Yosuke Konno

Efficacy of Rikkunshito on Chemotherapy-Induced Nausea and Vomiting in Patients With Uterine Corpus or Cervical Cancer Treated With Cisplatin-Based Regimen-Placebo-controlled, Double-Blind, Randomized Confirmatory Study (JORTC-KMP03)

Background: The current standard treatment for chemotherapy-induced nausea and vomiting (CINV) with standard antiemetics is insufficient. Rikkunshito, a Japanese traditional herbal medicine, has been shown to improve cisplatin-induced anorexia and functional dyspepsia, and our exploratory study found that rikkunshito has an additive beneficial effect on CINV in patients with uterine corpus and cervical cancer receiving cisplatin containing chemotherapy (JORTC KMP-02). Methods: One hundred eighty patients with uterine corpus or cervical cancer who were scheduled to receive treatment with a cisplatin based regimen as initial chemotherapy were enrolled across 17 Japanese institutions. Patients were randomized with a 1:1 equal allocation ratio to the rikkunshito group or placebo groups and given oral administration on days 1 to 5 with standard antiemetics (granisetron, aprepitant, and dexamethasone). The primary endpoint was complete response (CR; no vomiting or rescue medication) during the delayed phase (24-120 hours after cisplatin treatment). The secondary endpoints were complete control (CC; CR without significant nausea) and total control (TC; CR without nausea) rates during the overall (0-120 hours), acute (0-24 hours), and delayed phases, as well as the CR rate during the overall and acute phases, time to treatment failure, degree of nausea and appetite during the overall phase, and adherence to the intervention. Results: The CR rate in the delayed phase was similar between the rikkunshito group and control groups (50.6% vs 58.9%, P  = .2631), as were the secondary endpoints: CR rates in the overall and acute phases, CC and TC rates in the overall, acute, and delayed phases, degrees of nausea and appetite, and time to treatment failure. Conclusion: Rikkunshito had no additive effect on CINV prevention in patients with uterine corpus or cervical cancer who were treated with a cisplatin based regimen and standard antiemetics. Clinical Trial Registration: https://jrct.mhlw.go.jp/re/reports/detail/66957 , identifier jRCT1011190007

Patterns and predictors of site‐specific recurrence in cervical cancer after radical hysterectomy

AbstractAimThis study examines patterns and predictors of site‐specific recurrence to explore the causes of local recurrence of cervical cancer.MethodsRadical hysterectomy was performed in 121 patients (stage IB–IIB). Nerve‐sparing was performed whenever possible. The first recurrence in local, regional, and distant areas was examined. We investigated the possibility of nerve involvement in local recurrence, focusing on paravaginal tissues containing the pelvic plexus. We provide Supporting Information on local recurrence in the paravaginal area.ResultsLocal recurrence was an independent event from regional or distant recurrence. Local recurrence was seen only in high‐risk patients, while regional and distant recurrences were not or less related to the risk category. The independent risk factors by logistic regression for local, regional, and distant recurrence were parametrial invasion, vaginal invasion, and lymph node metastasis, respectively. Local recurrence showed a comparable or more significant negative impact on survival than distant recurrence. Among seven patients with local recurrences, five had a recurrence in the paravagina. The rate of paravaginal recurrence was one in 76 early‐stage and four in 45 locally advanced diseases. Four sites of paravaginal recurrence occurred on the nerve‐sparing side and two on the non‐nerve‐sparing side. Supporting Information demonstrated histological evidence of perineural spread into the pelvic plexus and perineural invasion of the primary tumor.ConclusionsA high percentage of local recurrences are in paravaginal tissue containing the pelvic plexus. The causal association of nerve‐sparing surgery and perineural invasion with local recurrence needs to be investigated in large prospective studies.

Prognostic significance of para-aortic node metastasis in endometrial cancer: Japanese Gynecologic Oncology Group Study JGOG2043 post hoc analysis

This study aimed to assess the prognostic significance of para-aortic lymphadenectomy (PALX) and para-aortic lymph node metastasis in endometrial cancer (EC) patients at risk of post-operative recurrence. Japanese Gynecologic Oncology Group (JGOG) 2043 was a randomized controlled trial assessing the efficacy of adjuvant chemotherapy in EC patients at risk for post-operative recurrence. A retrospective analysis included patients who underwent pelvic lymphadenectomy (PLX) alone or both PLX and PALX in JGOG2043. Data on positive lymph nodes and other clinicopathological risk factors were collected. PLX and PALX were performed on 402 patients, while PLX alone was conducted on 250 patients. Evaluating the effect of PALX on survival was challenging through a comparison of the outcomes of the 2 cohorts since PALX was predominantly administered to higher-risk patients. Patients with 2 or more metastases in para-aortic nodes exhibited significantly poorer overall survival than those with no or 1 metastasis, respectively (p<0.001, p=0.031). Multivariate analysis revealed that 2 or more metastases in para-aortic nodes is independent risk factors for disease-free survival (hazard ratio [HR]=1.72; 95% confidence interval [CI]=1.10-2.72; p=0.019) and are marginally significant for overall survival (HR=1.58; 95% CI=0.92-2.72; p=0.096) compared to no or a single metastasis. The clinical relevance of PALX was challenging to evaluate in the JGOG2043 cohort; however, the presence of 2 or more para-aortic node metastases was identified as an independent unfavorable prognostic factor in EC patients at risk of recurrence.

Prognostic impact of the number of resected pelvic nodes in endometrial cancer: Japanese Gynecologic Oncology Group Study JGOG2043 post hoc analysis

This study aimed to determine whether the number of resected pelvic lymph nodes (PLNs) affects the prognosis of endometrial cancer (EC) patients at post-operative risk of recurrence. JGOG2043 was a randomized controlled trial to assess the efficacy of three chemotherapeutic regimens as adjuvant therapy in EC patients with post-operative recurrent risk. A retrospective analysis was conducted on 250 patients who underwent pelvic lymphadenectomy alone in JGOG2043. The number of resected and positive nodes and other clinicopathologic risk factors for survival were retrieved. There were 83 patients in the group with less than 20 PLNs removed (group A), while 167 patients had 20 or more PLNs removed (group B). There was no significant difference in patients' backgrounds between the two groups, and the rate of lymph node metastasis was not significantly different. There was a trend toward fewer pelvic recurrences in group B compared with group A (3.5% vs. 9.6%; p=0.050). Although Kaplan-Meier analysis showed no statistically significant difference in survival rates between the two groups (5-year overall survival [OS]=90.3% vs. 84.3%; p=0.199), multivariate analysis revealed that resection of 20 or more nodes is one of the independent prognostic factors (hazard ratio=0.49; 95% confidence interval=0.24-0.99; p=0.048), as well as surgical stage, high-risk histology, and advanced age for OS. Resection of 20 or more PLNs was associated with improved pelvic control and better survival outcomes in EC patients at risk of recurrence who underwent pelvic lymphadenectomy alone and were treated with adjuvant chemotherapy.