Predictors for Long COVID and Differences in Long COVID Symptoms, Findings on Chest Imaging and Pulmonary Function between Hospitalized COVID-19 Patients with versus without Intensive Care Unit Admission.

INTRODUCTION: Many COVID-19 survivors suffer from persisting sequelae after acute disease. This is referred to as long COVID. The objectives of this study were to assess factors associated with long COVID and to analyze differences in persistent symptoms, findings on chest imaging, and pulmonary function between intensive care unit (ICU) and non-ICU hospitalized patients. METHODS: We conducted a retrospective study including patients hospitalized with COVID-19. Patients were stratified into ICU patients and non-ICU patients. We analyzed the outcomes of patients who were in clinical follow-up 6 months after discharge with persistent symptoms, radiological and/or functional abnormalities. Logistic regression was used to examine the association between long COVID and patient characteristics. RESULTS: A total of 549 patients were included. Eighty-one ICU patients (66%) and 146 (34%) non-ICU patients had persistent symptoms or abnormalities on chest imaging or lung function test minimally 6 months after discharge. Significantly more ICU patients had residual fibrotic abnormalities on chest CT and functional impairment. Female gender, myocardial infarction, OSAS, low PCO2 at admission, and longer hospital stay were associated with a higher risk of developing long COVID. Diabetes and treatment with tocilizumab were associated with a lower risk of developing long COVID. CONCLUSION: Of the patients hospitalized for COVID-19, 34-66% suffered from persistent symptoms, residual abnormalities on chest imaging, or reduced lung function at around 6 months after discharge. While persistent sequelae were more frequent in ICU patients, admission to the ICU was not found to be an independent risk factor for developing long COVID.

Effects of a time out consultation with the general practitioner on cancer treatment decision-making: a randomised controlled trial: Time out with the general practitioner and cancer treatment decision.

OBJECTIVE: Improving shared decision-making (SDM) enables more tailored cancer treatment decisions. We evaluated a Time Out consultation (TOC) with the general practitioner (GP), between cancer diagnosis and treatment decision, which aims at supporting SDM and improving continuity of primary care. This study aims to evaluate the effects of a TOC on perceived SDM, information provision and self-efficacy. METHODS: This randomised controlled trial included newly diagnosed patients with curable cancer (breast, lung, colorectal, gynaecologic and melanoma) from four Dutch hospitals. Primary outcome is perceived SDM and secondary outcomes are information provision and self-efficacy. RESULTS: One hundred fifty-four patients (control n = 77, intervention n = 77) - female: 75%, mean age: 61 (SD ± 11.9). In the intervention group, 80.5% (n = 62) had a TOC, of which 82.3% (n = 51) took place after treatment decision. Perceived SDM was lower in the intervention group (-8.9 [95% CI: 0.6-17.1]). Among those with a TOC before treatment decision (n = 11), perceived SDM was comparable to the control group (66.5 ± 27.2 vs. 67.9 ± 26.1). CONCLUSION: Even though patients are motivated to have a TOC, implementing a TOC between diagnosis and treatment decision is challenging. Effects of a timely TOC could not be established. Non-timely TOC decreased perceived SDM. Planning of the TOC should be optimised, and future research should establish if adequately timed TOC results in improved SDM in cancer patients.

Systematic evaluation of the efficacy-effectiveness gap of systemic treatments in extensive disease small cell lung cancer.

PURPOSE: The aim of this study is to assess how clinical outcomes in real-world (effectiveness) correspond to the outcomes in clinical trials (efficacy) of systemic treatments for extensive disease small cell lung cancer (ED SCLC). METHODS: All patients diagnosed with ED SCLC between 2008 and 2014 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. For every patient, an efficacy-effectiveness factor (EE factor) was calculated by dividing individual patients' overall survival (OS) by the pooled median OS assessed from clinical trials with the respective treatment. RESULTS: From 792 diagnosed patients, 568 (72%) started with first-line treatment. Overall, the median EE factor was 0.79 (P < .001 from 1.00). Poor performance status (ECOG≥2) and a higher age at diagnosis (age ≥ 65 years) were independent predictors for a lower EE factor. The EE gap was 43% in patients with both age ≥ 65 years and ECOG ≥2 (EE factor 0.57). The mean age and the proportion of patients with ECOG≥2 in real-world were different from those in clinical trials (mean age of 66 versus 62 years, and ECOG≥2 25% versus 17%; both P < .001). CONCLUSION: OS of patients with ED SCLC treated with systemic therapy in real-world practice is 21% shorter than for patients included in trials. Age at diagnosis and performance status partly explain this gap.

Real-world treatment patterns and outcomes of patients with extensive disease small cell lung cancer.

OBJECTIVE: Clinical outcome data on patients with extensive disease small cell lung cancer (ED SCLC) treated in routine practice is limited. The aim of this retrospective study is to present data on treatment patterns and survival in an unselected patient population with ED SCLC. METHODS: All patients diagnosed with ED SCLC between 2008 and 2014 in six Dutch large teaching hospitals (Santeon network) were included. We collected data on patient characteristics, systemic treatments, overall survival (OS), dose reductions (<80% of initial dose) and early discontinuation (<4 cycles). RESULTS: From 792 diagnosed patients, 568 (72%) started with first-line treatment. Of these patients, 41% received second-line treatment. Only 68 patients received third-line treatment. For all treated patients, the mean age was 66 years. The majority (72%) had a performance status (ECOG) of 0 or 1 at diagnosis. Median OS of treated patients was 7.4 months. Of all patients with first-line treatment, 26% received <4 cycles and dose reductions were observed in 29%. CONCLUSION: After first-line systemic treatment in ED SCLC the fraction of patients receiving subsequent lines of treatment is rapidly decreasing. This information is necessary as background for evaluation of the added value of future drugs under study for ED SCLC.

Needs with Regard to Decision Support Systems for Treating Patients with Incurable Non-small Cell Lung Cancer.

Treatment decision-making for patients with incurable non-small cell lung cancer (NSCLC) is complex due to the rapidly increasing number of treatments and discovery of new biomarkers. Decision support systems (DSS) could assist thoracic oncologists (TO) weighing of the pros and cons of treatments in order to arrive at an evidence-based and personalized treatment advice. Our aim is to inventory (1) TO's needs with regard to DSS in the treatment of incurable (stage IIIB/IV) NSCLC patients, and (2) preferences regarding the development of future tools in this field. We disseminated an online inventory questionnaire among all members of the Section of Oncology within the Society of Physicians in Chest Medicine and Tuberculosis. Telephone interviews were conducted to better contextualize the findings from the questionnaire. In total, 58 TO completed the questionnaire and expressed a need for new DSS. They reported that it is important for tools to include genetic and immune markers, to be sufficiently validated, regularly updated, and time-efficient. Also, future DSS should incorporate multiple treatment options, integrate estimates of toxicity, quality of life and cost-effectiveness of treatments, enhance communication between caregivers and patients, and use IT solutions for a clear interface and continuous updating of tools. With this inventory among Dutch TO, we summarized the need for new DSS to aid treatment decision-making for patients with incurable NSCLC. To meet the expressed needs, substantial additional efforts will be required by DSS developers, above already existing tools.

Systematic evaluation of the efficacy-effectiveness gap of systemic treatments in metastatic nonsmall cell lung cancer.

The divergence between clinical trial results and real-world outcomes is largely unknown for many cancer types. The present study aims overall to assess the efficacy-effectiveness gap (difference between outcomes in clinical trials and the real world) in systemic treatment for metastatic nonsmall cell lung cancer (NSCLC).All patients diagnosed with stage IV NSCLC between 2008 and 2014 within a network of seven Dutch large teaching hospitals (Santeon) were studied. For every patient, an efficacy-effectiveness (EE) factor was calculated by dividing individual patients' overall survival (OS) by the pooled median OS assessed from clinical trials with the respective treatment.From 2989 diagnosed patients, 1214 (41%) started with first-line treatment. For all studied regimens, real-world OS was shorter than OS reported in clinical trials. Overall, the EE factor was 0.77 (95% CI 0.70-0.85; p<0.001). Real-world patients completed their treatment plan less often and proceeded less frequently to further lines of treatment. These parameters together with Eastern Cooperative Oncology Group performance status explained 35% of the variation in EE factor.Survival of patients with metastatic NSCLC treated with chemotherapy or targeted therapy in real-world practice is nearly one-quarter shorter than for patients included in trials. Patients' performance status, earlier discontinuation and fewer subsequent lines of treatment partly explained this difference.

Recurrent Episodes of Nivolumab-Induced Pneumonitis after Nivolumab Discontinuation and the Time Course of Carcinoembryonic Antigen Levels: A Case of a 58-Year-Old Woman with Non-Small Cell Lung Cancer.

INTRODUCTION: The introduction of immune checkpoint inhibitors heralded a new era in the treatment of non-small cell lung cancer. However, nivolumab, an anti-PD-1 antibody, can cause serious adverse events that are mostly autoimmune related. CASE PRESENTATION: A 58-year-old woman was treated with nivolumab as second-line therapy for stage IV adenocarcinoma. The patient developed a nivolumab-induced recurrent pneumonitis preceding durable clinical remission after seven cycles of nivolumab. Although high-dose glucocorticosteroids were tapered to conform to contemporary guidelines, recurring episodes of pneumonitis occurred without nivolumab rechallenge. In addition, carcinoembryonic antigen (CEA) serum levels were associated with treatment response, since CEA decline correlated with a near complete radiological response and, conversely, elevated CEA serum levels were associated with progressive disease. CONCLUSIONS: In this case, we described recurrence of nivolumab-induced pneumonitis as a serious adverse event in immune checkpoint inhibitors. Our case illustrates that immune-related adverse events may correlate with antitumour activity, even after treatment discontinuation. In addition, this case suggests the possible clinical utility of CEA serum levels for the assessment of (durable) effects of immunotherapy.

Defining a standard set of patient-centred outcomes for lung cancer.

In lung cancer, outcome measurement has been mostly limited to survival. Proper assessment of the value of lung cancer treatments, and the performance of institutions delivering care, requires more comprehensive measurement of standardised outcomes.The International Consortium for Health Outcomes Measurement convened an international, multidisciplinary working group of patient representatives, medical oncologists, surgeons, radiation oncologists, pulmonologists, palliative care specialists, registry experts and specialist nurses to review existing data and practices. Using a modified Delphi method, the group developed a consensus recommendation ("the set") on the outcomes most essential to track for patients with lung cancer, along with baseline demographic, clinical and tumour characteristics (case-mix variables) for risk adjustment.The set applies to patients diagnosed with nonsmall cell lung cancer and small cell lung cancer. Our working group recommends the collection of the following outcomes: survival, complications during or within 6 months of treatment and patient-reported domains of health-related quality of life including pain, fatigue, cough and dyspnoea. Case-mix variables were defined to improve interpretation of comparisons.We defined an international consensus recommendation of the most important outcomes for lung cancer patients, along with relevant case-mix variables, and are working to support adoption and reporting of these measures globally.

Why do patients and caregivers seek answers from the Internet and online lung specialists? A qualitative study.

BACKGROUND: Since its launch in 2003, the Dutch Lung Cancer Information Center's (DLIC) website has become increasingly popular. The most popular page of the website is the section "Ask the Physician", where visitors can ask an online lung specialist questions anonymously and receive an answer quickly. Most questions were not only asked by lung cancer patients but also by their informal caregivers. Most questions concerned specific information about lung cancer. OBJECTIVE: Our goal was to explore the reasons why lung cancer patients and caregivers search the Internet for information and ask online lung specialists questions on the DLIC's interactive page, "Ask the Physician", rather than consulting with their own specialist. METHODS: This research consisted of a qualitative study with semistructured telephone interviews about medical information-seeking behavior (eg, information needs, reasons for querying online specialists). The sample comprised 5 lung cancer patients and 20 caregivers who posed a question on the interactive page of the DLIC website. RESULTS: Respondents used the Internet and the DLIC website to look for lung cancer-related information (general/specific to their personal situation) and to cope with cancer. They tried to achieve a better understanding of the information given by their own specialist and wanted to be prepared for the treatment trajectory and disease course. This mode of information supply helped them cope and gave them emotional support. The interactive webpage was also used as a second opinion. The absence of face-to-face contact made respondents feel freer to ask for any kind of information. By being able to pose a question instantly and receiving a relatively quick reply from the online specialist to urgent questions, respondents felt an easing of their anxiety as they did not have to wait until the next consultation with their own specialist. CONCLUSIONS: The DLIC website with its interactive page is a valuable complementary mode of information supply and supportive care for lung cancer patients and caregivers.

Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study.

BACKGROUND: Standard chemotherapy does not lead to long-term survival in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma is strongly dependent on vasculature with high vessel counts and high concentrations of serum vascular growth factors. Thalidomide has shown antiangiogenic activity, and we hypothesised that its use in the maintenance setting could improve outcomes. METHODS: In this open-label, multicentre, randomised phase 3 study, eligible patients had proven malignant pleural or peritoneal mesothelioma and had received a minimum of four cycles of first-line treatment containing at least pemetrexed, with or without cisplatin or carboplatin, and had not progressed on this treatment. Patients were randomly assigned (in a 1:1 ratio, stratified by previous first-line chemotherapy, histological subtype, and recruiting hospital) to receive thalidomide 200 mg per day (including a 2 week run in of 100 mg per day) plus active supportive care or active supportive care alone until disease progression. Patients were required to be registered and to start treatment with thalidomide within 10 weeks after the end of the first-line chemotherapy. Thalidomide was given for a maximum of 1 year or until unacceptable toxicity. The primary endpoint was time to progression. The primary analyses were by intention to treat. The study is registered, ISRCTN13632914. FINDINGS: Between May 11, 2004, and Dec 23, 2009, we randomly assigned 222 patients, 111 in each group (one patient on active supportive care later withdrew consent and was excluded from analyses). At the time of this final analysis, median follow-up was 33.1 months (IQR 22.3-66.8), and physician-reported disease progression had occurred in 104 patients in the thalidomide group and 107 in the active supportive care group; 92 patients in the thalidomide group and 93 in the active supportive care group had died. Median time to progression in the thalidomide group was 3·6 months (95% CI 3.2-4.1) compared with 3.5 months (2.3-4.8) in the active supportive care group (hazard ratio 0.95, 95% CI 0.73-1.20, p=0.72). 43 (39%) grade 3 or 4 adverse events were reported in the thalidomide group and 31 (28%) in the active supportive care group; neurosensory events were reported by two (2%) patients on thalidomide and none on active supportive care, cardiac events by two (2%) patients on thalidomide and three (3%) on active supportive care, and thromboembolic events by three (3%) patients on thalidomide and none on active supportive care. INTERPRETATION: No benefit was noted in time to progression with the addition of thalidomide maintenance to first-line chemotherapy. Different treatment strategies are needed to improve outcomes in patients with malignant mesothelioma. FUNDING: Dutch Cancer Society (KWF), Eli Lilly, NSW Dust Disease Compensation Board, University of Sydney, and Cancer Australia.

High Protein Oral Nutritional Supplements Enable the Majority of Cancer Patients to Meet Protein Intake Recommendations during Systemic Anti-Cancer Treatment: A Randomised Controlled Parallel-Group Study.

ESPEN guidelines recommend a minimum protein intake of 1.0 g/kg body weight (BW) per day to maintain or restore lean body mass in patients with cancer. During anti-cancer treatment, optimal protein intake is difficult to achieve. We investigated whether a high-protein, low-volume oral nutritional supplement (ONS) supports patients in meeting recommendations. A multi-centre, randomised, controlled, open-label, parallel-group study was carried out in nine hospitals (five countries) between January 2019 and July 2021 in colorectal and lung cancer patients undergoing first-line systemic treatment with chemo(radio-) or immunotherapy. Subjects were randomised (2:1) to receive Fortimel Compact Protein® or standard care. Protein intake was assessed with a 3-day food diary (primary outcome). BW was a secondary outcome. Due to challenges in recruitment, the study was terminated prematurely with 42 patients randomised (intervention group (IG) 28; control group (CG) 14). At T1 and T2, protein intake was statistically significantly higher in the IG compared to the CG (1.40 vs. 1.07 g/kg/day at T1, p = 0.008; 1.32 vs. 0.94 g/kg/day at T2, p = 0.002). At baseline, only 65% (IG) and 45% (CG) of patients met ESPEN minimum protein intake recommendations. However, at T1 and T2 in the IG, a higher proportion of patients met recommendations than in the CG (88% vs. 55% and 40%). No statistically significant difference between study groups was observed for BW. Mean compliance to the ONS was 73.4%. A high-protein, low-volume ONS consumed twice daily enables the majority of patients to reach minimal ESPEN protein recommendations.

Development and validation of a decision model for the evaluation of novel lung cancer treatments in the Netherlands.

Recent discoveries in molecular diagnostics and drug treatments have improved the treatment of patients with advanced (inoperable) non-squamous non-small cell lung cancer (NSCLC) from solely platinum-based chemotherapy to more personalized treatment, including targeted therapies and immunotherapies. However, these improvements come at considerable costs, highlighting the need to assess their cost-effectiveness in order to optimize lung cancer care. Traditionally, cost-effectiveness models for the evaluation of new lung cancer treatments were based on the findings of the randomized control trials (RCTs). However, the strict RCT inclusion criteria make RCT patients not representative of patients in the real-world. Patients in RCTs have a better prognosis than patients in a real-world setting. Therefore, in this study, we developed and validated a diagnosis-treatment decision model for patients with advanced (inoperable) non-squamous NSCLC based on real-world data in the Netherlands. The model is a patient-level microsimulation model implemented as discrete event simulation with five health events. Patients are simulated from diagnosis to death, including at most three treatment lines. The base-model (non-personalized strategy) was populated using real-world data of patients treated with platinum-based chemotherapy between 2008 and 2014 in one of six Dutch teaching hospitals. To simulate personalized care, molecular tumor characteristics were incorporated in the model based on the literature. The impact of novel targeted treatments and immunotherapies was included based on published RCTs. To validate the model, we compared survival under a personalized treatment strategy with observed real-world survival. This model can be used for health-care evaluation of personalized treatment for patients with advanced (inoperable) NSCLC in the Netherlands.

Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands.

BACKGROUND: Gefitinib, a tyrosine kinase inhibitor, is an effective treatment in advanced non-small cell lung cancer (NSCLC) patients with an activating mutation in the epidermal growth factor receptor (EGFR). Randomised clinical trials showed a benefit in progression free survival for gefitinib versus doublet chemotherapy regimens in patients with an activated EGFR mutation (EGFR M+). From a patient perspective, progression free survival is important, but so is health-related quality of life. Therefore, this analysis evaluates the Quality Adjusted progression free survival of gefitinib versus three relevant doublet chemotherapies (gemcitabine/cisplatin (Gem/Cis); pemetrexed/cisplatin (Pem/Cis); paclitaxel/carboplatin (Pac/Carb)) in a Dutch health care setting in patients with EGFR M+ stage IIIB/IV NSCLC. This study uses progression free survival rather than overall survival for its time frame in order to better compare the treatments and to account for the influence that subsequent treatment lines would have on overall survival analysis. METHODS: Mean progression free survival for Pac/Carb was obtained by extrapolating the median progression free survival as reported in the Iressa-Pan-Asia Study (IPASS). Data from a network meta-analysis was used to estimate the mean progression free survival for therapies of interest relative to Pac/Carb. Adjustment for health-related quality of life was done by incorporating utilities for the Dutch population, obtained by converting FACT-L data (from IPASS) to utility values and multiplying these with the mean progression free survival for each treatment arm to determine the Quality Adjusted progression free survival. Probabilistic sensitivity analysis was carried out to determine 95% credibility intervals. RESULTS: The Quality Adjusted progression free survival (PFS) (mean, (95% credibility interval)) was 5.2 months (4.5; 5.8) for Gem/Cis, 5.3 months (4.6; 6.1) for Pem/Cis; 4.9 months (4.4; 5.5) for Pac/Carb and 8.3 (7.0; 9.9) for gefitinib. CONCLUSIONS: In the Dutch health care setting, the previously established progression free survival benefit of first-line gefitinib in advanced NSCLC EGFR M+ patients in comparison to standard doublet chemotherapy is further supported by the Quality Adjusted PFS, which takes into account the additional health-related quality of life benefits of gefitinib over doublet chemotherapy.

Benefit of Concurrent Versus Sequential Chemoradiotherapy in Elderly Patients With Stage III Non-Small Cell Lung Cancer.

INTRODUCTION: Lung cancer is the largest cause of cancer-related deaths worldwide. Eighty-five percent of patients is diagnosed with non-small cell lung cancer (NSCLC). Almost a third of patients is aged over 75, but this group is poorly represented in clinical trials. This study compares the effects of therapy in non-operable stage III NSCLC in elderly patients compared to their younger counterparts. PATIENTS AND METHODS: This is a retrospective cohort study. Patients are divided into three groups; patients younger than 65, patients aged between 65 and 75 and patients of 75 years or older. Concurrent chemoradiotherapy is compared to sequential chemoradiotherapy using Cox regression analysis. The primary outcome is survival. A sub analysis is performed for the presence of toxicity using logistic regression. RESULTS: Seven hundred and fifty patients were diagnosed with stage III NSCLC and treated with concurrent (442) or sequential (308) chemoradiotherapy. Concurrent chemoradiotherapy provides a decreased HR of death of 0.72 (0.560-0.85) compared to sequential chemoradiotherapy, even when corrected for age. Elderly patients receiving concurrent chemoradiotherapy do not have a significantly larger risk of toxicity. CONCLUSIONS: Patients of all ages with stage III NSCLC benefit from concurrent chemoradiotherapy compared to sequential chemoradiotherapy. Age is not a deciding factor in this prospect, nor do the patients experience more severe toxicity than their younger counterparts.

Adjuvant Treatment Following Irradical Resection of Stage I-III Non-small Cell Lung Cancer: A Population-based Study.

Irradical (R1-2) resection for non-small cell lung cancer (NSCLC) is associated with a dismal prognosis. Adjuvant treatment attempts to improve survival outcomes, but evidence on the optimal strategy is limited. The purpose of this study was to compare overall survival (OS) between different adjuvant treatment strategies in these patients. Out of 8,528 patients with newly diagnosed NSCLC from 2015-2018, those with an R1-2 resection were identified from the Netherlands Cancer Registry. First, OS was compared between adjuvant treatment groups 'no therapy', 'radiotherapy (RT) only', 'chemotherapy only', and 'chemo- and radiotherapy (CRT)' using multinomial propensity score-weighted Cox regression analysis. Second, three 1:1 propensity score-matched sets were created for chemotherapy vs no chemotherapy, RT only vs no therapy, and CRT vs chemotherapy only. Kaplan-Meier and Cox regression analyses for OS were performed in each set. With a median follow-up of 23 months, 427 patients were selected. In the weighted regression analysis, compared to no adjuvant therapy, chemotherapy and CRT were associated with improved OS (HR 0.41, 95%CI: 0.22-0.76; and HR 0.55, 95%CI: 0.37-0.81, respectively), whereas RT was not (HR 1.04, 95%CI: 0.73-1.50). In the matched sets, OS was improved after chemotherapy (+/- RT) compared to no chemotherapy (HR 0.47, 95%CI: 0.32-0.69). No OS difference was observed between matched groups of RT only vs no adjuvant therapy (HR 1.13, 95%CI: 0.74-1.72), nor for CRT vs chemotherapy only (HR 1.37, 95%CI: 0.70-2.71). Adjuvant chemotherapy, but not radiotherapy, improves survival after an R1-2 resection in stage I-III NSCLC.

Cost-Effectiveness of Surveillance Scanning Strategies after Curative Treatment of Non-Small-Cell Lung Cancer.

BACKGROUND: After curative treatment of primary non-small-cell lung cancer (NSCLC), patients undergo intensive surveillance with the aim to detect recurrences from the primary tumor or metachronous second primary lung cancer as early as possible and improve overall survival. However, the benefit of surveillance is debated. Available evidence is of low quality and conflicting. Microsimulation modeling facilitates the exploration of the impact of different surveillance strategies and provides insight into the cost-effectiveness of surveillance. METHODS: A microsimulation model was used to simulate a range of computed tomography (CT)-based surveillance schedules, differing in the frequency and duration of CT surveillance. The impact on survival, quality-adjusted life-years, costs, and cost-effectiveness of each schedule was assessed. RESULTS: Ten of 108 strategies formed the cost-effectiveness frontier; that is, these were the strategies with the optimal cost-health benefit balance. Per person, the discounted QALYs of these strategies varied between 5.72 and 5.81 y, and discounted costs varied between €9892 and €19,259. Below a willingness-to-pay threshold of €50,000/QALY, no scanning is the preferred option. For a willingness-to-pay threshold of €80,000/QALY, surveillance scanning every 2 y starting 1 y after curative treatment becomes the best option, with €11,860 discounted costs and 5.76 discounted QALYs per person. The European Society for Medical Oncology guideline strategy was more expensive and less effective than several other strategies. CONCLUSION: Model simulations suggest that limited CT surveillance scanning after the treatment of primary NSCLC is cost-effective, but the incremental health-benefit remains marginal. However, model simulations do suggest that the guideline strategy is not cost-effective.

'Care for Outcomes': systematic development of a set of outcome indicators to improve patient-relevant outcomes for patients with lung cancer.

OBJECTIVES: Measuring quality of care is important, however many of the quality indicators used do not focus on outcome of treatment and aspects which are valuable for patients and physicians. The project 'Care for Outcomes' aims to establish a relevant set of outcome indicators for lung cancer. SETTING: Network of seven large, non-university teaching hospitals in the Netherlands (Santeon). METHODS: By reviewing the literature, a list of potential outcome indicators for patients with lung cancer was composed and subsequently prioritised by expert's opinion. Three external parties, with expertise on lung cancer, clinical management and public health, evaluated and reduced the list of indicators to a working set. Finally, the resulting selection of outcome indicators was tested for feasibility and discrimination in patient data, by collecting retrospective data and performing regression and survival analyses. PARTICIPANTS: Development of the indicator set in six Santeon hospitals. Retrospective cohort study in 5922 patients diagnosed with lung cancer (all types and stages). RESULTS: Selected outcome indicators were divided into three levels of outcome (tiers). The first tier about survival and the process of recovery include mortality, survival, positive resection margins, rethoracotomy after resection and quality of life at baseline and after 3, 6 and 12 months. Tier 2 concerning the sustainability of the recovery include complications after resection and toxicity after chemotherapy and/or radiation. Tier 3 about sustainability of health revealed no measurable outcomes. The retrospective data collection showed differences between hospitals and variation in case mix. CONCLUSION: A relevant set of outcome indicators for lung cancer was systematically developed. This set has the potential to compare quality of care between hospitals and inform patients with lung cancer about outcomes. The project is ongoing in the current Santeon Value-Based Health Care programme through quality and improvement cycles.

Evaluation of Serum Biomarker CEA and Ca-125 as Immunotherapy Response Predictors in Metastatic Non-small Cell Lung Cancer.

BACKGROUND/AIM: Treatment options for advanced non-small cell lung cancer (NSCLC) include immunotherapy. Elevated carcinoembryonic antigen (CEA) and cancer antigen 125 (Ca-125) levels are associated with poorer prognoses of resected NSCLC, but currently no predictive biomarkers exist for immunotherapy response. This study evaluated CEA and Ca-125 as predictive biomarkers for immunotherapy efficiency in patients with metastatic NSCLC. PATIENTS AND METHODS: The single-centre observational retrospective study includes NSCLC stage III/IV patients treated with programmed death-ligand 1 (PD-L1) inhibitors nivolumab or pembrolizumab. The primary study endpoint was treatment response assessed by CT-scan following RECIST-criteria 1.1. CEA/Ca-125 serum values were determined at initiation of treatment and repeated every 2 weeks. Values closest to the day of CT-scan were compared to baseline values. RESULTS: A total of 136 patients were treated with mono-immunotherapy. Of these, 73 patients were included in the CEA group and 53 patients were included in the Ca-125 group. Baseline CEA and Ca-125 ranged from 8.14 to 5,909 and 1.1 to 4,238 respectively. The sensitivity for Ca-125 as predictor for tumor response was 62.9% (95% CI=61.8%-63.6%), specificity 61.1% (95% CI=60.2%-62.0%), with a positive predictive value (PPV) of 75.9% (95% CI=75.2%-76.7%). For CEA, the sensitivity was 72.0% (95% CI=71.5%-72.5%), specificity 47.1% (95% CI 46.4%-47.8%), with a PPV of 80.0% (95% CI=79.6%-80.4%). CONCLUSION: Increased serum CEA might predict tumor progression in NSCLC patients treated with PD-L1 inhibitors. Unconfirmed progression accompanied by increased CEA would support discontinuation of the immunotherapy, while continuation would be advised when serum CEA is not increased.

Trends in Drug Costs and Overall Survival in Patients with Metastatic Non-small Cell Lung Cancer in The Netherlands Diagnosed from 2008 Through 2014.

BACKGROUND: The Value-Based Health Care concept defines patient value as patient-relevant outcomes divided by costs. The aim of the present study was to assess the development of systemic treatment costs over the years compared with changes in overall survival (OS) at the level of a diagnosis of stage IV non-small cell lung cancer (NSCLC). METHODS: All patients diagnosed (in 2008-2014) with stage IV NSCLC and treated with systemic treatment in six Dutch large teaching hospitals (Santeon network) were included. We collected data on OS and amounts of drug units (milligrams) for every drug in the applied systemic cancer treatments, until death. These amounts were multiplied by Dutch unit costs (Euros/mg) expressed in 2018 Euros to construct total drug costs per line of treatment per patient. Costs for day care visits were added for drugs requiring parenteral administration. RESULTS: Data were collected from 1214 patients. Median OS and mean total drug costs showed no significant variation over the years (p = 0.437 and p = 0.693, respectively). Mean total drug costs per 1 year of survival ranged from €20,665 to €26,438 during the period under study. Costs for first-line systemic treatment were significantly higher in 2011-2014 compared with 2008-2010. CONCLUSION: This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years.

Development and Evaluation of a Real-World Outcomes-Based Tool to Support Informed Clinical Decision Making in the Palliative Treatment of Patients With Metastatic NSCLC.

PURPOSE: To develop and evaluate a tool for patients with stage IV non-small-cell lung cancer and their thoracic oncologists (TOs) that provides insight into real-world effectiveness of systemic treatments to support informed clinical decision making in the palliative setting. METHODS: A participatory design approach was used to acquire insights from patients and TOs into preferences regarding the content and design of the web-based tool. Implementation was investigated by means of an adoption and usage rate. The appreciation of the tool was evaluated through a telephone survey with patients and a questionnaire for TOs. RESULTS: From clinical data of 2,989 patients with stage IV non-small-cell lung cancer diagnosed in one of the Santeon hospitals, an interface was developed to show treatments plus both real-world outcomes and clinical trial results after selecting patient characteristics (patients like me). This prototype of the tool was finalized after discussion in a focus group with four TOs and semi-structured interviews with six patients. The tool was implemented and used by TOs in three of six Santeon hospitals (50% adoption rate). The tool was used in 48 patients (29% usage rate), of which 17 participated in the telephone survey. Ten TOs responded to the questionnaire. The responses varied from positive reactions on the clear overview of treatment outcomes to statements that the tool rarely changed treatment decisions. Overall, the majority of patients and TOs scored the tool as of added value (71% and 83%, respectively). CONCLUSION: Our real-world data tool in metastatic lung cancer was appreciated in clinical practice by both patients and TOs. However, the efficacy of the implementation can be improved.