Table 1 Review eligibility criteria guided by the PICOS framework

Population

Adults (≥ 18 years) who were diagnosed with cancer of any type (except central nervous system (CNS)-related tumors/metastases) during adulthood and who received prior systemic treatment (i.e., chemotherapy, hormonal/endocrine therapy, or immunotherapy), alone or in combination with other treatments (e.g., concurrent radiotherapy), and who experienced cancer treatment-related cognitive impairment (CTRCI) as defined by any criteria. Studies that did not exclusively select participants based on the presence of CTRCI but that selected based on a CTRCI-associated condition (e.g., fatigue, insomnia, depression, stress, anxiety) will be included during title/abstract screening, and their full texts will be reviewed to determine if cognitive function was measured at baseline and relevant subgroup analyses were reported specific to those with CTRCI at baseline. If a subgroup analysis of participants with CTRCI at baseline was reported in the full text, the study will be retained. Studies with mixed populations of individuals with and without CTRCI at baseline will be excluded unless subgroup analyses were reported in the full text. Studies including participants actively receiving systemic therapy will be excluded because the focus of the CTRCI intervention would be on prevention not treatment. An exception to this would be people with cancer undergoing long-term hormonal therapy, such as tamoxifen or androgen deprivation therapy.

Intervention

Interventions to treat existing CTRCI (i.e., not prevent future CTRCI), including the following, alone or in combination:

 - Psychological interventions: cognitive behavioral therapy (CBT), cognitive rehabilitation or training, transcranial direct current stimulation, etc

 - Pharmacologic interventions: methylphenidate, modafinil, armodafinil, donepezil, erythropoietin, fluoxetine, memantine, ramipril, lithium, pioglitazone, etc

 - Other interventions: exercise programs, mindfulness-based stress reduction (MBSR), music therapy, Tai chi/qigong, yoga, acupuncture, light therapy, herbal supplements, nutraceuticals (e.g., omega-3 fatty acids), etc

All doses, frequencies, and durations of treatment will be eligible; however, we will consider the use of different nodes in network meta-analyses (NMAs) where these vary notably between studies. We will exclude studies evaluating interventions to prevent the development of CTRCI, as well as studies that do not report sufficient intervention detail (e.g., missing descriptions of psychological interventions, missing dosages of pharmacologic interventions).

Comparator

Any of the above interventions, placebo, treatment as usual, wait list, or no treatment

Outcome

The co-primary outcomes of interest for this review will be subjective and objective cognitive function. Secondary outcomes of interest will include measures of QoL/health-related QoL (e.g., Quality of Life Index–Cancer Version (QLI-C), Quality of Life–Cancer Survivor (QOL-CS)), mental and physical health symptoms (e.g., SF-36 composite scores), adherence to treatment, and harms, including overall and treatment-related harms, and harms associated with study withdrawal. Immediate effects will not be relevant (e.g., measured the same day as interventions administered).

Study design

Both parallel group and cross-over RCTs. Abstracts, commentaries, and letters will be excluded.