Background Matching treatment based on tumour molecular characteristics has revolutionized the treatment of some cancers and has given hope to many patients. Although personalized cancer care is an old concept, renewed attention has arisen due to recent advancements in cancer diagnostics including access to high-throughput sequencing of tumour tissue. Targeted therapies interfering with cancer specific pathways have been developed and approved for subgroups of patients. These drugs might just as well be efficient in other diagnostic subgroups, not investigated in pharma-led clinical studies, but their potential use on new indications is never explored due to limited number of patients. Methods In this national, investigator-initiated, prospective, open-label, non-randomized combined basket- and umbrella-trial, patients are enrolled in multiple parallel cohorts. Each cohort is defined by the patient’s tumour type, molecular profile of the tumour, and study drug. Treatment outcome in each cohort is monitored by using a Simon two-stage-like ‘admissible’ monitoring plan to identify evidence of clinical activity. All drugs available in IMPRESS-Norway have regulatory approval and are funded by pharmaceutical companies. Molecular diagnostics are funded by the public health care system. Discussion Precision oncology means to stratify treatment based on specific patient characteristics and the molecular profile of the tumor. Use of targeted drugs is currently restricted to specific biomarker-defined subgroups of patients according to their market authorization. However, other cancer patients might also benefit of treatment with these drugs if the same biomarker is present. The emerging technologies in molecular diagnostics are now being implemented in Norway and it is publicly reimbursed, thus more cancer patients will have a more comprehensive genomic profiling of their tumour. Patients with actionable genomic alterations in their tumour may have the possibility to try precision cancer drugs through IMPRESS-Norway, if standard treatment is no longer an option, and the drugs are available in the study. This might benefit some patients. In addition, it is a good example of a public–private collaboration to establish a national infrastructure for precision oncology. Trial registrations EudraCT: 2020-004414-35, registered 02/19/2021; ClinicalTrial.gov: NCT04817956, registered 03/26/2021.
HypothesisWe hypothesise that the validated HUNT Lung Cancer Risk Model would perform better than the NLST (USA) and the NELSON (Dutch‐Belgian) criteria in the Danish Lung Cancer Screening Trial (DLCST).MethodsThe DLCST measured only five out of the seven variables included in validated HUNT Lung Cancer Model. Therefore a ‘Reduced’ model was retrained in the Norwegian HUNT2-cohort using the same statistical methodology as in the original HUNT model but based only on age, pack years, smoking intensity, quit time and body mass index (BMI), adjusted for sex. The model was applied on the DLCST-cohort and contrasted against the NLST and NELSON criteria.ResultsAmong the 4051 smokers in the DLCST with 10 years follow-up, median age was 57.6, BMI 24.75, pack years 33.8, cigarettes per day 20 and most were current smokers. For the same number of individuals selected for screening, the performance of the ‘Reduced’ HUNT was increased in all metrics compared with both the NLST and the NELSON criteria. In addition, to achieve the same sensitivity, one would need to screen fewer people by the ‘Reduced’ HUNT model versus using either the NLST or the NELSON criteria (709 vs 918, p=1.02e-11 and 1317 vs 1668, p=2.2e-16, respectively).ConclusionsThe ‘Reduced’ HUNT model is superior in predicting lung cancer to both the NLST and NELSON criteria in a cost-effective way. This study supports the use of the HUNT Lung Cancer Model for selection based on risk ranking rather than age, pack year and quit time cut-off values. When we know how to rank personal risk, it will be up to the medical community and lawmakers to decide which risk threshold will be set for screening.
Small cell carcinoma of the urinary bladder is a rare subtype (incidence of 1–9/1,000,000), characterized by an aggressive behavior with early metastasis and poor prognosis. Chemotherapy, radiation, and surgery are the usual treatment options, but to date, no accepted standard treatment exists. Since small cell bladder cancer shares similar clinicopathological features with small cell lung cancer, the same type of chemotherapy has been used. Recently, immune checkpoint inhibitors have shown effect in small cell lung cancer, but data regarding small cell bladder cancer is insufficient. Here we present a case where a 73-year-old male with chemorefractory metastatic small cell bladder cancer received a successful treatment with immune checkpoint inhibitor pembrolizumab resulting in a major durable response and no side effects. To our knowledge, this is the second case report on successful treatment of the rare subtype of small cell bladder cancer with an immune checkpoint inhibitor, supporting the use of pembrolizumab as a therapeutic option for small cell bladder cancer. Serum neuron-specific enolase was a useful biomarker both for chemo- and immunotherapy response.
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