Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician's choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer.

OBJECTIVE: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. METHODS: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. RESULTS: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1-43.0) months. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49-1.10) and 0.64 (0.44-0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45-1.02) and 0.61 (0.41-0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3-5, 74% and 72%), respectively. CONCLUSION: Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03517449.

Pembrolizumab plus chemotherapy in Japanese patients with persistent, recurrent or metastatic cervical cancer: Results from KEYNOTE-826.

Pembrolizumab plus chemotherapy with or without bevacizumab demonstrated prolonged progression-free survival (PFS) and overall survival (OS) versus chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer in the phase 3, randomized, double-blind, placebo-controlled KEYNOTE-826 study. We report outcomes in patients enrolled in Japan. Patients received pembrolizumab 200 mg or placebo Q3W for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5) with or without bevacizumab 15 mg/kg. Dual primary endpoints were PFS per RECIST v1.1 by investigator assessment and OS in the global population; these were evaluated in patients with tumors with PD-L1 combined positive score (CPS) ≥1, all-comers, and PD-L1 CPS ≥10. Fifty-seven patients from Japan were randomized (pembrolizumab plus chemotherapy, n = 35; placebo plus chemotherapy, n = 22). Pembrolizumab plus chemotherapy improved PFS versus placebo plus chemotherapy in patients with PD-L1 CPS ≥1 (n = 51; hazard ratio [HR; 95% CI], 0.36 [0.16-0.77]), all-comers (n = 57; 0.45 [0.22-0.90]), and patients with PD-L1 CPS ≥10 (n = 25; 0.36 [0.12-1.07]). HRs (95% CI) for OS were 0.38 (0.14-1.01), 0.41 (0.17-1.00), and 0.37 (0.10-1.30), respectively. Incidence of grade 3-5 AEs was 94% in the pembrolizumab group and 100% in the placebo group. Consistent with findings in the global KEYNOTE-826 study, pembrolizumab plus chemotherapy with or without bevacizumab may prolong survival versus placebo plus chemotherapy with or without bevacizumab and had a manageable safety profile in Japanese patients with persistent, recurrent, or metastatic cervical cancer.

Prevalence of sarcopenia in patients with gynecological cancer.

BACKGROUND: The aim of the study was to investigate a prevalence of sarcopenia in patients with gynecological cancer in accordance with current diagnostic criteria of sarcopenia. METHODS: A series of 513 patients with gynecological cancer who were intended to newly receive initial or salvage treatment were recruited in a prospective study. Eligible patients were examined with dual energy X-ray absorptiometry and underwent handgrip strength test and the Short Physical Performance Battery before treatment. Sarcopenia was defined as both low skeletal muscle mass (skeletal muscle mass index) and low muscle strength (handgrip strength of <18.0 kg) or both low skeletal muscle mass index and low physical performance (Short Physical Performance Battery score of ≤9). RESULTS: A total of 475 patients (92.6%) were completely assessed in this study. Eligible patients' median age was 60 years (range: 29-89 years). Frequencies of patients with low skeletal muscle mass index, low hand grip strength and low Short Physical Performance Battery were 118 (24.8%), 70 (14.7%) and 80 (16.8%), respectively. Sarcopenia was finally identified in 45 patients (9.5%), which accounted for 38.1% of patients with low skeletal muscle mass index, 64.3% of the patients with low hand grip strength and 56.3% of the patients with low physical performance, respectively. CONCLUSIONS: The prevalence of sarcopenia of 9.5% in patients with gynecological malignancy who were scheduled to newly receive an initial or a salvage treatment. A large-scale, nation-wide study might be planned to elucidate an accurate prevalence of sarcopenia among gynecologic cancer patients.

Lenvatinib plus pembrolizumab in Japanese patients with endometrial cancer: Results from Study 309/KEYNOTE-775.

Study 309/KEYNOTE-775 is a phase 3 open-label, randomized trial of lenvatinib plus pembrolizumab versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer with progression after platinum-based therapy. Primary endpoints of superiority for lenvatinib plus pembrolizumab were met for progression-free survival (PFS) and overall survival (OS) in all-comers (ie, regardless of mismatch repair [MMR] status) and patients with MMR proficiency (pMMR). We present results for the Japanese subset. Patients were randomized to oral lenvatinib 20 mg/day plus intravenous pembrolizumab 200 mg every 3 weeks (Q3W; up to 35 cycles of pembrolizumab) or TPC (intravenous doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 QW [3 weeks on/1 week off]). Primary endpoints were PFS by blinded independent central review per RECIST version 1.1 and OS. One hundred four patients were randomized in Japan (data cutoff, October 26, 2020; median follow-up, 11.8 [range, 1.1-26.9] months). Hazard ratios (HRs) for PFS with lenvatinib plus pembrolizumab versus TPC were 1.04 (95% CI, 0.63-1.73) in patients with pMMR and 0.81 (0.50-1.31) in all-comers. Hazard ratios for OS were 0.74 (0.41-1.34) with pMMR and 0.59 (0.33-1.04) for all-comers. Adverse events were manageable and led to discontinuation of one/both study drugs in 36.5% of patients in the lenvatinib plus pembrolizumab group versus 7.8% in the TPC group. Similar to the global Study 309/KEYNOTE-775 results, this analysis suggested favorable efficacy and manageable safety with lenvatinib plus pembrolizumab after platinum-based chemotherapy in Japanese patients with advanced endometrial cancer and supports this combination as a new standard of care in this population.

Initial screening by immunohistochemistry is effective in universal screening for Lynch syndrome in endometrial cancer patients: a prospective observational study.

BACKGROUND: Few prospective reports of universal screening for Lynch syndrome exist for patients with endometrial cancer. In this study, we performed immunohistochemical staining for DNA mismatch repair-related genes (MLH1, MSH2, MSH6 and PMS2), to determine the extent to which Lynch syndrome can be diagnosed in endometrial cancer patients through universal screening. METHODS: We recruited 116 consecutive patients assumed to have uterine corpus malignancy from October 2019 to February 2021 in a prospective observational study. We performed immunohistochemical for mismatch repair-related proteins on samples from 100 patients who had surgicopathologically confirmed diagnoses of endometrial cancer. Samples with missing immunohistochemical results for any of the proteins had subsequent universal screening tests for microsatellite instability, DNA methylation of the MLH1 promoter region and mismatch repair genetics. RESULTS: We identified 19 (19.0%) patients with lost results for any of the proteins. All 19 patient samples had subsequent screening tests. We identified the microsatellite instability-high phenotype in 84.2% (16/19) of these patients and MLH1 methylation in 57.9% (11/19). Mismatch repair genetic testing detected two pathological variants, in MSH2 and MSH6, which indicated that the prevalence of Lynch syndrome was 2.0% in our cohort. Two cases of unclassified variant (MSH6) and one case of benign variant (PMS2) were also detected. CONCLUSIONS: Initial screening by immunohistochemical is an effective method in universal screening for Lynch syndrome in endometrial cancer patients.

Clinical relevance of addition of conventional treatment to concurrent chemoradiotherapy in patients with FIGO stage III-IV cervical cancer: a retrospective analysis of a Japanese cohort.

BACKGROUND: Concurrent chemoradiotherapy has limited therapeutic efficacy for stage III-IV cervical cancer. We aimed to identify a subgroup of patients with stage III-IV cervical cancer who benefit from concurrent chemoradiotherapy with additional treatment. METHODS: We retrospectively reviewed 120 patients with stage III-IV cervical cancer who were treated with concurrent chemoradiotherapy from 2002 to 2018. We compared overall survival between patients treated with concurrent chemoradiotherapy alone and those who received concurrent chemoradiotherapy with additional conventional treatments (systemic chemotherapy before and/or after concurrent chemoradiotherapy and/or extended-field radiation). Prognostic factors were statistically analysed. RESULTS: Overall, 44 (36.7%) and 21 (17.5%) patients were radiologically diagnosed with pelvic and para-aortic lymph node enlargement, respectively. The median tumour diameter was 5.7 cm. A total of 69 (57.5%) patients received no additional treatment, and 51 (42.5%) received additional treatment. Cox regression analysis identified the following prognostic factors: histological non-squamous cell carcinoma (hazard ratio, 3.9; 95% confidence interval, 1.8-8.2), tumour diameter of ≥6 cm (hazard ratio, 2.1; 95% confidence interval, 1.2-3.7), radiological pelvic lymph node enlargement (hazard ratio, 2.1; 95% confidence interval, 1.1-4.0) and radiological para-aortic lymph node enlargement (hazard ratio, 2.1; 95% confidence interval, 1.1-4.1). Even in the lowest risk group (no risk factors), the 5-year overall survival rate was lower in the additional treatment group than in the concurrent chemoradiotherapy alone group (78.7% vs. 80.9%, respectively; log-rank test, P = 0.79). CONCLUSIONS: Addition of conventional treatments to concurrent chemoradiotherapy might not improve survival in patients with advanced cervical cancer. Novel treatment strategies including immune checkpoint inhibitors should be considered for such patients.

Validity of skeletal muscle mass index measurements for assessing sarcopenia in patients with gynecological cancer.

BACKGROUND: The current study investigated an optimal method for using CT scan in detection of low skeletal muscle mass quantity (SMQ). METHODS: In total, 82 consecutive patients with gynecological cancers were examined using computed tomography (CT) and dual-energy X-ray absorptiometry (DEXA) before treatment. Low SMQ was defined as a DEXA-based skeletal muscle mass index (SMI) of <5.40 kg/m2. Furthermore, CT-based SMI values were measured by six evaluators, and each evaluator measured SMI values two times for each subject. The first SMI value and the average SMI value were used for analyses. Receiver operating characteristic (ROC) analyses were performed to evaluate the performance of CT-based SMI measurements for detecting low SMQ. Interobserver agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: In total, 23 patients (28.0%) were diagnosed with low skeletal muscle mass. All areas under the curve (AUC) values from twelve (six evaluators × two measurements) ROC curves were within the range of 0.8-0.9. AUC values based on a single measurement and those based on two measurements were almost the same. The ICC was 0.828 (95% CI 0.777-0.874, P < 0.001) when using a single measurement value and increased to 0.959 (95% CI 0.944-0.971, P < 0.001) when using the average of the two measurements. CONCLUSIONS: A single measurement CT-based SMI efficiently identified patients with low SMQ in a daily clinical setting. The reliability of SMI measurements might be further improved by using a mean value of two measurements compared with the use of a single measurement value.

A BMI-category distribution pattern of intrinsic and treatment-related prognostic factors in endometrial cancer.

OBJECTIVE: In patients with endometrial cancer, obesity is associated with favorable prognostic characteristics but not with prolonged survival. The aim of this study was to elucidate the reason for this clinical paradox. METHODS: We retrospectively reviewed 1173 patients with endometrial cancer. Patients were divided into a non-obese group [body mass index (BMI) < 30 kg/m2], class I obesity group (BMI 30-35 kg/m2) and class II obesity group (BMI ≥ 35 kg/m2). The relationship between clinicopathological factors and disease-specific survival (DSS) was analyzed by Cox regression analysis. To correct for three-time significance testing, we used the Bonferroni method, giving the level of probability at which findings were considered significant as P < 0.0167. RESULTS: Three disease-intrinsic variables-older age, advanced stage and high-risk histology-and three treatment-related variables-no hysterectomy, no lymphadenectomy and no chemotherapy-were independently associated with poor DSS. DSS was similar among the three groups of patients even though the proportion of patients with plural pretreatment-related unfavorable risk factors significantly decreased with increment of BMI category (40.1 vs. 27.5 vs. 17.6%, P = 0.0003). The proportion of patients with plural treatment-related unfavorable prognostic factors significantly increased with increment of BMI category (21.3 vs. 26.7 vs. 39.3%, P = 0.0072). CONCLUSIONS: Poor-quality surgical staging in obese women may result in worse than expected survival outcomes.

Clinical implication of psoas muscle mass measurement for predicting death within 3 months in patients with incurable uterine cervical or corpus malignancy.

OBJECTIVE: The aim of this study was to find a clinical marker for identifying refractory cancer cachexia. METHODS: We analyzed computed tomography imaging data, which included the third lumbar vertebra, from 94 patients who died of uterine cervix or corpus malignancy. The time between the date of examination and date of death was the most important attribute for this study, and the computed tomography images were classified into >3 months before death and ≤ 3 months before death. Psoas muscle mass index was defined as the left-right sum of the psoas muscle areas (cm2) at the level of third lumbar vertebra, divided by height squared (m2). RESULTS: A data set of 94 computed tomography images was obtained at baseline hospital visit, and a data set of 603 images was obtained at other times. One hundred (16.6%) of the 603 non-baseline images were scanned ≤3 months before death. Mean psoas muscle mass index change rates at >3 months before death and ≤3 months before death were -1.3 and -20.1%, respectively (P < 0.001). Receiver operating characteristic curve analysis yielded a cutoff value of -13.0%. The area under the curve reached a moderate accuracy level (0.777, 95% confidence interval 0.715-0.838). When we used the cutoff value to predict death within 3 months, sensitivity and specificity were 74.0 and 82.1%, respectively. CONCLUSIONS: Measuring change in psoas muscle mass index might be useful for predicting cancer mortality within 3 months. It could become a potential tool for identifying refractory cancer cachexia.

Validity of measuring psoas muscle mass index for assessing sarcopenia in patients with gynecological cancer.

OBJECTIVE: The current study evaluated the performance of psoas muscle mass measurement for detecting low skeletal muscle mass quantity. METHODS: A sample of 82 consecutive patients with gynecological cancers was examined using computed tomography and dual energy X-ray absorptiometric scan before treatment. Skeletal muscle mass index was measured by dual energy X-ray absorptiometric scan and its cut-off value was set at 5.40 kg/m2 for detecting low skeletal muscle mass. Psoas muscle mass index was manually measured with cross-sectional computed tomography imaging at the level of L3 by six evaluators. RESULTS: Low skeletal muscle mass index was identified in 23 (28.0%) patients. Two-way analysis of variance confirmed a significant main effect of skeletal muscle mass index on mean psoas muscle mass index values (P < 0.0001). A receiver operating characteristic curve obtained from a total of 492 psoas muscle mass index data points gathered from six evaluators produced an area under the curve value of 0.697 (95% confidence interval 0.649-0.744) and a cut-off value of 3.52 cm2/m2, with sensitivity of 79.0% and specificity of 59.6%. Using the cut-off value, the kappa coefficient for evaluating diagnostic agreement between skeletal muscle mass index (low vs. normal) and psoas muscle mass index (low vs. normal) was 0.308 (95% confidence interval 0.225-0.392), suggesting poor agreement. Fleiss' kappa produced a coefficient of 0.418 (95% confidence interval 0.362-0.473), suggesting moderate agreement. CONCLUSIONS: Although relevance between skeletal muscle mass index and psoas muscle mass index was confirmed, intensity of relevance between them was weak. Psoas muscle mass index measurement should be subordinated to skeletal muscle mass index measurement for detection of low skeletal muscle mass.

Diagnostic criteria of sentinel lymph node micrometastasis or macrometastasis based on tissue rinse liquid-based cytology in gynecological cancer.

OBJECTIVE: This study aimed to establish intraoperative diagnostic criteria of sentinel lymph node (SLN) micro-/macrometastasis on the basis of tissue rinse liquid-based cytology (TRLBC) in gynecological cancer. METHODS: We enrolled 214 patients with gynecological cancer who underwent rapid diagnosis of SLN metastasis on the basis of TRLBC from a total of 490 SLNs. For slides that were classified as positive for atypical cells on cytological inspection, we counted the number of clusters (an atypical cell mass consisted of three or more cells) and the number of single cells (an atypical cell other than clusters). Receiver operating characteristic (ROC) analysis was applied to determine the efficiency of predicting SLN micro-/macrometastasis. RESULTS: On cytological inspection, 36 slides were classified as positive for atypical cells, while 21 slides (4.3%) were true positive, 15 (3.1%) were false positive, and 454 (92.6%) were true negative. There were no false negative results in this study. The area under the ROC curve for the number of cluster was superior to that for the number of single cells for distinguishing micro-/macrometastasis from negative/isolated tumor cells (0.86 vs. 0.67, P = 0.032). The optimum cut-off value of the number of clusters was 5 for distinguishing these two categories. CONCLUSIONS: TRLBC is a highly sensitive alternative for detecting SLN metastasis as a rapid intraoperative diagnosis. Counting the number of atypical cell clusters might be useful for distinguishing micro-/macrometastasis from isolated tumor cells.

Bevacizumab-related gastrointestinal perforation in patients with three or more prior chemotherapy regimens: A real-world experience.

OBJECTIVE: Associations between the number of prior chemotherapy (CT) regimens and gastrointestinal (GI) perforation in patients receiving bevacizumab treatment has not been fully investigated. The aim of the study was to investigate the impact of ≥3 prior CT regimens on GI perforation. MATERIALS AND METHODS: We retrospectively investigated the medical records of 133 patients with gynecological cancer who received bevacizumab-containing treatment. Bevacizumab was intravenously administered at a dose of 15 mg/kg every 4 weeks. Incidence of GI perforation was compared between ≤2 and ≥3 prior CT groups. RESULTS: Twenty-three (17.3%) patients had a history of ≥3 CT; these patients received bevacizumab at 4-week intervals. The percentage of patients with prior surgery was significantly higher in the ≥3 prior CT group (95.7% vs. 70.0%, P = 0.008), while those with prior bowel resection was significantly higher in the ≥3 prior CT group (30.4% vs. 12.7%, P = 0.034). There was no significant difference in the mean number of bevacizumab cycles between the two groups (10.7 vs. 8.9, P = 0.19). While GI perforation was observed in three (2.7%) patients in the ≤2 prior CT group, no GI perforation was found in the ≥3 prior CT group (P > 0.99). CONCLUSION: A history of ≥3 prior CT did not increase the risk for GI perforation when bevacizumab is administered at a dose of 15 mg/kg every 4 weeks in our cases.

Imaging-based definition of lower uterine segment carcinoma to improve the detection sensitivity of probable Lynch syndrome.

OBJECTIVE: The aim of this study was to investigate a magnetic resonance imaging-based definition of lower uterine segment carcinoma. METHODS: We retrospectively reviewed 587 consecutive patients with endometrial cancer who underwent hysterectomy. Lower uterine segment carcinoma was determined through pathological examination and magnetic resonance imaging assessment. For imaging assessment, the location of the inner lining of the uterus was classified into four equal parts on a sagittal section image. A tumor was defined as lower uterine segment carcinoma when its thickest part was located in the second or the third part from the uterine fundus. Lower uterine segment carcinoma was further divided into lower uterine segment in a narrow sense, upon which diagnosis was exclusively based on pathological findings, and lower uterine segment in a broad sense that were the remaining lower uterine segment carcinomas except lower uterine segment carcinomas in a narrow sense. The relationship between lower uterine segment carcinoma and probable Lynch syndrome was investigated. Patients with loss of MSH2, MSH6, and PMS2 expression or those with tumors with loss of MLH1 and absence of MLH1 promoter methylation were diagnosed as probable Lynch syndrome. RESULTS: Lower uterine segment carcinoma was identified in 59 (10.2%) patients. Twenty-eight (47.5%) patients were categorized as lower uterine segment in a narrow sense and 31 (52.5%) as lower uterine segment in a broad sense. Among them, probable Lynch syndrome was identified in 12 (20.3%) cases. There was no difference in clinical profiles, including the prevalence of probable Lynch syndrome between the two categories. CONCLUSIONS: A magnetic resonance imaging-based expanded definition of lower uterine segment carcinoma is likely to secure characteristics equivalent to a conventional pathology-based definition of lower uterine segment carcinoma. The novel definition of lower uterine segment carcinoma might improve the detection of probable Lynch syndrome.

Cervical laser vaporization for women with cervical intraepithelial neoplasia-3.

OBJECTIVE: This study evaluated outcomes of laser vaporization of the cervix for women with cervical intraepithelial neoplasia (CIN)-3. METHODS: We retrospectively reviewed 161 consecutive patients with CIN3 who were treated with cervical laser vaporization between January 2008 and December 2012. At each follow-up visit, histologically confirmed CIN2, CIN3 and invasive carcinoma were defined as treatment failures, as were high-grade squamous intraepithelial lesion (HSIL) or atypical squamous cells that cannot exclude HSIL with subsequent treatment or lost to follow-up. Primary endpoints included long-term follow-up (at least 5 years of regular hospital visits) and treatment failure rate. Treatment failure rates were estimated by the Kaplan-Meier method. RESULTS: Patients' median age was 31 years old. Median follow-up period was 67 months (interquartile range: 52-74 months). Over 5 years, 70.8% continued their follow-up visits, but significantly more patients aged ≥35 years did so (86.4%) than did those aged ≤34 years (61.8%, P = 0.0009). Treatment failure was observed in 14 (8.7%) patients, 1 of whom progressed to invasive cancer (0.6%). Cumulative treatment failure rates were 1-year: 5.1%, 2-year: 6.4% and 5-year: 9.5%. Among patients who suffered treatment failures, 57.1% initial failures occurred within the first year and 71.4% within the first 2 years. CONCLUSIONS: Long-term oncologic outcomes of cervical vaporization in CIN3 remain at a suboptimal level. The importance of a minimum of 5 years of regular hospital visits should be emphasized to patients with CIN3 who are candidates for cervical laser vaporization, especially those aged ≤34 years.

A feasibility study of sentinel lymph node mapping by cervical injection of a tracer in Japanese women with early stage endometrial cancer.

OBJECTIVE: The aim of this study was to investigate the feasibility of sentinel lymph node mapping characterized by a cervical tracer injection in endometrial cancer. MATERIALS AND METHODS: This retrospective study was carried out using data for 57 patients with endometrial carcinoma who had undergone intraoperative sentinel lymph node mapping and subsequent surgical staging. Technetium colloid and/or indocyanine green was injected into the uterine cervix and a gamma-detecting probe and/or photodynamic eye camera system was used intraoperatively to locate hot spots. RESULTS: Of the 57 patients, 52 (91.2%) had FIGO Stage I disease. Successful unilateral or bilateral mapping occurred in 54 patients (94.7%) and 46 (80.7%), respectively. The median number of sentinel lymph nodes detected was two (range, 0-5). Following sentinel lymph node mapping, 41 patients (71.9%) underwent pelvic lymphadenectomy alone and 16 (28.1%) full lymphadenectomy. The median number of lymph nodes resected was 17 (range, 8-110). Sentinel lymph nodes were involved in four patients (7.0%), two with macrometastases and two with low-volume metastases. The sensitivity and negative predictive value for detecting lymph node metastasis were both 100%. CONCLUSION: Sentinel lymph node mapping with the use of cervical tracer injection is highly feasible in Japanese women with early stage endometrial cancer.

Therapeutic significance of full lymphadenectomy in early-stage ovarian clear cell carcinoma.

OBJECTIVES: This study evaluated the therapeutic significance of full lymphadenectomy in early-stage ovarian clear cell carcinoma (OCCC). METHODS: We retrospectively reviewed records of 127 consecutive patients with pT1/pT2 and M0 OCCC who were treated between January 1995 and December 2015. We compared survival outcomes between those who did and did not undergo para-aortic lymph node dissection (PAND), and analyzed independent prognostic factors (Cox proportional hazards model with backward stepwise elimination). RESULTS: Of the 127 patients, 36 (28%) did not undergo lymphadenectomy; 12 (10%) patients underwent pelvic lymph node dissection (PLND) only; and 79 (62%) patients underwent both PLND and PAND. Of the 91 patients with lymphadenectomy, 11 (12%) had lymph node metastasis (LNM). The PAND⁻ and PAND⁺ groups did not significantly differ in age, distribution of pT status, radiologically enlarged lymph nodes, positive peritoneal cytology, capsule rupture, peritoneal involvement, and combined chemotherapy. Cox regression multivariate analysis confirmed that older age (hazard ratio [HR]=2.1; 95% confidence interval [CI]=1.0-4.3), LNM (HR=4.4; 95% CI=1.7-11.6), and positive peritoneal cytology (HR=4.2; 95% CI=2.1-8.4) were significantly and independently related to poor disease-specific survival (DSS), but implementation of both PLND and PAND (HR=0.4; 95% CI=0.2-0.8) were significantly and independently related to longer DSS. CONCLUSION: Although few in number, there are some patients with early-stage OCCC who can benefit from full lymphadenectomy. Its therapeutic role should be continuously investigated in OCCC patients at potential risk of LNM.

Prognostic factors for patients with brain metastasis from gynecological cancer: a significance of treatment-free interval of more than 6 months.

OBJECTIVE: Treatment-free interval has been confirmed as a significant prognostic factor in recurrent gynecological cancers. However, treatment-free interval has not been evaluated in previous studies investigating brain metastasis from gynecological malignancies. The aim of the study was to establish a predictive model of survival period after brain metastasis from gynecological cancer. METHODS: Of a total of 2848 patients with gynecological cancer, patients with brain metastasis were included in the study. Data at the time of brain metastasis diagnosis, which included primary origin, presence of extracranial metastasis, the Eastern Cooperative Oncology Group (ECOG) performance status, the number of brain metastases, brain-metastasis free-interval, treatment-free interval and treatment for brain metastasis were collected. Survival data were analyzed using Kaplan-Meier methods and Cox proportional hazards models. RESULTS: Incidences of brain metastasis were 1.7% (47/2848). Median survival period after diagnosis of brain metastasis was 20 weeks (4-5 months). The 6-, 12- and 24-month survival rates after brain metastasis were 44.0%, 22.0% and 16.5%, respectively. Cox regression analysis showed that extracranial metastasis (hazard ratio [HR], 5.2; 95% confidence interval [CI]: 1.04-26.3), ECOG performance status of 3-4 (HR, 3.1; 95% CI: 1.20-7.91), treatment-free interval of <6 months (HR, 3.8; 95% CI: 1.09-13.1), and no anti-cancer treatment for brain metastasis (HR, 3.6; 95% CI: 1.34-9.41) were significantly and independently related to poor survival. CONCLUSION: Treatment-free interval should be assessed in a future study to verify prognostic predictors of brain metastasis from gynecological cancer.

Thoracic laminectomy with spinal fixation in a nonambulatory patient with metastatic vertebral tumor from endometrial carcinoma.

Vertebral metastasis from endometrial cancer is a rare event and requires emergency treatment at the onset of neurologic symptoms caused by spinal cord compression. We report a case of a metastatic vertebral tumor, according to the International Federation of Gynecology and Obstetrics classification, of stage IVb endometrial cancer with multiple lung metastases. Emergency irradiation to the spinal tumor was conducted as a result of a loss of ambulation. Thoracic laminectomy with spinal fixation was subsequently performed because the patient remained nonambulatory and her neurological function deteriorated. Spinal decompression surgery enabled her to regain the ability to walk. Complete remission was achieved by subsequent pelvic surgery followed by combined chemotherapy consisting of docetaxel and carboplatin. Finally, the patient had no evidence of disease 45 months after the initial treatment. Early recognition and expeditious treatment is crucial for neurological recovery from metastatic spinal cord compression.

Radicality of initial surgery for primary malignant melanoma of the vagina.

Radical surgery is considered not to improve the prognosis of primary malignant melanoma of the vagina (PMMV). This study was carried out to review the general consensus. A systematic review was performed on the basis of data from 10 patients in our cohort and 147 patients in the previous literature. The radicality of the initial surgery (RAINS) score was defined as the total number of points in terms of the resected organs. The target organs were the vagina, vulva, urethra, bladder, uterus, anus, rectum, pelvic lymph nodes, and inguinal lymph nodes. Overall survival (OS) according to the RAINS score was analyzed using the Kaplan-Meier method. Information on tumor stage, size, and depth of invasion was not obtained in 15, 47, and 43% of patients, respectively. The median follow-up period was 18 months. OS with a RAINS score of at least 7 was significantly longer than that with a RAINS score of up to 6 (median survival time, 41 vs. 19 months; log-rank test, P=0.037), despite the fact that the former group included significantly more patients with advanced-stage disease. A significant difference in OS was not found between patients with a RAINS score of at least 6 and up to 5. The therapeutic significance of radical surgery for PMMV has not been assessed appropriately in previous studies because of the lack of comparability among groups and differences in the definitions of surgical radicality. Patients with PMMV might benefit from initial surgery with appropriate surgical radicality, despite incomplete validation of the RAINS score.

Isolated tumor cells and micrometastases in regional lymph nodes in stage I to II endometrial cancer.

OBJECTIVE: The aim of this study was to clarify the clinical significance of isolated tumor cells (ITCs) or micrometastasis (MM) in regional lymph nodes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II endometrial cancer. METHODS: In this study, a series of 63 patients with FIGO stage I to II were included, who had at least one of the following risk factors for recurrence: G3 endometrioid/serous/clear cell adenocarcinomas, deep myometrial invasion, cervical involvement, lympho-vascular space invasion, and positive peritoneal cytology. These cases were classified as intermediate-risk endometrial cancer. Ultrastaging by multiple slicing, staining with hematoxylin and eosin and cytokeratin, and microscopic examination was performed on regional lymph nodes that had been diagnosed as negative for metastases. RESULTS: Among 61 patients in whom paraffin-embedded block was available, ITC/MM was identified in nine patients (14.8%). Deep myometrial invasion was significantly associated with ITC/MM (p=0.028). ITC/MM was an independent risk factor for extrapelvic recurrence (hazard ratio, 17.9; 95% confidence interval [CI], 1.4 to 232.2). The 8-year overall survival (OS) and recurrence-free survival (RFS) rates were more than 20% lower in the ITC/MM group than in the node-negative group (OS, 71.4% vs. 91.9%; RFS, 55.6% vs. 84.0%), which were statistically not significant (OS, p=0.074; RFS, p=0.066). Time to recurrence tended to be longer in the ITC/MM group than in the node-negative group (median, 49 months vs. 16.5 months; p=0.080). CONCLUSIONS: It remains unclear whether ITC/MM have an adverse influence on prognosis of intermediate-risk endometrial cancer. A multicenter cooperative study is needed to clarify the clinical significance of ITC/MM.