Study Protocol: Efficacy and Safety of Radioembolization (REM) as an Early Modality (EM) Therapy for Metastatic Breast Cancer (BR) to the Liver with Y90 (REMEMBR Y90).

PURPOSE: The primary objective of the REMEMBR Y90 study is to evaluate the efficacy of Yttrium-90 (Y90) radioembolization in patients with breast cancer metastases to the liver as a 2nd or 3rd line treatment option with systemic therapy by assessing liver-specific and overall progression-free survival. Secondary objectives include quality of life, overall survival benefit, and toxicity in relation to patients' tumor biology. MATERIALS AND METHODS: This trial is a multi-center, prospective, Phase 2, open-label, IRB-approved, randomized control trial in the final phases of activation. Eligible patients include those over 18 years of age with metastatic breast cancer to the liver with liver-only or liver-dominant disease, and history of tumor progression on 1-2 lines of chemotherapy. 60 patients will be randomized to radioembolization with chemotherapy versus chemotherapy alone. Permissible regimens include capecitabine, eribulin, vinorelbine, and gemcitabine within 2 weeks of enrollment for every patient. Patients receiving radioembolization will receive lobar or segmental treatment within 1-6 weeks of enrollment depending on their lesion. After final radioembolization, patients will receive clinical and imaging follow-up every 12-16 weeks for two years, including contrast-enhanced computed tomography or magnetic resonance imaging of the abdomen and whole-body positron emission tomography/computed tomography. DISCUSSION: This study seeks to elucidate the clinical benefit and toxicity of Y90 in patients with metastatic breast cancer to the liver who are receiving minimal chemotherapy. Given previous data, it is anticipated that the use of Y90 and chemotherapy earlier in the metastatic disease course would improve survival outcomes and reduce toxicity. LEVEL OF EVIDENCE: Level 1b, Randomized Controlled Trial. TRIAL REGISTRATION NUMBER: NCT05315687 on clinicaltrials.gov.

Rituximab treatment in patients with IVIg-dependent immune polyneuropathy: a prospective pilot trial.

We studied the effect of rituximab in allowing a reduction in dose of intravenous immune globulin (IVIg) in six patients with IVIg-dependent, relapsing immune polyneuropathy. Rituximab (375 mg/m(2) intravenously each week for 4 weeks) was administered in a prospective, open-label design to two patients with chronic inflammatory demyelinating polyneuropathy (CIDP), two with multifocal motor neuropathy (MMN), one with neuropathy and anti-myelin-associated glycoprotein (MAG) antibody neuropathy, and one with Sjögren syndrome (SS) ataxic neuropathy. The primary endpoint was a reduced cumulative IVIg dosage by at least 25% at 1 year after rituximab therapy compared to the previous year. Secondary endpoints included an improved summed strength score by at least 5 points on the Medical Research Council scale, an increased sensory score by at least 4 points, or an improved Rankin disability score by at least 1 grade. Total IVIg dosage decreased by greater than 25% in one patient with SS neuropathy and one with MMN; the dosage was unchanged in one with CIDP, slightly reduced in the patient with anti-MAG neuropathy, and increased in one with CIDP and another with MMN. There was no improvement in secondary endpoints. No adverse events occurred. In this small prospective study, rituximab did not reduce IVIg requirements in the majority of patients with IVIg-dependent, immune-mediated polyneuropathies.

New agents, combinations, and opportunities in the treatment of advanced and early-stage colon cancer.

There has been a dramatic improvement in outcomes for patients who have colon cancer over recent years. These improvements have come about largely because of the availability of new chemotherapy agents (irinotecan, oxaliplatin and capecitabine) and new biologic agents (bevacizumab and cetuximab). Large, well-designed clinical trials have resulted in the routine use of all of these agents in the treatment of patients who have metastatic disease, and this has led to improved survival for these patients. In earlier stage disease, oxaliplatin/5-FU-based chemotherapy has become a new standard of adjuvant therapy for many patients. Clinical research efforts are investigating the use of biologic agents along with chemotherapy for adjuvant treatment; it is hoped that this will translate into a greater cure rate for these patients.

Therapeutic apheresis in neurology critical care.

Therapeutic apheresis has been widely accepted in the treatment of neurological disorders that are understood to be mediated by humoral and/or cellular immunity. The clinical presumption is that well-established and/or unknown insults cause damage to nerves or their myelin sheaths. The rationale for apheresis treatments for these neurological disorders relates to removal of offending immune (or other) mediators, thus blunting the attack and permitting recovery of nerve and/or myelin. This review will concentrate on the role of therapeutic apheresis, in particular therapeutic plasma exchange, in neurological disorders that may frequently be seen by intensivists.