Purpose: While TP53 mutations are well known to be associated with adverse prognosis in hematological diseases, their functional impact remains incompletely understood. This study examines the spectrum of TP53 mutations across various hematologic malignancies and evaluates their functional impact. Materials and Methods: Using targeted sequencing panels, we analyzed TP53 mutations in the bone marrow aspiration samples of a retrospective cohort of 856 patients diagnosed with hematologic malignancies. To assess the impact of TP53 mutations, we applied the evolutionary action (EAp53) score and the relative fitness score (RFS), previously proposed functional scoring methods. The effects of variant allele frequency (VAF), disruptive mutations, EAp53 score, and RFS on overall survival (OS) were evaluated. Results: TP53 mutations were associated with inferior OS compared with wildtype TP53 (median OS 10.0 months versus not estimable; hazard ratio (HR) 4.6; p<0.001). In the acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome subgroups, TP53 mutations had a significant adverse impact on OS. (HRs 3.8, 4.2, 6.0, respectively; p<0.001, p=0.005, p<0.001, respectively). Patients with VAF >50% had significantly poorer OS compared to those with VAF ≤50% (median OS 7.5 months versus 22.8 months; HR 2.2, p=0.016). Moreover, patients in the high-risk RFS group (RFS >0.22) had significantly worse OS compared to those in the low-risk RFS group (RFS ≤0.22) (median OS 5.6 months versus 16.3 months; HR 2.2, p=0.041). However, no significant survival difference was observed between the EAp53 high-risk (>75) and low-risk (≤75) groups, or between patients with disruptive and non-disruptive mutations. Conclusion Our findings highlight VAF and RFS as valuable tools for stratifying TP53-mutant patients into high-risk and low-risk groups.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Background and Objectives: We analyzed the data of oropharyngeal squamous cell carcinoma (OPSCC) patients who had transoral surgery with/without adjuvant therapy and experienced recurrence. From the data, the treatment outcomes and prognostic factors of recurrent OPSCC were evaluated, and the predictive factors related to successful salvage treatment were identified.Subjects and Method We used data from patients who were diagnosed with OPSCC and received transoral surgery at the hospital from January 2005 to December 2019. Results: The 5-year survival rate of patients with recurrent OPSCC was 43.9%. The predictors of successful salvage treatment were adjuvant therapy and the p16 status. The 5-year survival rate following salvage treatment for patients who had recurrent OPSCC and also tested p16-positive was 64%; however, it was only 30% for patients who had recurrent OPSCC and tested p16-negative. The 5-year survival rate was 22% for patients who received adjuvant therapy and 64% for those who did not receive it. Conclusion In OPSCC patients who recurred after transoral surgery with/without adjuvant therapy, the salvage treatment success rate was 45%. In recurrent cancer, the HPV status was an important factor associated with successful salvage treatment, as the success rate of salvage treatment was remarkably high in patients who did not receive adjuvant therapy. Thus, we verified that it is crucial to conduct an initial surgery with clear margins and determine the optimal criteria for adjuvant therapy.

Background and Objectives: We analyzed the treatment results and prognostic factors of stage IV oral tongue squamous cell carcinoma (OTSCC) patients and explored the existence of subgroups with distinctive prognoses. In addition, the outcome of salvage therapy was analyzed in recurrent cases, and the survival rates and prognostic factors were investigated.Subjects and Method This study was conducted on patients who were diagnosed with OTSCC and underwent surgery at our hospital between June 2005 and January 2020. A total of 144 patients with stage IV OTSCC was enrolled. Results: A total of 64 recurrences, local (6), regional (21), distant metastasis (33), and locoregional (4), occurred. Seventy-five patients died because of disease progression during the course of study. The 5-year recurrence-free survival rate was 54.5%, and the 5-year disease-specific survival rate was 49.2%. Surgical margins, lymphovascular invasion (LVI), T classification, and lymph nodes (LNs) metastasis exhibited significant correlation with mortality. LVI and advanced T were statistically important factors for predicting distant metastasis. The treatment outcome of the T4N0 patient group without LN metastasis fared the best, while the treatment outcome of the T4N1-3 patient group with advanced T and N findings was the worst. Conclusion The major type of treatment failure in stage IV OTSCC patients was distant metastasis, and the related predictors of distant metastasis were LVI and advanced T. In the stage IV OTSCC patient group, there were subgroups with distinct prognosis according to the combination of T and N classification. The T4N0 group had the best survival rate, and the T4N1-3 group had the worst prognosis.

Background and Objectives: We analyzed the data of oropharyngeal squamous cell carcinoma (OPSCC) patients who had transoral surgery with/without adjuvant therapy and experienced recurrence. From the data, the treatment outcomes and prognostic factors of recurrent OPSCC were evaluated, and the predictive factors related to successful salvage treatment were identified.Subjects and Method We used data from patients who were diagnosed with OPSCC and received transoral surgery at the hospital from January 2005 to December 2019. Results: The 5-year survival rate of patients with recurrent OPSCC was 43.9%. The predictors of successful salvage treatment were adjuvant therapy and the p16 status. The 5-year survival rate following salvage treatment for patients who had recurrent OPSCC and also tested p16-positive was 64%; however, it was only 30% for patients who had recurrent OPSCC and tested p16-negative. The 5-year survival rate was 22% for patients who received adjuvant therapy and 64% for those who did not receive it. Conclusion In OPSCC patients who recurred after transoral surgery with/without adjuvant therapy, the salvage treatment success rate was 45%. In recurrent cancer, the HPV status was an important factor associated with successful salvage treatment, as the success rate of salvage treatment was remarkably high in patients who did not receive adjuvant therapy. Thus, we verified that it is crucial to conduct an initial surgery with clear margins and determine the optimal criteria for adjuvant therapy.

Background and Objectives: We analyzed the treatment results and prognostic factors of stage IV oral tongue squamous cell carcinoma (OTSCC) patients and explored the existence of subgroups with distinctive prognoses. In addition, the outcome of salvage therapy was analyzed in recurrent cases, and the survival rates and prognostic factors were investigated.Subjects and Method This study was conducted on patients who were diagnosed with OTSCC and underwent surgery at our hospital between June 2005 and January 2020. A total of 144 patients with stage IV OTSCC was enrolled. Results: A total of 64 recurrences, local (6), regional (21), distant metastasis (33), and locoregional (4), occurred. Seventy-five patients died because of disease progression during the course of study. The 5-year recurrence-free survival rate was 54.5%, and the 5-year disease-specific survival rate was 49.2%. Surgical margins, lymphovascular invasion (LVI), T classification, and lymph nodes (LNs) metastasis exhibited significant correlation with mortality. LVI and advanced T were statistically important factors for predicting distant metastasis. The treatment outcome of the T4N0 patient group without LN metastasis fared the best, while the treatment outcome of the T4N1-3 patient group with advanced T and N findings was the worst. Conclusion The major type of treatment failure in stage IV OTSCC patients was distant metastasis, and the related predictors of distant metastasis were LVI and advanced T. In the stage IV OTSCC patient group, there were subgroups with distinct prognosis according to the combination of T and N classification. The T4N0 group had the best survival rate, and the T4N1-3 group had the worst prognosis.

Background and Objectives: We analyzed the data of oropharyngeal squamous cell carcinoma (OPSCC) patients who had transoral surgery with/without adjuvant therapy and experienced recurrence. From the data, the treatment outcomes and prognostic factors of recurrent OPSCC were evaluated, and the predictive factors related to successful salvage treatment were identified.Subjects and Method We used data from patients who were diagnosed with OPSCC and received transoral surgery at the hospital from January 2005 to December 2019. Results: The 5-year survival rate of patients with recurrent OPSCC was 43.9%. The predictors of successful salvage treatment were adjuvant therapy and the p16 status. The 5-year survival rate following salvage treatment for patients who had recurrent OPSCC and also tested p16-positive was 64%; however, it was only 30% for patients who had recurrent OPSCC and tested p16-negative. The 5-year survival rate was 22% for patients who received adjuvant therapy and 64% for those who did not receive it. Conclusion In OPSCC patients who recurred after transoral surgery with/without adjuvant therapy, the salvage treatment success rate was 45%. In recurrent cancer, the HPV status was an important factor associated with successful salvage treatment, as the success rate of salvage treatment was remarkably high in patients who did not receive adjuvant therapy. Thus, we verified that it is crucial to conduct an initial surgery with clear margins and determine the optimal criteria for adjuvant therapy.

Background and Objectives: We analyzed the treatment results and prognostic factors of stage IV oral tongue squamous cell carcinoma (OTSCC) patients and explored the existence of subgroups with distinctive prognoses. In addition, the outcome of salvage therapy was analyzed in recurrent cases, and the survival rates and prognostic factors were investigated.Subjects and Method This study was conducted on patients who were diagnosed with OTSCC and underwent surgery at our hospital between June 2005 and January 2020. A total of 144 patients with stage IV OTSCC was enrolled. Results: A total of 64 recurrences, local (6), regional (21), distant metastasis (33), and locoregional (4), occurred. Seventy-five patients died because of disease progression during the course of study. The 5-year recurrence-free survival rate was 54.5%, and the 5-year disease-specific survival rate was 49.2%. Surgical margins, lymphovascular invasion (LVI), T classification, and lymph nodes (LNs) metastasis exhibited significant correlation with mortality. LVI and advanced T were statistically important factors for predicting distant metastasis. The treatment outcome of the T4N0 patient group without LN metastasis fared the best, while the treatment outcome of the T4N1-3 patient group with advanced T and N findings was the worst. Conclusion The major type of treatment failure in stage IV OTSCC patients was distant metastasis, and the related predictors of distant metastasis were LVI and advanced T. In the stage IV OTSCC patient group, there were subgroups with distinct prognosis according to the combination of T and N classification. The T4N0 group had the best survival rate, and the T4N1-3 group had the worst prognosis.