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The development of guidelines is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based...
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Context 1
... MBO is a frequent complication of ovarian cancer, the treatment given to patients is not based on high-level evidence. The available evidence on MBO has been summarised and integrated into a practical treatment algorithm (see Figure 5). In the medical management, corticosteroids (6-16 mg dexamethasone intravenously daily) may help to resolve MBO, with few side effects. ...
Context 2
... MBO is a frequent complication of ovarian cancer, the treatment given to patients is not based on high-level evidence. The available evidence on MBO has been summarised and integrated into a practical treatment algorithm (see Figure 5). In the medical management, corticosteroids (6-16 mg dexamethasone intravenously daily) may help to resolve MBO, with few side effects. ...
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The development of guidelines is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based...
The development of guidelines recommendations is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and...
Citations
... [ 18 F]FDG PET imaging plays a crucial role in the diagnostic evaluation of OC and is recommended in guidelines [5,30]; however, to optimize the diagnostic performance of PET in OC, it is necessary to overcome the inherent limitations of the tracer [ 18 F]FDG. ...
Background
[¹⁸F]Fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [¹⁸F]FDG PET has several inherent limitations. The novel oncologic PET-tracer fibroblast activation protein inhibitor (FAPI) has demonstrated promising results in multiple cancer types, including ovarian cancer, and could overcome the limitations of [¹⁸F]FDG PET; however, high-quality clinical studies are lacking. The primary objective of the present study is to compare the diagnostic accuracy of [⁶⁸Ga]Ga-FAPI-46 PET/CT and [¹⁸F]FDG PET/CT in ovarian cancer patients and to investigate how this potential difference impacts staging and patient management.
Methods and design
Fifty consecutive ovarian cancer patients will be recruited from Aalborg University Hospital, Denmark. This study will be a single-center, prospective, exploratory clinical trial that adheres to the standards for reporting diagnostic accuracy studies (STARD). This study will be conducted under continuous Good Clinical Practice monitoring. The eligibility criteria for patients are as follows: (1) biopsy verified newly diagnosed ovarian cancer or a high risk of ovarian cancer and referred for primary staging with [¹⁸F]FDG PET/CT; and (2) resectable disease, i.e., candidate for primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery. All recruited study subjects will undergo [⁶⁸Ga]Ga-FAPI-46 PET/CT at primary staging, before primary debulking surgery or neoadjuvant chemotherapy (Group A + B), in addition to conventional imaging (including [¹⁸F]FDG PET/CT). Study subjects in Group B will undergo an additional [⁶⁸Ga]Ga-FAPI-46 PET/CT following neoadjuvant chemotherapy prior to interval debulking surgery. The results of the study-related [⁶⁸Ga]Ga-FAPI-46 PET/CTs will be blinded, and treatment allocation will be based on common clinical practice in accordance with current guidelines. The histopathology of surgical specimens will serve as a reference standard. A recruitment period of 2 years is estimated; the trial is currently recruiting.
Discussion
To our knowledge, this trial represents the largest, most extensive, and most meticulous prospective FAPI PET study conducted in patients with ovarian cancer thus far. This study aims to obtain a reliable estimation of the diagnostic accuracy of [⁶⁸Ga]Ga-FAPI-46 PET/CT, shed light on the clinical importance of [⁶⁸Ga]Ga-FAPI-46 PET/CT, and examine the potential applicability of [⁶⁸Ga]Ga-FAPI-46 PET/CT for evaluating chemotherapy response.
Trial registration
clinicaltrials.gov: NCT05903807, 2nd June 2023; and euclinicaltrials.eu EU CT Number: 2023-505938-98-00, authorized 11th September 2023.
... However, there is no universally accepted scoring system endorsed by the ESMO-ESGO consensus conference (Level III, Grade C) 16 . Presently, the Fagotti score stands out as one of the most frequently utilized scoring systems in current practice, backed by several European professional societies (CNGOF, ESMO-ESGO) 9,17 Despite its widespread use, only the reproducibility of Fagotti's score through proofreading by the promoting team that developed it has been validated so far 18 . It should be noted that this score is sometimes incomplete, with areas that cannot be explored by surgeons. ...
Epithelial ovarian cancer is mostly discovered at the stage of peritoneal carcinosis. Complete cytoreductive surgery improves overall survival. The Fagotti score is a predictive score of resectability based on peritoneal laparoscopic exploratory. Our aim was to study the inter-observer concordance in an external validation of the Fagotti score. An observational, prospective, multicenter study was conducted using the Francogyn research network. The primary outcome was inter-observer concordance of the Fagotti score. 15 patients in which an ovarian mass was discovered were included. For each patient, the first exploratory laparoscopy before any treatment/chemotherapy was recorded. This bank of 15 videos was subject to blind review accompanied by a Fagotti score rating by 11 gynecological surgeons specializing in oncology. A total of 165 blind reviews were performed. Inter-observer concordance was very good for the Fagotti score with an intraclass correlation coefficient (ICC) of 0.83 [95% CI 0.71; 0.93]. Inter-observer concordance for the adjusted Fagotti score, which accounts for unexplorable areas with extensive carcinomatosis, resulted in an ICC of 0.64 [95% CI 0.46; 0.82]. According to the reviewers, the three least explorable parameters were mesentery involvement, stomach infiltration and liver damage. The ICC of the explorable Fagotti score, i.e. score with deletion of the parameters most often unexplored by laparoscopy, was 0.86 [0.75–0.94]. This study confirms the reproducibility of the Fagotti score during first assessment laparoscopies in cases of advanced ovarian cancer. The explorable Fagotti score has an equivalent or better inter-observer concordance than the Fagotti score.
... If a complete resection of the tumor is not possible, neoadjuvant chemotherapy followed by interval debulking surgery (IDS) or palliative treatment is recommended. For advanced-stage OC, a debulking procedure in combination with chemotherapy is the standard treatment [4]. ...
Ovarian cancer is one of the most common cancers among women and the most lethal malignancy of all gynecological cancers. Surgery is promising in the early stages; however, most patients are first diagnosed in the advanced stages, where treatment options are limited. Here, we present a 49-year-old patient who was first diagnosed with stage III ovarian cancer. After the tumor progressed several times under guideline therapies with no more treatment options available at that time, the patient received a fully individualized neoantigen-derived peptide vaccine in the setting of an individual healing attempt. The tumor was analyzed for somatic mutations via whole exome sequencing and potential neoepitopes were vaccinated over a period of 50 months. During vaccination, the patient additionally received anti-PD-1 therapy to prevent further disease progression. Vaccine-induced T-cell responses were detected using intracellular cytokine staining. After eleven days of in vitro expansion, four T-cell activation markers (namely IFN-ɣ, TNF-α, IL-2, and CD154) were measured. The proliferation capacity of neoantigen-specific T-cells was determined using a CFSE proliferation assay. Immune monitoring revealed a very strong CD4+ T-cell response against one of the vaccinated peptides. The vaccine-induced T-cells simultaneously expressed CD154, TNF, IL-2, and IFN-ɣ and showed a strong proliferation capacity upon neoantigen stimulation. Next-generation sequencing, as well as immunohistochemical analysis, revealed a loss of Beta-2 microglobulin (B2M), which is essential for MHC class I presentation. The results presented here implicate that the application of neoantigen-derived peptide vaccines might be considered for those cancer stages, where promising therapeutic options are lacking. Furthermore, we provide more data that endorse the intensive investigation of B2M loss as a tumor escape mechanism in clinical trials using anti-cancer vaccines together with immune-checkpoint inhibitors.
... Even with the application of the Response Evaluation Criteria in Solid Tumors (RECIST) [5], limitations persist. Consequently, there is a pressing need for precise outcome predictors to inform treatment decisions in the first-line setting, a concern recognized by both ESGO and ESMO [6]. ...
(1) Background: BRCA mutation and homologous recombination deficiency (HRD) are used to administrate PARP inhibitors (PARPi) maintenance therapy. It is known that PARPi efficacy is related to platinum sensitivity and that the latter can be demonstrated from the CA-125 elimination rate constant (KELIM). This study aims to investigate if KELIM can be another tool in the identification of patients that could be benefit from PARPi therapy.; (2) Methods: Retrospective analysis of patients with high-grade serous advanced ovarian cancer that underwent cytoreduction and was further tested for HRD status. The HRD status was tested either by myChoice HRD CDx assay or by RediScore assay. KELIM score was measured in both neoadjuvant and adjuvant settings with the online tool biomarker-kinetics.org.; (3) Results: Thirty-nine patients had available data for estimating both HRD status and KELIM score. When assuming KELIM as a binary index test with the value 1 as the cut-off point, the sensitivity was 0.86, 95% CI (0.64-0.97), and the specificity 0.83, 95% CI (0.59-0.96). On the other hand, when assuming KELIM as a continuous index test, the AUC was 81% and the optimal threshold, using the Youden index, was identified as 1.03 with a sensitivity of 85.7% and a specificity of 83.3%; (4) Conclusions: KELIM score seems to be a new, cheaper and faster tool to identify patients that can benefit from PARPi maintenance therapy.
... Furthermore, laparoscopy after neoadjuvant chemotherapy has been proposed as a triage tool, but its value remains controversial in the prediction of complete cytoreduction [13]. On the other hand, 15-20% of patients with advanced ovarian cancer will be poor responders to chemotherapy [14], so there is the need for accurate non-invasive chemosensitivity predictors to guide treatment decisions in the first-line setting, which is acknowledged by ESGO and ESMO [15]. ...
Simple Summary
Residual disease after cytoreduction in advanced ovarian cancer still remains the most important prognostic factor. Patients with high tumor load, especially in the upper abdomen, that cannot be completely debulked in the primary setting are offered neoadjuvant chemotherapy and reassessed after 3–4 cycles for interval debulking surgery. Imaging is the main tool for the decision if these patients can achieve complete cytoreduction. However, even with the use of the Response Evaluation Criteria in Solid Tumors (RECIST), conventional imaging has poor results in identifying which patients have unresectable disease. Therefore, the KELIM score appears as a new promising prognostic factor in the neoadjuvant setting. The aim of this study is to establish KELIM as prognostic factor for residual disease after interval debulking surgery and to urge the research community to plan future randomized control trials in order to add the KELIM score in future guidelines.
Abstract
(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.
... As a systemic disease, its treatment relies mainly on chemotherapy [4]. Nevertheless, a significant proportion of patients will not respond optimally to chemotherapy, thus, resulting in substantial reduction of progression-free and overall survival. ...
... Given the systemic nature of the disease at presentation, chemotherapy is considered the cornerstone of therapeutic modalities that are used in these patients; however, chemotherapy-resistance is not an unusual phenomenon and may exceed 50 % of the population depending on the preferred chemotherapy combinations [16]. The modern approach of systemic therapy of ovarian cancer offers a combination of a platinum compound with taxane and the addition of anti-angiogenic agents and poly-ADP ribose polymerase (PARP) inhibitors [4]. This offers the best response rate, which results in diminished rates of chemotherapy-resistance that may involve less than 20 % of patients [5]. ...
Objective: The chemotherapy response score (CRS) has been widely adopted as a predictive tool for ovarian cancer survival. In the present study, we seek to define differences in survival rates among patients grouped in the traditionally established three-tiered system and those who have not been offered debulking surgery.
Study design: We designed a retrospective cohort study involving women treated with chemotherapy and offered interval or late debulking surgery for ovarian cancer. Twenty-eight women were not considered for a debulking procedure for various reasons. Of the 89 women who were finally offered interval debulking or late debulking surgery, 28 had a CRS 1 score, 34 had a CRS 2 score and 27 had a CRS 3 score.
Results: Significant differences were noted in the progression-free survival (PFS) and overall survival (OS) of patients based on the CRS stratification, although survival rates were considerably longer for all three groups compared to those of patients who were not offered surgery. Cox regression univariate analysis revealed that suboptimal debulking and CRS 1 or no surgery had a significant negative impact on PFS and OS rates. The binary stratification of CRS (CRS 1-2 vs CRS 3) revealed comparable differences in the PFS and OS to those in the groups that were stratified as platinum resistant and platinum sensitive.
Conclusion: The chemotherapy response score is a significant determinant of ovarian cancer survival that helps evaluate the risk of early disease relapse and death and may soon be useful in guiding patient-tailored treatment.
... 8 The introduction of the high-resolution endovaginal probe allows detailed depiction of the pelvic anatomy, comparable to that achieved by pelvic MRI. [9][10][11][12][13][14] Transabdominal ultrasound using a convex array probe provides detailed views of the abdominal organs, visceral and retroperitoneal lymph nodes, and peritoneum, guiding the prediction of disease resectability. [15][16][17] Lastly, the use of a linear probe allows direct, high-resolution visualization of superficial structures, such as the peripheral lymph nodes (Figure 1). ...
... 18 19 This has led to the implementation of ultrasound next to pelvic MRI as the firstline modality in the assessment of locoregional stage in gynecologic cancers, according to the European Society of Gynecological Oncology (ESGO) guidelines. [9][10][11][12][13][14] Ultrasound has the advantages of having low cost with high availability, involving no radiation exposure and minimal discomfort to the patient. 20 21 Furthermore, ultrasound is an ideal tool for guiding core-needle biopsies to establish the histologic diagnosis, prior to expedited start of tailored therapy. ...
In recent years the role of diagnostic imaging by pelvic ultrasound in the diagnosis and staging of gynecological cancers has been growing exponentially. Evidence from recent prospective multicenter studies has demonstrated high accuracy for pre-operative locoregional ultrasound staging in gynecological cancers. Therefore, in many leading gynecologic oncology units, ultrasound is implemented next to pelvic MRI as the first-line imaging modality for gynecological cancer. The work herein is a consensus statement on the role of pre-operative imaging by ultrasound and other imaging modalities in gynecological cancer, following European Society guidelines.
... The EOC is the deadliest gynecological malignancy and an extremely heterogeneous disease [1][2][3]. The gold standard of newly diagnosed EOC includes optimal cytoreduction, namely primary or interval debulking surgery, along with platinum chemotherapy backbone, with carboplatinpaclitaxel regimen being the therapeutic mainstay frontline [2,3]. ...
... The EOC is the deadliest gynecological malignancy and an extremely heterogeneous disease [1][2][3]. The gold standard of newly diagnosed EOC includes optimal cytoreduction, namely primary or interval debulking surgery, along with platinum chemotherapy backbone, with carboplatinpaclitaxel regimen being the therapeutic mainstay frontline [2,3]. In the last decade, the advent of strategies in the maintenance setting targeting tumor angiogenesis and DNA repair, such as bevacizumab and PARP inhibitors (PARPi), has ushered in a new era of anticancer therapy for EOC [4]. ...
... The currently preferred regimens for chemoresistant disease include sequential use of non-platinum drugs (as reported in Supplementary Table S1). In this regard, residual toxicity from prior therapies, drug accessibility, and patient-clinician agreement may inform the treatment choice [2,3,6]. ...
Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Despite the latest advances, a major clinical issue in EOC is the disappointing prognosis related to chemoresistance in almost one-third of cases. Drug resistance relies on heterogeneous cancer stem cells (CSCs), endowed with tumor-initiating potential, leading to relapse. No biomarkers of chemoresistance have been validated yet. Recently, major signaling pathways, micro ribonucleic acids (miRNAs), and circulating tumor cells (CTCs) have been advocated as putative biomarkers and potential therapeutic targets for drug resistance. However, further investigation is mandatory before their routine implementation. In accordance with the increasing rate of therapeutic efforts in EOC, the need for biomarker-driven personalized therapies is growing. This review aims to discuss the emerging hallmarks of drug resistance with an in-depth insight into the underlying molecular mechanisms lacking so far. Finally, a glimpse of novel therapeutic avenues and future challenges will be provided.
... It may be considered in low-grade ovarian carcinomas (low-grade serous carcinomas, mucinous expansile subtype, endometrioid G1) FIGO stage IA or IC, as well as in patients with borderline ovarian tumors. 6 Our patient would therefore not be a candidate for fertility-sparing treatment, as she presents a grade 2 FIGO IC1 endometrioid ovarian adenocarcinoma. She was scheduled for robotic-assisted laparoscopic surgery, consisting of total hysterectomy, right salpingooophorectomy, bilateral sentinel lymph node mapping, peritoneal biopsies, peritoneal washing, and ometectomy. ...
... Int J Gynecol Cancer: first published as 10.1136/ijgc-2023-005201 on 5 February 2024. Downloaded fromTumor board exploration of the abdomino-pelvic peritoneum during the first surgery, given its questionable benefit in other situations and the increased morbidity it may entail.6 ...
... Peritoneal staging consisting of peritoneal biopsies, peritoneal washing, and infracolic omentectomy is indicated in restaging although the result does not change the indication for adjuvant treatment. Regarding lymph node staging (bilateral pelvic and para-aortic lymphadenectomy to the level of the renal vein), this can be omitted when we are performing restaging surgery and provided that its result will not alter subsequent patient management, due to the increased morbidity that it may entail.6 For a borderline tumor, staging would be completed by performing ometectomy, peritoneal washing, and multiple peritoneal biopsies (which may increase the stage in up to 30% of cases). ...
... The evidence-based, guideline-recommended standard treatment for advanced stage EOC consists of optimal cytoreductive surgery followed by 3-weekly carboplatin plus paclitaxel [7]. Efforts have been made to improve the standard two-drug regimen by adding a third cytotoxic agent; however, the results only demonstrated increased toxicity and failed to improve progression-free survival or overall survival [8,9]. ...
... Efforts have been made to improve the standard two-drug regimen by adding a third cytotoxic agent; however, the results only demonstrated increased toxicity and failed to improve progression-free survival or overall survival [8,9]. Carboplatin-based doublet is also the first choice in the second-line treatment of platinum-sensitive patients, while agents like liposomal doxorubicin, topotecan, weekly paclitaxel, or gemcitabine given as a single agent are used in platinum-resistant patients [7]. ...
Background: This phase II study evaluated the efficacy and safety of the histone deacetylase (HDAC) inhibitor, vorinostat, administered in combination with paclitaxel and carboplatin in patients with platinum sensitive recurrent ovarian cancer. Methods: Women with recurrent platinum-sensitive ovarian, peritoneal, or Fallopian tube carcinoma, a performance status of 0–2, and good overall organ function were eligible. Patients received 6 courses of paclitaxel (175 mg/m2) and carboplatin area under the curve (AUC) of 5.0 mg/mL/min administered via intravenous infusion on day 1 of a 3-week schedule. In addition, patients received vorinostat 400 mg orally once daily on days −4 through 10 of Cycle 1 and days 1 through 14 of each subsequent treatment cycle. The primary endpoints were progression-free survival (PFS) and adverse events. The secondary endpoints were the objective response rate and overall survival. Results: Fifty-five patients were included. CR was obtained in 14 patients (26.4%) and PR in 19 patients (35.8%), resulting in an ORR of 62.2%. Twenty patients (37.7%) had SD. The median duration of response (DoR) was 12.6 (range 6–128) months. The median PFS was 11.6 months (95% CI, 10.3–18.0; p < 0.001). Median OS was 40.6 months (95% Cl, 25.1–56.1). The most common treatment-related adverse events (all grades) were fatigue, anemia, thrombocytopenia, neutropenia, anorexia, nausea, pain, sensory neuropathy, myalgia, stomatitis and diarrhea. Conclusions: Vorinostat combined with carboplatin plus paclitaxel was tolerable and generated significant responses including a long median overall survival in recurrent platinum-sensitive ovarian cancer.
