Treatment Of Advanced Ovarian Cancer Research Articles

Case report: Long-term progression-free survival in advanced ovarian cancer treated with apatinib in first-line maintenance treatment

Ovarian cancer is one of the most common gynecological malignancies. The current first-line treatment strategies for advanced ovarian cancer include surgery, chemotherapy, and maintenance therapy. Bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi) are primary maintenance treatments for advanced ovarian cancer. Previously, many patients declined these therapies before medicare coverage because of high costs. Bevacizumab and apatinib are anti-tumor angiogenic agents. In this case study, we describe a patient with advanced ovarian cancer who underwent neoadjuvant chemotherapy, interval debulking surgery, and adjuvant chemotherapy. She declined bevacizumab and PARPi maintenance therapy owing to the prohibitive expenses. The patient was administered off-label apatinib and achieved a progression-free survival of 54 months. Thus, apatinib may offer substantial therapeutic value as a first-line maintenance therapy in advanced ovarian cancer.

Does maximal effort cytoreductive surgery after 6-cycles of chemotherapy play a role in the management of advanced ovarian cancer?

The current gold standard in the surgical management of advanced ovarian cancer recommended by ESGO and ASCO is complete resection of all visible disease. If this is not deemed possible in the upfront setting, then interval cytoreductive surgery should be undertaken after 3-4-cycles of neo-adjuvant chemotherapy. Occasionally, surgery in the interval setting may not be possible either due to factors associated with patient fitness, or due to persistence of disease in sites deemed unresectable on interval scanning. Limited published data assessing outcomes from surgery delayed to after 6-cycles of NACT (delayed cytoreductive surgery) suggests a potential benefit over no surgery and suggests that if interval cytoreductive surgery is not possible, then the clinician might consider delayed surgery on a case by case basis. We sought to review the outcomes of patients with Advanced Ovarian Cancer presenting to the Northern Gynaecological Oncology Centre who underwent delayed surgery. This study is a retrospective analysis looking at patients with epithelial ovarian cancer of FIGO stage IIIC and above, who were not deemed suitable to undergo either primary or interval cytoreductive surgery, referred to the Northern Gynaecological Oncology Centre Gateshead, UK, between January 2014 and December 2020. We compared survival outcomes in women receiving non-standard treatment for advanced ovarian cancer, comparing two groups of patients; those completing at least six cycles of platinum-based chemotherapy as part of their first-line treatment and not having surgery with those who received delayed cytoreductive surgery after completing of 6-cycles of primary chemotherapy. A total of 89 cases were included in the analysis and 78/89 patients had completed at least 6-cycles of primary chemotherapy in the first-line treatment setting without any attempt at surgical cytoreduction. 11/89 patients underwent DDS after completion of 6-cycles of primary chemotherapy. The majority of included cases 87/89 (98%) were high-grade serous ovarian cancer (HGSOC). Surgery and no-surgery groups were well matched in terms of stage comparison at presentation with an overall stage distribution of 62% FIGO stage IIIC, 10% stage IVA and 28% stage IVB. The surgery group were significantly younger than the no-surgery group with median age of 68 (interquartile range (IQR) 59-71years) and 77years (IQR 70-82years) (p < 0.01), respectively. The overall survival (OS) of the surgery and no-surgery groups was 25months and 23months, respectively (p = 0.38) with a median follow-up of 20months (IQR 11-29months). The 1year disease-specific mortality for both groups was 18%. Maximal effort cytoreductive surgery after 6-cycles is not associated with a survival benefit (even with complete cytoreduction) but may be considered in the context of symptomatic disease or for palliation of symptoms amenable to surgery.

Delay in Time to Adjuvant Chemotherapy and its Impact on Oncological Outcomes in Patients Undergoing Optimal Cytoreductive Surgery for Advanced Ovarian Cancer: Analysis of 1480 Cases From the Indian HIPEC Registry.

The impact of delay in initiation of adjuvant chemotherapy following optimal CRS in different settings of treatment for advanced ovarian cancer needs to be studied with special reference to CRS HIPEC. The 1480 advanced EOC patients underwent optimal CRS, followed by adjuvant chemotheraphy, with or without intraperitoneal (IP) chemotherapy in Normothermic or Hyperthermic form. Interval between the day of surgery and start of adjuvant chemotherapy and its impact on outcome was analyzed. CRS, CRS with IP or HIPEC was done in 400, 480, and 600 patients respectively. Median interval of starting adjuvant chemotherapy was 32 days CRS group, 34 days CRS + IP group and 41 days CRS + HIPEC group. Delay in chemotherapy impacted on recurrence free survival (RFS) in CRS + IV group (36 vs. 17 months: p = 0.02) and some impact in CRS + IP group (38 vs. 28 months; P 0.78) and no impact on CRS + HIPEC group (35 vs. 32 months; p = 0.17). Delay in starting adjuvant chemotherapy adversely affects RFS in patients undergoing optimal CRS alone. However, the delay didn't have an impact in the CRS + HIPEC group. Well-designed clinical studies are required to evaluate the impact of single dose of HIPEC.

The impact of inter-cycle treatment delays on overall survival in patients with advanced-stage ovarian cancer.

Chemotherapy forms the cornerstone of systemic treatment for advanced ovarian cancer, extending overall survival; however, drug-related toxicity can lead to treatment delays, potentially diminishing treatment efficacy. This study evaluated the impact of treatment delays on all-cause mortality of patients with ovarian cancer, to better inform decisions on patient management. This retrospective, population-based cohort study included 1517 women with advanced-stage ovarian cancer, receiving first-line adjuvant or neoadjuvant chemotherapy in 2014 and 2015. The frequency of inter-cycle delays >7 dayswas calculated using drug administration dates. Kaplan-Meier estimates were used to compare 2-year overall survival (OS) between patients who were delayed and those treated to schedule. Cox proportional hazards regression was used to investigate the impact of treatment delay on all-cause mortality. Inverse probability of treatment weighting propensity scores were used to adjust for confounding variables. Delays >7 days occurred in 35.3% of patients. Two-year OS probability was 62.7% in patients who experienced treatment delays >7 days (95% CI, 58.7-66.9) compared to 69.1% in those treated to schedule (95% CI, 66.2-72.0). Delays were not significantly associated with all-cause mortality when adjusted for confounders (HR 1.00 95% CI, 0.83-1.20, P = .9). Delays to chemotherapy treatment were not significantly associated with worsened survival in patients with advanced-stage ovarian cancer. These results can inform clinical decision making that prioritize toxicity management and quality of life for those treated with chemotherapy.

Poly(Adenosine Diphosphate Ribose) Polymerase (PARP) Inhibitors in the Treatment of Advanced Ovarian Cancer: A Narrative Review.

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors have appeared as a revolutionary approach to treating advanced ovarian cancer, particularly in patients with breast cancer (BRCA) mutations and homologous recombination deficiency (HRD). This narrative review explores PARP inhibitors' clinical efficiency, safety, and changing role in this context. PARP inhibitors, such as olaparib, niraparib, or rucaparib, provide considerable benefits regarding progression-free survival expansion and overall outcomes improvement in first-line maintenance and recurrent settings. The underlying mechanisms, patient selection criteria, and resistance patterns are discussed, alongside insights into combination therapies to overcome resistance and enhance therapeutic efficacy. Ongoing clinical trials and future potential for personalized therapy approaches using PARP inhibitors for advanced ovarian cancer are also highlighted. However, despite these drugs' phenomenal ability to revolutionize treatment protocols for such cancer types, several challenges remain: toxicity management, cost, and development of resistance will require more research to optimize their use or broaden patient populations who can benefit from them.

A randomized phase II study of secondary cytoreductive surgery in patients with relapsed ovarian cancer who have progressed on a PARP inhibitor as first-line maintenance therapy: the SOCCER-P study (KGOG 3067/JGOG 3036/APGOT-OV11)

BackgroundAlthough two recent phase III randomized controlled trials showed survival benefits of undergoing secondary cytoreductive surgery for an initial relapse of ovarian cancer, patients who received a poly-ADP ribose polymerase...

Pembrolizumab plus chemotherapy in frontline treatment of advanced ovarian cancer: Clinical and translational results from a phase 2 trial.

The efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC) is unknown. Additionally, modification of the tumor microenvironment following neoadjuvant therapy is not well understood. In this single-arm phase 2 trial (this study was registered at ClinicalTrials.gov: NCT02520154), eligible patients received up to 4 cycles of neoadjuvant chemotherapy followed by interval cytoreduction, 3 cycles of adjuvant intravenous carboplatin/weekly paclitaxel/pembrolizumab, and finally maintenance pembrolizumab until progression or toxicity (maximum 20 cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included feasibility, toxicity, and overall survival (OS). PD-L1 staining, multiplex immunofluorescence staining, RNA sequencing, reverse-phase protein array analyses were performed on pre- and post-chemotherapy samples. Thirty-one eligible patients were enrolled. Median PFS and OS was 14.88 (95% CI 12.39-23.00) and 57.43months (95% CI 30.88-not reached), respectively. Among those with PD-L1 combined positive score (CPS) ≥10, the median PFS and OS were not reached compared to those with CPS <10 (10.50 and 30.90months, respectively). Feasibility was met, with all patients completing their planned adjuvant cycles. Treatment discontinuation due to immune-related toxicity occurred in 6 patients (20%). Chemotherapy resulted in an infiltration of anti-tumor immune cells in the tumor microenvironment. Samples of patients with the best PFS demonstrated increased expression of NF-κB, TGF-β, and β-catenin signaling. Pembrolizumab with chemotherapy was feasible and resulted in PFS within the historical range for this EOC population. Patients with CPS ≥10 may benefit more from this regimen, and future studies should investigate this potential biomarker. This investigator-initiated trial was funded by Merck.

Niraparib Population Pharmacokinetics and Exposure-Response Relationships in Patients With Newly Diagnosed Advanced Ovarian Cancer

PurposeNiraparib is a poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor approved for the maintenance treatment of advanced ovarian cancer (OC). Niraparib was originally approved in recurrent OC at a fixed starting dose (FSD) of 300 mg once daily (QD). This analysis characterized the population pharmacokinetics (PK) of niraparib and evaluated the relationships between exposure, efficacy, and safety to support clinical use of an individualized dosing strategy, in which the starting dose of niraparib was adjusted based on patient characteristics to improve the benefit-risk profile. MethodsA population PK model was developed by pooling data from four niraparib clinical trials (PN001 [n = 104], QUADRA [n = 455], NOVA [n = 403], and PRIMA [n = 480]) in patients with solid tumors, including OC. Exposure-response analyses were conducted to explore the relationships of niraparib exposure with progression-free survival (PFS) and adverse events in the PRIMA study. A multivariate logistic regression model was also developed to estimate the probability of grade ≥3 thrombocytopenia, using data from patients enrolled in PRIMA and NOVA. The impact of an individualized starting dose (ISD) regimen (200 mg QD in patients with body weight [BW] <77 kg or platelet count [PLT] <150,000/µL, or 300 mg QD in patients with BW ≥77 kg and PLT ≥150,000/µL) on systemic exposure, efficacy, and safety was assessed. FindingsNiraparib disposition was best described by a 3-compartment model with linear elimination. Key covariates included baseline creatinine clearance, BW, albumin, and age, all of which had minor effects on niraparib exposure. Comparable model-predicted exposure up to the time of disease progression/death or censoring in the 300-mg FSD and 200-/300-mg ISD groups was consistent with the lower rate of dose reduction in the ISD groups. No consistent niraparib exposure-response relationship was observed for efficacy in all PRIMA patients (first-line OC), and no statistically significant difference was seen in PFS curves for patients receiving a niraparib dose of 200 mg versus 300 mg. In the multivariate regression model, performed using combined data from PRIMA and NOVA, higher niraparib exposure (area under the concentration-time curve at steady-state [AUCss]), lower BW, and lower PLT were associated with an increased risk of grade ≥3 thrombocytopenia. ImplicationsPopulation PK and exposure-response analyses support use of an ISD to improve the safety profile of niraparib, including reducing the rate of grade ≥3 thrombocytopenia, without compromising efficacy. Clinical trial registrationClinicalTrials.gov, NCT01847274 (NOVA), NCT00749502 (PN001), NCT02655016 (PRIMA), NCT02354586 (QUADRA), www.clinicaltrials.gov.

Influence of Intraoperative Fluid Management on Postoperative Outcome and Mortality of Cytoreductive Surgery for Advanced Ovarian Cancer-A Retrospective Observational Study.

Background: The surgical treatment of advanced ovarian cancer is associated with extensive tissue trauma, prolonged operating times and a considerable volume shift. It, therefore, represents a challenge for anaesthesiological management. Aim: The aim of this single-centre, retrospective, observational study was to investigate whether intraoperative extensive volume supply influences postoperative outcomes and long-term survival. Methods: The study included 73 patients with a mean (SD) age of 63 (13) years who underwent extensive tumour-reducing surgery for ovarian cancer between 2012 and 2015. The effect of the intraoperative fluid balance on postoperative complications, such as anastomotic insufficiency or pleural effusions, was investigated using logistic regression. Further, the influence of fluid balance, lactate and creatinine levels on 5-year survival was analysed in a Cox regression model. Associations between anaesthesia time and the intraoperative fluid balance were examined using Spearman's rank correlation coefficients. Results: The mean (SD) postoperative fluid balance in the considered patient cohort was 9.1 (3.4) litres (l) at a mean (SD) anaesthesia time of 529 (106) minutes. Cox regression did not reveal a statistically significant effect of the fluid balance, but it did reveal a statistically significant association between the lactate level 24 h following surgery and the 5-year survival (HR [95%-CI] fluid balance: 0.97 [0.85, 1.11]; HR [95%-CI] lactate: 1.79 [1.24, 2.58]). According to logistic regression, the intraoperative fluid balance was associated with an increased chance of postoperative complications in the considered patient cohort (OR [95%-CI] 1.28 [1.1, 1.54]). Conclusions: We could not detect a negative impact of an increased fluid balance on 5-year survival, but a negative impact on postoperative complications was found in our patient cohort.

Advanced Ovarian Cancer Patients’ Experiences of Surgical Treatment: A Qualitative Analysis

ObjectivesRecommended treatment for advanced ovarian cancer involves a combination of debulking surgery and chemotherapy. Surgery places a significant burden on a patient's physical, social, sexual, and emotional wellbeing. Existing research exploring the impact of surgery is often limited to questionnaire administration with large gaps between data collection time points, missing key aspects of the perioperative period. Little is known of the experience of ovarian cancer surgical treatment from a patient perspective. This research aims to qualitatively explore advanced ovarian cancer patients’ experience of surgery and identify areas in which quality of life may be impacted. MethodsSemi-structured telephone or face-to-face interviews were conducted with patients who had undergone combined surgical and chemotherapy treatment. Interviews were audio-recorded and transcribed verbatim. Transcripts were analyzed using an inductive approach to thematic analysis. ResultsTwenty ovarian cancer patients who had undergone debulking surgery participated in interviews lasting between 33 and 68 minutes. Qualitative analysis generated five key themes: (1) care services; (2) experiences of a stoma; (3) preoperative experience; (4) impact of surgery; and (5) coping mechanisms. ConclusionsUnderstanding the patient experience of surgical treatment for advanced ovarian cancer can help inform and improve future care. This research explored the ways in which a patient's quality of life is impacted by surgery and highlights areas in which further support may be needed. Knowledge of the patient experience may also aid decision-making for both clinicians and patients when considering different treatment pathways. Implications for Nursing PracticeResults highlighted two crucial points in the surgical pathway where patients' need for emotional support was significant: during pre-op and recovering from surgery as an inpatient. Nursing staff are key to providing reassurance during this time. Specialized stoma nurses were also essential for supporting patients to adapt to their stomas both physically and psychologically.

Evaluation of the efficacy of marine natural products against PARP-1/2 proteins in high-grade serous ovarian cancer: insights into MD and SMD simulations

High-grade serous ovarian cancer (HGSOC) is the most malignant and ubiquitous phenotype of epithelial ovarian cancer. Originating in the fallopian tubes and rapidly spreading to the ovaries, this highly heterogeneous disease is a result of serous tubal intraepithelial carcinoma. The proteins known as poly(ADP-ribose) polymerase (PARP) aid in the development of HGSOC by repairing the cancer cells that proliferate and spread metastatically. By using molecular docking to screen 1100 marine natural products (MNPs) from different marine environments against PARP-1/2 proteins, prominent PARP inhibitors (PARPi) were identified. Four compounds, alisiaquinone A, alisiaquinone C, ascomindone D and (+)-zampanolide referred to as MNP-1, MNP-2, MNP-3 and MNP-4, respectively, were chosen based on their binding affinity towards PARP-1/2 proteins, and their bioavailability and drug-like qualities were accessed using ADMET analysis. To investigate the structural stability and dynamics of these complexes, molecular dynamics simulations were performed for 200 ns. These results were compared with the complexes of olaparib (OLA), a PARPi that has been approved by the FDA for the treatment of advanced ovarian cancer. We determined that MNP-4 exhibited stronger binding energies with PARP-1/2 proteins than OLA by using MM/PBSA calculations. Hotspot residues from PARP-1 (E883, M890, Y896, D899 and Y907) and PARP-2 (Y449, F450, A451, S457 and Y460) showed strong interactions with the compounds. To comprehend the unbinding mechanism of MNP-4 complexed with PARP-1/2, steered molecular dynamics (SMD) simulations were performed. We concluded from the free energy landscape (FEL) map that PARP-1/2 are well-stabilised when the compound MNP-4 is bound rather than being pulled away from its binding pockets. This finding provides significant evidence regarding PARPi, which could potentially be employed in the therapeutic treatment of HGSOC. Communicated by Ramaswamy H. Sarma

An open, prospective, single arm, phase II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) with neoadjuvant chemotherapy in patients with advanced ovarian cancer: Interim analysis from the AK104-IIT-003 study.

e17552 Background: There is an unmet need to improve neoadjuvant chemotherapy (NAC) to decrease postoperative residual disease (R0 rate: 50%) and improve prognosis in ovarian cancer (OC). R0 rate and histopathological response of interval cytoreductive surgery (IDS) after NAC combined with immune checkpoint blockades were reported to be encouraging. Cadonilimab (AK104) is a tetravalent bispecific antibody targeting PD-1 and CTLA-4. In this study, we report the efficacy and safety of AK104 with NAC in patients with advanced-stage ovarian cancer (NCT05430906). Methods: This study is an open-label, prospective, single arm, phase II study of evaluating the efficacy and safety of cadonilimab combined with chemotherapy as neoadjuvant treatment for advanced ovarian cancer. Patients received neoadjuvant therapy of cadonilimab plus platinum-taxane chemotherapy (3 to 4 cycles) followed by surgery. Surgery would be performed within 30 days of completion of neoadjuvant therapy. The primary endpoint was the R0 rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), chemotherapy response score (CRS), pathologic complete response(pCR), progression-free survival (PFS), and safety. A sample size of 35 achieves 80% power to detect a difference of 0.2 using a two-sided Z-test to estimate the standard deviation with a significance level (alpha) of 0.1. And the sample size was expected to be 40 cases to ensure that the FAS set contains 35 cases for analysis. Results: 17 patients were enrolled from Dec 12, 2022, to Dec 6, 2023. The median patient age was 57 years (range 45–70 years), and most patients presented with high-grade serous carcinoma (94.1%) and stage IVa (5.9%), IVb disease (76.5%). 15 (88.2%) patients had undergone IDS, with an R0 resection rate of 66.7%. ORR was 94.1%, with 1patient achieved CR and 15 patients achieved PR. 11.8% achieved pathological complete response, and 17.6% had a chemotherapy response score (CRS) of 3. PFS or OS data are not mature by cut-off date. Safety and adverse event (AE) were analyzed after completion of neoadjuvant therapy. Treatment-related AEs (TRAEs) of any grade were evaluated for all study populations. TRAEs of any grade occurred in 13 (76.5%) patients. Grade ≥3 TRAEs occurred in 3 (17.6%) patients. The most common TRAEs were thyroid dysfunction (23.5%) and bone marrow suppression (17.6%). Grade ≥ 3 irAE (immune⁃mediated colitis) occurred in 1 (5.9%) patient. All of the TRAEs, including severe AEs, were manageable, with no new safety concerns in this study. Conclusions: This study showed promising activity with a durable clinical response, supporting the potential of NAC with bispecific antibody AK104 in advanced-stage ovarian cancer. Meanwhile, long-term efficacy evaluation still needs following up. Clinical trial information: NCT05430906 .

Utilization of PARP inhibitors in the management of ovarian cancer in Nigeria.

e13500 Background: Ovarian cancer remains a significant health concern globally, especially in countries with low Human Development Index (HDI), where there is a projected 96% increase in new cases and a 100% increase in associated deaths by 2040 compared to a 19% increase in new cases and a 28% increase in deaths in very High HDI countries. Over the years, significant strides have been made in the treatment of ovarian cancer, leading to a decrease in ovarian cancer-related mortality in High HDI countries. Poly (ADP-ribose) polymerase inhibitors (PARPi) are among the new and emerging treatment options, which have transformed the management of ovarian cancer, especially in patients with BRCA mutations. Methods: A cross-sectional survey was distributed to clinical and gynecologic oncologists practicing in Nigeria via email, text, WhatsApp, and telegram messaging. Clinical and gynecologic oncologists who are not involved in the treatment of patients with ovarian cancer and those who are not currently in practice were excluded. Results: Out of 36 respondents, 34 were analyzed. While PARP inhibitors are increasingly acknowledged (85.29% awareness), actual utilization remains modest (14.71%). The sole PARP inhibitor used is Olaparib. The majority of respondents (48.28%) who did not use PARP inhibitors cited both the lack of availability and the high cost of medications as the reasons. Key barriers to the use of PARP inhibitors include a combination of non-availability and cost (48.28%) and a combination of institutional protocols and socioeconomic status (20.59%). Conclusions: Despite increasing awareness, PARP inhibitor utilization in Nigerian ovarian cancer management is hindered by challenges, predominantly cost and availability. The study highlights a missed opportunity for optimizing advanced ovarian cancer treatment in Nigeria. [Table: see text]

Primary cytoreductive surgery followed by chemotherapy compared to neoadjuvant chemotherapy followed by cytoreduction as a treatment for stage III and IV ovarian cancer (literature review)

Standard treatment for advanced ovarian cancer (OC) consists of a combination of chemotherapy and cytoreductive surgery, but practice varies depending on the order of these 2 procedures: neoadjuvant chemotherapy followed by interval debulking surgery or primary cytoreduction followed by adjuvant chemotherapy. The aim of the work is to evaluate methods of treatment of OC of stages III, IV according to FIGO.The literature review includes publications in English from the PubMed, CochraneLibrary and Google Scholar databases on the use of neoadjuvant therapy and primary cytoreduction in late stages of OC (FIGO III–IV). 6 randomized controlled trials, 8 meta-analyses, 8 systematic reviews, 1 case report were identified. Data from publications were distributed according to the criteria for assessing the effectiveness of the treatment: overall and relapse-free survival, perioperative complications, quality of life of patients and the grade of cytoreduction.Neoadjuvant chemotherapy + interval debulking surgery is not inferior to primary debulking surgery + adjuvant chemotherapy in terms of survival outcomes in selected patients, but treatment with neoadjuvant chemotherapy + interval debulking surgery improves perioperative outcomes and optimal cytoreduction rates. It is needed to focus on finding optimal criteria for selecting patients in both groups in future studies of this issue. It is necessary to take into account X-ray, histological studies, the molecular subtype of the tumor, the patient’s condition, the qualifications of the surgical team, the drugs included in chemotherapy.

Microcosting Analysis of Advanced Ovarian Cancer: Real-World Evidence From the Perspective of a Reference Public Brazilian Hospital

ObjectivesEvaluate the cost of advanced ovarian cancer, using the microcosting technique, based on real-world evidence from the perspective of a reference Brazilian public hospital. MethodsRetrospective cohort study of patients newly diagnosed with advanced ovarian cancer in 2017 and followed-up for up to 5 years. A bottom-up microcosting method was applied, using the activity-based cost approach, which evaluates service costs based on activity consumption throughout patients’ journey. ResultsThe results indicate a median overall survival of 35.3 months and a median age of 57 years (33-80 years old). The average cost per patient was USD 34 991.595 over a period of 35.3 months, with admissions because of the disease progression and end-of-life care being the most relevant. ConclusionsThe results show that the costs of activities currently involved in the treatment of advanced ovarian cancer represent an important economic impact for the public health system. These data can support future analyses on the impact of incorporating new technologies for the treatment of ovarian cancer and on the financing and sustainability of the Brazilian public healthcare system.

The Use of CA-125 KELIM to Identify Which Patients Can Achieve Complete Cytoreduction after Neoadjuvant Chemotherapy in High-Grade Serous Advanced Ovarian Cancer.

(1) Background: Neoadjuvant chemotherapy followed by interval debulking surgery is used in the treatment of advanced ovarian cancer. However, no tool can safely predict if complete cytoreduction after 3-4 cycles can be achieved. This study aims to investigate if the KELIM score can be a triage tool in the identification of patients that will be ideal candidates for interval debulking surgery (IDS). (2) Methods: We retrospectively analyzed the records of patients with high-grade serous advanced ovarian cancer that were treated in the 1st Department of Obstetrics-Gynecology, 2012-2022, with neoadjuvant chemotherapy followed by IDS. Patient characteristics, oncological outcome and follow-up information were collected. The primary outcome was the association of the KELIM score with residual disease. (3) Results: 83 patients were categorized into two groups: Group A (51 patients) with favorable (≥1) and Group B (32 patients) with unfavorable (<1) KELIM scores. A statistically significant correlation between KELIM and residual disease (p < 0.05) exists, showing that patients with a favorable KELIM score can achieve a complete IDS. Furthermore, there was a statistically significant difference in overall survival (p = 0.017), but no difference was observed in progression-free survival (p = 0.13); (4) Conclusions: KELIM seems to safely triage patients after neoadjuvant chemotherapy and decide who will benefit from IDS.

Efficacy and safety of combination of poly-ADP-ribose polymerase inhibitor (PARPi) and chemotherapy compared with chemotherapy alone in treatment of recurrent ovarian carcinoma: a systematic review.

Platinum-based chemotherapy after surgical cytoreduction is the universal treatment for advanced ovarian cancer (OC), however, about eighty percent of patients experienced relapse and progression-free survival remained poor. Patients who relapsed within one year of treatment eventually become resistant to second-line chemotherapy. Poly-ADP-ribose polymerase inhibitors are a novel class of targeted therapy that could overcome these challenges by augmenting the chemotherapeutic activity of other cytotoxic agents. Cumulative Index to Nursing and Allied Health Literature (CINHAL), Cochrane and PubMed databases were searched for potentially relevant primary publications from 2011 to 2022 reporting on efficacy and safety of combination of a PARP inhibitor and chemotherapy versus chemotherapy in recurrent OC and reviewed. The outcomes of interest assessed qualitatively were progression-free survival (PFS) and grade 3 or higher adverse events (AEs) as measures of efficacy and safety respectively. Eight randomized controlled trials (RCTs) were included in the systematic review comprising 3,021 patients evaluated efficacy and safety of PARP inhibitors: Olaparib, niraparib and veliparib with combinations of bevacizumab, carboplatin, cisplatin, cediranib, cyclophosphamide and paclitaxel. 824 patients had 33 BRCA mutation while 1,430 had wild-type BRCA, an allele that confers increased risk of cancer. Most patients had platinum-sensitive cancers. There was significant prolongation of PFS with PARP inhibitor and chemotherapy combination compared to chemotherapy in all included trials except one which combined veliparib with cyclophosphamide. The prolongation of PFS was more remarkable in patients with BRCA mutation and occasionally patients with wild-type BRCA. Niraparib and veliparib were notably associated with grade 3 or higher anaemia, neutropenia, and thrombocytopenia, olaparib caused fatigue and gastrointestinal disturbances while bevacizumab and cediranib caused hypertension. This review suggested combined PARP inhibitor and chemotherapy significantly prolonged progression-free survival especially in patients with BRCA mutation compared to chemotherapy and the combined therapy is safe.

Limitations and potential of immunotherapy in ovarian cancer.

Ovarian cancer (OC) is the third most common gynecological cancer and alone has an emergence rate of approximately 308,069 cases worldwide (2020) with dire survival rates. To put it into perspective, the mortality rate of OC is three times higher than that of breast cancer and it is predicted to only increase significantly by 2040. The primary reasons for such a high rate are that the physical symptoms of OC are detectable only during the advanced phase of the disease when resistance to chemotherapies is high and around 80% of the patients that do indeed respond to chemotherapy initially, show a poor prognosis subsequently. This highlights a pressing need to develop new and effective therapies to tackle advanced OC to improve prognosis and patient survival. A major advance in this direction is the emergence of combination immunotherapeutic methods to boost CD8+ T cell function to tackle OC. In this perspective, we discuss our view of the current state of some of the combination immunotherapies in the treatment of advanced OC, their limitations, and potential approaches toward a safer and more effective response.

Application of 3D reconstruction and 3D printing technology in advanced ovarian cancer surgery: a retrospective study.

Advanced ovarian cancer is frequently accompanied by extensive peritoneal metastasis, complicating surgical interventions. This study aims to explore the application of 3D reconstruction and 3D printing technology in the treatment of advanced ovarian cancer. We conducted a retrospective analysis of 60 patients with stage III ovarian cancer who underwent cytoreductive surgery at Hebei University Affiliated Hospital between 2020 and 2023. Patients were randomly assigned to three groups: a 3D visualization group, a 3D visualization plus 3D printing group, and a traditional 2D CT imaging evaluation group. High-precision medical imaging techniques (e.g., CT, MRI) were employed to create digital 3D models, which were then converted into physical entities using 3D printing for surgical planning and simulation. Both the 3D visualization group and the 3D visualization plus 3D printing group demonstrated superior outcomes in terms of surgery duration and blood loss compared to the traditional 2D CT group, indicating the efficacy of 3D reconstruction and 3D printing in preoperative planning. Postoperative recovery indicators, such as hospital stay and time to first flatus, were also more favorable in the groups utilizing 3D technology. Although there were no significant differences in postoperative complications and recurrence rates among the three groups, the groups using 3D technology showed advantages in reducing certain complications. The results indicate that medical 3D technology has significant value in the surgical planning of advanced ovarian cancer, enhancing surgical precision and reducing intraoperative risks, which may aid in improving postoperative recovery.

Should We Abandon Intraperitoneal Chemotherapy in the Treatment of Advanced Ovarian Cancer? A Meta-Analysis.

Ovarian cancer is the gynaecological malignancy with the highest mortality and diagnosis often occurs in its advanced stages. Standard treatment in these cases is based on complete cytoreductive surgery with adjuvant intravenous chemotherapy. Other types of treatment are being evaluated to improve the prognosis of these patients, including intraperitoneal chemotherapy and antiangiogenic therapy. These may improve survival or time to relapse in addition to intravenous chemotherapy. The aim of this meta-analysis is to determine whether treatment with intravenous chemotherapy remains the gold standard, or whether the addition of intraperitoneal chemotherapy has a benefit in overall survival (OS) and disease-free interval (DFS). A literature search was carried out in Pubmed and Cochrane, selecting clinical studies and systematic reviews published in the last 10 years. Statistical analysis was performed using the hazard ratio measure in the RevMan tool. Intraperitoneal chemotherapy shows a benefit in OS and DFS compared with standard intravenous chemotherapy. The significant differences in OS (HR: 0.81 CI 95% 0.74-0.88) and in DFS (HR: 0.81 CI 95% 0.75-0.87) are statistically significant (p < 0.00001). There were no clinical differences in toxicity and side-effects. Intraperitoneal chemotherapy is an option that improves OS and DFS without significant toxicity regarding the use of intravenous chemotherapy alone. However, prospective studies are needed to determine the optimal dose and treatment regimen that will maintain the benefits while minimising side effects and toxicity and the profile of patients who will benefit most from this treatment.