Abstract
Lung cancer represents a major public health issue worldwide. Unfortunately, more than half of them are diagnosed at an advanced stage. Moreover, even if diagnosed early, diagnosis procedures and treatment can be difficult due to the frequent comorbidities observed in these patients. Some of these comorbidities have a common major risk factor, i.e. smoking, whereas others are unrelated to smoking but frequently observed in the general population. These comorbidities must be carefully assessed before any diagnostic and/or therapeutic decisions are made regarding the lung cancer. For example, in a patient with severe emphysema or with diffuse lung fibrosis, transthoracic needle biopsy can be contraindicated, meaning that in some instances a precise diagnosis cannot be obtained; in a patient with chronic obstructive pulmonary disease, surgery may be impossible or should be preceded by intensive rehabilitation; patients with interstitial lung disease are at risk of radiation pneumonitis and should not receive drugs which can worsen the respiratory insufficiency. Patients who belong to what are called “special populations”, e.g. elderly or HIV infected, should be treated specifically, especially regarding systemic treatment. Last but not least, psychosocial factors are of great importance and can vary from one country to another according to health insurance coverage.
Abstract
Comorbidities are frequent in patients with lung cancer and impact on their diagnostic and therapeutic management http://ow.ly/7ixJ307cpbL
Introduction
Lung cancer is the most frequent cause of death by cancer worldwide. Most lung cancers are diagnosed at an advanced stage, either locally or metastatic. Surgery is the main treatment for early-stage disease whereas concurrent chemotherapy and radiation therapy must be considered for locally advanced disease and chemotherapy for stage IV disease (or targeted therapies in case of EGFR mutations, V600E BRAF mutation, and ALK or ROS1 translocation).
With lung cancer being far more frequent in smokers and ex-smokers, these patients often have tobacco-related illnesses, mainly cardiovascular (ischaemic or hypertensive heart disease, lower limbs arteriopathy, etc.) and respiratory (chronic obstructive pulmonary disease (COPD), obstructive sleep apnoea, usual interstitial fibrosis. etc.) in nature. They can also have other comorbidities that are unrelated to tobacco use but that are frequent in the general population, e.g. diabetes and its complications (renal insufficiency, cardiovascular damage). These comorbidities can alter the performance status of the patients often more than the tumour development. Lung cancer is also more frequent in elderly patients because ageing is by itself a risk factor for the development of lung cancer. Of course, comorbidities are more frequent with ageing and more severe independent of the physiological alterations inherent to ageing. All these comorbidities can have deleterious effects on the diagnostic procedures and, moreover, on the treatment possibilities and thus must be carefully explored.
Epidemiology
Respiratory diseases
Chronic obstructive pulmonary disease and emphysema
COPD is the fourth leading cause of death worldwide. COPD and lung cancer are closely related, first because they share the same main risk factor, smoking exposure, which is found in 85–90% of those diagnosed with either COPD or lung cancer. However, COPD is also an independent risk factor for lung cancer, taking into account sex, age and smoking history. Smokers with COPD are five times more likely to develop lung cancer than smokers without COPD [1, 2]. The risk of developing lung cancer is correlated with the lung function measure forced expiratory volume in 1 s (FEV1) and with female sex [3]. Emphysema, which is frequently associated with COPD, also increases the risk of lung cancer [4]. Coexisting COPD is associated with worse survival outcomes after surgery in patients with early-stage (IA and IB) nonsmall cell lung cancer (NSCLC), especially in men and in squamous-cell carcinomas (5-year overall survival, 54.4% with COPD versus 69.0% without, p=0.0002) [5]. The association between COPD and lung cancer is explained by several mechanisms. Oxidative damage [6] and chronic inflammation enhance oncogenesis involving inflammatory mediators and DNA repair [7, 8]. Moreover, the irreversible airflow obstruction that characterises COPD can lead to airborne carcinogen retention. Genetic and epigenetic factors (CHRNA3/5, HHIP, TERT, DNA hypermethylation, miRNAs, etc.) might also be implicated in both lung cancer and COPD [9–11].
Bronchiectasis
Bronchiectasis is a chronic respiratory disease characterised by irreversible airway dilatation. It is caused by chronic inflammation and infections resulting in the destruction of the bronchial walls, and is associated with systemic inflammation [12]. Mechanisms that explain the relationship between lung cancer and bronchiectasis are poorly known. In the same way as in COPD, chronic inflammation leads to carcinogenesis. About 20% of cancers worldwide are caused by infections [13], thus recurrent microbial infections in bronchiectasis could favour lung cancer development [14]. Bronchiectasis has been shown as an independent risk factor of lung cancer in a large Asian population-based cohort (n=53 755, hazard ratio (HR) 2.36, 95% CI 2.19–2.55) [15].
Tuberculosis
Tuberculosis (TB) is a major cause of morbidity and mortality, especially in developing countries, with 9.6 million new cases and 1.5 million deaths annually worldwide [16]. In 2005, 426 457 cases of TB were reported in the World Health Organization (WHO) European region [17]. TB causes lung inflammation and fibrosis, and can increase the risk of lung cancer [18–22]. Numerous studies have demonstrated that TB increases the risk of developing lung cancer independently of smoking or environmental tobacco smoke exposure, with a relative risk (RR) of 1.8 in never-smoking patients (95% CI 1.4–2.2) [23]. The risk seems to be higher in the 5 years following TB infection [23, 24]. Interestingly, the association has proved significant with adenocarcinoma (RR 1.6, 95% CI 1.2–2.1), but not with other histologies [23]. Moreover, a history of pulmonary TB has been described as an independent, unfavourable prognostic factor for lung cancer survival in a prospective population-based Dutch cohort (HR 2.36, 95% CI 1.1–4.9) [25].
Interstitial lung diseases
Different studies suggest a link between interstitial lung diseases (ILDs) and lung cancer, through different pathogenetic mechanisms, including chronic inflammation and epithelial mesenchymal transition [26, 27]. Several recent studies have shown that the incidence of lung cancer is increased in patients with idiopathic pulmonary fibrosis, independently of smoking status, with an adjusted RR between 1.51 (95% CI 1.20–1.90, p<0.001) and 8.25 (95% CI 4.70–11.48, p<0.001) [28–30]. Moreover, idiopathic pulmonary fibrosis has been described as an independent risk factor for postoperative mortality and poor long-term survival, especially in patients with stage I/II NSCLC [31]. In patients with underlying ILD, lung cancers are mostly squamous-cell carcinomas and located at the periphery of the lung [32, 33]. ILD associated with systemic sclerosis is also associated with a higher risk of lung cancer, which can be due to the cellular injury caused by inflammation and fibrosis but also to the immunosuppressive therapy often used in this disease [34].
Diseases that promote the occurrence of lung cancer all have in common, besides tobacco exposure at least in COPD, the fact that they are accompanied by chronic inflammation, which increases the effects of exposure to other carcinogens. These diseases also impact the diagnosis and, more so, the treatment of these patients, and they often confer a worse prognosis.
Cardiovascular diseases
Cardiovascular diseases (CVDs) are observed in 23% of patients with lung cancer [35]. They can impact on survival and limit therapeutic options [36]. This high prevalence can be explained by several factors. First, the two pathologies share common main risk factors, i.e. smoking and age. Both COPD and CVD are associated with chronic inflammation, which could also explain the association between the two pathologies [37, 38]. In a recent Norwegian study, self-reported CVD was shown as an independent risk factor for the development of lung cancer in former smokers (HR 1.74, 95% CI 1.11–2.73) and current smokers (HR 1.38 95% CI 1.04–1.83) [39]. Most CVDs were associated with decreased survival in NSCLC patients, especially for stage I–IIIB patients. Heart failure, myocardial infarction and cardiac arrhythmias were associated with the worst prognoses, whereas hyperlipidaemia at baseline was associated with a better prognosis [40]. CVDs are also associated with an increased mortality related to treatments [40], and represent the most important cause of non-cancer death, especially for patients aged >60 years at diagnosis [41]. For all these reasons, management of CVD is important in lung cancer patients.
Other diseases
Human immunodeficiency virus and acquired immune deficiency syndrome
Today, 33.3 million people live with HIV infection worldwide. HIV infection increases the risk of cancer, which is becoming the leading cause of death in HIV-infected (HIV+) patients (22% in 2010 versus 11% in 2000), especially lung cancer (60% of cases) [42, 43]. The estimated incidence of cancer among HIV+ patients was 14 per 1000 person-years in 2006 in the French study ONCOVIH [44]. HIV+ lung cancer patients are younger than HIV-negative (HIV−) patients and present with more advanced disease. It has been reported that HIV+ patients are undertreated for lung cancer [45]. HIV is also associated with higher lung cancer-specific mortality. The increased risk of lung cancer in HIV+ patients is multifactorial: HIV+ patients are often heavy smokers (tobacco and cannabis) [46], but the risk remains higher after adjusting for tobacco. Immunodeficiency, especially CD4 lymphocyte cell count, seems to be an important predictive risk factor for malignancies in HIV (RR 2.2, 95% CI 1.3–3.6 to RR 8.5, 95% CI 4.3–16.7 for lung cancer, p<0.0001) [42]. Finally, HIV+ patients' lungs are weakened by various diseases, such as COPD, emphysema, bronchiectasis, ILD, pneumocystis or other infections, which also contributes to the risk of developing lung cancer [43]. Several prognostic factors have been identified, some of them common to all lung cancers, including performance status and TNM stage, and some of them specific to HIV infection, including CD4 count and highly active antiretroviral therapy (HAART) [47, 48]. However, the survival of HIV+ patients increased considerably with the advent of HAART and, thus, these patients are now reported to develop cancers that are related in part to ageing, such as lung cancer. In addition, the prognosis of HIV+ patients with lung cancer, which was quite sobering in the pre-HAART era, is now similar to HIV− patients [49].
Hepatitis B and C virus
Infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) are associated with significant morbidity and mortality among patients with cancer, especially in patients with haematologic malignancies. HBV infection seems to be associated with poor prognosis in patients with advanced NSCLC [50]. HBV reactivation, defined by the development of hepatitis in association with an increase in serum HBV DNA level, is a well-known complication in patients with cancer undergoing cytotoxic chemotherapy and can be lethal [51, 52]. The risk correlates with the HBV infection status prior to chemotherapy and with the degree of immunosuppression due to chemotherapy. The chemotherapeutic regimens for NSCLC are less intensive than those used for haematologic malignancies, but a study has reported HBV reactivation for nearly 20% of hepatitis B surface antigen (HBsAg)-positive NSCLC patients without antiviral prophylaxis [53]. HBV reactivation has also been described after the withdrawal of erlotinib in cases of EGFR mutation [54]. Consequently, it is important to screen for HBsAg and anti-hepatitis B core antigen in patients at a high risk for HBV infection (i.e. patients coming from high HBV-endemic regions, with a history of intravenous drug abuse, undergoing haemodialysis or who are HIV-positive, and homosexual men) before starting treatment. In cases of a high risk of reactivation, prophylactic lamivudine significantly reduced the prevalence of HBV reactivation in patients with haematologic malignancies and in patients with solid tumours [55, 56].
HCV infection is more common than HBV infection in patients with cancer [57]. Its role in hepatocellular carcinoma is well known, and its prevalence is reported to be higher in haematological cancers but not in lung cancer [58, 59]. HCV reactivation is described in haematologic malignancies [60], particularly in solid tumours [61, 62]. There is no specific attention to pay regarding lung cancer treatment, except to closely monitor alanine transaminase (ALT) and HCV viral load levels during and after chemotherapy.
Renal insufficiency
Chronic renal insufficiency is characterised by a glomerular filtration rate <60 mL·min−1·1.73 m−2 for more than 3 months. The Modification of Diet in Renal Disease method is recommended for the routine calculation of glomerular filtration rate in patients with cancer [63]. Renal function declines with age owing to renal mass shrinking, a reduction in renal blood flow and gradual loss of functioning nephrons [64]. Chronic renal disease is common in patients with lung cancer, even more so as 30% of patients with lung cancer are elderly [65], and it has an impact on survival in both early-stage and advanced lung cancer [66] and on the treatment: use of carboplatin rather than cisplatin, avoiding use of gemcitabine or pemetrexed etc.
Diabetes mellitus
Diabetes mellitus is one of the major public health problems worldwide and is associated with immunosuppression and vascular complications [67]. Approximately 8–18% of patients with cancer also have diabetes. Lung cancer and diabetes mellitus share common risk factors, explaining the association between these two diseases, such as age, diet and smoking. Hyperglycaemia has also been implicated in carcinogenesis, although its role is controversial. It is known that hyperinsulinaemia enhances the synthesis of insulin-like growth factor 1 (IGF-1), and that the binding of IGF-1 to its ligand IGF-1R activates the PI3K/AKT/mTOR pathway, which is implicated in carcinogenesis. Overproduction of reactive oxygen species could also increase the risk of cancer in diabetic patients: reactive oxygen species can damage DNA, contributing to mutagenesis and carcinogenesis [68]. The latest hypothesis is that the abundance of inflammatory cells in adipose tissue of diabetic patients could promote systemic inflammation and thus carcinogenesis [69]. Diabetes mellitus is associated with higher mortality in patients with lung cancer, increasing the risk of cardiovascular events, postoperative complications and susceptibility to infection [70–72].
Impact of comorbidities on lung cancer surgery
Comorbidity is associated with increased perioperative mortality. In a national prospective study by the French Society of Thoracic and Cardio-Vascular Surgery that included >15 000 patients, those with at least three comorbidities had approximately 2.5 times the risk of in-hospital death of patients with no comorbidity [73]. Smoking addiction, history of cancer, COPD, arterial hypertension and heart disease accounted for 70% of these comorbidities. In another series of ∼11 000 surgical patients, a significant association was observed between the Charlson index and postoperative death within 90 days (the adjusted odds ratio for a Charlson index of 2–3 was 1.54) [74].
Because of lung cancer progression, surgery cannot be delayed beyond a few weeks. This short period should, however, be used to optimise the patient's condition. Before surgery, therapeutic optimisation of respiratory, cardiac and renal diseases; diabetes mellitus; and nutritional status is mandatory. Screening for obstructive sleep apnoea syndrome, often undiagnosed, should be included in the preoperative assessment [75]. Despite the limited amount of data currently published, smoking cessation, physical therapy and pulmonary rehabilitation should be offered to reduce perioperative risks and long-term pulmonary disability [76, 77]. A recent French Epithor database analysis showed that underweight patients are at high risk of perioperative complications: in addition to preoperative rehabilitation including a nutritional programme, attention should be given to aggressive prophylactic respiratory therapy in the perioperative period (pre- and immediately after surgery) [78]. If perioperative management of cardiac diseases is well standardised, fewer recommendations have been proposed regarding cerebrovascular disease. Perioperative stroke is a rare complication (0.1%) [79] but characterised by a high perioperative mortality. To reduce the risk of perioperative stroke, antiplatelet/anticoagulant treatments should be continued whenever possible throughout the perioperative period. In patients with transient ischaemic attack or stroke in the preceding 6 months, carotid revascularization should be performed before lung surgery [80].
A functional assessment performed either initially or following therapeutic optimisation can demonstrate persistent high perioperative risk. The two most frequent situations leading to the consideration of other therapeutic options are lung function alteration and heart failure. Perioperative morbidity and mortality as well as long-term functional disability resulting from lung resection depend on the extent of resection as well as the patient's preoperative lung function. Calculating the predicted postoperative FEV1, the diffusing capacity of the lung for carbon monoxide (DLCO) or maximal oxygen uptake (V′O2max) have proved valuable in evaluating the pulmonary reserve of the patient. Patients with a predicted postoperative FEV1 or predicted postoperative DLCO<40% [81] or 30% [82, 83] before “major” resection have been identified as being at increased perioperative risk. A V′O2max <10 mL·kg−1·min−1 or <35% of predicted indicates a high risk for perioperative death [82, 83] or cardiopulmonary complications [81] if a major anatomic lung resection through thoracotomy is considered. Minimally invasive surgery and sub-lobar resections or non-surgical treatment options should then be discussed. It is worth noting, however, that lower lung function limits for sub-lobar resections remain to be defined.
Heart failure is a well-recognised factor for perioperative cardiac complications. In a large study of >159 000 non-cardiac procedures, overall mortality among patients with heart failure was 8.0%, more than triple the mortality in patients with neither coronary artery disease nor heart failure [84]. There is no defined lower limit of left ventricle ejection fraction (LVEF) for thoracic surgery, but a reduced LVEF of ≤35% was found to be a strong predictor of postoperative cardiac events following vascular surgery [85]. In another study, a LVEF of <30% was associated with increased rates of perioperative events compared with moderately reduced (LVEF 30–40%) or mildly reduced (LVEF 40–50%) left ventricle function [86]. It is recommended that patients with established or newly diagnosed heart failure who are scheduled for intermediate or high-risk non-cardiac surgery be therapeutically optimised. However, it can be necessary to allow at least 3 months after the initiation of heart failure to allow for therapy up-titration and possible improvement of left ventricular function [87]. Such a delay can be incompatible with carcinological imperatives.
Impact of comorbidities on lung cancer radiotherapy
Radiation therapy improves locoregional control and survival in patients diagnosed with NSCLC and small-cell lung cancer. The most frequently used treatment is three-dimensional conformal radiation therapy combined or not with chemotherapy or surgery. Stereotactic radiotherapy is an alternative to surgery for stage T1T2A lung cancer without involved nodes for patients who refuse or are not eligible for surgery. Irradiation of mediastinal tumours can induce radiation pneumonitis (RP). The total dose, fractionation schedule, irradiated lung volume and dosimetric factors are all related to the development of RP [88–90]. Concurrent or sequential chemotherapy has been shown to increase the risk of RP in some studies [91–95], but not in others [96–100]. Some patient-specific risk factors can influence the rate of symptomatic RP. Claude et al. found that age can increase the risk of RP [99]. In a prospective study of 96 patients who received three-dimensional conformal radiation therapy for stage IA–IIIB NSCLC, 40 patients (44%) had RP (grade ≥1) at 6 weeks, including 7 patients (7.8%) with severe RP (grade ≥2). An age >60 years was also significantly related with RP; however, this was not confirmed in other studies [91, 98, 101, 102]. A low Karnofsky performance status has been found to increase the risk of RP in one study [97], but not in others [91, 99]. There is also conflicting evidence regarding whether tumour location influences the risk of RP [92, 97, 102]. Monson et al. showed that the development of RP was significantly more common among patients with a smoking history than among those who never smoked [96]. Smoking seems to have a paradoxical role in RP: smoking history could increase the risk of RP as a result of pre-existing lung damage, but active smoking somehow protects the lungs from radiotherapy-induced damage. Yamaguchi et al. performed a retrospective analysis of 62 patients receiving thoracic radiotherapy and evaluated the association between subclinical ILD and fatal RP [103]. Eleven patients had an untreated and asymptomatic ILD and grade 2–5 RP was observed in 4 of these 11 patients. Subclinical ILD has been observed to significantly influence the development of grade 2–5 RP (p=0.0274) [104], with a significant trend for grade 5 (p=0.0785). Several patient-specific factors, including age, smoking history, tumour location, performance score, sex and treatments (chemotherapy regimen and schedule), have been proposed as potential predictors of RP, but these have not been consistently demonstrated across different studies.
Impact of comorbidities on the use of systemic treatment
Specific data concerning dose adaptation of systemic therapies (chemotherapies and targeted therapies) according to comorbidities are seldom seen in the literature, except with regards renal and hepatic failure. A review of medical cancer treatment of lung cancer associated with comorbidities has recently been published [105], emphasising the need for a better appraisal of the impact of comorbidities.
Chemotherapy
Cisplatin requires good hydration and consequently should not be used in patients with pre-existing reduced LVEF or who are at risk of pulmonary oedema. Anthracyclines are the best known of the chemotherapeutic agents that cause cardiotoxicity and are contraindicated in cases of reduced LVEF. Other agents such as etoposide or vinorelbine have also been occasionally associated with cardiotoxicity, and should be used with caution [106]. Regarding patients with chronic renal insufficiency, recommendations from the International Society of Geriatric Oncology (SIOG) summarise the recommended dosage adjustment of anticancer drugs [107]. The majority of cancer therapies used in lung cancer do not require dose adaptations for a glomerular filtration rate between 60 and 90 mL·min−1. Cisplatin is not recommended when clearance is lower than 60 mL·min−1 and carboplatin use is preferable. Pemetrexed is contraindicated when clearance is <45 mL·min−1. Dose adjustments for the main agents used in lung cancer are summarised in table 1. Some chemotherapies must also be adjusted to liver function, and those adjustments are summarised in table 2. Concerning patients on dialysis, there is no specific recommendation in the literature. Several case reports had shown that administration of chemotherapy is feasible before dialysis sessions [108].
Dose adjustments of lung cancer main chemotherapies in case of renal dysfunction
Dose adjustments of the main chemotherapies for lung cancer in cases of liver dysfunction
Chemotherapy-related exacerbation of ILD has been reported in 8.7–21% of cases [109, 110], notably with mitomycin, gemcitabine and docetaxel [111, 112], and these drugs should not be used in patients with ILDs. Platin salts, vinorelbine and etoposide are considered to be safe in patients with advanced NSCLC and ILD [110, 113]. Generally speaking, clinicians must be aware of this occasional complication during chemotherapy and closely monitor their patients. Bronchoalveolar lavage with cellular analysis (lymphocytes, eosinophils, neutrophils) should be performed whenever there is any doubt and followed by corticosteroid treatment.
Targeted therapy
Tyrosine-kinase inhibitors (TKI), at least erlotinib, gefitinib and crizotinib, are well known to induce ILD, even if there is no pre-existing fibrosis [114]. However, with regards patients with concurrent EGFR mutation and ALK translocation, TKI may not be systematically contraindicated in patients with pre-existing fibrosis; clinicians should decide on a case-by-case basis, considering patients' characteristics and other comorbidities [115]. TKI should also be given with dose adaptation in patients with renal failure [116, 117] or hepatic failure, but specific studies are lacking (tables 1 and 2).
Immunotherapy
Recently, the use of immune checkpoint inhibitors has generated considerable enthusiasm. Anti-programmed cell death protein 1 (PD1) drugs were first investigated with nivolumab as a second-line treatment of advanced NSCLC independent of programmed death-ligand 1 (PD-L1) expression by tumour cells [118, 119], or with pembrolizumab as a second-line [120] or first-line treatment in cases in which at least 50% of tumour cells expressed PD-L1 [121]. These drugs are either already approved or on the way to being approved, depending on the country. Anti-PD-L1 drugs are not yet approved but are at an advanced stage of clinical development, and include atezolizumab, durvalumab and avelumab. Treatment-related adverse events are quite different from those observed with chemotherapy and are generally speaking less severe. However, owing to the mechanism of action of these drugs, there are many immune-related adverse events that can affect the skin (pruritus and rash), gastrointestinal tract (colitis, sometimes severe), liver, pancreas (diabetes mellitus), pituitary gland (hypophysitis, hypothyroidism, etc.) and lung (ILD) [122]. While these new drugs are promising, a history of immune diseases or diseases requiring immunosuppressive therapy (such as corticosteroids) can preclude the use of such therapies and are exclusion criteria in all the above cited studies.
Special populations: elderly and HIV-infected patients
Elderly patients have long been excluded from clinical trials. However, in patients with a performance status of 0–2, carboplatin and weekly paclitaxel doublet chemotherapy has been associated with survival benefits compared to those of monotherapy and is now the new paradigm of treatment for these patients [123]. Recommendations for treatment of advanced NSCLC are lacking in HIV+ patients, because HIV seropositivity is an exclusion criteria in most trials. The management of these patients is difficult, partly because of the aggressive nature of the tumour and partly because of comorbidities and potential interactions between anticancer and antiretroviral therapies. A recent study has evaluated the combination of the front-line chemotherapy carboplatin-pemetrexed followed by maintenance pemetrexed in HIV+ patients with advanced NSCLC. These agents do not interact with HAART. This regimen was well tolerated and should become the standard first-line chemotherapy regimen for HIV+ patients [124].
Psychological and social factors
Some psychological and social factors could influence the outcome of patients with lung cancer. Because these factors can impact the tolerance of the treatments, they influence the selection of lung cancer treatment. In a Norwegian study of 24 324 lung cancer patients, the influence of income, education, age and place of residence on treatment was evaluated [125]. Surgery and radical and palliative radiotherapy were underused among the elderly and those with a lower socioeconomic status, which is of concern given the universal health coverage in this country. High-quality radiotherapy requires rigid immobilisation of patients and accurate positioning of their targets. For some tumour locations, especially for tumours located closed to the spinal cord, patients may need to wear a five-point mask covering the head, neck and shoulders to help them keep still. Wearing a mask can be a source of fears for some patients. Claustrophobic patients are unable to stay under a standard head mask throughout the treatment. One solution is to use an open-face hybrid mask which leaves the eyes, nose and mouth exposed [126, 127]. The mask is not in the field of view of the patient, which makes it much more comfortable. Hypnosis can also be useful in radiotherapy [128] and is an effective method to ease the simulation computed tomography scan and the first sessions of radiation therapy. Patients who benefit from hypnosis in the first and second sessions can then usually continue the treatment without hypnosis. It can be difficult for patients with dementia or psychosis to undergo radiation treatment. Besides the ethical aspects raised by the condition of such patients, they can find it difficult to keep still during the radiotherapy sessions and therefore can require premedication. The place of residence can also impact the choice of treatment. Indeed, a large distance between the patient's residence and the cancer centre could result in the patient being more tired because they have to travel every day, 5 days a week, for the radiation treatment; this can have a negative impact on the treatment outcome [129]. Finally, a lack of universal health coverage can impact chemotherapy use, especially in countries like the USA. In 2010 it was reported that only about 20% of patients in the USA aged >65 years received chemotherapy for advanced NSCLC and there was a correlation with income [130]. These US estimates contrast poorly with European estimates: in France, in 2010, a large majority of elderly patients with lung cancer were managed like their younger counterparts and only 16% of them had best supportive care as a unique treatment [131]. Even when health coverage is guaranteed, some psychosocial factors can play a role, such as the absence of a phone, mental disorders etc.
Conclusion
Contrary to other cancers, e.g. breast cancer, lung cancer often occurs in patients with comorbidities that can prevent the realisation of some diagnostic procedures and treatments. The high frequency of comorbidities is mainly due to a common risk factor, i.e. tobacco use, but also to the fact that the median age of patients with lung cancer is around 70 years, with the inherent development of CVDs, renal insufficiency, etc. that are related to an advanced age. In some situations, rehabilitation, i.e. the correction of metabolic disorders, can allow the appropriate treatment in most patients, including those who are frail.
Footnotes
Previous articles in this series: No. 1: Malhotra J, Malvezzi M, Negri E, et al. Risk factors for lung cancer worldwide. Eur Respir J 2016; 48: 889–902. No. 2: McDonald F, De Waele M, Hendriks LEL, et al. Management of stage I and II nonsmall cell lung cancer. Eur Respir J 2017; 49: 1600764.
Conflict of interest: None declared.
- Received August 30, 2016.
- Accepted November 25, 2016.
- Copyright ©ERS 2017
References
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- Abstract
- Abstract
- Introduction
- Epidemiology
- Impact of comorbidities on lung cancer surgery
- Impact of comorbidities on lung cancer radiotherapy
- Impact of comorbidities on the use of systemic treatment
- Special populations: elderly and HIV-infected patients
- Psychological and social factors
- Conclusion
- Footnotes
- References
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