Kayo Togawa

Predicting Chemotherapy Toxicity in Older Adults With Cancer: A Prospective Multicenter Study

PURPOSE Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity. PATIENTS AND METHODS Patients age ≥ 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P < .001). CONCLUSION A risk stratification schema can establish the risk of chemotherapy toxicity in older adults. Geriatric assessment variables independently predicted the risk of toxicity.

Implementing a Geriatric Assessment in Cooperative Group Clinical Cancer Trials: CALGB 360401

PURPOSE Factors captured in a geriatric assessment can predict morbidity and mortality in older adults, but are not routinely measured in cancer clinical trials. This study evaluated the implementation of a geriatric assessment tool in the cooperative group setting. PATIENTS AND METHODS Patients age ≥ 65 with cancer, who enrolled on cooperative group cancer trials, were eligible to enroll on Cancer and Leukemia Group B (CALGB) 360401. They completed a geriatric assessment tool before initiation of protocol therapy, consisting of valid and reliable geriatric assessment measures which are primarily self-administered and require minimal resources and time by healthcare providers. The assessment measures functional status, comorbidity, cognitive function, psychological state, social support, and nutritional status. The protocol specified criteria for incorporation of the tool in future cooperative group trials was based on the time to completion and percent of patients who could complete their portion without assistance. Patient satisfaction with the tool was captured. RESULTS Of the 93 patients who enrolled in this study, five (5%) met criteria for cognitive impairment and three did not complete the cognitive screen, leaving 85 assessable patients (median age, 72 years). The median time to complete the geriatric assessment tool was 22 minutes, 87% of patients (n = 74) completed their portion without assistance, 92% (n = 78) were satisfied with the questionnaire length, 95% (n = 81) reported no difficult questions, and 96% (n = 82) reported no upsetting questions. One hundred percent of health care professionals completed their portion. CONCLUSION This brief, primarily self-administered geriatric assessment tool met the protocol specified criteria for inclusion in future cooperative group clinical trials.

Long-term recovery after hematopoietic cell transplantation: predictors of quality-of-life concerns

This prospective longitudinal study examined the quality of life (QOL) after hematopoietic cell transplantation (HCT) and identified risk factors of poor QOL in 312 adult autologous and allogeneic HCT patients. Physical, psychological, social, and spiritual well-being was assessed before HCT, 6 months, and 1, 2, and 3 years after HCT. For all HCT patients, physical QOL was stable from before to after HCT (P > .05); psychologic (P < .001), social (P < .001), and spiritual (P = .03) QOL improved at 6 months. Study noncompleters (because of illness or death) had worse QOL. Allogeneic patients reported worse physical and psychologic well-being (P < .05). Older patients reported worse physical but better social well-being regardless of HCT type (P < .05). Two or more domains were affected by race/ethnicity, household income, and education in autologous patients, and by body mass index (BMI), decline in BMI, primary diagnosis, and chronic graft-versus-host disease (GVHD) in allogeneic patients (P < .05). At 3 years, 74% of HCT patients were employed full or part time. Older autologous patients with lower pre-HCT income were less likely to work (P < .05); allogeneic patients with chronic GVHD were less likely to work (P = .002). Multidisciplinary efforts to identify and support vulnerable subgroups after HCT need to be developed.

Longitudinal trajectory of sexual functioning after hematopoietic cell transplantation: impact of chronic graft-versus-host disease and total body irradiation

This prospective study described the trajectory of sexual well-being from before hematopoietic cell transplantation (HCT) to 3 years after in 131 allogeneic and 146 autologous HCT recipients using Derogatis Interview for Sexual Function and Derogatis Global Sexual Satisfaction Index. Sixty-one percent of men and 37% of women were sexually active pre-HCT; the prevalence declined to 51% (P = .01) in men and increased to 48% (P = .02) in women at 3 years post-HCT. After HCT, sexual satisfaction declined in both sexes (P < .001). All sexual function domains were worse in women compared with men (P ≤ .001). Orgasm (P = .002) and drive/relationship (P < .001) declined in men, but sexual cognition/fantasy (P = .01) and sexual behavior/experience (P = .01) improved in women. Older age negatively impacted sexual function post-HCT in both sexes (P < .01). Chronic graft-versus-host disease was associated with lower sexual cognition/fantasy (P = .003) and orgasm (P = .006) in men and sexual arousal (P = .05) and sexual satisfaction (P = .005) in women. All male sexual function domains declined after total body irradiation (P < .05). This study identifies vulnerable subpopulations that could benefit from interventional strategies to improve sexual well-being.

Use of Complementary Medications among Older Adults with Cancer

Little is known about complementary medication use among older adults with cancer, particularly those who are receiving chemotherapy. The objective of this study was to evaluate the prevalence of complementary medication use and to identify the factors associated with its use among older adults with cancer.

Abstract 872: Long-term and recent recreational physical activity reduces risk of triple negative and other subtypes of invasive breast cancer in the California Teachers Study

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Background. Evidence has accumulated showing that physical activity reduces breast cancer risk. Whether risk reduction pertains to all breast cancer or specific receptor-defined subtypes is unclear. Moreover, few studies have examined whether changes in the amount of physical activity during adulthood influence breast cancer risk. Methods. Among 108,907 women, ages 22 to 79 years with no history of breast cancer when they joined the California Teachers Study in 1995-1996 (baseline), 5,578 women were diagnosed with invasive breast cancer during follow-up through December, 2011. Subtypes were defined by the expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Cox proportional hazards models were fit to data to estimate adjusted hazard rate ratios (HRs) and 95% confidence intervals (CIs) associated with long-term and recent (within 3 years of baseline) recreational physical activity. Among 54,690 women who provided updated information on physical activity in 2005-2008, we also assessed whether changes in the level of physical activity since baseline influenced breast cancer risk (654 cases diagnosed during follow-up). Results. Long-term and recent recreational physical activity were inversely associated with risk of triple negative breast cancer (TNBC, both Ptrend ≤ 0.05), but not other subtypes (all Ptrend ≥ 0.07). The reduced risk of TNBC was limited to strenuous physical activity. A 50% (HR = 0.50, 95% CI = 0.29-0.86) lower risk of TNBC was observed among women in the highest (≥5.01 h/wk) versus lowest category (≤0.50 h/wk) of long-term strenuous recreational physical activity; this was not modified by baseline body mass index (<25 kg/m2 vs. ≥25 kg/m2), menopausal hormone therapy (MHT) use (never vs. ever), or the cessation of MHT use (former vs. recent). An inverse association between strenuous recreational physical activity and risk of luminal A-like (ER+ or PR+ plus HER2-) breast cancer was observed only among former MHT users (Ptrend: 0.02 for both long-term and baseline strenuous physical activity). Women who increased their level of recent recreational physical activity from ≤0.50 h/wk at baseline to ≥4.51 h/wk in 2005-2008 had a 32% (HR = 0.68, 95% CI = 0.47-0.99) lower risk of breast cancer overall than those who stayed at the lowest level. Conclusions. This study suggests that long-term strenuous physical activity is associated with lower risk of TNBC. Further, it shows that substantially increasing the amount of total recreational physical activity in adulthood decreases the risk of breast cancer. Citation Format: Huiyan Ma, Jessica Clague, Xinxin Xu, Yani Lu, Kayo Togawa, Sophia S. Wang, Christina A. Clarke, Eunjung Lee, Hannah L. Park, Jane Sullivan-Halley, Susan Neuhausen, Leslie Bernstein. Long-term and recent recreational physical activity reduces risk of triple negative and other subtypes of invasive breast cancer in the California Teachers Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 872. doi:10.1158/1538-7445.AM2015-872

Abstract A36: Recreational physical activity and the risk of pancreatic cancer in the California Teachers Study

Background: Pancreatic cancer is highly fatal; thus, preventive strategies are needed. Besides cessation of cigarette smoking, physical activity may reduce pancreatic cancer risk by improving insulin sensitivity and glucose tolerance. However, the existing data lack consistency and generally, physical activity has been measured only at one time point. We examined recreational physical activity during different periods of life as well as a cumulative, long-term physical activity measure in relation to the risk of pancreatic cancer in California Teachers Study (CTS). Methods: 120,921 women aged 22-84 years participating in the CTS with no history of pancreatic cancer were followed from 1995 through 2011. The self-administered baseline (1995-1996) questionnaire captured information on demographics, moderate and strenuous recreational physical activity during high school, between ages 18 and 24, 25 and 34, 35 and 44, and 45 and 54 years, and in the three years before baseline, and potential risk factors for pancreatic cancer such as body mass index (BMI), diabetes, alcohol consumption, cigarette smoking, and dietary fat intake. Incident diagnoses of invasive pancreatic cancer were identified through annual linkages with the California Cancer Registry. We calculated average number of hours per week for recreational physical activity during different periods of life and combined them into a long-term physical activity measure. We fit Cox proportional hazards models to data to estimate the hazard ratios (HR) of pancreatic cancer risk and their corresponding 95% confidence intervals (CI) associated with moderate and strenuous physical activity in each age/time period and over the “long-term.” For each analysis, the least active group (≤0.5 hours/week) served as the reference group. Multivariable models were stratified by age at baseline (in single years) and were adjusted for race, total pack-years of cigarette smoking, alcohol consumption and total dietary fat intake in the year before baseline, diabetes, and BMI at baseline. Furthermore, we tested for a linear trend in risk by fitting the median value of physical activity within each category; we also examined whether BMI, smoking status, and alcohol intake modified any physical activity association. Results: During 1,715,690 person-years of follow-up, 429 women were diagnosed with invasive pancreatic cancer. The average age at diagnosis of pancreatic cancer was 74 years. In the multivariable model, women with higher levels of long-term moderate/strenuous physical activity had lower risk of pancreatic cancer than the least active women (≤0.5 hours/week) although the 95% CI included one (2.51-5.5 hours/week: HR=0.76; 95% CI=0.56-1.02, >5.5 hours/week: HR=0.85; 95% CI=0.63-1.15) and no linear trend in pancreatic cancer risk was observed (Ptrend=0.35). In the analysis of physical activity during different periods of life, we observed a marginally significant decreasing trend in risk with increasing physical activity during ages 18-24 years (Ptrend=0.05). The stratified analysis indicated a decreasing trend in pancreatic cancer risk with increasing physical activity during ages 18-24 years among women who were overweight or obese at baseline (Ptrend=0.006), who never smoked cigarettes (Ptrend=0.02), and who consumed Conclusions: The CTS data suggest that a higher level of recreational physical activity in early adulthood modestly reduces the risk of pancreatic cancer development in subgroups of women. However, we lacked sufficient statistical power to demonstrate effect modification. Larger studies are needed to understand whether the effect of physical activity on pancreatic cancer varies by age at activity, BMI, smoking status, or alcohol intake. Citation Format: Kayo Togawa, Huiyan Ma, Jane Sullivan-Halley, Jessica Clague, Susan Neuhausen, Eunjung Lee, Dennis Deapen, Leslie Bernstein. Recreational physical activity and the risk of pancreatic cancer in the California Teachers Study. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A36.

Abstract A10: Risk factors for self-reported arm lymphedema among female breast cancer survivors in Health, Eating, Activity, and Lifestyle (HEAL) Study

Background: With increasing breast cancer survival, more women are experiencing complications from breast cancer therapy. Arm lymphedema (ALE), one of the most common post-treatment conditions, is associated with both physical and psychological challenges. As there is no definitive cure for ALE, preventive measures are desired; more research is needed to study modifiable factors. Although previous studies investigated ALE, data from long-term prospective cohort studies are sparse. This study aims to assess timing of ALE onset and to identify epidemiological characteristics associated with developing the condition using long-term follow-up data. Methods: Data were collected from 672 female breast cancer survivors aged 35-64 at diagnosis participating in the HEAL Study, a population-based, multi-center, multi-ethnic prospective cohort study. Women diagnosed with in situ, localized or regional breast cancer were recruited into the HEAL Study through SEER registries in New Mexico (Non-Hispanic Whites and Latinas), Los Angeles County (Blacks), and Western Washington (Non-Hispanic Whites). Participants provided information on sociodemographic factors, anthropometric factors, hormone use, and lifestyle factors at, on average, 6.2 months after diagnosis. Clinical information was abstracted from SEER registry records and hospital medical records. Women reported presence of ALE and date of first occurrence of ALE at two subsequent questionnaires that occurred, on average, 3.3 years (T1) and 10.2 years (T2) after diagnosis. Time to onset of ALE was calculated as the time from diagnosis until self-reported onset date. Cox proportional hazards models were fit and provided estimates of the hazard ratios (HR) for ALE and its 95% confidence interval (CI) using time since diagnosis as the time scale. Women who died or were lost to follow-up before T2 were censored at T1 because their ALE status after T1 was unknown. Results: During follow-up, 192 women (29%) experienced ALE; 34 (18%) of these women developed ALE more than three years after diagnosis. The median time to onset of ALE was 11 months (range; 0.5-135). Approximately 58% of women who reported ALE at T1 and completed T2 (n=109) had ALE at T2 (persistent ALE). In a multivariable model, receiving total/modified radical mastectomy (vs. partial/less than total mastectomy; HR=1.43, 95% CI=1.06-1.94), receiving chemotherapy (HR=1.58, 95% CI=1.15-2.17), having 10 or more lymph nodes (LN) removed (vs. no LN removed; HR=3.05, 95% CI=1.81-5.11), having body mass index (BMI)≥30 kg/m2 (vs. BMI<25 kg/m2; HR=1.59, 95% CI=1.09-2.32), and having hypertension (HR=1.47, 95% CI=1.04-2.07) all increased ALE risk. Stratifying by race, hypertension was a risk factor only for black women (HR=2.77, 95% CI=1.67-4.58). Contrary to findings from previous studies, we did not find that radiation therapy increased ALE risk (HR=1.18, 95% CI=0.87-1.58). Conclusions: This study suggests that ALE can occur years after the initial diagnosis and the majority of ALE persists for a long time. In addition to established risk factors, hypertension was a risk factor, particularly in black women. It is important to increase awareness that ALE can develop later in the survival trajectory and to investigate further the role of hypertension in ALE after breast cancer. Citation Format: Kayo Togawa, Jane Sullivan-Halley, Yani Lu, Ashley Wilder Smith, Catherine Alfano, Ikuyo Imayama, Anne McTiernan, Marian L. Neuhouser, Huiyan Ma, Rachel Ballard-Barbash, Leslie Bernstein. Risk factors for self-reported arm lymphedema among female breast cancer survivors in Health, Eating, Activity, and Lifestyle (HEAL) Study. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A10.