1.Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial)
Bo Seong YUN ; Kwang-Beom LEE ; Keun Ho LEE ; Ha Kyun CHANG ; Joo-Young KIM ; Myong Cheol LIM ; Chel Hun CHOI ; Hanbyoul CHO ; Dae-Yeon KIM ; Yun Hwan KIM ; Joong Sub CHOI ; Chae Hyeong LEE ; Jae-Weon KIM ; Sang Wun KIM ; Yong Bae KIM ; Chi-Heum CHO ; Dae Gy HONG ; Yong Jung SONG ; Seob JEON ; Min Kyu KIM ; Dae Hoon JEONG ; Hyun PARK ; Seok Mo KIM ; Sang-Il PARK ; Jae-Yun SONG ; Asima MUKHOPADHYAY ; Dang Huy Quoc THINH ; Nirmala Chandralega KAMPAN ; Grace J. LEE ; Jae-Hoon KIM ; Keun-Yong EOM ; Ju-Won ROH
Journal of Gynecologic Oncology 2024;35(5):e57-
Background:
Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests.
Methods
The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.
2.Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial)
Bo Seong YUN ; Kwang-Beom LEE ; Keun Ho LEE ; Ha Kyun CHANG ; Joo-Young KIM ; Myong Cheol LIM ; Chel Hun CHOI ; Hanbyoul CHO ; Dae-Yeon KIM ; Yun Hwan KIM ; Joong Sub CHOI ; Chae Hyeong LEE ; Jae-Weon KIM ; Sang Wun KIM ; Yong Bae KIM ; Chi-Heum CHO ; Dae Gy HONG ; Yong Jung SONG ; Seob JEON ; Min Kyu KIM ; Dae Hoon JEONG ; Hyun PARK ; Seok Mo KIM ; Sang-Il PARK ; Jae-Yun SONG ; Asima MUKHOPADHYAY ; Dang Huy Quoc THINH ; Nirmala Chandralega KAMPAN ; Grace J. LEE ; Jae-Hoon KIM ; Keun-Yong EOM ; Ju-Won ROH
Journal of Gynecologic Oncology 2024;35(5):e57-
Background:
Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests.
Methods
The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.
3.Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial)
Bo Seong YUN ; Kwang-Beom LEE ; Keun Ho LEE ; Ha Kyun CHANG ; Joo-Young KIM ; Myong Cheol LIM ; Chel Hun CHOI ; Hanbyoul CHO ; Dae-Yeon KIM ; Yun Hwan KIM ; Joong Sub CHOI ; Chae Hyeong LEE ; Jae-Weon KIM ; Sang Wun KIM ; Yong Bae KIM ; Chi-Heum CHO ; Dae Gy HONG ; Yong Jung SONG ; Seob JEON ; Min Kyu KIM ; Dae Hoon JEONG ; Hyun PARK ; Seok Mo KIM ; Sang-Il PARK ; Jae-Yun SONG ; Asima MUKHOPADHYAY ; Dang Huy Quoc THINH ; Nirmala Chandralega KAMPAN ; Grace J. LEE ; Jae-Hoon KIM ; Keun-Yong EOM ; Ju-Won ROH
Journal of Gynecologic Oncology 2024;35(5):e57-
Background:
Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests.
Methods
The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.
4.The effectiveness of systemic and endovascular intra-arterial thrombectomy protocol for decreasing door-to-recanalization time duration
Su Chel KIM ; Chang-Young LEE ; Chang-Hyun KIM ; Sung-Il SOHN ; Jeong-Ho HONG ; Hyungjong PARK
Journal of Cerebrovascular and Endovascular Neurosurgery 2022;24(1):24-35
Objective:
Variable treatment strategies and protocols have been applied to reduce time durations in the process of acute stroke management. The aim of this study is to investigate the effectiveness of our intra-arterial thrombectomy (IAT) protocol for decreasing door-to-recanalization time duration and improve successful recanalization.
Methods:
A systemic and endovascular protocol included door-to-image, image-to-puncture and puncture-to-recanalization. We retrospectively analyzed the patients of pre- (Sep 2012–Apr 2014) and post-IAT protocol (May 2014–Jul 2018). Univariate analysis was used for the statistical significance according to variable factors (age, gender, the location of occluded vessel, successful recanalization TICI 2b-3). Independent t-test was used to compare the time duration.
Results:
Among all 267 patients with acute stroke of anterior circulation, there were 50 and 217 patients with pre- and post-IAT protocol. Age, gender, and the location of occluded vessel have no statistical significance (p>0.05). In pre- and post-IAT group, successful recanalization was 39 of 50 (78.0%) and 185/217 (85.3%), respectively (p<0.05). Post-IAT (48.8%, 106/217) group had a higher tendency of good outcome than pre-IAT group (36.0%, 18/50) (p>0.05). Pre- and post-IAT group showed 61.7±21.4 vs. 25±16.0 (p<0.05), 102.0±29.8 vs. 82.7±30.4 (min) (p<0.05), and 79.1±47.5 vs. 58.4±75.3 (p<0.05) in three steps, respectively.
Conclusions
We suggest that the application of systemic and endovascular IAT protocols showed a significant time reduction for faster recanalization in patients with LVO. To build-up the well-designed IAT protocol through puncture-to-recanalization can be needed to decrease time duration and improve clinical outcome in recanalization therapy in acute stroke patients.
5.Effect of Waiting Time from Pathological Diagnosis to Definitive Concurrent Chemoradiation for Cervical Cancer on Overall Survival
Kyoung Won NOH ; Bomi KIM ; Chel Hun CHOI ; Tae-Joong KIM ; Jeong-Won LEE ; Byoung-Gie KIM ; Duk-Soo BAE ; Won Kyung CHO ; Won PARK ; Yoo-Young LEE
Cancer Research and Treatment 2022;54(1):245-252
Purpose:
This study aimed to evaluate the effect of waiting time, from diagnosis to initiation of definitive concurrent chemoradiation (CCRT), on overall survival in cervical cancer patients.
Materials and Methods:
Patients with cervical cancer who were treated with definitive CCRT between 2000 and 2017 were retrospectively reviewed. Time from initial pathological diagnosis to definitive CCRT was analyzed both as a continuous variable (per day) and as a categorical variable in two groups (group 1 ≤ median, group 2 > median). Patients with a waiting time of more than 60 days were excluded.
Results:
The median waiting time was 14 days (0-60). There were differences between group 1 and group 2 in age and chemotherapy regimens. However, no significant difference was found in the International Federation of Gynecology and Obstetrics stage, cell type, or the number of cycles of chemotherapy received during CCRT. A longer waiting time was associated with poorer overall survival on the Kaplan-Meier curve (group 1 vs. group 2, p=0.042). On multivariate analysis, intervals as either a continuous variable (hazard ratio [HR], 1.023; 95% confidence interval [CI], 1.006 to 1.040; p=0.007) or a categorical variable (HR, 1.513; 95% CI, 1.073 to 2.134; p=0.018), FIGO stage, cell type, and the number of cycles of chemotherapy received during CCRT were significant independent prognostic factors for overall survival.
Conclusion
A shorter waiting time from pathological diagnosis to definitive CCRT showed benefit on overall survival. Our findings suggest that an effort to minimize waiting times should be recommended in cervical cancer patients who are candidates for CCRT.
6.Predicting prognosis according to the updated WHO classification in patients with endocervical adenocarcinoma treated with surgery and radiotherapy
Won Kyung CHO ; Hyun-Soo KIM ; Won PARK ; Chi-Son CHANG ; Yoo-Young LEE ; Chel Hun CHOI ; Tae-Joong KIM ; Jeong-Won LEE ; Byoung-Gie KIM
Journal of Gynecologic Oncology 2022;33(6):e71-
Objective:
The recently updated World Health Organization classification divides endocervical adenocarcinomas (ADCs) into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) ADCs. This study aimed to investigate the differences in the clinical features and treatment outcomes between patients with HPVA and HPVI.
Methods:
We retrospectively reviewed the electronic medical records and pathology slides of 123 patients with endocervical ADC who underwent radical hysterectomy and adjuvant radiation therapy. Tumor characteristics, patterns of failure, and survival outcomes were compared between HPVA and HPVI ADCs.
Results:
Eighty-one (65.9%) and 42 (34.1%) patients were diagnosed with HPVA and HPVI ADCs, respectively. HPVI ADC showed more frequent positive vaginal resection margin (VRM) and peritoneal seeding than HPVA ADC. After a median follow-up of 58.1 months, local recurrence and distant metastasis were more frequently observed in HPVI ADC than in HPVA ADC. Both local recurrence-free survival (77.3% vs. 91.8%) and distant metastasis-free survival (50.1% vs. 73.7%) rates of HPVI ADC were lower than those of HPVA ADC. Disease-free survival was not significantly different between HPVI and HPVA ADCs.
Conclusion
We demonstrated that HPVI ADC exhibited higher rates of VRM involvement and peritoneal seeding than those of HPVA ADC, resulting in higher rates of local recurrence and distant metastasis. Further studies with larger populations are warranted to explore optimal treatment strategies based on the histological subtypes of endocervical ADC.
7.Early Metabolic Response Assessed Using 18F-FDG-PET/CT for Image-Guided Intracavitary Brachytherapy Can Better Predict Treatment Outcomes in Patients with Cervical Cancer
Nalee KIM ; Won PARK ; Won Kyung CHO ; Duk-Soo BAE ; Byoung-Gie KIM ; Jeong-Won LEE ; Tae-Joong KIM ; Chel Hun CHOI ; Yoo-Young LEE ; Young Seok CHO
Cancer Research and Treatment 2021;53(3):803-812
Purpose:
This study aimed to identify the prognostic value of early metabolic response assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiation therapy (RT) for cervical cancer.
Materials and Methods:
We identified 116 patients treated with definitive RT, including FDG-PET/CT–guided intracavitary brachytherapy, between 2009 and 2018. We calculated parameters including maximum (SUVmax) and mean standardized uptake values (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for baseline FDG-PET/CT (PETbase) and image-guided brachytherapy planning FDG-PET/CT (PETIGBT). Multivariable analyses of disease-free survival (DFS) and overall survival (OS) were performed.
Results:
We observed a time-dependent decrease in PET parameters between PETbase and PETIGBT; ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG were 65%, 61%, 78%, and 93%, respectively. With a median follow-up of 59.5 months, the 5-year DFS and OS rates were 66% and 79%, respectively. Multivariable analysis demonstrated that ΔSUVmax ≥ 50% was associated with favorable DFS (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.14 to 5.77) and OS (HR, 5.14; 95% CI, 1.55 to 17.01). Patients with ΔSUVmax ≥ 50% (n=87) showed better DFS and OS than those with ΔSUVmax < 50% (n=29) (DFS, 76% vs. 35%, p < 0.001; OS, 90% vs. 41%, p < 0.001, respectively). Adenocarcinoma was frequently observed in ΔSUVmax < 50% compared to ΔSUVmax ≥ 50% (27.6% vs. 10.3%, p=0.003). In addition, models incorporating metabolic parameters showed improved accuracy for predicting DFS (p=0.012) and OS (p=0.004) than models with clinicopathologic factors.
Conclusion
Changes in metabolic parameters, especially those in SUVmax by > 50%, can help improve survival outcome predictions for patients with cervical cancer treated with definitive RT.
8.Early Metabolic Response Assessed Using 18F-FDG-PET/CT for Image-Guided Intracavitary Brachytherapy Can Better Predict Treatment Outcomes in Patients with Cervical Cancer
Nalee KIM ; Won PARK ; Won Kyung CHO ; Duk-Soo BAE ; Byoung-Gie KIM ; Jeong-Won LEE ; Tae-Joong KIM ; Chel Hun CHOI ; Yoo-Young LEE ; Young Seok CHO
Cancer Research and Treatment 2021;53(3):803-812
Purpose:
This study aimed to identify the prognostic value of early metabolic response assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiation therapy (RT) for cervical cancer.
Materials and Methods:
We identified 116 patients treated with definitive RT, including FDG-PET/CT–guided intracavitary brachytherapy, between 2009 and 2018. We calculated parameters including maximum (SUVmax) and mean standardized uptake values (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for baseline FDG-PET/CT (PETbase) and image-guided brachytherapy planning FDG-PET/CT (PETIGBT). Multivariable analyses of disease-free survival (DFS) and overall survival (OS) were performed.
Results:
We observed a time-dependent decrease in PET parameters between PETbase and PETIGBT; ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG were 65%, 61%, 78%, and 93%, respectively. With a median follow-up of 59.5 months, the 5-year DFS and OS rates were 66% and 79%, respectively. Multivariable analysis demonstrated that ΔSUVmax ≥ 50% was associated with favorable DFS (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.14 to 5.77) and OS (HR, 5.14; 95% CI, 1.55 to 17.01). Patients with ΔSUVmax ≥ 50% (n=87) showed better DFS and OS than those with ΔSUVmax < 50% (n=29) (DFS, 76% vs. 35%, p < 0.001; OS, 90% vs. 41%, p < 0.001, respectively). Adenocarcinoma was frequently observed in ΔSUVmax < 50% compared to ΔSUVmax ≥ 50% (27.6% vs. 10.3%, p=0.003). In addition, models incorporating metabolic parameters showed improved accuracy for predicting DFS (p=0.012) and OS (p=0.004) than models with clinicopathologic factors.
Conclusion
Changes in metabolic parameters, especially those in SUVmax by > 50%, can help improve survival outcome predictions for patients with cervical cancer treated with definitive RT.
9.Increase of Vδ2 + T Cells That Robustly Produce IL-17A in Advanced Abdominal Aortic Aneurysm Tissues
In-Ho SEO ; Seung-Jun LEE ; Tae Wook NOH ; Jung-Hwan KIM ; Hyun-Chel JOO ; Eui-Cheol SHIN ; Su-Hyung PARK ; Young-Guk KO
Immune Network 2021;21(2):e17-
Abdominal aortic aneurysm (AAA) is a chronic dilation of the aorta with a tendency to enlarge and eventually rupture, which constitutes a major cause of cardiovascular mortality.Although T-cell infiltrates have been observed in AAA, the cellular, phenotypic, and functional characteristics of these tissue-infiltrating T cells are not fully understood. Here, we investigated the proportional changes of T-cell subsets—including CD4 + T cells, CD8 + T cells, and γδ T cells—and their effector functions in AAAs. We found that Vδ2 + T cells were presented at a higher frequency in aortic aneurysmal tissue compared to normal aortic tissue and PBMCs from patients with AAA. In contrast, no differences were observed in the frequencies of CD4 + , CD8 + , and Vδ1 + T cells. Moreover, we observed that the Vδ2 +T cells from AAA tissue displayed immunophenotypes indicative of CCR5 + non-exhausted effector memory cells, with a decreased proportion of CD16 + cells. Finally, we found that these Vδ2 + T cells were the main source of IL-17A in abdominal aortic aneurysmal tissue. In conclusion, our results suggest that increased Vδ2 + T cells that robustly produce IL-17A in aortic aneurysmal tissue may contribute to AAA pathogenesis and progression.
10.Significance of serum CA125 level in surgically resected cervical adenocarcinoma with adverse features
Nalee KIM ; Won PARK ; Won Kyung CHO ; Duk-Soo BAE ; Byoung-Gie KIM ; Jeong-Won LEE ; Chel Hun CHOI ; Tae-Joong KIM ; Yoo-Young LEE
Journal of Gynecologic Oncology 2021;32(5):e72-
Objective:
Unlike cervical squamous cell carcinoma, there are no consensus criteria for serum tumor markers in cervical adenocarcinoma. This study aimed to identify the prognostic value of preoperative carbohydrate antigen 125 (CA125) levels in cervical adenocarcinoma patients with adverse pathologic features.
Methods:
A total of 105 patients who underwent radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiation therapy were included. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Cox proportional hazard regression model.
Results:
Using a cutoff value of 50 U/mL, 83 and 22 patients had low- and high-CA125, respectively. Patients with high-CA125 had a larger tumor size, more frequent parametrial extension, and more frequent lymph node metastasis than those with low-CA125. During a median follow-up of 59.3 (interquartile range, 32.7–97.8) months, patients with high-CA125 showed inferior 5-year LRFS, DMFS, and OS rates compared to those with low-CA125 (38.5% vs. 70.0%; 37.0% vs. 69.4%; 43.6% vs. 78.1%, respectively, all p<0.05). In multivariable analysis, the high-CA125 remained significant prognostic factor for LRFS, DMFS, and OS (all p<0.05). Furthermore, 12 patients with high-CA125 at recurrence exhibited lower 5-year OS rates than 21 patients with low-CA125 at recurrence (0.0% vs. 51.3%, p=0.003).
Conclusion
In this retrospective analysis, the serum CA125 level at diagnosis and recurrence was related to the extent of disease and prognosis of cervical adenocarcinoma with adverse pathologic features. A CA125 level of ≥50 U/mL may be a prognostic surrogate marker for cervical adenocarcinoma in patients with the presence of adverse factors.

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