Measuring the Impact of Academic Cancer Network Development on Clinical Integration, Quality of Care, and Patient Satisfaction.

PURPOSE: Many US academic centers have acquired community practices to expand their clinical care and research footprint. The objective of this assessment was to determine whether the acquisition and integration of community oncology practices by Yale/Smilow Cancer Hospital improved outcomes in quality of care, disease team integration, clinical trial accrual, and patient satisfaction at network practice sites. METHODS: We evaluated quality of care by testing the hypothesis that core Quality Oncology Practice Initiative measures at network sites that were acquired in 2012 were significantly different after their 2016 integration into the network. Clinical and research integration were measured using the number of tumor board case presentations and total accruals in clinical trials. We used Press-Ganey scores to measure patient satisfaction pre- and postintegration. RESULTS: Mean Quality Oncology Practice Initiative scores at Smilow Care Centers were significantly higher in 2016 than in 2012 for core measures related to improvement in tumor staging ( z = 1.33; P < .05), signed consent and documentation plans for antineoplastic treatment ( z = 2.69; P < .01; and z = 2.36; P < .05, respectively), and appropriately quantifying and addressing pain during office visits ( z = 2.95; P < .05; and z = 3.1; P < .01, respectively). A total of 493 cases were presented by care center physicians at the tumor board in 2017 compared with 45 presented in 2013. Compared with 2012, Smilow Care Center clinical trial accrual increased from 25 to 170 patients in 2017. Last, patient satisfaction has remained at greater than the 90th percentile pre- and postintegration. CONCLUSION: The process of integration facilitates the ability to standardize cancer practice and provides a platform for quality improvement.

Phase I dose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer.

Background. Docetaxel and irinotecan have additive or synergistic activity in vitro and in vivo as well as differing toxicities and unique mechanisms of action. We conducted a phase I trial to determine the maximum-tolerated dose of docetaxel and irinotecan given on a weekly schedule. Methods. Eligible patients had advanced, incurable, solid tumors. Docetaxel was administered as a 1-hour infusion and escalated over four dose levels (25, 30, 35, and 40 mg/m(2)) followed by irinotecan administered over 30 minutes at a fixed dose of 50 mg/m(2). Treatment was administered weekly for four weeks followed by two weeks of rest. To improve tolerability, the schedule was modified to weekly administration for two weeks with one week of rest, and irinotecan was escalated over 3 dose levels (55, 60, and 65 mg/m(2)) with docetaxel fixed at 35 mg/m(2). Results. Forty-four patients were treated and the most common dose-limiting toxicity was diarrhea observed in 11% of patients. Severe neutropenia was rare (grade 4: 2%, grade 3: 23%). Other nonhematologic toxicities included nausea/vomiting, dehydration and fatigue. Partial responses occurred in two patients with pancreatic cancer, and one patient each with non-small cell lung and esophageal cancer. Conclusions. Weekly docetaxel and irinotecan is a promising non-cisplatin doublet with preliminary evidence of activity in advanced solid tumors. Diarrhea is the predominant dose-limiting toxicity but unlike the every 3 weeks schedule myelosuppression is modest. The recommended phase II doses are docetaxel 35 mg/m(2) and irinotecan 60 mg/m(2) on days 1 and 8 of a 21-day schedule. Phase II trials of this regimen are ongoing or planned in lung, head and neck, stomach, esophageal, and pancreatic cancers.

Double-minute MYC amplification and deletion of MTAP, CDKN2A, CDKN2B, and ELAVL2 in an acute myeloid leukemia characterized by oligonucleotide-array comparative genomic hybridization.

Chromosomal analysis and fluorescence in situ hybridization (FISH) have been routinely used in detecting recurrent chromosomal abnormalities in patients with various hematological malignancies. However, the genomic imbalances underlying many recurrent abnormalities could not be delineated due to the low resolution of chromosome analysis. We have performed oligonucleotide-array comparative genomic hybridization (oaCGH) in an AML case with a 15p/17p translocation, a suspected 9p21 deletion, monosomies of chromosomes X and 9, and 2 to 60 double minutes. The oaCGH findings confirmed the chromosomal observations and further characterized a 21.338-Mb 17p deletion, a 3.916-Mb deletion at 9p21.3 containing the MTAP, CDKN2A, CDKN2B, and ELAVL2 genes, and a 3.981-Mb 8q24 double minute containing the TRIB1, FAM84B, MYC, and PVT1 genes, with an average of 30 double minutes in each cell. FISH using MYC probes and bacterial artificial chromosome clone probes confirmed the genomic findings and revealed a progressional pattern for the 9p21.3 deletion. These results demonstrate the potential of oaCGH as a powerful diagnostic tool for characterizing genomic imbalances for patients with hematological malignancies.

Toxicity and activity of a twice daily high-dose bolus interleukin 2 regimen in patients with metastatic melanoma and metastatic renal cell cancer.

The standard q8h high-dose interleukin-2 (IL-2) regimen produces clear benefit for a subset of patients, but has limited acceptance because of its substantial acute toxicity including hypotension requiring pressors in 30% to 50%, the schedule is inconvenient for medical staff who must assess patients before each dose, and in some hospitals, the limited availability of monitored beds. We initiated a high-dose IL-2 program with a modified twice daily dosing schedule, limited the total number of doses per course to 8, and treated patients in an oncology ward without cardiac monitoring. Hypotension was managed preferentially with normal saline fluid boluses and/or delay in treatment. We conducted a retrospective chart review of 41 consecutive metastatic melanoma (n=33) and renal cancer (n=8) patients treated with the modified high-dose IL-2 regimen. The median number of IL-2 doses administered in the first cycle was 15. Overall toxicity was similar to published data for the q8h schedule, but only 9.79% of patients required pressors. Twenty-four percent of patients were transferred electively or emergently to the intensive care unit. There were no treatment-related deaths. The objective response rate was 12.5% and 0% in melanoma and renal cancer, respectively. Responses were durable, and 2 additional melanoma patients with mixed responses remain disease-free after resection of residual or recurrent sites of disease. In summary, the twice-daily IL-2 regimen has meaningful activity, may be more convenient to administer, reduces the need for elective monitored beds, and may be preferable for development of combinations with newer immune modulators.