Lung Cancer in the Netherlands

The Netherlands is a small European country with population of 17.45 million (September 2020) distributed over 41,543 km2.1Central Bureau for StatisticsPopulation counter.https://www.cbs.nl/nl-nl/visualisaties/bevolkingstellerDate accessed: September 16, 2020Google Scholar There are 79 hospitals (in total, 109 locations), which seven university medical centers, one cancer center, and 28 large teaching hospitals. On average, the within easy reach, as 99% Dutch inhabitants can reach hospital by car 30 minutes (Fig. 1).2Public health care.infoRegional & international: accessibility.https://www.volksgezondheidenzorg.info/onderwerp/ziekenhuiszorg/regionaal-internationaal/bereikbaarheid#node-reistijd-minuten-naar-dichtstbijzijnde-ziekenhuisDate August 26, General practitioners (GPs) “gatekeepers” in care system: general, referral GP mandatory access to nonemergency-based (as insurance does not cover costs otherwise). Common covered basic insurance, law all inhabitants. In lieu this, companies cannot refuse person this insurance. Standard work-up treatments defined so-called diagnosis-treatment combination (DBC) reimbursed This includes incurred Medicines Agency (EMA)-registered national authorities-approved interventions treatments. population-based registry records data on patients newly diagnosed have Netherlands.3Integraal Kankercentrum NederlandLung incidence.https://www.iknl.nl/kankersoorten/longkanker/registratie/incidentieDate Trained personnel actively collects demographics, diagnosis, staging, treatment from records, basis notification automated pathologic archive discharge diagnoses. Pathology confirmation secured means link Registry, survival status update through centralized civil registry.4Visser O. Siesling S. van Dijk J. Dijck J.A. Incidence 1999/2000: eleventh report Cancer Registry.https://research.utwente.nl/en/publications/incidence-of-cancer-in-the-netherlands-19992000-eleventh-report-oGoogle 2019, Netherlands, 14,500 lung tumors were 14,300 patients.3Integraal 2018, total 10,400 died cancer.5Integraal survival.https://www.iknl.nl/kankersoorten/longkanker/registratie/overlevingGoogle These numbers make fourth most common but highest number cancer-related deaths. past decades, incidence rates among male individuals been decreasing (from 72.62 per 100,000 years [world standardized rate] 1989 38.6 2019), whereas these increasing female period 12.0 33.1 rate], respectively). younger than 60 seem flatten or even slightly decrease during years. trends mostly reflect high tobacco consumption decades ago, also explains relatively mortality compared other (European) countries.6Ferlay Soerjomataram I. Dikshit R. et al.Cancer worldwide: sources, methods major patterns GLOBOCAN 2012.Int J Cancer. 2015; 136: E359-E386Crossref PubMed Scopus (18412) Google NSCLC accounts 70% cancers, SCLC 11%, carcinoids 1%, remaining 17% clinically (usually suspicion early-stage referred stereotactic radiotherapy without diagnosis). 49% stage IV (19% IVA, 30% IVB); percentages stages I, II, III 21%, 8%, respectively; 1% patients, was unknown. For between 2012 1-year overall (OS) rate 46%, 5-year OS 19% (median 10 mo). More specifically, III, 90%, 82%, 62%, 31%, respectively. SCLC, 75%, 60%, 61%, 23%, respectively.3Integraal Scholar,5Integraal government committed “smoke – free generation” initiative.7Rijksoverheid NederlandNational prevention agreement.https://www.rijksoverheid.nl/documenten/convenanten/2018/11/23/nationaal-preventieakkoordDate 19, goal that 2040, nobody will start smoking. To meet goal, several implemented. First, an increase value-added tax 20-cigarette package, target price euros package 2023. Second, 2020, smoking bans school yards, plain packaging, reduction selling points products.7Rijksoverheid addition, forbidden use products their grounds. 21.7% adults active smokers, 4% 2014.8Trimbos InstituteSmoking figures.https://www.trimbos.nl/kennis/cijfers/cijfers-rokenDate With mentioned previously, 2040 reduce percentage smokers 5% less. Currently, screening implemented standard Netherlands. However, after positive results randomized Dutch-Belgian NELSON trial, revealing cumulative ratio 0.76 (95% confidence interval: 0.61–0.94) deaths at volume-based, low-dose computed tomography (CT) no risk cancer,9de Koning H.J. der Aalst C.M. de Jong P.A. al.Reduced lung-cancer volume CT trial.N Engl Med. 2020; 382: 503-513Crossref (446) implementation being considered. ionizing radiation Therefore, alteration legislation each A multidisciplinary steering committee consisting pulmonologists, epidemiologists, radiologists, patient advocacy groups, others, preparing request approval be submitted political institutions. It expected process last extended period, it unsure whether obtained. Simultaneously, studies initiated collaboration countries, investigate further refinement (e.g., personalized interval, selection, blood, exhaled breath biomarkers). GPs refer symptoms signs suggestive pulmonologist, who establishes diagnosis cancer. Time first appointment pulmonologist compares favorably countries such Sweden United Kingdom. magnetic resonance imaging facilities available All positron emission tomography, sometimes another nearby hospital. Depending location(s) suspicious lesions, tissue obtained (a of) bronchoscopy, endobronchial ultrasound, endoscopic CT-guided biopsies. Imaging-guided biopsies usually performed interventional although some done pulmonologists. Furthermore, centers pulmonologists trained ultrasound if not, agreements made referral. According guidelines, discuss tumor boards staging recommendations. Adherence good, example, before curative treatment, almost (98.9%) discussed.10Dutch Institute Clinical Auditing, Jaarrapportage 2017: registraties.https://dica.nl/media/1583/DICA_Jaarrapportage_2017_-_Registraties.pdfDate remains physician coordinating throughout journey, contrast initiates prescribes systemic therapy.11Komiya T. Mackay C.B. Chalise P. Who treats cancer? Results global survey.Respir Investig. 2017; 55: 308-313Crossref (2) consensus meeting challenges harmonization molecular testing clinical predictive markers discussed.12van den Broek D. Hiltermann T.J.N. Biesma B. al.Implementation novel biomarkers non-small cell Netherlands: how deal complexity.Front Oncol. 2019; 9: 1521Crossref (3) guideline updated.13Dutch Federation Medical SpecialistsNon-Small Cell Lung Cancer—General.https://richtlijnendatabase.nl/richtlijn/niet_kleincellig_longcarcinoom/algemeen.htmlDate One important molecular-related items recommendation test every adenocarcinoma, squamous histology significant history, least aberrations following markers: KRAS, EGFR, BRAF, HER2, ALK, MET, ROS1, RET, NTRK1-3, NRG1, programmed death-ligand 1 expression (the latter advised carcinoma). Many pathology laboratories perform analyses using next-generation sequencing panels covering greater decision making primary progression owing resistance.14Steeghs E.M.P. Kroeze L.I. Tops B.B.J. al.Comprehensive routine diagnostic identify mutations, gene amplifications, microsatellite instability FFPE material.BMC 20: 291Crossref (8) detection fusions, fluorescent situ hybridization. As different fusions needs evaluated (ALK, NRG1), larger now more cost-effective RNA-based platforms, Nanostring Archer. current discussion centralization complex required give complete testing. Centralization preferred because complexity testing, appropriate management rather biopsies, cost-efficiency sufficient volume. interpretation becomes increasingly complex, recommends recommendations rare (incidence < 1%) unknown mutations (MTBs) Netherlands.13Dutch Scholar,15Predictive Analysis TherapyMolecular tumor.https://www.netwerk-path.nl/index.php/tumor-boardsDate 30, MTBs minimally consist extensive experience targeted therapy working designated (described Systemic Therapy section), pathologist expertise cancer, scientist sequencing, hybridization, Targeted resulting MTB workflow profiles highly adhered resulted response metastatic NSCLC.16Koopman Wekken A.J. ter Elst A. al.Relevance effectiveness board non-small-cell mutational profiles.JCO Precis 4: 393-410Crossref (13) Thoracic surgery both general thoracic surgeons (mainly community hospitals) cardiothoracic hospitals). 2384 resections performed: 83.6% (bi)lobectomies, 6.2% segmental resections, 5.5% wedge 4.5% pneumonectomies (unpublished data, courtesy Audit [DLCA]-Surgery, part Auditing). Video-assisted (VATS) introduced 2006 soon 78.0% VATS 2019.17Bollen E.C. Belgers E. Haren E.H. Siebenga De chirurgische behandeling longkanker via VATS-lobectomie, nieuw Nederland [Surgical lobectomy, new Netherlands].Ned Tijdschr Geneeskd. 2008; 152 ([in Dutch]): 1204-1209PubMed Robotic-assisted surgery, six 3.8% resections. robotic-assisted operations increasing, might, partly, accounted associated financial procedure limited evidence superiority VATS. centralized; 80 offered 2007 41 did so 2019. occurred quality conditions laid down nationwide SONCOS document platform societies involved care, medical, radiation, surgical oncology [www.soncos.org]). Since 2012, procedures (i.e., lung, wall, diaphragm, mediastinal tumors) registered DLCA-Surgery Auditing database control benchmarking outcomes. decline complications postoperative mortality.18Ten Berge M. Beck N. Heineman D.J. al.Dutch audit: audit comprising patients.Ann Thorac Surg. 2018; 106: 390-397Abstract Full Text PDF (23) Scholar,19Beck Hoeijmakers F. Wiegman E.M. al.Lessons learned Auditing: model assurance treatment.J Dis. 10: S3472-S3485Crossref (10) 19 including three operational proton facilities. across ensure patients. Radiation departments state-of-the-art linear accelerators intensity-modulated brain extracranial capabilities. Some MR-linacs, tomotherapy, Cyberknife, Gamma Knife, hyperthermia therapy. CT, imaging, tomography-CT integration departments. organized into represent subspecialties, Platform platform, institutions represented oncologist physicist. connection Society Oncology (NVRO) professional organizations Pulmonary Medicine Tuberculosis (NVALT), group. place research organize multicentric studies. separate Proton Therapy, according model-based approach.20Langendijk Lambin Ruysscher Widder Bos Verheij Selection protons aiming side effects: approach.Radiother 2013; 107: 267-273Abstract (264) coordinated group (DUPROTON). Quality assessment obligatory consists variety technical parameters minimum set follow-up, toxicity survival. Patients treated followed up extensively. upload central used research. guidelines completeness uploaded monitored. discussed yearly plans improvements needed continuous improvement/assessment cycle. Physical audits regularly include aspects oncology. algorithms first- second-line options advanced provided Figure 2A (targeted) characterized oncogenic drivers EGFR exon deletions/exon 21 L858R). FLAURA study data,21Soria J.C. Ohe Y. Vansteenkiste al.Osimertinib untreated EGFR-mutated cancer.N 378: 113-125Crossref (1662) first-line classical activating mutation osimertinib.Figure 2(A) First- (B) targetable driver. ECOG, Eastern Cooperative Group; PD-L1, 1.View Large Image ViewerDownload Hi-res image Download (PPT) expand knowledge, collaborate regional networks, together academic (comprehensive networks [CCNs]). Treatment (occurring ?5% T790M resistance mutation) concentrated Criteria expert center designation developed Physicians Diseases Tuberculosis.22Dutch (NVALT)Criteria voor Centra Longkanker patiënten met zeldzame DNA afwijkingen (Criteria Centers abnormality).https://www.nvalt.nl/vereniging/secties/son/concentratie-en-spreiding-van-oncologische-zorg/_/Concentratie%20en%20spreiding%20van%20zorg/SON%20Criteria%20Centra%20Zeldzame%20Mutaties%20longkanker%20finaal%20met%20datum%2021-09-2017.pdfDate Agreements reimburse therapies only when center. Using system treating high. goals (early) trials. TKIs regular summarized Table 1.Table 1Overview Possible Current TKI/Targeted Options Different Targets 2020)Mutation and/or Fusion NSCLCAvailable Drugs (Alphabetical Order)KRASOnly trialEGFRAfatinib, dacomitinib, erlotinib, erlotinib-bevacizumab, erlotinib-ramucirumab, gefitinib, osimertinibBRAFDabrafenib-trametinibALKAlectinib, brigatinib, ceritinib, crizotinib, lorlatinibROS1CrizotinibMET 14 skipping amplicationOnly trial/early programHER2 amplificationOnly trialRETOnly programNTRK1-3Only programNRG1Only trialTKI, tyrosine kinase inhibitor. Open table tab TKI, Regional effective introduce expensive like immune checkpoint inhibitors (ICIs) safely.23Smit H.J.M. Aerts Heuvel al.Effects level National Immunotherapy Registry.Lung 140: 107-112Abstract (12) ICI allowed predefined criteria summary): 20 need ICI, experienced pulmonologist; has MDT specific its related toxicities; least, besides dedicated dermatologist, gastroenterologist, endocrinologist.24Dutch immunotherapy section NVALT.https://www.nvalt.nl/vereniging/secties/son/concentratie-en-spreiding-van-oncologische-zorg/_/Concentratie%20en%20spreiding%20van%20zorg/Criteria%20immunotherapie%20september%202019.pdfDate reimbursement policy (discussed subsequently), combined platinum-doublet chemotherapy additive value judged low. Committee judgment oncological (cieBOM) started 1999 aim evaluate approved drugs harmonize introduction country. initiative society oncologists (NVMO) supported NVALT. cieBOM oncologists, advisors statistician, pharmacist, technologist advisor) evaluates EMA drugs, methods, indications field come agreement regarding new, often expensive, therapies. evaluation completion phase 2/3 trial (published peer-reviewed publication) based self-developed Palliative, Adjuvant, Specific Toxicity, Life, Impact Level Evidence (Table 2)25Dutch Association OncologyNVMO: about advice.https://www.nvmo.org/over-de-adviezen/Date aligned independent Healthcare (Zorginstuut Nederland).25Dutch contrary ESMO magnitude benefit scale,26Cherny N.I. Dafni U. Bogaerts al.ESMO-Magnitude Benefit Scale version 1.1.Ann 28: 2340-2366Abstract (209) Treatment, do allow gradual assessment. conclusion negative advice consequence IMPOWER 133) drug/treatment Unfortunately, automatically lead reimbursement.Table 2PASKWIL CriteriaCriteriaDescriptionCriteria adjuvant therapyPrimary end pointOS relevant pointGain DFSEvaluation DFS possible; preliminary reevaluated become available. retracted negative.DFS HR should <0.7Gain OSMinimum 3 follow-up>5%>3% 0.7Criteria palliative intentEfficacy Gain OS>12 wk 0.7 PFS>12 0.7ESMO-MCBS gradingAdded availableToxicity (difference) Lethal (absolute)<5% Acute, severe<25% Chronic invalidatingNot specifiedImpact treatmentTreatment burden acceptableCosts treatmentGiven median duration daysCost difference careDFS, disease-free survival; ESMO-MCBS, Magnitude Scale; HR, hazard ratio; OS, PASKWIL, Evidence; PFS, progression-free DFS, single-arm II drivers), “state art science” used. End-of-life home-centered hospital-centered.27Bekelman J.E. Halpern S.D. Blankart C.R. al.Comparison site death, utilization, expenditures dying 7 countries.JAMA. 2016; 315: 272-283Crossref (251) mainly generalists GPs. needed, specialists there designed integrated (with number, ranks Europe). receiving teams consultant. 65 collaborative overarching consortia. incorporate early southern discussions end-of-life indeed frequent Netherlands.28Evans Costantini Pasman H.R. al.End-of-life communication: retrospective survey representative practitioner four countries.J Pain Symptom Manage. 2014; 47: 604-619:e3Abstract (46) Scholar, 29Evans Vega Alonso decisions: cross-national preference surrogate decision-maker appointments.PLoS One. 8e57965Crossref (42) 30Evans Donker G.A. practice: cross-sectional, ‘cancer’, ‘organ failure’ ‘old-age/dementia’ patients.Palliat 965-975Crossref (33) result, intensive admittance months life low (3%–5%), 18% die hospital.31de Man Atsma Oosterveld-Vlug M.G. al.The intensity utilization colorectal final life.Cancer Control. 26 (1073274819846574)Crossref (6) Scholar,32Mieras H.R.W. Onwuteaka-Philipsen B.D. al.Is in-hospital higher received month life? cohort study.J 58: 805-811Abstract (4) still room improvement relatives indicate that, they satisfied choice