“High Tumor Burden” in Metastatic Non-Small Cell Lung Cancer: Defining the Concept

Abstract

Purpose Identifying patient characteristics that define a worse disease prognosis or “high tumor burden” (HTB) status is essential for clinical decision-making and treatment selection in metastatic non-small cell lung cancer (mNSCLC). We aimed to define this concept based on the experience of oncologists in clinical practice. Patients and Methods A representative sample of Spanish experts was selected and asked to complete an online survey regarding the definition of HTB according to their personal experience. Results HTB was identified by the oncologists (N = 81) as one of the principle factors influencing first-line treatment decision-making. According to the experts, HTB is mainly defined by the number of metastatic lesions (n = 45, 56%), location (n = 34, 42%), tumor size (sum of diameters of target lesions; n = 26, 32%) and liver involvement (n = 24, 30). High lactate dehydrogenase (LDH) levels were also associated with HTB. Almost half of respondents (n = 33, 41%) believed that one metastatic lesion was sufficient to consider a patient as presenting HTB, 72% (n = 58) considered that two were necessary and 99% (n = 80) three. Liver (n = 76, 100%) followed by brain (n = 65, 86%) were the main metastatic sites associated with HTB. Tumor size ranging from 6 cm to 10 cm as well as high LDH levels (three times the upper limit) defined the concept for 82% (n = 62) and 100% (n = 76) of oncologists, respectively. Conclusion In the real-world setting, according to experts, HTB is defined by the number of metastatic lesions, location of metastases, tumor size and by high LDH levels. Given the relevance of this concept, efforts should be made to unify its definition and to further explore its potential as a prognostic factor for mNSCLC patients.

Osteosarcoma: novel prognostic biomarkers using circulating and cell-free tumour DNA

“…Overall, the detection of pre-treatment ctDNA correlated with inferior survival outcomes (p<0.01, Figure 2A, Table1) and with a diseaserelated event (p=0.01, chi-square test), but not with tumour size (p=0.14, Student's t-test), gender (0.53) or age at presentation (p=0.92). ctDNA positivity did not have a significant association with outcome on multivariate analysis, however it should be noted that this model also included metastatic disease status at diagnosis which is known to be linked to increased tumour burden 40,41 , and thus higher probability of ctDNA detection. We also analysed post-operative plasma available from 17 of the 72 patients with OS in whom ctDNA was detected pre-treatment.…”

Cytokine release syndrome after treatment with immune checkpoint inhibitors: an observational cohort study of 2672 patients from Karolinska University Hospital in Sweden

“…All unique patients with CRS (n = 28) were included in the study and cases of recurrent CRS after rechallenge with ICI (n = 3) were noted separately in the data set. Tumor burden was defined as having at least two metastatic lesions, a minimum tumor size ranging from 6– 10 cm (corresponding to the sum of diameters), and LDH levels ≥3 times the ULN [14].…”

Pemetrexed and Platinum Plus Pembrolizumab in Patients With Metastatic Nonsquamous NSCLC by Tumor Burden at Baseline: A Post Hoc Efficacy Analysis of KEYNOTE-189

“…Baseline tumor burden generally defined by tumor volume, tumor diameter, location, or number of metastatic lesions 16 is being increasingly recognized as an important determinant of clinical outcomes and treatment decisions. 16 , 17 , 18 , 19 , 20 The presence of high tumor burden at baseline is considered a negative prognostic factor in various cancer types, including metastatic NSCLC.…”

“…Baseline tumor burden generally defined by tumor volume, tumor diameter, location, or number of metastatic lesions 16 is being increasingly recognized as an important determinant of clinical outcomes and treatment decisions. 16 , 17 , 18 , 19 , 20 The presence of high tumor burden at baseline is considered a negative prognostic factor in various cancer types, including metastatic NSCLC. 16 , 21 , 22 , 23 Preclinical studies 24 and emerging clinical evidence also indicate that the extent of tumor burden at baseline influences treatment responses and outcomes to ICI monotherapy in advanced NSCLC.…”

“… 16 , 17 , 18 , 19 , 20 The presence of high tumor burden at baseline is considered a negative prognostic factor in various cancer types, including metastatic NSCLC. 16 , 21 , 22 , 23 Preclinical studies 24 and emerging clinical evidence also indicate that the extent of tumor burden at baseline influences treatment responses and outcomes to ICI monotherapy in advanced NSCLC. 18 , 24 …”