Ka Yu Tse

Return to intended oncological therapy following advanced ovarian cancer surgery: a narrative review

Summary 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.

PET/Computed Tomography Transformation of Oncology

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.

Efficacy and Safety of Sacituzumab Govitecan in Patients With Advanced Solid Tumors (TROPiCS-03): Analysis in Patients With Advanced Endometrial Cancer

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.

The AOFOG recommendations on human papillomavirus vaccination in the Asia‐Pacific region

AbstractCervical 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.

Patient‐derived organoid culture in epithelial ovarian cancers—Techniques, applications, and future perspectives

AbstractEpithelial 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.

Patient-Initiated Follow-Up in Ovarian Cancer

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.

Tamoxifen use in recurrent ovarian cancer in a Chinese population: A 15 ‐year clinical experience in a tertiary referral center

AbstractAimTo review the clinical use and the effectiveness of tamoxifen in patients with advanced or recurrent ovarian cancer.MethodsA 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.ResultsA 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.ConclusionPatients 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.

Diffusion-weighted magnetic resonance imaging of primary cervical cancer in the detection of sub-centimetre metastatic lymph nodes

Abstract 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.

Association between IVIM parameters and treatment response in locally advanced squamous cell cervical cancer treated by chemoradiotherapy

To examine the associations of intravoxel incoherent motion (IVIM) parameters with treatment response in cervical cancer following concurrent chemoradiotherapy (CCRT). 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. 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). 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. • 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.

Inhibition of Aberrantly Overexpressed Polo-like Kinase 4 Is a Potential Effective Treatment for DNA Damage Repair–Deficient Uterine Leiomyosarcoma

Abstract 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.