Safety and feasibility of initiating a hepatic artery infusion pump chemotherapy program for unresectable colorectal liver metastases: A multicenter, retrospective cohort study
Muaddi, Hala; D'Angelica, Michael; Wiseman, Jason T; Dillhoff, Mary; Latchana, Nicholas; Roke, Rachel; Ko, Yoo-Joung; Carpizo, Darren; Spencer, Kristen; Fields, Ryan C; Williams, Gregory; Aucejo, Federico; Acevedo-Moreno, Lou-Anne; Billingsley, Kevin G; Walker, Brett S; Mayo, Skye C; Karanicolas, Paul J
INTRODUCTION/BACKGROUND:Hepatic artery infusion pump (HAIP) chemotherapy is a specialized therapy for patients with unresectable colorectal liver metastases (uCRLM). Its effectiveness was demonstrated from a high volume center, with uncertainty regarding the feasibility and safety at other centers. Therefore, we sought to assess the safety and feasibility of HAIP for the management of uCRLM at other centers. METHODS:We conducted a multicenter retrospective cohort study of patients with uCRLM treated with HAIP from January 2003 to December 2017 at six North American centers initiating the HAIP program. Outcomes included the safety and feasibility of HAIP chemotherapy. RESULTS:We identified 154 patients with HAIP insertion and the median age of 54 (48-61) years. The burden of disease was >10 intra-hepatic metastatic foci in 59 (38.3%) patients. Patients received at least one cycle of systemic chemotherapy before HAIP insertion. Major complications occurred in 7 (4.6%) patients during their hospitalization and 13 (8.4%) patients developed biliary sclerosis during follow-up. A total of 148 patients (96.1%) received at least one-dose of HAIP chemotherapy with a median of 5 (4-7) cycles. 78 patients (56.5%) had a complete or partial response and 12 (7.8%) received a curative liver resection. CONCLUSION/CONCLUSIONS:HAIP programs can be safely and effectively initiated in previously inexperienced centers with good response.
Immuno-oncologic care during COVID-19: Challenges and opportunities for improving clinical care and investigation
Spencer, Kristen; Singer, Eric A; Girda, Eugenia
Cancer care has been greatly impacted during the COVID-19 pandemic. The number of cases and deaths caused by the COVID-19 pandemic continues to escalate throughout the United States and the world. Worldwide, over 150 million people have been diagnosed with the coronavirus and more than 3 million have died. Now that we have gained additional experience with COVID-19, we are starting to learn its full impact on oncology care and its effects on the practice of medicine and clinical research.
A phase II/III study of perioperative nivolumab and ipilimumab in patients (pts) with locoregional esophageal (E) and gastroesophageal junction (GEJ) adenocarcinoma: Results of a safety run-in-A trial of the ECOG-ACRIN Cancer Research Group (EA2174). [Meeting Abstract]
Eads, Jennifer Rachel; Weitz, Michelle; Catalano, Paul J.; Gibson, Michael K.; Rajdev, Lakshmi; Khullar, Onkar; Lin, Steven H.; Gatsonis, Constantine; Wistuba, Ignacio Ivan; Sanjeevaiah, Aravind; Benson, Al Bowen; Bahary, Nathan; Spencer, Kristen Renee; Saba, Nabil F.; Hamilton, Stanley R.; Staley, Charles A.; Chakravarthy, Bapsi; Fisher, George A.; Wong, Terence Z.; O\Dwyer, Peter J.
PHASE 1 STUDY OF INCB086550, AN ORAL PD-L1 INHIBITOR, IN IMMUNE-CHECKPOINT NAIVE PATIENTS WITH ADVANCED SOLID TUMORS [Meeting Abstract]
Van Cutsem, Eric; Prenen, Hans; Delafontaine, Brant; Spencer, Kristen; Mitchell, Tara; Burris, Howard; Kotecki, Nuria; Kristeleit, Rebecca; Pinato, David; Sahebjam, Solmaz; Graham, Donna; Karasic, Thomas; Daniel, Jeannie; O\Hayer, Kevin; Geschwindt, Ryan; Piha-Paul, Sarina
The Evolving Role of Radiotherapy in Locally Advanced Rectal Cancer and the Potential for Nonoperative Management
Khullar, Karishma; Patel, Nell Maloney; Anderson, Cristan; Chundury, Anupama; Carpizo, Darren; Feingold, Daniel; Grandhi, Miral; Hochster, Howard; Jani, Krupa; Kennedy, Timothy; Langan, Russell; Spencer, Kristen; August, David; Jabbour, Salma K
Locally advanced rectal cancer has broadly been defined as T3, T4, or lymph node-positive disease. In the 1990s, adjuvant chemoradiation was considered the optimal management for locally advanced rectal cancer. However, the paradigm shifted when the German CAO/ARO/AIO-94 Rectal Cancer trial established neoadjuvant chemoradiation as the standard of care, based on reduced rates of toxicity and local recurrence, as well as higher rates of sphincter preservation compared with postoperative chemoradiation. Both short-course radiation and long-course chemoradiation are currently accepted methods for neoadjuvant treatment, with recent trials showing equivalence in outcomes. While surgery remains the cornerstone of treatment, there are data supporting the use of magnetic resonance imaging for risk stratification in rectal cancer and encouraging prospective data regarding nonoperative management. This review summarizes data on the evolution of treatment for locally advanced rectal cancer and discusses emerging evidence for nonoperative management.
A multicenter randomized phase 2 trial of atezolizumab as monotherapy or in combination with cobimetinib in biliary tract cancers (BTCs): A NCI Experimental Therapeutics Clinical Trials Network (ETCTN) study [Meeting Abstract]
Yarchoan, Mark; Cope, Leslie; Anders, Robert A.; Noonan, Anne; Goff, Laura W.; Goyal, Lipika; Lacy, Jill; Li, Daneng; Patel, Anuj; He, Aiwu R.; Abou-Alfa, Ghassan; Spencer, Kristen; Kim, Edward; Xavier, Stephanie; Ruggieri, Amanda; Davis, S. Lindsey; McRee, Autumn; Kunk, Paul; Zhu, Qingfeng; Wang-Gillam, Andrea; Poklepovic, Andrew; Chen, Helen; Sharon, Elad; Lesinski, Gregory B.; Azad, Nilo
A phase I trial of MK-2206 and hydroxychloroquine in patients with advanced solid tumors
Mehnert, Janice M; Kaveney, Amanda D; Malhotra, Jyoti; Spencer, Kristen; Portal, Daniella; Goodin, Susan; Tan, Antoinette R; Aisner, Joseph; Moss, Rebecca A; Lin, Hongxia; Bertino, Joseph R; Gibbon, Darlene; Doyle, Laurence A; White, Eileen P; Stein, Mark N
PURPOSE:Given the evidence that coordinate inhibition of AKT induces autophagy, we studied the combination of the AKT inhibitor, MK-2206 with hydroxychloroquine (HCQ) in patients with advanced solid tumors. METHODS:Patients were treated with weekly MK-2206 (135Â mg or 200Â mg) plus HCQ (200Â mg, 400Â mg or 600Â mg BID). RESULTS:Thirty-five patients were enrolled across 5 dose levels. Two DLTs of grade 3 maculo-papular rash were observed at dose level 2 (MK-2206 200Â mg weekly plus HCQ at 400Â mg BID) and 1 DLT of grade 3 fatigue at dose level 2B (MK-2206 135Â mg weekly plus HCQ 600Â mg BID). The maximum tolerated dose (MTD) was declared as dose level 2B. The most common adverse events attributed to MK-2206 were hyperglycemia (Nâ€‰=â€‰18; 51%), fatigue (Nâ€‰=â€‰17; 49%), maculo-papular rash (Nâ€‰=â€‰16; 46%), diarrhea (Nâ€‰=â€‰12; 34%), anorexia (Nâ€‰=â€‰11; 31%), and nausea (Nâ€‰=â€‰11; 31%). Patients experiencing adverse events attributed to HCQ were small in number (Nâ€‰=â€‰13) and primarily included fatigue (Nâ€‰=â€‰5; 14%) and maculo-papular rashes (Nâ€‰=â€‰3; 9%). Statistically significant effects on the pharmacokinetic properties of MK-2206 were observed in combination with HCQ. In addition, the plasma concentrations of HCQ in the combination with MK-2206 were significantly higher than the plasma levels of HCQ as monotherapy in prior studies. The best overall response of stable disease was observed in 5/34 (15%) patients. CONCLUSION:The combination of MK-2206 and hydroxychloroquine was tolerable, but with substantial number of drug-related AEs and minimal evidence of antitumor activity.
Conditional Survival Analysis of Metastatic Colorectal Cancer Patients Living â‰¥24 Months: A Single Institutional Study
Ali, Nadia D; Donohue, Kristen; Zandieh, Shadi; Chen, Chunxia; Moore, Dirk; Poplin, Elizabeth; Shah, Mihir M; Nosher, John; Gui, Bin; Jabbour, Salma K; Spencer, Kristen; Carpizo, Darren R
OBJECTIVES:The survival of patients with metastatic colorectal cancer (CRC) has been increasing over recent decades due to improvements in chemotherapy and surgery. There is a need to refine prognostic information to more accurately predict survival as patients survive for any given length of time to assist multidisciplinary cancer management teams in treatment decisions. MATERIALS AND METHODS:We performed a single center retrospective analysis of patients treated with metastatic CRC (unresectable and resectable) who survived >24 months between 2005 and 2015 (N=155). Patient tumor and treatment related variables were collected. Overall survival (OS) estimates conditional on surviving >24 months were compared with actuarial survival estimates of a cohort of patients (33,104 resected, 39,382 unresected) from the National Cancer Database (NCDB). RESULTS:With a median follow-up of 44.2 months, the median OS of resected patients (n=86) was not reached. The median OS of unresected patients was 75.9 months. The conditional survival probabilities of living 1, 2, or 3 years longer after 24 months of survival are 92%, 72%, and 52%, respectively, in unresectable patients and 98%, 92%, and 89% in patients who were resected. The corresponding NCDB 1, 2, and 3 year actuarial survival was 38%, 20%, and 11% for unresected patients and 68%, 46%, and 32% for resected. CONCLUSIONS:These results indicate that CRC patients who survive 24 months with metastatic colorectal cancer have an excellent prognosis and surgery may be appropriate in a subset of patients initially deemed unresectable.
Rethinking the Role of Radiation Therapy in the Treatment of Unresectable Hepatocellular Carcinoma: A Data Driven Treatment Algorithm for Optimizing Outcomes
Sayan, Mutlay; Yegya-Raman, Nikhil; Greco, Stephanie H; Gui, Bin; Zhang, Andrew; Chundury, Anupama; Grandhi, Miral S; Hochster, Howard S; Kennedy, Timothy J; Langan, Russell C; Malhotra, Usha; Rustgi, Vinod K; Shah, Mihir M; Spencer, Kristen R; Carpizo, Darren R; Nosher, John L; Jabbour, Salma K
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, with a majority of HCC patients not suitable for curative therapies. Approximately 70% of initially diagnosed patients cannot undergo surgical resection or transplantation due to locally advanced disease, poor liver function/underlying cirrhosis, or additional comorbidities. Local therapeutic options for patients with unresectable HCC, who are not suitable for thermal ablation, include transarterial embolization (bland, chemoembolization, radioembolization) and/or external beam radiation therapy (EBRT). Regarding EBRT specifically, technological advancements provide a means for safe and effective radiotherapy delivery in a wide spectrum of HCC patients. In multiple prospective studies, EBRT delivery in a variety of different fractionation schemes or in combination with transcatheter arterial chemoembolization (TACE) demonstrate improved outcomes, particularly with combination therapy. The Barcelona Clinic Liver Cancer classification provides a framework for treatment selection; however, given the growing complexity of treatment strategies, this classification system tends to simplify decision-making. In this review, we discuss the current literature regarding unresectable HCC and propose a modified treatment algorithm that emphasizes the role of radiation therapy for Child-Pugh score A or B patients with â‰¤3 nodules measuring >3 cm, multinodular disease or portal venous thrombosis.
NCI9782: A phase 1 study of talazoparib in combination with carboplatin and paclitaxel in patients with advanced solid tumors. [Meeting Abstract]
Turk, Anita Ahmed; Leal, Ticiana; Chan, Nancy; Wesolowski, Robert; Spencer, Kristen Renee; Malhotra, Jyoti; Lang, Joshua Michael; McNeel, Douglas G.; O\Regan, Ruth; Mehnert, Janice M.; Eickhoff, Jens C.; Liu, Glenn; Wisinski, Kari Braun