High expression of folate receptor alpha is associated with poor prognosis in patients with cervical cancer / 부인종양

Objective@#Folate receptor α (FRα) is a membrane protein expressed in various solid tumors but has limited expression in normal cells. Therefore, FRα is an attractive target for cancer treatment. This study aimed to investigate the relationship between FRα expression and the clinicopathological characteristics and survivals of cervical cancer. @*Methods@#This retrospective study included patients with cervical cancer who underwent primary surgery between 2000 and 2020 at our institution. Immunohistochemical staining of FRα was performed using an anti-folate-binding protein/FBP antibody. FRα-positive staining was defined as ≥5% of tumor staining and FRα-high as ≥50% tumor staining with ≥2+ intensity. The association between FRα expression and survival was assessed using multivariate Cox regression analysis, adjusting for established prognostic factors. @*Results@#Overall, 123 patients were identified, and 140 tumor samples, including 17 paired primary and metastatic samples, were evaluated. As histological types, 67 patients had squamous cell carcinoma (SCC), and 56 patients had non-SCC. All primary tumors were FRα-positive. High FRα expression was observed in 25% of the cases and differed according to histology (SCC vs. non-SCC, 14.9% vs. 37.5%, p=0.004). FRα expression was significantly higher in metastatic tumors than in primary (170 [IQR, 140–205] vs. 125 [IQR, 110–150], p=0.0006). High FRα expression was significantly associated with worse overall survival (hazard ratio, 6.73; 95% confidence interval, 2.21–20.53; p=0.001). @*Conclusion@#In cervical cancer, FRα expression was elevated in metastatic tumors and high expression was associated with a worse prognosis. Our study supports the development of FRα-targeted therapy for advanced cervical cancer.

Novel therapeutic approach for uterine leiomyosarcoma based on transcriptome analysis / 부인종양

Uterine leiomyosarcoma (ULMS) is one of the most aggressive gynecological malignancies. In the past decade, novel therapeutic agents such as trabectedin and pazopanib have been approved, but the prognosis of patients remains unsatisfactory. This study aimed to identify potential therapeutic targets for ULMS based on transcriptome analysis. Archival fresh-frozen tumor tissues of 6 ULMS and three leiomyoma samples were used in this study, and total RNA was extracted. First, transcriptome analysis identified 512 significantly differentially expressed genes, and subsequent pathway analysis using IPA software revealed that the functions of cell cycle-related kinases were significantly activated in ULMS. Moreover, our results were validated using 3 independent Gene Expression Omnibus datasets, including 40 ULMS. Therefore, we considered the kinases as novel therapeutic targets and evaluated the anti-cancer effects of several selective inhibitors against them. Most inhibitors exerted a higher anti-cancer effect than pazopanib in three leiomyosarcoma cell lines. Especially, CHEK1 or PLK1 inhibitors strongly induced cell cycle arrest and cell death, and the IC50s were lower nanomolar concentration. Moreover, the inhibitors suppressed the tumor growth in SK-UT-1 bearing mice models. In conclusion, we revealed the unique gene expression profiles of ULMS. CHEK1 and PLK1 are promising therapeutic targets for ULMS, and therefore, further clinical trials are highly anticipated to improve the prognosis of the patients.

The baseline recurrence risk of patients with intermediate-risk cervical cancer

Objective@#This study aimed to investigate the prognosis of patients with intermediate-risk cervical cancer and to evaluate the necessity of adjuvant therapy. @*Methods@#We conducted a retrospective chart review of patients with stage IB–II cervical cancer who underwent type III radical hysterectomy with pelvic lymphadenectomy between 2008 and 2017. In our institution, radical hysterectomy is performed as an open surgery and not as a minimally invasive surgery, and adjuvant therapy is not administered to patients with intermediate-risk cervical cancer. The intermediate-risk group included patients with 2 or more of the following factors: tumor size >4 cm, stromal invasion >1/2, and lymphovascular stromal invasion. Intermediaterisk patients with squamous cell carcinoma were included in the I-SCC group, whereas those with endocervical adenocarcinoma, usual type, or adenosquamous carcinoma were included in the I-Adeno group. @*Results@#There were 34 and 18 patients in the I-SCC and I-Adeno groups, respectively. The 5-year recurrence-free survival (RFS) and overall survival rates in the I-SCC group were 90.5% (95% confidence interval [CI], 85.3–95.7%) and 100% (95% CI, 100%), respectively, whereas those in the I-Adeno group were 54.9% (95% CI, 42.0–67.9%) and 76.1% (95% CI, 63.7–88.4%), respectively. Multivariate analysis revealed that endocervical adenocarcinoma, usual type, or adenosquamous carcinoma, and tumor size >4 cm had worse RFS. @*Conclusion@#The I-SCC group had good prognosis without adjuvant therapy; therefore, adjuvant therapy may be omitted in these patients. In contrast, the I-Adeno group had poor prognosis without adjuvant therapy; therefore, adjuvant therapy should be considered in their treatment.

The baseline recurrence risk of patients with intermediate-risk cervical cancer

Objective@#This study aimed to investigate the prognosis of patients with intermediate-risk cervical cancer and to evaluate the necessity of adjuvant therapy. @*Methods@#We conducted a retrospective chart review of patients with stage IB–II cervical cancer who underwent type III radical hysterectomy with pelvic lymphadenectomy between 2008 and 2017. In our institution, radical hysterectomy is performed as an open surgery and not as a minimally invasive surgery, and adjuvant therapy is not administered to patients with intermediate-risk cervical cancer. The intermediate-risk group included patients with 2 or more of the following factors: tumor size >4 cm, stromal invasion >1/2, and lymphovascular stromal invasion. Intermediaterisk patients with squamous cell carcinoma were included in the I-SCC group, whereas those with endocervical adenocarcinoma, usual type, or adenosquamous carcinoma were included in the I-Adeno group. @*Results@#There were 34 and 18 patients in the I-SCC and I-Adeno groups, respectively. The 5-year recurrence-free survival (RFS) and overall survival rates in the I-SCC group were 90.5% (95% confidence interval [CI], 85.3–95.7%) and 100% (95% CI, 100%), respectively, whereas those in the I-Adeno group were 54.9% (95% CI, 42.0–67.9%) and 76.1% (95% CI, 63.7–88.4%), respectively. Multivariate analysis revealed that endocervical adenocarcinoma, usual type, or adenosquamous carcinoma, and tumor size >4 cm had worse RFS. @*Conclusion@#The I-SCC group had good prognosis without adjuvant therapy; therefore, adjuvant therapy may be omitted in these patients. In contrast, the I-Adeno group had poor prognosis without adjuvant therapy; therefore, adjuvant therapy should be considered in their treatment.

Treatment strategies for patients with advanced ovarian cancer undergoing neoadjuvant chemotherapy: interval debulking surgery or additional chemotherapy? / 부인종양

OBJECTIVE: To treat advanced ovarian cancer, interval debulking surgery (IDS) is performed after 3 cycles each of neoadjuvant chemotherapy (NAC) and postoperative chemotherapy (IDS group). If we expect that complete resection cannot be achieved by IDS, debulking surgery is performed after administering additional 3 cycles of chemotherapy without postoperative chemotherapy (Add-C group). We evaluated the survival outcomes of the Add-C group and determined their serum cancer antigen 125 (CA125) levels to predict complete surgery. METHODS: A retrospective chart review of all stage III and IV ovarian, fallopian tube, and peritoneal cancer patients treated with NAC in 2007–2016 was conducted. RESULTS: About 117 patients comprised the IDS group and 26 comprised the Add-C group. Univariate and multivariate analyses revealed that Add-C group had an equivalent effect on progression-free survival (PFS; p=0.09) and overall survival (OS; p=0.94) compared with the IDS group. Multivariate analysis revealed that patients who developed residual disease after surgery had worse PFS (hazard ratio [HR]=2.18; 95% confidence interval [CI]=1.45–3.28) and OS (HR=2.33; 95% CI=1.43–3.79), and those who received <6 cycles of chemotherapy had worse PFS (HR=5.30; 95% CI=2.56–10.99) and OS (HR=3.05; 95% CI=1.46–6.38). The preoperative serum CA125 cutoff level was 30 U/mL based on Youden index method. CONCLUSIONS: Administering 3 additional cycles of chemotherapy followed by debulking surgery exhibited equivalent effects on survival as IDS followed by 3 cycles of postoperative chemotherapy. Preoperative serum CA125 levels of ≤30 U/mL may be a useful predictor of achieving complete surgery.

A novel prediction score for predicting the baseline risk of recurrence of stage I–II endometrial carcinoma / 부인종양

OBJECTIVE: To develop and validate a 3-year recurrence prediction score (RPS) system for predicting the baseline risk of recurrence of stage I–II endometrial carcinoma. METHODS: We reviewed 427 patients with International Federation of Gynecology and Obstetrics staging I–II endometrial carcinoma underwent surgery without any adjuvant therapy from 2005 to 2013. The patients were divided into 2 groups: the test cohort (n=251) comprising those who underwent surgery in odd-numbered years, and the validation cohort (n=176) comprising those who underwent surgery in even-numbered years. Multivariate analysis was performed using 7 candidate predictors to identify the risk factors for 3-year recurrence-free interval (RFI) in the test cohort. Each risk factor was scored based on logistic regression analyses of the test data set, and the sum of the risk factor scores was defined as the RPS system. We then applied the system in the validation cohort. RESULTS: Multivariate analysis revealed that the significant risk factors were age ≥60 years, pathological type II, positive cervical stromal invasion, and positive peritoneal cytology. In the test cohort, the 3-year RFI rates were 100%, 95.8%, 79.9%, and 33.3% for RPSs of 0, 1, 2, and 3, respectively. In the validation cohort, the 3-year RFI was significantly higher in the low-RPS group (RPS 0 or 1) than in the high-RPS group (RPS 2 or 3) (95.2% vs. 79.9%, p < 0.01). CONCLUSIONS: The RPS system shows significant reproducibility for predicting the baseline risk of recurrence. The system could potentially impact the choice of adjuvant therapy for stage I–II endometrial carcinoma.

Prognostic factors of synchronous endometrial and ovarian endometrioid carcinoma / 부인종양

OBJECTIVE: Gynecologists occasionally encounter synchronous endometrial and ovarian endometrioid carcinoma (SEO-EC) patients who show favorable prognosis than locally advanced or metastatic disease patients. This study aimed to elucidate prognostic factors of SEO-EC and identify patients who have a sufficiently low risk of recurrence without receiving adjuvant chemotherapy. METHODS: We retrospectively reviewed 46 patients with pathologically confirmed SEO-EC who underwent surgery at the National Cancer Center Hospital between 1997 and 2016. Immunohistochemical evaluation of DNA mismatch repair (MMR) protein expression were performed for both endometrial and ovarian tumors. Patient outcomes were analyzed according to clinicopathologic factors. RESULTS: From the multivariate analysis, cervical stromal invasion indicated a worse prognosis for progression-free survival (hazard ratio [HR]=6.85; 95% confidence interval [CI]=1.50–31.1) and overall survival (HR=6.95; 95% CI=1.15–41.8). Lymph node metastasis and peritoneal dissemination did not significantly affect survival. MMR deficiency was observed in 13 patients (28.3%), with both endometrial and ovarian tumors showing the same MMR expression status. MMR deficiency was not significantly associated with survival. Of 23 patients with lesions confined to only the uterine body and adnexa, only 2 had recurrence in the group receiving adjuvant therapy, while none of the 10 patients who did not receive adjuvant therapy had recurrence. CONCLUSION: SEO-EC patients with tumors localized to the uterine body and adnexa lesions had a low risk for recurrence and may not require adjuvant therapy. SEO-EC may have prognostic factors different from those of endometrial and ovarian cancer.

Baseline risk of recurrence in stage I–II endometrial carcinoma / 부인종양

OBJECTIVE: Though there are no evidences that postoperative therapy improves overall survival (OS) in stage I–II endometrial carcinoma, many women receive postoperative radiation or chemotherapy. This study aimed to investigate the baseline risk of recurrence after complete resection without any adjuvant therapies and to suppose the validity of postoperative therapy for stage I–II endometrial carcinoma. METHODS: Charts for patients with stage I–II endometrial carcinoma who underwent operation without postoperative therapy between January 2005 and December 2011 were retrospectively reviewed and the baseline risk of recurrence and prognosis were assessed. Risk classifications were performed according to European Society for Medical Oncology (ESMO) clinical practice guidelines and Japanese guideline written by Japan Society of Gynecologic Oncology Group. RESULTS: Among 374 patients who underwent complete resection, 311 were evaluable. Five-year recurrence rates by ESMO and Japanese were 2.6% and 3.1% in low-risk, 9.2% and 6.6% in intermediate-risk and 13.5% and 13.8% in high-risk group (p=0.003 and 0.015, respectively). High-risk group had worse OS compared with low- and intermediate-risk groups (5-year OS, low: 97.9% and 97.6%, intermediate: 97.9% and 98.8%, and high: 89.5% and 87.5%; p=0.003 and 0.008, respectively). Independent predictive factors of recurrence were age over 60 years, type 2 (estrogen-independent) and peritoneal cytology. CONCLUSION: ESMO and Japanese risk classification similarly stratify the baseline risk of recurrence. Patients with stage I–II endometrial carcinoma, especially low- and intermediate-risk diseases, have low recurrence rate and favorable OS, and the benefit of postoperative therapy might be small.

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy / 부인종양

OBJECTIVE: Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. METHODS: Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I–II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. RESULTS: FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. CONCLUSION: Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I–II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies.

Salvage para-aortic lymphadenectomy in recurrent cervical cancer after visualization with 3-dimensional computed tomography angiography

We report a case of salvage lymphadenectomy for an isolated metastatic lesion in the para-aortic lymph node (LN) in a 49-year old woman with a history of cervical cancer, initially treated with radical hysterectomy and adjuvant radiotherapy. Preoperative 3-dimensional (3D) computed tomography (CT) angiography clearly revealed a huge retro-crural metastatic LN with distinct demarcation. A metastatic lesion, more than 10 cm in size, was located behind the vena cava, aorta, and left kidney, encompassing the left renal and lumbar arteries. The metastatic LN was excised along with the left kidney. On histologic examination, the tumor was found to have invaded the pelvis of the left kidney. Compared with conventional imaging techniques, 3D CT angiography can more clearly visualize such lesions. Thus, 3D CT angiography provides useful anatomical information, such as the exact size and location, and provides clear visualization and demarcation.

Hyperthermic intrathoracic chemotherapy with cisplatin for ovarian cancer with pleural metastasis

Intrathoracic metastasis of ovarian cancer has poor prognosis regardless of treatment modality. Recent development of surgical techniques and the new concept of direct infusion of chemotherapeutic agents with hyperthermia could help with the treatment of disseminated diseases in ovarian cancer. Using video-assisted thoracoscopic surgery and intracavitary chemotherapy with hyperthermia, we tried hyperthermic intrathoracic chemotherapy for a case of stage IV high-grade serous ovarian cancer with pleural metastasis. There was no high-grade complication related to the procedure. The patient is alive without disease at 32 months after initial treatment.

Asian society of gynecologic oncology workshop 2010 / 부인종양

This workshop was held on July 31-August 1, 2010 and was organized to promote the academic environment and to enhance the communication among Asian countries prior to the 2nd biennial meeting of Australian Society of Gynaecologic Oncologists (ASGO), which will be held on November 3-5, 2011. We summarized the whole contents presented at the workshop. Regarding cervical cancer screening in Asia, particularly in low resource settings, and an update on human papillomavirus (HPV) vaccination was described for prevention and radical surgery overview, fertility sparing and less radical surgery, nerve sparing radical surgery and primary chemoradiotherapy in locally advanced cervical cancer, were discussed for management. As to surgical techniques, nerve sparing radical hysterectomy, optimal staging in early ovarian cancer, laparoscopic radical hysterectomy, one-port surgery and robotic surgery were introduced. After three topics of endometrial cancer, laparoscopic surgery versus open surgery, role of lymphadenectomy and fertility sparing treatment, there was a special additional time for clinical trials in Asia. Finally, chemotherapy including neo-adjuvant chemotherapy, optimal surgical management, and the basis of targeted therapy in ovarian cancer were presented.