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Background: Exercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood. Objectives: The effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors. Methods: Eleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14+CD16- and CD14+CD16+ monocytes using flow cytometry. Results: Exercise training decreased IL-1ß+CD14+CD16- proportion (24.6%, p=0.016), IL-1ß+CD14+CD16- mean fluorescence intensity (MFI) (−9989, p=0.014), IL-1ß+CD14+CD16+ MFI (−11101, p=0.02), and IL-6+CD14+CD16- proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14+CD16- (−63, p=0.002) and CD14+CD16+ (−18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14+CD16+ concentrations being decreased at 1 h post without changes in intracellular cytokine production. Conclusions: Exercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production.

Purpose: Understanding quality of life (QOL) implications of individual components of breast cancer treatment is important as systemic therapies continue to improve oncologic outcomes. We hypothesized that adjuvant radiation therapy does not significantly impact QOL domains in breast cancer patients undergoing chemotherapy., Methods: Data was drawn from three prospective studies in women with localized breast cancer being treated with chemotherapy from March 2014 to December 2019. Patient-reported measures were collected at baseline (pretreatment) and post-treatment using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) measure, which consists of 5 subscales. Changes in mean QOL scores in patients who received radiotherapy were compared to those who did not using a one-sided noninferiority method. Statistical significance was determined below 0.05 to meet noninferiority., Results: In a sample of 175 patients, 131 were treated with radiation and 44 had no radiation. The sample consisted mostly of stage I-II breast cancer (78%) with hormone receptor positive (59%) disease, receiving either neoadjuvant (36%) or adjuvant chemotherapy (64%). Mean change in QOL for the group treated with radiation compared to no radiation was noninferior with respect to Physical Well-Being (P = .0027), Social/Family Well-Being (P = .0002), Emotional Well-Being (P = .0203), FACIT-Fatigue Subscale (P = .0072), and the Total FACIT-F score (P = .0005); however, mean change in QOL did not meet noninferiority for Functional Well-Being (P = .0594)., Conclusion: Patient-reported QOL from baseline to post-treatment, using the Total FACIT-F score, was noninferior in patients treated with versus without radiation therapy. This finding, in addition to individualized QOL subscales, provides important information in the informed decision-making process when discussing the effects of locoregional radiation on QOL in localized breast cancer patients treated with chemotherapy., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Published by Elsevier Inc.)

Competing Interests: Declaration of Competing Interest This research was partially supported by the UNC Geriatric Oncology Training Grant (UNC-GO, Grant No. T32-CA233419) and a National Research Service Award Post-Doctoral Traineeship from the Agency for Healthcare Research and Quality sponsored by The Cecil G. Sheps Center for Health Services Research, The University of North Carolina at Chapel Hill (Grant No. T32-HS000032). The study was also partially supported by the UNC Lineberger Comprehensive Cancer Center's University Cancer Research Fund (UCRF).

Background: Alpelisib is an oral α-specific class I PI3K inhibitor approved in combination with fulvestrant for the treatment of PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. The tolerability of this drug with the oral chemotherapy capecitabine is unknown., Patients and Methods: This phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of alpelisib (250 mg or 300 mg daily for 3-weeks) with capecitabine (1000 mg/m 2 twice daily for 2-weeks followed by a 1-week rest period) in patients with metastatic HER2-negative breast cancer, regardless of PIK3CA mutation status., Results: Eighteen patients were treated with alpelisib-capecitabine. Half of the patients had HR+ breast cancer, and 16 had prior systemic therapy for metastatic disease. The MTD of alpelisib was 250 mg daily in combination with capecitabine 1000 mg/m 2 twice daily. DLTs included hyperglycemia, QTc prolongation, fatigue, and chest pain. The most common grade 3 adverse event (AE) was hyperglycemia (28%). No grade 4 AEs were observed. Three patients discontinued therapy due to an AE. One-third of patients required dose reduction of both alpelisib and capecitabine. Four patients experienced a partial response and 8 patients experienced stable disease. The median progression-free survival was 9.7 months (95% CI 2.8-13.5 months) and median overall survival was 18.2 months (95% CI 7.2-35.2 months). Twelve patients had PIK3CA mutation testing completed, of these 2 had known or likely deleterious PIK3CA mutation., Conclusion: This study provides safety data for an oral combination therapy of alpelisib-capecitabine and defines tolerable doses for further study., Competing Interests: Disclosure YA reports consulting income from Exact Sciences, AstraZeneca and Pfizer. C.K.A. reports research funding provided by PUMA, Lilly, Merck, Seattle Genetics, Nektar, Tesaro, G1-Therapeutics, ZION, Novartis, Pfizer, Astra Zeneca, Elucida, Caris, Incyclix; consulting for Genentech, Eisai, IPSEN, Seattle Genetics, Astra Zeneca, Novartis, Immunomedics, Elucida, Athenex, Roche; royalties from UpToDate, Jones and Bartlett. L.A.C. reports research funding from Genentech/Roche, AstraZeneca, Lilly, Novartis, Veracyte, Nanostring. C.M.P. is an equity stockholder and board of director member of BioClassifer LLC and is listed as inventor on patent applications for the Breast PAM50 assay. E.C.D. reports consulting income from Sanofi, research funding from Novartis, Genentech, Bayer, Pfizer, and Merck and a family member who received past consulting income from Novartis. L.A.C reports research funding from AstraZeneca, Genentech/Roche, Lilly, Merck, Nanostring, Novartis, SeaGen, and Veracyte. P.K.M. is a full-time employee and equity stockholder with Veracyte., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Palbociclib is a widely used treatment for advanced breast cancer in older adults. However, the existing evidence regarding its safety and tolerability in this age group is inconsistent and limited to retrospective subgroup or pooled analyses., Materials and Methods: We conducted a prospective single-arm multicenter phase 2 study to evaluate the safety and tolerability of palbociclib in participants aged 70 years or older with advanced hormone receptor-positive breast cancer. Participants were given palbociclib in combination with their physician's choice of endocrine therapy (letrozole or fulvestrant). The primary endpoint was the incidence of grade 3+ adverse events (AEs) by six months. Secondary endpoints included AE-related dose delays, dose reductions, early discontinuations, and hospitalizations. Additionally, we compared these endpoints by age groups (70-74 and ≥ 75 years)., Results: Of the 90 participants (median age 74 years [70-87]) enrolled, 75.6% (95% confidence interval [CI], 65.4-84.0) had grade 3+ AEs by six months. The most frequent grade 3+ AEs were neutropenia (61%), fatigue (4%), and nausea (3%). Febrile neutropenia was uncommon (1.1%). Due to AEs, 36% had dose delays, 34% had dose reductions, 10% had early discontinuations, and 10% had hospitalizations. Compared to those aged 70-74 years, participants aged ≥75 years had higher rates of early discontinuations (5.9% vs 15.9%, a difference of 9.5% [95% CI 3.5%-22.5%])., Discussion: Palbociclib has an overall favorable safety profile in adults aged ≥70 with advanced breast cancer. However, adults ≥75 years had a trend toward higher rates of AE-related early discontinuations compared to those 70-74 years. Further research is needed to evaluate tolerability and improve the delivery of palbociclib in older adults., Clinicaltrials: gov:NCT03633331., (Published by Elsevier Ltd.)

Introduction: Geriatric assessment (GA)-guided supportive care programs have been successful in improving treatment outcomes for older adults with solid-organ cancers. This study aimed to evaluate the feasibility of a GA-guided supportive care program among older adults treated for multiple myeloma (MM)., Materials and Methods: The study utilized an existing registry of adults with plasma cell disorders at the University of North Carolina. Patients with MM, aged 60 or older, and having a GA-identified deficit in one or more problem area were offered referrals to supportive care resources during routine visits. Problem areas included physical function deficits, polypharmacy, and anxiety or depression. Patients with physical function deficits were offered referral to physical therapy (PT), those with polypharmacy to an Oncology Clinical Pharmacist Practitioner (CPP), and those with mental health symptoms to the Comprehensive Cancer Support Program (CCSP)., Results: Of the 58 individuals identified as having at least one deficit on the GA, PT was the most commonly identified relevant resource (79%), followed by CPP visits (57%). Among individuals that were offered referral(s) to at least one new supportive care resource, the acceptance rate was 50%. Referral acceptance rates were highest among those recommended for a CPP visit (55% of those approached) and lowest for CCSP (0%)., Discussion: The study examined the feasibility and acceptability of a referral program for supportive care resources among older adults with MM who have deficits on GA. The most commonly identified deficit was physical functioning, followed by polypharmacy and mental health. The study found that physical interventions and referrals to CPPs were the most accepted interventions. However, the low proportion of patients who accepted physical therapy referrals indicates the need for tailored and more personalized approaches. Further research is needed to explore the feasibility and impact of supportive care referral programs for older adults with MM., Competing Interests: Declaration of Competing Interest The authors have no conflicts to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Older patients with cancer often require acute care treatment through emergency department (ED) visits and hospitalizations. This study investigates acute care utilization through ED visits and hospitalizations during treatment and in the two years following the completion of primary treatment for early stage breast cancer (EBC) in women aged 65 and older., Materials and Methods: A retrospective analysis including descriptive statistics, univariate analysis, and relative risk analysis of 256 women with EBC was performed through medical record review of demographics, comorbidities, disease characteristics, treatment details, and causes of hospitalizations and ED visits., Results: Both hospitalizations and ED visits were significantly more frequent for patients in the post-primary treatment period compared to during treatment (hospitalizations: 22% post-primary treatment vs 13% during treatment, 95% confidence interval [CI] of true difference = 2.5%-15.5; ED visits: 21% post-primary treatment vs 10% during treatment, 95% CI of true difference = 4.8%-17.2%). Both hospitalizations (79% versus 32%, 95% CI of true difference = 28.7%-65.3%) and ED visits (42% versus 12%, 95% CI of true difference = 9.1%-50.9%) were more often breast cancer related during primary treatment compared to following treatment. Following treatment, EBC related hospitalizations were most often for disease progression (42%) and EBC related ED visits were most often for post-systemic therapy complications (43%). Significant predictors for EBC related hospitalizations in the two years following treatment included stage III disease (relative risk [RR] = 8.77, 95% CI = 2.50-30.82), having underwent mastectomy (RR = 12.51, 95% CI = 2.91-53.78), and having received chemotherapy (RR = 3.95, 95% CI = 1.18-13.23). However, chemotherapy does not appear to be a significant predictor for hospitalization when controlling for stage III disease (RR = 2.22, 95% CI = 0.61-8.05), whereas stage III disease remains a significant risk factor when controlling for chemotherapy (RR = 6.09, 95% CI = 1.58-23.52)., Discussion: Our findings suggests that stage III disease, undergoing mastectomy, and chemotherapy treatment predict higher likelihood of EBC related hospitalization following primary treatment in older EBC patients, with stage III disease likely the strongest risk factor., Competing Interests: Declaration of Competing Interest The authors declare that they have no relevant financial or non-financial conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Older adults with plasma cell disorders (PCDs) experience cognitive dysfunction that may be attributable to the disease and associated therapies. Yet, this has seldom been reported in the literature. Our objectives were to describe cognitive function (objective and patient-reported) in adults with PCDs and to explore clinical correlates of cognitive impairment., Materials and Methods: Participants completed a geriatric assessment between March 2018 and February 2020. Cognitive function was evaluated using two objective measures - Montreal Cognitive Assessment (MoCA, cutpoint <26) and Blessed Orientation Memory Concentration Test (BOMC, cutpoint >4) - and two patient-reported outcome (PRO) measures - Patient-Reported Outcomes Measurement Information System Cognitive Function (PROMIS-CF, cutpoint <45) and European Organization for Research and Treatment of Cancer Cognitive Functioning subscale (EORTC-CF, cutpoint <75). Spearman correlations examined relationships among these measures and log binomial regression was used to examine characteristics associated with cognitive impairment, as defined by the MoCA and PROMIS-CF measures., Results: Among 86 participants with a mean age of 69 (range: 46-91), the prevalence of cognitive dysfunction was between 20% (BOMC) and 63% (MoCA). There was moderate correlation among objective measures (r = 0.51, p < 0.0001), moderate to high correlation among PRO measures (r = 0.69, p < 0.0001), but no correlation between objective and PRO measures. Factors associated with objective impairment included ≤ high school education (RR 1.46, p = 0.009), living alone (RR 1.42, p = 0.02), relapsed/refractory disease (RR 1.39, p = 0.04), empirically de-intensified induction therapy (RR 1.62, p = 0.008), frailty (RR 1.49, p = 0.04), and peripheral vascular disease (RR 1.54, p = 0.002). Factors associated with PRO impairment included social isolation (RR 3.43, p = 0.003), depression (RR 3.30, p = 0.004) and anxiety (RR 4.43, p = 0.0002), frailty (RR 3.60, p = 0.02), falls in the previous 6 months (RR 2.53, p = 0.02), and deficits in physical function (RR 4.44, p = 0.01). Older age was not associated with either objective or PRO impairment., Discussion: Cognitive impairment, using objective and PRO screening measures, was relatively common in adults with PCDs. Cancer-related factors and medical comorbidities were associated with objective cognitive impairment whereas psychosocial and functional factors were associated with PRO impairment., Competing Interests: Declaration of Competing Interest Samuel M. Rubinstein reports personal fees from Janssen, personal fees from Sanofi Genzyme, personal fees from EUSA Pharma, personal fees from Roche Diagnostics, personal fees from Glaxo Smith Kline outside the submitted work. William A. Wood reports grants from Pfizer, grants from Genentech, personal fees from Teladoc, personal fees from Koneksa Health outside the submitted work. Sascha A. Tuchman reports grants and personal fees from Caelum, grants and personal fees from Sanofi Genzyme, grants and personal fees from Janssen, grants from Karyopharm, personal fees from Oncopeptides outside the submitted work. All other authors have nothing to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Newer adjuvant treatment options for non-metastatic breast cancer have increased survival. There is a need to investigate whether demographic and clinical characteristics of women with hormone receptor-positive, human epidermal growth receptor 2-negative non-metastatic breast cancer (stages I-III) differentially influence treatment decisions in older (age 65 or older) versus younger patients (under age 65)., Methods: In a retrospective electronic medical record review, prevalence ratio with 95% confidence interval for treatment decisions in older vs younger patients was calculated using log binomial regression adjusted for race, stage, and total number of comorbidities., Results: In a sample of 537 patients, 66% were age < 65 and 34% age ≥ 65. Older patients included a higher proportion of White women (85% vs 75%, P = .02), higher number of comorbidities (P ≤0.0001), and lower stage tumors (P = .0004). In multivariable analysis, age ≥ 65 was independently associated with fewer mastectomies (95% CI 0.65-0.96, P = .02), more lumpectomies (95% CI 1.05-1.42, P = .01), and less receipt of radiation treatment (95% CI 0.78-0.97, P = .01) and/or chemotherapy (95% CI 0.73-0.95, P = .006). In multivariate analysis, stage was independently significant for all treatment modalities, except endocrine therapy, and race was not., Conclusions: This study suggests that age, in addition to breast cancer stage, is a predictor of treatment modality, independent of race and number of comorbidities. Treatment modality reflects a combination of patient preference and clinician assessment of fitness for current standard of care., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Findings from a brief geriatric assessment (GA) in a cohort of adults with multiple myeloma (MM) are presented, with particular attention to the utility of the GA in identifying important deficits in adults judged to have a normal Karnofsky Performance Status (KPS ≥ 80)., Materials and Methods: Adults age 18 and older with MM were recruited into an observational study from 2018 to 2020. A modified Cancer and Aging Research Group (CARG) GA was administered at enrollment. Enrollees also completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients Core 30 questionnaire (QLQ-C30), with subscales of physical, social, role, and cognitive functioning (range 0-100; higher values indicate better function). Data were analyzed using descriptive statistics for the full cohort and stratified by concurrent KPS (score < 80 vs ≥ 80)., Results: Among 89 adults, the mean age was 69.1 years, 68% were aged ≥65 years, and 70% were white. In this cohort, 78% had KPS ≥ 80. Among those with KPS ≥ 80, functional impairments (Timed Up and Go ≥14 s and dependence in ≥1 instrumental activity of daily living) were seen in 30% and 21%, respectively, with 11% reporting ≥1 fall in the prior 6 months. At least two GA-identified deficits were detected in 50% of the overall cohort and in 41% of those with KPS ≥ 80. Among those with KPS ≥ 80, self-reported physical impairment on EORTC QLQ-C30 was noted by 34%., Conclusion: Using a modified CARG GA and EORTC questionnaire, functional impairments were identified among adults considered to have a good performance status based on a KPS (≥ 80). Future studies should focus on using GA measures for therapy assignment and identifying opportunities for intervening upon GA-identified deficits., Competing Interests: Declaration of Competing Interest The authors have no conflicts to disclose. The study received support from the North Carolina University Cancer Research Fund. Jensen receives salary support from National Cancer Institute grant T32-CA233419. Wood reports grants from Pfizer, personal fees from Teladoc, and equity in Koneksa Health outside the submitted work., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Cognitive impairment (CI) increases chemotherapy toxicity risk with need to understand this association utilizing publicly available short screening tools. We evaluated this utilizing a lower threshold on a short screening tool in older adults with cancer., Materials and Methods: We analyzed data from the Cancer and Aging Research Group (CARG) Chemotherapy Toxicity Risk tool (CARG score) development and validation cohorts (n = 703), which recruited adults age ≥ 65 with cancer from academic centers. Cognition was evaluated with the Blessed Orientation-Memory-Concentration test (BOMC). Patients with BOMC score ≥ 11 were excluded. Utilizing cut-points for older adults, we considered moderate BOMC scores (5-10) as potential CI. Logistic regression was used for analysis., Results: Patient baseline characteristics included: mean age 73; 85% white; 63% college or higher education; 250 (36%) potential CI; 385 (55%) severe toxicity. Patients with potential CI were more likely non-white (p ≤ 0.01) and to have high school or lower education (p ≤ 0.01) and high CARG score (p = 0.04). Potential CI was associated with increased severe toxicity risk (OR = 1.54, p ≤ 0.01). After adjusting for CARG score, this association became nonsignificant (OR = 1.35; p = 0.08). Among patients with lower education (n = 258; 36.7%), potential CI remained associated with severe toxicity, even after adjusting for CARG score (OR = 1.87, p = 0.03)., Conclusions: Our findings suggest potential cognitive impairment, defined by BOMC score 5-10, in older adults with cancer and lower education is associated with increased severe toxicity risk. Future studies are needed to validate these findings. Healthcare providers should consider cognitive testing before treatment for these vulnerable patients., Competing Interests: Declaration of Competing Interest None to disclose., (Copyright © 2019. Published by Elsevier Ltd.)

Objectives: The Mental Health Index (MHI) is widely used as a measure of mental health status, but has not been evaluated in the geriatric oncology population. This study evaluated the MHI-17 in a geriatric oncology population, to establish validity and scoring rules., Materials and Methods: The Carolina Senior Registry (NCT01137825) was used to obtain data for 686 patients with cancer 65 and older who completed the MHI-17. The 17-item patient-reported measure produces one total score summing across four domains: anxiety, depression, positive affect, and sense of belonging. Cronbach's alpha (α), confirmatory factor analyses (CFA), item-response theory (IRT) analyses, and differential item functioning (DIF) analyses were used to evaluate internal consistency and validity., Results and Discussion: The revised MHI retained the 13 best-fitting items from the MHI-17 and resulted in a final model that included two subscales: anxiety (four items, RMSEA 0.11; CFI 0.99; TLI 0.98) and depression (9 items, RMSEA 0.10; CFI 0.96; TL 0.95). IRT analyses of the four anxiety items indicated good fit (RMSEA 0.08) and precise measurement of adults with poor mental health, and the nine depression items also fit well (RMSEA 0.05). No meaningful differences were found by sex, education, or treatment stage. Scores were developed to provide meaningful norms. The new MHI-13 is a shorter, more accurate way to assess mental health in older adults with cancer and most importantly allows clinicians to separately identify anxiety and/or depression - a clinically important distinction as treatment differs among these two types of mental health impairment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Our aim was to evaluate the prognostic impact of three inflammatory markers - neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) - on overall survival (OS) in older adults with cancer., Materials and Methods: Our sample includes 144 patients age ≥ 65 years with solid tumor cancer who completed a cancer-specific Geriatric Assessment (GA) from 2010 to 2014 and had pretreatment CBC with differential. NLR was dichotomized a previously reported cut-off value of 3.5, while PLR and LMR were dichotomized at the median. Cox proportional hazards models evaluated whether NLR, PLR and LMR were predictive of OS independent of covariates including a recently developed 3-item GA-derived prognostic scale consisting of (1) "limitation in walking several blocks", (2) "limitation in shopping", and (3) "≥ 5% unintentional weight loss in 6 months"., Results: Median age was 72 years, 53% had breast cancer, 27% had stage 4 cancer, 14% had Karnofsky Performance Status (KPS) < 80, 11% received less intensive than standard treatment for stage, and 39% had NLR > 3.5. In univariable analysis, higher NLR and PLR and lower LMR were significantly associated with worse OS. NLR remained a significant predictor of OS (HR = 2.16, 95% CI; 1.10-4.25, p = .025) after adjusting for cancer type, stage, age, KPS, treatment intensity, and the GA-derived prognostic scale., Conclusion: NLR > 3.5 is predictive of poorer OS in older adults with cancer, independent of traditional prognostic factors and the GA-derived prognostic scale., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: The agreement between clinician- and patient-reported toxicities and their association with poor tolerance to therapy were assessed in an older population receiving curative radiotherapy (RT)., Materials and Methods: Patients ≥ 65 years old with newly-diagnosed head and neck or lung cancer receiving curative RT ± chemotherapy were enrolled on a prospective, observational study. Agreement between clinician (CTCAEv4.02) and patient (PRO-CTCAE, EORTC QLQ-C30) report of toxicities were assessed at baseline, during treatment, and post-treatment. The association of clinician- and patient-reported symptoms with poor tolerance to therapy (defined as hospitalization, >3-day treatment delay, change in treatment regimen, or death) was assessed., Results: Among 45 patients, median age was 71, 60% had head and neck cancer, and 47% received concurrent chemotherapy with RT. In comparing CTCAE vs PRO-CTCAE, there was good agreement at baseline except for fatigue, anorexia, and pain, where clinicians under-reported the severity. The discrepancy increased during treatment with clinicians reporting lower severity in ≥50% of matched pairs for 4/10 symptoms assessed. At follow-up, clinicians under-reported severity in ≥50% of pairs for 7/10 symptoms. CTCAE vs EORTC QLQ-C30 mirrored these findings. Patient-reported symptoms of nausea and dysphagia at 2 weeks and clinician-observed symptoms of nausea and dysphagia at 4 weeks were associated with poor tolerance to therapy., Conclusion: Clinicians under-report toxicities during and after curative RT in older patients with head and neck or lung cancer. Select toxicities reported by patients early in treatment and clinicians later in treatment were associated with poor tolerance to cancer therapy, providing valuable complementary information., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: A geriatric assessment (GA) assesses functional age of older patients with cancer and is a well-established tool predictive of toxicity and survival. The objective of this study was to investigate the prognostic value of individual GA items., Materials and Methods: 546 patients with cancer ≥ 65 years completed GA from 2009 to 2014 and were followed for survival status for a median of 3.7 years. The GA consisted of function, nutrition, comorbidity, cognition, psychological state, and social activity/support domains. GA items with p < 0.05 in univariable analyses for overall survival (OS) were entered into multivariable stepwise selection procedure using a Cox proportional hazards model. A prognostic scale was constructed with significant GA items retained in the final model., Results: Median age was 72 years, 49% had breast cancer, and 42% had stage 3-4 cancer. Three GA items were significant prognostic factors, independent of traditional factors (cancer type, stage, age, and Karnofsky Performance Status): (1) "limitation in walking several blocks", (2) "limitation in shopping", and (3) "≥ 5% unintentional weight loss in 6 months". A three-item prognostic scale was constructed with these items. In comparison with score 0 (no positive items), hazard ratios for OS were 1.85 for score 1, 2.97 for score 2, and 8.67 for score 3. This translated to 2-year estimated survivals of 85%, 67%, 51% and 17% for scores of 0, 1, 2 and 3, respectively., Conclusions: This three-item scale was a strong independent predictor of survival. If externally validated, this could be a streamlined tool with broader applicability., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions., Patients and Methods: We reviewed 14 Alliance for Clinical Trials in Oncology trials that enrolled CLL and/or NHL patients between 2004-2014. Toxicity was assessed per the NCI-CTCAE (version 3-5). Probabilities of experiencing grade three or four hematologic and non-hematologic toxicities were modeled as a function of clinical and disease-related factors using logistic regression., Results: 1199 patients (409 age ≥ 65; 790 age < 65) were analyzed; 438 received only biologic therapy (145 age ≥ 65; 293 age < 65), and 761 received biologic + chemotherapy (264 age ≥ 65; 497 age < 65). The odds of grade three or four hematologic [odds ratio (OR) 1.70; p = 0.009: 95% CI (1.57-1.84)] and non-hematologic toxicities [OR 1.47; p = 0.022; 95% CI (1.39-1.55)] were increased in older patients with CLL, as well as odds of grade three or four non-hematologic toxicities [OR 1.89; p = 0.017; 95% CI (1.64-2.17)] in older patients with NHL. Grade three or four hematologic toxicities were associated with inferior OS and PFS in older patients with NHL [HR 3.14; p = 0.006; 95% CI (2.25-4.39) for OS and 3.06; p = 0.011; 95% CI (2.10-4.45) for PFS], though not in CLL. A prognostic model predicting grade three or four toxicities was also developed., Conclusions: CLL and NHL patients ≥ 65 year encounter more toxicities than younger patients even when treated with novel biologic agents. Development of grade three or four hematologic toxicities lead to inferior PFS and OS in NHL but not in CLL., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Time-to-treatment-failure (TTF) is the interval from chemotherapy initiation to premature discontinuation. We evaluated TTF based on age., Methods: Pooled analyses were conducted with first-line chemotherapy trials for advanced NSCLC (CALGB 9730, 30203, and 30801). Comparisons among patients who were 65 years and older and 70 years and older were performed for TTF (primary endpoint), reasons for early chemotherapy cessation, grade 3+ adverse events, and overall survival., Results: Among 1006 patients, 460 (46%) were older than 65 years of age. One hundred forty-five older patients (32% of this age cohort) completed all six planned chemotherapy cycles as did 170 (32%) younger patients. Median TTF was 2.9 months (95% confidence interval: 2.7- 3.2) in older patients and 3 months (95% confidence interval: 2.9-3.5) in younger patients; adjustment for performance status and stratification by chemotherapy by trial yielded no statistically significant age-based difference in TTF. However, reasons for early chemotherapy cessation differed between age groups (multivariate p = 0.004). Older patients were less likely to discontinue from cancer progression (41% versus 55%) and more likely from toxicity or patient choice (16% and 15%, respectively) compared to younger patients (13% and 6%, respectively). Older patients were more likely to experience grade 3+ adverse events (86% versus 79%) with no statistically significant difference in survival. An age cutpoint of 70+ years showed no difference in TTF, a lower trend of early cessation due to cancer progression, and somewhat shorter older patient survival., Conclusions: TTF was comparable between older and younger patients; but different, age-based, and potentially modifiable reasons account for it., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objective: Chemotherapy preference refers to a patient's interest in receiving chemotherapy. This study examined whether chemotherapy preference was associated with toxicity, efficacy, quality of life (QoL), and functional outcomes during and after completion of adjuvant chemotherapy in older women with breast cancer., Materials and Methods: This study is a secondary analysis of CALGB 49907, a randomized trial that compared standard adjuvant chemotherapy versus capecitabine in patients age 65 years or older with breast cancer. A subset of 145 patients completed a questionnaire to describe chemotherapy preference pre-treatment. The association of this pre-treatment preference with the patient's perception of self-health, predicted and actual QoL, patient- and professional-reported toxicity, mental health, self-rated function, and survival was studied during and after treatment., Results: The median age of patients was 71 years and 47% had a high preference for chemotherapy. On baseline demographics, the low preference group had a higher proportion of white patients (95% vs. 78%, p = 0.004). Before treatment, low chemotherapy preference was associated with greater nausea/vomiting (p = 0.008). Mid-treatment, low preference was associated with lower QoL, worse social, emotional and physical function (all p ≤ 0.02) and worse nausea/vomiting, cancer symptoms and financial worries (all p < 0.05). The association noted mid-treatment, resolved after treatment completion except with financial worries which persisted at 24 months. Low preference was associated with higher rates of grade 3-5 adverse events (53% vs. 34%, p = 0.02) but was not associated with survival., Conclusions: Low chemotherapy preference prior to treatment initiation was associated with lower QoL, worse physical symptoms and self-rated function and more adverse events mid-treatment. There is no association of chemotherapy preference with survival., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Actual weight-based (AWB) chemotherapy dosing is recommended for obese patients in the 2012 ASCO Clinical Practice Guideline. CALGB 49907, which utilized ABW-based adjuvant chemotherapy dosing, was a phase 3 trial in women age≥65years with early stage breast cancer, providing the opportunity to examine impact of such dosing on toxicities and outcome in older patients with breast cancer., Materials and Methods: Adverse event data were available for 615 of 633 enrolled patients. Objectives were to assess grade≥3 hematologic/non-hematologic toxicities by treatment arm, age, study entry BSA/BMI, and relapse-free (RFS) and overall survival (OS) by BSA/BMI., Results: The 615 patients were sub-grouped by BSA (quartiles) and standard BMI categories, with BMI underweight/normal weight categories combined. Overall, grade≥3 non-hematologic and hematologic toxicities occurred in 39.8% and 28.3% of patients, respectively. There were no significant differences in grade≥3 toxicities among BSA quartiles. However, more grade≥3 hematologic toxicities occurred in the underweight/normal weight BMI subgroup compared to overweight/obese subgroups (p=0.048). Type of chemotherapy and age had no impact on toxicity occurrence by BSA/BMI categories. RFS was superior in the 25th-50th BSA percentile patients in univariate analysis (p=0.042), as was OS in both univariate and multivariate analyses (p=0.007, p=0.009, respectively). No differences in RFS or OS were found by BMI categories., Conclusion: Obesity was not correlated with adverse relapse or survival outcome, and grade≥3 toxicities were not greater with ABW-based dosing. This supports safety and efficacy of ABW-based dosing as per the 2012 ASCO clinical practice guideline. ClinicalTrials.gov Identifier: NCT00024102 (49907)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Computerized tomography (CT) imaging is routine in oncologic care and can be used to measure muscle quantity and composition that may improve prognostic assessment of older patients. This study examines the association of single-slice CT-assessed muscle measurements with a frailty index in older adults with cancer., Materials and Methods: Using the Carolina Senior Registry, we identified patients with CT imaging within 60days ± of geriatric assessment (GA). A 36-item Carolina Frailty Index was calculated. Cross-sectional skeletal muscle area (SMA) and Skeletal Muscle Density (SMD) were analyzed from CT scan L3 lumbar segments. SMA and patient height (m 2 ) were used to calculate skeletal muscle index (SMI). Skeletal Muscle Gauge (SMG) was calculated by multiplying SMI×SMD., Results: Of the 162 patients, mean age 73, 53% were robust, 27% pre-frail, and 21% frail. Significant differences were found between robust and frail patients for SMD (29.4 vs 24.1 HU, p<0.001) and SMG (1188 vs 922AU, p=0.003), but not SMI (41.9 vs 39.5cm 2 /m 2 , p=0.29). After controlling for age and gender, for every 5 unit decrease in SMD, the prevalence ratio of frailty increased by 20% (PR=1.20 [1.09, 1.32]) while the prevalence of frailty did not differ based on SMI., Conclusions: Muscle mass (measured as SMI) was poorly associated with a GA-based frailty index. Muscle density, which reflects muscle lipid content, was more associated with frailty. Although frailty and loss of muscle mass are both age-related conditions that are predictive of adverse outcomes, our results suggest they are separate entities., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: This study aims to (1) describe the activities, function, and health-related quality of life (HRQOL) of a large sample of older adults (age ≥65) with cancer, (2) identify the associations with demographics, cancer type, comorbid conditions, and ability to participate in activities and functional status., Materials and Methods: The Health Registry/Cancer Survivorship Cohort is an institutional database designed to aid cancer survivorship research. The registry includes three measures of patient-reported HRQOL: FACT-G and PROMIS® Global measures for physical and mental health. Other measures included in the registry are cancer type, date from diagnosis, number of comorbid conditions and specific conditions and their limitations in daily activity, and self-reported daily activity/function., Results: Our sample consists of 768 older adults with cancer, mean age 72years, 60% female, and 90% White. Mean scores for HRQOL: FACT-G (85, range: 25-108), PROMIS-physical (48, range: 16-67) and, PROMIS-mental (51, range: 21-67). In multivariable models, Black race, one or more comorbid conditions, and Gastrointestinal cancer (p<.05), and patient- reported decreased levels of activities/function were all independently associated with poor HRQOL (p<.0001)., Conclusions: Older Black adults with cancer, those that have high comorbidity burden, with gastrointestinal cancers and those that report decreased ability to participate in daily activities/function reported poorer HRQOL. As geriatric oncology moves towards trying to identify who may need supportive services, this study demonstrated that a one question patient-reported level of activities and functional ability were independently associated with physical, mental, and cancer-specific HRQOL., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Immune checkpoint inhibitors (ICIs) rely on the presence of ongoing immune response to exert their antitumor effect. Little is known whether an age-related decline in immune function negatively influences antitumor response and in so doing diminishes the efficacy of ICIs in elderly subjects. We performed a meta-analysis to compare the efficacy of ICIs between younger and older patients., Patients and Methods: PubMed and the ASCO databases were searched up to September 2015. We included randomized controlled trials (RCTs) of ICIs (ipilimumab, tremelimumab, nivolumab and pembrolizumab) reporting subgroup comparison of overall survival (OS) and/or progression-free survival (PFS) based on age cutoffs. The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated., Results: A total of 5265 patients from nine RCTs of ICI were included. When patients are dichotomized into younger and older groups with an age cut-off of 65-70 years, ICIs improved OS in both younger (HR, 0.75; 95% CI, 0.68-0.82) and older (HR, 0.73; 95% CI, 0.62-0.87) groups. An improvement in PFS was observed in younger (HR, 0.58; 95% CI, 0.40-0.84) and older (HR, 0.77; 95% CI, 0.58-1.01) patients. Subgroup analyses according to ICI and tumor type showed a consistent survival benefit in both younger and older groups except for the subgroup of older patients treated in 4 trials of anti-programmed cell death protein-1 (PD-1) monoclonal antibody (HR, 0.86; 95% CI, 0.41-1.83)., Conclusions: A benefit in OS with ICIs was significant in both younger and older patients with a cut-off age of 65-70 years., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Although older patients represent the most rapidly growing segment of the oncology population, clinical care is guided by very little data on patient-reported outcomes, particularly satisfaction with healthcare. Using a large cancer center registry, we sought to describe factors associated with satisfaction with care for older and younger oncology patients., Methods: Data were collected through the University of North Carolina Health Registry Cancer Survivorship Cohort. Satisfaction was measured with the Patient Satisfaction Questionnaire Short Form. Quality of life (QOL) measures included were the Promis Global short form and the Functional Assessment of Cancer Therapy General (FACT-G)., Results: A total of 2385 patients were included. 460 (20%) were aged 70 and above (older group). Older patients reported significantly higher levels of satisfaction in domains of time spent with doctor (scores 3.84 versus 3.73 p=0.03) and financial aspects (scores 4.03 versus 3.44 p<0.001) compared to younger patients. In multivariable analysis, higher QOL scores and higher self-reported ECOG performance status were associated with higher satisfaction scores. African American race was associated with lower satisfaction scores in all age groups. QOL was more closely correlated with satisfaction in older patients compared to younger patients., Conclusions: Older patients with cancer report higher levels of satisfaction with care, in part due to lesser financial burden of care. Better QOL is associated with satisfaction with care in older patients. Use of patient-reported outcomes such as patient satisfaction may help improve patient-centered geriatric oncology care., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The immune system plays an important role in cancer pathogenesis. A low lymphocyte-to-monocyte ratio (LMR), as a simple biomarker of host immune system, has been suggested to be related to poor prognosis in various cancers. We performed a systematic review and meta-analysis to quantify the prognostic value of LMR on clinical outcomes in non-hematologic solid tumors., Patients and Methods: We searched PubMed and the ASCO online database of meeting abstracts up to July 2015 for relevant studies. We included studies assessing the prognostic impact of pre-treatment LMR on clinical outcomes in patients with non-hematologic solid tumors. The primary outcome was overall survival (OS) and the secondary outcomes were cancer-specific survival (CSS) and disease-free survival (DFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated., Results: A total of 11,197 patients from 29 studies were included. LMR lower than the cut-off was associated with poor OS (HR, 1.73; 95% CI, 1.55-1.93; P<0.001), CCS (HR, 1.56; 95% CI, 1.27-1.91; P<0.001) and DFS (HR, 1.56; 95% CI, 1.31-1.86; P<0.001). The effect of LMR on OS was observed in among various tumor types and across disease stages. The median cut-off value for LMR was 3.0 (range=2.0-5.3). Subgroup analysis according to cut-off value (<3.0, 3.0 to <4.0, 4.0 to <5.0, and ≧5.0) showed a significant prognostic value of LMR on OS in all subgroups., Conclusions: A low pre-treatment LMR seems to represent an unfavorable and robust prognostic factor for clinical outcomes in patients with non-hematologic malignancies., Funding: None., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Sarcopenia is the age-related loss of muscle mass, strength, and function. It is a common finding in older patients and is associated with decreased life expectancy and potentially higher susceptibility to chemotherapy toxicity. This study describes the prevalence of sarcopenia in older adults with early stage colorectal cancer., Materials and Methods: Patients ≥70 years old who underwent surgical resection for stage I-III colorectal cancer between 2008 and 2013 were identified from the medical record. Sarcopenia was assessed by measuring the total muscle area on computerized tomography (CT) images obtained prior to surgery. Total muscle area was measured at the level of L3 and normalized using each patient's height to produce a skeletal muscle index (SMI). Sarcopenia was defined using sex- and body mass index (BMI)-specific threshold values of SMI., Results: Eighty-seven patients were included, with a median age of 77 years (70-96). Twenty-five men (60% of 42) and 25 women (56% of 45) had sarcopenia. Sarcopenic patients had significantly lower BMI (p=0.03) compared to non-sarcopenic patients. There was a positive correlation between BMI and SMI for both men (r=0.44) and women (r=0.16)., Conclusion: Sarcopenia is highly prevalent among older patients with early stage colorectal cancer. BMI alone is a poor indicator of lean body mass and improved methods of screening for sarcopenia are necessary. CT scans are a viable option for identifying sarcopenic patients in whom timely interventions may improve survival, quality of life, and functional outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Large numbers of older adults (aged 65years or older) are surviving cancer; however, many survivors report decreased quality of life (QOL) and limitations in activities of daily living (ADL) and instrumental activities of daily living (IADL) both during and after treatment [1-3]. Occupational and physical therapy (OT/PT) are services focused on improving functional status and QOL that are largely unexplored and underutilized in cancer survivorship care [4,5]., Methods/design: This is a randomized, single-blind, two-arm, single institution pilot study. Eighty-two patients will be recruited from a university-affiliated outpatient oncology clinic. Inclusion criteria include the following: aged 65years or older, diagnosis of cancer within 5years, English speaking, has at least one functional deficit, and able to safely participate in an outpatient rehabilitation program. Exclusion criteria are: currently receiving rehabilitation or eligible for hospice. Consented patients will be randomized into two groups: (1) the CARE (CAncer REhabilitation) Program consisting of outpatient OT/PT and (2) standard of care., Primary Outcome: change in Nottingham Extended Activities of Daily Living (NEADL) scores from baseline to 3months between CARE and control., Discussion: This study is one of the first RCTs aimed at examining the effect of OT/PT in older adults with cancer. If positive, findings from this study will suggest the potential for outpatient OT/PT to improve the functional ability and QOL of older adults with cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Colorectal cancer (CRC) diagnosis and treatment can have substantial detrimental impacts on health related quality of life (HRQOL) and physical function. This is especially true for older CRC patients and is of paramount concern in chemotherapy treatment decision making; yet, few studies to date have focused on understanding and managing fatigue in older CRC patients. We present the design of a study to evaluate the feasibility and impact of a home-based, self-directed physical activity intervention on fatigue in older CRC patients receiving adjuvant chemotherapy treatment. Secondary aims pertain to intervention impact on HRQOL, physical function, and self-efficacy for managing fatigue., Methods/design: Multi-site, randomized controlled trial of physical activity intervention compared to usual care in a sample of older adults undergoing adjuvant chemotherapy for CRC. Forty CRC patients will be recruited and study questionnaires/assessments will be performed at baseline, 3 months, and after completion of adjuvant chemotherapy. The primary outcome is a comparison of the change in fatigue from baseline to 3 months between Intervention and Control arms. We will also compare changes in engagement in physical activity, HRQOL, physical function, and self-efficacy. Exploratory analyses will compare Intervention and Control arms with regard to changes in muscle mass and a biomarker aging that is known to increase during chemotherapy (p16(INK4a))., Discussion: If positive, findings from this pilot study would suggest the potential for improving the care of older persons with CRC undergoing adjuvant chemotherapy through a home-based physical activity intervention to manage fatigue, HRQOL, and physical function., Trial Registration: NCT02191969., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Occupational and physical therapy (OT/PT) services seek to reduce morbidity, mortality, and improve the quality of life of individuals; however, little is known about the needs and use of OT/PT for older adults with cancer. The goal of this study was to describe the functional deficits and their associations with other factors, and to examine the use of OT/PT after a noted functional deficit., Materials and Methods: This study analyzed data from an institution-based registry that included geriatric assessments of older adults with cancer linked to billing claims data. Logistic regression was used to model predictors of functional deficits. Use of OT/PT was determined and validated with medical chart review., Results: 529 patients with cancer, a median age of 71, 78% were female, 87% Caucasian, 57% married, 53% post-secondary education, and 63% with breast cancer were included. In a multivariable model, the odds of having any functional deficits increased with age [5 year OR: 1.31, 95% CI: (1.10, 1.57)] were higher for those with a high school diploma versus those with advanced degrees [OR: 1.66, 95% CI: (1.00, 2.77)] and were higher for patients with comorbidities [OR: 1.15, 95% CI: (1.10, 1.21)]. Of patients with functional deficits only 9% (10/111) received OT/PT within 12 months of a noted deficit., Discussion: The odds of having any potentially modifiable functional deficit were higher in patients with increasing age, comorbid conditions, and with less than a college degree. Few were referred for OT/PT services suggesting major underutilization of these potentially beneficial services., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Emerging results support the value of geriatric assessment (GA) in determining the risk and benefits of cancer treatment in older adults. A brief GA tool consisting of valid and reliable measures has been developed; however, little data exist on the ability to perform the GA in community oncology clinics. The objective of this study was to determine the feasibility of performing the GA in the community., Materials and Methods: Patients aged ≥65 were eligible. The GA included a health care provider assessment of performance status, cognitive function, a Timed Up and Go test, and a self-administered patient questionnaire that evaluated measures of functional status, comorbidity, psychological state, social support, and nutritional status., Results: From 2009 to 2013, 1088 patients were assessed including 339 (31%) from seven community clinics across North Carolina. The median amount of time to complete the patient-report portion of the GA was 19min in the academic center versus 22min in the community. The median amount of time to complete the entire GA was 23min in the academic center and 30min in community settings. Significantly more patients in the community required assistance completing the questionnaire (24% vs. 14%); however, most patients required no assistance (76%)., Conclusion: A brief GA can be performed in community oncology clinics. The time to complete the professional assessments and patient self-assessments were similar in both settings. Future studies are planned to determine if such assessments can improve cancer care for older patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: National guidelines suggest that women with hormone receptor positive breast cancer be considered for adjuvant endocrine treatment with an aromatase inhibitor (AI). Joint symptoms (arthralgia) are a common AI side-effect. There is a need for effective approaches to arthralgia management that enable survivors to remain on AI therapy while optimizing as pain-free a life as possible. This feasibility study investigates a 6-week self-directed walking program in a sample of elderly female breast cancer survivors on AIs reporting joint pain., Intervention: Walk With Ease (WWE) goal--minimum 30 min of walking 5 days a week (150 min per week). Eligibility: age >65; Stage I-III breast cancer; ≥3 months of AI therapy; self-reported joint pain/stiffness., Measures: (1) walking--number of days/week and number of minutes/walk, (2) visual analog scales (VAS) for joint pain, fatigue and stiffness, and (3) arthritis self-efficacy (ASE) to manage joint pain and fatigue., Statistics: t-tests, correlation coefficients and effect sizes., Results: Sample target of 20 was achieved--mean age 71 (65-87), 85% Caucasian, mean BMI 29. Proportion walking 150 min/week increased from 21% at baseline to 50% at 6 weeks (p < 0.001). Mean joint pain at baseline (39.7 + 26.9) decreased 10% (p = 0.63), fatigue (37.4+33.3) decreased 19% (p = 0.31), joint stiffness (46.1 + 27.2) decreased 32% (p = 0.07)., Conclusions: A self-directed walking program among elderly breast cancer survivors on AI therapy significantly increased total time of walking per week over a 6 week period. Joint pain, stiffness, and fatigue also decreased, although not significantly. Testing within a larger sample is warranted., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Treating older patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer is often challenging. This is largely due to the issues providers face in making decisions in the setting of limited efficacy and toxicity data specific to older women in addition to the competing challenges of managing comorbidity and preserving functional status. Here, we discuss currently available treatment regimens and other important issues to consider when treating older patients with metastatic, HER2-positive disease., (© 2013.)

Objectives: Patients ≥ 65 years old ("older") are often not included in randomized clinical trials (RCT), but when they are, care in an RCT might improve quality of life (QoL). We conducted a prospective comparison of QoL among older women receiving standard chemotherapy from the same cooperative group physicians in an RCT vs. an observational study ("off-trial")., Methods: Older women with invasive, non-metastatic breast cancer (n=150 RCT; 530 off-trial) were included. Linear mixed-effects models tested associations between chemotherapy on- vs. off-trial and changes in EORTC (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire) QoL scores over 24 months, controlling for pre-treatment QoL, age, education, tumor factors, comorbidity, and other covariates., Results: Anthracycline regimens were used by 58% of women treated on-trial vs. 54% of those treated off-trial. Women in the RCT reported an adjusted mean increase of 13.7 points (95% CI 10.2, 17.1) in global QoL at 24 months (vs. mid-treatment), while women treated off-trial had only an adjusted improvement of 7.0 points (95% CI 3.5, 10.4; p=.007 for difference in mean changes). Women in the RCT had significantly greater improvement in emotional function than those treated off-trial, controlling for baseline; they also had greater reductions in therapy side effects and fatigue at 24 months than women off-trial, controlling for covariates., Conclusion: There may be different QoL trajectories for older women undergoing breast cancer chemotherapy on- vs. off-trial. If confirmed, the results suggest that the extra monitoring and communication within an RCT could provide the infrastructure for interventions to address symptoms and improve QoL for the growing older cancer population., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Lipemia interference in blood samples is usually determined by adding exogenous substances that cause turbidity or by using ultracentrifugation to clarify the sample. However, there are a number of problems associated with these methods, which make it difficult to ascertain with certainty that lipemia is the cause of interference. We assessed a novel method for evaluating lipemia interference., Methods: Lipemic and non-lipemic serum samples, with similar HDL cholesterol concentrations, were mixed in various proportions (5 concentrations) and assayed for HDL and triglycerides. Thus, matched HDL samples with increasing triglycerides concentrations were tested. We then calculated the percent recovery for HDL for each mixture., Results: Six matched sets of samples had HDL recoveries ranging from 95.9% to 101.1% (n=6 sets, 5 concentrations per set, total of 30 concentrations), with HDL concentrations ranging from 0.78 to 2.16 mmol/l. Triglycerides concentrations in these samples ranged from 1.06 to 9.78 mmol/l for the 30 concentrations., Conclusions: We determined that there was no triglycerides interference on the HDL method performed on the Hitachi S40 Clinical Analyzer up to a triglycerides concentration of 9.78 mmol/l. This matching method is simple to perform and proved useful in evaluating interference due to lipemia., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Purpose: Pretreatment preferences for adjuvant therapy were examined and compared with actual treatment received., Patients and Methods: Before definitive surgery, women with node-negative breast cancer were asked to indicate their preference for adjuvant therapy in response to 3 different clinical scenarios. The scenarios provided precise risk, benefit, and side effect information with low-, moderate-, or high-risk risk of death from breast cancer. Contingency table and Spearman rank correlation coefficients were used to examine associations. Kruskal-Wallis rank sum tests were used for group comparisons, with the Friedman rank sum test being used for correlated samples., Results: A total of 75 women enrolled between February 2002 and April 2005; 24% were aged > 65 years. After definitive surgery, 21% of women had ductal carcinoma in situ, and 89% had receptor-positive disease. There was a significant correlation between risk of recurrence and aggressiveness of treatment preferred (P < .001). After surgical staging, the high-risk group received more aggressive treatment compared with the low-risk group (P = .004). In the 51 women with invasive receptor-positive tumors, there was a significant difference (P = .002) in aggressiveness of treatment received based on risk of recurrence. Only 45% of the women received what they had preferred for the level of their risk before surgery. Women were more likely to receive a less aggressive therapy than they preferred initially (P = .0002)., Conclusion: This study is among the first to correlate pretreatment preference for therapy with the actual therapy received. Less than half of women received their indicated preference before definitive surgery, with most women receiving less aggressive therapy. Future studies will need to examine this discrepancy.

Background: Tamoxifen is standard adjuvant treatment for postmenopausal women with hormone-receptor-positive breast cancer. We assessed the benefit of adding chemotherapy to adjuvant tamoxifen and whether tamoxifen should be given concurrently or after chemotherapy., Methods: We undertook a phase 3, parallel, randomised trial (SWOG-8814, INT-0100) in postmenopausal women with hormone-receptor-positive, node-positive breast cancer to test two major objectives: whether the primary outcome, disease-free survival, was longer with cyclophosphamide, doxorubicin, and fluorouracil (CAF) given every 4 weeks for six cycles plus 5 years of daily tamoxifen than with tamoxifen alone; and whether disease-free survival was longer with CAF followed by tamoxifen (CAF-T) than with CAF plus concurrent tamoxifen (CAFT). Overall survival and toxicity were predefined, important secondary outcomes for each objective. Patients in this open-label trial were randomly assigned by a computer algorithm in a 2:3:3 ratio (tamoxifen:CAF-T:CAFT) and analysis was by intention to treat of eligible patients. Groups were compared by stratified log-rank tests, followed by Cox regression analyses adjusted for significant prognostic factors. This trial is registered with ClinicalTrials.gov, number NCT00929591., Findings: Of 1558 randomised women, 1477 (95%) were eligible for inclusion in the analysis. After a maximum of 13 years of follow-up (median 8.94 years), 637 women had a disease-free survival event (tamoxifen, 179 events in 361 patients; CAF-T, 216 events in 566 patients; CAFT, 242 events in 550 patients). For the first objective, therapy with the CAF plus tamoxifen groups combined (CAFT or CAF-T) was superior to tamoxifen alone for the primary endpoint of disease-free survival (adjusted Cox regression hazard ratio [HR] 0.76, 95% CI 0.64-0.91; p=0.002) but only marginally for the secondary endpoint of overall survival (HR 0.83, 0.68-1.01; p=0.057). For the second objective, the adjusted HRs favoured CAF-T over CAFT but did not reach significance for disease-free survival (HR 0.84, 0.70-1.01; p=0.061) or overall survival (HR 0.90, 0.73-1.10; p=0.30). Neutropenia, stomatitis, thromboembolism, congestive heart failure, and leukaemia were more frequent in the combined CAF plus tamoxifen groups than in the tamoxifen-alone group., Interpretation: Chemotherapy with CAF plus tamoxifen given sequentially is more effective adjuvant therapy for postmenopausal patients with endocrine-responsive, node-positive breast cancer than is tamoxifen alone. However, it might be possible to identify some subgroups that do not benefit from anthracycline-based chemotherapy despite positive nodes., Funding: National Cancer Institute (US National Institutes of Health)., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Women with hormone receptor-positive breast cancer continue to be at risk for recurrence and mortality for many years after diagnosis. Previous clinical trials established 5 years of endocrine therapy as a standard of care for both premenopausal and postmenopausal women, resulting in long-lasting benefit over shorter durations of treatment. Until recently, trials testing durations of tamoxifen longer than 5 years have not shown additional benefit, but the ATLAS (Adjuvant Tamoxifen, Longer Against Shorter) trial, reported in 2007, showed a small but significant reduction in risk of recurrence with 10 compared with 5 years of tamoxifen therapy. Aromatase inhibitors (AIs) improve relapse-free survival (RFS) in postmenopausal women when they are used sequentially with, or replace, tamoxifen for a total of 5 years of therapy. Extension of endocrine therapy to 10 years in the National Cancer Institute of Canada Clinical Trials Group MA.17 trial demonstrated that 5 years of letrozole therapy following 5 years of tamoxifen therapy results in an improvement in RFS, but not overall survival, in postmenopausal women. Trials testing durations of AI therapy for longer than 5 years are ongoing. Selection of candidates for extended endocrine therapy should balance recurrence risk, toxicity of treatment, and comorbidities that might impact life expectancy and risk of side effects.

Women with hormone receptor-positive breast cancer have traditionally been treated with 5 years of adjuvant tamoxifen to reduce their risk of subsequent recurrent disease. Among those who experience subsequent disease recurrence, the majority do so after 5 years, suggesting that longer durations of endocrine therapy might be beneficial. Two options tested include longer tamoxifen and, in postmenopausal women, a switch to an aromatase inhibitor (AI). In the National Cancer Institute of Canada Cooperative Trials Group MA.17 trial, we tested the AI letrozole given to postmenopausal women for 5 years after tamoxifen as extended adjuvant therapy because of its efficacy in patients with advanced breast cancer in progression on previous tamoxifen. The first interim analysis (median, 2.4 patient years) showed substantial benefits from letrozole, and all patients were unblinded and offered the option of letrozole. Despite two thirds of the patients crossing over to letrozole, an intent-to-treat analysis at 54 months' follow-up continued to demonstrate the strong beneficial effect of extended adjuvant letrozole. Furthermore, significant benefit was demonstrated among patients who had been randomized to placebo but elected to take letrozole after a prolonged washout from previous tamoxifen (late extended adjuvant therapy). A trial examining the merits of > 5 years of treatment with an AI, MA.17R, is ongoing, as are a number of other trials of duration of therapy. This article reviews results from MA.17 and the design of these trials of duration.

Aromatase inhibitors (AIs) are important adjunctive therapy for postmenopausal women with hormone receptor-positive, early-stage breast cancer. At the present time, AIs have no role for the management of breast cancer in premenopausal women. We report on several cases of the inadvertent use of AI therapy among women with residual ovarian function. A common experience in these cases was the onset of chemotherapy-related amenorrhea before initiation of AI therapy, which confounded assessment of true menopausal status. We believe clinicians should be aware of the potential ovarian reserve among women with treatment-related amenorrhea so as to avoid use of AI therapy in patients in whom there is uncertainty about menopausal status.

Anthracyclines have been incorporated into adjuvant chemotherapy regimens for breast cancer since the 1980s. A metaanalysis confirmed that regimens containing anthracyclines result in better disease-free and overall survival than standard CMF (cyclophosphamide/methotrexate/5-fluorouracil), with a proportional reduction of 11% in risk of death at 10 years with the addition of these agents. Dose escalation of doxorubicin results in outcome improvement up to a threshold dose beyond which no further improvement is seen. Epirubicin, with its better toxicity profile, can be escalated to higher doses than doxorubicin, with better outcomes associated with higher dose levels. Tumors expressing HER2/neu may respond better to anthracycline-containing regimens than to standard CMF, but this remains controversial. Newer regimens combining anthracyclines with taxanes may offer a slight additional advantage in terms of disease-free and overall survival in some patient populations. The scheduling of treatment is important, with recent results of dose-dense scheduling showing a greater survival benefit than conventional scheduling. Ongoing clinical trials should further define the best choice of anthracycline and the optimal dose and schedule of treatment.