Neoadjuvant Chemotherapy For Ovarian Cancer Research Articles

Venous thromboembolism during neoadjuvant chemotherapy for ovarian cancer

ObjectiveTo determine the incidence of venous thromboembolism in patients with advanced epithelial ovarian cancer undergoing neoadjuvant chemotherapy in UK gynecological cancer centers. Secondary outcomes included incidence and timing of venous...

Pathologic response to neoadjuvant chemotherapy in ovarian cancer and its association with outcome: A surrogate marker of survival

ObjectiveWe aimed to validate whether pathologic response (pR) to neoadjuvant chemotherapy (NACT) using a three-tier chemotherapy response score (CRS) is associated with clinical outcome in ovarian cancer (OC) and could be used as surrogate marker for survival. MethodsWe conducted a retrospective study of OC patients with FIGO stage III/IV disease who received NACT and graded response as no or minimal (CRS 1), partial (CRS 2), or complete/near-complete (CRS 3) pR using tissue specimens obtained from omentum. Uni- and multivariate survival analyses were performed accounting for age, FIGO stage, debulking and BRCA status as well as neoadjuvant use of bevacizumab. ResultsCRSs 1, 2 and 3 were found in 41(31%), 62 (47%) and 30 (22%) of the 133 examined cases. Response to NACT was associated with significantly improved progression-free (PFS, p < 0.001) and overall survival (OS, p = 0.011). Complete/ near-complete pathologic response (CRS3) was associated with improved PFS (median 24.8 vs. 12.5 months, unadjusted HR 0.28 [95%CI 0.15–0.54], p < 0.001; adjusted hazard ration (aHR) 0.31 [95% CI 0.14–0.72], p = 0.007) and OS (median 63.3 vs. 32.1 months, unadjusted HR 0.27 [95%CI 0.10–0.68], p = 0.006; aHR 0.32 [95% CI 0.09–1.11], p = 0.072) when compared to no or minimal response (CRS1). ConclusionsWe validate a three-tier CRS for assessment of pathologic response to NACT in OC and demonstrate its prognostic independence of BRCA status or neoadjuvant bevacizumab use. Improving pR rates may be a useful goal of NACT in OC with the expectation of improved survival. The CRS may be a useful endpoint in clinical trials in OC.

Change of Fagotti score is associated with outcome after neoadjuvant chemotherapy for ovarian cancer

ObjectiveTo investigate whether a change in the Fagotti score (ΔFagotti) following neoadjuvant chemotherapy is predictive of resection to no residual disease (R0) and survival in women diagnosed with ovarian cancer.MethodsWomen...

Neoadjuvant chemotherapy for ovarian cancer: Avoiding 'needless hurt'?

Linked article: This is a mini commentary on C. Marchetti et al., pp.1579–1588 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17558.

Do surgeons overestimate diaphragmatic peritoneal disease in interval debulking surgery of ovarian cancer?

IntroductionCytoreductive surgery is a key point in ovarian cancer treatment. Substantial morbidity may be consecutive to this major radical surgery. However, the objective of no residual tumor (CC-0) had demonstrated its clear improvement of prognosis. Could macroscopically-driven interval debulking surgery (IDS) overestimate active cancer cells and be unnecessarily morbid? Materials and methodsThis retrospective cohort study was conducted in Center Leon Berard Cancer Center between 2000 and 2018. We included women with advanced epithelial ovarian cancer who received neoadjuvant chemotherapy and underwent an IDS including resection of peritoneal metastases on the diaphragmatic domes. The primary endpoint was the pathological outcome of peritoneal resections of diaphragmatic domes. ResultsPeritoneal resections of diaphragmatic domes consisted of 117 patients. 75 patients required resection of nodules from the right cupola only, 2 patients from the left cupola only, and 40 patients bilaterally. Pathological analysis of the diaphragmatic domes found that 84.6% of samples demonstrated the presence of malignant cells, and only 12.8% found no tumor involvement. Pathology analysis could not be performed for 3 patients (2.6%) (vaporization). ConclusionSurgical evaluation after neoadjuvant chemotherapy in ovarian cancer does not often overestimate peritoneal involvement by active carcinomatosis. Potential surgical morbidity due to peritoneal resection in IDS is admissible.

Neoadjuvant Chemotherapy in Ovarian Cancer: Are There Racial Disparities in Use and Survival?

We investigated racial and ethnic disparities in treatment sequence [i.e., neoadjuvant chemotherapy (NACT) plus interval debulking surgery (IDS) versus primary debulking surgery (PDS) plus adjuvant chemotherapy] among patients with ovarian cancer and its contribution to disparities in mortality. Study included 37,566 women ages ≥18 years, diagnosed with stage III/IV ovarian cancer from the National Cancer Database (2004-2017). Logistic regression was used to compute ORs and 95% confidence intervals (CI) for racial and ethnic disparities in treatment sequence. Cox proportional hazards regression was used to estimate HRs and 95% CI for racial and ethnic disparities in all-cause mortality. Non-Hispanic Black (NHB) and Asian women were more likely to receive NACT plus IDS relative to PDS plus adjuvant chemotherapy than non-Hispanic White (NHW) women (OR: 1.12; 95% CI: 1.02-1.22 and OR: 1.12; 95% CI: 0.99-1.28, respectively). Compared with NHW women, NHB women had increased hazard of all-cause mortality (HR: 1.14; 95% CI: 1.09-1.20), whereas Asian and Hispanic women had a lower hazard of all-cause mortality (HR: 0.81; 95% CI: 0.74-0.88 and HR: 0.83; 95% CI: 0.77-0.88, respectively), which did not change after accounting for treatment sequence. NHB women were more likely to receive NACT plus IDS and experience a higher all-cause mortality rates than NHW women. Differences in treatment sequence did not explain racial disparities in all-cause mortality. Further evaluation of racial and ethnic differences in treatment and survival in a cohort of patients with detailed treatment information is warranted.

Patterns of treatment and survival outcomes with use of neoadjuvant chemotherapy in ovarian cancer (481)

Patterns of treatment and survival outcomes with use of neoadjuvant chemotherapy in ovarian cancer (481)

Improved T-cell Immunity Following Neoadjuvant Chemotherapy in Ovarian Cancer.

Although local tissue-based immune responses are critical for elucidating direct tumor-immune cell interactions, peripheral immune responses are increasingly recognized as occupying an important role in anticancer immunity. We evaluated serial blood samples from patients with advanced epithelial ovarian cancer (EOC) undergoing standard-of-care neoadjuvant carboplatin and paclitaxel chemotherapy (including dexamethasone for prophylaxis of paclitaxel-associated hypersensitivity reactions) to characterize the evolution of the peripheral immune cell function and composition across the course of therapy. Serial blood samples from 10 patients with advanced high-grade serous ovarian cancer treated with neoadjuvant chemotherapy (NACT) were collected before the initiation of chemotherapy, after the third and sixth cycles, and approximately 2 months after completion of chemotherapy. T-cell function was evaluated using ex vivo IFNγ ELISpot assays, and the dynamics of T-cell repertoire and immune cell composition were assessed using bulk and single-cell RNA sequencing (RNAseq). T cells exhibited an improved response to viral antigens after NACT, which paralleled the decrease in CA125 levels. Single-cell analysis revealed increased numbers of memory T-cell receptor (TCR) clonotypes and increased central memory CD8+ and regulatory T cells throughout chemotherapy. Finally, administration of NACT was associated with increased monocyte frequency and expression of HLA class II and antigen presentation genes; single-cell RNAseq analyses showed that although driven largely by classical monocytes, increased class II gene expression was a feature observed across monocyte subpopulations after chemotherapy. NACT may alleviate tumor-associated immunosuppression by reducing tumor burden and may enhance antigen processing and presentation. These findings have implications for the successful combinatorial applications of immune checkpoint blockade and therapeutic vaccine approaches in EOC.

CHRONO: randomized trial of the CHROnology of surgery after Neoadjuvant chemotherapy for Ovarian cancer

BackgroundIn patients treated for advanced ovarian cancer not suitable for complete primary surgery, interval surgery after three courses of neoadjuvant chemotherapy has been considered standard management since the EORTC randomized...

ASO Visual Abstract: Cytoreductive Surgery with or Without HIPEC after Neoadjuvant Chemotherapy in Ovarian Cancer: A Phase III Clinical Trial

ASO Visual Abstract: Cytoreductive Surgery with or Without HIPEC after Neoadjuvant Chemotherapy in Ovarian Cancer: A Phase III Clinical Trial

The Evaluation Value of CT in the Efficacy of Neoadjuvant Chemotherapy in Ovarian Cancer Patients.

Aim To discuss the evaluation value of CT in the efficacy of neoadjuvant chemotherapy in patients with ovarian cancer. Methods The clinical, pathological, and CT imaging information of 72 patients with ovarian cancer treated in our hospital from January 2018 to January 2022 were retrospectively analyzed. CT examination and pathological examination were compared to evaluate the efficacy of neoadjuvant chemotherapy. Results Using the CRS grading system, 26 cases (36.11%) scored 1, 42 cases (58.33%) scored 2, and 4 cases (5.56%) scored 3. CRS grading system scores of 1, 2, 3, and 4–7 patients were compared, P > 0.05. The CT manifestations of lymphadenectasis, degree of peritoneal thickening, ascites, and maximum length diameter of the mass were compared between the patients before and after chemotherapy, P < 0.05. According to RECIST 1.1, there were 1 (1.39%) CR, 38 (52.78%) PR, 29 (40.28%) SD, and 4 (5.56%) PD. The comparison was done between RECIST 1.1 and CRS grading system, P > 0.05. Conclusion CT could be used to evaluate the efficacy of neoadjuvant chemotherapy for ovarian cancer.

Incidence and patient characteristics of venous thromboembolism during neoadjuvant chemotherapy for ovarian cancer.

There is paucity of data on venous thromboembolism (VTE) in patients receiving neoadjuvant chemotherapy (NACT) for advanced stage ovarian cancer. We explored the incidence and predictors of VTE in this patient population. We performed a retrospective review of women with primary ovarian, fallopian tube or peritoneal cancer who received NACT between January 2012 and October 2018 at Cooper University Hospital. Patients with history of VTE, heparin therapy or direct oral anticoagulant use prior to cancer diagnosis were excluded. The primary outcome was incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE) after cancer diagnosis. We explored demographic and clinical variables associated with VTE. Of 90 patients included, 25 (28%) were diagnosed with VTE and 16 (64%) had PE. Eight patients were diagnosed after cancer diagnosis prior to the start of chemotherapy and 17 patients during NACT. Most patients had stage III disease and serous adenocarcinoma. There was a trend towards increased risk of VTE for Black patients (OR 3.22; CI 0.997-10.42; P = 0.051). Significantly fewer patients with VTE had debulking surgery (60% vs. 88%, P = 0.005). The risk of DVT increased by 8.7% per year of age (OR 1.087; 95% CI 1.01-1.17). Obesity, smoking status, medical comorbidities, disease stage, histology, invasive diagnostic surgery, and length of NACT were not associated with VTE. The incidence of VTE during neoadjuvant chemotherapy is high. Older age and Black race may increase the risk of VTE, and this morbid complication may adversely impact cancer treatment.

Cost-Effectiveness of Venous Thromboembolism Prophylaxis During Neoadjuvant Chemotherapy for Ovarian Cancer.

Two recent clinical trials have demonstrated that direct oral anticoagulants (DOACs) are effective as venous thromboembolism (VTE) prophylaxis in patients with moderate-to-high risk ambulatory cancer initiating chemotherapy. Patients with advanced ovarian cancer receiving neoadjuvant chemotherapy are at particularly increased risk of VTE. We performed a cost-effectiveness analysis from a health system perspective to determine if DOACs are a feasible prophylactic strategy in this population. A simple decision tree was created from a health system perspective, comparing two strategies: prophylactic DOAC taken for 18 weeks during chemotherapy versus no VTE prophylaxis. Rates of VTE (7.3% DOAC v 13.6% no treatment), major bleeding (2.6% v 1.3%), and clinically relevant nonmajor bleeding (4.6% v 3.3%) were modeled. Cost estimates were obtained from wholesale drug costs, published studies, and Medicare reimbursement data. Probabilistic, one-way, and two-way sensitivity analyses were performed. In the base case model, DOAC prophylaxis is more costly and more effective than no therapy (incremental cost-effectiveness ratio = $256,218 in US dollars/quality-adjusted life year). In one-way sensitivity analyses, reducing the DOAC cost by 32% or raising the baseline VTE rate above 18% renders this strategy potentially cost-effective with an incremental cost-effectiveness ratio below $150,000 in US dollars/quality-adjusted life year. Further confirmation of the true baseline VTE rate among women initiating neoadjuvant chemotherapy for ovarian cancer will determine whether prophylactic dose DOAC is a value-based strategy. Less costly VTE prophylaxis options such as generic DOACs (once available) and aspirin also warrant investigation.

Emerging Trends in Neoadjuvant Chemotherapy for Ovarian Cancer.

Epithelial ovarian cancer remains a leading cause of death amongst all gynecologic cancers despite advances in surgical and medical therapy. Historically, patients with ovarian cancer underwent primary tumor reductive surgery followed by postoperative chemotherapy; however, neoadjuvant chemotherapy followed by interval tumor reductive surgery has gradually become an alternative approach for patients with advanced-stage ovarian cancer for whom primary tumor reductive surgery is not feasible. Decision-making about the use of these approaches has not been uniform. Hence, it is essential to identify patients who can benefit most from neoadjuvant chemotherapy followed by interval tumor reductive surgery. Several prospective and retrospective studies have proposed potential models to guide upfront decision-making for patients with advanced ovarian cancer. In this review, we summarize important decision-making models that can improve patient selection for personalized treatment. Models based on clinical factors (clinical parameters, radiology studies and laparoscopy scoring) and molecular markers (circulating and tumor-based) are useful, but laparoscopic staging is among the most informative diagnostic methods for upfront decision-making in patients medically fit for surgery. Further research is needed to explore more reliable models to determine personalized treatment for advanced epithelial ovarian cancer.

Machine learning: Automated tumor to stroma ratios to predict response in neoadjuvant chemotherapy

Objective: Most patients undergoing neoadjuvant chemotherapy for ovarian cancer respond to standard therapy; however, there are no standards for assessing response. This study utilized pretreatment and interval debulking pathologic samples to measure the tumor-to-stroma ratio (TSR) with a high-throughput automated method to predict neoadjuvant chemotherapy outcomes.

Trends in Primary Treatment and Median Survival Among Women With Advanced-Stage Epithelial Ovarian Cancer in the US From 2004 to 2016

Three published clinical trials1-3 that randomized women with advanced-stage ovarian cancer to primary cytoreductive surgery before adjuvant chemotherapy or neoadjuvant chemotherapy before interval cytoreductive surgery found no evidence of a progression-free or overall survival advantage for either approach. However, those studies did demonstrate a reduction in surgical morbidity in women assigned to neoadjuvant chemotherapy. Nonetheless, most gynecologic oncologists believe that primary surgical treatment is the preferred approach for advanced ovarian cancer.4 Since the publication of the first of those 3 randomized trials in 2010,1 the use of neoadjuvant chemotherapy for ovarian cancer has increased in the US.5 The objective of this study was to examine and compare time trends in the use of neoadjuvant chemotherapy and the median survival among women with advanced-stage epithelial ovarian cancer in the United States.

Abstract A36: Developing a novel treatment for advanced ovarian cancer by targeting the c-Met pathway

Abstract Approximately one-third of epithelial ovarian tumors exhibit higher levels of c-Met, a receptor tyrosine kinase, activated by Hepatocyte Growth Factor (HGF). c-Met plays an important role in the growth and metastasis of tumor cells. Increased c-Met expression is associated with decreased survival and resistance to chemotherapy in various tumors. More recently, our team identified c-Met overexpression as a mechanism of resistance to neoadjuvant chemotherapy (NACT) in ovarian cancer (OC). The c-Met pathway has been explored as a therapeutic target in various solid tumors, and antibodies targeting c-Met have been proposed as novel anticancer agents. This project aims to investigate the effectiveness of a c-Met monoclonal antibody-drug conjugate (c-Met ADC) in OC models. Here we show that the anti-c-Met antibody alone effectively diminishes c-Met signaling (phosphorylation of c-Met and downstream Akt) but does not inhibit OC cell proliferation. In contrast, the c-Met ADC significantly decreases viability and induces apoptosis in c-Met-expressing OC cells. To validate c-Met expression as a predictor of resistance to NACT in OC, we analyzed c-Met expression in matched pre- and post-treatment samples collected from OC patients undergoing treatment with NACT and in a tissue microarray containing 20 ovarian tumors post-NACT. Detectable c-Met was recorded in ~50% of post-NACT specimens. We evaluated the in vitro antitumor activity of c-Met-ADC on the primary cells isolated from patients, before and after NACT, to assess tumor cell sensitivity to c-Met ADC. The results from these studies support the development of c-Met-ADC as a novel treatment for OC. Citation Format: Anusha Chaparala, Wendy M. Swetzig, Anna E. Strohl, Jian-Jun Wei, Daniela Matei, Shohreh Shahabi. Developing a novel treatment for advanced ovarian cancer by targeting the c-Met pathway [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A36.

Risk of venous thromboembolism in patients receiving neoadjuvant chemotherapy for ovarian cancer.

6073 Background: To identify the incidence of newly occurring venous thromboembolism (VTE) in patients with ovarian cancer receiving neoadjuvant chemotherapy (NACT). Methods: Using our prospectively maintained ovarian cancer database, we identified all ovarian cancer patients who received NACT at our institution from 4/15-9/18. VTE events included clinically diagnosed deep venous thrombosis (DVT) or pulmonary embolism (PE). Patients who presented with VTE prior to induction of NACT or patients on anticoagulation therapy prior to diagnosis were excluded. The incidence of newly occurring thrombotic events were categorized according to treatment phases, defined as 1) NACT prior to interval debulking surgery (IDS); 2) intraoperative and 30-day post-IDS; and 3) adjuvant chemotherapy. Results: 290 patients underwent NACT during the study period. Thirty-eight patients (13%) who presented with VTE, 12 (4%) on anticoagulation at presentation, and 4 (1.4%) seeking only a second opinion were excluded from analysis. Of the 236 evaluable patients, the overall rate of VTE during all treatment phases was 15% (35/236). In treatment phase I, 11% (27/236) of patients experienced VTE during NACT. In phase II, an additional 2.5% (6/236) developed VTE in the intraoperative and 30-day postoperative period. In phase III, an additional 0.8% (2/236) experienced a thrombotic event &gt;30 days postoperatively. Sevety-seven percent (27/35) of VTE events occured during phase I. Conclusions: Patients receiving NACT for advanced ovarian cancer are at high risk for the development of clinically detectable thromboembolic events. The highest rate of new VTE events was seen during induction of NACT, a phase of treatment traditionally without any prophylactic anticoagulation. Further research regarding the timing of thromboprophylaxis for this patient population is warranted. [Table: see text]

The Value of Contrast-Enhanced CT in the Detection of Residual Disease After Neo-Adjuvant Chemotherapy in Ovarian Cancer

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

Comparison of Long-Term Survival Rates of Primary Surgery and Surgery After Neoadjuvant Chemotherapy in Ovarian Cancer

Comparison of Long-Term Survival Rates of Primary Surgery and Surgery After Neoadjuvant Chemotherapy in Ovarian Cancer