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  • Hong, Min Hee  (2)
  • Jung, Inkyung  (2)
  • Park, Young Min  (2)
  • 1
    Online Resource
    Online Resource
    Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
    Springer Science and Business Media LLC ; 2020
    In:  BMC Cancer Vol. 20, No. 1 ( 2020-12)
    Details
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Abstract: We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics. Methods Tumors from HNSCC patients were transplanted into immunodeficient mice and propagated via subsequent implantation. We evaluated established PDXs by histology, genomic profiling, and in vivo anti-cancer efficacy testing to confirm them as the authentic in vivo platform. Results From 62 HNSCCs, 15 (24%) PDXs were established. The primary cancer types were tongue (8), oropharynx (3), hypopharynx (1), ethmoid sinus cancer (1), supraglottic cancer (1), and parotid gland (1); six PDXs (40%) were established from biopsy specimens from advanced HNSCC. PDXs mostly retained donor characteristics and remained stable across passages. PIK3CA (H1047R), HRAS (G12D), and TP53 mutations (H193R, I195T, R248W, R273H, E298X) and EGFR , CCND1 , MYC , and PIK3CA amplifications were identified. Using the acquisition method, biopsy showed a significantly higher engraftment rate when compared with that of surgical resection (100% [6/6] vs. 16.1% [9/56] , P   〈  0.001). Specimens obtained from metastatic sites showed a significantly higher engraftment rate than did those from primary sites (100% [9/9] vs. 11.3% [6/53] , P   〈  0.001). Three PDX models from HPV-positive tumors were established, as compared to 12 from HPV-negative (15.8% [3/19] and 27.9% [12/43] respectively, P  = 0.311), suggesting that HPV positivity tends to show a low engraftment rate. Drug responses in PDX recapitulated the clinical responses of the matching patients with pan-HER inhibitors and pan-PI3K inhibitor. Conclusions Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    URL: Article
    DOI: 10.1186/s12885-020-06786-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041352-X
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  • 2
    Online Resource
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    Preoperative durvalumab (D) with or without tremelimumab (T) for resectable head and neck squamous cell carcinoma (HNSCC): Updated results with high dimensional profiling of circulating immune cells.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 6072-6072
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 6072-6072
    Abstract: 6072 Background: Although PD-1 blockade has improved survival in patients with recurrent and/or metastatic HNSCC, safety and efficacy of neoadjuvant immunotherapy with PD-L1 inhibitor with or without CTLA-4 inhibitor has not been investigated. Here, we report the updated results of the safety and efficacy of a preoperative D with or without T (D+/-T) in patients with resectable HNSCC, accompanied with high dimensional profiling of circulating immune cells. Methods: Patients with locally advanced but resectable HNSCC were eligible. Enrolled patients were randomized into D or D+T, stratified by primary site and human papilloma virus (HPV) infection status. A single dose of preoperative D (1500mg) or D+T (1500mg+75mg) was administered, with surgery planned 2 to 8 weeks later for curative resection. Postoperative (chemo) radiation was prescribed based on standard guidelines, followed by maintenance with D every 4 weeks for 1 year. Dynamic changes in circulating immune cells were tracked with mass cytometry. The primary objective was to determine the local recurrence rate. Secondary endpoints included pathologic response, safety, survival outcome, and exploration of immune dynamics. Results: As of January 25th 2022 for the interim analysis, a total of 45 patients were completely enrolled and received surgical resection (D: 21 patients, D+T: 24 patients). Oropharyngeal cancer was most common (n = 23; 51.1%) and HPV-mediated cancer was observed in 20 patients (44.4%). Neoadjuvant D+/-T had acceptable safety profiles and was not associated with delays in surgery or unexpected adverse events. Tumor shrinkage was observed in 31 patients (68.9%), with 15.6% of average tumor shrinkage (range; 100.0% to -80.0%). Major pathologic response (no more than 10% of viable tumor cells) was achieved in 3 patients (6.7%), including 2 cases with pathologic complete response (4.4%). During median follow-up duration of 407 days after surgery, local recurrence and systemic recurrence were documented in 9 patients (20.0%) and 7 patients (15.6%), respectively. Median disease-free survival and overall survival was 910 days and not reached, respectively. High dimensional immune profiling with mass cytometry revealed that D+T disproportionally increased the frequency of regulatory T cells accompanied with the upregulation of their functional markers, which was absent in patients treated with D monotherapy. Conclusions: These updated data suggested that preoperative D+/-T was safe and feasible and had the potential to provide clinical benefits for patients with resectable HNSCC. Distinct immunologic changes in circulating immune cells were induced by each treatment regimen, warranting further investigation. The trial is ongoing and the updated outcomes with immune correlates will be presented in this ASCO. Clinical trial information: NCT03737968.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.6072
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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