Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study.

OBJECTIVES: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. METHODS/MATERIALS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.

Determination of ovarian transposition through prediction of postoperative adjuvant therapy in young patients with early stage cervical cancer undergoing surgery: a Korean multicenter retrospective study (KGOG 1042).

OBJECTIVE: We aimed to predict the risk of postoperative adjuvant therapy using preoperative variables in young patients with early stage cervical cancer. The predicted risk can guide whether ovarian transposition should be performed during surgery. METHODS: In total, 886 patients with stage IB1-IIA cervical cancer aged 20-45 years who underwent modified radical or radical hysterectomy between January 2000 and December 2008 were included. Preoperative variables, preoperative laboratory findings, International Federation of Gynaecology and Obstetrics stage, tumor size, and pathological variables were collected. Patients with high risk factors or those who met the Sedlis criteria were considered adjuvant therapy risk (+); others were considered adjuvant therapy risk (-). A decision-tree model using preoperative variables was constructed to predict the risk of adjuvant therapy. RESULTS: Of 886 patients, 362 were adjuvant therapy risk (+) (40.9%). The decision-tree model with four distinct adjuvant therapy risks using tumor size and age were generated. Specifically, patients with tumor size ≤2.45 cm had low risk (49/367; 13.4%), those with tumor size ≤3.85 cm and >2.45 cm had moderate risk (136/314; 43.3%), those with tumor size >3.85 cm and age ≤39.5 years had high risk (92/109; 84.4%), and those with tumor size >3.85 cm and age >39.5 years had the highest risk (85/96; 88.5%). CONCLUSION: The risk of postoperative adjuvant therapy in young patients with early stage cervical cancer can be predicted using preoperative variables. We can decide whether ovarian transposition should be performed using the predicted risk.

Self-obtained vaginal samples for HPV DNA testing to detect HPV-related cervical disease.

OBJECTIVE: To investigate if a self-obtained vaginal sample (SOVAS) contains sufficient DNA for a human papillomavirus (HPV) test and if the results are comparable to those obtained via cervical samples (CS) collected by a physician. METHODS: One hundred and fifty-one women who had abnormal cervical smears or who were HPV-positive were enrolled. Self-sampling was done after reading instructions and watching a 2-min-long video, whereas CS was obtained with a cervical cytobrush during a gynecologic examination. RESULTS: A multiplex real-time polymerase chain reaction-based assay detected the prevalence of any type of HPV to be 67.5% in the SOVAS and 57.4% in the CS, and that of high-risk (HR-) HPV to be 58.7% in the SOVAS and 48.6% in the CS. The sensitivity of detection of HR-HPV in the SOVAS was 100% (95% confidence interval [CI] -0.09 to 0.32) for high-grade squamous intraepithelial lesion, 78% (95% CI -0.09 to 0.13) for atypical squamous cells of undetermined significance or worse, and 95% (95% CI -0.01 to 0.25) for low-grade squamous intraepithelial lesion or worse, which was statistically within the non-inferiority margin compared with that of CS. CONCLUSION: Our study shows that the collection of a SOVAS is feasible and it is comparable to a CS for HPV DNA testing. Future studies are required to investigate the feasibility and cost-effectiveness of a mail-delivered SOVAS for cervical cancer screening.

Real-World Experience of Pembrolizumab Monotherapy in Patients with Recurrent or Persistent Cervical Cancer: A Korean Multi-Center Retrospective Study (KGOG1041).

This study investigated the antitumor activity and safety of pembrolizumab in patients with recurrent cervical cancer in real-world practice. We conducted a multi-center retrospective study of patients with recurrent or persistent cervical cancer treated with pembrolizumab at sixteen institutions in Korea between January 2016 and March 2020. The primary endpoints were the objective response rate (ORR) and safety. Data were available for 117 patients. The median age was 53 years (range, 28-79). Sixty-four (54.7%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥2. Forty-nine (41.9%) patients were stage ≥III at diagnosis. Eighty-eight (75.2%) patients had squamous cell carcinoma. The median number of prior chemotherapy lines was two (range, 1-6). During the median follow-up of 4.9 months (range, 0.2-35.3), the ORR was 9.4%, with three complete responses and eight partial responses. The median time to response was 2.8 months (range 1.3-13.1), and the median duration of response (DOR) was not reached. In the population of patients with favorable performance status (ECOG ≤1) (n = 53), the ORR was 18.9%, and the median DOR was 8.9 months (range, 7.3-10.4). Adverse events occurred in 55 (47.0%) patients, including eight (6.8%) patients who experienced grade ≥3 events, and two of them were suspicious treatment-related deaths. Pembrolizumab had modest antitumor activity in patients with recurrent cervical cancer comparable to that found in previously reported clinical trials. However, in patients with favorable performance status, pembrolizumab showed effective antitumor activity. Some safety profiles should be carefully monitored during treatment.

The Prognostic Model of Pre-Treatment Complete Blood Count (CBC) for Recurrence in Early Cervical Cancer.

The aim of the present study was to investigate the prognostic role of the pre-treatment complete blood count (CBC) profile as a predictive marker of survival, recurrence, and death in early stage squamous cell carcinoma and adenocarcinoma of the cervix. The pre-treatment CBC profiles of the patients from nine tertiary medical centers in South Korea who were treated surgically for early stage cervical cancer were reviewed. Statistical models by the Akaike's information criterion (AIC) were developed using CBC profiles to calculate individuals' risk scores for clinical outcomes. A total of 1443 patients were included in the study and the median follow-up was 63.7 months with a range of 3-183 months. Univariate analyses identified the components of CBC that were significantly related to clinical outcomes including white blood cell (WBC), hemoglobin, neutrophil, and platelet levels. The models developed using CBC profiles and the conventional clinical predictive factors provided individuals' risk scores that were significantly better in predicting clinical outcomes than the models using the conventional clinical predictive factors alone. Pre-treatment CBC profiles including WBC, hemoglobin, neutrophil, lymphocyte, and platelet levels were found to be a potential biomarker for survival prognosis in early cervical cancer.

An extremely rare elderly case of proximal epithelioid sarcoma of the vulva: case report with a review of literatures.

We experienced an extremely rare case of proximal epithelioid sarcoma (PES) of the vulva in a 77-year-old woman. After history taking and physical examination, the patient was tentatively diagnosed as having Bartholin's cyst in the right labium. Based on histopathological and immunohistochemical (IHC) findings, however, a final diagnosis of PES of the vulva was made. After receiving CyberKnife treatment, the patient survived but with recurrent episodes and poor prognosis. In conclusion, our case indicates that patients with PES of the vulva should be appropriately managed with radiotherapy after a differential diagnosis based on histopathological and IHC findings.

Prognostic Model for Survival and Recurrence in Patients with Early-Stage Cervical Cancer: A Korean Gynecologic Oncology Group Study (KGOG 1028).

PURPOSE: We aimed to develop and validate individual prognostic models in a large cohort of cervical cancer patients that were primarily treated with radical hysterectomy. MATERIALS AND METHODS: We analyzed 1,441 patients with early-stage cervical cancer treated between 2000 and 2008 from the Korean Gynecologic Oncology Group multi-institutional cohort: a train cohort (n=788) and a test cohort (n=653). Models predicting the risk for overall survival (OS), disease- free survival (DFS), lymphatic recurrence and hematogenous recurrence were developed using Cox analysis and stepwise backward selection and best-model options. The prognostic performance of each model was assessed in an independent patient cohort. Model-classified risk groups were compared to groups based on traditional risk factors. RESULTS: Independent risk factors for OS, DFS, lymphatic recurrence, and hematogenous recurrence were identified for prediction model development. Different combinations of risk factors were shown for each outcome with best predictive value. In train cohort, area under the curve (AUC) at 2 and 5 years were 0.842/0.836 for recurrence, and 0.939/0.882 for OS. When applied to a test cohort, the model also showed accurate prediction result (AUC at 2 and 5 years were 0.799/0.723 for recurrence, and 0.844/0.806 for OS, respectively). The Kaplan-Meier plot by proposed model-classified risk groups showed more distinctive survival differences between each risk group. CONCLUSION: We developed prognostic models for OS, DFS, lymphatic and hematogenous recurrence in patients with early-stage cervical cancer. Combining weighted clinicopathologic factors, the proposed model can give more individualized predictions in clinical practice.

Comparison of laparoscopic and abdominal radical hysterectomy in early stage cervical cancer patients without adjuvant treatment: Ancillary analysis of a Korean Gynecologic Oncology Group Study (KGOG 1028).

OBJECTIVE: We compared two groups of early stage cervical cancer patients treated with different surgical methods without adjuvant treatment using retrospective multicenter data previously collected for Korean Gynecologic Oncology Group (KGOG) study designed for developing prognostic models. METHOD: We initially assessed data from the multi-institutional cohort with early stage (IB-IIA) cervical cancer patients treated with radical hysterectomy without adjuvant treatment between 2000 and 2008. Propensity score matching was performed to compare disease-free survival (DFS) and overall survival (OS) of patients with laparoscopic to abdominal radical hysterectomy. Additionally, survival comparison was performed in patients with tumor size <2 cm. RESULTS: After matching, 119 patients with laparoscopic radical hysterectomy were compared with 357 patients with abdominal radical hysterectomy (median follow-up of 63.9 months). Inferior DFS was observed in the laparoscopy group (HR 2.738 [95% CI 1.326-5.650], p = 0.005) with a significant difference in pelvic (HR 5.110 [95% CI 1.817-14.473], p < 0.001) and hematogenous recurrence (HR 3.171 [95% CI 1.059-9.494], p = 0.03), but OS was not significantly different between two groups (p = 0.624). In subgroup analysis in the patient with tumor size <2 cm (laparoscopy 62 vs. laparotomy 186, median follow-up of 69.1 months), laparoscopy was associated with lower rate of DFS (HR 12.987 [95% CI 1.451-116.244], p = 0.003), but no significant difference in OS was observed between groups. Regarding OS, number of events is lacking, and inferior DFS in the laparoscopy group may be compensated by better response to radiation therapy in pelvic recurrence. CONCLUSIONS: In this analysis, laparoscopic radical hysterectomy was associated with lower rates of DFS but not OS in early stage cervical cancer patients without adjuvant treatment. Further larger scale studies are needed.

Prognostic significance of pretreatment lymphocyte percentage and age at diagnosis in patients with locally advanced cervical cancer treated with definite radiotherapy.

OBJECTIVE: This study aimed to evaluate the prognostic impact of age at diagnosis, and pretreatment hematologic markers, including lymphocyte percentage and the neutrophil-to-lymphocyte ratio (NLR), in patients with locally advanced cervical cancer (LACC) treated with definitive radiotherapy (RT). METHODS: A total of 392 patients with LACC (stage IIb to IVa) treated with cisplatin-based concurrent chemoradiotherapy or RT alone between 2001 and 2012 were retrospectively enrolled. Clinical data and pretreatment complete blood counts were extracted from electronic medical records of the patients, and analyzed. Treatment outcomes, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: Low lymphocyte percentage and a high NLR were associated with younger age, advanced stage, larger tumor size, lymph nodes metastasis, and treatment failure. The cut-off value for lymphocyte percentage and NLR was determined using a receiver operating characteristic curve. In univariate analysis, low lymphocyte percentage (≤24%) was associated with poor PFS and OS, while high NLR (>2.8) was significantly associated only with PFS. In multivariate analysis, both lymphocyte percentage (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.40-0.85; P=0.005) and NLR (HR, 1.55; 95% CI, 1.07-2.25; P=0.022) had independent prognostic value for PFS. Compared to younger patients (age ≤50 years), older patients (age >60 years) had a lower risk of death. CONCLUSION: Although the lymphocyte percentage did not remain significant in multivariate analysis for OS, it was predictive of PFS and OS. Thus, lymphocyte percentage is a simple hematologic parameter with a significant prognostic value in patients with LACC treated with definitive RT.

Anticancer and radiosensitizing effects of the cyclin-dependent kinase inhibitors, AT7519 and SNS­032, on cervical cancer.

Cyclin-dependent kinases (CDK) are considered to be potential targets of anticancer drugs that can interrupt the uncontrolled division of cancer cells. In this study, we selected two selective CDK inhibitors, AT7519 and SNS­032, from current clinical trials and examined their anticancer and radiosensitizing effects in a cervical cancer model. SNS­032 was found to be more potent than AT7519, with a lower half maximal inhibitory concentration (IC50) value. Both AT7519 and SNS­032 induced the apoptosis, premature senescence and cytostasis of cervical cancer cells, which led to the attenuation of tumor growth in vivo. Moreover, using these CDK inhibitors together with radiation synergistically inhibited tumor growth in a human xenograft tumor model. The concomitant activation of the p53 tumor suppressor and the suppression of cell cycle checkpoint responses mediated by Chk1 led to the cytostasis of cervical cancer cells. Finally, AT7519 and SNS­032 inhibited cancer cell migration, invasion and angiogenesis in vitro, and suppressed lung metastases in a spontaneous metastasis model. On the whole, the findings of this study indicate that the utilization of AT7519 and SNS­032 as part of an adjuvant treatment may help control cervical cancer progression.

Prognostic Importance of the Site of Recurrence in Patients With Metastatic Recurrent Cervical Cancer.

PURPOSE: The clinical characteristics and outcomes of patients with metastatic recurrent cervical cancer remain poorly understood. The goals of the present study were to investigate the survival outcomes according to the recurrence site in a large cohort of cervical cancer patients. METHODS AND MATERIALS: Of 1322 patients with primary cervical cancer from 2000 to 2013, 205 with recurrence after primary or adjuvant postoperative radiation were enrolled retrospectively. Aggressive salvage therapy (AST), which was defined as salvage therapy that aimed not only to relieve symptoms but also to ablate recurrent tumors by the single or combined application of surgical resection of local recurrence, metastasectomy, or metastasis-directed irradiation, followed by chemotherapy, was performed according to our institutional guidelines. The patterns of recurrence, application rate and mode of AST, and survival outcomes were evaluated retrospectively under approval from the institutional review board. RESULTS: Regarding the pattern of recurrence, distant-only (DO) recurrence was most common (59.5%), followed by combined (21.5%), central (cervix or vaginal stump; 10.7%), and pelvic (pelvic lymph nodes or pelvic side wall; 8.3%) recurrence. Two subgroups (distant lymph nodes and lung parenchyma) of the DO group demonstrated remarkably good prognosis and were categorized as type A DO; the other subgroups were labeled type B DO. Patients with type A DO recurrence constituted 36% of all recurrences and 83.8% of them received AST. The 5-year overall survival rates were significantly greater in the type A DO group than in the other groups (44.8% in the type A DO group, 12.6% in the pelvic group, and 6.8% in the type B DO group). CONCLUSIONS: We identified a patient subgroup with favorable outcomes after salvage therapy, type A DO, defined as recurrence in the distant lymph nodes only or in the lung parenchyma only. A future prospective trial is needed to investigate whether AST improves survival in this group.

Preoperative assessment of lymph node metastasis in endometrial cancer: A Korean Gynecologic Oncology Group study.

BACKGROUND: Previously proposed criteria for preoperatively identifying endometrial cancer patients at low risk for lymph node metastasis remain to be verified. For this purpose, a prospective, multicenter observational study was performed. METHODS: Eligible patients with histologically confirmed endometrial cancer underwent magnetic resonance imaging (MRI) and serum cancer antigen 125 (CA 125) testing before surgery. The following criteria were used to identify low-risk patients: 1) endometrioid-type cancer, 2) no evidence of deep myometrial invasion on MRI, 3) no enlarged lymph nodes on MRI, 4) no suspicious metastasis out of the uterine corpus, and 5) serum CA 125 levels less than 35 U/mL. Systematic pelvic and/or para-aortic lymphadenectomy was performed for all patients. The primary endpoint was estimation of the negative predictive value (NPV). RESULTS: From January 2012 to December 2014, 529 patients from 20 hospitals in 3 Asian countries were consecutively enrolled. According to our criteria, 272 patients (51.4%) were categorized into the low-risk group. Fifty-three of the 529 patients (10.0%) had lymph node metastases; these patients included 8 (2.9%) falsely categorized as low-risk. The sensitivity and specificity of the criteria were 84.9% and 55.5%, respectively. The NPV of 97.1% was higher than the predefined target endpoint of 96%. CONCLUSIONS: The low-risk criteria based on preoperative tests were confirmed to be reliable and accurate for identifying patients at low risk for lymph node metastasis. These criteria may facilitate patient counseling and surgical decision making. Cancer 2017;123:263-272. © 2016 American Cancer Society.

Salvage stereotactic body radiotherapy for locally recurrent uterine cervix cancer at the pelvic sidewall: Feasibility and complication.

AIMS: To determine the feasibility of stereotactic body radiotherapy (SBRT) in patients with pelvic sidewall recurrence of uterine cervical cancer after radical hysterectomy or definitive radiotherapy. METHODS: We retrospectively reviewed 23 patients with locally recurrent uterine cervical cancer limited to the pelvic sidewall who were treated with SBRT at our institution between January 2003 and May 2010. The SBRT dose ranged from 27 to 45 Gy (median, 39 Gy) in three fractions, and the fractional SBRT dose ranged from 9 to 15 Gy (median, 13 Gy). RESULTS: The 2-year overall survival, local progression-free survival and disease progression-free survival rates were 43%, 65% and 52%, respectively. Patients with small tumors (gross tumor volume <30 cm(3) ) had a significantly longer 2-year overall survival rate and 2-year local progression-free survival rate than did patients with large tumors (overall survival rate: 89% vs 12%; P = 0.0001 and local progression-free survival: 85% vs 0%; P = 0.0199). There were three cases (13%) of severe toxicities (rectovaginal fistula). Pelvic pain relief was achieved in all patients. In particular, 10 of 14 patients (71%) achieved analgesic (nonsteroidal anti-inflammatory drug or narcotic) reduction of 50% or more from baseline. CONCLUSION: SBRT is a feasible treatment option for women with pelvic sidewall tumors from recurrent uterine cervical cancer, especially for small recurrent tumors. However, SBRT should be used carefully in the treatment of large tumors, as the incidence of severe late toxicity increases with the size of the tumor.

Suppressor of cytokine signaling (SOCS) genes are silenced by DNA hypermethylation and histone deacetylation and regulate response to radiotherapy in cervical cancer cells.

Suppressor of cytokine signaling (SOCS) family is an important negative regulator of cytokine signaling and deregulation of SOCS has been involved in many types of cancer. All cervical cancer cell lines tested showed lower expression of SOCS1, SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry result for SOCS proteins in human cervical tissue also confirmed that normal tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to the regulation of SOCS in other types of cancer, DNA methylation contributed to SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3 expression, however, SOCS5 expression was neither affected by DNA methylation nor histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred radioresistance to HeLa cells, which implied SOCS signaling regulates the response to radiation in cervical cancer. In this study, we have shown that SOCS expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3 expression could contribute to the radiosensitive phenotype in cervical cancer.

Efficacy of fibrin sealant in reducing hemorrhage after a loop electrosurgical excision procedure.

BACKGROUND/AIMS: We examined the association of fibrin sealant use with post-operative hemorrhage in patients who underwent a loop electrosurgical excision procedure (LEEP). METHODS: We retrospectively collected clinicopathologic data of 344 patients who underwent LEEP at our institute between 2007 and 2009. We defined hemorrhage which occurred between 1 and 30 days after LEEP and required electrocautery to achieve hemostasis as severe secondary hemorrhage (SSH). We determined whether or not the use of fibrin sealant during LEEP was associated with a decreased occurrence of SSH. In addition, we examined the associations of other clinicopathologic variables with SSH and fibrin sealant use. RESULTS: SSH occurred in 6 of 200 patients (3%) with fibrin sealant and in 12 of 144 patients (8%) without fibrin sealant. Based on univariate analysis, the use of fibrin sealant was associated with SSH (p = 0.028). However, age, surgeons and pathologic diagnosis were not associated with SSH. Based on multivariate analysis, the use of fibrin sealant was associated with less SSH (p = 0.033, OR = 0.328, 95% CI 0.117-0.917). CONCLUSION: Fibrin sealant use reduces the incidence of severe post-operative hemorrhage after LEEP.

Characteristics of thyroid incidentalomas detected by pre-treatment [F]FDG PET or PET/CT in patients with cervical cancer.

OBJECTIVE: Considering the increased use of [(18)F]FDG PET or PET/CT, the clinical significance of thyroid incidentalomas is the subject of controversy. The aim of this study was to determine the incidence of malignancies associated with thyroid incidentalomas detected by pre-treatment PET or PET/CT in patients with cervical cancer. METHODS: We retrospectively reviewed the medical records of patients with cervical cancer who had thyroid incidentalomas detected by pre-treatment PET or PET/CT and were treated at our institute between January 2001 and December 2009. RESULTS: Of 327 patients who underwent pre-treatment PET or PET/CT, 33 patients had thyroid incidentalomas (10.1%) and 4 patients were diagnosed with thyroid malignancies by percutaneous needle aspiration (PCNA) or surgery. To put it concretely, of 33 patients with thyroid incidentaloma, 16 patients had a diffuse uptake and 17 patients had a focal uptake. Four of 17 patients with focal uptake were diagnosed with thyroid malignancies (23.5%). One patient with a focal uptake had an atypical cell based on PCNA, but did not undergo additional studies. The mean SUV(max) of thyroid malignancies did not differ from that of benign thyroid diseases. CONCLUSION: Thyroid incidentalomas are frequently detected by pre-treatment PET or PET/CT in patients with cervical cancer. Focal uptake on PET or PET/CT has a high risk of thyroid cancer.

Clinicopathologic factors for central recurrence in patients with locally advanced bulky cervical cancer.

OBJECTIVE: Locally advanced bulky cervical cancer (LABCC) is characterized by poor local control. The objective of this study was to identify the clinicopathologic variables associated with one-year central-only recurrence, which will serve as criteria for adjuvant hysterectomy after radiation (AHR) in patients with LABCC. STUDY DESIGN: Between January 2000 and August 2007, we retrospectively evaluated outcomes in 225 patients with LABCC who were initially treated with radiation or chemoradiation. RESULTS: Among the 225 patients with LABCC, there were 41 recurrences within one year after treatment (8 central-only and 33 pelvis and/or distant site recurrences). Age, stage, and treatment type were not associated with the one-year central-only recurrences, but tumor size ≥8cm had a statistically significant association based on multivariate analysis (OR, 5.39; 95% CI, 1.15-25.31; p=0.03). The combination of non-squamous cell (non-SCC) type and tumor size ≥8cm had a significantly higher rate of recurrence within one year (OR, 43.0; 95% CI, 4.78-386.68; p<0.01). CONCLUSIONS: Of patients with LABCC, those with non-SCC tumors ≥8cm in size were at high risk for early central-only recurrence after cisplatin-based chemoradiation, and represent the subset of patients for whom AHR is beneficial.

Risk of metastatic ovarian involvement in nongynecologic malignancies.

OBJECTIVE: The objectives were to evaluate the risk of malignant adnexal tumors in women with nongynecologic malignancies and to identify variables associated with the risk of malignant adnexal tumors. METHODS: The eligibility criteria included the diagnosis of a nongynecologic malignancy and adnexal tumors, which were resected or subjected to biopsy at our institute between 1999 and 2010. The risk of malignant adnexal tumors was assessed by dividing the number of patients with metastatic tumors to the adnexa or primary adnexal cancers by the total number of patients. The association of clinicopathologic variables with the risk of malignant adnexal tumors was evaluated using the Fisher exact test and binary logistic regression analysis. In patients with metastatic tumors to the adnexa, the association of clinicopathologic variables with overall survival after adnexal surgery was examined using the log-rank test. RESULTS: In 166 patients with adnexal tumors, 41 benign tumors, 113 metastatic tumors to the adnexa, and 12 primary adnexal cancers were diagnosed. Age older than 46 years, a tumor type associated with a high risk for malignant adnexal tumors, and bilateral tumors significantly increased the risk of malignant adnexal tumors. The overall survival of the patients with stomach cancer was significantly worse than the patients with colorectal or breast cancers. CONCLUSION: One hundred twenty-five of the 166 patients with nongynecologic malignancies who had adnexal tumors managed surgically were shown to have malignant tumors, and most of the tumors were metastatic from primary sites. The risk of malignant adnexal tumors was associated with age, nongynecologic malignancy, and bilaterality.

Randomized clinical trial of weekly vs. triweekly cisplatin-based chemotherapy concurrent with radiotherapy in the treatment of locally advanced cervical cancer.

PURPOSE: To compare compliance, toxicity, and outcome of weekly and triweekly cisplatin administration concurrent with radiotherapy in locally advanced cervical cancer. METHODS AND MATERIALS: In this open-label, randomized trial, 104 patients with histologically proven Stage IIB-IVA cervical cancer were randomly assigned by a computer-generated procedure to weekly (weekly cisplatin 40 mg/m(2), six cycles) and triweekly (cisplatin 75 mg/m(2) every 3 weeks, three cycles) chemotherapy arms during concurrent radiotherapy. The difference of compliance and the toxicity profiles between the two arms were investigated, and the overall survival rate was analyzed after 5 years. RESULTS: All patients tolerated both treatments very well, with a high completion rate of scheduled chemotherapy cycles. There was no statistically significant difference in compliance between the two arms (86.3% in the weekly arm, 92.5% in the triweekly arm, p > 0.05). Grade 3-4 neutropenia was more frequent in the weekly arm (39.2%) than in the triweekly arm (22.6%) (p = 0.03). The overall 5-year survival rate was significantly higher in the triweekly arm (88.7%) than in the weekly arm (66.5%) (hazard ratio 0.375; 95% confidence interval 0.154-0.914; p = 0.03). CONCLUSIONS: Triweekly cisplatin 75-mg/m(2) chemotherapy concurrent with radiotherapy is more effective and feasible than the conventional weekly cisplatin 40-mg/m(2) regimen and may be a strong candidate for the optimal cisplatin dose and dosing schedule in the treatment of locally advanced cervical cancer.