scholarly journals Hyperprogressive disease rarely occurs during checkpoint inhibitor treatment for advanced melanoma

2020 ◽  
Author(s):  
M. Schuiveling ◽  
E. H. J. Tonk ◽  
R. J. Verheijden ◽  
K. P. M. Suijkerbuijk
Keyword(s):  
Tumor Growth ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Tumor Burden ◽  
Advanced Melanoma ◽  
Tumor Growth Rate ◽  
Biological Entity ◽  
Melanoma Patients

Abstract Introduction Hyperprogression, characterized by a rapid acceleration in tumor growth, is a novel pattern of progression recently described in patients treated with immune checkpoint inhibitors. This study aims to assess the incidence of hyperprogression in patients with advanced melanoma treated with checkpoint inhibitors. Methods Clinical and radiological findings of all advanced melanoma patients who started checkpoint inhibitors between January 2013 and March 2019 in a tertiary academic center in the Netherlands were analyzed. Change in tumor burden was calculated by assessing volumetric tumor growth using the criteria as defined by immune Response Evaluation Criteria in Solid Tumors version 1.1. Hyperprogression was defined as a time to treatment failure less than 2 months with doubling of tumor burden and a twofold increase in tumor growth rate during treatment. Possible hyperprogression was defined as the presence of the first two criteria in the absence of a pre-baseline scan. Results Out of 206 treatment episodes in 168 patients, 75 were evaluable for hyperprogression and 87 for possible hyperprogression. Hyperprogression was observed in one patient (1.3%) and possible hyperprogression was observed in one patient (1.1%). Conclusion Hyperprogression is rare in melanoma patients treated with immune checkpoint inhibitors. Our data question if hyperprogression really is a biological entity in metastatic melanoma.

Optimizing Sequence of PD-L1 Immune-Checkpoint Inhibitors and Radiation Therapy in Bladder Cancer

2020 ◽  
Vol 6 (3) ◽  
pp. 295-302
Author(s):  
Côme Tholomier ◽  
Gautier Marcq ◽  
Surashri Shinde-Jadhav ◽  
Mina Ayoub ◽  
Jia Min Huang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radiation Therapy ◽  
Tumor Growth ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Combined Therapy ◽  
Tumor Growth Rate ◽  
Significant Difference ◽  
Rate Of Response

BACKGROUND: New bladder preserving strategies are needed for muscle invasive bladder cancer (MIBC). Combined therapy of immune-checkpoint inhibitors and radiation was shown to have synergistic antitumoral effects in preclinical studies. OBJECTIVES: We aim to evaluate whether the sequence of administration of this combined therapy impacts antitumoral response. METHODS: We developed an in-vivo syngeneic MIBC mouse model where murine bladder cancer cells (MB49) were injected subcutaneously in the right flank of C57BL/6 mice. Mice were then randomized to the following treatments: control, anti-programmed cell death ligand 1 (PD-L1) alone, radiation alone (XRT) consisting of 6.25 Gy x2 fractions, concurrent anti-PD-L1 with XRT, neoadjuvant anti-PD-L1 followed by XRT, or XRT followed by adjuvant anti-PD-L1 therapy. Tumor growth, survival, and rate of response were analyzed. RESULTS: Total of 60 mice were randomized. One-way analysis of variance showed statistically significant difference in tumor growth rate across the treatment arms (p = 0.029). Importantly, timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) did not alter either tumor growth or survival (p > 0.05). The rate of response was also similar in each combination arm (p > 0.05). CONCLUSION: Combining anti-PD-L1 immunotherapy and radiation therapy offers optimal antitumoral responses. Timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) does not appear to affect outcomes. Whether the toxicity profile differs across various sequential deliveries of combination therapy requires further evaluation.

scholarly journals Immunotherapy by Immune Checkpoint Inhibitors and Nuclear Medicine Imaging: Current and Future Applications

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 371 ◽  
Author(s):  
Pierre Decazes ◽  
Pierre Bohn
Keyword(s):  
Nuclear Medicine ◽  
Radionuclide Imaging ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Imaging Modality ◽  
Evaluation Criteria ◽  
Tumor Growth Rate ◽  
Nuclear Medicine Imaging ◽  
Therapeutic Evaluation

Immunotherapy by using immune checkpoint inhibitors is a revolutionary development in oncology. Medical imaging is also impacted by this new therapy, particularly nuclear medicine imaging (also called radionuclide imaging), which uses radioactive tracers to visualize metabolic functions. Our aim was to review the current applications of nuclear medicine imaging in immunotherapy, along with their limitations, and the perspectives offered by this imaging modality. Method: Articles describing the use of radionuclide imaging in immunotherapy were researched using PubMed by April 2019 and analyzed. Results: More than 5000 articles were analyzed, and nearly 100 of them were retained. Radionuclide imaging, notably 18F-FDG PET/CT, already has a major role in many cancers for pre-therapeutic and therapeutic evaluation, diagnoses of adverse effects, called immune-related adverse events (IrAE), and end-of-treatment evaluations. However, these current applications can be hindered by immunotherapy, notably due to atypical response patterns such as pseudoprogression, which is defined as an increase in the size of lesions, or the visualization of new lesions, followed by a response, and hyperprogression, which is an accelerated tumor growth rate after starting treatment. To overcome these difficulties, new opportunities are offered, particularly therapeutic evaluation criteria adapted to immunotherapy and immuno-PET allowing us to predict responses to immunotherapy. Moreover, some new technological solutions are also promising, such as radiomic analyses and body composition on associated anatomical images. However, more research has to be done, notably for the diagnosis of hyperprogression and pseudoprogression. Conclusion: Immunotherapy, by its major impact on cancer and by the new patterns generated on images, is revolutionary in the field of medical images. Nuclear medicine imaging is already established and will be able to help meet new challenges through its plasticity.

scholarly journals Antibiotics are associated with decreased progression-free survival of advanced melanoma patients treated with immune checkpoint inhibitors

2019 ◽  
Vol 8 (4) ◽  
pp. e1568812 ◽  
Author(s):  
Arielle Elkrief ◽  
Layal El Raichani ◽  
Corentin Richard ◽  
Meriem Messaoudene ◽  
Wiam Belkaid ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Melanoma Patients

scholarly journals Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH?

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1940 ◽  
Author(s):  
Maartje G. Schouwenburg ◽  
Karijn P.M. Suijkerbuijk ◽  
Rutger H.T. Koornstra ◽  
Anouk Jochems ◽  
Michiel C.T. van Zeijl ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Elevated Serum ◽  
Subsequent Treatment ◽  
Advanced Melanoma ◽  
Term Survival ◽  
Melanoma Patients

The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (≥2× upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4–5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH.

Determination of clinical benefit among patients with radiological stable disease to immune checkpoint inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9041-9041
Author(s):  
Jia Luo ◽  
Song Wu ◽  
Hira Rizvi ◽  
Qu Zhang ◽  
Jacklynn V. Egger ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
External Validation ◽  
Objective Response ◽  
Proliferation Index ◽  
Tumor Growth Rate ◽  
Discovery Cohort ◽  
Similar Survival

9041 Background: SD is a common but ambiguous outcome in patients receiving immune checkpoint inhibitors (ICIs) and likely represents a heterogenous mix of responders and non-responders. This study aimed to characterize SD and identify the subset of patients with SD who are benefiting from treatment. The ability to distinguish whom among patients with SD is actually benefiting from treatment would facilitate drug development and improve precision in correlative research. Methods: A systematic review was performed to characterize SD in ICI trials. SD and objective response was compared to proliferation index using TCGA gene expression data. To identify a subgroup of SD with outcomes mirroring responders, we examined a discovery cohort of NSCLC treated with ICIs and had RECIST assessment. In patients with best overall response (BOR) of SD, serial cutpoints of two variables, % BOR and PFS, were tested to define a subgroup with similar survival as PR-minor (patients with partial response [PR] and % shrinkage < median among responders). Results were then tested in two external validation cohorts (n = 326, n = 381). Results: Among trials of ICIs (59 studies, 14,280 patients), SD ranged from 16-42% in different tumor types and was associated with disease-specific proliferation index (Spearman rho = -0.75, p = 0.03), a proxy of tumor kinetics, rather than relative response to ICIs. In a discovery cohort of 1220 patients with NSCLC who were treated with ICIs, 26% had SD, 19% had PR/CR, and 55% had PD. Outcomes among those with SD ranged widely (OS range 0.5-76 months, PFS range 0.2-49 months). The subset of SD with PFS > 6 months and no tumor growth mirrored PR-minor (OS HR 1.0) and was proposed as the definition of “SD-responder”. SD-responders (n = 87) represented 7% (95% CI 6-9%) of the overall population and 28% (95% CI 23-33%) of the SD population. This definition was confirmed in two validation cohorts from trials of NSCLC treated with durvalumab. Conclusions: RECIST-defined SD to immunotherapy is common, heterogenous, and may largely reflect tumor growth rate rather than ICI response. In patients with NSCLC and SD to ICIs, PFS > 6 months and no tumor growth (̃1/3 of SD) may be considered “SD responders.” This definition may improve the efficiency of and insight derivable from clinical and translational research.

scholarly journals 55 Baseline glycolytic tumor burden predicts response and survival in NSCLC and melanoma patients treated with immune checkpoint inhibitors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A62-A63
Author(s):  
Saulo Silva ◽  
Carlos Wagner Wanderley ◽  
Jose Flavio Marin ◽  
Mariana De Macedo ◽  
Ellen Nascimento ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Progressive Disease ◽  
Checkpoint Inhibitors ◽  
Tumor Burden ◽  
Toxic Metabolite ◽  
Predictive Tool ◽  
Metabolic Remodeling ◽  
Melanoma Patients ◽  
Nsclc Patients

BackgroundTumor metabolic remodeling is considered one of the hallmarks of cancers and has been implicated in immune evasion. Highly glycolytic tumors can lead to immune suppression by both nutrient competition and toxic metabolite accumulation. Immune checkpoint inhibitors (ICIs) are essential in treating melanoma and non-small cell lung cancer (NSCLC) patients, but novel predictive biomarkers can significantly contribute to clinical practice. Herein we analyzed the predictive and prognostic value of baseline metabolic tumor volumes in NSCLC and melanoma patients treated with ICIs.MethodsThis retrospective, single-center study includes patients with metastatic NSCLC or melanoma and a baseline 18F-FDG-PET/CT (PET) performed before ICI. PET studied parameters were SUV (maximum standardized uptake value), wMTV (whole metabolic tumor value), and wTLG (whole total lesion glycolysis). Best response rates were analyzed through RECIST. High or low glycolytic tumor burden (GTB) patients were defined according to SUV, wMTV, and wTLG cut-offs that best discriminate progressive disease. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and curves were compared with log-rank.ResultsAmong 151 patients included, 107 had NSCLC and 44 melanoma. Regarding NSCLC patients, there was a significant correlation between GTB and responses among all PET parameters (figure 1). Noteworthily, only one patient with a low wTLG (<146) showed progressive disease after ICIs (figure 2C). In regard to the potential in predicting response to ICIs, the area under the curve (AUC) obtained for each glycolytic parameter was higher than that for PD-L1 expression (figure 2D-H). Furthermore, when patients were categorized according to ICI exposure (1st or ≥ 2nd line), AUC for glycolytic parameters was higher in ≥ 2nd line versus 1st line (figure 3). Lastly, a low GTB was associated with improved PFS (figure 4) and OS (figure 5).Regarding melanoma patients, wMTV and wTLG were significantly associated with response (figure 6), and a low GTB was significantly associated with improved PFS and OS (figure 7).Abstract 55 Figure 1Abstract 55 Figure 2Abstract 55 Figure 3Abstract 55 Figure 4Abstract 55 Figure 5Abstract 55 Figure 6Abstract 55 Figure 7ConclusionsGTB accessed through a baseline PET is associated with survival and response to ICIs in NSCLC and melanoma patients, suggesting that the tumor metabolism might impact immune responses and be a promising predictive tool.Ethics ApprovalThe study obtained ethics approval by Sírio-Libanês Hospital institutional review board. Study participants were not required to give an informed consent before taking part.

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