AboutMesothelioma.Net

Preoperative Staging of Mesothelioma by 18F-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography Fused Imaging

Friday, October 17, 2008

Source: European Journal of Cardio-Thoracic Surgery

Full Title: Preoperative Staging of Mesothelioma by 18F-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography Fused Imaging and Mediastinoscopy Compared to Pathological Findings After Extrapleural Pneumonectomy

Disease staging is one of the fundamental steps in the development of a treatment plan for patients with mesothelioma. Effective measurement of tumor spread and the identification of distant metastases are important indications of long-term prognosis and, therefore, are determinate conditions in deciding which patients are eligible for radical surgery and which patients will be treated less invasively. Generally speaking, patients who are considered Stage I-III for pleural mesothelioma may be acceptable for “curative” surgeries such as extrapleural pneumonectomy, while patients with Stage IV disease are excluded from these procedures and will be treated palliatively. Staging is designed to separate out patients so those in the disease’s later stages do not undergo operations that are associated with significant surgical complications and extended recovery time when their long-term prognosis is not hopeful.

Historically, however, there have been difficulties in the accurate determination of stage because of mesothelioma’s unique behavior and morphological form. Unlike most other cancers which present as an individualized tumor with clear boundaries (even if there are multiple tumors, they generally fit this same individualized pattern), pleural mesothelioma presents as a diffuse malignancy that grows along tissue surfaces, with little distinction between malignant and non-malignant areas. This can make determining the full extent of tumor infiltration difficult to properly image. CT is the standard technology in diagnostic imaging for mesothelioma and MRI can be used to supplement its results, but these technologies have known limitations in determining a number of important tumor states, including tumor involvement of the chest wall and diaphragm, as well as a fundamental inability to identify distant metastatic events or to determine lymph node status. PET can be used to identify distant metastases, but it has poor spatial resolution, so precise localization is difficult. Mediastinoscopy is used to determine the status of the mediastinal lymph nodes, but it is an invasive procedure and is limited in its ability to target all of the important lymph nodes.

Because of these difficulties, some of which are common to all cancers and some of which are specific to pleural mesothelioma, researchers have developed a number of new technologies to aid physicians in their ability to accurately diagnose and stage malignant events. One of these new systems is integrated PET/CT, which combines PET’s ability to identify distant metastases with CT’s high resolution imaging of internal anatomic structures. A number of studies on this technology’s use for mesothelioma have been published and the results have been quite promising. Continuing this researching, researchers in Denmark have recently published an article on their use of PET/CT in the preoperative staging of patients with pleural mesothelioma. In their article, “Preoperative Staging of Mesothelioma by 18F-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography Fused Imaging and Mediastinoscopy Compared to Pathological Findings After Extrapleural Pneumonectomy,” the authors demonstrate PET/CT’s advancements over CT for pre-operative staging and they recommend its greater use in the staging of mesothelioma, but they also show that it cannot replace mediastinoscopy for the analysis of nodal status.

Overview of the Study

42 patients were enrolled in the study between October 2003 and October 2006. All patients had histologically-confirmed mesothelioma, epitheloid subtype. All patients received neoadjuvant chemotherapy prior to their staging assessments, which were conducted by CT and PET/CT. The results of the scans were interpreted separately and blinded from the other. Patients whose PET/CT results indicated any non-resectable tumor infiltration of the chest wall or of structures in the mediastinum, or any evidence of distant metastases, were not given surgery, although patients whose results indicated possible N2 or N3 metastases were still referred for mediastinoscopy for histological determination of stage. If these results also showed positive N2 or N3 metastatic status, the patients did not undergo surgery.

All other patients were referred for extrapleural pneumonectomy.

The study was interested in two major topics:

1. The ability of PET/CT compared to CT to detect inoperative stages of mesothelioma; and,
2. The validity of PET/CT’s results for staging, when compared against mediastinoscopy and final staging determined at EPP

Results

CT vs. PET/CT for Preoperative Staging

The results of the CT vs. PET/CT analysis showed a clear benefit to PET/CT. Of the 42 patients who were screened, PET/CT discovered: T4 disease in 7 patients, while CT did not show any; 14 patients with N2 or N3 disease, while CT only showed 7 patients; and 7 cases of distant metastases, while CT, again, did not show any. These findings resulted in an “upstage migration” of 8 cases: CT disclosed only one case as Stage IV disease, while PET/CT identified nine Stage IV cases (including the one identified by CT). In total, PET/CT excluded 12 of the 42 cases as non-resectable due to T4/M1 status, while CT did not exclude any.

PET/CT vs. Mediastinoscopy

PET/CT identified 30 patients with potentially-resectable disease. Of these patients, 14 indicated possible N2/N3 status, but they were not excluded from surgical consideration without histological confirmation of the findings. All 30 patients were then referred for mediastinoscopy. 6 patients demonstrated histologically-confirmed N2 metastases, which reduced the number of patients eligible for extrapleural pneumonectomy to 24.

All of these patients then received an EPP.

PET/CT vs. Final EPP Staging Results

Of the 24 patients who underwent EPP, 2 had undiagnosed T4 disease that PET/CT missed. T-stage was lower in 1 patient, equal in 13 and higher in 10. These results led to the following stage migration: percentage of patients identified as Stage I was reduced from 63% to 21%, while Stage IV patients increased from 4% to 12%. When compared to both mediastinoscopy and EPP staging, PET/CT correctly identified a number of N-stage cases, but it was also less accurate then both: it under-staged 3 patients when compared to mediastinoscopy and 7 when compared to final staging completed during EPP.

Conclusion

Mesothelioma remains a very difficult disease to treat effectively, and only a subset of patients are eligible for the invasive procedures that are necessary to possibly extend survival times for the disease. The need for accurate staging technologies is not unique to the treatment of pleural mesothelioma, but the difficulties of the disease complicate it. CT has been used, but it has well-known limitations for mesothelioma staging. PET/CT has showed great promise in other studies and the authors of the article describing the present study conclude that PET/CT is an important advancement in the surgical staging of pleural mesothelioma, but that it doesn’t alleviate the need for invasive, yet more accurate, diagnostic techniques such as mediastinoscopy. PET/CT can improve the selection of patients for EPP, especially when compared with CT, but the authors state that more work needs to be done to develop more accurate, non-invasive techniques.

Labels: mesothelioma, pleuralmesothelioma, staging

posted by Belluck & Fox at 3:23 PM
Link to this article

The Impact of Lymph Node Station on Survival in 348 Patients with Surgically Resected Malignant Pleural Mesothelioma

Wednesday, October 15, 2008

Source: The Journal of Thoracic and Cardiovascular Surgery

Full Title: The Impact of Lymph Node Station on Survival in 348 Patients with Surgically Resected Malignant Pleural Mesothelioma: Implications for Revision of the American Joint Committee on Cancer Staging System

The current system for staging cases of pleural mesothelioma is based on a TNM model, where the determination of disease stage is based on the relationship between tumor status (T stage), lymph node status (N stage) and the presence or absence of distant metastases (M stage). This system was proposed in 1995, validated through a number of reports and subsequently accepted as the standard mesothelioma staging system by the American Joint Committee on Cancer Staging System, as well as by the Union Internationale Contre le Cancer.

However, a number of questions regarding its underlying classification structure have existed since it was initially proposed. Writing in the journal The Journal of Thoracic and Cardiovascular Surgery, physicians from the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City state that the current staging system was designed to be adjusted as more and better data regarding the classification of nodal status was developed. The authors of the article note that the staging system uses the lymph node map developed for lung cancer staging, but that pleural mesothelioma may require a different pattern map because lymphatic drainage from the pleura may differ from that of the lung.

To answer these questions, as well as others regarding the nodal classification system in mesothelioma patients, the physicians from MSKCC conducted a study on patients with pleural mesothelioma who were treated at their institution and they have recently published their results in an article entitled “The Impact of Lymph Node Station on Survival in 348 Patients with Surgically Resected Malignant Pleural Mesothelioma: Implications for Revision of the American Joint Committee on Cancer Staging System.”

Overview of the Study

The staging system is only applicable to surgical patients, so the retrospective study that the physicians conducted was limited to those patients who underwent either extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D). 348 patients were finally selected for analysis. The sample population, as is common with all forms of mesothelioma, was heavily male gender with the epitheloid histological subtype. 222 patients received EPP, while 126 underwent P/D. Most patients were Stage III at time of surgery.

These patient records were analyzed on a number of fronts, including nodal status (both individual and concurrent metastases), common nodal station involvement, surgical procedures and time to survival.

Results

Overall median survival for the entire patient cohort was 15 months, with significant variations in survival when patients were analyzed for differences in nodal status, as well as histological subtype and overall stage. Patients with N0 or N1 status demonstrated a 19-month median survival time, while patients positive for N2, N2/N1 or internal thoracic node metastases demonstrated a 10-month median survival. Patients with only N2 status did not differ significantly from patients who were positive for both N2 and N1, but multiple N2 nodal stations were indicative of more restricted median survival time.

Other variations in survival were also reported: epitheloid vs. non-epitheloid histology, with non-epitheloid disease associated with worse survival; male gender vs. female gender, with men demonstrating a worse prognosis then women; Stage III/IV patients were associated with shorter survival than were Stage I/II patients.

Conclusion

In the discussion section of the article, the authors considered the importance of their findings in relation to the current staging system. Their results show that pleural mesothelioma is most likely to metastasize to N2 nodes, rather than to N1 nodes. The authors also note that because patients positive for only N1 nodes were associated with longer median survival than were patients positive any form of N2 metastases, the staging system should likely be changed to incorporate this distinction.

These results also confirmed an earlier study these physicians conducted which found that nodal metastasis is common in patients with pleural mesothelioma—nearly 50% of the patient cohort demonstrated some lymph node involvement.

Along with the differences in survival between N1 and N2 status, the results also demonstrated that metastases in multiple N2 nodal stations correlates with a worse prognosis than does N2 status in only one station. Because of this, the authors also state that the staging system could possibly be adjusted to show that multiple N2 stations reflect a higher stage than does a single N2 station.

The authors close the article with a call for larger study on the impact of nodal status on mesothelioma prognosis. Their research indicates grounds for revision of the staging system, but a larger, multicenter study would be needed to confirm these findings.

Labels: mesothelioma, pleuralmesothelioma, staging

posted by Joseph DiCastro at 3:44 PM
Link to this article

Diagnosis, Staging, and Surgical Treatment of Malignant Pleural Mesothelioma

Tuesday, September 23, 2008

Source: Current Treatment Options in Oncology

Advances in diagnostic technologies and treatment-related procedures for mesothelioma patients have led to enhanced survival times for a number of different patient classes. These advances have allowed physicians to diagnose the disease sooner than they’ve previously been able to diagnose it, which allows treatments for mesothelioma to begin at an earlier time as well. However, not all patients are eligible for these new procedures and most still receive a diagnosis in the disease’s later stages when radical surgery is not an option. Because of this, research into pleural mesothelioma and peritoneal mesothelioma continues on a number of important fronts.

A series of articles on mesothelioma have recently been published in Current Treatment Options in Oncology, an important medical journal that features expert commentary on contemporary treatment practices for a number of different cancers. One of these recent articles is a report on the diagnosis, staging and surgical treatment of pleural mesothelioma. The article describes the current thinking on these topics and provides a detailed overview of the current mesothelioma staging system.

Overview of the Article

The article is divided into three basic sections: Diagnosis, Staging and Surgical Management. The section on mesothelioma diagnosis describes the “clinical and radiological presentation” of the disease, as well as some of the steps and procedures involved with pathology analysis. The section on staging describes, in detail, the current staging system used for pleural mesothelioma patients. The final section describes various treatment protocols featuring surgical intervention.

Mesothelioma Diagnosis

When the disease is in its earliest stages, the results of physical examinations are “non-specific,” but they quickly become more serious as the disease progresses. CT (computed tomography) scans are the preferred imaging modality for most cases of mesothelioma. MRI features enhanced resolution and soft-tissue contrast over CT, but for basic diagnostic purposes the images provided by CT are more than adequate. CT’s principal failing is poor presentation of chest wall involvement and tumor infiltration of certain pleural structures, so MRI may be indicated for these particular purposes, but CT is adequate for most cases of preoperative staging.

The article also discusses a study conducted by Dr. Harvey I. Pass that showed how three-dimensional CT imaging can be used to conduct pre-operative tumor volume analysis. Dr. Pass found that CT was able to measure tumor bulk and to predict survival times among patients with different levels of tumor volume, so CT is said to have both diagnostic value and prognostic value.

Another common imaging system in mesothelioma diagnosis is PET (positron emission tomography). PET is an important diagnostic modality because it specializes in the identification of distant metastases, something that CT is simply unable to do. Because radical surgery requires patients to be in the best overall health, any evidence of distant tumor seeding is a negative indicator for this kind of procedure. Even as staging is PET’s primary function in mesothelioma treatments, there is evidence that indicates PET can also be used to predict median survival in some patients.

Imaging technologies are the standard non-invasive diagnostic procedures, but a definitive diagnosis requires pathology assessment. The most common procedures that physicians deploy for sample extraction and analysis are thoracentesis, thoracoscopy and VATS. Due to its highly invasive nature, thoracotomy is not indicated for exploratory surgery.

When the sample has been removed, a pathologist must examine the specimen for malignant indications. Immunohistochemistry analysis is the standard testing methodology to determine a diagnosis. Because no single marker is 100% positive for mesothelioma, most of these analyses test against a panel of antibodies and use a combination of positive stainings and negative findings to determine a complete diagnosis.

For more information, please read mesothelioma diagnosis.

Mesothelioma Staging

A variety of staging systems have been proposed for mesothelioma, but all of them have had some notable downsides. The current system in use was developed by the International Mesothelioma Staging Systems group and is a 4-stage system that is based on a TNM model that represents an individual’s present state of tumor spread (T), lymph node status (N) and existence of metastases (M). Within each of these designations, there are individual status designations and the final staging decision is based on combining the statuses of each of the constituent models. The T value measures the extent of tumor bulk and spread, and has 5 possible values: T1a, T1b, T2, T3, T4, with T1a the best case scenario for mesothelioma patients, meaning limited tumor bulk, with no involvement of the visceral pleura. The N status has 4 possible values: N0-N3, again with N0 the best case, meaning no lymph node involvement. The M status is a value of 0 or 1, meaning no distant metastases or any evidence of distant metastases.

These designations are then put together to determine an individual patient’s current stage. The staging system is as follows:

For more information, please read: mesothelioma stages.

Surgical Management of Mesothelioma

Most patients who are diagnosed with mesothelioma receive a diagnosis later in life. Because of this, accurate staging of patients is an important element in developing a treatment plan, especially a plan that can include surgery. Older patients are less likely to tolerate the invasive surgery and extensive recovery associated with mesothelioma surgeries. Patients with no evidence of metastases and limited tumor involvement are the target patients for surgical intervention and multimodal therapy. Those with M1 status are immediately not considered for radical surgery. For patients who are between the best and worse cases though, a judgment call must me made by their physicians as to appropriate an treatment course.

Multimodal protocols featuring surgery, chemotherapy and localized radiotherapy remain the best way to extend median survival for eligible patients, but there is still much research being conducted on which combination of modes is the most effective in treating mesothelioma, so definitive statements on treatment methods are not yet possible. The role of pleurectomy/decortication vs. extrapleural pneumonectomy is one of the most controversial questions among mesothelioma physicians. A number of studies have been done, but the choice often comes down to the choice of individual surgeons. There are a number of other controversial questions as well, such as the the question of whether chemotherapy should be deployed in an adjuvant or a neoadjuvant manner for greatest treatment efficacy.

For more information on mesothelioma treatments, please read: Mesothelioma Treatments: Surgery and Mesothelioma Treatments: Chemotherapy and Radiation.

Conclusion

Even as research as improved the efficacy of our treatments, mesothelioma still remains one of the most difficult of all cancers to treat effectively. The work that is currently being conducted by physicians and researchers is an important step in changing the dynamics of mesothelioma treatment and diagnosis.

Labels: diagnosis, mesothelioma, staging, surgery, treatments

posted by Belluck & Fox at 4:03 PM
Link to this article