Relatives' Unmet Needs in the Last Year of Life of Patients With Advanced Cancer: Results of a Dutch Prospective, Longitudinal Study (eQuiPe).

Objective(s): Unmet needs of relatives of patients with advanced cancer not only reduce their own health-related quality of life, but may also negatively affect patients' health outcomes. The aim of this study was to assess changes in relatives' unmet needs of patients with advanced cancer in the last year of life and to identify differences in unmet needs by gender and type of relationship. Methods: Relatives of patients with advanced cancer in the Netherlands were included in a prospective, longitudinal, observational study. Relatives' unmet needs were measured every 3 months with an adapted version of the Problems and Needs in Palliative Care (PNPC) questionnaire Caregiver form (44 items, 12 domains). Questionnaires completed in the patients' last year of life were analyzed. Change of unmet needs in the last year, and differences in unmet needs by gender and type of relationship were analyzed. Results: A total of 409 relatives were included with a median of 4 unmet needs in the patient's last year. Unmet needs were most prevalent at all time points during the last year in the domains "caring for the patient" (highest need = 35%) and "psychological issues" (highest need = 40%). The number of unmet needs of relatives did not change significantly during the last year of life (P=.807). There were no significant differences in the number of unmet needs between male and female partners and between partners and other relatives. Conclusion: The most unmet needs for relatives were in the domains "caring for the patient" and "psychological issues." Professional support should focus on these items. Within these domains, it seems especially important that relatives get more knowledge and support about what scenarios to expect and how to deal with them.

Trajectories of health-related quality of life and symptom burden in patients with advanced cancer towards the end of life: Longitudinal results from the eQuiPe study.

BACKGROUND: Support for health-related quality of life (HRQOL) is an essential part of cancer care in the final stages of life, yet empirical guidance regarding HRQOL and symptom trajectories is lacking. AIM: To assess the change in HRQOL and symptom burden in the last year of life in patients with advanced cancer and its association with health care-related factors, cancer-specific treatment, and comorbidity. METHODS: A prospective, multicenter, observational study in patients with advanced cancer (eQuiPe). Three monthly questionnaires included European Organization for Research and Treatment of Cancer Quality of Life-C30 and reported continuity of care. Multivariable mixed-effects analysis was used to assess the association between HRQOL and health care-related factors. RESULTS: A total of 762 deceased patients were included with a mean age of 66 (SD, 10) years and 52% were male. The most common primary tumors were lung (29%), colorectal (20%), and breast cancer (13%). Mean overall HRQOL decreased in the last 9 months of life, with the greatest decrease in the last 3 months (ß -16.2). Fatigue, pain, appetite loss, dyspnea, constipation, and nausea worsened significantly in the last year of life. Multimorbidity (ß -7.5) and a better reported continuity of care (ß 0.7) were both significantly associated with the trajectory of HRQOL. CONCLUSION: Mean overall HRQOL begins to decline 9 months before death, highlighting the need for early identification and (re)assessment of different symptoms as aspects of HRQOL follow different trajectories. Multimorbidity and reported continuity of care may be associated with the trajectory of HRQOL.

Dyadic coping and its association with emotional functioning in couples confronted with advanced cancer: Results of the multicenter observational eQuiPe study.

OBJECTIVE: How patients and their partners cope with advanced cancer as a couple, may impact their emotional functioning (EF). The aim of this study was to assess dyadic coping (DC) of couples confronted with advanced cancer and its association with EF. METHODS: Actor-partner interdependence models were used to analyze baseline data of 566 couples facing advanced cancer participating in an observational study on quality of care and life. Measures included the DC Inventory and the European Organization for Research and Treatment of Cancer quality of life questionnaire (EOQLQ-C30). RESULTS: Negative DC (mean 86-88) was most often used and common DC (both mean 66) was least often used. We found small to moderate interdependence (r = 0.27-0.56) between patients' and partners' DC perceptions. Compared to partners, patients were more satisfied with their DC (p < 0.001). Partners' satisfaction with DC was positively associated with their own (B = 0.40, p < 0.001) and patients' (B = 0.23, p = 0.04) EF. We found positive actor (patients B = 0.37 B = 0.13, p = 0.04) and partner (both B = 0.17, p < 0.05) associations for negative DC in patients and partners. Partners' supportive DC was negatively associated with patients (B = -0.31, p = 0.03) and partners' EF (B = -0.34, p = 0.003). CONCLUSIONS: This study highlight the importance of DC (especially from the partners' perspective) for EF in advanced cancer but also identifies differences in the experience of patients and their partners. Future research is needed to understand the mechanisms of such relations and the common and unique support options that may facilitate adjustment in patients with advanced cancer and their partners.

A population-based study describing characteristics, survival and the effect of TKI treatment on patients with EGFR mutated stage IV NSCLC in the Netherlands.

INTRODUCTION: Since 2011, treatment guidelines advise targeted therapy (tyrosine kinase inhibitor, TKI) for patients with activating epidermal growth factor receptor (EGFR) mutations (EGFR+) in non-small cell lung cancer (NSCLC). We describe characteristics, first line treatment and survival of patients diagnosed with EGFR+ NSCLC in a European population, focussing on age, gender and trends over time and compare to the whole group and EGFR-. METHODS: All patients with non-squamous NSCLC stage IV, diagnosed 2011-2018, were identified from the population-based Netherlands Cancer Registry (N = 31,291). RESULTS: Among all, 7.0% were registered to be EGFR+, with highest prevalence in females <40 years (16%). Median overall survival (OS) ranged from 3.5 months in the EGFR- group >65 years to 23.6 months in the EGFR+ group <50 years treated with TKI. Over time, OS for the whole group increased by 0.6 months, of which 33% due to TKI treatment in EGFR+. The increase was strongest in females <50 years, where median OS almost doubled to 12.4 months. In the EGFR+, multivariable hazard of death was most strongly associated with the use of TKI (HR 0.45(0.41-0.49)). Of the patients with EGFR+ this space need or not, 71% received TKI treatment. Being young reduced the hazard of death (HR 0.71(95%CI:0.59-0.85)) irrespective of treatment, while male gender increased the hazard of death (HR 1.22(95%CI:1.11-1.33)). CONCLUSION: At population level, TKI treatment in patients with non-squamous NSCLC stage IV EGFR+  has very strong beneficial effects on outcome. Of the improvement in OS that was made over the years for the whole group, about one third seems to be attributed to TKI treatment in EGFR+ patients.

The relation between psychological profiles and quality of life in patients with lung cancer.

OBJECTIVE: Previous studies in patients with lung cancer examined the association between psychological factors with quality of life (QoL), as well as the association between psychological factors with sociodemographic and medical characteristics. However, knowledge about the impact of combinations of psychological characteristics on QoL is still lacking. Therefore, the current study aimed to identify psychological profiles, covering multiple psychological factors. Additionally, the association between these profiles with QoL and with sociodemographic and medical characteristics was explored. METHODS: Patients with lung cancer (n = 130, mean age = 68.3 ± 8.6 years; 49% men) completed questionnaires focusing on sociodemographic information, anxiety and depressive symptoms (HADS), coping (COPE-easy), perceived social support (PSSS), and QoL (WHOQOL-BREF). Medical information was extracted from patients' medical records. A step-3 latent profile analysis was performed to identify the psychological profiles. Multinomial logit models were used to explore the medical and sociodemographic correlates of the profiles and the relation with QoL. RESULTS: Four psychological profiles were identified as follows: (1) anxious, extensive coping repertoire (33%); (2) depressive, avoidant coping (23%); (3) low emotional symptoms, active/social coping (16%); and (4) low emotional symptoms, limited coping repertoire (29%). QoL in profile 1 (QoL = 6.59) was significantly different from QoL in profile 3 (QoL = 8.11, p = .001) and profile 4 (QoL = 7.40, p = .01). QoL in profile 2 (QoL = 6.43) was significantly different from QoL in profile 3 (QoL = 8.11, p = .003) and profile 4 (QoL = 7.40, p = .02). Regarding QoL, no other significant differences were found. Sociodemographic and medical characteristics were not distinctive for the profiles (all p values > .05). CONCLUSION: Determining psychological profiles of patients with lung cancer in an early stage provides information that may be helpful in aligning care with patients' unique needs, as it will help in more adequately selecting those patients who are in need of psychological screening and/or psychological treatment as compared with determining scores on single psychological factors.

Tumour growth rate as a tool for response evaluation during PD-1 treatment for non-small cell lung cancer: a retrospective analysis.

BACKGROUND: Immune checkpoint inhibitors have emerged as a standard of care treatment for non-small cell lung cancer (NSCLC). To get insight into variations in tumour growth kinetics and their potential predictive values for outcome, we evaluated tumour growth rate (TGR) in patients receiving programmed cell death 1 (PD-1) checkpoint inhibitors. PATIENTS AND METHODS: Differences in TGR before and after the start of treatment were calculated by entering the sum of the longest diameters from computer tomography scans before and after the initiation of therapy into a formula that assumes volumetric exponential tumour growth. TGR variations, possible predictors for TGR changes and its relationship to overall survival (OS) were studied. For comparison, tumour response was assessed using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. RESULTS: Among the 58 evaluable patients, 37 patients (64%) showed deceleration of TGR and 16 patients (27%) showed an acceleration of TGR after initiation of therapy, with a significant difference in median OS of 18.0 months versus 6.0 months (hazard ratio 0.35, 95% CI 0.18-0.71) between these groups. Four patients (7%) were defined as having hyperprogressive disease. In five patients (9%), tumour growth remained stable. These TGR categories were not significantly different according to age, sex, histology, smoking or previous radiotherapy. Of the patients defined as having progressive disease by RECIST version 1.1 at first follow-up, 40% showed response to checkpoint inhibitors by a decrease in TGR. CONCLUSION: Tumour growth kinetics can be used as a clinically relevant predictor for OS in anti-PD-1-treated patients with NSCLC, and may provide additional information to RECIST measurements.

Psychosocial consequences of diagnosis and treatment of lung cancer and evaluation of the need for a lung cancer specific instrument using focus group methodology.

OBJECTIVES: Patients with lung cancer (LC) have high rates of psychosocial symptoms and international guidelines recommend regular psychosocial screening during treatment. This study evaluates psychosocial consequences of diagnosis and treatment of LC in a qualitative way and evaluates the need for a LC specific screening instrument. METHODS: Focus group meetings with LC patients were divided by treatment type. Patients discussed psychological and social consequences of diagnosis and treatment. Major themes were identified using content analysis. Themes were re-evaluated in a subsequent focus group, in accordance with the European Organization for Research and Treatment of Cancer (EORTC) guidelines. RESULTS: Patients reported a range of psychosocial consequences, such as frustration due to physical limitations, fear of recurrence, sadness of leaving behind partner and children, and disappointing social support. Patients treated with palliative intent specifically indicated insecurities about the future. Patients from all treatment modalities indicated a need for family support during treatment. No themes specific to LC arose. CONCLUSIONS: Patients with LC are coping with a range of psychosocial consequences, independent of the type of treatment they receive. Fear of recurrence/metastasis and insecurity about the future were more prominent in patients receiving palliative chemotherapy. Themes were not specific to LC; therefore, a screening instrument specific for the LC population does not seem required. However, the current standard for screening is considered insufficiently sensitive and a stepped screening approach with specific screening tools and a clinical interview is suggested as usual care.

Influence of the Acidic Beverage Cola on the Absorption of Erlotinib in Patients With Non-Small-Cell Lung Cancer.

PURPOSE: Erlotinib depends on stomach pH for its bioavailability. When erlotinib is taken concurrently with a proton pump inhibitor (PPI), stomach pH increases, which results in a clinically relevant decrease of erlotinib bioavailability. We hypothesized that this drug-drug interaction is reversed by taking erlotinib with the acidic beverage cola. The effects of cola on erlotinib bioavailability in patients not treated with a PPI were also studied. PATIENTS AND METHODS: In this randomized, cross-over, pharmacokinetic study in patients with non-small-cell lung cancer, we studied intrapatient differences in absorption (area under the plasma concentration time curve [AUC0-12h]) after a 7-day period of concomitant treatment with erlotinib, with or without esomeprazole, with either cola or water. At the 7th and 14th day, patients were hospitalized for 1 day for pharmacokinetic sampling. RESULTS: Twenty-eight evaluable patients were included in the analysis. In patients treated with erlotinib and esomeprazole with cola, the mean AUC0-12h increased 39% (range, -12% to 136%; P = .004), whereas in patients not treated with the PPI, the mean AUC0-12h was only slightly higher (9%; range, -10% to +30%; P = .03) after erlotinib intake with cola. CONCLUSION: Cola intake led to a clinically relevant and statistically significant increase in the bioavailability of erlotinib during esomeprazole treatment. In patients not treated with the PPI, the effects of cola were marginal. These findings can be used to optimize the management of drug-drug interactions between PPIs and erlotinib.

Comorbidity in Patients With Small-Cell Lung Cancer: Trends and Prognostic Impact.

INTRODUCTION: We evaluated the trends in the prevalence of comorbidity and its prognostic impact in a cohort of unselected patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: All patients (n = 4142) diagnosed with SCLC from 1995 to 2012 were identified from the population-based Netherlands Cancer Registry in the Eindhoven region. RESULTS: The prevalence of comorbidity increased from 55% in 1995 to 1998 to 76% in 2011 to 2012 and multimorbidity (ie, ≥ 2 concomitant diseases) from 23% to 51%. The prevalence of a comorbidity increased with age. Among the men, hypertension, cardiac disease, and diabetes, in particular, became more common (increased from 11% to 35%, from 19% to 36%, and from 7% to 18%, respectively). In the women, the rate of pulmonary disease, hypertension, and cardiac disease increased the most (increased from 18% to 30%, from 12% to 28%, and from 11% to 24%, respectively). Multimorbidity was associated with a slightly increased hazard of death, independent of treatment in those with limited-stage SCLC (hazard ratio [HR] for ≥ 2 comorbidities vs. no comorbidities, 1.2; 95% confidence interval [CI], 1.0-1.4). The prognostic effects of multimorbidity resulted from treatment in those with extensive-stage SCLC (HR for ≥ 2 comorbidities vs. no comorbidities, final model, 1.2; 95% CI, 1.0-1.2). The prognostic impact of the specific comorbidities varied, with digestive disease reducing the hazard and cardiac disease increasing the hazard in those with limited-stage SCLC (HR for digestive disease vs. no digestive disease, 0.7 [95% CI, 0.5-0.9], and HR for cardiac vs. no cardiac disease, 1.2 [95% CI, 1.0-1.3]). Also, cardiac and cerebrovascular disease increased the hazard in those with extensive-stage SCLC (HR 1.2 [95% CI, 1.0-1.3] and HR 1.3 [95% CI, 1.1-1.6], respectively). CONCLUSION: Comorbidity among patients with SCLC is very common and has been increasing. Multimorbidity was associated with a slightly increased hazard of death in those with limited-stage SCLC, independent of treatment. However, the prognostic effects in those with advanced-stage SCLC resulted from treatment. Digestive disease favorably affected survival and cardiac disease negatively affected the prognosis for those with limited-stage SCLC, and cardiac and cerebrovascular diseases had a negative prognostic effect for those with extensive-stage SCLC. With the burden of comorbidities in patients with SCLC increasing, more attention to individualized treatment approaches is needed.

Improvement in population-based survival of stage IV NSCLC due to increased use of chemotherapy.

This study aimed to investigate which factors were associated with the administration of chemotherapy for patients with stage IV non-small cell lung cancer (NSCLC), and their relation to survival at a population-based level. All patients with NSCLC stage IV from 2001 to 2012 were identified in the Netherlands Cancer Registry in the Eindhoven area (n = 5,428). Chemotherapy use and survival were evaluated by logistic and Cox regression analyses, respectively. The proportion of patients receiving chemotherapy increased from 30% in 2001 to 48% in 2012. Higher rates were found among younger patients [multivariable odds ratio (OR(≤ 64_vs._≥ 75_years)): 1.8 (95%CI 1.6-2.1)], high socioeconomic status [OR(high_vs._low): 1.8 (95%CI 1.6-2.2)], no comorbidity [OR0_vs._≥ 2 : 1.5 (95%CI 1.3-1.8)], diagnosed in recent years [OR(2010-2012_vs._2001-2003): 2.0 (95%CI 1.6-2.3)] and adenocarcinoma [ORsquamous_vs._adenocarcinoma : 0.8 (95%CI 0.6-0.9)]. Having liver metastasis was associated with reduced odds (OR(liver_ vs._brain): 0.8 (95%CI 0.7-1.0). The variation between hospitals was large, up to OR 2.0 (95%CI 1.5-2.6). Median survival increased from 18 weeks in 2001-2003 to 21 weeks in 2010-2012 (log-rank p = 0.007), and was 35 weeks in patients with and 10 weeks without chemotherapy. The multivariable hazard of death reduced significantly over time [HR(2001-2003_vs._2010-2012): 1.1 (95%CI 1.0-1.2), HR(2004-2005_vs._2010-2012): 1.2 (95%CI 1.1-1.3)] and only remained significant for 2004-2006 after additional adjustment for chemotherapy [final multivariable model, HR(2004-2006_vs._2010-2012): 1.1 (95%CI 1.0-1.2)]. Besides, prognostic factors were having chemotherapy [final multivariable model: HR 0.4 (95%CI 0.4-0.4)], female sex [HRmale_vs._female : 1.1 (95%CI 1.0-1.1)], socioeconomic status [HR(intermediate_and_high_vs._low) both 0.9 (95%CI 0.9-1.0)], comorbidity [HR(unknown_vs._≥ 2): 1.3 (95%CI 1.2-1.5)], histology [HRother_vs._adenocarcinoma : 1.1 (95%CI 1.1-1.2)], and location of metastasis [range: 1.2 (HR(lymph_nodes_vs._brain)) - 1.6 (HR(liver_vs._brain))]. In conclusion, population-based survival increased due to increasing administration rates of chemotherapy. The administration of chemotherapy was affected by hospital of diagnosis and both patient and tumour characteristics. Identifying patients who benefit from chemotherapy should become a key issue.

EUS-FNA of enlarged necrotic lymph nodes may cause infectious mediastinitis.

Transesophageal endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a minimally invasive technique to investigate the mediastinum. Although EUS-FNA can be considered in general as a safe technique, complications do occur. We here report an infectious complication of EUS-FNA that occurred after puncture of a large malignant necrotic mediastinal lymph node.

Persistent rat cytomegalovirus (RCMV) infection of the salivary glands contributes to the anti-RCMV humoral immune response.

The salivary glands are the major sites of persistent replication of rat cytomegalovirus (RCMV). At several months post infection (pi), infectious RCMV is usually still produced in the salivary glands but not in any other organ or tissue of the rat. To investigate whether the persistence of RCMV in the salivary glands is crucial to the pathogenesis of viral infection, we monitored the progression of RCMV-induced disease in rats from which the salivary glands had been surgically removed (desalivated) as well as in sham-operated rats, both after a lethal and sublethal challenge with RCMV. Desalivation did not have a significant effect on either RCMV-induced morbidity or mortality. As expected, at 1 year pi, relatively high levels of infectious virus were detected in the salivary glands of sham-operated rats, whereas neither infectious virus nor RCMV DNA could be detected in liver, spleen and lungs of these animals. Infectious virus and viral DNA were also undetectable in organs from desalivated animals at 1 year pi. Surprisingly, a difference was found between desalivated and sham-operated rats in the titers of anti-RCMV IgG antibodies, which were significantly higher in sham-operated rats than in desalivated animals at 183, 295 and 365 days pi. This finding indicates that the persistence of RCMV in the salivary glands may contribute significantly to the anti-RCMV humoral immunity of infected rats.