The Landsteiner lung cancer research platform (LALUCA)

Lung cancer is the most common cause of cancer-related deaths and the second most frequently diagnosed cancer worldwide [1]. As in the rest of the world, lung cancer is a major health burden in Austria comprising 19% of all cancer deaths. With 2402 male and 1472 female deaths in 2017, it is the most frequent cause of cancer-related deaths in males and the second most frequent cause in females. Furthermore, the lung cancer incidence has shown a steady increase over the last five decades, comprising 11% of all newly diagnosed cancers [2]. Diagnosis and staging of lung cancer is a complex multistep process and the management of these patients requires a multidisciplinary and multimodal approach to determine the optimal treatment strategy, which includes surgery, radiotherapy, immunotherapy, chemotherapy and targeted approaches for tumors with driver mutations as well as individual combinations of all of the above [3].

The identification of driver mutations in a subset of tumors has altered the therapeutic landscape and substantially improved survival outcomes in lung cancer [4]. Therefore, efficient and effective molecular testing of lung cancer specimens is crucial. Due to the increasing number of molecular biomarkers, multiplexed assays such as next generation sequencing (NGS) are used to detect a multitude of drugable mutations in a single workflow [4].

Real-world data on routine practice of lung cancer management in Austria is scarce [2]. Gaining information on the diverse and complex population of lung cancer patients as a whole, however, is crucial as the enrolment of patients in clinical cancer trials has been shown to be highly selective including patients several years younger, with superior performance status and less comorbidities at the start of first line therapy than patients in the clinical setting [5‐7]. Generalizability of recommendations based on clinical trials is therefore limited, as the results of clinical trials may reflect only outcomes under best-case scenarios. This results in a potential gap of information on patient outcomes especially among older patients or patients with comorbidities. The collection of real-world data complements the results from clinical trials by enabling us to gain insights into the incidence, characteristics and treatment reality of lung cancer patients and to improve healthcare policy decisions [7].

The Landsteiner lung cancer research platform (LALUCA) is a multicenter, clinical registry with prospective data obtained from lung cancer patients, with the aim of documenting data on molecular testing, diagnostic and treatment modalities as well as the course of disease. This article describes in detail the objectives, the methodology used and the implementation of the LALUCA registry.

The LALUCA registry continuously recruits unselected lung cancer patients from two high volume sites in Vienna, Austria, since its implementation in 2020. Using a custom web-based platform, comprehensive and detailed information on molecular testing, diagnostic and treatment modalities as well as the course of disease is collected in a real-world clinical dataset.

To date, several registries have been implemented to record and evaluate the burden of cancer in the Austrian population. On a national level, the Austrian national cancer registry serves as a data collection tool for epidemiological purposes. It collects data on incidence, prevalence, mortality, and survival probability of all types of cancer based on the entire population of Austria since its implementation in 1983 [11]. Following the development of the Austrian national cancer registry, regional registries have emerged in Carinthia, Salzburg, Tyrol and Vorarlberg, which collect and provide epidemiological data for the national cancer registry, while also using their data to improve the quality of care in their Federal State [12‐15]. In recent years, hospital-based clinical quality data registers have evolved in Lower and Upper Austria, pooling data from 24 and 11 hospitals, respectively. As Lower and Upper Austria are the Federal States with the second and third highest population in Austria, these registries gather data from areas populated by 1.7 and 1.5 million inhabitants, respectively [8]. Thus, both registries, combining web-based software tools with teams for quality management, provide detailed and comprehensive data on cancer patients in their respective Federal State [16, 17]. The Federal State of Vienna encompasses a population as large as 2 million inhabitants [8]. Between 2018 and 2020 the incidence rates of tracheal and lung cancer were the highest in Vienna with a total of 1028 cases compared to 964 and 728 cases in Lower and Upper Austria, respectively [9]. Within this patient collective, the LALUCA registry currently includes approximately 400 new patients on a yearly basis.

The LALUCA registry stands out among national and international lung cancer registries. In accordance with the current national guidelines all NSCLC patients in the LALUCA registry undergo reflex testing with an extended NGS biomarker panel; however, internationally the practice of reflex testing has been reported in only 14 of 21 European countries [18, 19]. Moreover, only a third of European laboratories use single gene testing for epidermal growth factor receptor (EGFR) mutations followed by further testing with NGS in only 45% of cases [20]. The LALUCA registry offers real-world NGS data on a wide variety of histological subtypes including squamous carcinomas and small cell lung cancer and collects crucial data for the assessment of molecular biomarkers. Furthermore, the registry has an extensive collection of surgical and oncologic treatments, which also allows the investigation of clinical consequences of NGS testing on therapeutic concepts. To the best of our knowledge, these advantages set the LALUCA registry apart from other international registries such as the Danish lung cancer registry, which cannot provide information on curative or palliative treatment intent or specify oncological treatment, or the National Lung Cancer Audit UK, which only requires EGFR mutation status, ALK and ROS1 fusion status and PD-L1 expression for minimal completion of a patient thereby limiting detailed information on molecular biomarkers in their overall dataset [21‐23]. Additionally, our platform facilitates the collection of key data on specific supportive therapies and the investigation on changes in the diagnostic and therapeutic approach over the course of time in all types and stages of lung cancer in contrast to other international registries which only record the planned primary treatment such as the Swedish National Lung Cancer Register or only include advanced NSCLC patients such as the German CRISP registry [23, 24]. Future directions of our registry include investigations of incorporation of guideline recommendations regarding molecular testing for the assessment of quality of care as well as investigations of real-world patient outcomes in specific therapeutic settings for the complementation of trial results with data from a diverse and complex patient population.

The design of the LALUCA registry has some clear strengths: first, a multidisciplinary team of clinicians was involved in establishing the registry design and determining variables included in the dataset. The engagement of clinicians has shown improvement in the quality and usefulness of cancer registry data by ensuring the collection of relevant variables [26]. Due to the fast changes in the field of oncology, the clinicians’ perspective and a close interdisciplinary collaboration are imperative to understand which data variables are required to assess new clinical practices and to shed light on current treatment paradigms [25, 26]. Second, data entry in the LALUCA registry is performed by specially trained DEP using a data dictionary, specially curated by clinicians, for uniform interpretation of definitions and standardized input of data. Standardization and clear definition of variables reduces high interobserver variability of DEP that has been found to be an issue in other registries [27]. Especially, the involvement of clinicians in the development of data dictionaries for data standardization has been recommended to establish clear data definitions and thereby quality data [25]. Third, in the rapidly progressing field of oncology, the importance for registries to remain flexible and adaptive in order to stay relevant has been demonstrated [26, 28]. All variables included in the registry need to be carefully evaluated in order to be relevant and useful, as too many variables result in an increased workload of text mining and data entry for the registry team without adding additional benefit [28]. Accordingly, the LALUCA registry was updated to include re-evaluated variables, adding the newly relevant while omitting the obsolete. Furthermore, high data quality of the LALUCA registry is guaranteed by quality assurance monitoring and data quality checks which involve the detection and correction of missing or erroneous data.

A limitation of our registry, however, is that while the LALUCA registry recruits a representative sample of lung cancer patients, it does not cover the majority of patients diagnosed with lung cancer in the Federal State of Vienna, yet. The Steering Committee of the registry, though, has already reached out to other high volume lung cancer sites in Vienna and other cities, to further expand data collection.

In conclusion, the LALUCA registry has been designed to create high quality clinical data on lung cancer. With its primary focus on comprehensive NGS data and its high number of patients, it offers an important platform to investigate real-world practice and to evaluate the quality of care for patients with lung cancer.