1.Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy
Hyunki PARK ; Haeyoung KIM ; Won PARK ; Won Kyung CHO ; Nalee KIM ; Tae Gyu KIM ; Young-Hyuck IM ; Jin Seok AHN ; Yeon Hee PARK ; Ji-Yeon KIM ; Seok Jin NAM ; Seok Won KIM ; Jeong Eon LEE ; Jonghan YU ; Byung Joo CHAE ; Sei Kyung LEE ; Jai-Min RYU
Radiation Oncology Journal 2024;42(3):210-217
Purpose:
This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC).
Materials and Methods:
We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45–65 Gy in 15–30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan–Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model.
Results:
During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00–3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57–14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI.
Conclusion
In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.
2.Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy
Hyunki PARK ; Haeyoung KIM ; Won PARK ; Won Kyung CHO ; Nalee KIM ; Tae Gyu KIM ; Young-Hyuck IM ; Jin Seok AHN ; Yeon Hee PARK ; Ji-Yeon KIM ; Seok Jin NAM ; Seok Won KIM ; Jeong Eon LEE ; Jonghan YU ; Byung Joo CHAE ; Sei Kyung LEE ; Jai-Min RYU
Radiation Oncology Journal 2024;42(3):210-217
Purpose:
This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC).
Materials and Methods:
We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45–65 Gy in 15–30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan–Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model.
Results:
During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00–3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57–14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI.
Conclusion
In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.
3.Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy
Hyunki PARK ; Haeyoung KIM ; Won PARK ; Won Kyung CHO ; Nalee KIM ; Tae Gyu KIM ; Young-Hyuck IM ; Jin Seok AHN ; Yeon Hee PARK ; Ji-Yeon KIM ; Seok Jin NAM ; Seok Won KIM ; Jeong Eon LEE ; Jonghan YU ; Byung Joo CHAE ; Sei Kyung LEE ; Jai-Min RYU
Radiation Oncology Journal 2024;42(3):210-217
Purpose:
This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC).
Materials and Methods:
We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45–65 Gy in 15–30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan–Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model.
Results:
During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00–3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57–14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI.
Conclusion
In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.
4.Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study (K-MASTER-13)
Dong-Hoe KOO ; Minkyu JUNG ; Yeul Hong KIM ; Hei-Cheul JEUNG ; Dae Young ZANG ; Woo Kyun BAE ; Hyunki KIM ; Hyo Song KIM ; Choong-kun LEE ; Woo Sun KWON ; Hyun Cheol CHUNG ; Sun Young RHA
Cancer Research and Treatment 2024;56(4):1136-1145
Purpose:
Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC).
Materials and Methods:
Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity.
Results:
RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D.
Conclusion
A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.
5.Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists
Soomin AHN ; Yoonjin KWAK ; Gui Young KWON ; Kyoung-Mee KIM ; Moonsik KIM ; Hyunki KIM ; Young Soo PARK ; Hyeon Jeong OH ; Kyoungyul LEE ; Sung Hak LEE ; Hye Seung LEE
Journal of Pathology and Translational Medicine 2024;58(3):103-116
Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2–negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti–programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.
6.Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy
Hyunki PARK ; Haeyoung KIM ; Won PARK ; Won Kyung CHO ; Nalee KIM ; Tae Gyu KIM ; Young-Hyuck IM ; Jin Seok AHN ; Yeon Hee PARK ; Ji-Yeon KIM ; Seok Jin NAM ; Seok Won KIM ; Jeong Eon LEE ; Jonghan YU ; Byung Joo CHAE ; Sei Kyung LEE ; Jai-Min RYU
Radiation Oncology Journal 2024;42(3):210-217
Purpose:
This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC).
Materials and Methods:
We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45–65 Gy in 15–30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan–Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model.
Results:
During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00–3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57–14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI.
Conclusion
In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.
7.Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy
Hyunki PARK ; Haeyoung KIM ; Won PARK ; Won Kyung CHO ; Nalee KIM ; Tae Gyu KIM ; Young-Hyuck IM ; Jin Seok AHN ; Yeon Hee PARK ; Ji-Yeon KIM ; Seok Jin NAM ; Seok Won KIM ; Jeong Eon LEE ; Jonghan YU ; Byung Joo CHAE ; Sei Kyung LEE ; Jai-Min RYU
Radiation Oncology Journal 2024;42(3):210-217
Purpose:
This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC).
Materials and Methods:
We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45–65 Gy in 15–30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan–Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model.
Results:
During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00–3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57–14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI.
Conclusion
In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.
8.A Standardized Pathology Report for Gastric Cancer: 2nd Edition
Young Soo PARK ; Myeong-Cherl KOOK ; Baek-hui KIM ; Hye Seung LEE ; Dong-Wook KANG ; Mi-Jin GU ; Ok Ran SHIN ; Younghee CHOI ; Wonae LEE ; Hyunki KIM ; In Hye SONG ; Kyoung-Mee KIM ; Hee Sung KIM ; Guhyun KANG ; Do Youn PARK ; So-Young JIN ; Joon Mee KIM ; Yoon Jung CHOI ; Hee Kyung CHANG ; Soomin AHN ; Mee Soo CHANG ; Song-Hee HAN ; Yoonjin KWAK ; An Na SEO ; Sung Hak LEE ; Mee-Yon CHO ;
Journal of Gastric Cancer 2023;23(1):107-145
The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements.The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
9.A standardized pathology report for gastric cancer: 2nd edition
Young Soo PARK ; Myeong-Cherl KOOK ; Baek-hui KIM ; Hye Seung LEE ; Dong-Wook KANG ; Mi-Jin GU ; Ok Ran SHIN ; Younghee CHOI ; Wonae LEE ; Hyunki KIM ; In Hye SONG ; Kyoung-Mee KIM ; Hee Sung KIM ; Guhyun KANG ; Do Youn PARK ; So-Young JIN ; Joon Mee KIM ; Yoon Jung CHOI ; Hee Kyung CHANG ; Soomin AHN ; Mee Soo CHANG ; Song-Hee HAN ; Yoonjin KWAK ; An Na SEO ; Sung Hak LEE ; Mee-Yon CHO ;
Journal of Pathology and Translational Medicine 2023;57(1):1-27
The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
10.Preclinical investigation of patient-derived cervical cancer organoids for precision medicine
Hyang Sook SEOL ; Ju Hee OH ; Eunhye CHOI ; SangMin KIM ; Hyunki KIM ; Eun Ji NAM
Journal of Gynecologic Oncology 2023;34(3):e35-
Objective:
Advanced cervical cancer is still difficult to treat and in the case of recurrent cancer, it is desirable to utilize personalized treatment rather than uniform treatment because the type of recurrence is different for each individual. Therefore, this study aimed to establish a patient-derived organoid (PDO) platform to determine the effects of chemotherapy, radiation therapy, and targeted therapy in cervical cancer.
Methods:
We established organoids from 4 patients with various types of cervical cancer. The histopathological and gene profiles of these organoid models were compared to determine their characteristics and the maintenance of the patient phenotype. Each type of organoid was also subjected to anticancer drug screening and radiation therapy to evaluate its sensitivity.
Results:
We established PDOs to recapitulate the main elements of the original patient tumors, including the DNA copy number and mutational profile. We selected 7 drugs that showed growth inhibition in cervical cancer organoids out of 171 using an Food and Drug Administration -approved drug library. Moreover, adenocarcinoma and large-cell neuroendocrine carcinoma showed resistance to radiation therapy. whereas squamous cell carcinoma and villoglandular carcinoma showed a significant response to radiotherapy.
Conclusion
Our results showed that patient-derived cervical cancer organoids can be used as a platform for drug and radiation sensitivity testing. These findings suggest that patient-derived cervical cancer organoids could be used as a personalized medicine platform and may provide the best treatment options for patients with various subtypes of cervical cancer.

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