Patients with cancer receiving high-dose Interleukin-2 (IL-2) therapy experience alterations in cognitive functioning (Musselman et al., 2013) including changes in concentration, attention, short-term memory, executive functioning, language, and orientation (Mann, Dail, & Bailey, 2015) during treatment. Patients and care partners also report in online forums that cognitive symptoms were inadequately screened for and they were uninformed about potential cognitive alterations during and after treatment (Ejneary, 2011). Severe cognitive symptoms may result in early cessation of IL-2 treatment, which results in deficient treatment response. IL-2 is a cytokine produced naturally by the body. High-dose (HD) IL-2 is an immunotherapy produced synthetically and is used as a treatment in patients diagnosed with metastatic renal cell carcinoma (MRCC) to achieve remission or minimize the disease. HD IL-2 is defined as 600,000 IU/kg of IL-2 administered intravenously as a 15-minute bolus every 8-hours for up to 14 treatment doses. These 14 doses comprise one treatment hospitalization; patients can receive up to four treatment hospitalizations (Dutcher et al., 2014). The cognitive symptom trajectory has yet to be described. As such, a description of how symptoms change with each dose within and across hospitalizations is essential to maximize treatment delivery, potentially increasing remission rates in the IL-2 population.
The purpose of this study was to describe IL-2—induced cognitive symptoms (language, concentration, confusion, attention, short-term memory, and orientation) longitudinally from the perspective of the patient, care partner, and primary nurse who have first-hand knowledge of symptoms during the treatment course.
This exploratory, descriptive study used a mixed-methods case study approach to examine the cognitive symptom trajectory in ten IL-2 cases using qualitative and quantitative data. Each IL-2 case consisted of the IL-2 patient, care partner, and primary nurse. The patient completed two scales, the Montreal Cognitive Assessment (MoCA) and the Attentional Function Index (AFI), evaluating cognitive symptoms at pre- and post-treatment for each hospitalization, and a semi-structured recorded interview after treatment ended. The care partner completed a semi-structured journal entry every 8-hours at the time when a dose of IL-2 was administered, and a semi-structured recorded interview after treatment ended. The primary nurse completed a semi-structured recorded interview after treatment ended providing medical expertise/insight into the treatment trajectory.
The AFI is a 13-item scale with scores ranging from 0-100 measuring perceived changes in attention and working memory (Cimprich, Visovatti, & Ronis, 2011). Higher scores indicate better perceived attention and cognitive stamina (Asher & Myers, 2015). The Montreal Cognitive Assessment (MoCA) measures global cognitive functioning with a maximum total score of 30, and normal scores ranging from 26 to 30 (Rossetti, Lacritz, Cullum, & Weiner, 2011).
Of the nine IL-2 cases currently enrolled, six have completed the study, and three are currently receiving treatment. Nine IL-2 patients have been admitted for two treatment hospitalizations, while three cases have completed all four treatment hospitalizations. Seven of the nine IL-2 patients were white males ranging from 37 to 60 years of age. Two of the IL-2 patients were black females ranging between 45 and 60 years of age. Seven of the IL-2 patients had their spouse as their inpatient care partner, one care partner was a daughter and one care partner was a significant other. All 19 primary nurses were white, comprised of 18 females and 1 male. Nursing experience ranged from 1.5 to 28 years, with a mean of 13 years.
Our preliminary quantitative analysis suggests that cognitive symptoms can be grouped into three symptom trajectories: stable, mixed, or worsening. Total scores on the AFI decreased anywhere from 50 to 135 points from pre- to post-treatment time points indicating worsening perceived attentional functioning, with the largest change in cognitive fatigue during the first treatment hospitalization across all patients. In all but the first hospitalization, average total scores decreased by approximately 1-point from pre- to post-treatment measurement time points on the MoCA. For all patients, the most common changes were in the visuospatial executive function, attention, abstraction, and orientation domains.
Although quantitative measures were only administered at pre- and post-treatment, each case informant provided unique insight into the trajectory of cognitive symptoms. For example, one care partner stated, “[After dose 8], he said he felt the most ‘beat up’ so far. I can definitely tell a difference today…an increase in sleepiness, fatigue and attention span. Today was by far the worst I’d seen. He slept most of the day and he was not able to communicate very clearly. He really just had no energy.” One patient stated that his biggest challenge was, “Having the ability to focus. My brain could not multi-task. So trying to do things...if there was somebody changing the trash, and the TV on, and you know someone taking my vitals, and a doctor asking me questions, my brain couldn't process all of those things.” One of the primary nurses noted, “Yesterday morning before [the patient] decided to quit [treatment], he said that he was having trouble and that he was just thinking slower. That he had dropped a Gatorade bottle, and it took him a minute to realize that.” These qualitative reports from the patient, care partner and nurse allowed us to identify symptom changes at the time of each IL-2 dose while also providing context into each symptom trajectory.
The use of a case study approach allowed for in-depth exploration of the cognitive symptom trajectory from individuals closest to the symptom experience. Although IL-2 patients only completed measurement scales at two time points (pre- and post-treatment) for each hospitalization, care partners proved to be essential in providing qualitative rich descriptions of symptoms experienced during high-dose IL-2 treatment, and how symptoms changed with each IL-2 dose. Additionally, the care partner played a unique role in identifying and reporting symptoms when the patient may be cognitively impaired. In the future, specific interventions can be developed for patients receiving IL-2 based on their cognitive symptom trajectory.