Olaparib plus bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer: Japan subset from the PAOLA-1/ENGOT-ov25 trial / 부인종양

Objective@#The addition of maintenance olaparib to bevacizumab demonstrated a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the PAOLA-1/ENGOT-ov25 trial (NCT02477644). We evaluated maintenance olaparib plus bevacizumab in the Japan subset of PAOLA-1. @*Methods@#PAOLA-1 was a randomized, double-blind, phase III trial. Patients received maintenance olaparib tablets 300 mg twice daily or placebo twice daily for up to 24 months, plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. This prespecified subgroup analysis evaluated investigator-assessed PFS (primary endpoint). @*Results@#Of 24 randomized Japanese patients, 15 were assigned to olaparib and 9 to placebo. After a median follow-up for PFS of 27.7 months for olaparib plus bevacizumab and 24.0 months for placebo plus bevacizumab, median PFS was 27.4 versus 19.4 months, respectively (hazard ratio [HR]=0.34; 95% confidence interval [CI]=0.11–1.00). In patients with tumors positive for homologous recombination deficiency, the HR for PFS was 0.57 (95% CI=0.16–2.09). Adverse events in the Japan subset were generally consistent with those of the PAOLA-1 overall population and with the established safety and tolerability profiles of olaparib and bevacizumab. @*Conclusion@# @*Results@#in the Japan subset of PAOLA-1 support the overall conclusion of the PAOLA-1 trial demonstrating that the addition of maintenance olaparib to bevacizumab provides a PFS benefit in patients with newly diagnosed, advanced ovarian cancer.

Lymphadenectomy issues in endometrial cancer / 부인종양

Objectives@#This review aims to introduce preoperative scoring systems to predict lymph node metastasis (LNM) and ongoing clinical trials to investigate the therapeutic role of lymphadenectomy for endometrial cancer. @*Methods@#We summarized previous reports on the preoperative prediction models for LNM and evaluated their validity to omit lymphadenectomy in our recent cohorts. Next, we compared characteristics of two ongoing lymphadenectomy trials (JCOG1412, ECLAT) to examine the survival benefit of lymphadenectomy in endometrial cancer, and described the details of JCOG1412. @*Results@#Lymphadenectomy has been omitted for 64 endometrial cancer patients who met lowrisk criteria to omit lymphadenectomy using our scoring system (LNM score) and no lymphatic failure has been observed. Other two models also produced comparable results. Two randomized phase III trials to evaluate survival benefit of lymphadenectomy are ongoing for endometrial cancer. JCOG1412 compares pelvic lymphadenectomy alone with pelvic and para-aortic lymphadenectomy to evaluate the therapeutic role of para-aortic lymphadenectomy for patients at risk of LNM. For quality assurance of lymphadenectomy, we defined several regulations, including lower limit of the number of resected nodes, and submission of photos of dissected area to evaluate thoroughness of lymphadenectomy in the protocol. The latest monitoring report showed that the quality of lymphadenectomy has been well-controlled in JCOG1412. @*Conclusion@#Our strategy seems reasonable to omit lymphadenectomy and could be generalized in clinical practice. JCOG1412 is a high-quality lymphadenectomy trial in terms of the quality of surgical procedures, which would draw the bona-fide conclusions regarding the therapeutic role of lymphadenectomy for endometrial cancer.

The 2020 Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer / 부인종양

The fifth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was published in 2020. The guidelines contain 6 chapters—namely, (1) overview of the guidelines; (2) epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (3) recurrent epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (4) borderline epithelial tumors of the ovary; (5) malignant germ cell tumors of the ovary; and (6) malignant sex cord-stromal tumors. Furthermore, the guidelines comprise 5 algorithms—namely, (1) initial treatment for ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (2) treatment for recurrent ovarian cancer, fallopian tube cancer, and primary peritoneal cancer; (3) initial treatment for borderline epithelial ovarian tumor; (4) treatment for malignant germ cell tumor; and (5) treatment for sex cord-stromal tumor. Major changes in the new edition include the following: (1) revision of the title to “guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer”; (2) involvement of patients and general (male/female) participants in addition to physicians, pharmacists, and nurses; (3) clinical questions (CQs) in the PICO format; (4) change in the expression of grades of recommendation and level of evidence in accordance with the GRADE system; (5) introduction of the idea of a body of evidence; (6) categorization of references according to research design; (7) performance of systematic reviews and meta-analysis for three CQs; and (8) voting for each CQ/recommendation and description of the consensus.

Lymphadenectomy for primary ovarian cancer: a systematic review and meta-analysis / 부인종양

Objective@#To assess the effectiveness of lymphadenectomy at primary debulking surgery (PDS) on the survival of patients with epithelial ovarian cancer (EOC). @*Methods@#We searched PubMed, Ichushi, and the Cochrane Library. Randomized controlled trials (RCTs) and retrospective cohort studies comparing survival of women with EOC undergoing lymphadenectomy at PDS with that of women without lymphadenectomy were included. We performed a meta-analysis of overall survival (OS), progression-free survival (PFS), and adverse events. @*Results@#For advanced-stage EOC, 2 RCTs including 1,074 women and 7 cohort studies comprising 3,161 women were evaluated. Meta-analysis revealed that lymphadenectomy was associated with improved OS (hazard ratio [HR]=0.80; 95% confidence interval [CI]=0.70– 0.90). However, meta-analysis of 2 RCTs revealed no significant difference in OS between the lymphadenectomy and no-lymphadenectomy groups (OS: HR=1.02; 95% CI=0.85–1.22).For early-stage EOC, 1 RCT comprising 268 women and 4 cohort studies comprising 14,228 women were evaluated. Meta-analysis showed that lymphadenectomy was associated with improved OS (HR=0.75; 95% CI=0.68–0.82). A RCT of early-stage EOC reported that lymphadenectomy was not associated with improved OS (HR=0.85; 95% CI=0.49–1.47).Surgery-related deaths were similar in both groups (risk ratio [RR]=1.00; 95% CI=0.99–1.01);however, blood transfusion was required less frequently in the no-lymphadenectomy group (RR=0.74; 95% CI=0.63–0.86). @*Conclusions@#Meta-analysis of RCTs and observational studies suggest that lymphadenectomy was associated with improved OS in advanced- and early-stage EOC.However, results from RCTs demonstrate that lymphadenectomy was not associated with improved OS in advanced- and early-stage EOC.

Lymphadenectomy for primary ovarian cancer: a systematic review and meta-analysis / 부인종양

Objective@#To assess the effectiveness of lymphadenectomy at primary debulking surgery (PDS) on the survival of patients with epithelial ovarian cancer (EOC). @*Methods@#We searched PubMed, Ichushi, and the Cochrane Library. Randomized controlled trials (RCTs) and retrospective cohort studies comparing survival of women with EOC undergoing lymphadenectomy at PDS with that of women without lymphadenectomy were included. We performed a meta-analysis of overall survival (OS), progression-free survival (PFS), and adverse events. @*Results@#For advanced-stage EOC, 2 RCTs including 1,074 women and 7 cohort studies comprising 3,161 women were evaluated. Meta-analysis revealed that lymphadenectomy was associated with improved OS (hazard ratio [HR]=0.80; 95% confidence interval [CI]=0.70– 0.90). However, meta-analysis of 2 RCTs revealed no significant difference in OS between the lymphadenectomy and no-lymphadenectomy groups (OS: HR=1.02; 95% CI=0.85–1.22).For early-stage EOC, 1 RCT comprising 268 women and 4 cohort studies comprising 14,228 women were evaluated. Meta-analysis showed that lymphadenectomy was associated with improved OS (HR=0.75; 95% CI=0.68–0.82). A RCT of early-stage EOC reported that lymphadenectomy was not associated with improved OS (HR=0.85; 95% CI=0.49–1.47).Surgery-related deaths were similar in both groups (risk ratio [RR]=1.00; 95% CI=0.99–1.01);however, blood transfusion was required less frequently in the no-lymphadenectomy group (RR=0.74; 95% CI=0.63–0.86). @*Conclusions@#Meta-analysis of RCTs and observational studies suggest that lymphadenectomy was associated with improved OS in advanced- and early-stage EOC.However, results from RCTs demonstrate that lymphadenectomy was not associated with improved OS in advanced- and early-stage EOC.

Clinical and MRI Characteristics of Uterine Cervical Adenocarcinoma: Its Variants and Mimics

Adenocarcinoma currently accounts for 10–25% of all uterine cervical carcinomas and has a variety of histopathological subtypes. Among them, mucinous carcinoma gastric type is not associated with high-risk human papillomavirus (HPV) infection and a poor prognosis, while villoglandular carcinoma has an association with high-risk HPV infection and a good prognosis. They show relatively characteristic imaging findings which can be suggested by magnetic resonance imaging (MRI), though the former is sometimes difficult to be distinguished from lobular endocervical glandular hyperplasia. Various kinds of other tumors including squamous cell carcinoma should be also differentiated on MRI, while it is currently difficult to distinguish them on MRI, and HPV screening and pathological confirmation are usually necessary for definite diagnosis and further patient management.

Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis / 부인종양

OBJECTIVE: We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). METHODS: Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. RESULTS: The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001). CONCLUSION: Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.

Preliminary Study on the Physical and Psychological Effects of Traditional Japanese Massage Therapy in Cancer Survivors / 日本温泉気候物理医学会雑誌

Objective: The aim of this preliminary study was to assess whether traditional Japanese massage therapy confers benefits to body and mind not only in healthy women but also cancer survivors. Design: A case control study Settings/Location: Tsukuba University of Technology, Ibaraki, Japan Subjects: Five women who underwent surgery for uterine cervical or endometrial cancer (stage 1a1-2a; cancer survivors group) and five healthy women of the same generation (healthy women group) were recruited. All had chronic muscle stiffness of the neck and shoulder and wanted to receive massage therapy. Interventions: All participants received traditional Japanese massage therapy consisting of eight 40-min massage sessions over 4 weeks. Outcome Measures: Visual analogue scale (VAS) to assess the severity of the subjective symptom of muscle stiffness in the neck and shoulder; salivary cortisol, secretory immunoglobulin A (s-IgA), and chromogranin A (CgA) from saliva; state anxiety, trait anxiety, and depression. Results: Regarding immediate changes in variables by therapy, there were significant differences between the cancer survivors group and the healthy women group in VAS, s-IgA, and CgA. VAS, salivary cortisol, and state anxiety scores decreased, and s-IgA and CgA increased in both groups. After the four weeks of sessions, there were significant differences between the cancer survivors group and the healthy women group in VAS, CgA, and depression. VAS, trait anxiety, and depression scores decreased in both groups. Conclusions: These results imply that traditional Japanese massage therapy may confer physical and psychological benefits to cancer survivors as well as to healthy women. Further studies with a larger sample size are needed.

Preliminary Study on the Physical and Psychological Effects of Traditional Japanese Massage Therapy in Cancer Survivors / 日本温泉気候物理医学会雑誌

<B>Objective: </B>The aim of this preliminary study was to assess whether traditional Japanese massage therapy confers benefits to body and mind not only in healthy women but also cancer survivors.<BR><B>Design: </B>A case control study<BR><B>Settings/Location:</B> Tsukuba University of Technology, Ibaraki, Japan<BR><B>Subjects: </B>Five women who underwent surgery for uterine cervical or endometrial cancer (stage 1a1-2a; cancer survivors group) and five healthy women of the same generation (healthy women group) were recruited. All had chronic muscle stiffness of the neck and shoulder and wanted to receive massage therapy.<BR><B>Interventions: </B>All participants received traditional Japanese massage therapy consisting of eight 40-min massage sessions over 4 weeks.<BR><B>Outcome Measures: </B>Visual analogue scale (VAS) to assess the severity of the subjective symptom of muscle stiffness in the neck and shoulder; salivary cortisol, secretory immunoglobulin A (s-IgA), and chromogranin A (CgA) from saliva; state anxiety, trait anxiety, and depression.<BR><B>Results: </B>Regarding immediate changes in variables by therapy, there were significant differences between the cancer survivors group and the healthy women group in VAS, s-IgA, and CgA. VAS, salivary cortisol, and state anxiety scores decreased, and s-IgA and CgA increased in both groups. After the four weeks of sessions, there were significant differences between the cancer survivors group and the healthy women group in VAS, CgA, and depression. VAS, trait anxiety, and depression scores decreased in both groups.<BR><B>Conclusions: </B>These results imply that traditional Japanese massage therapy may confer physical and psychological benefits to cancer survivors as well as to healthy women. Further studies with a larger sample size are needed.