Trying to define “high tumor burden” in non-small cell lung cancer: A Delphi survey.
Authors: Mielgo-Rubio Xabier , Sereno Maria , Higuera Oliver , Cervera Raquel , Cabezon-Gutierrez Luis 
Published: June 2022

e21061 Background: High tumor burden (HTB) has been introduced in several solid tumors as clinical biomarker with negative prognostic value and has also been proposed as a clinical marker in patients with advanced non-small-cell lung cancer (NSCLC). There is no homogeneous definition for HTB in NSCLC and it is unknown whether is useful for guiding therapeutic decisions and how could be used by oncologists in real-world setting. Methods: A panel of 5 oncologists specialized in the management of NSCLC patients elaborated a questionnaire with 26 statements about HTB in advanced NSCLC using a modified Delphi method with a 9-point Likert scale of agreement for each statement. The aim was to define HTB concept and analyze its role in treatment decisions. Statements were grouped into 4 areas: clinical and pathological characteristics, metastatic involvement, clinical symptoms/scenarios and therapeutic implication. 66 Spanish oncologists with a minimum experience of 5 years treating at least 100 lung cancer patients per month were selected to participate. The questionnaire was fulfilled electronically by an internet specific website and all participants were asked to complete it twice: a first round (from December 2020 to February 2021) followed by a deliberation period about first results and then a second round (from June to August 2021). Results: 50 (76%) of the 66 selected experts fulfilled the questionnaire in the first round reaching consensus in 8 (31%) of the 26 statements. 33 (66%) of previous 50 experts fulfilled the questionnaire in the second round reaching consensus in 8 additional statements: 16 (61%) of the 26 statements in total. Consensus was reached in the following statements: HTB is relevant for the initial approach in advanced NSCLC; HTB is equivalent to aggressive disease; HTB is defined by a sum of the longest diameter of target lesions ≥10cm or a primary tumor with a diameter of ≥10 cm, an increase of LDH 2 ≥ ULN, hepatic involvement, lymphangitis, pericardial effusion, brain involvement that cannot be addressed with local techniques, or an oncological emergency; HTB is not defined by an elevation of tumor markers or symptomatic brain involvement; the threshold for the number of metastatic sites that defines HTB is 3; presence of HTB is important in selecting first and second-line treatment; and first treatment option to treat a patient with HTB is a combo of chemotherapy and immunotherapy regardless PDL1 status. On the other hand, consensus was not reached to define HTB by other important factors in clinical practice as high symptomatic burden, ECOG ≥2, weight loss > 10%, presence of pleural effusion or symptomatic bone metastases. Conclusions: Our Delphy survey results show there are only a few factors with a moderate strength of consensus about the definition and therapeutic implication of HTB concept and underscores the need to investigate its prognostic and predictive value as well as an involvement in therapeutic decisions.