Pseudoprogression in Previously Treated Patients with Non–Small Cell Lung Cancer Who Received Nivolumab Monotherapy

Fujimoto, Daichi; Yoshioka, Hiroshige; Kataoka, Yuki; Morimoto, Takeshi; Hata, Tae; Kim, Young Hak; Tomii, Keisuke; Ishida, Tadashi; Hirabayashi, Masataka; Hara, Satoshi; Ishitoko, Manabu; Fukuda, Yasushi; Hwang, Moon Hee; Sakai, Naoki; Fukui, Motonari; Nakaji, Hitoshi; Morita, Mitsunori; Mio, Tadashi; Yasuda, Takehiro; Sugita, Takakazu; Hirai, Toyohiro

doi:10.1016/j.jtho.2018.10.167

Cited by 89 publications

(80 citation statements)

References 15 publications

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“…We defined progression‐free survival 1 (PFS1) as the time from initial immunotherapy to RECIST 1.1‐defined first progressive disease or death, progression‐free survival 2 (PFS2) as the time from RECIST 1.1‐defined first progressive disease to iRECIST‐defined first progressive disease or death, and immune‐related progression‐free survival (iPFS) as the first date at which progression criteria were met (i.e., the date of iUPD) provided that iCPD was confirmed at the next assessment. For patients with tumor progression evaluated per the RECIST 1.1, pseudoprogression (PsPD) was defined among patients who met the conventional response criteria for progressive disease but later showed reduced tumor burden …”

Section: Methodsmentioning

confidence: 99%

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Patterns of response in metastatic NSCLC during PD‐1 or PD‐L1 inhibitor therapy: Comparison of the RECIST 1.1 and iRECIST criteria

Liang

Chen

et al. 2020

Thoracic Cancer

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Background Immunotherapy plays an important role in advanced non‐small cell lung cancer (NSCLC). However, radiological evaluation is challenging due to the potential inflammatory effects of immunotherapy, which can lead to atypical response patterns. Identifying these atypical responses is critical to making treatment decisions and prognostication. Methods We performed a retrospective analysis of consecutive advanced NSCLC patients treated with immunotherapy (alone or in combination). We collected patients' clinical and pathological data, analyzed the proportion of patients who continued immunotherapy beyond progressive disease (PD) per RECIST 1.1, and compared the differences in response patterns between the RECIST 1.1 and iRECIST criteria. Results A total of 43 patients treated at the Peking Union Medical College, China from January 2018 to April 2019 were included. Continued immunotherapy beyond PD per RECIST 1.1 was observed in 10 (33.3%, 10/30) patients, of which there were discordant assessments (30%, 3/10) between the RECIST 1.1 and iRECIST, which were evaluated as PD by RECIST 1.1 and immune unconfirmed PD by iRECIST. Among seven patients with immune confirmed PD, one (1/30, 3.3%) had pseudoprogression. Patients who continued immunotherapy beyond PD (n = 10) experienced significantly prolonged overall survival (not reached vs. 8.1 months: hazard ratio, 2.8; 95% confidence interval: 2.7–13.6, P = 0.03) compared with patients who did not continue immunotherapy beyond PD (n = 20). Conclusions RECIST 1.1 evaluation underestimated the benefit of immunotherapy. Further research is required to optimize iRECIST and establish some criteria for selecting patients who will benefit from continued immunotherapy beyond PD per RECIST 1.1.

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Section: Methodsmentioning

confidence: 99%

“…For patients with tumor progression evaluated per the RECIST 1.1, pseudoprogression (PsPD) was defined among patients who met the conventional response criteria for progressive disease but later showed reduced tumor burden. 21,23…”

Section: Patterns Of Responsementioning

confidence: 99%

Patterns of response in metastatic NSCLC during PD‐1 or PD‐L1 inhibitor therapy: Comparison of the RECIST 1.1 and iRECIST criteria

Liang

Chen

et al. 2020

Thoracic Cancer

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“…In melanoma patients, it has been shown that this phenomenon can occur in lymph nodes, but more commonly in non-nodal locations such as the kidneys, liver, lungs, peritoneum, adrenal glands, and chest and abdominal walls [26]. Finally, patients experiencing a pseudoprogression have been shown to have a shorter duration of response than patients with a typical response, but a better chance of survival than patients with typical progression [27].…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Imaging of tumour response to immunotherapy

et al. 2020

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A wide range of cancer immunotherapy approaches has been developed including non-specific immune-stimulants such as cytokines, cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive T cell therapy. Among them, ICIs are the most commonly used and intensively studied. Since 2011, these drugs have received marketing authorisation for melanoma, lung, bladder, renal, and head and neck cancers, with remarkable and long-lasting treatment response in some patients. The novel mechanism of action of ICIs, with immune and T cell activation, leads to unusual patterns of response on imaging, with the advent of so-called pseudoprogression being more pronounced and frequently observed when compared to other anticancer therapies. Pseudoprogression, described in about 2-10% of patients treated with ICIs, corresponds to an increase of tumour burden and/or the appearance of new lesions due to infiltration by activated T cells before the disease responds to therapy. To overcome the limitation of response evaluation criteria in solid tumors (RECIST) to assess these specific changes, new imaging criteria-so-called immune-related response criteria and then immune-related RECIST (irRECIST)-were proposed. The major modification involved the inclusion of the measurements of new target lesions into disease assessments and the need for a 4-week re-assessment to confirm or not confirm progression. The RECIST working group introduced the new concept of "unconfirmed progression", into the irRECIST. This paper reviews current immunotherapeutic approaches and summarises radiologic criteria to evaluate new patterns of response to immunotherapy. Furthermore, imaging features of immunotherapy-related adverse events and available predictive biomarkers of response are presented.

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“…Even though challenging for patients and clinicians, tumor pseudo-progression in a computer tomography (CT) scan or 18F-FDG-PET might precede a good clinical response to immunotherapy. 48 Importantly, the immune activity can emit PET signals similar to those from tumors, and therefore, 18F-FDG-PET cannot differentiate a true progression from a F I G U R E 1 A metabolic-tumor-stroma score (MeTS) to describe the tumor metabolic and cellular heterogeneity and to assess the quality of anti-tumor immune response pseudo-progression. 49,50 Cancer-associated fibroblasts (CAFs) can account for a high proportion of the tumor stroma and can contribute to the uptake of 18F-FDG.…”

Section: Warburg Effec T In Tumor S Tromal Cell Smentioning

confidence: 99%

The immunological Warburg effect: Can a metabolic‐tumor‐stroma score (MeTS) guide cancer immunotherapy?

Siska

Singer

Evert

et al. 2020

Immunological Reviews

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The "glycolytic switch" also known as the "Warburg effect" is a key feature of tumor cells and leads to the accumulation of lactate and protons in the tumor environment.Intriguingly, non-malignant lymphocytes or stromal cells such as tumor-associated macrophages and cancer-associated fibroblasts contribute to the lactate accumulation in the tumor environment, a phenomenon described as the "Reverse Warburg effect." Localized lactic acidosis has a strong immunosuppressive effect and mediates an immune escape of tumors. However, some tumors do not display the Warburg phenotype and either rely on respiration or appear as a mosaic of cells with different metabolic properties. Based on these findings and on the knowledge that T cell infiltration is predictive for patient outcome, we suggest a metabolic-tumor-stroma score to determine the likelihood of a successful anti-tumor immune response: (a) a respiring tumor with high T cell infiltration ("hot"); (b) a reverse Warburg type with respiring tumor cells but glycolytic stromal cells; (c) a mixed type with glycolytic and respiring compartments; and (d) a glycolytic (Warburg) tumor with low T cell infiltration ("cold"). Here, we provide evidence that these types can be independent of the organ of origin, prognostically relevant and might help select the appropriate immunotherapy approach. K E Y W O R D Sacidification, GLUT, immunotherapies, lactate, T cell, Warburg

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Pseudoprogression in Previously Treated Patients with Non–Small Cell Lung Cancer Who Received Nivolumab Monotherapy

Cited by 89 publications

References 15 publications

Patterns of response in metastatic NSCLC during PD‐1 or PD‐L1 inhibitor therapy: Comparison of the RECIST 1.1 and iRECIST criteria

Patterns of response in metastatic NSCLC during PD‐1 or PD‐L1 inhibitor therapy: Comparison of the RECIST 1.1 and iRECIST criteria

Imaging of tumour response to immunotherapy

The immunological Warburg effect: Can a metabolic‐tumor‐stroma score (MeTS) guide cancer immunotherapy?

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