1. Fuerst, Mark L.

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SAN FRANCISCO-Enrolling children in early phase clinical trials in the last 6 months of life does not appear to substantially alter end-of-life care, increase use of invasive interventions, or increase hospital use, according to a new study.

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"Pediatric patients who were enrolled in early phase clinical trials in the last 6 months of life received palliative care consultation significantly later in treatment. Not surprisingly, these children also had more frequent clinic visits, likely as a result of trial requirements. However, enrollment in early phase clinical trials did not significantly delay advance care planning. Trial enrollment also did not increase health care resource use; these children did not receive more invasive procedures, for example, blood draws or interventions, such as intubation or CPR. They also were not admitted to the hospital or intensive care unit more often," said lead author Prasanna Ananth, Instructor in Pediatrics at Dana-Farber/Boston Children's Cancer & Blood Disorders Center in Boston.


Early phase clinical trials are critical to enhancing therapies for children with advanced cancer. However, trial enrollment, which typically occurs when cancer relapses or progresses, may alter aspects of the approach to end-of-life care.


One prior study looked exclusively at children with solid tumors and focused on specific elements of end-of-life care, that is, timing of the do-not-attempt resuscitation (DNAR) order. "We examined this as well, but broadened the scope to include children with various types of cancers," explained Ananth. "We looked at elements of end-of-life care, including timing of palliative care consultation, DNAR orders, and advance care planning conversations, and further investigated the overall hospital care experience."


Ananth presented the results of the study at the ASCO 2016 Palliative Care in Oncology Symposium (Abstract 151).


Studying Children at End of Life

The researchers posed questions such as: Did children who enrolled in early phase trials in the last 6 months of life undergo more procedures? Were they admitted to the hospital or intensive care unit more often? Did they visit the emergency room or clinic more often for unplanned reasons?


The single-center, retrospective cohort study of 125 pediatric patients with advanced cancer, ages 6 months-21 years, who died in 2010-2014 at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. The researchers examined electronic medical records to identify frequencies of medical procedures (e.g., lab draws, imaging, transfusions, intubations, central line placement, bone marrow biopsies), clinic visits, and hospital admissions. They also assessed timing of pediatric palliative care consultation, initial advance care planning discussion, and entry of a DNAR order in the chart, in relation to date of death. Patients enrolled in early phase clinical trials for at least one cycle were compared with those not enrolled in clinical trials in the last 6 months of life.


The study included 125 patients, median age 11.6 years at death, who were diagnosed with solid tumors (42%), brain tumors (41%), and hematologic malignancies (18%). One-quarter were enrolled in early phase trials. The two cohorts did not significantly differ in baseline demographic or clinical characteristics, frequencies of medical procedures, or hospital admissions.


Study Results

Early phase patients had a higher median number of clinic visits (18.5) compared to those not enrolled in clinical trials (14.1). The vast majority (83%) of patients across both cohorts received pediatric palliative care. Initial pediatric palliative care consultation occurred significantly closer to death for early phase patients (median 58 days before death) as compared to those not enrolled in clinical trials (median 85 days before death).


Virtually all (91%) of the patients had discussions on advance care planning. There was no difference in median time of initial discussion before death between the two groups-33 median days before death in the early phase group versus 43 days in those not enrolled in clinical trials. Almost all (86%) of the patients had DNAR orders entered, which were placed a median of 11 days before death in early phase patients as compared to 27 days in those not enrolled in clinical trials.


Practice Implications

"Pediatric patients enrolled in early phase clinical trials near the end of life had more frequent clinic visits and later palliative care consultation. However, trial enrollment did not significantly delay advance care planning or increase frequencies of medical procedures and hospital admissions," Ananth concluded. "These results suggest that early phase clinical trial enrollment does not substantially compromise end-of-life care for children with advanced cancer, but patients may benefit from earlier pediatric palliative care involvement."


With the Cancer Moonshot Initiative and growing interest in personalized cancer therapy, "there has been a national move toward enrolling children with advanced cancer who have not responded to conventional therapies in early phase clinical trials," said Ananth. "These trials carry great potential in moving the field of pediatric oncology forward, particularly as we learn more about the genetic underpinnings of childhood cancer. As children who enroll in these trials tend to have progressive or relapsed cancer, it is important to consider the patient experience in enrolling in such trials and to ensure that we are not posing undue burdens at a vulnerable time in the illness course."


Mark L. Fuerst is a contributing writer.