Alemtuzumab induced ST-segment elevation and acute myocardial dysfunction

AbstractCardiac toxicity as a side effect of chemotherapeutic agents has been well reported in the literature. Cardiac toxicity secondary to alemtuzumab has been reported, presenting as congestive heart failure and arrhythmias. Here we report a case of acute myocardial dysfunction after administration of a test dose of alemtuzumab. Our patient was a 66-year-old man with a history of small lymphocytic lymphoma/chronic lymphocytic lymphoma who received a test dose of alemtuzumab. Twenty minutes post administration, the patient developed nausea, vomiting, rigors, and tachycardia. Electrocardiography (ECG) showed acute ST-segment elevations in contiguous leads V2–V6, I, and AVL with no associated chest pain. Bedside echocardiogram showed akinesis of the anterior septum, apex, distal anterior wall, and decreased left ventricular ejection fraction. Cardiac catheterization showed non-critical occlusive disease and no intervention was undertaken. Post-catheterization ECG revealed resolution of ST segment elevations, TWI in V4–V6, and prolongation of corrected QT. Repeat echocardiogram 10 days after the event demonstrated no improvement in wall motion or ejection fraction. We discuss the possible mechanisms causing ST-elevations and acute myocardial dysfunction after treatment with alemtuzumab.<Learning objective: Alemtuzumab can cause acute myocardial dysfunction after administration of a test dose. Considering that this is a serious adverse effect, detailed cardiac evaluation and a high level of caution are recommended before administration of alemtuzumab. While no clear etiology could be identified for this side effect, excessive and acute cytokine release triggered by alemtuzumab administration is a possible explanation. This could be potentially attenuated by using anti-interleukin-6 or tumor necrosis factor inhibitors.

Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes

Background: Favorable toxicity and survival outcomes after dose escalated stereotactic MR guided adaptive radiation therapy (SMART) have been recently published for locally advanced (LA) and borderline resectable (BR) pancreatic cancer. Perioperative morbidity and mortality are not well understood after ablative radiation therapy, which may temper enthusiasm for offering surgery. Objectives: The purpose of this study was to investigate survival and toxicity in resected pancreas cancer patients after neoadjuvant ablative SMART. Methods: In this IRB approved analysis, we retrospectively reviewed 33 consecutive patients with resectable, BR, and LA pancreatic cancer based on NCCN 2.2021 staging criteria who were treated at 2 institutions from 2017-2020 with neoadjuvant SMART 50 Gy in 5 fractions on a 0.35T MR Linac and later underwent definitive surgical resection. Overall survival (OS) and locoregional control (LRC) were evaluated by Kaplan-Meier method. Results: Median follow up was 22.4 months from diagnosis and 17.8 months from last day of RT. Most had BR (55%), otherwise initially resectable (33%) or LA (12%) pancreatic cancer. Median duration of induction chemotherapy was 3.5 (SD 1.6) months with most common regimens being FOLFIRINOX (74%), gemcitabine/abraxane (24%) and FOLFOX (3%). Performance status was ECOG 0, 1, 2 in 16 (48.5%), 12 (36.4%), and 5 (15.2%), respectively. Whipple was performed in 27 (82%) of patients, distal pancreatectomy in 4 (12%), and total pancreatectomy in 2 (6%). The median duration from SMART completion to surgery was 6.9 weeks (4.7-44.1). R0 resections were achieved in 28 (84.8%) of patients with the rest being R1, all in BR patients. Vascular resection/reconstruction was performed of the portal vein (PV) in 8 (24.2%) patients, SMV in 4 (12%), SMA in 1 (3%), and common hepatic artery in 2 (6%). Vascular resection/reconstruction was performed in all LA patients. Median OS, 1-year OS, and 2-year OS from diagnosis were 29.6 months, 93.8%, 81.5%, respectively. Median OS from RT was not yet reached; 1-year OS was 90.9%. LRC at 1 and 2 years was 97% and 93%, respectively. Radiation related acute and late grade 3+ gastrointestinal toxicity was seen in 2 (6%) and 2 (6%) patients. Post-op mortality at 30 and 90 days was seen 2 (6%) and 3 (9%) of patients with 1 death from GI bleed attributed to surgery and 1 death from hepatic ischemia related to PV resection. Conclusions: To the best of our knowledge, this is the first report suggesting that surgery for pancreas cancer after dose escalated 5-fraction SMART is feasible. Further clarification is needed with respect to ideal patient selection and timing for surgery, the safety of arterial versus venous resection/reconstruction, and histopathologic response after delivery of ablative versus non-ablative radiation dose

Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes

Background: Favorable toxicity and survival outcomes after dose escalated stereotactic MR guided adaptive radiation therapy (SMART) have been recently published for locally advanced (LA) and borderline resectable (BR) pancreatic cancer. Perioperative morbidity and mortality are not well understood after ablative radiation therapy, which may temper enthusiasm for offering surgery. Objectives: The purpose of this study was to investigate survival and toxicity in resected pancreas cancer patients after neoadjuvant ablative SMART. Methods: In this IRB approved analysis, we retrospectively reviewed 33 consecutive patients with resectable, BR, and LA pancreatic cancer based on NCCN 2.2021 staging criteria who were treated at 2 institutions from 2017-2020 with neoadjuvant SMART 50 Gy in 5 fractions on a 0.35T MR Linac and later underwent definitive surgical resection. Overall survival (OS) and locoregional control (LRC) were evaluated by Kaplan-Meier method. Results: Median follow up was 22.4 months from diagnosis and 17.8 months from last day of RT. Most had BR (55%), otherwise initially resectable (33%) or LA (12%) pancreatic cancer. Median duration of induction chemotherapy was 3.5 (SD 1.6) months with most common regimens being FOLFIRINOX (74%), gemcitabine/abraxane (24%) and FOLFOX (3%). Performance status was ECOG 0, 1, 2 in 16 (48.5%), 12 (36.4%), and 5 (15.2%), respectively. Whipple was performed in 27 (82%) of patients, distal pancreatectomy in 4 (12%), and total pancreatectomy in 2 (6%). The median duration from SMART completion to surgery was 6.9 weeks (4.7-44.1). R0 resections were achieved in 28 (84.8%) of patients with the rest being R1, all in BR patients. Vascular resection/reconstruction was performed of the portal vein (PV) in 8 (24.2%) patients, SMV in 4 (12%), SMA in 1 (3%), and common hepatic artery in 2 (6%). Vascular resection/reconstruction was performed in all LA patients. Median OS, 1-year OS, and 2-year OS from diagnosis were 29.6 months, 93.8%, 81.5%, respectively. Median OS from RT was not yet reached; 1-year OS was 90.9%. LRC at 1 and 2 years was 97% and 93%, respectively. Radiation related acute and late grade 3+ gastrointestinal toxicity was seen in 2 (6%) and 2 (6%) patients. Post-op mortality at 30 and 90 days was seen 2 (6%) and 3 (9%) of patients with 1 death from GI bleed attributed to surgery and 1 death from hepatic ischemia related to PV resection. Conclusions: To the best of our knowledge, this is the first report suggesting that surgery for pancreas cancer after dose escalated 5-fraction SMART is feasible. Further clarification is needed with respect to ideal patient selection and timing for surgery, the safety of arterial versus venous resection/reconstruction, and histopathologic response after delivery of ablative versus non-ablative radiation dose

Model for End-Stage Liver Disease and Sodium Velocity Predicts Overall Survival in Nonmetastatic Hepatocellular Carcinoma Patients

Background & Aims. The significance of short-term changes in model for end-stage liver disease and Sodium (MELD-Na) following hepatocellular carcinoma (HCC) diagnosis is unknown. In this report, we explore the value of the rate of short-term changes in MELD-Na as an independent predictor of mortality in patients with nonmetastatic HCC. Methods. We reviewed a cohort of patients diagnosed with nonmetastatic HCC at our institution between 2001 and 2011. We evaluated potential predictors of overall survival, including baseline MELD-Na and the change in MELD-Na over 90 days. We explored survival times of cohorts grouped by baseline MELD-Na and the change in MELD-Na. Results. 182 patients met eligibility criteria. With a median follow-up of 21 months for surviving patients, 110 deaths were observed (60%). Median MELD-Na at the time of diagnosis was 9.7 (IQR 7.5 to 13.9). The median changes in percentage of MELD-Na over 90 days were an increase of 9% (IQR -4% to 55%). Multivariable Cox proportional hazards modeling demonstrated that both baseline MELD-Na (HR=1.07 per unit increase, 95% CI 1.03 to 1.11, p<0.001) and changes in MELD-Na exceeding 40% (HR=3.69, 95% CI 2.39 to 5.69, p<0.001) were independently associated with increased mortality risk. Median survival among patients whose changes in MELD-Na were greater than 40% was 4.5 months, and median survival among the 131 other patients was 25.8 months (p<0.001). Conclusions. We identified a subset of HCC patients who have extremely poor prognosis by incorporating the rate of short-term change in MELD-Na to baseline MELD-Na score

A Phase II Study of Pelareorep (REOLYSIN®) in Combination with Gemcitabine for Patients with Advanced Pancreatic Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with 1 and 5-year survival rates of similar to 18% and 7% respectively. FOLFIRINOX or gemcitabine in combination with nab-paclitaxel are standard treatment options for metastatic disease. However, both regimens are more toxic than gemcitabine alone. Pelareorep (REOLYSIN (R)), a proprietary isolate of reovirus Type 3 Dearing, has shown antitumor activity in clinical and preclinical models. In addition to direct cytotoxic effects, pelareorep can trigger antitumor immune responses. Due to the high frequency of RAS mutations in PDAC, we hypothesized that pelareorep would promote selective reovirus replication in pancreatic tumors and enhance the anticancer activity of gemcitabine. Chemotherapy-naive patients with advanced PDAC were eligible for the study. The primary objective was Clinical Benefit Rate (complete response (CR) + partial response (PR) + stable disease (SD) >= 12 weeks) and secondary objectives include overall survival (OS), toxicity, and pharmacodynamics (PD) analysis. The study enrolled 34 patients; results included one partial response, 23 stable disease, and 5 progressive disease. The median OS was 10.2 months, with a 1- and 2-year survival rate of 45% and 24%, respectively. The treatment was well tolerated with manageable nonhematological toxicities. PD analysis revealed reovirus replication within pancreatic tumor and associated apoptosis. Upregulation of immune checkpoint marker PD-L1 suggests future consideration of combining oncolytic virus therapy with anti-PD-L1 inhibitors. We conclude that pelareorep complements single agent gemcitabine in PDAC.Oncolytics Biotech Inc.; National Cancer Institute P30 Cancer Center Support Grant [CA054174]Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]