Aging and cancer.
01 Dec 1988-Journal of Clinical Oncology (American Society of Clinical Oncology)-Vol. 6, Iss: 12, pp 1903-1911
TL;DR: Physicians and oncologists need to be prepared for the projected increase of cancer in older persons and a new subspecialty is evolving: geriatric oncology.
Abstract: The world's population is aging. Older age is associated with an increase in the incidence of cancer, especially cancer of the breast, lung, prostate, and colon. The management of older patients with cancer is biased by the simple fact of their chronologic age. Underscreening, understaging, less aggressive therapy, lack of participation in clinical trials, or no treatment at all reflect this bias. Although an age-related reduction in the physiologic function of many organs occurs with age, these are not contraindications to treatment with surgery, radiation therapy, or chemotherapy. Chronologic age alone should not be used as a guide for cancer management. Rather, physiologic function or existence of comorbid conditions should be major factors in determining treatment. As a result of the impending need for improved cancer management in older persons, a new subspecialty is evolving: geriatric oncology. This field stresses an important interaction between geriatricians and oncologists, development of research directed at the problems of cancer in older persons, and education at all levels with respect to cancer prevention, cancer detection, and cancer therapy. Physicians and oncologists need to be prepared for the projected increase of cancer in older persons.
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TL;DR: Recent data generated by several laboratories suggest that both aging and age-related neurodegenerative diseases are accompanied by an increase in SASP-expressing senescent cells of non-neuronal origin in the brain, and this increase correlates with Neurodegeneration.
197 citations
TL;DR: In October 2003, during the 12th Congress of Oriental Medicine in Taipei, the National Palace Museum organized an enormously pertinent exhibit derived largely from the museum's collection of ancient medical texts that includes classics on numerous topics that pertain to the origins of both Western medicine and the history of complementary and alternative medicine.
Abstract: In October 2003, during the 12th Congress of Oriental Medicine in Taipei, the National Palace Museum organized an enormously pertinent exhibit in Gallery 313 derived largely from the museum’s collection of ancient medical texts that includes classics on numerous topics. It is entitled Life is Worth More than Gold: A Special Exhibition of Ancient Medicinal Classics. In the English translation of the Chinese description clues are embedded that pertain to the origins of both Western medicine and the history of complementary and alternative medicine (CAM) as briefly described: “Disease has always been a great topic of concern in human society. From prayers and spells to the birth of medicine as a rational science, man has been able to develop all sorts of medical treatments to combat against different illnesses and ailments, because, as the Chinese proverb has it, ‘life is worth more than a thousand gold pieces.’ Towards the end of the Eastern Han (the 3rd century), typhoid was rampant in China, and the fatality rate was extremely high. Chang Chung-ching, with his extensive clinical experience, wrote the Treatise on Cold-Induced Febrile and Miscellaneous Diseases, and thereby established the foundations for ‘treatment based on differentiation of symptom-complex’ in traditional Chinese medicine. After that, as governments began setting up medical institutions and experiences of private doctors came to be valued, many important medicinal theories, treatments and much pharmaceutical knowledge were gradually organized systematically. Advancements in pharmacology were particularly notable. For example, the Newly-Revised Materia Medica issued by Emperor Kao-tsung of the T’ang dynasty in the 10th year of his reign (659) was the first pharmacological encyclopedia edited and published by the government, and a copy was taken to Japan by Japanese emissaries soon after its completion.”
177 citations
TL;DR: Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible.
Abstract: Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma), mechanisms of intercellular transference of genetic information (exosomes), and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning.
141 citations
TL;DR: These epigenetic changes in the GATA genes in lung cancer are tumor-specific, relate to the loss of GATA gene expression, and occur increasingly in the elderly.
Abstract: Purpose: In lung cancer, DNA hypermethylation is known to be a common event. Experimental Design: Gene expression and methylation status of GATA-4, GATA-5, and GATA-6 were analyzed with cell lines and primary human lung cancers. Methylation profiles of primary lung cancers were analyzed and correlated with clinical as well as histopathological data. Results: Complete methylation was detected by methylation-specific PCR for both GATA-4 and GATA-5 in four cell lines (H358, DMS-53, A549, and H1299), all of which had no expression by reverse transcription-PCR analysis. Demethylation with 5-aza-2′deoxycytidine restored expression in each case. GATA-6 was ubiquitously expressed in all of the six cell lines. GATA-4 bisulfite sequencing revealed complete methylation of the GATA-4 promoter in H358 cells, correlating well with its lack of expression at the mRNA level. Only a few CpG sites showed methylation by bisulfite sequencing within the GATA-4 promoter in a cell line that expressed the gene. In 63 cases of primary lung cancers, GATA-4 and GATA-5 promoter methylation was detected in (42 of 63) 67% and (26 of 63) 41%, respectively. GATA-6 remained unmethylated both in cell lines and primary tumors. Six autopsy specimens of normal lung tissue showed no aberrant promoter hypermethylation for the GATA genes. Correlation of concomitant GATA-4 and GATA-5 methylation with clinicopathological parameters only found a statistically significant increase in methylation frequency with increasing patient age ( P Conclusions: These epigenetic changes in the GATA genes in lung cancer are tumor-specific, relate to the loss of GATA gene expression, and occur increasingly in the elderly.
139 citations
TL;DR: Patients aged 75 years and older had significantly less intensive clinical staging workups and use of surgical and radiation therapies compared with patients aged 65 to 74 years and patients aged 50 to 64 years, suggesting that age bias is likely to be widespread.
Abstract: A chart review study was done of 242 Stages A2 to D1 cancer patients to determine whether the age of patients with prostate cancer influenced their physicians' management strategies. Ten hospitals of varying size, medical-school affiliation, and patient socioeconomic status participated in this study. Patterns of prostate cancer care were examined using sets of branching logic standards in the form of criteria maps. A chart-based comorbidity index was used to control for the effect of coexisting diseases on cancer management. Regression models indicated that patient age affected the intensity of both the diagnostic evaluation and therapy, even after controlling for independent factors such as comorbid disease and individual hospital differences. Patients aged 75 years and older had significantly less intensive clinical staging workups and use of surgical and radiation therapies compared with patients aged 65 to 74 years and patients aged 50 to 64 years. In conjunction with similar results noted in studies of elderly patients with other malignancies, these results suggest that age bias is likely to be widespread. Physicians need to consider life expectancy, the ability of the patient to tolerate diagnostic procedures and therapies, and the quality of life in making treatment decisions.
136 citations
References
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TL;DR: The average age at first infirmity can be raised, thereby making the morbidity curve more rectangular, and present data allow calculation of the ideal average life span, approximately 85 years.
Abstract: The average length of life has risen from 47 to 73 years in this century, but the maximum life span has not increased Therefore, survival curves have assumed an ever more rectangular form Eighty per cent of the years of life lost to nontraumatic, premature death have been eliminated, and most premature deaths are now due to the chronic diseases of the later years Present data allow calculation of the ideal average life span, approximately 85 years Chronic illness may presumably be postponed by changes in life style, and it has been shown that the physiologic and psychologic markers of aging may be modified Thus, the average age at first infirmity can be raised, thereby making the morbidity curve more rectangular Extension of adult vigor far into a fixed life span compresses the period of senescence near the end of life Health-research strategies to improve the quality of life require careful study of the variability of the phenomena of aging and how they may be modified
3,007 citations
TL;DR: The special considerations important to the proper evaluation of elderly patients are discussed, some current controversies in the field are highlighted, and recent progress in the management of several common clinical problems in the elderly are reviewed.
Abstract: OVER the next several decades the practice of medicine in the United States will be increasingly influenced by the health care needs of our rapidly enlarging elderly population. Just as children are not merely young versions of adults, the elderly are not simply old adults. They require special approaches and an understanding of the physiologic, psychosociological, and pathologic impacts of aging. This paper discusses the special considerations important to the proper evaluation of elderly patients, highlights some current controversies in the field, and reviews recent progress in the management of several common clinical problems in the elderly. Coupling Longevity with . . .
210 citations
TL;DR: Logistic regression analyses of subsamples of breast, lung, and colorectal cancer patients indicate that age is significantly inversely related to receipt of both subsequent chemotherapy and radiation therapy, controlling for stage of disease and presence of co‐morbid disease.
Abstract: Increases in cancer incidence and mortality reflect the larger numbers of elderly in the population. Using a mortality sample of 1891 biopsy-confirmed cancer patients, analyses reveal older breast, prostate, and cervical-uterine cancer victims were more likely to be diagnosed with metastases. Logistic regression analyses of subsamples of breast (N = 224), lung (N = 513), and colorectal (N = 299) cancer patients indicate that age is significantly inversely related to receipt of both subsequent chemotherapy and radiation therapy, controlling for stage of disease and presence of co-morbid disease. Exceptions to this relationship are the use of radiation therapy among nonmetastatic lung cancer patients and all breast cancer patients. The implications of these findings for current cancer control programs are discussed.
169 citations
TL;DR: Aspects of ovarian cancer as it pertains especially to elderly women (those 65 years or older) are examined according to age/stage relationships at initial diagnosis and age variations in treatment and survival.
161 citations
TL;DR: Attenuated chemotherapy with lower doses of DAT is the preferred induction regimen for elderly patients with acute nonlymphocytic leukemia since it causes fewer early deaths, allows a better quality of life, and yields survival times as durable as intensive therapy.
Abstract: Between July 1, 1981 and November 1, 1982, 45 patients with acute nonlymphocytic leukemia (age, greater than or equal to 70 years) were randomly assigned to receive induction chemotherapy using either daunorubicin, cytosine arabinoside, and 6-thioguanine in full dosage (F DAT) or an attenuated schedule of the same drugs (At DAT) as part of an Eastern Cooperative Oncology Group controlled trial. Forty patients were deemed evaluable, 20 on each arm. The overall complete remission (CR) rate for all patients in both arms was 28% (11/40). There was no significant difference in CR rates between the two arms. There were 12 early deaths (less than 60 days) in the F DAT arm compared with only five early deaths on the At DAT arm (P = .05). Due primarily to this early death rate, the median survival for the F DAT group was 29 days v 159 days for the At DAT groups (P = .02). The range of survival of the patients in CR for the At DAT group given either one or two cycles of induction therapy was 121 to 414 days, while the survival range for the F DAT CR patients was 121-186 + days. The median survival for those not achieving CR was 14 days for the F DAT group v 80 days for the At DAT (P less than .02). Fifty-nine percent of the At DAT patients spent greater than 100 days out of the hospital v 12% for the F DAT group. Attenuated chemotherapy with lower doses of DAT is the preferred induction regimen for elderly patients with acute nonlymphocytic leukemia since it causes fewer early deaths, allows a better quality of life, and yields survival times as durable as intensive therapy.
146 citations