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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Dermatomyositis &#40;DM&#41; is a well-known inflammatory myopathy usually associated with malignant diseases&#44; including lung cancer&#46; However&#44; there are few reports on epidermal growth factor receptor &#40;EGFR&#41; mutation-positive non-small cell lung cancer &#40;NSCLC&#41; complicated by DM&#59; EGFR mutations in these cases are uncommon&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;2</span></a> Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor &#40;TKI&#41; generally used as first-line treatment for common EGFR mutation &#40;i&#46;e&#46;&#44; exon 19 deletion&#47;L858R&#41;-positive NSCLC&#46; Osimertinib therapy for DM-associated NSCLC has not been reported previously&#46; Here&#44; we report a case of EGFR exon 19 mutation-positive DM-associated lung adenocarcinoma treated with osimertinib&#46; Informed consent was obtained from the patient&#44; and the study was conducted in accordance with the Helsinki Declaration&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 45-year-old Asian woman with a 26-pack-year smoking history presented with edema on her face and dorsal surface of her hands and feet&#44; erythema over both eyelids &#40;heliotrope rash&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#44; papules on the dorsal surface of the hands &#40;Gottron&#39;s papules&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#44; and muscle weakness in both legs&#46; She had a low-grade fever and both legs were tender to the touch&#46; She had left cervical lymphadenopathy&#46; Her serum creatine phosphokinase level was elevated &#40;161<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41;&#44; and magnetic resonance imaging of her legs showed myositis and fasciitis&#46; Although the serum myositis-specific autoantibody levels were normal&#44; she was diagnosed with DM&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Computed tomography and &#91;18F&#93;-fluorodeoxyglucose positron emission tomography showed a pulmonary nodule in the right lung&#59; bilateral neck&#44; supraclavicular&#44; mediastinal&#44; and hilar lymphadenopathy&#59; and multiple hepatic nodules &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#44; D&#41;&#46; Her serum carcinoembryonic antigen level was elevated &#40;122&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#46; A biopsy of a left cervical lymph node revealed an adenocarcinoma&#46; Immunohistochemical staining of the tumor specimen was positive for CK7 and TTF-1 and negative for p63 and the estrogen receptor&#46; These results suggested that the lung was the primary site of the adenocarcinoma&#46; Additional analysis of the tumor specimen revealed an EGFR mutation &#40;exon 19 deletion&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">After further investigation&#44; the patient was diagnosed with primary lung adenocarcinoma&#44; cT1bN3M1c&#44; stage IVB&#44; and DM&#46; Treatment with osimertinib and prednisolone 20<span class="elsevierStyleHsp" style=""></span>mg per day was initiated&#46; On follow-up three months later&#44; the tumor lesions had shrunk markedly&#44; and her serum carcinoembryonic antigen level was normal&#46; The symptoms of DM also improved&#46; She developed a mild rash as a side effect of osimertinib use but did not develop interstitial lung disease &#40;ILD&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In this case report&#44; we have presented two important clinical observations&#46; First&#44; common EGFR mutation-positive lung adenocarcinoma may occur in patients with DM&#46; To our knowledge&#44; this is the first English case report of common EGFR mutation-positive DM-associated NSCLC&#46; The most common histopathological type of DM-associated lung cancer is small-cell lung cancer &#40;44&#37;&#41;&#59; adenocarcinoma accounts for only 17&#37; of the cases&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> EGFR mutations are commonly associated with adenocarcinoma&#44; which may be the reason EGFR mutation-positive DM-associated NSCLC is extremely rare&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Second&#44; osimertinib may be safely used for EGFR mutation-positive NSCLC complicated with DM&#46; EGFR-TKIs have been reported to induce ILD at a higher rate than cytotoxic anticancer drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> Moreover&#44; in a large multicenter clinical trial&#44; the incidence of ILD was reported to be higher in patients who received osimertinib than in those who received gefitinib&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> especially in the Japanese subset&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> As severe acute interstitial pneumonia often develops in DM patients&#44; clinicians may hesitate to use osimertinib for DM-associated NSCLC&#46; Our patient did not have DM-related ILD and did not develop osimertinib-induced ILD&#46; Therefore&#44; osimertinib may be used cautiously for patients with DM-associated NSCLC without DM-related ILD&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">It is speculated that the mechanism underlying osimertinib-induced ILD is different from that underlying first or second generation EGFR-TKIs and may be associated with T cell activity&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> More data should be accumulated to evaluate the safety of osimertinib therapy for NSCLC complicated with autoimmune diseases&#44; including DM&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0040" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public&#44; commercial&#44; or not-for-profit sectors&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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Vol. 56. Issue 12.
Pages 822-823 (December 2020)
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Vol. 56. Issue 12.
Pages 822-823 (December 2020)
Scientific Letter
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Osimertinib for the Treatment of EGFR Mutation-Positive Lung Adenocarcinoma Complicated With Dermatomyositis
El osimertinib como tratamiento del adenocarcinoma de pulmón con mutación positiva del EGFR complicado con dermatomiositis
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Masahiro Yamasakia,
Corresponding author
myamasanjp@yahoo.co.jp

Corresponding author.
, Naoko Matsumotoa, Shota Nakanob, Kazuma Kawamotoa, Masaya Taniwakia, Yusuke Izumia, Masaya Otoharaa, Shinji Nabeshimac, Nobuyuki Ohashid, Noboru Hattoric
a Department of Respiratory Disease, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Naka-ku, Hiroshima, Japan
b Department of Rheumatology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Naka-ku, Hiroshima, Japan
c Department of Molecular and Internal Medicine, Institute of Biomedical & Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan
d Ohashi Clinic, Naka-ku, Hiroshima, Japan
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Dear Editor:

Dermatomyositis (DM) is a well-known inflammatory myopathy usually associated with malignant diseases, including lung cancer. However, there are few reports on epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) complicated by DM; EGFR mutations in these cases are uncommon.1,2 Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor (TKI) generally used as first-line treatment for common EGFR mutation (i.e., exon 19 deletion/L858R)-positive NSCLC. Osimertinib therapy for DM-associated NSCLC has not been reported previously. Here, we report a case of EGFR exon 19 mutation-positive DM-associated lung adenocarcinoma treated with osimertinib. Informed consent was obtained from the patient, and the study was conducted in accordance with the Helsinki Declaration.

A 45-year-old Asian woman with a 26-pack-year smoking history presented with edema on her face and dorsal surface of her hands and feet, erythema over both eyelids (heliotrope rash, Fig. 1A), papules on the dorsal surface of the hands (Gottron's papules, Fig. 1B), and muscle weakness in both legs. She had a low-grade fever and both legs were tender to the touch. She had left cervical lymphadenopathy. Her serum creatine phosphokinase level was elevated (161U/L), and magnetic resonance imaging of her legs showed myositis and fasciitis. Although the serum myositis-specific autoantibody levels were normal, she was diagnosed with DM.

Fig. 1.

(A, B) Dermatological findings after the first examination of the patient. (A) Visible erythema over both eyelids (heliotrope rash) with facial edema. (B) Papules (Gottron's papules) and edema on the dorsal surface of the hands are visible. (C) Chest computed tomography (CT) scan showing primary lesion in the right lung, lower lobe (arrow). (D) Chest CT scan showing mediastinal lymphadenopathy.

(0.2MB).

Computed tomography and [18F]-fluorodeoxyglucose positron emission tomography showed a pulmonary nodule in the right lung; bilateral neck, supraclavicular, mediastinal, and hilar lymphadenopathy; and multiple hepatic nodules (Fig. 1C, D). Her serum carcinoembryonic antigen level was elevated (122.2ng/mL). A biopsy of a left cervical lymph node revealed an adenocarcinoma. Immunohistochemical staining of the tumor specimen was positive for CK7 and TTF-1 and negative for p63 and the estrogen receptor. These results suggested that the lung was the primary site of the adenocarcinoma. Additional analysis of the tumor specimen revealed an EGFR mutation (exon 19 deletion).

After further investigation, the patient was diagnosed with primary lung adenocarcinoma, cT1bN3M1c, stage IVB, and DM. Treatment with osimertinib and prednisolone 20mg per day was initiated. On follow-up three months later, the tumor lesions had shrunk markedly, and her serum carcinoembryonic antigen level was normal. The symptoms of DM also improved. She developed a mild rash as a side effect of osimertinib use but did not develop interstitial lung disease (ILD).

In this case report, we have presented two important clinical observations. First, common EGFR mutation-positive lung adenocarcinoma may occur in patients with DM. To our knowledge, this is the first English case report of common EGFR mutation-positive DM-associated NSCLC. The most common histopathological type of DM-associated lung cancer is small-cell lung cancer (44%); adenocarcinoma accounts for only 17% of the cases.1 EGFR mutations are commonly associated with adenocarcinoma, which may be the reason EGFR mutation-positive DM-associated NSCLC is extremely rare.

Second, osimertinib may be safely used for EGFR mutation-positive NSCLC complicated with DM. EGFR-TKIs have been reported to induce ILD at a higher rate than cytotoxic anticancer drugs.3 Moreover, in a large multicenter clinical trial, the incidence of ILD was reported to be higher in patients who received osimertinib than in those who received gefitinib,4 especially in the Japanese subset.5 As severe acute interstitial pneumonia often develops in DM patients, clinicians may hesitate to use osimertinib for DM-associated NSCLC. Our patient did not have DM-related ILD and did not develop osimertinib-induced ILD. Therefore, osimertinib may be used cautiously for patients with DM-associated NSCLC without DM-related ILD.

It is speculated that the mechanism underlying osimertinib-induced ILD is different from that underlying first or second generation EGFR-TKIs and may be associated with T cell activity.6 More data should be accumulated to evaluate the safety of osimertinib therapy for NSCLC complicated with autoimmune diseases, including DM.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

The authors declare no conflict of interest.

Acknowledgments

We would like to thank Editage (www.editage.jp) for English language editing.

References
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A.J. Beel, D.S. Demos, A. Chung, C. Liao, N.S. Lui.
Ground-glass opacity heralding invasive lung adenocarcinoma with prodromal dermatomyositis: a case report.
J Cardiothorac Surg, 13 (2018), pp. 20
[2]
C.S. Zhong, E. Russell-Goldman, G.F. Murphy, V.E. Nambudiri.
Paraneoplastic hypomyopathic dermatomyositis associated with EGFR exon-20 insertion NSCLC.
J Thorac Oncol, 14 (2019), pp. e128-e130
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Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case–control study.
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J.C. Soria, Y. Ohe, J. Vansteenkiste, T. Reungwetwattana, B. Chewaskulyong, K.H. Lee, et al.
Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer.
N Engl J Med, 378 (2018), pp. 113-125
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Osimertinib versus standard-of-care EGFR-TKI as first-line treatment for EGFRm advanced NSCLC: FLAURA Japanese Subset.
Jpn J Clin Oncol, 49 (2019), pp. 29-36
[6]
T. Uchida, K. Kaira, O. Yamaguchi, A. Mouri, A. Shiono, Y. Yu Miura, et al.
Different incidence of interstitial lung disease according to different kinds of EGFR-tyrosine kinase inhibitors administered immediately before and/or after anti-PD-1 antibodies in lung cancer.
Thorac Cancer, 10 (2019), pp. 975-979
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