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.Advantages of laparoscopy in gynecologic surgery in elderly patients
Jaewon NA ; Young Eun CHUNG ; Il-Yeo JANG ; Yoo-Young LEE ; Tae-Joong KIM ; Jeong-Won LEE ; Byoung-Gie KIM ; Chi-Son CHANG ; Chel Hun CHOI
Obstetrics & Gynecology Science 2024;67(2):243-252
Objective:
Geriatric patients requiring gynecological surgery is increasing worldwide. However, older patients are at higher risk of postoperative morbidity and mortality, particularly cardiopulmonary complications. Laparoscopic surgery is widely used as a minimally invasive method for reducing postoperative morbidities. We compared the outcomes of open and laparoscopic gynecologic surgeries in patients older than 55 years.
Methods:
We included patients aged >55 years who underwent gynecological surgery at a single tertiary center between 2010 and 2020, excluding vaginal or ovarian cancer surgeries were excluded. Surgical outcomes were compared between the open surgery and laparoscopic groups, with age cutoff was set at 65 years for optimal discriminative power. We performed linear or logistic regression analyses to compare the surgical outcomes according to age and operation type.
Results:
Among 2,983 patients, 28.6% underwent open surgery and 71.4% underwent laparoscopic surgery. Perioperative outcomes of laparoscopic surgery were better than those of open surgery in all groups. In both the open and laparoscopic surgery groups, the older patients showed worse overall surgical outcomes. However, age-related differences in perioperative outcomes were less severe in the laparoscopic group. In the linear regression analysis, the differences in estimated blood loss, transfusion, and hospital stay between the age groups were smaller in the laparoscopy group. Similar results were observed in cancer-only and benign-only cohorts.
Conclusion
Although the surgical outcomes were worse in the older patients, the difference between age groups was smaller for laparoscopic surgery. Laparoscopic surgery offers more advantages and safety in patients aged >65 years.
5.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.
6.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.
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.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.
9.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.
10.Combination of a pulmonary recruitment maneuver and intraperitoneal bupivacaine for the reduction of postoperative shoulder pain in gynecologic laparoscopy: a randomized, controlled trial
Minae CHO ; Chul Jung KIM ; Tae Soo HAHM ; Yoo Young LEE ; Tae Joong KIM ; Jeong Won LEE ; Byoung Gie KIM ; Duk Soo BAE ; Chel Hun CHOI
Obstetrics & Gynecology Science 2020;63(2):187-194
OBJECTIVE: To compare the efficacy of a pulmonary recruitment maneuver using lower airway pressure (30 cm H2O) and intraperitoneal bupivacaine, alone or in combination, for reducing shoulder pain after gynecologic laparoscopy.METHODS: A prospective controlled study was performed in a teaching hospital with patients who underwent elective gynecologic laparoscopic surgery. Two hundred eighty-seven patients were randomized into 1 of 4 groups: group A, placebo; group B, intraperitoneal instillation of bupivacaine; group C, CO2 removal by a pulmonary recruitment maneuver; group D, combination of intraperitoneal bupivacaine and pulmonary recruitment maneuver. The interventions were performed at the end of surgery. Shoulder pain was recorded on a visual analog scale (VAS) at 1, 6, 12, and 24 hours postoperatively.RESULTS: The overall incidence of shoulder pain was 49.8% and the incidence tended to gradually decrease from group A to group D (59.0% in group A, 54.8% in group B, 44.4% in group C, and 41.5% in group D; P=0.026). In addition, the VAS scores gradually decreased from group A to D, although a statistically significant difference was only found at 6 hours postoperatively (P=0.03). There were no complications related to the interventions.CONCLUSION: The combination of a pulmonary recruitment maneuver with intraperitoneal bupivacaine significantly reduced shoulder pain after gynecologic laparoscopy.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01039441

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