Circulating tumor DNA molecular analyses and real-world evidence outcomes of FGFR2 amplified gastroesophageal cancers.

PURPOSE: In addition to the existing biomarkers HER2 and PD-L1, FGFR2b has become an area of interest for the development of new targeted-based treatment. Given that clinical evaluation of FGFR2 targeted therapy is underway, we sought to elucidate the genomic landscape of FGFR2amp in gastroesophageal cancer (GEC) using a circulating tumor DNA (ctDNA) platform. MATERIALS AND METHODS: We retrospectively evaluated the Guardant Health database from 2017 to 2022 for patients with GECs with Guardant360 ctDNA next-generation sequencing (NGS) performed. We assessed co-occurring genetic alterations for patients who harbored FGFR2amp versus FGFR2null. We also explored real-world evidence database with Guardant Health, publicly available genomic databases (MSK cohort using cBioPortal), and pooled clinical data from large-volume cancer centers for FGFR2amp GECs. RESULTS: Less than 4% of patients with GEC in the Guardant Health database were identified to be FGFR2amp. The most commonly co-occurring gene mutations were TP53, CTNNB1, CDH1, and RHOA. Upon interrogation of the MSK cohort, these same genes were not significant on tissue NGS in the FGFR2amp cohort of GEC. In the pooled institutional cohort, we noted that FGFR2amp tumors were most commonly involving the gastroesophageal junction (GEJ). The overall survival of these patients was noted at 13.1 months. CONCLUSION: FGFR2 is a validated target in GECs, and the contexture of FGFR2amp will be important in defining patient subgroups with responses to FGFR2-directed therapy. Using ctDNA to provide a more detailed genomic landscape in patients with GECs will allow the advancement of targeted therapy in the near future for these aggressive cancers.

Initial Experience Using Laparoscopic HIPEC for Gastric Cancer with Peritoneal Metastasis: Safety and Outcomes.

BACKGROUND: Peritoneal metastases (PM) develop in approximately 20% of patients with gastric cancer (GC). For selected patients, treatment of PM with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results. This report aims to describe the safety and perioperative outcomes of laparoscopic HIPEC for GC/PM. METHODS: This retrospective cohort study evaluated patients who had GC and PM treated with laparoscopic HIPEC (2018-2022). The HIPEC involved cisplatin and mitomycin C (MMC) or MMC alone. The primary end point was perioperative safety. RESULTS: The 22 patients in this study underwent 27 procedures. The mean age was 58 ± 13 years. All the patients were Eastern Cooperative Oncology Group (ECOG) 0 or 1 (55 and 45%, respectively). Five patients underwent a second laparoscopic HIPEC, with a median of 126 days (interquartile range [IQR], 117-166 days) between procedures. The median peritoneal carcinomatosis index (PCI) was 4 (IQR, 2-9), and the median hospital stay was 2 days (IQR, 1-3 days). No 30-day readmissions or complications occurred. Eight patients (36%) underwent gastrectomy (CRS ± HIPEC). After an average follow-up period of 11 months, 7 (32%) of the 22 patients were alive. The median overall survival was 11 months (IQR, 195-739 days) from the initial procedure and 19.3 months (IQR, 431-1204 days) from the diagnosis. CONCLUSIONS: Laparoscopic HIPEC appears to be safe with minimal perioperative complications. Approximately one third of the patients undergoing initial laparoscopic HIPEC ultimately proceeded to cytoreduction and gastrectomy. Preliminary survival data from this highly selected cohort suggest that the addition of laparoscopic HIPEC to systemic chemotherapy does not compromise other treatment options. These initial results suggest that laparoscopic HIPEC may offer benefit to patients with GC and PM and aid in the selection of patients who may benefit from curative-intent resection.

Tumor Regression Grade and Overall Survival following Gastrectomy with Preoperative Therapy for Gastric Cancer.

BACKGROUND: Pre-/perioperative chemotherapy is well-established for management of locoregional gastric cancer (LRGC). The American Joint Committee on Cancer advocates histopathologic assessment of tumor regression grade (TRG) but does not endorse a specific schema. We sought to examine the prognostic value of the recently revised National Comprehensive Cancer Network (NCCN) definition of TRG specifying TRG0 as no disease in primary tumor or lymph nodes. PATIENTS AND METHODS: Patients with clinical-stage T2+/N+/M0 LRGC receiving preoperative chemotherapy and curative-intent gastrectomy were identified (2000-2020). TRG using the current NCCN definition was retrospectively assigned. Factors associated with TRG were examined using ordinal logistic regression and overall survival (OS) was assessed using the Kaplan-Meier method and Cox regression. RESULTS: Among 117 patients, the most common chemotherapy regimen was epirubicin, cisplatin, plus fluorouracil or capecitabine (ECF/ECX) (n = 48, 41%), followed by folinic acid, fluorouracil, and oxaliplatin (FOLFOX) (n = 30, 26%), and fluorouracil, leucovorin, oxaliplatin, plus docetaxel (FLOT) (n = 13, 11%). TRG3 was the most common histopathologic response (n = 68, 58%), followed by TRG2 (n = 25, 21%), TRG1 (n = 18, 15%), and, lastly, TRG0 (n = 6, 5.1%). The only preoperative factor independently associated with lower TRG was gastroesophageal junction tumor location (OR 0.24, p = 0.012). Higher TRG was independently associated with worse OS in a stepwise fashion (HR 1.49, p = 0.026). Posttreatment pathologic lymph node status was the strongest prognostic factor (HR 1.93, p = 0.026). Independent prognostic value of TRG and ypT stage could not be shown due to substantial overlap. CONCLUSIONS: TRG using the contemporary NCCN definition is associated with OS in LRGC. TRG0 is uncommon but with excellent prognosis. ypN status is the strongest prognostic factor and the revised NCCN definition acknowledging this is appropriate.

RNA Expression-based Analysis to Predict Response in Patients with Metastatic Mismatch Repair Proficient Colorectal Cancer Treated with Regorafenib and Nivolumab.

Introduction We previously conducted a phase I/Ib study (NCT03712943) with regorafenib and nivolumab in patients with refractory metastatic mismatch repair proficient (pMMR) colorectal cancer (CRC). This study aimed to investigate the role of Xerna™ TME Panel in predicting the treatment response. Methods 22 archival pretreatment tumor samples were subjected to the Xerna™ TME Panel, a machine learning-based RNA-sequencing biomarker assay. The Xerna TME subtypes were evaluated for correlation with overall survival (OS), progression free survival (PFS), disease control rate (DCR), and other biomarkers including KRAS, PD-L1, CD8 expression, and Treg cells in tumor microenvironment. Results Based on Xerna™ TME Panel, four patients with immune active (IA) subtype and six patients with immune suppressed (IS) subtype were classified as biomarker-positive, and five with angiogenic (A) subtype and seven with immune desert (ID) subtype were biomarker-negative. While not reaching statistical significance, Xerna TME biomarker-positive patients seemed to have longer median PFS (7.9 vs. 4.1 months, P=0.254), median OS (15.75 vs. 11.9 months, P=0.378), and higher DCR (70% vs. 58%, P=0.675). The IA subtype in our cohort had higher levels of CD4+ FOXP3+ Treg cells, whereas the A subtype showed lower levels of Treg cells. Conclusion Xerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC who were treated with regorafenib plus nivolumab might be of value for predictive clinical benefit. Further studies are needed to evaluate the predictive role of Xerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC.

Outcomes of 350 Robotic-assisted Esophagectomies at a High-volume Cancer Center: A Contemporary Propensity-score Matched Analysis.

OBJECTIVE: To evaluate perioperative and oncologic outcomes in our RAMIE cohort and compare outcomes with contemporary OE controls. SUMMARY OF BACKGROUND DATA: RAMIE has emerged as an alternative to traditional open or laparoscopic approaches. Described in all esophagectomy techniques, rapid adoption has been attributed to both enhanced visualization and technical dexterity. METHODS: We retrospectively reviewed patients who underwent RAMIE for malignancy. Patient characteristics, perioperative outcomes, and survival were evaluated. For perioperative and oncologic outcome comparison, contemporary OE controls were propensity-score matched from NSQIP and NCDB databases. RESULTS: We identified 350 patients who underwent RAMIE between 2010 and 2019. Median body mass index was 27.4, 32% demonstrated a Charlson Comorbidity Index >4. Nodal disease was identified in 50% of patients and 74% received neoadjuvant chemoradiotherapy. Mean operative time and blood loss were 425 minutes and 232 mL, respectively. Anastomotic leak occurred in 16% of patients, 2% required reoperation. Median LOS was 9 days, and 30-day mortality was 3%. A median of 21 nodes were dissected with 96% achieving an R0 resection. Median survival was 67.4 months. 222 RAMIE were matched 1:1 to the NSQIP OE control. RAMIE demonstrated decreased LOS (9 vs 10 days, P = 0.010) and reoperative rates (2.3 vs 12.2%, P = 0.001), longer operative time (427 vs 311 minutes, P = 0.001), and increased rate of pulmonary embolism (5.4% vs 0.9%, P = 0.007) in comparison to NSQIP cohort. There was no difference in leak rate or mortality. Three hundred forty-three RAMIE were matched to OE cohort from NCDB with no difference in median overall survival (63 vs 53 months; P = 0.130). CONCLUSION: In this largest reported institutional series, we demonstrate that RAMIE can be performed safely with excellent oncologic outcomes and decreased hospital stay when compared to the open approach.

Evaluation of Tumor DNA Sequencing Results in Patients with Gastric and Gastroesophageal Junction Adenocarcinoma Stratified by TP53 Mutation Status.

BACKGROUND: Gastric cancer (GC) and gastroesophageal junction adenocarcinomas (GEJ) are molecularly diverse. TP53 is the most frequently altered gene with approximately 50% of patients harboring mutations. This qualitative study describes the distinct genomic alterations in GCs and GEJs stratified by TP53 mutation status. PATIENTS AND METHODS: Tumor DNA sequencing results of 324 genes from 3741 patients with GC and GEJ were obtained from Foundation Medicine. Association between gene mutation frequency and TP53 mutation status was examined using Fisher's exact test. Functional gene groupings representing molecular pathways suggested to be differentially mutated in TP53 wild-type (TP53WT) and TP53 mutant (TP53MUT) tumors were identified. The association of the frequency of tumors containing a gene mutation in the molecular pathways of interest and TP53 mutation status was assessed using Fisher's exact test with a P-value of <.01 deemed statistically significant for all analyses. RESULTS: TP53 mutations were noted in 61.6% of 2946 GCs and 81.4% of 795 GEJs (P < .001). Forty-nine genes had statistically different mutation frequencies in TP53WT vs. TP53MUT patients. TP53WT tumors more likely had mutations related to DNA mismatch repair, homologous recombination repair, DNA and histone methylation, Wnt/B-catenin, PI3K/Akt/mTOR, and chromatin remodeling complexes. TP53MUT tumors more likely had mutations related to fibroblast growth factor, epidermal growth factor receptor, other receptor tyrosine kinases, and cyclin and cyclin-dependent kinases. CONCLUSION: The mutational profiles of GCs and GEJs varied according to TP53 mutation status. These mutational differences can be used when designing future studies assessing the predictive ability of TP53 mutation status when targeting differentially affected molecular pathways.

Phase I Study of Lenvatinib and Capecitabine with External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma.

BACKGROUND: Neoadjuvant chemoradiation with fluoropyrimidine followed by surgery and adjuvant chemotherapy has been the standard treatment of locally advanced stages II and III rectal cancer for many years. There is a high risk for disease recurrence; therefore, optimizing chemoradiation strategies remains an unmet need. Based on a few studies, there is evidence of the synergistic effect of VEGF/PDGFR blockade with radiation. METHODS: In this phase I, dose-escalation and dose-expansion study, we studied 3 different dose levels of lenvatinib in combination with capecitabine-based chemoradiation for locally advanced rectal cancer. RESULTS: A total of 20 patients were enrolled, and 19 were eligible for assessment of efficacy. The combination was well tolerated, with an MTD of 24 mg lenvatinib. The downstaging rate for the cohort and the pCR was 84.2% and 37.8%, respectively. Blood-based protein biomarkers TSP-2, VEGF-R3, and VEGF correlated with NAR score and were also differentially expressed between response categories. The NAR, or neoadjuvant rectal score, encompasses cT clinical tumor stage, pT pathological tumor stage, and pN pathological nodal stage and provides a continuous variable for evaluating clinical trial outcomes. CONCLUSION: The combination of lenvatinib with capecitabine and radiation in locally advanced rectal cancer was found to be safe and tolerable, and potential blood-based biomarkers were identified. CLINICAL TRIAL REGISTRATION: NCT02935309.

The effect of histologic grade on neoadjuvant treatment outcomes in esophageal cancer.

BACKGROUND AND OBJECTIVES: The gold standard for locoregional esophageal cancer (LEC) treatment includes preoperative chemoradiation and surgical resection, with possible perioperative or adjuvant systemic therapy. With few data associating histologic grade and prognosis in LEC patients receiving neoadjuvant chemoradiation followed by resection, we seek to evaluate this association. METHODS: Our institutional esophagectomy database between 1999 and 2019 was queried, selecting esophageal adenocarcinoma patients who completed neoadjuvant therapy (NAT), followed by esophagectomy. Propensity-score matching of low- and high-histologic grade groups was performed to assess survival metrics using initial clinical grade (cG) and final pathologic grade (pG). We performed a multivariable logistic regression to study predictors of pathologic complete response as a secondary objective. RESULTS: A total of 518 patients met the inclusion criteria. Kaplan-Meier analysis of the matched dataset showed no difference in initial or 5-year recurrence-free survival or overall survival (OS) between cG1 and cG2 versus cG3 based on original grade. When matched according to pG, cG1-2 had improved median survival parameters compared to cG3, with 5-year OS for cG1-2 of 45% versus 27% (p = 0.001). Higher pG, pathologic N stage, and poor response to NAT are predictors of poor survival. CONCLUSION: Patients with post-NAT pG1-2 demonstrated improved survival. Integrating histologic grade into postneoadjuvant staging may be warranted.

Phase 2 study of copanlisib in combination with gemcitabine and cisplatin in advanced biliary tract cancers.

BACKGROUND: Biliary tract cancer (BTC) has a poor prognosis despite treatment with first-line gemcitabine and cisplatin. In BTC, PI3K/AKT pathway activation has been shown to increase resistance to chemotherapy, which may be overcome with PI3K inhibition. This phase 2 study evaluated the safety and efficacy of copanlisib, a PI3K inhibitor, with gemcitabine and cisplatin in advanced BTCs. The role of PTEN expression in outcomes was also explored. METHODS: Patients with advanced/unresectable BTC received gemcitabine, cisplatin, and copanlisib as their first-line treatment. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were the response rate (RR), median overall survival (OS)/PFS, and safety profile. An assessment of PTEN expression by immunohistochemistry was also performed along with molecular profiling. RESULTS: Twenty-four patients received at least 1 dose of the study drug. The PFS rate at 6 months was 51%; the median OS was 13.7 months (95% CI, 6.8-18.0 months), and the median PFS was 6.2 months (95% CI, 2.9-10.1 months). Nineteen patients were evaluable for RR: 6 patients achieved a partial response (31.6%), and 11 (57.9%) had stable disease. The most common grade 3/4 adverse events were a decreased neutrophil count (45.83%), anemia (25%), increased lipase (25%), and hypertension (20.8%). Twenty patients had tissue evaluable for the PTEN status. The PFS for low (n = 9) and high PTEN expression (n = 11) was 8.5 and 4.6 months, respectively (P = .19). The median OS for low and high PTEN expression groups was 17.9 and 7.0 months, respectively (P = .19). CONCLUSIONS: The addition of copanlisib to gemcitabine and cisplatin does not improve PFS at 6 months. However, future studies using PTEN as a potential biomarker should be considered. LAY SUMMARY: The addition of copanlisib, a PI3K inhibitor, to standard chemotherapy for advanced biliary tract cancers was assessed for efficacy and safety. Twenty-four patients with advanced biliary tract cancer received treatment in this study. There was no difference in survival with the addition of copanlisib in comparison with standard chemotherapy. Copanlisib may be more effective and increase survival in patients with low PTEN expression levels. Further studies are needed to confirm this. No unexpected adverse events occurred.

A phase 1/2 trial of ibrutinib in combination with pembrolizumab in patients with mismatch repair proficient metastatic colorectal cancer.

BACKGROUND: MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC. METHODS: This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively. CONCLUSION: Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC. CLINICALTRIALS. GOV IDENTIFIER: NCT03332498.

Chemotherapy Versus Chemotherapy Plus Chemoradiation as Neoadjuvant Therapy for Resectable Gastric Adenocarcinoma: A Multi-institutional Analysis.

OBJECTIVE: We compare neoadjuvant chemotherapy (CT) to neoadjuvant chemotherapy plus chemoradiation (CRT) for patients with gastric adenocarcinoma (GA). SUMMARY OF BACKGROUND DATA: The optimal neoadjuvant therapy regimen for resectable GA is not defined. METHODS: Utilizing data from 2 high-volume cancer centers, we analyzed patients who underwent surgery for localized GA from 1/1/2000-12/31/2017. Standard CT regimens were used according to treatment period. We compared propensity matched cohorts based on age, sex, race, histology, and clinical stage. RESULTS: Four-hundred five patients (age 62 ± 12 year, 58% male, 56% White) were analyzed. 231 (57%) received CRT and 174 (43%) received CT. Groups differed based on histopathologic characteristics including preoperative stage (p = 0.013). To control for these differences, propensity matched cohorts of 113 CT and 113 CRT patients were compared. CRT had similar frequencies of microscopically negative resections to CT (93% vs 91%, p = 0.81), but higher rates of complete pathologic response (15% vs 4%, p = 0.003) and lower pathologic stage (p = 0.002). Completion of intended perioperative therapy occurred in 63% of CT and 91% of CRT patients (p < 0.001). Median DFS was 45mo (95%CI: 20-70) in the CT group and 113mo (95%CI: 75-151) in the CRT group (p = 0.018). Median OS was 53mo (95%CI: 30-77) versus 120mo (95%CI: 101-138); p = 0.015. CONCLUSIONS: In this multi-institutional comparison of neoadjuvant CT and CRT for resectable GA, CRT is associated with higher rates of completed perioperative therapy, higher rates of complete pathologic response, lower pathologic stage, and improved survival.Level of Evidence: Level III.

Impact of histology classification on pathologic treatment response and overall survival in distal esophageal cancer patients: a propensity matched analysis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has been linked to superior pathologic treatment response compared to esophageal adenocarcinoma (EAC) after neoadjuvant chemoradiation. However, the impact of histology on survival remains unclear. It has been suggested, based on epidemiologic similarities, that distal EAC should be grouped with gastric cancers as an entity distinct from distal ESCC, but there is little data to support this recommendation. We therefore aim to compare pathologic treatment response (PTR) and overall survival (OS) in patients with distal EAC versus distal ESCC. METHODS: This retrospective cohort study included patients who underwent esophagectomy for distal esophageal malignancy. Histologic sub-groups were matched (1:1) using a propensity-score matching approach. Pre-operative clinical parameters, oncologic outcomes and survival were compared between groups. RESULTS: 1031 distal EC patients, with a median age of 64.4 years and a male preponderance (86.5%), underwent esophagectomy at our institution between 1999 and 2019. 939 (91.1%) patients had a diagnosis of EAC and 92 (8.9%) had ESCC. A higher proportion of ESCC patients were female (26.1% vs. 12.1%; P < 0.01) and non-white (12.0% vs. 3.8%; P < 0.01). Propensity-score sub-analysis identified 75 matched pairs. Rates of pathologic complete response (58.0% vs. 48.9%; P = 0.67) and OS (43.0 vs. 52.0 months; P = 0.808) were not significantly different between matched groups. CONCLUSIONS: Although traditionally known to have a better overall PTR compared to EAC, ESCC patients in our large series did not show any improvement in PTR or OS. Treatment recommendations for patients with EAC and ESCC should consider tumor location in addition to histology.

Is Preoperative G-Tube Use Safe for Esophageal Cancer Patients?

Objective: Gastrostomy tubes (g-tubes) have been used with caution prior to esophageal resection due to the risks of inoculation metastasis and of injury to the gastric conduit used for reconstruction. In this study, we aim to evaluate the safety of preoperative g-tube placement by comparing outcomes in patients undergoing esophageal resection with and without prior g-tube use.Method: We retrospectively reviewed our institution's database of 1113 esophagectomies performed between 1994 and 2018. We included only patients who received neoadjuvant therapy and identified 65 patients who received preoperative nutritional support through a g-tube (GT+) and 657 who did not (GT-). Demographics, postoperative complications, survival, and cancer recurrence rates were compared between GT + and GT- using Chi-squared and Kaplan-Meier survival analyses.Results: Seven-hundred twenty-two patients (122 female, 600 male) with a median age of 63.2 (28.2-86.3) met our inclusion criteria. Between GT+ (n = 65) and GT- (n = 657), there were no significant differences in anastomotic leak rates (11.5% vs 10.9%; p = 0.901), postoperative mortality (3.1% vs 3.9%; p = 0.765), or overall complications (63.1% vs 65.1%; p = 0.746). GT + was associated with a significantly lower overall survival compared to GT- (32.5 m vs 92.9 m; p = 0.003), and tumor recurrence rates were similar (30.6% vs 31.8%; p = 0.851). There were no cases documenting damage to the gastric conduit caused by prior g-tube placement.Conclusions: G-tube usage was not associated with increased tumor recurrence, anastomotic leak rates, or overall complication rates in this study. Our data suggest that g-tube usage is safe for patients with esophageal cancer requiring preoperative nutrition.

Clinical Factors and Outcomes of Octogenarians Receiving Curative Surgery for Esophageal Cancer.

BACKGROUND: The incidence of esophageal cancer is increasing in the United States. Although neoadjuvant therapy (NAT) for locally advanced cancers followed by surgical resection is the standard of care, there are no clearly defined guidelines for patients aged ≥79 y. METHODS: Query of an institutional review board-approved database of 1031 esophagectomies at our institution revealed 35 patients aged ≥79 y from 1999 to 2017 who underwent esophagectomy. Age, gender, tumor location, histology, clinical stage, Charlson Comorbidity Index (CCI), NAT administration, pathologic response rate to NAT, surgery type, negative margin resection status, postoperative complications, postoperative death, length of stay, 30- and 90-d mortality, and disease status parameters were analyzed in association with clinical outcome. RESULTS: The median age of the octogenarian cohort was 82.1 y with a male preponderance (91.4%). American Joint Committee on Cancer clinical staging was stage I for 20% of patients, stage II for 27% of patients, and stage III for 50% of patients, which was not statistically significant compared with the younger cohort (P = 0.576). Within the octogenarian group, 54% received NAT compared with 67% in the younger group (P = 0.098). There was no difference in postoperative complications (P = 0.424), postoperative death (P = 0.312), and recurrence rate (P = 0.434) between the groups. However, CCI was significantly different between the octogenarian and nonoctogenarian cohort (P = 0.008), and octogenarians had shorter overall survival (18 versus 62 mo, P<0.001). None of the other parameters assessed were associated with clinical outcomes. CONCLUSIONS: Curative surgery is viable and safe for octogenarians with esophageal cancer. Long-term survival was significantly shorter in the octogenarian group, suggesting the need for better clinical selection criteria for esophagectomy after chemoradiation and that identification of complete responders for nonoperative management is warranted.

Outcomes of Gastric Resection in the Establishment of a Comprehensive Oncologic Robotic Program.

BACKGROUND: Robotic-assisted gastrectomy is increasingly utilized for the treatment of gastric malignancies. However, the benefits of robotic surgery have been questioned. This study describes short-term outcomes in the establishment of a comprehensive robotic program for gastric malignancies. MATERIALS AND METHODS: Patients who underwent robotic-assisted gastric resections between 2013 and 2018 were studied. Preoperative measures and surgical outcomes were analyzed. Finally we studied and analyzed robotic and open gastrectomy for the management of gastric adenocarcinoma (GC) at the same institution between 2000 and 2018 for quality benchmarking. RESULTS: Forty six patients (pts.) underwent robotic-assisted gastric resections. 26 (56.5%) were male, with a median age of 62 y (range: 29-87). Pathology included GC, gastrointestinal stromal tumors, neuroendocrine tumors, metastatic lesions, and benign processes. 19 pts. underwent total gastrectomy, 16 distal gastrectomy, four subtotal gastrectomy, and seven wedge resection. Pts. undergoing distal gastrectomy and wedge resection experienced shorter operative times and length of stay than total gastrectomy (P < 0.01; P < 0.01). Four operations (8.8%) were converted to open and 13 pts (28.3%) had postoperative complications, including an 8.7% readmission rate. Median lymph nodes retrieved during total, subtotal, and distal gastrectomy were 20 (13-46), 12.5 (0-26), and 16.5 (0-34), respectively. All pts. underwent margin negative resection. Median follow-up for GC was 21 mo, and 60% of pts. received adjuvant therapy at a median of 59d (range: 23-106). CONCLUSIONS: Robotic gastrectomy is a feasible alternative to open gastrectomy. Our results will help establish benchmarks to improve perioperative outcomes, especially length of stay and time to initiation of therapy.

Biomarker Analysis from a Phase I/Ib Study of Regorafenib and Nivolumab in Mismatch Repair-Proficient Advanced Refractory Colorectal Cancer.

Previously, we reported the modest but durable anticancer activity of regorafenib/nivolumab in mismatch repair-proficient (pMMR) refractory colorectal cancer in our I/Ib study. Our finding suggests the necessity of biomarkers for better selection of patients. Baseline clinical and pathological characteristics, blood and tumor samples from the patients in the trial were collected and evaluated to discover potential biomarkers. The obtained samples were assessed for immunohistochemistry, ELISA and RNA sequencing. Their correlations with clinical outcome were analyzed. A high albumin level was significantly associated with improved progression-free survival (PFS), overall survival (OS) and disease control. Non-liver metastatic disease showed prolonged PFS and OS. Low regulatory T-cell (Treg) infiltration correlated with prolonged PFS. Low MIP-1ß was associated with durable response and improved OS significantly. Upregulation of 23 genes, including CAPN9, NAPSA and ROS1, was observed in the durable disease control group, and upregulation of 10 genes, including MRPS18A, MAIP1 and CMTR2, was associated with a statistically significant improvement of PFS. This study suggests that pretreatment albumin, MIP-1ß, non-liver metastatic disease and Treg infiltration may be potential predictive biomarkers of regorafenib/nivolumab in pMMR colorectal cancer. Further studies are needed to confirm these findings.

Totally minimally invasive laparoscopic robot-assisted Ivor Lewis esophagectomy: improved technique and outcomes over 200 cases.

Background: Surgical resection of esophageal and gastroesophageal junction cancers is a very complex procedure with step learning curve. New technologies have made minimally invasive surgery possible, but challenges still remain for wide spread adoption of these techniques. This article aims to describe the outcomes and salient technical points of a totally minimally invasive, laparoscopic, robot-assisted Ivor Lewis esophagectomy (LRAMIE). Methods: Retrospective observational cohort study performed at a specialty cancer center using a prospectively maintained institutional database. Patients undergoing LRAMIE (laparoscopic abdomen, robotic chest) from 2014-2023 were included. Patients undergoing transhiatal and three-field esophagectomy were excluded. Operative and postoperative outcomes were compared over the study period to identify potential associations between outcomes over time. Results: Two-hundred patients were identified who underwent LRAMIE. Median age was 65 years and most were male (87.5%). The open conversion rate was 1% (n=2), which occurred within the first 30 cases. Operative time and blood loss were improved at the 60-case mark (P<0.001). Anastomotic stricture rate improved after 50 cases, and leak rate improved after 80 cases. Postoperative length of stay improved at both 50 and 100 cases with a median LOS of 6 days after 100 cases. Rate of postoperative pneumonia, 30- and 90-day mortality were reduced after 100 cases, although not statistically significant for mortality due to too few events. Conclusions: Totally minimally invasive Ivor Lewis esophagectomy at a high-volume center is a safe procedure. Operative outcomes improved significantly after 50-80 cases, followed by improvement in anastomotic results and postoperative outcomes, with corresponding excellent oncologic outcomes.