Michelle Christine Janelsins

PURPOSE: Primary treatment modification (PTM; changes in treatment dose or agents from standard guidelines) is common among older adults with advanced cancer because of aging-related vulnerabilities. Geriatric assessment evaluates aging-related factors to inform personalized treatment. We compared treatment tolerability between PTM guided by geriatric assessment–guided management (PTM-GAM) and PTM determined by usual oncologic care (PTM-UC). METHODS: This secondary analysis of the GAP70+ study (ClinicalTrials.gov identifier: NCT02054741 ; PI: Mohile) was restricted to patients age 70+ years with incurable solid tumors who initiated systemic therapy with a PTM (N=298). PTM-GAM (n = 169) was guided by GA results and management recommendations, whereas PTM-UC (n = 129) was based solely on oncologist evaluation. Tolerability outcomes within 3 months of treatment initiation included grade 3 to 5 toxicity, secondary dose reduction (any unplanned decrease in dose after treatment initiation), decline in activities of daily living (ADL), and unplanned hospitalization. Associations were evaluated using multivariable cluster-weighted generalized estimating equation models. RESULTS: The mean age was 77 years, and GI cancers were most common (37%). Overall, 59% experienced ≥1 grade 3 to 5 toxicity. Compared with PTM-UC, PTM-GAM was associated with a lower risk of grade 3 to 5 toxicity (relative risk, 0.77 [95% CI, 0.65 to 0.91]). Secondary dose reductions occurred in 22% of patients, with lower risk in PTM-GAM (RR, 0.47 [95% CI, 0.30 to 0.72]). PTM-GAM was associated with a nonsignificant reduction in unplanned hospitalization (RR, 0.69 [95% CI, 0.45 to 1.03]). No difference was observed in ADL decline (RR, 1.04 [95% CI, 0.74 to 1.48]). CONCLUSION: Older adults with advanced cancer who received GA-guided PTM had a 23% lower risk of grade 3 to 5 toxicities and a 53% lower risk of secondary dose reduction compared with PTM based on usual oncologic care. These findings underscore the role of geriatric assessment in optimizing treatment decisions and improving tolerability.

Background: Interventions for cancer‐related cognitive impairment are understudied, particularly during therapy. Methods: Patients with cancer receiving chemotherapy reporting cognitive problems were randomized to one of four study arms for 6 weeks in this phase 2 randomized controlled trial with a 2 × 2 factorial design. Study arms included: Exercise for Cancer Patients©® (EXCAP)–ibuprofen, EXCAP–placebo, ibuprofen only, and placebo only. EXCAP is a home‐based, low to moderate‐intensity, progressive walking and resistance exercise prescription. Cognitive and biologic assessments were conducted at baseline and post‐intervention. Results: Eighty‐six participants were randomized (mean age, 53.60; 88.37% female). Between‐group analyses showed that participants in the EXCAP–placebo group demonstrated significantly better attention performance on the Trail Making Test compared to the placebo group (−21.57 seconds, p < .001; Cohen’s d = –1.31; 95% CI, –2.18 to –0.44; lower times indicate better performance). The ibuprofen only group showed greater improvements than the placebo group (−11.27‐second difference, p = 0.05; Cohen’s d = –0.73; 95% CI, –1.57 to 0.11). Both EXCAP–ibuprofen and EXCAP–placebo participants exhibited improvements on the FACT‐Cog “comments from others” compared to placebo (Cohen’s d = 1.00; 95% CI, 0.35 to 1.65 and Cohen’s d = 0.65; 95% CI, –0.01 to 1.31). On Rapid Visual Processing mean latency, participants in the EXCAP‐placebo group had a significant improvement compared to placebo (Cohen's d = −1.10; 95% CI, −1.97 to −0.23); those receiving ibuprofen had an improvement compared to placebo, which revealed a trend after adjusting for reading score (Cohen's d = −1.04; 95% CI, −2.06 to −0.01). The ibuprofen group performed less well on the Hopkins Verbal Learning Test‐Revised delayed compared to those not receiving ibuprofen (Cohen’s d = –0.64; 95% CI, –1.21 to –0.07). Conclusions: Exercise and low‐dose ibuprofen improved some domains of cognitive function, although effects were not observed across all measures. Phase 3 trials are needed.

Background: Cancer-related cognitive decline (CRCD) is a significant problem; interventions are needed to mitigate CRCD for older adults (aged ≥65 years). Objective: Our objective was to develop and evaluate the usability of Memory and Attention Adaptation Training–Geriatrics (MAAT-G), a CRCD intervention for older adults with breast cancer undergoing systemic treatment. Methods: We conducted an intervention adaptation study to develop MAAT-G. MAAT-G is a cognitive behavioral therapy–based intervention delivered by a health professional over the course of 10 weekly individual workshops via videoconferencing. To develop MAAT-G, the contextual, cohort-based, maturity, and specific challenge framework was used for preliminary adaptations. Patient advocate collaborators guided further refinement, reviewing MAAT-G workshop content, the participant workbook, and intervention delivery via videoconferencing to optimize relevance and usability for older adults. The usability of MAAT-G and its videoconferencing delivery were subsequently evaluated in 4 older adults with breast cancer using the System Usability Scale (score range 0‐100; >67 being above average) and through semistructured qualitative interviews. Results: Numerous adaptations were made to address the unique needs of older patients using the contextual, cohort-based, maturity, and specific challenge framework and patient advocate feedback. Usability testing included 4 female patients with breast cancer (mean age 73.3, SD 3.77; range 67-77 years). Patients were receiving systemic therapy (2 receiving adjuvant therapy and 2 receiving advanced-stage disease therapy). One patient had an educational level lower than high school; 3 had some college education or higher. All 4 patients completed study procedures, including 10 MAAT-G workshop sessions (100% intervention adherence). The mean System Usability Scale score was 90.6 (SD 13.51), indicating good usability. Conclusions: MAAT-G is a behavioral intervention developed to mitigate CRCD. It is designed specifically for older adults and showed above-average usability in this population.

Background: Cancer-related fatigue is a debilitating side effect among patients with cancer. Exercise is recommended to manage cancer-related fatigue; however, clinical guidelines lack specificity on modality, intensity, and duration. This study aimed to determine the optimal doses of walking to mitigate cancer-related fatigue. Methods: In a nationwide, prospective cohort study of patients with stage I-IIIC breast cancer, we assessed walking volume (metabolic equivalent task [MET] hours per week) via Aerobics Center Longitudinal Study Physical Activity measure and cancer-related fatigue via Multidimensional Fatigue Symptom Inventory at prechemotherapy (T1), 1 month postchemotherapy (T2), and 6 months postchemotherapy (T3). A receiver operating characteristic curve analysis identified a cut point for walking volume needed for a clinically meaningful cancer-related fatigue reduction from T1 to T2 (−4.5 points Multidimensional Fatigue Symptom Inventory score). Linear mixed models controlling for age, body mass index, and other modes of moderate-vigorous intensity exercise characterized cancer-related fatigue at each time point. Results: Among 577 participants (mean age = 53.4 years; 76% stage I-II), higher walking volume was associated with lower general, emotional, physical, overall cancer-related fatigue, and higher vigor postchemotherapy (T2; all P < .05). Those who walked at least 4.3 MET hours per week, equivalent to walking 88-172 minutes at a low-intensity pace (<2.5 mph) or 43-83 minutes at a moderate-intensity pace (2.6-4.5 mph) at pre, during, and postchemotherapy demonstrated statistically significantly lower cancer-related fatigue at postchemotherapy (T2) compared with those who walked less than 4.3 MET hours per week (P < .05). Conclusions: Our data indicate that higher walking volume was associated with lower cancer-related fatigue, and a minimum walking volume of 88-172 minutes at a low-intensity pace or 43-83 minutes of moderate-intensity pace may attenuate cancer-related fatigue following chemotherapy.

Background: Cancer-related cognitive impairment is a significant concern, yet data assessing long-term changes from pretreatment baselines are limited. Methods: In this large nationwide study, patients with breast cancer and lymphoma and controls were assessed at pre-chemotherapy, post-chemotherapy, 6-month, 1-year, and 2-year follow-ups. Cognitive function was measured using self-reported and performance-based assessments. The analysis included 225 participants: breast cancer (41 patients/36 controls) and lymphoma (73 patients/75 controls). Cognitive trajectories were estimated using longitudinal linear mixed models, adjusting for demographic, clinical, and psychosocial factors. A minimal clinically important difference cutoff identified changes over time in perceived cognitive impairment. Results: Patients with breast cancer reported greater cognitive complaints than controls, with declines in FACT-Cog Total (β = −17.17, P < .001), Perceived Cognitive Impairment (β = −11.09, P < .001), and Perceived Cognitive Abilities (β = −3.60, P = .03) from pre-chemotherapy to 2-year follow-up. Declines were observed in memory (Rey Auditory Verbal Learning Test [RAVLT] Immediate Recall: β = −1.53, P = .04) and executive function (phone fluency: β = −1.53, P = .02) at 1 year. Patients with lymphoma also showed more complaints, with declines in Perceived Cognitive Impairment (β = −6.19, P = .01), poorer RAVLT Immediate (β = −1.62, P < .001), Delayed Recall (β = −1.72, P < .001), and phone fluency (β = −2.46, P < .001) from pre-chemotherapy to 1-year follow-up. Conclusion: Compared with controls, patients with breast cancer and lymphoma showed persistent cognitive worsening up to 1-year posttreatment, and patients with breast cancer reported perceived impairment at 2 years compared with controls.

PURPOSE: Cancer-related cognitive impairment (CRCI) and cancer-related fatigue (CRF) are reported by approximately 75% of patients receiving chemotherapy for breast cancer and both have been linked to inflammation. We sought to test whether an inflammation polygenic risk score (iPRS) might be associated with CRCI and/or CRF. METHODS: Using data from the UK Biobank, we developed an iPRS for the INFLA-Score, a composite measure of C-reactive protein, white cell count, platelet count, and neutrophil-lymphocyte ratio. The iPRS was evaluated for association with CRCI and CRF among women with nonmetastatic breast cancer enrolled in two completed multisite clinical trials: URCC08106 and URCC10055. CRCI and CRF were measured before and after standard-of-care chemotherapy using the FACT-Cog and Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF), respectively. Linear regression evaluated the change in FACT-Cog and MFSI scores; logistic regression evaluated binary outcomes of any versus no worsening of scores. Analyses were adjusted for patient and treatment factors. We also performed exploratory genome-wide analyses. RESULTS: The cohort included 802 women who received chemotherapy (anthracycline-based = 51.8%; previous surgery = 85.0%) at a median age of 55 years (range = 22-81). The iPRS was associated with a significant decrease in MFSI-SF score (β = –3.29 [95% CI, –6.25 to –0.34]; P = .029) and lower odds of decreased MFSI-SF score (odds ratio, 0.66 [95% CI, 0.47 to 0.93]; P = .016) following chemotherapy. This negative relationship was partially explained by a positive correlation of the iPRS with prechemotherapy MFSI-SF score (β = 4.33 [95% CI, 0.23 to 8.43]; P = .038). The iPRS was not associated with a change in FACT-Cog score (β = –1.12; P = .627), but single nucleotide polymorphism rs9365961 was (β = –10.05; P = 1.46 × 10 ⁻⁸ ). CONCLUSION: If validated, the iPRS could identify patients in need of supportive care interventions to reduce CRF.

Figure S2 shows a quantile-quantile plot from the GWAS

Table S4 shows a multivariable model of hematuria including the PRS, rare variants, and clinical factors

Table S3 shows bivariate associations of patient, cancer, and treatment factors with hematuria

Table S2 shows the association of known prognostic factors with time to biochemical recurrence