ObjectivesThe landmark ADAURA study recently demonstrated a significant disease-free survival benefit of adjuvant osimertinibin patients with resected EGFR-mutated lung adenocarcinoma. However,... Show moreObjectivesThe landmark ADAURA study recently demonstrated a significant disease-free survival benefit of adjuvant osimertinibin patients with resected EGFR-mutated lung adenocarcinoma. However, data on prevalence rates and stage distribution of EGFR mutations in non-small cell lung cancer in Western populations are limited since upfront EGFR testing in early stage lung adenocarcinoma is not common practice. Here, we present a unique, real-world, unselected cohort of lung adenocarcinoma to aid in providing a rationale for routine testing of early stage lung cancers for EGFR mutations in the West-European population.Material and methodsWe performed routine unbiased testing of all cases, regardless of TNM stage, with targeted next-generation sequencing on 486 lung adenocarcinoma cases between 01- January 2014 and 01 February 2020. Clinical and pathological data, including co-mutations and morphology, were collected. EGFR-mutated cases were compared to KRAS-mutated cases to investigate EGFR-specific characteristics.ResultsIn total, 53 of 486 lung adenocarcinomas (11%) harboured an EGFR mutation. In early stages (stage 0-IIIA), the prevalence was 13%, versus 9% in stage IIIB-IV. Nine out of 130 (7%) stage IB-IIIA patients fit the ADAURA criteria. Early stage cases harboured more L858R mutations (p = 0.02), fewer exon 20 insertions (p = 0.048), fewer TP53 co-mutations (p = 0.007), and were more frequently never smokers (p = 0.04) compared to late stage cases with EGFR mutations. The KRAS-mutated cases were distributed more evenly across TNM stages compared to the EGFR-mutated cases.ConclusionAs (neo-)adjuvant targeted therapy regimes enter the field of lung cancer treatment, molecular analysis of early stage non-small cell lung cancer becomes relevant. Testing for EGFR mutations in early stage lung adenocarcinoma holds a substantial yield in our population, as our number needed to test ratio for adjuvant osimertinib was 14.4. The observed differences between early and late stage disease warrant further analysis to work towards better prognostic stratification and more personalised treatment. Show less
Hollander, D. den; Dirkson, A.R.; Verberne, S.; Kraaij, W.; Oortmerssen, G. van; Gelderblom, H.; ... ; Husson, O. 2022
Purpose Treatment with the tyrosine kinase inhibitor (TKI) imatinib in patients with gastrointestinal stromal tumours (GIST) causes symptoms that could negatively impact health-related quality of... Show morePurpose Treatment with the tyrosine kinase inhibitor (TKI) imatinib in patients with gastrointestinal stromal tumours (GIST) causes symptoms that could negatively impact health-related quality of life (HRQoL). Treatment-related symptoms are usually clinician-reported and little is known about patient reports. We used survey and online patient forum data to investigate (1) prevalence of patient-reported symptoms; (2) coverage of symptoms mentioned on the forum by existing HRQoL questionnaires; and (3) priorities of prevalent symptoms in HRQoL assessment.Methods In the cross-sectional population-based survey study, Dutch GIST patients completed items from the EORTC QLQ-C30 and Symptom-Based Questionnaire (SBQ). In the forum study, machine learning algorithms were used to extract TKI side-effects from English messages on an international online forum for GIST patients. Prevalence of symptoms related to imatinib treatment in both sources was calculated and exploratively compared.Results Fatigue and muscle pain or cramps were reported most frequently. Seven out of 10 most reported symptoms (i.e. fatigue, muscle pain or cramps, facial swelling, joint pain, skin problems, diarrhoea, and oedema) overlapped between the two sources. Alopecia was frequently mentioned on the forum, but not in the survey. Four out of 10 most reported symptoms on the online forum are covered by the EORTC QLQ-C30. The EORTC-SBQ and EORTC Item Library cover 9 and 10 symptoms, respectively.Conclusion This first overview of patient-reported imatinib-related symptoms from two data sources helps to determine coverage of items in existing questionnaires, and prioritize HRQoL issues. Combining cancer-generic instruments with treatment-specific item lists will improve future HRQoL assessment in care and research in GIST patients using TKI. Show less
Introduction: With the introduction of tyrosine kinase inhibitors and systemic antibodies, including immune checkpoint inhibitors, the survival of advanced-stage cancer patients has improved for... Show moreIntroduction: With the introduction of tyrosine kinase inhibitors and systemic antibodies, including immune checkpoint inhibitors, the survival of advanced-stage cancer patients has improved for many tumor types. These patients are increasingly referred for radiotherapy, but it is unclear whether radiotherapy combined with these drugs is safe. No international guidelines exist on whether or how to combine these drugs with radiotherapy. Therefore, we investigated the current clinical practice in the Netherlands regarding hypofractionated radiotherapy in patients using targeted drugs and immunotherapy.Materials and methods: We sent a survey to all 21 Dutch radiotherapy institutes. Dedicated radiation oncologists, medical oncologists and pulmonologists were asked to fill out the survey. The questions explored their familiarity with the combination of targeted drugs and immunotherapy with radiotherapy, the encountered clinical difficulties and factors influencing treatment decisions.Results: The survey was filled out by 54 respondents from 19 different institutes. The median annual number of patients per radiation oncologist referred for radiotherapy when using targeted drugs or immunotherapy was 10 and 15, respectively. Despite this high number, only 11% of the radiation oncologists stated that they had sufficient information (resources) for adequate treatment decision making. Among all physicians, 44% stated that there was insufficient knowledge within their institute regarding this topic. Only 17% stated that there was a multidisciplinary protocol available. The application of radiotherapy treatment adaptations (technique, dose, fractionation, field size) varied widely. Generally, there seemed to be no consensus regarding the expected toxicity of combined drug-radiotherapy treatments and the expected risk of tumor flare upon temporary drug discontinuation.Conclusion: There is no consensus amongst involved medical specialties on expected toxicity. Consequently, it is necessary to perform clinical studies examining the safety of combined drug-radiotherapy treatments, to add radiotherapy to phase I-III clinical trials for new drugs and to incorporate outcomes into multidisciplinary, evidence-based guidelines. Show less
Gastrointestinal stromal tumor (GIST) is a rare mesenchymal malignancy in the gastrointestinal tract. Since the introduction of imatinib in 2002, a tyrosine kinase inhibitor (TKI) that targets Bcr... Show moreGastrointestinal stromal tumor (GIST) is a rare mesenchymal malignancy in the gastrointestinal tract. Since the introduction of imatinib in 2002, a tyrosine kinase inhibitor (TKI) that targets Bcr-Abl, KIT and PDGFR, treatment of patients with advanced GIST has been spectacularly improved. In this rapidly evolving field, more insight is needed the treatment and follow-up of GIST patients. The focus for this thesis is on treatment strategies and follow-up in GIST patients in daily clinical practice using a large comprehensive multicenter database. Show less
Erp, N.P. van; Wit, D. de; Guchelaar, H.J.; Gelderblom, H.; Hessing, T.J.; Hartigh, J. den 2013
