Early response of bone metastases can predict tumor response in patients with non‑small‑cell lung cancer with bone metastases in the treatment with nivolumab

Nakata, Eiji; Sugihara, Shinsuke; Sugawara, Yumi; Kozuki, Toshiyuki; Harada, Daijiro; Nogami, Naoyuki; Nakahara, Ryuichi; Furumatsu, Takayuki; Tetsunaga, Tomonori; Kunisada, Toshiyuki; Ozaki, Toshifumi

doi:10.3892/ol.2020.11856

Cited by 15 publications

(19 citation statements)

References 31 publications

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“…Consistently, a retrospective experience including 16 NSCLC patients treated with nivolumab evidenced that an early application of MDA criteria may predict response and prognosis according to RECIST 1.1 (Nakata et al 2020). We demonstrated that patients experiencing a bone-speci c objective response (PR/CR) had longer median OS and PFS.…”

Section: Discussionmentioning

confidence: 77%

Bone-specific Response According to MDA Criteria Predicts Immunotherapy Efficacy Among Advanced Non-small Cell Lung Cancer (NSCLC) Patients.

Giglio

Deiana

Federico

2022

Preprint

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Purpose: Baseline bone metastasis has been associated with poor response to immunotherapy for advanced non-small cell lung cancer (NSCLC). RECIST criteria may be limited for bone-specific response evaluation. Whether their assessment through MDA criteria predict immunotherapy efficacy is unknown.Materials and methods: We conducted a single-center retrospective study to assess the use of MDA criteria in evaluating bone metastasis in NSCLC treated with immunotherapy. Radiological imaging were reviewed to classify bone lesions as osteolytic, osteoblastic, or mixed. Bone response to treatments data were classified according to MDA criteria.Results: 222 patients received single-agent immunotherapy. The presence of bone metastasis increased the risk of death both in the univariate (HR: 1.46, 95% CI, 1.05-2.03, p=0.024) and in the multivariate model (HR: 1.61,95 % CI, 1.10-2.36, p=0.015). According to MDA criteria, 57.3% of patients obtained a progressive disease as best response, 29.5% a stable disease, 11.4% a partial response and 1.6% a complete response. Bone-specific objective response was associated with a significantly increased median overall survival (11.3 vs. 3.1 months, p=0.027) and longer median progression-free survival (6 vs. 2.1 months, p=0.056). The median time to bone failure (TBF) was 2.4 months (IQR, 1.67-3.0). In 25.7% of cases, TBF was shorter than progression-free survival according to RECIST 1.1 criteria. TBF was positively correlated with overall survival (HR=0.73, p= 0.00019).Conclusions: MDA criteria represent a reliable tool in assessing bone-specific response, offering a more accurate evaluation to sooner predict survival outcomes or treatment failure compared to RECIST criteria for advanced NSCLC patients receiving immunotherapy.

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Section: Discussionmentioning

confidence: 77%

Bone-specific Response According to MDA Criteria Predicts Immunotherapy Efficacy Among Advanced Non-small Cell Lung Cancer (NSCLC) Patients.

Giglio

Deiana

Federico

2022

Preprint

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“…Inconsistent outcomes of ICIs on bone lesions were also revealed, although only a few patients were involved in the current few studies and case reports [ 113 , 114 ]. For NSCLC patients with bone metastases who were treated with nivolumab, 9 out of 12 patients developed metastatic progression in Schmid et al's study [ 115 ], while eight osteolytic lesions in 6 patients, out of 15 patients, had osteosclerotic changes in Nakata et al's study [ 116 ]. Contrary results also appeared in two case reports of nivolumab combined with radiotherapy in pleomorphic lung cancer patients.…”

Section: Clinical Effects Of Immune Checkpoint Inhibitors To Bone Metastasismentioning

confidence: 99%

“…In another case report, the bone metastasis in the lower extremity and the primary lung tumor were significantly ameliorated in 2 patients treated with pembrolizumab [ 119 ]. Nakata et al considered that assessing the early response of bone metastases with MD Anderson response classification criteria (MDA criteria) can be helpful to predict the prognosis of NSCLC patients with bone metastases [ 116 ]. The osteosclerotic change suggests the suppression of tumor and a better prognosis, while an increased number of bone metastases is associated with a higher risk of bone metastasis progression after nivolumab treatment [ 116 ].…”

Section: Clinical Effects Of Immune Checkpoint Inhibitors To Bone Metastasismentioning

confidence: 99%

Immune Checkpoint Inhibitor Therapy for Bone Metastases: Specific Microenvironment and Current Situation

Liu

Wang

et al. 2021

Journal of Immunology Research

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The treatment of bone metastases is a thorny issue. Immunotherapy may be one of the few hopes for patients with unresectable bone metastases. Immune checkpoint inhibitors are the most commonly used immunotherapy drugs currently. In this review, the characteristics and interaction of bone metastases and their immune microenvironment were systematically discussed, and the relevant research progress of the immunological mechanism of tumor bone metastasis was reviewed. On this basis, we expounded the clinical application of immune checkpoint inhibitors for bone metastasis of common tumors, including non-small-cell lung cancer, renal cell carcinoma, prostate cancer, melanoma, and breast cancer. Then, the deficiencies and limitations in current researches were summarized. In-depth basic research on bone metastases and optimization of clinical treatment is needed.

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“…It was tested in metastatic prostate cancer in combination with radiotherapy and suggested clinical antitumor activity [79]. Nivolumab therapy was recently tested in lung cancer metastases into the bone and showed that 40% of the treated patients had osteosclerotic change on CT scans, indicating successful treatment of bone lesions [80]. The small amount of monoclonal antibodies used for bone metastases often have skeletal related events as indication of efficacy but lack bone cancer pain as direct outcome measure.…”

Section: Monoclonal Antibody Therapymentioning

confidence: 99%

Bone Cancer Pain, Mechanism and Treatment

Sliepen¹

2021

Recent Advances in Bone Tumours and Osteoarthritis

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The world health organization (WHO) has predicted a global amount of 19 million cancer cases by 2025. Breast, prostate and lung cancer are common cancer types and show metastasis in 60 to 84% of the cases, with 75 to 90% experiencing life-altering cancer-induced bone pain (CIBP), characterized by continuous, dull progressive pain with movement-induced incident peaks and random breakthrough spikes. Therefore, it is the most difficult pain condition to treat. CIBP is a unique type of pain with neuropathic and nociceptive components. Briefly, an invading tumor cell disturbs the healthy balance of the bone resulting in an acidic microenvironment, activating sensory fibers in the bone. The invaded tumor cell and adjacent stromal cells secrete mediators initiating an immune response with transcriptional signaling, resulting in increased cytokines and growth factors. Sensory nerve fibers are damaged and start to sprout, causing ectopic firing, and as tumors grow in size they activate mechanoreceptors. Aside from bisphosphonates and antibody therapy, CIBP is treated by a range of NSAIDs to strong opioids, but remains undertreated in one-third of cases. This chapter discusses the accompanying CIBP of bone tumors, the mechanism of action and current treatments.

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Early response of bone metastases can predict tumor response in patients with non‑small‑cell lung cancer with bone metastases in the treatment with nivolumab

Cited by 15 publications

References 31 publications

Bone-specific Response According to MDA Criteria Predicts Immunotherapy Efficacy Among Advanced Non-small Cell Lung Cancer (NSCLC) Patients.

Bone-specific Response According to MDA Criteria Predicts Immunotherapy Efficacy Among Advanced Non-small Cell Lung Cancer (NSCLC) Patients.

Immune Checkpoint Inhibitor Therapy for Bone Metastases: Specific Microenvironment and Current Situation

Bone Cancer Pain, Mechanism and Treatment

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