Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06521060
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2023-12-03
Brief Title:
The Role of Pre-Surgical Tru - Cut Biopsy in the Management of Atypical Myometrial Lesions
Sponsor:
None
Organization:
None
Study Overview
Official Title:
The Role of Pre-Surgical Tru - Cut Biopsy in the Management of Atypical Myometrial Lesions
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MYSTR
Brief Summary:
The Tru-cut biopsy TCB for targeting pelvic tumors is well established in gynecologic oncology However its reliability for differentiating of uterine sarcoma in myoma-like uterine lesions has been confirmed by only a few studies which were either retrospective or provided only pilot result on the limited number of prospectively enrolled patients N34 Proving that preoperative TCB can provide accurate information about the histological nature of the tumor would have great impact for setting an adequate tailored oncologically safe approach especially in patients with sonographically atypical lesions Additionally the biopsy should be safe with transcervical transuterine cavity in organ biopsy approaches preferred to avoid the risk of needle canal contamination if sarcoma is diagnosed The purpose of this study is to evaluate the accuracy of the Tru-cut biopsy TCB of sonographically atypical myometrial lesions as a complementary diagnostic method in the preoperative management of patients scheduled for uterus preserving procedure or hysterectomy Additionally we aim to assess the impact of this procedure on patients quality of life and clinical management MYSTR is a single arm prospective multicentric cohort study
Detailed Description:
A total of 250 patients is planned to be enrolled accounting for an estimated 15 dropout rate Study data will be collected and managed using REDCap Research Electronic Data Capture open-source platform which allows for the secure collection of research data via a web-based interface REDCap was developed by Vanderbilt University in Nashville Tennessee is used by Charles University in Prague under a standing agreement to allow the usage of REDCap for academic and research purposes The REDCap platform environment is compliant with 21 CFR Part 11 FISMA HIPAA and GDPR
Patients will be identified at each of the participating site If a patient meets all inclusion criteria she will be informed about the study and asked to sign an informed consent ICF All patients referred for TCB will have their blood count and baseline coagulation parameters checked prior to performing the biopsy to eliminate bleeding complications All patients will undergo a standard-of-care ultrasound examination with a focus on the description of the fibroid with atypical features according to the MUSA statement andor Basel sarcoma scale score BSS A patient will be included in the study if she will meet one or more of the following MUSA criterion irregular tumor borders cystic areas in the lesion as a sign of central necrosis nonuniform echogenicity moderate-to-abundant intralesional vascularity and an absence of calcifications andor BSS total score 1
The patient will be further referred to MRI imaging optional and will undergo TCB within 4 weeks after US exam In selected centers which will decide to participate in this optional part of the trial all patients with 1 MUSA criterion andor BSS total score 1 based on the US examination will be referred for MRI imaging Images will be acquired with 3T MRI The sequences parameters Sagittal T2 Coronal T2 Axial T2 Axial DWI Axial T1 3D DIXON Axial Perfusion T1 3D Axial T1 3D DIXON post contrast will be evaluated in accordance with European Society of Urogenital Radiology ESUR guidelines Two experienced readers in gynecologic oncology imaging will review all MRI images and calculate the MRI score
The tru-cut biopsy is performed as an out-patient procedure without the need of any anesthesia in lithotomic position Using an automatic biopsy gun and 18-gauge disposable core tissue biopsy needle four tissue cylinder samples are taken from the tumor If the localization of the lesion and anatomical conditions allow the transcervical approach without breaking the continuity of the perimetrium is preferred If the lesion is localized in the uterine doom or targetable by the uterine cavity the transcervical canal approach is feasible and should be considered If both above-described methods are not feasible a transvaginal approach is also possible In all cases transvaginal US is used for correct navigation Patients will be observed for 30 minutes following the biopsy and then discharged Other follow up of the patients will be done 24 hours and two weeks after the procedure via phone with the assessment of the patients pain overall experience and eventual complications
Intraoperative and early post-procedural complications will be evaluated and adverse events will be assessed on the 14th post-TCB day according to the Clavien-Dindo Surgical complications classification Pain will be assessed during the TCB 30 minutes after the procedure and after 24 hours using the Numeric rating scale NRS Overall experience will be assessed using questionnaire FACIT-TS-G Version 4 30 minutes after the procedure
Specimen evaluation will be conducted at each participating site by dedicated experienced pathologist according to standard diagnostic procedures The biological nature of spindle cell leiomyocellular tumors will be determined according to Table 2 modified from the WHO classification of female genital tumors 2020
If necessary immunohistochemical or molecular examination will be used For smooth muscle lesions the gene mutation status of PTEN pRb TP53 MTAP ATRX and DAXX will be analyzed In lesions of other histological types RNA next-generation sequencing will be performed optionally accompanied by immunohistochemical examination These examinations are routinely performed as a part of standardized diagnostic procedures and will not be covered by the projects expenses Histology findings from other than the main sight that will fail to meet the characteristics of conventional leiomyoma either from TCB or definitive histology result will undergo a second evaluation at the main site by a senior gyneco-pathologist Following samples will be stored in biobanks at each respective institution tumor sample DNA isolated from one snap-frozen TCB sample representative formalin-fixed paraffin-embedded FFPE tumor tissue block and representative FFPE non-tumor myometrial tissue block both harvested during curative surgery All samples will be collected with the intention to be used for future translational and exploratory research including studies that aim to evaluate the association between biomarkers and clinical-surgical-pathological characteristics All samples will be stored in the biobank at the respective institution Participation in the translatory part is not obligatory for the trial participation but is highly recommended A separate consent form will be provided to the patient to obtain permission for all biological material storage and future translational studies Based on the histology result obtained from the TCB patients will be categorized into three groups Subsequent clinical management will be determined according to the appropriate group
Subgroup 1 Patients with a typical benign histological result of TCB will undergo elective surgery within 8 weeks from receiving the results with a preference of a minimally invasive approach ie most often laparoscopic myomectomy or laparoscopic hysterectomy
Subgroup 2 Patients with an atypical histological result of TCB ie other than conventional leiomyoma but with no signs of malignancy will undergo elective surgery within 6 weeks from receiving the results with a preference of laparoscopy but excluding unprotected power morcellation of pathological tissue
Uncontained morcellation will be used strictly for tumors with benign TCB histology and nonsuspicious perioperative appearance of resected uterine tumor Contained morcellation technique will be strictly preferred for all other tumors ie with non-standard TCB histology andor atypical or suspicious perioperative appearance or standard TCB histology and atypical or suspicious perioperative appearance
Subgroup 3 Patients with a histological result from the TCB that are clearly malignant or suspicious for malignancy undergo open surgery specifically abdominal hysterectomy In cases of women with incomplete reproductive plans open resection of the tumor may be performed after detailed consultation with the oncogynecological team and the patient a secondary hysterectomy may be added based on the result of definitive histology The procedure should be done as soon as possible with a maximum interval between the result of TCB histology and elective surgery no more than 3 weeks
In cases of tumors without penetration through the uterine serosa according to US and perioperatively and without requiring morcellation for the specimen evacuation total laparoscopic hysterectomy can be performed
Subgroup 4 In case of invalid TCB histology result the patient will undergo contained morcellation during laparoscopic procedure or open surgery within 4 weeks after the TCB
The definitive histology results from the surgery will be evaluated using the same histopathological criteria as in TCB histology Definitive histology will be compared with the histological results from the pre-surgical TCB
For the primary endpoint analysis the accuracy of the histological results from TCB will be established using the definitive postoperative histological results as a reference standard
The sample size of 217 patients with sonographically atypical myometrial lesions was calculated to establish the accuracy of the diagnostic method with the degree of estimate precision of 007 95 confidence and 80 power assuming ratio between patients with without atypical lesion as per final pathology of 2377 as based on the retrospective database data Considering a possible dropout or unavailability of data in 15 of the patients the final sample size reaches 250 patients Analysis was computed using PASS 13 Power Analysis and Sample Size Software 2014 NCSS LLC Kaysville Utah USA ncsscomsoftwarepass
If this trial proves the accuracy of TCB of myometrial lesion it could provide a new diagnostic tool and significantly impact the clinical practice
A positive study outcome could establish level A evidence for a change of international standards and implement prehabilitation into a routine clinical practice On a national level the study aims to standardize and improve the care for gynecological patients with sonographic atypical myometrial lesions A primary endpoint final analysis is intended for publication in a top medical journal The study could also provide prospective genomic characterization analyses of myometrial tumors as well as the exploratory analysis of the reliability of individual imaging methods in the preliminary selection of patients with atypical myometrial findings
Patients will be identified at each of the participating site If a patient meets all inclusion criteria she will be informed about the study and asked to sign an informed consent ICF All patients referred for TCB will have their blood count and baseline coagulation parameters checked prior to performing the biopsy to eliminate bleeding complications All patients will undergo a standard-of-care ultrasound examination with a focus on the description of the fibroid with atypical features according to the MUSA statement andor Basel sarcoma scale score BSS A patient will be included in the study if she will meet one or more of the following MUSA criterion irregular tumor borders cystic areas in the lesion as a sign of central necrosis nonuniform echogenicity moderate-to-abundant intralesional vascularity and an absence of calcifications andor BSS total score 1
The patient will be further referred to MRI imaging optional and will undergo TCB within 4 weeks after US exam In selected centers which will decide to participate in this optional part of the trial all patients with 1 MUSA criterion andor BSS total score 1 based on the US examination will be referred for MRI imaging Images will be acquired with 3T MRI The sequences parameters Sagittal T2 Coronal T2 Axial T2 Axial DWI Axial T1 3D DIXON Axial Perfusion T1 3D Axial T1 3D DIXON post contrast will be evaluated in accordance with European Society of Urogenital Radiology ESUR guidelines Two experienced readers in gynecologic oncology imaging will review all MRI images and calculate the MRI score
The tru-cut biopsy is performed as an out-patient procedure without the need of any anesthesia in lithotomic position Using an automatic biopsy gun and 18-gauge disposable core tissue biopsy needle four tissue cylinder samples are taken from the tumor If the localization of the lesion and anatomical conditions allow the transcervical approach without breaking the continuity of the perimetrium is preferred If the lesion is localized in the uterine doom or targetable by the uterine cavity the transcervical canal approach is feasible and should be considered If both above-described methods are not feasible a transvaginal approach is also possible In all cases transvaginal US is used for correct navigation Patients will be observed for 30 minutes following the biopsy and then discharged Other follow up of the patients will be done 24 hours and two weeks after the procedure via phone with the assessment of the patients pain overall experience and eventual complications
Intraoperative and early post-procedural complications will be evaluated and adverse events will be assessed on the 14th post-TCB day according to the Clavien-Dindo Surgical complications classification Pain will be assessed during the TCB 30 minutes after the procedure and after 24 hours using the Numeric rating scale NRS Overall experience will be assessed using questionnaire FACIT-TS-G Version 4 30 minutes after the procedure
Specimen evaluation will be conducted at each participating site by dedicated experienced pathologist according to standard diagnostic procedures The biological nature of spindle cell leiomyocellular tumors will be determined according to Table 2 modified from the WHO classification of female genital tumors 2020
If necessary immunohistochemical or molecular examination will be used For smooth muscle lesions the gene mutation status of PTEN pRb TP53 MTAP ATRX and DAXX will be analyzed In lesions of other histological types RNA next-generation sequencing will be performed optionally accompanied by immunohistochemical examination These examinations are routinely performed as a part of standardized diagnostic procedures and will not be covered by the projects expenses Histology findings from other than the main sight that will fail to meet the characteristics of conventional leiomyoma either from TCB or definitive histology result will undergo a second evaluation at the main site by a senior gyneco-pathologist Following samples will be stored in biobanks at each respective institution tumor sample DNA isolated from one snap-frozen TCB sample representative formalin-fixed paraffin-embedded FFPE tumor tissue block and representative FFPE non-tumor myometrial tissue block both harvested during curative surgery All samples will be collected with the intention to be used for future translational and exploratory research including studies that aim to evaluate the association between biomarkers and clinical-surgical-pathological characteristics All samples will be stored in the biobank at the respective institution Participation in the translatory part is not obligatory for the trial participation but is highly recommended A separate consent form will be provided to the patient to obtain permission for all biological material storage and future translational studies Based on the histology result obtained from the TCB patients will be categorized into three groups Subsequent clinical management will be determined according to the appropriate group
Subgroup 1 Patients with a typical benign histological result of TCB will undergo elective surgery within 8 weeks from receiving the results with a preference of a minimally invasive approach ie most often laparoscopic myomectomy or laparoscopic hysterectomy
Subgroup 2 Patients with an atypical histological result of TCB ie other than conventional leiomyoma but with no signs of malignancy will undergo elective surgery within 6 weeks from receiving the results with a preference of laparoscopy but excluding unprotected power morcellation of pathological tissue
Uncontained morcellation will be used strictly for tumors with benign TCB histology and nonsuspicious perioperative appearance of resected uterine tumor Contained morcellation technique will be strictly preferred for all other tumors ie with non-standard TCB histology andor atypical or suspicious perioperative appearance or standard TCB histology and atypical or suspicious perioperative appearance
Subgroup 3 Patients with a histological result from the TCB that are clearly malignant or suspicious for malignancy undergo open surgery specifically abdominal hysterectomy In cases of women with incomplete reproductive plans open resection of the tumor may be performed after detailed consultation with the oncogynecological team and the patient a secondary hysterectomy may be added based on the result of definitive histology The procedure should be done as soon as possible with a maximum interval between the result of TCB histology and elective surgery no more than 3 weeks
In cases of tumors without penetration through the uterine serosa according to US and perioperatively and without requiring morcellation for the specimen evacuation total laparoscopic hysterectomy can be performed
Subgroup 4 In case of invalid TCB histology result the patient will undergo contained morcellation during laparoscopic procedure or open surgery within 4 weeks after the TCB
The definitive histology results from the surgery will be evaluated using the same histopathological criteria as in TCB histology Definitive histology will be compared with the histological results from the pre-surgical TCB
For the primary endpoint analysis the accuracy of the histological results from TCB will be established using the definitive postoperative histological results as a reference standard
The sample size of 217 patients with sonographically atypical myometrial lesions was calculated to establish the accuracy of the diagnostic method with the degree of estimate precision of 007 95 confidence and 80 power assuming ratio between patients with without atypical lesion as per final pathology of 2377 as based on the retrospective database data Considering a possible dropout or unavailability of data in 15 of the patients the final sample size reaches 250 patients Analysis was computed using PASS 13 Power Analysis and Sample Size Software 2014 NCSS LLC Kaysville Utah USA ncsscomsoftwarepass
If this trial proves the accuracy of TCB of myometrial lesion it could provide a new diagnostic tool and significantly impact the clinical practice
A positive study outcome could establish level A evidence for a change of international standards and implement prehabilitation into a routine clinical practice On a national level the study aims to standardize and improve the care for gynecological patients with sonographic atypical myometrial lesions A primary endpoint final analysis is intended for publication in a top medical journal The study could also provide prospective genomic characterization analyses of myometrial tumors as well as the exploratory analysis of the reliability of individual imaging methods in the preliminary selection of patients with atypical myometrial findings
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None