Trial Title:
Pre-planning Mathematical Models in EUS-guided Laser Ablation of Pancreatic Lesions
NCT ID:
NCT05549960
Condition:
Pancreatic Neoplasms
Conditions: Official terms:
Pancreatic Neoplasms
Conditions: Keywords:
Endoscopic ultrasound
Local ablation
Laser Fiber
mathematical model
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Device
Intervention name:
The medical device used in this study is a 980 nm wavelength diode laser with maximum output of 30 W (EUFOTON Laser Spectrum).
Description:
EUS will be performed with a FUJIFILM EG- 580UT linear endoscope. LA will be performed
with a 980 nm laser light (EUFOTON Laser Spectrum) guided by a 300 μm optical fiber
(EUFOTON). AN EUS-21 gauge needle (Boston Scientific Expect Slimline) will be used for
the optical fiber placement.
The protrusion of the fiber end from the needle tip should be 5 mm. After the correct
placement of the fiber inside the tumor, the ablation treatment can start. Once inside
the lesion, the needle will be slightly retracted, and the fiber will be gently pushed
out of the needle tip by a length of 5 mm. The fiber will be placed at the top of the
lesion, and the laser will be turned on. The laser settings estimated by the mathematical
model will be used. The total number of ablations will depend on the radiological
characteristics of the lesion and location. Special attention must be paid to have 1 cm
between the fiber tip, the walls of the main vessels, and any metal stents that may be
present.
Arm group label:
pancreatic lesions
Summary:
Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer death in Western
countries. More than 50% of the patients with PDAC has a local advanced or metastatic
disease at the time of the diagnosis. There is a growing interest in the investigation of
novel and alternative therapeutic strategies which could be used in synergy with
radiotherapy and chemotherapy. These methods include echoendoscopic (EUS) guided
locoregional ablation to reduce the tumoral mass.
The most studied technique is the radiofrequency ablation (RFA). Another interesting
technique involves the use of the laser source at a wavelength of 1064 nm. Among all the
ablative methods, LA is the only one that allows the use of a thinner needle. These
features make LA a suitable option for treating focal lesions in high-risk areas or in
hard-to-reach locations. A previous study demonstrated the feasibility of this technique
in pancreatic solid lesions.
In order to perform a study aimed at the complete treatment of the lesion, it is
necessary to identify the laser parameters which are specific to the size and location of
the lesion.
The present protocol presents a prospective interventional study aimed at the analysis
and applicability of predictive mathematical models for the calculation of laser settings
in the ablation of pancreatic lesion by means of a EUS-guided LA.
Detailed description:
Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer death in Western
countries, with an estimation of 57,600 new cases and 47,050 deaths in 2020 in USA.
Since the number of deaths due to this lethal disease is rapidly increasing, it is
estimated to become the second leading cause of tumor-related death by 2030.
The high mortality rate of PDAC is due to several causes, including: i) a poor early
diagnosis, ii) the severe biological aggressiveness, and iii) the lack of response to the
systemic therapies.
At present, surgical resection, i.e., pancreatectomy, represents the only widely accepted
treatment option with the potential to increase long-term survival. However, only 20% of
the patients are appropriate surgical candidates at the time of the diagnosis. In the
majority of the patients, the disease is at an advanced or metastatic stadium, and the
surgical resection does not represent a possible option. In these last cases, only
palliative solutions are available.
Nowadays there is a growing interest in the investigation of novel and alternative
therapeutic strategies which could be used in synergy with radiotherapy and chemotherapy.
These methods include the inoculation o antitumoral agents within the lesion, through
laparoscopic, percutaneous or echoendoscopic (EUS) guidance and locoregional ablation to
reduce the tumoral mass.
This solution may be particularly beneficial for those patients who are stable after the
chemotherapy, without any signs of disease regression neither progression. The ablation
can be obtained with different kinds of energy sources, including radiofrequency,
microwave and laser.
The first study of EUS-guided LA on human patients was conducted by Di Matteo and
collaborators who recently performed a prospective study on the feasibility of EUS-guided
LA in cases of inoperable and locally advanced PDAC. A total of 9 patients with stage III
pancreatic cancer were screened and underwent EUS-guided LA. The fiber was placed in the
upper part of the lesion and the following laser power parameters were applied: 2 W for
800 J, 1000 J, or 1200 J; 3 W for 800 J, 1000 J, or 1200 J; 4 W for 800 J, 1000 J, or
1200 J. The application time automatically ranges between 200 and 600 s, according to the
power values. No difficulty was experienced in the technical execution of the procedure.
The fiber was clearly visible within the targeted lesion, for the entire duration of the
application of laser energy. During the procedure, the tip of the fiber was progressively
surrounded by a hyperechoic area. This effect did not compromise the endosonographic
visualization of the needle inside the lesion. At the end of the ablation, the EUS
highlighted a hyperechoic area along the path of the probe, surrounded by non-homogeneous
tissue with hyperechoic areas. No relevant complications were found. Control CT scans
after 24 hours, 7 days and 30 days showed well-defined coagulative necrotic areas. The
average ablation volumes obtained at 800 J decreased by 85% (1.18 cm3 after 24 hours
against 0.17 cm3 after 30 days). The average ablation volumes obtained at 1000 J
decreased by 76% (3.16 cm3 after 24 hours against 0.80 cm3 after 30 days). Finally, the
mean ablation volumes at 1200 J decreased by 44% after 30 days from treatment (1.77 cm3
after 24 hours against 0.98 cm3 after 30 days). According to these results, the 4 W /
1000 J power configuration achieved the largest ablation volume, without clinical
complications.
In order to perform a study aimed at the complete treatment of the lesion, it is
necessary to identify the laser parameters which are specific to the size and location of
the lesion. As identified in a recent study by Paiella, the choice of settings and
handling of the laser device requires a certain learning curve. Therefore, a predictive
mathematical model of the setting parameters can be very beneficial to simplify the
ablative procedure. Furthermore, in the absence of correct parameters, several potential
complications can occur, such as acute pancreatitis, bleeding from adjacent vascular
structures, duodenal perforation or lesion of the biliary tract.
The effectiveness of predictive models for LA has already been demonstrated in some ex
vivo and preclinical studies, both on the pancreas and on other tissues.
Considering all the aspects above, the present protocol presents a prospective
interventional study aimed at the analysis and applicability of predictive mathematical
models for the calculation of laser settings in the ablation of pancreatic lesion by
means of a EUS-guided LA.
The investigators will use a mathematical model for the calculation of the laser
parameters (power, treatment time), taking into account the size of the tumor and some
anatomical characteristics, such as the proximity of blood vessels. The aims of this
study fall within the objectives of the European project LASER OPTIMAL (Laser Ablation:
Selectivity and Monitoring for Optimal Tumor Removal, GA 759159,
http://www.laseroptimal.polimi.it/) of which Professor Saccomandi is Principal
Investigator and Dr. Di Matteo is an expert for clinical procedures.
This is a prospective interventional study involving two Italian centers, the Operative
Digestive Endoscopy UOC of Fondazione Policlinico Universitario Campus Bio-Medico (the
"Coordinating Center") and the Department of Mechanical Engineering of Politecnico di
Milano.
This is a non-controlled, non-randomized interventional feasibility study with a
non-commercial purpose.
The Operative Digestive Endoscopy UOC of Fondazione Policlinico Universitario Campus
Bio-Medico will be responsible for enrolling patients and performing the medical
procedures. The Department of Mechanical Engineering of Politecnico di Milano will work
on the laser parameters estimation using a mathematical model. Pre-operative radiological
images of the candidates will be used for the purpose.
Patients with stage III and IV PDAC; non-functioning or functioning neuroendocrine
tumors; pancreatic metastases from renal cell carcinoma will be evaluated and included in
the study if eligible.
All patients will be followed at the Coordinating Center from enrollment to death or the
end of the study.
Description of study procedures:
1. Preoperative radiological image acquisition.
MR images collected within 7 days before the LA EUS-guided procedure will be used by
the study collaborators to reconstruct the patient's model. The tumor size and some
anatomical features, such as the proximity of blood vessels, will be used in the
patient's model. Techniques of image segmentation, 3D geometry reconstruction, and
mathematical simulation of laser-tissue interaction will be used to estimate the
optimal parameters for the laser (power, energy, time), according to the procedure
described by Scott et al. Specifically, Mimics Innovation Suite software will be
used to obtain the 3D geometry of the anatomical part of interest (pancreas, tumor,
surrounding structures). This will then be imported into finite element
computational software (Comsol Multiphysics) allowing the correct and
patient-specific settings to be calculated.
2. Estimation of laser parameter settings with the mathematical model
The mathematical model is based on finite element simulations implemented using the
commercial Comsol Multiphysics software, as previously proposed by Scott et al.
Laser settings will be based on values calculated in the Di Matteo and coworkers's
experimentation, as previously performed by Saccomandi et al. on ex vivo models.
This part of the study will be carried out in collaboration with the Department of
Mechanical Engineering of Politecnico di Milano as part of the European LASEROPTIMAL
project (www.laseroptimal.polimi.it), coordinated by Paola Saccomandi, and for which
Dr. Di Matteo is an external expert.
3. LA EUS-guided
EUS will be performed with a FUJIFILM EG- 580UT linear endoscope. Procedures will be
performed on the patient under deep sedation, positioned on the left flank.
Prophylactic antibiotics will be administered immediately before the procedure and for
the following 3 days (ceftriaxone 1 g twice daily intravenously). LA will be performed
with a 980 nm laser light (EUFOTON Laser Spectrum) guided by a 300 μm optical fiber
(EUFOTON). An 22 Gauge needle (Boston Scientific Expect Slimline) will be used for the
optical fiber placement.
The protrusion of the fiber end from the needle tip should be 5 mm. After the correct
placement of the fiber inside the tumor, the ablation treatment can start. Once inside
the lesion, the needle will be slightly retracted, and the fiber will be gently pushed
out of the needle tip by a length of 5 mm. The fiber will be placed at the top of the
lesion, and the laser will be turned on. The laser settings estimated by the mathematical
model will be used. The total number of ablations will depend on the radiological
characteristics of the lesion and location. Special attention must be paid to have 1 cm
between the fiber tip, the walls of the main vessels, and any metal stents that may be
present.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologic diagnosis of pancreatic ductal adenocarcinoma (stage III or IV);
- Inoperable neuroendocrine tumor;
- Pancreatic metastasis from renal clear cell cancer;
- Stable situation or progression after chemotherapeutic treatment;
- Age >18 years;
- Acquisition of signed Informed Consent;
- Performance status 0-1-2 (ECOG).
Exclusion Criteria:
- Absolute contraindications to general anaesthesia or deep sedation;
- Absence of suitable ultrasound acoustic window for the procedure;
- Known bleeding disorders that cannot be sufficiently corrected with clotting factors
or fresh frozen plasma (FFP);
- Use of anticoagulants that cannot be discontinued;
- International normalized ratio (INR) >1.5 or platelet count <50,000;
- Pregnancy or lactation;
- Inability to sign informed consent;
- Other concomitant neoplastic diseases.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Serena Stigliano
Address:
City:
Rome
Zip:
00191
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Serena Stigliano
Phone:
3381203363
Email:
s.stigliano@policlinicocampus.it
Start date:
February 1, 2023
Completion date:
December 1, 2023
Lead sponsor:
Agency:
Campus Bio-Medico University
Agency class:
Other
Collaborator:
Agency:
Politecnico di Milano
Agency class:
Other
Source:
Campus Bio-Medico University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05549960
