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Article ; Online: Beauty is in the explainable artificial intelligence (XAI) of the "agnostic" beholder.

Laios, Alexandros / De Jong, Diederick / Kalampokis, Evangelos

2023 Volume 12, Issue 2, Page(s) 226–229

Language	English
Publishing date	2023-01-06
Publishing country	China
Document type	Editorial ; Comment
ZDB-ID	2901601-0
ISSN	2219-6803 ; 2218-676X
ISSN (online)	2219-6803
ISSN	2218-676X
DOI	10.21037/tcr-22-2664
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Future of AI in Ovarian Cancer Research: The Large Language Models Perspective.

Laios, Alexandros / Theophilou, Georgios / De Jong, Diederick / Kalampokis, Evangelos

Cancer control : journal of the Moffitt Cancer Center

2023 Volume 30, Page(s) 10732748231197915

Abstract: Conversational large language model (LLM)-based chatbots utilize neural networks to process natural language. By generating highly sophisticated outputs from contextual input text, they revolutionize the access to further learning, leading to the ... ...

Abstract	Conversational large language model (LLM)-based chatbots utilize neural networks to process natural language. By generating highly sophisticated outputs from contextual input text, they revolutionize the access to further learning, leading to the development of new skills and personalized interactions. Although they are not developed to provide healthcare, their potential to address biomedical issues is rather unexplored. Healthcare digitalization and documentation of electronic health records is now developing into a standard practice. Developing tools to facilitate clinical review of unstructured data such as LLMs can derive clinical meaningful insights for ovarian cancer, a heterogeneous but devastating disease. Compared to standard approaches, they can host capacity to condense results and optimize analysis time. To help accelerate research in biomedical language processing and improve the validity of scientific writing, task-specific and domain-specific language models may be required. In turn, we propose a bespoke, proprietary ovarian cancer-specific natural language using solely in-domain text, whereas transfer learning drifts away from the pretrained language models to fine-tune task-specific models for all possible downstream applications. This venture will be fueled by the abundance of unstructured text information in the electronic health records resulting in ovarian cancer research ultimately reaching its linguistic home.
MeSH term(s)	Humans ; Female ; Ovarian Neoplasms/diagnosis ; Language ; Communication ; Electronic Health Records
Language	English
Publishing date	2023-08-25
Publishing country	United States
Document type	Editorial
ZDB-ID	1328503-8
ISSN	1526-2359 ; 1073-2748
ISSN (online)	1526-2359
ISSN	1073-2748
DOI	10.1177/10732748231197915
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Article ; Online: A Systematic Review of Systematic Reviews on the Use of Aromatase Inhibitors for the Treatment of Endometriosis: The Evidence to Date.

Peitsidis, Panagiotis / Tsikouras, Panagiotis / Laganà, Antonio Simone / Laios, Alexandros / Gkegkes, Ioannis D / Iavazzo, Christos

Drug design, development and therapy

2023 Volume 17, Page(s) 1329–1346

Abstract: Endometriosis is a chronic gynecologic condition that affects around 6-10% of reproductive age women. This clinical entity is characterized with pelvic pain, dysmenorrhea, dyspareunia, and infertility which are the most often presenting symptoms. ... ...

Abstract	Endometriosis is a chronic gynecologic condition that affects around 6-10% of reproductive age women. This clinical entity is characterized with pelvic pain, dysmenorrhea, dyspareunia, and infertility which are the most often presenting symptoms. Aromatase P450 is the key enzyme for ovarian estrogen biosynthesis and there is evidence that endometriotic lesions express aromatase and are able to synthesize their own estrogens. Aromatase inhibitors (AIs) are potent drugs that suppress the estrogen synthesis via suppression of aromatase. We performed a systematic review of systematic reviews and narrative reviews on the use of aromatase inhibitors in the medical management of endometriosis. We searched: PubMed (1950-2022), Google Scholar (2004-2022), Cochrane Library (2010-2022) and Researchgate (2010-2022). The search included the following medical subject headings (MeSH) or keywords: "Aromatase Inhibitors" AND "Endometriosis" AND "Systematic reviews" OR "Systematic review" AND "Reviews" OR "Reviews" AND "Endometriosis". The electronic database search yielded initially 12,106 studies from the different databases. Further assessment of the studies resulted in exclusion of (n = 12,015) studies due to duplicates and irrelevance; Finally, 24 studies were selected for inclusion, 5 were Systematic reviews and 19 were Narrative reviews. The 5 systematic reviews were assessed by AMSTAR-2 criteria and were found to have low quality. Narrative reviews were assessed with SANRA criteria and were found to have high-quality aromatase inhibitors are potent drugs that can manage the endometriosis-related symptoms in cases where initial medical management has failed to show positive results. However, their use is limited by the adverse effects that are linked with menopausal symptoms. aromatase inhibitors can be administered as an alternative treatment in patients. Future studies with randomized design are required to reach safer conclusions and further investigation. These studies should define the therapeutic dose, new add-back therapy modalities. Future directions should examine the most-appropriate way of administration and the duration of therapy.
MeSH term(s)	Female ; Humans ; Aromatase/therapeutic use ; Aromatase Inhibitors/therapeutic use ; Aromatase Inhibitors/pharmacology ; Endometriosis/drug therapy ; Endometriosis/pathology ; Estrogens ; Systematic Reviews as Topic
Chemical Substances	Aromatase (EC 1.14.14.1) ; Aromatase Inhibitors ; Estrogens
Language	English
Publishing date	2023-05-04
Publishing country	New Zealand
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	2451346-5
ISSN	1177-8881 ; 1177-8881
ISSN (online)	1177-8881
ISSN	1177-8881
DOI	10.2147/DDDT.S315726
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Article: Breast Cancer Patients at Increased Risk of Developing Type II Endometrial Cancer: Relative and Absolute Risk Estimation and Implications for Counseling.

Portela, Sara / Cunningham, Aimee / Laios, Alexandros / Hutson, Richard / Theophilou, Georgios

Cureus

2021 Volume 13, Issue 1, Page(s) e12981

Abstract: Introduction Breast cancer (BC) is a recognized risk factor for endometrial cancer (EC). Emerging literature indicates that it confers a higher risk of type II EC (T2EC) than type I EC (T1EC). Although some surgeons offer a prophylactic hysterectomy to ... ...

Abstract	Introduction Breast cancer (BC) is a recognized risk factor for endometrial cancer (EC). Emerging literature indicates that it confers a higher risk of type II EC (T2EC) than type I EC (T1EC). Although some surgeons offer a prophylactic hysterectomy to BC patients referred for risk-reducing bilateral salpingo-oophorectomy, insufficient evidence prevents this from being the standard practice. We aimed to quantify their absolute risk and relative risk (RR) of developing both EC subtypes and identify a higher-risk group that could be considered for prophylactic hysterectomy. Methodology This retrospective service evaluation compared patients diagnosed with BC between 2008 and 2014, who subsequently developed EC within 10 years to those who did not. Absolute risk and RR were calculated using the numbers of regional BC and EC cases within this group, alongside 2009 UK female population and EC incidence statistics. Binary logistic regression generated adjusted odds ratios (ORs) for patient- and disease-specific variables. Results A total of 45 BC patients developed EC, 24 had T1EC and 21 had T2EC. Their RR of developing EC was greater than that of the general population (RR: 12.44, p < 0.0001). Notably, this was higher for T2EC (RR: 33.96, p < 0.001) than T1EC (RR: 8.63, p < 0.0001). Nonetheless, the absolute risk remained low. Tamoxifen exposure was significantly more prevalent among T2EC patients (adjusted OR: 79.61, p = 0.003). Increased age at BC diagnosis was associated with T1EC (adjusted OR: 1.10, p = 0.043) and T2EC (adjusted OR: 1.13, p = 0.03). Neither smoking status nor family history of BC was significantly associated with any outcome. Conclusion Women with BC were more likely to develop T2EC than T1EC, and although the absolute risk was low, the cumulative risk was substantial enough to warrant vigilance. Tamoxifen exposure was significantly predictive of EC, particularly T2EC, and might facilitate risk estimation. Older women at BC diagnosis who receive tamoxifen treatment should be screened and closely monitored for EC. However, given the limitations of normal screening methods for the detection of T2EC, counseling for a prophylactic hysterectomy should also be considered. Clarification of the menopausal status will help make more meaningful recommendations.
Language	English
Publishing date	2021-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.12981
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Article: Optimal MRI interval for detection of asymptomatic recurrence in surgically treated early cervical cancer by use of a mathematical model.

Laios, A / Gubbala, K / Lampe, R / Tolis, A

Hippokratia

2016 Volume 20, Issue 1, Page(s) 4–8

Abstract: Introduction: Applications of mathematical modeling may provide an insight into the timing of surveillance modalities. We aimed to determine the optimal magnetic resonance imaging (MRI) interval for the detection of surgically treated early cervical ... ...

Abstract	Introduction: Applications of mathematical modeling may provide an insight into the timing of surveillance modalities. We aimed to determine the optimal magnetic resonance imaging (MRI) interval for the detection of surgically treated early cervical cancer asymptomatic recurrence by using a mathematical model for volumetric tumor growth time. Methods: We assumed that tumor volume increases by a factor equal to the basis of natural logarithms (e~2.718) at constant time intervals. Using a mathematical formula, the tumor volume (V) was converted to diameter (D), which could be expressed as a function of time (t), given an initial diameter Di (corresponding to initial volume Vi) and a constant DT, where DT is the time required for volumetric tumor growth by a factor (e). Three different DTs were used for demonstration of the model, i.e. 20, 100 and 400 days. Results: Assuming complete surgical clearance, a worst-case scenario for a 20-day DT indicated that a 20 μm cervical tumor would need at least 12 months to reach 10 mm in diameter, which would be detected with an annual surveillance interval MRI. Over a 5-year (60 months) follow-up, nearly five surveillance MRIs would be required if the threshold of 10 mm was desired. For a 100-day DT over a 5-year (60 months) follow-up, a single only MRI would be required, if the threshold of 10 mm was desired. In the case of an indolent tumor (DT is 400 days), the model would not recommend a surveillance MRI to detect asymptomatic recurrence. A positive linear association between optimal MRI intervals and volumetric tumor DTs was demonstrated. Conclusion: In the absence of evidence, we postulate annual MRI scanning is probably the shortest interval, which can be clinically useful for optimization of routine surveillance follow-up protocols in surgically treated early cervical cancer. This mathematical model requires proper verification in prospective clinical studies. Hippokratia 2016, 20(1): 4-8.
Language	English
Publishing date	2016-04-04
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2491943-3
ISSN	1790-8019 ; 1108-4189
ISSN (online)	1790-8019
ISSN	1108-4189
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Article ; Online: Outcomes of ovarian transposition in cervical cancer; an updated meta-analysis.

Laios, Alexandros / Otify, Mohamed / Papadopoulou, Argyro / Gallos, Ioannis D / Ind, Thomas

BMC women's health

2022 Volume 22, Issue 1, Page(s) 305

Abstract: Background: Cervical cancer is the most common indication for ovarian transposition in reproductive-age women. Ovarian transposition should be performed in premenopausal women undergoing pelvic irradiation to preserve ovarian function, and prevent early ...

Abstract	Background: Cervical cancer is the most common indication for ovarian transposition in reproductive-age women. Ovarian transposition should be performed in premenopausal women undergoing pelvic irradiation to preserve ovarian function, and prevent early menopause. As women become more knowledgeable about their fertility options, it is still unclear who will benefit from the intervention. We updated our previous meta-analysis of ovarian function preservation, symptomatic ovarian cysts, and metastases to the transposed ovaries following ovarian transposition in cervical cancer patients to further guide current clinical practice. Methods: A systematic search of Medline, Embase, Web of Science, and The Cochrane Library databases, dating from January 1980 to July 2021, was conducted. We computed the summary proportions of women who had ovarian function preservation, non-ovarian cyst formation and metastases to the transposed ovaries following ovarian transposition by random-effects meta-analysis and we explored study heterogeneity by type of radiotherapy. Results: There were 29 publications reporting on 1160 women with cervical cancer who underwent ovarian transposition. In the group that underwent surgery alone, 91% of the women had preserved ovarian function (95% CI 83-100), 89% (95% CI 80-99) of women who did not develop ovarian cysts, and 99% (95% CI 1-5) of women who did not suffer metastases to the transposed ovaries. In the surgery ± brachytherapy (BR) group, the proportion of women with the preserved ovarian function was 93% (95% CI 76-113), 84% (95% CI 69-103) of women who did not develop ovarian cysts, and 99% (95% CI 82-120) of women who did not suffer metastases to the transposed ovaries. In the external beam pelvic radiotherapy (EBRT) ± BR ± surgery group, the proportion of women with the preserved ovarian function was 61% (95% CI 55-69), and 95% (95% CI 85-107) of women who developed ovarian cysts. There were no metastases to the transposed ovaries in that group. Conclusions: In women with cervical cancer, ovarian transposition offers a significant preservation of the ovarian function. Despite an expected incidence of ovarian cyst formation, it carries almost no risk for metastases to the transposed ovaries.
MeSH term(s)	Brachytherapy ; Female ; Humans ; Ovarian Cysts ; Pelvis ; Uterine Cervical Neoplasms/surgery
Language	English
Publishing date	2022-07-22
Publishing country	England
Document type	Journal Article ; Meta-Analysis
ZDB-ID	2050444-5
ISSN	1472-6874 ; 1472-6874
ISSN (online)	1472-6874
ISSN	1472-6874
DOI	10.1186/s12905-022-01887-8
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Article ; Online: A systematic review and meta-analysis of the use of ultrasound to diagnose borderline ovarian tumours.

Otify, M / Laios, A / Elshamy, T / D'Angelo, A / Amso, N N

European journal of obstetrics, gynecology, and reproductive biology

2019 Volume 244, Page(s) 120–127

Abstract: Borderline ovarian tumours (BOTs) are difficult to diagnose preoperatively. The ability to distinguish between BOTs and other ovarian cancer types prior to surgery could have a profound impact on patient childbearing counselling and surgical planning. ... ...

Abstract	Borderline ovarian tumours (BOTs) are difficult to diagnose preoperatively. The ability to distinguish between BOTs and other ovarian cancer types prior to surgery could have a profound impact on patient childbearing counselling and surgical planning. Ultrasound (US) pattern recognition by an expert examiner can be an excellent tool for the discrimination of benign and malignant ovarian masses. With respect to US features, most studies were based on well-known risk models. Nevertheless, very few studies have solely evaluated the utility of ultrasound in diagnosing BOTs. We aimed to evaluate the use of US in identifying BOTs solely from benign and malignant ovarian tumours in isolation from risk models. We performed a systematic literature review to identify publications that evaluated the use of US to differentiate between BOTs and malignant and/or benign ovarian tumours using Pubmed, Web of Science and the Cochrane Library. We performed a meta-analysis of the diagnostic sensitivity and specificity studies. We computed the summary estimates for sensitivity and specificity of US in diagnosing BOTs using the bivariate approach of Reitsma in the mada package in R. The initial search resulted in 24,737 publications. Hundred and seven publications were screened, and five studies contained diagnostic data. Different US criteria applied to identify BOTs. Four out of five studies including 244 women with BOTs and 965 women with benign or malignant tumours were suitable for the meta-analysis. Pooling of the results from four studies showed an overall sensitivity of 0.660 (95 % CI: 0.597 - 0.718) and specificity of 0.854 (95 % CI: 0.728 - 0.927). The overall US accuracy was uniform in sensitivity and variable in specificity. A low false positive rate, 0.146 (95 % CI: 0.073 - 0.272) was observed. US correctly identified BOTs in more than six out of 10 women for potential ovarian sparing surgery, whereas it correctly identified the absence of BOTs in more than eight out of 10 symptomatic women. More carefully designed studies are needed to evaluate the use of pre-operative US for the diagnosis of BOTs.
MeSH term(s)	Female ; Humans ; Ovarian Neoplasms/diagnostic imaging ; Ultrasonography
Language	English
Publishing date	2019-11-23
Publishing country	Ireland
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	190605-7
ISSN	1872-7654 ; 0301-2115 ; 0028-2243
ISSN (online)	1872-7654
ISSN	0301-2115 ; 0028-2243
DOI	10.1016/j.ejogrb.2019.11.016
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Article: Exploring the Potential Role of Upper Abdominal Peritonectomy in Advanced Ovarian Cancer Cytoreductive Surgery Using Explainable Artificial Intelligence.

Laios, Alexandros / Kalampokis, Evangelos / Mamalis, Marios Evangelos / Thangavelu, Amudha / Hutson, Richard / Broadhead, Tim / Nugent, David / De Jong, Diederick

Cancers

2023 Volume 15, Issue 22

Abstract: The Surgical Complexity Score (SCS) has been widely used to describe the surgical effort during advanced stage epithelial ovarian cancer (EOC) cytoreduction. Referring to a variety of multi-visceral resections, it best combines the numbers with the ... ...

Abstract	The Surgical Complexity Score (SCS) has been widely used to describe the surgical effort during advanced stage epithelial ovarian cancer (EOC) cytoreduction. Referring to a variety of multi-visceral resections, it best combines the numbers with the complexity of the sub-procedures. Nevertheless, not all potential surgical procedures are described by this score. Lately, the European Society for Gynaecological Oncology (ESGO) has established standard outcome quality indicators pertinent to achieving complete cytoreduction (CC0). There is a need to define what weight all these surgical sub-procedures comprising CC0 would be given. Prospectively collected data from 560 surgically cytoreduced advanced stage EOC patients were analysed at a UK tertiary referral centre.We adapted the structured ESGO ovarian cancer report template. We employed the eXtreme Gradient Boosting (XGBoost) algorithm to model a long list of surgical sub-procedures. We applied the Shapley Additive explanations (SHAP) framework to provide global (cohort) explainability. We used Cox regression for survival analysis and constructed Kaplan-Meier curves. The XGBoost model predicted CC0 with an acceptable accuracy (area under curve [AUC] = 0.70; 95% confidence interval [CI] = 0.63-0.76). Visual quantification of the feature importance for the prediction of CC0 identified upper abdominal peritonectomy (UAP) as the most important feature, followed by regional lymphadenectomies. The UAP best correlated with bladder peritonectomy and diaphragmatic stripping (Pearson's correlations > 0.5). Clear inflection points were shown by pelvic and para-aortic lymph node dissection and ileocecal resection/right hemicolectomy, which increased the probability for CC0. When UAP was solely added to a composite model comprising of engineered features, it substantially enhanced its predictive value (AUC = 0.80, CI = 0.75-0.84). The UAP was predictive of poorer progression-free survival (HR = 1.76, CI 1.14-2.70, P: 0.01) but not overall survival (HR = 1.06, CI 0.56-1.99, P: 0.86). The SCS did not have significant survival impact. Machine Learning allows for operational feature selection by weighting the relative importance of those surgical sub-procedures that appear to be more predictive of CC0. Our study identifies UAP as the most important procedural predictor of CC0 in surgically cytoreduced advanced-stage EOC women. The classification model presented here can potentially be trained with a larger number of samples to generate a robust digital surgical reference in high output tertiary centres. The upper abdominal quadrants should be thoroughly inspected to ensure that CC0 is achievable.
Language	English
Publishing date	2023-11-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15225386
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Article ; Online: RoBERTa-Assisted Outcome Prediction in Ovarian Cancer Cytoreductive Surgery Using Operative Notes.

Laios, Alexandros / Kalampokis, Evangelos / Mamalis, Marios Evangelos / Tarabanis, Constantine / Nugent, David / Thangavelu, Amudha / Theophilou, Georgios / De Jong, Diederick

Cancer control : journal of the Moffitt Cancer Center

2023 Volume 30, Page(s) 10732748231209892

Abstract: Introduction: Contemporary efforts to predict surgical outcomes focus on the associations between traditional discrete surgical risk factors. We aimed to determine whether natural language processing (NLP) of unstructured operative notes improves the ... ...

Abstract	Introduction: Contemporary efforts to predict surgical outcomes focus on the associations between traditional discrete surgical risk factors. We aimed to determine whether natural language processing (NLP) of unstructured operative notes improves the prediction of residual disease in women with advanced epithelial ovarian cancer (EOC) following cytoreductive surgery. Methods: Electronic Health Records were queried to identify women with advanced EOC including their operative notes. The Term Frequency - Inverse Document Frequency (TF-IDF) score was used to quantify the discrimination capacity of sequences of words (n-grams) regarding the existence of residual disease. We employed the state-of-the-art RoBERTa-based classifier to process unstructured surgical notes. Discrimination was measured using standard performance metrics. An XGBoost model was then trained on the same dataset using both discrete and engineered clinical features along with the probabilities outputted by the RoBERTa classifier. Results: The cohort consisted of 555 cases of EOC cytoreduction performed by eight surgeons between January 2014 and December 2019. Discrete word clouds weighted by n-gram TF-IDF score difference between R0 and non-R0 resection were identified. The words 'adherent' and 'miliary disease' best discriminated between the two groups. The RoBERTa model reached high evaluation metrics (AUROC .86; AUPRC .87, precision, recall, and F1 score of .77 and accuracy of .81). Equally, it outperformed models that used discrete clinical and engineered features and outplayed the performance of other state-of-the-art NLP tools. When the probabilities from the RoBERTa classifier were combined with commonly used predictors in the XGBoost model, a marginal improvement in the overall model's performance was observed (AUROC and AUPRC of .91, with all other metrics the same). Conclusion/implications: We applied a sui generis approach to extract information from the abundant textual surgical data and demonstrated how it can be effectively used for classification prediction, outperforming models relying on conventional structured data. State-of-art NLP applications in biomedical texts can improve modern EOC care.
MeSH term(s)	Humans ; Female ; Cytoreduction Surgical Procedures ; Machine Learning ; Electronic Health Records ; Natural Language Processing ; Carcinoma, Ovarian Epithelial/surgery ; Ovarian Neoplasms/surgery
Language	English
Publishing date	2023-10-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	1328503-8
ISSN	1526-2359 ; 1073-2748
ISSN (online)	1526-2359
ISSN	1073-2748
DOI	10.1177/10732748231209892
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Article ; Online: Ovarian transposition and cervical cancer.

Laios, Alexandros / Duarte Portela, Sara / Papadopoulou, Argyro / Gallos, Ioannis D / Otify, Mohamed / Ind, Thomas

Best practice & research. Clinical obstetrics & gynaecology

2021 Volume 75, Page(s) 37–53

Abstract: Cervical cancer is the fourth most common female malignancy worldwide. As the focus of treatment is shifting towards balancing oncological outcomes with reproductive benefit, women are becoming increasingly aware of their fertility options. Cervical ... ...

Abstract	Cervical cancer is the fourth most common female malignancy worldwide. As the focus of treatment is shifting towards balancing oncological outcomes with reproductive benefit, women are becoming increasingly aware of their fertility options. Cervical cancer is one of the primary malignancies where transposition of the ovaries may be indicated. Ovarian transposition should be performed in pre-menopausal women, undergoing pelvic irradiation to preserve ovarian function and prevent early menopause. The review discusses the available literature and synthesises a concise summary for gynaecologic oncology surgeons to counsel affected women. The paradoxical controversy, leading to its under use is acknowledged, due to the scarcity of published data with regard to functional outcomes, and the lack of clinical trials. In cervical cancer, ovarian transposition remains a safe fertility preservation (FP) option, which is associated with high ovarian function preservation, an acceptable rate of ovarian cysts and a negligible risk for metastases in the transposed ovaries.
MeSH term(s)	Female ; Fertility ; Fertility Preservation ; Genital Neoplasms, Female ; Humans ; Ovary ; Uterine Cervical Neoplasms/surgery
Language	English
Publishing date	2021-02-26
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2050090-7
ISSN	1532-1932 ; 1521-6934
ISSN (online)	1532-1932
ISSN	1521-6934
DOI	10.1016/j.bpobgyn.2021.01.013
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