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1.
Onco Targets Ther ; 16: 1015-1020, 2023.
Article in English | MEDLINE | ID: mdl-38050583

ABSTRACT

Objective: Combined small cell lung cancer (C-SCLC) is a relatively rare subtype of small cell lung cancer (SCLC) which combines SCLC and any component of non-small cell carcinoma (NSCLC). Patients diagnosed with C-SCLC are currently recommended to receive the same treatment as SCLC cases in the absence of clear evidence suggesting different strategies. The genomic profiling of C-SCLC is rarely studied. Herein, we report a case of extensive-stage C-SCLC harboring the KIF5B-RET fusion before first-line therapy and with persistent sensitivity to fourth-line selpercatinib treatment is reported. Materials and Methods: Molecular and pathological features were evaluated using transbronchial lung biopsy, immunohistochemical (IHC) staining and next-generation sequencing (NGS). Results: NGS revealed the KIF5B-RET fusion in the C-SCLC tumor. The patient had a progression-free survival (PFS) surpassing 14 months after selpercatinib treatment, with ongoing clinical response in 4th-line treatment. Conclusion: This case highlights the importance of comprehensive molecular testing in C-SCLC for selecting the optimal treatment. Although RET fusion is rare in patients with C-SCLC, its identification and treatment with selective RET inhibitors may contribute to clinical benefits.

2.
J Cancer Res Clin Oncol ; 149(10): 7247-7258, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36907910

ABSTRACT

PURPOSE: We aim to explore the predictive value of neuroendocrine differentiation (NED) in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone or docetaxel as first-line therapy. METHODS: We retrospectively analyzed data of 262 mCRPC patients receiving abiraterone or docetaxel as first-line mCRPC treatment. NED was evaluated using prostate biopsy samples at the time of mCRPC by immunohistochemical staining. Kaplan-Meier curves and Cox regression were used to assess the association between NED and treatment outcomes including PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS). RESULTS: NED was confirmed in 100/262 (38.2%) mCRPC patients, with 76/100 (76.0%) and 24/100 (24.0%) men harboring NED < 10% and NED ≥ 10%, respectively. 203/262 (77.5%) and 59/262 (22.5%) patients received abiraterone and docetaxel, respectively. In abiraterone treatment, NED was associated with a significantly shorter median PSA-PFS (mPSA-PFS, 7.5 vs. 10.3-Mo, P < 0.001), median rPFS (mrPFS, 15.9 vs. 19.5-Mo, P = 0.010), and median OS (mOS, 23.2 vs. 34.3-Mo, P = 0.014)). Likewise, for mCRPC patients receiving docetaxel, the positive detection of NED also predicted shorter mPSA-PFS (3.8 vs. 5.9-Mo, P = 0.052), mrPFS (8.4 vs. 20.4-Mo, P = 0.016) and mOS (13.6 vs. 29.0-Mo, P = 0.033). The adverse prognostic trait of NED is consistent in most subgroups. Additionally, patients' survival outcomes deteriorated as the NED proportion grew in both therapies. After propensity score matching, NED-positive patients showed comparable prognosis in abiraterone and docetaxel therapy. CONCLUSION: For mCRPC patients receiving abiraterone or docetaxel, NED and its proportion were critical predictive factors. NED detection at mCRPC might aid in predicting patients' outcomes and optimizing treatment decisions.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Male , Humans , Female , Docetaxel , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Prostate-Specific Antigen , Retrospective Studies , Treatment Outcome , Disease-Free Survival , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
3.
BMC Med ; 20(1): 237, 2022 07 22.
Article in English | MEDLINE | ID: mdl-35864546

ABSTRACT

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort. METHODS: This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method. RESULTS: The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort. CONCLUSIONS: M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.


Subject(s)
Adenocarcinoma , Carcinoma, Intraductal, Noninfiltrating , Prostatic Neoplasms , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Intraductal, Noninfiltrating/pathology , Homologous Recombination/genetics , Humans , Male , Prostate/pathology , Prostatic Neoplasms/pathology
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