Imperial College London

Prof. Christina Fotopoulou

Faculty of MedicineDepartment of Surgery & Cancer

Chair in Gynaecological Cancer Surgery
 
 
 
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Contact

 

c.fotopoulou

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

387 results found

Nout R, Calaminus G, Planchamp F, Chargari C, Lax SF, Martelli H, McCluggage WG, Morice P, Pakiz M, Schmid MP, Stunt J, Timmermann B, Vokuhl C, Orbach D, Fotopoulou Cet al., 2023, ESTRO/ESGO/SIOPe guidelines for the management of patients with vaginal cancer., Radiother Oncol, Vol: 186

Primary vaginal malignancies are rare, comprising only 2% of all female genital tract malignancies in adults and 4.5% in children. As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) jointly with the European Society for Radiotherapy & Oncology (ESTRO) and the European Society of Pediatric Oncology (SIOPe) developed evidence-based guidelines in order to improve the management of patients with vaginal cancer within a multidisciplinary setting. ESTRO/ESGO/SIOPe nominated practicing clinicians who are involved in the management of vaginal cancer patients and have demonstrated leadership through their expertise in clinical care and research, their national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (13 experts across Europe comprising the international development group). To ensure that the statements were evidence based, the current literature was reviewed and critically appraised. In the case of absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 112 independent international practitionners in cancer care delivery and patient representatives and their comments and input were incorporated and addressed accordingly. These guidelines cover comprehensively the diagnostic pathways as well as the surgical, radiotherapeutical and systemic management and follow-up of adult patients (including those with rare histological subtypes) and pediatric patients (vaginal rhabdomyosarcoma and germ cell tumours) with vaginal tumours.

Journal article

Berek JS, Matias-Guiu X, Creutzberg C, Fotopoulou C, Gaffney D, Kehoe S, Lindemann K, Mutch D, Concin N, Endometrial Cancer Staging Subcommittee, FIGO Women's Cancer Committeeet al., 2023, FIGO staging of endometrial cancer: 2023., J Gynecol Oncol, Vol: 34

INTRODUCTION: Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies. METHODS: The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system. RESULTS: Based on the existing evidence, the substages were defined as follows: Stage I (IA1): non-aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non-aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low-grade endometrioid carcinomas limited to the uterus with simultaneous low-grade endometrioid ovarian involvement; (IB) non-aggressive histological types involv

Journal article

Tsibulak I, Fotopoulou C, 2023, Tumor biology and impact on timing of surgery in advanced epithelial ovarian cancer., Int J Gynecol Cancer

Recent advances in epithelial ovarian cancer research have led to a shift in treatment strategy from the traditional 'organ-centric' to a personalized tumor biology-based approach. Nevertheless, we are still far behind an individualized approach for cytoreductive surgery in advanced ovarian cancer; the gold standard of primary treatment in combination with systemic agents. The impact of tumor biology on treatment sequence is still understudied. It is obvious, that response to platinum-based therapy is crucial for the success of neoadjuvant chemotherapy. While high-grade serous and endometrioid tumors are commonly characterized by an excellent response, other subtypes are considered poor responders or even resistant to platinum. Undoubtedly, neoadjuvant chemotherapy may filter poor responders, but to date, we still do not have appropriate alternatives to platinum-based chemotherapy in the neoadjuvant and first-line setting and 'adjusting' systemic treatment in cases of poor response to neoadjuvant chemotherapy remains elusive. Primary cytoreduction is still considered the gold standard for fit patients with operable tumor dissemination patterns, especially for those ovarian cancer subtypes that show poor response to platinum. Of note, even in high-grade serous ovarian cancer, approximately 20% of tumors are platinum resistant and the benefit of neoadjuvant chemotherapy in this subgroup is limited. Interestingly, these tumors are associated with the mesenchymal molecular subtype, which in turn correlates with high risk for residual disease after cytoreductive surgery and is characterized by the worst survival outcome among high-grade ovarian cancers. This leads to the question, how to best tailor surgical radicality at the onset of patients' presentation to avoid associated morbidity and with a moderate benefit. Here, we give an overview of recent advances of interaction between tumor biology and surgery in ovarian cancer.

Journal article

Nout RA, Calaminus G, Planchamp F, Chargari C, Lax S, Martelli H, McCluggage WG, Morice P, Pakiz M, Schmid MP, Stunt J, Timmermann B, Vokuhl C, Orbach D, Fotopoulou Cet al., 2023, ESTRO/ESGO/SIOPe Guidelines for the management of patients with vaginal cancer., Int J Gynecol Cancer, Vol: 33, Pages: 1185-1202

Primary vaginal malignancies are rare, comprising only 2% of all female genital tract malignancies in adults and 4.5% in children. As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) jointly with the European Society for Radiotherapy & Oncology (ESTRO) and the European Society of Pediatric Oncology (SIOPe) developed evidence-based guidelines in order to improve the management of patients with vaginal cancer within a multidisciplinary setting.ESTRO/ESGO/SIOPe nominated practicing clinicians who are involved in the management of vaginal cancer patients and have demonstrated leadership through their expertise in clinical care and research, their national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (13 experts across Europe comprising the international development group). To ensure that the statements were evidence based, the current literature was reviewed and critically appraised.In the case of absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 112 independent international practitionners in cancer care delivery and patient representatives and their comments and input were incorporated and addressed accordingly.These guidelines cover comprehensively the diagnostic pathways as well as the surgical, radiotherapeutical and systemic management and follow-up of adult patients (including those with rare histological subtypes) and pediatric patients (vaginal rhabdomyosarcoma and germ cell tumours) with vaginal tumours.

Journal article

Berek JS, Matias-Guiu X, Creutzberg C, Fotopoulou C, Gaffney D, Kehoe S, Lindemann K, Mutch D, Concin N, Endometrial Cancer Staging Subcommittee, FIGO Women's Cancer Committeeet al., 2023, FIGO staging of endometrial cancer: 2023., Int J Gynaecol Obstet, Vol: 162, Pages: 383-394

INTRODUCTION: Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies. METHODS: The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system. RESULTS: Based on the existing evidence, the substages were defined as follows: Stage I (IA1): non-aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non-aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low-grade endometrioid carcinomas limited to the uterus with simultaneous low-grade endometrioid ovarian involvement; (IB) non-aggressive histological types involv

Journal article

Khassan T, Smitten E, Wood N, Fotopoulou C, Morrison J, MacDonald M, Baxter K, Edmondson RJet al., 2023, MDT practice determines treatment pathway for patients with advanced ovarian cancer: A multi-centre observational study., Eur J Surg Oncol, Vol: 49, Pages: 1504-1510

OBJECTIVE: To investigate decision making for patients with advanced ovarian cancer as a possible explanation of geographical variation in treatment patterns. METHODS: We carried out a multi-centre observational study in multidisciplinary teams meetings for five major UK cancer centres. All patients presenting to five cancer centres with advanced ovarian cancer over a six-week period. The GO-MDT-MODe tool was used to provide a measure of participation and quality of case discussion for all cases of advanced ovarian cancer. MDT scores were correlated with surgical data extracted from national audit data. Data were recorded for overall MDT performance. RESULTS: A total of 870 case discussions, including 145 cases of advanced ovarian cancer, were observed. MDTs varied in structure, format and time allocation between centres. Cluster analysis showed significant variation in quality and participation of discussion between centres (p < 0.0025) and this correlated with the proportion of patients in the wider cancer alliance undergoing surgery. CONCLUSIONS: We have shown that at least part of the variation in practice seen in the UK correlates with different behaviours within MDTs. Increasing time for discussion and encouraging participation from all staff groups may increase proportions of patients undergoing optimal treatment regimens.

Journal article

Smith P, Bradley T, Gavarró LM, Goranova T, Ennis DP, Mirza HB, De Silva D, Piskorz AM, Sauer C, Al-Khalidi S, Funingana I-G, Reinius MAV, Giannone G, Lewsley L-A, Stobo J, McQueen J, Bryson G, Eldridge M, BriTROC Investigators, Macintyre G, Markowetz F, Brenton JD, McNeish IAet al., 2023, The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma, Nature Communications, Vol: 14, Pages: 1-15, ISSN: 2041-1723

The drivers of recurrence and resistance in ovarian high grade serous carcinoma remain unclear. We investigate the acquisition of resistance by collecting tumour biopsies from a cohort of 276 women with relapsed ovarian high grade serous carcinoma in the BriTROC-1 study. Panel sequencing shows close concordance between diagnosis and relapse, with only four discordant cases. There is also very strong concordance in copy number between diagnosis and relapse, with no significant difference in purity, ploidy or focal somatic copy number alterations, even when stratified by platinum sensitivity or prior chemotherapy lines. Copy number signatures are strongly correlated with immune cell infiltration, whilst diagnosis samples from patients with primary platinum resistance have increased rates of CCNE1 and KRAS amplification and copy number signature 1 exposure. Our data show that the ovarian high grade serous carcinoma genome is remarkably stable between diagnosis and relapse and acquired chemotherapy resistance does not select for common copy number drivers.

Journal article

Cunnea P, Curry EW, Christie EL, Nixon K, Kwok CH, Pandey A, Wulandari R, Thol K, Ploski J, Morera-Albert C, McQuaid S, Lozano-Kuehne J, Clark JJ, Krell J, Stronach EA, McNeish IA, Bowtell DDL, Fotopoulou Cet al., 2023, Spatial and temporal intra-tumoral heterogeneity in advanced HGSOC: implications for surgical and clinical outcomes, Cell Reports Medicine, Vol: 4, Pages: 1-20, ISSN: 2666-3791

Limited evidence exists on the impact of spatial and temporal heterogeneity of high-grade serous ovarian cancer (HGSOC) on tumor evolution, clinical outcomes, and surgical operability. We perform systematic multi-site tumor mapping at presentation and matched relapse from 49 high-tumor-burden patients, operated up front. From SNP array-derived copy-number data, we categorize dendrograms representing tumor clonal evolution as sympodial or dichotomous, noting most chemo-resistant patients favor simpler sympodial evolution. Three distinct tumor evolutionary patterns from primary to relapse are identified, demonstrating recurrent disease may emerge from pre-existing or newly detected clones. Crucially, we identify spatial heterogeneity for clinically actionable homologous recombination deficiency scores and for poor prognosis biomarkers CCNE1 and MYC. Copy-number signature, phenotypic, proteomic, and proliferative-index heterogeneity further highlight HGSOC complexity. This study explores HGSOC evolution and dissemination across space and time, its impact on optimal surgical cytoreductive effort and clinical outcomes, and its consequences for clinical decision-making.

Journal article

Chargari C, Tanderup K, Planchamp F, Chiva L, Humphrey P, Sturdza A, Tan LT, van der Steen-Banasik E, Zapardiel I, Nout RA, Fotopoulou Cet al., 2023, ESGO/ESTRO quality indicators for radiation therapy of cervical cancer., Int J Gynecol Cancer, Vol: 33, Pages: 862-875

BACKGROUND: The European Society of Gynaecological Oncology (ESGO) has previously defined and established a list of quality indicators for the surgical treatment of cervical cancer. As a continuation of this effort to improve overall quality of care for cervical cancer patients across all aspects, ESGO and the European SocieTy for Radiotherapy and Oncology (ESTRO) initiated the development of quality indicators for radiation therapy of cervical cancer. OBJECTIVE: To develop a list of quality indicators for radiation therapy of cervical cancer that can be used to audit and improve clinical practice by giving to practitioners and administrators a quantitative basis to improve care and organizational processes, notably for recognition of the increased complexity of modern external radiotherapy and brachytherapy techniques. METHODS: Quality indicators were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for identification of potential quality indicators and documentation of scientific evidence, consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians (n=99). RESULTS: Using a structured format, each quality indicator has a description specifying what the indicator is measuring. Measurability specifications are detailed to define how the quality indicators will be measured in practice. Targets were also defined for specifying the level which each unit or center should be aiming to achieve. Nineteen structural, process, and outcome indicators were defined. Quality indicators 1-6 are general requirements related to pretreatment workup, time to treatment, upfront radiation therapy, and overall management, including active participation in clinical research and the decision making process within a structured multidisciplinary team. Quality indicators 7-17 are related to treatment indicators. Quality indicators 18

Journal article

Nelson G, Fotopoulou C, Taylor J, Glaser G, Bakkum-Gamez J, Meyer LA, Stone R, Mena G, Elias KM, Altman AD, Bisch SP, Ramirez PT, Dowdy SCet al., 2023, Enhanced recovery after surgery (ERAS®) society guidelines for gynecologic oncology: Addressing implementation challenges - 2023 update., Gynecol Oncol, Vol: 173, Pages: 58-67

BACKGROUND: Despite evidence supporting its use, many Enhanced Recovery After Surgery (ERAS) recommendations remain poorly adhered to and barriers to ERAS implementation persist. In this second updated ERAS® Society guideline, a consensus for optimal perioperative care in gynecologic oncology surgery is presented, with a specific emphasis on implementation challenges. METHODS: Based on the gaps identified by clinician stakeholder groups, nine implementation challenge topics were prioritized for review. A database search of publications using Embase and PubMed was performed (2018-2023). Studies on each topic were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded by an international panel according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS implementation challenge topics are based on best available evidence. The level of evidence for each item is presented accordingly. CONCLUSIONS: The updated evidence base and recommendations for stakeholder derived ERAS implementation challenges in gynecologic oncology are presented by the ERAS® Society in this consensus review.

Journal article

Reid I, Sharma A, Gogbashian A, Kaur B, Fotopoulou Cet al., 2023, Germ cell cancer in pregnancy - Successfully treated with chemotherapy and surgery., Gynecol Oncol Rep, Vol: 47, ISSN: 2352-5789

A 31-year-old primigravida, with spontaneous singleton pregnancy, presented in 21 weeks of gestation with abdominal pain. Abdominal ultrasound (USS) and Magnetic Resonance Imaging (MRI) showed a 12 × 14cm large complex lesion arising from the right ovary suspicious for an ovarian malignancy. The radiological staging demonstrated no further metastatic disease; however, it also revealed a 6 cm lesion in the contralateral ovary, consistent with a dermoid cyst. After tumour board discussion the patient underwent a mid-line laparotomy with right oophorectomy, cytology, and peritoneal and omental staging, under oral tocolysis with indomethacin. The left presumed ovarian dermoid was left in situ to avoid additional surgical and obstetrical morbidity. Histology confirmed a grade 3 immature teratoma with primitive neuroepithelium focally present on the capsular surface and atypical cells in the cytology amounting to a stage 1 C2 disease at least. Due to high-risk disease, she was offered adjuvant treatment. The patient received one cycle of intravenous paclitaxel, etoposide, and cisplatin chemotherapy, in an adjuvant setting. She underwent an elective caesarean section at 36 weeks, with the safe delivery of a healthy baby girl. After 6 weeks of her delivery, she received three further cycles of etoposide, and cisplatin to complete her course of adjuvant chemotherapy. Three months after the last chemotherapy cycle, she underwent a laparoscopic removal of the left ovarian dermoid that had increased in size to 8 cm. Final histology revealed no immature elements. To this point, 2 years after initial diagnosis, both mother and child are healthy with no long-term complications. The patient has resumed her normal menstrual cycle and being in remission, she wishes soon to try for a second child. To our knowledge, this is the only reported case of ovarian immature teratoma in pregnancy treated successfully with surgery and adjuvant iv pac

Journal article

Chargari C, Tanderup K, Planchamp F, Chiva L, Humphrey P, Sturdza A, Tan LT, van der Steen-Banasik E, Zapardiel I, Nout RA, Fotopoulou Cet al., 2023, ESGO/ESTRO quality indicators for radiation therapy of cervical cancer., Radiother Oncol, Vol: 183

BACKGROUND: The European Society of Gynaecological Oncology (ESGO) has previously defined and established a list of quality indicators for the surgical treatment of cervical cancer. As a continuation of this effort to improve overall quality of care for cervical cancer patients across all aspects, ESGO and the European SocieTy for Radiotherapy and Oncology (ESTRO) initiated the development of quality indicators for radiation therapy of cervical cancer. OBJECTIVE: To develop a list of quality indicators for radiation therapy of cervical cancer that can be used to audit and improve clinical practice by giving to practitioners and administrators a quantitative basis to improve care and organizational processes, notably for recognition of the increased complexity of modern external radiotherapy and brachytherapy techniques. METHODS: Quality indicators were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for identification of potential quality indicators and documentation of scientific evidence, consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians (n = 99). RESULTS: Using a structured format, each quality indicator has a description specifying what the indicator is measuring. Measurability specifications are detailed to define how the quality indicators will be measured in practice. Targets were also defined for specifying the level which each unit or center should be aiming to achieve. Nineteen structural, process, and outcome indicators were defined. Quality indicators 1-6 are general requirements related to pretreatment workup, time to treatment, upfront radiation therapy, and overall management, including active participation in clinical research and the decision making process within a structured multidisciplinary team. Quality indicators 7-17 are related to treatment indicators. Quality indicators

Journal article

Fotopoulou C, Khan T, Bracinik J, Glasbey J, Abu-Rustum N, Chiva L, Fagotti A, Fujiwara K, Ghebre R, Gutelkin M, Konney TO, Ng J, Pareja R, Seenivasagam RK, Sehouli J, Surappa STS, Bhangu A, Leung E, Sundar Set al., 2023, Outcomes of Gynecologic Cancer Surgery During the COVID-19 Pandemic: An International, Multicenter, Prospective CovidSurg-Gynecologic Oncology Cancer Study, Obstetrical and Gynecological Survey, Vol: 78, Pages: 277-278, ISSN: 0029-7828

Journal article

Burns EM, Quyn A, Lexicon Collaboration of UKPEN and the ACPGBI Advanced Cancer subcommittee, 2023, The 'Pelvic exenteration lexicon': Creating a common language for complex pelvic cancer surgery., Colorectal Dis, Vol: 25, Pages: 888-896

AIM: Pelvic exenteration surgery is an umbrella term for a multitude of operative techniques for locally advanced and recurrent pelvic malignancy. Currently, there is heterogeneity in the operative description that limits the interpretation of patient outcome and collaboration between units through standardized data collection. Our study aims to develop a consensus lexicon to describe the operative components of extended and exenteration pelvic surgery. METHOD: This study adopted a mixed-methods approach using semi-structured interviews, questionnaires, focus groups and validation exercises involving pelvic exenteration experts from centres in the UK. Qualitative data were collected, and descriptive statistics are presented. RESULTS: We identified eight headings with 32 subheadings that encompass all components of the extent of the potential surgery. The lexicon was validated by 15 UK specialists. A 'high-complexity pelvic exenteration' was defined as encompassing 'conventional pelvic exenteration' with the extension of surgery to remove bony structures or the structures in the pelvic sidewall. Pelvic sidewall structures include major vessels, sciatic nerves and/or bone. Bony structures include the sacrum and/or pubic bones. CONCLUSION: This pelvic exenteration lexicon will permit classification of the surgical approach used that will improve data synthesis, allow more accurate activity recording for audit and ultimately improved outcomes for patients.

Journal article

Hu Z, Cunnea P, Zhong Z, Lu H, Osagie OI, Campo L, Artibani M, Nixon K, Ploski J, Santana Gonzalez L, Alsaadi A, Wietek N, Damato S, Dhar S, Blagden SP, Yau C, Hester J, Albukhari A, Aboagye EO, Fotopoulou C, Ahmed Aet al., 2023, Data from The Oxford Classic Links Epithelial-to-Mesenchymal Transition to Immunosuppression in Poor Prognosis Ovarian Cancers

<jats:p>&lt;div&gt;AbstractPurpose:&lt;p&gt;Using RNA sequencing, we recently developed the 52-gene–based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier.&lt;/p&gt;Experimental Design:&lt;p&gt;We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (&lt;i&gt;n&lt;/i&gt; = 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs.&lt;/p&gt;Results:&lt;p&gt;We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition–high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; &lt;i&gt;P&lt;/i&gt; = 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; &lt;i&gt;P&lt;/i&gt; &lt; 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors.&lt;/p&gt;Conclusions:&lt;p&gt;The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.&lt;/p&gt;&lt;/div&

Other

Hu Z, Cunnea P, Zhong Z, Lu H, Osagie OI, Campo L, Artibani M, Nixon K, Ploski J, Santana Gonzalez L, Alsaadi A, Wietek N, Damato S, Dhar S, Blagden SP, Yau C, Hester J, Albukhari A, Aboagye EO, Fotopoulou C, Ahmed Aet al., 2023, Supplementary Information from The Oxford Classic Links Epithelial-to-Mesenchymal Transition to Immunosuppression in Poor Prognosis Ovarian Cancers

<jats:p>&lt;p&gt;Supplementary Figures and Tables&lt;/p&gt;</jats:p>

Other

Hu Z, Cunnea P, Zhong Z, Lu H, Osagie OI, Campo L, Artibani M, Nixon K, Ploski J, Santana Gonzalez L, Alsaadi A, Wietek N, Damato S, Dhar S, Blagden SP, Yau C, Hester J, Albukhari A, Aboagye EO, Fotopoulou C, Ahmed Aet al., 2023, Supplementary Information from The Oxford Classic Links Epithelial-to-Mesenchymal Transition to Immunosuppression in Poor Prognosis Ovarian Cancers

<jats:p>&lt;p&gt;Supplementary Figures and Tables&lt;/p&gt;</jats:p>

Other

Hu Z, Cunnea P, Zhong Z, Lu H, Osagie OI, Campo L, Artibani M, Nixon K, Ploski J, Santana Gonzalez L, Alsaadi A, Wietek N, Damato S, Dhar S, Blagden SP, Yau C, Hester J, Albukhari A, Aboagye EO, Fotopoulou C, Ahmed Aet al., 2023, Table S2 from The Oxford Classic Links Epithelial-to-Mesenchymal Transition to Immunosuppression in Poor Prognosis Ovarian Cancers

<jats:p>&lt;p&gt;Table S2. The QuPath classification results for the immunohistochemistry of CAPS in SOC tissue microarrays.&lt;/p&gt;</jats:p>

Other

Hu Z, Cunnea P, Zhong Z, Lu H, Osagie OI, Campo L, Artibani M, Nixon K, Ploski J, Santana Gonzalez L, Alsaadi A, Wietek N, Damato S, Dhar S, Blagden SP, Yau C, Hester J, Albukhari A, Aboagye EO, Fotopoulou C, Ahmed Aet al., 2023, Data from The Oxford Classic Links Epithelial-to-Mesenchymal Transition to Immunosuppression in Poor Prognosis Ovarian Cancers

<jats:p>&lt;div&gt;AbstractPurpose:&lt;p&gt;Using RNA sequencing, we recently developed the 52-gene–based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier.&lt;/p&gt;Experimental Design:&lt;p&gt;We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (&lt;i&gt;n&lt;/i&gt; = 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs.&lt;/p&gt;Results:&lt;p&gt;We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition–high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; &lt;i&gt;P&lt;/i&gt; = 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; &lt;i&gt;P&lt;/i&gt; &lt; 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors.&lt;/p&gt;Conclusions:&lt;p&gt;The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.&lt;/p&gt;&lt;/div&

Other

Hu Z, Cunnea P, Zhong Z, Lu H, Osagie OI, Campo L, Artibani M, Nixon K, Ploski J, Santana Gonzalez L, Alsaadi A, Wietek N, Damato S, Dhar S, Blagden SP, Yau C, Hester J, Albukhari A, Aboagye EO, Fotopoulou C, Ahmed Aet al., 2023, Table S2 from The Oxford Classic Links Epithelial-to-Mesenchymal Transition to Immunosuppression in Poor Prognosis Ovarian Cancers

<jats:p>&lt;p&gt;Table S2. The QuPath classification results for the immunohistochemistry of CAPS in SOC tissue microarrays.&lt;/p&gt;</jats:p>

Other

Harter P, Bogner G, Chiva L, Cibula D, Concin N, Fotopoulou C, Gonzalez-Martin A, Guyon F, Heinzelmann-Schwarz V, Kridelka F, Mahner S, Marmé F, Marth C, Morice P, Novák Z, Papadia A, Ray-Coquard I, Redecha M, Redondo A, Schwameis R, Sehouli J, Undurraga M, Van Gorp T, Vergote Iet al., 2023, Statement of the AGO Kommission Ovar, AGO Study Group, NOGGO, AGO Austria, Swiss AGO, BGOG, CEEGOG, GEICO, and SFOG regarding the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in epithelial ovarian cancer., Bull Cancer

An international joint statement about the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer was published in 2016, warning about the uncritical use of HIPEC outside controlled studies. This statement has now been updated after the most recent literature was reviewed by the participating study groups and societies. HIPEC became a treatment option in patients with advanced colon cancer after positive results of a randomized trial comparing surgery and HIPEC versus palliative treatment alone. Although this trial did not compare the added value of HIPEC to surgery alone, HIPEC for the treatment of peritoneal metastases was in the subsequent years generalized to many other cancer types associated with peritoneal carcinomatosis including epithelial ovarian cancer (EOC). In the meantime, new evidence from prospective randomized trials specifically for EOC-patients emerged, with however contradicting results and several quality aspects that made the interpretation of their findings critical. Moreover, three additional trials in colorectal cancer failed to confirm the previously presumed survival benefit through the implementation of HIPEC in peritoneally disseminated colorectal cancers. Based on a still unclear and inconsistent landscape, the authors conclude that HIPEC should remain within the remit of clinical trials for EOC-patients. Available evidence is not yet sufficient to justify its broad endorsement into the routine clinical practice.

Journal article

Martinez A, Lecuru F, Bizzarri N, Chargari C, Ducassou A, Fagotti A, Fanfani F, Scambia G, Cibula D, Díaz-Feijoo B, Gil Moreno A, Angeles MA, Muallem MZ, Kohler C, Luyckx M, Kridelka F, Rychlik A, Gerestein KG, Heinzelmann V, Ramirez PT, Frumovitz M, Ferron G, Betrian S, Filleron T, Fotopoulou C, Querleu D, PAROLA Study groupet al., 2023, PARa-aOrtic LymphAdenectomy in locally advanced cervical cancer (PAROLA trial): a GINECO, ENGOT, and GCIG study., Int J Gynecol Cancer, Vol: 33, Pages: 293-298

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) fails to detect approximately 25% of aortic lymph node metastasis in patients with PET/CT stage IIIC1 cervical cancer. Surgical staging could lead to treatment modification and to improved para-aortic and distant control. PRIMARY OBJECTIVES: To demonstrate if chemoradiation with tailored external beam radiation field based on surgical staging and pathologic examination of the para-aortic lymph node is associated with improved 3-year disease-free survival compared with patients staged with PET/CT staging only. STUDY HYPOTHESIS: Surgical staging followed by tailored chemoradiation will improve disease-free survival while avoiding unnecessary prophylactic extended-field chemoradiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 cervical cancer. TRIAL DESIGN: This is an international multicenter, randomized, phase III study. Eligible patients will be randomized 1:1 between PET/CT staging followed by chemoradiation (control arm), or surgical staging followed by tailored chemo-radiation (experimental arm). Randomization will be stratified by tumor stage according to TNM classification, center, and adjuvant treatment. MAJOR INCLUSION/EXCLUSION CRITERIA: Main inclusion criteria are histologically proven PET/CT FIGO stage IIIC1 cervical cancer. Main exclusion criteria include unequivocal positive common iliac or para-aortic lymph node at pre-therapeutic imaging PET/CT. PRIMARY ENDPOINTS: The primary endpoint is disease-free survival defined as the time from randomization until first relapse (local, regional, or distant), or death from any cause. SAMPLE SIZE: 510 eligible patients ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The estimated date for completing accrual will be Q2 2027. The estimated date for presenting results will be Q4 2030. TRIAL REGISTRATION NUMBER: NCT05581121.

Journal article

Sundar S, Nordin A, Morrison J, Wood N, Ghaem-Maghami S, Nieto J, Phillips A, Butler J, Burton K, Gornall R, Dobbs S, Glasspool R, Peevor R, Ledermann J, McNeish I, Ratnavelu N, Duncan T, Frost J, Lim K, Michael A, Brockbank E, Gajjar K, Taylor A, Bowen R, Andreou A, Ganesan R, Nicum S, Edmondson R, Clayton R, Balega J, Rolland P, Maxwell H, Fotopoulou Cet al., 2023, British Gynaecological Cancer Society Recommendations for Evidence Based, Population Data Derived Quality Performance Indicators for Ovarian Cancer, CANCERS, Vol: 15

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Angeles MA, Boria F, Shushkevich AB, Bizzarri N, Theofanakis C, Schivardi G, Kacperczyk-Bartnik J, Strojna AN, Bilir E, Mahner S, Gultekin M, Cibula D, Rodolakis A, Lorusso D, Mirza MR, Fagotti A, Ledermann J, Fotopoulou C, Ramirez PTet al., 2022, Interviews conducted at the European Society of Gynaecological Oncology 2022 Congress: a ENYGO-IJGC Fellows initiative, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 33, Pages: 12-18, ISSN: 1048-891X

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Kim SI, Kim JH, Lee S, Cho H, van Driel WJ, Sonke GS, Bristow RE, Park S-Y, Fotopoulou C, Lim MCet al., 2022, Hyperthermic intraperitoneal chemotherapy for epithelial ovarian cancer: A meta-analysis, GYNECOLOGIC ONCOLOGY, Vol: 167, Pages: 547-556, ISSN: 0090-8258

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Strojna AN, Kacperczyk-Bartnik J, Angeles MA, Bizzarri N, van Ramshorst GH, Theofanakis C, Bilir E, Razumova Z, Nikolova T, Selcuk I, Wan Y-LL, Zalewski K, Lanner M, Pletnev A, Pareja R, Fotopoulou C, Kehoe S, Bak J, Ramirez PTet al., 2022, ENYGO-IJGC scientific writing and publication course: 2021 meeting summary, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 32, Pages: 1599-1605, ISSN: 1048-891X

Journal article

Yang Y, Li H, Fotopoulou C, Cunnea P, Zhao Xet al., 2022, Toll-like receptor-targeted anti-tumor therapies: Advances and challenges, Frontiers in Immunology, Vol: 13, Pages: 1-37, ISSN: 1664-3224

Toll-like receptors (TLRs) are pattern recognition receptors, originally discovered to stimulate innate immune reactions against microbial infection. TLRs also play essential roles in bridging the innate and adaptive immune system, playing multiple roles in inflammation, autoimmune diseases, and cancer. Thanks to the immune stimulatory potential of TLRs, TLR-targeted strategies in cancer treatment have proved to be able to regulate the tumor microenvironment towards tumoricidal phenotypes. Quantities of pre-clinical studies and clinical trials using TLR-targeted strategies in treating cancer have been initiated, with some drugs already becoming part of standard care. Here we review the structure, ligand, signaling pathways, and expression of TLRs; we then provide an overview of the pre-clinical studies and an updated clinical trial watch targeting each TLR in cancer treatment; and finally, we discuss the challenges and prospects of TLR-targeted therapy.

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Fotopoulou C, Khan T, Bracinik J, Glasbey J, Abu-Rustum N, Chiva L, Fagotti A, Fujiwara K, Ghebre R, Gutelkin M, Konney TO, Ng J, Pareja R, Seenivasagam RK, Sehouli J, Surappa STS, Bhangu A, Leung E, Sundar Set al., 2022, Outcomes of gynecologic cancer surgery during the COVID-19 pandemic: an international, multicenter, prospective CovidSurg-Gynecologic Oncology Cancer study, AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, Vol: 227, ISSN: 0002-9378

Journal article

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