Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Neoplastic Cells, Circulating

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neoplasm Metastasis

Neoplastic Processes

Carcinoma, Bronchogenic

Bronchial Neoplasms

Ryan Dittamore, MBA

The purpose of this study is to establish the circulating tumor cell (CTC) assay as a surrogate for tissue diagnosis of suspected primary lung cancer. This is done through evaluating clinical and molecular markers to stratify the outcome/survival in patients with thoracic malignancies treated at Yale University/Yale-New Haven Hospital, University of California San Diego/Moores Cancer Center, Billings Clinic Cancer Center.

Cell solution plated onto slides and frozen for storage

Circulating Tumor Cells in Non-Small Cell Lung Carcinoma

Phase 2 Study of Circulating Tumor Cell in Non-Small Cell Lung Carcinoma

After informed consent of the patients, a single tube of blood will be drawn and processed according to the standard protocol. These blood draws will occur upon patient screening or rather the baseline of their treatment, a 6-12 week follow-up, as well as a 12 month follow-up.Furthermore, a biopsy will be taken between baseline and 6-12 week follow-up which will be used upon results of CTC enumeration to illustrate concordance. Epic Sciences staff is fully blinded to the clinical data of the patients until final analysis. Patients will be considered CTC positive at a count of greater than 2 CTCs per ml of blood.

Based on the blood draws from the primary outcome, Epic will utilize the identified CTCs as biopsy material for lung cancer subtyping that distinguishes between adenocarcinoma (ACA), squamous cell carcinoma (SCC) from other types of primary lung cancer. Lung cancer histology will be evaluated for each patient sample: Two slides will be run with the ACA-CTC assay (TTF1 or Napsin A) and two slides will be run with the SCC-CTC (p63) assay. For the purpose of assay development and validation, we have all already procured a validated set of patient samples with known histology.

For patients ultimately diagnosed with lung cancer and deemed to be surgical candidates, surgical intervention will be performed. In accordance to a standard practice mediastinal lymph node dissection will accompany the surgery. Nodal staging for each patient in the trial with diagnosed lung cancer will be evaluated clinically and pathologically. Clinical staging will be determined by the treating clinician prior to information being available from surgery and recorded in the case report form. The diagnostic accuracy of the clinical stage will be determined by comparison with the pathological stage which will be abstracted from the pathology report for surgically staged patients. We will determine the sensitivity and specificity of the CTC count as a test that identifies patients who will ultimately be "upstaged" from N0 to N1 or from N1 to N2-3 at the time of surgical staging when comparing the clinical and pathological stage.

This measure will work to establish the prognostic value of the initial test by drawing the correlation with outcome data. For the 260 patients recruited to this clinical trial, stage specific Kaplan-Meier overall and disease free survival curves for the population will be generated after 2 years of follow-up. For each stage, the results of the CTCs will then be used to separate the population for each stage into a low CTC and high CTC group to determine if the disease free survival curves for each stage separate on the basis of the assay and are statistically significant using a retrospective analysis of the prospectively collected data, this will determine if knowledge of the CTC assay provides useful information about disease free survival beyond that which is obtained by clinical staging alone.

Yale University

Billings Clinic

University of California, San Diego

National Cancer Institute (NCI)

Epic Sciences

7 days minimum non-invasive ventilation at 2 levels of pressure (BPAP) to the intervention.

non-invasive ventilation in two pressure levels 7 days before surgery

Manufacturer (VPAP ST)

Nicolas PALEIRON, MD

Surgical treatment is the standard treatment for localized forms of lung cancer non-small cell. It allows a 5-year survival exceeding 50% for complete resection of the tumor. This is a heavy treatment, resulting in a mortality of 4 to 8% and a morbidity of 20-60%. Securing this procedure is a major public health issue. The non-invasive ventilation is a technique commonly used postoperatively in acute respiratory distress and in the treatment of sleep apnea syndromes. Through its effect on oxygenation and pulmonary function parameters, the non-invasive ventilation achieved during 7 days minimum before the intervention could significantly reduce postoperative complications in patients with an obstructive or restrictive disorder, obesity or chronic heart failure.

The aim of the study is to demonstrate that the non-invasive ventilation in two pressure levels achieved during at least 7 days before surgery lung resection (lobectomy or segmentectomy) halved the pulmonary and cardiovascular postoperative patients with obstructive ventilatory disorder or restrictive, obesity or chronic heart failure.

Non-Invasive Ventilation Preoperative Lung Resection Surgery

Evaluation of Non-Invasive Ventilation Preoperative Lung Resection Surgery

Demonstrate that the non-invasive ventilation in two pressure levels achieved during at least 7 days before surgery lung resection (lobectomy or segmentectomy) halved the pulmonary and cardiovascular postoperative patients with obstructive ventilatory disorder or restrictive, obesity or chronic heart failure.

Identify subgroups of patients benefiting most from a non-invasive ventilation preoperatively and safety of this technique preoperatively.

Ministry of Health, France

University Hospital, Brest

Necrosis

Soft Tissue Neoplasms

Radiofrequency ablation is an inpatient procedure typically requiring one overnight stay in the hospital.

Radiofrequency ablation of pulmonary malignancies

Quality of life assessment is administered prior to the Radiofrequency ablation procedure and every 3 months for 1 year following the procedure.

Quality of life assessment

Pain scores are obtained prior to the procedure, daily X 7 starting on the day of surgery, and then every 3 months for 1 year.

Assessment of pain

James Luketich, MD

The purpose of this study is to assess short and long term outcomes after radiofrequency ablation (RFA) of pulmonary malignancies in patients who are not candidates for surgical resection. This study will evaluate the efficacy of RFA for the treatment of lung tumors by assessing its impact on local tumor control, progression free survival, overall survival, dyspnea score and quality of life (QOL).

The use of RF ablation in pulmonary tissue is not new. However previous reports have primarily been descriptions of technique and early procedural outcomes. Follow-up studies have been lacking. This study will provide information on outcomes such as rates of clinical response, overall survival, progression-free survival, dyspnea and QOL.

The determination of the efficacy of this technique with this study could make an important contribution to the management of patients with pulmonary malignancies with high operative risk for resection. A minimally invasive alternative for tumor destruction could potentially improve quality of life by controlling local tumor progression and could provide longer survival when compared to current non-surgical options. This pilot study will determine the potential utility and effectiveness of RFA treatment of lung tumors, and whether to further evaluate this therapy in prospective randomized clinical trials compared to other conventional modalities.

Lung cancer is currently the most common cause of cancer-related death in the USA and represents the second most common malignancy in both men and women with 171,400 new cases in the year 1999. Unfortunately, the majority of patients present with advanced disease. Despite advances in the management of this disease, the best 5-year survival for stage I remains around 70% for patients who have undergone surgical resection. Complete resection provides the best chance for cure and remains the gold standard of therapy for patients with acceptable surgical risk.

The role of surgical resection of pulmonary metastasis in selected patients is widely accepted, and a survival advantage of aggressive surgical therapy has been demonstrated. Surgical series have demonstrated 5-year survival of 25-42% in the surgical treatment of pulmonary metastasis from different primaries including colorectal cancer osteogenic sarcoma, melanoma, and others. In a prospective study of 5,206 cases of lung metastasectomy, the International Registry of Lung Metastases reported an actuarial survival of 36% at 5 years and 26% at 10 years. These results compared favorably with those who had an incomplete resection achieving a survival of 13% at 5 years and 7% at 10 years.

The standard resections for primary lung cancer include lobectomy or pneumonectomy depending on the size and location of the tumor. Limited resections, including segmentectomy or wedge resection of the lung, are the standard treatment for limited metastases and are good alternatives for patients with primary lung cancer and poor lung function who cannot tolerate a larger resection. However, a prospective randomized trial to address the role of limited resection for primary lung cancer was performed by the Lung Cancer Study Group in 276 patients with T1N0 NSCLC. Patients in the limited resection group suffered a 50-75% increase in local recurrence rate, but no survival difference was seen between the two groups. Limited resection however should continue to be viewed as a good option for metastasectomy but a compromising operation for primary lung cancer.

The treatment options for patients with pulmonary malignancies who have severe comorbidities or poor pulmonary function are limited. These patients are many times not considered for surgical resection because of the excessive risk of undergoing an invasive operation and are often treated with external beam radiation and/or chemotherapy. In the case of pulmonary metastases occurring after previous pulmonary resection, further resection is sometimes not feasible due to limited residual pulmonary parenchyma or dense adhesions.

After the widespread application of radiofrequency ablation (RFA) for the destruction of unresectable liver tumors, this technique has been considered as an alternative therapy for the ablation of other solid tumors. The initial experience in the treatment of lung tumors with RFA indicates that the technique appears to be safe and feasible for ablation of peripheral lung nodules.

The U.S. Food and Drug Administration approved RFA for coagulation necrosis of soft tissue tumors. In addition, RFA has been widely used for treatment of pulmonary nodules in France, Germany, Japan, Korea, and the People's Republic of China.

Radiofrequency ablation systems are comprised of three components: a radiofrequency generator, an active electrode, and dispersive electrodes. The RF energy is introduced into the tissue via the active electrode. As the RF energy (alternating current) moves from the active electrode to the dispersive electrode (i.e., the electrosurgical return pad) and then back to the active electrode, the ions within the tissue oscillate in an attempt to follow the change in the direction of the alternating current. This movement results in frictional heating of the tissue, and as the temperature within the tissue becomes elevated beyond 60°C, cells begin to die. It is this phenomenon that causes the region of necrosis surrounding the electrode.

The advantage of such a thermal intervention system is the capacity to heat tissue to a lethal temperature in a specific anatomic location. The advantages of such a procedure in the treatment of non-resectable hepatic and renal lesions are reduced surgical trauma, shorter procedure time, shorter hospitalization, and a faster recovery time. In the treatment of lung nodules, this allows for destruction of lung tumors with minimal damage to surrounding normal lung tissue.

Coagulation necrosis of soft tissue due to RF ablation has been reported in liver, kidney, breast, and lung tissues. Radiofrequency ablation of primary and metastatic hepatic lesions has been reported to result in necrosis encompassing 70% to 98% of tumors treated. To date, little has been reported on the use of RF ablation to address pulmonary nodules. In a presentation of three case studies, follow-up CT imaging noted that cells within the region of the thermal lesions were fibrotic and in only one of the three patients was residual disease detected. Using positron emission tomography (PET) imaging of the lung, a series of ten patients noted that within the boundaries of the thermal lesions there was no evidence of metabolic activity.

A pre-clinical study was undertaken in a porcine model in order to determine the capacity of RF energy to induce necrosis of lung tissue. Using differing power settings and length of application times, it was determined that the thermal lesions produced in the porcine lung tissue were complete and entire, with no procedure-related complications. Animals survived to 3, 7 and 28 days post-RF ablation were active and showed no evidence of detrimental effects of the RF-induced necrosis on respiratory capacity or function. The regions of necrosis were affected by conductive heat loss via air and blood flow and the presence of bronchi, which resulted in invagination of the thermal lesion boundary; however, all cells within the boundaries were nonviable.

Determining the effectiveness of the RF ablation usually involves follow-up computed tomography (CT) scans. CT imaging provides an assessment of tissue changes following an ablation, which can manifest as central cavitation of the lesion with decreased tissue density measured by a decrease in Hounsfield units (Hu). As complementary modality, positron emission tomography (PET) can be used to determine tissue viability within the lesion, which can be useful in the follow-up of these patients. In particular, patients with questionable response to RFA as determined by CT scan can benefit from PET scanning, by determining the presence of residual disease. The patient is injected with a radio-labeled sugar (typically 18 Fluoro-deoxyglucose or FDG) prior to the PET scan and viability is determined based upon the uptake of the FDG by cells, since FDG is taken up by cells with high metabolic activity, such as tumors, infection, or inflammation. In a small pilot study, monitoring with PET noted no viable tissue within the boundaries of the thermal lesions induced in pulmonary nodules.

In the investigators' initial experience at the University of Pittsburgh Medical Center, they treated 18 patients with RFA and included primary and metastatic lung tumors. Selected patients were not candidates for complete surgical resection based on surgical risk, multiple lesions, poor pulmonary reserve or refusal of further surgery. Twenty-eight lung nodules were treated with RFA in 18 patients (12 male, 6 female). Tumors included metastatic carcinoma (9), sarcoma (6) or lung cancer (3). Mean age was 52 years (range, 27-95). Thoracic surgeons performed RFA by mini-thoracotomy (5) or CT-guided percutaneously (13) under general anesthesia in the operating room. In both approaches, the patient was positioned in the lateral decubitus position. In the CT-guided procedures we employ the services of a CT technician and the thoracic surgeon places a small finder needle into the center of the lung nodule. The surgeon confirms successful central placement of the finder needle during CT imaging, and the LeVeen™ needle electrode size is chosen according to the diameter of the target lesion. The needle electrode has a diameter of 14 gauge with a 15 cm shaft length and is introduced in the center of the lesion under CT guidance. Several applications in different locations within the lesion may be required for larger masses, with the therapy beginning at the most distal area and progressing proximally. Chest tubes were required in 46% (n=13) of percutaneous procedures. Mean length of stay was 3 days (range, 1-7 days). Complications included recurrent pneumothorax (1/18), pneumonitis (6/18), small pleural effusion (7/18) and transient renal failure (1/18). One death occurred from hemoptysis 19 days post-RFA of a central nodule. This patient had also received recent brachytherapy. After a mean follow-up of 4 months (range, 1-11 months), computed tomography revealed resolution with decreased density of treated sites less than 4 cm. Six patients (33%) died of progressive metastatic disease during the follow-up period.

Even though RFA has been used to treat lung tumors in over 300 patients worldwide, there is still a need to further define the role of RFA for pulmonary malignancies. In particular the effects of RFA on dyspnea and quality of life as well as follow-up studies are lacking.

Study of Outcomes of Radiofrequency Ablation of Lung Tumors

A Prospective Study of Outcomes of Radiofrequency Ablation of Lung Tumors

RITA Medical Systems

University of Pittsburgh

Professor

Nervous System Diseases

Immune System Diseases

Blood and Lymph Conditions

Rare Diseases

Myasthenia Gravis

Thymoma

Thymus Neoplasms

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases

Autoimmune Diseases of the Nervous System

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Neuromuscular Diseases

Neoplasms by Histologic Type

Lymphatic Diseases

Pulmonary lobectomy and thymectomy procedures will be performed by da Vinci SP Surgical System.

da Vinci SP Surgical System, instruments, and accessories in pulmonary lobectomy and thymectomy for benign and malignant disease.

Robotic-Assisted Surgery

David Rice, MD

To confirm the safety and performance of the da Vinci SP Surgical System, Instruments and Accessories in pulmonary lobectomy, and in thymectomy procedures.

Primary performance:

The primary endpoint will be assessed as the ability to complete the planned da Vinci SP-assisted thoracic procedure without conversion to an alternate approach. Conversion to an alternate approach comprises undocking of the da Vinci SP to complete the planned procedures using other methods, such as open, VATS, or multiport robotic (da Vinci SI or X/Xi)

Primary Safety:

The primary safety endpoint will be assessed as the incidence of all intra-operative and post-operative adverse events that occur through the 30-day follow-up period.

SP Thoracic IDE Study

A Prospective, Multi-Center Investigation of the da Vinci SP Surgical System in Pulmonary and Lobectomy for Benign and Malignant Disease

Performance defined as the ability to complete the planned da Vinci SP-assisted pulmonary lobectomy and thymectomy procedures without conversion to an alternate approach

Safety defined as the incidence of all intra-operative and post-operative adverse events that occur through the 30-day follow-up period.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Circulating Tumor Cells in Non-Small Cell Lung Carcinoma	NCT01830426	Primary Lung Ca...		19 Years -	Epic Sciences
Non-Invasive Ventilation Preoperative Lung Resection Surgery	NCT01685580	Surgery for Pri...	Manufacturer (V...	18 Years -	University Hospital, Brest
Study of Outcomes of Radiofrequency Ablation of Lung Tumors	NCT00280189	NSCLC Pulmonary Metas...	Radiofrequency ... Quality of life... Assessment of p...	18 Years -	University of Pittsburgh
Non-Invasive Ventilation Preoperative Lung Resection Surgery	NCT01685580	Surgery for Pri...	Manufacturer (V...	18 Years -	University Hospital, Brest
Study of Outcomes of Radiofrequency Ablation of Lung Tumors	NCT00280189	NSCLC Pulmonary Metas...	Radiofrequency ... Quality of life... Assessment of p...	18 Years -	University of Pittsburgh
Non-Invasive Ventilation Preoperative Lung Resection Surgery	NCT01685580	Surgery for Pri...	Manufacturer (V...	18 Years -	University Hospital, Brest
Circulating Tumor Cells in Non-Small Cell Lung Carcinoma	NCT01830426	Primary Lung Ca...		19 Years -	Epic Sciences
SP Thoracic IDE Study	NCT05150210	Primary Lung Ca... Benign Lung Dis... Thymoma Myasthenia Grav...	Robotic-Assiste...	21 Years -	Intuitive Surgical

Spots Global Cancer Trial Database for primary lung cancer