Ignite Creation Date:
2024-05-19 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06412211
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-05-14
First Post:
2024-05-07
Brief Title:
A Clinical Feasibility Study of a Photoacoustic Finder
Sponsor:
Seoul St Marys Hospital
Organization:
Seoul St Marys Hospital
Study Overview
Official Title:
Clinical Utility of Photoacoustic Finder in Sentinel Lymph Node Detection in Breast Cancer - Pilot Study
Status:
ACTIVE_NOT_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:
None
Brief Summary:
Determining the prognosis of breast cancer relies significantly on axillary staging by sentinel lymph node biopsy SLNb The SLNb is generally performed using radioisotopes blue dyes or both to improve the false negative rate However a gamma probe with radioisotopes involves ionizing radiation and blue dye detection relies on visual inspection by an operator To overcome these limitations the photoacoustic finder PAF was developed as a highly sensitive non-radioactive detector that uses only blue dye and a photoacoustic signal to detect SLNs To evaluate the PAF its performance was compared with the standard SLN detection method for breast cancer patients
Detailed Description:
-Introduction The presence of lymphatic metastases in breast cancer patients is an important prognostic factor for survival and accurate staging leads to appropriate adjuvant treatment Sentinel lymph node biopsy SLNb is a standard method used to confirm regional axillary lymphatic metastases in breast cancer patients Sentinel lymph nodes SLNs are a group of initial lymph nodes LNs located in proximity to the tumor and connected via lymphatic vessels LVs hypothetically the first ones that a primary tumor drains in the regional lymphatic basin If metastatic tumor cells are not confirmed in the excised SLNs the incidence of morbidities such as lymphedema can be reduced by omitting unnecessary axillary lymph node dissection ALND The SLNb procedure is a dual-modal method utilizing a radioactive tracer eg 99mTc andor blue dye to identify the SLNs The radioactive tracer and blue dye are administered before surgery and absorbed by the lymphatic system and eventually they flow into the SLNs During the surgical procedures the SLNs are identified through visual inspection of blue-dyed LVs and radioactivity detection using a gamma probe The identified SLNs are subsequently excised and sent for pathological examination to assess the potential metastatic tumor
The dual-modal method enhances the accuracy and efficiency of SLN identification by leveraging the distinct advantages of each method However the radioactive isotopes in the SLNb surgery present an inherent radiation exposure risk and necessitate specialized facilities and skilled medical personnel These factors introduce complexities into the surgical procedure and create obstacles for the implementation of SLNb in local hospitals Moreover the administration of radioactive material typically requires cooperation with a nuclear medicine department which restricts direct usage by the surgeon and may impact surgical scheduling Lastly because radioactive isotopes do not provide visual information the intuitive identification of SLNs is challenging On the other hand blue dye visually stains the lymphatic network enabling the intuitive identification of SLNs without radiation exposure However relying on visual inspection of blue-dyed SLNs may introduce inter-physician variability and potential inaccuracies in identifying SLNs owing to variable lesion characteristics such as the presence of adipose tissue and blood These limitations make it challenging to see blue dye within LNs ultimately leading to reduced sensitivity in the SLN detection
Photoacoustic PA imaging or sensing is a non-ionizing technique that utilizes the intrinsic light absorption properties of biological tissue components To generate PA signals a nanosecond pulsed laser induces repeated instantaneous thermal expansions within a sample creating acoustic waves These acoustic waves are then captured by an ultrasound transducer and analyzed to confirm the presence of specific constituents within the sample PA sensing technology can detect dye-stained LNs with high sensitivity and provide a real-time quantitative representation This method can precisely determine the presence or absence of dyed SLNs that may have been indistinguishable through visual inspection Consequently it can facilitate SLNb procedures without radioactive materials In our previous studies a cutting-edge system known as the photoacoustic finder PAF was successfully deviesed It is remarkably efficacious in detecting SLNs while maintaining a high signal-to-noise ratio SNR The PAF combines a solid-state dye SSD laser handpiece and a transparent ultrasound transducer TUT in a precisely coaxial configuration This study describes preclinical trials of the PAF which confirmed its ability to accurately detect blue-dyed SLNs
This cross-sectional clinical study was conducted ex vivo to validate the feasibility of using the PAF in a clinical setting The process confirms the signal from excised LNs identified by the dual-modal method and the PAF before sending them to pathology To determine its detection performance the effectiveness of PAF is compared to the detection rate of standard SLNb The results establish the clinical feasibility of using PAF for SLNb providing a non-radioactive alternative
-Study design This study was conducted as a cross-sectional open-label single-arm ex vivo study within a single institution to investigate the efficacy of PAF compared to standard dual-modal methods for SLN detection in the treatment of breast cancer The SLNb procedures followed international guidelines using both radioisotope and blue dye mapping SLNs were identified using gamma probe and blue dye visual inspection then resected and labeled to reconfirm the with gamma probe and blue dye visual inspection Subsequently PAF was employed to capture signals from the LNs To minimize potential errors such as labeling mistakes and LN delivery errors the PAF system was placed in the operating room The study enrolled women diagnosed with breast cancer who presented to the Department of Breast Surgery at St Marys Hospital Seoul The Republic of Korea
-Sentinel lymphnode biopsy The SLNb was performed in accordance with established international guidelines utilizing both radioisotope and blue dye mapping methods Five surgical oncologists participated in the study all of whom were experienced in performing standard dual-modal SLNb and understood the clinical protocol The radioisotope 01 mL of 99mTc-phytate was administered into the subdermal lymphatic flexus under the areola within 30 minutes to 8 hours prior to operation When the surgery started the operator confirmed the location of the tumor Then a blue dye indigo carmine 2-5 ml was injected peritumorally or periareolarly prior to incision with subsequent massaging for 1 minute following injection The axillary nodal basin was closely examined using a handheld gamma probe to detect radioactive signals and visually examined by the naked eye to detect grossly blue-dyed LNs The identification of SLNs continued until either no further signal was detected by the gamma probe or blue-dyed LNs were no longer found in the nodal basins within the operation field For this study SLNs were defined as LNs with a gamma probe signal greater than 10 of the maximum signal value andor visibly stained with blue dye Additionally based on the surgeons experience abnormally palpable LNs that were not detected by gamma probe and visual inspection were also excised and these were labeled as non-SLNs The SLNs and non-SLNs were further examined by PAF and subsequently were forwarded to the pathology department for frozen section analysis
-Sample Size To determine the required sample size for testing the non-inferiority of PAF and the dual-modal method the non-inferiority chi-square sample size estimator was utilized employing a non-inferiority margin of 5 a significance level alpha of 5 and a power 1-beta of 80 Drawing from prior research and based on experimental data from tests it was assumed that the visual detection rate would be approximately 78 for SLNs and 84 for PAF Calculations revealed that a total of 157 SLNs would be necessary corresponding to approximately 15 SLNs per patient thus requiring the enrollment of 115 patients to fulfill the sample size requirements with an anticipated 10 drop-out
-Static Analysis Methods
The primary endpoints which were the SLN detection rates for the gamma probe visual inspection and PAF were defined as follows
Detection rate Number of detected SLNsTotal number of SLNs 100
The secondary endpoints encompassed the results of a non-inferiority analysis conducted using the chi-square test Additionally the sensitivity and specificity were assessed through ROC curve analysis as part of the additional endpoints Regarding primary and secondary endpoints SLNs were specifically examined excluding non-SLNs to minimize potential surgeon subjectivity
The Wilcoxon Mann-Whitney U-Test was performed to determine the cutoff for the PAF and the statistical significances between 99mTc- blue- and non-injected groups were compared In a non-inferiority analysis a chi-square test was performed to compare the risk differences for 99mTc blue and PAF nodes The independent samples t-test was used for other normal distributions such as age and BMI All statistical analyses in this study were conducted using MATLAB R2022a with the Statistics and Machine Learning Toolbox
The dual-modal method enhances the accuracy and efficiency of SLN identification by leveraging the distinct advantages of each method However the radioactive isotopes in the SLNb surgery present an inherent radiation exposure risk and necessitate specialized facilities and skilled medical personnel These factors introduce complexities into the surgical procedure and create obstacles for the implementation of SLNb in local hospitals Moreover the administration of radioactive material typically requires cooperation with a nuclear medicine department which restricts direct usage by the surgeon and may impact surgical scheduling Lastly because radioactive isotopes do not provide visual information the intuitive identification of SLNs is challenging On the other hand blue dye visually stains the lymphatic network enabling the intuitive identification of SLNs without radiation exposure However relying on visual inspection of blue-dyed SLNs may introduce inter-physician variability and potential inaccuracies in identifying SLNs owing to variable lesion characteristics such as the presence of adipose tissue and blood These limitations make it challenging to see blue dye within LNs ultimately leading to reduced sensitivity in the SLN detection
Photoacoustic PA imaging or sensing is a non-ionizing technique that utilizes the intrinsic light absorption properties of biological tissue components To generate PA signals a nanosecond pulsed laser induces repeated instantaneous thermal expansions within a sample creating acoustic waves These acoustic waves are then captured by an ultrasound transducer and analyzed to confirm the presence of specific constituents within the sample PA sensing technology can detect dye-stained LNs with high sensitivity and provide a real-time quantitative representation This method can precisely determine the presence or absence of dyed SLNs that may have been indistinguishable through visual inspection Consequently it can facilitate SLNb procedures without radioactive materials In our previous studies a cutting-edge system known as the photoacoustic finder PAF was successfully deviesed It is remarkably efficacious in detecting SLNs while maintaining a high signal-to-noise ratio SNR The PAF combines a solid-state dye SSD laser handpiece and a transparent ultrasound transducer TUT in a precisely coaxial configuration This study describes preclinical trials of the PAF which confirmed its ability to accurately detect blue-dyed SLNs
This cross-sectional clinical study was conducted ex vivo to validate the feasibility of using the PAF in a clinical setting The process confirms the signal from excised LNs identified by the dual-modal method and the PAF before sending them to pathology To determine its detection performance the effectiveness of PAF is compared to the detection rate of standard SLNb The results establish the clinical feasibility of using PAF for SLNb providing a non-radioactive alternative
-Study design This study was conducted as a cross-sectional open-label single-arm ex vivo study within a single institution to investigate the efficacy of PAF compared to standard dual-modal methods for SLN detection in the treatment of breast cancer The SLNb procedures followed international guidelines using both radioisotope and blue dye mapping SLNs were identified using gamma probe and blue dye visual inspection then resected and labeled to reconfirm the with gamma probe and blue dye visual inspection Subsequently PAF was employed to capture signals from the LNs To minimize potential errors such as labeling mistakes and LN delivery errors the PAF system was placed in the operating room The study enrolled women diagnosed with breast cancer who presented to the Department of Breast Surgery at St Marys Hospital Seoul The Republic of Korea
-Sentinel lymphnode biopsy The SLNb was performed in accordance with established international guidelines utilizing both radioisotope and blue dye mapping methods Five surgical oncologists participated in the study all of whom were experienced in performing standard dual-modal SLNb and understood the clinical protocol The radioisotope 01 mL of 99mTc-phytate was administered into the subdermal lymphatic flexus under the areola within 30 minutes to 8 hours prior to operation When the surgery started the operator confirmed the location of the tumor Then a blue dye indigo carmine 2-5 ml was injected peritumorally or periareolarly prior to incision with subsequent massaging for 1 minute following injection The axillary nodal basin was closely examined using a handheld gamma probe to detect radioactive signals and visually examined by the naked eye to detect grossly blue-dyed LNs The identification of SLNs continued until either no further signal was detected by the gamma probe or blue-dyed LNs were no longer found in the nodal basins within the operation field For this study SLNs were defined as LNs with a gamma probe signal greater than 10 of the maximum signal value andor visibly stained with blue dye Additionally based on the surgeons experience abnormally palpable LNs that were not detected by gamma probe and visual inspection were also excised and these were labeled as non-SLNs The SLNs and non-SLNs were further examined by PAF and subsequently were forwarded to the pathology department for frozen section analysis
-Sample Size To determine the required sample size for testing the non-inferiority of PAF and the dual-modal method the non-inferiority chi-square sample size estimator was utilized employing a non-inferiority margin of 5 a significance level alpha of 5 and a power 1-beta of 80 Drawing from prior research and based on experimental data from tests it was assumed that the visual detection rate would be approximately 78 for SLNs and 84 for PAF Calculations revealed that a total of 157 SLNs would be necessary corresponding to approximately 15 SLNs per patient thus requiring the enrollment of 115 patients to fulfill the sample size requirements with an anticipated 10 drop-out
-Static Analysis Methods
The primary endpoints which were the SLN detection rates for the gamma probe visual inspection and PAF were defined as follows
Detection rate Number of detected SLNsTotal number of SLNs 100
The secondary endpoints encompassed the results of a non-inferiority analysis conducted using the chi-square test Additionally the sensitivity and specificity were assessed through ROC curve analysis as part of the additional endpoints Regarding primary and secondary endpoints SLNs were specifically examined excluding non-SLNs to minimize potential surgeon subjectivity
The Wilcoxon Mann-Whitney U-Test was performed to determine the cutoff for the PAF and the statistical significances between 99mTc- blue- and non-injected groups were compared In a non-inferiority analysis a chi-square test was performed to compare the risk differences for 99mTc blue and PAF nodes The independent samples t-test was used for other normal distributions such as age and BMI All statistical analyses in this study were conducted using MATLAB R2022a with the Statistics and Machine Learning Toolbox
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