Association between baseline tumour burden and outcome in patients with cancer treated with next-generation immunoncology agents

Tarantino, Paolo; Marra, Antonio; Gandini, Sara; Minotti, Marta; Pricolo, Paola; Signorelli, Giulia; Locatelli, M.; Belli, Carmen; Bellomi, Massimo; Curigliano, Giuseppe

doi:10.1016/j.ejca.2020.08.026

Cited by 12 publications

(5 citation statements)

References 14 publications

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“…TB at baseline showed no significant association with survival in our cohort, with tumor burden defined as either sum of longest diameters of all lesions or sum of volumes of all lesions. This is in contrast to earlier work, showing significantly increased mortality among patients with higher TB at baseline ( 23 , 24 ). Our study, however, specifically excludes patients treated with ICI as adjuvant to surgery.…”

Section: Discussioncontrasting

confidence: 99%

“…Another potential factor contributing to this discrepancy between our results and previous studies is the lack of an established gold standard for tumor burden assessment. Indeed, while previous works mainly focus on RECIST 1.1 ( 5 , 24 ), such an analysis underestimates tumor burden in cases where multiple lesions are present in the same organ. Based on our results, patients with high tumor burden at baseline should not be excluded from ICI protocols or clinical trials because of concerns of a worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

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Improved Survival Prediction by Combining Radiological Imaging and S-100B Levels Into a Multivariate Model in Metastatic Melanoma Patients Treated With Immune Checkpoint Inhibition

et al. 2022

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PurposeWe explored imaging and blood bio-markers for survival prediction in a cohort of patients with metastatic melanoma treated with immune checkpoint inhibition.Materials and Methods94 consecutive metastatic melanoma patients treated with immune checkpoint inhibition were included into this study. PET/CT imaging was available at baseline (Tp0), 3 months (Tp1) and 6 months (Tp2) after start of immunotherapy. Radiological response at Tp2 was evaluated using iRECIST. Total tumor burden (TB) at each time-point was measured and relative change of TB compared to baseline was calculated. LDH, CRP and S-100B were also analyzed. Cox proportional hazards model and logistic regression were used for survival analysis.ResultsiRECIST at Tp2 was significantly associated with overall survival (OS) with C-index=0.68. TB at baseline was not associated with OS, whereas TB at Tp1 and Tp2 provided similar predictive power with C-index of 0.67 and 0.71, respectively. Appearance of new metastatic lesions during follow-up was an independent prognostic factor (C-index=0.73). Elevated LDH and S-100B ratios at Tp2 were significantly associated with worse OS: C-index=0.73 for LDH and 0.73 for S-100B. Correlation of LDH with TB was weak (r=0.34). A multivariate model including TB change, S-100B, and appearance of new lesions showed the best predictive performance with C-index=0.83.ConclusionOur analysis shows only a weak correlation between LDH and TB. Additionally, baseline TB was not a prognostic factor in our cohort. A multivariate model combining early blood and imaging biomarkers achieved the best predictive power with regard to survival, outperforming iRECIST.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Improved Survival Prediction by Combining Radiological Imaging and S-100B Levels Into a Multivariate Model in Metastatic Melanoma Patients Treated With Immune Checkpoint Inhibition

et al. 2022

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“…Tumor burden has been associated with multiple metastatic organs or elevated levels of LDH, but no consistent definition of this term exists so far, even though its assessment is very relevant in the clinical routine. Only lately the sum of diameters of the metastases before treatment start has been used as a definition of tumor burden for melanoma treated with pembrolizumab and melanoma and small lung cancer treated with ICB [19, 28].…”

Section: Discussionmentioning

confidence: 99%

Correlation of Baseline Tumor Burden with Clinical Outcome in Melanoma Patients Treated with Ipilimumab

Angelova-Toshkina,

Weide,

Tietze

et al. 2023

Oncology

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Introduction: Tumor burden is a frequently mentioned parameter; however, a commonly accepted definition is still lacking. Methods: In this double center prospective and retrospective study 76 patients with unresectable stage III or stage IV melanoma treated with ipilimumab were included. We defined the baseline tumor burden (BTB) as the global sum of all metastases’ longest diameters before treatment start and correlated the calculated BTB with disease control rate (DCR), progression free survival (PFS), overall survival (OS) and with the baseline levels of LDH, S100B and sULPB2. Results: BTB correlated significantly with DCR (p=0.009), PFS (p=0.002), OS (p=0.032) and the occurrence of NRAS mutation (p= 0.006). BTB was also correlated to baseline serum levels of LDH (p= 0.011), S100B (p=0.027) and SULBP (p<0.0001). Multivariate analysis revealed that BPB and LDH were independently correlated with PFS and OS. With increasing BTB, disease control was less likely; no patient with a BTB >200mm achieved disease control. For patients with brain metastasis no correlation of BTB with DCR (p=0.251), PFS (p=0.059) or OS (p=0.981) was observed. Discussion/Conclusion: Calculated BTB is an independent prognostic factor for patients with metastatic melanoma treated with ipilimumab. Using calculated BTB as a definition of tumor burden may help to increase comparability of outcome of therapies in future studies.

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“…A disbalance in the disease burden between the immunotherapy and targeted therapy groups might explain this difference in the present retrospective study. There are clear signals that patients with low-burden disease have higher chances of treatment efficacy regardless of whether it is immunotherapy [30][31][32] or targeted therapy. 33,34 Nevertheless, a possible explanation for better immunotherapy outcomes might be the duration of tumour response.…”

Section: Immunotherapymentioning

confidence: 99%

The outcome in patients with BRAF‐mutated metastatic melanoma treated with anti‐programmed death receptor‐1 monotherapy or targeted therapy in the real‐world setting

Kopecký,

Pásek,

Lakomý

et al. 2024

Cancer Medicine

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BackgroundImmunotherapy and targeted therapy are currently two alternative backbones in the therapy of BRAF‐mutated malignant melanoma. However, predictive biomarkers that would help with treatment selection are lacking.MethodsThis retrospective study investigated outcomes of anti‐programmed death receptor‐1 monotherapy and targeted therapy in the first‐line setting in patients with metastatic BRAF‐mutated melanoma, focusing on clinical and laboratory parameters associated with treatment outcome.ResultsData from 174 patients were analysed. The median progression‐free survival (PFS) was 17.0 months (95% CI; 8–39) and 12.5 months (95% CI; 9–14.2) for immunotherapy and targeted therapy, respectively. The 3‐year PFS rate was 39% for immunotherapy and 25% for targeted therapy. The objective response rate was 72% and 51% for targeted therapy and immunotherapy. The median overall (OS) survival for immunotherapy has not been reached and was 23.6 months (95% CI; 16.1–38.2) for targeted therapy, with a 3‐year survival rate of 63% and 40%, respectively. In a univariate analysis, age < 70 years, a higher number of metastatic sites, elevated serum LDH and a neutrophil–lymphocyte ratio above the cut‐off value were associated with inferior PFS regardless of the therapy received, but only serum LDH level and the presence of lung metastases remained significant predictors of PFS in a multivariate analysis.ConclusionsPresent real‐world data document the high effectiveness of immunotherapy and targeted therapy. Although targeted therapy had higher response rates, immunotherapy improved PFS and OS. While the prognostic value of LDH was confirmed, the potential use of blood cell count‐derived parameters to predict outcomes needs further investigation.

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Association between baseline tumour burden and outcome in patients with cancer treated with next-generation immunoncology agents

Cited by 12 publications

References 14 publications

Improved Survival Prediction by Combining Radiological Imaging and S-100B Levels Into a Multivariate Model in Metastatic Melanoma Patients Treated With Immune Checkpoint Inhibition

Improved Survival Prediction by Combining Radiological Imaging and S-100B Levels Into a Multivariate Model in Metastatic Melanoma Patients Treated With Immune Checkpoint Inhibition

Correlation of Baseline Tumor Burden with Clinical Outcome in Melanoma Patients Treated with Ipilimumab

The outcome in patients with BRAF‐mutated metastatic melanoma treated with anti‐programmed death receptor‐1 monotherapy or targeted therapy in the real‐world setting

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