Publications
414 results found
Papalois K-B, Fotopoulou C, 2024, Infrastructural and public health awareness gaps for the diagnosis and treatment of ovarian cancer: A literature review., Arch Gynecol Obstet, Vol: 309, Pages: 1807-1813
Ovarian cancer (OC) is the sixth most common cancer in women. This literature review and thematic analysis presents gaps in Health Literacy including public knowledge on symptoms, risk, and screening for OC. We have identified a strong variation in national and international Healthcare Infrastructure, and access to specialized care, and treatment guidelines; all inequalities that have a direct impact on patient prognosis and survival. Promoting health behaviors such as self-efficacy, signposting, and regular surveying have the potential to improve health literacy and patient outcomes. Furthermore, increased funding, access to high-volume centers, and homogenization of treatment guidelines may reduce inequalities and improve prognosis.
Fotopoulou C, Eriksson AG, Planchamp F, et al., 2024, European Society of Gynaecological Oncology expanded quality indicators and accreditation for cervical cancer management., Int J Gynecol Cancer, Vol: 34, Pages: 480-489
Mutch D, Gaffney D, Matias-Guiu X, et al., 2024, Response: Analysis of adjuvant therapy in early staged endometrioid endometrial cancer-FIGO 2023 classification., Int J Gynaecol Obstet
Gaffney D, Matias-Guiu X, Mutch D, et al., 2024, 2023 FIGO staging system for endometrial cancer: The evolution of the revolution., Gynecol Oncol, Vol: 184, Pages: 245-253
Embracing the complex and diverse nature of the heterogenous group of malignancies that are included under the umbrella of "endometrial cancer" (EC) to better align prognosis with treatment recommendations, requires a more comprehensive staging system. Our goal at the development of the new FIGO staging was to provide 1) high accuracy in the predictive prognosis for a patient with EC, which is the genuine purpose of a staging system, and 2) identification of distinct treatment relevant subgroups. Since the publication of the 2009 staging system by the International Federation of Gynecology and Obstetrics (FIGO) 14 years ago (1, 2), our understanding of the biology and natural history of EC has undergone a radical transformation. The TGCA results in 2013 (3), and the many validation reports published since then (4-9), have taught us that "EC" is composed of at least four distinct molecularly defined diseases. Strong histopathologic markers reflecting tumor biology such as lymph vascular space invasion (LVSI) were identified. Importantly, anatomical borders were shown to lose their prognostic relevance for EC patients in the presence of dominant tumor biology-markers such as molecular subtypes/LVSI (10, 11). This emphasizes the integration of these novel markers into a prognostic staging system that aims to be relevant to patients. The 2023 FIGO staging system for EC harmonizes and integrates old and new knowledge on anatomic, histopathologic, and molecular features (12). It requires a change in our perception of a staging system, from a traditional purely anatomical borders-based system to an integrated staging system integrating anatomical borders and tumor biology as pivotal prognostic factors for EC patients while providing important information for treatment decision making. Therefore, the 2023 FIGO staging system demonstrates the logical next step in the evolution of the revolution in a patient-centric staging approach. Below, we elucid
Fotopoulou C, Eriksson AG, Baiocchi G, et al., 2024, Surgery for gynecological cancers in the era of personalized medicine: a novel paradigm., Int J Gynecol Cancer, Vol: 34
Harter P, Bogner G, Chiva L, et al., 2024, 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, Vol: 111, Pages: 277-284
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.
Dabi Y, Rockall A, Razakamanantsoa L, et al., 2024, O-RADS MRI scoring system has the potential to reduce the frequency of avoidable adnexal surgery., Eur J Obstet Gynecol Reprod Biol, Vol: 294, Pages: 135-142
OBJECTIVE: To assess the potential impact of the O-RADS MRI score on the decision-making process for the management of adnexal masses. METHODS: EURAD database (prospective, European observational, multicenter study) was queried to identify asymptomatic women without history of infertility included between March 1st and March 31st 2018, with available surgical pathology or clinical findings at 2-year clinical follow-up. Blinded to final diagnosis, we stratified patients into five categories according to the O-RADS MRI score (absent i.e. non adnexal, benign, probably benign, indeterminate, probably malignant). Prospective management was compared to theoretical management according to the score established as following: those with presumed benign masses (scored O-RADS MRI 2 or 3) (follow-up recommended) and those with presumed malignant masses (scored O-RADS MRI 4 or 5) (surgery recommended). RESULTS: The accuracy of the score for assessing the origin of the mass was of 97.2 % (564/580, CI95% 0.96-0.98) and was of 92.0 % (484/526) for categorizing lesions with a negative predictive value of 98.1 % (415/423, CI95% 0.96-0.99). Theoretical management using the score would have spared surgery in 229 patients (87.1 %, 229/263) with benign lesions and malignancy would have been missed in 6 borderline and 2 invasive cases. In patients with a presumed benign mass using O-RADS MRI score, recommending surgery for lesions >= 100 mm would miss only 4/77 (4.8 %) malignant adnexal tumors instead of 8 (50 % decrease). CONCLUSION: The use of O-RADS MRI scoring system could drastically reduce the number of asymptomatic patients undergoing avoidable surgery.
Ledermann JA, Matias-Guiu X, Amant F, et al., 2024, ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease, Annals of Oncology, Vol: 35, Pages: 248-266, ISSN: 0923-7534
The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.
Yumru Celiksoy H, Dickie C, Seckl MJ, et al., 2024, Effectiveness of adjuvant systemic therapy following complete cytoreductive surgery in patients with recurrent granulosa cell tumours of the ovary., Sci Rep, Vol: 14
Aim of the present analysis is to compare the impact of antihormonal therapy versus cytotoxic chemotherapy versus a watch a wait approach on disease-free survival (DFS) in the adjuvant setting of patients who underwent complete cytoreductive surgery(CRS) for recurrent adult type granulosa cell tumours of the ovary (GCT). Moreover, we wished to identify prognostic risk factors for recurrence. We included recurrent GCT-patients who underwent CRS resulting in total macroscopic tumour clearance, treated in two gynaecological cancer centres over a 20-year period (2000-2020). CRS was performed for 51 recurrences in 26 GCT-patients. Adjuvant systemic treatments were as follows: chemotherapy in 21 cases, hormonotherapy in 10 cases, no systemic treatment in 20 cases. There were no statistically significant differences in DFS between chemotherapy, hormonotherapy and no systemic treatment: median DFS was 57, 36 and 57 months, respectively (p = 0.616). Extra-pelvic and/or multifocal tumour dissemination were found to be independent predictive factors for subsequent recurrences. In the cases with both lower and upper abdominal involvement (n = 18), patients who received chemotherapy (n = 9) had longer DFS than those who had hormonotherapy (n = 2) or no adjuvant therapy (n = 7) at all: median DFS was 36, 13 and 15 months, respectively (p = 0.9). Our findings do not encourage the administration of adjuvant therapy following complete CRS for GCT-relapse. Selected high-risk patients with disseminated disease may derive clinical benefit from additional chemotherapy, larger-scale multicentre studies are warranted to define treatment algorithms for this rare disease.
Fotopoulou C, Eriksson AG, Yagel I, et al., 2024, Surgery for Recurrent Epithelial Ovarian Cancer., Curr Oncol Rep, Vol: 26, Pages: 46-54
To review evidence around the value and challenges of surgery for recurrent epithelial ovarian cancer (ROC). Both cytoreductive and palliative aspects will be addressed RECENT FINDINGS: Prospective and retrospective evidence demonstrates a significantly longer remission derived from the combination of surgical and systemic modalities as opposed to systemic treatment alone in carefully selected ROC-patients who have relapsed more than 6 months from the end of their 1st line platinum-based chemotherapy. Nevertheless, this benefit appears to be limited when total macroscopic tumor clearance is not achieved. Selection algorithms to identify optimal surgical candidates are of paramount importance to prevent surgical morbidity without the equivalent oncological benefit. In the palliative setting, the risks and benefits of salvage surgery need to be counterbalanced with the advances of conservative techniques for optimal care. Well-defined selection algorithms to identify those who will benefit from surgery in the relapsed setting appear to be the key to oncologic and surgical success.
Concin N, Matias-Guiu X, Fotopoulou C, et al., 2024, Response: FIGO staging of endometrial cancer 2023., Int J Gynaecol Obstet, Vol: 164, Pages: 369-372
Morrison J, Baldwin P, Hanna L, et al., 2024, British Gynaecological Cancer Society (BGCS) vulval cancer guidelines: An update on recommendations for practice 2023., Eur J Obstet Gynecol Reprod Biol, Vol: 292, Pages: 210-238
Fotopoulou C, Hall M, Lord R, et al., 2024, Perspectives of Healthcare Professionals on the Management and Treatment of Advanced Ovarian Cancer in the UK: Results From the KNOW-OC Survey., Clin Oncol (R Coll Radiol), Vol: 36, Pages: e1-e10
AIMS: New treatment options for advanced ovarian cancer have the potential to significantly change the treatment pathway in the UK. Understanding the structures and responsibilities of multidisciplinary teams/tumour boards (MDT) and regional variations will enable services to adapt more effectively to these changes. MATERIALS AND METHODS: The KNOW-OC survey was conducted in 2020 to understand the views of a selected group of 66 healthcare professionals (HCPs) involved in advanced ovarian cancer care in UK hospitals. RESULTS: The results showed that MDT involvement in the management of advanced ovarian cancer varied depending on pathway stage and line of relapse, with 98.5% of HCPs responding that the MDT was involved in decisions at initial presentation, but only 40.9% for patients with multiple relapses. The MDT was mostly responsible for determining whether the patients would undergo primary or interval cytoreductive surgery according to 75.8% of respondents, and most HCPs (80.3%) stated that tumour dissemination patterns were the most important factor influencing this decision. The most commonly assessed biomarkers at the time of the survey were CA125, gBRCA and tBRCA. Homologous recombination deficiency was viewed as the second most important factor for determining prognosis, but few centres had access to testing at the time of survey completion. The use of active surveillance was expected to decrease in favour of first-line targeted therapies. Nearly all (98.5%) HCPs agreed there is a role for secondary cytoreductive surgery for the treatment of recurrence (for carefully selected patients). CONCLUSIONS: The results highlighted UK-specific geographical variation in the views of HCPs on MDT involvement and specific practices, such as molecular biomarker testing, and the overall treatment approach. Together, these findings improve the understanding of reported clinical practice across the UK for ovarian cancer and provide insight into decision-making associated wi
Lakhiani A, Cummins C, Kumar S, et al., 2023, Analysis of Anxiety, Depression and Fear of Progression at 12 Months Post-Cytoreductive Surgery in the SOCQER-2 (Surgery in Ovarian Cancer-Quality of Life Evaluation Research) Prospective, International, Multicentre Study., Cancers (Basel), Vol: 16, ISSN: 2072-6694
Patients with ovarian cancer (OC) often experience anxiety, depression and fear of progression (FOP); however, it is unclear whether surgical complexity has a role to play. We investigated the prevalence of anxiety, depression and FOP at 12 months post-cytoreductive surgery and investigated associations with surgical complexity, patient (age, ethnicity, performance status, BMI) and tumour (stage, disease load) factors. One hundred and forty-one patients with FIGO Stage III-IV OC, who did not have disease progression at 12 months post-surgery, completed the Hospital Anxiety and Depression Scale and FOP short-form questionnaire. Patients underwent surgery with low (40.4%), intermediate (31.2%) and high (28.4%) surgical complexity scores. At 12 months post-surgery, 99 of 141 (70%) patients with advanced OC undergoing surgery experienced clinically significant anxiety, 21 of 141 (14.9%) patients experienced moderate to severe depression and 37 of 140 (26.4%) experienced dysfunctional FOP. No associations were identified between the three different surgical complexity groups with regards to anxiety, depression or FOP scores. Unsurprisingly, given the natural history of the disease, most patients with OC suffer from anxiety, depression and fear of progression after completion of first-line cancer treatment. Surgical complexity at the time of surgery is not associated with a deleterious impact on anxiety, depression or FOP for patients with OC. Patients with OC experience a profound mental health impact and should be offered mental health support throughout their cancer journey.
Angeles MA, De Vitis LA, Cucinella G, et al., 2023, Highlights from the 24th European Congress on Gynaecological Oncology in Istanbul: an ENYGO-IJGC Fellows compilation., Int J Gynecol Cancer
Kim JH, Cho H-W, Park EY, et al., 2023, Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis., Int J Gynecol Cancer, Vol: 33, Pages: 1913-1920
OBJECTIVE: To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers. METHOD: A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics. RESULTS: A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival. CONCLUSION: Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer. STUDY REGISTRATION: The systemic revie
Kim JH, Kim SI, Park EY, et al., 2023, Impact of postoperative residual disease on survival in epithelial ovarian cancer with consideration of recent frontline treatment advances: A systematic review and meta-analysis, Gynecologic Oncology, Vol: 179, Pages: 24-32, ISSN: 0090-8258
Background: Current treatment strategies for primary epithelial ovarian cancer (EOC) have significantly evolved, and the value of complete cytoreduction has not yet been reassessed. The study aimed to investigate the impact of residual disease after cytoreductive surgery for EOC on survival outcomes within the recent paradigm of frontline ovarian cancer treatment. Methods: We searched relevant literature from the MEDLINE, Embase, and Cochrane Library databases to identify randomized controlled trials and prospective clinical trials of primary EOC published between 1 January 2000 and 22 September 2022. To evaluate the impact of postoperative residual tumors on progression-free survival (PFS) and OS, we constructed a linear regression model for log-transformed median PFS and OS. Patients who did or did not receive first-line maintenance therapy were examined. Results: A total of 97 trials with 43,260 patients were included:2476 received poly(ADP-ribose) polymerase (PARP) inhibitors and 6587 received bevacizumab. Multivariable analysis of the linear regression model of all studies revealed that the median OS increased by 12.97% for every 10% increase in complete cytoreduction rates, independent of the use of systemic maintenance. In the subgroup analysis of patients receiving maintenance therapies, the effect of complete tumor clearance was potentiated, with a median OS increase of 19.13% for every 10% increase in complete cytoreduction rates. Conclusion: Total macroscopic tumor clearance at the initial presentation of EOC significantly prolongs OS. Our results establish the importance of complete surgical cytoreduction, even after the introduction of recent advances in frontline treatment for EOC.
Armbrust R, Fotopoulou C, Sehouli J, 2023, The role of neoadjuvant chemotherapy in advanced ovarian cancer: The right treatment to the right patient - Ensuring optimal outcomes in advanced ovarian cancer., BJOG
Bergamini A, Ramaswami R, Froeling F, et al., 2023, Fertility outcomes following surgery and multiagent chemotherapy in malignant ovarian germ cell tumor survivors: a survey study., Int J Gynecol Cancer, Vol: 33, Pages: 1750-1756
OBJECTIVE: To assess fertility outcomes in long-term survivors of malignant ovarian germ cell tumors treated with fertility-sparing surgery with or without additional chemotherapy. METHODS: Women diagnosed and treated for malignant ovarian germ cell tumors at Charing Cross Hospital or Mount Vernon Cancer Centre between 1977 and 2015 were included. Questionnaires assessing fertility issues were sent to patients treated with fertility-sparing surgery. Fertility outcomes were evaluated according to the treatment received. The effect of the mean total dose of cyclophosphamide and cisplatin was assessed. RESULTS: A total of 146 patients were sent the questionnaire; 77 (56.5%) patients were included in the analysis. A total of 49 (64%) patients received platinum-based chemotherapy after surgery, 39 (79.6%) of these with cisplatin, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide, and etoposide, while 10 (20.4%) with bleomycin, etoposide, and cisplatin. After any treatment, 39/46 patients (85%) became pregnant: the conception rate was not different between those receiving surgery only and those receiving also chemotherapy (85.7% vs 84.4%, p=1.0). Live birth rate was 80.4% (37/46), with no statistically significant difference between the treatment groups (p=0.42). Median age of women achieving conception was 29 years (IQR 26-33). The probability of live birth at 5 years was 48% and 40% for patients in the surgery only and chemotherapy group, respectively (p=0.55). Infertility and miscarriage rates did not differ significantly between the two treatment groups (p=0.30 and p=0.32). The mean doses of cisplatin and cyclophosphamide received by patients failing and achieving conception were not different (p=0.10, p=0.47). CONCLUSIONS: Our results suggest that fertility may not be hampered in patients with malignant ovarian germ cell tumor treated with fertility-sparing surgery or receiving additional chemotherapy.
Smith P, Bradley T, Gavarró LM, et al., 2023, Author Correction: The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma., Nat Commun, Vol: 14
Fotopoulou C, 2023, First do no harm' revisited in ovarian cancer cytoreduction, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, ISSN: 1470-0328
Berek JS, Matias-Guiu X, Creutzberg C, et al., 2023, FIGO staging of endometrial cancer: 2023, JOURNAL OF GYNECOLOGIC ONCOLOGY, Vol: 34, ISSN: 2005-0380
Nout R, Calaminus G, Planchamp F, et 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.
Tsibulak I, Fotopoulou C, 2023, Tumor biology and impact on timing of surgery in advanced epithelial ovarian cancer, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, ISSN: 1048-891X
Khassan T, Smitten E, Wood N, et al., 2023, MDT practice determines treatment pathway for patients with advanced ovarian cancer: A multi-centre observational study, EJSO, Vol: 49, Pages: 1504-1510, ISSN: 0748-7983
Nelson G, Fotopoulou C, Taylor J, et al., 2023, Enhanced Recovery After Surgery (ERAS<SUP>®</SUP>) Society Guidelines for Gynecologic Oncology: Addressing Implementation Challenges-2023 Update Comment, OBSTETRICAL & GYNECOLOGICAL SURVEY, Vol: 78, Pages: 476-477, ISSN: 0029-7828
Berek J, Matias-Guiu X, Creutzberg C, et al., 2023, FIGO staging of endometrial cancer: 2023, INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS, Vol: 162, Pages: 383-394, ISSN: 0020-7292
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Nout RA, Calaminus G, Planchamp F, et al., 2023, ESTRO/ESGO/SIOPe Guidelines for the management of patients with vaginal cancer, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 33, Pages: 1185-1202, ISSN: 1048-891X
Smith P, Bradley T, Gavarró LM, et 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.
Cunnea P, Curry EW, Christie EL, et 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.
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