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  • 1
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    An increased relative eosinophil count as a predictive dynamic biomarker in non‐small cell lung cancer patients treated with immune checkpoint inhibitors
    Wiley ; 2023
    In:  Thoracic Cancer
    Details
    In: Thoracic Cancer, Wiley
    Abstract: An increased relative eosinophil count (REC) has potential as a predictive biomarker for a beneficial clinical response and outcome to cancer immunotherapies. Therefore, the present study investigated the impact of an increased posttreatment REC on the prognosis of non‐small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). Methods We retrospectively reviewed all 151 patients diagnosed with NSCLC and treated with ICI monotherapy and blood test data between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Results A total of 151 patients with a mean age of 69 years were included. REC after 4 weeks of initial ICI monotherapy was higher than pretreatment REC in 87 patients but not in 64. REC after 4 weeks of the ICI treatment with and without an increased REC were 4.4 and 1.8%, respectively ( p 〈 0.001). Disease control rates (DCR) were significantly higher in patients with than in those without an increased REC (84% vs. 47%, p 〈 0.001). The median overall survival (OS) of lung cancer patients with or without an increased REC were 674 and 234 days, respectively. A Kaplan–Meier univariate analysis revealed a significant difference in OS between the two groups ( p 〈 0.001). A Cox proportional regression analysis identified an increased REC as an independent predictor of OS ( p = 0.003). Conclusion ICI‐treated NSCLC patients with an increased REC after 4 weeks of treatment had a better DCR and prognosis than the other patients examined.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Article
    DOI: 10.1111/1759-7714.15191
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 2
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    A single dose of pembrolizumab treatment causing a profound and durable response in lung cancer
    Wiley ; 2022
    In:  Thoracic Cancer Vol. 13, No. 4 ( 2022-02), p. 648-652
    Details
    In: Thoracic Cancer, Wiley, Vol. 13, No. 4 ( 2022-02), p. 648-652
    Abstract: Profound and durable responses to a single dose of pembrolizumab in lung cancer are rare. We encountered a non‐small cell lung cancer patient showing a deep and durable response with a single dose of pembrolizumab. A 79‐year‐old man reported bloody sputum for several weeks and visited a general physician. A chest x‐ray revealed a tumor shadow in the right middle lung field at that time, and the patient was referred to our hospital. He was diagnosed with adenocarcinoma of the lung by transbronchial biopsy. The expression of programmed death ligand 1 in tumor cells was 100% by immunostaining. Based on the above, immunotherapy with pembrolizumab was performed as first‐line therapy. Cancer cells had significantly shrunk at the end of the first cycle. The patient had grade‐3 immune‐related hepatitis at the end of the first cycle. Pembrolizumab treatment was stopped and prednisolone (80 mg/body) was initiated. Subsequently, liver function normalized, and prednisolone was tapered and discontinued. Since then, no tumor recurrence has been detected for 1.5 years without treatment. There have been few reports of profound and durable responses to a single dose of pembrolizumab in lung cancer. The results indicate that a single dose of pembrolizumab alone may be sufficient to cause durable response and serious immune‐related adverse events in some cases.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v13.4
    DOI: 10.1111/1759-7714.14314
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2559245-2
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  • 3
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    Pretreatment eosinophil counts as a predictive biomarker in non‐small cell lung cancer patients treated with immune checkpoint inhibitors
    Wiley ; 2023
    In:  Thoracic Cancer
    Details
    In: Thoracic Cancer, Wiley
    Abstract: The peripheral blood eosinophil count prior to treatment has potential as a predictive biomarker for a beneficial clinical response to cancer immunotherapies. Therefore, the present study investigated the impact of the eosinophil count on overall survival (OS) in non‐small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI). Methods We retrospectively reviewed all patients diagnosed with NSCLC and treated with ICI monotherapy between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Results A total of 166 patients were included. Fifty‐five patients had an eosinophil count of less than 100 cells/μL (Eo  〈  100). Nighty‐eight patients had an eosinophil count of 100 cells/μL or more, but less than 500 cells/μL (100 ≤ Eo  〈  500). Thirteen patients had an eosinophil count of 500 cells/μL or more (Eo ≥500). The median OS of all lung cancer patients was 476 days. The median OS of lung cancer patients with Eo 〈 100, 100 ≤ Eo 〈 500, and Eo ≥500 was 339, 667, and 143 days, respectively. A Kaplan–Meier univariate analysis showed a significant difference in OS between these three groups ( p   〈  0.001). A Cox proportional regression analysis identified 100 ≤ Eo 〈 500 ( p  = 0.04), ECOG PS score ≥ 2 ( p  = 0.02), tumor size ≥5 cm ( p  = 0.02), and PD‐L1 ≥ 1% ( p  = 0.01) as independent predictors of OS. Conclusion OS was significantly longer in ICI‐treated NSCLC patients with a pretreatment eosinophil count of 100 ≤ Eo 〈 500 than in the other patients and, thus, has potential as a new predictive biomarker.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Article
    DOI: 10.1111/1759-7714.15100
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 4
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    Abstract 2837: Adiponectin knockout enhances intestinal carcinogenesis in Min and wild-type mice
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2837-2837
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2837-2837
    Abstract: Obesity-associated cancers, including colon cancer, are increasing in Western countries. It has been demonstrated that increased amounts of visceral fat and decreased levels of plasma adiponectin (APN) are associated with development of human colorectal cancer. Thus, we here investigated the function of APN in intestinal carcinogenesis. Male APN+/+, APN+/- or APN-/- C57BL/6J mice were injected with azoxymethane (AOM) once a week for 6 weeks, which led to the development of intestinal tumors. C57BL/6J mice with each genotype were sacrificed at the age of 55 weeks, and the number and size of colorectal tumors were examined by pathological study. Furthermore, these strains of mice were also crossed with Min mice (C57BL/6J background) to assess the effects of APN on intestinal polyp formation. At the age of 9 and 12 weeks, Min mice each with the APN genotype were sacrificed, and the number and size of intestinal polyps were examined by pathological study. Levels of adipocytokine and phosphorylation of AMPK were also evaluated to clarify the effect of APN on intestinal tumor development. The incidence of AOM-induced tumors was 40% of APN+/+, 50% of APN+/- and 71% (p & lt;0.05) of male APN-/- C57BL/6J mice, respectively. Multiplicities of AOM-induced tumors in each genotype were 0.5±0.7, 0.6±0.7 and 1.1±1.0 (p & lt;0.05), respectively. The total number of intestinal polyps developed in 9-week-old male APN+/- Min and APN-/-Min mice increased 2.4- and 3.2-fold compared with those in APN+/+Min mice, respectively, and was further enhanced at 12 weeks of age, being 3.2- and 3.4-fold, respectively. Studies with female mice gave similar results. Phosphorylation levels of AMPK in intestinal epithelial cells were decreased in APN-/- mice compared with APN+/+ mice. Among serum adipocytokines, levels of serum Pai-1 increased in APN-/- C57BL/6J mice and APN-/-Min mice with AOM injection. Activation of AMPK by metformin treatment suppressed Pai-1 expression in Min mice. AOM-induced colorectal aberrant crypt foci in APN-/- C57BL/6J mice were decreased by a Pai-1 blocker. In conclusion, APN-deficient mice developed more intestinal tumors. Decreased phosphorylation of AMPK and increased levels of Pai-1 were observed in APN-deficient mice compared with wild-type mice. APN and its receptors might be good targets for developing colorectal cancer chemopreventive agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2837. doi:10.1158/1538-7445.AM2011-2837
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-2837
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
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    Miliary brain metastases from lung adenocarcinoma with EGFR ( L858R ) and CTNNB1 mutations
    Wiley ; 2023
    In:  Thoracic Cancer Vol. 14, No. 34 ( 2023-12), p. 3419-3420
    Details
    In: Thoracic Cancer, Wiley, Vol. 14, No. 34 ( 2023-12), p. 3419-3420
    Abstract: A 76‐year‐old man was referred to our hospital with a cough. Chest computed tomography (CT) revealed a 45‐mm mass in the lingular segment of the left upper lobe. Transbronchial tumor biopsies showed adenocarcinoma. Contrast‐enhanced CT and bone scintigraphy revealed lung, pleura, and bone metastases. The patient was diagnosed with left upper lobe adenocarcinoma cT2bN3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx Target Test Multi‐CDx system revealed positivity for epidermal growth factor receptor (EGFR) (L858R) and CTNNB1 mutations. Based on these findings, the patient was treated with osimertinib (80 mg/day) as first‐line therapy. Six months later, the tumor increased in size, indicating progressive disease. Osimertinib was stopped and second‐line therapy with carboplatin (area under the curve 5) and pemetrexed (500 mg/m2) was initiated. After three cycles of chemotherapy, the patient developed dementia and disorientation. Contrast‐enhanced magnetic resonance imaging of the head showed miliary brain metastases. Miliary dissemination is a rare form of brain metastasis. Miliary patterns of lung metastases have been strongly associated with the EGFR exon 19 deletion. The radiological features of miliary brain metastases of non‐small cell lung cancer with the exon 19 deletion have been reported. To the best of our knowledge, this is the first case report of lung cancer with miliary brain metastases and co‐mutations of EGFR (L858R) and CTNNB1. In conclusion, co‐mutations of EGFR (L858R) and CTNNB1 and the discontinuation of EGFR‐tyrosine kinase inhibitor may contribute to the development of miliary brain metastases. Further case studies are warranted.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v14.34
    DOI: 10.1111/1759-7714.15144
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2559245-2
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  • 6
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    Early mortality factors in immune checkpoint inhibitor monotherapy for advanced or metastatic non-small cell lung cancer
    Springer Science and Business Media LLC ; 2023
    In:  Journal of Cancer Research and Clinical Oncology Vol. 149, No. 7 ( 2023-07), p. 3139-3147
    Details
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 149, No. 7 ( 2023-07), p. 3139-3147
    Abstract: Immune checkpoint inhibitors (ICI) are a promising treatment, but may cause hyperprogressive disease and early death. The present study investigated early mortality factors in ICI monotherapy for lung cancer. Patients and methods We retrospectively reviewed all patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) and treated with ICI monotherapy (nivolumab, pembrolizumab, and atezolizumab) between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Early death was defined as patients who died within 60 days of ICI treatment. Results A total of 166 patients were included. The majority of patients (87%) had an Eastern cooperative oncology group (ECOG) Performance status (PS) of 0/1. There were 21 early deaths. Significant differences were observed in ECOG PS, the histological type, liver metastasis, tumor size, the white blood cell count, neutrophils (%), lymphocytes (%), the neutrophil-to-lymphocyte ratio in serum (sNLR), C-reactive protein (CRP), and albumin between the groups with or without early death. Univariate logistic regression analyses identified ECOG PS score ≥ 2, liver metastasis, tumor size ≥ 5 cm, neutrophils ≥ 69%, lymphocytes  〈  22%, sNLR ≥ 4, CRP ≥ 1 mg/dl, and albumin  〈  3.58 g/dl as significant risk factors for early death. A multivariate logistic regression analysis revealed that liver metastasis (Odds ratio [OR], 10.3; p  = 0.008), ECOG PS score ≥ 2 (OR, 8.0; p  = 0.007), and a smoking history (OR, 0.1; p  = 0.03) were significant risk factors for early death. Conclusion Liver metastases, ECOG PS score ≥ 2, and a non-smoking history are early mortality factors in ICI monotherapy for advanced or metastatic NSCLC.
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    URL: Article
    DOI: 10.1007/s00432-022-04215-7
    RVK:
    XA 52301
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 7
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    Late‐onset acute type 1 diabetes mellitus 7 months after discontinuation of pembrolizumab against lung cancer
    Wiley ; 2023
    In:  Thoracic Cancer Vol. 14, No. 1 ( 2023-01), p. 81-84
    Details
    In: Thoracic Cancer, Wiley, Vol. 14, No. 1 ( 2023-01), p. 81-84
    Abstract: Immune‐related adverse events (irAEs) occur in rare cases, even after the completion of immune checkpoint inhibitor (ICI) therapy. We encountered a lung cancer patient diagnosed with acute‐onset type 1 diabetes mellitus (DM) 7 months after the cessation of ICI. A 68‐year‐old woman was referred to our hospital for chest abnormalities. She was diagnosed with lung adenocarcinoma cT4N2M1c, stage IVB. Immunostaining showed that the expression of programmed death ligand 1 in tumor cells was negative. A genetic analysis using the Oncomine Dx Target Test Multi‐CDx System revealed that the primary tumor was positive for ERBB2. Combined immunotherapy with carboplatin, pemetrexed, and pembrolizumab was performed as first‐line therapy, followed by maintenance therapy with pemetrexed plus pembrolizumab, which was successful. After the seventh course, maintenance therapy was stopped because only the primary tumor showed local enlargement. Local chest radiotherapy (66 Gy/33 Fr) was performed, and the patient was followed up. HbA1c was 4.9% 3 months after the completion of pembrolizumab, and dry mouth and polyuria occurred after 5 months. Seven months later, the patient developed diabetic ketoacidosis with a blood glucose of 348 mg/dL and an HbA1c of 11.3%. Antiglutamic acid decarboxylase antibodies were negative and urinary C‐peptide was 9.3 μg/day. The patient was diagnosed with acute‐onset type 1 diabetes and received insulin therapy. There has been no case report of type 1 diabetes diagnosed 7 months after the last administration of an ICI. These results indicate that irAE needs to be considered even after the cessation of ICI.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v14.1
    DOI: 10.1111/1759-7714.14736
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2559245-2
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  • 8
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    Complete and durable response of pulmonary large‐cell neuroendocrine carcinoma to pembrolizumab
    Wiley ; 2022
    In:  Cancer Reports Vol. 5, No. 8 ( 2022-08)
    Details
    In: Cancer Reports, Wiley, Vol. 5, No. 8 ( 2022-08)
    Abstract: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive tumor with a poor prognosis and standard therapy has not yet been established. Case A 65‐year‐old male with a cough for 2 months presented to our hospital. He was clinically diagnosed with non small cell lung cancer cT3N1M0 stage IIIA and underwent right pneumonectomy. The final diagnosis was pulmonary LCNEC pT3N1M0 stage IIIA. Multiple subcutaneous masses were detected 4 months after surgery, and biopsy revealed postoperative recurrence and metastasis. Chemotherapy with carboplatin plus etoposide was initiated. Subcutaneous masses increased and multiple new brain metastases developed after two cycles. Additional tests revealed that epidermal growth factor receptor and anaplastic lymphoma kinase were negative, and the programmed death ligand 1 (PD‐L1) expression rate in tumor cells was 40% (22C3 clones). The primary cells infiltrating the tumor were CD3‐positive T cells and CD138‐positive plasma cells. Second‐line treatment with pembrolizumab was started. The shrinkage of subcutaneous masses was observed after one cycle, and the tumor had completely disappeared after six cycles. Treatment was continued for approximately 2 years. This response has been maintained for 4 years and is still ongoing. Conclusion Pembrolizumab may be used as a treatment option for pulmonary LCNEC.
    Type of Medium: Online Resource
    ISSN: 2573-8348 , 2573-8348
    URL: Issue
    URL: Article
    DOI: 10.1002/cnr2.v5.8
    DOI: 10.1002/cnr2.1589
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2920367-3
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  • 9
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    Non‐small cell lung cancer with EGFR ( L858R and E709X ) and CNNB1 mutations responded to afatinib
    Wiley ; 2023
    In:  Thoracic Cancer Vol. 14, No. 4 ( 2023-02), p. 423-426
    Details
    In: Thoracic Cancer, Wiley, Vol. 14, No. 4 ( 2023-02), p. 423-426
    Abstract: Lung cancer with complex epidermal growth factor receptor (EGFR) and CTNNB1 comutations is rare, and the efficacy of tyrosine kinase inhibitors (TKIs) is generally poor. Here, we encountered a lung cancer patient with complex EGFR (L858R and E709X) and CTNNB1 comutations who successfully responded to afatinib. A 78‐year‐old woman visited our hospital with a cough and bloody sputum that had worsened over the past year. She had multiple mass shadows in both lungs and nodular shadows in the bronchi. The patient was diagnosed with lung adenocarcinoma cT4N3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx target test multi‐CDx system revealed positivity for EGFR (L858R and E709X) and CTNNB1 mutations. The expression of programmed death ligand 1 (22C3 clones) in tumor cells was negative by immunostaining. The patient was treated with afatinib as first‐line therapy and achieved clinical improvement and a partial response and is continuing treatment 1 year later. Case reports of lung cancer patients with EGFR/CTNNB1 comutations are rare, and TKIs are not considered to be effective. We herein present the first case report of lung cancer with the co‐occurrence of uncommon and complex EGFR (L858R and E709X) and CTNNB1 mutations that was successfully treated with afatinib.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v14.4
    DOI: 10.1111/1759-7714.14775
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 10
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    Dramatic response to immunochemotherapy followed by salvage surgery in an elderly lung cancer patient
    Wiley ; 2022
    In:  Thoracic Cancer Vol. 13, No. 3 ( 2022-02), p. 510-513
    Details
    In: Thoracic Cancer, Wiley, Vol. 13, No. 3 ( 2022-02), p. 510-513
    Abstract: Immune checkpoint inhibitors (ICIs) have caused a paradigm shift in the treatment of lung cancer. Here, we encountered a case of inoperable locally advanced squamous cell carcinoma of the lung that became operable with pembrolizumab‐based immunochemotherapy and achieved a pathological complete response. An 82‐year‐old man suspected of having lung cancer was referred to our hospital. The patient was clinically diagnosed with left upper lobe squamous cell carcinoma cT2aN3M0 c‐stage IIIC. Immunostaining revealed the expression of programmed death‐ligand 1 in 60% of tumor cells. The cancer cells disappeared after two cycles of chemotherapy with carboplatin and nanoparticle albumin‐bound paclitaxel plus pembrolizumab. As the abnormal accumulation of 18 F‐fluorodeoxyglucose (FDG) on FDG‐positron emission tomography/computed tomography before chemotherapy almost disappeared after pembrolizumab‐based immunochemotherapy, left upper lobectomy and lymph node dissection were performed. No cancer cells were pathologically detected from the resected tissue. Therefore, ICIs combined with chemotherapy may enable inoperable advanced lung cancer patients to undergo surgery and achieve a complete response.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    URL: Article
    DOI: 10.1111/tca.v13.3
    DOI: 10.1111/1759-7714.14293
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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