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Objectives: Pretreatment biomarkers are needed to identify patients with non‐small‐cell lung cancer (NSCLC) likely to have worse survival. This ensures that only patients with a real chance of benefit receive immune checkpoint inhibitor (ICI) treatment. In this study, we examined the associations of baseline nutritional and inflammatory biomarkers with overall survival in a real‐world cohort of NSCLC patients who received ICIs. Materials and Methods: We used prospectively collected data from the OncoLifeS data biobank. The cohort included 500 advanced‐stage NSCLC patients treated with ICIs from May 2015 to June 2021. Biomarkers were evaluated within 2 weeks before ICI treatment: neutrophil‐to‐lymphocyte ratio, C‐reactive protein (CRP), Glasgow prognostic score, CRP/albumin ratio (CAR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index. For each biomarker, low‐ and high‐risk groups were defined using literature‐based cut‐offs. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were estimated using adjusted survival analysis. Results: Most patients were male (60.8%), the mean baseline age was 65 ± 9 years, and 88% had stage IV disease. For each biomarker, low‐risk patients had better overall survival (all, p < 0.001), with CAR and PNI showing the strongest associations. In multivariable analyses a combined CAR/PNI risk score had a stronger association with overall survival (aHR 3.09, 95% CI 2.36–4.06) than CAR alone (aHR 2.22, 95% CI 1.79–2.76) or PNI alone (aHR 2.09, 95% CI 1.66–2.61). Conclusion: These results highlight the potential value of nutritional and inflammatory biomarkers, in particular CAR and PNI, in identifying NSCLC patients with highest mortality risk before starting ICI treatment. [ABSTRACT FROM AUTHOR]

Background: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC.Methods: We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more.Results: Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P=0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy.Conclusions: Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533 .). [ABSTRACT FROM AUTHOR]

Background The detection of driver aberrations such as EGFR and ALK, in tumour tissue or plasma has become important for treating lung cancer patients. The aim of this study is to explore the feasibility of detecting therapy-guiding aberrations in RNA, isolated from platelet and plasma samples. Methods We applied a hybridization capture-based NGS approach on 10 platelet-derived RNA samples with 13 known variants. For validation, we applied RNA-based ddPCR focussing on T790M, L858R and E19del in EGFR, codon 12 and 13 of KRAS and the ALK-EML4/KIF5B fusions on both cell free plasma RNA and platelet RNA. Results For none of the platelet-derived RNA samples we detected the known variant with targeted RNA sequencing despite having sufficient unique reads (1.23x10^5 to 1.4x10^6). We next applied ddPCR to determine presence of mutated transcripts at a higher sensitivity (sensitivity of the assays reached down to 0.07%). No ALK fusion droplets were detected in platelet and plasma samples derived from two patients with a known ALK fusion gene in tumour tissues detected by our assay despite having high droplet counts for the GUSB housekeeping gene indicating that RNA quality was good. For EGFR total droplet counts were very low in both platelets and plasma, indicating low abundance of EGFR transcripts. No EGFR mutant droplets were observed in platelet and plasma samples derived from 8 and 6 patients with known variants, respectively. None of the expected KRAS mutations were detected in 5 plasma-derived RNA samples, with again only very low numbers of wild type KRAS droplets. In RNA derived from platelets, KRAS mutant positive droplets were detected in 3 out of 9 samples with variant allele frequency of 0.07%, 0.11% and 0.55%. Two of the three samples were derived from one patient, but obtained at different time points. Wild type KRAS droplet counts were very high in all platelet samples indicating that KRAS transcripts were highly abundant in platelets. Conclusions In conclusion, the fraction of tumour-derived RNA transcripts in plasma and platelets appears to be very low or undetectable. Our data indicates that plasma and platelet-derived RNA is not a good source to identify tumour cell specific genomic aberrations. Legal entity responsible for the study University of Groningen, University Medical Center Groningen. Funding Dutch Cancer Society. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Context: Lung cancer is associated with significant distress, poor quality of life, and a median prognosis of less than one year. Benefits of shared decision making (SDM) have been described for multiple diseases, either by the use of decisions aids or as part of supportive care interventions.Objectives: The objective of this study was to summarize the effects of interventions facilitating SDM on distress and health care utilization among patients with lung cancer.Methods: We performed a systematic literature search in the CINAHL, Cochrane, EMBASE, MEDLINE, and PsychINFO databases. Studies were eligible when conducted in a population of patients with lung cancer, evaluated the effects of an intervention that facilitated SDM, and measured distress and/or health care utilization as outcomes.Results: A total of 12 studies, detailed in 13 publications, were included: nine randomized trials and three retrospective cohort studies. All studies reported on a supportive care intervention facilitating SDM as part of their intervention. Eight studies described effects on distress, and eight studies measured effects on health care utilization. No effect was found in studies measuring generic distress. Positive effects, in favor of the intervention groups, were observed in studies using anxiety-specific measures (n = 1) or depression-specific measures (n = 3). Evidence for reductions in health care utilization was found in five studies.Conclusion: Although not supported by all studies, our findings suggest that facilitating SDM in the context of lung cancer may lead to improved emotional outcomes and less aggressive therapies. Future studies, explicitly studying the effects of SDM by using decision aids, are needed to better elucidate potential benefits. [ABSTRACT FROM AUTHOR]

Purpose: Molecular tumor boards (MTBs) are considered beneficial for treatment decision making for patients with cancer with uncommon, rare, or complex mutational profiles. The lack of international MTB guidelines results in significant variation in practices and recommendations. Therefore, periodic follow-up is necessary to assess and govern MTB functioning. The objective of this study was to determine the effectiveness of MTB treatment recommendations for patients with rare and complex mutational profiles as implemented in the MTB of the University Medical Center Groningen (UMCG-MTB) in 2019-2020., Patients and Methods: A retrospective follow-up study was carried out to determine the clinical outcome of patients with uncommon or rare (combinations of) molecular aberrations for whom targeted therapy was recommended as the next line of treatment by the UMCG-MTB in 2019 and 2020., Results: The UMCG-MTB recommended targeted therapy as the next line of treatment in 132 of 327 patients: 37 in clinical trials, 67 in the on-label setting, and 28 in the off-label setting. For on- and off-label treatment recommendations, congruence of recommended and received treatment was 85% in patients with available follow-up (67/79). Treatment with on-label therapy resulted in a response rate of 50% (21/42), a median progression-free survival (PFS) of 6.3 months [interquartile range (IQR) 2.9-14.9 months], and median overall survival (OS) of 15.8 months (IQR 6.4-34.2 months). Treatment with off-label therapy resulted in a response rate of 53% (8/15), a median PFS of 5.1 months (IQR 1.9-7.3 months), and a median OS of 17.7 months (IQR 5.1-23.7 months)., Conclusion: Treatment with MTB-recommended next-line targeted therapy for patients with often heavily pretreated cancer with rare and complex mutational profiles resulted in positive overall responses in over half of patients. Off-label use of targeted therapies, for which there is sufficient rationale as determined by an MTB, is an effective treatment strategy. This study underlines the relevance of discussing patients with rare and complex mutational profiles in an MTB., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Mutational signatures (MS) are gaining traction for deriving therapeutic insights for immune checkpoint inhibition (ICI). We asked if MS attributions from comprehensive targeted sequencing assays are reliable enough for predicting ICI efficacy in non-small cell lung cancer (NSCLC)., Methods: Somatic mutations of m = 126 patients were assayed using panel-based sequencing of 523 cancer-related genes. In silico simulations of MS attributions for various panels were performed on a separate dataset of m = 101 whole genome sequenced patients. Non-synonymous mutations were deconvoluted using COSMIC v3.3 signatures and used to test a previously published machine learning classifier., Results: The ICI efficacy predictor performed poorly with an accuracy of 0.51 -0.09 +0.09 , average precision of 0.52 -0.11 +0.11 , and an area under the receiver operating characteristic curve of 0.50 -0.09 +0.10 . Theoretical arguments, experimental data, and in silico simulations pointed to false negative rates (FNR) related to panel size. A secondary effect was observed, where deconvolution of small ensembles of point mutations lead to reconstruction errors and misattributions., Conclusion: MS attributions from current targeted panel sequencing are not reliable enough to predict ICI efficacy. We suggest that, for downstream classification tasks in NSCLC, signature attributions be based on whole exome or genome sequencing instead., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HCD: None to declare; KC: None to declare; GF: None to declare; HJMG: Consulting or Advisory Role: Novartis, Lilly. TJNH: Advisory/consultancy fees from AstraZeneca, Bristol-Myers-Squibb, Illumina, Merck Sharp Dohme, Roche, and research grants/funding from AstraZeneca, Hoffmann-La Roche. BM: None to declare; ES: Honoraria/speakers fee: Bio-Rad, Roche, Agena Bioscience, Illumina, Lilly; Consulting or Advisory Role: MSD/Merck, Astellas, Bayer, BMS, Agena Bioscience, Janssen Cilag (Johnson & Johnson), Novartis, Roche, AstraZeneca, Amgen, Lilly; Research Funding: Biocartis, Bio-Rad, Roche, Agena Bioscience, AstraZeneca, InVitae/Archer (all paid to UMCG); Travel, Accommodations, Expenses: Roche Molecular Diagnostics, Bio-Rad. PJV: None to declare; GAL: Research grant from Boehringer-Ingelheim. Owns shares in Genomics PLC.; BvE: None to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: This phase I study primarily addresses the safety and tolerability of Stereotactic radiotherapy on the primary tumor combined with double Immune Checkpoint Inhibition (SICI) in patients with non-small cell lung cancer (NSCLC). Increasing the release of neoantigens by radiotherapy might enhance response to immunotherapy. Especially, by targeting trunk mutations in the primary tumor., Materials and Methods: In three sequential cohorts, immunotherapy regimes combined with stereotactic body radiotherapy (SBRT) on the primary tumor (1x20 Gy on 9 cc) were studied in stage IIIB/IV NSCLC patients progressing on chemotherapy. The first cohort (n = 3) received durvalumab. The second (n = 6) received a combination of tremelimumab and durvalumab followed by durvalumab monotherapy. The third cohort (n = 6) was similar except that the combination was reversed. Descriptive statistics were used to assess safety parameters and the exploratory outcomes of efficacy. Adverse events were reported using NCI CTCAE version 4.03. Exhaled breath was analyzed at baseline., Results: Fifteen patients were included. Median irradiated volume was 9.13 cc, on a median primary tumor volume of 79 cc. There were seven patients with grade 1-2, and two patients with grade 3 treatment related adverse events. There was 1 dose limiting toxicity (colitis) with double immunotherapy., Conclusion: The combination of SBRT to the primary tumor and double immunotherapy in advanced NSCLC patients is safe and feasible., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment. However, it remains unclear as to whether changes in Health-Related Quality-of-Life (HRQoL) are associated with the age of lung cancer patients treated using ICIs. This study aimed to evaluate this possible association and to compare ICI-treated patients' HRQoL scores with normative data of an age-matched non-cancer general population., Methods: Lung cancer patients from the OncoLifeS data-biobank were included if they were treated with ICIs, irrespective of other treatments, at the University Medical Center Groningen between 2015 and 2021 and had completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30), both at the start of ICI treatment and after six months. Association of age as a continuous variable (per 10 years) and changes in HRQoL scores between baseline and 6 months was assessed using multivariable regression analyses. Clinical relevance of differences in HRQoL scores between OncoLifeS and the general population was classified into trivial, small, medium, and large, for three age groups (<60, 60-69 and ≥ 70 years)., Results: 151 patients were included with a mean age of 65.8 years. An increase in age per 10 years was associated with a larger decrease in the summary HRQoL score(β = -3.28,CI95%-6.42;-0.14), physical(β = -4.8, CI95% -8.71;-0.88), cognitive(β = -4.51,CI95%-8.24;-0.78), role functioning(β = -5.41,CI95%-10.78;-0.05), symptom burden(β = -3.66,CI95%-6.6;-0.73), and smaller negative changes in financial difficulties(β = 6.5 95 % CI 3.16; 9.85). OncoLifeS HRQoL scores were lower than those of the general population and differences were most often classified as large and medium., Conclusion: Older lung cancer patients experience larger deteriorations in most HRQoL domains after 6 months of ICI treatment. Also, these patients showed significantly lower HRQoL scores compared to the general population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Extended interval (EI) dosing for immune checkpoint inhibitor (ICI) mono- or consolidation therapy initiated due to the COVID-19 pandemic led to a significant reduction in ICI-related site visits for patients with stage III and IV non-small cell lung cancer. Here we report the safety and efficacy compared to standard dose (SD) schedules., Method: In this retrospective analysis, patients who received ICI mono- or consolidation therapy, or adjuvant ICI therapy were assessed. Safety and efficacy of EI dosing with data of SD schedules were compared., Results: One hundred seventeen patients received EI dosing for ICI and 88 patients SD. Patient characteristics were comparable. We observed 237 adverse events in the EI dosing cohort versus 118 in the SD group (P= .02). Overall, there was no difference in the occurrence of grade ≥3 adverse events (EI dosing: 21/237 [8.9%]; SD group: 20/118 [17.0%], P = .42), except for the pembrolizumab EI dosing cohort. Of all patients who received an EI dosing schedule, however, only 8 (6.8%) were reduced to SD because of toxicity. In 5 (4.3%) patients ICI was permanently stopped because of severe toxicity compared to 11 (12.5%) discontinuations in the SD group. Short-term treatment interruption occurred with similar frequencies in both groups. Progression-free survival and overall survival were comparable in patients receiving pembrolizumab and in those receiving adjuvant durvalumab. Progression-free survival and OS were better in the EI dosing cohort of nivolumab., Conclusion: EI dosing for ICI did not lead to an increase of clinically relevant toxicities resulting in dose reduction and/or treatment discontinuation. Efficacy of EI dosing of pembrolizumab and durvalumab were comparable to SD. Based on our safety and efficacy data EI dosing for ICI seems a safe and effective strategy., (Copyright © 2021. Published by Elsevier Inc.)

Background: Programmed cell death protein 1 (PD-1) antibody treatment is standard of care for melanoma and non-small-cell lung cancer (NSCLC). Accurately predicting which patients will benefit is currently not possible. Tumor uptake and biodistribution of the PD-1 antibody might play a role. Therefore, we carried out a positron emission tomography (PET) imaging study with zirconium-89 ( 89 Zr)-labeled pembrolizumab before PD-1 antibody treatment., Patients and Methods: Patients with advanced or metastatic melanoma or NSCLC received 37 MBq (1 mCi) 89 Zr-pembrolizumab (∼2.5 mg antibody) intravenously plus 2.5 or 7.5 mg unlabeled pembrolizumab. After that, up to three PET scans were carried out on days 2, 4, and 7. Next, PD-1 antibody treatment was initiated. 89 Zr-pembrolizumab tumor uptake was calculated as maximum standardized uptake value (SUV max ) and expressed as geometric mean. Normal organ uptake was calculated as SUV mean and expressed as a mean. Tumor response was assessed according to (i)RECIST v1.1., Results: Eighteen patients, 11 with melanoma and 7 with NSCLC, were included. The optimal dose was 5 mg pembrolizumab, and the optimal time point for PET scanning was day 7. The tumor SUV max did not differ between melanoma and NSCLC (4.9 and 6.5, P = 0.49). Tumor 89 Zr-pembrolizumab uptake correlated with tumor response (P trend = 0.014) and progression-free (P = 0.0025) and overall survival (P = 0.026). 89 Zr-pembrolizumab uptake at 5 mg was highest in the spleen with a mean SUV mean of 5.8 (standard deviation ±1.8). There was also 89 Zr-pembrolizumab uptake in Waldeyer's ring, in normal lymph nodes, and at sites of inflammation., Conclusion: 89 Zr-pembrolizumab uptake in tumor lesions correlated with treatment response and patient survival. 89 Zr-pembrolizumab also showed uptake in lymphoid tissues and at sites of inflammation., Competing Interests: Disclosure MJ reports consultancy fees from AstraZeneca (paid to UMCG). JBH reports consultancy roles for Achilles Therapeutics, BioNTech, BMS, GSK, Immunocore, Instil Bio, Molecular Partners, MSD, Merck Serono, Neogene Therapeutics, Novartis, Pfizer, PokeAcel, Roche/Genentech, Sanofi, T-Knife, and Third Rock Ventures and research grants from Amgen, Asher-Bio, BMS, BioNTech, MSD, Novartis, and Neogene Therapeutics (paid to the Netherlands Cancer Institute). WT reports fees from Merck, Sharp, Dohme, and Bristol-Myers-Squibb (paid to UMCG). EGEdV reports an advisory role at Daiichi Sankyo, NSABP, and Sanofi and research funding from Amgen, AstraZeneca, Bayer, Chugai Pharma, Crescendo, CytomX Therapeutics, G1 Therapeutics, Genentech, Nordic Nanovector, Radius Health, Regeneron, Roche, Servier, and Synthon (paid to UMCG). GAPH reports consulting and advisory role at Amgen, Roche, MSD, BMS, Pfizer, Novartis, and Pierre Fabry and research funding from BMS and Seerave (paid to UMCG). TJNH reports consultancy fees (paid to UMCG) from BMS, MSD, Merck, Boehringer, AstraZeneca, and Roche. AJvdW reports an advisory role at Janssen, Takeda, and Boehringer-Ingelheim (paid to UMCG) and research funding from AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche, and Takeda. MNL-dH reports research funding from Merck, Bayer, and Amgen (paid to UMCG). HJMG reports an advisory role at Eli Lilly, MSD, BMS, and Novartis. All other authors have declared no conflicts of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: Phase III studies of checkpoint inhibitors changed the therapeutic landscape for lung cancer. In 2015 the Dutch Society of Chest Physicians (NVALT) introduced a national immunotherapy registry for patients with lung cancer; quality standards for hospitals were implemented. At population level we studied clinical benefit in daily practice and in patients who are underrepresented in phase III trials., Materials and Methods: From the initial introduction of checkpoint inhibitors in the Netherlands patients were centrally registered. Educational programs and quality control were provided under supervision of NVALT. The largest immunotherapy providing hospitals were compared to hospitals who provided less checkpoint inhibitors as marker of experience. Patients characteristics, treatment and side effects, response rate and survival were studied., Results: A total of 2676 patients were registered, 2302 with follow up data were evaluated. Between October 2015 and December 2017 a gradual increase from 12 to 30 qualified hospitals showed no major toxicity differences. Toxicity led to a hospital admission rate of 9.1 with an average duration of 10.4 days. Overall tumor response was 21.8 % and median overall survival 12.6 months. Overall survival was not significantly different for patients aged ≥ 75 years, those having brain metastases or selected auto-immune diseases before start checkpoint inhibitors compared to younger patients or those without, respectively. Survival outcomes were worse in patients with PS 2+, non-smokers, and patients who received any palliative radiotherapy (HR 2.1, 95 % CI 1.7-2.7; 1.3, 95 % CI 1.0-1.6 and 1.2, 95 % CI 1.1-1.4, respectively)., Conclusions: Changes in the therapeutic landscape did not lead to major differences in quality of care between hospitals. Elderly patients, those with brain metastases or selected auto-immune disease underrepresented in clinical trials did not do worse on checkpoint inhibitors, except for those with PS 2 + ., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data., Methods: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices., Results: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs., Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The use of patient-reported outcome measures is increasingly advocated to support high-quality cancer care. We therefore investigated the added value of the Distress Thermometer (DT) when combined with known predictors to assess one-year survival in patients with lung cancer., Methods: All patients had newly diagnosed or recurrent lung cancer, started systemic treatment, and participated in the intervention arm of a previously published randomised controlled trial. A Cox proportional hazards model was fitted based on five selected known predictors for survival. The DT-score was added to this model and contrasted to models including the EORTC-QLQ-C30 global QoL score (quality of life) or the HADS total score (symptoms of anxiety and depression). Model performance was evaluated through improvement in the -2 log likelihood, Harrell's C-statistic, and a risk classification., Results: In total, 110 patients were included in the analysis of whom 97 patients accurately completed the DT. Patients with a DT score ≥5 (N = 51) had a lower QoL, more symptoms of anxiety and depression, and a shorter median survival time (7.6 months vs 10.0 months; P = 0.02) than patients with a DT score <5 (N = 46). Addition of the DT resulted in a significant improvement in the accuracy of the model to predict one-year survival (P < 0.001) and the discriminatory value (C-statistic) marginally improved from 0.69 to 0.71. The proportion of patients correctly classified as high risk (≥85% risk of dying within one year) increased from 8% to 28%. Similar model performance was observed when combining the selected predictors with QoL and symptoms of anxiety or depression., Conclusions: Use of the DT allows clinicians to better identify patients with lung cancer at risk for poor outcomes, to further explore sources of distress, and subsequently personalize care accordingly., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: ALK rearrangement detection using FISH is the standard test to identify patients with non-small cell lung carcinoma (NSCLC) eligible for treatment with ALK inhibitors. Recently, ALK protein expression in resectable NSCLC showed predictive value. We evaluated tumor response rate and survival after crizotinib treatment of patients with advanced NSCLC with ALK activation using both dichotomous immunohistochemical (IHC) staining and FISH. Experimental Design: Patients with stage IV NSCLC treated with crizotinib were selected. Tumor response was assessed. ALK rearrangements were detected by FISH (Vysis ALK-break-apart FISH-Probe KIT) and IHC [Ventana ALK (D5F3) CDx assay]. Cohorts of patients with ALK-FISH-positive advanced NSCLC from four other hospitals were used for validation. Results: Twenty-nine consecutive patients with ALK-positive advanced NSCLC diagnosed by FISH and/or IHC on small biopsies or fine-needle aspirations (FNA) were treated with ALK inhibitors. All ALK-IHC-positive patients responded to crizotinib except three with primary resistance. No tumor response was observed in 13 ALK-FISH-positive but ALK-IHC-negative patients. This was confirmed in an external cohort of 16 patients. Receiver operator characteristic (ROC) curves for ALK-IHC and ALK-FISH compared with treatment outcome showed that dichotomous ALK-IHC outperforms ALK-FISH [tumor response area under the curve: (AUC), 0.86 vs. 0.64, P = 0.03; progression-free survival (PFS): AUC 0.86 vs. 0.36, P = 0.005; overall survival (OS): AUC, 0.78 vs. 0.41, P = 0.01, respectively]. Conclusions: Dichotomous ALK-IHC is superior to ALK-FISH on small biopsies and FNA to predict tumor response and survival to crizotinib for patients with advanced NSCLC. Our data strongly suggest adapting the guidelines and using dichotomous ALK-IHC as standard companion diagnostic test to select patients with NSCLC who benefit from ALK-targeting therapy. Clin Cancer Res; 23(15); 4251-8. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Two patients presented with transient thyrotoxicosis within 2-4 weeks after starting treatment with nivolumab. This thyrotoxicosis turned into hypothyroidism within 6-8 weeks. Temporary treatment with a beta blocker may be sufficient.

Background: Symptomatic malignant pleural effusion (MPE) occurs frequently in patients with metastatic cancer. The associated prognosis is poor and the success rate of talc pleurodesis (TP) is low. Indwelling pleural catheters (IPCs) are commonly inserted when TP has been unsuccessful., Methods: We compared talc pleurodesis with the use of an indwelling pleural catheter in patients with recurrent MPE in a multicenter randomized controlled trial (superiority design). The primary endpoint was improvement from baseline in Modified Borg Score (MBS) 6weeks after randomized treatment. Secondary endpoints were hospitalization days, re-interventions, and adverse events., Results: Dyspnea improved significantly (p<0.01) after either treatment, but the magnitude of this improvement did not differ significantly between arms (median 3 and 1 for TP:IPC respectively in rest, p=0.16, (TP 13:IPC 16) and 3 and 1 during exercise, p=0.72 (TP 13:IPC 17)). There was no difference in dyspnea during exercise between TP and IPC at week 6 following treatment, while at rest TP patients (n=13) reported less dyspnea than IPC patients (n=18) (median 0 vs 1, p=0.002). Compared to TP, patients with an IPC had significantly less hospital days during randomized treatment (median: 0 vs 5, p<0.0001), and total hospitalizations for all causes (median: 1.6 vs 1.0, p=0.0035). Fewer IPC patients underwent more than one re-intervention (7/45 vs 15/43, p=0.09). The mean number of re-interventions was lower following IPC (0.21 vs 0.53, p=0.05). Equal number of adverse events occurred., Conclusions: IPC was not superior in the primary endpoint, improvement of the modified Borg scale (MBS). However, IPC patients had lower hospital stay, fewer admissions and fewer re-interventions. The IPC is an effective treatment modality in patients with symptomatic malignant pleural effusion., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Improved survival rates from cancer have increased the need to understand the health-related problems of cancer treatment. We aimed to develop and validate the "Cancer Survivor Core Set" representing the most relevant health-related problems in adult cancer survivors using the International Classification of Functioning, Disability, and Health (ICF)., Methods: First, a Delphi study was conducted to select ICF categories representing the most relevant health-related problems. There were three Dutch expert panels, one each for lung, colorectal, and breast cancer. Each panel comprised lay experts and professionals. The experts reached within- and between-panel consensus in two rounds (≥70 % agreement). Second, a validation study was performed. Generic cancer survivorship questionnaires assessing health-related problems or quality of life among cancer survivors were selected. Items of selected questionnaires were linked to the best-fitting ICF category and to the selected ICF categories from the Delphi study, respectively., Results: In total, 101 experts were included, of which 76 participated in both rounds, reaching consensus on 18 ICF categories. The Distress Thermometer and Problem List, the Impact of Cancer (v2), and the Quality of Life in Adult Cancer Survivors questionnaires were selected for the validation study, which led to the inclusion of one additional ICF category., Conclusions: The developed Cancer Survivor Core Set consisted of 19 ICF categories representing the most relevant health-related problems in adult cancer survivors: five from the "body functions and structures" component, eight from the "activities and participation" component, and six from the "environmental factors" component., Highlights: • Many adult cancer survivors have persistent health-related problems. • The Cancer Survivor Core Set was developed using the Delphi method. • The patients' perspectives were prioritized in this Delphi study • Content validity was confirmed by validated cancer survivorship questionnaires. • The Cancer Survivor Core Set may help optimize care for cancer survivors., Competing Interests: The authors declare that they have no conflicts of interest.

Purpose: Traditionally, general practitioners (GPs) are not involved in cancer-related treatment decisions, despite their often long relationship with patients, and their unique position to explore patients' values, especially with older patients. Therefore, we designed a randomised controlled trial to study the effect, on self-efficacy related to treatment decisions, of a conversation about treatment goals between GPs and patients with cancer in a palliative setting., Methods: We aim to include 168 patients aged ≥70 years with a diagnosis of non-curable cancer, due to consult their oncologist about treatment options. In the intervention group, patients will consult their GP using an Outcome Prioritisation Tool (OPT). The control group will receive care as usual. The primary outcome will be the score on a decision self-efficacy scale after the consultation with the oncologist. Secondary outcomes will be symptoms of depression, anxiety, or fatigue. In an embedded observational study of the intervention group, we aim to assess the prioritisation of treatment goals (i.e., OPT scores), and their determinants, over a six-month period., Conclusions: The OPTion study should provide relevant information about the effect on self-efficacy of a consultation between GPs and older patients with cancer, concerning preferred treatment goals in a palliative setting. Dutch Trial Register NTR5419., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)