Treatment Of Advanced Ovarian Cancer Research Articles

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.

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.

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.

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.

Evaluating socioeconomic status, racial, and US geographic regional differences in biomarker testing and treatment in advanced ovarian cancer.

175 Background: Disparities in access and use of biomarker testing have been reported in patients (pts) with advanced ovarian cancer (AOC) that may result in worse outcomes. This study aimed to characterize socioeconomic status (SES), racial, and US regional differences in the use of biomarker testing and first-line maintenance (1LM) therapy among pts with AOC. Methods: We retrospectively included pts ≥18 years old who were diagnosed with AOC from Jan 2019–Mar 2022 from the nationwide electronic health record-derived Flatiron Health database. Use of biomarker testing (BRCA mutation [BRCAm] only and homologous recombination deficiency [HRD] not including BRCAm tests) and 1LM therapy (PARP inhibitor ± bevacizumab, bevacizumab monotherapy, or other 1LM) were evaluated by SES (scored 1 [low]–5 [high]), race, and US region, using descriptive statistics and chi-squared testing. Results: Of 907 pts included, 91% were from community clinics; median age was 68 years. Overall, 87% (n=787/907) of all pts were BRCAm tested (test type: 31% [n=247/787] germline, 52% [n=411/787] somatic, and 16% [n= 129/787] unknown testing type); 28% (n=255/907) were HRD tested. Of pts who were germline BRCAwt, 22% (n=45/201) underwent additional HRD testing. Of all non-BRCAm pts (defined as germline or somatic BRCAwt or BRCAunknown pts), 28% (218/772) underwent HRD testing; they were more likely to have had surgery (91% vs 71%) vs those who were not HRD tested. Pts with SES score 1 and Black pts had numerically lower testing rates vs the overall population and the relationship between BRCAm testing rates and SES was significant ( P &lt;0.05) (Table). Of all biomarker-tested pts, 49% (n=387/788) received 1LM therapy (71% [n=96/135] of BRCAm, 68% [n=54/80] of BRCAwt/HRD-positive, and 47% [n=55/118] of HRD-negative pts). Among non-biomarker-tested pts, 82% (n=98/119) did not receive 1LM therapy. 1LM therapy use was comparable across SES, race, and US region. Conclusions: While most pts with AOC underwent BRCAm testing, some differences in biomarker-testing rates by SES and race were observed in our study. Further exploration of these differences is required to better understand potential disparities in testing, treatment, and outcomes.[Table: see text]

Social network trust relationship environment based advanced ovarian cancer treatment decision-making model: An approach based on linguistic information with experts’ multiple confidence levels

Advanced ovarian cancer is the deadliest gynecologic cancer in World. The survival rate is not significant, and it depends on how well cancer responds to treatment. Generally, the treatment decision depends on Gynecologic oncology experts, which treatment is best for the patient. However, a Gynecologic oncology expert’s limited rationality and personality traits strongly impact a patient’s treatment decision. In addition, according to the American Cancer Society, a patient’s treatment decision may change if Gynecologic oncology experts change. To solve this kind of medical problem, we design a group decision-making model (GDM) based on linguistic preference relations (LPRs) with multiple confidence levels like confidence and doubting levels of experts to analyse experts’ treatment decision opinions digitally for improving the survival rate of patients. In a GDM, consistency analysis and obtaining expert weights are two keys. Hence, this paper design an LPRs with confidence and doubting levels (LPRs-CDLs) based GDM model under a unique consistency improvement algorithm and Pythagorean linguistic trust relations social network analysis driven expert weight determination. First, we define the additive consistency of LPRs-CDLs based on minimum confidence and maximum doubting levels. Second, a consistency reaching process (CRP) algorithm with convergence theorem is offered to improve the consistency of experts’ opinion decisions. Third, develop a trust propagation model based on Pythagorean linguistic trust relations under a social network environment for expert’s weights determination. Then, a social network trust relationship-based GDM model with LPRs-CDLs information is presented to the advanced ovarian cancer patient’s treatment final decision. Finally, we show the rationality of this study with some comparative analysis.

Perspectives of Healthcare Professionals on the Management and Treatment of Advanced Ovarian Cancer in the UK: Results From the KNOW-OC Survey

AimsNew treatment options for advanced ovarian cancer have the potential to significantly change the treatment pathway in the UK. Understanding the structures and responsibilities of multidisciplinary teams/tumour boards (MDT) and regional variations will enable services to adapt more effectively to these changes. Materials and methodsThe KNOW-OC survey was conducted in 2020 to understand the views of a selected group of 66 healthcare professionals (HCPs) involved in advanced ovarian cancer care in UK hospitals. ResultsThe results showed that MDT involvement in the management of advanced ovarian cancer varied depending on pathway stage and line of relapse, with 98.5% of HCPs responding that the MDT was involved in decisions at initial presentation, but only 40.9% for patients with multiple relapses. The MDT was mostly responsible for determining whether the patients would undergo primary or interval cytoreductive surgery according to 75.8% of respondents, and most HCPs (80.3%) stated that tumour dissemination patterns were the most important factor influencing this decision. The most commonly assessed biomarkers at the time of the survey were CA125, gBRCA and tBRCA. Homologous recombination deficiency was viewed as the second most important factor for determining prognosis, but few centres had access to testing at the time of survey completion. The use of active surveillance was expected to decrease in favour of first-line targeted therapies. Nearly all (98.5%) HCPs agreed there is a role for secondary cytoreductive surgery for the treatment of recurrence (for carefully selected patients). ConclusionsThe results highlighted UK-specific geographical variation in the views of HCPs on MDT involvement and specific practices, such as molecular biomarker testing, and the overall treatment approach. Together, these findings improve the understanding of reported clinical practice across the UK for ovarian cancer and provide insight into decision-making associated with updates to recommendations for best practice (e.g. European Society for Medical Oncology/European Society of Gynaecological Oncology consensus statements) and the introduction of new treatment options.

Synoptic Reporting for Pretreatment CT Examination in Patients With Advanced Ovarian Cancer: Impact on Documentation of Disease Sites and Physician Satisfaction.

BACKGROUND. Imaging reports that consistently document all disease sites with a potential to increase surgical complexity or morbidity can facilitate ovarian cancer treatment planning. OBJECTIVE. The aims of this study were to compare simple structured reports and synoptic reports from pretreatment CT examinations in patients with advanced ovarian cancer in terms of completeness of documenting involvement of clinically relevant anatomic sites as well as to evaluate physician satisfaction with synoptic reports. METHODS. This retrospective study included 205 patients (median age, 65 years) who underwent contrast-enhanced abdominopelvic CT before primary treatment of advanced ovarian cancer from June 1, 2018, to January 31, 2022. A total of 128 reports generated on or before March 31, 2020, used a simple structured report (free text organized into sections); 77 reports generated on or after April 1, 2020, used a synoptic report (a list of 45 anatomic sites relevant to ovarian cancer management, each of which was classified in terms of disease absence versus presence). Reports were reviewed for completeness of documentation of involvement of the 45 sites. For patients who underwent neoadjuvant chemotherapy based on diagnostic laparoscopy findings or underwent primary debulking surgery with suboptimal resection, the EMR was reviewed to identify surgically established sites of disease that were unresectable or challenging to resect. Gynecologic oncology surgeons were electronically surveyed. RESULTS. The mean report turnaround time was 29.8 minutes for simple structured reports versus 54.5 minutes for synoptic reports (p < .001). A mean of 17.6 of 45 sites (range, four to 43 sites) were mentioned by simple structured reports versus 44.5 of 45 sites (range, 39-45) for synoptic reports (p < .001). Forty-three patients had surgically established unresectable or challenging-to-resect disease; involvement of anatomic site(s) with such disease was mentioned in 37% (11/30) of simple structured reports versus 100% (13/13) of synoptic reports (p < .001). All eight surveyed gynecologic oncology surgeons completed the survey. CONCLUSION. A synoptic report improved completeness of pretreatment CT reports in patients with advanced ovarian cancer, including for established sites of unresectable or challenging-to-resect disease. CLINICAL IMPACT. The findings indicate the role of disease-specific synoptic reports in facilitating referrer communication and potentially guiding clinical decision-making.

Pilot randomized trial of an acceptance-based telehealth intervention for women with ovarian cancer and PARP inhibitor-related fatigue

ObjectivePoly(ADP-ribose) polymerase inhibitors (PARPi) have dramatically changed treatment for advanced ovarian cancer, but nearly half of patients experience significant fatigue. We conducted a two-site pilot randomized trial to evaluate the feasibility, acceptability, and preliminary efficacy of a brief, acceptance-based telehealth intervention (REVITALIZE) designed to reduce fatigue interference in patients on PARPi. MethodsFrom June 2021 to April 2022, 44 participants were randomized 1:1 to REVITALIZE (6 weekly one-on-one sessions+booster) or enhanced usual care. Feasibility was defined as: ≥50% approach-to-consent among potentially eligible patients and ≥70% completion of 12-week follow-up assessment; acceptance was <20% participants reporting burden and <20% study withdrawal. Fatigue, anxiety, depression, and quality of life were assessed at baseline, 4-, 8- and 12-weeks. ResultsAmong 44 participants (mean age = 62.5 years, 81.8% stage III/IV disease), the study was feasible (56.4% approach-to-consent ratio, 86.3% completion of 12-week assessment) and acceptable (0% reporting burden, 11.3% study withdrawal). At 12-week follow-up, REVITALIZE significantly reduced fatigue interference (Cohen's d = 0.94, p = .008) and fatigue severity (d = 0.54, p = .049), and improved fatigue levels (d = 0.62, p = .04) relative to enhanced usual care. REVITALIZE also showed promise for improved fatigue self-efficacy, fatigue catastrophizing, anxiety, depression, and quality of life (ds = 0.60–0.86, p ≥ .05). Compared with enhanced usual care, REVITALIZE participants had fewer PARPi dose reductions (6.7% vs. 19.0%), and dose delays (6.7% vs. 23.8%). ConclusionsAmong fatigued adults with ovarian cancer on PARPi, a brief, acceptance-based telehealth intervention was feasible, acceptable, and demonstrated preliminary efficacy in improving fatigue interference, severity, and levels. REVITALIZE is a novel, scalable telehealth intervention worthy of further investigation.

Neoadjuvant Chemotherapy plus Interval Cytoreductive Surgery with or without Hyperthermic Intraperitoneal Chemotherapy (NIHIPEC) in the Treatment of Advanced Ovarian Cancer: A Multicentric Propensity Score Study.

Epithelial ovarian cancer (EOC) is primarily confined to the peritoneal cavity. When primary complete surgery is not possible, neoadjuvant chemotherapy (NACT) is provided; however, the peritoneum-plasma barrier hinders the drug effect. The intraperitoneal administration of chemotherapy could eliminate residual microscopic peritoneal tumor cells and increase this effect by hyperthermia. Intraperitoneal hyperthermic chemotherapy (HIPEC) after interval cytoreductive surgery could improve outcomes in terms of disease-free survival (DFS) and overall survival (OS). A multicenter, retrospective observational study of advanced EOC patients who underwent interval cytoreductive surgery alone (CRSnoH) or interval cytoreductive surgery plus HIPEC (CRSH) was carried out in Spain between 07/2012 and 12/2021. A total of 515 patients were selected. Progression-free survival (PFS) and OS analyses were performed. The series of patients who underwent CRSH or CRSnoH was balanced regarding the risk factors using a statistical analysis technique called propensity score matching. A total of 170 patients were included in each subgroup. The complete surgery rate was similar in both groups (79.4% vs. 84.7%). The median PFS times were 16 and 13 months in the CRSH and CRSnoH groups, respectively (Hazard ratio (HR) 0.74; 95% CI, 0.58-0.94; p = 0.031). The median OS times were 56 and 50 months in the CRSH and CRSnoH groups, respectively (HR, 0.88; 95% CI, 0.64-1.20; p = 0.44). There was no increase in complications in the CRSH group. The addition of HIPEC after interval cytoreductive surgery is safe and increases DFS in advanced EOC patients.

Descriptive review of current practices and prognostic factors in patients with ovarian cancer treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC): a multicentric, retrospective, cohort of 234 patients.

Ovarian cancer (OC) is the primary cause of mortality in women diagnosed with gynecological cancer. Our study assessed pressurized intraperitoneal aerosol chemotherapy (PIPAC) as treatment for peritoneal surface metastases (PSM) from recurrent or progressive OC and conducted survival analyses to identify prognostic factors. This retrospective cohort study, conducted across 18 international centers, analyzed the clinical practices of patients receiving palliative treatment for PSM from OC who underwent PIPAC. All patients were initially treated appropriately outside any clinical trial setting. Feasibility, safety, and morbidity were evaluated along with objective endpoints of oncological response. Multivariate analysis identified prognostic factors for OS and PFS. From 2015-2020, 234 consecutive patients were studied, from which 192 patients were included and stratified by platinum sensitivity for analysis. Patients with early recurrence, within one postoperative month, were excluded. Baseline characteristics were similar between the groups regarding platinum sensitivity (platinum sensitive (PS) and resistant (PR)), but chemotherapy frequency differed, as did PCI before PIPAC. Median PCI decreased in both groups after three cycles of PIPAC (PS 16 vs. 12, p < 0.001; PR 24 vs. 20, p = 0.009). Overall morbidity was 22%, with few severe complications (4-8%) or mortality (0-3%). Higher pathological response and longer OS (22 vs. 11m, p = 0.012) and PFS (12 vs. 7m, p = 0.033) were observed in the PS group. Multivariate analysis (OS/PFS) identified ascites (HR 4.02, p < 0.001/5.22, p < 0.001), positive cytology at first PIPAC (HR 3.91, p = 0.002/1.96, p = 0.035), and ≥ 3 PIPACs (HR 0.30, p = 0.002/0.48, p = 0.017) as independent prognostic factors of overall survival/progression-free survival. With low morbidity and mortality rates, PIPAC is a safe option for palliative treatment of advanced ovarian cancer. Promising results were observed after 3 PIPAC, which did improve the peritoneal burden. However, further research is needed to evaluate the potential role of PIPAC as an independent prognostic factor.

Impact of the time interval between primary or interval surgery and adjuvant chemotherapy in ovarian cancer patients.

Primary debulking surgery (PDS), interval debulking surgery (IDS), and platinum-based chemotherapy are the current standard treatments for advanced ovarian cancer (OC). The time to initiation of adjuvant chemotherapy (TTC) could influence patient outcomes. We conducted a multicenter retrospective cohort study of advanced (International Federation of Gynecology and Obstetrics (FIGO) stage III or IV) OC treated between 2014 and 2018 to assess progression-free survival (PFS) and overall survival (OS) in relation to TTC. All patients underwent a germline multigene panel for BRCA1/2 evaluation. Among the 83 patients who underwent PDS, a TTC ≥ 60 days was associated with a shorter PFS (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.04-3.93, p = 0.038), although this association lost statistical significance when adjusting for residual disease (HR 1.52, 95% CI 0.75-3.06, p = 0.244, for TTC and HR 2.73, 95% CI 1.50-4.96, p = 0.001, for residual disease). Among 52 IDS patients, we found no evidence of an association between TTC and clinical outcomes. Ascites, type of chemotherapy, or germline BRCA1/2 mutational status did not influence TTC and were not associated with clinical outcomes in PDS or IDS patients. In conclusion, longer TTC seems to negatively affect prognosis in patients undergoing PDS, especially those with residual disease.

Discussion article: do we understand the role of local treatments after oligoprogression of ovarian cancer on PARP inhibitors?

The development of poly(ADP‐ribose) polymerase (PARP) inhibitors has been the most significant breakthrough in the treatment of advanced ovarian cancer over recent decades, with olaparib being the first drug of this class. The drug showed its efficacy at many stages of the treatment of various oncological diseases, but its maximum clinical efficacy is demonstrated in the initial treatment of BRCA-associated or HRD-positive ovarian cancer. In the phase III SOLO1 (n = 391) and PAOLA-1 (n = 806) clinical trials, treatment with olaparib reduced the relative risk of disease progression by 67% and 59%, and the risk of death by 45% and 38%, respectively. At the same time, the treatment of patients with disease progression after therapy with PARP inhibitors causes reasonable concerns in clinicians, which is associated with many aspects, primarily with the lack of individually developed approaches to the management of this category of patients. This discussion article through the example of the treatment of a particular patient allows to summarize the current data on the features of the tumour process after disease progression on PARP inhibitors and possible ways to resolve the issue of drug resistance in such patients. In the clinical case under discussion, the maintenance therapy with olaparib after combination treatment in a 50-year-old woman with metachronous multiple primary BRCA-associated malignancies (breast cancer in 2005, ovarian cancer in 2018) allowed to achieve a 2-year cancer remission, after which the oligoprogression of ovarian cancer was observed. PET-CT showed a left iliac lymph node metastasis without other progressive manifestations of the disease, after which a left laparoscopic iliac lymphadenectomy was performed, and the olaparib therapy was continued until progression or intolerable toxicity. The duration of olaparib therapy from the date when the local treatment was performed is 23 months as of this writing. The article states the detailed rationale behind choosing the non-standard management and presents the results of recent studies that support the decisions made.

Transient fluid flow improves photoimmunoconjugate delivery and photoimmunotherapy efficacy

Circulating drugs in the peritoneal cavity is an effective strategy for advanced ovarian cancer treatment. Photoimmunotherapy, an emerging modality with potential for the treatment of ovarian cancer, involves near-infrared light activation of antibody-photosensitizer conjugates (photoimmunoconjugates) to generate cytotoxic reactive oxygen species. Here, a microfluidic cell culture model is used to study how fluid flow-induced shear stress affects photoimmunoconjugate delivery to ovarian cancer cells. Photoimmunoconjugates are composed of the antibody, cetuximab, conjugated to the photosensitizer, and benzoporphyrin derivative. Longitudinal tracking of photoimmunoconjugate treatment under flow conditions reveals enhancements in subcellular photosensitizer accumulation. Compared to static conditions, fluid flow-induced shear stress at 0.5 and 1 dyn/cm2 doubled the cellular delivery of photoimmunoconjugates. Fluid flow-mediated treatment with three different photosensitizer formulations (benzoporphyrin derivative, photoimmunoconjugates, and photoimmunoconjugate-coated liposomes) led to enhanced phototoxicity compared to static conditions. This study confirms the fundamental role of fluid flow-induced shear stress in the anti-cancer effects of photoimmunotherapy.

Pilot randomized trial of a telehealth intervention for women with advanced ovarian cancer and PARP inhibitor-related fatigue.

e24122 Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) have dramatically changed the treatment of advanced ovarian cancer and are increasingly used in other cancers. However, PARPi cause significant fatigue in nearly half of patients. Psychosocial interventions have shown promise for treating cancer-related fatigue, but there is limited evidence for use in patients with advanced cancers. Moreover, most fatigue interventions have been delivered in person over many sessions, limiting their accessibility and scalability. Methods: We conducted a pilot randomized trial of REVITALIZE, a 6-session telehealth intervention developed and refined by our group, compared with enhanced usual care among 35 fatigued patients with advanced or recurrent ovarian cancer on PARPi at two sites, Dana-Farber Cancer Institute and University of Pennsylvania. REVITALIZE was based on acceptance and commitment-based behavioral therapy and addressed modifiable contributors to PARPi-related fatigue. The trial tested the feasibility, acceptability, and preliminary efficacy of REVITALIZE through 3-month follow-up. Exit interviews were conducted with all REVITALIZE patients. Results: Among 35 participants (mean age=62.5 years, 83% stage III/IV disease, 46% first-line maintenance therapy), the trial met or exceeded its acceptability and feasibility goals. Exit interviews further indicated high acceptability. Relative to enhanced usual care, REVITALIZE significantly reduced fatigue interference at 12-week follow-up (Cohen’s d=.94, p=.008) and fatigue severity (d=.54, p=.049), while improving current fatigue levels (d=.62, p=0.04). REVITALIZE participants also reported improved fatigue self-efficacy, fatigue catastrophizing, depression, anxiety, and quality of life (ds=.60-.86). REVITALIZE participants were also numerically less likely to experience PARPi dose reductions compared with enhanced usual care (7% vs. 17%), and less likely to have dose delays (7% vs. 22%). Conclusions: Among fatigued adults with advanced ovarian cancer on PARPi, a brief telehealth intervention based on acceptance and commitment therapy showed strong feasibility, acceptability, and preliminary efficacy with improvements in fatigue, anxiety, depression, and quality of life outcomes. REVITALIZE is a novel, scalable telehealth intervention worthy of further investigation in patients with advanced cancers with PARPi-related fatigue. The study is supported by the National Comprehensive Cancer Network (NCCN) through a grant provided by AstraZeneca. Neither NCCN or AstraZeneca are the sponsors of this study. Clinical trial information: NCT04525183 .

Understanding differences in the rates of BRCA/HRD testing and treatment in 1st line maintenance in patients with ovarian cancer treated by gynecologic oncologists compared to other providers: A quality initiative by Integra Connect (IC) PrecisionQ.

5576 Background: The role of PARPi in the treatment of advanced ovarian cancer (aOC) has expanded in recent years. In this context, South Carolina Oncology Associates (SCOA) partnered with Integra Connect (IC) on a quality initiative (QI) to evaluate the rate of BRCA and HRD testing in newly diagnosed OC patients and the use of maintenance therapy in the 1st line (1L) setting in aOC. Patients with aOC at SCOA are typically managed by gynecologic oncologists. Methods: Using the IC Precision Q real-world database of over 1 million cancer patients across 275 sites of care, we assessed newly diagnosed OC patients evaluated via medical chart curation from 1/1/2020 to 6/30/2022 for BRCA and HRD testing at SCOA (N = 81) and other oncology practices (N = 1,045). We also studied the use of maintenance therapy in patients with stage II-IV OC who completed platinum-based chemotherapy from 1/1/2020 to 6/30/2022 at SCOA (N = 75) and other oncology practices (N =899). SCOA was compared to other oncology practices in terms of provider specialty treating the patient, rates of HRD and BRCA testing, and use of 1L maintenance treatment in patients with or without BRCA or HRD mutations. Descriptive analyses were used. Proportions were compared using a two tailed two sample z-test. Results: Among newly diagnosed patients at SCOA, 95% of patients with OC were primarily managed by a gynecologic oncologist compared to 5% at other practices. The rate of BRCA testing at SCOA was 81% (66 of 81) compared to 75% (788 of 1045) and HRD testing was 60% (49 of 81) compared to 39% (403 of 1045) at other oncology practices in the IC database. The difference in HRD testing was significant (p &lt; 0.01). The use of 1L maintenance regardless of biomarker status was 64% (48 of 75) at SCOA compared to 50% (449 of 899) at other practices. The difference in 1L maintenance use was significant (p&lt;0.05). PARPi were used at SCOA for maintenance therapy in 82% (38 of 46) of patients compared to 74% (314 of 427) at other practices. The use of maintenance in BRCA or HRD positive patients was 84% (21 of 25) at SCOA compared to 75% (151 of 201) for other practices. Conclusions: In this real-world study, treatment by gynecologic oncologists was associated with higher rates of BRCA and HRD testing and higher use of 1L maintenance treatment in patients with aOC compared to other practices. These findings underscore the importance of gynecologic oncologists in the management of aOC to ensure optimal testing and adherence to treatment guidelines.

Safety and feasibility of hyperthermic intraperitoneal chemotherapy during interval cytoreductive surgery in patients with advanced high‐grade serous ovarian, fallopian tube, peritoneal cancer in an Australian context

To assess the safety and feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreduction surgery (CRS) in advanced high-grade serous ovarian, fallopian tube and peritoneal cancer within an Australian context. Data were collected from 25 consecutive patients undergoing CRS and HIPEC from December 2018 to July 2022 at the Peritoneal Malignancy Service at the Mater Hospital Brisbane, Australia. Data collected included demographics, clinical variables, surgical procedures and complications and intra-operative and post-operative indexes of morbidity. Twenty-five women who underwent CRS and HIPEC from December 2018 to July 2022 were included in analysis. Findings indicate that CRS with HIPEC is associated with low morbidity. While judicious patient selection is imperative, HIPEC during CRS was well tolerated by all patients and morbidity was comparable to results from the previously reported OVHIPEC-1 trial. HIPEC appears to be a safe and feasible addition to CRS for the treatment of advanced ovarian cancer in Australian practice.

A Predictive Score after Neoadjuvant Chemotherapy for Optimal Cytoreduction at Interval Debulking Surgery in Advanced Epithelial Ovarian Cancer

Background: Ovarian cancer is the seventh most common cancer and eighth most common cause of death of female. More than 75% patients are diagnosed at Stage (III - IV) and their 5-year survival rate is (25-50%) . Primary debulking surgery (PDS) followed by adjuvant chemotherapy is the cornerstone treatment for advanced ovarian cancer. Unfortunately, primary debulking surgery is not always feasible and not associated with optimal cytoreduction. Recently, neoadjuvant chemotherapy followed by Interval Debulking Surgery (NACT- IDS) is increasingly adopted. (NACT-IDS) improves optimal cytoreduction and reduces complications in comparison with PDS . However, a significant proportion of patients cannot be optimally cytoreduced even after NACT-IDS and causes futile laparotomy. So, it is necessary to develop a Predictive Score for Cytoreduction (PSC) after NACT for optimal cytoreduction at (IDS). Objective: To find out a predictive score after NACT for optimal cytoreduction at IDS in advanced epithelial ovarian cancer. Method: This was a prospective observational study conducted among 55 patients of advanced ovarian cancer to develop a predictive score after NACT at IDS in department of Gynecological Oncology of BSMMU, from January 2020 to December 2020. Result: Among the 55 patients with advanced epithelial ovarian cancer 44(80%) could be optimally cytoreduced whereas in 11(20%) suboptimal cytoreduction occurred. The sensitivity, specificity, Negative predictive value (NPV), Positive predictive value (PPV) and accuracy of CA-125 for prediction of optimal cytoreduction was 87.5%, 30.8%,85.7%,34.1% and 47.3% respectively. It was observed that 37 (84.1%) have peritoneal cancer index within 0-16 in optimal cytoreduction (R0) and 3 (27.3%) in non-R0 (p value 0.001). The sensitivity, specificity, NPV, PPV and accuracy of Peritoneal Cancer Index (PCI) for prediction of optimal cytoreduction was 62.5%, 89.7%, 85.4% 74.1% and 81.8% respectively. PSC after NACT for optimal cytoreduction at (IDS) was 3 and it indicates 83.3% Patients could be optimally cytoreduced limiting the rate of suboptimal cytoreduction in 16.7%. Conclusion: The result of the present study showed that PSC after NACT influences Optimal cytoreduction (R &lt;1cm) at (IDS). So, this study concluded that IDS after NACT should be performed in patients with a PSC up to 2 to avoid suboptimal cytoreduction. Bangladesh Medical Res Counc Bull 2022; 48: 154-159

Muscle loss during cancer therapy is associated with poor outcomes in advanced ovarian cancer.

Data evaluating change in body composition during treatment of advanced cancer are limited. Here we evaluated computed tomography (CT)-based changes in muscle mass during treatment for advanced ovarian cancer (OC) and association with outcomes. We analyzed the preoperative and posttreatment skeletal muscle index (SMI), skeletal muscle area normalized for height of 109 patients with advanced OC who underwent primary surgery and platinum-based chemotherapy from 2006 to 2016. Based on an SMI less than 39 cm2/m2, 54.1% of patients were never sarcopenic, 24.8% were sarcopenic on both CT scans, and 21.1% were newly sarcopenic upon treatment completion. Patients who lost muscle during treatment had the worst survival of the 3 groups identified: median survival 2.6 years vs 4.6 years if sarcopenic on both CT scans and 4.8 years if never sarcopenic. Loss of muscle portends a poor prognosis among patients with OC. Additional research is needed to better understand and best mitigate these changes.