In recent years, with the aging of the population, the impact of malignant tumors on the survival of elderly patients has become more and more obvious. Surveys in the United States show that tumors are the leading cause of death among people aged 60-79 years, >50% of tumor patients are >65 years old, >70% of tumor-related deaths occur above 65 years old, and it is expected that more than 70% of patients with initial cancer diagnosis in the United States will be >65 years old in 2030. How to treat this special population of elderly oncology patients is a real problem faced by clinical staff. Because of the unique nature of this patient population and the lack of guidance for a particular geriatric oncology disease, the National Comprehensive Cancer Network (NCCN) geriatric oncology guidelines released this year provide an important reference for clinicians. Prediction of survival time for elderly patients Actual age is not indicative of expected survival time, functional status, or treatment complications, nor is it scientific to predict survival time for each elderly patient based on the physician’s personal experience. Walter et al. showed that among elderly women aged 75 years, 25% of those in good general condition had a survival time of up to 17 years, 50% of those in fair health had a predicted survival time of 12 years, and 25% of those in poor general condition had a predicted survival time of no more than 7 years. The 2-year and 4-year mortality risk models based on the functional status, age and gender of elderly patients, and the understanding of the survival pattern of the elderly population will provide a favorable basis for the formulation of rational treatment strategies. Clinical and research status of geriatric oncology An analysis of data from nearly 30,000 oncology patients in the United States shows that the proportion of elderly patients who can participate in clinical studies is decreasing with increasing age, and the proportion of patients over 65 and 75 years of age participating in clinical studies has decreased from about 60% to about 10%. Older breast cancer patients had the highest percentage of participation in clinical studies, and patients with central nervous system tumors had the lowest percentage of participation. In most tumors, older patients are in the majority, e.g., lung cancer patients are in the majority, yet clinical data are almost exclusively from non-elderly patients, with only a few small samples of subgroups of older patients analyzed. It is clear that the treatment of the elderly cannot be guided by studies of non-elderly patients. Despite the lack of evidence-based evidence for the treatment of elderly tumors, the treatment of the elderly should not be ignored, and clinical experience tells us that the use of effective drugs in elderly patients should not be restricted solely on the basis of age, but the application of treatments that clearly affect quality of life and have no survival benefit should be avoided. Clinical guidelines for guidelines We should first assess patients based on their functional status, co-morbidities and life expectancy before we can develop an appropriate treatment strategy. The assessment includes risk assessment of the tumor disease itself, including clinical stage, risk of recurrence progression, etc.; assessment of comorbid conditions that interfere with tumor treatment and tolerability, including malnutrition, sensory impairment, combination medications, social support, depression, dementia, falls, etc.; and assessment of the patient’s desired goals for treatment. On this basis, stratification was performed according to the time to tumor death or life expectancy and the risk of comorbidities. Intermediate and high-risk individuals must be further evaluated for functional dependence and comorbidities, and the patient’s desired goals must be assessed again and treated separately according to the three levels of functional status. Low-risk individuals may be treated with symptom control and supportive care. The guidelines also address the general principles of treatment in surgery, radiology and internal medicine and the characteristics of certain tumors in elderly patients. The Comprehensive Geriatric Assessment (CGA) system is the core of geriatric oncologic assessment, which is different from the Karnofsky Physical Status (KPS) score and the Eastern Cooperative Oncology Group (ECOG) score. Even for patients with good KPS or ECOG scores, some of them have poor functional status and cannot tolerate conventional treatment. Li (Li et al.) evaluated 700 elderly oncology patients ≥65 years old in China, and showed that 12% of patients with ECOG score 0-2 were completely unable to take care of themselves in daily life. And the CGA assessment system includes several aspects of functional status, comorbidities, compound medication, socioeconomic status, geriatric syndrome and nutritional status, which are mainly divided into three parts: (i) functional assessment; (ii) comorbidity assessment; and (iii) compound medication assessment. Functional assessment The degree of functional dependence and impairment often reflects the real health and physical function of the elderly, which is the core of CGA assessment and an important basis for treatment selection. The functional assessment is mainly the ability to perform activities of daily living (ADL) and the ability to use the tools of daily living (IADL). ADL is mainly the basic functions of normal indoor living, including the ability to take care of oneself such as eating, dressing and bathing, while IADL is the complex functions that can maintain independence of movement in the community, including taking transportation, managing money, taking medication, shopping, making phone calls, cleaning, etc. In older patients, having independent IADL is associated with tolerable chemotherapy and prolonged survival. Assessments can also be combined with laboratory tests to assess patients’ risk of reduced function and increased mortality; for example, studies have found that elevated interleukin-6 (IL-6) and D-dimer are associated with functional dependence and mortality in community-dwelling solitaries ≥71 years of age, and that ≥70 years of age, elevated IL-6 and C-reactive protein are associated with slow walking and decreased grip strength, and elevated D-dimer is associated with decreased cognitive function. In the future, testing for inflammatory markers (IL-6, D-dimer) may be able to predict the physiological age of older patients. Comorbidity assessment As patients age, comorbidities such as heart disease, renal failure, dementia, depression, anemia, and osteoporosis also increase significantly, significantly affecting the treatment and tolerability of the tumor, and attention must be paid to the interaction between comorbidities and tumor in elderly patients. Comorbidity affects the efficacy of tumor through the following three ways: (1) severe comorbidity makes the adverse effects of treatment too obvious; (2) the interaction between comorbid diseases and tumor treatment affects patient’s function; (3) tumor treatment does not prolong patient’s survival due to comorbid diseases. Therefore, patients should be evaluated for comorbid diseases before treatment. Oncology treatment may interfere with comorbidities and affect patients’ functional status (e.g. renal insufficiency); increase the risk of oncology treatment due to severe comorbidities (e.g. cardiomyopathy); renal insufficiency, diabetes mellitus, pulmonary disease, smoking and cardiac insufficiency reduce life expectancy. One study found that disease-free survival (DFS) was shorter in colorectal cancer patients with comorbid diabetes mellitus (DM) than in those without DM. The assessment of comorbidities should also include an evaluation of their severity, with special attention to GI problems, renal insufficiency, heart disease, DM, anemia, dementia, depression, osteoporosis, pulmonary disorders, smoking, and alcohol use. Other evaluations Drug-drug and drug-patient interactions are also important issues in the treatment of elderly patients, with more comorbidities, more significant compounding and more adverse drug reactions and drug-drug interactions. Beers et al. established a method to detect potential risks when prescribing multiple drugs in elderly patients. Samsa et al. also studied the safety of older patients when polypharmacy was prescribed, and the application of these tools minimized the risk when polypharmacy was prescribed to older patients. The CGA system also includes assessment of concurrent use of multiple medications, assessment of nutritional status, assessment of cognitive function, assessment of socioeconomic status, and assessment of geriatric syndromes, particularly dementia, depression, falls, delirium, and osteoporosis. Other issues that should be noted The guideline is equally concerned with common symptoms in older patients that can lead to functional dependence, especially in those with pre-existing IADL dependence. Severe symptoms can lead to functional decline and compromise treatment. For example, in patients with advanced tumors, more than 50-70% of patients will experience tumor-related fatigue, which is even more severe than pain or nausea and vomiting, and will lead to a rapid decline in function in elderly patients and compromise prognosis. Of course, the CGA system cannot be used for all elderly patients, and some specialty assessment methods can be used as a supplement to CGA for a more comprehensive evaluation of specific problems. Summary Using the CGA system, appropriate patients can be selected for effective and safe treatment. Based on the screening and CGA system, elderly patients will be classified into high, medium and low risk groups. For the high and medium risk groups, the degree of functional dependence and concurrent diseases will be further evaluated, while for the low risk patients, only symptom control or palliative care is required. Patients in the medium- and high-risk groups will be divided into functionally independent, moderately impaired, and major functionally impaired and/or with comorbid disease groups based on their functional assessment. Patients who are functionally independent and without serious co-morbidities can receive most normal treatment without regard to age, and symptom control or supportive treatment only if there are contraindications; for patients with moderate functional impairment, whether or not they have co-morbidities, they are prone to treatment complications, and individualized treatment should be considered for this group, with special consideration of their treatment dose, and symptom control or supportive treatment only is still considered if there are contraindications If there is a contraindication, only symptom control or supportive therapy should be considered; for those with major functional impairment and/or comorbidities, only supportive therapy should be given regardless of the presence or absence of serious co-morbidities. The CGA system provides clinical guidance on the use of the Comprehensive Geriatric Assessment (CGA) system in classifying patients into treatable, modifiable, and supportive populations. Internal therapy Subgroup analysis of some previous studies found that patients aged ≥70 years did not tolerate chemotherapy significantly differently from non-elderly patients, but the elderly patients in these clinical studies were screened and may be healthier than the general elderly population, and the results of the studies are not representative of the status of all elderly patients. The analysis of 60 patients aged ≥70 years before and after chemotherapy by Chen (Chen et al.) showed that elderly patients generally tolerated the adverse effects of chemotherapy with limited effects on functional dependence, complications, and quality of life, and that treatment of elderly patients should be observed and monitored promptly. Hurria et al. found that patients ≥73 years old, with gastrointestinal and urinary tract tumors, using standard chemotherapy regimens, polypharmacy, relapsing within 6 months, functional dependence and lacking social support were prone to grade ≥3 adverse reactions after chemotherapy in a model established with 500 elderly patient data. Extermanna et al. developed a mathematical model that predicts adverse reactions after chemotherapy in elderly patients, and he also summarized the current clinical applications of CGA, including prediction of chemotherapy toxicity, probability of survival, perioperative complications, and prolonged postoperative hospital stay.The continued expansion of CGA in clinical applications will bring the treatment of elderly patients into the era of individualization. Studies in the elderly have found age-related cardiotoxicity of anthracyclines and trastuzumab-related cardiotoxicity (CHF). Cerebellar neurotoxicity due to cytarabine was strongly correlated with age (>60 years) and reduced renal function. The myelosuppressive effect of chemotherapy is significantly higher from the age of 65 years, and the application of growth factors reduces myelosuppression by 50%. For some tumors, the reduction in drug dose may sacrifice efficacy, necessitating the use of colony-stimulating factors and shortening the length of stay in elderly patients. Aging is associated with infections resulting from granulocyte decline after treatment with cyclophosphamide + doxorubicin + vincristine + prednisone (CHOP) regimens for large cell lymphoma, and NCCN guidelines recommend prophylactic use of growth factors when treating lymphoma patients ≥65 years of age with CHOP or CHOP-like regimens. With aging, decreased glomerular filtration rate (GFR) leads to decreased drug excretion, allowing accumulation of drugs (platinum, methotrexate, bleomycin) excreted via the kidneys, leading to increased toxicity. Elderly patients with oncology, genitourinary tumors, multiple myeloma, and those with previous renal disease often develop renal dysfunction and should avoid drugs with nephrotoxicity as much as possible. When assessing renal function, the blood creatinine index does not reflect the renal function status, and creatinine clearance should be selected for assessment in order to adjust the drug dose. In the treatment of elderly patients, special attention should be paid to certain drugs: the risk of arterial thrombosis, gastrointestinal perforation and hypertension due to bevacizumab. In addition, the ECOG4599 study showed that a subgroup analysis of patients ≥70 years of age found that chemotherapy combined with bevacizumab did not prolong patient survival compared with chemotherapy alone. In addition, the panel recommends that elderly lymphoma patients should be closely monitored for hepatitis B virus (HBV) activity status when using rituximab. Surgical treatment One study analyzed the postoperative risk of 460 oncology patients ≥70 years old by CGA and showed that postoperative complications were more frequent in complex procedures than in moderate and simple procedures, but there were no differences in complication rates and prolonged hospital stays among patients at different age stages (70-74, 75-79, and ≥80 years old) in each procedure. Preoperative prediction of patients’ postoperative risk showed that age was not the primary consideration for surgery, that general condition and co-morbidities were more important than age, and that patients should also undergo postoperative follow-up to return to preoperative function as soon as possible. The guidelines also recommend preoperative evaluation using standard surgical assessment tools. Radiotherapy Elderly patients who are unable to undergo surgery and chemotherapy may benefit from radical or palliative radiotherapy. For patients who cannot tolerate conventional radiotherapy, hyperfractionated radiotherapy is an option, which has been shown to be effective and well tolerated in the treatment of elderly patients, and age is not a limiting factor. Simultaneous radiotherapy for elderly patients should be treated with great caution, especially for elderly locally advanced non-small cell lung cancer. The dose of chemotherapy drugs needs to be adjusted to reduce toxic effects, and amphotericin is available for radiotherapy of head and neck tumors. The NCCN guidelines for the treatment of geriatric oncology realize the concept of humane treatment for patients, and pay more attention to the functional status of elderly patients than their actual age through screening and functional assessment of elderly patients; pay attention to and objectively assess the life expectancy of elderly patients, so that treatment can be more in line with the desired goals of the elderly; pay attention to comorbidities and compound drug use, so that treatment can avoid reducing life expectancy and functional impairment as much as possible; pay attention to the control and management of symptoms in the elderly, so that patients can maintain their life expectancy and functional impairment. The goal is to maintain a better quality of life and tolerability for patients by focusing on the control and management of geriatric symptoms. The goals of treatment benefit for elderly oncology patients are to prolong survival, maintain and improve quality of life and function, and provide better symptom relief. Enabling patients to benefit from treatment and avoid reducing life expectancy and tolerability is a new challenge for us. The guidelines not only provide us with knowledge and methods, but also enable us to develop new concepts and to put them into practice through our actions. The field of geriatric oncology is challenging and an area that increasingly requires attention. We will put theory into clinical practice through continuous learning and careful practice, and we will continue to be progressive and innovative.