Vibrational Spectroscopy for Endometrial Cancer Diagnosis (SPEED)

Application of Vibrational Biospectroscopy as a Novel Diagnostic Tool in Endometrial Cancer

The purpose of this study is to investigate the ability of vibrational spectroscopic techniques, Raman spectroscopy and Attenuated Total Reflection - Fourier Transform Infrared spectroscopy (ATR-FTIR), to accurately differentiate endometrial tissue, lymph nodes and blood samples with womb cancer or endometrial hyperplasia from healthy controls.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Hyperplasia; Endometrial Cancer
• Intervention / Treatment: Behavioral: Information about clinical risk factors for endometrial cancer and endometrial hyperplasia; Procedure: Blood and endometrial tissue sampling; Procedure: Lymph node sampling

Detailed Description

Womb cancer is the sixth most common cancer in women, with rising incidence worldwide. Current diagnostic strategies are time consuming, invasive and have limited accuracy, furthermore there is no population-wide screening. Treatment depends on patients' health, type of disease and spread at the time of diagnosis. Most women will be offered surgery, however the role of lymph node dissection in early stage disease remains controversial.

There is therefore a need for an objective, accurate test, able to detect pre-cancer and cancer early and able to identify metastatic node involvement, so that lymph node excision is performed only when necessary.

Attenuated Total Reflection - Fourier Transform Infrared (ATR-FTIR) spectroscopy and Raman spectroscopy are non-invasive, objective techniques that use the interaction of light within tissues to gain detailed information about the chemical composition of biological samples. These methods have shown tremendous potential for improving diagnosis and treatment of cancer.

This study aims to use Vibrational Spectroscopy to examine blood plasma and serum, endometrial biopsies via Pipelle device and pelvic/para-aortic lymph nodes for the presence of endometrial pre-cancer and cancer changes. The analyses will be performed on fresh (wet) as well as dried samples.

The ultimate goal is to develop a point-of-care test and an intra-operative tool for endometrial cancer screening and diagnosis. Such a test could speed up endometrial cancer diagnosis, reduce treatment delays and individualise patients care.

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: Roberta Schiemer, MBBS; Phone Number: 0115 969 1169; Email: roberta.schiemer@nottingham.ac.uk
• Study Contact Backup: Name: Ketankumar Gajjar, MD; Phone Number: 0115 969 1169; Email: ketankumar.gajjar@nuh.nhs.uk

Study Locations

• United Kingdom
  • England
    • Nottingham, England, United Kingdom, NG5 1PB
      • Recruiting
      • Nottingham University Hospitals NHS Trust
      • Contact: Roberta Schiemer, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women undergoing hysterectomy with a histological diagnosis of primary cancer of the endometrium (irrespective of subtype), or endometrial hyperplasia (with or without atypia) and women undergoing hysterectomy for a benign indication.

Description

Inclusion Criteria:

1. Endometrial cancer group:

   • Established histopathological diagnosis of cancer of the endometrium (any stage and subtype)
   • Patients must be eligible for primary staging surgery (any route, e.g. laparoscopy and laparotomy)

2. Endometrial hyperplasia group:

   • Established histopathological diagnosis of endometrial hyperplasia (with or without atypia)
   • Treatment with hysterectomy deemed necessary

3. Control group

   • Healthy with benign disease, non-malignancy
   • Undergoing hysterectomy (any route, e.g. laparoscopy and laparotomy)

Exclusion Criteria:

• Patient's refusal / inability to consent
• Synchronous gynaecological cancer (ovary, cervix, fallopian tubes)
• Previous pelvic radiotherapy
• Previous hysterectomy
• Undiagnosed vaginal bleeding
• Previous endometrial ablation

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1 Endometrial Cancer: Women with histological diagnosis of cancer of the endometrium (any type) undergoing hysterectomy	Behavioral: Information about clinical risk factors for endometrial cancer and endometrial hyperplasia; age, race, parity, body mass index, last menstrual period, menstrual cycle type, hypertension, type II diabetes, anovulation, polycystic ovary syndrome, indication for hysterectomy and smoking history. Other epidemiologic risk factors including tamoxifen exposure, history of breast cancer, current hormone therapy use, anticoagulant use, oral contraception use, family history of endometrial, breast or colon cancer.; Procedure: Blood and endometrial tissue sampling; All women will undergo planned hysterectomy.; Venous blood sample will be collected prior to surgery.; Endometrial sampling via Pipelle device will be performed immediately prior to hysterectomy; Endometrial biopsy from the hysterectomy specimen will be obtained under direct vision The plasma and serum obtained from the blood samples will be analysed with ATR-FTIR and Raman spectroscopes. Spectra from both wet and dry specimens will be recorded. All tissue samples retrieved will be placed in Phosphate Buffered Solution for transfer to the histopathology laboratory. Spectra will be collected from the fresh samples with ATR-FTIR and Raman spectroscopes. Spectral analyses will subsequently be repeated on dry samples post fixation and processing. All tissue samples will undergo haematoxylin and eosin staining after spectral analysis for standard histopathological confirmation.; Procedure: Lymph node sampling; Lymph nodes will be excised if recommended as part of the standard treatment for endometrial cancer. Each node will be cut in half or in quarters, depending on size, to expose the core. Wet and dry spectral analysis will be performed, followed by staining for histopathological confirmation.
Group 2 Endometrial Hyperplasia: Women with histological diagnosis of endometrial hyperplasia (with or without atypia) undergoing hysterectomy	Behavioral: Information about clinical risk factors for endometrial cancer and endometrial hyperplasia; age, race, parity, body mass index, last menstrual period, menstrual cycle type, hypertension, type II diabetes, anovulation, polycystic ovary syndrome, indication for hysterectomy and smoking history. Other epidemiologic risk factors including tamoxifen exposure, history of breast cancer, current hormone therapy use, anticoagulant use, oral contraception use, family history of endometrial, breast or colon cancer.; Procedure: Blood and endometrial tissue sampling; All women will undergo planned hysterectomy.; Venous blood sample will be collected prior to surgery.; Endometrial sampling via Pipelle device will be performed immediately prior to hysterectomy; Endometrial biopsy from the hysterectomy specimen will be obtained under direct vision The plasma and serum obtained from the blood samples will be analysed with ATR-FTIR and Raman spectroscopes. Spectra from both wet and dry specimens will be recorded. All tissue samples retrieved will be placed in Phosphate Buffered Solution for transfer to the histopathology laboratory. Spectra will be collected from the fresh samples with ATR-FTIR and Raman spectroscopes. Spectral analyses will subsequently be repeated on dry samples post fixation and processing. All tissue samples will undergo haematoxylin and eosin staining after spectral analysis for standard histopathological confirmation.
Group 3 Controls: Healthy women undergoing hysterectomy for a benign reason	Behavioral: Information about clinical risk factors for endometrial cancer and endometrial hyperplasia; age, race, parity, body mass index, last menstrual period, menstrual cycle type, hypertension, type II diabetes, anovulation, polycystic ovary syndrome, indication for hysterectomy and smoking history. Other epidemiologic risk factors including tamoxifen exposure, history of breast cancer, current hormone therapy use, anticoagulant use, oral contraception use, family history of endometrial, breast or colon cancer.; Procedure: Blood and endometrial tissue sampling; All women will undergo planned hysterectomy.; Venous blood sample will be collected prior to surgery.; Endometrial sampling via Pipelle device will be performed immediately prior to hysterectomy; Endometrial biopsy from the hysterectomy specimen will be obtained under direct vision The plasma and serum obtained from the blood samples will be analysed with ATR-FTIR and Raman spectroscopes. Spectra from both wet and dry specimens will be recorded. All tissue samples retrieved will be placed in Phosphate Buffered Solution for transfer to the histopathology laboratory. Spectra will be collected from the fresh samples with ATR-FTIR and Raman spectroscopes. Spectral analyses will subsequently be repeated on dry samples post fixation and processing. All tissue samples will undergo haematoxylin and eosin staining after spectral analysis for standard histopathological confirmation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vibrational Spectroscopy diagnostic accuracy	The primary outcome of the study will be to evaluate the correct classification of cases of endometrial cancer, endometrial hyperplasia and controls by Raman and ATR-FTIR spectral analysis, compared to histopathology as the standard of reference. The outcome will be measured with sensitivity, specificity, positive/negative predictive values and likelihood ratios. The diagnostic accuracy will be documented for pipelle samples, endometrial samples from hysterectomy specimens, pelvic/para-aortic lymph nodes, blood serum and plasma.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Discriminating wavenumbers	Identification of the most important wavenumbers that distinguish between normal, hyperplasia and cancer	Baseline
Sub-analysis of endometrial cancer and hyperplasia sub-types	sub-analysis of segregation percentages for pre-cancerous changes (non-atypical / atypical hyperplasia) and cancer subtypes	Baseline
Test reliability	Calculation of inter- and intra- user classification variability	Baseline
Multivariate analysis of patient and tumour characteristics	Multivariate analysis of variance will be calculated to account for factors potentially affecting test performance (histological subtype, menopausal status, age, co-morbidities, hormonal treatment)	Baseline

Collaborators and Investigators

• Sponsor: Nottingham University Hospitals NHS Trust
• Investigators: Principal Investigator: Ketankumar Gajjar, MD, Nottingham University Hospitals NHS Trust

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 19, 2020
• Primary Completion (ANTICIPATED): August 1, 2023
• Study Completion (ANTICIPATED): November 1, 2024

Study Registration Dates

• First Submitted: August 23, 2021
• First Submitted That Met QC Criteria: August 23, 2021
• First Posted (ACTUAL): August 30, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 30, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: endometrial cancer; Spectroscopy; endometrial hyperplasia; Raman spectroscopy; uterine neoplasm; cancer of the endometrium; Fourier Transform Infrared spectroscopy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Hyperplasia; Endometrial Hyperplasia; Endometrial Neoplasms
• Other Study ID Numbers: 19ON033

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No