Details of a Researcher - Oya, Mototsugu

Papers - Oya, Mototsugu

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Resolving the Crab pulsar wind nebula at teraelectronvolt energies

H. E. S. S. Collaboration, H. Abdalla, F. Aharonian, F. Ait Benkhali, E. O. Angüner, M. Arakawa, C. Arcaro, C. Arm, M. Backes, M. Barnard, Y. Becherini, J. Becker Tjus, D. Berge, K. Bernlöhr, R. Blackwell, M. Böttcher, C. Boisson, J. Bolmont, S. Bonnefoy, P. Bordas, J. Bregeon, F. Brun, P. Brun, M. Bryan, M. Büchele, T. Bulik, T. Bylund, M. Capasso, S. Caroff, A. Carosi, S. Casanova, M. Cerruti, N. Chakraborty, T. Ch, S. Ch, R. C. G. Chaves, A. Chen, S. Colafrancesco, B. Condon, I. D. Davids, C. Deil, J. Devin, P. deWilt, L. Dirson, A. Djannati-Ataï, A. Dmytriiev, A. Donath, V. Doroshenko, L. O'C. Drury, J. Dyks, K. Egberts, G. Emery, J. -P. Ernenwein, S. Eschbach, S. Fegan, A. Fiasson, G. Fontaine, S. Funk, M. Füßling, S. Gabici, Y. A. Gallant, F. Gaté, G. Giavitto, D. Glawion, J. F. Glicenstein, D. Gottschall, M. -H. Grondin, J. Hahn, M. Haupt, G. Heinzelmann, G. Henri, G. Hermann, J. A. Hinton, W. Hofmann, C. Hoischen, T. L. Holch, M. Holler, D. Horns, D. Huber, H. Iwasaki, A. Jacholkowska, M. Jamrozy, D. Jankowsky, F. Jankowsky, L. Jouvin, I. Jung-Richardt, M. A. Kastendieck, K. Katarzyński, M. Katsuragawa, U. Katz, D. Khangulyan, B. Khélifi, J. King, S. Klepser, W. Kluźniak, Nu. Komin, K. Kosack, M. Kraus, G. Lamanna, J. Lau, J. Lefaucheur, A. Lemière, M. Lemoine-Goumard, J. -P. Lenain, E. Leser, T. Lohse, R. López-Coto, I. Lypova, D. Malyshev, V. Mar, A. Marcowith, C. Mariaud, G. Martí-Devesa, R. Marx, G. Maurin, P. J. Meintjes, A. M. W. Mitchell, R. Moderski, M. Mohamed, L. Mohrmann, C. Moore, E. Moulin, T. Murach, S. Nakashima, M. de Naurois, H. Ndiyavala, F. Niederwanger, J. Niemiec, L. Oakes, P. O'Brien, H. Odaka, S. Ohm, M. Ostrowski, I. Oya, M. Panter, R. D. Parsons, C. Perennes, P. -O. Petrucci, B. Peyaud, Q. Piel, S. Pita, V. Poireau, A. Priyana Noel, D. A. Prokhorov, H. Prokoph, G. Pühlhofer, M. Punch, A. Quirrenbach, S. Raab, R. Rauth, A. Reimer, O. Reimer, M. Renaud, F. Rieger, L. Rinchiuso, C. Romoli, G. Rowell, B. Rudak, E. Ruiz-Velasco, V. Sahakian, S. Saito, D. A. Sanchez, A. Santangelo, M. Sasaki, R. Schlickeiser, F. Schüssler, A. Schulz, H. Schutte, U. Schwanke, S. Schwemmer, M. Seglar-Arroyo, M. Senniappan, A. S. Seyffert, N. Shafi, I. Shilon, K. Shiningayamwe, R. Simoni, A. Sinha, H. Sol, A. Specovius, M. Spir-Jacob, Ł. Stawarz, R. Steenkamp, C. Stegmann, C. Steppa, T. Takahashi, J. -P. Tavernet, T. Tavernier, A. M. Taylor, R. Terrier, D. Tiziani, M. Tluczykont, C. Trichard, M. Tsirou, N. Tsuji, R. Tuffs, Y. Uchiyama, D. J. van der Walt, C. van Eldik, C. van Rensburg, B. van Soelen, G. Vasileiadis, J. Veh, C. Venter, P. Vincent, J. Vink, F. Voisin, H. J. Völk, T. Vuillaume, Z. Wadiasingh, S. J. Wagner, R. M. Wagner, R. White, A. Wierzcholska, R. Yang, H. Yoneda, D. Zaborov, M. Zacharias, R. Zanin, A. A. Zdziarski, A. Zech, A. Ziegler, J. Zorn, N. Żywucka

2019.09

The Crab nebula is one of the most studied cosmic particle accelerators,
shining brightly across the entire electromagnetic spectrum up to very
high-energy gamma rays. It is known from radio to gamma-ray observations that
the nebula is powered by a pulsar, which converts most of its rotational energy
losses into a highly relativistic outflow. This outflow powers a pulsar wind
nebula (PWN), a region of up to 10~light-years across, filled with relativistic
electrons and positrons. These particles emit synchrotron photons in the
ambient magnetic field and produce very high-energy gamma rays by Compton
up-scattering of ambient low-energy photons. While the synchrotron morphology
of the nebula is well established, it was up to now not known in which region
the very high-energy gamma rays are emitted. Here we report that the Crab
nebula has an angular extension at gamma-ray energies of 52 arcseconds
(assuming a Gaussian source width), significantly larger than at X-ray
energies. This result closes a gap in the multi-wavelength coverage of the
nebula, revealing the emission region of the highest energy gamma rays. These
gamma rays are a new probe of a previously inaccessible electron and positron
energy range. We find that simulations of the electromagnetic emission
reproduce our new measurement, providing a non-trivial test of our
understanding of particle acceleration in the Crab nebula.

Accidental Hypothermia Treated by Hemodialysis in the Acute Phase: Three Case Reports and a Review of the Literature.

Tetsushi Murakami, Tadashi Yoshida, Arata Kurokochi, Kimiharu Takamatsu, Yu Teranishi, Keisuke Shigeta, Satoshi Tamaki, Shinya Morita, Ryuichi Mizuno, Mototsugu Oya

Internal medicine (Tokyo, Japan) (JAPAN SOC INTERNAL MEDICINE) 58 ( 18 ) 2743 - 2748 2019.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 0918-2918

Accidental hypothermia is defined as a core body temperature <35°C. Even with the use of multiple active rewarming methods, it has a high mortality rate. No standard treatment strategy for moderate or severe hypothermia in the absence of cardiac arrest has yet been established. We herein report three patients with severe or moderate accidental hypothermia who were treated by hemodialysis in the acute phase. This case report with a literature review describes the usefulness of hemodialysis for the treatment of moderate and severe accidental hypothermia without cardiac arrest.

[Risk Classification and Nivolumab plus Ipilimumab Combination Therapy for Treatment of Renal Cell Carcinoma].

Oya M, Tajima Y, Kabu K

Gan to kagaku ryoho. Cancer & chemotherapy 46 ( 9 ) 1397 - 1404 2019.09

Research paper (scientific journal), Joint Work, ISSN 0385-0684

The International Metastatic Renal Cell Carcinoma Database Consortium(IMDC)classification is often used to predict the prognosis of patients treated with molecularly targeted agents. In this review, the authors describe the prognostic value of the neutrophil-lymphocyte ratio and C-reactive protein for Japanese patients with renal cell carcinoma. Both markers may help identify which patients are likely to have a poor prognosis despite molecularly targeted therapy. In these circumstances, the CheckMate 214 trial showed that nivolumab plus ipilimumab combination therapy was superior to sunitinib for the treatment of patients with intermediate/poor prognosis. As a consequence, the combination of nivolumab plus ipilimumab is now positioned as standard first-line treatment for renal cell carcinoma, and the IMDCclassification is recommended as an aid in treatment decisions. Although careful management of immune-related adverse events is necessary, nivolumab plus ipilimumab combination therapy is expected to improve the outcomes of renal cell carcinoma for which the prognosis is otherwise generally poor.

Erectile function recovery at 12 months after radical prostatectomy for prostate cancer is not associated with overall survival.

Toshikazu Takeda, Nicole E Benfante, Melissa Assel, John P Mulhall, Mototsugu Oya, Karim A Touijer

International journal of urology : official journal of the Japanese Urological Association (WILEY) 26 ( 9 ) 934 - 935 2019.09

Research paper (scientific journal), Joint Work, ISSN 0919-8172

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Risk classification and nivolumab plus ipilimumab combination therapy for treatment of renal cell carcinoma

Oya M., Tajima Y., Kabu K.

Japanese Journal of Cancer and Chemotherapy (Japanese Journal of Cancer and Chemotherapy) 46 ( 9 ) 1397 - 1404 2019.09

ISSN 03850684

© 2019 Japanese Journal of Cancer and Chemotherapy Publishers Inc.. All rights reserved. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) classification is often used to predict the prognosis of patients treated with molecularly targeted agents. In this review, the authors describe the prognostic value of the neutrophil-lymphocyte ratio and C-reactive protein for Japanese patients with renal cell carcinoma. Both markers may help identify which patients are likely to have a poor prognosis despite molecularly targeted therapy. In these circumstances, the CheckMate 214 trial showed that nivolumab plus ipilimumab combination therapy was superior to sunitinib for the treatment of patients with intermediate/poor prognosis. As a consequence, the combination of nivolumab plus ipilimumab is now positioned as standard first-line treatment for renal cell carcinoma, and the IMDC classification is recommended as an aid in treatment decisions. Although careful management of immune-related adverse events is necessary, nivolumab plus ipilimumab combination therapy is expected to improve the outcomes of renal cell carcinoma for which the prognosis is otherwise generally poor.

A Novel Risk-based Approach Simulating Oncological Surveillance After Radical Nephroureterectomy in Patients with Upper Tract Urothelial Carcinoma.

Keisuke Shigeta, Eiji Kikuchi, Takayuki Abe, Masayuki Hagiwara, Koichiro Ogihara, Tadatsugu Anno, Kota Umeda, Yuto Baba, Tansei Sanjo, Kazunori Shojo, Shuji Mikami, Ryuichi Mizuno, Mototsugu Oya

European urology oncology (ELSEVIER) 3 ( 6 ) 756 - 763 2019.08

Research paper (scientific journal), Joint Work, Accepted

BACKGROUND: The current guideline lacks evidence for creating individualized surveillance strategies for upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). OBJECTIVE: To create a novel risk model and to simulate individualized surveillance duration that dynamically illustrates the changing risk relationship of UTUC-related death and non-UTUC death, considering the impact of cigarette smoking. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study comprised 714 pTa-T4N0M0 UTUC patients, with a median follow-up duration of 65mo. There were 279 (39.1%) nonsmokers, 260 (36.4%) current smokers, and 175 (24.5%) ex-smokers. INTERVENTION: All patients underwent RNU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The risks of UTUC death and non-UTUC death over time were estimated using parametric models for time to failure with Weibull distributions. Age-specific, stage-specific, and smoking status-specific surveillance durations were simulated based upon Weibull estimates. RESULTS AND LIMITATIONS: The hazard rate (HR) of non-UTUC death gradually increased over time in all age groups regardless of the smoking status, whereas that of UTUC-related death decreased markedly according to the pathological T (pT) stage and was affected by the smoking status. Among current smokers, the baseline HR of UTUC-related death in pT3/4 was higher than that of pT ≤2 and remained high even 10yr after RNU. Among heavy smokers, the HR of UTUC-related death in all pT stages was highest at baseline and remained high after RNU, compared with nonsmokers, current smokers, or ex-smokers. We simulated specific time points when the risk of non-UTUC death was greater than that of UTUC-related death. Among patients ≥80yr of with pT3N0M0, the risk of non-UTUC death was greater than that of UTUC-related death 1yr after RNU in nonsmokers, but 7yr for heavy smokers. CONCLUSIONS: Our result revealed that smokers bear a long-term risk burden of UTUC-related death more than the risk of non-UTUC death. For UTUC smokers, longer-term surveillance duration is recommended even in elderly stage. PATIENT SUMMARY: In the present study, we evaluated the risk transition of upper tract urothelial carcinoma (UTUC)-related death and non-cancer-related death over time. We found that smoking weighed a huge impact upon UTUC-related death compared with death from other cause, and therefore, we created a more individualized surveillance duration model.

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Impact of pegfilgrastim as primary prophylaxis for metastatic castration-resistant prostate cancer patients undergoing cabazitaxel treatment: an open-label study in Japan.

Takeo Kosaka, Hiroji Uemura, Makoto Sumitomo, Kenichi Harada, Mikio Sugimoto, Narihiko Hayashi, Kazuhiro Yoshimura, Satoshi Fukasawa, Evelyne Ecstein-Fraisse, Yoshinori Sunaga, Mototsugu Oya

Japanese journal of clinical oncology (OXFORD UNIV PRESS) 49 ( 8 ) 766 - 771 2019.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 0368-2811

BACKGROUND: Cabazitaxel is an efficacious treatment for patients with metastatic castration-resistant prostate cancer who have previously progressed on docetaxel, but febrile neutropenia during the first cycle is a frequent complication. Asian patients are at increased risk of febrile neutropenia. Although primary prophylaxis with granulocyte colony-stimulating factor can reduce the incidence, its efficacy has not been prospectively demonstrated in Japanese patients with cabazitaxel treatment. METHODS: PEGAZUS, a prospective, single-arm study conducted at eight clinical sites in Japan, enrolled 21 heavily pretreated patients with metastatic castration-resistant prostate cancer. Patients received cabazitaxel 25 mg/m2 every 3 weeks, up to 10 cycles. Oral prednisolone 10 mg was taken daily. Pegfilgrastim 3.6 mg was administered at least 24 h after the cabazitaxel infusion. The primary endpoint was the incidence of febrile neutropenia in the first cycle. RESULTS: The median number of treatment cycles was seven. The relative dose intensity of cabazitaxel was 67.4% (range, 53.2-91.3%). Two of 21 patients (9.5%) experienced febrile neutropenia in the first cycle. This rate was lower than the rate (43%) previously observed without prophylactic granulocyte colony-stimulating factor in a similar patient population. Six patients showed a prostate-specific antigen response (28.6%). Three of four patients evaluable for tumor response had stable disease and one had progressive disease. Grade ≥3 diarrhea was not observed. Primary prophylaxis with granulocyte colony-stimulating factor significantly reduced the incidence of febrile neutropenia in this study. CONCLUSIONS: Cabazitaxel plus granulocyte colony-stimulating factor is safe and effective for Japanese patients with metastatic castration-resistant prostate cancer who have previously progressed on docetaxel. Clinical trial registration: ClinicalTrials.gov (NCT02441894).

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Efficacy of systemic therapy for metastatic non clear renal cell carcinoma

Mizuno R., Takamatsu K., Hayakawa N., Tanaka N., Kosaka T., Oya M.

INTERNATIONAL JOURNAL OF UROLOGY 26 192 - 192 2019.08

ISSN 0919-8172

Serum Lactate Dehydrogenase Before Nivolumab Treatment Could Be a Therapeutic Prognostic Biomarker for Patients With Metastatic Clear Cell Renal Cell Carcinoma.

Suguru Shirotake, Kimiharu Takamatsu, Ryuichi Mizuno, G O Kaneko, Koshiro Nishimoto, Mototsugu Oya, Masafumi Oyama

Anticancer research (INT INST ANTICANCER RESEARCH) 39 ( 8 ) 4371 - 4377 2019.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 0250-7005

BACKGROUND/AIM: The purpose of this retrospective study was to identify the predictive biomarkers of response to pretreatment for patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab. MATERIALS AND METHODS: The subjects were 54 patients treated with nivolumab for mRCC with a clear cell component (mccRCC) between September 2016 and February 2018. We analyzed the impact of serum biomarkers (lactate dehydrogenase [LDH], neutrophil-to-lymphocyte ratio, and C-reactive protein) on patients treated with nivolumab. We adopted the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model using six clinical factors (0=favorable, 1 or 2=intermediate, 3 to 6=poor risk groups, respectively). RESULTS: The prognostic risk classification (non-poor vs. poor) and serum LDH levels were correlated with the objective response of nivolumab treatment for mccRCC. Elevated serum LDH levels at baseline were an independent biomarker for progression-free survival (PFS) of mccRCC patients receiving nivolumab [HR=2.268 (95%CI=1.014-5.051), p=0.046]. Notably, high LDH levels were associated with a poorer PFS for patients in the favorable-risk group. CONCLUSION: Serum LDH levels at baseline before nivolumab treatment were associated with the objective response and clinical outcome of nivolumab treatment.

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Prospctive study of tadarafil treatment in patients treated with prostate brachytherapy

Hayakawa N., Mizuno R., Kikuchi E., Takamatsu K., Oya M.

INTERNATIONAL JOURNAL OF UROLOGY 26 76 - 77 2019.08

ISSN 0919-8172

PRETREATMENT ABSOLUTE MONOCYTE COUNT IS A NOVEL BIOMARKER FOR PREDICTING WORSE CLINICAL OUTCOME IN CHEMO-RESISTANT UROTHELIAL CARCINOMA PATIENTS TREATED WITH PEMBROLIZUMAB

Koichiro Ogihara, Eiji Kikuchi, Takashi Okabe, Ryo Yamashita, Shunsuke Yoshimine, Suguru Shirotake, Ryuto Nakazawa, Kazuhiro Matsumoto, Ryuichi Mizuno, Satoshi Hara, Masafumi Oyama, Takeshi Masuda, Masashi Niwakawa, Mototsugu Oya

JOURNAL OF UROLOGY (LIPPINCOTT WILLIAMS & WILKINS) 26 9 - 10 2019.08

Joint Work, ISSN 0919-8172

限局性前立腺がんに対する腫瘍発生領域の臨床的検討

高松公晴, 松本一宏, 服部盛也, 田中伸之, 武田利和, 森田伸也, 小坂威雄, 水野隆一, 篠島利明, 菊地栄次, 浅沼宏, 大家基嗣

泌尿器外科 (医学図書出版(株)) 32 ( 8 ) 1011 - 1012 2019.08

ISSN 0914-6180

Interstitial pneumonitis in a castration-resistant prostate cancer patient receiving cabazitaxel after thoracic radiation therapy: a case report.

Yoshinori Yanai, Takeo Kosaka, Hiroshi Hongo, Mototsugu Oya

BMC cancer (BMC) 19 ( 1 ) 720 - 720 2019.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 1471-2407

BACKGROUND: Interstitial pneumonitis is a rare reaction in a previously irradiated area of pulmonary or thoracic lesion after treatment with anticancer drugs such as taxanes. CASE PRESENTATION: A 66-year-old man presented with a fever and dyspnea after treatment with cabazitaxel for castration-resistant prostate cancer. He was treated with an intravenous broad-spectrum antimicrobial agent, however he complained of dyspnea and had a pulse oximetric saturation of 80% while breathing room air. The patients had been treated for bone metastases with 37.5 Gy to the thoracic spine (Th 7) as a local radiotherapy. Radiological images showed pulmonary interstitial opacities in the irradiated field of the both lungs. The steroid pulse therapy was started. The patient's dyspnea disappeared and the interstitial opacities had also improved. CONCLUSIONS: This report is a case of interstitial pneumonitis in a castration-resistant prostate cancer patient receiving cabazitaxel after thoracic radiation therapy.

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特集ハイリスク前立腺癌を深掘りする-その変遷とM0 CRPCの最新治療企画にあたって

大家基嗣

臨床泌尿器科 (株式会社医学書院) 73 ( 8 ) 509 - 509 2019.07

ISSN 0385-2393

Brachytherapy seeds as a nidus for urethral stone formation: A case report.

Ken Kamisawa, Takeo Kosaka, Hiroshi Hongo, Ryuichi Mizuno, Mototsugu Oya

IJU case reports 2 ( 4 ) 206 - 208 2019.07

Joint Work

Introduction: Iatrogenic foreign bodies can cause urolithiasis. However, iodine seeds used in brachytherapy are not a known cause of stone formation. We report a rare case of urethral stone formation with brachytherapy seeds determined to be the nidus, which occurred 9 years after permanent seed brachytherapy for prostate cancer. Case presentation: An 87-year-old man with a history of prostate cancer treated with brachytherapy presented to our hospital with macroscopic hematuria. He underwent transurethral resection of the mucosa with erythema 4 years after brachytherapy. Cystoscopy revealed urethral stones on the bladder neck. Transurethral lithotripsy was performed and the nidus of stone formation was revealed to be an aggregate of iodine seeds. Conclusion: In the course of the long-term follow-up after brachytherapy for prostate cancer, the possibility of the formation of the urethral stone associated with iodine seeds should be considered when gross hematuria is observed.

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Particle balance investigation with the combination of the hydrogen barrier model and rate equations of hydrogen state in long duration discharges on an all-metal plasma facing wall in QUEST

Hanada K., Yoshida N., Hasegawa M., Hatayama A., Okamoto K., Takagi I, Hirata T., Oya Y., Miyamoto M., Oya M., Shikama T., Kuzmin A., Wang Z. X., Long H., Idei H., Nagashima Y., Nakamura K., Watanabe O., Onchi T., Watanabe H., Tokunaga K., Higashijima A., Kawasaki S., Nagata T., Shimabukuro S., Takase Y., Murakami S., Gao X., Liu H., Qian J., Raman R., Ono M.

NUCLEAR FUSION 59 ( 7 ) 2019.07

ISSN 0029-5515

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Clinically complete response to abiraterone acetate in a patient with metastatic castration-resistant prostate cancer.

Yoshinori Yanai, Takeo Kosaka, Hiroshi Hongo, Mototsugu Oya

IJU case reports 2 ( 4 ) 187 - 189 2019.07

Joint Work

Introduction: Abiraterone acetate in combination with prednisone is now widely used for the treatment of castration-resistant prostate cancer. Case presentation: A 62-year-old patient with a bone metastatic castration-resistant prostate cancer was started on abiraterone acetate at a dose of 1000 mg a day along with 10 mg prednisone. In spite of castrate testosterone level, the laboratory test showed a relatively high level of serum testosterone, which was 21 ng/dL. Within 6 months, the patient achieved a complete prostate-specific antigen response. Follow-up bone scintigraphy demonstrated no area of intense uptake. He had a history of hyperlipidemia and was started on atorvastatin at home just after starting abiraterone acetate. Conclusion: This report is a rare case of a clinically complete response to abiraterone acetate in a patient with metastatic castration-resistant prostate cancer.

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CKD 患者におけるがん化学療法─透析患者を中心に Ⅱ　がん薬物療法の特性　6　分子標的薬-チロシンキナーゼ阻害薬

水野隆一, 大家基嗣

臨床透析 (日本メディカルセンター) 35 ( 7 ) 782 - 789 2019.06

ISSN 0910-5808

Complete response with early introduction of cabazitaxel in a patient with multiple lung metastases of castration-resistant prostate cancer following the early detection of metastases using liquid biopsy: a case report.

Takeo Kosaka, Hiroshi Hongo, Mototsugu Oya

BMC cancer (BMC) 19 ( 1 ) 562 - 562 2019.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 1471-2407

BACKGROUND: Cabazitaxel (CBZ) chemotherapy for metastatic castration-resistant prostate cancer (mCRPC) is believed to be palliative because the radiological response rate is low and a durable response is rare. Here, we describe a rare case of a patient with mCRPC who was treated with CBZ chemotherapy and showed a durable radiological response and a complete biochemical response. CASE PRESENTATION: A 43-year-old man with prostate cancer and metastasis of the pubic bone underwent neoadjuvant androgen deprivation and docetaxel therapy, followed by laparoscopic prostatectomy, extended lymphadenectomy, and metastatectomy in 2014. Pathological examination revealed residual adenocarcinoma in the prostate and pubic bone (pathological T stage 3b, positive surgical margin). Following the operation, he received adjuvant radiation therapy (66 Gy) to the pelvic floor. His serum prostate-specific antigen (PSA) level decreased to < 0.01 ng/mL but gradually increased following docetaxel chemotherapy. Imaging findings indicated five tiny nodules in the bilateral lungs. Biopsy specimens are difficult to obtain and might not reflect the precise extent of the disease owing to heterogeneity in patients with CRPC. Thus, we performed liquid biopsy to isolate circulating tumor cells (CTCs), and overall 156 CTCs were detected per 7.5 mL. Almost all CTCs were androgen receptor-negative in the nucleus. We diagnosed the five nodules as lung metastases from docetaxel-resistant CRPC with few AR-signaling-dependent cancer cells. The patient was initiated on CBZ chemotherapy (25 mg/m2) according to the standard protocol in August 2016, instead of using a second-generation AR-targeting agent. After 2 cycles of CBZ chemotherapy, PSA level decreased to < 0.01 ng/mL and the lung metastases completely disappeared, with a reduced CTC count of < 5. To date, the patient has been receiving intermittent CBZ chemotherapy. CONCLUSIONS: We presented a rare case of a patient with mCRPC who was successfully treated with early CBZ chemotherapy. The early detection of metastasis using liquid biopsy enabled the introduction of early CBZ chemotherapy for docetaxel-resistant mCRPC.

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Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup 3-year follow-up analysis from the Phase III CheckMate 025 study.

Yoshihiko Tomita, Satoshi Fukasawa, Nobuo Shinohara, Hiroshi Kitamura, Mototsugu Oya, Masatoshi Eto, Kazunari Tanabe, Mitsuru Saito, Go Kimura, Junji Yonese, Masahiro Yao, Hirotsugu Uemura

Japanese journal of clinical oncology (OXFORD UNIV PRESS) 49 ( 6 ) 506 - 514 2019.06

Research paper (scientific journal), Joint Work, ISSN 0368-2811

BACKGROUND: Nivolumab treatment resulted in superior efficacy and safety versus everolimus treatment in the 2-year follow-up of the CheckMate 025 Phase III study, with consistent results in the global population and the Japanese population. Here, we report the 3-year follow-up in both groups. METHODS: Patients were randomized 1:1 to nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10 mg orally once daily until progression/intolerable toxicity. The primary endpoint was overall survival (OS). Key secondary endpoints included objective response rate, progression-free survival, safety and patient-reported quality of life. RESULTS: Of 410 and 411 patients randomized to nivolumab and everolimus, 37 and 26 were Japanese, respectively. The median OS for the global population was 25.8 months with nivolumab and 19.7 months with everolimus (hazard ratio 0.74; 95.5% confidence interval [CI]: 0.63-0.88; P = 0.0005); in the Japanese population, median OS was 45.9 months and not reached (hazard ratio 1.08; 95% CI: 0.50-2.34; P = 0.85), respectively. The investigator-assessed objective response rate was 26% versus 5% with nivolumab versus everolimus (odds ratio [OR] 6.19; 95% CI: 3.82-10.06) in the global population and 43% versus 8% in the Japanese population (OR 6.80; 95% CI: 1.60-28.91; P = 0.0035), respectively. The incidence of any-grade treatment-related adverse events was lower with nivolumab versus everolimus in both the global patient population (80% versus 89%) and the Japanese population (81% versus 100%). CONCLUSIONS: At the 3-year follow-up, the efficacy and safety results of CheckMate 025 are generally consistent in the global and the Japanese populations.

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