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  • 1
    In: BMJ Open, BMJ, Vol. 13, No. 1 ( 2023-01), p. e062659-
    Abstract: Neoadjuvant chemotherapy (NAC) has been demonstrated effective in several tumours, but its benefit has not yet been elucidated in colorectal cancer, especially locally advanced colorectal cancer (LACRC). Methods and analysis This is a single-arm, open-label, prospective phase II exploratory clinical trial. Patients with LACRC will receive four cycles of NAC with 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI), followed by operation and then adjuvant chemotherapy with capecitabine and oxaliplatin for two to five cycles or single-agent capecitabine for five cycles, or observation. The primary endpoint is the rate of tumour regression grade (TRG) 0–2 in the resected tumour tissue, which is evaluated by experienced pathologists according to the Ryan R TRG grading system. Secondary endpoints include objective response rate, pathologic complete response, microscopically complete resection rate, progression-free survival, distant metastasis-free survival, overall survival, toxicity and compliance to study treatment, molecular markers, quality of life to study treatment and the number of patients with 30-day postoperative mortality. The objective of this study is to analyse the efficacy and safety of FOLFOXIRI as the NAC regimen in patients with LACRC and to identify a promising treatment strategy in this setting. Ethics and dissemination Written informed consent will be required from and provided by all patients enrolled. The study protocol has been approved by the independent ethics committee of West China Hospital, Sichuan University (approval number: 2021403). This study will demonstrate the potential benefit of NAC with the FOLFOXIRI regimen. Results will be shared with policymakers and the academic community to promote the clinical management of colon cancer. Trial registration number NCT05018182 .
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2599832-8
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  • 2
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 10, No. 2 ( 2022-02), p. e003716-
    Abstract: Although immune checkpoint blockade (ICB) has been proven to achieve a persistent therapeutic response in various tumor types, only 20%–40% of patients benefit from this treatment. Radiotherapy (RT) can enhance tumor immunogenicity and improve the ICB response, but the outcome achieved by combining these two modalities remains clinically unsatisfactory. We previously uncovered that lysine-specific demethylase 4C (KDM4C) is a regulator of radiosensitivity in lung cancer. However, the role of KDM4C in antitumor immunity has not yet been investigated. Methods Infiltrating immune cells in our mouse tumor model were screened by flow cytometry. An in vivo subcutaneous transplanted tumor model and in vitro conditioned culture model were constructed to detect the quantitative and functional changes in CD8 + T cells. RNA sequencing and chromatin immunoprecipitation-PCR assays were used to explore the downstream regulatory mechanism of KDM4C in antitumor immunity. A C57BL/6 mouse tumor model was developed to evaluate the efficacy and safety of a triple therapy (the KDM4C-specific inhibitor SD70 plus RT and an anti-PD-L1 antibody) in lung cancer in vivo. Results Genetical or pharmacological inhibition of KDM4C specifically increased CD8 + T cell infiltration; promoted the proliferation, migration and activation of CD8 + T cells; and alleviated CD8 + T cell exhaustion in mouse tumor tissues. Mechanistically, KDM4C inhibition increased the binding of H3K36me3 to the CXCL10 promoter region, thus inducing CXCL10 transcription and enhancing the CD8 + T cell mediated antitumor immune response. More importantly, among the tested regimens, the triple therapy achieved the best therapeutic efficacy with tolerable toxicity in lung cancer. Conclusions Our data reveal a crucial role for KDM4C in antitumor immunity in lung cancer and indicate that targeting KDM4C in combination with radioimmunotherapy might be a promising synergistic strategy in lung cancer.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 2719863-7
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  • 3
    Online Resource
    Online Resource
    BMJ ; 2017
    In:  Archives of Disease in Childhood Vol. 102, No. 12 ( 2017-12), p. 1185-1185
    In: Archives of Disease in Childhood, BMJ, Vol. 102, No. 12 ( 2017-12), p. 1185-1185
    Type of Medium: Online Resource
    ISSN: 0003-9888 , 1468-2044
    Language: English
    Publisher: BMJ
    Publication Date: 2017
    detail.hit.zdb_id: 1481191-1
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  • 4
    Online Resource
    Online Resource
    BMJ ; 2019
    In:  International Journal of Gynecologic Cancer Vol. 29, No. 8 ( 2019-10), p. 1264-1270
    In: International Journal of Gynecologic Cancer, BMJ, Vol. 29, No. 8 ( 2019-10), p. 1264-1270
    Abstract: Vaginal brachytherapy was recommended for patients with intermediate-risk endometrial cancer, however, optimal radiotherapy modalities for intermediate-high- or high-risk patients remains controversial. Previous studies have mainly focused on survival outcomes and have seldom taken cost issues into consideration, especially for high-risk patients. The purpose of this study is to compare the survival outcomes and costs associated with two adjuvant radiotherapy modalities in the management of patients with early-stage, intermediate- to high-risk endometrial cancer. Methods According to ESMO-ESCO-ESTRO criteria, 238 patients with stage I/II, intermediate- to high-risk endometrial cancer who underwent radiotherapy from January 2003 to December 2015 at our institution were reviewed. The vaginal brachytherapy group and external beam radiation therapy combined with the vaginal brachytherapy group were propensity score-matched at a 1:1 ratio. The Kaplan–Meier method and Cox proportional hazards regression model were used. Results A total of 361 patients met our inclusion criteria, the median age of the patients was 58 years (range, 28–85). All were diagnosed with stage I–II endometrial cancer (324 with stage I and 37 with stage II; 350 with endometrioid adenocarcinoma; and 10 with mucinous carcinoma). The median follow-up time was 60.5 months (range, 3–177). Among 119 matched pairs, no significant differences were found in overall (10.9% vs 8.4%, P=0.51), locoregional (4.2% vs 1.7%, P=0.45), or distant recurrence rates (6.7% vs 6.7%, P=1.0) between the two groups. There were also no differences in the 5-year overall (94.8% vs 93.9%, P=0.78) or progression-free survival (90.0% vs 84.4%, P=0.23) between the two groups. The rates of acute and late toxicity were significantly higher in the external beam radiation therapy combined with vaginal brachytherapy vs the vaginal brachytherapy group (all P 〈 0.05), except for the acute hematological toxicity rate (17.6% vs 9.2%, P=0.06). External beam radiation therapy combined with vaginal brachytherapy had a higher median cost ($2759 vs $937, P 〈 0.001) and longer median radiotherapy duration (41 days vs 17 days, P 〈 0.001) than vaginal brachytherapy. Conclusion Vaginal brachytherapy was associated with similar local control and long-term survival outcomes relative to the combination of external beam radiotherapy and vaginal brachytherapy and it also minimizes radiation-related complications, reduces medical costs, and shortens radiotherapy duration. Vaginal brachytherapy may be the optimal radiation modality for patients with early-stage endometrial cancer at intermediate to high risk.
    Type of Medium: Online Resource
    ISSN: 1048-891X , 1525-1438
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2009072-9
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