Management Of Recurrent Ovarian Cancer Research Articles

Oncologic outcomes of secondary cytoreductive surgery in the era of poly (ADP-ribose) polymerase inhibitors maintenance (549)

Oncologic outcomes of secondary cytoreductive surgery in the era of poly (ADP-ribose) polymerase inhibitors maintenance (549)

Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer

(Abstracted from N Engl J Med 2021;385:2123–2131) Standard of care treatment for advanced ovarian cancer involves primary macroscopic resection of all tumor followed by platinum-based combination chemotherapy with or without additional systemic therapy including bevacizumab or a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor. The Descriptive Evaluation of Preoperative Selection Criteria for Operability in Recurrent Ovarian Cancer (DESKTOP) series aims to assess the role of surgery in management of recurrent ovarian cancer.

Role of involved-site radiation in the management of recurrent ovarian malignancies: a single institutional experience

Objectives: Radiation therapy is commonly used to preserve local control in patients with oligometastatic disease. The objective of this study was to evaluate our institutional experience utilizing involved-site radiation (ISRT) in the management of recurrent ovarian cancer. Methods: Twenty-eight patients with recurrent ovarian cancer treated with ISRT between 2008-2019 were identified from our institutional database. A retrospective review of patient charts was performed. ISRT was delivered to sites of gross disease for all the patients who developed localized oligorecurrence following prior lines of chemotherapy to preserve local control. Results: The median age of diagnosis was 53 years range (23-70 years). Serous cystadenocarcinoma was the most common histological type (60.7%), followed by endometroid (14.3%) and clear cell subtypes (10.7%). Most patients had stage 3C (46.4%) at initial diagnosis. Many patients (79%) underwent initial optimal debulking, followed by platinum-based adjuvant chemotherapy. ISRT was considered mostly for patients who had recurrent disease confined to the pelvis (85.7%). The median time from the initial diagnosis to the initiation of ISRT was 49 months, and the median follow-up time after ISRT was 9.5 months (range 0-51 months). Most of the patients had a median of 2 recurrences (range 0-8) before receiving ISRT. The median radiation dose was 48 Gy (range 38-66 Gy). The median time to initiate additional chemotherapy after the ISRT was 2 months (range 0-23 months). The one-year rates of local control and distal progression following ISRT were 78% and 64.7%, respectively. The one-year overall survival rate after completion of ISRT was 72.5%. A majority of patients with recurrent disease following ISRT were treated with additional chemotherapy (10/19), and one patient with an out of field recurrence was managed with complete resection of distal metastases. The median time to initiate additional chemotherapy after the ISRT was 2 months (range 0-23 months). All patients tolerated ISRT well, and no ≥ grade 3 toxicities were observed. Conclusions: ISRT in recurrent ovarian cancer offers reasonable local control in well-selected patients with oligo-recurrences of ovarian cancer. Treatment was well-tolerated and may offer an alternative to interval-debulking surgery or chemotherapy in selected patients.

PARP inhibitors in ovarian cancer: An overview of the practice-changing trials.

Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the management of recurrent ovarian cancer in patients with BRCA-mutations and beyond. Olaparib was the first PARP inhibitor to gain approval as maintenance therapy for patients with newly diagnosed, advanced BRCA-mutated ovarian cancer establishing a new standard of care. At the end of 2020, as a result of the SOLO1, PRIMA, and PAOLA-1 phase III trials, we are now in an era where three maintenance PARP inhibitor strategies have FDA and European Medicines Agency approval in the first-line setting. In this review, we provide an overview of the key PARP inhibitor trials that have changed clinical practice, discuss directing therapy according to biomarker status (BRCA and homologous recombination deficiency) and future strategies in ovarian cancer and other gynecological malignancies.

831P Efficacy of platinum-based chemotherapy in platinum-resistant ovarian cancer: A systematic review with pooled analysis of outcomes

Current management of recurrent ovarian cancer (OC) is based on the amount of time between completion of latest platinum-based treatment and relapse. Patients with platinum-free interval (PFI) < 6 mo. are considered to be platinum-resistant (PROC) and to have low response rate (RR) to platinum-based chemotherapy.

Efficacy of platinum-based chemotherapy in platinum-resistant ovarian cancer: A systematic review with pooled analysis of outcomes.

e18076 Background: Current management of recurrent ovarian cancer (OC) is based on the amount of time between the completion of penultimate platinum-based treatment and the detection of relapse. Patients with platinum-free interval (PFI) &lt; 6 mo. are considered to be platinum-resistant (PROC) and to have low response rate (RR) probability to platinum-based chemotherapy. Methods: We searched PubMed database for all prospective and retrospective full-text articles and abstracts on the treatment of patients with PROC for all years between 01/01/2000 and 01/06/2019 in English language. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) tool was used to ensure transparent reporting of the results. Study inclusion criteria were: 1) morphologically confirmed epithelial ovarian cancer; 2) standard definition of PROC as a disease that recurred within 6 months after completion of platinum-based chemotherapy; 3) treatment with platinum- or non-platinum chemotherapy with agents that are routinely used for OC; 4) no concomitant therapy with targeted or investigational agents; 5) clearly defined RR for patients with PROC and criteria used for response assessment. Pooled analysis of outcomes and multiple linear regression analysis was conducted to assess the impact of platinum salts on probability of response. Results: We identified 7156 articles and screened them for title and abstract. After the review process we selected 197 studies for further analysis. Of them, 52 (n = 1320) and 145 (n = 6937) trials assessed efficacy of platinum- and non-platinum based chemotherapy respectively. Among patients treated with platinum-based and non-platinum chemotherapy RR was 36.04% (95% CI 33.45-38.63) and 14.85% (95% CI 14.01-15.68) respectively. Pooled median progression-free survival was 5.8 mo. and 3.75 mo. respectively. In multiple linear regression model administration of platinum-based chemotherapy was the strongest predictor of objective response with B value 0.503 (p &lt; 0.001). Among platinum agents cisplatin (RR 39.9%: 95% CI 35.8-44.0%) and carboplatin (RR 42.3%; 95% CI 37.0-47.6%) were associated with better rates of objective response compared to oxaliplatin (RR 28.1%; 95% CI 23.9-32.3). Conclusions: This systematic review shows that patients with 'platinum-resistant' ovarian carcinoma may derive significant benefit from reintroduction of platinum agents and their value should be evaluated in further randomized trials.

Robotic Tumor Debulking off External Iliac Vessels for the Management of Recurrent Ovarian Cancer

To show a surgical video in which an isolated mass was resected off the external iliac vessels for the management of recurrent ovarian cancer. Case report. Tertiary referral center in New Haven, Connecticut. This is a step-by-step demonstration of a robotic tumor debulking in a patient with isolated recurrence of epithelial ovarian cancer [1-3]. The patient is a 70-year-old woman with Lynch syndrome who received a diagnosis for stage IIC high-grade serous ovarian adenocarcinoma and underwent complete debulking in 1996. She had most recently been on pembrolizumab for microsatellite instability-high tumor until February 2019, when she received a diagnosis for isolated hypermetabolic mass in close proximity to the external iliac vessels and right iliac fossa. The patient was placed in dorsal low lithotomy Trendelenburg position, and 15° leftward tilt of the table was obtained to expose the right pelvic sidewall and iliac fossa. To optimally target the surgical field of interest, all robotic trocars were placed in a straight line starting from 5 cm above symphysis pubis on the left side to left subcostal line between the midline vertical and the left midclavicular lines, as per the manufacturer's port placement guidelines (Fig. 1). Robotic resection of the tumor nodule off the external iliac vessels was successfully performed with adequate range of motion provided by the arms and without any complications. Trocar placement should be tailored to the site of surgical interest. Robotic-assisted laparoscopy should be considered as a valid alternative to the traditional open approach, when managing solitary masses in patients with recurrent ovarian cancer.

1008P - A real-world analysis of the treatment of advanced ovarian cancer with PARPIs

BackgroundPoly ADP-ribose polymerase inhibitors (PARPIs) have received US and European regulatory approvals for the treatment of BRCA-associated ovarian cancer. The approval of PARPIs in rapid succession has resulted in a paradigm shift in the management of recurrent ovarian cancer. Methods2,116 ovarian cancer patients (pts) in advanced/metastatic (adv/met) lines of therapy from Jan 2016 to Oct 2018 in EU5 (France, Germany, Spain, Italy, UK) were identified within Oncology Dynamics, an IQVIA oncology-syndicated cross-sectional survey collecting anonymized patient-level data. Maintenance therapy was also investigated in 534 pts. ResultsPlatinum-based regimens for the treatment of adv/met ovarian cancer pts decreased from 56% in 2017 to 50% by Oct 2018. In contrast, the use of PARPIs increased from 9% to 14%. A reduction in the administration of PARPIs was noted in all platinum-based regimens (▾15% and ▾13% in 2nd and 3rd+ lines adv/met) and in non-platinum chemotherapy (▾8% and ▾9% in 2nd and 3rd+ lines adv/met). However, in platinum-sensitive ovarian cancer pts, there has been an increase of PARPIs in 2nd and 3rd+ lines (given to 27% and 29% pts, respectively). The use in the 1st line adv/met setting has also increased by 3% (administered to 8% of pts). Prior to PARPIs, most of the pts were treated with platinum-based regimens (97%). As maintenance treatment, PARPIs have been most used in 2nd (26%) and 3rd+ line (22%) in platinum-sensitive adv/met ovarian cancer. 93% of adv/met ovarian cancer pts treated with PARPIs had an ECOG status of≤1 and most suffered no comorbidities (50%). Peritoneum was the most common metastatic site (63%), followed by lymph nodes (38%). Nearly all pts had been tested for BRCA1/2 and 79% of them presented mutations. Progression was the most common reason for stopping treatment with PARPIs (72%); and anaemia, nausea, vomiting, neutropenia, and rash were the most common side effects on historic patient records. ConclusionsPARPIs have certainly shown a meaningful impact on progression-free survival in pts with platinum-sensitive recurrent ovarian cancer, without any deleterious impact on the quality of life. The use of PARPIs is rising in the platinum-sensitive ovarian cancer population in clinical practice. Legal entity responsible for the studyIQVIA. FundingIQVIA. DisclosureA. Martinez de Pinillos: Full / Part-time employment: IQVIA C. Anger: Full / Part-time employment: IQVIA L. Mendoza: Full / Part-time employment: IQVIA

ASO Author Reflections: BRCA Mutation Status for Personalizing Management of Recurrent Ovarian Cancer-A Multicenter Study.

ASO Author Reflections: BRCA Mutation Status for Personalizing Management of Recurrent Ovarian Cancer-A Multicenter Study.

Correction to: BRCA Mutation Status to Personalize Management of Recurrent Ovarian Cancer: A Multicenter Study.

In the original version of the article, Angelo Minucci's last name was spelled incorrectly. It is correct as shown here. The original article has been corrected.

BRCA Mutation Status to Personalize Management of Recurrent Ovarian Cancer: A Multicenter Study.

The aim of this study was to assess the correlation between BRCA mutation status and disease presentation, treatment strategy, and survival in a multicenter series of recurrent high-grade serous ovarian cancer (HGSOC) women. A consecutive series of recurrent HGSOC patients with partially or fully platinum-sensitive disease admitted to the Gynecologic Oncology Units of the Catholic University of the Sacred Heart and Sapienza University of Rome. Main eligibility criteria were known BRCA 1/2 germline mutation status and a minimum follow-up period from recurrence of at least 6months. Overall, 126 patients met the eligibility criteria, of whom 76 (60%) were BRCA wild-type (BRCAwt) and 50 (40%) were BRCA 1/2 germline mutation carriers (BRCAmut). Among the latter, 37 (74%) patients presented with BRCA1 mutation, and 13 (26%) presented with BRCA2. No differences were found regarding patterns of disease presentation between BRCAwt and BRCAmut women. BRCAmut patients had the best post-recurrence survival (PRS) regardless of having received secondary cytoreductive surgery (SCS) or not, with a 5-year PRS of 73% in non-resected women versus 78% in resected women (p = 0.558). Conversely, BRCAwt patients who underwent complete SCS had a significantly longer PRS compared with BRCAwt patients who did not receive surgery (5-year PRS of 54% vs. 42%; p = 0.048). Recurrent ovarian cancer BRCAmut patients have the best prognosis regardless of SCS, whereas PRS in BRCAwt women can improve when complete SCS is performed. The identification and incorporation of predictive biomarkers such as BRCA status to tailor the medical and surgical approach is paramount to the success of recurrent HGSOC treatments.

A systematic review of patient values, preferences and expectations for the treatment of recurrent ovarian cancer

Background and objectivesIt is our belief that patient preference should play a significant role in disease management of recurrent ovarian cancer. Since cure is seldom an endpoint in this circumstance, patients' attitudes toward the risks and benefits of chemotherapy versus palliation are relevant. MethodsMedline, Embase, CINAHL and PsycINFO from were searched from January 1, 2000 to December 13, 2016 for studies of values, preferences or expectations of women with platinum-sensitive recurrent or refractory ovarian cancer. ResultsTen studies representing five countries met inclusion criteria. Although there was regional variation in preference for palliation over treatment, certain themes emerged. 1) Patients, even in the context of counselling overestimated the curative capability of chemotherapy. In one study 92% of patients had high expectations of healing after completing an expectation of treatment checklist. Another study observed that patients are often overwhelmed by information provided at diagnosis and there can be a discrepancy between what patients report to have heard and what the clinicians said. 2) Patients who had previously tolerated chemotherapy well were more likely to be accepting of the side-effects of chemotherapy. 3) Patients were more willing to accept chemotherapy and the related side effects when treatment was of curative intent or when overall survival was increased. 4) Patients valued both overall and progression free survival. 5) A significant minority (24%) consistently chose treatment over palliation. 6) Patients were more willing to accept the side effects of chemotherapy than were their health care providers. ConclusionsThese findings, in aggregate, highlight the importance of communication with patients regarding prognosis, adverse effects and symptom management to help negotiate the decision making process. Chemotherapy in the recurrent setting should be managed on a case by case basis, combining both medical constraints and consideration to patient preferences.

The role of F18-FDG PET/CT in predicting secondary optimal de-bulking in patients with recurrent ovarian cancer

Background and objectivesThe decision to perform secondary cytoreductive surgery for recurrent ovarian cancer is generally determined by clinical criteria. The aim of this study was to assess the predictive capability of FDG-PET/CT in identifying patients for whom secondary optimal debulking can be obtained. MethodsWe reviewed the records of all women with suspected recurrent ovarian cancer (CA-125 levels >35 U/ml and/or clinical symptoms), at two medical centers, between January 2004 and December 2013. Patients in whom CT scans were negative, indeterminate or indicative of localized disease, were referred for preoperative FDG-PET/CT study. We analyzed the outcomes of those who subsequently underwent cytoreductive surgery. ResultsOf 282 women with suspected recurrent ovarian cancer, 48 underwent FDG-PET/CT. The 24 for whom localized disease was detected on PET/CT, subsequently underwent secondary debulking surgery. Patients with PET/CT evidence of multifocal recurrent sites were referred for chemotherapy. Tumor debulking was optimal in 20 patients, and suboptimal in 4. The positive predictive value of PET/CT for optimal debulking was 83.3%. ConclusionsThe findings extend prior reports on the role of FDG-PET/CT in the management of recurrent ovarian cancer, to the prediction of secondary optimal debulking. Future studies should aim to investigate the impact on survival.

Laparoscopic-based score assessment combined with a multiple disciplinary team in management of recurrent ovarian cancer: A single-center prospective study for personalized surgical therapy.

The aim of the study was to evaluate the effect of laparoscopic-based score combined with a multiple disciplinary team (MDT) for predicting optimal cytoreduction and perform personalized surgical treatment in recurrent ovarian cancer (ROC).The study is a single-center, prospective investigation. From March 2013 to May 2015, the consecutive treated patients with platinum-sensitive ROC were collected in Yangpu Hospital. The appropriated patients were enrolled into the study to perform the laparoscopic-based PIV (predictive index value) score assessment with an MDT for predicting optimal cytoreduction. The PIV cutoff value was confirmed to be 8. Patients of PIV <8 received laparoscopic/laparotomy secondary surgery following chemotherapy, and the ones with PIV ≥8 did chemotherapy alone. Sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV), and overall accuracy for each range of PIV score were calculated. All recruited patients participated in follow-up observation. Overall survival was recorded.In total, 58 eligible ROC patients received laparoscopy assessment. Forty-one patients of PIV <8 received secondary cytoreductive surgeries. Twenty-three (23/41 56.1%) attained optimal cytoreduction. However, 8 of 23 achieved completed cytoreduction. Also, 17 patients of PIV ≥8 underwent chemotherapy alone. Sensitivity, specificity, PPV, NPV, and overall accuracy for PIV ≥8 were 60%, 100%, 100%, 25%, and 64.7%, respectively. Overall survival in patients performing optimal cytoreduction was significantly higher than in those undergoing suboptimal cytoreduction or chemotherapy alone (45.9 ± 2.5 vs 36.7 ± 4.3 months, P = .047; 45.9 ± 2.5 vs 35.8 ± 3.4 months, P = .027).Laparoscopic-based score assessment plus MDT helps to identify the appropriate patients to perform optimal secondary cytoreduction and provide a personalized surgical approach in management of ROC.

Beyond the Beyond: First Case of 9 Cytoreductive Surgeries in a Long-Surviving Ovarian Cancer Patient: Case Report

The role of surgery in recurrent ovarian cancer (ROC) is debated. Multiple prospective and retrospective series reported improved survival with optimal secondary surgical cytoreduction, but definitive results from randomized trials are needed. Up to the fourth cytoreductive surgery for recurrent disease in an attempt to improve patients' prognosis has been reported. We report the first case of multiple ROC in an Italian woman, 50 years old at diagnosis, who underwent 9 cytoreductive surgeries during her 17 years of disease with no serious postoperative complications. Multiple surgeries should not be considered as the standard treatment for ROC. In carefully selected patients, optimal cytoreductive surgery performed by highly specialized gynecologic oncologists might represent a useful tool in adjunction to chemotherapy for the management of ROC.

Hormonotherapy in the Management of Recurrent Ovarian Cancer

Hormonotherapy in the Management of Recurrent Ovarian Cancer

TRX-E-002-1 Induces c-Jun-Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo.

Chemoresistance is a major hurdle in the management of patients with epithelial ovarian cancer and is responsible for its high mortality. Studies have shown that chemoresistance is due to the presence of a subgroup of cancer cells with stemness properties and a high capacity for tumor repair. We have developed a library of super-benzopyran analogues to generate potent compounds that can induce cell death in chemoresistant cancer stem cells. TRX-E-002-1 is identified as the most potent analogue and can induce cell death in all chemoresistant CD44(+)/MyD88(+) ovarian cancer stem cells tested (IC50 = 50 nmol/L). TRX-E-002-1 is also potent against spheroid cultures formed from cancer stem cells, chemosensitive CD44(-)/MyD88(-) ovarian cancer cells, and heterogeneous cultures of ovarian cancer cells. Cell death was associated with the phosphorylation and increased levels of c-Jun and induction of caspases. In vivo, TRX-E-002-1 given as daily intraperitoneal monotherapy at 100 mg/kg significantly decreased intraperitoneal tumor burden compared with vehicle control. When given in combination with cisplatin, animals receiving the combination of cisplatin and TRX-E-002-1 showed decreased tumor burden compared with each monotherapy. Finally, TRX-E-002-1 given as maintenance treatment after paclitaxel significantly delayed disease recurrence. Our results suggest that TRX-E-002-1 may fill the current need for better therapeutic options in the control and management of recurrent ovarian cancer and may help improve patient survival. Mol Cancer Ther; 15(6); 1279-90. ©2016 AACR.

Long-term Benefit of Tumor Volume-Directed Involved Field Radiation Therapy in the Management of Recurrent Ovarian Cancer.

This study aimed to report on long-term effectiveness of involved field radiation therapy (IFRT) in the salvage of localized recurrent ovarian cancer (ROC). A retrospective analysis of 27 patients with a diagnosis of epithelial ovarian cancer who received tumor volume-directed IFRT for localized extraperitoneal recurrences (either as consolidation after cytoreductive surgery (CRS) or as attempted salvage if unresectable) forms the basis of this report. All patients were heavily pretreated with multiple chemotherapy regimens. Involved field radiation therapy was primarily with external beam (median dose, 50.4 Gy). Local recurrence-free survival (LRFS) was defined as freedom from in-field recurrences and was considered as a measure of effectiveness of radiotherapy. Statistical analyses evaluated association between disease-free survival, overall survival, LRFS, and various prognostic factors. Comparison was also made with a similar but unmatched cohort with localized recurrences salvaged by additional chemotherapy instead of local therapies (NIFRT group). Of 27 patients, 17 had optimal CRS before RT. The actuarial survival at 5 and 10 years (in parenthesis) from date of radiation were LRFS (70% and 60%), overall survival (30% and 19%), and disease-free survival (33% and 20%). None of the NIFRT patients survived beyond 5 years from initiation of salvage chemotherapy. Long-term follow-up in this selected series confirmed the benefit of IFRT (±CRS) in localized ROC. Chemotherapy salvage in a similar NIFRT group was not equivalent, suggesting a role for locoregional therapies in selected patients with ROC.

Comparison of Robotics, Laparoscopy and Laparotomy in the Management of Recurrent Ovarian Cancer

Comparison of Robotics, Laparoscopy and Laparotomy in the Management of Recurrent Ovarian Cancer

Platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer.

ObjectiveThe concept of platinum sensitivity and cross-resistance among platinum agents are widely known in the management of recurrent ovarian cancer. The aim of this study was to evaluate two hypotheses regarding the validity of the concept of platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer.MethodsIn this retrospective study, the clinical data of patients with recurrent cervical cancer, who had a history of receiving cisplatin based chemotherapy (including concurrent chemoradiotherapy [CCRT] with cisplatin) and who received second-line chemotherapy at the time of recurrence between April 2004 and July 2012 were reviewed.ResultsIn total, 49 patients-34 squamous cell carcinomas (69.4%) and 15 non-squamous cell carcinomas (30.6%)-were enrolled. The median age was 53 years (range, 26 to 79 years). Univariate and multivariate analysis showed that a platinum free interval (PFI) of 12 months has a strong relationship with the response rate to second-line chemotherapy. Upon multivariate analysis of survival after second-line platinum-based chemotherapy, a PFI of 12 months significantly influenced both progression-free survival (hazard ratio [HR], 0.349; 95% confidence interval [CI], 0.140 to 0.871; p=0.024) and overall survival (HR, 0.322; 95% CI, 0.123 to 0.842; p=0.021). In patients with a PFI of less than 6 months, the difference of progression-free survival between patients with re-administration of cisplatin (3.0 months) and administration of cisplatin analogue (7.2 months) as second-line chemotherapy was statistically significant (p=0.049, log-rank test).ConclusionThe concept of platinum sensitivity could be applied to recurrent cervical cancer and there is a possibility of noncross-resistance of cisplatin analogue with cisplatin.