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Female Urogenital Diseases and Pregnancy Complications

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Cola

Women with histological diagnosis of cancer of the endometrium (any type) undergoing hysterectomy

Women with histological diagnosis of endometrial hyperplasia (with or without atypia) undergoing hysterectomy

Healthy women undergoing hysterectomy for a benign reason

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.

Information about clinical risk factors for endometrial cancer and endometrial hyperplasia

* 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.

Blood and endometrial tissue 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.

Lymph node sampling

Roberta Schiemer, MBBS

Ketankumar Gajjar, MD

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.

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.

Specimens will be retained for the duration of the study

Vibrational Spectroscopy for Endometrial Cancer Diagnosis

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

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.

Identification of the most important wavenumbers that distinguish between normal, hyperplasia and cancer

sub-analysis of segregation percentages for pre-cancerous changes (non-atypical / atypical hyperplasia) and cancer subtypes

Calculation of inter- and intra- user classification variability

Multivariate analysis of variance will be calculated to account for factors potentially affecting test performance (histological subtype, menopausal status, age, co-morbidities, hormonal treatment)

Nottingham University Hospitals NHS Trust

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Methionine

Lymph node sampling will take place pretreatment and pre-surgery. Participants receive 12 weeks of chemotherapy (vincristine, dactinomycin and cyclophosphamide). They are then evaluated to determine how the tumor responded to treatment. Twelve additional weeks of chemotherapy (vincristine and dactinomycin) is given, followed by evaluation for tumor response. No further treatment is given, and participants are observed closely. Myeloid growth factor is given if needed.

Participants also receive \^1\^1C-methionine as described in the intervention section.

Lymph node sampling will take place pretreatment and pre-surgery. Participants receive 12 weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide). The tumor is evaluated to determine how it responded to treatment. Radiation therapy and/or surgical resection is performed to destroy or remove the remaining tumor. Twelve additional weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide) is given, followed by evaluation for tumor response. If delayed for medical reasons, radiation therapy and/or surgical resection is done at this time. Participants then receive 16 weeks of additional chemotherapy (vincristine, dactinomycin and cyclophosphamide). No further treatment is given, and participants are observed closely. Myeloid growth factor will be given if needed.

Participants also receive \^1\^1C-methionine as described in the intervention section.

Lymph node sampling takes place pretreatment and pre-surgery. Participants receive 12 weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide). The tumor is evaluated for treatment response. Radiation therapy and/or surgical resection is done. Twelve weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide) is followed by evaluation for tumor response. If delayed for medical reasons, radiation therapy and/or surgical resection is done at this time. Participants receive 16 weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide) followed by 12 weeks of maintenance treatment (bevacizumab, sorafenib, oral cyclophosphamide). No further treatment is given, and participants are observed closely. Myeloid growth factor is given if needed.

Participants also receive \^1\^1C-methionine as described in the intervention section.

Lymph node sampling takes place pretreatment and pre-surgery. Participants receive 6 weeks (2 cycles) chemotherapy (vincristine and irinotecan). The tumor is evaluated for treatment response. 3 cycles of chemotherapy \[vincristine, doxorubicin, cyclophosphamide/ifosfamide, etoposide (or etoposide phosphate) (VDC/IE)\] are given. Dexrazoxane is given prior to each dose of doxorubicin. Radiation therapy begins at week 4 or 20 (depending on tumor location) while receiving vincristine and irinotecan. 2 cycles of VDC/IE, 4 cycles of modified vincristine, dactinomycin, cyclophosphamide (VAC), then 2 cycles of modified vincristine/irinotecan (total of 54 weeks). High risk participants also receive additional maintenance therapy beginning week 55 with anti-angiogenic chemotherapy (bevacizumab, sorafenib, cyclophosphamide). Myeloid growth factor is given as needed.

Participants also receive \^1\^1C-methionine as described in the intervention section.

Dosage and route of administration:

* \< 1 year of age=0.025 mg/kg intravenously (IV)
* \> 1 year and \< 3 years= 0.05 mg/kg IV
* ≥ 3 years=1.5 mg/m\^2 IV. Maximum dose 2 mg in all participants.

Dosage and route of administration:

* \< 1 year=0.025 mg/kg IV push
* ≥ 1 year=0.045 mg/kg IV push over 1 to 5 minutes.

Dosage and route of administration:

During VAC chemotherapy:

* \< 3 years of age = 40 mg/kg IV
* ≥ 3 years of age = 1200 mg/m\^2 IV, with MESNA.

During maintenance for intermediate-risk participants:

* oral cyclophosphamide 50 mg/m\^2/dose/day (liquid or tablet)

Surgery will be performed for the primary site tumor with the goal of removing tumor cells while maintaining function in the organ or adjacent organs involved.

Surgical Resection

Radiation therapy will be delivered at approximately week 13 (intermediate risk) or week 19 (high risk) after initiation of chemotherapy. Certain patients will receive radiation at week 4.

Radiation

Dosage and route of administration: 15 mg/kg/dose/day IV.

Dosage and route of administration: 90 mg/m\^2/dose twice daily.

If a participant's chemotherapy has been delayed or modified for hematologic toxicity, or if participant experiences a significant life-threatening toxicity due to bone marrow suppression, myeloid growth factor (either filgrastim or peg-filgrastim) will be given per institutional practice.

High Risk participants receive filgrastim 5 micrograms/kg/day (maximum 300 micrograms) subcutaneously beginning 24-36 hours after the last dose of chemotherapy. Continue at least 7 days, or until the ANC ≥750/µL whichever comes last. Sargramostim or peg-filgrastim may not be used.

Myeloid Growth Factor

Clinical and/or imaging evaluation of regional lymph nodes will be conducted pretreatment and preoperatively as part of staging. This will aid in determining the efficacy of this procedure in defining involved lymphatics in "at risk" patients.

Lymph Node Sampling

Dosage and Route Administration: During interval compressed therapy - irinotecan 50mg/m\^2 IV (maximum dose 100 mg/day) daily x 5.

Dosage and Route of Administration: During interval compressed therapy - Age \> 1 year: 1800 mg/m\^2/day IV x 5 Age \<1 year: treat with 50% doses calculated on a m\^2 basis.

Dosage and Route of Administration:

Age \>1 year 100 mg/m\^2/day IV x 5 Age \< 1 year treat with 50% doses calculated on a m\^2 basis

Dosage and Route of Administration: Used in substitution for etoposide in participants who experience allergic reaction. It will be administered 100 mg/m\^2/day IV.

Etoposide Phosphate

Dosage and route of Administration:

Age ≥1 year, 37.5 mg/m\^2 IV over 1 hour x 2 days Age \<1 year, 18.75 mg/m\^2 (i.e., a 50% dose reduction) IV over 1 hour x 2 days.

Dosage and Route of Administration: Dexrazoxane dose should be 10x that of doxorubicin.

Age ≥1 year, 375 mg/m\^2 IV over 15-30 minutes Age \<1 year, 187l.5 mg/m\^2 (i.e., a 50% dose reduction) IV over 15-30 minutes.

Participants receive \^1\^1C-methionine to relate the distribution, intensity and change in \^1\^1C-methionine CTPET imaging of the primary site to tumor control and patient outcome.

^1^1C-methionine

Matthew J. Krasin, MD

This study will treat participants with newly diagnosed, low, intermediate and high risk rhabdomyosarcoma (RMS) using multi-modality risk-adapted therapy with standard or intensified dose chemotherapy, radiation and surgical resection. Intermediate and high risk participants will receive an additional 12 weeks (4 cycles) of maintenance therapy with anti-angiogenic chemotherapy.

PRIMARY OBJECTIVE:

* Estimate event-free survival for intermediate risk participants treated with vincristine, dactinomycin and cyclophosphamide with the addition of maintenance anti-angiogenic therapy.

SECONDARY OBJECTIVES:

* Estimate the false negative rate and incidence of additional positive lymph nodes in participants undergoing sentinel lymph node biopsy followed by limited nodal dissection.
* Maintain a high local control rate in participants treated with surgery and/or limited volume proton and photon radiation without dose escalation.
* Define the incidence and type of failure in participants who receive risk-adapted local therapy relative to the primary tumor volume.
* Establish the feasibility of delivering 4 cycles of maintenance anti-angiogenic chemotherapy in intermediate and high risk patients following standard chemotherapy.
* Estimate the event free survival for high risk patients receiving interval dose compressed therapy and maintenance anti-angiogenic therapy.
* Define the incidence of CTC grade 3 and higher toxicities (and specific grade 1-2 toxicities) related to proton beam therapy.

Participants will be stratified based on both a pretreatment staging system and a post-surgery surgico/pathologic clinical grouping system. Treatment for low-risk (subset 1) participants will consist of chemotherapy and radiation. Low-risk (subset 2) and intermediate-risk participants will receive chemotherapy and radiation and/or undergo surgery to destroy/remove the tumor. Intermediate-risk participants will also receive 16 weeks of maintenance chemotherapy. High-risk participants will receive chemotherapy and radiation therapy. High-risk participants will also receive additional maintenance therapy with anti-angiogenic chemotherapy.

Risk-Adapted Focal Proton Beam Radiation and/or Surgery in Patients With Low, Intermediate and High Risk Rhabdomyosarcoma Receiving Standard or Intensified Chemotherapy

To estimate event-free survival for intermediate risk participants treated by vincristine-dactinomycin-cyclophosphamide (VAC) with the addition of maintenance anti-angiogenic therapy

To estimate event-free survival for high risk participants.

Estimate the false negative rate and incidence of additional positive lymph nodes in participants undergoing sentinel lymph node biopsy followed by limited nodal dissection.

Maintain a high local control rate in participants treated with surgery and / or limited volume proton and photon radiation without dose escalation

Define the incidence and type of failure in participants who receive risk-adapted local therapy relative to the primary tumor volume

Establish the feasibility of delivering 4 cycles of maintenance antiangiogenic chemotherapy (bevacizumab / sorafenib / low dose cyclophosphamide) in intermediate risk patients following standard chemotherapy.

Establish the feasibility of delivering 4 cycles of maintenance antiangiogenic chemotherapy (bevacizumab / sorafenib / low dose cyclophosphamide) in high risk patients following standard chemotherapy.

Define the incidence of CTC grade 3 and higher toxicities (and specific grade 1-2 toxicities) related to proton beam therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Vibrational Spectroscopy for Endometrial Cancer Diagnosis	NCT05026073	Endometrial Can... Endometrial Hyp...	Information abo... Blood and endom... Lymph node samp...	18 Years - 90 Years	Nottingham University Hospitals NHS Trust
Risk-Adapted Focal Proton Beam Radiation and/or Surgery in Patients With Low, Intermediate and High Risk Rhabdomyosarcoma Receiving Standard or Intensified Chemotherapy	NCT01871766	Rhabdomyosarcom...	Vincristine Dactinomycin Cyclophosphamid... Surgical Resect... Radiation Bevacizumab Sorafenib Myeloid Growth ... Lymph Node Samp... Irinotecan Ifosfamide Etoposide Etoposide Phosp... Doxorubicin Dexrazoxane ^1^1C-methionin...	- 21 Years	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for lymph node sampling