Acute Pancreatitis Associated with Eosinophilic Gastroduodenitis: A Case Report / 대한췌담도학회지

Acute pancreatitis caused by eosinophilic gastroenteritis is a rare disease, and little has been reported so far. Diagnosing eosinophilic gastroenteritis is difficult because the symptoms and laboratory findings are not specific. We report a rare case of eosinophilic gastroenteritis related to acute pancreatitis as a possible cause of idiopathic acute pancreatitis. A 61-year-old man visited the hospital complaining of epigastric pain. Although no pancreatic abnormalities were confirmed on imaging studies, the patient showed hyperamylasemia and hyperlipasemia. Serum eosinophil fractions were initially normal. However, they were elevated on follow-up examinations, and a large number of eosinophils were observed in the biopsies of the stomach and duodenum, which led to the diagnosis of eosinophilic gastroduodenitis related to acute pancreatitis.

RAD51/geminin/γH2AX immunohistochemical expression predicts platinum-based chemotherapy response in ovarian high-grade serous carcinoma / 부인종양

Objective@#The RAD51 assay is a recently developed functional assay for homologous recombination deficiency (HRD) that reflects real-time HRD status. We aimed to identify the applicability and predictive value of RAD51 immunohistochemical expression in pre- and post-neoadjuvant chemotherapy (NAC) samples of ovarian high-grade serous carcinoma (HGSC). @*Methods@#We evaluated the immunohistochemical expression of RAD51/geminin/γH2AX in ovarian HGSC before and after NAC. @*Results@#In pre-NAC tumors (n=51), 74.5% (39/51) showed at least 25% of γH2AX-positive tumor cells, suggesting endogenous DNA damage. The RAD51-high group (41.0%, 16/39) showed significantly worse progression-free survival (PFS) compared to the RAD51-low group (51.3%, 20/39) (p=0.032). In post-NAC tumors (n=50), the RAD51-high group (36.0%, 18/50) showed worse PFS (p=0.013) and tended to present worse overall survival (p=0.067) compared to the RAD51-low group (64.0%, 32/50). RAD51-high cases were more likely to progress than RAD51-low cases at both 6 months and 12 months (p=0.046 and p=0.019, respectively). Of 34 patients with matched pre- and post-NAC RAD51 results, 44% (15/34) of pre-NAC RAD51 results were changed in the post-NAC tissue, and the RAD51 high-to-high group showed the worst PFS, while the low-to-low group showed the best PFS (p=0.031). @*Conclusion@#High RAD51 expression was significantly associated with worse PFS in HGSC, and post-NAC RAD51 status showed higher association than pre-NAC RAD51 status. Moreover, RAD51 status can be evaluated in a significant proportion of treatment-naïve HGSC samples. As RAD51 status dynamically changes, sequential follow-up of RAD51 status might reflect the biological behavior of HGSCs.

Major clinical research advances in gynecologic cancer in 2022: highlight on late-line PARP inhibitor withdrawal in ovarian cancer, the impact of ARIEL-4, and SOLO-3 / 부인종양

In the 2022 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Ovarian cancer: long-term follow-up data, new poly (ADP-ribose) polymerase (PARP) inhibitors, overall survival (OS) issues with PARP inhibitor monotherapy, hyperthermic intraperitoneal chemotherapy, immunotherapy, and antibody-drug conjugate; 2) Cervical cancer: surgery in early stage disease, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Corpus cancer: follow-up regimen, immune checkpoint inhibitor, WEE1 inhibitor, selective inhibitor of nuclear export. A special note was made on the withdrawal of PARP inhibitor from the market for heavily pretreated ovarian cancer patients based on the final OS results of ARIEL-4 and SOLO-3 due to concerns of increased risk of death.

Role of diagnostic laparoscopy in deciding primary treatment in advanced-stage ovarian cancer / 부인종양

Objective@#We evaluated the usefulness of preoperative diagnostic laparoscopy for treatment planning in patients with advanced-stage ovarian cancer. @*Methods@#We retrospectively analyzed 614 patients diagnosed with advanced-stage ovarian cancer between January 2010 and May 2018. Primary debulking surgery (PDS) or neoadjuvant chemotherapy (NAC) followed by interval debulking surgery were selected based on preoperative laparoscopic (Group 1, n=192) and computed tomography findings (Group 2, n=422). The primary outcomes in the PDS and NAC groups were suboptimal cytoreduction (residual disease >1 cm) rate and non-high-grade serous carcinoma (non-HGSC) rate, respectively. @*Results@#The patients who underwent PDS in group 1 and group 2 were 49 (25.5%) and 279 (66.1%), respectively. The suboptimal cytoreduction rate after PDS was lower in Group 1 than in Group 2 (2.0% vs 11.1%, p=0.023). Moreover, Group 1 showed a tendency toward a lower proportion of non-HGSC patients who underwent NAC than that in Group 2 (9.1% vs. 15.4%, p=0.069). Further, Group 1 showed lower rates of postoperative morbidity than Group 2 (5.2% vs. 10.4%, p=0.033). However, Kaplan–Meier analysis showed no significant differences in survival outcomes between the 2 groups. @*Conclusion@#Diagnostic laparoscopy reduced the suboptimal cytoreduction rate in the PDS group and the implementation rate of NAC in non-HGSC patients. Moreover, it reduced postoperative morbidity without affecting survival in both groups. Thus, diagnostic laparoscopy is a valuable diagnostic tool for determining the primary treatment.

Application of precision medicine based on next-generation sequencing and immunohistochemistry in ovarian cancer: a real-world experience / 부인종양

Objective@#To evaluate the landscape of gene alterations and immunohistochemistry (IHC) profiles of patients with ovarian cancer for targeted therapy and investigate the real-world experience of applying precision medicine. @*Methods@#Patients diagnosed with ovarian cancer between January 2015 and May 2021 at Severance Hospital and who underwent tumor next-generation sequencing (NGS) were reviewed. Data on germline mutation, IHC markers for mismatch repair deficiency (MMRd), programmed death ligand 1 (PD-L1) expression, and human epidermal growth factor receptor 2 (HER2) expression were acquired. The use of matched therapy and its clinical outcomes were evaluated. @*Results@#Of the 512 patients who underwent tumor NGS, 403 underwent panel-based germline testing. In patients who underwent both tests, tumor NGS identified 39 patients (9.7%) with BRCA mutations and 16 patients (4.0%) with other homologous recombination repair (HRR)-associated gene mutations, which were not found in germline testing. The most common single nucleotide variants were TP53 (82.2%), ARID1A (10.4%), PIK3CA (9.7%), and KRAS (8.4%). Copy number aberrations were found in 122 patients. MMRd was found in 3.2% of patients, high PD-L1 expression in 10.1%, and HER2 overexpression in 6.5%. Subsequently, 75 patients (14.6%) received a poly (ADP-ribose) polymerase inhibitor based on BRCA mutation and 11 patients (2.1%) based on other HRR-associated gene mutations. Six patients (1.2%) with MMRd underwent immunotherapy. Twenty-eight patients (5.5%) received other matched therapies targeting HER2, fibroblast growth factor receptor, folate receptor alpha, RAS, and PIK3CA. @*Conclusion@#A comprehensive review of germline mutation, IHC, and tumor NGS helped identify candidates for precision therapy in patients with ovarian cancer, a proportion of whom received matched therapy.

Biomarker-guided targeted therapy in platinum-resistant ovarian cancer (AMBITION; KGOG 3045): a multicentre, open-label, five-arm, uncontrolled, umbrella trial / 부인종양

Objective@#Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options. @*Methods@#This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m2 D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1). @*Results@#Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2–10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed. @*Conclusion@#This study, the first biomarker-driven umbrella trial in platinum-resistant recurrent ovarian cancer, suggests clinical utility with biomarker-driven targeted therapy. All treatment combinations were manageable, and without unexpected toxicities.

PARP inhibitors in ovarian cancer: overcoming resistance with combination strategies / 부인종양

The use of PARP inhibitors (PARPi) in patients with epithelial ovarian cancer is expanding, with the transition from use in recurrent disease to the first-line setting. This is accompanied with an increasing population of patients who develop acquired PARPi resistance. Coupled with those patients with primary PARPi resistance, there is an urgent need to better understand mechanisms of resistance and identify means to overcome this resistance. Combination therapy offers the potential to overcome innate and acquired resistance, by either working synergistically with PARPi or by restoring homologous recombination deficiency, targeting the homologous recombination repair pathway through an alternate strategy. We discuss mechanisms of PARPi resistance and data on novel combinations which may restore PARPi sensitivity.

Prognostic value of complete metabolic response on 18F-FDG-PET/CT after three cycles of neoadjuvant chemotherapy in advanced high-grade serous ovarian cancer / 부인종양

Objective@#We investigated the prognostic value of complete metabolic response (CMR) on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) after 3 cycles of neoadjuvant chemotherapy (NAC) in advanced high-grade serous ovarian cancer (HGSC). @*Methods@#PET/CT at baseline and after 3 cycles of NAC were performed; peak standardized uptakes were measured. PET parameters were compared with NAC parameter: cancer antigen-125 (CA-125) normalization before interval debulking surgery (IDS) and chemotherapy response score (CRS) to predict platinum-sensitivity. Kaplan-Meier analysis was used to determine correlations between PET parameters and survival. Prognostic factors were obtained by multivariate Cox regression analysis. @*Results@#Between 2007 and 2020, 102 patients were recruited: 19 (18.6%) were designated as CMR group and 83 (81.4%) as non-CMR group. CMR after 3 cycles of NAC showed the highest accuracy in predicting platinum-sensitivity (area under the curve [AUC]=0.729; 95% confidence interval [CI]=0.552–0.823; p=0.017), compared with CA-125 normalization before IDS (AUC=0.626; 95% CI=0.542–0.758; p=0.010) and CRS (AUC=0.613; 95% CI=0.490–0.735; p=0.080). CMR demonstrated better prognosis than non-CMR in progression-free survival (PFS) (median PFS, 23.9 months vs. 16.4 months; p=0.021) and overall survival (OS) (median OS, not reached vs. 69.7 months; p=0.025). In multivariate analysis, CMR was associated with a lower risk of recurrence (adjusted hazard ratio [aHR]=0.50; 95% CI=0.27–0.92; p=0.027) and death (aHR=0.23; 95% CI=0.05–0.99; p=0.048). @*Conclusion@#CMR after 3 cycles of NAC can be a prognostic factor for both recurrence and death in advanced HGSC.

Indocyanine green fluorescent image-guided inguinal sentinel lymph node biopsy in vulvar cancer

Objective@#To demonstrate near-infrared fluorescence image-guided inguinal sentinel lymph node (SLN) biopsy in patients with vulvar cancer. @*Methods@#A 40-year-old woman with a 3-cm-sized palpable left vulvar mass was diagnosed with vulvar cancer on biopsy with protrusion into the vaginal cavity. Pelvic contrast-enhanced magnetic resonance imaging and F-18 fluorodeoxyglucose positron-emission tomography-computed tomography showed a small ulcerative enhancing lesion confined to the left vulva without distant metastasis. The patient was scheduled for radical vulvectomy with a left inguinal SLN biopsy. Indocyanine green was injected directly into the vulvar mass to map lymphatic drainage. A 4-cm-sized linear incision was made on the left inguinal crease, and the lymphatic channels of the left inguinal area were dissected under fluorescent image guidance using a 1588 Advanced Imaging Modalities Platform laparoscopic camera (Stryker, Kalamazoo, MI, USA). @*Results@#Fluorescence image-guided left inguinal SLN biopsy and radical vulvectomy were performed. The pathologic diagnosis confirmed vulvar adenoid cystic carcinoma with metastasis to the left inguinal lymph node (International Federation of Gynecology and Obstetrics stage IIIA). The patient was discharged without complications and received adjuvant radiotherapy. @*Conclusion@#This video demonstrates a successful ICG fluorescence image-guided left inguinal SLN biopsy in a vulvar cancer patient using a laparoscopic camera. Mapping of inguinal SLNs in patients with vulvar cancer may help in retaining surgical radicality while minimizing operative complications.

Impact of the Learning Curve on the Survival of Abdominal or Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The objective of this study was to define the learning curve required to attain satisfactory oncologic outcomes of cervical cancer patients who were undergoing open or minimally invasive surgery for radical hysterectomy, and to analyze the correlation between the learning curve and tumor size. @*Materials and Methods@#Cervical cancer patients (stage IA-IIA) who underwent open radical hysterectomy (n=280) or minimal invasive radical hysterectomy (n=282) were retrospectively reviewed. The learning curve was evaluated using cumulative sum of 5-year recurrence rates. Survival outcomes were analyzed based on the operation period (“learning period,” P1 vs. “skilled period,” P2), operation mode, and tumor size. @*Results@#The 5-year disease-free and overall survival rates between open and minimally invasive groups were 91.8% and 89.0% (p=0.098) and 96.1% and 97.2% (p=0.944), respectively. The number of surgeries for learning period was 30 and 60 in open and minimally invasive group, respectively. P2 had better 5-year disease-free survival than P1 after adjusting for risk factors (hazard ratio, 0.392; 95% confidence interval, 0.210 to 0.734; p=0.003). All patients with tumors < 2 cm had similar 5-year disease-free survival regardless of operation mode or learning curve. Minimally invasive group presented lower survival rates than open group when tumors ≥ 2 cm in P2. Preoperative conization improved disease-free survival in patients with tumors ≥ 2 cm, especially in minimally invasive group. @*Conclusion@#Minimally invasive radical hysterectomy required more cases than open group to achieve acceptable 5-year disease-free survival. When tumors ≥ 2 cm, the surgeon’s proficiency affected survival outcomes in both groups.

A single-arm phase II study of olaparib maintenance with pembrolizumab and bevacizumab in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer (OPEB-01) / 부인종양

Background@#The optimal treatment of BRCA wild-type patients with platinum-sensitive recurrent ovarian cancer remains unknown. Recently, there is an increase in the evidence to support the role of the combination of a poly(adenosine diphosphate-ribose) polymerase inhibitor, anti-angiogenic agents, and immunotherapy as maintenance therapy in BRCA wild-type patients with platinum-sensitive recurrence. We hypothesized that adding pembrolizumab and bevacizumab to olaparib maintenance can increase progression-free survival (PFS) in BRCA wild-type patients with platinum-sensitive recurrent ovarian cancer. @*Methods@#BRCA wild-type patients who received two previous courses of platinum-containing therapy, achieved complete or partial response to last treatment, and the treatment-free interval is >6 months after the penultimate platinum-based chemotherapy offered olaparib maintenance with pembrolizumab and bevacizumab. Forty-four patients will be included from 4 sites across Singapore and Korea. The primary endpoint of the study is 6-month PFS rate.

Comparison of Serum Anti-Mullerian Hormone-Level Changes in Single-Port Laparoscopic Endometriotic and Non-Endometriotic Ovarian Cyst Enucleations

Objectives@#This study compared serum anti-Mullerian hormone (AMH) levels in endometriotic cysts (ECs) with those in non-ECs and analyzed changes thereof after single-port laparoscopic (SPL) ovarian cyst enucleation using vasopressin injection. @*Methods@#In total, 180 patients (EC group, n = 112; non-EC group, n = 68) who underwent SPL ovarian cyst enucleation were retrospectively reviewed. Their AMH levels were checked preoperatively, on postoperative day 10 (POD10), and on postoperative month 3 (POM3). Changes in AMH levels were analyzed according to tumor type and vasopressin use. @*Results@#The median initial and postoperative serum AMH levels in the EC group were significantly lower than those in the nonEC group (preoperation: 2.0 vs 3.8 ng/mL, P < 0.001; POD10: 1.0 vs 3.2 ng/mL, P < 0.001; POM3: 1.2 vs 3.6 ng/mL, P < 0.001). The postoperative decrease in AMH levels was higher in the EC group than the non-EC group on POD10 (0.8 vs 0.5 ng/mL, P = 0.011) but not on POM3 (0.7 vs 0.5 ng/mL, P = 0.164). Vasopressin injection during EC enucleation had no significant effect on the decrease in AMH levels on POD10 (vasopressin group vs non-vasopressin group: 1.0 vs 0.8 ng/mL, P = 0.253) and POM3 (vasopressin group vs nonvasopressin group: 1.4 vs 1.1 ng/mL, P = 0.242). @*Conclusions@#AMH levels were lower at baseline and had higher decreasing rates after SPL surgery in the EC group relative to the nonEC group. Vasopressin injection might not protect the ovary from the postoperative decrease in AMH levels.

CT-Based Fagotti Scoring System for Non-Invasive Prediction of Cytoreduction Surgery Outcome in Patients with Advanced Ovarian Cancer

Objective@#To construct a CT-based Fagotti scoring system by analyzing the correlations between laparoscopic findings and CT features in patients with advanced ovarian cancer. @*Materials and Methods@#This retrospective cohort study included patients diagnosed with stage III/IV ovarian cancer who underwent diagnostic laparoscopy and debulking surgery between January 2010 and June 2018. Two radiologists independently reviewed preoperative CT scans and assessed ten CT features known as predictors of suboptimal cytoreduction. Correlation analysis between ten CT features and seven laparoscopic parameters based on the Fagotti scoring system was performed using Spearman’s correlation. Variable selection and model construction were performed by logistic regression with the least absolute shrinkage and selection operator method using a predictive index value (PIV) ≥ 8 as an indicator of suboptimal cytoreduction. The final CT-based scoring system was internally validated using 5-fold cross-validation. @*Results@#A total of 157 patients (median age, 56 years; range, 27–79 years) were evaluated. Among 120 (76.4%) patients with a PIV ≥ 8, 105 patients received neoadjuvant chemotherapy followed by interval debulking surgery, and the optimal cytoreduction rate was 90.5% (95 of 105). Among 37 (23.6%) patients with PIV < 8, 29 patients underwent primary debulking surgery, and the optimal cytoreduction rate was 93.1% (27 of 29). CT features showing significant correlations with PIV ≥ 8 were mesenteric involvement, gastro-transverse mesocolon-splenic space involvement, diaphragmatic involvement, and para-aortic lymphadenopathy. The area under the receiver operating curve of the final model for prediction of PIV ≥ 8 was 0.72 (95% confidence interval: 0.62–0.82). @*Conclusion@#Central tumor burden and upper abdominal spread features on preoperative CT were identified as distinct predictive factors for high PIV on diagnostic laparoscopy. The CT-based PIV prediction model might be useful for patient stratification before cytoreduction surgery for advanced ovarian cancer.

Comparison of single-port laparoscopy and laparotomy in early ovarian cancer surgical staging

Objectives@#The aims of this study were to assess the feasibility of single-port laparoscopic surgical staging (SPLS) in early ovarian cancer and to compare the surgical outcomes of SPLS with those of staging laparotomy. @*Methods@#Between January 2014 and December 2018, 40 patients underwent SPLS and 41 patients underwent staging laparotomy at Yonsei Cancer Center. The patients were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I ovarian cancer. Variables such as patient age, body mass index (BMI), tumor size, FIGO stage, and perioperative surgical outcomes and survival outcomes of SPLS and laparotomy were compared. @*Results@#The total operation time was similar between the 2 groups (SPLS: 201.4 vs. laparotomy: 203.0 minutes, P=0.806). The median tumor diameters in the SPLS and laparotomy groups were 11.0 (2.5–28 cm) and 15.4 (6–40 cm), respectively (P=0.001). The SPLS group had lower tumor spillage rate (5.0% vs. 19.5%, P=0.047), less intraoperative blood loss (102.0 vs. 371.5 mL, P<0.001), less postoperative pain, and shorter postoperative hospital stay (5 vs. 9.5 days, P<0.001). The intraoperative major complication rate was similar between groups (2.5% vs. 4.9%, P=0.571). There was no significant difference in progression-free survival between the 2 groups (P=0.945). There were no deaths in either group. @*Conclusion@#SPLS is feasible in early ovarian cancer and has better perioperative surgical outcomes, in some aspects, than staging laparotomy without compromising survival outcomes. SPLS could be performed in patients suspected to have early ovarian cancer.

CT-Based Fagotti Scoring System for Non-Invasive Prediction of Cytoreduction Surgery Outcome in Patients with Advanced Ovarian Cancer

Objective@#To construct a CT-based Fagotti scoring system by analyzing the correlations between laparoscopic findings and CT features in patients with advanced ovarian cancer. @*Materials and Methods@#This retrospective cohort study included patients diagnosed with stage III/IV ovarian cancer who underwent diagnostic laparoscopy and debulking surgery between January 2010 and June 2018. Two radiologists independently reviewed preoperative CT scans and assessed ten CT features known as predictors of suboptimal cytoreduction. Correlation analysis between ten CT features and seven laparoscopic parameters based on the Fagotti scoring system was performed using Spearman’s correlation. Variable selection and model construction were performed by logistic regression with the least absolute shrinkage and selection operator method using a predictive index value (PIV) ≥ 8 as an indicator of suboptimal cytoreduction. The final CT-based scoring system was internally validated using 5-fold cross-validation. @*Results@#A total of 157 patients (median age, 56 years; range, 27–79 years) were evaluated. Among 120 (76.4%) patients with a PIV ≥ 8, 105 patients received neoadjuvant chemotherapy followed by interval debulking surgery, and the optimal cytoreduction rate was 90.5% (95 of 105). Among 37 (23.6%) patients with PIV < 8, 29 patients underwent primary debulking surgery, and the optimal cytoreduction rate was 93.1% (27 of 29). CT features showing significant correlations with PIV ≥ 8 were mesenteric involvement, gastro-transverse mesocolon-splenic space involvement, diaphragmatic involvement, and para-aortic lymphadenopathy. The area under the receiver operating curve of the final model for prediction of PIV ≥ 8 was 0.72 (95% confidence interval: 0.62–0.82). @*Conclusion@#Central tumor burden and upper abdominal spread features on preoperative CT were identified as distinct predictive factors for high PIV on diagnostic laparoscopy. The CT-based PIV prediction model might be useful for patient stratification before cytoreduction surgery for advanced ovarian cancer.

Early Assessment of Response to Neoadjuvant Chemotherapy with 18F-FDG-PET/CT in Patients with Advanced-Stage Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The aim of this study was to evaluate the ability of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) after one cycle of neoadjuvant chemotherapy (NAC) to predict chemotherapy response before interval debulking surgery (IDS) in advanced-stage ovarian cancer patients. @*Materials and Methods@#Forty consecutive patients underwent 18F-FDG-PET/CT at baseline and after one cycle of NAC. Metabolic responses were assessed by quantitative decrease in the maximum standardized uptake value (SUVmax) with PET/CT. Decreases in SUVmax were compared with cancer antigen 125 (CA-125) level before IDS, response rate by Response Evaluation Criteria in Solid Tumors criteria before IDS, residual tumor at IDS, and I chemotherapy response score (CRS) at IDS. @*Results@#A 40% cut-off for the decrease in SUVmax provided the best performance to predict CRS 3 (compete or near-complete pathologic response), with sensitivity, specificity, and accuracy of 81.8%, 72.4%, and 72.4%, respectively. According to this 40% cut-off, there were 17 (42.5%) metabolic responders (≥ 40%) and 23 (57.5%) metabolic non-responders (< 40%). Metabolic responders had higher rate of CRS 3 (52.9% vs. 8.7%, p=0.003), CA-125 normalization (< 35 U/mL) before IDS (76.5% vs. 39.1%, p=0.019), and no residual tumor at IDS (70.6% vs. 31.8%, p=0.025) compared with metabolic non-responders. There were significant associations with progression-free survival (p=0.021) between metabolic responders and non-responders, but not overall survival (p=0.335). @*Conclusion@#Early assessment with 18F-FDG-PET/CT after one cycle of NAC can be useful to predic response to chemotherapy before IDS in patients with advanced-stage ovarian cancer.

Major clinical research advances in gynecologic cancer in 2019 / 부인종양

In 2019, 12 topics were selected as the major research advances in gynecologic oncology. Herein, we first opted to introduce the significant clinical activity of pembrolizumab in women with advanced cervical cancer based on the results of the phase 2 KEYNOTE-158 trial. Thereafter, we reviewed 5 topics, including systemic lymphadenectomy in the advanced stage with no gross residual tumor, secondary cytoreductive surgery in recurrent ovarian cancer according to the results of Gynecologic Oncology Group-213 trial, dose-dense weekly paclitaxel scheduling as first-line chemotherapy, the utility of intraperitoneal therapy in the advanced stage, and an update on poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Additionally, we conducted a thorough review of emerging data from several clinical trials on PARP inhibitors according to drug, target population, and combined usage. For uterine corpus cancer, we reviewed adjuvant therapy for high-risk disease and chemotherapy in advanced/recurrent disease. For the field of radiation oncology, we discussed the utility of neoadjuvant chemotherapy added to chemoradiotherapy and the treatment of radiation-induced cystitis using hyperbaric oxygen. Finally, we discussed the use of individualized therapy with humanized monoclonal antibodies (trastuzumab emtansine and sacituzumab govitecan-hziy) and combination therapy (fulvestrant plus alpesilib, fulvestrant plus anastrozole, and ribociclib plus endocrine therapy) for women with advanced breast cancer.

Comparison between weekly versus 3-weekly paclitaxel in combination with carboplatin as neoadjuvant chemotherapy in advanced ovarian cancer / 부인종양

OBJECTIVE@#To compare the efficacy and toxicity of dose-dense weekly paclitaxel and 3-weekly carboplatin (ddPC) as neoadjuvant chemotherapy (NAC) with the standard 3-weekly regimen.@*METHODS@#A retrospective study of patients diagnosed with stage IIIc and IV ovarian cancer who received at least one cycle of NAC followed by interval debulking surgery between August 2015 and January 2018 was conducted. Patient characteristics, clinical and pathological response to NAC, surgical and survival outcome, and adverse event were compared.@*RESULTS@#A total of 23 patients in the ddPC group and 50 patients in the standard group received a median of 3 cycles of NAC. Rate of grade ≥3 neutropenia was significantly higher in the ddPC group than the standard (82.6% vs. 22.0%, p<0.001). Patients in the ddPC group underwent dose-reduction more frequently (34.8% vs. 4.00%, p=0.001). Normalization of cancer antigen-125 post-NAC occurred more frequently in the ddPC group (73.9% vs. 46.0%, p=0.030). No residual disease rate (43.5% vs. 60.0%, p=0.188) and chemotherapy response score of 3 (34.8% vs. 26.0%, p=0.441) were not statistically different between two groups. There was no statistical difference in progression free survival (PFS) at 2 years (36.3% vs. 28.4%, p=0.454). Cox proportional hazard model showed that ddPC was not a significant determinant of PFS (p=0.816).@*CONCLUSION@#There was no difference between both regimens in terms of NAC response and survival outcomes. However, ddPC group showed higher hematologic toxicity requiring dose reduction.

A Single-Center, Retrospective Study of Bevacizumab-Containing Neoadjuvant Chemotherapy followed by Interval Debulking Surgery for Ovarian Cancer

PURPOSE: We evaluated whether adding bevacizumab to current platinum-based chemotherapy could improve clinical outcomes without affecting safety.MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with pathologically confirmed ovarian cancer who received neoadjuvant chemotherapy (NAC) at Yonsei Cancer Hospital. We divided the patients into groups based on the use of bevacizumab for NAC (CP group: carboplatin+paclitaxel vs. BCP group: bevacizumab+carboplatin+paclitaxel) and compared patient characteristics, responses to NAC, and surgical and survival outcomes between the two groups. Overall, 88 patients in the CP group and 16 patients in the BCP group received NAC. The primary endpoint was survival outcomes. Complete resection rate after interval debulking surgery (IDS), cancer antigen 125 (CA-125) normalization after NAC, and chemotherapy response score were secondary endpoints.RESULTS: After NAC treatment, all patients underwent IDS. There were no significant differences in adverse events during NAC or postoperative complications between the two groups (p=0.293 and p=0.485, respectively). There were also no significant differences in CA-125 normalization after NAC (42.0% vs. 43.8%, p=0.899) or complete resection rate after IDS (47.7% vs. 56.3%, p=0.530). However, although the BCP group did not show longer overall survival (OS) (log-rank p=0.854), they had significantly longer progression-free survival (PFS) than the CP group (log-rank p=0.048).CONCLUSION: Bevacizumab-containing NAC might be safe and provide longer PFS than chemotherapy alone in patients with advanced ovarian cancer. However, further study is necessary to investigate the impact of bevacizumab-containing NAC on OS.

Comparison between weekly versus 3-weekly paclitaxel in combination with carboplatin as neoadjuvant chemotherapy in advanced ovarian cancer / 부인종양

OBJECTIVE: To compare the efficacy and toxicity of dose-dense weekly paclitaxel and 3-weekly carboplatin (ddPC) as neoadjuvant chemotherapy (NAC) with the standard 3-weekly regimen.METHODS: A retrospective study of patients diagnosed with stage IIIc and IV ovarian cancer who received at least one cycle of NAC followed by interval debulking surgery between August 2015 and January 2018 was conducted. Patient characteristics, clinical and pathological response to NAC, surgical and survival outcome, and adverse event were compared.RESULTS: A total of 23 patients in the ddPC group and 50 patients in the standard group received a median of 3 cycles of NAC. Rate of grade ≥3 neutropenia was significantly higher in the ddPC group than the standard (82.6% vs. 22.0%, p<0.001). Patients in the ddPC group underwent dose-reduction more frequently (34.8% vs. 4.00%, p=0.001). Normalization of cancer antigen-125 post-NAC occurred more frequently in the ddPC group (73.9% vs. 46.0%, p=0.030). No residual disease rate (43.5% vs. 60.0%, p=0.188) and chemotherapy response score of 3 (34.8% vs. 26.0%, p=0.441) were not statistically different between two groups. There was no statistical difference in progression free survival (PFS) at 2 years (36.3% vs. 28.4%, p=0.454). Cox proportional hazard model showed that ddPC was not a significant determinant of PFS (p=0.816).CONCLUSION: There was no difference between both regimens in terms of NAC response and survival outcomes. However, ddPC group showed higher hematologic toxicity requiring dose reduction.