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  1. Article ; Online: The need of radiotherapy optimization for glioblastomas considering immune responses.

    Nishioka, Kentaro / Takahashi, Shuhei / Mori, Takashi / Uchinami, Yusuke / Yamaguchi, Shigeru / Kinoshita, Manabu / Yamashina, Masaaki / Higaki, Hajime / Maebayashi, Katsuya / Aoyama, Hidefumi

    Japanese journal of radiology

    2023  Volume 41, Issue 10, Page(s) 1062–1071

    Abstract: Glioblastoma is the most common of malignant primary brain tumors and one of the tumors with the poorest prognosis for which the overall survival rate has not significantly improved despite recent advances in treatment techniques and therapeutic drugs. ... ...

    Abstract Glioblastoma is the most common of malignant primary brain tumors and one of the tumors with the poorest prognosis for which the overall survival rate has not significantly improved despite recent advances in treatment techniques and therapeutic drugs. Since the emergence of immune checkpoint inhibitors, the immune response to tumors has attracted increasing attention. Treatments affecting the immune system have been attempted for various tumors, including glioblastomas, but little has been shown to be effective. It has been found that the reason for this is that glioblastomas have a high ability to evade attacks from the immune system, and that the lymphocyte depletion associated with treatment can reduce its immune function. Currently, research to elucidate the resistance of glioblastomas to the immune system and development of new immunotherapies are being vigorously carried out. Targeting of radiation therapy for glioblastomas varies among guidelines and clinical trials. Based on early reports, target definitions with wide margins are common, but there are also reports that narrowing the margins does not make a significant difference in treatment outcome. It has also been suggested that a large number of lymphocytes in the blood are irradiated by the irradiation treatment to a wide area in a large number of fractionations, which may reduce the immune function, and the blood is being recognized as an organ at risk. Recently, a randomized phase II trial comparing two types of target definition in radiotherapy for glioblastomas was conducted, and it was reported that the overall survival and progression-free survival were significantly better in a small irradiation field group. We review recent findings on the immune response and the immunotherapy to glioblastomas and the novel role of radiotherapy and propose the need to develop an optimal radiotherapy that takes radiation effects on the immune function into account.
    MeSH term(s) Humans ; Glioblastoma/radiotherapy ; Glioblastoma/drug therapy ; Brain Neoplasms/radiotherapy ; Immunotherapy/methods ; Progression-Free Survival ; Immunity ; Clinical Trials, Phase II as Topic ; Randomized Controlled Trials as Topic
    Language English
    Publishing date 2023-04-18
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 2488907-6
    ISSN 1867-108X ; 1867-1071
    ISSN (online) 1867-108X
    ISSN 1867-1071
    DOI 10.1007/s11604-023-01434-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Correction: Treatment outcomes of radiotherapy with concurrent weekly cisplatin in older patients with locally advanced head and neck squamous cell carcinoma.

    Uchinami, Yusuke / Yasuda, Koichi / Kano, Satoshi / Otsuka, Manami / Hamada, Seijiro / Suzuki, Takayoshi / Tsushima, Nayuta / Takahashi, Shuhei / Fujita, Yoshihiro / Miyazaki, Tomohiko / Higaki, Hajime / Taguchi, Jun / Shimizu, Yasushi / Sakashita, Tomohiro / Homma, Akihiro / Aoyama, Hidefumi

    Discover. Oncology

    2024  Volume 15, Issue 1, Page(s) 18

    Language English
    Publishing date 2024-01-25
    Publishing country United States
    Document type Published Erratum
    ISSN 2730-6011
    ISSN (online) 2730-6011
    DOI 10.1007/s12672-024-00868-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Treatment outcomes of radiotherapy with concurrent weekly cisplatin in older patients with locally advanced head and neck squamous cell carcinoma.

    Uchinami, Yusuke / Yasuda, Koichi / Kano, Satoshi / Otsuka, Manami / Hamada, Seijiro / Suzuki, Takayoshi / Tsushima, Nayuta / Takahashi, Shuhei / Fujita, Yoshihiro / Miyazaki, Tomohiko / Higaki, Hajime / Taguchi, Jun / Shimizu, Yasushi / Sakashita, Tomohiro / Homma, Akihiro / Aoyama, Hidefumi

    Discover. Oncology

    2023  Volume 14, Issue 1, Page(s) 226

    Abstract: Background: Tri-weekly cisplatin and radiotherapy (CDDP + RT) is a standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) but is sometimes challenging to complete in older patients. Weekly CDDP + RT has shown mild ... ...

    Abstract Background: Tri-weekly cisplatin and radiotherapy (CDDP + RT) is a standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) but is sometimes challenging to complete in older patients. Weekly CDDP + RT has shown mild toxicity compared to tri-weekly CDDP + RT for LA-HNSCC and is a promising option for older adults. We aimed to report the treatment outcomes and prognostic factors in patients with LA-HNSCC treated with weekly CDDP + RT.
    Methods: We analyzed patients aged ≥ 70 years who started weekly CDDP + RT for LA-HNSCC between July 2006 and October 2022. LA-HNSCC includes cancer in the oropharynx, hypopharynx, or larynx with a clinical stage of 3 or 4 without distant metastases based on the Union for International Cancer Control staging system 8th edition. The radiation dose of 70 Gy was delivered in 35 fractions by 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, or proton beam therapy. The primary endpoint was the 3-year overall survival (OS), and the secondary endpoints were the 3-year progression-free survival (PFS) and 3-year cause-specific survival (CSS). The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used to evaluate statistical significance. A Cox proportional hazards model was used for the multivariate analysis of prognostic factors.
    Results: The median age of the 49 patients was 72 (range: 70-78) years. The median CDDP dose was 200 (40-280) mg/ m
    Conclusions: Weekly CDDP + RT in older patients led to good survival outcomes with an acceptable rate of adverse events. CDDP should be administered at a dose of at least 200 mg/m
    Language English
    Publishing date 2023-12-08
    Publishing country United States
    Document type Journal Article
    ISSN 2730-6011
    ISSN (online) 2730-6011
    DOI 10.1007/s12672-023-00844-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Brain metastases in Japanese NSCLC patients: prognostic assessment and the use of osimertinib and immune checkpoint inhibitors-retrospective study.

    Higaki, Hajime / Nishioka, Kentaro / Otsuka, Manami / Nishikawa, Noboru / Shido, Motoyasu / Minatogawa, Hideki / Nishikawa, Yukiko / Takashina, Rikiya / Hashimoto, Takayuki / Katoh, Norio / Taguchi, Hiroshi / Kinoshita, Rumiko / Yasuda, Koichi / Mori, Takashi / Uchinami, Yusuke / Koizumi, Fuki / Fujita, Yoshihiro / Takahashi, Shuhei / Hattori, Takahiro /
    Nishiyama, Noriaki / Aoyama, Hidefumi

    Radiation oncology (London, England)

    2023  Volume 18, Issue 1, Page(s) 25

    Abstract: Background: The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA) has not been validated for use with Japanese non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) and the factors impacting survival ... ...

    Abstract Background: The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA) has not been validated for use with Japanese non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) and the factors impacting survival need to be assessed.
    Methods: We retrospectively analyzed 294 NSCLC patients who were newly diagnosed with BM between 2013 and 2020 and had received radiotherapy for BM initially at the Hokkaido Cancer Center. We evaluated the effect on the prognosis of Lung-molGPA items, the expression of PD-L1 (classified as high, low, and no expression), and the treatment history. The main outcome was the survival measured from the day of the diagnosis of BM, and log-rank tests were performed to evaluate the results.
    Results: The median overall survival (OS) times for adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, 2.5‒3.0, and 3.5‒4.0) were 5.5, 14.8, 28.3, and 39.0 months (p < 0.0001), respectively. The median survival times for non-adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, and 2.5‒3.0) were 3.2, 11.0, and 16.0 months (p = 0.0011), respectively. In adenocarcinoma patients with gene mutations, osimertinib significantly improved the outcome (median OS: 34.2 and 17.6 months with and without osimertinib, respectively (p = 0.0164)). There was no significant difference in the OS between patients who were initially treated with tyrosine-kinase inhibitor for BM and those who initially received radiotherapy (p = 0.5337). In patients tested for PD-L1 expression, the median survival times after the diagnosis of BM were 5.6, 22.5, and 9.3 months for the high-, low- and no-expression groups (p = 0.2198), respectively. Also, in patients with high PD-L1 expressions, those with ICI had survival (median OS, 8.6 months) than those without (median OS, 3.6 months).
    Conclusions: We confirmed that Lung-molGPA successfully classified Japanese NSCLC patients with BM by the prognosis. Osimertinib prolonged survival of EGFR-positive NSCLC patients with BM, and ICI was effective in patients with high PD-L1 expressions.
    MeSH term(s) Humans ; Adenocarcinoma/pathology ; B7-H1 Antigen/genetics ; Brain Neoplasms/secondary ; Carcinoma, Non-Small-Cell Lung/pathology ; East Asian People ; Immune Checkpoint Inhibitors ; Lung Neoplasms/pathology ; Mutation ; Prognosis ; Retrospective Studies
    Chemical Substances B7-H1 Antigen ; Immune Checkpoint Inhibitors ; osimertinib (3C06JJ0Z2O)
    Language English
    Publishing date 2023-02-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2224965-5
    ISSN 1748-717X ; 1748-717X
    ISSN (online) 1748-717X
    ISSN 1748-717X
    DOI 10.1186/s13014-023-02218-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Distribution of human papilloma virus genotypes and treatment outcomes in definitive radiotherapy for cervical cancer.

    Kinoshita, Rumiko / Mitamura, Takashi / Kato, Fumi / Hattori, Takahiro / Higaki, Hajime / Takahashi, Shuhei / Fujita, Yoshihiro / Otsuka, Manami / Koizumi, Fuki / Uchinami, Yusuke / Mori, Takashi / Nishioka, Kentaro / Hashimoto, Takayuki / Ito, Yoichi M / Watari, Hidemichi / Aoyama, Hidefumi

    Journal of radiation research

    2022  Volume 64, Issue 2, Page(s) 463–470

    Abstract: Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV ... ...

    Abstract Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38 months (range 4-142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use.
    MeSH term(s) Female ; Humans ; Uterine Cervical Neoplasms/radiotherapy ; Uterine Cervical Neoplasms/pathology ; Human Papillomavirus Viruses ; Papillomavirus Infections ; Papillomaviridae/genetics ; Treatment Outcome ; Genotype
    Language English
    Publishing date 2022-12-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 603983-2
    ISSN 1349-9157 ; 0449-3060
    ISSN (online) 1349-9157
    ISSN 0449-3060
    DOI 10.1093/jrr/rrac086
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Graded Prognostic Assessment (GPA) for Patients With Lung Cancer and Brain Metastases: Initial Report of the Small Cell Lung Cancer GPA and Update of the Non-Small Cell Lung Cancer GPA Including the Effect of Programmed Death Ligand 1 and Other Prognostic Factors.

    Sperduto, Paul W / De, Brian / Li, Jing / Carpenter, David / Kirkpatrick, John / Milligan, Michael / Shih, Helen A / Kutuk, Tugce / Kotecha, Rupesh / Higaki, Hajime / Otsuka, Manami / Aoyama, Hidefumi / Bourgoin, Malie / Roberge, David / Dajani, Salah / Sachdev, Sean / Gainey, Jordan / Buatti, John M / Breen, William /
    Brown, Paul D / Ni, Lisa / Braunstein, Steve / Gallitto, Matthew / Wang, Tony J C / Shanley, Ryan / Lou, Emil / Shiao, Jay / Gaspar, Laurie E / Tanabe, Satoshi / Nakano, Toshimichi / An, Yi / Chiang, Veronica / Zeng, Liang / Soliman, Hany / Elhalawani, Hesham / Cagney, Daniel / Thomas, Evan / Boggs, Drexell H / Ahluwalia, Manmeet S / Mehta, Minesh P

    International journal of radiation oncology, biology, physics

    2022  Volume 114, Issue 1, Page(s) 60–74

    Abstract: Purpose: Patients with lung cancer and brain metastases represent a markedly heterogeneous population. Accurate prognosis is essential to optimally individualize care. In prior publications, we described the graded prognostic assessment (GPA), but a GPA ...

    Abstract Purpose: Patients with lung cancer and brain metastases represent a markedly heterogeneous population. Accurate prognosis is essential to optimally individualize care. In prior publications, we described the graded prognostic assessment (GPA), but a GPA for patients with small cell lung cancer (SCLC) has never been reported, and in non-small cell lung cancer (NSCLC), the effect of programmed death ligand 1 (PD-L1) was unknown. The 3-fold purpose of this work is to provide the initial report of an SCLC GPA, to evaluate the effect of PD-L1 on survival in patients with NSCLC, and to update the Lung GPA accordingly.
    Methods and materials: A multivariable analysis of prognostic factors and treatments associated with survival was performed on 4183 patients with lung cancer (3002 adenocarcinoma, 611 nonadenocarcinoma, 570 SCLC) with newly diagnosed brain metastases between January 1, 2015, and December 31, 2020, using a multi-institutional retrospective database. Significant variables were used to update the Lung GPA.
    Results: Overall median survival for lung adenocarcinoma, SCLC, and nonadenocarcinoma was 17, 10, and 8 months, respectively, but varied widely by GPA from 2 to 52 months. In SCLC, the significant prognostic factors were age, performance status, extracranial metastases, and number of brain metastases. In NSCLC, the distribution of molecular markers among patients with lung adenocarcinoma and known primary tumor molecular status revealed alterations/expression in PD-L1 50% to 100%, PD-L1 1% to 49%, epidermal growth factor receptor, and anaplastic lymphoma kinase in 32%, 31%, 30%, and 7%, respectively. Median survival of patients with lung adenocarcinoma and brain metastases with 0, 1% to 49%, and ≥50% PD-L1 expression was 17, 19, and 24 months, respectively (P < .01), confirming PD-L1 is a prognostic factor. Previously identified prognostic factors for NSCLC (epidermal growth factor receptor and anaplastic lymphoma kinase status, performance status, age, number of brain metastases, and extracranial metastases) were reaffirmed. These factors were incorporated into the updated Lung GPA with robust separation between subgroups for all histologies.
    Conclusions: Survival for patients with lung cancer and brain metastases has improved but varies widely. The initial report of a GPA for SCLC is presented. For patients with NSCLC-adenocarcinoma and brain metastases, PD-L1 is a newly identified significant prognostic factor, and the previously identified factors were reaffirmed. The updated indices establish unique criteria for SCLC, NSCLC-nonadenocarcinoma, and NSCLC-adenocarcinoma (incorporating PD-L1). The updated Lung GPA, available for free at brainmetgpa.com, provides an accurate tool to estimate survival, individualize treatment, and stratify clinical trials.
    MeSH term(s) Adenocarcinoma ; Adenocarcinoma of Lung ; Anaplastic Lymphoma Kinase ; B7-H1 Antigen ; Brain Neoplasms/secondary ; Carcinoma, Non-Small-Cell Lung/pathology ; ErbB Receptors ; Humans ; Lung Neoplasms/pathology ; Prognosis ; Retrospective Studies ; Small Cell Lung Carcinoma
    Chemical Substances B7-H1 Antigen ; Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2022-03-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 197614-x
    ISSN 1879-355X ; 0360-3016
    ISSN (online) 1879-355X
    ISSN 0360-3016
    DOI 10.1016/j.ijrobp.2022.03.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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