Outcome-Related Signatures Identified by Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated after Starting Hu14.18-IL2.

PURPOSE: We analyzed whole transcriptome sequencing in tumors from 23 patients with stage III or IV melanoma from a pilot trial of the anti-GD2 immunocytokine, hu14.18-IL2, to identify predictive immune and/or tumor biomarkers in patients with melanoma at high risk for recurrence. EXPERIMENTAL DESIGN: Patients were randomly assigned to receive the first of three monthly courses of hu14.18-IL2 immunotherapy either before (Group A) or after (Group B) complete surgical resection of all known diseases. Tumors were evaluated by histology and whole transcriptome sequencing. RESULTS: Tumor-infiltrating lymphocyte (TIL) levels directly associated with relapse-free survival (RFS) and overall survival (OS) in resected tumors from Group A, where early responses to the immunotherapy agent could be assessed. TIL levels directly associated with a previously reported immune signature, which associated with RFS and OS, particularly in Group A tumors. In Group A tumors, there were decreased cell-cycling gene RNA transcripts, but increased RNA transcripts for repair and growth genes. We found that outcome (RFS and OS) was directly associated with several immune signatures and immune-related RNA transcripts and inversely associated with several tumor growth-associated transcripts, particularly in Group A tumors. Most of these associations were not seen in Group B tumors. CONCLUSIONS: We interpret these data to signify that both immunologic and tumoral cell processes, as measured by RNA-sequencing analyses detected shortly after initiation of hu14.18-IL2 therapy, are associated with long-term survival and could potentially be used as prognostic biomarkers in tumor resection specimens obtained after initiating neoadjuvant immunotherapy.

Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma.

Phase I testing of the hu14.18-IL2 immunocytokine (IC) in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m2/day. Preclinical data in IC-treated tumor-bearing mice with low tumor burden documented striking antitumor effects. Patients with completely resectable recurrent stage III or stage IV melanoma were scheduled to receive 3 courses of IC at 6 mg/m2/day i.v. on days 1, 2 and 3 of each 28-day course. Patients were randomized to complete surgical resection either following neoadjuvant (Group A) or prior to adjuvant (Group B) IC course 1. Primary objectives were to: (1) evaluate histological evidence of anti-tumor activity and (2) evaluate recurrence-free survival (RFS) and OS. Twenty melanoma patients were randomized to Group A (11 patients) or B (9 patients). Two Group B patients did not receive IC due to persistent disease following surgery. Six of 18 IC-treated patients remained free of recurrence, with a median RFS of 5.7 months (95% confidence interval (CI) 1.8-not reached). The 24-month RFS rate was 38.9% (95% CI 17.5-60.0%). The median follow-up of surviving patients was 50.0 months (range: 31.8-70.4). The 24-month OS rate was 65.0% (95% CI 40.3-81.5%). Toxicities were similar to those previously reported. Exploratory tumor-infiltrating lymphocyte (TIL) analyses suggest prognostic value of TILs from Group A patients. Prolonged tumor-free survival was seen in some melanoma patients at high risk for recurrence who were treated with IC.

A Quantitative Study of Triggered Palliative Care Consultation for Hospitalized Patients With Advanced Cancer.

CONTEXT: Unplanned cancer-related hospital admissions often herald entry into the final phase of life. Hospitalized patients with advanced cancer have a high symptom burden and a short life expectancy, which may warrant palliative care intervention. OBJECTIVES: To identify the impact of implementing triggered palliative care consultation (TPCC) as part of standard care for patients admitted to the solid-tumor oncology service with advanced cancer. METHODS: We conducted a prospective, sequential, three-cohort study to evaluate TPCC feasibility and impact using patient-reported outcomes, electronic medical records to identify resource utilization, and surveys of oncologists' perspectives on TPCC. RESULTS: Sixty-five patients were evaluated before TPCC implementation (Cohort 1). Seventy patients (Cohort 2) were evaluated after initiation of TPCC, and 68 patients (Cohort 3) were evaluated after modifications based on implementation barriers identified in Cohort 2. The percentage of patients correctly identifying their cancer as incurable increased from 65% in Cohort 1 to 94% in Cohorts 2 and 3. TPCC had minimal impact on hospice utilization, cost of care, survival, patient-reported symptoms, and patient satisfaction, likely because of the limited nature of the intervention. Implementation was challenging, with only 60% of patients in Cohort 2 and 62% in Cohort 3 receiving TPCC. Overall, the intervention was viewed favorably by 74% of oncologists. CONCLUSION: Although TPCC was viewed favorably, implementation was logistically challenging because of short stays, high-acuity symptoms, and individual provider resistance. TPCC improved patients' understanding of their cancer. This population demonstrates high palliative care needs, warranting further research into how best to deliver care.