October 2018 Webinar | Older Adults and Colorectal Cancer
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This webinar discusses older adults and colorectal cancer. It provides an overview of assessing older adult patients, including through geriatric assessment and measuring sarcopenia. Geriatric assessment can predict toxicity from cancer treatment and identify impairments. Sarcopenia is common in colon cancer patients and associated with increased toxicity. Cancer survivors face both short and long-term effects from treatments and are at risk for various health conditions. Interventions seek to help survivors not just live but thrive after cancer.
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October 2018 Webinar | Older Adults and Colorectal Cancer
- 1. Older Adults and Colorectal cancer
- 2. TODAY’S WEBINAR SPEAKER(S) Grant R. Williams, MD QUESTIONS Ask a question in the panel on the RIGHT SIDE of your screen WEBINAR ARCHIVE FightCRC.org/webinar TWEET ALONG Follow along via Twitter – use the hashtag #CRCWebinar POST WEBINAR Expect an email with links to the material & a short survey.
- 3. We are using LogMeIn GoToWebinar platform The side control panel can be adjusted using the orange arrow Questions are asked by opening the “Questions” tab – the arrow opens the box Not all questions are addressed during the presentation depending on time and quantity, but if necessary will be followed up individually If you are new to GoToWebinar and experience streaming problems, shut down other high bandwidth services such as Facebook, IM, or hangout systems during presentation The “Audio” tab allows you to select either your computer or phone to listen in WEBINAR TECH
- 4. RESOURCES TABOO-TY PODCAST MINI MAGAZINES YOUR GUIDE IN THE FIGHT
- 5. FIGHTCOLORECTALCANCERDISCLAIMER The information and services provided by Fight Colorectal Cancer are for general informational purposes only. The information and services are not intended to be substitutes for professional medical advice, diagnoses or treatment. If you are ill, or suspect that you are ill, see a doctor immediately. In an emergency, call 911 or go to the nearest emergency room. Fight Colorectal Cancer never recommends or endorses any specific physicians, products or treatments for any condition.
- 6. Dr.GrantWilliams As both a Geriatrician and Oncologist, Dr. Williams’ research is focused on refining treatment selection and improving the outcomes of older adults with cancer. His research involves the use of geriatric assessment and novel biomarkers, such molecular markers of aging and body composition, to better evaluate functional age and developing interventional clinical trials to improve the tolerance and outcomes of older adults undergoing cancer treatment. Dr. Williams is an Assistant Professor in the Divisions of Hematology/Oncology & Gerontology, Geriatrics, and Palliative Care at the Institute for Cancer Outcomes and Survivorship at The University of Alabama at Birmingham.
- 8. Grant R. Williams Fight Colorectal Cancer October 31st, 2018 Colorectal cancer in the older adult
- 9. Outline •Assessing the Older Adult with Cancer •Geriatric Assessment •Sarcopenia •Cancer Survivorship
- 10. Age at diagnosis of cancer in general population Median age at cancer diagnosis in US is 67 ! Seer 2009-2013 0 500 1000 1500 2000 2500 Ratesper100,000 Cancer Incidence Age-Specific Incidence Rates
- 13. Aging is a heterogeneous process Chronological age insufficient!
- 14. Outcomes in older adults with cancer highly variable Cancer Diagnosis Cancer treatment Good Intermediate Poor Outcomes
- 15. Assessing Older Adults with Cancer •Remains a clinical challenge •Chronological age and performance status alone insufficient •Better ways to assess older adults are needed
- 17. What is a Geriatric Assessment? Definition: A multidimensional, interdisciplinary diagnostic process focusing on determining an older person’s medical, psychosocial, and functional capabilities • Requires evaluation of multiple issues and domains • Involves both evaluation and management Challenges • Requires time, specialized personnel, and expertise • Insufficient numbers of geriatricians to do it
- 18. Brief Geriatric Assessment Hurria et al. Cancer, 2005. DOMAIN ASSESSMENT MEASURE Health Professional Patient Reported Functional Status Timed Up and Go Physician Rated Karnofsky Performance Status (KPS) Activities of Daily Living (ADL) Instrumental Activities of Daily Living (IADL) Karnofsky Self Reported Performance No. of Falls in the last 6 months Comorbidity Number and Type of Comorbid Conditions Number of Medications Vision Assessment Hearing Assessment Cognition Blessed Orientation Memory Concentration Test Psychological Mental Health Index 17 Social Social Activity Limitation Measure (MOS) Social Support Survey (MOS) Nutrition Body Mass Index Unintentional Weight Loss in 6 Months 5 minutes 20-25 minutes
- 20. “Stages of aging” using Geriatric Assessment • Fit (Excellent, Good) – No functional impairment – No significant comorbidity – No geriatric syndromes • Vulnerable (Good, Fair) – Dependence in an IADL but not ADL – Comorbidities but not severe or life-threatening – No geriatric syndromes other than mild memory disorder or mild depression • Frail (Poor) – Dependence in an ADL – 3 or more comorbidities or one life-threatening – A clinically significant geriatric syndrome
- 21. •Allows for accurate life-expectancy estimate •Can predict treatment-related toxicity and other outcomes •Uncovers problems not found routinely •Many problems have beneficial interventions • Improve function • Quality of life • Survival The Value of Geriatric Assessment in Oncology Wildiers et al. J Clin Oncol, 2014.
- 22. Prevalence of Geriatric Conditions in Newly Diagnosed Patients with Colorectal Cancer Koroukian et al. JCO, 2006.
- 23. Impact of Geriatric Conditions on Survival in Patients with Colon Cancer Koroukian et al. J Ger Onc, 2011
- 24. Geriatric Assessment Predicts Toxicity Risk factors for Grade 3-5 Toxicity OR (95% CI) Score Age ≥73 yrs 1.8 (1.2-2.7) 2 GI/GU cancer vs. other cancer 2.2 (1.4-3.3) 3 Standard dose vs. reduced 2.1 (1.3-3.5) 3 Polychemotherapy vs. single agent 1.8 (1.1-2.7) 2 Hemoglobin (male: <11, female: <10) 2.2 (1.1-4.3) 3 Creatinine Clearance (Jelliffe –ideal wt) <34 2.5 (1.2-5.6) 3 1 or more falls in last 6 months 2.3 (1.3-3.9) 3 Hearing impairment (fair or worse) 1.6 (1.0-2.6) 2 Limited in walking 1 block (MOS) 1.8 (1.1-3.1) 2 Assistance required in medication intake 1.4 (0.6-3.1) 1 Decreased social activity (MOS) 1.3 (0.9-2.0) 1 Possible score range: 0-25 Hurria et al. J Clin Oncol, 2011.
- 25. Hurria et al. J Clin Oncol, 2011. Geriatric Assessment Predicts Toxicity
- 26. Jolly et al. The Oncologist, 2015. Detecting Impairments
- 27. Implementing Interventions Magnuson et al., Curr Geri Reports, 2014
- 30. Sarcopenia...
- 31. Background • Losses in muscle mass and muscle strength occur as part of the aging process - Tzankoff, Norris. J. Appl. Physiol., 1997. - Morley. Family Practice, 2012.
- 32. “there is probably no decline in structure and function more dramatic than the decline in lean body mass or muscle mass over the decades of life.” - Rosenberg, 1997
- 33. Measuring body composition Skeletal muscle Subcutaneous adipose tissue Visceral adipose tissue L3 Skeletal muscle index [SMI] [SMI]= [red area]/(height(m) 2) Sarcopenia = low SMI
- 35. Martin et al. J Clin Oncol, 2013. Identical BMI (30kg/m2) Identical SMI (30cm2/m2)
- 36. Martin et al. J Clin Oncol, 2013.
- 38. Multifactorial causes of muscle losses in the patients with cancer Williams et al. Journal of Geriatric Oncology. 2018
- 39. Sarcopenia in Colon Cancer • Low muscle mass is common amongst adults diagnosed with cancer, and not just the elderly population • Associated with increased chemotherapy toxicities, surgical complications, and inferior survival 26.8 44.6 58.3 0 10 20 30 40 50 60 70 <60 60-<70 >70 PERCENTAGE AGE % Sarcopenic - Caan et al. CEBP. 2017
- 40. But muscle mass is not the only measure of interest Skeletal muscle density (SMD) ≈ myosteatosis The density of skeletal muscle is inversely related to muscle fat content
- 41. How to Choose Steak?
- 42. The Impact of Sarcopenia on Toxicity and Pharmacokinetics of 5- Fluorouracil in Colorectal Cancer Williams et al, Cancer Chemotherapy and Pharmacology. 2017 69% 39% 23% 23% 75% 50% 33% 33% 0% 10% 20% 30% 40% 50% 60% 70% 80% G2 Toxicity G3/4 Toxicity G3/4 Heme Toxicity G3/4 Non-Heme Toxicity and Sarcopenia Non-Sarcopenic Sarcopenic 58% 25% 8% 25% 85% 62% 46% 31% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% G2 Toxicity G3/4 Toxicity G3/4 Heme Toxicity G3/4 Non-Heme Toxicity and Skeletal Muscle Gauge SMG ≥1475 AU SMG <1475 AU
- 43. Du BOIS D, Du BOIS ER – Arch Intern Med, 1916.
- 44. Incidence of dose-limiting toxicity in Colon Cancer Ali et al. Cancer Medicine. 2016.
- 45. Survivorship...
- 46. Bluethmann et al. CEBP. 2016.
- 47. What is the cost of a cure? Short-term side effects • Side effects from chemotherapy, surgery, and radiation therapy Long-term side effects • Less understood and recognized Cardiovascular dysfunction, reduced pulmonary function, endocrine abnormalities, neuropathy, cognitive dysfunction, secondary cancers, chronic fatigue…
- 48. Chronic Health Conditions in Adult Survivors of Childhood Cancers Oeffinger et al. NEJM 2006
- 49. All-cause mortality among 5-year survivors from the Childhood Cancer Survivor Study Bhatia et al. JCO 2015 ©2015 by American Society of Clinical Oncology
- 50. The effect of adjuvant chemotherapy on biomarkers of aging • Goal: To understand whether cytotoxic agents promote molecular aging • Prospectively obtained blood from 33 women with stage I-III breast cancer and evaluated the expression of P16INK4a (marker of senescence) • Median increase in log2 p16INK4a of 0.81, equivalent to 14.7 years! Sanoff et al. JNCI, 2015.
- 51. Prevalence of impairments among cancer survivors and a noncancer population Characteristic Cancer group, No. (%)† Noncancer group, No. (%)† P‡ Functional limitations ADL limitations 794 (31.9) 2959 (26.9) <.001 Bathing or showering 335 (13.3) 1172 (10.2) <.001 Dressing 212 (8.4) 728 (6.4) <.001 Eating 81 (3.3) 271 (2.5) .033 Getting in or out of bed or chair 352 (14.2) 1369 (12.5) .022 Walking 671 (27.0) 2570 (23.2) <.001 Using toilet 146 (5.7) 586 (5.3) .373 IADL limitations 1220 (49.5) 4606 (42.3) <.001 Using telephone 218 (8.2) 812 (6.9) .023 Doing light housework 424 (17.2) 1562 (13.9) <.001 Doing heavy housework 1083 (44.0) 4035 (36.9) <.001 Preparing meals 409 (15.9) 1540 (13.5) .003 Shopping 443 (17.2) 1716 (14.9) .007 Managing money 266 (10.0) 1086 (9.5) .434 Geriatric syndromes 1456 (60.8) 5661 (53.9) <.001 Falls 633 (25.9) 2288 (21.6) <.001 Incontinence 375 (15.6) 1220 (11.1) <.001 Osteoporosis 593 (24.3) 2103 (19.8) <.001 Vulnerability or frailty Vulnerability (VES-13 ≥ 3) 1184 (45.8) 4513 (39.5) <.001 Frailty 1910 (79.6) 7722 (73.4) <.001 Poor or fair self-rated health status 661 (27.4) 2191 (20.9) <.001 Mohile et al. JNCI. 2009.
- 52. Survivorship Care • Development of survivorship care plans • Details treatments received and follow- up care plans • Survivorship clinics • More studies focused on the long-term impact of cancer and its therapies
- 53. Cardiovascular Morbidity in Survivors of Colorectal Cancer Kenzik… Williams. JCO 2018.
- 54. • Our mission is to reduce the burden of cancer and its sequelae across all segments of the population, through interdisciplinary research, health promotion, and education. • We seek to design interventions and therapies to help survivors not only survive, but thrive. https://www.uab.edu/medicine/icos/
- 55. Acknowledgments
- 56. Questions???
- 57. Q & A SNAP A #STRONGARMSELFIE In 2018, up to $55,000 will be donated thanks to our sponsors: Bayer, Fujifilm, Myriad Genetics and Taiho Oncology! Flex a “strong arm” & post it to Twitter or Instagram using the hashtag #StrongArmSelfie
- 58. CONTACT US CALL TOLL FREE 1.877.427.2111
Editor's Notes
- Cancer is predominately a disease of aging. The majority of cancer diagnoses and the vast majority of cancer deaths occur in adults over the age of 65. Given changing demographics, it is anticipated that 70% of all cancer diagnoses will be in older adults by 2030.
- We begin our lives as infants and progress through developmental stages that are fairly predictable
- At about the 2nd to 3rd decade of life, the developmental process ceases and the aging process begins. And unlike the development process that progresses predictably, the aging process is heterogeneous. The pace of aging varies between individuals based on Genetic, Environmental, and Lifestyle factors that influence the aging process.. Differences between individuals may not be a recognizable at early ages in the 4th or 5th decade, but become are more apparent over time
- Using our two patients as examples, when older patients are diagnosed and treated for cancer, their outcomes are highly variable even when patients of a similar age undergo identical treatment. Some older adults tolerate standard therapies well and have similar benefits as younger patients, whereas others have significant toxicity and poor tolerability. This variability makes treating this population particularly challenging. We know the health status of patients at the time of a cancer diagnosis has a significant impact on patient outcomes, and it is these assessments of older adults that are a focus of my research.
- Such as biomarkers that could better predict outcomes
- First off, many of you may not think of Geriatric Assessment as a ‘biomarker of aging’, but it does successfully fulfill many of the criteria for a good biomarker and is a novel concept in oncology Comprehensive geriatric assessment (CGA) is defined as a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional limitations of a frail older person in order to develop a coordinated plan to maximize overall health with aging [1,2]. The health care of an older adult extends beyond the traditional medical management of illness. It requires evaluation of multiple issues, including physical, cognitive, affective, social, financial, environmental, and spiritual components that influence an older adult's health. CGA is based on the premise that a systematic evaluation of frail, older persons by a team of health professionals may identify a variety of treatable health problems and lead to better health outcomes.
- NARRATION: CGA can help stratify patients into different groups. Similar to cancer staging which is critical to treatment decision-making, the GA can help assess the aging process. Fit patients are those that are typically enrolled in clinical trials and should get standard of care. Frail patents are at high risk for adverse outcomes and risks of therapy may outweigh the benefits. Best supportive care may be warranted. The toughest group of patients for decision-making is the vulnerable group—we have limited data regarding the safety and efficacy of treatment, but given that these patients may have a reasonable life expectancy and/or symptoms from cancer, cancer treatment should be considered and the risks and benefits weighted carefully.
- Narration This slide demonstrates that comorbidity, disability, and geriatric syndromes are distinct entities for older patients with newly diagnosed colorectal cancer. While comorbidity is the most prevalent, patients can have different combinations of these characteristics with 15.7% having all 3.
- Narration This study revealed that functional limitations (or disability) and geriatric syndromes increases adverse outcomes above and beyond comorbidities. This also reflects the concept of multimorbidity, which takes into account all of the characteristics that impact outcome, not just comorbidity. Evaluating multimorbidity is a more comprehensive approach to identifying factors that increase the risk of adverse outcomes for older patients with cancer.
- Hurria and colleagues have developed a predictive model for grade 3 to 5 chemotherapy toxicity based on data from 500 patients with different cancers and different cancer stages. Utilizing selected clinical and geriatric assessment discussed earlier they developed a model that was able to accurately predict moderate to severe chemotherapy toxicity Grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death)
- ROC: 0.72 This study reported on grade 3 to 5 toxicity; however, some grade 2 toxicities (diarrhea, neuropathy) may also be relevant to the geriatric population.
- In this subsample, 550 (69%) had at least 1 GA-identified deficit, 222 (28%) had 1 deficit, 140 (18%) had 2 deficits, and 188 (24%) had >3 deficits. Specifically, 43% reported taking >9 medications daily, 28% had decreased social activity, 25% had >4 comorbidities, 23% had >1 impairment in instrumental activities of daily living, 18% had a Timed Up and Go time >14 seconds, 18% had >5% unintentional weight loss, and 12% had a Mental Health Index score <76. Conclusion. Within this sample of older cancer patients who were rated as functionally normal by KPS, GA identified important deficits that could affect treatment tolerance and outcomes. KPS of 80 and above= ECOG 0-1 - Able to carry on normal activity and to work; no special care needed. (with some signs of dz.)
- More recently my focus has shifted to sarcopenia and age-related changes in body composition.
- World clean jerk weight lifting records
- So how do we measure sarcopenia? - Outside oncology, frequently assessed via DEXA scan or BIA, but in oncology, have an overabundance of CT and MRI imaging
- Muscle mass and strength follows a fairly dependable curve, not unlike osteoporosis, in that individuals reach peak muscle mass and strength in early life and then slowly lose both with increasing age past the 3-4 decade of life.
- Muscle loss in patients with cancer is multifactorial. Older patients with cancer face the triple threat of age-related cancer-related, and treatment related loses of muscle
- More prevalent with increasing age, but present across the spectrum
- Using advanced imaging techniques such as CT or MRI, we are also able to evaluate the composition of skeletal muscle. Skeletal Muscle Density (or Attenuation) is a non-invasive radiological technique to indirectly assess muscle fat content, known as myosteatosis The red area represents skeletal muscle within the normal range of radiodensity (+30 to +150 HU), the yellow represents +1 to +29 HU, and the blue represents 0 to -29 HU.
- This is similar to how we choose our steak. Now what you look for in a good steak is different from what you want in your own muscle.
- Of the 70 patients from the original study, 25 had available CT imaging. Goal: Explore the impact of body composition, in particular sarcopenia, on the pharmacokinetics of 5-fluorouracil (5FU) in a cohort of patients receiving FOLFOX +/- bevacizumab for colorectal cancer Sarcopenic patients had numerically higher first cycle AUCs of 5FU, although not statistically significant
- BSA dosing was originally derived, in 1916 using eight patients, by DuBois and DuBois to adjust for basal metabolic rates in estimating the human starting dose from animal doses. This formula was used by Freireich in the1960s to achieve uniformity in dosing patients who were being treated with phase I cytotoxics. However, there is no scientific basis for such use of BSA, and there is growing evidence that this approach is, in fact, invalid. BSA dosing is associated with high pharmacokinetic variability and is a poor indicator of optimal drug exposure. On this point, Baker et al reviewed 33 investigational agents and found that BSA-based dosing reduced interpatient variability for only five (15%). Moreover, the reduction in clearance variability was between 15%and 35%, which indicates that only up to one third of the variability was explained by BSA. Felici et al reported the variability in clearance of the most commonly used cytotoxics to be between 25% and 70%, with most drugs showing variability above 35%. They concluded: “BSA failed to individualize the effects of the majority of agents explored.” (Beumer et al, JCO 2012 editorial).
- More recently my focus has shifted to sarcopenia and age-related changes in body composition.
- As cancer treatments have improved, cancer cure rates are higher today than ever before and cancer survivors are a growing population. Who are these survivors? This effects not only oncologists, but all physicians that care for these patients.
- What is the cost of a cure?
- To better understanding of the long-term side effects of cancer and its treatments, it is useful to look at survivors of childhood cancers. In a large study examining the health status of adults who received a diagnosis of childhood cancer compared to that of their siblings. Showed high rates of illness related to chronic health conditions compared to siblings. Adjusted relative risk of a chronic condition in survivor compared with sibling was 3.3. Important to realize these are mostly survivors of leukemia (~30%), Lymphomas (27%), and CNS tumors (13%). Mean ages of 26.6.
- Figure displays the all-cause mortality of 5-year survivors of childhood cancer compared with age-adjusted expected survival rates in the US population. The absolute excess risk for deaths from recurrence declined with time, whereas the AER for deaths from secondary cancers and cardiovascular causes increased. Subsequent to 45 years after diagnosis, recurrence accounted for only 7% of the excess number of deaths, whereas secondary cancers and cardiovascular causes accounted for 51% and 26% of the excess number of deaths, respectively
- Background: Senescence is strongly associated with activation of the INK4/ARF (CDKN2a) locus on human chromosome 9p21.3, which encodes the p16INK4a and ARF tumor suppressor proteins. Expression of p16INK4a decreased with chemotherapy in only one patient, who was later found to have congenital p53 deficiency (Li-Fraumeni syndrome) The principal limitation of this study is the reliance on markers that can be only easily assayed in the peripheral blood. We were able to reproducibly show that breast cancer chemotherapy leads to a durable increase in PBTL p16INK4a expression, but we were unable to show an effect of chemotherapy on LTL and IL-6.
- Study of a nationally representative sample of older patients who provided detailed information on the 2003 Medicare Current Beneficiary Survey to compare the prevalence of disability, geriatric syndromes, poor self-rated health, and vulnerability and frailty between those with and without a personal history of cancer and to estimate the independent association of a cancer diagnosis with these predictors of poor health outcomes. Conclusions: Diagnosis of a non-skin cancer was associated with increased levels of having disability, having geriatric syndromes, and meeting criteria for vulnerability and frailty.
- So how are we to care for this growing population? The issues surrounding cancer survivorship have been widely recognized. The IOM Committee on Cancer Survivorship in 2005 urged a new focus on the period after cancer treatment. The goal of the nearly 500-page report From Cancer Patient to Cancer Survivor: Lost in Transition was to improve the quality of life for the more than 10 million people in the United States who are adult cancer survivors. 1) Survivorship care plans- to help empower all clinicians, but particularly PCP, in caring for cancer survivors 2) Survivorship clinics- specialized clinics focused on the health and well-being of cancer survivors (developing here at UAB) 3) More studies on the long-term impact of cancer and its treatments, to better shape our long-term care of these patients