2016 and 2022 at Johns Hopkins Hospital were retrospectively collected. Cox regression univariate and multivariate analyses identified features associated with survival outcomes. Association between risk factors and site of recurrences was conducted via logistic regression with initial recurrences grouped into intrahepatic-only, extrahepatic-only, and concurrent intra- and extrahepatic recurrence. ResultsThe 1- and 2-year recurrence-free survival (RFS) rates were 46% and 22%, respectively. The 1- and 2-year overall survival (OS) rates were 95% and 88%, respectively. The median OS was 71.7 months. Multivariate analysis identified age <60 years, N2 nodal status, R1 liver margin, and higher preoperative carcinoembryonic antigen as top prognostic factors for worse RFS. Additionally, patients with left-sided primary tumors had a higher risk of intrahepatic-only recurrence, whereas mutant KRAS was associated with a higher risk of extrahepatic recurrence with or without liver recurrence. ConclusionThese results from a recent cohort of patients treated with current standard-of-care therapies identify features associated with elevated risk and specific patterns of recurrence. These insights into CRLM recurrence patterns support a larger prospective study to identify subgroups of patients who may require additional therapies to prevent recurrence.

Evidence for the evolving role of neoadjuvant and perioperative immunotherapy in resectable non-small cell lung cancer.

The treatment of early-stage non-small cell lung cancer (NSCLC) is becoming increasingly complex. Standard of care management for the past decade has been adjuvant chemotherapy following curative intent resection regardless of nodal status or tumour profile. With the increased incorporation of immunotherapy in NSCLC, especially in the locally advanced, unresectable, or metastatic settings, multiple studies have sought to assess its utility in early-stage disease. While there are suboptimal responses to neoadjuvant chemotherapy alone, there is a strong rationale for the use of neoadjuvant immunotherapy in tumour downstaging, based upon the concept of enhanced T cell priming at the time of a high tumour antigen burden, and demonstrated clinically in other solid tumours, such as melanoma. In the NSCLC cancer setting, currently over 20 combinations of chemoimmunotherapy in the neoadjuvant and perioperative setting have been studied with results variable. Multiple large phase III studies have demonstrated that neoadjuvant chemoimmunotherapy combinations result in significant advances in pathological response, disease free and overall survival which has led to practice change across the world. Currently, combination immunotherapy regimens with novel agents targeting alternate immunomodulatory pathways are now being investigated. Given this, the landscape of treatment in resectable early-stage NSCLC has become increasingly complex. This review outlines the literature of neoadjuvant and perioperative immunotherapy and discusses its potential benefits and complexities and ongoing considerations into future research.

Surveillance-Associated Anxiety After Curative-Intent Cancer Surgery: A Systematic Review.

Regular surveillance imaging is commonly used after curative-intent resection of most solid-organ cancers to enable prompt diagnosis and management of recurrent disease. Given the fear of cancer recurrence, surveillance may lead to distress and anxiety ("scanxiety") but its frequency, severity, and management among cancer survivors are poorly understood. A systematic review of the PubMed, Embase, CINAHL, and PsycINFO databases was conducted to evaluate existing literature on anxiety and emotional experiences associated with surveillance after curative-intent cancer surgery as well as interventions aimed at reducing scanxiety. Across the 22 included studies encompassing 8693 patients, reported rates of scanxiety varied significantly, but tended to decrease as time elapsed after surgery. Qualitative studies showed that scanxiety arises from various factors innate to the surveillance experience and is most prevalent in the scan-to-results waiting period. Common risk factors for scanxiety included sociodemographic and cancer-related characteristics, low coping self-efficacy, pre-existing anxiety, and low patient well-being. Conversely, reassurance was a positive aspect of surveillance reported in several studies. Trials evaluating the impact of interventions all focused on modifying the surveillance regimen compared with usual care, but none led to reduced rates of scanxiety. Although scanxiety is nearly universal across multiple cancer types and patient populations, it is transient and generally limited in severity. Because existing trials evaluating interventions to reduce scanxiety have not identified effective strategies to date, future research is needed to identify interventions aimed at reducing their impact on high-risk individuals.

Genome-Derived Ampullary Adenocarcinoma Classifier and Postresection Prognostication

Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use. To test external validity of the prognostic value of the hidden genome classifier of AA. This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020. The multilevel meta-feature regression model previously trained on a prospectively sequenced cohort of 3411 patients (1001 pancreatic adenocarcinoma, 165 distal bile duct adenocarcinoma, and 2245 colorectal adenocarcinoma) was applied to AA sequencing data to quantify the relative proportions of parental cell of origin. Genomic classification was correlated with immunohistologic subtype (intestinal [INT] or pancreatobiliary [PB]) and with overall survival (OS), using the log-rank test and Cox proportional hazard models. Among 192 patients with AA (median age, 69.0 [IQR, 60.0-74.0] years and 134 were male [64%]), concordance between immunohistologic and genomic subtypes was 55%. Most INT subtype tumors were categorized into the colorectal genomic subtype (43 of 57 [72.9%]). Of the 114 PB subtype tumors, 29 had a pancreatic genomic profile (25.4%) and 24 had a distal bile duct genomic profile (21.1%). Whereas the standard immunohistologic subtypes were not associated with survival (log rank P = .26), predicted genomic probabilities were correlated with survival probability. Genomic scores with higher colorectal probability were associated with higher survival probability; higher pancreatic and distal bile duct probabilities were associated with lower survival probability. The AA genomic classifier is reproducible with available molecular testing in a diverse international cohort of patients and improves stratification of the divergent clinical outcomes beyond standard immunohistologic classification. These data provide a molecular classification that may be incorporated into clinical trials for prospective validation.

Molecular markers of proliferation, DNA repair, and immune infiltration defines high-risk subset of resectable retroperitoneal sarcomas

IntroductionFor retroperitoneal sarcomas (RPS), aggressive surgical resection offers the only chance for a cure; however, 5-year survival remains below 65%. Therefore, there is a critical need to identify drivers of poor clinical outcomes. Materials and methodsTo identify biomarkers of tumors likely to recur following curative intent resection, we performed genomic and transcriptomic sequencing for 47 and 34 patients, respectively, with non-metastatic RPS at a single, high-volume sarcoma center. ResultsAt the DNA level, alterations in TERT were associated with poor disease-free survival (DFS) and overall survival (OS). Increased RNA expression of gene sets related to growth signaling and DNA repair were associated with poor DFS and OS. Infiltration of CD8+ T-Cells and activated dendritic cells were associated with poor DFS and OS. ConclusionThese findings may help to better identify and treat non-metastatic, high-risk RPS.

Chemotherapy switch for nonresponse or progression on neoadjuvant chemotherapy for pancreatic adenocarcinoma.

Patients with localized pancreatic adenocarcinoma who do not respond to neoadjuvant therapy present a challenge. We sought to define the characteristics and outcomes of those patients to guide clinical practice. Patients included were those without evidence of biochemical or radiographic response and no evidence of distant progression at the first reassessment after initiation of therapy. Of the 45 patients in the cohort, 23 (51.1%) proceeded to surgical exploration with all but one of those undergoing resection. The median overall survival of the study cohort was 28.6 and 48.6 months in those who underwent resection. A total of 13 patients (28.9%) underwent chemotherapy switch (CS) during their course of neoadjuvant therapy. The CS cohort demonstrated higher rates of radiologic progression (25% vs. 10%, p = 0.329), new or worse vascular involvement (58.3% vs. 30%, p = 0.082), and CA 19-9 increase (30.8% vs. 12.9%, p = 0.209) at initial re-staging. Despite this, overall survival was similar between the two groups (20.7vs. 28.7 months, p = 0.674). Non-responders to first-line neoadjuvant therapy have poor rates of curative-intent resection. However, resection should be undertaken when feasible. CS may be considered in patients who do not respond to first-line chemotherapy.

Preoperative platelet count as an independent predictor of long-term outcomes among patients undergoing resection for intrahepatic cholangiocarcinoma.

An elevated platelet count may reflect neoplastic and inflammatory states, with cytokine-driven overproduction of platelets. The objective of this study was to evaluate the prognostic utility of high platelet count among patients undergoing curative-intent liver surgery for intrahepatic cholangiocarcinoma (ICC). An international, multi-institutional cohort was used to identify patients undergoing curative-intent liver resection for ICC (2000-2020). A high platelet count was defined as platelets >300 *109/L. The relationship between preoperative platelet count, cancer-specific survival (CSS), and overall survival (OS) was examined. Among 825 patients undergoing curative-intent resection for ICC, 139 had a high platelet count, which correlated with multifocal disease, lymph nodes metastasis, poor to undifferentiated grade, and microvascular invasion. Patients with high platelet counts had worse 5-year (35.8% vs. 46.7%, p = 0.009) CSS and OS (24.8% vs. 39.8%, p < 0.001), relative to patients with a low platelet count. After controlling for relevant clinicopathologic factors, high platelet count remained an adverse independent predictor of CSS (HR = 1.46, 95% CI 1.02-2.09) and OS (HR = 1.59, 95% CI 1.14-2.22). High platelet count was associated with worse tumor characteristics and poor long-term CSS and OS. Platelet count represents a readily-available laboratory value that may preoperatively improve risk-stratification of patients undergoing curative-intent liver resection for ICC.

Anxiety and depression are common in surgical oncology patients: Results of a prospective cohort study

BackgroundThe oncology patient population is vulnerable to elevated levels of anxiety and depression. These states of psychological distress have been associated with negative effects on treatment course and outcomes, but reported prevalence rates are varied. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) questionnaires are screening tools that can be utilized to assess the levels of anxiety and depression, respectively. MethodsThis prospective, surgeon-blinded study assessed the preoperative prevalence of anxiety and depression in patients with abdominal malignancies who underwent curative-intent resection. Postoperative outcomes and survival were assessed. ResultsOverall, 218 patients were enrolled and included in the final analysis. Patients were stratified into groups by severity of anxiety and depression. 67 (31 %) patients reported at least mild anxiety as defined by GAD-7 score of 5 +, and 74 (34 %) patients reported at least mild depression, as defined by PHQ-9 score of 5 +. Functional status as defined by Eastern Cooperative Oncology Group scores was associated with anxiety (P = 0.003) and depression (P = 0.024). Depression was associated with race and ethnicity (P = 0.014) and marital status (P = 0.021), with Hispanic/Latino and unpartnered patients reporting higher rates of depression. ConclusionAnxiety and depression are common in the surgical oncology population, affecting a third of the patient population in this prospective study. In addition to a thorough social assessment, the GAD-7 and PHQ-9 questionnaires can be utilized preoperatively to identify patients with psychological distress. SynopsisAnxiety and depression were assessed preoperatively in patients with abdominal malignancies who underwent curative-intent resection. These states of psychological distress were highly prevalent, affecting a third of the population, and significantly associated with certain vulnerable groups.

Development of an artificial intelligence–based model to predict early recurrence of neuroendocrine liver metastasis after resection

PurposeWe sought to develop an artificial intelligence (AI)–based model to predict early recurrence (ER) after curative-intent resection of neuroendocrine liver metastases (NELMs). MethodsPatients with NELM who underwent resection were identified from a multi-institutional database. ER was defined as recurrence within 12 months of surgery. Different AI-based models were developed to predict ER using 10 clinicopathologic factors. ResultsOverall, 473 patients with NELM were included. Among 284 patients with recurrence (60.0%), 118 patients (41.5%) developed an ER. An ensemble AI model demonstrated the highest area under receiver operating characteristic curves of 0.763 and 0.716 in the training and testing cohorts, respectively. Maximum diameter of the primary neuroendocrine tumor, NELM radiologic tumor burden score, and bilateral liver involvement were the factors most strongly associated with risk of NELM ER. Patients predicted to develop ER had worse 5-year recurrence-free survival and overall survival (21.4% vs 37.1% [P = .002] and 61.6% vs 90.3% [P = .03], respectively) than patients not predicted to recur. An easy-to-use tool was made available online: (https://altaf-pawlik-nelm-earlyrecurrence-calculator.streamlit.app/). ConclusionAn AI-based model demonstrated excellent discrimination to predict ER of NELM after resection. The model may help identify patients who can benefit the most from curative-intent resection, risk stratify patients according to prognosis, as well as guide tailored surveillance and treatment decisions including consideration of nonsurgical treatment options.