Is cancer biology different in older patients?

The Lancet Healthy Longevity - Tập 2 - Trang e663-e677 - 2021
Yannick Van Herck1,2, Annelies Feyaerts2, Shabbir Alibhai3, Demetris Papamichael4, Lore Decoster5, Yentl Lambrechts1,2, Michael Pinchuk2, Oliver Bechter1,2, Jaime Herrera-Caceres6, Frédéric Bibeau7, Christine Desmedt8, Sigrid Hatse1,2, Hans Wildiers1,2
1Laboratory of Experimental Oncology, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium
2Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium
3Department of Medicine, Princess Margaret Cancer Centre, University Health Network & University of Toronto, Toronto, Canada
4Department of Medical Oncology, Bank of Cyprus Oncology Centre, Nicosia, Cyprus
5Department of Medical Oncology, Vrije Universiteit Brussel, University Hospitals Brussels, Brussels, Belgium
6Department of Surgical Oncology (Urological Oncology), University Health Network & University of Toronto, Toronto, Canada
7Department of Pathology, Caen University Hospital, University of Caen Normandie, Caen, France
8Laboratory for Translational Breast Cancer Research, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium

Tài liệu tham khảo

Kontis, 2017, Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble, Lancet, 389, 1323, 10.1016/S0140-6736(16)32381-9 Abbafati, 2020, Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019, Lancet, 396, 1160, 10.1016/S0140-6736(20)30977-6 Foreman, 2018, Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories, Lancet, 392, 2052, 10.1016/S0140-6736(18)31694-5 Pilleron, 2019, Global cancer incidence in older adults, 2012 and 2035: a population-based study, Int J Cancer, 144, 49, 10.1002/ijc.31664 DeSantis, 2019, Cancer statistics for adults aged 85 years and older, 2019, CA Cancer J Clin, 69, 452, 10.3322/caac.21577 Soto-Perez-de-Celis, 2018, Association between patient-reported hearing and visual impairments and functional, psychological, and cognitive status among older adults with cancer, Cancer, 124, 3249, 10.1002/cncr.31540 Sharma, 2016, Polypharmacy and potentially inappropriate medication use in geriatric oncology, J Geriatr Oncol, 7, 346, 10.1016/j.jgo.2016.07.010 Nightingale, 2015, Evaluation of a pharmacist-led medication assessment used to identify prevalence of and associations with polypharmacy and potentially inappropriate medication use among ambulatory senior adults with cancer, J Clin Oncol, 33, 1453, 10.1200/JCO.2014.58.7550 Mohile, 2011, Association of cancer with geriatric syndromes in older Medicare beneficiaries, J Clin Oncol, 29, 1458, 10.1200/JCO.2010.31.6695 Mohamed, 2020, Associations of polypharmacy and inappropriate medications with adverse outcomes in older adults with cancer: a systematic review and meta-analysis, Oncologist, 25, e94, 10.1634/theoncologist.2019-0406 Zhang, 2019, Malnutrition and overall survival in older adults with cancer: a systematic review and meta-analysis, J Geriatr Oncol, 10, 874, 10.1016/j.jgo.2019.03.002 Zhang, 2020, Malnutrition and overall survival in older patients with cancer, Clin Nutr, 40, 966, 10.1016/j.clnu.2020.06.026 Bullock, 2020, Relationship between markers of malnutrition and clinical outcomes in older adults with cancer: systematic review, narrative synthesis and meta-analysis, Eur J Clin Nutr, 74, 1519, 10.1038/s41430-020-0629-0 Dunne, 2019, Cachexia and sarcopenia in older adults with cancer: a comprehensive review, Cancers (Basel), 11, 10.3390/cancers11121861 Williams, 2019, Sarcopenia & aging in cancer, J Geriatr Oncol, 10, 374, 10.1016/j.jgo.2018.10.009 Wang, 2020, Cancer-related fatigue and biochemical parameters among cancer patients with different stages of sarcopenia, Support Care Cancer, 28, 581, 10.1007/s00520-019-04717-0 Williams, 2020, Assessment of sarcopenia measures, survival, and disability in older adults before and after diagnosis with cancer, JAMA Netw Open, 3, 10.1001/jamanetworkopen.2020.4783 Ligibel, 2020, Sarcopenia in aging, obesity, and cancer, Transl Cancer Res, 9, 5760, 10.21037/tcr-2019-eaoc-05 Oflazoglu, 2020, Prevalence and related factors of sarcopenia in newly diagnosed cancer patients, Support Care Cancer, 28, 837, 10.1007/s00520-019-04880-4 Zhang, 2020, Sarcopenia as a predictor of mortality in women with breast cancer: a meta-analysis and systematic review, BMC Cancer, 20, 172, 10.1186/s12885-020-6645-6 Pergolotti, 2020, Embracing the complexity: older adults with cancer-related cognitive decline-a young International Society of Geriatric Oncology position paper, J Geriatr Oncol, 11, 237, 10.1016/j.jgo.2019.09.002 Jayani, 2020, Association between a cognitive screening test and severe chemotherapy toxicity in older adults with cancer, J Geriatr Oncol, 11, 284, 10.1016/j.jgo.2019.10.004 Aparicio, 2013, Geriatric factors predict chemotherapy feasibility: ancillary results of FFCD 2001-02 phase III study in first-line chemotherapy for metastatic colorectal cancer in elderly patients, J Clin Oncol, 31, 1464, 10.1200/JCO.2012.42.9894 Extermann, 2012, Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score, Cancer, 118, 3377, 10.1002/cncr.26646 Gurney, 2015, The impact of patient comorbidity on cancer stage at diagnosis, Br J Cancer, 113, 1375, 10.1038/bjc.2015.355 Wildiers, 2020, Anticancer drugs are not well tolerated in all older patients with cancer, Lancet Healthy Longev, 1, e43, 10.1016/S2666-7568(20)30001-5 Hurria, 2008, Clinical pharmacology of cancer therapies in older adults, Br J Cancer, 98, 517, 10.1038/sj.bjc.6604201 Nightingale, 2019, Clinical pharmacology of oncology agents in older adults: a comprehensive review of how chronologic and functional age can influence treatment-related effects, J Geriatr Oncol, 10, 4, 10.1016/j.jgo.2018.06.008 Gomes, 2020, Age-induced accumulation of methylmalonic acid promotes tumour progression, Nature, 585, 283, 10.1038/s41586-020-2630-0 Gu, 2020, Association between depression and healthcare expenditures among elderly cancer patients, BMC Psychiatry, 20, 131, 10.1186/s12888-020-02527-x Wang, 2020, Prognostic value of depression and anxiety on breast cancer recurrence and mortality: a systematic review and meta-analysis of 282,203 patients, Mol Psychiatry, 25, 3186, 10.1038/s41380-020-00865-6 Gajra, 2015, Predictors of chemotherapy dose reduction at first cycle in patients age 65 years and older with solid tumors, J Geriatr Oncol, 6, 133, 10.1016/j.jgo.2014.12.002 Wildiers, 2007, Mastering chemotherapy dose reduction in elderly cancer patients, Eur J Cancer, 43, 2235, 10.1016/j.ejca.2007.06.013 Kagan, 2008, Ageism in cancer care, Semin Oncol Nurs, 24, 246, 10.1016/j.soncn.2008.08.004 Bidoli, 2019, Worldwide age at onset of female breast cancer: a 25-year population-based cancer registry study, Sci Rep, 9, 10.1038/s41598-019-50680-5 Schonberg, 2010, Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival, J Clin Oncol, 28, 2038, 10.1200/JCO.2009.25.9796 Lodi, 2017, Breast cancer in elderly women and altered clinico-pathological characteristics: a systematic review, Breast Cancer Res Treat, 166, 657, 10.1007/s10549-017-4448-5 Malik, 2013, Undertreated breast cancer in the elderly, J Cancer Epidemiol, 2013, 10.1155/2013/893104 Wang, 2018, Molecular features in young vs elderly breast cancer patients and the impacts on survival disparities by age at diagnosis, Cancer Med, 7, 3269, 10.1002/cam4.1544 Azim, 2015, Genomic aberrations in young and elderly breast cancer patients, BMC Med, 13, 266, 10.1186/s12916-015-0504-3 Anderson, 2011, Incidence of breast cancer in the United States: current and future trends, J Natl Cancer Inst, 103, 1397, 10.1093/jnci/djr257 de Munck, 2011, Implementation of trastuzumab in conjunction with adjuvant chemotherapy in the treatment of non-metastatic breast cancer in the Netherlands, Breast Cancer Res Treat, 129, 229, 10.1007/s10549-011-1451-0 Jenkins, 2014, Age-specific changes in intrinsic breast cancer subtypes: a focus on older women, Oncologist, 19, 1076, 10.1634/theoncologist.2014-0184 de Kruijf, 2014, Comparison of frequencies and prognostic effect of molecular subtypes between young and elderly breast cancer patients, Mol Oncol, 8, 1014, 10.1016/j.molonc.2014.03.022 Mealey, 2020, Mutational landscape differences between young-onset and older-onset breast cancer patients, BMC Cancer, 20, 212, 10.1186/s12885-020-6684-z Selenica P, Pareja F, Tadros A, et al. Genomic landscape of breast cancer occurring in elderly individuals. 2019 San Antonio Breast Cancer Symposium; San Antonio, TX; Dec 10–14, 2019 (abstr P4–05–08). Kalinsky, 2009, PIK3CA mutation associates with improved outcome in breast cancer, Clin Cancer Res, 15, 5049, 10.1158/1078-0432.CCR-09-0632 Biganzoli, 2012, Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA), Lancet Oncol, 13, e148, 10.1016/S1470-2045(11)70383-7 Gennari, 2004, Breast carcinoma in elderly women: features of disease presentation, choice of local and systemic treatments compared with younger postmenopasual patients, Cancer, 101, 1302, 10.1002/cncr.20535 Pinto, 2013, Trastuzumab for patients with HER2 positive breast cancer: delivery, duration and combination therapies, Breast, 22, S152, 10.1016/j.breast.2013.07.029 Aapro, 2012, Triple-negative breast cancer in the older population, Ann Oncol, 23, vi52, 10.1093/annonc/mds189 Dreyer, 2013, Triple negative breast cancer: clinical characteristics in the different histological subtypes, Breast, 22, 761, 10.1016/j.breast.2013.01.009 Syed, 2014, Biological characteristics and clinical outcome of triple negative primary breast cancer in older women – comparison with their younger counterparts, PLoS One, 9, 10.1371/journal.pone.0100573 Bouchalova, 2015, BCL2 is an independent predictor of outcome in basal-like triple-negative breast cancers treated with adjuvant anthracycline-based chemotherapy, Tumour Biol, 36, 4243, 10.1007/s13277-015-3061-7 Yang, 2016, New insights on PI3K/AKT pathway alterations and clinical outcomes in breast cancer, Cancer Treat Rev, 45, 87, 10.1016/j.ctrv.2016.03.004 Liu, 2019, MAP2K4 interacts with Vimentin to activate the PI3K/AKT pathway and promotes breast cancer pathogenesis, Aging (Albany NY), 11, 10697, 10.18632/aging.102485 Guo, 2017, Prognostic and clinicopathological value of GATA binding protein 3 in breast cancer: a systematic review and meta-analysis, PLoS One, 12 Mehra, 2005, Identification of GATA3 as a breast cancer prognostic marker by global gene expression meta-analysis, Cancer Res, 65, 11259, 10.1158/0008-5472.CAN-05-2495 Pham, 2013, MAP3K1: genomic alterations in cancer and function in promoting cell survival or apoptosis, Genes Cancer, 4, 419, 10.1177/1947601913513950 Maani, 2019, NF1 patients receiving breast cancer screening: Insights from the Ontario high risk breast screening program, Cancers (Basel), 11, E707, 10.3390/cancers11050707 Corso, 2018, Prognosis and outcome in CDH1-mutant lobular breast cancer, Eur J Cancer Prev, 27, 237, 10.1097/CEJ.0000000000000405 Shenoy, 2019, CDH1 (E-cadherin) mutation and gastric cancer: genetics, molecular mechanisms and guidelines for management, Cancer Manag Res, 11, 10477, 10.2147/CMAR.S208818 Rabello, 2013, Altered expression of MLL methyltransferase family genes in breast cancer, Int J Oncol, 43, 653, 10.3892/ijo.2013.1981 Hudeček, 2020, Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials, NPJ Breast Cancer, 6, 15, 10.1038/s41523-020-0155-1 Adams, 2014, Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199, J Clin Oncol, 32, 2959, 10.1200/JCO.2013.55.0491 Denkert, 2018, Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy, Lancet Oncol, 19, 40, 10.1016/S1470-2045(17)30904-X Loi, 2019, Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers, J Clin Oncol, 37, 559, 10.1200/JCO.18.01010 Desmedt, 2018, Immune infiltration in invasive lobular breast cancer, J Natl Cancer Inst, 110, 768, 10.1093/jnci/djx268 Berben, 2020, Age-related remodelling of the blood immunological portrait and the local tumor immune response in patients with luminal breast cancer, Clin Transl Immunology, 9, 10.1002/cti2.1184 Giroux Leprieur, 2012, Delay between the initial symptoms, the diagnosis and the onset of specific treatment in elderly patients with lung cancer, Clin Lung Cancer, 13, 363, 10.1016/j.cllc.2011.11.010 Zhong, 2018, Comparison of clinicopathological and molecular features between young and old patients with lung cancer, Int J Clin Exp Pathol, 11, 1031 Goodgame, 2009, Risk of recurrence of resected stage I non-small cell lung cancer in elderly patients as compared with younger patients, J Thorac Oncol, 4, 1370, 10.1097/JTO.0b013e3181b6bc1b Sterlacci, 2012, The elderly patient with surgically resected non-small cell lung cancer–a distinct situation?, Exp Gerontol, 47, 237, 10.1016/j.exger.2011.12.008 Sacher, 2016, Association between younger age and targetable genomic alterations and prognosis in non-small-cell lung cancer, JAMA Oncol, 2, 313, 10.1001/jamaoncol.2015.4482 Tsao, 2012, Clinical outcomes and biomarker profiles of elderly pretreated NSCLC patients from the BATTLE trial, J Thorac Oncol, 7, 1645, 10.1097/JTO.0b013e31826910ff Dong, 2016, EGFR, ALK, RET, KRAS and BRAF alterations in never-smokers with non-small cell lung cancer, Oncol Lett, 11, 2371, 10.3892/ol.2016.4235 Boldrini, 2018, Expression profiling and microRNA regulation of the LKB1 pathway in young and aged lung adenocarcinoma patients, Biomed Rep, 9, 198 Ye, 2014, Analysis of the molecular and clinicopathologic features of surgically resected lung adenocarcinoma in patients under 40 years old, J Thorac Dis, 6, 1396 Velcheti, 2014, Programmed death ligand-1 expression in non-small cell lung cancer, Lab Invest, 94, 107, 10.1038/labinvest.2013.130 Lin, 2015, Programmed death-ligand 1 expression predicts tyrosine kinase inhibitor response and better prognosis in a cohort of patients with epidermal growth factor receptor mutation-positive lung adenocarcinoma, Clin Lung Cancer, 16, e25, 10.1016/j.cllc.2015.02.002 Perrotta, 2019, Immune checkpoint blockade for advanced NSCLC: a new landscape for elderly patients, Int J Mol Sci, 20, 10.3390/ijms20092258 Zhang, 2016, The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis, Oncotarget, 7, 78985, 10.18632/oncotarget.12587 Eberhard, 2005, Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib, J Clin Oncol, 23, 5900, 10.1200/JCO.2005.02.857 Choi, 2018, EGFR exon 19 deletion is associated with favorable overall survival after first-line gefitinib therapy in advanced non-small cell lung cancer patients, Am J Clin Oncol, 41, 385, 10.1097/COC.0000000000000282 Lohinai, 2017, KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS mutation and bone metastasis, Sci Rep, 7, 10.1038/srep39721 Awad, 2016, MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression, J Clin Oncol, 34, 721, 10.1200/JCO.2015.63.4600 Giordano, 2018, Differential microRNA expression profiles between young and old lung adenocarcinoma patients, Am J Transl Res, 10, 892 Paik, 2011, Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations, J Clin Oncol, 29, 2046, 10.1200/JCO.2010.33.1280 Bergethon, 2012, ROS1 rearrangements define a unique molecular class of lung cancers, J Clin Oncol, 30, 863, 10.1200/JCO.2011.35.6345 Shaw, 2014, Crizotinib in ROS1-rearranged non-small-cell lung cancer, N Engl J Med, 371, 1963, 10.1056/NEJMoa1406766 Peters, 2017, Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer, N Engl J Med, 377, 829, 10.1056/NEJMoa1704795 Solomon, 2014, First-line crizotinib versus chemotherapy in ALK-positive lung cancer, N Engl J Med, 371, 2167, 10.1056/NEJMoa1408440 Mazières, 2015, Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort, J Clin Oncol, 33, 992, 10.1200/JCO.2014.58.3302 Vuong, 2018, Clinicopathological implications of MET exon 14 mutations in non-small cell lung cancer–a systematic review and meta-analysis, Lung Cancer, 123, 76, 10.1016/j.lungcan.2018.07.006 Paik, 2020, Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations, N Engl J Med, 383, 931, 10.1056/NEJMoa2004407 Wolf, 2020, Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer, N Engl J Med, 383, 944, 10.1056/NEJMoa2002787 Brody, 2017, PD-L1 expression in advanced NSCLC: insights into risk stratification and treatment selection from a systematic literature review, Lung Cancer, 112, 200, 10.1016/j.lungcan.2017.08.005 Srivastava, 2012, Myeloid suppressor cells and immune modulation in lung cancer, Immunotherapy, 4, 291, 10.2217/imt.11.178 Ortiz, 2014, Myeloid-derived suppressor cells in the development of lung cancer, Cancer Immunol Res, 2, 50, 10.1158/2326-6066.CIR-13-0129 Chen, 2015, Myeloid-derived suppressor cells promote age-related increase of lung cancer growth via B7-H1, Exp Gerontol, 61, 84, 10.1016/j.exger.2014.12.001 Bray, 2018, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer J Clin, 68, 394, 10.3322/caac.21492 Boyle, 2019, Updated recommendations of the International Society of Geriatric Oncology on prostate cancer management in older patients, Eur J Cancer, 116, 116, 10.1016/j.ejca.2019.04.031 Pettersson, 2018, Age at diagnosis and prostate cancer treatment and prognosis: a population-based cohort study, Ann Oncol, 29, 377, 10.1093/annonc/mdx742 Zhang, 2013, Age and racial differences among PSA-detected (AJCC stage T1cN0M0) prostate cancer in the U.S.: a population-based study of 70,345 men, Front Oncol, 3, 312, 10.3389/fonc.2013.00312 Dinerman, 2017, Population-based study of the incidence and survival for intraductal carcinoma of the prostate, Urol Oncol, 35, 673.e9, 10.1016/j.urolonc.2017.08.015 Goldberg, 2020, Clinical-genomic characterization unveils more aggressive disease features in elderly prostate cancer patients with low-grade disease, Eur Urol Focus Calvocoressi, 2018, Prostate cancer aggressiveness and age: impact of p53, BCL-2 and microvessel density, J Investig Med, 66, 1142, 10.1136/jim-2018-000804 Jędroszka, 2017, Markers of epithelial-to-mesenchymal transition reflect tumor biology according to patient age and Gleason score in prostate cancer, PLoS One, 12, 10.1371/journal.pone.0188842 Schaefer, 2013, Distinct ERG rearrangement prevalence in prostate cancer: higher frequency in young age and in low PSA prostate cancer, Prostate Cancer Prostatic Dis, 16, 132, 10.1038/pcan.2013.4 Matsugasumi, 2017, Morphometric analysis of prostate zonal anatomy using magnetic resonance imaging: impact on age-related changes in patients in Japan and the USA, BJU Int, 120, 497, 10.1111/bju.13823 Dinerman, 2017, Intraductal carcinoma of the prostate: a risk for rapid recurrence, Urology, 105, e1, 10.1016/j.urology.2017.03.030 Hollemans, 2019, Large cribriform growth pattern identifies ISUP grade 2 prostate cancer at high risk for recurrence and metastasis, Mod Pathol, 32, 139, 10.1038/s41379-018-0157-9 Fenton, 2018, Prostate-specific antigen-based screening for prostate cancer evidence report and systematic review for the us preventive services task force, JAMA, 319, 1914, 10.1001/jama.2018.3712 Sun, 2017, Influence of age on seven putative prostate tumor markers: a cohort study in Chinese men, Asian J Androl, 19, 463, 10.4103/1008-682X.175787 Palsdottir, 2019, Are Prostate specific-antigen (PSA) and age associated with the risk of ISUP grade 1 prostate cancer? Results from 72 996 individual biopsy cores in 6 083 men from the Stockholm3 study, PLoS One, 14, 10.1371/journal.pone.0218280 Klatte, 2012, Age-specific PCA3 score reference values for diagnosis of prostate cancer, World J Urol, 30, 405, 10.1007/s00345-011-0749-1 Hennenlotter, 2020, Age-adapted prostate cancer gene 3 score interpretation - suggestions for clinical use, Clin Lab, 66, 10.7754/Clin.Lab.2019.190714 Vertosick, 2020, Prespecified 4-Kallikrein marker model at age 50 or 60 for early detection of lethal prostate cancer in a large population based cohort of asymptomatic men followed for 20 years, J Urol, 204, 281, 10.1097/JU.0000000000001007 Zhao, 2017, Associations of luminal and basal subtyping of prostate cancer with prognosis and response to androgen deprivation therapy, JAMA Oncol, 3, 1663, 10.1001/jamaoncol.2017.0751 García-Perdomo, 2018, Association between TMPRSS2:ERG fusion gene and the prostate cancer: systematic review and meta-analysis, Cent European J Urol, 71, 410 Song, 2018, Predictive significance of TMRPSS2-ERG fusion in prostate cancer: a meta-analysis, Cancer Cell Int, 18, 177, 10.1186/s12935-018-0672-2 Schuurman, 2020, Melanoma in older patients: declining gap in survival between younger and older patients with melanoma, Acta Oncol, 59, 4, 10.1080/0284186X.2019.1643914 Weiss, 2016, Impact of aging on host immune response and survival in melanoma: an analysis of 3 patient cohorts, J Transl Med, 14, 299, 10.1186/s12967-016-1026-2 Ciocan, 2013, Distinctive features of melanoma and its management in elderly patients: a population-based study in France, JAMA Dermatol, 149, 1150, 10.1001/jamadermatol.2013.706 Macdonald, 2011, Malignant melanoma in the elderly: different regional disease and poorer prognosis, J Cancer, 2, 538, 10.7150/jca.2.538 Shen, 2014, Characteristics and associations of high-mitotic-rate melanoma, JAMA Dermatol, 150, 1048, 10.1001/jamadermatol.2014.635 Cavanaugh-Hussey, 2015, Older age is associated with a higher incidence of melanoma death but a lower incidence of sentinel lymph node metastasis in the SEER Databases (2003-2011), Ann Surg Oncol, 22, 2120, 10.1245/s10434-015-4538-8 Bauer, 2011, BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site, Pigment Cell Melanoma Res, 24, 345, 10.1111/j.1755-148X.2011.00837.x Menzies, 2011, BRAF mutation by age-decade and body mass index in metastatic melanoma, J Clin Oncol, 29, 10.1200/jco.2011.29.15_suppl.8507 Devitt, 2011, Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma, Pigment Cell Melanoma Res, 24, 666, 10.1111/j.1755-148X.2011.00873.x Thomas, 2013, Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study, J Clin Oncol, 31, 4252, 10.1200/JCO.2013.51.3002 Heppt, 2017, Prognostic significance of BRAF and NRAS mutations in melanoma: a German study from routine care, BMC Cancer, 17, 536, 10.1186/s12885-017-3529-5 Geller, 2009, Factors related to the presentation of thin and thick nodular melanoma from a population-based cancer registry in Queensland Australia, Cancer, 115, 1318, 10.1002/cncr.24162 Kalkhoran, 2010, Historical, clinical, and dermoscopic characteristics of thin nodular melanoma, Arch Dermatol, 146, 311, 10.1001/archdermatol.2009.369 Kvaskoff, 2015, Solar elastosis and cutaneous melanoma: a site-specific analysis, Int J Cancer, 136, 2900, 10.1002/ijc.29335 Thomas, 2010, Associations of cumulative sun exposure and phenotypic characteristics with histologic solar elastosis, Cancer Epidemiol Biomarkers Prev, 19, 2932, 10.1158/1055-9965.EPI-10-0686 Huismans, 2014, Primary melanoma location on the scalp is an important risk factor for brain metastasis: a study of 1,687 patients with cutaneous head and neck melanomas, Ann Surg Oncol, 21, 3985, 10.1245/s10434-014-3829-9 Gardner, 2017, Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis, Melanoma Res, 27, 477, 10.1097/CMR.0000000000000382 Ozao-Choy, 2017, The prognostic importance of scalp location in primary head and neck melanoma, J Surg Oncol, 116, 337, 10.1002/jso.24679 Xie, 2017, Impact of scalp location on survival in head and neck melanoma: a retrospective cohort study, J Am Acad Dermatol, 76, 494, 10.1016/j.jaad.2016.08.009 Shaikh, 2012, The contribution of nodular subtype to melanoma mortality in the United States, 1978 to 2007, Arch Dermatol, 148, 30, 10.1001/archdermatol.2011.264 Akbani, 2015, Genomic classification of cutaneous melanoma, Cell, 161, 1681, 10.1016/j.cell.2015.05.044 Ekedahl, 2013, The clinical significance of BRAF and NRAS mutations in a clinic-based metastatic melanoma cohort, Br J Dermatol, 169, 1049, 10.1111/bjd.12504 Long, 2011, Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma, J Clin Oncol, 29, 1239, 10.1200/JCO.2010.32.4327 Thomas, 2015, Association between NRAS and BRAF mutational status and melanoma-specific survival among patients with higher-risk primary melanoma, JAMA Oncol, 1, 359, 10.1001/jamaoncol.2015.0493 Dummer, 2017, Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial, Lancet Oncol, 18, 435, 10.1016/S1470-2045(17)30180-8 Johnson, 2015, Impact of NRAS mutations for patients with advanced melanoma treated with immune therapies, Cancer Immunol Res, 3, 288, 10.1158/2326-6066.CIR-14-0207 Taylor, 2007, Tumor-infiltrating lymphocytes predict sentinel lymph node positivity in patients with cutaneous melanoma, J Clin Oncol, 25, 869, 10.1200/JCO.2006.08.9755 Clemente, 1996, Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma, Cancer, 77, 1303, 10.1002/(SICI)1097-0142(19960401)77:7<1303::AID-CNCR12>3.0.CO;2-5 Krynitz, 2015, Cutaneous malignant melanoma in the Swedish organ transplantation cohort: a study of clinicopathological characteristics and mortality, J Am Acad Dermatol, 73, 106, 10.1016/j.jaad.2015.03.045 Siegel, 2020, Colorectal cancer statistics, 2020, CA Cancer J Clin, 70, 145, 10.3322/caac.21601 Ferlay, 2010, Estimates of cancer incidence and mortality in Europe in 2008, Eur J Cancer, 46, 765, 10.1016/j.ejca.2009.12.014 Yang, 2018, Proximal shift of colorectal cancer with increasing age in different ethnicities, Cancer Manag Res, 10, 2663, 10.2147/CMAR.S166548 Kotake, 2015, Tumour characteristics, treatment patterns and survival of patients aged 80 years or older with colorectal cancer, Colorectal Dis, 17, 205, 10.1111/codi.12826 Patel, 2013, Elderly patients with colon cancer have unique tumor characteristics and poor survival, Cancer, 119, 739, 10.1002/cncr.27753 Derwinger, 2010, Age aspects of demography, pathology and survival assessment in colorectal cancer, Anticancer Res, 30, 5227 Wu, 2019, Prognoses of different pathological subtypes of colorectal cancer at different stages: a population-based retrospective cohort study, BMC Gastroenterol, 19, 164, 10.1186/s12876-019-1083-0 Vedeld, 2017, CpG island methylator phenotype identifies high risk patients among microsatellite stable BRAF mutated colorectal cancers, Int J Cancer, 141, 967, 10.1002/ijc.30796 Barault, 2008, Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases, Cancer Res, 68, 8541, 10.1158/0008-5472.CAN-08-1171 Jia, 2016, No association of CpG island methylator phenotype and colorectal cancer survival: population-based study, Br J Cancer, 115, 1359, 10.1038/bjc.2016.361 Bläker, 2019, The association between mutations in BRAF and colorectal cancer-specific survival depends on microsatellite status and tumor stage, Clin Gastroenterol Hepatol, 17, 455, 10.1016/j.cgh.2018.04.015 Aasebø, 2019, Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: a population-based cohort of metastatic colorectal cancer patients, Cancer Med, 8, 3623, 10.1002/cam4.2205 Aparicio, 2014, High prevalence of deficient mismatch repair phenotype and the V600E BRAF mutation in elderly patients with colorectal cancer, J Geriatr Oncol, 5, 384, 10.1016/j.jgo.2014.08.002 Sorbye, 2015, High BRAF mutation frequency and marked survival differences in subgroups according to KRAS/BRAF mutation status and tumor tissue availability in a prospective population-based metastatic colorectal cancer cohort, PLoS One, 10, 10.1371/journal.pone.0131046 Phipps, 2012, BRAF mutation status and survival after colorectal cancer diagnosis according to patient and tumor characteristics, Cancer Epidemiol Biomarkers Prev, 21, 1792, 10.1158/1055-9965.EPI-12-0674 Dai, 2020, Prognostic value of KRAS mutation status in colorectal cancer patients: a population-based competing risk analysis, PeerJ, 8, 10.7717/peerj.9149 Fariña-Sarasqueta, 2010, The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients, Ann Oncol, 21, 2396, 10.1093/annonc/mdq258 Berg, 2010, DNA sequence profiles of the colorectal cancer critical gene set KRAS-BRAF-PIK3CA-PTEN-TP53 related to age at disease onset, PLoS One, 5, 10.1371/journal.pone.0013978 Carini, 2017, Colorectal carcinogenesis: role of oxidative stress and antioxidants, Anticancer Res, 37, 4759 Vogelstein, 1993, The multistep nature of cancer, Trends Genet, 9, 138, 10.1016/0168-9525(93)90209-Z Markowitz, 2009, Molecular origins of cancer: molecular basis of colorectal cancer, N Engl J Med, 361, 2449, 10.1056/NEJMra0804588 Nagtegaal, 2020, The 2019 WHO classification of tumours of the digestive system, Histopathology, 76, 182, 10.1111/his.13975 De Palma, 2019, The molecular hallmarks of the serrated pathway in colorectal cancer, Cancers (Basel), 11, 10.3390/cancers11071017 Li, 2017, Impact of age and mismatch repair status on survival in colorectal cancer, Cancer Med, 6, 975, 10.1002/cam4.1007 Dejea, 2014, Microbiota organization is a distinct feature of proximal colorectal cancers, Proc Natl Acad Sci USA, 111, 18321, 10.1073/pnas.1406199111 Arnold, 2017, Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials, Ann Oncol, 28, 1713, 10.1093/annonc/mdx175 Issa, 2004, CpG island methylator phenotype in cancer, Nat Rev Cancer, 4, 988, 10.1038/nrc1507 Jass, 2005, Serrated adenoma of the colorectum and the DNA-methylator phenotype, Nat Clin Pract Oncol, 2, 398, 10.1038/ncponc0248 Pritchard, 2011, Colorectal cancer molecular biology moves into clinical practice, Gut, 60, 116, 10.1136/gut.2009.206250 Bylsma, 2020, Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: a systematic review and meta-analysis, Cancer Med, 9, 1044, 10.1002/cam4.2747 Sanz-Garcia, 2017, BRAF mutant colorectal cancer: prognosis, treatment, and new perspectives, Ann Oncol, 28, 2648, 10.1093/annonc/mdx401 Kopetz, 2019, Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer, N Engl J Med, 381, 1632, 10.1056/NEJMoa1908075 Serebriiskii, 2019, Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients, Nat Commun, 10, 10.1038/s41467-019-11530-0 Juo, 2014, Prognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and meta-analysis, Ann Oncol, 25, 2314, 10.1093/annonc/mdu149 Molina-Cerrillo, 2020, BRAF mutated colorectal cancer: new treatment approaches, Cancers (Basel), 12, 10.3390/cancers12061571 Aparicio, 2013, Deficient mismatch repair phenotype is a prognostic factor for colorectal cancer in elderly patients, Dig Liver Dis, 45, 245, 10.1016/j.dld.2012.09.013 Mlecnik, 2020, Multicenter international society for immunotherapy of cancer study of the consensus immunoscore for the prediction of survival and response to chemotherapy in stage III colon cancer, J Clin Oncol, 38, 3638, 10.1200/JCO.19.03205 Pagès, 2018, International validation of the consensus immunoscore for the classification of colon cancer: a prognostic and accuracy study, Lancet, 391, 2128, 10.1016/S0140-6736(18)30789-X Malka, 2020, Immune scores in colorectal cancer: where are we?, Eur J Cancer, 140, 105, 10.1016/j.ejca.2020.08.024 Chatsirisupachai, 2021, An integrative analysis of the age-associated multi-omic landscape across cancers, Nat Commun, 12, 10.1038/s41467-021-22560-y