Viñolas et al. BMC Psychol (2020) 8:123 https://doi.org/10.1186/s40359-020-00489-z RESEARCH ARTICLE Open Access Assessment of the psychosocial and economic impact according to sex in non‑small cell lung cancer patients: an exploratory longitudinal study N. Nuria Viñolas1,2* , Rosario Garcia‑Campelo3, Margarita Majem4, Enric Carcereny5, Dolores Isla6, José Luis Gonzalez‑Larriba7, Juan Coves8, Javier De‑Castro9, Manuel Domine10, Piar Lianes11, Angel Artal12, Jordi Remon13, Enriqueta Felip14 and Pilar Garrido15 Abstract Background: Little is known about the impact of sex on lung cancer patients from the psychological, economic and social perspectives. This study was designed to explore the psychosocial and economic impact according to sex of metastatic non-small cell lung cancer (mNSCLC) in patients and caregivers. Methods: Exploratory study of two cohorts of patients starting first-line treatment for mNSCLC. The following questionnaires were administered at baseline, 4 months later and following the first and second disease progression: APGAR, relationship impact scale, DUKE-UNC scale, economic impact in patients and caregiver, and Zarit scale. It was planned to include 1250 patients to get an 80% possibility of detecting as significant (p < 0.05) effect sizes less than 0.19 between men and women. Univariate comparisons were made between the tests applied to men and women. Overall survival was estimated with Kaplan–Meier method. Cox analyses were done to estimate hazard ratios (HRs) with 95% CI. Results: 333 patients were included. Most families reported to continue being functional despite the lung cancer diagnosis. Regardless of sex, they did not perceive changes in their partner relationship. Most patients felt their social support was normal. Roughly 25% of people reported a worsening in their economic situation, without remarkable differences by sex. Statistically significant differences were found between both groups regarding the caregiver’s relationship to the patient (more parents were the caregiver in females than in males, p < 0.0001) and the caregiver’s employment situation (more employed caregivers in females) (p < 0.0001). Most caregivers of both sexes considered that taking care of their relative did not pose a significant burden. Conclusions: This study provides a preliminary insight into sex-related characteristics in the management of advanced NSCLC and its impact on the emotional, social and economic burden of patients and their caregivers, and recall the high priority of researching in cancer from a sex perspective. Nevertheless, due to the low recruitment rate and the relevant loss of patients during the follow-up, it was difficult to find differences by sex. Trial registration: ClinicalTrials.gov identifier: NCT02336061. *Correspondence: nvinolas@clinic.cat 1 Medical Oncology Department, Hospital Clínic i Provincial de Barcelona, Carrer Villarroel, 170, 08036 Barcelona, Spain Full list of author information is available at the end of the article © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat​iveco​mmons​.org/licen​ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat​iveco​ mmons​.org/publi​cdoma​in/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Viñolas et al. BMC Psychol (2020) 8:123 Page 2 of 9 Ethics committee: Comité Ético de Investigación Clínica del Hospital Clínic de Barcelona, Spain. Reference number: HCB/2014/0705. Keywords: Carcinoma, Non-small-cell lung, Caregivers, Sex characteristics Background from stress, including changes in their usual routines, Following the GLOBOCAN 2018 estimates of cancer changes in family roles, personal health conditions, and worldwide incidence and mortality, in both sexes com- occupational and financial disruption [11]. bined, lung cancer is the most commonly diagnosed Lung cancer seems to have a greater economic impact cancer (11.6% of the total cases) and the leading cause of than other tumors, due to its poor prognosis and the sig- cancer death (18.4% of the total cancer deaths) globally nificance of its symptoms, which can lead to incapacity and among males, and the second in females [1]. Accord- for the patient (and occasionally the caregiver) in con- ing to data from the Spanish Statistics National Institute tinuing to perform their job role [12]. Most caregivers (INE), in 2017 there were a total of 22,089 (17,241 men of patients with NSCLC suffer financial and social harm and 4848 women) deaths in Spain due to lung cancer [2], from the patient’s diagnosis as their social and leisure which corresponds to a mortality rate of 71.38/100,000 activities are reduced and they are forced to reduce their inhabitants (125.56/100,000 in men and 28.39/100,000 working hours [13]. The economic costs associated with inhabitants in women) [3]. the disease are due to the large number of symptoms About 80% of lung cancers are non-small cell lung can- presented by these patients and their severity, increasing cer (NSCLC) and around 40% of patients have metastatic with the progression of the disease and deterioration in disease at the time of diagnosis [4]. the quality of life. There are no data published to date on Historically, lung cancer has been viewed as a male the overall cost of the disease in Spain. disease, but during the past years there has been a dra- The present study aimed to explore the differences matic increase in the incidence in women, attributed to in the influence lung cancer has on women compared a significant increase in tobacco consumption; indeed, to that on men in terms of social, family and economic according to the last inform from the Spanish Asso- impact. ciation Against Cancer [5], the percentage of smoking women is approaching to that in men (18% vs. 27%). As Methods the incidence of lung cancer in women has increased, sig- Trial design nificant sex-based differences in epidemiology, biology, This study is a multicenter, prospective, observational, and treatment responses have become evident [6, 7]. In epidemiological, follow-up exploratory study of two spite of it, little is known about the impact of sex in lung cohorts of patients with metastatic NSCLC (male and cancer patients from the psychological, economic and female), carried out by the Spanish Association for Lung social perspectives [8]. Cancer Research in Women (ICAPEM). Cancer research and clinical trials have historically focused on efficacy parameters, toxicity and quality of Patient selection life. However, there is an increasing interest to evaluat- Eligible patients were ≥ 18 years old, had cytological or ing the disease’s impact from other perspectives such as histologically confirmed metastatic NSCLC, an East- caregivers, family functionality and finances, both in the ern Cooperative Oncology Group performance status patients and their family setting. (ECOG PS) ≤ 3 and no previous systemic treatment for At the time of disease progression, the burden of symp- metastatic NSCLC. toms and the problems related to social and caregivers Patients meeting all selection criteria who were going support become more evident. Similarly, the economic to start first-line treatment for metastatic NSCLC were resources can be also influenced [9]. It is expected that included in the study. The treatment chosen during the some patients become more dependent, require more study depended on the oncologist’s judgment. No treat- resources and time from caregivers. Eventually, caregiv- ment recommendations or restrictions were stated in the ers have to reduce their working hours or seek for addi- study protocol. tional help. The caregiver role in Spain has traditionally assigned to family, usually women [10] but now that Evaluations during the study lung cancer is no longer considered a men’s disease, little Information on the demographic variables, medical his- is known about the influence of sex´s patients from the tory, social and economic impact was collected. All the caregivers’ perspective. Around 20–50% caregivers suffer patients’ clinical information (including assessment of Viñolas et al. BMC Psychol (2020) 8:123 Page 3 of 9 treatment response) was recorded in the correspond- detecting as significant (p < 0.05) effect sizes less than ing medical records of the investigator, obtained as part 0.19 between men and women. The effect size serves to of routine care, together with responses to the various make the differences or relationships between differ- questionnaires administered to the patient and their pri- ent variables with different values comparable, thereby mary caregiver (Table 1). All questionnaires were filled allowing us to measure the strength of the relationship in baseline, 3–4 months later (at the time of first tumor between two variables. According to the Cohen classi- evaluation) and following the first and second disease fication, which defined Cohen’s d [20] for quantitative progression. In order to evaluate family functionality, variables, a difference is considered to be large when the validated Spanish version of the APGAR question- the effect size is greater than 0.8, medium if it is greater naire was used [14]. The Family APGAR was developed than 0.5 and small if it is greater than 0.2 [21]. In this in 1978 [15], and it is a 5-item questionnaire (with each study, 0.19 was taken as a reference, which should ena- item rates on a 3-point scale) measuring five constructs ble us to detect small to large figures as significant. (adaptability, partnership, growth, affection, and resolve). Descriptive tables of the baseline and demographic The validated Spanish version of Duke-UNC-11 scale characteristics of the patients are presented, as well as was used to measure each individual’s perception of the the results obtained from the self-administered ques- degree and type of social support available/received [16]. tionnaires. All patients’ clinical and tumor characteris- The caregiver burden in this study was assessed using the tics at the time of diagnosis of the metastatic advanced 22-item Zarit scale, which presents 22 items expressed disease were provided. as statements on how people who take care of a patient Univariate comparisons were made between the tests feel: the caregiver must select the statement that best applied to men and women. In the case of quantitative suits how they feel. It uses a 5-point scale from 0 (never) variables, the Student’s t-test was used. Overall survival to 4 (almost always), with a higher score indicating a was estimated with Kaplan–Meier method. Median higher burden. This scale has been validated in Spain by survival times with 95% confidence intervals (CI) were Martin et al. [17]. To assess the impact of the disease on calculated. Cox analyses were done to estimate hazard the economy of patients and their caregivers, an ad-hoc ratios (HRs) with 95% CI. designed questionnaire based on other previously pub- All statistical tests were two-sided. The significance lished [18, 19] was used. level was established at a value of α = 0.05. The statisti- Clinical procedures for tumor evaluation and assess- cal analyses were performed using SAS version 9.4. ment of the response to treatment were conducted in accordance with the site’s usual practice. Patients were Results followed until the patient’s death was documented or up Between February 2015 and February 2017, 333 patients to a maximum of 24 months after the end of treatment. (229 men and 104 women) from 20 Spanish hospitals were included.The study was prematurely closed due Statistical analysis to a low recruitment rate. Most of demographic and Approximately 1250 patients were planned to be baseline patients’ characteristics were similar between included. With this size, there was an 80% possibility of female and male (Table 2), with only significant dif- ferences in the number of smokers/former-smokers (97% of male and 63% of female, p = 0.0001) and the Table 1 Psychosocial and economic status proportion of married/partnered (73% of male and assessment questionnaires (see these questionnaires 49% of female, p = 0.0002). 217 men and 85 women on the “Additional files”) received chemotherapy as first line treatment, 7 men and 19 women were treated with EGFR TKI inhibitors, Order Patient Caregiver 4 men and 5 women received an ALK TKI inhibitor, 1 Family impact scale: APGAR​ a Caregiver economic impact and 1 man and 2 women received immune checkpoint scale inhibitors. 78 out of 104 men and 29 out of 39 women 2 Relationship impact scale ­ ARITc Caregiver burden scale: Z reported second-line treatment: docetaxel was the most 3 Socio-affective impact scale administered drug (20 men and 9 women), followed by (perceived support): DUKE- UNCb nivolumab (20 men and 7 women). 4 Patient economic impact scale The 15-monhts overall survival (OS) was 56% (95% CI a 45.4–65.9%) and 37% (95% CI 30.3–44.1%) for female Score: 7–10 functional; 4–6 moderately dysfunctional; 0–3 severely dysfunctional and male, respectively, p = 0.0034. The median OS b Score: ≥ 32, normal support; < 32, low support was also longer in women but did not reach statistical c Score: ≤ 46, no burden; > 46 and < 56, slight burden; ≥ 56: intense burden Viñolas et al. BMC Psychol (2020) 8:123 Page 4 of 9 Table 2 Baseline characteristics of patients significance (17.1 vs 11.0 months, HR 0.732 (95% CI Parameter Arm A Arm B p value 0.534–1.005), p = 0.0524) (Fig. 1). Main baseline responses to the study questionnaires (Male) (Female) by patients and their caregivers are summarized in (N = 229) (N = 104) Tables 3 and 4. Most families were considered func- n % n % tional (high score in APGAR questionnaire: 83% of men and women) and, those who had a partner said their Age, years 0.0010b relationship had not changed (69% of men and 61% of Mean (SD) 65 (8.8) 62 (10.4) women) or even had improved (27% of men and 39% Median (Q1, Q3) 66 (60, 72) 61 (55, 69) of women). 77% of men (177/229) and 82% of women Range 36–84 37–85 (85/104) thought their social support was normal. Comorbidities 0.2809b According to the patients’ economic questionnaire, 132 Mean (SD) 3 (2.1) 3 (2.1) of the 195 men and 43 of the 96 women who answered Median (Q1, Q3) 2 (1, 4) 2 (1, 4) the questionnaire, were retired at the beginning of the Range 1–10 1–10 study. Around a quarter of interviewed people said ECOG 0.1643c their economic situation was a little worse than before 0 91 40 29 28 suffering the disease, without remarkable differences by 1 107 47 60 58 sex. 2 23 9 10 9 Statistically significant differences were found 3 2 1 1 1 between both groups regarding the caregiver’s rela- Missing 6 3 4 4 tionship to the patient, with more parents being the Smoking habits < 0.0001d caregiver in females than in males (p < 0.0001), and the Smoker/ex-smoker 222 97 66 63 caregiver’s employment situation (more employed car- Non-smoker 7 3 38 37 egivers for female patients, p < 0.0001) (Table 4). 60% of Marital status 0.0002c caregivers of male patients (38/63) and 76% of caregiv- Single 25 11 19 18 ers of female who answered the economic question- Married/Partnered 168 73 51 49 naire and who were working, had not changed their Widowed 9 4 13 13 working hours. More than 80% of caregivers of both Divorced 4 2 6 6 sexes who answered the Zarit questionnaire, consid- Missing 23 10 15 14 ered that taking care of their relative did not pose a sig- Educational level 0.0098c nificant burden (Table 4). No education 25 11 9 9 Due to the relevant loss of patients during the fol- Basic 118 52 37 35 low-up, it was difficult to find differences by sex in Higher 31 13 26 25 the responses to the different questionnaires. Accord- Missing 55 24 32 31 ing to the family APGAR questionnaire, most families Histology 0.0082c remained functional across the study (Additional file 1: Adenocarcinoma 158 69 87 84 Online Resource 1): mean functionality levels were Squamous cell 44 19 8 8 similar in men and women over time. The relation- Others 27 12 8 8 ship with the partner did not change or improved dur- Mutationsa ing the course of the disease in a vast majority of men EGFR+ 11 5 21 20 and women. The social support of the patient (Duke- ALK+ 4 2 5 5 UNC-11 scale) remained normal throughout the study, BRAF+ 1 1 1 1 without appreciable differences between mean social Italic values are statistically significant support scores in both sexes (Additional file 2: Online a EGFR mutation status was not determined in 67 men (29%) and 8 (8%) Resource 2). The vast majority of patients considered women; ALK mutation status was not determined in 103 men (45%) and 26 the disease did not affect their household finances (25%) women; BRAF mutation status was not determined in 200 men (87%) and 93 (90%) women across the study, although a quarter of interviewed b Wilcoxon signed-rank test patients reported a minimum negative economic c Fisher’s exact test impact after lung cancer diagnosis, without remark- d Chi-squared test able differences by sex. No remarkable differences were found between the mean caregiver’s burden (Zarit scale) across the study by sex (Additional file 3: Online Resource 3), nor in the economic evaluations. Viñolas et al. BMC Psychol (2020) 8:123 Page 5 of 9 Cumulative survival 1.0 Female (N=99 C=45) 0.9 0.8 Male (N=227 C=92) 0.7 Cumulative Probability 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Time (months) (p-value=0.0524) Female Male Parameter p-value N 99 227 Events 54 (54.5%) 135 (59.5%) Censored 45 (45.5%) 92 (40.5%) Median 17.1 95% CI (11.5-24.1) 11.0 95% CI (9.3-13.6) Log-Rank: 3.764 HR: 0.732 95% CI (0.534-1.005) LR:0.0524 HR:0.0535 at 15 55.7% 95% CI (45.4%-65.9%) 37.2% 95% CI (30.3%-44.1%) Diff: 18.5% 0.0034 months Fig. 1 Survival by sex Discussion smoking history, comorbidities, different driver muta- The Association for Lung Cancer Research in Women tion pattern or differences in histology. In this study (ICAPEM) published a consensus paper in 2017 where a women were more likely than men to have adenocar- detailed analysis of the sex perspective in lung cancer was cinoma. While some studies showed that women with done [8]. One of the main conclusions was that there was adenocarcinoma had better outcomes than women with a lack of information about evaluating social, economic squamous cell carcinoma [28, 29], others have seen that and emotional impact on women with lung cancer and women had better disease-free survival and OS than their caregivers/relatives. This study was set up to doing a men regardless of stage, smoking status and histology first approach to this issue. [7, 30]. Therefore, at present, the reasons why women To the best of our knowledge, this is the first longi- with NSCLC live significantly longer than men remain tudinal study to investigate the impact of advanced elusive [8]. lung cancer on patients and their caregivers from a The presence of no-relative caregivers was anecdotic sex perspective. As expected [22, 23] there were more in both groups, as has been reported in most of studies smokers/ex-smokers men than women (38 out of 104 [31–33]. More men than women had their partners as diagnosed women have never smoked). Also, there were caregivers, and more women than men had their par- more men than women with a partner. As reported in ents as caregivers. In most of studies, partners were the previous studies [24–27], median survival to 15 months most frequent family caregivers of cancer patients [13, and overall survival were longer in women than in 34, 35], mainly spouses, probably due to the social role men. Several reasons have been proposed to explain that women still adopt. In a similar way, more family the improved survival of women with NSCLC, such as caregivers of female patients were employed, while the Viñolas et al. BMC Psychol (2020) 8:123 Page 6 of 9 Table 3 Baseline responses to the study questionnaires: Table 4 Baseline responses to the study questionnaires: patients patients’ caregivers Parameter Arm A Arm B p ­valuec Parameter Arm A Arm B (Male) (Female) (Male patients) (Female patients) (N = 229) (N = 104) (N = 229) (N = 104) n % n % n % n % Family functionality (APGAR) 0.6961 Functional 190 83 86 83 Relationship to the patient Moderately dysfunctional 10 4 5 5 Parents 23 10 25 24 Severely dysfunctional 2 1 2 2 Partner 141 62 45 43 Missing 27 12 11 10 Brother/sister 13 6 6 6 Partner ­relationship a 0.3235 Other family member 1 1 2 2 n 137 – 46 – No relative 6 2 5 5 Improved 37 27 18 39 Missing 45 19 21 20 Worsened 3 2 0 0 Work situation of the r­ elativea Not changed 94 69 28 61 Retired 55 24 26 25 Missing 3 2 0 0 Self-employed 10 4 6 6 Social support (DUKE) 0.5372 Employed 39 17 35 33 Normal 177 77 85 82 Unemployment benefits 8 4 4 4 Low 7 3 5 5 Home-maker 44 19 2 2 Missing 45 20 14 13 No income 10 4 4 4 Economic ­situation b 0.3476 Missing 63 28 27 26 Better 0 0 1 1 Changes in working ­hoursb The same 121 53 49 47 No 38 17 25 24 A little bit worse 55 24 29 28 Change in the schedule 17 7 12 12 Much worse 18 8 10 10 Reduced 0 0 5 4 Missing 35 15 15 14 Stop working 8 4 3 3 a Missing 166 72 59 57 Score obtained for the question “How has your relationship with your partner changed during the last month?” This item only applies to patients who have Caregiving burden (Zarit scale)c a partner (134/157 men who answered that question and 46/63 women who No burden 116 51 54 52 answered that question) b Slight burden 19 8 7 7 Score obtained for the question “Has the disease you suffer from affected your household finances in any way?” This item only applies to patients who have Intense burden 10 4 4 4 a partner (134/157 men who answered that question and 46/63 women who Missing 84 37 39 37 answered that question) a c This question applies only to family members Fisher’s exact test b This question applies only to those not hired by the patient c Score: ≤ 46 no burden; 47–55 slight burden; ≥ 56 intense burden percentage of family caregivers of female patients being home-maker was anecdotic. derive from the results of the scale validation study in A large majority of caregivers of both sexes reported Spain, carried out in a psychogeriatric centre, with- that taking care of their relative did not pose a signifi- out considering whether it was useful and valid in any cant baseline burden. Findings from previous studies group of caregivers regardless of the characteristics of in this area pointed that caregivers of cancer patients the person they care for. However, other studies con- experienced a high level of burden [13, 36–38]. This sider a score of 24 as the cut-off score to identify car- apparent discrepancy might be due to the interpreta- egivers with possible mental distress who were in need tion of the Zarit Burden Inventory in Spain [39]. This of further assessment and continued intervention, fol- questionnaire uses a 5-point scale from 0 (never) to 4 lowing the interpretation of Schreiner et al. [41]. (almost always), with a higher score indicating a higher No differences by sex were found throughout the study burden. In Spain, a score ≤ 46 is considered as “No bur- in family functionality, nor perception of social sup- den”, 47–55 “light burden” and ≥ 56 “Intense burden”. port, but around a quarter of interviewed patients said As stated by Ribé et al. [40], those cut points probably their economic situation was a little worse after the lung Viñolas et al. BMC Psychol (2020) 8:123 Page 7 of 9 cancer diagnosis, without remarkable differences by Additional file 2. Online Resource 2: Social support (Duke-UNC-11 scale) sex. In addition, no remarkable differences were found by sex over time. between the mean caregiver’s burden across the study by Additional file 3. Online Resource 3: Caregiving burden (Zarit scale) by sex. Nevertheless, the high loss of patients and caregivers’ patient sex over time. responses to the questionnaires during the study, limited the statistical power for detecting significant changes/dif- Abbreviations ferences in outcomes. APGAR​: Relationship impact scale; CI: Confidence interval; DUKE-UNC: Scale, economic impact in patients and caregiver; ECOG: Eastern Cooperative Oncol‑ Other limitations of this study and directions for future ogy Group performance status; HR: Hazard ratios; ICAPEM: Spanish Association research should be noted. First, as it was not possible for Lung Cancer Research in Women; INE: Spanish Statistics National Institute; to reach the planned sample size, the statistical power mNSCLC: Metastatic non-small cell lung cancer; NSCLC: Non-small cell lung cancer; OS: Overall survival. for detecting significant correlates of study outcomes is limited: indeed, with the final sample size we reached, Acknowledgements our study only have a power of 0.44 to detect as signifi- The authors thank the patients and the medical and nursing staff from all the participating institutions. Juan Manuel López Zafra, for their advice on the cant (p < 0.05) an OR of 1.4 (or its equivalent effect size economic aspects of the study. María Die Trill for their advice on the election of 0.19). Therefore, these results should be interpreted of psychological scales of the study. Statistics and Data Management: Pivotal. in an exploratory way to raise hypotheses that should Support for third-party writing assistance for this manuscript was provided by Pivotal. be addressed in subsequent studies. Second, as stated above, the longitudinal design of the study led to the Authors’ contributions loss of a significant number of patients and caregivers NV, RGC and PG designed the study. NV and PG wrote the first draft of the manuscript (writing assistance was provided by Pivotal) and all other authors who responded to the questionnaires in subsequent vis- contributed to its revision. All authors were involved in the data collection its. Some of those could be due to a natural selection of and clinical management of the patients in this study. All authors read and patients with a better prognosis and, therefore, with a approved the final manuscript. longer survival; in addition, we cannot rule out that some Funding patients with a worse prognosis died before the first eval- This study was supported by an unrestricted educational grant from Roche, uation, which was performed 3–4 months after inclusion, which covered monitoring, data analysis and medical writing assistance that was provided by an external Contract Research Organisation. at the time of the first tumor evaluation (usual practice). It is highly recommended to do a thorough monitoring Availability of data and materials of this kind of studies and to use recapture strategies The datasets during and/or analysed during the current study available from the corresponding author on reasonable request. such as telephone calls after each visit. Third, Spain has a National Healthcare System that covers the main costs of Ethics approval and consent to participate diseases, including treatments (pharmacological and oth- The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines. Before starting the study, written ers), hospitalisation, outpatient visits and tests. In addi- informed consent was obtained from all patients. The protocol was approved tion, the low percentage of people who acknowledged by the Ethics Committee of Hospital Clinic: Comité Ético de Investigación that their economic situation had worsened due to the Clínica del Hospital Clínic i Provincial de Barcelona, Spain (Reference number: HCB/2014/0705). disease, may also be related to the Mediterranean culture, where it is not appropriate to talk about money. Consent for publication Not applicable. Competing interests Conclusion Dr. Angel Artal has nothing to declare. Dr. Dolores Isla has nothing to declare. Despite its limitations, the present study provides a pre- Dr. Enric Carcereny has nothing to declare. Dr. Juan Coves reports personal fees from boehringer ingelheim, personal fees from BMS, personal fees from liminary insight into sex-related characteristics in the Roche, personal fees from ASTRAZENECA, personal fees from NOVARTIS, management of advanced NSCLC and its impact on the personal fees from MSD, personal fees from LILLY, outside the submitted work; emotional, social and economic burden of patients and Dr. Enriqueta Felip reports personal fees from ABBVIE, personal fees from ASTRA ZENECA, personal fees from BERGENBIO, personal fees from BLUE PRINT their caregivers, and recall the high priority of research- MEDICINES, personal fees from BOEHRINGER INGELHEIM, personal fees from ing in cancer from a sex perspective. BRISTOL-MYERS SQUIBB, personal fees from CELGENE, personal fees from ELI LILLY, personal fees from GUARDANT HEALTH, personal fees from JANSSEN, personal fees from MEDSCAPE, personal fees from MERCK KGaA, personal fees Supplementary information from MERCK SHARP & DOHME, personal fees from NOVARTIS, personal fees Supplementary information accompanies this paper at https​://doi. from PFIZER, personal fees from priME ONCOLOGY, personal fees from ROCHE, org/10.1186/s4035​9-020-00489​-z. personal fees from SAMSUNG, personal fees from TAKEDA, personal fees from TOUCHTIME, outside the submitted work; and Board: Grífols (Independent Member). Dr. Javier De castro reports other from ASTRA ZENECA, other from Additional file 1. Online Resource 1: Family functionality (APGAR ques‑ BOEHRINGER INGELHEIM, other from BRISTOL MYERS SQUIBB, other from tionnaire) by sex over time. MERCK SHARP AND DOHME, other from HOFFMANN ROCHE, other from TAKEDA, other from NOVARTIS, other from PFIZER, outside the submitted work. Dr. Jose Luis Gonzalez Larriba has nothing to declare. Dr. Jordi Remon Viñolas et al. BMC Psychol (2020) 8:123 Page 8 of 9 reports other from MSD, other from BOEHRINGER, other from PFIZER, personal 6. Donington JS, Colson YL. Sex and gender differences in non-small cell fees and other from OSE IMMUNOTHERAPEUTICS, other from BMS, other from lung cancer. Semin Thorac Cardiovasc Surg. 2011;23(2):137–45. https​:// ASTRAZENECA, other from ROCHE, outside the submitted work. Dr. Manuel doi.org/10.1053/j.semtc​vs.2011.07.001. Domine reports personal fees from Abbvie, personal fees from Astra-Zeneca, 7. Watanabe K, Sakamaki K, Nishii T, Yamamoto T, Maehara T, Nakayama personal fees from BMS, personal fees from Boehringer Ingelheim, personal H, Masuda M. Gender differences in the recurrence timing of patients fees from Celgene, personal fees from MSD, personal fees from Pfizer, personal undergoing resection for non-small cell lung cancer. Asian Pac J Cancer fees from Roche, outside the submitted work. Dr. Margarita Majem reports Prev. 2018;19(3):719–24. https​://doi.org/10.22034​/APJCP​.2018.19.3.719. grants from ROCHE, during the conduct of the study; personal fees from 8. Isla D, Majem M, Vinolas N, Artal A, Blasco A, Felip E, Garrido P, Remon ROCHE, grants from BMS, personal fees from MSD, personal fees and other J, Baquedano M, Borras JM, Die Trill M, Garcia-Campelo R, Juan O, Leon from ASTRA ZENECA, outside the submitted work; Dr. Nuria Viñolas reports C, Lianes P, Lopez-Rios F, Molins L, Planchuelo MA, Cobo M, Paz-Ares L, grants from Roche, during the conduct of the study; personal fees from Roche, Trigo JM, de Castro J. A consensus statement on the gender perspec‑ other from BMS, personal fees from Pfizer, other from Boeringher ingelheim, tive in lung cancer. Clin Transl Oncol. 2017;19(5):527–35. https​://doi. personal fees and other from Lilly, other from Astra zeneca, outside the sub‑ org/10.1007/s1209​4-016-1578-x. mitted work. Dr. Pilar Garrido reports grants from ROCHE, during the conduct 9. Temel JS, Pirl WF, Lynch TJ. Comprehensive symptom management in of the study; other from MSD, personal fees and other from BMS, personal patients with advanced-stage non-small-cell lung cancer. Clin Lung fees and other from BOERINGHER INGELHEIM, personal fees and other from Cancer. 2006;7(4):241–9. https​://doi.org/10.3816/CLC.2006.n.001. PFIZER, personal fees and other from NOVARTIS, other from LILLY, other from 10. Steptoe A, Demakakos P, de Oliveira C, Wardle J. Distinctive biological GUARDANT HEALTH, other from ABBVIE, personal fees and other from ASTRA correlates of positive psychological well-being in older men and women. ZENECA, other from SYSMEX, other from BLUE PRINT, other from TAKEDA, per‑ Psychosom Med. 2012;74(5):501–8. https​://doi.org/10.1097/PSY.0b013​ sonal fees from GILEAD, personal fees from ROVI, personal fees and other from e3182​4f82c​8. ROCHE, outside the submitted work. Dr. Pilar Lianes has nothing to declare. Dr.. 11. Mosher CE, Champion VL, Azzoli CG, Hanna N, Jalal SI, Fakiris AJ, Birdas Rosario Garcia Campelo reports grants from Roche, during the conduct of the TJ, Okereke IC, Kesler KA, Einhorn LH, Monahan PO, Ostroff JS. Eco‑ study; personal fees and other from Roche, personal fees and other from BMS, nomic and social changes among distressed family caregivers of lung personal fees and other from MSD, personal fees and other from PFIZER, per‑ cancer patients. 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