Metastatic Gastrointestinal Malignancies Research Articles

Outcomes With Malignancy-Associated High-Risk Pulmonary Embolism: A Nationwide Analysis

ObjectiveTo examine the characteristics and outcomes among patients with high-risk pulmonary embolism (PE) and malignancy. Patients and MethodsThe Nationwide Readmissions Database was used to identify hospitalizations with high-risk PE from January 1, 2016, to December 31, 2019. The main outcome was the difference in all-cause in-hospital mortality. ResultsAmong 28,547 weighted hospitalizations with high-risk PE, 4,825 (16.9%) had malignancy. Admissions with malignancy had a lower prevalence of other comorbid conditions except for anemia and coagulopathy. The use of systemic thrombolysis, catheter-directed interventions, and surgical embolectomy was less common among admissions with malignancy, whereas the use of inferior vena cava filter was more common among those with malignancy. All-cause in-hospital mortality was higher among admissions with malignancy even after adjustment (adjusted odds ratio, 1.91; 95% CI, 1.72 to 2.11; P<.001). Metastatic genitourinary, gastrointestinal (other than colorectal), and lung malignancies were associated with the highest incidence of in-hospital mortality. The incidence of intracranial hemorrhage (3.9% vs 3.1%; P=.056) and the composite of non–intracranial hemorrhage bleeding (21.9% vs 20.6%; P=.185) was not different between admissions with and without malignancy. However, admissions with malignancy had higher incidence of gastrointestinal bleeding. ConclusionIn this nationwide analysis of patients admitted with high-risk PE, malignancy was independently associated with an increased risk of in-hospital mortality. The risk was highest among patients with metastatic genitourinary, gastrointestinal, and lung malignancies. Advanced therapies were less frequently used among patients with malignancy.

Use of acupuncture with acupressure in addition to standard-of-care cryotherapy to decrease chemotherapy-associated neuropathy in patients with gastrointestinal malignancies receiving oxaliplatin-based chemotherapy: Study protocol for a randomized, controlled pilot and feasibility study

BackgroundOxaliplatin is a key chemotherapeutic agent in the treatment of local and metastatic gastrointestinal (GI) malignancies. Dose density and treatment adherence can be limited by chemotherapy-induced peripheral neuropathy (CIPN). Early research suggests CIPN incidence and severity may be mitigated by acupuncture, but rigorous data in GI oncology patients is limited. Here, we describe the protocol of a randomized, waitlist-controlled pilot study testing the use of preemptive of acupuncture plus acupressure to decrease CIPN and chemotherapy-related toxicities. MethodsPatients with a GI malignancy (n = 56) with planned 5-fluorouracil (5-FU) and oxaliplatin IV (FOLFOX, FOLFIRINOX) every 2 weeks are being recruited. Additional concurrent anti-neoplastic agents may be used. Enrolled patients are randomized 1:1 to a 3-month intervention of Arm A: acupuncture with acupressure and standard-of-care treatment, or Arm B: standard-of-care alone. In Arm A, on days 1 and 3 of each chemotherapy cycle a standardized acupuncture protocol is administered and patients are taught self-acupressure to perform daily between chemotherapy treatments. Patients in both arms are given standard-of-care oral and peripheral (hands/feet) ice chip cryotherapy during oxaliplatin administration. CIPN and other symptoms are assessed at baseline, 6 weeks, and 3 months from registration. The primary endpoint is CIPN severity at 3 months (EORTC-CIPN 20). Additional endpoints evaluate CIPN incidence (CTCAE, Neuropen, tuning fork); incidence of pain, fatigue, nausea, oral dysesthesia, and anxiety; and feasibility (recruitment, retention, adherence, acceptability). If warranted, trial results will inform the design of a multi-center trial to expand testing of the intervention to a larger patient cohort.

Nationwide utilization of palliative care in patients admitted for GI malignancies.

e24114 Background: Gastrointestinal (GI) cancers account for a large proportion of cancer-related deaths and are often associated with significant impairment in quality of life, even at earlier stages. Although guidelines recommend early palliative care (PC) involvement in all patients with advanced cancer, and select patients at earlier stages, implementation of these practices has been highly variable. Methods: Using the National Inpatient Sample (NIS) database, we selected all adult patients admitted with a primary diagnosis of any GI malignancy from 2016 to 2020. We compared demographic characteristics as well as differences in in-hospital mortality, total hospital charges, and length of stay for patients who received a palliative care consultation during the admission and those who did not, with a goal of elucidating biases and informing future quality improvement efforts. Multivariate logistic regression analysis was conducted to adjust for confounders. Results: There were 1,123,075 admissions with a primary diagnosis of a GI malignancy from 2016 to 2020, which represented 0.8% of total adult admissions.10.5% of admissions included a PC consultation. Rate of PC consultation varied based on the site of primary malignancy (see table). Patients for whom PC was consulted were older (69.3 vs. 66.2 years, p &lt; 0.01), less likely to be white (62.7% vs. 67.1%, p &lt; 0.01), and more likely to have Medicare (60.4 vs. 55.5, p &lt; 0.01). These patients were 12.8 times more likely to die during admission (mortality 24.2% vs. 1.9%, p &lt; 0.01), had longer lengths of stay (8.5 vs. 6.9 days, p &lt; 0.01) and lower total charges (84,400.2 vs. 96,637.6 USD, p &lt; 0.01). Conclusions: Early PC involvement in cancer care has been associated with improvement in quality of life and decreases in costs and readmissions. Rates of PC involvement in our cohort were overall low. Different rates of consultations for different races signal possible provider bias. The significantly higher mortality in patients who received a PC consult reflects the still current practice of involving PC only at the end of life. Quality improvement efforts should focus on eliminating biases and implementing strategies to maximize early palliative care utilization among patients with locally advanced or metastatic GI malignancies. [Table: see text]

Prognostic impact of immune-related adverse events on survival outcomes in metastatic gastrointestinal cancer: A single-institutional experience.

801 Background: Immune checkpoint inhibitors (ICIs) have several approved indications in the treatment of gastrointestinal (GI) malignancies including metastatic disease. The adverse events related to ICI use or Immune related adverse events (irAEs) are now being more readily recognized. The association between the occurrence of irAEs and survival outcomes is not well understood. Whereas complete tolerability of ICIs with minimal irAEs may be indicative of a lack of response, the development of moderate to severe irAEs could result in significant morbidity and mortality especially in already advanced disease. This dilemma has provided an impetus to present our 5-year single institutional experience wherein we aim to determine the impact of irAEs on survival outcomes in metastatic GI malignancies. Methods: We retrospectively reviewed a cohort of adult patients who received ICIs for metastatic GI malignancies at the Cleveland Clinic foundation between 2017-2022 by utilizing an outpatient oncology pharmacy database. ICIs of interest included atezolizumab, ipilimumab, nivolumab and pembrolizumab. The occurrence of irAEs was as determined by primary oncologist. The primary and secondary outcomes were overall survival (OS) and progression free survival (PFS) in patients based on irAE presence, respectively. Results: There was a total of 151 patients who received ICIs for various metastatic GI malignancies. Among these, 38 unique irAEs were identified constituting 25% of the entire cohort. The table shows their distribution by organ system and type of GI malignancy. We observed hyper progressive disease in 3% of irAE cohort. Grade 3-4 irAEs requiring hospitalization occurred in 32% of all irAEs, median hospital length of stay of 5 (range:1-15) days with 11% resulting in death. 26 % discontinued treatment due to irAEs while 44% had palliative care consultations/hospice transition soon after. The median OS rates in patients who had irAEs vs those who didn’t, respectively, were 10 months [95% confidence interval (CI, 5-NA)] vs. 9 months [95% confidence interval (CI, 6-12)], p=0.85. There was also no statistically significant difference in median PFS between both groups (p=0.76). Conclusions: In our single institution cohort of metastatic gastrointestinal cancer patients, despite significant morbidity from irAEs, the prognosis was similar as previous studies suggesting a better outcome in patients with irAEs compared to those who did not experience irAEs.[Table: see text]

Malignant ascites as a marker of peritoneal carcinomatosis burden in patients with colorectal and gastroesophageal cancer.

455 Background: Malignant ascites occurs frequently in patients with gastric cancer (GC) and colorectal cancer (CRC) with peritoneal metastasis (PM). The presence of PM and malignant ascites have been independently reported to confer resistance to systemic therapy and poorer prognosis. However, the occurrence of malignant ascites as a function of increasing peritoneal carcinomatosis burden has been less studied and reported. Methods: We reviewed prospective cohorts of gastric cancer and colorectal cancer patients with PM. The first cohort was a prospective group of GCPM patients receiving bi-directional systemic and peritoneal-directed therapies (catheter-based intraperitoneal chemotherapy and/or pressurized intraperitoneal aerosol chemotherapy respectively) at a tertiary oncology center in Singapore. Clinico-pathological data, including Peritoneal Cancer Index (PCI) and the presence or absence of ascites based on diagnostic laparoscopy, was collected. To orthogonally validate the hypothesis of malignant ascites as a function of peritoneal carcinomatosis burden in gastrointestinal malignancies, we studied the relationship between ascites, PM and survival in an independent cohort of metastatic CRC patients eligible for first-line systemic treatment enrolled in two randomized clinical trials in different Italian cancer centers. Results: In the first cohort of 82 patients with GCPM, the median PCI was 19 (inter-quartile range (IQR) 8 – 26) in the group with ascites and 3 (IQR 1 – 12) in the group without ascites (p=0.005), suggesting ascites occurs with higher PM burden. The median overall survival (OS) was poorer in patients with ascites (13.4 vs 16.4 months, HR 1.6, 95% CI 0.9 – 2.8, p=0.082). The median OS in patients with PCI of &lt;7 was 17.3 months (95% 12.0 – 22.7) and 13.8 months (95% CI 11.0 – 16.6) in those with PCI score &gt;7. In the validation cohort of 900 CRC patients, presence of malignant ascites and PM resulted in poorer survival compared to patients with PM and no malignant ascites (HR for OS PM with ascites vs PM without ascites 2.01 (95% CI 1.37 - 2.96), p&lt;0.001). Interestingly, those with PM and ascites had a poorer survival to those with stage IV disease without peritoneal involvement, while those with PM without ascites did not have a statistically significant difference (PM with malignant ascites vs. no peritoneal disease, HR for OS 2.14, 95% CI 1.57 – 3.01, p=0.007; PM without ascites vs no peritoneal disease, HR for OS 1.10, 95% CI 0.91 – 1.34). Conclusions: Our study of patients with colorectal or gastric cancer and peritoneal metastases suggest the presence of malignant ascites as a function of increased peritoneal carcinomatosis burden among patients with metastatic gastrointestinal malignancies, with correspondingly poorer survival outcomes.

A phase II study of hypofractionated radiation therapy to augment immune response in patients with metastatic gastrointestinal malignancies progressing on immune therapy (ARM-GI).

TPS817 Background: Metastatic disease remains a consistent challenge for patients with gastrointestinal (GI) malignancies. Multiple immune checkpoint inhibitors (ICI) have been FDA approved for several GI indications. Still, patients will progress on these therapies, either immediately or after initial response. Palliative radiation therapy (RT) is an effective treatment that can be delivered to symptomatic metastases. It also has been reported to lead to an abscopal effect, which is an induction of response in a distant tumor. This is thought to result from increased tumor immunogenicity, tumor microenvironment modulation, and immune cell recruitment. Thus, palliative RT could not only relieve symptoms, but also potentially reinvigorate the immune response, prolong ICI efficacy, and delay next-line systemic therapy that carries risks of unknown efficacy and tolerability. Ongoing studies seek to elucidate prognostic and predictive biomarkers of the abscopal effect. However, cohorts of patients with GI malignancies are limited, so there remains a need for research in combining RT and immunotherapy in the context of metastatic GI cancer. ARM-GI aims to study the radiation-augmented immune response in patients with metastatic GI cancers progressing on immunotherapy. Methods: ARM-GI is a phase 2, single arm study. Key eligibility criteria include confirmed metastatic GI malignancy, progressive disease per RECIST v1.1 on any ICI, and at least 2 metastases, one of which can be safely left unirradiated. The target prescription dose is 30 Gy in 5 fractions to symptomatic sites through intensity modulated RT or stereotactic body RT. Patients will continue the same immunotherapy after RT and be evaluated per RECIST v1.1 longitudinally. The primary endpoint is overall response rate (ORR) per RECIST v1.1. Secondary endpoints include ORR per iRECIST, progression free survival, overall survival, local control in radiated lesion(s), effect of distant radiation on unirradiated target lesions, incidence of new metastatic lesions, safety by CTCAE v5.0, and time to new systemic therapy. The study will enroll 28 patients, with recruitment ongoing. Serial peripheral blood samples are collected for exploratory studies that will analyze for association with disease response and quantification of changes in circulating immune cell subsets after RT compared to baseline. Clinical trial information: NCT04221893 .

An Investigation of Insulin Resistance and Cachexia Relation in Patients with Metastatic Gastrointestinal Malignancies

Background: Insulin resistance has been suggested as one of the known metabolic disorders during cachexia. This study hypothesized that cachexia in cancer patients might be related to insulin resistance as early as cachexia development.&#x0D; Methods: This study was performed on 46 patients with metastatic gastrointestinal cancer. Anthropometric characteristics and biochemical markers were assessed at baseline, second and third month. Insulin resistance was assessed using the homeostasis model assessment-estimated insulin resistance (HOMA IR) method. SFQ-36 questions were used to assess the patients' quality of life at baseline, second and third months.&#x0D; Results: Anthropometric characteristic was significantly associated between pre-cachectic and non-pre-cachectic patients in third month. Cholesterol (P-value = 0.93), albumin (P-value: 0.82), and serum creatinine (P-value = 0.88) in pre-cachectic patients decreased over three months. There was an increasing trend of insulin resistance between pre-cachectic and non-pre-cachectic patients in third month. Cholesterol had an upward trend with a significant relation in cachectic patients [(P-value = 0.00), (P-value = 0.03), (P-value = 0.01)]. We detected a decreasing trend of insulin resistance between cachectic and non-cachectic patients from second to third month (P-value = 0.04). SFQ evaluation had no significant relation with cachectic status.&#x0D; Conclusion: Previous studies showed that the use of NSAIDs, progesterone’s, corticosteroids, COX-2 inhibitors, anabolic agents and drugs targeting inflammatory cytokines may be beneficial for improving of symptoms of cachexia. Significant relation between anthropometric variables with pre-cachexia and cachectic conditions was concluded. Patients' outcome and its relation with insulin resistance demonstrated a significant relation between the cachectic and non-cachectic patients in the third month. We also detected the increased serum cholesterol level in cachectic patients, moreover, higher cholesterol levels in expired cachectic patients than in the living.

Circulating tumor DNA for diagnosis, prognosis and treatment of gastrointestinal malignancies.

Minimally invasive detection of circulating tumor DNA (ctDNA) in peripheral blood or other body fluids of patients with gastrointestinal malignancies via liquid biopsy has emerged as a promising biomarker. This is urgently needed, as conventional imaging and plasma protein-derived biomarkers lack sensitivity and specificity in prognosis, early detection of relapse or treatment monitoring. This review summarizes the potential role of liquid biopsy in diagnosis, prognosis and treatment monitoring of gastrointestinal malignancies, including upper gastrointestinal, liver, bile duct, pancreatic and colorectal cancer. CtDNA can now be part of the clinical routine as a promising, highly sensitive and specific biomarker with a broad range of applicability. Liquid-biopsy based postoperative relapse prediction could lead to improved survival by intensification of adjuvant treatment in patients identified to be at risk of early recurrence. Moreover, ctDNA allows monitoring of antineoplastic treatment success, with identification of potentially developed resistance or therapeutic targets during the course of treatment. It may also assist in early change of chemotherapy in metastatic gastrointestinal malignancies prior to imaging findings of relapse. Nevertheless, clinical utility is dependent on the tumor’s entity and burden.

Feasibility of using a computerized food frequency questionnaire (FFQ) to assess dietary patterns in patients with advanced gastrointestinal (GI) malignancies.

465 Background: Identification of poor dietary patterns is important for the optimal management of patients with metastatic GI malignancies who suffer from high rates of malnutrition and sarcopenia which are associated with increased rates of treatment-related toxicity and worsened survival. Dietary records or recall methods and FFQs are available but have high patient burden and are seldom utilized in oncology settings outside of formal nutritional consultations. Thus, we evaluated the feasibility of conducting serial assessments of dietary patterns using a novel computerized FFQ technology. Methods: Assessments of diet using the computerized FFQ, nutritional status (NUTRISCORE), QOL and anorexia/cachexia burden (FAACT), anxiety/depression (HADS) and taste burden were done at the time of initiation of first-line chemotherapy (baseline) and 3 months later. The FFQ was done independently either at home on personal computer after visit or via iPad in infusion room. Dietary quality was defined by the Healthy Eating Index 2010 (HEI) score, which was automatically calculated by the computerized FFQ software. Feasibility was defined as at least 70% of patients completing baseline and 3-month assessments. Spearman’s correlations were used to determine associations between measures. Results: 29 patients with advanced (metastatic or unresectable) GI cancers were enrolled and 23 completed the baseline FFQ (8 colorectal, 5 pancreas, 5 gastroesophageal, 5 other). Median age was 58 (20-78) with M:F ratio of 10:13. The overall completion rate of baseline and 3-month assessments was 81.8%, meeting the pre-defined feasibility criteria. The mean baseline HEI score was 65 (range 38-88). Of patients who completed both baseline and 3-month assessments, the mean HEI score remained stable at 58 with changes in specific HEI components including a 20% decline in the seafood and plant protein score and a 13% decline in the whole grain score and small improvements in other areas (e.g. empty calories, dairy). There were no significant correlations between baseline HEI score and other assessments. Conclusions: It is feasible to use a computerized FFQ to assess for longitudinal changes in eating patterns and dietary quality in patients with advanced GI cancers, particularly when patients can complete the assessments during chemotherapy infusions. Preliminary findings also suggest that the FFQ can be helpful for highlighting areas in which diet quality could be improved. Additional analysis of other computerized FFQ data (e.g. macro/micronutrient consumption) is ongoing.

Role of Immune Checkpoint Inhibitors in Gastrointestinal Malignancies.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several solid and hematological malignancies. ICIs are not only able to produce long and durable responses, but also very well tolerated by patients. There are several approved indications of use of ICIs in treatment of metastatic gastrointestinal malignancies including gastric, esophageal, colorectal and hepatocellular carcinoma. In addition, ICIs can be used in microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB) tumors in chemotherapy-resistant setting. Despite having good efficacy and superior safety profile, ICIs are clinically active in small subset of patients, therefore, there is a huge unmet need to enhance their efficacy and discover new predictive biomarkers. There are several ongoing clinical trials that are exploring the role of ICIs in various gastrointestinal cancers either as single agent or in combination with chemotherapy, radiation therapy, targeted agents or other immunotherapeutic agents. In this review, we discuss the published and ongoing trials for ICIs in gastrointestinal malignancies, including esophageal, gastric cancer, pancreatic, hepatocellular, biliary tract, colorectal and anal cancers. Specifically, we focus on the use of ICIs in each line of therapy and discuss the future directions of these agents in each type of gastrointestinal cancer.

Sensitivity and Specificity of the NETest: A Validation Study

Background: Secretory tumor markers traditionally measured in patients with neuroendocrine tumors (NET) are lacking sensitivity and specificity, and consequently they are of limited clinical utility. The NETest, a novel blood multigene RNA transcript assay, has been found to be highly sensitive and specific. We sought to validate the sensitivity of the NETest in a population of metastatic well-differentiated NETs of gastroenteropancreatic and lung origin and to evaluate NETest specificity in a mixed population of metastatic non-NET gastrointestinal (GI) malignancies and healthy individuals. Design and Methods: Forty-nine patients with metastatic NETs, 21 patients with other metastatic GI cancers, and 26 healthy individuals were enrolled in the study. Samples were sent in a blinded fashion to a central laboratory, and an NETest value of 0–13% was considered normal. Results: Using 13% as the upper limit of normal, the sensitivity of the NETest was 98% (95% CI 89–100%). The overall specificity was 66% (95% CI 51–79%), with 16 false-positive results. Specificity was 81% (95% CI 62–92%) among 26 healthy individuals and 48% (95% CI 26–70%) among patients with other GI malignancies. Using an updated normal range of 0–20%, sensitivity was unchanged, but specificity improved to 100% among healthy participants and to 67% among patients with other cancers. Conclusions: The sensitivity of the NETest is exceptionally high (>95%) in a population of metastatic, well-differentiated NETs. Specificity within a healthy population of patients is exceptionally high when using a normal range of 0–20% but relatively low when evaluating patients with other GI malignancies.

Immune Checkpoint Inhibitors in Locally Advanced, Unresectable, and Metastatic Upper Gastrointestinal Malignancies.

Upper gastrointestinal (UGI) malignancies including esophageal, gastroesophageal junction (GEJ), and gastric cancers have a poor prognosis in the metastatic setting. Treatment with cytotoxic chemotherapy remains the treatment of choice in the first-line setting with the addition of trastuzumab, a monoclonal antibody against HER-2, if the tumor is HER2-positive. Before the era of checkpoint inhibitors, there were only few treatment options after failure of the first-line systemic therapy. We extensively searched the English written literature for peer-reviewed manuscripts regarding the use of checkpoint inhibitors in advanced stage and metastatic UGI cancer. We also searched and reviewed ongoing clinical trials from Clinicaltrials.gov. Checkpoint inhibition is a promising therapeutic option in UGI cancers, which have overexpression of PD-L1, high mutation burden, or microsatellite instability. Checkpoint inhibitors that are being investigated or are approved in advanced UGI malignancies include PD-1 antibodies, nivolumab and pembrolizumab, PD-L1 antibody, avelumab, and CTLA-4 inhibitors, ipilimumab and tremelimumab. Based on recent and ongoing studies, eligible patients who have progressed beyond the first-line cytotoxic chemotherapy may benefit from immunotherapy. This review outlines the checkpoint inhibitors that are currently or previously being investigated for patients with metastatic UGI cancers.

Pembrolizumab in gastrointestinal (GI) malignancies with defective DNA mismatch repair (dMMR): A single institution experience.

e23081 Background: Defective DNA mismatch repair is associated with increased mutation load and expression of neoantigens. Increased activity of PD-1 inhibitor is reported in patients with GI cancers with dMMR. Here, we describe our experience at Huntsman Cancer Institute with PD-1 inhibition in subjects with GI malignancies with dMMR. Methods: Retrospective chart review of patients with metastatic GI malignancies with dMMR, treated with pembrolizumab at Huntsman Cancer Institute between July 15, 2015 and February 6, 2017. Results: A total of 9 patients were identified that received at least 1 dose of pembrolizumab [colorectal (CRC) n = 4; extrahepatic cholangiocarcinoma (EHCC) n = 2; pancreatic adenocarcinoma (PDAC) n = 2; adenocarcinoma of the appendix n = 1]. Five patients received concurrent cytoxic chemotherapy at some point in treatment. Median number of doses given: 6.5 (3-18). Median age: 61 years (33-73 years). Eight patients were evaluable for response per RECIST. Two patients had complete responses (EHCC and CRC). Two patients had a partial response: PDAC (-57%, time to progression [TTP] +11 months) and CRC (-38%, TTP +6 months). Three patients had stable disease: PDAC (-28%, TTP +5 months), CRC (-6%), and adenocarcinoma of the appendix. One patient with CRC died from upper GI bleeding. Two patients experienced toxicities requiring discontinuation of pembrolizumab. The first patient experienced grade 3 hyperthyroidism and adrenal insufficiency. The second patient had an incidental finding of pneumonitis and enlarged mediastinal lymph nodes on restaging CT scan, biopsy showed non-necrotizing granulomas consistent with sarcoidosis. One patient had grade 2 pneumonitis that was treated and resolved on steroids. This patient continues on pembrolizumab. Conclusions: Single-institution data seem to confirm activity of PD-1 inhibitor in GI malignancies that harbor dMMR. At time of abstract submission, six patients remain on single agent pembrolizumab. Complete responses were seen in CRC and EHCC. Two patients (PDAC and CRC) attained a partial response. Updated responses for all patients will be presented during the meeting.

Pembroliuzmab in gastrointestinal (GI) malignancies with defective DNA mismatch repair (dMMR): A single institution experience.

792 Background: Defective DNA mismatch repair is associated with increased mutation load and expression of neoantigens. Increased activity of PD-1 inhibitor is reported in patients with GI cancers with dMMR. Here, we describe our experience at Huntsman Cancer Institute with PD-1 inhibition in subjects with GI malignancies with dMMR. Methods: Retrospective chart review of patients with metastatic GI malignancies with dMMR, treated with pembrolizumab at Huntsman Cancer Institute between July 15, 2015 and September 26, 2016. Results: A total of 9 patients were identified that received at least 1 dose of pembrolizumab (colorectal n=5; cholangiocarcinoma n=2; pancreatic n=2). Of the 9 patients, 5 received concurrent cytoxic chemotherapy. Median number of doses given was 3 (range 1 to 17). Three patients received pembrolizumab on clinical trial with concomitant mFOLFOX6. Five patients have restaging scans at the time of abstract submission. The first patient has cholangiocarcinoma and experienced a -73% response per RECIST criteria from baseline (time to progression +8 months). The second patient has pancreatic adenocarcinoma and showed a total -56.7% response per RECIST criteria from baseline (time to progression +5 months). The third patient has colorectal carcinoma and had stable disease by RECIST at restaging after 2 months (biochemical response with a 50% decrease in CEA). The fourth patient has cholangiocarcinoma and had a biochemical response with a 50% decrease in CA 19-9 and a mixed response on first restaging scan (time to progression +3.5 months). All 4 of these patients continue to have response to therapy at the time of abstract submission. The fifth patient who had colorectal cancer and died from upper GI bleeding. Restaging CT scans showed response to therapy after 6 weeks of treatment. Four additional patients initiated treatment recently and have yet to undergo restaging scans. Conclusions: Single-institution data seem to confirm activity of PD-1 inhibitor in GI malignancies that harbor dMMR. All 5 restaged patients demonstrated response to PD-1 inhibition by RECIST criteria or decreased tumor marker. Updated responses for all patients will be presented during the meeting.

2O - Phase 1 study of ramucirumab (R) plus durvalumab (D) in patients (pts) with locally advanced and unresectable or metastatic gastrointestinal or thoracic malignancies (NCT02572687); Phase 1a results

2O - Phase 1 study of ramucirumab (R) plus durvalumab (D) in patients (pts) with locally advanced and unresectable or metastatic gastrointestinal or thoracic malignancies (NCT02572687); Phase 1a results

Determinants of Palliative Care Utilization Among Patients Hospitalized With Metastatic Gastrointestinal Malignancies.

Gastrointestinal tract cancers account for a significant proportion of the national cancer burden. We sought to explore patient- and hospital-level determinants of palliative care utilization among patients hospitalized with metastatic gastrointestinal tract cancers using a national database. An analysis of the 2012 National Inpatient Sample was performed. International Classification of Diseases, Ninth Revision codes were used to identify hospital discharges associated with metastatic digestive tract cancers and patient/hospital covariates for inclusion in a logistic regression model. Total charges and length of stay were analyzed in a linear regression model. Compared to males, females were more likely to receive inpatient palliative care (adjusted odds ratio [OR] 1.12, P = .002). No difference was seen between white and Asian patients (adjusted OR 1.2, P = .11) or Native Americans patients (adjusted OR 1.4, P = .22). However, relative to white patients, African Americans (adjusted OR 1.13, P = .02) and Hispanics (adjusted OR 1.25, P = .001) had significantly higher odds of inpatient palliative care. Medicare patients were least likely to receive palliative care compared to those with Medicaid or commercial payers. Length of stay during these hospitalizations was longer in African Americans ( P = .0001), Asians ( P = .0001), and Native Americans ( P = .03) compared to white patients. No difference was seen when total charges were compared between white and African American patients ( P = .08). Conversely, total charges were higher in Hispanics ( P = .005) and Asians ( P = .001) relative to white patients. Gender and racial differences exist in utilization of inpatient palliative care among patients hospitalized with metastatic gastrointestinal tract cancers.

Present and future role of surgery in metastatic gastrointestinal malignancies.

Metastases from gastrointestinal malignancies are systemic or abdominal disseminations of cancer cells. From a biological perspective surgical resections are questionable but case series show that for some tumour types, surgery influences survival outcome. This review focuses on management and indications for surgery in recent literature of these metastatic gastrointestinal malignancies. A few gastrointestinal malignancies have emerged to be candidates for surgery in case of metastatic disease. Surgery can be considered in selected cases with liver metastases or abdominal dissemination of colorectal cancer, metastases from gastrointestinal stromal tumours or neuroendocrine tumours. On the contrary, recent publications do not support surgery for metastatic disease of any other gastrointestinal origin. The literature has ample examples of small series and anecdotal cases of successful surgical interventions for most tumour types but no new evidence has been presented to support broader indications for surgery. The evidence base for surgery of different metastatic gastrointestinal malignancies is unchanged. There are some clarifications when to perform surgery and the timing of surgery in regard to combined treatments. No new tumour types are added to potential candidates for surgery.

Dynamic monitoring of plasma amino acids and carnitine during chemotherapy of patients with alimentary canal malignancies and its clinical value.

ObjectiveThe aim of this study was to observe the plasma amino acid and carnitine characteristics in patients with metastatic gastrointestinal malignancies during chemotherapy and to identify markers for the early diagnosis and evaluation of adverse reactions and prognosis of the digestive tract malignant tumor patients.MethodsBlood samples of 30 patients with metastatic gastrointestinal malignancies were collected at four time points: before chemotherapy, the first day after chemotherapy (+1 day), bone marrow depression period (+14 days), and hematopoietic recovery period (+21 days). The plasma amino acids and carnitine from those 30 patients were determined by high-performance liquid chromatography–tandem mass spectrometry method. Simultaneously, the levels of 21 amino acids were detected in 30 healthy individuals, who were considered as control. Biochemical indexes were also detected at four time points, adverse reactions were recorded during the chemotherapy process, and patients were followed up for 1 year to observe time to progression (TTP) and progression-free survival (PFS).ResultsCompared to healthy people in the control group, patients with malignancies showed significantly increased levels of plasma amino acids such as Arg, Asp, Cit, Gly, Orn, Tyr, Val, and carnitine (such as C2). The levels of compounds such as C3, Asn, Leu, Lys, Pip, Pro, C0, C5:1 decreased significantly before chemotherapy. The levels of Cit, Cys, Lys, Pro, Tyr, Val, C0, and C2 decreased significantly on the second day of chemotherapy (+1 day), whereas the level of C3 increased significantly. During myelosuppression (+14 days), the levels of Asp, Cit, Met, and Orn were observed to still decrease significantly, whereas the level of Val appeared to increase significantly. The levels of Asp, Glu, and Met were clearly different among patients with gastric carcinoma, rectal cancer, and colon cancer. Compared to the control group, aspartate amino transferase and alanine aminotransferase were found to be higher in eight patients with hypocarnitinemia, yet TTP, PFS, and RR (response rate) were lower. No significant difference was observed for adverse reactions. The indexes in 12 patients with citrullinemia showed no difference compared with control group. All the results showed statistically significant differences (P<0.05).ConclusionReal-time monitoring of plasma amino acids and carnitine in patients with metastatic gastrointestinal malignancies can directly reflect the body’s metabolism and nutritional status. The results provide a reference for nutrition therapy or support for patients with alimentary canal malignancies. Hypocarnitinemia is a risk factor for gastrointestinal cancer patients and affects TTP, PFS, and RR by liver function. This study shows that tandem mass spectrometry can be used to detect blood amino acids and carnitine spectrum may be used for an early diagnosis and evaluation of adverse reactions and prognosis of the digestive tract malignant tumor patients.

Gender and racial variations in palliative care utilization among patients hospitalized with metastatic gastrointestinal malignancies.

e17565 Background: Increased healthcare resource utilization has been demonstrated among patients with advanced malignancies. We sought to explore patient and hospital level determinants of inpatie...

Germline TYMS genotype is highly predictive in patients with metastatic gastrointestinal malignancies receiving capecitabine-based chemotherapy.

This work was initiated to extend data on the effect of pharmacogenetics and chemotherapy pharmacokinetics (PK) on clinical outcome in patients with gastrointestinal malignancies. We assessed 44 gene polymorphisms in 16 genes (TYMS, MTHFR, GSTP1, GSTM1, GSTT1, DPYD, XRCC1, XRCC3, XPD, ERCC1, RECQ1, RAD54L, ABCB1, ABCC2, ABCG2 and UGT2B7) in 64 patients with metastatic colorectal cancer (CRC) receiving capecitabine/oxaliplatin and 76 patients with advanced gastroesophageal cancer (GEC) receiving epirubicin/cisplatin/capecitabine, respectively. Plasma concentrations of anticancer drugs were measured for up to 24h, and results were submitted to population PK analysis. We calculated the association between gene polymorphisms, chemotherapy exposure, tumor response, progression-free survival (PFS), overall survival (OS) and chemotherapy-related toxicity using appropriate statistical tests. Patients with a low clearance of 5FU were at increased risk of neutropenia (P<0.05) and hand-foot syndrome (P=0.002). DPYD T85C, T1896C and A2846T mutant variants were associated with diarrhea (P<0.05) and HFS (P<0.02), and IVS14+1G>A additionally with diarrhea (P<0.001). The TYMS 2R/3G, 3C/3G or 3G/3G promoter variants were associated with worse PFS in the CRC (HR=2.0, P<0.01) and GEC group (HR=5.4, P<0.001) and worse OS in the GEC group (HR=4.7, P<0.001). The GSTP1 A313G mutant variant was associated with a higher PFS (HR=0.55, P=0.001) and OS (HR=0.60, P=0.002) in the CRC group. Germline polymorphisms of DPYD, TYMS and GSTP1 have a significant effect on toxicity and clinical outcome in patients receiving capecitabine-based chemotherapy for advanced colorectal or gastroesophageal cancer. These data should further be validated in prospective clinical studies.