Gastrointestinal Oncology Service Research Articles

Lack of Availability and Efficacy of Phase I and Basket Trials for Patients With Gastrointestinal Cancers.

In the modern era of targeted and immune-based therapies, investigator and patient expectations of availability and efficacy in phase I trials have increased. We assessed availability of, and benefit from, early drug development trials, specifically in patients with gastrointestinal cancers. We reviewed computerized referral records of the Early Drug Development Service at our institution to identify patients internally referred from our Gastrointestinal Oncology Service in calendar year 2018. End points were treatment on a trial, 3- and 6-month progression-free survival (PFS), and any tumor shrinkage. Of 394 gastrointestinal cancer patients referred in 2018, 54 enrolled on a trial and 53 (13.5%) were treated (1 withdrew before treatment): 34 on immune-based and 19 on targeted (3 to phase II basket) studies. None of the 52 patients who had exhausted standard therapy achieved 6-month PFS, two (3.8%) met 3-month PFS with tumor growth below Response Evaluation Criteria in Solid Tumors progression at 3 months, and both came off study for progression at 4 months. One patient who was to receive an irinotecan-based regimen as standard therapy instead received irinotecan plus an investigational targeted agent and remained stable for 8 months. No patients achieved any degree of tumor shrinkage. The most common reasons for nonaccrual were lack of available protocol treatment openings and failure to meet eligibility criteria for specific trials. Thus, availability and benefit from investigational treatment in this treatment-refractory gastrointestinal cancer patient population was extremely modest. Expectations regarding both availability and efficacy of phase I investigational therapy in gastrointestinal cancer patients likely exceed what our experience suggests.

Benefit of early-phase targeted, basket, and immune-based trials for patients with chemorefractory gastrointestinal (GI) cancers.

e15700 Background: Historically, phase I trials were designed to establish phase II tolerable doses of new drugs. Efficacy concerns were secondary. In the modern era of targeted and immune-based therapies, investigator and patient expectations of efficacy in such trials have increased. Patients (pts) who have exhausted standard treatment options often seek participation in phase I drug development or phase II basket studies, with hope for therapeutic benefit. We assessed the benefit to pts with chemorefractory GI cancers from investigational early drug development trials at our institution. Methods: We reviewed the referral records of our Early Drug Development and Immunotherapy Services to identify pts referred from our GI Oncology Service in 2018. As pts are typically not referred unless with performance status 0-1, and normal liver, renal, and marrow function, those requesting early phase studies but not meeting these criteria were excluded from this analysis. End points were enrollment on a trial, 3 and 6-month PFS, and tumor shrinkage. Results: Of 245 GI Oncology pts referred in 2018, 26 (11%) were accrued to a trial: 14 to immune-based (1 withdrew before treatment) and 12 to targeted (3 to phase II basket): median age 53 (range 23-76); 15 female. GI cancer types included: colon (7), pancreas (7), cholangiocarcinoma (4), rectal (3), and appendiceal, peritoneal mesothelioma, small bowel, unknown primary, and gastric (1). Most common reasons for non-accrual were lack of available treatment spots and failure to meet eligibility criteria for specific trials. Of 22 pts with adequate follow up at time of analysis, none achieved 6-month PFS; one (5%) met 3-month PFS with tumor growth below RECIST criteria at 3 months and came off study for progression at 4 months. No pts achieved any degree of tumor shrinkage while receiving trial drugs. Conclusions: Phase I and phase II basket options for chemorefractory GI cancers were limited relative to demand. Benefit from investigational treatment in this patient population was limited; expectations may be overstated. Further research is underway to evaluate pts’ expectations for therapeutic benefit from early phase targeted and immune-based trials.

Self-Care Support for Patients with Gastrointestinal Cancer: iCancerHealth.

Patient-centered symptom assessment and management tools allow patients to perform self-assessments and engage in self-symptom management. Efficacious tools exist for reducing symptom distress; however, little is known about feature-specific use. This article evaluates the feasibility of the iCancerHealth app as an adjunct to usual patient education regarding cancer symptoms and medication management. We conducted a single-arm, pilot study grounded in the health outcomes model. Our evaluation included (1) enrollment rates, (2) 2-month utilization rates, (3) patient acceptability, and (4) clinician satisfaction with the provider-side application. English-speaking, adult patients receiving care in the gastrointestinal oncology service of a comprehensive cancer center were invited to participate. Research coordinators enrolled consenting participants who had a personal, Internet-connected device; participants registered and used the platform to complete the baseline symptom assessment in clinic. Participants were reminded weekly to use the app and to perform a symptom report 4 to 6 weeks later. A total of 64 patients were approached, of which 57 (89%; 95% exact confidence interval [CI], 79-96%) enrolled. About half were ≥ 60 years old and 40% were women. Fifty-three patients (93%; 95% exact CI, 85-99%) accessed at least one app feature, at least once, from home. The most frequently used (86%) feature was Health Tracker in which participants monitored and reported symptoms; followed by My Inbox (63%) and My Medications features (60%). The mean acceptability score was 24.8 (standard deviation = 4.2), indicating good acceptability. Clinicians reported that the app was most acceptable with regard to facilitating in-person interactions that occurred after app use. In a sample of adults with various stages of gastrointestinal malignancies, the iCancerHealth app was utilized at a high rate. Features that focused on symptoms and medication side effects plus communication with clinicians were used most frequently. This extends our understanding of preferences and specific feature use with patient-centered technologies.

Characteristics and Outcomes of Ethics Consultations on a Comprehensive Cancer Center's Gastrointestinal Medical Oncology Service.

The goal of this paper is to review and describe the characteristics and outcomes of ethics consultations on a gastrointestinal oncology service and to identify areas for systems improvement and staff education. This is a retrospective case series derived from a prospectively-maintained database (which includes categorization of the primary issues, contextual ethical issues, and other case characteristics) of the ethics consultation service at Memorial Sloan Kettering Cancer Center. The study analyzed all ethics consultations requested for patients on the gastrointestinal medical oncology service from September 2007 to January 2016. A total of 64 patients were identified. The most common primary ethical issue was the DNR order (39%), followed by medical futility (28%). The most common contextual issues were dispute/conflict between staff and family (48%), dispute/conflict intra-family (16%), and cultural/ethnic/religious issues (16%). The majority of ethical issues leading to consultation were resolved (84%); i.e., the patient, surrogate, and/or healthcare team followed the recommendation of the ethics consultant. 22% had a DNR order prior to the ethics consult and 69% had a DNR order after the consult. In this population of patients on a gastrointestinal oncology service, ethics consultations are most often called regarding patients with advanced cancers and the most common ethical conflicts arose between families and the health care team over goals of care at the end of life, specifically related to the DNR order and perceived futility of continued/escalation of treatment. Ethics consultations assisted with conflict resolution. Conflicts might be reduced with improved communication about prognosis and earlier end of life care planning.

Interview with Dr Ghassan K Abou-Alfa.

Ghassan K Abou-Alfa joined the Gastrointestinal Oncology Service at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College in New York back in 2001. Dr Abou-Alfa specializes in the treatment of gastrointestinal malignancies. Dr Abou-Alfa received his medical degree from the American University of Beirut, Lebanon, and completed his post-doctoral training at Yale University School of Medicine. His research is dedicated to finding novel therapies and improving the effectiveness of the current therapies for hepatocellular carcinoma, cholangiocarcinoma and gallbladder cancer, while continuing to understand the basic mechanisms of the diseases and its therapy. Dr Abou-Alfa has invested several years in helping develop multi-tyrosine kinases and more immune-modulator therapies. Dr Abou-Alfa has many publications in the field. He led on many occasions international teams of investigators. Dr Abou-Alfa serves as the chair of the National Cancer Institute (NCI) Task Force for Hepatobiliary Cancers and the chair of the AIDS Malignancy Consortium (AMC) Non-AIDS Defining Malignancies (NADC) Liver/GI Task Force. Dr Abou-Alfa also co-chairs the hepatobiliary cancers subgroup of the Alliance cooperative group, and is a cadre member of both the gastrointestinal cancers and pharmacogenomics and population pharmacology committees. Dr Abou-Alfa who has lectured worldwide on the subject on gastrointestinal malignancies, is also a strong advocate for raising awareness and support for improving the outcome of patients with this disease, and enhancing oncologic education worldwide.

Study Using the NCCN Guidelines for Palliative Care to Screen Patients for Palliative Care Needs and Referral to Palliative Care Specialists

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Palliative Care recommend screening all patients for palliative care (PC) needs and to call a PC consult when referral criteria are met. The goal of this pilot project was to evaluate the feasibility of implementing the screening and referral components of the NCCN Guidelines for Palliative Care in patients admitted to the Gastrointestinal Oncology Service (GIOS) at a comprehensive cancer center (CCC). Floor nurses performed the initial screening of all patients admitted to the 2 teams-Team A and Team B-of the GIOS on one floor of Memorial Hospital for 3 months. In addition, only the patients admitted to Team A were evaluated according to the referral criteria, triggering a PC consult if results were positive. Nurses were surveyed regarding satisfaction with and the acceptability of screening. During the study period, 229 (90%) total admissions were screened, with 169 (73%) having positive results. Of the Team A admissions, 72 (64%) met the referral criteria. More consults occurred for patients in Team A (47 vs 15; P=.001). In 30% of the referral criteria-triggered consults, the PC needs were manageable by the primary team. Nurses reported screening to be easy and quick (<5 minutes per patient) but only somewhat helpful. Being unfamiliar with many patients and families, floor nurses often felt unable to screen them accurately for some issues. In conclusion, screening was feasible, increasing access to PC, but accuracy and usefulness are concerns. With a consult indicated in 64% patients, yet with 30% being manageable by the primary team, the current criteria may be too sensitive for the inpatient environment of a CCC. More evaluation is needed before widespread implementation can be recommended.

Feasibility of screening hospitalized cancer patients for palliative care.

9094 Background: The National Comprehensive Cancer Network Palliative Care (PC) Guideline recommends screening all oncology patients for PC needs, and to call a PC consult when referral criteria are met. There are no data on the feasibility or impact of this approach. The aim of this pilot study was to assess the feasibility of PC screening in patients admitted to a comprehensive cancer center (CCC). Methods: Design: Observational study. From 11/1/10 to 1/31/11, floor nurses screened all patients the day after admission under the two teams (“Team A” and “Team B”) of the Gastrointestinal Oncology Service at Memorial Sloan-Kettering Cancer Center. Team A patients were also evaluated by the referral criteria. Endpoints: Patients screened ‘positive’ if they had advanced disease and any of the clinical situations nominated in the Guideline. The referral criteria triggered PC consults in Team A patients; clinical judgment triggered Team B consults. Outcomes: Screening rates, nursing satisfaction survey, clinical and operational metrics. Results: Ninety percent (229 of 254) of admissions were screened. Both Teams’ patients were seriously ill (see Table), and it was no surprise that 63% (145 of 229) screened positive. Survey respondents (response rate 50%) rated screening as simple, quick and helpful, although nurses scored the extent of disease wrong in 16%. Sixty eight percent (55 of 780) of Team A patients who screened positive met the referral criteria. This generated more consults on Team A, but the effect on key outcomes was not significant (n.s.). Conclusions: Screening for PC was feasible in this setting, but is a challenging concept in terms of reliability, validity and timing. The value to a CCC of increasing PC access via referral criteria needs evaluation in well-designed trials. [Table: see text]

Thromboembolism is common and influences prognosis in patients with pancreatic cancer, study reports

Thromboembolism is common and influences prognosis in patients with pancreatic cancer, study reports

An Emerging Entity: Pancreatic Adenocarcinoma Associated with a Known BRCA Mutation: Clinical Descriptors, Treatment Implications, and Future Directions

BRCA1 and BRCA2 germline mutations are associated with an elevated risk for pancreas adenocarcinoma (PAC). Other BRCA-associated cancers have been shown to have greater sensitivity to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors with better clinical outcomes than in sporadic cases; however, outcomes in BRCA-associated PAC have not been reported. Patients with a known BRCA1 or BRCA2 mutation and a diagnosis of PAC were identified from the Gastrointestinal Oncology Service, Familial Pancreas Cancer Registry, and Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center. Fifteen patients, five male, with a BRCA1 (n = 4) or BRCA2 (n = 11) mutation and PAC and one patient with a BRCA1 mutation and acinar cell carcinoma of the pancreas were identified. Seven female patients (70%) had a prior history of breast cancer. Four patients received a PARP inhibitor alone or in combination with chemotherapy; three demonstrated an initial radiographic partial response by Response Evaluation Criteria in Solid Tumors whereas one patient had stable disease for 6 months. Six patients received platinum-based chemotherapy first line for metastatic disease; five of those patients had a radiographic partial response. BRCA mutation-associated PAC represents an underidentified, but clinically important, subgroup of patients. This is of particular relevance given the ongoing development of therapeutic agents targeting DNA repair, which may potentially offer a significant benefit to a genetically selected population. We anticipate that further study and understanding of the clinical and biologic features of BRCA-mutant PAC will aid in the identification of tissue biomarkers indicating defective tumor DNA repair pathways in sporadic PAC.

Combined Modality Treatment of Resectable and Borderline Resectable Pancreas Cancer: Expert Consensus Statement

Department of Radiation Oncology, Rush University Medical Center, Chicago, IL; Division of Surgical Oncology, University of California at San Diego, San Diego, CA; Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York; Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Pancreaticobiliary Cancer, Digestive Diseases Institute, Virginia Mason Medical Center, Seattle, WA; Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX