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1.  Cognitive Effects of Cancer and its Treatments at the Intersection of Aging: What do we Know; What do we Need to Know? 
Seminars in oncology  2013;40(6):10.1053/j.seminoncol.2013.09.006.
There is a fairly consistent, albeit non-universal body of research documenting cognitive declines after cancer and its treatments. While few of these studies have included those 65 and older, it is logical to expect that older patients are at risk of cognitive decline. In this paper, we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies. There are a striking number of common underlying potential biological risks and pathways for the development of cancer, cancer-related cognitive declines, and aging processes, including the development of a frail phenotype. Candidate shared pathways include changes in hormonal milieu, inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic susceptibility, decreased brain blood flow or disruption of the blood-brain barrier, direct neurotoxicity, decreased telomere length, and cell senescence. There are also similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with “normal” aging and Alzheimer’s disease. Disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects. From what we do know, frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline after cancer and its treatments. This and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk of cognitive decline. Further research is needed to understand the interactions between aging, genetic predisposition, lifestyle factors and frailty phenotypes to best identify the sub-groups of older patients at greatest risk for decline and to develop behavioral and pharmacological interventions targeting this group. We recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group, including cognitive function and trajectories of frailty. Clinicians and their older patients can advance the field by active encouragement of and participation in research designed to improve the care and outcomes of the growing population of older cancer patients.
doi:10.1053/j.seminoncol.2013.09.006
PMCID: PMC3880205  PMID: 24331192
2.  Research priorities in geriatric oncology for 2013 and beyond 
Cancer forum  2013;37(3):216-221.
The incidence of cancer increases with advanced age. Unfortunately, there is a significant lack of evidence regarding the safety and efficacy of treatments. The oncology community also lacks information regarding which older patients are most likely to benefit from treatment without undue toxicities. Interventions to lower symptoms and reduce long-term complications from cancer and cancer treatment in older patients are urgently needed. Establishing research priorities in geriatric oncology could help guide researchers and focus efforts on interventions that have the highest likelihood of improving outcomes. The Cancer and Aging Research Group, in partnership with the National Institute on Aging and National Cancer Institute, held linked conferences as part of a U13 grant in September of 2010 and November of 2012, summarising the gaps in knowledge in geriatric oncology and recommending ways to close these gaps. The overall purpose of this review is to highlight the important research priorities in geriatric oncology from the literature and from the previous U13 meetings. More evidence regarding the treatment of older cancer patients is urgently needed given the rapid aging of the population.
PMCID: PMC4206081  PMID: 25346565
3.  Barriers to Treatment in Patients With Locally Advanced Breast Cancer 
Delays between presentation and treatment could have a significant effect on breast cancer mortality. The authors hypothesized that patient, physician, and system barriers are all responsible for treatment delays. Therefore, a study was conducted to define prevalent barriers to treatment from the patient’s perspective. A modified 43-item Likert-scale questionnaire was administered to patients with clinical stage III locally advanced breast cancer (LABC) who had experienced a delay in treatment of 3 months or more. Between October 2008 and January 2010, 153 patients presented with LABC; 43 patients (28.1%) met eligibility, and 40 completed the questionnaire. Among the patient barriers reported, 38% of patients delayed care for fear of losing their breast and 47% awaited previously scheduled routine appointments instead of seeking care. Among the physician barriers reported, 20% of physicians of initial contact did not believe the breast lump/symptom was related to cancer and 15% did not believe it needed a biopsy. Among the system barriers reported, the most prevalent were delays in performing diagnostic tests and obtaining insurance authorization for tests, treatment, or physician visits. Substantial delays were seen in 28.1% of patients from presentation to when they sought therapy at City of Hope Comprehensive Cancer Center. The high prevalence of patient barriers versus physician/system barriers suggests that increased educational efforts for patients and health care professionals are needed.
PMCID: PMC4159358  PMID: 24142820
4.  Determining Chemotherapy Tolerance in Older Patients With Cancer 
Older adults with cancer constitute a heterogeneous group of patients who pose unique challenges for oncology care. One major concern is how to identify patients who are at a higher risk for chemotherapy intolerance, because a standard oncology workup may not always be able to distinguish an older individual’s level of risk for treatment-related complications. Geriatric oncologists incorporate tools used in the field of geriatrics, and have developed the Comprehensive Geriatric Assessment to enhance the standard oncology workup. This assessment pinpoints problems with daily activities, comorbidities, medications, nutritional status, cognitive function, psychological state, and social support systems, all of which are risk factors for treatment vulnerability in older adults with cancer. Additional tools that also serve to predict chemotherapy toxicity in older patients with cancer are now available to identify patients at higher risk for morbidity and mortality. Together, these instruments complement the standard oncology workup by providing a global assessment, thereby guiding therapeutic interventions that may improve a patient’s quality of life and clinical outcomes.
PMCID: PMC4159075  PMID: 24335684
5.  Caregivers of Older Adults with Cancer 
Seminars in oncology nursing  2012;28(4):221-225.
Objective
To review key aspects of family caregiving as it applies to older adults with cancer, discuss the implications of caregiving on the physical and emotional health of caregivers, and discuss future research needs to optimize the care of older adults with cancer and their caregivers.
Data Sources
Literature Review
Conclusions
The number of older adults with cancer is on the rise and these older adults have significant caregiving needs. There is a physical, emotional, and financial toll associated with caregiving.
Implications for Nursing Practice
As the US population ages, it will be even more important that we identify vulnerable older adults, understand their caregiving needs, and mobilize healthcare and community resources to support and assist their caregivers.
doi:10.1016/j.soncn.2012.09.004
PMCID: PMC4096853  PMID: 23107179
Geriatric Oncology; Family Caregiver; Caregiver Strain; Older Adult with Cancer
6.  CA125 Level Association with Chemotherapy Toxicity and Functional Status in Older Women with Ovarian Cancer 
Objective
Older women with ovarian cancer have increased cancer-related mortality and chemotherapy toxicity. CA125 is a sensitive biomarker for tumor burden. The study evaluates the association between CA125, geriatric assessment (GA), and treatment toxicity.
Methods
This is a secondary subset analysis of patients age ≥65 with ovarian cancer accrued to a multicenter prospective study that developed a predictive toxicity score for older adults with cancer. Clinical and geriatric covariates included sociodemographics, GA (comorbidity, social support, functional, nutritional, psychological, cognitive status), treatment, and labs. Utilizing bivariate analyses, we determined the association of abnormal CA125 (≥35 U/mL) with baseline GA, grade 3–5 toxicity (CTCAE v.3), dose adjustments, and hospitalization. Logistic regression analysis was used to check for potential confounder for association between CA125 and chemotherapy toxicity.
Results
Fifty-one (10%) of 500 patients accrued to the primary study had a diagnosis of ovarian (92%), peritoneal (4%), or fallopian tube (4%) cancer. Median age was 72 (range, 65–86). Forty-six patients (90%) had stage III–IV disease. Twenty-three patients (45%) received first-line chemotherapy, and 34 (67%) received platinum-doublet therapy. Thirty-six (71%) had an abnormal CA125. Grade 3–5 toxicity occurred in 19 patients (37%). Abnormal CA125 was associated with assistance with instrumental activities of daily living (IADL) (p<0.05), lower performance status (p=0.05), grade 3–5 toxicity (p=0.03), non-heme toxicity (p=0.04), and dose reductions (p=0.01). No association between CA125 level and total toxicity score was observed.
Conclusions
Among older women with ovarian cancer, abnormal CA125 was associated with poor pre-treatment functional status and an increased probability of chemotherapy toxicity and dose reduction.
doi:10.1097/IGC.0b013e318299438a
PMCID: PMC3772622  PMID: 23765208
CA125; older women; ovarian cancer; chemotherapy toxicity; functional status
7.  Oncologists’ recommendations for adjuvant endocrine therapy in older adults of varying health states 
Clinical breast cancer  2010;10(2):136-143.
Introduction
Currently, evidence supports the use of adjuvant endocrine therapy with aromatase inhibitors in postmenopausal patients with hormone-receptor positive breast cancer. The goal of the current study is to understand the impact of patient age and health status on the decision of the oncologist to recommend adjuvant endocrine therapy (with or without chemotherapy) in older women with hormone-receptor positive breast cancer.
Methods
An on-line survey was conducted, with questions related to treatment of a hypothetical patient of varying age and health status with a T2N2 hormone-receptor positive, HER2-negative breast cancer. Treatment options included chemotherapy and endocrine therapy, endocrine therapy alone, or no therapy. With recommendation of endocrine therapy, respondents were further asked to specify use of either tamoxifen or aromatase inhibitors. A generalized linear mixed-effects model was used to determine the impact of age and health status on treatment recommendations.
Results
As the hypothetical patient’s age increased or health status deteriorated, oncologists were less likely to recommend a combination of chemotherapy and endocrine therapy (P<0.0001 for both). In contrast, oncologists were more likely to recommend endocrine therapy alone with advanced age (P<0.0001) and deteriorating health status (P<0.0001). With respect to the type of endocrine therapy selected, oncologists were more likely to choose treatment with aromatase inhibitors as opposed to tamoxifen (P<0.01), irrespective of age or health status. No therapy was infrequently recommended, constituting 2% of responses on average.
Conclusions
With increasing age and declining health status, oncologists were more likely to recommend treatment with endocrine therapy alone as opposed to the combination of chemotherapy with endocrine therapy. Oncologists were most likely to recommend use of aromatase inhibitors, irrespective of age or health status.
doi:10.3816/CBC.2010.n.018
PMCID: PMC4011553  PMID: 20353934
8.  Hematopoietic Stem Cell Transplantation for Hematologic Malignancies in Older Adults: Geriatric Principles in the Transplant Clinic 
Hematopoietic cell transplantation (HCT) provides a life-prolonging or potentially curative treatment option for patients with hematologic malignancies. Given the high transplant-related morbidity, these treatment strategies were initially restricted to younger patients, but are increasingly being used in older adults. The incidence of most hematologic malignancies increases with age; with the aging of the population, the number of potential older candidates for HCT increases. Autologous HCT (auto-HCT) in older patients may confer a slightly increased risk of specific toxicities (such as cardiac toxicities and mucositis) and have modestly lower effectiveness (in the case of lymphoma). However, auto-HCT remains a feasible, safe, and effective therapy for selected older adults with multiple myeloma and lymphoma. Similarly, allogeneic transplant (allo-HCT) is a potential therapeutic option for selected older adults, although fewer data exist on allo-HCT in older patients. Based on currently available data, age alone is not the best predictor of toxicity and outcomes; rather, the comorbidities and functional status of the older patient are likely better predictors of toxicity than chronologic age in both the autologous and allogeneic setting. A comprehensive geriatric assessment (CGA) in older adults being considered for either an auto-HCT or allo-HCT may identify additional problems or geriatric syndromes, which may not be detected during the standard pretransplant evaluation. Further research is needed to establish the utility of CGA in predicting toxicity and to evaluate the quality of survival in older adults undergoing HCT.
PMCID: PMC4010196  PMID: 24453296
9.  Toxicity of Bevacizumab in Combination with Chemotherapy in Older Patients 
The Oncologist  2013;18(4):408-414.
Heart disease is more common in those who do not receive bevacizumab. Older patients who receive bevacizumab with chemotherapy have higher odds of developing a grade 3–5 toxicity compared with those who receive chemotherapy alone.
Learning Objectives
Compare characteristics of older patients that receive bevacizumab plus chemotherapy to those treated with chemotherapy alone for advanced NSCLC and CRC.Compare outcomes between older patients treated with bevacizumab plus chemotherapy to chemotherapy alone for advanced NSCLC and CRC.Describe toxicities in older patients treated with bevacizumab plus chemotherapy for advanced NSCLC and CRC.
Background.
Bevacizumab leads to improved survival for patients with metastatic colorectal cancer (CRC) or non-small cell lung cancer (NSCLC) when added to chemotherapy. Little is known about factors associated with receipt of bevacizumab, or whether bevacizamab is associated with increased toxicity when added to chemotherapy.
Patients and Methods.
We conducted a prospective study of patients aged ≥65 years, which evaluated the association between geriatric assessment (GA) metrics and chemotherapy toxicity. We examined differences in characteristics and outcomes of patients with CRC and NSCLC cancers who received bevacizumab with chemotherapy versus chemotherapy alone.
Results.
From a total of 207 patients, 27 (13%) received bevacizumab plus chemotherapy and 180 (87%) received chemotherapy alone. Groups were similar in sociodemographic and cancer characteristics. There were no baseline differences in GA domains except that patients with heart disease were less likely to receive bevacizumab (4% vs. 26%, p = .01). Seventy-eight percent of patients who had bevacizumab had grade 3–5 toxicity compared to only 57% who received chemotherapy alone (p = .06). Patients receiving bevacizumab were more likely to develop grade 3 hypertension than those who received chemotherapy alone (15% vs. 2%, p < .01). In multivariable analysis, factors associated with grade 3 or more toxicity included: bevacizumab (OR: 2.86, p = .04), CRC (OR: 2.54, p < .01), and baseline anemia (OR: 2.58, p = .03).
Conclusion.
Heart disease was more common in those who did not receive bevacizumab. Older patients who receive bevacizumab with chemotherapy have a higher odds of developing a grade 3–5 toxicity compared with those who receive chemotherapy alone.
doi:10.1634/theoncologist.2012-0351
PMCID: PMC3639527  PMID: 23576485
Chemotherapy; Geriatric assessment; Bevacizumab; Drug toxicity; Health services for the aged
10.  A Novel Approach to Improve Health Status Measurement in Observational Claims-based Studies of Cancer Treatment and Outcomes 
Journal of geriatric oncology  2013;4(2):157-165.
Objectives
To develop and provide initial validation for a multivariate, claims-based prediction model for disability status (DS), a proxy measure of performance status (PS), among older adults. The model was designed to augment information on health status at the point of cancer diagnosis in studies using insurance claims to examine cancer treatment and outcomes.
Materials and Methods
We used data from the 2001–2005 Medicare Current Beneficiary Survey (MCBS), with observations randomly split into estimation and validation subsamples. We developed an algorithm linking self-reported functional status measures to a DS scale, a proxy for the Eastern Cooperative Oncology Group (ECOG) PS scale. The DS measure was dichotomized to focus on good [ECOG 0–2] versus poor [ECOG 3–4] PS. We identified potential claims-based predictors, and estimated multivariate logistic regression models, with poor DS as the dependent measure, using a stepwise approach to select the optimal model. Construct validity was tested by determining whether the predicted DS measure generated by the model was a significant predictor of survival within a validation sample from the MCBS.
Results and Conclusion
One-tenth of beneficiaries met the definition for poor DS. The base model yielded high sensitivity (0.79) and specificity (0.92); positive predictive value=48.3% and negative predictive value=97.8%, c-statistic=0.92 and good model calibration. Adjusted poor claims-based DS was associated with an increased hazard of death (HR=3.53, 95% CI 3.18, 3.92). The ability to assess DS should improve covariate control and reduce indication bias in observational studies of cancer treatment and outcomes based on insurance claims.
doi:10.1016/j.jgo.2012.12.005
PMCID: PMC3685201  PMID: 23795223
Medicare; cancer; health status; observational study; treatment selection bias; functional status
11.  Challenges in the Management of Older Patients with Colon Cancer 
The majority of patients with colon cancer are over the age of 65. Their treatment poses multiple challenges to the oncologist, as these patients may have age-related comorbidities, polypharmacy, and physical or physiologic changes associated with older age. These challenges include limited data on the ability to predict tolerance to anti-cancer therapy and the appropriate use of treatment modalities in the setting of comorbidity and concurrent frailty. The low number of older patients enrolled on large clinical trials results in a paucity of evidence to guide the oncologist in the appropriate management of this population. In early stage disease, clinical dilemmas arise regarding the ability of older patients to undergo successful curative surgical procedures and the risk/benefit ratio of adjuvant chemotherapy. The management of metastatic disease raises questions regarding the clinical benefit of various anti-cancer therapies and the role of combination therapy with possible increased toxicity in the non-curative setting. Overall, the available evidence demonstrates that fit older patients are able to tolerate treatment and derive similar clinical benefits as younger patients. Limited data are available to guide treatment for less fit, more vulnerable older patients. This lack of data leads to variations in treatment patterns in older adults, making them less likely to receive standard therapies. This review will provide an overview of the available data regarding the management of older adults with colon cancer in the adjuvant and metastatic settings.
PMCID: PMC3932187  PMID: 22308516
Colon cancer; Elderly; Older Adults
12.  Cognitive function in older women with breast cancer treated with standard chemotherapy and capecitabine on Cancer and Leukemia Group B 49907 
Cognitive changes in older women receiving chemotherapy are poorly understood. We examined self-reported cognitive function for older women who received adjuvant chemotherapy on Cancer and Leukemia Group B (CALGB) 49907. CALGB 49907 randomized 633 women aged ≥65 with stage I–III breast cancer to standard adjuvant chemotherapy (cyclophosphamide–methotrexate–5-fluoro-uracil or doxorubicin–cyclophosphamide) versus capecitabine. We examined self-reported cognitive function in 297 women (CALGB 361002) who enrolled on the quality of life substudy and had no gross impairment on cognitive screening. Women were evaluated using an 18-item instrument at six time points (baseline through 24 months). At each time point for each patient, we calculated a cognitive function score (CFS) defined as the mean response of items 1–18 and defined impairment as a score >1.5 standard deviations above the overall average baseline score. Differences in scores by patient characteristics were evaluated using a Kruskal–Wallis test. A linear mixed-effects model was used to assess CFSs by treatment over time. Among 297 women, the median age was 71.5 (range 65–85) and 73 % had performance status of 0. Baseline depression and fatigue were reported in 6 and 14 % of patients, respectively. The average CFS at baseline was 2.08 (corresponding to “normal ability”), and baseline cognitive function did not differ by treatment regimen (p = 0.350). Over 24 months, women reported minimal changes at each time point and insignificant differences by treatment arm were observed. In a healthy group of older women, chemotherapy was not associated with longitudinal changes in self-reported cognitive function.
doi:10.1007/s10549-013-2562-6
PMCID: PMC3920483  PMID: 23681403
Cognitive function; Older women; Breast cancer; Age
13.  A planned, prospective comparison of short-term quality of life outcomes among older breast cancer patients treated with standard chemotherapy in a randomized clinical trial vs. an observational study: CALGB #49907 and #369901✰ 
Journal of geriatric oncology  2013;4(4):353-361.
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.
doi:10.1016/j.jgo.2013.05.004
PMCID: PMC3910230  PMID: 24472479
Older patients; Breast cancer; Chemotherapy; Quality of Life; Randomized clinical trials; Observational studies
14.  Managing Breast Cancer in the Older Patient 
Breast cancer is a disease associated with aging, with almost one-half of all new breast cancer cases diagnosed annually in the United States occurring in women age 65 and older. Recent data suggest that although breast cancer outcomes in younger women have shown substantial improvement as a result of advances in treatment and screening, the benefits in older women have been less pronounced. Although older adults have been under-represented on cancer clinical trials there is an emerging body of literature to help guide treatment decisions. For early stage breast cancer, the discussion regarding treatment options involves balancing the reduction in risk of recurrence gained by specific therapies with the potential for increased treatment-related toxicity potentially exacerbated by physiological decline or comorbidities that often co-exist in the older population. A key component of care of the older adult is the recognition that chronologic age alone cannot guide the management of an older individual with breast cancer; rather, treatment decisions must also take into account an individual’s functional status, estimated life expectancy, the risks and benefits of the therapy, potential barriers to treatment, and patient preference. This article reviews the available evidence for therapeutic management of early-stage breast cancer in older adults, and highlights data from geriatric oncology literature that provides a basis on which to facilitate evidence-based treatment.
PMCID: PMC3906632  PMID: 24472802
breast cancer; older patient; therapeutic management; geriatric oncology
15.  Survivorship education for Latina breast cancer survivors: Empowering Survivors through education 
Psicooncologia  2013;10(1):57-68.
Objectives
Nueva Luz is an English and Spanish quality of life (QOL) intervention developed to address the educational needs of Latina breast cancer survivors and provide strategies to assist in their transition into survivorship.
Methods
A qualitative approach was used to evaluate the English and Spanish educational intervention (Nueva Luz). A purposive sample of eight Latina breast cancer survivors was selected from the group who received the intervention to participate in a digitally recorded interview. Data was analyzed using thematic analysis.
Results
Findings provide evidence that the one-on-one tailored approach is a feasible and acceptable method of providing a bilingual psychosocial intervention. The provision of printed bilingual information along with the verbal instruction from a bilingual and culturally competent health care provider can be effective in helping Latina breast cancer survivor’s transition successfully into survivorship, improve QOL and contribute to better patient outcomes
Conclusions
The study informs our understanding of the cultural context in patient education content and delivery of psychosocial interventions. The findings may also have relevance for other ethnic minority cancer survivors.
doi:10.5209/rev_PSIC.2013.v10.41947
PMCID: PMC3888314  PMID: 24416043
16.  Feasibility of Computer-Based Self-Administered Cancer-Specific Geriatric Assessment in Older Patients With Gastrointestinal Malignancy 
The Oncologist  2013;18(1):64-72.
A computer-based cancer specific geriatric assessment was developed and tested among patients age 70 and older receiving treatment for gastrointestinal malignancies at the Dana-Farber Cancer Institute. The feasibility endpoints were met, although half of the sample required assistance and the results did not affect immediate clinical decision-making.
Background.
The Cancer-Specific Geriatric Assessment (CSGA) is a primarily self-administered paper survey of validated measures.
Methods.
We developed and tested the feasibility of a computer-based CSGA in patients ≥70 years of age who were receiving treatment for gastrointestinal malignancies at the Dana-Farber Cancer Institute. From December 2009 to June 2011, patients were invited to complete the CSGA at baseline (start of new treatment) and follow-up (at the first of 4 months later or within 4 weeks of completing treatment). Feasibility endpoints were proportion of eligible patients consented, proportion completing CSGA at baseline and follow-up, time to complete CSGA, and proportion of physicians reporting CSGA results that led to a change in clinical decision-making.
Results.
Of the 49 eligible patients, 38 consented (76% were treatment naive). Median age was 77 years (range: 70–89 years), and 48% were diagnosed with colorectal cancer. Mean physician-rated Karnofsky Performance Status was 87.5 at baseline (SD 8.4) and 83.5 at follow-up (SD 8). At baseline, 92% used a touchscreen computer; 97% completed the CSGA (51% independently). At follow-up, all patients used a touchscreen computer; 71% completed the CSGA (41% independently). Mean time to completion was 23 minutes at baseline (SD 8.4) and 20 minutes at follow-up (SD 5.1). The CSGA added information to clinical assessment for 75% at baseline (n = 27) and 65% at follow-up (n = 17), but it did not alter immediate clinical decision-making.
Conclusion.
The computer-based CSGA feasibility endpoints were met, although approximately half of patients required assistance. The CSGA added information to clinical assessment but did not affect clinical decision-making, possibly due to limited alternate treatment options in this subset of patients.
doi:10.1634/theoncologist.2012-0241
PMCID: PMC3556258  PMID: 23287880
Gastrointestinal cancer; Geriatric oncology; Geriatric assessment; Clinical decision-making
17.  Early breast cancer in the older woman 
Clinics in geriatric medicine  2011;28(1):10.1016/j.cger.2011.10.002.
SYNOPSIS
Breast cancer is a disease associated with aging; there is a rise in both breast cancer incidence and mortality with increasing age. With the aging of the US population, the number of older adults diagnosed with breast cancer and the number of breast cancer survivors is on the rise. The majority of cases of breast cancer are diagnosed with early stage (non-metastatic) potentially curable disease. This article will review the treatment of early stage breast cancer in older adults including a focus on the risks and benefits of surgery, radiation therapy, endocrine therapy, chemotherapy, and trastuzumab. Although the majority of studies to date demonstrate that older adults experience similar benefits from most multimodality treatments for breast cancer as compared to younger adults, these studies have primarily been performed in healthy and fit older adults. There are limited data at the extremes of age or in those patients with significant comorbidity or functional decline. A primary question facing the doctor and patient is whether the breast cancer is likely to impact the patient’s life expectancy or quality of life. If so, then the risks and benefits of treatment must be considered with a final decision regarding therapy made in the context of the patient’s preferences. This article will review the toxicities (both short- and long-term) from common cancer therapies in early breast cancer. Finally, the decision as to type of secondary screening and prevention of future breast cancers must also be weighed against the life expectancy of the older adult.
doi:10.1016/j.cger.2011.10.002
PMCID: PMC3874410  PMID: 22326036
18.  Geriatric Assessment in Oncology Practice 
Journal of the American Geriatrics Society  2009;57(0 2):10.1111/j.1532-5415.2009.02503.x.
There is no standard tool for assessing the “functional age” of an older adult with cancer, although it is widely recognized that chronological age does not capture the heterogeneous physiologic and functional status of older adults. Integrating a “geriatric assessment” into oncology research and clinical practice would help fill this void. Geriatric assessment covers factors that predict morbidity and mortality in older adults, including functional status, comorbidity, cognition, psychological state, nutritional status, and social support. This assessment provides a broader overall understanding of individual characteristics that affect life expectancy. In addition, this assessment identifies areas of vulnerability among older adults for which further evaluation or intervention is indicated. In this article, we will discuss the utility of a geriatric assessment in oncology practice, review data that attest to the benefits of the assessment, and issue a call for further research into how we can integrate this assessment into oncology care. Doing so will help us to develop targeted interventions and optimize cancer outcomes in this rapidly growing population.
doi:10.1111/j.1532-5415.2009.02503.x
PMCID: PMC3845875  PMID: 20122022
geriatric assessment; cancer; aging; oncology
19.  In Reply 
The Oncologist  2013;18(12):1331.
It remains challenging to incorporate comprehensive geriatric assessment (CGA) into prospective clinical trials, but efforts continue to test the efficacy of CGA-guided interventions for information about how the CGA data should be utilized to modify treatment.
doi:10.1634/theoncologist.2013-0303
PMCID: PMC3868429  PMID: 24336119
20.  Feasibility and toxicity of dose-dense adjuvant chemotherapy in older women with breast cancer 
Breast cancer research and treatment  2008;117(1):10.1007/s10549-008-0116-0.
Introduction
The objective of this study was to examine the feasibility and toxicity of adjuvant dose-dense chemotherapy in older women with breast cancer.
Methods
A search of the Memorial Sloan-Kettering Cancer Center (MSKCC) breast cancer database was performed to identify all patients age 60 and older who underwent an initial consultation with a breast medical oncologist between October 1, 2002 and June 28, 2005. Inclusion criteria were: (1) age ≥ 60, (2) follow-up care obtained at MSKCC, (3) intent to treat with adjuvant dose-dense AC-T (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 weeks for 4 cycles followed by paclitaxel 175 mg/m2 every 2 weeks for 4 cycles, with white blood cell growth factor support).
Results
One hundred sixty-two patients (mean age 66, range 60–76) with breast cancer, stages I (n = 5), II (n = 111), and III (n = 46) according to the sixth edition of the AJCC staging system, were included in this analysis. Forty-one percent (n = 67) experienced a grade 3 or 4 toxicity, 9% a grade 3 infection (n = 14), 6% grade 3 fatigue (n = 9), 5% neutropenic fever (n = 8), and 4% thromboembolic events (n = 7). Twenty-two percent (n = 36) did not complete the planned 8 cycles of treatment. There was no statistically significant association between age and either toxicity or treatment discontinuation. In multivariate analysis including age, pretreatment hemoglobin, and comorbidity, the presence of comorbidity (Charlson score ≥ 1) and a lower baseline hemoglobin score were associated with an increased risk of any grade 3 or 4 toxicity.
Conclusions
We found that the risk of toxicity depended more on comorbid medical conditions and baseline hemoglobin value than age in this cohort of older adults receiving dose-dense adjuvant chemotherapy.
doi:10.1007/s10549-008-0116-0
PMCID: PMC3811071  PMID: 18622739
Breast Cancer; Dose-Dense Chemotherapy; Older Patient
21.  Use of Complementary Medications among Older Adults with Cancer 
Cancer  2012;118(19):4815-4823.
BACKGROUND
Little is known about complementary medication use among older adults with cancer, particularly those undergoing chemotherapy. The purpose of this study was to evaluate the prevalence of complementary medication use and to identify factors associated with its use among older adults with cancer.
METHODS
The prevalence of complementary medication use (defined as herbal agents, minerals, or other dietary supplements excluding vitamins) was evaluated in a cohort of adults aged ≥65 years who were about to start chemotherapy for their cancer. The association between complementary medication use and patient characteristics (sociodemographics; comorbidity; functional, nutritional, psychological, and cognitive status); medication use (number of medications and concurrent vitamin use); and cancer characteristics (type and stage) was analyzed.
RESULTS
The cohort included 545 patients [mean age 73 years (range 65–91); 52% female] with cancer (61% Stage IV). Seventeen percent (N=93) of these patients reported using ≥1 complementary medications [mean number of complementary medications among users was 2 (range 1–10)]. Complementary medication use was associated with: 1) earlier cancer stage, with 29% of those with stages I–II vs. 17% with III–IV (OR=2.05, 95% CI:1.21–3.49); and 2) less impairment with instrumental activities of daily living (OR=1.39, 95% CI:1.12–1.73).
CONCLUSIONS
Complementary medication use was reported by 17% of older adults with cancer and was more common among those with less advanced disease (receiving adjuvant potentially curative treatment) and higher functional status. Further studies are needed to determine the association between complementary medication use and cancer outcomes among older adults.
doi:10.1002/cncr.27427
PMCID: PMC3366170  PMID: 22359348
Herbals; Complementary Medicine; Older Adults; Cancer; Chemotherapy
22.  Cardiovascular Outcomes in Women With Advanced Breast Cancer Exposed to Chemotherapy 
Purpose
Quantify incidence of cardiovascular outcomes in patients with advanced breast cancer receiving cardiotoxic and non-cardiotoxic chemotherapy.
Methods
Identified all women at a Midwestern health system with initial diagnosis of AJCC stage III/IV breast cancer (1995–2003) and random sample of 50 women initially diagnosed with stage I/II who progressed to stage III/IV. Calculated rate of new cardiovascular outcomes (heart failure, dysrhythmia and ischemia events) for cardiotoxic (anthracycline or trastuzumab) and non-cardiotoxic agents.
Results
Of 315 patients, 90.5% (N=285) received systemic cancer therapy; 67.7% (n=193) received cardiotoxic drugs. Older patients were less likely to receive cardiotoxic agents (86.4% ≤ 59 years vs. 31.9% aged 70+). Adjusting for age, race, stage, surgery/radiation, ER/PR status and diagnosis year, rate of new cardiac events was higher in patients exposed to cardiotoxic drugs compared to those exposed to non-cardiotoxic drugs (adjusted hazard ratio=2.5, 95% CI 0.9, 7.2). Patients with cardiac event history (relative risk=3.2, 95% CI 2.0–5.1) and those with heart failure history (relative risk=5.9, 95% CI 2.4–14.6) were more likely to receive non-cardiotoxic treatment. Heart failure events occurred steadily over time; after 3 years follow-up 16% exposed to cardiotoxic drugs experienced an event, and 8% of those exposed to non-cardiotoxic drugs experienced an event.
Conclusions
Patients with cardiac comorbidity are less likely to receive cardiotoxic agents. Use of cardiotoxic agents is common, treatment is related to patient and tumor characteristics and is associated with substantial risk of cardiotoxicity that persists during patient’s remaining lifespan.
doi:10.1002/pds.3239
PMCID: PMC3785307  PMID: 22419528
breast cancer; chemotherapy; cardiotoxic agents; cardiotoxicity risk
24.  Geriatric Oncology Research to Improve Clinical Care 
Nature reviews. Clinical oncology  2012;9(10):571-578.
Summary
The incidence of cancer increases with advanced age. The Cancer and Aging Research Group (CARG), in partnership with the National Institute on Aging and National Cancer Institute, held a conference in September of 2010 which summarized the gaps in knowledge in geriatric oncology and recommendations to close these gaps. One recommendation was that the comprehensive geriatric assessment (CGA) should be incorporated within geriatric oncology research. The information from the CGA can be used to stratify patients into risk categories to better predict their tolerance of cancer treatment. CGA can also be used to follow functional consequences from treatment. Other recommendations were to design trials for older adults with study endpoints that address the needs of the older and/or vulnerable adult with cancer and to build better infrastructure to accommodate the needs of older adults to improve their representation in trials. In this review, we utilize a case-based approach to highlight gaps in knowledge regarding the care of older adults with cancer, discuss our current state of knowledge regarding best practice patterns, and identify opportunities for research in geriatric oncology. More evidence regarding the treatment of older patients with cancer is urgently needed given the rapid aging of the population.
doi:10.1038/nrclinonc.2012.125
PMCID: PMC3738437  PMID: 22825377

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