Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

In this arm the investigators use a robotic system to perform resection of the rectum harboring the tumor trying to do that while being oncologically safe. The robotic system that we use is the da Vinci Si (Intuitive Surgical, Inc.,Sunnyvale,CA) Interventions used are total operative time, margin assessment, conversion rate to open surgery, baseline demographics, preoperative data and postoperative data

In this arm the investigators use a Laparoscopy system to perform resection of the rectum harboring the tumor trying to do that while being oncologically safe.

Interventions used are total operative time, margin assessment, conversion rate to open surgery, baseline demographics, preoperative data and postoperative data

Investigators compare the preparation time of the procedure in the operating room and the actual operative time

Total Operative time

In this intervention investigators measure the proximal, distal and the important circumferential radial margin away from the tumor to determine if this arm is oncologically safe or not.

Margin assessment

In this interversion investigators try to measure how much is this arm feasible to completely perform the procedure whether robotically or laparoscopically without conversion to open surgery

Conversion rate to open surgery

These include gender, age, ASA and BMI. All these data are analyzed and compared in both groups

Baseline demographics

These include distance of the tumor from the anal verge, clinical stage, whether preoperative chemoradiation "CRT", presence of residual tumor after CRT. All were analyzed and compared

Preoperative data

These include pathological stage, number of harvested lymph nodes and immediate postoperative outcome within one month (days of return of bowel function, days of hospital stay, complications, if any, like anastomotic leakage, ileus,wound problems and others, rate of reoperation, rate of readmission \& 30-days mortality. All were analyzed and compared

Postoperative data

Yasser A Debakey, Msc

This is a prospective randomized controlled study that was conducted on patients of both sexes and definite age group at National Cancer Institute-Egypt and with adenocarcinoma of the rectum located within 15 cm from the anal verge. Tumor localization was categorized as the upper rectum (distal border of tumor is from 10 to 15 cm from the anal verge), middle rectum (5 to 10 cm from the anal verge) or lower rectum (less than 5 cm from the anal verge) as measured by colonoscopy and digital rectal examination. Patients were classified into two groups; robotic assisted rectal surgery and conventional laparoscopic rectal surgery.Baseline demographics (gender, age, ASA, BMI), preoperative data (distance of the tumor from the anal verge, clinical stage, whether preoperative chemoradiation (CRT), presence of residual tumor after CRT, intraoperative data (preparation time, actual operative time, estimated blood loss, conversion rate to open surgery), postoperative data (pathological stage, number of harvested lymph nodes, macroscopic completeness of resection in the form of proximal margin, distal margin, circumferential radial margin) and immediate postoperative outcome within one month (days of return of bowel function, days of hospital stay, complications, if any, like anastomotic leakage, ileus,wound problems and others, rate of re-operation, rate of readmission \& 30-days mortality) were analyzed and compared.The criteria for patients selection were the following: histological diagnosis of adenocarcinoma of rectum, no anesthesiological contraindications to minimally invasive surgery, age ≤ 75 years, American Society of Anesthesiologists (ASA) ≤ 2 \& the procedures performed by the same surgical team. Patients with metastatic disease, malignant bowel obstruction and those with irresectable tumor were excluded from our study.Preoperative workup (endoscopy with biopsies, radiological imaging including pelvic MRI, liver ultrasound, chest X-ray and routine abdominal and digital rectal examinations) was routinely carried out. The assignment of patients to either group was done by a permuted block randomization. It was an open-labeled study. The study was approved by the institutional review board of National Cancer Institute-Cairo University. All patients provided written informed consent.

Undoubtedly, robotic systems have largely penetrated the surgical field.For any new operative approach to become an accepted alternative to conventional methods, it must be proved safe and result in comparable outcomes. The purpose of this study is to compare the short-term operative as well as oncologic outcomes of robotic assisted and laparoscopic rectal cancer resection.

This is a prospective randomized controlled study that was conducted on all patients of both sexes and definite age group attending the National Cancer Institute and with adenocarcinoma of the rectum located within 15 cm from the anal verge who were eligible to be included in the study. Tumor localization was categorized as the upper rectum (distal border of tumor is from 10 to 15 cm from the anal verge), middle rectum (5 to 10 cm from the anal verge) or lower rectum (less than 5 cm from the anal verge) as measured by colonoscopy and digital rectal examination. Patients were classified into two groups; robotic assisted rectal surgery "The robotic system that we use is the da Vinci Si(Intuitive Surgical, Inc.,Sunnyvale,CA)" and conventional laparoscopic rectal surgery. Baseline demographics (gender, age, ASA, BMI), preoperative data (distance of the tumor from the anal verge, clinical stage, whether preoperative chemo-radiation "CRT", presence of residual tumor after CRT), intraoperative data (preparation time, actual operative time, estimated blood loss, conversion rate to open surgery), postoperative data (pathological stage, number of harvested lymph nodes, macroscopic completeness of resection in the form of proximal margin, distal margin, circumferential radial margin) and immediate postoperative outcome within one month (days of return of bowel function, days of hospital stay, complications, if any, like anastomotic leakage, ileus, wound problems and others, rate of reoperation, rate of readmission \& 30-days mortality) were analyzed and compared.The criteria for patients selection were the following: histological diagnosis of adenocarcinoma of rectum, no anesthesiological contraindications to minimally invasive surgery, age ≤ 75 years, ASA ≤ 2 \& the procedures performed by the same surgical team. Patients with metastatic disease, malignant bowel obstruction (MBO) and those with irresectable tumor were excluded from our study. Preoperative workup (endoscopy with biopsies, radiological imaging including pelvic MRI, liver ultrasound, chest X-ray and routine abdominal and digital rectal examinations) was routinely carried out. The assignment of patients to either group was done by a permuted block randomization. It was an open-labeled study i.e. patients, investigators (surgeons, researchers) and data collectors knew which procedure will be done to which patients. The study was approved by the institutional review board of the National Cancer Institute, Cairo University. All patients provided written informed consent.

Robotic-assisted Versus Conventional Laparoscopic Approach for Rectal Cancer Surgery

Robotic-assisted Versus Conventional Laparoscopic Approach for Rectal Cancer Surgery, First Egyptian Academic Center Experience, Randomized Controlled Trial (RCT)

the surgical margins are considered adequate if the proximal, distal and circumferential radial margins are at least 5 cm, 2 cm and 0.1 cm respectively

National Cancer Institute, Egypt

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Cetuximab

Immunoglobulins

Antineoplastic Agents, Immunological

Three patients will receive 10mg Cetuximab-IRDye800cv I.V. four days prior to surgery.

Patients will receive 25mg Cetuximab-IRDye800cv I.V. four days prior to surgery.

Patients will receive 50mg Cetuximab-IRDye800cv I.V. four days prior to surgery.

Patients will receive 75mg cetuximab + 15 mg Cetuximab-IRDye800CW I.V. four days prior to surgery.

Patients will receive 75mg cetuximab + 25 mg Cetuximab-IRDye800CW I.V. four days prior to surgery.

After having established the optimal cetuximab-IRDye800CW dose we will extent the study by including up to 70 patients for this specific dose (as determined in phase 1).

Pre-operatively administration of Cetuximab-IRDye800CW for intra operative margin assessment using a fluorescent antibody-based optical tracer

Cetuximab-IRDye800CW

Max J.H. Witjes, MD, PhD

Floris J. Voskuil, MD

Surgery remains a main pillar in the treatment of head and neck squamous cell carcinoma (HNSCC). The margin status is the main prognostic factor of local tumor control in surgically treated HNSCC and will determine the postoperative treatment strategy. A margin of ≤1 mm of normal tissue is considered a positive margin and requires either a re-operation or postoperative chemoradiation with a combination of cisplatin and 5-FU, which substantially increases morbidity. Margins wider than 1 mm but less than 5 mm require re-operation, or, if that is not possible, post-operative radiotherapy without the concomitant use of chemotherapy. Currently, no technology is available in the operating room, which reliably supports tumor excision in terms of margin status. In fact, surgeons can only combine pre- operative imaging data with tactile and visual information during surgery for assessing tumor margins with limited accuracy. With the introduction of molecular imaging techniques using near infrared (NIR) fluorescent optical contrast agents coupled to targeted compounds, new avenues have opened up for intra-operative assessment of tumor margins. Tracers are based on antibodies directed against Vascular Endothelial Growth Factor-A, i.e. bevacizumab-IRDye800CW, in patients with breast cancer or against Epidermal Growth Factor Receptor, i.e. cetuximab-IRDye800CW, in patients with HNSCC. First trials have shown that systemic administration of these compounds is safe and tumor specific. These findings prompted us to design this innovative application in a clinical trial for the intraoperative assessment of tumor margins during surgical treatment of HNSCC using cetuximab-IRDye800CW.

Surgery remains a main pillar in the treatment of head and neck squamous cell carcinoma (HNSCC). The margin status is the main prognostic factor of local tumor control in surgically treated HNSCC and will determine the postoperative treatment strategy. A margin of ≤1 mm of normal tissue is considered a positive margin and requires either a re-operation or postoperative chemoradiation with a combination of cisplatin and 5-FU, which substantially increases morbidity. Margins wider than 1 mm but less than 5 mm require re-operation, or, if that is not possible, post-operative radiotherapy without the concomitant use of chemotherapy. Currently, no technology is available in the operating room, which reliably supports tumor excision in terms of margin status. In fact, surgeons can only combine pre- operative imaging data with tactile and visual information during surgery for assessing tumor margins with limited accuracy. With the introduction of molecular imaging techniques using near infrared (NIR) fluorescent optical contrast agents coupled to targeted compounds, new avenues have opened up for intra-operative assessment of tumor margins. Tracers are based on antibodies directed against Vascular Endothelial Growth Factor-A, i.e. bevacizumab-IRDye800CW, in patients with breast cancer or against Epidermal Growth Factor Receptor, i.e. cetuximab-IRDye800CW, in patients with HNSCC. First trials have shown that systemic administration of these compounds is safe and tumor specific. These findings prompted us to design this innovative application in a clinical trial for the intraoperative assessment of tumor margins during surgical treatment of HNSCC using cetuximab-IRDye800CW. The study is subsidized by the Dutch Cancer Foundation.

Objectives The main purpose is to establish the intraoperative use of cetuximab-IRDye800CW as a reliable marker for residual tumor in resection margins after surgical removal of HNSCC. The objective is to establish the positive predictive value of cetuximab-IRDye800CW fluorescence as a marker for a tumor positive resection margin.

Study design The study is designed as a phase 1-2, single center prospective cross sectional diagnostic study in patients with HNSCC that require surgical excision. First, a dose finding study will be performed in 9 patients using 10, 25 and 50 mg of cetuximab-IRDye800CW with three patients per dose cohort. In the first and only performed study at the University of Alabama (UAB) using cetuximab-IRDye800CW in the visualization of HNSCC, the dose found to be optimal was 25mg/m2. We therefore think that a sufficient dose will be found within the proposed range. The most optimal dose from the three studied doses will be used in the second part of the study which will include a cohort of 70 patients. The choice of cetuximab-IRDye800CW dose will be a balance between the lowest dose vs. a clinically usable tumor to background ration (TBR) on the fluorescence images.

During the second phase of the study tumor margins will be studied in a cohort of 70 patients to determine the positive predictive value of optical imaging to identify positive margins. Based on historical data retrieved from our HNSCC database at UMCG we anticipate in a cohort of 70 patients at least 14 (20%) margin-positive patients and a 90% EGFR overexpression rate. We anticipate a sensitivity of 90% of the cetuximab-IRDye800CW conjugate based on the EGFR overexpression rate, which we will be able to measure with sufficient precision ( 95%CI of 60-96%).

Study population Patients eligible for inclusion should suffer from a squamous cell carcinoma in the head and neck region (HNSCC) of which the head and neck tumor board of the UMCG has advised to be treated by surgical removal.

Patient related study procedures Tracer administration: patients will visit the hospital four days prior to the planned surgery of their HNSCC. The cetuximab-IRDye800CW will be injected by slow infusion and patients will be monitored for potential side effects. The dose will be either 10, 25 or 50 mg of cetuximab-IRDye800CW which is less or equal to 10% of the dose of cetuximab when used for curative treatment of HNSCC (usually 400mg/m2 loading dose and 250mg/m2 maintenance dose).

Pre-operative fluorescence imaging, spectroscopy and assessment of tracer concentration/stability Only during phase 1, patient will undergo pre-operative imaging and spectroscopy measurement one day prior to surgery. Furthermore, 6 blood samples will be drawn and tissue will be collected at different time point during the study for assessment of tracer concentration/stability.

Intraoperative fluorescence imaging and spectroscopy Study aims: The aim is to identify squamous cell carcinoma as fluorescent spots in the margin of a tumor resection specimen or in the wound bed in the patient.

Parameters: Fluorescence imaging and spectroscopy: Fluorescence images will provide an overview of where cetuximab-IRDye800CW fluorescence is located in the resection specimen and the wound bed in the patients. The intra operative camera is very sensitive for cetuximab-IRDye800CW fluorescence. One drawback is that on the fluorescence image the exact depth from which the fluorescence signal is generated cannot be established. Furthermore, most likely there will be background fluorescence signals from normal tissue. Therefore, confirmation of the fluorescence signal on images requires quantification of the fluorescence signal. This can be performed by using a spectroscopy technique (MDSFR spectroscopy) that can quantify (in M/m3) specifically IRDye800CW-fluorescence by placing a fiber tip in contact with the tissue. This spectroscopy technique has a shallow sampling depth of 1-2 mm. If fluorescence is generated from deeper layers, the signal of spectroscopy will be low (only background signal from muscle, connective tissue and salivary glands). If the IRDye800CW-fluorescence signal is generated from tumor in the resection margin the fluorescence signal will be much higher because SCC-tumor cells overexpress EGFR. The parameter that will be established is the threshold level at which background cetuximab-IRDye800CW spectroscopy signal can be separated from much higher spectroscopy signals of cetuximab-IRDye800CW accumulated in tumor.

Pathology: The tumor specimen will be processed for histology according to the current standard used in clinical cancer care. Diagnosis on margins, selected histological features necessary for clinical decision making will be provided. Next to this fluorescence images will be collected from the tumor specimen and biopsies. Margin width and number of positive margins will be noted and correlated to the location of fluorescent locations in the margins. From this positive predictive value will be calculated.

Burden, risks and benefit related to participation Burden - Time investment: Patients need to make one extra visit to the UMCG four days before their planned surgery that will take approximately 2 hours. Usually patients are admitted one day prior to the planned surgery. Therefore the measurements one day before surgery will not require extra time investment Burden-extra procedures: 1) Intravenous administration of cetuximab-IRDye800CW. 2) Fluorescence images will be taken from the tumor one day prior to surgery in the first cohort of nine patients. 3) The estimated time for taking fluorescence images and spectroscopy measurements is approximately 30min. Therefore the time under general anesthesia will be prolonged. The usual time of surgical procedures for removal of HNSCC ranges from 2 hours to 15 hours, depending on complexity of the surgical procedure. 4) from the wound bed in the patient that exists after tumor excision, biopsies will be taken in the ongoing general anesthesia, of spots positive of cetuximab-IRDye800CW as seen on the fluorescence imaging and confirmed by spectroscopy.

Risks: Allergic reactions to cetuximab have been reported but this is considered a low risk. No preclinical or clinical study reported higher than grade 2 adverse events. the first study with cetuximab-IRDye800CW no serious events were reported in six patients.

Benefit: Patients will have no benefit from this study directly. Surgery will be planned as usual. During surgery, no decisions will be made based on the fluorescence imaging. The benefit of this study will be the establishment of usefulness of cetuximab-IRDye800CW during surgery to identify margins containing tumors. The results of these types of study will be at least beneficial for other patients with cancer in the future. Clinical experience will be obtained with fluorescent labeled antibody in intra operative margin assessment during surgery of HNSCC.

Phase 1: 3x3 Dose-escalation with 3 different doses Cetuximab-IRDye800CW Phase 2: Prospective cross sectional diagnostic study. After having established the optimal cetuximab-IRDye800CW dose we will extent the study by including up to 70 patients.

Image Guided Surgery for Margin Assessment of Head and Neck Cancer Using Cetuximab-IRDye800CW cONjugate

The primary endpoint for the feasibility study (9 patients) will be confirmation of the clinically applicable dose of cetuximab-IRDye800CW. The aim is to obtain at least a TBR higher than 2 by fluorescence imaging with the intra operative camera. This number has been found to give sufficient demarcation of tumor to normal tissue on wide field images.

Determine a threshold level of fluorescence that can discriminate between EGFR distribution in normal tissue and a margin with EGFR-positive tumor.

By ex vivo imaging and MDSFR spectroscopy of the excised specimen

Identification of the tissues that show IRDye800CW-fluorescence in the surgical wound bed after tumor removal

Localisation patterns of cetuximab-IRDye800CW in the tumor and normal tissue by microscopy

The assessment of the minimal thickness of the non-fluorescent margin of the excised specimen with histopathology and fluorescence microscopy. This will provide us the first data on the relationship between margin thickness when fluorescence cannot be detected.

UMC Utrecht

Erasmus Medical Center

University Medical Center Groningen

MD, PhD

Skin and Connective Tissue Diseases

Breast Neoplasms

Carcinoma in Situ

Breast Carcinoma In Situ

Breast Diseases

Skin Diseases

Central Nervous System Depressants

Anesthetics

Fluorodeoxyglucose F18

A single intravenous injection of 18F-FDG (0.80 MBq/kg) is given between 30 minutes and 3 hours before tumor resection.

Surgical resection of the breast tumor (= main specimen) under general anesthesia.

The main specimen is imaged using the Aura 10 PET-CT Specimen Imager (XEOS Medical, Ghent, Belgium). In case of positive margins, the surgeon will perform oriented cavity shaving. The cavity shaves and lymph nodes (if any) are also imaged using the Aura 10 PET-CT Specimen Imager (for scientific purposes only).

The main specimen and if applicable the cavity shaves and lymph node(s) are processed following standard-of-care routine: from tissue samples to HE-stained and IHC-stained sections. The histopathological margin status shall be reported according to the ASCO-CAP guidelines, and shall be compared to the PET-CT images of the resected specimens.

high-resolution PET-CT specimen imaging.

Menekse Göker, med.

Menekse Göker, MD

Breast-conserving surgery (BCS) has become the standard-of-care for surgical management of the majority of women with early-stage breast cancer. Successful BCS entails excision of the tumor with an adequate amount of surrounding healthy breast parenchyma, such that negative resection margins are obtained. Despite efforts to obtain tumor-free margins, approximately 20-30% of women still require reoperation.

The rationale of this study is to examine the contribution of the adjunctive use of perioperative high-resolution PET-CT specimen imaging in early-stage breast cancer to the identification of all positive resection margins during breast-conserving surgery. Histopathological findings of the breast tumor specimen are applied as the gold standard.

After a successful screening phase and after informed consent is provided, the patient will enroll the study. The preparations for the BCS proceed following the routine protocol (i.e. as if the patient would not participate in the study). In addition to these standard preparations, on the day of surgery the patient will receive a study-specific injection with a low dose of a radiotracer substance (18F-FDG; 0.8 MBq/kg). Before injection, the blood sugar level will be measured by a small finger prick. If the blood sugar level is good, the radiotracer substance will be intravenously administered. The injection is given at the nuclear medicine department between 30 minutes and 3 hours before surgery. After the injection was given, the patient will be transferred to the operating theatre. The breast tumor will be removed in the same way as if the patient is not participating in the study. As soon as the tumor is excised, it will be imaged using the specimen PET-CT scanner in the operating theatre. While waiting for these 3D images, the surgeon will remove the lymph nodes, if applicable. The breast surgeon will then evaluate the 3D images of the removed breast tumor. In case of suspected positive margins, the surgeon will excise additional breast tissue to ensure that all tumor tissue is excised during this surgery. For scientific purposes only and if available, the cavity shaves and resected lymph nodes will also be imaged with the specimen PET-CT scanner. No clinical decisions that could affect further treatment will be based on this. After surgery, all excised tissues will be sent to the pathology department. This is standard routine and is also done for patients not participating in the study. A routine follow-up visit will be planned with the surgeon. During that routine visit, a staff member of the study team will ask additional study-related questions regarding possible complications. If the latter is not possible during the standard follow-up visit, a staff member of the study team will contact the patient by phone call 1-3 weeks after surgery. The study is completed after this follow-up visit or phone call.

Specimen PET-CT Imaging for Intraoperative Margin Assessment in Breast Cancer

High-resolution PET-CT Imaging for Intraoperative Margin Assessment in Early-stage Breast Cancer: a Prospective Multicentric Interventional Clinical Study

The primary effectiveness endpoint is a measure of perioperative success in addressing positive margins of the invasive component with the adjunctive use of high-resolution PET-CT specimen imaging as detected by permanent pathology in the IDC subgroup.

A measure of perioperative success in addressing positive margins of the invasive component with the adjunctive use of high-resolution PET-CT specimen imaging as detected by permanent pathology in:

* the total study population excluding the DCIS subgroup (IDC + ILC + NAT);
* the ILC subgroup;
* the NAT subgroup.

A measure of perioperative success in addressing any positive margin with the adjunctive use of high-resolution PET-CT specimen imaging as detected by permanent pathology in:

* the total study population (IDC + DCIS + ILC + NAT);
* the IDC subgroup;
* the DCIS subgroup;
* the ILC subgroup;
* the NAT subgroup.

A measure of perioperative success in obtaining final negative margins of the invasive component as detected by permanent pathology (1) by the additional use of high-resolution PET-CT imaging and (2) by additional use of standard-of-care in:

* the total study population excluding DCIS (IDC + ILC + NAT);
* the IDC subgroup;
* the ILC subgroup;
* the NAT subgroup.

A measure of perioperative success in obtaining final negative margins (invasive and/or in situ component) as detected by permanent pathology (1) by the additional use of high-resolution PET-CT imaging and (2) by additional use of standard-of-care in:

* the total study population (IDC + DCIS + ILC + NAT);
* the IDC subgroup;
* the DCIS subgroup;
* the ILC subgroup;
* the NAT subgroup.

A measure of the number of patients with final positive resection margins of the invasive component after BCS in:

* the total study population excluding DCIS (IDC + ILC + NAT);
* the IDC subgroup;
* the ILC subgroup;
* the NAT subgroup.

A measure of the number of patients with final positive resection margins (invasive and/or in situ component) after BCS in:

* the total study population (IDC + DCIS + ILC + NAT);
* the IDC subgroup;
* the DCIS subgroup;
* the ILC subgroup;
* the NAT subgroup.

Sensitivity, specificity, positive and negative predictive value, failure rate and, interobserver reproducibility of high-resolution PET-CT imaging based on the invasive component of:

* the total study population excluding DCIS (IDC + ILC + NAT);
* the IDC subgroup;
* the ILC subgroup;
* the NAT subgroup.

Sensitivity, specificity, positive and negative predictive value, failure rate and, interobserver reproducibility of high-resolution PET-CT imaging based on any margin of:

* the total study population (IDC + DCIS + ILC + NAT);
* the IDC subgroup;
* the DCIS subgroup;
* the ILC subgroup;
* the NAT subgroup.

The number of patients that require a second or a third surgery due to positive margins at initial primary breast-conserving surgery and the type of repeat surgery (BCS or mastectomy).

The volume (mm³) of resected main specimen, and possible cavity shaves after PET-CT imaging and possible cavity shaves after standard-of-care approach.

A measure of success in detecting malignant cells in resected lymph nodes and cavity shaves with the adjunctive use of high-resolution PET-CT specimen imaging as detected by permanent pathology.

XEOS Medical

This is a single arm study, which will involve all patients qualifying for Breast Conservation Therapy as a part of their breast cancer management excluding patients undergoing neoadjuvant therapy for inoperable disease.

Zenith FLIM Diagnostics

Brad Schoengood

Our investigational team has developed a technology to visualize the operative margins in 'real time,' in other words during the operation while the patient is still on the table. While different surgeons use different operative techniques, our technique involves removing the main lumpectomy specimen, marking two of its borders with suture to orient the specimen for correct pathologic evaluation.

The FLIM (Fluorescent Lifetime Imaging Microscopy) technique can differentiate between cancerous and noncancerous specimens using a complex algorithm that essentially utilizes a definitive delta between the metabolic activities of diseased and non-diseased tissue. The research coordinator along with the surgeon will be able to insert the lumpectomy specimen followed by the 6 shaved margins (one by one) in a matter of minutes once the specimens have been resected. To be clear, the FLIM analysis will be taking place in- vitro. The device is invitro test and would be tested against the gold standard the pathologist biopsy.

FLIM analysis by the surgeon will not take more than several minutes, therefore not adding any significant time for patient to be under anesthesia. All specimens will be removed from the patient's body prior to their evaluation by the FLIM technique. Our team will not be making decisions based on FLIM analysis during this early phase of study. In other words, even if FLIM suggests a positive margin still exists in the body, our team will not act on these results by resecting additional tissue at this stage. FLIM margin results will be compared directly with pathology results for accuracy of the findings.

The purpose of this study is to evaluate the effectiveness of the investigational Zenith FLIM Diagnostics imaging device that's modality is a direct support during lumpectomy cancer surgery to achieve the common goal of improving patient quality of life by decreasing rates of re-operation. The team is fully dedicated to bringing the Gold Standard in the operating room, enabling margin assessment, in real time, at the histological detail.

Our operative technique involves removing the main lumpectomy specimen, marking two of its borders with suture to orient the specimen for correct pathologic evaluation. Next, we take 6 shave margins in all directions around the lumpectomy cavity (superior, inferior, medial, lateral, posterior, anterior) and anchor an orientation stitch at the far side of the margin, again, for pathologist to understand which side was farthest away from the lumpectomy specimen.

The research coordinator along with the surgeon will be able to insert the lumpectomy specimen into the Zenith FLIM device followed by the 6 shaved margins (one by one) in a matter of minutes once the specimens have been resected. To be clear, the Zenith FLIM analysis will be taking place in-vitro. The machine will be placed a good distance from the patient, in an ante-room, and does not require sterility. Of course, if the surgeon breaks sterility while handing off the specimens for FLIM analysis, he or she will have to re-sterilize as would be standard if sterile conditions are broken for any other reasons (having to re-scrub because sterility is broken is a common procedure). Once the specimens are placed in the Zenith FLIM, the specimens will no longer be sterile, but there is no need to maintain sterility of the specimens once they are in-vitro. In fact, even in the absence of Zenith FLIM analysis, once the specimens are placed in cups for pathologic evaluation, they are no longer sterile. In other words, loss of sterility of the specimen is a necessity of the operation regardless of Zenith FLIM analysis.

The device is an in-vitro test and would be tested against the gold standard: the pathologic evaluation of resected tissue. The test results would not be used for any diagnosis. Neither the test nor the unit comes in contact with patients under any circumstance. The Zenith FLIM margin results will be compared directly with pathology. The effectiveness of the Zenith FLIM Diagnostics margin results will be compared directly with pathology and evaluated in this study.

Real-time Diagnosis and Visualization of Tumor Margins in Excised Breast Specimens Using Zenith FLIM Diagnostics

Tumor distance from margin in all 6 dimensions compared to final histopathologic diagnosis/confirmation in testing for accuracy of the Zenith FLIM.

Laser LabCorp

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Penile Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Penile Diseases

Male Urogenital Diseases

Penile Cancer

Patients receive 75mg of Cetuximab, followed by 15mg Cetuximab-IRDye800CW I.V. two days prior to surgery.

Patients will receive 75mg Cetuximab followed by 15mg Cetuximab-IRDye800CW two days prior to surgery

The main treatment modality for Penile Squamous Cell Carcinoma (PSCC) is surgery with curative intent. In organ sparing surgery a tumor-positive margin of up to 36% exist. Tumor-positive surgical margins are an independent risk factor for local recurrence, which has been reported to be up to 18%. Tumor-positive margins always lead to extra, penile sparing surgery, which leads to longer hospitalization, higher exposure to anesthetic interventions and a worse psychological outcome.

Currently, no intraoperative imaging technique that provides real time feedback for resection margins exists in PSCC. Molecular fluorescence-guided Surgery (MFGS) using targeted near-infrared (NIR) optical contrast agents like for example Cetuximab-800CW is a promising technique to accommodate this need. Epidermal Growth Factor Receptor (EGFR) is overexpressed in PSCC and has safely and successfully been used as target for molecular imaging, particularly for assessment for tumor margins in head and neck squamous cell carcinoma (ICON study, UMCG1).

The main treatment modality for Penile Squamous Cell Carcinoma (PSCC) is surgery with curative intent. There is no difference in mortality between organ sparing surgery and radical surgery, and for optimal cosmetic and functional results small resection (3-5mm) margins are used. In organ sparing surgery a tumor-positive margin of up to 36% exist. Tumor-positive surgical margins are an independent risk factor for local recurrence, which has been reported to be up to 18%. These local remaining tumor depositions can be continuous or discontinuous from the main tumor, which makes it hard for the treating surgeon to recognize them clinically. Tumor-positive margins always lead to extra, penile sparing surgery, which leads to longer hospitalization, higher exposure to anesthetic interventions and a worse psychological outcome.

Currently, no intraoperative imaging technique that provides real time feedback for resection margins exists in PSCC. Molecular fluorescence-guided Surgery (MFGS) using targeted near-infrared (NIR) optical contrast agents like for example Cetuximab-800CW is a promising technique to accommodate this need. Epidermal Growth Factor Receptor (EGFR) is overexpressed in PSCC and has safely and successfully been used as target for molecular imaging, particularly for assessment for tumor margins in head and neck squamous cell carcinoma (ICON study, UMCG1).

Objectives:

The purpose of the current study is to determine the feasibility of using MFGS using Cetuximab-800CW as an intraoperative margin assessment tool for penile carcinoma.

Study design:

The study is a single-center prospective, phase1 feasibility study. In total, fifteen patients with biopsy proven PSCC will be included. 2-4 days before surgery, a predose of 75mg 'cold' cetuximab will be administered intravenously, followed by 15mg of cetuximab-800CW intravenously, with 1 hour between start of the cold dose and the cetuximab-800CW. After 3 patients are included, an interim analysis will be performed. If a tumor to background of \>2 is obtained with either in vivo or ex-vivo analysis, the next 12 patients will be included. If a TBR of \<2 is reached, the dose of cetuximab-800CW will be increased to 25mg with the same predosing scheme, 75mg of cold cetuximab. When 3 patients are included in the second dose group, a second interim analysis will be performed. If a tumor to background of \>2 is obtained by ex-vivo analysis, 12 patients more will be included. If a TBR of \<2 is found, the study will be terminated.

Study population:

Patients with histologically proven PSCC who meet all in- and exclusion criteria, and are opted for primary surgery as their treatment.

Patient related study procedures:

After written informed consent is obtained, patients will receive an intravenous administration of 75mg 'cold' cetuximab followed by 15mg of cetuximab-800CW 1 hour after the administration of the predose. 2-4 days after the injection of the imaging agent, fluorescence imaging is performed intraoperatively, both in vivo and ex vivo. 1 day after surgery, fluorescence imaging will again be performed during pathological processing on the excised tissue. Both intraoperatively and during the pathology process, fluorescence will be quantified by MDSFR/SFF spectroscopy.

Main study parameters/endpoints:

The main objective of this feasibility study is to investigate whether cetuximab-800CW could be used for margin assessment during surgery in patients with PSCC.

Burden, risks and benefit related to participation.

Burden:

The extra burden the patients associated with the study procedure is an extra visit to the hospital 2-4 days before surgery for the administration of cetuximab-800CW. This will take approximately 2 hours. Also, the surgical procedure will be prolonged 15-20 minutes due to fluorescence imaging and spectroscopy measurements.

Risks:

Risks to study participants are mainly related to the risks of the administration of the imaging agent. No preclinical or clinical study reported higher than grade 2 adverse events using cetuximab-800CW, moreover, these studies used significant higher doses of the investigational product. Previous studies with cetuximab-800CW reported no imaging agent related serious events. Currently, a phase 2 trial is performed at the UMCG with Cetuximab-800CW (NCT03134846), no grade 2 or higher imaging agent related serious advents were reported so far.

Benefit:

Patients will have no benefit from this study directly. Surgery will be planned as usual. During surgery, no decisions will be made based on the fluorescence imaging.

Image Guided Penile Cancer Surgery

Fluorescent Guided Surgery in Penile Carcinoma Using Cetuximab-800IRDyeCW

The main purpose is to establish the intraoperative use of cetuximab-800CW as a reliable marker for residual tumor in resection margins after surgical removal of PSCC. The objective is to establish the feasibility of cetuximab-800CW fluorescence at the dose of 75/15 mg predose/dose combination as a marker for a tumor positive resection by comparing the spot to background ratios for tumor positive and tumor negative margins. A tumor to background ratio of \>2.0 is aspired.

To quantify sensitivity and positive predictive value of cetuximab-800CW fluorescence of PSCC ex vivo using optical molecular imaging and MDSFR/SFF versus standard immunohistochemistry.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Robotic-assisted Versus Conventional Laparoscopic Approach for Rectal Cancer Surgery	NCT03589131	Rectal Cancer	Total Operative... Margin assessme... Conversion rate... Baseline demogr... Preoperative da... Postoperative d...	16 Years - 75 Years	National Cancer Institute, Egypt
Image Guided Surgery for Margin Assessment of Head and Neck Cancer Using Cetuximab-IRDye800CW cONjugate	NCT03134846	Head and Neck S... Margin Assessme...	Cetuximab-IRDye...	18 Years -	University Medical Center Groningen
Specimen PET-CT Imaging for Intraoperative Margin Assessment in Breast Cancer	NCT04999917	Breast Cancer Breast Cancer I... Breast Cancer i...	high-resolution...	18 Years -	XEOS Medical
Real-time Diagnosis and Visualization of Tumor Margins in Excised Breast Specimens Using Zenith FLIM Diagnostics	NCT04683120	Oncology Breast Cancer Cancer Diagnosi... Margins of Exci... Margins, Tumor-...	Zenith FLIM Dia...	18 Years -	Laser LabCorp
Image Guided Surgery for Margin Assessment of Head and Neck Cancer Using Cetuximab-IRDye800CW cONjugate	NCT03134846	Head and Neck S... Margin Assessme...	Cetuximab-IRDye...	18 Years -	University Medical Center Groningen
Specimen PET-CT Imaging for Intraoperative Margin Assessment in Breast Cancer	NCT04999917	Breast Cancer Breast Cancer I... Breast Cancer i...	high-resolution...	18 Years -	XEOS Medical
Image Guided Penile Cancer Surgery	NCT05376202	Penile Cancer Margin Assessme...	Cetuximab-IRDye...	18 Years -	University Medical Center Groningen

Spots Global Cancer Trial Database for margin assessment