ORIGINAL ARTICLE /ARTICLE ORIGINAL DOSSIER
Cancer in the Older Person
Cancer de la personne âgée
L. Balducci
Revised: 09 January 2012 , Accepted: 31 January 2012
© Springer-Verlag France 2012
Abstract The incidence and mortality rate of cancer increases with age. With a worldwide increase in life expec- tancy, the clinical problems associated with cancer and old age are becoming more and more widespread. The clinical questions relating to cancer and old age can be divided into three main areas: 1) Why does the incidence and prevalence of cancer increase with age? 2) Does age affect the biology of cancer? 3) Is the prevention and treatment of cancer beneficial to elderly patients? 4) What are the psycho- social consequences of treating elderly patients with cancer?
KeywordsPrevalence · Elderly cancer patient · The combination of cancer and old age
Résumé L’incidence et la mortalité du cancer augmentent avec l’âge. Avec l’espérance de vie de la population qui aug- mente dans le monde entier, les problèmes cliniques liés au cancer et à l’âge se retrouvent de plus en plus souvent ass- ociés. Les questions cliniques posées par le cancer au grand âge peuvent s’organiser autour de trois axes : 1) pourquoi l’incidence et la prévalence du cancer augmentent-elles avec l’âge ? 2) L’âge affecte-t-il l’évolution biologique du cancer ? 3) La prévention du cancer et les traitements bénéficient-ils aux sujets âgés ? 4) Quelles sont les résultats psychosociaux de la prise en charge des patients âgés atteints de cancer ?
Mots clésIncidence · Prévalence · Patient âgé atteint de cancer · Cancer et grand-âge combinés
The incidence and the mortality of cancer increase with age [32,54,55]. As the life expectancy of the population is increasing around the world, one may presume that the clinical problems related to cancer and aging will become increasingly common.
The clinical questions related to cancer and aging include:
– Why does the incidence and prevalence of cancer increase with age?
– Does age affect the biology of cancer?
– Are cancer prevention and treatment beneficial to older individuals?
– Is cancer a major cause of morbidity, mortality, and disability in the elderly?
– What are the social issues involved in the management of the older cancer patients?
Association of cancer and aging
At least three non mutually exclusive mechanisms explain the association of cancer and aging:
– Carcinogenesis is a time consuming process that may be aborted when a person dies at a younger age [42].
The importance of this factor is demonstrated by a recent epidemiologic paradox: the incidence of lung cancer has increased as people stopped smoking, because ex smokers are very unlikely to die of coronary or respiratory disease [42]. They now live long enough to develop cancer.
– Older tissues are primed to the action of environmental carcinogens, because to some extent the molecular changes of aging mimick early carcinogenic changes [2].
A number of studies revealed that this is the case in humans, not just in laboratory animals. The incidence of acute myelogenous leukemias increases after cytotoxic chemotherapy in patients who received the treatment after age 65 [34]. Also, the incidence of cancer is fourfold higher among individuals who have the shortest telomeres [35,53]. The telomere length may reflect the biological age of a person.
– The environment of the aging body may favor the devel- opment of cancer. Of special interest are immune- senescence and endocrine senescence. Increased insulin resistance is a hallmark of aging and is associated with
L. Balducci (*)
H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612 USA e-mail : [email protected] DOI 10.1007/s11839-012-0352-8
increased concentrations of insulin in the circulation.
Insulin may act as a very powerful tumor growth factor.
Of interest, Russian investigators have prolonged the rodent life-span with the use of metformin, a substance that re-establishes the sensitivity to insulin and delays the development of cancer in these animals [3].
For all these reasons chemoprevention of cancer may be particularly effective in older individuals. Chemoprevention consists in the administration of substances that block or offset carcinogenesis [27].
Who are the older patients?
Aging is associated with a progressive decline in the func- tional reserve of multiple organ systems, increased preva- lence of chronic diseases, and a number of conditions known as“geriatric syndromes”, that reduce a person life- expectancy, tolerance of stress and ability of independent living [50]. These changes are poorly reflected in chrono- logic age, so that each patient’s physiologic age should be independently assessed.
The assessment of physiologic age is best done with a comprehensive geriatric assessment (CGA) (summarized in Table 1). The basic ADLs includes transferring, grooming, ability to go to the bathroom, to dress and to eat. The IADLs are activities necessary for independent living, and include use of transportation, ability to take medications, to provide to one’s own meal, to be able to use the telephone and to manage money.
Comorbidity, may be associated with a reduction both in life-expectancy and treatment tolerance [8,43,45]. Comor- bidity may be assessed as number of comorbid conditions or as a comorbidity index reflecting the severity of each condition. At the Moffitt Cancer Center, the Cumulative Index Rating Scale-Geriatric (CIRS-G) is commonly used [43]. In addition to being very comprehensive, the CIRS-G has the advantage that it may be converted into the Charl- son’s index, another comorbidity index of widespread use [43]. Two forms of comorbidity have special interest for the older cancer patient, depression and anemia [12,15].
Both conditions may be reversible and may compromise patient’s function and treatment tolerance. The Geriatric Depression Scale is a simple 30 items, self administered questionnaire very sensitive to sub-clinical depression, and is a practical instrument to screen older individuals [15].
The optimal level of hemoglobin is controversial [12].
Ideally, the hemoglobin should be kept at≥12 gm/dl, because below that level the incidence of functional dependence, fatigue, and chemotherapy-related toxicity increase [12].
Geriatric syndromes include a number of conditions, due to different causes, that are typical, albeit not exclusive, of
advanced age, and are associated with decreased survival and increased risk of functional dependence [7]. The early recognition of geriatric syndromes is important because some of them (such as depression) may be reversed and others (dementia, failure to thrive, falls, neglect and abuse, severe osteoporosis) may be stopped and managed.
The Folstein Minimental Status (MMS) is a short instru- ment that may detect mild as well as advanced dementia, and is administered by an expert interviewer over 15 minutes.
Because of its practicality, the MMS is utilized in different institutions to screen older individuals for dementia [38].
The MMS is not sensitive to progressive cognitive changes, that may lead to dementia, though they do not represent dementia yet. These conditions may identify patients at risk for cognitive deterioration during cancer treatment, but their detection requires prolonged and complex assess- ments interpretable only by an experienced professional...
The presence of one or more geriatric syndrome generally suggests the need for at least a part-time caregiver, and for special precautions aimed to manage these specific condi- tions. In addition to shortening life’s expectancy and increas- ing the risk fo treatment–related toxicity, comorbidity may Table 1 Examples of CGA and potential clinical applications.
Functional status Activities of Daily (ADL) and Instrumental Activities of Daily Living (IADL)
Relation to life-expectancy, functional dependence and tolerance of stress Comorbidity
Number of comorbid conditions and comorbidity indices
Mental status
Relation to life-expectancy and tolerance of stress
Folstein Minimental status Relation to life-expectancy and dependence
Emotional conditions Geriatric Depression Scale (GDS)
Relation to survival; may indicate motivation to receive treatment Nutritional Status
Mininutritional assessment (MNA)
Reversible condition;
possible relationship to survival
Polypharmacy Risk of drug interactions Geriatric syndromes
Delirium, dementia,
depression, falls, incontinence, spontaneous bone fractures, Neglect and abuse, failure to thrive.
Relationship to survival Functional dependence
influence cancer growth and represents a cause of polyphar- macy which may also alter the treatment tolerance.
The causes of polypharmacy [16,19,20] are multiple and include comorbidity, the consultation of several different health care specialists, and the use of multiple over the counter preparations. Polypharmacy is a major cause of adverse drug reactions and interactions of drugs, as well as of out of the pocket health-related costs.
The risk of malnutrition increases with age and malnutri- tion is an independent risk factor for the toxicity of chemo- therapy [30]. Most causes of malnutrition are multiple, and include: reduced food intake due to isolation, depression, poverty, and anorexia from polypharmacy, reduced thresh- old for bitter and increased threshold for sweet flavor, gastric atrophy and hypomobility, reduced splancnic circulation.
The mininutritional assessment (MNA) allows to identify patients who are malnourished and those at risk of malnutri- tion [28], and is widely used because it is at the same time comprehensive and user-friendly.
The estimation of risk of mortality at 5 years [22], of surgical complications, and of chemotherapy related toxicity is currently based on the CGA [14,29,56]. In addition the CGA allows to identify conditions that might interfere with cancer treatment, including the assessment of the home care- giver. The role of the caregiver in the management of older patients with cancer cannot be over-emphasized [31,51].
Under ideal circumstances, the caregiver is the best ally of the practitioner: in addition to providing a reliable presence in case of emergency, assuring timely medical attention to the older patient, the caregiver may act as the spoke-person for the family, and may be invaluable to mediate the conflicts that often occur within an extended family. It behooves to the practitioner, therefore, to help in the selection of the caregiver, to counsel and support the caregiver.
A number of laboratory tests may be used to assess phys- iologic age. These include the concentration of inflammatory markers in the circulation, as age is considered as a form of chronic and progressive inflammation [23,48], and the length of leukocytes telomeres [11].
A combination of physical and laboratory tests are included in the assessment of the so called allostatic load and of the so called“Frailty Index.”[50] These instruments currently are considered experimental but they may have an important role for assessment of the physiologic age of older cancer patients in the future.
Decisions related to the prevention and treatment in cancer in the older aged person should be then based on the physiologic, not the chronologic age of the patient. In particular the decision involves the following questions:
– Is the patient going to die of cancer or with cancer?
– Is the patient able to tolerate the treatment of cancer?
– Is the patient going to suffer the complications of cancer.
Cancer Prevention in the Older Aged person Primary cancer prevention includes elimination of environ- mental carcinogens and administration of substances that may offset carcinogenesis (chemoprevention) [27] (Table 2).
Secondary prevention includes the screening of asympto- matic individuals at risk for cancer.
Being more vulnerable to environmental carcinogens, older individuals may benefit from primary prevention to a greater extent than the younger ones.
Despite these encouraging results, none of these sub- stances may be recommended as yet for chemoprevention of cancer in older individuals. None of them have reduced the cancer related mortality. All of them have potentially serious complications.
The aim of secondary cancer prevention is to diagnose the cancer at an earlier stage, when it may still be curable. The accuracy of screening tests may improve with age, due to increased prevalence of common cancers [54,55], but at the same time reduced life expectancy and occurrence of more indolent tumors may lessen the benefits of screening older individuals.
Several screening strategies are currently in use, and some of them may be beneficial to older individuals.
Breast cancer
Serial mammography reduced by 20-30% cancer-related mor- tality in women aged 50-70 [10]. The benefits of serial screen- ing mammography after age 70 may be inferred from the Surveillance, Epidemiology and End Results (SEER) data.
Breast cancer mortality was reduced for women aged 70-79 undergoing at least two mammographic evaluations after 70 [13,36] and the benefits of mammography were seen up to age 85 even in patients with moderate comorbidity [44].
Cancer of the large bowel
Serial examinations of voided stools for fecal occult blood (FOB) reduced the mortality from cancer of the large bowel
Table 2 Substances that prevent cancer in humans.
Substance Cancer
Selective Estrogen Receptor Modulators (SERMs) including tamoxifen
and raloxifene
Breast
Aromatase Inhibitors (examestane) Breast 5-α-hydroxilase inhibitors (finsteride;
dusteride)
Prostate Non steroid anti-inflammatory agents Large bowel
Cis-retinoic acid Head and neck
in persons aged 50-80 [37]. The effectiveness of serial syg- moidoscopic or colonoscopic examinations is supported by retrospective studies [9]. In a recent decision analysis full colonoscopy every ten years was recommended as the most cost effective screening strategy [9].
Lung Cancer
Serial CT of the Chest in current and ex smokers have been associated with a relative 20% reduction on the mortality from lung cancer and a 6.7% overall mortality reduction [18] in patients up to age 80.
Prostate cancer
The screening of asymptomatic individuals for prostate cancer is still controversial. In a randomized controlled study serial assessment of serum PSA resulted in no benefit [40], whereas in another study reduced the cancer related mortality [1], albeit to a very low extent. Screening asymp- tomatic men aged 70 and older for prostate cancer is contra- indicated according to the United States Preventive Services Task Force, because it may cause more damage from unnec- essary procedures, than benefits [46].
Barriers to cancer prevention in the elderly The discussion of cancer prevention in the elderly would not be complete without illustrating a number of age- related barriers that do hamper most efforts [26]. This includes that poorly defined but very real form of bias called
“ageism”that encompasses a number of prejudices, such as the assumption that prevention is not beneficial to older indi- viduals, as they develop more indolent cancers, or because they have only few years to live, or the theory that older individuals are not entitled to the same care as the younger ones, as they have already benefited from their share of health-related expenses. Cultural barriers are also operative.
The rate of screening mammography is lower for minority older women, especially Hispanic women.
Cancer Treatment in the Older Person in USA Forms of cancer treatment include: surgery, radiation ther- apy, hormonal therapy, cytotoxic chemotherapy and targeted therapy. Recent development in surgery and radiation therapy have made these interventions safer in patients of all ages. Of special interest is the so called“radiosurgery” that consists in ablation of cancer without invasive surgery,
and intensity modulated radiation therapy that spares the majority of normal tissues [17,41]. Hormonal therapy of cancer of the breast with aromatase inhibitors and of cancer of the prostate with LH-RH analogs may cause osteoporosis and increased risk of bone fractures [50].
The main complications of cytotoxic chemotherapy in older individuals include myelotoxicity, that is a drop in white blood cell count and in platelet count that may make the patient more susceptible to infections and bleeding respectively, and mucositis that is painful and may lead to rapid dehydration [52]. Neutropenia may be prevented with the prophylactic use of myelopoietic growth factors (filgras- tim and peg-filgrastim) that are recommended in older indi- viduals for moderately toxic chemotherapy [6]. Mucositis may be ameliorated by keratinocyte growth factors and by hypersaturated phosphate suspensions. With the increase in the number of cancer survivors chronic complications of chemotherapy are also of concern. These include myelodys- plasia and acute myelogenous leukemia, chronic neuropathy, chronic cardiomyopathy and possibly dementia. It is not clear yet whether chemotherapy is associated with increased risk of functional dependence.
Targeted therapy includes a number of newly developed drugs that inhibit specific steps of cancer growth [47].
The prototype of targeted therapy is imatinib, that inhibits the thyrosine kinase encoded by BCR/ABL translocation in chronic myelogenous leukemia, and is responsible for the growth of the neoplasm. Though targeted therapy is gener- ally better tolerated than cytotoxic chemotherapy, it also has a number of complications whose risks may increase with age. In addition to imatinib and new generation tyrosine kinase inhibitors nilotinib and desatinib, promising forms of targeted therapy for solid tumors have been developed.
Supportive Care of the older cancer patient.
In addition to ameliorating the complications of treatment, such as neutropenia and mucositis, supportive care involves the management of symptoms that include pain and fatigue, and the emotional and social support of the older person.
Pain
Though the perception of pain may decrease with age [21], pain is a major cause of disability in older individuals with cancer. Effective pain management is essential to maintain the function as well as the interpersonal relations of the patients. The practitioner should be aware that the ability of expressing pain may be impaired by cognitive decline as well as cultural prejudices. Inadequate report of pain may be responsible of under-treatment of pain in as many as 50% of older cancer patients.
Visual pain scales appear more reliable than numeric scales, and vertical scales more reliable than the horizontal ones [21]. Of the vertical scales the pain thermometer is the most commonly used.
In the absence of verbal communication, repetitive pain behavior, such as grimaces, restlessness, or cries indicates the patient is suffering and deserves proper management.
The mainstay of cancer pain management is pharmaco- logical. Acetaminophen may be preferable to non-steroidal anti-inflammatory drugs (NSAIDs), because of lower risk of gastro-intestinal and renal complications.
Two pharmacologic aspects of aging may influence the effectiveness of opioids, especially morphine and hydromor- phone, that share the same pharmacology. First, the reduced GFR may be associated with increased half-life of morphine- 6-glucuronide, which is responsible of the analgesic activity, and of morphine-3-glucuronide, that is responsible of some of the complications. Second, the progressive reduction in brain mass that occurs with aging [21], may shift the ratio between theμand the δopioid receptors and enhance the vulnerability of older individuals to opioid complications, especially delirium, nausea and constipation. Given the uncertainty about the pharmacology of opioids in older individuals it appears reasonable to titrate the doses slowly and to start using sustained-release preparation only when the daily dose is well established.
The use of intrathecal infusions of opioids may obviate many of the problems related to the oral or parenteral admin- istration, but this route of administration is complicated and costly and it is not recommended unless a patient has a life expectancy of at least three months.
Fatigue
Fatigue is a sensation of tiredness that is not relieved by sleep or rest and is a major cause of disability in older indi- viduals [4,5,12]. It has also been associated with reduced life-expectancy [4,25]. The mechanisms of fatigue are largely unknown. Fatigue appears associated with anemia and correction of anemia may improve fatigue [24,39].
Though the optimal hemoglobin levels to improve fatigue is 12 gm/dl, the current recommendations is not to use Eryth- ropoietic stimulating Agents (ESA) for hemoglobin levels higher than 10 gm/dl, due to concern that ESA may promote cancer growth and cause venous thrombosis [12]. Fatigue may be caused by an increased concentration of inflamma- tory cytokines in the circulation that is typical both of cancer and aging [33]. It is controversial whether depression is associated with fatigue.
In addition to the correction of anemia and depression, management of fatigue may include exercise and drugs such as modafinil or methylphenidate, though the value of these interventions is not conclusively proven.
Family Caregiver
The caregiver is pivotal in the management of older indivi- duals with chronic diseases. The ideal caregiver should be able of timely response in face of emergency, to provide transportation to treatment centers, to support the patient emotionally and to act as the spoke-person of the family.
These duties may take a medical and emotional toll on the caregiver and it is the responsibility of the practitioner to support the caregiver with proper information and advise.
In general the caregiver is an older partner with health problems of his/her own or an adult child who must balance the care of the older parent with the demands of his/her profession and the care of his/her family. This situation has been called the Aeneas syndrome from the painting of Raffaello in the Vatican “Stanzes” where the Trojan hero leaves the burning city carrying his father on his back and his son by the hand [49].
Conclusions
Cancer in older individuals is an increasingly common problem, due to the increase life-expectancy of the Western population.
The association of aging and cancer may be accounted for by the length of carcinogenesis, the increased susceptibility of aging tissues to environmental carcinogens and possibly by changes in the body environment that favor the develop- ment of cancer.
The behavior of cancer may change with the age of the patient: some cancers (AML, lymphoma, ovarian cancer), may become more aggressive and others (breast and lung cancer) more indolent (Table 3).
Any medical intervention in older individuals with cancer needs to take into account life-expectancy, tolerance of antineoplastic treatment, and presence of medical or social conditions that may interfere with the intervention. A comprehensive geriatric assessment (CGA) is the best estab- lished way to account for the diversity of the older popula- tion. Several form of user-friendly screening tests to identify the individuals that most may benefit from the CGA are being studied.
While older individuals appear almost ideal candidate for chemoprevention of cancer, non of the current chemo- preventative agents appear to have clear clinical indications in older individuals.
Early detection of breast, colorectal, and lung cancer with screening appear beneficial for all individuals with a life-expectancy of at least five years.
Of the various forms of cancer treatment, cytotoxic chemotherapy is the one that may most be influenced by the age of the patient.
Finally it is important to emphasize the need of more data on effectiveness, acute toxicity, and long term outcome of older cancer patients treated with cytotoxic chemotherapy.
Conflict of interest :the author doesn’t have any conflict of interest to declare.
References
1. Andriole GL, Crawford ED, Grubb RL, et al (2009) Mortal- ity results from a randomized prostate cancer screening trial.
N Engl J Med 360:1310–9
2. Anisimov V (2004) Aging as a risk factor in multistage carcino- genesis. In: Balducci L, Lyman GH, Ershler WB, Extermann M (eds) Comprehensive geriatric Oncology. Taylor & Francis, Lon- don and New York, pp 75–101
3. Anisimov VN, Egormin PA, Piskunova TS, et al (2010) Metfor- min extends life-span of HER/2neu transgenic mice and in com- bination with melatonin inhibits growth of transplantable tumors in vivo. Cell Cyle 9:189–97
4. Avlund K (2010) Fatigue in older adults: an early indicator in the aging process. Aging Clin Exper Res 22:100–15
5. Balducci L (2003) Management of cancer pain in geriatric patients J Supp Oncol 1:175–91
6. Balducci L (2009) Pharmacologic of antineoplastic medications in Older cancer patients. Oncology 23:78–85
7. Balducci L (2010) Anemia, fatigue, and aging. Transfus Clin Biol 17:375–81
8. Balducci L, Colloca G, Cesari S, et al (2010) Assessment and treatment of elderly patients with cancer. Surg Oncol 19:117–23 9. Burt RW (2000) Colon cancer Screening. Gastroenterology
119:837–53
10. Chen W, Kimura M, Kim S, et al (2011) Longitudinal versus cross-sectional evaluation of leukocyte Telomere length dynam- ics: age dependent telomere shortening is the rule. J Gerontol A boil Sci Med Sci 66:312–9
11. Clendenen TV, Koenig KL, Arslan AA, et al (2011) Factors Associated with Inflammation markers: a cross-sectional study.
Cytokine 56:769–78
12. Covinsky KE, Kahana E, Chin MH, et al (1999) Depressive Symptoms and three year mortality in older hospitalized medical patients. Ann Int Med 130:563–9
13. Dean PB (2002) The rationale and current controversies of mam- mographic screening for breast cancer. Scan J Surg 91:288–92 14. Extermann M, Boler I, Reich RR, et al (2011) Predicting the risk
of chemotherapy toxicity in older patients: The Chemotherapy Toxicity Assessment Scale in High Age patients (CRASH) score. Cancer, Epub ahead of print
15. Extermann M (2000) Measurement and impact of comorbidity in older cancer patients. Crit Rev Oncol Hematol 35:181–200 16. Folstein ME, Folstein SE, McHugh PR (1975) A Mini Mental
State: a practical method for grading the cognitive status of patients for the clinician. J Psychiatr Res 12:189–98
17. Fox SA, Roetzheim RG (2004) Barriers to cancer prevention in the older person. In: Balducci L, Lyman GH, Ershler WH, Exter- mann M (eds) Taylor and Francis, London and New York, pp 376–84
18. Frazier AL, Colditz GA, Fuchs CS (2000) Cost-effectiveness of screening for colorectal cancer in the general population. JAMA 284:1954–61
19. Gallagher P, Barry P, O’Mahony D (2007) Inappropriate prescrib- ing in the elderly. J Clin Pharm Ther 32:113–21
20. Gallagher P, Ryan C, Byrne S, et al (2008) STOPP (Screening Tool of Older Person’s Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation.
Int J Clin Pharmacol Ther 46(2):72–83
21. Gonsalves W, Ganti AK (2011) Targeted anti-cancer therapy in the elderly. Crit Rev Oncol Hematol 78:227–42
22. Guigoz Y, Vellas B, Garry PJ (1997) Mininutritional assessment:
a practical assessment tool for grading the nutritional state of elderly patients. In: Facts, research, interventions in geriatrics.
Serdi Publishing Company, New York, pp 15–60
23. Haley WH, Burton AM, LaMonda LA (2004) Family Caregiving Issues for Older Cancer Patients. In: Balducci L, Lyman GH, Ershler WB, Extermann M (eds) Comprehensive geriatric Oncol- ogy. Taylor and Francis, London and New York, pp 843–52 24. Hardy SE, Studenski SA (2008) Fatigue and function over 3 years
in older adults. J Gerontol A Biol Sci Med Sci 63:1389–92 25. Hardy SE, Studenski SA (2008) Fatigue predicts mortality in
older adults J Am Ger Soc 56:1910–4
26. Hoffman RM (2011) Clinical practice: screening for prostate cancer. N Engl J Med 365:2013–9
27. Hong WK, Spitz MR, Lippman SM (2000) Chemoprevention in the 21st century: genetics, Risk Modeling, and Molecular targets.
J Clin Oncol 18(Suppl):9s–18s
28. Hughes VA, Roubenoff R, Wood M, et al (2004) Anthropometric assessment of 10 years changes in body composition in the elderly. Am J Clin Nutr 80:475–82
Table 3 Neoplasms whose behavior may change with the patient’s age.
Cancer Direction of change in behavior Mechanism
Acute Myelogenous Leukemia (AML)
Less responsive to cytotoxic chemotherapy Seed: increased prevalence of MDR-1 and of leukemia involving the pluripotent stem cell
Non Hodgkin’s Lymphoma
Decreased disease free and overall survival Soil: increased circulating concentration of Il-6
Breast cancer More indolent –Seed: higher prevalence of hormone-receptor rich,
well differentiated, slowly proliferating tumors;
–Soil: endocrine senescence Ovarian cancer Reduced response to chemotherapy
and reduced survival
Unknown Lung cancer More likely to present at an early stage Unknown
29. Hurria A, Togawa K, Mohile SG, et al (2011) Predicting Chemo- therapy Toxicity in Older Adults with Cancer. J Clin Oncol 29:3457–65
30. Jyrkkä J, Enlund H, Korhonen MJ, et al (2009) Pattern of drug use and factors associated with polypharmacy and excessive polypharmacy in elderly persons: results of the Kuopio 75+
study: a cross sectional analysis. Drugs Aging 26(6):493–503 31. Kristjansson SR, Nesbakken A, Jordøy MS, et al (2010) Compre-
hensive Geriatric Assessment Can Predict Complications in elderly patients after elective surgery for colorectal cancer: a pro- spective observation cohort study. Crit Rev Oncol Hematol 76:208–17
32. LaVecchia C, Lucchini F, Negri E, et al (2004) Cancer mortality in the Elderly. In: Balducci L, Lyman GH, Ershler WB, Exter- mann M (eds) Comprehensive geriatric Oncology. Taylor & Fran- cis, London and New York, pp 29–37
33. Luciani A, Jacobsen PB, Extermann M, et al (2008) Fatigue and functional dependence in older cancer patients. Am J Clin Oncol 31:424–30
34. Lyman GH, Dale DC, Wolff DA, et al (2010) Acute myelogen- ouds leukemia or myelodysplastic syndromes in randomized con- trolled clinical trials of cytotoxic chemotherapy with granulocyte colony-stimulating factors: a systematic review. J Clin Oncol 28:2914–24
35. Ma H, Zou Z, Wei S, et al (2011) Shortened Telomere length is associated with increased risk fo cancer. A meta-analysis. PLoS1 6:e20466
36. Mccarthy EP, Burns RB, Freund KM, et al (2000) Mammography use, breast cancer stage at diagnosis, and survival among older women. J Am Ger Soc 48:1226–33
37. McPherson CP, Swenson KK, Lee MW (2002) The effects of mammographic detection and comorbidity on the survival of older women with breast cancer. J Am Ger Soc 50:1061–8 38. Mohile SG, Fan L, Reeve E, et al (2011) Association of cancer
with geriatric Syndromes in Older medicare beneficiaries. J Clin Oncol 29:1458–64
39. Moreh E, Jacobs JM, Stessman J (2010) Fatigue function and mortality in older adults. J gerontol A Biol Sci Med Sci 65:887–95
40. National Lung Screening Trial Research Team (2011) Reduced lung cancer mortality with low-dose computerized tomography screening. N Engl J med 365:395–409
41. Niranjan A, Lunsford ND, Emerick RL (2012) Stereotactic radio- surgery for patients with metastatic brain tumors: development of a consensus radiosurgery guideline recommendation. Proc Neurol Surg 25:123–8
42. Peto J (2011) The lung cancer incidence falls in ex-smokers: mis- conception 2. Br J Cancer 304:389
43. Piccirillo JF, Tierney RM, Costa I, et al (2004) Prognostic impor- tance of comorbidity in a hospital-based cancer registry. JAMA 291:2441–7
44. Randolph WM, Goodwin JS, Mahnken JD, et al (2002) Regular mammography use is associated with elimination of age-related disparities in size and stage of breast cancer at diagnosis. Ann Int Med 137:783–90
45. Read WL, Tierney RM, Page NC, et al (2004) Differential prog- nostic impact of comorbidity. J Clin Oncol 22:3099–103 46. Schröder FH, Hugosson J, Roobol MJ, et al (2009) Screening
and Prostate Cancer mortality in a randomized European Trial.
N Engl J Med 360:1320–8
47. Shayne M, Balducci L (2011) Hematopietic Groth Factors in Older cancer patients. Cancer treatment Res 157:383–402 48. Sigh T, Newman AB (2011) Inflammatory markersin Population
Studies of Aging. Aging Res Rev 10:319–29
49. Tonia T, Bohlius J (2011) Ten years of meta-analysis on erythro- poiesis stimulating agents in cancer patients. Cancer Treat Res 157:217–38
50. VanderWalde A, Hurria A (2011) Aging and osteoporosis in breast and prostate cancer. CA Cancer J Clin 61:139–56 51. Weitzner MA, Haley WE, Chen H (2000) The family caregiver of
the older cancer patient. Hematol Oncol Clin 14:269–82 52. Whyte RI (2010) Stereotactic Radiosurgery for Lung Tumors.
Semin Thor Cardiovasc Surg 22:59–66
53. Willeit P, Willeit J, Kloss-Blandstätter A, et al (2011) Fifteen year follow up of the association between telomere length and incident cancer and cancer mortality. JAMA 306:42–4
54. Yancik RM, Ries LA (2004) Cancer in older persons: an interna- tional issues in an aging world. Sem Oncol 31:128–36
55. Yancik RM, Ries LA (2004) Cancer in the older person: magni- tude of the problem and efforts to advance the aging/cancer research interface. In: Balducci L, Lyman GH, Ershler WB, Extermann M (eds) Comprehensive geriatric Oncology. Taylor
& Francis, London and New York, pp 38–46
56. Yourman LC, Lee SJ, Schomberg MA, et al (2012) Prognostic Indices for Older Adults: a systematic review. JAMA 307:182–8
