1.Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study
Daisuke AOKI ; Tsutomu TABATA ; Satoshi YANAGIDA ; Toshiaki NAKAMURA ; Eiji KONDO ; Junzo HAMANISHI ; Kenichi HARANO ; Kosei HASEGAWA ; Takeshi HIRASAWA ; Kensuke HORI ; Shinichi KOMIYAMA ; Motoki MATSUURA ; Hidekatsu NAKAI ; Hiroko NAKAMURA ; Jun SAKATA ; Kazuhiro TAKEHARA ; Munetaka TAKEKUMA ; Yoshihito YOKOYAMA ; Yoichi KASE ; Shuuji SUMINO ; Junpei SOEDA ; Ai KATO ; Ajit SURI ; Aikou OKAMOTO ; Toru SUGIYAMA
Journal of Gynecologic Oncology 2024;35(5):e114-
Objective:
To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.
Methods:
This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs).
Results:
20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively.
Conclusion
The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.
2.Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study
Daisuke AOKI ; Tsutomu TABATA ; Satoshi YANAGIDA ; Toshiaki NAKAMURA ; Eiji KONDO ; Junzo HAMANISHI ; Kenichi HARANO ; Kosei HASEGAWA ; Takeshi HIRASAWA ; Kensuke HORI ; Shinichi KOMIYAMA ; Motoki MATSUURA ; Hidekatsu NAKAI ; Hiroko NAKAMURA ; Jun SAKATA ; Kazuhiro TAKEHARA ; Munetaka TAKEKUMA ; Yoshihito YOKOYAMA ; Yoichi KASE ; Shuuji SUMINO ; Junpei SOEDA ; Ai KATO ; Ajit SURI ; Aikou OKAMOTO ; Toru SUGIYAMA
Journal of Gynecologic Oncology 2024;35(5):e114-
Objective:
To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.
Methods:
This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs).
Results:
20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively.
Conclusion
The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.
3.Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study
Daisuke AOKI ; Tsutomu TABATA ; Satoshi YANAGIDA ; Toshiaki NAKAMURA ; Eiji KONDO ; Junzo HAMANISHI ; Kenichi HARANO ; Kosei HASEGAWA ; Takeshi HIRASAWA ; Kensuke HORI ; Shinichi KOMIYAMA ; Motoki MATSUURA ; Hidekatsu NAKAI ; Hiroko NAKAMURA ; Jun SAKATA ; Kazuhiro TAKEHARA ; Munetaka TAKEKUMA ; Yoshihito YOKOYAMA ; Yoichi KASE ; Shuuji SUMINO ; Junpei SOEDA ; Ai KATO ; Ajit SURI ; Aikou OKAMOTO ; Toru SUGIYAMA
Journal of Gynecologic Oncology 2024;35(5):e114-
Objective:
To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.
Methods:
This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs).
Results:
20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively.
Conclusion
The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.
4.4. Alignment of the 2022 Revision of the Model Core Curriculum for Medical Education in Japan with the‘Standards of the National Medical Practitioners Qualifying Examination'
Hiroyuki KOMATSU ; Masanaga YAMAWAKI ; Masatomi IKUSAKA ; Masato ETO ; Yasuhiko KONISHI ; Keiichiro SUZUKI ; Shoichi SHIMADA ; Osamu NOMURA ; Yasushi MATSUYAMA ; Harumi GOMI ; Akira YAMAMOTO ; Takeshi ONOUE ; Hitoshi HASEGAWA ; Hideki TAKAMI ; Hitoaki OKAZAKI
Medical Education 2023;54(2):157-163
In this revision, we have attempted to align the Model Core Curriculum for Medical Education competency, "problem-solving ability based on specialized knowledge," with the "Standards of National Examination for Medical Practitioners." The major diseases and syndromes in "Essential Fundamentals" correspond to the basic diseases in Table 1 of the Core Curriculum, symptoms, physical and laboratory examinations, and treatment in "General Medicine" correspond to the items in Table 2 of the Core Curriculum, and the diseases in "Medical Theory" correspond to the diseases in PS-02 of the Core Curriculum. The validity of the diseases in the Core Curriculum was verified using the evaluation results of the examination level classification of the "Research for Revision of National Examination Criteria." Approximately 690 diseases were conclusively selected. This revision mentions the number of diseases in the Core Curriculum for the first time. Hopefully, this will lead to a deeper examination of diseases that should be studied in medical schools in the future.
5.Impact of COVID-19 on gynecologic cancer treatment in Japan: a nationwide survey by the Japan Society of Gynecologic Oncology (JSGO)
Yuya NOGAMI ; Hiroaki KOMATSU ; Takeshi MAKABE ; Yuri HASEGAWA ; Yoshihito YOKOYAMA ; Kei KAWANA ; Aikou OKAMOTO ; Mikio MIKAMI ; Hidetaka KATABUCHI ;
Journal of Gynecologic Oncology 2022;33(1):e8-
Objective:
As coronavirus disease 2019 (COVID-19) rages on, it is a challenging task to balance resources for treatment of COVID-19 and malignancy-based treatment. For the development of optimal strategies, assessing the conditions and constrains in treatment during the COVID-19 pandemic is pertinent. This study reported about a nationwide survey conducted by the Japan Society of Gynecologic Oncology.
Methods:
We interviewed 265 designated training facilities about the state of their clinical practice from the time period between March and December 2020. We asked the facility doctors in charge to fill a web-based questionnaire.
Results:
A total of 232 facilities (87.5%) responded. A decrease in the number of outpatient visits was reported, and the major reason attributed was reluctance of patients to visit hospitals rather than facility restrictions. The actual number of surgeries decreased by 3.9%, compared to 2019. There was a significant difference when the variable of “Prefectures operating under special safety precautions” or not was introduced. There was no increase in the rate of advanced stages in the three cancer types studied. However, 34.1% participants perceived COVID-19 affected management and prognosis.
Conclusion
Refraining from visiting hospitals based on the patient's judgment may be expected to be an issue in the future. No significant decrease in surgeries was observed, and it would seem that there were few forced changes in treatment plans, but “the State of Emergency” had an impact. There was no increase in the rate of advanced cancers, but this will need to be monitored.
6.A Practical Grading Scale for Predicting Outcomes of Radiosurgery for Dural Arteriovenous Fistulas: JLGK 1802 Study
Hirotaka HASEGAWA ; Masahiro SHIN ; Jun KAWAGISHI ; Hidefumi JOKURA ; Toshinori HASEGAWA ; Takenori KATO ; Mariko KAWASHIMA ; Yuki SHINYA ; Hiroyuki KENAI ; Takuya KAWABE ; Manabu SATO ; Toru SERIZAWA ; Osamu NAGANO ; Kyoko AOYAGI ; Takeshi KONDOH ; Masaaki YAMAMOTO ; Shinji ONOUE ; Kiyoshi NAKAZAKI ; Yoshiyasu IWAI ; Kazuhiro YAMANAKA ; Seiko HASEGAWA ; Kosuke KASHIWABARA ; Nobuhito SAITO ;
Journal of Stroke 2022;24(2):278-287
Background:
and Purpose To assess the long-term outcomes of intracranial dural arteriovenous fistula (DAVF) treated with stereotactic radiosurgery (SRS) alone or embolization and SRS (Emb-SRS) and to develop a grading system for predicting DAVF obliteration.
Methods:
This multi-institutional retrospective study included 200 patients with DAVF treated with SRS or Emb-SRS. We investigated the long-term obliteration rate and obliteration-associated factors. We developed a new grading system to estimate the obliteration rate. Additionally, we compared the outcomes of SRS and Emb-SRS by using propensity score matching.
Results:
The 3- and 4-year obliteration rates were 66.3% and 78.8%, respectively. The post-SRS hemorrhage rate was 2%. In the matched cohort, the SRS and Emb-SRS groups did not differ in the rates of obliteration (P=0.54) or post-SRS hemorrhage (P=0.50). In multivariable analysis, DAVF location and cortical venous reflux (CVR) were independently associated with obliteration. The new grading system assigned 2, 1, and 0 points to DAVFs in the anterior skull base or middle fossa, DAVFs with CVR or DAVFs in the superior sagittal sinus or tentorium, and DAVFs without these factors, respectively. Using the total points, patients were stratified into the highest (0 points), intermediate (1 point), or lowest (≥2 points) obliteration rate groups that exhibited 4-year obliteration rates of 94.4%, 71.3%, and 60.4%, respectively (P<0.01).
Conclusions
SRS-based therapy achieved DAVF obliteration in more than three-quarters of the patients at 4 years of age. Our grading system can stratify the obliteration rate and may guide physicians in treatment selection.
7.Rats (Residents-as-Teachers) Fellowship
Tadayuki HASHIMOTO ; Takuya SAIKI ; Shunsuke KOSUGI ; Takeshi KANAZAWA ; Yuichi HASEGAWA ; Toshiki KIDO ; Yuki OTSUKA ; Makoto KIKUKAWA
Medical Education 2021;52(6):525-531
Residents have teaching roles in clinical practice, and the importance of these roles has been pointed out. This is due to their proximity to learners as Near-Peers. There are two aspects to consider: cognitive proximity, which allows them to share what learners don’t know, and spatial proximity, which allows us to share time and space for an extended period. Residents-as-teachers programs, which aim to improve teaching skills for residents, are being developed all over the world, but are still rare in Japan. We are conducting research to determine what teaching competencies residents should have. We are running a one-year fellowship based on the results of that research. The scale of the program has gradually increased, and in 2020, due to COVID-19, the fellowship went online. We restructured the fellowship in terms of Study/Workload, Enhancing Engagement, and Technical Issues. We received high satisfaction ratings for the online implementation.
8.Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer
Aikou OKAMOTO ; Eiji KONDO ; Toshiaki NAKAMURA ; Satoshi YANAGIDA ; Junzo HAMANISHI ; Kenichi HARANO ; Kosei HASEGAWA ; Takeshi HIRASAWA ; Kensuke HORI ; Shinichi KOMIYAMA ; Motoki MATSUURA ; Hidekatsu NAKAI ; Hiroko NAKAMURA ; Jun SAKATA ; Tsutomu TABATA ; Kazuhiro TAKEHARA ; Munetaka TAKEKUMA ; Yoshihito YOKOYAMA ; Yoichi KASE ; Shuuji SUMINO ; Junpei SOEDA ; Ajit SURI ; Daisuke AOKI ; Toru SUGIYAMA
Journal of Gynecologic Oncology 2021;32(2):e16-
Objective:
To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer.
Methods:
This Phase 2 open-label, single-arm study enrolled Japanese women with homologous recombination deficiency-positive relapsed, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of therapy. The starting dose of niraparib was 300 mg administered once daily in continuous 28-day cycles until objective progressive disease, unacceptable toxicity, consent withdrawal or discontinuation. The primary endpoint, objective response rate (ORR), was assessed by the investigator using RECIST version 1.1. Safety evaluations included the incidence of treatment-emergent adverse events (TEAEs), including serious TEAEs.
Results:
Twenty women were enrolled and the confirmed ORR in the full analysis set (FAS) was 35.0% (7/20), consisting of 1 complete response and 6 partial responses. Disease control rate in the FAS was 90.0%. The most frequently reported TEAEs (>50%) were anemia, nausea, and platelet count decreased. One patient (5.0%) had TEAEs leading to discontinuation of niraparib whereas reductions or interruptions were reported in 14 (70.0%) and 15 (75.0%) patients, respectively. The median dose intensity (202.9 mg daily) corresponded to a relative dose intensity of 67.6%.
Conclusion
Efficacy and safety of niraparib in heavily pretreated Japanese women was comparable to that seen in an equivalent population of non-Japanese women. No new safety signals were identified.
9.A Juvenile Case of Folding Plasty for Mitral Active Infectious Endocarditis
Takeshi Yuasa ; Kazutaka Horiuchi ; Takafumi Terada ; Shunsuke Nakata ; Masahiko Hasegawa ; Kenzo Yasuura
Japanese Journal of Cardiovascular Surgery 2013;42(3):211-214
We report a case of mitral active infectious endocarditis in a 15-year-old boy successfully managed by folding plasty without any prosthetic devices. He was admitted to our hospital because of high fever and general fatigue. Echocardiography revealed a vegetation of 15×18 mm attached to the anterior commissure area of the mitral valve with severe mitral regurgitation. Brain MRI showed acute brain infarction without symptoms, and enhanced computed tomography also showed multiple infarctions of the spleen and the left kidney. Staphylococcus aureus was identified in the venous blood culture. We diagnosed active mitral infectious endocarditis with multiple systemic embolization and disseminated intravascular coagulation. After antibiotic therapy for 9 days, mitral valve surgery was performed with cardiopulmonary bypass and cold blood cardioplegia through a median sternotomy and a left atriotomy. A giant vegetation was attached to the damaged mitral leaflet of the AC to A1 and P1. The vegetation and damaged leaflet were removed by an ultrasonic aspirator and resected. Removal of the superficial vegetation with the aspiration method enabled preservation of more than half of the A1 and half of the P1 for valve repair. The anterior commissure annulus without a leaflet was reconstructed by compression suture. Furthermore, in a procedure similar to folding plasty, leaflet A1 was folded down and sutured to annulus P1, and a simple suture technique was involved to the left cut edges of leaflet A1 and P1. The postoperative course was uneventful. Two years after surgery, the patient was well with no recurrence of infection and trivial mitral regurgitation on echocardiography.
10.Chemotherapy for Gastrointestinal Cancer in Elderly Outpatients in Mountainous Area
Takeshi HASEGAWA ; Takashi MIYAKE
Journal of the Japanese Association of Rural Medicine 2012;60(5):597-601
Our hospital is located in a mountainous region of Toyota City, Aichi Prefecture. In the sphere covered by our health services, about 34% of the population is 65 years or older. The graying of the community has been progressing rapidly in the past years. Many elderly people do not have a car. Only available means of transport for them are community bus servicers operated once or twice a week. The situation makes them feel disinclined to go to take physicals or visit the hospital for health screening. When we happen to detect gastrointestinal cancer in aged persons, it is often in an advanced state or too late for surgical removal, or a relapse. For some of such cases, we consider the possibilities of chemotherapy.
Between April 2005 and June 2010, we performed laparotomies (including exploratory operations) on people aged 70 or older with gastrointestinal cancer. Of the patients excluding those with severe cognitive impairment and those in failing health, 25 patients underwent S-1monotherapy postoperatively. The results were no less favorable than those of the cases of younger patients who had received S-monotherapy or other forms of chemotherapy for gastrointestinal cancer. Although this comparison was not adequate because the number of cases of elderly patients was too small, our hospital regards S-1 monotherapy as one of the chemotherapeutic regimens beneficial to old people with gastrointestinal cancer and helpful in maintaining the patient's qualuty of life.


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