Ignite Creation Date:
2024-05-11 @ 8:30 AM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06401304
Status:
RECRUITING
Last Update Posted:
2024-05-06
First Post:
2024-04-27
Brief Title:
Oncologic Cosmetic and Patient Reported Outcomes in Value-Based Breast Surgery OnCoPRO Value
Sponsor:
Uppsala University
Organization:
Uppsala University
Study Overview
Official Title:
Oncologic Cosmetic and Patient Reported Outcomes in Value-Based Breast Surgery A Multicentre Cohort Study
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OncoPROValue-1
Brief Summary:
The study aspires to provide outcomes on surgery quality of life and time-to-event outcomes following the development and validation of a standardised surgical assessment tool in a shared decision-making framework for patients with pre-invasive or invasive breast cancer with breast conservation
Detailed Description:
Oncoplastic breast-conserving surgery OPBCS has gained increasing popularity over the last years and tends to be considered the standard of care in surgical practice OPBCS allows for the resection of larger volumes and tumors with acceptable cosmesis by incorporating different techniques that have evolved mainly from mastopexy mammoplasty and breast reduction or volume replacement techniques such as perforator flap reconstruction
However no randomized controlled trial data on indications methods decision-making and outcomes are available and present practice is largely based on evidence from cohort data derived from single- or multi-institutional series Along with that the fact that surgical decision-making in OPBCS is highly individualized renders any effort for standardization of these operations highly challenging and controversial This is a multifactorial phenomenon owing to anatomic differences such as breast volume breast shape lesion volume localization ptosis body mass index BMI but also patient preference and availability of surgical techniques Efforts for standardization of techniques based on tumor location breast size and ptosis have been made but they do not address the principle of tailored treatment and do not cover all clinical scenarios
On the other hand breast-conserving surgery BCS followed by whole breast irradiation WBI yields comparable to better outcomes compared with mastectomy without WBI in terms of survival but much better in terms of quality of life QoL and patient-reported outcomes and measures PROMS even when compared to the reconstructed breast At the same time OPBCS seems to yield superior cosmesis and patient satisfaction compared to traditional wide local excisions WLE but it is unclear whether this comes at the cost of increased morbidity or unnecessary revisionary procedures with an impact on the delivery of systemic treatment QoL and health economy In addition patient preference is a factor that precludes randomization to the method of operation in the traditional meaning as it would not be ethical to randomize surgery that may be unnecessarily extensive or oncologically dubious Moreover surgeon and patient preferences and expectations may involve bias which is hard to define and a non-randomized study on the subject of WLE vs OPBCS could inevitably be unclear in how to address this inherent flaw
PROMS such as QoL and cosmesis are even more important in the case of benign lesions that need to be operated on This has to do with the fact that no compromises need to be made for the sake of a radical breast cancer operation as well as that benign breast surgery is more common in women of younger age There despite the instinctive assessment that a well-placed incision should have better outcomes there is a complete lack of high-quality data on the matter
At the same time the decision-making process of the choice of surgical technique is a phenomenon poorly investigated surgeons tend to offer the techniques they are most comfortable with and offer therapy per patient preference largely dependent on the health setting This may account for the lack of consistency in identifying factors related to re-excision postoperative complications and PROMS In this procedure patient preference has shown to vary depending on surgical consultation not only on the choice not to undergo mastectomy but also on the extent of BCS Another fact that needs to be taken into account is that despite that several classification systems and algorithms have been proposed everyday clinical practice represents more of a continuum On the other hand standard surgical assessment performed by breast surgeons is likely to reflect personal preferences techniques one may be most comfortable with as well as variances in healthcare provision
This may account for the lack of consistency in practice resulting either in involved margins and requiring re-excision with consequences on cosmesis and patient satisfaction undertreatment or the unnecessary utilization of OPBCS in cases where simpler could produce equivalent results with less operative time complications or need for contralateral symmetrization overtreatment Therefore any objective associations between the method of BCS and outcomes remain to be elucidated
The rationale is to investigate whether the development of a tool for surgical decision-making may facilitate the identification of appropriate surgical techniques for each patient
The trial aims to investigate whether the application of a structured approach to select an appropriate surgical technique may have an impact on PROMS complications QoL and health-economy In that way the effect of rationalized versus empiric employment of operative techniques OPBCS vs WLE may be elucidated Additionally it will allow for the accumulation of evidence regarding OPBCS in a way that does not come in conflict with ethics patient preference and real-world clinical practice Moreover the study will aspire to investigate whether there may be a more objective manner to define the minimum required type of surgery to obtain clear margins whilst maintaining breast function and form in a manner compatible with patient preference and optimal quality of life As this is a multifaceted question it is appropriate to examine it separately for different subgroups volume replacement or displacement Last but not least the study may help elucidate the impact of locoregional and systemic oncologic treatment radiotherapy local andor locoregional and chemotherapy immunotherapy and endocrine therapy in PROMS on the type of surgical treatment the patient has received The design is intended to be highly pragmatic Therefore the systematic restructuring and the capitalization of the routinely available preoperative patient data will be used towards the effort of developing a clinical decision-making tool
The study will look into surgical outcomes complications re-excision rates conversion to mastectomy patient-reported outcomes and experience time-to-event outcomes local recurrence-free survival locoregional recurrence-free survival disease-free survival and overall survival as well as health economy factors These will be examined on an individual participant level and a subgroup level such as per oncoplastic reconstructive principle volume displacement vs volume replacement different oncoplastic techniques eg mastopexies vs reduction vs perforator flaps onco-cosmetic surgery or not concomitant contralateral symmetrization or not
Oncoplastic breast-conserving surgery OPBCS has gained increasing popularity over the last years and tends to be considered the standard of care in surgical practice OPBCS allows for the resection of larger volumes and tumors with acceptable cosmesis by incorporating different techniques that have evolved mainly from mastopexy mammoplasty and breast reduction
Variables that need to be prospectively registered and available
1 Lesion biology data - Invasive cancer YN
- Pure DCIS YN
- Tumour type 1 Invasive Ductal Carcinoma Non-specific type IDC-NST 2 Invasive Lobular Carcinoma ILC 3 Mixed ductolobular carcinoma 4 Other invasive subtypes 5 Ductal Carcinoma In Situ DCIS
- Nuclear Grade
- Estrogen Receptor ER
Progesterone Receptor PR
Human Epidermal growth factor Receptor type 2 HER2 status or erbb-2 status
Ki67 optional
Any gene signature test optional
Tumour Infiltrating Lymphocytes TIL and Programmed Death Ligand-1 PDL-1 provided that their report becomes standard of care optional
For surgery following neoadjuvant Residual Cancer Burden optional Can be replicated from postoperative data in non-discordant cases
2 Baseline Radiologic Assessment
- Tumor size d maximum diameter in cm If there is a discrepancy then the size of the modality Mammogram US MRI on which the decision is made needs to be registered
- Localization in the chest Clock axis cm from NAC to be divided into the following categories during harmonization Upper Outer Quadrant Junction between Upper and Lower Outer Quadrant Lower outer quadrant Junction between Lower Outer and Lower Inner Quadrant Lower Inner Quadrant Junction between Lower and Upper Inner Quadrant Upper Inner Quadrant Junction between Inner and Outer Upper Quadrant Retroareolar Multiple site ipsilateral cancers previously described as multifocal or multicentric
- Tumor size max size and Optimal Resection Volume ORV 4 3π d 2 13 d maximum diameter in cm
- Calculated Resection Ratio CRR ORV BrV where BrV stands for Breast Volume see below
3 Baseline patient assessment
Age at operation
Comorbidities Charlson Comorbidity Index
Smoking
Diabetes Mellitus with end-organ damage
Neoadjuvant therapy
Body mass index BMI
Ptosis to be assessed according to the Regnault classification as follows 1 first degree nipple at the level of the infra-mammary fold 2 second degree nipple below the level of the infra-mammary fold but above the level of the most dependent inferior part of the breast contour and 3 third degree nipple below the level of the infra-mammary fold and sitting at the most dependent inferior part of the breast contour
Breast volume estimate
Acceptable alternatives
i Longo Formula ii Breast Cups iii Bra cup size if available literature on the conversion of cup size to volume is available All measurements will be cross-validated by review of preoperative mammograms and calculation of the volume with either the Kalbhen or the Katariya formulae
Kalbhen formula BrV 0784x H x W x C where H is anteroposterior distance W is mediolateral distance C mammographic compression all in centimeters on the craniocaudal projection of the mammogram CC image Katariya formula BrVπ12W2H on the CC image
Tumor size max size and Optimal Resection Volume ORV 4 3π d 2 1 3 d maximum diameter in cm
Calculated Resection Ratio CRR ORV BrV
The rationale behind the recommendation
To avoid mastectomy to avoid volume displacement with asymmetry or the need for contralateral symmetrization to avoid wide local excision with poor cosmetic outcomes
This assessment will be cross-validated by the team of local PIs
d Intraoperative data
- Type of volume replacement The following alternatives are available Lateral Intercostal Artery Perforator LICAP Lateral Thoracic Artery Perforator LTAP Lateral Hybrid combination of LTAP and LICAP Lateral advancement flap LAF Mini Latissimus Dorsi Muscle sparing TDAP Medial or Anterior Intercostal Artery Perforator MICAPAICAP Abdominal Advancement Flap AAF
Single perforator-based flap
Technique of placement trapdoor pendulum propeller optional
Tumour localization technique regardless of type ink coal guidewire seed Type of localization to be reported
Axillary procedure None SLND Axillary biopsy TAD ALND
Specimen weight in grams gr
Specimen shape dimensions and volume Actual Resection Volume ARV The proposed methods are weight0958 or volumetry by registration of shape and dimensions
Specimens are either rectangular and the volume is provided by the formula V h x w x l or elliptical and the volume is provided by the formula V 43 x h2 x w2 x l2 0654 x h x w x l where h height cm w width cm and l length cm of the specimen
Operative time min
Perioperative antibiotics YN
Extended antibiotic administration YN
Use of drains
Day surgery YN
Length of stay days
e Postoperative data
e1 Pathology report
Invasive cancer YN
Pure DCIS YN
Tumour type 1 IDC 2 ILC 3 Mixed 4 Other invasive 5 DCIS 6 Unknown
Nuclear Grade 123
Estrogen Receptor ER
Progesterone Receptor PR
HER2 positive negative
Ki67 -- Tumour Infiltrating Lymphocytes TIL and Programmed Death Ligand-1 PDL-1 provided that their report becomes standard of care
Radical excision YN internationally defined as no tumour-on-ink for IBC and 2mm for pure DCIS National variations in practice will be accepted if they modify the decision-making
Need for reoperation for complication or margin control YN
Type of reoperation Re-excision Mastectomy
Actual Resection Ratio ARR defined as Specimen volumeBreast volume
Number of lymph nodes retrieved Sentinel and total optional
Number of lymph nodes with metastases to define pN status
Type of metastasis optional
e2 Complications at 28 days Report type
Fat necrosis report Grade according to scale from Lovey et al as follows
0 No fat necrosis
1 Asymptomatic fat necrosis only radiologic and or cytologic findings
2 Symptomatic fat necrosis not requiring medication palpable mass with or without mild pain
3 Symptomatic fat necrosis requiring medication palpable mass with significant pain
4 Symptomatic fat necrosis requiring surgical intervention
Alleged infection clinical diagnosis
Infection Verified with culture
Bleeding
Symptomatic seroma requiring intervention
Reporting of complications per the Clavien Dindo CD classification and Comprehensive Complication Index 20 CCI 20 score
e3 Type of NeoAdjuvant Systemic therapy None Chemotherapy Endocrine Therapy Monoclonal antibodies CDK 4-6 inhibitors or other
e4 Type of Adjuvant Radiotherapy None whole breast irradiation reduced dose whole breast irradiation partial breast irradiation plus minus nodalregional irradiation f Patient Reported Outcomes Optional Questionnaires accepted
EORTC QLQ-c-30 BreastQ preoperative and postoperative modules Diseases of the Arm Shoulder and Hand DASH score
g Health-economy outcomes
h Long-term follow-up Ipsilateral Local recurrence Ipsilateral Locoregional recurrence Distant Recurrence Breast Cancer-Specific Survival Overall Survival All in months
However no randomized controlled trial data on indications methods decision-making and outcomes are available and present practice is largely based on evidence from cohort data derived from single- or multi-institutional series Along with that the fact that surgical decision-making in OPBCS is highly individualized renders any effort for standardization of these operations highly challenging and controversial This is a multifactorial phenomenon owing to anatomic differences such as breast volume breast shape lesion volume localization ptosis body mass index BMI but also patient preference and availability of surgical techniques Efforts for standardization of techniques based on tumor location breast size and ptosis have been made but they do not address the principle of tailored treatment and do not cover all clinical scenarios
On the other hand breast-conserving surgery BCS followed by whole breast irradiation WBI yields comparable to better outcomes compared with mastectomy without WBI in terms of survival but much better in terms of quality of life QoL and patient-reported outcomes and measures PROMS even when compared to the reconstructed breast At the same time OPBCS seems to yield superior cosmesis and patient satisfaction compared to traditional wide local excisions WLE but it is unclear whether this comes at the cost of increased morbidity or unnecessary revisionary procedures with an impact on the delivery of systemic treatment QoL and health economy In addition patient preference is a factor that precludes randomization to the method of operation in the traditional meaning as it would not be ethical to randomize surgery that may be unnecessarily extensive or oncologically dubious Moreover surgeon and patient preferences and expectations may involve bias which is hard to define and a non-randomized study on the subject of WLE vs OPBCS could inevitably be unclear in how to address this inherent flaw
PROMS such as QoL and cosmesis are even more important in the case of benign lesions that need to be operated on This has to do with the fact that no compromises need to be made for the sake of a radical breast cancer operation as well as that benign breast surgery is more common in women of younger age There despite the instinctive assessment that a well-placed incision should have better outcomes there is a complete lack of high-quality data on the matter
At the same time the decision-making process of the choice of surgical technique is a phenomenon poorly investigated surgeons tend to offer the techniques they are most comfortable with and offer therapy per patient preference largely dependent on the health setting This may account for the lack of consistency in identifying factors related to re-excision postoperative complications and PROMS In this procedure patient preference has shown to vary depending on surgical consultation not only on the choice not to undergo mastectomy but also on the extent of BCS Another fact that needs to be taken into account is that despite that several classification systems and algorithms have been proposed everyday clinical practice represents more of a continuum On the other hand standard surgical assessment performed by breast surgeons is likely to reflect personal preferences techniques one may be most comfortable with as well as variances in healthcare provision
This may account for the lack of consistency in practice resulting either in involved margins and requiring re-excision with consequences on cosmesis and patient satisfaction undertreatment or the unnecessary utilization of OPBCS in cases where simpler could produce equivalent results with less operative time complications or need for contralateral symmetrization overtreatment Therefore any objective associations between the method of BCS and outcomes remain to be elucidated
The rationale is to investigate whether the development of a tool for surgical decision-making may facilitate the identification of appropriate surgical techniques for each patient
The trial aims to investigate whether the application of a structured approach to select an appropriate surgical technique may have an impact on PROMS complications QoL and health-economy In that way the effect of rationalized versus empiric employment of operative techniques OPBCS vs WLE may be elucidated Additionally it will allow for the accumulation of evidence regarding OPBCS in a way that does not come in conflict with ethics patient preference and real-world clinical practice Moreover the study will aspire to investigate whether there may be a more objective manner to define the minimum required type of surgery to obtain clear margins whilst maintaining breast function and form in a manner compatible with patient preference and optimal quality of life As this is a multifaceted question it is appropriate to examine it separately for different subgroups volume replacement or displacement Last but not least the study may help elucidate the impact of locoregional and systemic oncologic treatment radiotherapy local andor locoregional and chemotherapy immunotherapy and endocrine therapy in PROMS on the type of surgical treatment the patient has received The design is intended to be highly pragmatic Therefore the systematic restructuring and the capitalization of the routinely available preoperative patient data will be used towards the effort of developing a clinical decision-making tool
The study will look into surgical outcomes complications re-excision rates conversion to mastectomy patient-reported outcomes and experience time-to-event outcomes local recurrence-free survival locoregional recurrence-free survival disease-free survival and overall survival as well as health economy factors These will be examined on an individual participant level and a subgroup level such as per oncoplastic reconstructive principle volume displacement vs volume replacement different oncoplastic techniques eg mastopexies vs reduction vs perforator flaps onco-cosmetic surgery or not concomitant contralateral symmetrization or not
Oncoplastic breast-conserving surgery OPBCS has gained increasing popularity over the last years and tends to be considered the standard of care in surgical practice OPBCS allows for the resection of larger volumes and tumors with acceptable cosmesis by incorporating different techniques that have evolved mainly from mastopexy mammoplasty and breast reduction
Variables that need to be prospectively registered and available
1 Lesion biology data - Invasive cancer YN
- Pure DCIS YN
- Tumour type 1 Invasive Ductal Carcinoma Non-specific type IDC-NST 2 Invasive Lobular Carcinoma ILC 3 Mixed ductolobular carcinoma 4 Other invasive subtypes 5 Ductal Carcinoma In Situ DCIS
- Nuclear Grade
- Estrogen Receptor ER
Progesterone Receptor PR
Human Epidermal growth factor Receptor type 2 HER2 status or erbb-2 status
Ki67 optional
Any gene signature test optional
Tumour Infiltrating Lymphocytes TIL and Programmed Death Ligand-1 PDL-1 provided that their report becomes standard of care optional
For surgery following neoadjuvant Residual Cancer Burden optional Can be replicated from postoperative data in non-discordant cases
2 Baseline Radiologic Assessment
- Tumor size d maximum diameter in cm If there is a discrepancy then the size of the modality Mammogram US MRI on which the decision is made needs to be registered
- Localization in the chest Clock axis cm from NAC to be divided into the following categories during harmonization Upper Outer Quadrant Junction between Upper and Lower Outer Quadrant Lower outer quadrant Junction between Lower Outer and Lower Inner Quadrant Lower Inner Quadrant Junction between Lower and Upper Inner Quadrant Upper Inner Quadrant Junction between Inner and Outer Upper Quadrant Retroareolar Multiple site ipsilateral cancers previously described as multifocal or multicentric
- Tumor size max size and Optimal Resection Volume ORV 4 3π d 2 13 d maximum diameter in cm
- Calculated Resection Ratio CRR ORV BrV where BrV stands for Breast Volume see below
3 Baseline patient assessment
Age at operation
Comorbidities Charlson Comorbidity Index
Smoking
Diabetes Mellitus with end-organ damage
Neoadjuvant therapy
Body mass index BMI
Ptosis to be assessed according to the Regnault classification as follows 1 first degree nipple at the level of the infra-mammary fold 2 second degree nipple below the level of the infra-mammary fold but above the level of the most dependent inferior part of the breast contour and 3 third degree nipple below the level of the infra-mammary fold and sitting at the most dependent inferior part of the breast contour
Breast volume estimate
Acceptable alternatives
i Longo Formula ii Breast Cups iii Bra cup size if available literature on the conversion of cup size to volume is available All measurements will be cross-validated by review of preoperative mammograms and calculation of the volume with either the Kalbhen or the Katariya formulae
Kalbhen formula BrV 0784x H x W x C where H is anteroposterior distance W is mediolateral distance C mammographic compression all in centimeters on the craniocaudal projection of the mammogram CC image Katariya formula BrVπ12W2H on the CC image
Tumor size max size and Optimal Resection Volume ORV 4 3π d 2 1 3 d maximum diameter in cm
Calculated Resection Ratio CRR ORV BrV
The rationale behind the recommendation
To avoid mastectomy to avoid volume displacement with asymmetry or the need for contralateral symmetrization to avoid wide local excision with poor cosmetic outcomes
This assessment will be cross-validated by the team of local PIs
d Intraoperative data
- Type of volume replacement The following alternatives are available Lateral Intercostal Artery Perforator LICAP Lateral Thoracic Artery Perforator LTAP Lateral Hybrid combination of LTAP and LICAP Lateral advancement flap LAF Mini Latissimus Dorsi Muscle sparing TDAP Medial or Anterior Intercostal Artery Perforator MICAPAICAP Abdominal Advancement Flap AAF
Single perforator-based flap
Technique of placement trapdoor pendulum propeller optional
Tumour localization technique regardless of type ink coal guidewire seed Type of localization to be reported
Axillary procedure None SLND Axillary biopsy TAD ALND
Specimen weight in grams gr
Specimen shape dimensions and volume Actual Resection Volume ARV The proposed methods are weight0958 or volumetry by registration of shape and dimensions
Specimens are either rectangular and the volume is provided by the formula V h x w x l or elliptical and the volume is provided by the formula V 43 x h2 x w2 x l2 0654 x h x w x l where h height cm w width cm and l length cm of the specimen
Operative time min
Perioperative antibiotics YN
Extended antibiotic administration YN
Use of drains
Day surgery YN
Length of stay days
e Postoperative data
e1 Pathology report
Invasive cancer YN
Pure DCIS YN
Tumour type 1 IDC 2 ILC 3 Mixed 4 Other invasive 5 DCIS 6 Unknown
Nuclear Grade 123
Estrogen Receptor ER
Progesterone Receptor PR
HER2 positive negative
Ki67 -- Tumour Infiltrating Lymphocytes TIL and Programmed Death Ligand-1 PDL-1 provided that their report becomes standard of care
Radical excision YN internationally defined as no tumour-on-ink for IBC and 2mm for pure DCIS National variations in practice will be accepted if they modify the decision-making
Need for reoperation for complication or margin control YN
Type of reoperation Re-excision Mastectomy
Actual Resection Ratio ARR defined as Specimen volumeBreast volume
Number of lymph nodes retrieved Sentinel and total optional
Number of lymph nodes with metastases to define pN status
Type of metastasis optional
e2 Complications at 28 days Report type
Fat necrosis report Grade according to scale from Lovey et al as follows
0 No fat necrosis
1 Asymptomatic fat necrosis only radiologic and or cytologic findings
2 Symptomatic fat necrosis not requiring medication palpable mass with or without mild pain
3 Symptomatic fat necrosis requiring medication palpable mass with significant pain
4 Symptomatic fat necrosis requiring surgical intervention
Alleged infection clinical diagnosis
Infection Verified with culture
Bleeding
Symptomatic seroma requiring intervention
Reporting of complications per the Clavien Dindo CD classification and Comprehensive Complication Index 20 CCI 20 score
e3 Type of NeoAdjuvant Systemic therapy None Chemotherapy Endocrine Therapy Monoclonal antibodies CDK 4-6 inhibitors or other
e4 Type of Adjuvant Radiotherapy None whole breast irradiation reduced dose whole breast irradiation partial breast irradiation plus minus nodalregional irradiation f Patient Reported Outcomes Optional Questionnaires accepted
EORTC QLQ-c-30 BreastQ preoperative and postoperative modules Diseases of the Arm Shoulder and Hand DASH score
g Health-economy outcomes
h Long-term follow-up Ipsilateral Local recurrence Ipsilateral Locoregional recurrence Distant Recurrence Breast Cancer-Specific Survival Overall Survival All in months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None