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A novel point-of-care system for high-speed real-time polymerase chain reaction testing for epidermal growth factor receptor mutations in bronchial lavage fluids after transbronchial biopsy in patients with non-small cell lung cancer.

Sakamoto T, Kodani M, Takata M, Chikumi H, Nakamoto M, Nishii-Ito S, Ueda Y, Izumi H, Makino H, Touge H, Takeda K, Yamasaki A, Yanai M, Tanaka N, Igishi T, Shimizu E - Int. J. Oncol. (2015)

Bottom Line: We investigated whether our system for detecting EGFR mutations was valid by comparing test results with those obtained using a commercialized EGFR mutation test.We also demonstrated a dramatic effect of early erlotinib administration, based on ultrarapid PCR results, for a 52-year-old woman suffering from respiratory failure due to severe intrapulmonary metastases with poor performance status.In conclusion, ultrarapid PCR combined with EBUS-GS-TBB enabled rapid and reliable point-of-care testing for EGFR mutations.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Japan.

ABSTRACT
Epidermal growth factor receptor (EGFR) gene mutation testing is essential for choosing appropriate treatment options in patients with advanced non-small cell lung cancer (NSCLC). However, a time delay occurs between histological diagnosis and molecular diagnosis in clinical situations. To minimize this delay, we developed a novel point-of-care test for EGFR mutations, based on a high-speed real-time polymerase chain reaction (PCR) system designated here as ultrarapid PCR combined with highly accurate bronchoscopic sampling. We investigated whether our system for detecting EGFR mutations was valid by comparing test results with those obtained using a commercialized EGFR mutation test. We obtained small amounts of bronchial lavage fluids after transbronchial biopsies (TBBs) were performed on enrolled patients (n=168) who underwent endobronchial ultrasonography using a guide sheath (EBUS-GS). EGFR mutation analysis was performed by ultrarapid PCR immediately after EBUS-GS-TBBs were obtained (on the same day). After pathological diagnoses of NSCLC, EGFR mutation status in formalin-fixed, paraffin- embedded samples was confirmed by the PCR-invader method, and the concordance rates between the PCR methods were compared. The total diagnostic yield of EBUS-GS-TBB was 91.0%. The positive concordance rates for detecting 19del and L858R with the ultrarapid PCR and PCR-invader methods were both 100%. Negative concordance rates were 97.2 and 98.1%, respectively. We also demonstrated a dramatic effect of early erlotinib administration, based on ultrarapid PCR results, for a 52-year-old woman suffering from respiratory failure due to severe intrapulmonary metastases with poor performance status. In conclusion, ultrarapid PCR combined with EBUS-GS-TBB enabled rapid and reliable point-of-care testing for EGFR mutations.

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Dramatic effect of EGFR-TKI for a poor PS EGFR mutant. A chest CT scan obtained before treatment (A) and at 2 weeks after the administration of erlotinib (B) are shown. The diffuse granular shadow of the bilateral lung field had mostly disappeared after the initiation of therapy. Consequently, the patient’s PS score improved from 3 to 1.
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f4-ijo-46-04-1473: Dramatic effect of EGFR-TKI for a poor PS EGFR mutant. A chest CT scan obtained before treatment (A) and at 2 weeks after the administration of erlotinib (B) are shown. The diffuse granular shadow of the bilateral lung field had mostly disappeared after the initiation of therapy. Consequently, the patient’s PS score improved from 3 to 1.

Mentions: A 52-year-old non-smoking female, without previous illness, was admitted to our hospital because of a dry cough and dyspnea at rest. Her performance status (PS) was 3 on admission. Her chest CT scan showed numerous bilateral diffuse granular lung shadows and a 20 mm-diameter nodular shadow on the lower right lobe (Fig. 4A). Whole body bone scintigraphy was performed later, revealing an abnormal accumulation in the fifth lumbar vertebra. Suspecting that she had advanced lung cancer, we immediately performed an EBUS-GS-TBB against the primary lesion of the lower right lobe. By 60 min after performing the EBUS-GS-TBB procedure, we obtained a positive result for the E746-A750del mutation by ultrarapid PCR. Because she had respiratory failure and a poor PS on admission, she was not eligible for cytotoxic chemotherapy. Therefore, it was deemed appropriate to initiate EGFR-TKI therapy as soon as possible. The following day, we started EGFR-TKI therapy (erlotinib 150 mg orally every 24 h), after obtaining a definitive pathological diagnosis of adenocarcinoma by an immunohistochemical method. Two weeks later, the diffuse and numerous granular shadows of bilateral lung field had mostly disappeared (Fig. 4B). Moreover, her respiratory failure and poor PS score were dramatically improved before PCR-invader results were provided.


A novel point-of-care system for high-speed real-time polymerase chain reaction testing for epidermal growth factor receptor mutations in bronchial lavage fluids after transbronchial biopsy in patients with non-small cell lung cancer.

Sakamoto T, Kodani M, Takata M, Chikumi H, Nakamoto M, Nishii-Ito S, Ueda Y, Izumi H, Makino H, Touge H, Takeda K, Yamasaki A, Yanai M, Tanaka N, Igishi T, Shimizu E - Int. J. Oncol. (2015)

Dramatic effect of EGFR-TKI for a poor PS EGFR mutant. A chest CT scan obtained before treatment (A) and at 2 weeks after the administration of erlotinib (B) are shown. The diffuse granular shadow of the bilateral lung field had mostly disappeared after the initiation of therapy. Consequently, the patient’s PS score improved from 3 to 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356493&req=5

f4-ijo-46-04-1473: Dramatic effect of EGFR-TKI for a poor PS EGFR mutant. A chest CT scan obtained before treatment (A) and at 2 weeks after the administration of erlotinib (B) are shown. The diffuse granular shadow of the bilateral lung field had mostly disappeared after the initiation of therapy. Consequently, the patient’s PS score improved from 3 to 1.
Mentions: A 52-year-old non-smoking female, without previous illness, was admitted to our hospital because of a dry cough and dyspnea at rest. Her performance status (PS) was 3 on admission. Her chest CT scan showed numerous bilateral diffuse granular lung shadows and a 20 mm-diameter nodular shadow on the lower right lobe (Fig. 4A). Whole body bone scintigraphy was performed later, revealing an abnormal accumulation in the fifth lumbar vertebra. Suspecting that she had advanced lung cancer, we immediately performed an EBUS-GS-TBB against the primary lesion of the lower right lobe. By 60 min after performing the EBUS-GS-TBB procedure, we obtained a positive result for the E746-A750del mutation by ultrarapid PCR. Because she had respiratory failure and a poor PS on admission, she was not eligible for cytotoxic chemotherapy. Therefore, it was deemed appropriate to initiate EGFR-TKI therapy as soon as possible. The following day, we started EGFR-TKI therapy (erlotinib 150 mg orally every 24 h), after obtaining a definitive pathological diagnosis of adenocarcinoma by an immunohistochemical method. Two weeks later, the diffuse and numerous granular shadows of bilateral lung field had mostly disappeared (Fig. 4B). Moreover, her respiratory failure and poor PS score were dramatically improved before PCR-invader results were provided.

Bottom Line: We investigated whether our system for detecting EGFR mutations was valid by comparing test results with those obtained using a commercialized EGFR mutation test.We also demonstrated a dramatic effect of early erlotinib administration, based on ultrarapid PCR results, for a 52-year-old woman suffering from respiratory failure due to severe intrapulmonary metastases with poor performance status.In conclusion, ultrarapid PCR combined with EBUS-GS-TBB enabled rapid and reliable point-of-care testing for EGFR mutations.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Japan.

ABSTRACT
Epidermal growth factor receptor (EGFR) gene mutation testing is essential for choosing appropriate treatment options in patients with advanced non-small cell lung cancer (NSCLC). However, a time delay occurs between histological diagnosis and molecular diagnosis in clinical situations. To minimize this delay, we developed a novel point-of-care test for EGFR mutations, based on a high-speed real-time polymerase chain reaction (PCR) system designated here as ultrarapid PCR combined with highly accurate bronchoscopic sampling. We investigated whether our system for detecting EGFR mutations was valid by comparing test results with those obtained using a commercialized EGFR mutation test. We obtained small amounts of bronchial lavage fluids after transbronchial biopsies (TBBs) were performed on enrolled patients (n=168) who underwent endobronchial ultrasonography using a guide sheath (EBUS-GS). EGFR mutation analysis was performed by ultrarapid PCR immediately after EBUS-GS-TBBs were obtained (on the same day). After pathological diagnoses of NSCLC, EGFR mutation status in formalin-fixed, paraffin- embedded samples was confirmed by the PCR-invader method, and the concordance rates between the PCR methods were compared. The total diagnostic yield of EBUS-GS-TBB was 91.0%. The positive concordance rates for detecting 19del and L858R with the ultrarapid PCR and PCR-invader methods were both 100%. Negative concordance rates were 97.2 and 98.1%, respectively. We also demonstrated a dramatic effect of early erlotinib administration, based on ultrarapid PCR results, for a 52-year-old woman suffering from respiratory failure due to severe intrapulmonary metastases with poor performance status. In conclusion, ultrarapid PCR combined with EBUS-GS-TBB enabled rapid and reliable point-of-care testing for EGFR mutations.

Show MeSH
Related in: MedlinePlus