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Introduction: Patients with advanced ovarian cancer often require radical cytoreductive surgery and chemotherapy, with or without targeted therapy. Return to intended oncological therapy after surgery is a crucial metric, as delay can worsen survival. The concept of return to intended oncological therapy is important because it highlights the need for not just successful surgical outcomes, but also the ability to continue with the comprehensive cancer treatment plan., Methods: A comprehensive review of the literature was conducted to identify relevant English language studies published from January 2010 to September 2024., Results: Delayed return to intended oncological therapy after surgery was associated with poor survival outcomes in ovarian cancer. This narrative review investigates how pre-operative counselling and education; optimisation of the patient's medical condition; meticulous surgical planning and execution; early recognition of complications; and comprehensive postoperative care influence return to intended therapy in gynaecological surgery. Effective multidisciplinary care involving anaesthetists; nurses; physiotherapists; dietitians; psychologists; and the patient's relatives or friends, can prevent complications and ensure timely return to intended oncological therapy., Discussion: Awareness and management of factors affecting return to intended oncological therapy are essential for improving outcomes in patients with advanced ovarian cancer. We highlight the importance of multidisciplinary care (including enhanced recovery after surgery programmes) and the factors affecting these including age; nutrition; and occurrence of postoperative complications., (© 2025 The Author(s). Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Background: Indolent systemic mastocytosis (ISM), the most frequent subtype of systemic mastocytosis, requires better understanding., Objective: To better understand the diagnostic journey, symptom severity, impact on quality of life and work/activities, and health care utilization of ISM., Methods: Survey data were collected from 40 adults with documented ISM meeting World Health Organization 2016 criteria, including validated questionnaires (ISM Symptom Assessment Form [ISM-SAF] and Short Form Quality of Life Survey [SF-12v1]). Spearman correlation coefficients determined the associations between the ISM-SAF Total Symptom Score (TSS) and SF-12v1 scores. ISM burden was compared based on moderate/severe compared with mild TSS scores using Kruskal-Wallis and Fisher exact tests., Results: Patients were aged 56.0 ± 13.0 years, 65.0% female, 62.5% White, and 22.5% Hispanic patients. ISM diagnosis took >2 years in 40%, required ≥6 visits in 47.5%, and was considered moderately/extremely difficult in 50% of patients. Nearly half experienced symptoms daily and rated severity somewhat/significantly worsened since diagnosis. The overall TSS was 27.4 ± 16.2 (mean ± standard deviation). SF-12 Physical Component Summary (PCS) (46.7 ± 11.4) and Mental Component Summary (MCS) (47.6 ± 10.2) scores were lower than the general population score of 50. Moderate correlations (P < .001) were found between TSS and the PCS (ρ = -0.6406; P < .001) and MCS (ρ = -0.5104; P < .001). Compared with patients with mild severity (TSS < 28; n = 21), patients with moderate/severe severity (TSS ≥ 28; n = 19) evidenced significantly higher skin and gastrointestinal symptom scores (both, P ≤ .001). ISM's impact on ability to work for pay was associated with TSS (P = .004). Symptom-directed treatment had limited effect., Conclusion: ISM was self-reported as a burdensome condition in half the patients that markedly affected daily living., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the performance of cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for the triage of high-risk HPV-positive cervical samples., Design: Retrospective analyses of archival samples collected from a large-scale prospective randomised controlled trial., Setting/sample: HPV-positive women recruited from the general cervical screening population., Methods: 403 HPV-positive samples including 113 normal, 173 low-grade cervical intraepithelial neoplasia (LG-CIN), 114 HG-CIN and three cervical cancers. All samples were assessed by liquid-based cytology, HPV genotyping and PAX1/SOX1 methylation., Main Outcome Measures: AUC (area under the curve), sensitivity and specificity for cytology, HPV16/18 genotyping and PAX1/SOX1 methylation for high-grade (HG) premalignant cervical lesions., Results: PAX1 was more sensitive than cytology and HPV16/18 genotyping in detecting a HG lesion (CIN2+). The sensitivity for PAX1, SOX1, cytology and HPV16/18 were 73.5% (95% CI: 65.5-81.5), 41.9% (95% CI: 32.9-50.8), 48.7% (95% CI: 39.7-57.8) and 36.8% (95% CI: 28.0-45.5), respectively, and their respective specificities were 70.3% (95% CI: 65.0-75.6), 83.6% (95% CI: 79.3-87.9), 77.6% (95% CI: 72.8-82.5) and 67.1% (95% CI: 61.7-72.6), respectively. Overall, PAX1 gave the best AUC at 0.72. Adding SOX1 to PAX1 did not improve the AUC (0.68). Three hundred and twenty-two women who did not have a HG lesion at baseline were followed up for two rounds of screening. Fewer women developed a HG lesion with a normal baseline PAX1 compared to women with a normal baseline cytology or negative HPV16/18 (8.4% vs. 14.5% and 17.5%, respectively)., Conclusion: PAX1 triage for referral to colposcopy in HPV-positive women may be superior to cytology and HPV16/18 genotyping., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC. Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/- bevacizumab in rGCCC., Methods: DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/- bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator's choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinum-based chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti-PD-1, anti-programmed death-ligand 1, or anti-programmed death-ligand 2 agent. The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers., Trial Registration: ClinicalTrials.gov Identifier: NCT06023862., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Purpose: Patients with advanced endometrial cancer (EC) who progress on or after platinum-based therapy and immunotherapy have poor prognosis. We report efficacy and safety of sacituzumab govitecan (SG), a trophoblast cell-surface antigen 2 (Trop-2)-directed antibody-drug conjugate, in patients with advanced EC., Methods: TROPiCS-03 (ClinicalTrials.gov identifier: NCT03964727) is a multicohort, open-label, phase II basket study in patients with metastatic solid tumors. Eligible patients in the EC cohort received SG 10 mg/kg once on days 1 and 8 every 3 weeks. Primary end point was objective response rate (ORR) by investigator's assessment per RECIST v1.1. Secondary end points included clinical benefit rate (CBR; complete and partial response, and stable disease ≥6 months), duration of response (DOR), and progression-free survival (PFS) per investigator assessment, overall survival, and safety. Trop-2 expression of archival or baseline tumor specimens was analyzed by immunohistochemistry., Results: At data extraction date, 41 patients were enrolled. Median follow-up was 5.8 months (range, 0.7-19.3); median previous therapies was three (range, 1-6); and 85% of patients received previous chemotherapy and immunotherapy. ORR was 22% (95% CI, 11 to 38); CBR was 32% (95% CI, 18 to 48). Median DOR was 8.8 months (95% CI, 2.8 to not estimable); median PFS was 4.8 months (95% CI, 2.8 to 9.8). Trop-2 exploratory analysis was conducted retrospectively for 39 patients. Tumor Trop-2 protein was highly expressed in EC, showing limited correlation with efficacy. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 73% of patients. Study drug discontinuation due to TRAEs was 5%. Two deaths occurred, deemed unrelated to SG., Conclusion: Findings from TROPiCS-03 showed encouraging efficacy of SG with a manageable toxicity profile in a heavily pretreated population with advanced EC. Safety findings were consistent with the known SG safety profile.

Cervical cancer remains a disease burden in Asia. The Asia and Oceania Federation of Obstetrics and Gynecology envisages a need to produce a set of recommendations on the implementation of human papilloma virus vaccination program for both lower-middle-income countries (LMICs) and high-income countries (HICs), with an attempt to harmonize the practices yet allow flexibility to cater for different cultures, religions, needs and background of individual countries/cities. International guidelines and literature were sought, and recommendations were made in seven selected areas, including (i) the target groups for vaccination, (ii) the doses of vaccination including the use of single-dose vaccination, (iii) the types of vaccines, (iv) suggestions for special populations including those with previous HPV infection, human immunodeficiency virus carriers, and lesbian, gay, bisexual, transgender, questioning/queer group, (v) inter-changeability and the need of revaccination/booster, (vi) novel technologies and vaccines, and (vii) public education., (© 2024 The Author(s). Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Transient halting of transcription activity on the damaged chromatin facilitates DNA double-strand break (DSB) repair. However, the molecular mechanisms that facilitate transcription recovery following DSB repair remain largely undefined. Notably, failure to restore gene expression in a timely manner can compromise transcriptome signatures and may impose deleterious impacts on cell identity and cell fate. Here, we report PHF8 as the major demethylase that reverses transcriptionally repressive epigenetic modification laid down by the DYRK1B-EHMT2 pathway. We found that PHF8 concentrates at laser-induced DNA damage tracks in a DYRK1B-dependent manner and promotes timely resolution of local H3K9me2 to facilitate the resumption of transcription. Moreover, PHF8 also assists in the recovery of ribosomal DNA (rDNA) transcription following the repair of nucleolar DSBs. Taken together, our findings uncover PHF8 as a key mediator that coordinates transcription activities during the recovery phase of DSB responses., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: Uterine leiomyosarcoma (LMS) is an aggressive sarcoma and a subset of which exhibits DNA repair defects. Polo-like kinase 4 (PLK4) precisely modulates mitosis, and its inhibition causes chromosome missegregation and increased DNA damage. We hypothesize that PLK4 inhibition is an effective LMS treatment., Experimental Design: Genomic profiling of clinical uterine LMS samples was performed, and homologous recombination (HR) deficiency scores were calculated. A PLK4 inhibitor (CFI-400945) with and without an ataxia telangiectasia mutated (ATM) inhibitor (AZD0156) was tested in vitro on gynecologic sarcoma cell lines SK-UT-1, SKN, and SK-LMS-1. Findings were validated in vivo using the SK-UT-1 xenograft model in the Balb/c nude mouse model. The effects of CFI-400945 were also evaluated in a BRCA2-knockout SK-UT-1 cell line. The mechanisms of DNA repair were analyzed using a DNA damage reporter assay., Results: Uterine LMS had a high HR deficiency score, overexpressed PLK4 mRNA, and displayed mutations in genes responsible for DNA repair. CFI-400945 demonstrated effective antitumor activity in vitro and in vivo. The addition of AZD0156 resulted in drug synergism, largely due to a preference for nonhomologous end-joining DNA repair. Compared with wild-type cells, BRCA2 knockouts were more sensitive to PLK4 inhibition when both HR and nonhomologous end-joining repairs were impaired., Conclusions: Uterine LMS with DNA repair defects is sensitive to PLK4 inhibition because of the effects of chromosome missegregation and increased DNA damage. Loss-of-function BRCA2 alterations or pharmacologic inhibition of ATM enhanced the efficacy of the PLK4 inhibitor. Genomic profiling of an advanced-stage or recurrent uterine LMS may guide therapy., (©2024 The Authors; Published by the American Association for Cancer Research.)

Objectives: The study aimed to compare the diagnostic accuracies of 2-[ 18 F]FDG PET/CT and contrast-enhanced CT (ceCT) after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer (OC)., Materials and Methods: This study consisted historical observational cohort and prospective validation cohort. Patients with newly diagnosed stage III-IV OC scheduled for NACT were recruited, with imaging performed after three to six cycles of NACT before interval debulking surgery. Nineteen regions in the abdominopelvic cavity were scored for the presence and absence of disease, referenced to the intra-operative findings or histological specimens. Diagnostic metrics were compared using McNemar's test., Results: In the historical cohort (23 patients, age 58 ± 13), 2-[ 18 F]FDG PET had an overall accuracy (Acc) 82%, sensitivity (Sen) 38%, specificity (Spe) 97%, positive predictive value (PPV) 79% and negative predictive value (NPV) 82%; ceCT had an overall Acc 86%, Sen 64%, Spe 93%, PPV 75% and NPV 89%. In the prospective cohort (46 patients, age 59 ± 9), 2-[ 18 F] FDG PET had an overall Acc 87%, Sen 48%, Spe 98%, PPV 84% and NPV 88%; ceCT had an overall Acc 89%, Sen 66%, Spe 95%, PPV 77% and NPV 91%. No significant difference was demonstrated between the two imaging modalities (p > 0.05). High false-negative rates were observed in the right subdiaphragmatic space, omentum, bowel mesentery and serosa. High omental metabolic uptake after NACT was associated with histological non-responders (p < 0.05)., Conclusion: 2-[ 18 F]FDG PET/CT had no additional value over ceCT with comparable diagnostic accuracy in detecting disease after NACT in advanced OC., Clinical Relevance Statement: 2-[ 18 F]FDG PET/CT is not superior to contrast-enhanced CT in determining disease after neoadjuvant chemotherapy in advanced ovarian cancer; contrast-enhanced CT should be suffice for surgical planning before interval debulking surgery., Key Points: • Additional value of 2-[ 18 F]FDG PET/CT over contrast-enhanced CT is undefined in detecting disease after neoadjuvant chemotherapy. • 2-[ 18 F]FDG PET/CT has comparable diagnostic accuracy compared to contrast-enhanced CT. • Contrast-enhanced CT will be suffice for surgical planning after neoadjuvant chemotherapy., (© 2024. The Author(s).)

Background: Systemic mastocytosis (SM), a rare condition affecting about 32,000 individuals in the United States, is often misdiagnosed or underdiagnosed owing to its nonspecific symptoms and the need for invasive biopsies., Objective: Our aim was to identify, classify, and characterize the natural history of patients with SM., Methods: In a retrospective cohort study, administrative data from a large managed care organization was used to identify patients with confirmed SM, based on World Health Organization criteria. Demographic data, delay to diagnosis, disease progression, and health care resource utilization were examined., Results: Of 116 patients with confirmed SM, 77% had indolent SM, 2% had smoldering SM, 12% had SM with associated hematologic neoplasm, 9% had aggressive SM, and none had mast cell leukemia. In all, 5 patients were misclassified as having a less advanced SM subtype initially and 3 were completely undiagnosed (missed diagnosis). The average delay to diagnosis of SM was 58.3 plus or minus 73.1 months. In all, 18% of patients progressed from a nonadvanced form of SM (indolent or smoldering SM) to an advanced form of SM (aggressive SM, SM with associated hematologic neoplasm, or mast cell leukemia) over an average of 88.3 plus or minus 82.7 months. Patients with SM had increased health care utilization, including increases in their numbers of hospital admissions, emergency room visits, urgent care visits, and specialty provider visits, after diagnosis versus before., Conclusions: Rare diseases such as SM would benefit from increased understanding and awareness to improve diagnostic accuracy. Prospective studies are needed to better characterize this patient population and determine the type of follow-up needed to recognize advanced forms of SM so that appropriate treatment can be implemented., Competing Interests: Supported by Blueprint Medicines (Cambridge, Mass) through an unrestricted grant to Kaiser Permanente Southern California, as well as by the National Heart, Lung and Blood Institute (grant to R.S.Z.) Disclosure of potential conflict of interest: for Kaiser Permanente Southern California: R. S. Zeiger has received grants from Aerocrine, 10.13039/100004328Genentech, 10.13039/501100004628MedImmune/10.13039/100004325AstraZeneca, Merck, 10.13039/100004330GlaxoSmithKline, Teva, and Quest; has warrants from DBV Technologies; and has provided consultant activity for AstraZeneca, Bayer, Regeneron/Sanofi, Merck, and Genentech/Novartis. K. Miller, D. Powell, B. Lampson, C. Yuen, D. Cattie, T. Green, and E. Sullivan are employed by Blueprint Medicines. The rest of the authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)

Introduction: Chemotherapy is crucial in treating gestational trophoblastic neoplasia (GTN), but its impact on gonadotoxicity is unclear., Materials and Methods: This case-control study included 57 GTN patients and 19 age-matched patients with molar pregnancies (MP) in 2012-2018. Multiples of the median (MoM) of the serum AMH levels were compared between the two groups, and between patients using single-agent and combination chemotherapy, at baseline, 6, 12, and 24 months after treatment. Their pregnancy outcomes were also compared., Results: There was no significant difference in the MoM of serum AMH between GTN and MP groups at all time points. Single-agent chemotherapy did not adversely affect the MoM. However, those receiving combination chemotherapy had lower MoM than those receiving single-agent chemotherapy at all time points. The trend of decline from the baseline was marginally significant in patients with combination chemotherapy, but the drop was only significant at 12 months (Z = -2.69, p = 0.007) but not at 24 months (Z = -1.90; p = 0.058). Multivariable analysis revealed that combination chemotherapy did not affect the MoM. There was no significant difference in the 4-year pregnancy rate and the livebirth rate between the single-agent and combination groups who attempting pregnancy, but it took 1 year longer to achieve the first pregnancy in the combination group compared to the single-agent group (2.88 vs. 1.88 years)., Conclusion: This study showed combination chemotherapy led to a decreasing trend of MoM of serum AMH especially at 12 months after treatment, but the drop became static at 24 months. Although pregnancy is achievable, thorough counseling is still needed in this group especially those wish to achieve pregnancy 1-2 years after treatment or with other risk factors., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Over the last quarter of a century, fluorine-18-fluorodeoxyglucose (FDG) PET/computed tomography (CT) has revolutionized the diagnostic algorithm of ovarian cancer, impacting on the initial disease evaluation including staging and surgical planning, treatment response assessment and prognostication, to the most important role in detection of recurrent disease. The role of FDG PET/CT is expanding with the adoption of new therapeutic agents. Other non-FDG tracers have been explored with fibroblast activation protein inhibitor being promising. Novel tracers may provide the basis for future theragnostic work. This article will review the evolution and impact of PET/CT in ovarian cancer management., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Epithelial ovarian cancer (EOC) is a heterogeneous disease composed of different cell types with different molecular aberrations. Traditional cell lines and mice models cannot recapitulate the human tumor biology and tumor microenvironment (TME). Patient-derived organoids (PDOs) are freshly derived from patients' tissues and are then cultured with extracellular matrix and conditioned medium. The high concordance of epigenetic, genomic, and proteomic landscapes between the parental tumors and PDOs suggests that PDOs can provide more reliable results in studying cancer biology, allowing high throughput drug screening, and identifying their associated signaling pathways and resistance mechanisms. However, despite having a heterogeneity of cells in PDOs, some cells in TME will be lost during the culture process. Next-generation organoids have been developed to circumvent some of the limitations. Genetically engineered organoids involving targeted gene editing can facilitate the understanding of tumorigenesis and drug response. Co-culture systems where PDOs are cultured with different cell components like immune cells can allow research using immunotherapy which is otherwise impossible in conventional cell lines. In this review, the limitations of the traditional in vitro and in vivo assays, the use of PDOs, the challenges including some tips and tricks of PDO generation in EOC, and the future perspectives, will be discussed., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The aim of this study was to compare the diagnostic efficacy of colposcopic-directed biopsy and four-quadrant biopsy in detecting high-grade cervical intra-epithelial neoplasia (CIN). Women attending three women's clinics for routine cervical screening were recruited. Colposcopy was arranged for women with any cytologic abnormalities greater than atypical squamous cells of undetermined significance (ASCUS), two consecutive ASCUS results or positive HPV testing. During colposcopy, a cervical biopsy was taken from the most suspicious area, but more than one biopsy was allowed. Four-quadrant biopsies at 3, 6, 9 and 12 o'clock and an endocervical curettage were also taken in all cases. A total of 1522 colposcopies were performed in 1311 subjects from June 2010 to August 2017, with 118 cases of high-grade CIN diagnosed. Colposcopic-directed biopsy detected 50.8% of the 118 high-grade CIN, while four-quadrant biopsy detected 86.4% ( p < 0.0001). Twenty-seven cases (22.9%) of high-grade CIN were diagnosed in women with normal or unsatisfactory colposcopy. Among the 64 cases with low-grade colposcopic impression, four-quadrant biopsy detected significantly more high-grade CIN (53 cases, 82.8%) than colposcopic-directed biopsy (35 cases, 56.3%) ( p = 0.0011). Four-quadrant cervical biopsies should be considered for all women with an abnormal smear or positive HPV testing, especially in patients with low-grade/normal/unsatisfactory colposcopy.

Skeletal dysplasias are a group of diseases characterized by bone and joint abnormalities, which can be detected during prenatal ultrasound. Next-generation sequencing has rapidly revolutionized molecular diagnostic approaches in fetuses with structural anomalies. This review studies the additional diagnostic yield of prenatal exome sequencing in fetuses with prenatal sonographic features of skeletal dysplasias. This was a systematic review by searching PubMed for studies published between 2013 and July 2022 that identified the diagnostic yield of exome sequencing after normal karyotype or chromosomal microarray analysis (CMA) for cases with suspected fetal skeletal dysplasias based on prenatal ultrasound. We identified 10 out of 85 studies representing 226 fetuses. The pooled additional diagnostic yield was 69.0%. The majority of the molecular diagnoses involved de novo variants (72%), while 8.7% of cases were due to inherited variants. The incremental diagnostic yield of exome sequencing over CMA was 67.4% for isolated short long bones and 77.2% for non-isolated cases. Among phenotypic subgroup analyses, features with the highest additional diagnostic yield were an abnormal skull (83.3%) and a small chest (82.5%). Prenatal exome sequencing should be considered for cases with suspected fetal skeletal dysplasias with or without a negative karyotype or CMA results. Certain sonographic features, including an abnormal skull and small chest, may indicate a potentially higher diagnostic yield.

Background: Despite the introduction of cervical cancer screening and human papillomavirus (HPV) vaccines, the utilization pattern was not standardized. The aim of this study was to elicit the current prevention care in Asia-Oceania., Methods: An online questionnaire was circulated to different countries/cities in Asia-Oceania. The primary objective was to evaluate the coverage of HPV vaccination and cervical screening programs. The secondary objectives were to study the structures of these programs. Five case scenarios were set to understand how the respondents manage the abnormal screening results., Results: Fourteen respondents from 10 countries/cities had participated. Cervical cancer ranked the first in Myanmar and Nepal. About 10%-15% did not have national vaccination or screening program. The estimated coverage rate for vaccination and screening varied from less than 1% to 70%, which the coverage ran in parallel with the incidence and mortality rates of cervical cancer. All regions approved HPV vaccines, although only four provided free or subsidized programs for nonavalent vaccine. Cervical cytology remained the most common screening tool, and 20%-30% relied heavily on visual inspection using acetic acid. The screening age groups varied in different regions. From the case scenarios, it was noted that some respondents tended to offer more frequent screening tests or colposcopy than recommended by international guidelines., Conclusion: This study revealed discrepancy in the practice of cervical cancer prevention in Asia-Oceania especially access to HPV vaccines. There is an urgent need for a global collaboration to eliminate cervical cancer by public education, reforming services, and medical training., (© 2023 Japan Society of Obstetrics and Gynecology.)

This study aimed to assess the feasibility of patient-initiated follow-up (PIFU) in combination with regular tumour marker monitoring as an alternative to conventional hospital follow-up for ovarian cancer survivors. Women who had recently completed treatment for ovarian cancer and had a raised pre-treatment tumour marker were recruited. Participants were allocated to PIFU (intervention group) or conventional hospital follow-up (control group) according to their own preference. Both groups had regular tumour marker monitoring. The change in fear of cancer recurrence (FCR) score as measured by the FCR inventory, and the supportive care need (SCN) scores as measured by the SCN survey at baseline and at 6 months between PIFU and hospital follow-up were compared. Out of 64 participants, 37 (58%) opted for hospital follow-up and 27 (42%) opted for PIFU. During the 6-month study period, there was no significant difference in the change of FCR between the two groups ( p = 0.35). There was a significant decrease in the sexuality unmet needs score in the intervention group from baseline to 6-month FU (mean difference -8.7, 95% confidence interval -16.1 to -1.4, p = 0.02). PIFU with tumour marker monitoring is a feasible follow-up approach in ovarian cancer survivorship care. FCR and SCN were comparable between PIFU and conventional hospital follow-up.

Objective: The dilemma in treating cervical high-grade squamous intraepithelial lesion (HSIL) is how to achieve complete excision to minimize the risk of cervical cancer while sparing the anatomy of the cervix and its ability to function during pregnancy. The optimal management for positive margins after excisional treatment is still controversial. This study was conducted to determine the clinical and histologic predictors of residual/recurrent HSIL and assess the outcome of women with positive margin., Materials and Methods: This retrospective cohort study included 386 women who had excisional treatment for HSIL during 1st January 2012 to 31st December 2015 in a university-affiliated hospital., Results: Overall, 212 (54.9%) women had negative margins and 155 (40.2%) had positive margins. The cumulative rate of residual/recurrent HSIL at 2 and 5 years was 15.7% and 16.8% respectively in positive margins and 1.8% and 5.0% respectively in negative margins (p < 0.001). Of women who had residual/recurrent HSIL, significantly more women had positive margins compared to negative margins (74.1% vs 25.9%, p = 0.001). Positive margin was significantly associated with higher rate of subsequent abnormal cervical smear (48.2% vs 28.9%, p < 0.001), requiring further colposcopy (32.1% vs 14.4%, p < 0.001) and further treatment for SIL (7.5% vs 4.8%, p < 0.001) compared to negative margin., Conclusion: Most women (85%) with positive margin went without residual/recurrent HSIL, of which the option of close surveillance with cytology is reasonable. Repeat excision may be considered in selected women with positive margin, endocervical glandular involvement and those who are older or unable to comply with follow-up., Competing Interests: Declaration of competing interest No potential conflict of interest relevant to this article was reported., (Copyright © 2023. Published by Elsevier B.V.)

Lymph node status is important in predicting the prognosis and guiding adjuvant treatment in endometrial cancer. However, previous studies showed that systematic lymphadenectomy conferred no therapeutic values in clinically early-stage endometrial cancer but might lead to substantial morbidity and impact on the quality of life of the patients. The sentinel lymph node is the first lymph node that tumor cells drain to, and sentinel lymph node biopsy has emerged as an acceptable alternative to full lymphadenectomy in both low-risk and high-risk endometrial cancer. Evidence has demonstrated a high detection rate, sensitivity and negative predictive value of sentinel lymph node biopsy. It can also reduce surgical morbidity and improve the detection of lymph node metastases compared with systematic lymphadenectomy. This review summarizes the current techniques of sentinel lymph node mapping, the applications and oncological outcomes of sentinel lymph node biopsy in low-risk and high-risk endometrial cancer, and the management of isolated tumor cells in sentinel lymph nodes. We also illustrate a revised sentinel lymph node biopsy algorithm and advocate to repeat the tracer injection and explore the presacral and paraaortic areas if sentinel lymph nodes are not found in the hemipelvis.

High-risk human papillomavirus (HR-HPV) testing has become an increasing important strategy in primary cervical cancer screening in recent years. It warrants the evaluation of molecular-based HPV tests for accuracy and efficacy of screening. The performance of Roche Cobas 4800 HPV test was validated and compared with Digene Hybrid Capture 2 (HC2) high-risk HPV DNA test for primary screening in a large Chinese screening cohort. Of 6345 women screened, overall agreement between Cobas and HC2 was 92.23% (95% CI: 91.57-92.89). The inter-assay agreement was correlated with the severity of underlying biology, with an increasing concordance found in samples with more severe abnormalities. Most of the discordant samples had the test signal strength closer to the test limits of the detection than concordant samples, reflecting a low viral load and infection of a cluster of low-risk HPV in these samples. The Cobas test demonstrated significantly higher specificity in identifying CIN2+/CIN3+ cases than HC2 test (66.46% vs 43.67% and 65.42% vs 42.86%, p<0.001), with comparable sensitivity in clinical evaluation. Increased specificity of Cobas test would accent women having the highest risk of developing CIN2+, with the potential to reduce unnecessary colposcopy referral in a screening population., Competing Interests: The authors have declared that no competing interests exist.

The accurate prediction of malignancy for a pelvic mass detected on ultrasound allows for appropriate referral to specialised care. IOTA simple rules are one of the best methods but are inconclusive in 25% of cases, where subjective assessment by an expert sonographer is recommended but may not always be available. In the present paper, we evaluate the methods for assessing the nature of a pelvic mass, including IOTA with subjective assessment by expert ultrasound, RMI and ROMA. In particular, we investigate whether ROMA can replace expert ultrasound when IOTA is inconclusive. This prospective study involves one cancer centre and three general units. Women scheduled for an operation for a pelvic mass underwent a pelvic ultrasound pre-operatively. The final histology was obtained from the operative sample. The sensitivity, specificity and accuracy for each method were compared with the McNemar test. Of the 690 women included in the study, 171 (25%) had an inconclusive IOTA. In this group, expert ultrasound was more sensitive in diagnosing a malignant mass compared to ROMA (81% vs. 63%, p = 0.009) with no significant difference in the specificity or accuracy. All assessment methods involving IOTA had similar accuracies and were more accurate than RMI or ROMA alone. In conclusion, when IOTA was inconclusive, assessment by expert ultrasound was more sensitive than ROMA, with similar specificity.

Non-epithelial cancers arising from the ovary are uncommon malignancies. Germ cell tumors of the ovary arise from primordial germ cells, and sex cord-stromal tumors of the ovary represent a cluster of tumors arising from the sex cord and stromal compartment. Most patients diagnosed with germ cell tumors are young adults and adolescent females. In contrast, ovarian sex cord-stromal tumors more commonly occur in a mature age group. Advances in the adjuvant management of non-epithelial ovarian cancer following optimal surgical and pathological staging have improved patient survival outcomes. In addition, active surveillance is preferentially assigned to patients diagnosed with stage I germ cell tumor, stage 1A grade 1 immature teratoma, stage 1A yolk sac tumor, and stage 1AI sex cord-stromal tumors. This article discusses the importance of selecting the adjuvant treatment approach most suitable to the patients' surgical and pathological stages, thereby safeguarding patient outcomes., Competing Interests: Conflicts of interest Aya El Helali: No conflict of interest. Gladys Shuk Tak Kwok: No conflict of interest. Ka Yu Tse: No conflict of interest, (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To examine the associations of intravoxel incoherent motion (IVIM) parameters with treatment response in cervical cancer following concurrent chemoradiotherapy (CCRT)., Materials and Methods: Forty-five patients, median age of 58 years (range: 28-82), with pre-CCRT and post-CCRT MRI, were retrospectively analysed. The IVIM parameters pure diffusion coefficient (D) and perfusion fraction (f) were estimated using the full b-value distribution (BVD) as well as an optimised subsample BVD. Dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC) were used to measure observer repeatability in tumour delineation at both time points. Treatment response was determined by the response evaluation criteria in solid tumour (RECIST) 1.1 between MRI examinations. Mann-Whitney U tests were used to test for significant differences in IVIM parameters between treatment response groups., Results: Pre-CCRT tumour delineation repeatability was good (DSC = 0.81) while post-CCRT delineation repeatability was moderate (DSC = 0.67). Values of D and f had good repeatability at both time points (ICC > 0.80). Pre-CCRT f estimated using the full BVD and optimised subsample BVD were found to be significantly higher in patients with partial response compared to those with stable disease or disease progression (p = 0.01 and 95% CI = -0.02-0.00 for both cases)., Conclusion: Pre-CCRT f was associated with treatment response in cervical cancer with good observer repeatability. Similar discriminative ability was also observed in estimated pre-CCRT f from an optimised subsample BVD., Key Points: • Pre-treatment tumour delineation and IVIM parameters had good observer repeatability. • Post-treatment tumour delineation was worse than at pre-treatment, but IVIM parameters retained good ICC. • Pre-treatment perfusion fraction estimated from all b-values and an optimised subsample of b-values were associated with treatment response., (© 2021. European Society of Radiology.)

Frozen sections of uterine smooth muscle tumors are infrequently required, and related diagnostic difficulties are seldom discussed. We analyzed the clinicopathologic features of 112 frozen sections of uterine smooth muscle tumors and determined the accuracy, reasons for deferrals, and causes of interpretational errors. Most patients (median age, 45 y) presented with pelvic mass symptoms (53%). The main reasons for a frozen section examination were an abnormal gross appearance including loss of the usual whorled pattern of leiomyoma (36 cases, 32.1%), and intraoperative discovery of an abnormal growth pattern and extrauterine extension of a uterine tumor (28 cases, 25%). There were 9 leiomyosarcomas and 103 leiomyomas, including 18 benign histologic variants. An accurate diagnosis of malignancy was achieved in all leiomyosarcomas, with the exception of a myxoid leiomyosarcoma. In 99 cases (88%), the frozen section diagnosis concurred with the permanent section diagnosis (false positives, 0.9%; false negatives, 0%). Misinterpretation of stromal hyalinization as tumor cell necrosis in a leiomyoma with amianthoid-like fibers was a major discrepancy. Two minor discrepancies did not lead to a change in management. The diagnosis was deferred in 10 cases (8.9%) because of stromal alterations, unusual cellular morphology, uncertain type of necrosis, and abnormal growth patterns. Thus, although various stromal and cellular alterations can cause diagnostic uncertainty, leading to deferrals, frozen section diagnosis of uterine smooth muscle tumors has a high accuracy rate. While a definitive frozen section diagnosis of malignancy may be made when there is unequivocal atypia, indisputable mitotic figures, and tumor cell necrosis, it is important to remember that nonmyogenic mesenchymal tumors may also mimic uterine smooth muscle tumors. In a frozen section setting, it would be sufficient to issue a diagnosis of "malignant mesenchymal tumor." For tumors that do not meet the criteria for malignancy, issuing a frozen section diagnosis of "atypical mesenchymal tumor and defer the histologic subtyping to the permanent sections" is appropriate., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To review the clinical use and the effectiveness of tamoxifen in patients with advanced or recurrent ovarian cancer., Methods: A retrospective review of clinical records was conducted in patients who received tamoxifen for the treatment of ovarian cancer between 2002 and 2016. We reviewed the clinical setting that it was given, duration of use, patients' tolerability, clinical benefit and progression-free survival. We also attempted to identify predictive markers for response., Results: A total of 92 patients received tamoxifen during this 15-year period. The patients received a median of 2.5 lines of chemotherapy before switching to tamoxifen, and they remained on tamoxifen for a median of 5.6 months (range 0-85 months), with 24 patients receiving it for more than 12 months. Seventy-six patients continued on tamoxifen for more than 2 months. In this group, 75 patients had an evaluable response, either by CA 125 or clinically and clinical benefit rate (defined as complete, partial response and static disease) was seen in 42 patients (56%), with majority of patients having static disease. The median progression-free survival was 5.3 months (95% confidence interval, 2.6-8.1). Tamoxifen was well tolerated. Hormone receptor status was not demonstrated to predict response., Conclusion: Patients with advanced ovarian cancer who have failed previous lines of chemotherapy may achieve static disease with tamoxifen with minimal side effects. Tamoxifen may still have a role in the era of molecular target therapy., (© 2020 The Authors. Asia-Pacific Journal of Clinical Oncology Published by John Wiley & Sons Australia, Ltd.)

Background: The existing staging systems of uterine leiomyosarcoma (uLMS) cannot classify the patients into four non-overlapping prognostic groups. This study aimed to develop a prediction model to predict the three-year survival status of uLMS., Methods: In total, 201 patients with uLMS who had been treated between June 1993 and January 2014, were analyzed. Potential prognostic indicators were identified by univariate models followed by multivariate analyses. Prediction models were constructed by binomial regression with 3-year survival status as a binary outcome, and the final model was validated by internal cross-validation., Results: Nine potential parameters, including age, log tumor diameter, log mitotic count, cervical involvement, parametrial involvement, lymph node metastasis, distant metastasis, tumor circumscription and lymphovascular space invasion were identified. 110 patients had complete data to build the prediction models. Age, log tumor diameter, log mitotic count, distant metastasis, and circumscription were significantly correlated with the 3-year survival status. The final model with the lowest Akaike's Information Criterion (117.56) was chosen and the cross validation estimated prediction accuracy was 0.745., Conclusion: We developed a prediction model for uLMS based on five readily available clinicopathologic parameters. This might provide a personalized prediction of the 3-year survival status and guide the use of adjuvant therapy, a cancer surveillance program, and future studies.

Introduction: Sentinel lymph node dissection is widely used in the staging of endometrial cancer. Variation in surgical techniques potentially impacts diagnostic accuracy and oncologic outcomes, and poses barriers to the comparison of outcomes across institutions or clinical trial sites. Standardization of surgical technique and surgical quality assessment tools are critical to the conduct of clinical trials. By identifying mandatory and prohibited steps of sentinel lymph node (SLN) dissection in endometrial cancer, the purpose of this study was to develop and validate a competency assessment tool for use in surgical quality assurance., Methods: A Delphi methodology was applied, included 35 expert gynecological oncology surgeons from 16 countries. Interviews identified key steps and tasks which were rated mandatory, optional, or prohibited using questionnaires. Using the surgical steps for which consensus was achieved, a competency assessment tool was developed and subjected to assessments of validity and reliability., Results: Seventy percent consensus agreement standardized the specific mandatory, optional, and prohibited steps of SLN dissection for endometrial cancer and informed the development of a competency assessment tool. Consensus agreement identified 21 mandatory and three prohibited steps to complete a SLN dissection. The competency assessment tool was used to rate surgical quality in three preselected videos, demonstrating clear separation in the rating of the skill level displayed with mean skills summary scores differing significantly between the three videos (F score=89.4; P<0.001). Internal consistency of the items was high (Cronbach α=0.88)., Conclusion: Specific mandatory and prohibited steps of SLN dissection in endometrial cancer have been identified and validated based on consensus among a large number of international experts. A competency assessment tool is now available and can be used for surgeon selection in clinical trials and for ongoing, prospective quality assurance in routine clinical care., Competing Interests: Competing interests: AO reports grants and personal fees from Surgical Performance PTY LTD, grants from Medtronic, outside the submitted work; NRA-R reports grants from Stryker/Novadaq, outside the submitted work; MF reports grants from Astra Zeneca, grants from Tesaro/GSK, grants and personal fees from Stryker, grants from Biom’Up, outside the submitted work; ML reports Ad hoc consulting from Intuitive Surgical, serves on advisory board for Ethicon, partial grant support from NIH/NCI Memorial Sloan Kettering Cancer Center Support, outside the submitted work; TEI reports personal fees from Medtronic, personal fees from Intuitive Surgical, outside the submitted work; RK reports personal fees from Intuitive Surgical Inc., personal fees from Medtronic, personal fees from Medicaroid, outside the submitted work, and President of SERGS and Council Member of IGCS; HF reports personal fees from Intuitive Surgical Inc, outside the submitted work; JP reports personal fees from Intuitive Surgical Inc., outside the submitted work; AA reports grants and a site PI, speaker fees and serves on advisory board for Astrazeneca, serves on the advisory board for GSK, grants and grats and site Co-PI and speaker fees from Merck, speaker fees from Sanofi, grants from Pfizer, grants from Clovis, grants from CancerCare Manitoba Foundation, grants from Canadian Clinical Trials group, outside the submitted work., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Since the outbreak of COVID-19, there have already been over 26 million people being infected and it is expected that the pandemic will not end in near future. Not only the daily activities and lifestyles of individuals have been affected, the medical practice has also been modified to cope with this emergency catastrophe. In particular, the cancer services have faced an unprecedented challenge. While the services may have been cut by the national authorities or hospitals due to shortage of manpower and resources, the medical need of cancer patients has increased. Cancer patients who are receiving active treatment may develop various kinds of complications especially immunosuppression from chemotherapy, and they and their carers will need additional protection against COVID-19. Besides, there is also evidence that cancer patients are more prone to deteriorate from COVID-19 if they contract the viral infection. Therefore, it is crucial to establish guidelines so that healthcare providers can triage their resources to take care of the most needed patients, reduce less important hospitalization and visit, and to avoid potential complications from treatment. The Asia and Oceania Federation of Obstetrics and Gynecology (AOFOG) hereby issued this opinion statement on the management of gynecological cancer patients during the COVID-19., (© 2021 Japan Society of Obstetrics and Gynecology.)

Aim: Few real-world studies have reported detailed management and dose adjustment strategies of adverse events (AEs) of ovarian cancer (OC) patients treated with the poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib. This case series aimed to describe olaparib AEs in Chinese OC patients in real-life settings and to explore dose modification strategies., Methods: We conducted a detailed examination of the clinical records of OC patients who were treated with olaparib at the Gynecologic Oncology Unit in Hong Kong from September 2015 to December 2019, including baseline characteristics, treatment outcomes, AEs, and management strategies, particularly dose modifications., Results: Nineteen patients were included, with a median olaparib treatment duration of 12 (range: 3-30) months. For recurrent platinum-sensitive cases (n = 16), the median progression-free survival was 16.0 months (95% confidence interval: 9.5-22.5). Eighteen (95%) patients experienced AE(s) of any grade, including four (21%) who experienced grade ≥3 AE(s). The most common AEs were as follows: nonhematologic fatigue (68%), nausea (42%), vomiting (26%), decreased appetite (26%), dyspepsia (21%), dizziness (21%), anemia (37%), neutropenia (26%), and thrombocytopenia (21%). Four specific cases involving anemia, lower limb lymphedema, myeloid neoplasm, and erythema nodosum are discussed separately. Eight patients required dose interruption or reduction due to AEs, of which five patients attempted and tolerated dose re-escalation., Conclusion: In this study, most AEs were mild, but rare AEs were observed. In OC patients, olaparib AE management with dose reductions followed by re-escalations was feasible, including for anemia., (© 2021 John Wiley & Sons Australia, Ltd.)

Objective: To examine the associations of histogram features of T2-weighted (T2W) images and apparent diffusion coefficient (ADC) with treatment response in locally advanced cervical cancer (LACC) following concurrent chemoradiotherapy (CCRT)., Materials and Methods: Fifty-eight patients who underwent a 4-week CCRT regimen with MRI prior to treatment (pre-CCRT) and after treatment (post-CCRT) were retrospectively analysed. Histogram features were calculated from volumes of interest (VOIs) from one radiologist on T2W images and ADC maps. VOIs from two radiologists were used to assess observer repeatability in delineation and feature values at both time-points with the Dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC). Treatment response was defined as a 90% reduction in tumour volume. Paired Mann-Whitney U tests were used to determine if features changed significantly between examinations. Two-sample Mann-Whitney U tests were used to identify features that were significantly different between response groups. Receiver operating characteristic (ROC) analysis was done on significantly different MRI features between treatment response groups., Results: Pre-CCRT delineation and feature repeatability were generally good (DSC > 0.700; ICC > 0.750). Post-CCRT repeatability was low (DSC < 0.700; ICC < 0.750), but ADC mean and percentiles retained good ICC scores. All features, except for T2W Kurtosis , significantly changed between examinations. Post-CCRT ADC 50 was the only feature that demonstrated both good observer variability and significant differences between treatment response groups (p = 0.036) and had an AUC of 0.701 with a cut-off of 1.357 × 10 -6 mm 2 /s., Conclusion: ADC and T2W histogram features could be used to track changes in LACC tumours undergoing CCRT. Post-CCRT ADC 50 was associated with treatment response with good observer repeatability., Key Points: • Pre-treatment tumour delineation and histogram feature values had good observer repeatability, while these were less repeatable at post-treatment. • MRI histogram analysis could be used to track changes in the tumour as it undergoes concurrent chemoradiotherapy. • Post-treatment median ADC was associated with treatment response and had good repeatability.

Recent changes in the classification of cervical adenocarcinomas have re-categorized serous carcinoma as potentially nonexistent. However, clinical and pathological profiles of cervical adenocarcinomas with serous-like morphological features have not been systematically evaluated using the latest taxonomy and biomarkers. We studied 14 cases of primary cervical carcinomas with serous-like morphologies (papillary and micropapillary patterns). None of these cases exhibited evidence of serous carcinoma involving the upper tracts. Patient ages ranged between 34 and 86 years, most presented with abnormal uterine bleeding. Histologically, ten cases were classified as human papillomavirus (HPV)-associated carcinomas (eight usual-type endocervical adenocarcinomas and two adenosquamous carcinomas), of which six exhibited a papillary pattern and four had a micropapillary pattern. The four remaining cases were HPV-independent gastric-type adenocarcinomas, which displayed a papillary pattern in one case and a micropapillary pattern in three others. All ten HPV-associated carcinomas displayed block positive p16 and wild-type p53 by immunohistochemistry, with nine of them confirmed by HPV testing. Two of the four gastric-type adenocarcinomas had mutation-type p53, one of which also being p16 block positive. HER2 overexpression was demonstrated in 3/14 (21.4%) cases (2 HPV-associated and 1 HPV-independent). PD-L1 expression was identified in 4/10 (40%) cases, all HPV-associated. Targeted next-generation sequencing was performed in two cases with a micropapillary pattern, revealing a missense variant in ATM in an HPV-associated tumor and missense variants in TP53 and SMARCB1 in an HPV-independent tumor. The results demonstrated that primary endocervical adenocarcinomas can mimic the appearance of serous carcinoma, while not representing serous carcinoma. Serous-like papillary and micropapillary patterns may be present in both HPV-associated and HPV-independent cervical carcinomas, but none of the cases studied were unequivocally serous upon detailed analysis. Our findings support the exclusion of "cervical serous carcinoma" from existing classifications of cervical adenocarcinoma.

Objective: To assess clinical and psychosocial outcomes of nurse-led follow-up in survivorship care of gynaecological malignancies., Methods: Women with endometrial or ovarian cancer who were attending regular post-treatment follow-up at a tertiary referral centre were randomised into two groups-group-1: telephone follow-up by nurses and group-2: gynaecologists-led clinic follow-up. Women in group-1 were asked about their symptoms and quality of life (QoL) by nurses. Women in group-2 were followed up by gynaecologists and underwent symptom reviews and physical examinations. All ovarian cancer patients in both groups also had CA125 measured. All recruited women completed a QoL questionnaire (EORTC QLQ-C30), HADS-anxiety questionnaire and symptom checklist., Results: 385 women (215 with endometrial and 170 with ovarian cancer) were randomised. There was no significant difference in the detection of recurrence according to the two follow-up protocols. However, women in the nurse-led arm scored higher on emotional (p = 0.023) and cognitive functioning (p = 0.012). Those in the gynaecologist-led arm scored higher on the HADS-anxiety scale (p = 0.001) and were more likely to report symptoms., Conclusions: Our results demonstrate a preliminary non-inferiority of nurse-led follow-up, with improved psychological morbidity and QoL. Thus, nurse-led follow-up can be considered an effective substitute for hospital-based care., (© 2020 John Wiley & Sons Ltd.)

Objectives: To evaluate MRI texture analysis in differentiating clinicopathological characteristics of cervical carcinoma (CC)., Methods: Patients with newly diagnosed CC who underwent pre-treatment MRI were retrospectively reviewed. Texture analysis was performed using commercial software (TexRAD). Largest single-slice ROIs were manually drawn around the tumour on T2-weighted (T2W) images, apparent diffusion coefficient (ADC) maps and contrast-enhanced T1-weighted (T1c) images. First-order texture features were calculated and compared among histological subtypes, tumour grades, FIGO stages and nodal status using the Mann-Whitney U test. Feature selection was achieved by elastic net. Selected features from different sequences were used to build the multivariable support vector machine (SVM) models and the performances were assessed by ROC curves and AUC., Results: Ninety-five patients with FIGO stage IB~IVB were evaluated. A number of texture features from multiple sequences were significantly different among all the clinicopathological subgroups (p < 0.05). Texture features from different sequences were selected to build the SVM models. The AUCs of SVM models for discriminating histological subtypes, tumour grades, FIGO stages and nodal status were 0.841, 0.850, 0.898 and 0.879, respectively., Conclusions: Texture features derived from multiple sequences were helpful in differentiating the clinicopathological signatures of CC. The SVM models with selected features from different sequences offered excellent diagnostic discrimination of the tumour characteristics in CC., Key Points: • First-order texture features are able to differentiate clinicopathological signatures of cervical carcinoma. • Combined texture features from different sequences can offer excellent diagnostic discrimination of the tumour characteristics in cervical carcinoma.

We conducted a prospective randomized controlled trial with two screening rounds to evaluate the effectiveness of combining HPV testing with liquid-based cytology (LBC) as a co-test, compared to LBC only in cervical cancer screening of a Chinese population. First, 15,955 women aged 30-60 were randomized at a 1:1 ratio into an intervention group (Digene Hybrid Capture 2 HPV test with LBC) and a control group (LBC alone). Women in the intervention group would be referred for colposcopy and biopsy immediately if they were found to have high-risk HPV regardless of cytology results. The detection of cervical intraepithelial neoplasia grade 2 or above (CIN2+) lesions was significantly higher in the intervention group compared to the control (0.95% vs. 0.38%, OR 2.50, 95% CI 1.65-3.88). At the subsequent round of screening approximately 36 months later, CIN2+ detection was significantly lower in the intervention group (0.08% vs. 0.35%, OR 0.23, 95% CI 0.08-0.57). Over the two rounds of screening, the total detection of CIN2+ was higher in the intervention group (1.01% vs. 0.66%, OR 1.53, 95% CI 1.09-2.19). There was a fourfold increase (10.6% vs. 2.4%, p < 0.001) in the number of colposcopies performed in the intervention arm. Adding a high-risk HPV test to cytology for primary cervical screening led to earlier detection of clinically significant preinvasive lesions, resulting in a reduced detection of CIN2+ lesions in subsequent rounds and an increased rate of colposcopy., (© 2020 UICC.)

OBJECTIVE. This article discusses the emerging roles of 18 F-FDG PET/CT and DWI in the assessment of peritoneal carcinomatosis in ovarian carcinoma from diagnostic accuracy to disease prognostication with gross pathologic correlation. CONCLUSION. PET/CT and DWI have incremental clinical values over conventional modalities with high predictive values of incomplete cytoreduction in ovarian carcinoma. The respective quantitative metrics offer evaluation of tumor burden with prognostic value in ovarian carcinoma.

Rationale and Objectives: To evaluate the diagnostic performance of contrast-enhanced computed tomography (CT) in predicting residual disease following neo-adjuvant chemotherapy (NACT) in stage III/IV ovarian cancer., Materials and Methods: This was a retrospective observational cohort study including consecutive patients with primary stage III/IV ovarian cancer who received NACT before interval debulking surgery. CT findings before interval debulking surgerywere correlated with histological/surgical findings. Diagnostic characteristics were calculated on patient-based and lesion-based analyses. False negative results on peritoneal carcinomatosis detection were correlated with lesion size and site., Results: On patient-based analysis, CT (n = 58) had a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 92.16%, 57.14%, 94.00%, 50.00%, and 87.93%. On lesion-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 63.01%, 73.47%, 82.51%, 50.00%, and 66.51%. False negative results were associated with lesion size (p < 0.001). The diagnostic performance of CT on the detection of peritoneal carcinomatosis was low at the subdiaphragmatic spaces, bowel serosa and mesentery (p < 0.001)., Conclusion: CT had low negative predictive value in determining residual disease following NACT on both patient-based and lesion-based analyses, especially for non-measurable lesions and at the subdiaphragmatic spaces, bowel serosa and mesentery., (Copyright © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: To evaluate the additional value of diffusion kurtosis imaging (DKI) in the characterization of cervical carcinoma., Materials and Methods: Seventy-five patients (56.9 ± 13.4 years) with histologic-confirmed cervical carcinoma were included. Diffusion-weighted imaging (DWI) was acquired on a 3T MRI with five b values (0, 500, 800, 1000, and 1500 s/mm 2 ). Data were analyzed based on DKI model (5 b values) and conventional DWI (0 and 1000 s/mm 2 ). Largest single-slice region of interest (ROI) and volume of interest (VOI) were drawn around the tumor. Mean diffusivity (MD), mean kurtosis (MK), and apparent diffusion coefficient (ADC) of cervical carcinoma and normal myometrium were measured and compared. MD, MK, and ADC of cervical carcinoma were compared among histologic subtypes, tumor grades, and FIGO stages., Results: ROI- and VOI-derived DKI parameters and ADC were all in excellent consistency (intraclass correlation coefficient, ICC > 0.90, respectively). Cervical carcinoma had significantly lower MD, ADC, and higher MK than normal myometrium (p < 0.001). MD and ADC showed significant differences between histologic subtypes and FIGO stages, lower in squamous cell carcinoma than adenocarcinoma and higher in FIGO I-II than FIGO III-IV (p < 0.050), but not with tumor grade. No difference was observed in MK for different clinicopathologic features tested., Conclusion: ROI and VOI analyses were in excellent consistency. MD and ADC were able to distinguish histologic subtypes and separating FIGO stages, MK could not. DKI showed no clear added value over conventional DWI in the characterization of cervical carcinoma., (Copyright © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Magnetic resonance imaging (MRI) has limited accuracy in detecting pelvic lymph node (PLN) metastasis. This study aimed to examine the use of intravoxel incoherent motion (IVIM) in classifying pelvic lymph node (PLN) involvement in cervical cancer patients., Methods: Fifty cervical cancer patients with pre-treatment magnetic resonance imaging (MRI) were examined for PLN involvement by one subspecialist and one non-subspecialist radiologist. PLN status was confirmed by positron emission tomography or histology. The tumours were then segmented by both radiologists. Kruskal-Wallis tests were used to test for differences between diffusion tumour volume (DTV), apparent diffusion coefficient (ADC), pure diffusion coefficient (D), and perfusion fraction (f) in patients with no malignant PLN involvement, those with sub-centimetre and size-significant PLN metastases. These parameters were then considered as classifiers for PLN involvement, and were compared with the accuracies of radiologists., Results: Twenty-one patients had PLN involvement of which 10 had sub-centimetre metastatic PLNs. DTV increased (p = 0.013) while ADC (p = 0.015), and f (p = 0.006) decreased as the nodal status progressed from no malignant involvement to sub-centimetre and then size-significant PLN metastases. In determining PLN involvement, a classification model (DTV + f) had similar accuracies (80%) as the non-subspecialist (76%; p = 0.73) and subspecialist (90%; p = 0.31). However, in identifying patients with sub-centimetre PLN metastasis, the model had higher accuracy (90%) than the non-subspecialist (30%; p = 0.01) but had similar accuracy with the subspecialist (90%, p = 1.00). Interobserver variability in tumour delineation did not significantly affect the performance of the classification model., Conclusion: IVIM is useful in determining PLN involvement but the added value decreases with reader experience.

Female genital melanomas are rare. At diagnosis, most affected patients have advanced disease. Surgery remains the primary treatment, and adjuvant therapy is largely ineffective. Recently, immune checkpoints and the mitogen-activated protein kinase pathway have been explored as treatment targets. However, evaluation of these biomarkers in genital melanomas is limited. We evaluated the clinicopathological features of 20 vulvar, 32 vaginal, and three cervical melanomas and assessed programmed cell death ligand 1 (PD-L1) expression, CD8 tumor-infiltrating lymphocyte density, mismatch repair proteins, VE1 immunohistochemistry, and KIT and BRAF mutations. The median age of the patients was 66 years, and median tumor sizes were 25, 30, and 20 mm for vulvar, vaginal, and cervical tumors, respectively. Mean mitotic figures were 18, 19, and 30 per mm 2 . Thirty-seven patients (67%) had operable tumors. After a median follow-up of 15 months, only nine patients (16%) were alive. Eight of the nine survivors did not have lymph node metastasis. Using 5% as the threshold, PD-L1 expression was observed in 55%, 50%, and 33% of vulvar, vaginal, and cervical tumors, respectively, when the Roche SP263 antibody was used and 20%, 53%, and 0%, respectively, when the Dako 28-8 antibody was used. The median CD8 tumor-infiltrating lymphocyte density was significantly higher in vulvar/vaginal than cervical melanomas and correlated with PD-L1 expression. No cases exhibited loss of mismatch repair proteins. Five cases harbored KIT mutations, three of which were hotspots. BRAF V600E mutation was not detected. Univariable analysis showed that tumor size greater than or equal to 33 mm, mitotic figures of greater than or equal to 10 per mm 2 , lymph node metastasis, and low CD8+ tumor-infiltrating lymphocyte density were adverse prognostic factors. Thus, patients with genital melanomas have a poor prognosis, and evaluation of multiple biomarkers is necessary to identify patients who may benefit from immunotherapy or targeted therapy.

Background and purpose: Adaptive radiotherapy (ART) can compensate for the dosimetric impacts induced by anatomic and geometric variations in patients with nasopharyngeal carcinoma (NPC); Yet, the need for ART can only be assessed during the radiation treatment and the implementation of ART is resource intensive. Therefore, we aimed to determine tumoral biomarkers using pre-treatment MR images for predicting ART eligibility in NPC patients prior to the start of treatment. Methods: Seventy patients with biopsy-proven NPC (Stage II-IVB) in 2015 were enrolled into this retrospective study. Pre-treatment contrast-enhanced T1-w (CET1-w), T2-w MR images were processed and filtered using Laplacian of Gaussian (LoG) filter before radiomic features extraction. A total of 479 radiomics features, including the first-order ( n = 90), shape ( n = 14), and texture features ( n = 375), were initially extracted from Gross-Tumor-Volume of primary tumor (GTVnp) using CET1-w, T2-w MR images. Patients were randomly divided into a training set ( n = 51) and testing set ( n = 19). The least absolute shrinkage and selection operator (LASSO) logistic regression model was applied for radiomic model construction in training set to select the most predictive features to predict patients who were replanned and assessed in the testing set. A double cross-validation approach of 100 resampled iterations with 3-fold nested cross-validation was employed in LASSO during model construction. The predictive performance of each model was evaluated using the area under the receiver operator characteristic (ROC) curve (AUC). Results: In the present cohort, 13 of 70 patients (18.6%) underwent ART. Average AUCs in training and testing sets were 0.962 (95%CI: 0.961-0.963) and 0.852 (95%CI: 0.847-0.857) with 8 selected features for CET1-w model; 0.895 (95%CI: 0.893-0.896) and 0.750 (95%CI: 0.745-0.755) with 6 selected features for T2-w model; and 0.984 (95%CI: 0.983-0.984) and 0.930 (95%CI: 0.928-0.933) with 6 selected features for joint T1-T2 model, respectively. In general, the joint T1-T2 model outperformed either CET1-w or T2-w model alone. Conclusions: Our study successfully showed promising capability of MRI-based radiomics features for pre-treatment identification of ART eligibility in NPC patients., (Copyright © 2019 Yu, Lam, To, Tse, Cheng, Fan, Lo, Or, Chan, Hui, Chan, Hui, Ngai, Lee, Au, Yip, Zhang and Cai.)

Background: The Arias-Stella reaction (ASR) can mimic endometrial clear cell carcinoma (ECCC) in small biopsies, especially when drug or pregnancy history is unknown. A panel of immunohistochemical markers comprising napsin A, hepatocyte nuclear factor-1-beta (HNF-1β), estrogen and progesterone receptors (ER, PR) has been found useful in confirming a diagnosis of ECCC. However, the detailed characterization of how expression of this combination of markers in the ECCC mimics ASR has yet to be thoroughly evaluated., Design: The frequency and extent of napsin A, HNF-1β, ER, and PR expression in ASR were assessed in a large series. For napsin A, any cytoplasmic staining was considered positive while only nuclear staining was deemed to be positive for HNF-1β, ER, and PR. Immunohistochemical histoscores based on the intensity and extent of staining were calculated., Results: Forty cases were gestational and 10 were nongestational ASR. In 19 (38%), the reaction was extensive and involved >50% of the glands. A stromal decidual change was found in 31 (77.5%) of the gestational and 3 (30%) of the nongestational cases. Napsin A was positive in all gestational and 8 of 10 (80%) nongestational ASR. All ASR showed HNF-1β expression. ER expression was reduced in 37 (92.5%) and lost in 3 (7.5%) gestational ASR, and reduced in 9 (90%) and lost in 1 (10%) of nongestational ASR. None of the ASR in our series expressed PR., Conclusions: Naspin A and HNF-1β were frequently expressed in both gestational and nongestational ASR, and ER expression was usually either reduced or loss. Interpretation of these markers in small biopsies containing atypical clear cells should be made with caution.