Abstract Objective The aim of this study was to determine the incidence rate of lower-extremity lymphedema after systematic lymphadenectomy in patients with uterine corpus malignancies and to ...elucidate risk factors for this type of lymphedema. Methods A retrospective chart review was carried out for all patients with uterine corpus malignant tumor managed at Hokkaido Cancer Center between 1991 and 2007. Patients who did not undergo lymphadenectomy as a treatment or died of cancer/intercurrent disease were excluded from this study. All living patients included in this study had hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy and their medical records were reviewed. We identified patients with postoperative lower-extremity lymphedema (POLEL). Logistic regression analysis was used to select the risk factors for POLEL. Results Of 286 patients evaluated, 103 (37.8%) had POLEL. Multivariate analysis confirmed that adjuvant radiation therapy (OR = 5.2, 95% CI = 2.1–12.7), resection of more than 31 lymph nodes (OR = 2.6, 95% CI = 1.4–4.9), and removal of circumflex iliac nodes to the distal external iliac nodes (CINDEIN) (OR = 6.1, 95% CI = 1.3–28.2) were independent risk factors for POLEL. Conclusion Adjuvant radiation therapy should be avoided in patients who undergo systematic lymphadenectomy if an alternative postoperative strategy is possible. Although reducing the number of resected lymph nodes is not appropriate from a therapeutical point of view, elimination of CINDEIN dissection may be helpful in reducing the incidence of POLEL. The clinical significance of CINDEIN dissection needs to be investigated by a randomized controlled trial.
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.
Pembrolizumab plus chemotherapy with or without bevacizumab demonstrated prolonged progression‐free survival and overall survival compared with chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer in the phase 3 KEYNOTE‐826 study. In this subset analysis of patients enrolled in Japan in the KEYNOTE‐826 study, pembrolizumab plus chemotherapy with or without bevacizumab was associated with prolonged progression‐free survival and overall survival in this setting.
Abstract
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.
In patients with endometrial cancer, obesity is associated with disease-intrinsic, favorable prognostic characteristics. Lack of survival advantage in obese women may be attributable to poor-quality surgical staging.
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.
Study 309/KEYNOTE‐775 is a phase 3 open‐label, randomized trial of lenvatinib plus pembrolizumab versus treatment of physician’s choice in patients with advanced endometrial cancer with progression after platinum‐based therapy. We present results for the Japanese subset of this clinical trial. Similar to results from the global study, 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.
Abstract
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.
Abstract
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.
We first reported the prevalence of sarcopenia stringently confirmed in accordance with the current international standard in patients with gynecological cancer.
This study evaluated outcomes of laser vaporization of the cervix for women with cervical intraepithelial neoplasia (CIN)-3.
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.
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.
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.
Abstract
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.
Psoas muscle mass measurement by using computed tomography should be subordinated to skeletal muscle mass index measurement by using dual energy X-ray absorptiometric scan for detection of sarcopenia.
Abstract
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.
Concurrent chemoradiotherapy has limited therapeutic efficacy for stage III–IV cervical cancer. Even if systematic chemotherapy or extended-field radiation added to concurrent chemoradiotherapy might not improve survival in patients with advanced cervical cancer.
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.
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.
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).
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.
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