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1P - Comprehensive assessment of gene mutations revealed overlapping responses for PARPi and chemotherapy in ovarian cancer cells

Presentation Number
1P
Lecture Time
12:20 - 12:25
Speakers
  • Alessandra Tozzi (Basel, Switzerland)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

PARP inhibitors (PARPi) have revolutionized the therapeutic landscape of epithelial ovarian cancer (EOC) treatment, showing outstanding benefits in regards to progression-free survival, especially in patients carrying BRCA1/2 mutations or harboring defects in homologous recombination repair. Yet, it remains uncertain which PARPi to choose and how to select responders by using clinical and molecular characteristics, especially in forefront therapy when platinum sensitivity is unknown.

Methods

Through a systematic literature review and the exploration of publicly available CRISPR-Cas9 library screens and Genomics of Drug Sensitivity in Cancer data, we identified potential genes linked with PARPi response. Using a CRISPR-Cas9 mutagenesis assay, we functionally tested 33 genes for PARPi and carboplatin response in six ovarian cancer (OC) cells lines.

Results

ATM was the only tested gene which induced olaparib sensitivity in a cell line-independent manner. Acquired olaparib sensitivity was also observed upon Cas9-mediated loss of MUS81, NBN, RAD51/B/C, RNASEH2A, PALB2, XRCC1, and XRCC3 in at least 3 out of 6 cell lines. As the major survival benefit of PARPi treatment was reported in chemo-sensitive tumors, we next assessed the effect of top candidate genes on olaparib, niraparib, talazoparib, and carboplatin response. Interestingly, we observed identical effects in a gene- and drug compound-independent manner on acquired drug sensitivity, supporting the strong correlation of cancer cell response to PARPi and chemotherapy. In contrast, we identified CDK12 as an essential gene for cell proliferation/survival in ovarian cancer cells, independent of PARPi and chemotherapy treatment.

Conclusions

Our data suggest a general mechanism of response to PARPi and chemotherapy as demonstrated by various overlapping gene dependencies. The screen of the genetic status of the genes identified correlated with PARPi sensitivity may allow better stratification of patients with increased benefit to this treatment.

Legal entity responsible for the study

The authors.

Funding

Swiss National Science Foundation (CRSII5_171037), Griesbach-Hallenstein Foundation (Walter Edwin Griesbach Award and Olga Hallenstein Award), Department of Biomedicine, University Hospital Basel and University of Basel.

Disclosure

All authors have declared no conflicts of interest.

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2P - Spectrum of BRCA1, BRCA1, ATM and PALB2 alleles in ovarian cancer patients from North Caucasus

Presentation Number
2P
Lecture Time
12:25 - 12:30
Speakers
  • Evgeny Imyanitov (Saint-Petersburg, Russian Federation)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

North Caucasus hosts several large ethnic groups, which preserved their national identity through the course of history. These populations are likely to have a unique pattern of disease-predisposing alleles reflecting the genetic background of their ancestors.

Methods

This study involved 180 ovarian cancer (OC) patients from Chechnya (n = 68), Kabardino-Balkaria (n = 49), North Ossetia (n = 32), Ingushetia (n = 16) and Dagestan (n = 15). The entire coding sequences of BRCA1, BRCA2, ATM and PALB2 genes were analyzed by next-generation sequencing.

Results

OC patients belonging to various ethnic groups had high frequency of BRCA1/2 mutations ranging from 18% to 33%. There were founder pathogenic alleles detected in Chechens (BRCA1 c.3629_3630delAG; 9 out of 15 BRCA1/2 mutations) and North Ossetians (BRCA2 c.6341delC; 6 out 8 BRCA1/2 mutations). Interestingly, Chechen BRCA1 c.3629_3630delAG allele was not present among patients of Ingush ethnicity, despite these nations are believed to have common roots. BRCA2 Q3299X mutation was repeatedly observed across several ethnic groups. Patients from Kabardino-Balkaria had unusually high frequency of germ-line ATM truncating alleles (3/49, 6%); all 3 ATM mutations were represented by distinct ATM pathogenic variants. There were no instances of PALB2 germ-line mutations.

Conclusions

Genetic analysis of ovarian cancer patients is efficient in revealing ethnicity-specific BRCA1/2 mutations. Contribution of BRCA1/2 pathogenic alleles in OC morbidity is high across various ethnic groups. Founder BRCA1/2 alleles are characteristic for some but not all North Caucasus nations.

Legal entity responsible for the study

The authors.

Funding

This study has been supported by the Russian Science Foundation, grant 21-75-30015.

Disclosure

All authors have declared no conflicts of interest.

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3P - Identification of novel biomarkers of response to ATR inhibitors in ARID1A mutant ovarian clear cell carcinoma.

Presentation Number
3P
Lecture Time
12:30 - 12:35
Speakers
  • James R. Stewart (London, United Kingdom)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Ovarian clear cell carcinoma (OCCC) is characterised by a high prevalence of ARID1A mutations and chemotherapy resistance. We previously found that loss of ARID1A causes ATR inhibitor (ATRi) sensitivity, which led to the phase II ATARI clinical trial (NCT04065269). We aim to identify novel genetic determinants of ATRi response in ARID1A-mutant OCCC.

Methods

A genome wide CRISPR knockout (CRISPRn) screen was performed in OCCC TOV21G cells. CRISPR prime gene-editing was used to introduce PPP2R1A p.R183 mutations. In vitro and in vivo ATRi sensitivity was assessed in PPP2R1A isogenic models. Cell cycle analysis was performed via flow cytometry. Phospho-proteomic profiling was performed using mass spectrometry.

Results

A CRISPRn screen in ARID1A mutant OCCC cells identified protein phosphatase 2 (PP2A) complex subunits as ATRi response genes. In OCCC, PPP2R1A missense mutations cause amino acid substitutions at residue p.R183. Characterisation of a cohort of OCCC primary tumours revealed a higher prevalence of structural subunit (PPP2R1A) mutations than previously reported (50%) which frequently co-occurred with ARID1A mutations. ARID1A-mutant OCCC cells with heterozygous PPP2R1A p.R183P or p.R183W mutations displayed enhanced ATRi sensitivity in vitro and in vivo. The most profound cell-cycle defect caused by PPP2R1A missense mutation was an ATRi-induced reduction in active S phase. ATRi exposure in PPP2R1A mutants increased 53BP1 bodies, a mark of residual DNA damage in mitosis. Phospho-proteomic profiling of PPP2R1A mutant OCCC cells revealed the selective increase in phosphorylation of Lysine Deficient Protein Kinase 1 (WNK1) following ATRi exposure, as well as increased phosphorylation of the WNK1 substrate Oxidative Stress Response Kinase 1 (OSR1). Depletion of WNK1 rescued ATRi sensitivity and S phase defects in PPP2R1A mutant cells suggesting a novel role for this kinase.

Conclusions

The ability of PPP2R1A missense mutations to enhance ATRi sensitivity in tumours cells with pre-existing ARID1A mutations suggests that the co-occurrence of these mutations may be better predictors of ATRi sensitivity than either mutation alone. Increased phosphorylation of WNK1 may drive ATRi sensitivity in PPP2R1A mutant cells.

Legal entity responsible for the study

The authors.

Funding

Cancer Research UK.

Disclosure

S. Banerjee: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Genmabs; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Merck Sereno; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Oxcerna; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Shattuk Labs; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Immunogen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Mersana; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche. C. Lord: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: KGaG; Financial Interests, Institutional, Research Grant: Artios; Financial Interests, Personal, Advisory Board: Syncona; Financial Interests, Personal, Advisory Board: Sun Pharma; Financial Interests, Personal, Advisory Board: Gerson Lehrman; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Vertex; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Dark Blue Therapeutics; Financial Interests, Personal, Stocks/Shares: Tango; Financial Interests, Personal, Stocks/Shares: Ovibio; Financial Interests, Personal, Stocks/Shares: Enedra Tx; Financial Interests, Personal, Stocks/Shares: Hysplex; Financial Interests, Personal, Stocks/Shares: Tesselate. All other authors have declared no conflicts of interest.

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4P - Targeting PI3K/AKT/mTOR pathway in platinum-resistant ovarian high-grade serous carcinoma: Translational analysis from the randomized phase II OCTOPUS Trial.

Presentation Number
4P
Lecture Time
12:35 - 12:40
Speakers
  • Gaia Giannone (London, United Kingdom)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

In arm 1 of the phase II randomised OCTOPUS trial (ISRCTN16426935), no significant differences in Progression-Free Survival (PFS) or Overall Survival were observed with the addition of vistusertib (V), a dual mTORC1/2 inhibitor, to weekly paclitaxel (wP) in platinum-resistant/refractory ovarian high-grade serous carcinoma. However, preliminary immunohistochemistry (IHC) data suggested that PTEN status may be predictive of benefit of addition of V to wP. Aim: We evaluated if PTEN expression (scored using quantitative digital IHC) or specific genomic features might be predictive of V benefit. We also compared genomic profiles in archival and study entry specimens.

Methods

PTEN expression in archival samples (N=68) was scored using QuPath Histo-score (H-score; range 0-300), and compared to pathologist scoring. In archival (N=43) and study entry (N=35) samples, DNA copy number (CN) and CN signature exposure were assessed using shallow whole genome sequencing; target sequencing was performed using a custom panel (Illumina AmpliSeq).

Results

Digital quantification of PTEN status was feasible with a high correlation between QuPath and pathologist scores (r=0.94, p<0.0001 for tumour; r=0.70, p=0.009 for non-tumour). H-score variability was lower in non-tumour than in tumour cells. Patients with low PTEN tumours (defined as tumour<non-tumour H-score) showed a longer PFS compared with those with PTEN proficient (tumour≥non-tumour H-score) in the V+wP arm [respectively 9.4 vs 4.1 months (mo) p=0.003] but not in the wP arm (4.8 vs 4.2 mo p=0.60). There was no difference in overall ploidy, rates of focal somatic CN alterations or CN signature exposure between diagnosis and relapse. However, high exposure to CN signature 4 (defined as ≥median signature 4 exposure across all samples) appeared associated with longer PFS (5.4 vs 3.3 mo p=0.125) in the V+wP arm but worse outcome in the wP arm (2.3 vs 4.6 mo p=0.018).

Conclusions

PTEN loss by IHC and high exposure to CN signature 4 both appear to be associated with longer PFS in patients treated with V+wP. Validation in further sample sets will be required.

Clinical trial identification

ISRCTN16426935 (EudraCT 2014-005221-12).

Legal entity responsible for the study

NHS Greater Glasgow and Clyde/University of Glasgow.

Funding

The study has been funded by AstraZeneca, CRUK, the Imperial/China Scholarship Councill, the NIHR Imperial Biomedical Research Centre, Ovarian Cancer Action, Imperial College London.

Disclosure

G. Giannone: Financial Interests, Personal, Other: Mylan; Financial Interests, Personal, Research Grant, ESMO Translational Fellowship: ESMO. A.R. Clamp: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Other, research funding: AstraZeneca. R.M. Glasspool: Financial Interests, Personal, Invited Speaker: AstraZeneca, GlaxoSmithKline, Clovis Oncology; Financial Interests, Personal, Advisory Board: AstraZeneca, GlaxoSmithKline, Clovis Oncology; Financial Interests, Institutional, Other, Research funding: Clovis Oncology, Boehringer Ingelheim; Financial Interests, Personal, Other, Funding to attend virtual conferences: GlaxoSmithKline; Financial Interests, Institutional, Other, Drug Donation Scheme: GlaxoSmithKline. S. Banerjee: Financial Interests, Institutional, Other, Educational Grants: AstraZeneca, GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Genmabs, Immunogen, MSD, Merck Sereno, Mersana, Oncxerna, Seagen, Shattuck Labs; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Clovis, Immunogen, MSD, Mersana, Pfizer, Roche. I. McNeish: Financial Interests, Personal, Invited Speaker: AstraZeneca, GlaxoSmithKline/Tesaro, Clovis Oncology, Roche, Epsila, Takeda, Scancell, Theolytics; Financial Interests, Personal, Advisory Board: AstraZeneca, GlaxoSmithKline/Tesaro, Clovis Oncology, Roche, Epsila, Takeda, Scancell, Theolytics; Financial Interests, Institutional, Other, Institutional grant income: AstraZeneca. All other authors have declared no conflicts of interest.

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5P - HOX Gene Dysregulation in Endometrioid Ovarian Cancer

Presentation Number
5P
Lecture Time
12:40 - 12:45
Speakers
  • Praveena Idaikkadar (Guildford, United Kingdom)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

HOX genes are a group of 39 genes known best for their role in embryonal development. Their function in oncogenesis is an exciting and rapidly developing field. They have been shown to be important in proliferation, epithelial-to-mesenchymal transition and Platinum resistance in other types of cancer, but this is the first study of their role in endometrioid ovarian cancer.

Methods

HOX gene expression was examined in endometrioid ovarian cancer cell lines and tissue using public databanks. This was then verified using Nanostring gene expression assays in a cohort of 56 FFPE samples from patients with EOC. Immunohistochemistry using HOX antibodies was also used to validate gene expression data. HXR9, a small molecule inhibitor of HOX, was used to test the sensitivity of EOC cell line TOV-112D to HOX inhibition using the MTS cell proliferation assay and Incucyte live cell analysis system. HXR9 was also tested for synergy with Platinum chemotherapy using a BLISS analysis and the ability to reverse platinum reistance using a colony formation assay.

Results

Widespread HOX gene dysregulation was observed in public databanks in both EOC cell lines and tumour tissue. This was mirrored in my cohort of 56 patients with EOC. In particular, HOX B5 was over-expressed and HOX D10 was under-expressed in both RNA expression assays and at a protein level. However, there was no correlation between HOX gene expression and clinico-pathological variable such as stage, grade, time to progression or overall survival. HXR9 was able to effectively kill TOV-112D cells with an IC50 40uM. HXR9 worked in synergy with Cisplatin to kill more cells with BLISS values > 10. HXR9 was able to overcome Platinum resistance in the colony formation assay.

Conclusions

HOX genes are dysregulated in endometrioid ovarian cancer and can be targeted for therapeutic purposes. HXR9 is able to kill EOC in a cell line model and work synergistically with Platinum chemotherapy, helping to overcome platinum resistance which is the number one clinical challenge facing patients with advanced ovarian cancer.

Legal entity responsible for the study

University of Surrey.

Funding

GRACE Charity.

Disclosure

All authors have declared no conflicts of interest.

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6P - Urine Spectroscopy coupled with Artificial Intelligence: proof of concept for a new diagnostic tool to detect gynecological cancers

Presentation Number
6P
Lecture Time
12:45 - 12:50
Speakers
  • Francesco Vigo (Basel, Switzerland)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Cancer screening methods transformed cancer management in the last decades. Ideally, a screening tool should be simple, non-invasive, cost-effective, and reliable. These criteria are only partially met for gynecological cancers, for the available screening methods; thus, newer, non-invasive techniques are being investigated. This study assesses the potential of combining Attenuated Total Reflection Fourier-Transform Infrared Spectroscopy (ATR-FTIR) in urine samples with machine learning (ML) algorithms to differentiate tumor patients from healthy controls.

Methods

251 patients were recruited from the gynecological unit of the University Hospital Basel, 72 diagnosed with cancer (22 ovarian, 10 cervical, 25 endometrial, 24 breast, 1 vaginal) and 179 control with confirmed benign histology. After collection, samples were aliquoted and immediately frozen at -80C°. After thawing, 20 μl were deposited on ATR-FTIR crystal and directly measured. Each sample’s spectrum was created averaging 24 measurements, repeated 3 times, obtaining a total of 18072 spectra. Outliers were excluded using a Density-based spatial clustering algorithm. The data obtained were then processed using an “in-house” built algorithm to solve the binary classification of healthy VS cancerous patients.

Results

All data were preprocessed using standardization and constant removal to eliminate noise and went through a Least absolute shrinkage and selector operator (LASSO) feature selection process to select the most valuable parts of the spectra and reduce computational complexity. A set of classification algorithms was tested, including Support Vector Machines, Logistic Regression, Random Forest (RF), and Decision Trees. RF was the most performing reaching an accuracy of 90%. The final model was validated by using a 10-fold cross-validation technique.

Conclusions

This study presents promising results in using ATR-FTIR combined with ML Algorithms to detect urine samples from gynecological tumor patients VS healthy controls. Although we provide a significantly larger data volume than other published studies, further research in larger sample sizes is required to confirm the results and establish a possible screening method.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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7P - Improving Cervical Cancer Screening in Rural India Over a 5 Year Period by Training Paramedical Staff To Use Visual Inspection with Acetic Acid and Thermal Ablation: A Comparison of Cervical Cancer Rates Between Villages With and Without Training

Presentation Number
7P
Lecture Time
12:55 - 13:00
Speakers
  • Sasmith R. Menakuru (Muncie, IN, United States of America)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Cervical cancer is one of the leading cancers among women in India, and there is an increased need for screening as morbidity and mortality from the malignancy can be prevented. The prevention and control of cervical cancer requires a multidisciplinary effort to not only improve awareness but also to establish primary and secondary prevention strategies. As the population in remote villages do not have ease of access to major hospitals, the training of paramedical staff may be a viable option for screening women for cervical cancer.

Methods

19 rural villages with a combined population of 21,798 of whom 4121 were women above the age of 21 who never underwent screening for cervical cancer were selected. 10 villages with a population of 2113 females were willing to partake in the training of paramedical staff to screen for cervical cancer. The results of the number of positives and false positives were recorded over a 5-year span. The other 9 villages with a female population of 1968 that opted out of training paramedical staff were also followed during the same time period. Women who tested positive on VIA were treated with thermal ablation or referred to a higher medical center.

Results

Of the 2113 women screened for cervical cancer by paramedical staff, VIA came back positive in 19.64%. It was found that on biopsy 1.7% had high grade intraepithelial and 1.17% had low grade intraepithelial. 1.98% had cervical intraepitheial neoplasia stage 2 and above. In the 9 villages where training was not done the rates of screening were poor as only 20 women were screened.

Conclusions

There is an ever-growing need for cervical cancer screening in the rural areas of India, and the authors believe that screening through the usage of paramedical staff may be a good option as VIA and thermal ablation are easily done. Our results show that the overall diagnosis rates and the uptake of screening was more in villages with paramedical staff. We believe the implementation of paramedical staff who are trained in VIA and thermal ablation would ultimately lead to a reduction in the rates of cervical cancer and would better health for women in the rural areas.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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8P - 20 years of cervical cancer screening program and the impact on hospitalization rates in the public health system in a state of Brazil

Presentation Number
8P
Lecture Time
13:00 - 13:05
Speakers
  • Ana Maria F. Silva (Aracaju, Brazil)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Cervical cancer is one of the leading causes of death by neoplasia in the world. In Brazil, it is the 3rd cause of women's death by neoplasia. Since its implantation, 20 years ago, the federal program to prevent cervical cancer frequently had logistic and technical difficulties, especially in remote areas. Morbimortality studies are necessary to evaluate the evolution of the prevention program.

Methods

The present study evaluated cervical cancer hospitalizations in the state of Sergipe between 2008 and 2015. The data was extracted from a public database containing information about the unified public health system. The variables age, city of residence and type of hospitalization (clinical or surgical) were analyzed. Changes in hospitalization rates after the introduction of Papanicolaou test as a priority in primary care were considered through a temporal analysis using Joinpoint regression software. For this purpose, it was devised a linear logarithmic model that includes points and calculate the difference from a statistically significant value using a Monte-Carlo permutation test. The Average Annual Percent Change (AAPC), Annual Percent Change (APC) and temporal tendencies in hospitalization frequencies were calculated.

Results

873 hospitalizations were analyzed, the median age was 46 years. Surgical hospitalizations correspond to 67%.The temporal analysis showed a yearly decrease in hospitalizations of about 10%, both for the population living in the capital and in other cities of the state. When the hospitalizations in the whole state were divided by age subgroups, there was a statistically significant reduction in the subgroups 40 to 59 years and 60 years or more.

Conclusions

A consistent reduction in cervical cancer hospitalizations was observed in the state of Sergipe in the analyzed time period. This suggests an improvement after 20 years of the cervical cancer prevention program. Better access to diagnostic methods and appropriate treatment allow for more effective interventions, with fewer hospitalizations. There is, however, a long way to go, especially with regard to expanding health care for the population across the state, also aiming at reducing mortality rates.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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9P - A prospective study of Gefitinib in Patients With Recurrent or Metastatic Carcinoma Cervix

Presentation Number
9P
Lecture Time
13:05 - 13:10
Speakers
  • Abhishek Krishna (Mysore, India)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Cervical cancer is the fourth most common cancers among women worldwide. Although the cure rates in early-stage disease are good, 30% to 40% of patients in advanced-stage disease ultimately develop locoregional or distal recurrence or both. The prognosis of recurrent cervical carcinoma is very poor, and treatment of such patients remains a challenge. Because of the limited success and significant toxicity with cytotoxic chemotherapy drugs in such subset of patients, interest has grown in EGFR targeted therapeutics. This prospective study defines the role of gefitinib in recurrent or metastatic cervical carcinoma.

Methods

The eligible criteria were patients with locoregional recurrence or distant metastasis, not suitable for curative surgery or re-irradiation or for active chemotherapy due to low performance score, patients who developed progression of disease during the salvage chemotherapy; and patients who developed severe toxicity during the course of chemotherapy and therefore could not continue it. Eligible patients were treated with gefitinib at a dose of 250 mg/d orally. It was continued until disease progression or till development of intolerable adverse effects.

Results

A total of 30 patients were enrolled. Median age was 55 years and median disease-free interval was 15 months. Median duration of gefitinib therapy was 6 months. 4 patients had complete response, 8 patient had partial response, 8 patients had stable disease, and 10 patients had progressive disease. None of the patient had severe drug related toxicity.

Conclusions

Gefitinib is tolerated and effective in recurrent or metastatic cervical carcinoma. Further studies are warranted to identify patients who are more likely to benefit from gefitinib.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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10P - Ten-year survival outcome and patterns of failure analysis of patients with localized adenocarcinoma cervix - Our experience from a tertiary cancer care center

Presentation Number
10P
Lecture Time
13:10 - 13:15
Speakers
  • David K. Simson (New Delhi, India)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Presently, the treatment of localized adenocarcinoma cervix patients is the same as squamous cell carcinoma. This study analyzes the long-term survival outcome and pattern of failure of adenocarcinoma patients treated at our institute.

Methods

All ladies diagnosed and treated with localized adenocarcinoma cervix at our institute between 2012 and 2018 were included. These patients were followed up till January 2022. The stages of all patients at the time of diagnosis were restaged according to FIGO 2018. The patient, treatment, and follow-up details were collected from the electronic filing system. Lost-to-follow-up patients were contacted through telephone. The statistical analysis was done using SPSS 23.0.

Results

Adenocarcinoma constituted 7.8% (66 out of 847 patients) of the entire cervical cancer patients detected during the study period – 44% of patients presented with either stage I or II. There were no patients with stage IVa. The median age was 53.5 years (66.7 % were 55 years or less). 69.7% of adenocarcinoma were HPV-associated. The treatment modalities undergone by these patients include radical concurrent chemoradiation and brachytherapy (36.4%), surgery alone (30.3%), surgery followed by adjuvant radiation in (15.2%), and surgery followed by concurrent chemoradiation in (18.2%). All the patients who underwent radiotherapy used the intensity-modulated radiotherapy technique for external beam radiotherapy and image-based adaptive brachytherapy. A few patients (16.7%) received neoadjuvant chemotherapy (NACT) before undergoing curative treatments. The median follow-up period was 54 months. The 10-year overall survival (OS) was 62.2% (84.2% in stage I, 56% in stage II, and 53.1% in stage III). The OS of those who received NACT was 72.7 percent versus 59.9% who did not receive it. Most of the patients who recurred had distant metastasis (64.3%), and the median disease-free interval of those who had distant metastasis was 7 months (2 - 30).

Conclusions

Further molecular studies should be done to better understand this distinctly different subset of cervical cancer patients to tailor the treatment modalities.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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11P - Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer

Presentation Number
11P
Lecture Time
13:15 - 13:20
Speakers
  • Tullio Golia D'Auge (Rome, Italy)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) trial on patterns of care and surgery-related morbidity in early-stage cervical cancer.

Methods

This is a retrospective, multi-institutional study evaluating 90-day surgery-related outcomes of patients undergoing treatment for early-stage cervical cancer before (period I: 01/01/2016-06/01/2018) and after (period II: 01/01/2019-06/01/2021) the publication of the results of the LACC trial.

Results

Charts of 1,295 patients were evaluated: 581 (44.9%) and 714 (55.1%) before and after the publication of the LACC trial, respectively. After the publication of the LACC trial the number of patients treated with minimally-invasive radical hysterectomy decreased from 64.9% to 30.4% (p<0.001). Overall, 90-day complications occurred in 110 (18.9%) and 119 (16.6%) patients in the period I and period II, respectively (p=0.795). Similarly, the number of severe (grade 3 or worse) complications did not differ between the two periods (38 (6.5%) vs. 37 (5.1%); p=0.297). Overall and severe 90-day complications were consistent between periods even evaluating stage IA (p=0.471), IB1 (p=0.929), and IB2 (p=0.074), separately.

Conclusions

The present investigation highlighted that in referral centers the shift from minimally invasive to open radical hysterectomy does not influence 90-day surgery-related morbidity.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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12P - Any size of lymph node metastasis should be considered N1 in patients with cervical cancer

Presentation Number
12P
Lecture Time
13:20 - 13:25
Speakers
  • David Cibula (Prague, Czech Republic)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Classification of lymph node metastases according to the size into macrometastases >2 mm (MAC), micrometastases 0.2 - 2 mm (MIC) and isolated tumor cells <0.2 mm (ITC) was adopted from breast cancer to other tumour types. In cervical cancer, MAC is well established as one of the main prognostic factors, indicating adjuvant treatment after primary surgery, while the impact of MIC and ITC has been subject of controversy. The aim of this study was to identify the cut-off for the minimal size of metastasis which is not associated with negative prognosis.

Methods

Data of 967 cervical cancer patients, T1a1 L1 - T2b stages, after primary surgical treatment with curative intent, including SLN biopsy followed by pathological ultrastaging, were obtained from the SCANN (Surveillance in Cervical CANcer) study. The size of SLN metastasis was considered a continuous variable, and multiple testing was performed for cut-offs ranging from 0.01 to 1.0 mm in 0.01 mm intervals. DFS in each subgroup was compared with the N0 cohort and each N1 group (> cut-off) using Log rank test.

Results

Positive SLN was found in 172 (18%) patients. Based on traditional classification, MAC, MIC, and ITC was the largest metastasis in 79 (8%), 54 (5%), and 39 (4%) cases. Patients with MAC and MIC had significantly shorter DFS than those with N0 disease (HR 2.20, p=0.003; HR 2.87, p < 0.001) with no difference between them (p=0.484). When subgroups were analysed using cut-off method, all patients with metastases ≥0.4 mm had significantly shorter DFS when compared to the N0 (HR = 2.311; p=0.04). The significance of metastases <0.4 mm could not be assessed due to the lack of power (<80%).

Conclusions

Lymph node metastases in patients with cervical cancer are associated with significantly negative impact on DFS irrespective of their size. No cut-off value for a minimal size of metastasis without negative prognostic impact can be found. Therefore, traditional classification to MAC/MIC/ITC should not be adopted in cervical cancer and the management should be uniform irrespective of the size of metastasis.

Legal entity responsible for the study

The authors.

Funding

Charles University, Prague (UNCE 204065 and PROGRES Q28/LF1).

Disclosure

All authors have declared no conflicts of interest.

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