Alliance for clinical trials in Oncology (Alliance) trial A022101/NRG-GI009: a pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur).

BACKGROUND: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. METHODS: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. DISCUSSION: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05673148, registered December 21, 2022.

The role of specialized pro-resolving mediators (SPMs) in inflammatory arthritis: A therapeutic strategy.

Rheumatoid arthritis (RA) is classified as a persistent inflammatory autoimmune disorder leading to the subsequent erosion of articular cartilage and bone tissue originating from the synovium. The fundamental objective of therapeutic interventions in RA has been the suppression of inflammation. Nevertheless, conventional medicines that lack target specificity may exhibit unpredictable effects on cell metabolism. In recent times, there has been evidence suggesting that specialized pro-resolving mediators (SPMs), which are lipid metabolites, have a role in facilitating the resolution of inflammation and the reestablishment of tissue homeostasis. SPMs are synthesized by immune cells through the enzymatic conversion of omega-3 fatty acids. In the context of RA, there is a possibility of dysregulation in the production of these SPMs. In this review, we delve into the present comprehension of the endogenous functions of SPMs in RA as lipids that exhibit pro-resolutive, protective, and immunoresolvent properties.

Adjuvant Chemoradiation in Patients with Lymph Node-Positive Biliary Tract Cancers: Secondary Analysis of a Single-Arm Clinical Trial (SWOG 0809).

BACKGROUND: SWOG 0809 is the only prospective study of adjuvant chemotherapy followed by chemoradiation focusing on margin status in patients with extrahepatic cholangiocarcinoma (EHCC) and gallbladder cancer (GBCA); however, the effects of adjuvant therapy by nodal status have never been reported in this population. METHODS: Patients with resected EHCC and GBCA, stage pT2-4, node-positive (N+) or margin-positive (R1) who completed four cycles of chemotherapy followed by radiotherapy were included. Cox regression was used to compare overall survival (OS), disease-free survival (DFS), local recurrence, and distant metastasis by nodal status. DFS rates were compared with historical data via a one-sample t-test. RESULTS: Sixty-nine patients [EHCC, n = 46 (66%); GBCA, n = 23 (33%)] were evaluated, with a median age of 61.7 years and an R0 rate of 66.7% and R1 rate of 33.3%. EHCC versus GBCA was more likely to be N+ (73.9% vs. 47.8%, p = 0.03). Nodal status did not significantly impact OS (hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.86-4.54, p = 0.11) or DFS (HR 1.63, 95% CI 0.77-3.44, p = 0.20). Two-year OS was 70.6% for node-negative (N0) disease and 60.9% for N+ disease, while 2-year DFS was 62.5% for N0 tumors and 49.8% for N+ tumors. N+ versus N0 tumors showed higher rates of distant failure (42.2% vs. 25.0%, p = 0.04). The 2-year DFS rate in N+ tumors was significantly higher than in historical controls (49.8% vs. 29.7%, p = 0.004). CONCLUSIONS: Adjuvant therapy is associated with favorable outcome independent of nodal status and may impact local control in N+ patients. These data could serve as a benchmark for future adjuvant trials, including molecular-targeted agents.

Current Practices in Hepatic Artery Infusion (HAI) Chemotherapy: An International Survey of the HAI Consortium Research Network.

BACKGROUND: An increasing number of hepatic artery infusion (HAI) programs have been established worldwide. Practice patterns for this complex therapy across these programs have not been reported. This survey aimed to identify current practice patterns in HAI therapy with the long-term goal of defining best practices and performing prospective studies. METHODS: Using SurveyMonkeyTM, a 28-question survey assessing current practices in HAI was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses, and the frequency of categories was calculated. Scores for rank-order questions were generated by calculating average ranking for each answer choice. RESULTS: Thirty-six (72%) HCRN members responded to the survey. The most common intended initial indications for HAI at new programs were unresectable colorectal liver metastases (uCRLM; 100%) and unresectable intrahepatic cholangiocarcinoma (uIHC; 56%). Practice patterns evolved such that uCRLM (94%) and adjuvant therapy for CRLM (adjCRLM; 72%) have become the most common current indications for HAI at established centers. Referral patterns for pump placement differed between uCRLM and uIHC, with most patients referred while receiving second- and first-line therapy, respectively, with physicians preferring to evaluate patients for HAI while receiving first-line therapy for CRLM. Concern for extrahepatic disease was ranked as the most important factor when considering a patient for HAI. CONCLUSIONS: Indication and patient selection factors for HAI therapy are relatively uniform across most HCRN centers. The increasing use of adjuvant HAI therapy and overall consistency of practice patterns among HCRN centers provides a robust environment for prospective data collection and randomized clinical trials.

Disparities in treatment and survival in early-stage hepatocellular carcinoma in California.

BACKGROUND AND OBJECTIVES: Curative intent therapy is the standard of care for early-stage hepatocellular carcinoma (HCC). However, these therapies are under-utilized, with several treatment and survival disparities. We sought to demonstrate whether the type of facility and distance from treatment center (with transplant capabilities) contributed to disparities in curative-intent treatment and survival for early-stage HCC in California. METHODS: We performed a retrospective analysis of the California Cancer Registry for patients diagnosed with stage I or II primary HCC between 2005 and 2017. Primary and secondary outcomes were receipt of treatment and overall survival, respectively. Multivariable logistic regression and Multivariable Cox proportional hazards regression were used to evaluate associations. RESULTS: Of 19 059 patients with early-stage HCC, only 36% (6778) received curative-intent treatment. Compared to Non-Hispanic White patients, Hispanic patients were less likely, and Asian/Pacific Islander patients were more likely to receive curative-intent treatment. Our results showed that rural residence, public insurance, lower neighborhood SES, and care at non-National Cancer Institute-designated cancer center were associated with not receiving treatment and decreased survival. CONCLUSIONS: Although multiple factors influence receipt of treatment for early-HCC, our findings suggest that early intervention programs should target travel barriers and access to specialist care to help improve oncologic outcomes.

Utility of combined gadoxetic acid and ferumoxytol-enhanced liver MRI for preoperative detection of colorectal cancer liver metastases: a pilot study.

BACKGROUND: Colorectal cancer (CRC) is the second-leading cause of cancer-related death worldwide and resection of CRC metastases confined to the liver is the treatment of choice when feasible. Ferumoxytol is an off-label contrast agent that opacifies vasculature and may be helpful in distinguishing metastases from small hemangiomas and blood vessels on gadoxetic acid-enhanced magnetic resonance imaging (MRI). PURPOSE: To compare the diagnostic accuracy of MRI using a standard gadoxetic acid protocol and a combined gadoxetic acid/ferumoxytol protocol in patients with suspected colorectal hepatic metastases. MATERIAL AND METHODS: In this institutional review board-approved, single-institution, retrospective study, eight patients underwent gadoxetic acid-enhanced liver MRI, supplemented with additional T1-weighted ferumoxytol enhanced sequences. Two radiologists in consensus identified all metastases using all available sequences, which served as the reference standard. Two different radiologists reviewed each exam twice, once using the standard protocol and once with additional ferumoxytol sequences. The detection rate was estimated as the predicted probability of a metastasis along with the 95% confidence interval (CI) using hierarchical logistic regression models. RESULTS: A total of 49 metastases were identified. The mean diameter was 10 mm, measured in greatest axial dimension (median=7 mm; range=2-70 mm). Readers 1 and 2 had detection rates of 69.6% (95% CI = 48.2-85.0) and 53.1% (95% CI = 35.2-70.3) for gadoxetic acid alone and 98.0% (95% CI = 86.3-99.7) and 83.5% (95% CI = 59.3-94.7) for combined protocol. CONCLUSION: In this preliminary investigation, adding ferumoxytol-enhanced sequences to gadoxetic acid liver MRI protocol increased the detection rate of CRC hepatic metastases and may aid in preoperative decision making.

Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial.

Importance: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood. Objective: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics. Design, Setting, and Participants: Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment. Intervention: The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care). Main Outcomes and Measures: The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program. Results: The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32). Conclusions and Relevance: In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT03269994.

Hepatic Artery Infusion Pumps: A Surgical Toolkit for Intraoperative Decision-Making and Management of Hepatic Artery Infusion-Specific Complications.

BACKGROUND: Hepatic artery infusion (HAI) is a liver-directed therapy that delivers high-dose chemotherapy to the liver through the hepatic arterial system for colorectal liver metastases and intrahepatic cholangiocarcinoma. Utilization of HAI is rapidly expanding worldwide. OBJECTIVE AND METHODS: This review describes the conduct of HAI pump implantation, with focus on common technical pitfalls and their associated solutions. Perioperative identification and management of common postoperative complications is also described. RESULTS: HAI therapy is most commonly performed with the surgical implantation of a subcutaneous pump, and placement of its catheter into the hepatic arterial system for inline flow of pump chemotherapy directly to the liver. Intraoperative challenges and abnormal hepatic perfusion can arise due to aberrant anatomy, vascular disease, technical or patient factors. However, solutions to prevent or overcome technical pitfalls are present for the majority of cases. Postoperative HAI-specific complications arise in 22% to 28% of patients in the form of pump pocket (8%-18%), catheter (10%-26%), vascular (5%-10%), or biliary (2%-8%) complications. The majority of patients can be rescued from these complications with early identification and aggressive intervention to continue to deliver safe and effective HAI therapy. CONCLUSIONS: This HAI toolkit provides the HAI team a reference to manage commonly encountered HAI-specific perioperative obstacles and complications. Overcoming these challenges is critical to ensure safe and effective pump implantation and delivery of HAI therapy, and key to successful implementation of new programs and expansion of HAI to patients who may benefit from such a highly specialized treatment strategy.

Locoregional Liver-Directed Therapies to Treat Unresectable Colorectal Liver Metastases: A Review

An estimated 70% of patients with colorectal cancer will develop liver metastases during the course of their disease. While the first-line treatment for hepatic metastases is resection, most patients with colorectal liver-only or liver-dominant metastases (CRLM) present with unresectable disease and are not surgical candidates. In the past decade, locoregional liver-directed therapies have demonstrated safety and efficacy in the treatment of patients with unresectable CRLM and chemotherapy-refractory disease. These treatments can be used to attempt conversion to surgical resectability, can control local disease progression, and have the potential to prolong survival. However, they have not yet become the standard of care in many practices. Each treatment has unique risks, and the clinical data are heterogeneous and thus difficult to interpret. In this article, we will review the most recent, high-impact literature on 3 common locoregional therapies used in the treatment of patients with unresectable CRLM: hepatic artery infusion pump chemotherapy, stereotactic body radiation therapy, and selective internal radiation therapy with yttrium-90 embolization. Ultimately, for this patient population, clinical decision-making requires a multidisciplinary discussion which should take into account individual patient characteristics and clinical expertise available at the treatment facility.

Considerations and barriers to starting a new HAI pump program: an international survey of the HAI Consortium Research Network.

BACKGROUND: Widespread implementation of HAI pump chemotherapy has been limited by logistic and feasibility concerns. Recent studies demonstrating excellent outcomes have fueled renewed enthusiasm and multiple new programs have emerged. This survey aims to identify barriers critical to establish a successful HAI program. METHODS: Using SurveyMonkey™, a 17-question survey assessing factors required for establishing a successful program was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses. Frequency of categories and average rank scores for each choice were calculated. RESULTS: Twenty-eight HCRN members responded to the survey. Implementation time varied, with 15 institutions requiring less than a year. Most programs (n = 17) became active in the past 5 years. Medical and surgical oncology were ranked most important for building a program (average ranking scores: 7.96 and 6.59/8). Administrative or regulatory approval was required at half of the institutions. The top 3 challenges faced when building a program were related to regulatory approval (6.65/9), device/equipment access (6.33/9), and drug (FUDR) access (6.25/9). CONCLUSION: Development of successful programs outside of historically established centers is feasible and requires a multidisciplinary team. Future collaborative efforts are critical for sustainability of safe/effective new programs.

Impact of Primary Tumor Laterality on Adjuvant Hepatic Artery Infusion Pump Chemotherapy in Resected Colon Cancer Liver Metastases: Analysis of 487 Patients.

BACKGROUND: Hepatic artery infusion (HAI) chemotherapy is associated with overall survival (OS) in patients with resected colon cancer liver metastases (CLM). The prognostic impact of primary tumor location in CLM following hepatic resection in patients receiving regional HAI is unknown. This study seeks to investigate the prognostic impact of HAI in relation to laterality in this patient population. METHODS: Consecutive patients with resected CLM, with known primary tumor site treated with and without HAI, were reviewed from a prospective institutional database. Correlations between HAI, laterality, other clinicopathological factors, and survival were analyzed, and Cox proportional hazard regression was used to determine whether laterality was an independent prognostic factor. RESULTS: From 1993 to 2012, 487 patients [182 with right colon cancer (RCC), 305 with left colon cancer (LCC)] were evaluated with a median follow-up of 6.5 years. Fifty-seven percent (n = 275) received adjuvant HAI. Patients with RCC had inferior 5-year OS compared with LCC (56% vs. 67%, P = 0.01). HAI was associated with improved 5-year OS in both RCC (68% vs. 45%; P < 0.01) and LCC (73% vs. 55%; P < 0.01). On multivariable analysis, HAI remained associated with improved OS (HR 0.52; 95% CI 0.39-0.70; P < 0.01) but primary tumor site did not (HR 0.83; 95% CI 0.63-1.11; P = 0.21). Additional significant prognostic factors on multivariable analysis included age, number of tumors, node-positive primary, positive margins, RAS mutation, two-stage hepatectomy, and extrahepatic disease. Cox proportional hazard regression determined no significant interaction between HAI and laterality on OS [parameter estimate (SEM), 0.12 (0.28); P = 0.67]. CONCLUSIONS: Our data show an association of adjuvant HAI and increased OS in patients who underwent curative hepatectomy, irrespective of primary tumor location. Laterality should therefore not impact decision-making when offering adjuvant HAI.

Chemotherapy After Diagnosis of Malignant Bowel Obstruction is Associated with Superior Survival for Medicare Patients with Advanced Malignancy.

BACKGROUND: Although malignant bowel obstruction (MBO) often is a terminal event, systemic therapies are advocated for select patients to extend survival. This study aimed to evaluate factors associated with receipt of chemotherapy after MBO and to determine whether chemotherapy after MBO is associated with survival. METHODS: This retrospective cohort study investigated patients 65 years of age or older with metastatic gastrointestinal, gynecologic, or genitourinary cancers who were hospitalized with MBO from 2008 to 2012 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Fine and Gray models were used to identify factors associated with receipt of chemotherapy accounting for the competing risk of death. Cox models identified factors associated with overall survival. RESULTS: Of the 2983 MBO patients, 39% (n = 1169) were treated with chemotherapy after MBO. No differences in receipt of chemotherapy between the surgical and medical patients were found in the univariable analysis (subdistribution hazard ratio [SHR], 0.96; 95% confidence interval [CI], 0.86-1.07; p = 0.47) or multivariable analysis (SHR, 1.12; 95% CI, 1.00-1.26; p = 0.06). Older age, African American race, medical comorbidities, non-colorectal and non-ovarian cancer diagnoses, sepsis, ascites, and intensive care unit stays were inversely associated with receipt of chemotherapy after MBO (p < 0.05). Chemotherapy with surgery was associated with longer survival than surgery (adjusted hazard ratio [aHR], 2.97; 95% CI, 2.65-3.34; p < 0.01) or medical management without chemotherapy (aHR, 4.56; 95% CI, 4.04-5.14; p < 0.01). Subgroup analyses of biologically diverse cancers (colorectal, pancreatic, and ovarian) showed similar results, with greater survival related to chemotherapy (p < 0.05). CONCLUSIONS: Chemotherapy plays an integral role in maximizing oncologic outcome for select patients with MBO. The data from this study are critical to optimizing multimodality care for these complex patients.

Two-Stage Hepatectomy for Bilateral Colorectal Liver Metastases: A Multi-institutional Analysis.

BACKGROUND: Two-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management, and outcomes of patients completing TSH in major hepatobiliary centers in the United States (US). METHODS: A retrospective review from five liver centers in the US identified patients who completed a TSH procedure for bilateral CRLM. RESULTS: From December 2000 to March 2016, a total of 196 patients were identified. The majority of procedures were performed using an open technique (n = 194, 99.5%). The median number of tumors was 7 (range 2-33). One-hundred and twenty-eight (65.3%) patients underwent portal vein embolization. More patients received chemotherapy prior to the first stage than chemotherapy administration preceding the second stage (92% vs. 60%, p = 0.308). Median overall survival (OS) was 50 months, with a median follow-up of 28 months (range 2-143). Hepatic artery infusion chemotherapy was administered to 64 (32.7%) patients with similar OS as those managed without an infusion pump (p = 0.848). Postoperative morbidity following the second-stage resection was 47.4%. Chemotherapy prior to the second stage did not demonstrate an increased complication rate (p = 0.202). Readmission following the second stage was 10.3% and was associated with a decrease in disease-free survival (p = 0.003). OS was significantly decreased by positive resection margins and increased estimated blood loss (EBL; p = 0.036 and p = 0.05, respectively). CONCLUSION: This is the largest TSH series in the US and demonstrates evidence of safety and feasibility in the management of bilateral CRLM. Outcomes are influenced by margin status and operative EBL.

Management of early hepatocellular carcinoma: results of the Delphi consensus process of the Americas Hepato-Pancreato-Biliary Association.

BACKGROUND: There are many potential treatment options for patients with early stage hepatocellular carcinoma (HCC) and practice patterns vary widely. This project aimed to use a Delphi conference to generate consensus regarding the management of small resectable HCC. METHODS: A base case was established with review by members of AHPBA Research Committee. The Delphi panel of experts reviewed the literature and scored clinical case statements to identify areas of agreement and disagreement. Following initial scoring, discussion was undertaken, questions were amended, and scoring was repeated. This cycle was repeated until no further likelihood of reaching consensus existed. RESULTS: The panel achieved agreement or disagreement consensus regarding 27 statements. The overarching themes included that resection, ablation, transplantation, or any locoregional therapy as a bridge to transplant were all appropriate modalities for early or recurrent HCC. For larger lesions, consensus was reached that radiofrequency ablation and microwave ablation were not appropriate treatments. CONCLUSION: Using a validated system for identifying consensus, an expert panel agreed that multiple treatment modalities are appropriate for early stage HCC. These consensus guidelines are intended to help guide physicians through treatment modalities for early HCC; however, clinical decisions should continue to be made on a patient-specific basis.

Adjuvant Hepatic Artery Infusion Chemotherapy is Associated With Improved Survival Regardless of KRAS Mutation Status in Patients With Resected Colorectal Liver Metastases: A Retrospective Analysis of 674 Patients.

OBJECTIVE: To investigate the impact of adjuvant hepatic artery infusion (HAI) in relation to KRAS mutational status in patients with resected colorectal cancer liver metastases (CRLM). BACKGROUND: Patients with KRAS-mutated CRLM have worse outcomes after resection. Adjuvant HAI chemotherapy improves overall survival after liver resection. METHODS: Patients with resected CRLM treated at MSKCC with and without adjuvant HAI who had available KRAS status (wild-type, WT; mutated, MUT) were reviewed from a prospectively maintained institutional database. Correlations between KRAS status, adjuvant HAI, clinical factors, and outcomes were analyzed. Cox proportional hazard model was used to adjust for confounders. RESULTS: Between 1993 and 2012, 674 patients (418 KRAS-WT, 256 MUT) with a median follow up of 6.5 years after resection were evaluated. Fifty-four percent received adjuvant HAI. Tumor characteristics (synchronous disease, number of lesions, clinical-risk score, 2-stage hepatectomy) were significantly worse in the HAI group; however, there were more patients with resected extrahepatic metastases in the no-HAI group. In KRAS-WT tumors, 5-year survival was 78% for patients treated with HAI versus 57% for patients without HAI [hazard ratio (HR) 0.51, P < 0.001]. In KRAS-MUT tumors, 5-year survival was 59% for patients treated with HAI versus 40% for patients without HAI (HR 0.56, P < 0.001). On multivariate analysis, HAI remained associated with improved OS (HR 0.53, P < 0.002) independent of KRAS status and other clinicopathologic factors. CONCLUSION: Adjuvant HAI after resection of CRLM is independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant HAI may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM.

Is Hepatectomy Justified for BRAF Mutant Colorectal Liver Metastases?: A Multi-institutional Analysis of 1497 Patients.

OBJECTIVE: To analyze clinical outcomes and prognostic variables of patients undergoing hepatic resection for BRAF mutant (BRAF-mut) colorectal liver metastases (CRLM). BACKGROUND: Outcomes following hepatectomy for BRAF-mut CRLM have not been well studied. METHODS: All patients who underwent hepatectomy for CRLM with complete resection and known BRAF status during 2001 to 2016 at 3 high-volume centers were analyzed. RESULTS: Of 4124 patients who underwent hepatectomy for CRLM, 1497 had complete resection and known BRAF status. Thirty-five (2%) patients were BRAF-mut, with 71% of V600E mutation. Compared with BRAF wild-type (BRAF-wt), BRAF-mut patients were older, more commonly presented with higher ASA scores, synchronous, multiple and smaller CRLM, underwent more major hepatectomies, but had less extrahepatic disease. Median overall survival (OS) was 81 months for BRAF-wt and 40 months for BRAF-mut patients (P < 0.001). Median recurrence-free survival (RFS) was 22 and 10 months for BRAF-wt and BRAF-mut patients (P < 0.001). For BRAF-mut, factors associated with worse OS were node-positive primary tumor, carcinoembryonic antigen (CEA) >200 µg/L, and clinical risk score (CRS) ≥4. Factors associated with worse RFS were node-positive primary tumor, ≥4 CRLM, and positive hepatic margin. V600E mutations were not associated with worse OS or RFS. A case-control matching analysis on prognostic clinicopathologic factors confirmed shorter OS (P < 0.001) and RFS (P < 0.001) in BRAF-mut. CONCLUSIONS: Patients with resectable BRAF-mut CRLM are rare among patients selected for surgery and more commonly present with multiple synchronous tumors. BRAF mutation is associated with worse prognosis; however, long-term survival is possible and associated with node-negative primary tumors, CEA ≤ 200 µg/L and CRS < 4.

Neoadjuvant Immunotherapy-Based Systemic Treatment in MMR-Deficient or MSI-High Rectal Cancer: Case Series.

Treatment options for locally advanced rectal cancer have continued to consist largely of chemotherapy, chemoradiation, and/or surgical resection. For patients who are unable to undergo these therapeutic modalities or who do not to experience a response to them, treatment options are limited. We report 3 cases of mismatch repair-deficient (dMMR) locally advanced adenocarcinoma of the rectum that showed significant response with neoadjuvant immunotherapy-based systemic treatment. The first patient was not eligible for standard therapy because of a history of radiotherapy to the prostate with concurrent comorbidities and therefore received single-agent pembrolizumab. The second patient did not respond to total neoadjuvant chemoradiation and subsequently received combined nivolumab and ipilimumab. The third patient had a known family history of Lynch syndrome and presented with locally advanced rectal cancer and a baseline carcinoembryonic antigen level of 1,566 ng/mL. She was treated using neoadjuvant pembrolizumab and FOLFOX (folinic acid, fluorouracil, oxaliplatin). In this small series, we suggest that single-agent and combined-modality neoadjuvant immunotherapy/chemotherapy appear to be safe and effective treatment options for patients with (dMMR) locally advanced rectal cancer. Our findings encourage further studies to investigate the role of neoadjuvant immunotherapy as a viable treatment strategy in this population.

Is minimally invasive surgery of lesions in the right superior segments of the liver justified? A multi-institutional study of 245 patients.

BACKGROUND: Controversy exists regarding the safety and feasibility of minimally invasive resection for lesions in segments 7 or 8. We compare outcomes of minimally invasive surgery (MIS) and Open parenchymal sparing liver resections at two high-volume centers. METHODS: From 2003 to 2016 we identified patients who underwent MIS or Open resections for lesions in segments 7 or 8 at two institutions (MSKCC and SGH). Outcomes were compared using univariate and multivariate analyses. RESULTS: Two-hundred and forty-five patients underwent resection of lesions in segments 7 or 8 (MIS 30% and Open 70%). Compared to the Open group, the MIS group had longer operative time (223 ± 88 vs 188 ± 72 minutes, P = .003), lower blood loss (297 ± 287 vs 448 ± 670 mL, P = .03), and shorter mean length of stay (5.2 ± 7.4 vs 8.3 ± 11.7 days, P < .001), which remained significant on multivariate analysis. No differences in Pringle time, rate of postoperative complications, or R0 resections were detected. CONCLUSIONS: With appropriately selected patients treated by experienced MIS hepatopancreatobiliary surgeons, MIS resection of segments 7 or 8 is safe with similar rates of complications and R0 resections, with significantly less blood loss and shorter length of stay.