BACKGROUND:The programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) is used as a biomarker to predict benefit from immune checkpoint blockade (ICB) in patients with non-small cell lung cancer (NSCLC). However, additional biomarkers are needed. The potential of kinase activity profiling of peripheral blood mononuclear cells (PBMCs) for predicting response to ICB was previously shown in a discovery study. The goal of this prospective study is to evaluate the predictive value of blood-based kinase profiling for ICB response in patients with NSCLC and to compare the performance and added value to TPS. METHODS:Advanced stage patients with NSCLC, treated with anti-programmed cell death protein 1 ICB (±chemotherapy) were included in this multicenter study (N=210 patients). PBMCs were collected prior to ICB treatment and profiled using a peptide microarray with multiple kinase substrates (PamChip). Classification analysis was performed to discriminate between patients with or without progressive disease by Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 <24 weeks after treatment start. A predictive model was first established based on TPS and kinase activity profiles. Subsequently, the performance of the model was tested in a second (validation) cohort. RESULTS:In the validation cohort, a significantly higher progression-free survival (PFS) rate was observed for patients with predicted benefit than for patients without predicted benefit according to the kinome-based prediction model (HR=0.56, p=0.01), which tended better compared with TPS alone (HR=0.66, p=0.07). When the kinome-based model was combined with TPS, the difference in PFS between patients with and without predicted benefit was further increased (HR=0.38, p<0.001). PFS rates were also higher for patients with predicted benefit in subgroups with decreased PD-L1 expression (TPS <1% (HR=0.46, p=0.027) and TPS 1-50% (HR=0.20, p=0.005)). CONCLUSIONS:This study shows the predictive value of kinase activity profiling of PBMCs for ICB response in advanced NSCLC, which was superior compared with TPS. In particular, for patients with NSCLC with TPS <50%, combining TPS with the blood-based kinase test may identify patients with limited benefit from ICB. TRIAL REGISTRATION NUMBER:NTR7015/NL6828.
Pemetrexed is a cornerstone in chemo(immunotherapy) of non‐small cell lung cancer and mesothelioma; however, it is contraindicated in patients with renal impairment due to severe toxicity concerns. Therefore, a large proportion of patients is withheld from effective chemo(immunotherapy). We performed an intra‐patient 3 + 3 dose escalation renal impairment study (eGFR < 45 mL/min). The pemetrexed dose was calculated based on renal function to reach a target AUC, and patients received oral folinic acid prophylaxis 45 mg four times daily on Days 2–15 of each cycle. Endpoints included safety (incidence of hematological and non‐hematological toxicity, treatment delays) and pharmacokinetics in line with regulatory guidance for renal impairment trials. Six patients with an estimated glomerular filtration rate (eGFR) between 26 and 41 mL/min were included. All patients were successfully escalated to the full dose. Adverse event patterns and pharmacokinetics were comparable to those in patients with normal renal function. Grade I/II anemia occurred in five patients (already present at baseline). One occurrence of grade IV neutropenia was observed, which resolved without intervention. Moreover, in three patients, a 1‐week treatment delay occurred. Treatment resulted in a response in four patients ( n = 1 complete response, n = 2 partial response, n = 1 stable disease). Pemetrexed can be safely administered in patients with impaired renal function when the dose is calculated based on renal function and folinic acid prophylaxis is administered, thereby enabling an effective treatment modality for patients that, thus far, could not be treated.
Introduction: The impact of an immune checkpoint inhibitor (ICI)-based systemic treatment strategy with or without local radical treatment (LRT) on outcomes for patients with NSCLC and synchronous oligometastatic disease (sOMD) is unknown. Methods: Multicenter retrospective study including adequately staged patients, with sOMD NSCLC (maximum five metastases in three organs [European Organization for Research and Treatment of Cancer definition]) between January 1, 2015 and December 31, 2022, treated with a first-line ICI-based versus chemotherapy-only regimen. Primary end points were progression-free survival and overall survival (OS) for an ICI-based versus chemotherapy-only strategy. Subgroup analyses were performed for patients who were deemed candidates for LRT in the multidisciplinary meeting and those proceeding to LRT. Results: A total of 416 patients were included, treated with chemotherapy-ICI (n = 138) or chemotherapy-only (n = 278), 319 out of 416 were deemed candidates by multidisciplinary meetings for LRT, whereas 192 (60%) proceeded to LRT. The median OS was significantly longer in the chemotherapy-ICI compared with the chemotherapy-only group (33.6 versus 15.9 mo, hazard ratio [HR] = 0.5, 95% confidence interval [CI]: 0.4-0.7, p < 0.001), in the subgroups who were candidate for LRT (36.1 versus 17.2 mo, HR = 0.5, 95% CI: 0.4-0.7, p < 0.001) and those proceeding to LRT (not reached versus 23.1 mo, HR = 0.4, 95% CI: 0.2-0.7, p < 0.001). In multivariate analysis, an ICI-based strategy was associated with improved survival in the total group (HR = 0.6, 95% CI: 0.4- 0.9, p < 0.001), in those with intention of LRT (HR = 0.6, 95% CI: 0.4-0.9, p = 0.02) and those who proceeded to LRT (HR = 0.3, 95% CI: 0.1-0.6, p = 0.002). Conclusions: An ICI-based systemic treatment strategy (+/- LRT) is associated with improved survival compared with chemotherapy-only (+/- LRT) for patients with sOMD NSCLC. Prospective randomized trial data are necessary to identify patients most likely to benefit from adding LRT. (c) 2025 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.
Objective To assess the degree of openness of communication about illness and death between patients with advanced cancer and their relatives during the last three months of the patient’s life, and its association with relatives’ characteristics and bereavement distress. Methods We used data from bereaved relatives of patients with advanced cancer from the prospective, longitudinal, multicenter, observational eQuipe study. Univariate and multivariable linear regression analyses were used to assess the association between the degree of openness of communication (measured using the validated Caregivers’ Communication with patients about Illness and Death scale), the a priori defined characteristics of the relatives, and the degree of bereavement distress (measured using the Impact of Event Scale). Results A total of 160 bereaved relatives were included in the analysis. The average degree of open communication about illness and death between patients with advanced cancer and their relatives was 3.86 on a scale of 1 to 5 ( SE = 0.08), A higher degree of open communication was associated with a lower degree of bereavement distress ( p = 0.003). No associations were found between the degree of open communication and the relatives’ age ( p = 0.745), gender ( p = 0.196), level of education ( p > 0.773), (religious) worldview ( p = 0.435), type of relationship with the patient ( p > 0.548), or level of emotional functioning before the patient’s death ( p = 0.075). Conclusions Open communication about illness and death between patients and relatives seems to be important, as it is associated with a lower degree of bereavement distress. Healthcare professionals can play an important role in encouraging the dialogue. However, it is important to keep in mind that some people not feel comfortable talking about illness and death.
Objectives: Timely diagnosis of lung cancer (LC) is crucial to achieve optimal patient care and outcome. Moreover, the number of procedures required to obtain a definitive diagnosis can have a large influence on the life expectancy of a patient. Here, adherence with existing Dutch guidelines for timeliness and type and number of invasive and imaging procedures was assessed. Materials and methods: 1096 patients with suspected LC were enrolled in this multicenter prospective study (NL9146). The overall survival, time from referral to the first appointment with the pulmonologist, time to diagnosis and treatment, and the number of imaging and invasive procedures were evaluated. Patients were divided into different diagnostic groupsearly- and advanced stage non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), large cell neuroendocrine carcinoma of the lung (LCNEC), patients without LC and patients without a definitive diagnosis. Results: The majority of patients (66 %) received a definitive diagnosis within 5 weeks, although the time to diagnosis of early-stage LC patients and patients without LC was significantly longer comparted to advanced stage LC. An increase in invasive procedures was seen for early-stage LC compared to advanced stage LC and for 13 % of the advanced stage non-squamous NSCLC patients up to three additional invasive procedures were performed solely to obtain sufficient material for NGS. For patients without a definitive diagnosis, 50 % did undergo at least one invasive procedure, while 11 % did not wish to undergo any invasive procedures. Conclusion: These insights could aid in improved LC diagnostics and efficient implementation of new techniques like liquid biopsy and artificial intelligence. This may lead to more timely LC care, a decreased number of invasive procedures, less variability between the diagnostic trajectory of different patients and aid in obtaining a definitive diagnosis for all patients.
[This corrects the article DOI: 10.1183/23120541.00239-2022.].
e20576 Background: Treatment with immune checkpoint inhibitors (ICI) has become part of the standard of care for patients with advanced stage non-small cell lung cancer (NSCLC). Unfortunately, its success is limited to a subset of treated patients, while ICI treatment is associated with immune-related adverse events. The predictive value of kinase activity profiling of peripheral blood mononuclear cells (PBMCs) was previously shown in a discovery study (Hurkmans et al., JITC 2020). The aim of the current study was to perform a prospective and blinded validation of the predictive value of kinase activity profiles of PBMCs for response to ICI treatment in patients with NSCLC in a standardized setting. Preliminary results for this study were presented before (De Joode et al. 2022), here we present results for a significantly extended validation cohort with a follow-up of at least 1 year. Methods: PBMCs from patients with advanced stage NSCLC included in this observational multicenter study were collected prior to ICI treatment. Tyrosine kinase activity of PBMCs was profiled using a micro-array with 144 different peptide-substrates (Pamchip). Classification analysis was performed to discriminate between patients with or without progressive disease (RECIST v1.1) within 24 weeks after start of treatment. Only patients treated with first-line pembrolizumab ± chemotherapy were included. Results: A predictive model was first established based on kinase activity profiles, determined in a calibration cohort (N = 61) and subsequently applied to an independent validation cohort (N = 136). The predictive accuracy of the model in the validation cohort was 62% (CI95 = 53-70%). Interestingly, the accuracy improved when the model was combined with PD-L1 expression: for patients with a PD-L1 score < 50%, the accuracy for predicting progressive disease at 24 weeks was 68% (CI95 = 57-78%). Here, significant lower progression free survival (PFS) rates were observed for patients for whom progression was predicted compared to those for whom no progression was predicted (p = 0.0003, hazard ratio = 2.6, CI95 = 1.6-4.3).The 1-year PFS for patients with predicted progression was only 13% (CI95 = 5-31%) which implies a NPV of 87%. PFS rates were also lower for patients with predicted progression in the subgroups with PD-L1 score < 1% (p = 0.03, hazard ratio = 2.2, CI95 = 1.1-4.3) and PD-L1 score 1-49% (p = 0.002, hazard ratio = 5.0, CI95 = 1.8-14). The predictive kinase activity signature appears to be T-cell related, which will be further investigated to improve understanding of the underlying biology. Conclusions: In this prospective validation study the predictive value of kinase activity profiling of PBMCs for response to first-line ICI therapy of patients with advanced NSCLC was confirmed. The final aim is to apply the kinome analysis in clinical practice.
Atezolizumab is a programmed death-ligand 1 (PD-L1) checkpoint inhibitor for the treatment of different forms of cancer. The subcutaneous formulation of atezolizumab has recently received approval. However, treatment with atezolizumab continues to be expensive, and the number of patients needing treatment with this drug continues to increase. We propose two alternative dosing regimens for subcutaneous atezolizumab to reduce drug expenses while ensuring effective exposure; one may be directly implemented in the clinic. We developed two alternative dose interval prolongation strategies based on pharmacokinetic modeling and simulation. The first dosing regimen was based on patients’ weight while maintaining equivalent systemic drug exposure by adhering to Food and Drug Administration (FDA) guidelines for in silico dose adjustments. The second dosing regimen aimed to have a minimum atezolizumab concentration above the 6 µg/mL threshold, associated with 95
Identification of actionable mutations in advanced stage non-squamous non-small-cell lung cancer (NSCLC) patients is recommended by guidelines as it enables treatment with targeted therapies. In current practice, mutations are identified by next-generation sequencing of tumor DNA (tDNA-NGS), which requires tissue biopsies of sufficient quality. Alternatively, circulating tumor DNA (ctDNA) could be used for mutation analysis. This prospective, multicenter study establishes the diagnostic value of ctDNA analysis by droplet digital PCR (ctDNA-ddPCR) in patients with primary lung cancer. CtDNA from 458 primary lung cancer patients was analyzed using a panel of multiplex ddPCRs for EGFR (Ex19Del, G719S, L858R, L861Q and S768I), KRAS G12/G13 and BRAF V600 mutations. For 142 of 175 advanced stage non-squamous NSCLC patients tDNA-NGS results were available to compare to ctDNA-ddPCR. tDNA-NGS identified 98 mutations, of which ctDNA-ddPCR found 53 mutations (54%), including 32 of 45 (71%) targetable driver mutations. In 2 of these 142 patients, a mutation was found by ctDNA-ddPCR only. In 33 advanced stage patients lacking tDNA-NGS results, ctDNA-ddPCR detected 15 additional mutations, of which 7 targetable. Overall, ctDNA-ddPCR detected 70 mutations and tDNA-NGS 98 mutations in 175 advanced NSCLC patients. Using an up-front ctDNA-ddPCR strategy, followed by tDNA-NGS only if ctDNA-ddPCR analysis is negative, increases the number of mutations found from 98 to 115 (17%). At the same time, up-front ctDNA-ddPCR reduces tDNA-NGS analyses by 40%, decreasing the need to perform (additional) biopsies.
To reduce the number of missed or misdiagnosed lung nodules on CT scans by radiologists, many Artificial Intelligence (AI) algorithms have been developed. Some algorithms are currently being implemented in clinical practice, but the question is whether radiologists and patients really benefit from the use of these novel tools. This study aimed to review how AI assistance for lung nodule assessment on CT scans affects the performances of radiologists. We searched for studies that evaluated radiologists' performances in the detection or malignancy prediction of lung nodules with and without AI assistance. Concerning detection, radiologists achieved with AI assistance a higher sensitivity and AUC, while the specificity was slightly lower. Concerning malignancy prediction, radiologists achieved with AI assistance generally a higher sensitivity, specificity and AUC. The radiologists' workflows of using the AI assistance were often only described in limited detail in the papers. As recent studies showed improved performances of radiologists with AI assistance, AI assistance for lung nodule assessment holds great promise. To achieve added value of AI tools for lung nodule assessment in clinical practice, more research is required on the clinical validation of AI tools, impact on follow-up recommendations and ways of using AI tools.
OBJECTIVE:Advanced cancer has a major impact on both patients and their relatives. To allow for personalized support, it is important to recognize which relatives will experience a decline in emotional functioning during the patient's last year of life, when this decline will occur, and what factors are associated with it. This study aimed to examine the trajectory of emotional functioning of relatives during that time and the characteristics associated with changes in this trajectory. METHODS:A prospective, longitudinal, multicenter, observational study in patients with advanced cancer and their relatives was conducted (eQuiPe). We analyzed relatives' changes in emotional functioning in the patient's last year using the EORTC QLQ-C30 and assessed associations with sociodemographic and care characteristics using multivariable mixed-effects analysis. RESULTS:409 relatives completed ≥1 questionnaires during the patient's last year of life. Mean age was 64 years, 61% were female and 75% were the patient's partner. During this year, mean emotional functioning declined significantly over time from 73.9 to 64.6 (p = 0.023, effect size = 0.43). The type of relationship between relatives and patients (p = 0.002), patient' sleep problems (p = 0.033), and continuity of care (p = 0.002) were significantly associated with changes in emotional functioning. CONCLUSIONS:Relatives' emotional functioning declined during the patient's last year of life. Support for them, especially partners and relatives of patients with sleep problems, is important. Relatives who experienced more continuity of care had a less steep decline in emotional functioning.
To assess the association of gastrointestinal problems, received nutritional care, and nutritional care needs with quality of life (QoL) in patients with advanced cancer. A cross-sectional analysis within the observational prospective eQuiPe cohort study on experienced quality of care and QoL in patients with advanced cancer was performed. QoL and gastrointestinal problems were measured using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30. Received nutritional care (yes/no) and nutritional care needs (yes/a little bit/no) were measured by two questions. Gastrointestinal problems were categorized as clinically important based on the Giesinger thresholds. Univariable and multivariable linear regression analyses adjusted for age, gender, and treatment were used to analyze the association of gastrointestinal problems, received nutritional care, and nutritional care needs with QoL. Half of the 1080 patients with advanced cancer had clinically important gastrointestinal problems, 17
Objectives: Pathologic subtyping of tissue biopsies is the gold standard for the diagnosis of lung cancer (LC), which could be complicated in cases of e.g. inconclusive tissue biopsies or unreachable tumors. The diagnosis of LC could be supported in a minimally invasive manner using protein tumor markers (TMs) and circulating tumor DNA (ctDNA) measured in liquid biopsies (LBx). This study evaluates the performance of LBx-based decision-support algorithms for the diagnosis of LC and subtyping into small- and non-small-cell lung cancer (SCLC and NSCLC) aiming to directly impact clinical practice.Materials and Methods: In this multicenter prospective study (NL9146), eight protein TMs (CA125, CA15.3, CEA, CYFRA 21-1, HE4, NSE, proGRP and SCCA) and ctDNA mutations in EGFR, KRAS and BRAF were analyzed in blood of 1096 patients suspected of LC. The performance of individual and combined TMs to identify LC, NSCLC or SCLC was established by evaluating logistic regression models at pre-specified positive predictive values (PPV) of >= 95% or >= 98%. The most informative protein TMs included in the multi-parametric models were selected by recursive feature elimination.Results: Single TMs could identify LC, NSCLC and SCLC patients with 46%, 25% and 40% sensitivity, respectively, at pre-specified PPVs. Multi-parametric models combining TMs and ctDNA significantly improved sensitivities to 65%, 67% and 50%, respectively. Conclusion: In patients suspected of LC, the LBx-based decision-support algorithms allowed identification of about two-thirds of all LC and NSCLC patients and half of SCLC patients. These models therefore show clinical value and may support LC diagnostics, especially in patients for whom pathologic subtyping is impossible or incomplete.
AIM:This study aims to assess the quality of life and quality of care as experienced by patients with advanced cancer and their relatives while taking their interdependency into account.METHODS:A prospective multicentre observational study (eQuiPe study) was conducted. Quality of life scores (EORTC QLQ-C30) was compared to a matched normative population and logistic regression analyses were conducted to assess the relation between high emotional functioning (EF, measured with the EORTC QLQ-C30) and experienced quality of care (IN-PATSAT32, CQ-index PC).RESULTS:In total, 1103 (65%) patients and 831 (71%) relatives completed the baseline questionnaire, including 699 unique patient-relative couples. Patients experienced lower EF than the normative population (78 versus 87, p < .001). Compared to patients, relatives reported clinically relevantly lower EF (69 versus 78, p < .001). Being more satisfied with care in general (p < .05) and clarity about the key health-care provider (p < .05) was positively associated with high EF in patients. For relatives, experienced continuity of care (p < .01) and information for the patient (p < .05) were positively associated with high EF. The EF of patients (p < .001) and relatives (p < .001) were positively associated with each other and continuity of care as perceived by relatives was positively associated with high EF in patients (p < .01).CONCLUSIONS:Patients with advanced cancer reported low levels of EF but their relatives reported even lower levels of EF. Experienced integrated organisation and satisfaction with care were positively related to EF. The interdependent relation between patients' and relatives' EF and their care experiences suggests that a family-centred approach can optimise palliative cancer care.TRIAL REGISTRATION:The eQuiPe study is registered as NTR6584 in the Netherlands Trial Register.
Introduction: Despite radical intent therapy for patients with stage III non-small-cell lung cancer (NSCLC), cumulative incidence of brain metastases (BM) reaches 30%. Current risk stratification methods fail to accurately identify these patients. As radiomics features have been shown to have predictive value, this study aims to develop a model combining clinical risk factors with radiomics features for BM development in patients with radically treated stage III NSCLC. Methods: Retrospective analysis of two prospective multicentre studies. Inclusion criteria: adequately staged [ 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG-PET-CT), contrast-enhanced chest CT, contrast-enhanced brain magnetic resonance imaging/CT] and radically treated stage III NSCLC, exclusion criteria: second primary within 2 years of NSCLC diagnosis and prior prophylactic cranial irradiation. Primary endpoint was BM development any time during follow-up (FU). CT-based radiomics features ( N = 530) were extracted from the primary lung tumour on 18-FDG-PET-CT images, and a list of clinical features ( N = 8) was collected. Univariate feature selection based on the area under the curve (AUC) of the receiver operating characteristic was performed to identify relevant features. Generalized linear models were trained using the selected features, and multivariate predictive performance was assessed through the AUC. Results: In total, 219 patients were eligible for analysis. Median FU was 59.4 months for the training cohort and 67.3 months for the validation cohort; 21 (15%) and 17 (22%) patients developed BM in the training and validation cohort, respectively. Two relevant clinical features (age and adenocarcinoma histology) and four relevant radiomics features were identified as predictive. The clinical model yielded the highest AUC value of 0.71 (95% CI: 0.58–0.84), better than radiomics or a combination of clinical parameters and radiomics (both an AUC of 0.62, 95% CIs of 0.47–076 and 0.48–0.76, respectively). Conclusion: CT-based radiomics features of primary NSCLC in the current setup could not improve on a model based on clinical predictors (age and adenocarcinoma histology) of BM development in radically treated stage III NSCLC patients.
The death of a loved one is considered to be the most stressful of all life events. However, the impact of bereavement on quality of life varies between individuals. The aim of our study was to assess emotional functioning (EF), which is a domain of quality of life, of bereaved relatives after the death of their loved one and its associated factors.
IntroductionPrevious studies have shown interference between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy in the cell cycle, thus reducing efficacy. In this randomised controlled trial we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR-mutated nonsmall cell lung cancer (NSCLC).Materials and methodsTreatment-naïve patients with an activatingEGFRmutation, ECOG performance score of 0–3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2–16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival, objective response rate (ORR) and toxicity.ResultsBetween April 2014 and September 2016, 22 patients were randomised equally into both arms; the study was stopped due to slow accrual. Median follow-up was 64 months. Median PFS was 8.8 months (95% CI 4.2–18.8) for CPE and 10.3 months (95% CI 7.1–15.5; hazard ratio (HR) 0.78, 95% CI 0.32–1.91) for erlotinib monotherapy; when compensating for number of days receiving erlotinib, PFS of the CPE arm was superior (HR 0.32, 95% CI 0.10–1.01; p=0.02). ORR was 64% for CPEversus55% for erlotinib monotherapy. Median overall survival was 30.9 months (95% CI 18.5–61.9 months) for CPE compared to 17.2 months (95% CI 11.5–45.5 months) for erlotinib monotherapy (HR 0.66, 95% CI 0.27–1.65 months). Patients treated with CPE had higher rates of treatment-related fatigue, anorexia, weight loss and renal toxicity.ConclusionIntercalating erlotinib with cisplatin-pemetrexed provides a longer PFS compared to erlotinib alone inEGFR-mutated NSCLC at the expense of more toxicity.
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.