Elective Checkpoint Inhibitor Discontinuation in Metastatic Solid Tumor Patients: A Case Series.

Introduction: Checkpoint inhibitor (CKI) therapy has markedly altered the survival of patients with many solid tumors. It appears clear that 10-40% of patients with a number of metastatic cancers can achieve lengthy remissions following CKI therapy. The optimal duration of treatment or whether treatment can ever be safely stopped is still controversial. Based on melanoma-derived data, we tested whether CKI treatment could safely be discontinued in patients with other solid tumors. Methods: A retrospective analysis was performed in adults with metastatic solid tumors treated with CKI-based therapy. Patients with solid tumors who achieved complete remission on 2 sequential scans at least 3 months apart during ongoing treatment were identified from our computerized patient database. Patient data was analyzed for patient characteristics, as well as progression-free and overall survival. Results: A total of 69 non-melanoma solid tumor patients were treated with CKI-based regimens in our clinic and 14 achieved complete remission (20.3%). Five patients were female (35.7%) and the remaining nine were male (64.3%). A 100% progression-free survival was observed for these patients. The median duration of complete remission was over 20 months from the time of elective treatment discontinuation. Median overall survival was not reached in this cohort. One patient died of no cancer-related causes. Conclusions: Based on this retrospective case series, elective treatment discontinuation in patients who achieved complete remission appears feasible. All patients remained in a durable complete remission after treatment discontinuation. We hypothesize that appropriate selection of patients for early treatment discontinuation may decrease their economic burden related to ongoing treatment, limit potential toxicity, and improve quality of life.

Outcome of Elective Checkpoint Inhibitor Discontinuation in Patients with Metastatic Melanoma Who Achieved a Complete Remission: Real-World Data.

Checkpoint inhibitor therapy for metastatic melanoma has dramatically improved outcomes. Currently, 20 to 40% of treated patients achieve lengthy remissions. It is not clear whether patients in remission require ongoing therapy or if treatment can be safely discontinued. A retrospective chart review was performed of patients who underwent elective treatment discontinuation after two negative scans three months apart. Of 132 checkpoint inhibitor-treated patients, 46 achieved a complete response (34.8%) and electively discontinued therapy. The progression-free survival was 97.5% at 1 year and 94.7% at 3 years following treatment discontinuation. The median duration of follow-up was 26 months. In total, 4 of 46 individuals (8.7%) eventually relapsed (median time to relapse: 27 months). The median disease-specific survival of the entire cohort was not reached and was 100% at 4 years from the start of therapy. Two patients eventually died, one from melanoma and the other from an unrelated illness. We have identified an elective treatment discontinuation strategy that is generalizable to a variety of checkpoint inhibitor ± targeted therapy regimens. We found that most complete remissions remained durable after elective treatment discontinuation. We hypothesize that this approach could decrease potential drug toxicities, reduce the treatment-related financial burden, and improve patients' quality of life.

3-Methylglutaric acid in energy metabolism.

3-methylglutaric (3MG) acid is a conspicuous C6 dicarboxylic organic acid classically associated with two distinct leucine pathway enzyme deficiencies. 3MG acid is excreted in urine of individuals harboring deficiencies in 3-hydroxy-3-methylglutaryl (HMG) CoA lyase (HMGCL) or 3-methylglutaconyl CoA hydratase (AUH). Whereas 3MG CoA is not part of the leucine catabolic pathway, it is likely formed via a side reaction involving reduction of the α-ß trans double bond in the leucine pathway intermediate, 3-methylglutaconyl CoA. While the metabolic basis for the accumulation of 3MG acid in subjects with deficiencies in HMGCL or AUH is apparent, the occurrence of 3MG aciduria in a host of unrelated inborn errors of metabolism associated with compromised mitochondrial energy metabolism is less clear. Herein, a novel mitochondrial biosynthetic pathway termed "the acetyl CoA diversion pathway", provides an explanation. The pathway is initiated by defective electron transport chain function which, ultimately, inhibits acetyl CoA entry into the TCA cycle. When this occurs, 3MG acid is synthesized in five steps from acetyl CoA via a novel reaction sequence, providing a metabolic rationale for the connection between 3MG aciduria and compromised mitochondrial energy metabolism.

Interfacility transport of patients admitted to the ICU: perceived needs of family members.

INTRODUCTION: Limited research has been published regarding the needs of immediate family members with respect to the transport of critically ill loved ones. Furthermore, very little information exists on transport teams members' perception of the needs of the family members. METHODS: During a 9-month period, a 25-item questionnaire was given to family members of adult patients who were transported by air or ground. All patients were admitted into an adult intensive care unit at a major university teaching hospital. Family members were asked to rank the relative importance of each item with regard to informational or situational needs. The identical questionnaire was given to the critical care transport teams employed by the hospital. The team members were asked to indicate what they thought the family members ranked as important. RESULTS: Forty-two of 100 family members (42%) returned the questionnaire by mail. All 13 (100%) critical care transport team members completed surveys as well. Statistical comparisons indicated that family members and team members differed significantly on 13 of 25 items. Team members generally underestimated the importance of these items to family members. CONCLUSION: These findings suggest that, in this sample, transporting crew members often misperceived family members informational and situational needs.