Immune-related response assessment during PD-1 inhibitor therapy in advanced non-small-cell lung cancer patients

Nishino, Mizuki; Ramaiya, Nikhil H.; Chambers, Emily S.; Adeni, Anika E.; Hatabu, Hiroto; Jänne, Pasi A.; Hodi, F. Stephen; Awad, Mark M.

doi:10.1186/s40425-016-0193-2

Cited by 104 publications

(93 citation statements)

References 36 publications

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“…(1–4) Median TTP by irRECIST was longer at 11.4 months, which was expected because of the modified definition of PD by irRECIST that requires confirmation and allows new lesions in the measurements. (20,21,24)…”

Section: Discussionmentioning

confidence: 99%

“…Initial tumor responses in 56 of the 160 included NSCLC patients been previously reported. (24) The medical records and imaging studies of these patients were retrospectively reviewed with the approval of the Dana Farber/Harvard Cancer Center institutional review board. The study was in compliance with Health Insurance Portability and Accountability Act and all patients provided written informed consent.…”

Section: Methodsmentioning

confidence: 99%

“…to quantify tumor burden changes using immune-related RECIST (irRECIST), based on previously published studies. (12,20,21,24) Unidimensional, RECIST-defined measurements were used in irRECIST because they have been shown to have higher reproducibility compared to bidimensional measurements used in WHO criteria and irRC, and are in alignment with the RECIST-based assessments used in most of the solid tumor trials performed in the past decade. (15,16,21,25–27) In brief, target lesions (≥10 mm in the longest diameter for non-nodal lesions and ≥15 mm in short axis for nodal lesions) were selected on baseline scans, allowing up to 2 lesions per organ and up to 5 lesions in total as in RECIST1.1.…”

Section: Methodsmentioning

confidence: 99%

“…(15,16,21,25–27) In brief, target lesions (≥10 mm in the longest diameter for non-nodal lesions and ≥15 mm in short axis for nodal lesions) were selected on baseline scans, allowing up to 2 lesions per organ and up to 5 lesions in total as in RECIST1.1. (18,24,28,29) Measurements of target lesions were performed on baseline and all follow-up CT scans throughout therapy. If new lesions were noted on the follow-up scans, the measurements of the new lesions were included in the sum of the measurements.…”

Section: Methodsmentioning

confidence: 99%

“…(12,20,21,24) Confirmation on 2 consecutive scans at least 4 weeks apart was required for irPD. (11,14,20,21,24) Time to progression using irRECIST (irTTP) was obtained in each patient, allowing the inclusion of new lesion measurements and requiring confirmation of PD. (20,21) TTP according to conventional RECIST1.1 was also obtained in each patient, where appearance of new lesions or tumor burden increase ≥20% and 5 mm comparing to the nadir immediately defined PD without requiring confirmation.…”

Section: Methodsmentioning

confidence: 99%

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Tumor Response Dynamics of Advanced Non–small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome

Nishino

Dahlberg

Adeni

et al. 2017

Clinical Cancer Research

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Purpose We evaluated tumor burden dynamics in advanced non-small-cell lung cancer (NSCLC) patients treated with commercial PD-1 inhibitors to identify imaging markers associated with improved overall survival (OS). Experimental Design The study included 160 advanced NSCLC patients treated with commercial nivolumab or pembrolizumab monotherapy as a part of clinical care. Tumor burden dynamics were studied for the association with OS. Results Tumor burden change at best overall response (BOR) ranged from −100% to +278% (median: +3.5%). Response rate (RR) was 18% (29/160). Current and former smokers had a higher RR than never smokers (p=0.04). Durable disease control for at least 6 months was noted in 26 patients (16%), which included 10 patients with stable disease as BOR. Using a landmark analysis, patients with <20% tumor burden increase from baseline within 8 weeks of therapy had longer OS than patients with ≥20% increase (median OS:12.4 vs. 4.6 months, p<0.001). Patients with <20% tumor burden increase throughout therapy had significantly reduced hazards of death (HR=0.24, Cox p<0.0001) after adjusting for smoking (HR=0.86, p=0.61) and baseline tumor burden (HR=1.55, p=0.062), even though some patients met criteria for RECIST progression while on therapy. One patient (0.6%) had atypical response pattern consistent with pseudoprogression. Conclusions Objective response or durable disease control was noted in 24% of advanced NSCLC patients treated with commercial PD-1 inhibitors. A tumor burden increase of <20% from baseline during therapy was associated with longer OS, proposing a practical marker of treatment benefit. Pseudoprogression is rare in NSCLCs treated with PD-1 inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Tumor Response Dynamics of Advanced Non–small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome

Nishino

Dahlberg

Adeni

et al. 2017

Clinical Cancer Research

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A Comparison of Response Patterns for Progression-Free Survival and Overall Survival Following Treatment for Cancer With PD-1 Inhibitors

2018

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Key Points Question Does the treatment effect size differ between overall survival and progression-free survival for PD-1 (programmed cell death 1) inhibitors used in patients with advanced solid tumors, and are overall survival and progression-free survival correlated? Findings This meta-analysis of 12 randomized clinical trials found no significant correlation between overall survival and progression-free survival in terms of medians and gains in medians, but their hazard ratios were significantly correlated. The protective effects of treatment were greater for overall survival than for progression-free survival. Meaning Progression-free survival cannot adequately capture the benefit of PD-1 inhibitors; thus, overall survival should remain the gold standard end point for trials of PD-1 inhibitors.

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A Pathologically Friendly Strategy for Determining the Organ‐specific Spatial Tumor Microenvironment Topology in Lung Adenocarcinoma Through the Integration of snRandom‐seq and Imaging Mass Cytometry

Sun,

Teng,

Liu

et al. 2024

Advanced Science

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Heterogeneous organ‐specific responses to immunotherapy exist in lung cancer. Dissecting tumor microenvironment (TME) can provide new insights into the mechanisms of divergent responses, the process of which remains poor, partly due to the challenges associated with single‐cell profiling using formalin‐fixed paraffin‐embedded (FFPE) materials. In this study, single‐cell nuclei RNA sequencing and imaging mass cytometry (IMC) are used to dissect organ‐specific cellular and spatial TME based on FFPE samples from paired primary lung adenocarcinoma (LUAD) and metastases. Single‐cell analyses of 84 294 cells from sequencing and 250 600 cells from IMC reveal divergent organ‐specific immune niches. For sites of LUAD responding well to immunotherapy, including primary LUAD and adrenal gland metastases, a significant enrichment of B, plasma, and T cells is detected. Spatially resolved maps reveal cellular neighborhoods recapitulating functional units of the tumor ecosystem and the spatial proximity of B and CD4+ T cells at immunogenic sites. Various organ‐specific densities of tertiary lymphoid structures are observed. Immunosuppressive sites, including brain and liver metastases, are deposited with collagen I, and T cells at these sites highly express TIM‐3. This study originally deciphers the single‐cell landscape of the organ‐specific TME at both cellular and spatial levels for LUAD, indicating the necessity for organ‐specific treatment approaches.

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Immune-related response assessment during PD-1 inhibitor therapy in advanced non-small-cell lung cancer patients

Cited by 104 publications

References 36 publications

Tumor Response Dynamics of Advanced Non–small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome

Tumor Response Dynamics of Advanced Non–small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome

A Comparison of Response Patterns for Progression-Free Survival and Overall Survival Following Treatment for Cancer With PD-1 Inhibitors

A Pathologically Friendly Strategy for Determining the Organ‐specific Spatial Tumor Microenvironment Topology in Lung Adenocarcinoma Through the Integration of snRandom‐seq and Imaging Mass Cytometry

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