Faculty Profiles - TOYOOKA Shinichi

Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Locally Advanced Non-small-cell Lung Cancer Treated with Trimodality Therapy. International journal

Shimpei Tsudaka, Hiromasa Yamamoto, Hiroki Sato, Kuniaki Katsui, Ken Suzawa, Kazuhiko Shien, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Katsuyuki Kiura, Susumu Kanazawa, Shinichi Toyooka

Annals of surgical oncology 28 ( 9 ) 4880 - 4890 2021.2

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Current evidence suggests that the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor in several types of cancer. In this study, we aimed to evaluate the prognostic impact of clinicopathological factors, including postoperative NLR, in patients with locally advanced non-small-cell lung cancer (LA-NSCLC) who underwent surgery after chemoradiotherapy (CRT) with or without postoperative adjuvant chemotherapy. METHODS: The medical records of LA-NSCLC patients treated with trimodality therapy at our institution between June 1999 and May 2019 were reviewed. The association between several clinicopathological factors and overall survival (OS) was analyzed. RESULTS: A total of 168 patients were included in this study. Regarding the prognosis, the 5-year OS rate was 68.1%, and the 2-year recurrence-free survival rate was 66.1% in the entire population. In multivariate analysis, we identified that high postoperative NLR, not pretreatment or preoperative NLR, was one of the independent factors for unfavorable OS (NLR high vs NLR low; hazard ratio = 2.45, 95% confidence interval: 1.53-3.94, p < 0.001). In addition, among patients with high postoperative NLR, patients who received postoperative adjuvant chemotherapy showed significantly better 5-year OS compared with those who did not (p = 0.016). On the other hand, postoperative adjuvant chemotherapy had no impact on the prognosis in patients with low NLR (p = 0.19). CONCLUSIONS: Our results suggest that high postoperative NLR was not only an independent unfavorable prognostic factor in patients with LA-NSCLC who were treated with trimodality therapy, but also a promising indicator for postoperative treatment in this population.

DOI： 10.1245/s10434-021-09690-9

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Lung stereotactic body radiation therapy for elderly patients aged ≥ 80 years with pathologically proven early-stage non-small cell lung cancer: a retrospective cohort study. International journal

Kenta Watanabe, Kuniaki Katsui, Soichiro Sugiyama, Kotaro Yoshio, Masahiro Kuroda, Takao Hiraki, Katsuyuki Kiura, Yoshinobu Maeda, Shinichi Toyooka, Susumu Kanazawa

Radiation oncology (London, England) 16 ( 1 ) 39 - 39 2021.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Stereotactic body radiation therapy (SBRT) is an established therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). Many elderly patients are medically inoperable owing to comorbidities. Therefore, SBRT may be a useful therapy for elderly patients. However, the application of SBRT for patients aged ≥ 80 years has not been completely elucidated. Therefore, this study aimed to assess the clinical utility of SBRT for elderly patients aged ≥ 80 years with pathologically proven early-stage NSCLC. METHODS: We retrospectively evaluated the data of patients aged ≥ 80 years with pathologically proven primary NSCLC who underwent SBRT at our institution between January 2009 and March 2020. Treatment outcomes and toxicities were analyzed. We used the Kaplan-Meier method to estimate survival curves and the log-rank test to compare the survival curves. We performed univariate and multivariate Cox regression analyses. p-values < 0.05 were regarded significant. RESULTS: Sixty-four patients (65 lesions) were included, and the median follow-up period was 38.7 (range 3.5-95.7) months. The median age was 82.9 (range 80.0-94.8) years. Sixteen patients were medically operable, and 48 patients were medically inoperable. The prescribed dose of SBRT was either 48 Gy in four fractions or 60 Gy in 10 fractions. The median survival time was 60.0 months (95% confidence interval, 43.5-71.1). The 1-, 3-, and 5-year local control, cancer-specific survival, progression-free survival, and overall survival rates were 98.4%, 98.4%, 81.0%, and 88.9%; 90.1%, 93.7%, 58.9%, and 68.3%; and 87.4%, 83.5%, 38.2%, and 47.5%, respectively. Multivariate analysis revealed that inoperability and solid nodules were the predictors of poor overall survival after SBRT in elderly patients. Two patients (3.1%) had grade 3 radiation pneumonitis, and one patient (1.6%) had grade 5 radiation pneumonitis. CONCLUSIONS: SBRT was feasible in patients aged ≥ 80 years with NSCLC. It achieved good local control with minimal toxicity. SBRT may be beneficial in elderly patients with early-stage NSCLC.

DOI： 10.1186/s13014-021-01769-7

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Preoperative Cumulative Smoking Dose on Lung Cancer Surgery in a Japanese Nationwide Database. International journal

Yugo Tanaka, Hiroyuki Yamamoto, Masami Sato, Shinichi Toyooka, Morihito Okada, Shunsuke Endo, Yukio Sato, Kenji Suzuki, Yoshimasa Maniwa, Eriko Fukuchi, Hiroaki Miyata, Masayuki Chida

The Annals of thoracic surgery 2021.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Smoking is a known risk factor for postoperative mortality and morbidity. However, the significance of cumulative smoking dose in preoperative risk assessment has not been established. We examined the influence of preoperative cumulative smoking dose on surgical outcomes after lobectomy for primary lung cancer. METHODS: A total of 80,989 patients with primary lung cancer undergoing lobectomy from 2014 to 2016 were enrolled. Preoperative cumulative smoking dose was categorized by pack-years (PY): nonsmokers, PY = 0; light smokers, 0 < PY < 10; moderate smokers, 10 ≤ PY < 30; and heavy smokers, 30 ≤ PY. The risk of short-term outcomes was assessed according to PY by multivariable analysis adjusted for other covariates. RESULTS: Postoperative 30-day mortality, as well as pulmonary, cardiovascular, and infectious complications, increased with preoperative PY. Multivariable analysis revealed that the odds ratios (ORs) for postoperative mortality compared with nonsmokers were 1.76 for light smokers (P = .044), 1.60 for moderate smokers (P = .026), and 1.73 for heavy smokers (P = .003). The ORs for pulmonary complications compared with nonsmokers were 1.20 for light smokers (P = .022), 1.40 for moderate smokers (P < .001), and 1.72 for heavy smokers (P < .001). Heavy smokers had a significantly increased risk of postoperative cardiovascular (OR, 1.26; P = .002) and infectious (OR, 1.39; P = .007) complications compared with nonsmokers. CONCLUSIONS: The risk of mortality and morbidity after lung resection could be predicted according to preoperative cumulative smoking dose. These findings contribute to the development of strategies in perioperative management of lung resection patients.

DOI： 10.1016/j.athoracsur.2021.01.055

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The prognostic nutritional index is correlated negatively with the lung allocation score and predicts survival after both cadaveric and living-donor lobar lung transplantation.

Haruchika Yamamoto, Seiichiro Sugimoto, Junichi Soh, Toshio Shiotani, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Masaomi Yamane, Shinichi Toyooka

Surgery today 51 ( 10 ) 1610 - 1618 2021.2

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The prognostic nutritional index (PNI), calculated based on the serum albumin levels and the total lymphocyte count, has been identified as a predictor of clinical outcomes in various fields of surgery. In this study, we investigated the relationship between the PNI and the lung allocation score (LAS) as well as the impact of the PNI on the outcomes of both cadaveric lung transplantation (CLT) and living-donor lobar lung transplantation (LDLLT). METHODS: We reviewed retrospective data for 127 recipients of lung transplantation (LT), including 71 recipients of CLT and 56 recipients of LDLLT. RESULTS: The PNI was correlated significantly and negatively with the LAS (r = - 0.40, P = 0.0000037). Multivariate analysis revealed that age (P = 0.00093), BMI (P = 0.00087), and PNI (P = 0.0046) were independent prognostic factors of a worse outcome after LT. In a subgroup analysis, survival after both CLT (P = 0.015) and LDLLT (P = 0.041) was significantly worse in the low PNI group than in the high PNI group. CONCLUSION: Preoperative nutritional evaluations using the PNI can assist with the assessment of disease severity in LT recipients and may predict survival after both CLT and LDLLT.

DOI： 10.1007/s00595-021-02244-2

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The prognostic impact of sarcopenia on elderly patients undergoing pulmonary resection for non-small cell lung cancer.

Akihiro Miura, Hiromasa Yamamoto, Hiroki Sato, Yasuaki Tomioka, Toshio Shiotani, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Surgery today 51 ( 7 ) 1203 - 1211 2021.2

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The number of elderly patients who undergo surgery is increasing, even though they are at a high risk due to a decreased physical strength. Furthermore, sarcopenia is generally associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: This study included NSCLC patients ≥ 65 years old who underwent pulmonary resection in our hospital between 2012 and 2015. Sarcopenia was assessed using the psoas muscle mass index based on computed tomography at the level of the third lumbar vertebra. We elucidated the impact of sarcopenia on short- and long-term outcomes after surgery. RESULTS: We enrolled 259 patients, including 179 with sarcopenia. Patients with sarcopenia before surgery tended to have postoperative complications (p = 0.0521), although they did not show a poor prognosis. In patients with sarcopenia, a multivariate analysis revealed that postoperative complications and the progression of sarcopenia 1 year after surgery were significant risk factors for a poor prognosis (p = 0.0169 and 0.00370, respectively). CONCLUSIONS: The progression of sarcopenia after surgery is associated with a poor prognosis in elderly NSCLC patients with sarcopenia. A strategy to prevent postoperative progressive sarcopenia may be necessary for improving the clinical outcome of this population.

DOI： 10.1007/s00595-020-02221-1

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Successful Bronchoscopic Treatment for Postoperative Bronchopleural Fistula Using N-butyl-2-cyanoacrylate (NBCA): Report of a Post-completion Pneumonectomy Case with a History of Induction Chemoradiotherapy Followed by Bilobectomy for Advanced Lung Cancer.

Toshio Shiotani, Hiromasa Yamamoto, Riko Katsube, Yasuaki Tomioka, Ken Suzawa, Kentaroh Miyoshi, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Junichi Soh, Masaomi Yamane, Shinichi Toyooka

Acta medica Okayama 75 ( 1 ) 91 - 94 2021.2

Language：English Publishing type：Research paper (scientific journal)

Bronchopleural fistula (BPF) is a severe complication following lung resection. We present the case of a patient with a history of advanced lung cancer, who had undergone induction chemoradiotherapy followed by right middle and lower lobectomy, and who developed BPF after completion right pneumonectomy. Although we had covered the bronchial stump with an omental pedicled flap, BPF was found on postoperative day 19. We covered the fistula with n-butyl-2-cyanoacrylate (NBCA) using bronchoscopy. Although we had to repeat the NBCA treatment, we ultimately cured the patient's BPF and no recurrence was observed up to 15.2 months after surgery.

DOI： 10.18926/AMO/61440

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Long-term Follow-up of Living-Donor Kidney Transplantation after Cadaveric Lung Transplantation.

Toshio Shiotani, Seiichiro Sugimoto, Kota Araki, Yasuaki Tomioka, Kentaroh Miyoshi, Shinji Otani, Masaomi Yamane, Shinichi Toyooka

Acta medica Okayama 75 ( 1 ) 87 - 89 2021.2

Language：English Publishing type：Research paper (scientific journal)

Although chronic kidney disease (CKD) commonly develops after lung transplantation (LT), living-donor kid-ney transplantation (LDKT) for CKD after LT is known to provide favorable outcomes. We describe the long-term follow-up findings of a patient who underwent LDKT after bilateral cadaveric LT. A 37-year-old male underwent LDKT for CKD 18 years after receiving bilateral cadaveric LT. He developed chronic lung allograft dysfunction (CLAD) 20 years after the LT; however, at 26 years after the initial LT, he is still alive with no pro-gression of CLAD or CKD. KT could be a viable option for CKD even after LT in Japan.

DOI： 10.18926/AMO/61439

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Lung Laceration Caused by Short Hookwire Placement Before Video-Assisted Thoracoscopic Surgery. International journal

Kazuaki Munetomo, Yusuke Matsui, Toshihiro Iguchi, Takao Hiraki, Hiromasa Yamamoto, Shinichi Toyooka, Susumu Kanazawa

Cardiovascular and interventional radiology 44 ( 2 ) 339 - 341 2021.2

Volumetric PET Parameters Predict Prognosis after Definitive Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-Small Cell Lung Cancer.

Kuniaki Katsui, Takeshi Ogata, Akihiro Tada, Soichi Sugiyama, Kotaro Yoshio, Masahiro Kuroda, Katsuyuki Kiura, Yoshinobu Maeda, Shinichi Toyooka, Takao Hiraki, Susumu Kanazawa

Acta medica Okayama 75 ( 1 ) 15 - 23 2021.2

Language：English Publishing type：Research paper (scientific journal)

The aim of this study was to investigate whether volumetric positron emission tomography (PET) parameters are prognostic predictors in stage III non-small cell lung cancer patients receiving definitive concurrent chemo-radiotherapy (CCRT) with cisplatin/docetaxel. Cases involving definitive CCRT were reviewed retrospectively, and the maximum standardized uptake value, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. The relationships between these PET parameters and prognosis were analyzed. MTV and TLG were significant predictors of distant metastasis-free survival (DMFS) (p = 0.0003 and 0.0005, respectively) and progression-free survival (PFS) (p = 0.001 and 0.0007, respectively). The three-year DMFS rates in patients with low and high MTV were 13.3% and 64.6%, respectively, and the corresponding values in those with low and high TLG were 13.3% and 65.2%, respectively. The three-year PFS rates in patients with low and high MTV were 13.3% and 57.8%, respectively, and the corresponding values in patients with low and high TLG were 13.3% and 57.8%, respectively. However, MTV and TLG were not predictors of local control or overall sur-vival. We demonstrated that volumetric PET parameters were predictors of patients receiving definitive CCRT. Our findings contradict the findings of previous reports and warrant further research to validate them.

DOI： 10.18926/AMO/61429

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Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (edition 2.1)

Yoichi Naito, Hiroyuki Aburatani, Toraji Amano, Eishi Baba, Toru Furukawa, Tetsu Hayashida, Eiso Hiyama, Sadakatsu Ikeda, Masashi Kanai, Motohiro Kato, Ichiro Kinoshita, Naomi Kiyota, Takashi Kohno, Shinji Kohsaka, Keigo Komine, Itaru Matsumura, Yuji Miura, Yoshiaki Nakamura, Atsushi Natsume, Kazuto Nishio, Katsutoshi Oda, Naoyuki Oda, Natsuko Okita, Kumiko Oseto, Kuniko Sunami, Hideaki Takahashi, Masayuki Takeda, Shimon Tashiro, Shinichi Toyooka, Hideki Ueno, Shinichi Yachida, Takayuki Yoshino, Katsuya Tsuchihara

International Journal of Clinical Oncology 26 ( 2 ) 233 - 283 2021.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

<title>Abstract</title><sec>
<title>Background</title>
To promote precision oncology in clinical practice, the Japanese Society of Medical Oncology, the Japanese Society of Clinical Oncology, and the Japanese Cancer Association, jointly published “Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment” in 2017. Since new information on cancer genomic medicine has emerged since the 1st edition of the guidance was released, including reimbursement for NGS-based multiplex gene panel tests in 2019, the guidance revision was made.

</sec><sec>
<title>Methods</title>
A working group was organized with 33 researchers from cancer genomic medicine designated core hospitals and other academic institutions. For an impartial evaluation of the draft version, eight committee members from each society conducted an external evaluation. Public comments were also made on the draft. The finalized Japanese version was published on the websites of the three societies in March 2020.

</sec><sec>
<title>Results</title>
The revised edition consists of two parts: an explanation of the cancer genomic profiling test (General Discussion) and clinical questions (CQs) that are of concern in clinical practice. Particularly, patient selection should be based on the expectation that the patient's post-test general condition and organ function will be able to tolerate drug therapy, and the optimal timing of test should be considered in consideration of subsequent treatment plans, not limited to treatment lines.

</sec><sec>
<title>Conclusion</title>
We expect that the revised version will be used by healthcare professionals and will also need to be continually reviewed in line with future developments in cancer genome medicine.

</sec>

DOI： 10.1007/s10147-020-01831-6

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Other Link： http://link.springer.com/article/10.1007/s10147-020-01831-6/fulltext.html

Staged surgery for empyema and lung gangrene caused by pseudoaneurysm after radiofrequency ablation. International journal

Kentaro Nakata, Seiichiro Sugimoto, Masaomi Yamane, Shinichi Toyooka

Interactive cardiovascular and thoracic surgery 32 ( 5 ) 831 - 833 2021.1

Language：English Publishing type：Research paper (scientific journal)

Lung gangrene is a potentially fatal disease, and primary or staged surgery, depending on the patient's condition, is reported to be useful. We describe successful management, by staged surgery, of a rare case of empyema and lung gangrene complicating lung radiofrequency ablation. The patient, who was a diabetic with colorectal pulmonary metastases, underwent embolization of a pulmonary artery pseudoaneurysm in the right basal segment that developed after lung radiofrequency ablation. He subsequently developed lung gangrene caused by lung ischaemia, and empyema, necessitating pleural decortication followed by open-window thoracostomy. Subsequently, right basal segmentectomy was performed, with thoracostoma closure. Staged surgery might be beneficial for high-risk patients with empyema and lung gangrene caused by lung ischaemia.

DOI： 10.1093/icvts/ivaa331

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Allele-Specific Role of ERBB2 in the Oncogenic Function of EGFR L861Q in EGFR-Mutant Lung Cancers

Hiroki Sato, Michael Offin, Daisuke Kubota, Helena A. Yu, Clare Wilhelm, Shinichi Toyooka, Romel Somwar, Mark G. Kris, Marc Ladanyi

Journal of Thoracic Oncology 16 ( 1 ) 113 - 126 2021.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Inc.

Introduction: Unlike common EGFR mutations, many less common EGFR mutations remain poorly characterized in terms of oncogenic function and drug sensitivity. Here, we characterize the subset of lung adenocarcinoma harboring EGFR L861Q through both preclinical and clinical investigations. Methods: We reviewed clinical and genomic data from patients with EGFR-mutant lung cancer. We established cells expressing EGFR mutations and performed functional analysis of L861Q in comparison with common EGFR mutations. Results: Among the patients with lung cancer, 3.4% (47 of 1367) possess an EGFR L861Q mutation. Of the patients with L861Q, 23.4% (11 of 47) had a concurrent exon 18 mutation (typically involving G719). In vitro studies revealed that the oncogenic activity of L861Q is dependent on asymmetric dimerization. Cells expressing L861Q were less sensitive to EGFR-specific inhibitors compared with cells expressing L858R but were similarly sensitive to pan-ERBB inhibitors. In cells expressing L861Q, ERBB2 phosphorylation was markedly higher compared with cells expressing L858R, and an enhanced interaction between EGFR and ERBB2 was observed in coimmunoprecipitation studies. In addition, treatment with osimertinib enhanced expression of the antiapoptotic protein MCL1, and knockdown of ERBB2 suppressed the expression of MCL1 in L861Q, raising the possibility of differential allele-specific cross-phosphorylation of ERBB2. Moreover, compared with EGFR-specific inhibitors, pan-ERBB inhibitors exerted superior growth inhibitory effects on cells expressing compound L861Q/G719X mutations. Conclusions: Our results suggest that ERBB2 plays a previously unrecognized role in EGFR L861Q-driven tumorigenesis, and pan-ERBB inhibitors are likely to be more effective than selective EGFR tyrosine kinase inhibitors in this setting.

DOI： 10.1016/j.jtho.2020.09.019

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Papers - TOYOOKA Shinichi