Outcomes of Hepatic Artery-Based Therapies and Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

BACKGROUND: Treatment of unresectable colorectal liver metastases (UCRLM) includes locoregional and systemic therapy. A comprehensive analysis capturing long-term outcomes of these treatment options has not been performed. OBJECTIVE: A systematic review and meta-analysis was performed to calculate pooled outcomes of hepatic artery infusion with systemic chemotherapy (HAI-S), transarterial chemoembolization with systemic chemotherapy (TACE-S), transarterial radioembolization with systemic chemotherapy (TARE-S), doublet (FOLFOX, FOLFIRI), and triplet chemotherapy (FOLFOXIRI). METHODS: Outcomes included overall survival (OS), progression-free survival (PFS), rate of conversion to resection (CTR), and response rate (RR). RESULTS: A total of 32, 7, 9, and 14 publications were included in the HAI-S, TACE-S, and TARE-S chemotherapy arms. The 6/12/24/36-month OS estimates for HAI-S, TACE-S, TARE-S, FOLFOX, FOLFIRI, and FOLFOXIRI were 97%/80%/54%/35%, 100%/83%/40%/14%, 82%/61%/34%/21%, 96%/83%/53%/36%, and 96%/93%/72%/55%. Similarly, the 6/12/24/36-month PFS estimates were 74%/44%/19%/14%, 66%/20%/9%/3%, 57%/23%/10%/3%, 69%/30%/12%/7%, and 88%/55%/18%/11%. The corresponding CTR and RR rates were 31, 20%, unmeasurable (TARE-S), 35, 53; and 49, 45, 45, 50, 80%, respectively. The majority of chemotherapy studies included first-line therapy and liver-only metastases, whereas most HAI-S studies were pretreated. On subgroup analysis in first-line setting with liver-only metastases, the HAI-S arm had comparable outcomes to FOLFOXIRI and outperformed doublet chemotherapy regimens. Although triplet chemotherapy appeared to outperform other arms, high toxicity and inclusion of potentially resectable patients must be considered while interpreting results. CONCLUSIONS: HAI-S and multiagent chemotherapy are effective therapies for UCRLM. To make definitive conclusions, a randomized trial with comparable patient characteristics and line of therapy will be required. The upcoming EA2222 PUMP trial may help to address this question.

Surgical Resection Alone is Associated With Higher Long-Term Survival Than Multiagent Chemotherapy Alone for Patients With Localized Biliary Tract Cancers.

INTRODUCTION: We compared long-term survival of patients with localized biliary tract cancers (BTCs) treated with either surgical resection or multiagent chemotherapy. METHODS: Patients with localized BTC [gallbladder adenocarcinoma, extrahepatic cholangiocarcinoma, intrahepatic cholangiocarcinoma] were identified within the National Cancer Database (2010-2017). Piecewise-constant hazard modeling was used to estimate hazard ratios (HRs) at prespecified intervals: 0-30 d, 31-60 d, 61-90 d, and >90 d post-treatment. RESULTS: A total of 5988 patients with localized BTC were identified: 2697 (45.0%) received multiagent chemotherapy and 3291 (55.0%) underwent surgical resection. Patients with gallbladder adenocarcinoma or extrahepatic cholangiocarcinoma who were treated with surgical resection had an associated decline in overall survival (OS) as compared to those treated with multiagent chemotherapy within 0-30 d of treatment initiation (gallbladder adenocarcinoma [adjusted HR = 3.94, 95% confidence interval [CI]: 1.77-8.80]; extrahepatic cholangiocarcinoma [adjusted HR = 4.88, 95% CI: 2.76-8.61]). However, there was an associated improvement in OS for patients treated with surgical resection after 90 d from treatment initiation (gallbladder adenocarcinoma [adjusted HR = 0.36, 95% CI: 0.28-0.46]; extrahepatic cholangiocarcinoma [adjusted HR = 0.27, 95% CI: 0.24-0.32]). Among patients with intrahepatic cholangiocarcinoma, those who underwent surgical resection had an associated improvement in OS at 31-60 d (adjusted HR = 0.63, 95% CI: 0.40-0.99) and a further associated increase in OS at 61-90 d (adjusted HR = 0.34, 95% CI: 0.21-0.54) and after 90 d (HR = 0.23, 95% CI: 0.21-0.27) of treatment initiation. CONCLUSIONS: For patients with localized BTC, surgical resection alone is associated with improved long-term survival outcomes compared to multiagent chemotherapy alone.

Characterization of an oligometastatic state in patients with metastatic pancreatic adenocarcinoma undergoing systemic chemotherapy.

PURPOSE/OBJECTIVES: Most patients with pancreatic adenocarcinoma (PDAC) will present with distant metastatic disease at diagnosis. We sought to identify clinical characteristics associated with prolonged overall survival (OS) in patients presenting with metastatic PDAC. MATERIALS/METHODS: Patients presenting with metastatic PDAC that received treatment at our institution with FOLFIRINOX or gemcitabine-based chemotherapies between August 1, 2011 and September 1, 2017 were included in the study. Metastatic disease burden was comprehensively characterized radiologically via individual diagnostic imaging segmentation. Landmark analysis was performed at 18 months, and survival curves were estimated using the Kaplan-Meier method and compared between groups via the log-rank test. ECOG and Charlson Comorbidity Index (CCI) were calculated for all patients. RESULTS: 121 patients were included with a median age of 62 years (37-86), 40% were female, 25% had ECOG 0 at presentation. Of the 121 patients included, 33% (n = 41) were alive at 12 months and 25% (n = 31) were alive at 18 months. Landmark analysis demonstrated a significant difference between patients surviving <18 months and ≥18 months regarding the presence of lung only metastases (36% vs. 16%, p = 0.04), number of organs with metastases (≥2 vs. 1, p = 0.04), and disease volume (mean of 19.1 cc vs. 1.4 cc, p = 0.04). At Year 1, predictors for improved OS included ECOG status at diagnosis (ECOG 0 vs. ECOG 1, p = 0.04), metastatic disease volume at diagnosis (≤0.1 cc vs. >60 cc, p = 0.004), metastasis only in the liver (p = 0.04), and normalization of CA 19-9 (p < 0.001). At Year 2, the only predictor of improved OS was normalization of the CA 19-9 (p = 0.03). In those patients that normalized their CA 19-9, median overall survival was 16 months. CONCLUSIONS: In this exploratory analysis normalization of CA-19-9 or volumetric metastatic disease burden less than 0.2 cc demonstrated a remarkable OS, similar to that of patients with non-metastatic disease. These metrics are useful for counseling patients and identifying cohorts that may be optimal for trials exploring metastatic and/or local tumor-directed interventions.

Efficacy of Immune Checkpoint Inhibition and Cytotoxic Chemotherapy in Mismatch Repair-Deficient and Microsatellite Instability-High Pancreatic Cancer: Mayo Clinic Experience.

PURPOSE: Pancreatic cancer (PC) carries a poor prognosis with high rates of unresectable/metastatic disease at diagnosis, recurrence after resection, and few systemic therapy options. Deficient mismatch repair (dMMR)/high microsatellite instability (MSI-H) PCs demonstrated uncharacteristically poor outcomes in KEYNOTE-158, evaluating pembrolizumab in MSI-H solid tumors. Our study aggregates the Mayo Clinic experience with dMMR/MSI-H PCs, characterizing the clinical, molecular, and treatment response patterns with a focus on response to immune checkpoint inhibitors (ICIs). METHODS: Retrospective data were collected from the electronic medical record from December 2009 to February 2023. Patients were included if they had a pathologically confirmed pancreatic malignancy and had (1) deficient expression of mismatch repair (MMR) proteins by tumor immunohistochemistry, (2) pathogenic mutation of MMR genes on genomic sequencing, and/or (3) MSI-H by polymerase chain reaction. RESULTS: Thirty-two patients were identified for inclusion, with all stages of disease represented. Sixteen of these patients underwent surgery or chemoradiotherapy. Of these patients, uncharacteristically favorable responses were seen, with a recurrence rate of only 19% (n = 3) despite a median follow-up of 25 months. In the palliative setting, excellent responses to ICI were seen, with overall response rate (ORR) of 75% (20% complete response). Median time to disease progression was not reached. Response rates to cytotoxic chemotherapy in the palliative setting were poor, with 30% ORR and median time to progression of 4 months. We observed a high rate of discrepancy between MMR and MSI testing methods, representing 19% of the entire cohort and 26% of evaluable cases. CONCLUSION: Our data argue for the preferential use of ICI over cytotoxic chemotherapy in any patient with dMMR/MSI-H PC requiring systemic therapy, including in the metastatic and adjuvant/neoadjuvant settings.

Differences in the surgical management of early-stage hepatocellular carcinoma at minority versus non-minority-serving hospitals.

BACKGROUND: We examined differences in surgical intervention at minority-serving hospitals versus non-minority-serving hospitals among patients with early-stage hepatocellular carcinoma. We also investigated associations between surgical management and overall survival, stratified by minority-serving hospital status. METHODS: Patients with early-stage hepatocellular carcinoma, defined as cT1, were identified within the National Cancer Database (2004-2018). The primary outcome was surgical intervention (resection, ablation, or transplantation). The proportion of minority (non-Hispanic Black or Hispanic) patients treated at each facility was determined, and hospitals in the top decile were considered minority-serving hospitals. RESULTS: A total of 46,703 patients with early-stage hepatocellular carcinoma were identified, of whom 4,214 (9.0%) were treated at minority-serving hospitals. Patients treated at minority-serving hospitals were less likely to undergo surgical intervention than patients treated at non-minority-serving hospitals (odds ratio = 0.87, 95% confidence interval: 0.81-0.94). Minority patients treated at non-minority-serving hospitals were less likely to undergo surgical intervention than White patients (odds ratio = 0.86, 95% confidence interval: 0.82-0.90) and had a further associated decrease in the likelihood of surgical intervention when treated at minority-serving hospitals (odds ratio = 0.81, 95% confidence interval: 0.69-0.94). Regardless of minority-serving hospital status, surgery was associated with improved overall survival. There were no clinically meaningful differences in overall survival between White and minority patients who underwent surgery either at minority-serving hospitals or non-minority-serving hospitals. CONCLUSIONS: Patients with early-stage hepatocellular carcinoma had an associated decrease in the likelihood of surgical intervention when treated at minority-serving hospitals. Minority patients treated at minority-serving hospitals had an associated decrease in the likelihood of surgery, but to a lesser extent when treated at non-minority-serving hospitals. Surgery was associated with improved overall survival regardless of minority or minority-serving hospital status.

Outcome of Patients With Early-Stage Mismatch Repair Deficient Colorectal Cancer Receiving Neoadjuvant Immunotherapy: A Systematic Review.

PURPOSE: We conducted a systematic review to evaluate the outcome of patients with early-stage (stages I-III) mismatch repair deficient (dMMR) colorectal cancer (CRC) receiving neoadjuvant immunotherapy (NIT) with immune checkpoint inhibitor (ICI)-based regimens. METHODS: MEDLINE, Scopus, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched for publications reporting the outcome of patients with early-stage dMMR CRC receiving NIT. The primary outcome measures were the complete response (CR) rate (clinical CR [cCR] or pathologic CR [pCR]) and the incidence of grade 3 or higher toxicities. RESULTS: The search identified 37 publications that included 423 patients with colon (n = 326, 77%) and rectal (n = 97,23%) cancers aged 19-82 years; most patients had stage III CRC (88%). Approximately 67% of patients received monotherapy with anti-PD-1 agents; the rest received dual ICIs (ipilimumab plus nivolumab). The CR rate (pCR + cCR) in the overall population was 72% (305 of 423). The R0 resection and pCR rates were 99.3% and 70% among the patients undergoing surgery, respectively. Only four (0.9%) patients had primary resistance to NIT. After median follow-up periods ranging from 4 to 27 months, 3 (0.7%) patients progressed after an initial response. Grade 3 or higher toxicities were uncommon (6.3%), rarely delaying planned surgery. CONCLUSION: NIT in patients with early-stage dMMR CRC is associated with a high response rate, low primary resistance to immunotherapy and cancer recurrence rate, and an excellent safety profile. The findings of the present systematic review support further investigation of NIT in patients with early-stage dMMR CRC, with a particular emphasis on the organ-preserving potential of this strategy.

Disparities in guideline-compliant care for patients with pancreatic ductal adenocarcinoma at minority-versus non-minority-serving hospitals.

BACKGROUND: We examined disparities in guideline-compliant care at minority-serving hospitals (MSH) versus non-MSH among patients with localized or metastatic pancreatic adenocarcinoma (PDAC). METHODS: Patients with PDAC were identified within the National Cancer Database (2004-2018). Guideline-compliant care was defined as surgery + chemotherapy ± radiation therapy for localized and chemotherapy for metastatic disease. Facilities in the top decile of minority patients treated were considered MSH. RESULTS: A total of 190,950 patients were identified and most (59.6%) had metastatic disease. Overall, 6.4% of patients with localized and 8.2% of patients with metastatic disease were treated at MSH. Patients treated at MSH were less likely to receive guideline-compliant care (localized: OR = 0.78, 95% CI: 0.67-0.91; metastatic: OR = 0.77, 95% CI: 0.67-0.88). Minority patients were less likely to receive guideline-compliant care at non-MSH (localized: OR = 0.71, 95% CI: 0.67-0.75; metastatic: OR = 0.85, 95% CI: 0.82-0.89) or MSH (localized: OR = 0.85, 95% CI: 0.74-0.98; metastatic: OR = 0.91, 95% CI: 0.82-0.99). Patients treated at non-MSH or MSH who received guideline-compliant care were more likely to have higher OS regardless of stage or race. CONCLUSIONS: MSH patients were less likely to receive guideline-compliant care and minority patients were less likely to receive guideline-compliant care regardless of MSH status. Guideline-compliant care was associated with improved OS.

Tumor Mutational Burden in Real-World Patients With Pancreatic Cancer: Genomic Alterations and Predictive Value for Immune Checkpoint Inhibitor Effectiveness.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is largely considered a nonimmunogenic malignancy; however, approximately 1%, of patients may have tumors with deficient mismatch repair, high microsatellite instability, or high tumor mutational burden (TMB ≥10 mutations/Mb), which may be predictive of response to immune checkpoint inhibitor (ICI) therapy. We sought to analyze outcomes of patients with high-TMB and pathogenic genomic alterations observed in this population. METHODS: This study included patients with PDAC who underwent comprehensive genomic profiling (CGP) at Foundation Medicine (Cambridge, MA). Clinical data were obtained from a US-wide real-world clinicogenomic pancreatic database. We report genomic alterations in those with high and low TMB, and compare outcomes on the basis of receipt of single-agent ICI or therapy regimens not containing ICI. RESULTS: We evaluated 21,932 patients with PDAC who had tissue CGP data available, including 21,639 (98.7%) with low-TMB and 293 (1.3%) with high-TMB. Among patients with high-TMB, a greater number of alterations were observed in BRCA2, BRAF, PALB2, and genes of the mismatch repair pathway, whereas fewer alterations were observed in KRAS. Among patients who received an ICI (n = 51), those with high-TMB had more favorable median overall survival when compared with the low-TMB subset (25.7 v 5.2 months; hazard ratio, 0.32; 95% CI, 0.11 to 0.91; P = .034). CONCLUSION: Longer survival was observed in patients with high-TMB receiving ICI compared with those with low-TMB. This supports the role of high-TMB as a predictive biomarker for efficacy of ICI therapy in PDAC. Additionally, we report higher rates of BRAF and BRCA2 mutations and lower rates of KRAS mutation among patients with PDAC and high-TMB, which to our knowledge, is a novel finding.

Impact of perioperative chemotherapy on survival in patients with cholangiocarcinoma undergoing curative resection.

BACKGROUND: Most patients with localized cholangiocarcinoma (CCA) endure cancer relapse after curative resection underscoring the importance of systemic therapy. The current study attempts to determine the impact of perioperative chemotherapy (PC) on survival in patients with CCA undergoing resection. METHODS: Patients diagnosed with CCA undergoing curative-intent resection between January 1, 2000, and December 31, 2019, in a tertiary care center were included. Cox proportional hazard modeling was used to determine the impact of PC on disease-free survival (DFS) and overall survival (OS). In addition, a nomogram was constructed to estimate 3-year DFS. RESULTS: Among the 182 patients included in the analysis, 102 underwent surgery alone, and 80 received surgery plus PC. Forty-two patients received neoadjuvant therapy, and 38 patients received adjuvant therapy. On multivariate analysis, PC was significantly associated with an improved DFS (HR, 95% CI: 0.63, 0.41-0.98; p = 0.04) and OS (HR, 95% CI: 0.46, 0.27-0.78; p < 0.01). In the interaction analysis, the survival benefit was especially seen in patients with positive resection margins and tumor size > 5 cm. CONCLUSION: In patients with CCA undergoing curative resection, receipt of PC was associated with improved DFS and OS. The nomogram constructed from this database provides an estimate of 3-year DFS after surgical resection. Randomized trials are needed to define the optimal regimen and sequence.

Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess the recurrence risk and patient selection for adjuvant chemotherapy. We performed a meta-analysis of post-operative ctDNA in stage I-IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3568 patients with evaluable ctDNA in CRC patient post-curative-intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results showed that the pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA-positive versus -negative patients in all stages was 7.27 (95% CI 5.49-9.62), p < 0.00001. Subgroup analysis revealed pooled HRs of 8.14 (95% CI 5.60-11.82) and 4.83 (95% CI 3.64-6.39) for stages I-III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA-positive versus -negative patients in all stages was 10.59 (95% CI 5.59-20.06), p < 0.00001. Circulating tumor DNA (ctDNA) analysis has revolutionized non-invasive cancer diagnostics and monitoring, with two primary forms of analysis emerging: tumor-informed techniques and tumor-agnostic or tumor-naive techniques. Tumor-informed methods involve the initial identification of somatic mutations in tumor tissue, followed by the targeted sequencing of plasma DNA using a personalized assay. In contrast, the tumor-agnostic approach performs ctDNA analysis without prior knowledge of the patient's tumor tissue molecular profile. This review highlights the distinctive features and implications of each approach. Tumor-informed techniques enable the precise monitoring of known tumor-specific mutations, leveraging the sensitivity and specificity of ctDNA detection. Conversely, the tumor-agnostic approach allows for a broader genetic and epigenetic analysis, potentially revealing novel alterations and enhancing our understanding of tumor heterogeneity. Both approaches have significant implications for personalized medicine and improved patient outcomes in the field of oncology. The subgroup analysis based on the ctDNA method showed pooled HRs of 8.66 (95% CI 6.38-11.75) and 3.76 (95% CI 2.58-5.48) for tumor-informed and tumor-agnostic, respectively. Our analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.

Phase II Trial of Trifluridine/Tipiracil Plus Irinotecan in Patients with Advanced, Refractory Biliary Tract Carcinoma.

BACKGROUND: We sought to determine the safety and efficacy of trifluridine/tipiracil in combination with irinotecan in a phase II trial setting for refractory, advanced unresectable biliary tract carcinoma (BTC). METHODS: A total of 28 patients (27 were evaluable) with advanced BTCs who progressed on at least one prior systemic therapy were enrolled and were treated with trifluridine/tipiracil 25 mg/m2 (days 1-5 of 14-day cycle) and irinotecan 180 mg/m2 (day 1 of the 14-day cycle). The primary endpoint for the study was 16-week progression-free survival (PFS16) rate. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were pre-specified secondary endpoints. RESULTS: Of 27 patients, PFS16 rate was 37% (10/27; 95% CI: 19%-58%), thereby meeting the criteria for success for the primary endpoint. The median PFS and OS of the entire cohort were 3.9 months (95% CI: 2.5-7.4) and 9.1 months (95% CI: 8.0-14.3), respectively. In the patients evaluable for tumor response (n = 20), the ORR and DCR were 10% and 50%, respectively. Twenty patients (74.1%) had at least one grade 3 or worse adverse event (AE), and 4 patients (14.8%) had grade 4 AEs. A total of 37% (n = 10/27) and 51.9% (n = 14/27) experienced dose reductions in trifluridine/tipiracil and irinotecan, respectively. Delay in therapy was noted in 56% of the patients while 1 patient discontinued the therapy, primarily due to hematologic AEs. CONCLUSION: The combination of trifluridine/tipiracil plus irinotecan is a potential treatment option for patients with advanced, refractory BTCs with good functional status and no targetable mutations. A larger randomized trial is needed to confirm these results. (ClinicalTrials.gov Identifier: NCT04072445).

The predictive impact of dual somatostatin receptor/fluorodeoxyglucose (FDG) positron emission tomography (PET) in metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs): review of literature and a single institution experience.

Treatment with radiolabelled somatostatin analogs, a form of peptide receptor radionuclide therapy (PRRT), has changed the management of patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). There is a subgroup of patients who have suboptimal benefit and rapidly progress on PRRT, indicating that accurate prognostic and predictive markers are urgently needed. Currently, most of the literature concentrate on the prognostic impact of the dual positron emission tomography (PET) scan with very few information regarding the predictive value. We report a case series and review the literature to summarizes the predictive value of combined somatostatin receptor (SSTR) and fluorodeoxyglucose (FDG) PET in metastatic GEP-NETs. We conducted a review of the literature for data published from 2010 to 2021 in MEDLINE, Embase, the National Institutes of Health trial registry, Cochrane CENTRAL, and published proceedings from major gastrointestinal and neuroendocrine cancer meetings. Our main criteria included all published prospective and retrospective data in which the predictive value of dual PET scans using SSTR and FDG was correlated with PRRT response in patients with metastatic GEP-NETs. We summarized clinical outcomes including progression-free survival (PFS), overall survival (OS), and post-therapy complications associated with PRRT according to FDG avidity. We excluded studies that did not include FDG PET scan, GEP patients, studies with no clear predictive value of the FDG PET scan, and studies that did not report a direct correlation between FDG avidity and primary outcome. Additionally, we summarized our institutional experience in eight patients who progressed during or within the first year of PRRT treatment. Our search identified 1306 articles; most of them showed only the prognostic value of Integrated SSTR/FDG PET imaging biomarker in GEP-NETs. Only three studies (n=75 patients) met our inclusion criteria and retrospectively investigated the predictive value of dual SSTR and FDG imaging in subjects being considered for PRRT. The results confirmed that FDG avidity correlates with advanced NET grades. Lesions that are both SSTR and FDG avid had early disease progression. In one study, at multivariate analysis, FDG PET results were independently predictive of lower PFS for PRRT. In our case series, there were eight patients with metastatic well-differentiated GEP-NETs (grades 2 and 3) who progressed within one year of PRRT. Seven of them had positive FDG PET scan at the time of progression. In conclusion, Dual SSTR/FDG PET imaging has a potential predictive impact for PRRT in GEP-NETs. It permits the capturing of the disease complexity and aggressiveness, which correlates with PRRT response. Therefore, prospective future trials should validate the predictive value of dual SSTRs/FDG PET for better PRRT stratification.

Why the Treatment Sequence Matters: Interplay Between Chemotherapy Cycles Received, Cumulative Dose Intensity, and Survival in Resected Early-stage Pancreas Cancer.

OBJECTIVE: To define the optimal threshold of perioperative chemotherapy completion and relative dose intensity (RDI) for patients with resected pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Many patients who undergo pancreatectomy for PDAC fail to initiate or complete recommended perioperative chemotherapy. The association between the amount of perioperative chemotherapy received and overall survival (OS) is not well-defined. METHODS: Single-institution analysis of 225 patients who underwent pancreatectomy for stage I/II PDAC (2010-2021). Associations between OS, chemotherapy cycles completed, and RDI were analyzed. RESULTS: Regardless of treatment sequence, completion of ≥67% of recommended cycles was associated with improved OS compared with no chemotherapy [median OS: 34.5 vs 18.1 months; hazard ratio (HR): 0.43; 95% CI: 0.25-0.74] and <67% of cycles (median OS: 17.9 months; HR: 0.39; 95% CI: 0.24-0.64). A near-linear relationship existed between cycles completed and the RDI received (ß = 0.82). A median RDI of 56% corresponded to the completion of 67% of cycles. Receipt of ≥56% RDI was associated with improved OS compared with no chemotherapy (median OS: 35.5 vs 18.1 months; HR: 0.44; 95% CI: 0.23-0.84) and <56% RDI (median OS: 27.2 months; HR: 0.44; 95% CI: 0.20-0.96). Neoadjuvant chemotherapy is associated with increased odds of receiving ≥67% of recommended cycles (odds ratio: 2.94; 95% CI: 1.45-6.26) and ≥56% RDI (odds ratio: 4.47; 95% CI: 1.72-12.50). CONCLUSIONS: Patients with PDAC who received ≥67% of recommended chemotherapy cycles or ≥56% cumulative RDI had improved OS. Neoadjuvant therapy was associated with increased odds of receiving ≥67% of cycles and ≥56% cumulative RDI and should be considered in all patients with resectable PDAC.

A glimpse into the future of esophageal carcinoma in the United States: predicting the future incidence until 2040 based on the current epidemiological data.

Background: Esophageal carcinoma is the sixth most common cause of death worldwide. With the changing paradigm of esophageal carcinoma, we sought to estimate the future burden of esophageal carcinoma by histology, age, sex, and race, which could help plan prevention, control, and treatment strategies for this cancer. Methods: Surveillance, Epidemiology, and End Results (SEER) 14 registries were utilized to obtain incidence data from 2000 to 2016. We applied age-period-cohort models to estimate future esophageal carcinoma incidence rates and the estimated disease burden by multiplying incidence forecasts by corresponding US Census population projections. Results: Our forecasting study suggests that the incidence (per 100,000 persons) of esophageal adenocarcinoma for the age group 40-65 years will increase from 2.12 in 2021 to 3.86 in 2040, which corresponds to an 82% increase over the course of 19 years (3.2% per year, 95% CI: -2.3% to 9.1%). In addition, we found a considerable decrease in the incidence of esophageal squamous cell carcinoma in the current age groups 40-65 years (-2.7% per year) and >65 years (-4.6% per year). Conclusions: Preventive efforts of esophageal adenocarcinoma should primarily target males of age up to 65 years and females of current age 40 to 65 years who will make up the older age group (>65 years) in 2040.

Successful infusional 5-fluorouracil administration in a patient with vasospastic angina.

A 48-year-old female with metastatic colon adenocarcinoma and history of pre-existing coronary vasospasm with ventricular tachycardia (VT) successfully tolerated de novo 5-fluorouracil (5-FU) chemotherapy infusions with prophylactic administration and optimization of anti-spasm medications. 5-FU has been reported to produce severe cardiotoxic side effects, including coronary vasospasm, ventricular arrhythmias, and sudden cardiac death, and is not typically reported in individuals with pre-existing coronary vasospasm.