The Importance of Prognostic Factors in Mesothelioma

As published in the Annals ofCardiothoracic Surgery November 2012 issue.

There is no doubt that malignant pleural mesothelioma (MPM) needs better non-invasive and accurate prognostication (the ability to predict medical outcomes of a treatment or disease) for several reasons, including but not limited to the following: a median survival of 12 months with first line therapy; a median survival of 24 months when treated in a multimodal approach; a staging system currently undergoing a major update, not to mention the diffuse nature of the disease and its variable biology.

Better prognostication in MPM would mean the ability to better differentiate among patients, hopefully at the time of diagnosis. For patients with a poor prognostic, either palliative therapy or no therapy may be appropriate. If prognostic factors indicate that long term survival is possible, aggressive treatment or novel protocols would be justified.

Typically, prognostication in MPM has been approached by studying many variables, usually one at a time and at many centers, all with limited numbers of patients. This is approach is problematic because prognostication cannot function in a vacuum and the majority of these findings remain unsubstantiated in other MPM populations. For example, Although MPM patients tend to be older individuals who are frequently functionally impaired and may have difficulty with aggressive therapy, there is still a significant number of MPM patients with a favorable biology in a multimodal approach, who benefit from intense therapy.

Such variables that can be studied can be purely clinical, such as patient demographics that are frequently combined with standard laboratory values including white blood cell count or platelet count. Other scientists have focused on radiologic parameters by examining CT and PET scans.

Some of the most advanced research being accomplished today uses a molecular pathologic approach, by studying genomics, microRNA, epigenetics or proteomics in order to define single or combinations of candidate prognostic biomarkers from tissue or blood. The future of prognostic biomarkers in MPM will most likely involve a multi-institutional consortium of centers which will harvest tissue, blood and other specimens in a protocol using the same standard operating procedures in order to minimize extraneous differences which could lead to false positive results.

As new research platforms develop, it will be crucial to make sure that an ongoing registry which incorporates solid demographics as well as documentation of specimen archiving be available to the mesothelioma community. At this time the National Mesothelioma Virtual Tissue Bank fulfills that role in the United States, and is adding new sites to ensure that substances and tissues for MPM prognostication will be available for continuing research.

Click here to view the full article.

Analysis of the Updated IASLC Staging Database for Mesothelioma Patients

As published in the Annals of Cardiothoracic Surgery November 2012 issue.

In collaboration with the International Mesothelioma Interest Group (IMIG), the International Association for the Study of Lung Cancer (IASLC) decided to update the staging system for malignant pleural mesothelioma (MPM) by developing a large international database.

It is widely known that an accurate staging system is essential for assessing the benefit of new MPM therapies. However until the mid-1990s, no such evidence-based staging systems existed and few utilized the TNM (tumor, node, metastasis) system which was developed to achieve consensus on one globally recognized standard for classifying the extent of the cancer spread by using the size and extension of the primary tumor, its lymphatic involvement and the presence of metastases to classify the progression of cancer. Eventually these revisions, including adopting the TNM system, were incorporated and accepted by the UICC (International Union Against Cancer) and the AJCC (American Joint Commission on Cancer) as the international MPM staging system.

This article succinctly reviews information from analyses of the IASLC database which is currently the largest multicenter and international database in MPM and identifies areas in which the current staging system should be revised.

As IASLC and IMIG investigators continue to expand their database, they expect the data gathered will more accurately reflect the clinicopathological and treatment-related prognostic factors which significantly influence overall survival based on the TNM staging system, tumor histology, gender, age and type of operation. 

Click here to view the full article.

Johnson Family Pledges $500,000 to Help Early Detection and Treatment of Veterans

LOS ANGELES, CA. On the same day that a new California law takes effect which humanely limits the time defense lawyers can depose mesothelioma plaintiffs to 7 hours, the John Johnson family, whose personal tragedy helped galvanize the new law, announced their pledge of $500,000 for mesothelioma medical research.

Johnson Family.

"We want to help other families avoid what happened to ours," said Sue Johnson, whose husband John Johnson, a military veteran stricken with the asbestos-caused cancer, collapsed after a grueling deposition and died within 24 hours.

The Johnson family has pledged the donation to the Pacific Mesothelioma Center ("PMC"). They have asked that the donation be used to help initiate a collaborative research and clinical care program between the PMC and the Department of Veterans affairs.

"Dr. [Robert] Cameron did everything he could surgically to save John," said Mrs. Johnson, "but by the time he was diagnosed, he was already stage III. We'd like to help the VA find and use new ways to diagnose mesothelioma as early as possible, so that patients have a fighting chance to survive."

The money will be used to help launch of the Admiral Zumwalt Mesothelioma Research and Treatment Program within the Department of Veterans Affairs.  A key component of the proposed program is early detection.

"The Johnson family's generosity is truly amazing," said attorney Roger Worthington, of the Worthington & Caron law firm, who represents the Johnson family. "When the legal system failed the Johnson family, they stepped up and helped change the law. When the VA missed an opportunity to diagnose Mr. Johnson much earlier, the Johnson family again stepped up to improve the way veterans are diagnosed and treated at the VA."

John Johnson, USMC

The Admiral Zumwalt Mesothelioma Research and Treatment Program is an initiative proposed jointly by Mr. Worthington and PMC. "The family of Admiral Elmo Zumwalt, who died from mesothelioma nearly twelve years ago to the day, has expressed a desire to lend their father's name for a comprehensive program to help veterans," said Mr. Worthington, noting that nearly a third of Americans diagnosed with mesothelioma were exposed to asbestos while serving in the military.

John Johnson proudly served his Country as a member of the United States Marine Corps where, in the spirit of "Semper Fi,"  it is said: "Once a Marine, always a Marine. Commitment never dies." Through their efforts to improve the medical and legal options available to others diagnosed with mesothelioma, the Johnson family has ensured that John's commitment to Corps and Country will never die.

For more information, contact Worthington & Caron, PC.  Email: john@worthingtoncaron.com; Phone: 1-800-831-9399; Worthington & Caron, PC is  law firm located in San Pedro, California that has dedicated its practice to representing patients diagnosed with asbestos-related mesothelioma since 1990.

New Depo Limit Law To Become Effective January 1st---What a Difference a Year Makes!

On January 1, 2013, California Code of Civil Procedure Section 2025.290 will become effective limiting plaintiff depositions in most civil cases to no more than seven (7) hours over two days, or 14 hours of total testimony.

Previously there were no state-wide statutory limits on the length of plaintiff depositions. This omission in the law often allowed defense counsel to subject plaintiffs to prolonged and repetitive questioning, causing undue stress and exhaustion.

The new law was motivated by the plight of John Johnson, a 68 year-old veteran of the U.S. Marines and retired plumber who was diagnosed with mesothelioma and filed a lawsuit against the companies responsible for his asbestos exposure in October 2011. In the case, we presented a declaration from Dr. Robert Cameron imploring the court to limit Mr. Johnson’s deposition to 12 hours, as Mr. Johnson was a stage III patient who had just emerged from an 11 hour surgery and was undergoing post-surgery radiation. Dr. Cameron warned the court that interrogation in excess of 12 hours would “hasten his demise.” The court limited the deposition to 20 hours but later granted another 5 hours over our objections and a second declaration from Dr. Cameron.

The deposition began on December 19, 2011 and, after 10 sessions conducted over 35 days, was concluded on January 23, 2012. As predicted by Dr. Cameron, the rigors of the process produced a dramatic decline in Mr. Johnson’s condition. Knowing that unless he completed the mandated 25 hours, none of his testimony could be used in the lawsuit which would be his wife Sue’s only source of financial support, Mr. Johnson could not be deterred from finishing the job. Mr. Johnson passed away less than 24 hours after completing the deposition.

This unfathomable, but not unanticipated, result was a rallying call for Worthington& Caron, P.C. and other plaintiffs’ attorneys who had long sought to impose reasonable limits on defense deposition questioning. Working together with the support of Mr. Johnson’s wife, Sue Johnson, the effort gained media attention and finally the support of key California lawmakers. The measure was passed by the California legislature on August 29, 2012 and signed into law by Governor Jerry Brown on September 17, 2012.

As 2012 comes to an end, we reflect back on the tragic events involving John Johnson and extend our warmest and sincerest wishes to his family as they spend their first Holiday season without him. We hope they find some satisfaction in knowing that their government took notice of their nightmare and acted quickly and decisively to keep other Californians from enduring it in the future.

Section 2025.290 is a long-overdue measure which provides a defense to the basic civil liberties of asbestos cancer patients and other seriously injured plaintiffs. These are people for whom time is precious. They want to get well. They can’t work. They have mounting bills. They weren’t looking for a lawsuit but, like John Johnson, have no other potential source of financial resources. We applaud the California legislature and Governor Brown for the protections that injured plaintiffs will get to begin enjoying in the New Year!

John M. Caron

December 20, 2012

New Biomarker May Allow Earlier Diagnosis of Mesothelioma

Mesothelioma can be difficult to diagnose and early diagnosis is even more challenging due to the long latency period and similarity of symptoms to many common ailments. Researchers of the New York University Langone Medical Center have identified a new biomarker, the protein fibulin-3, which may allow for earlier diagnosis, higher efficiency of treatment and a more optimistic prognosis.

Researchers compared fibulin-3 levels from plasma and effusion samples from 142 patients with mesothelioma, 136 cancer-free individuals who had been exposed to asbestos, 93 patients with effusions not due to mesothelioma, and 91 patients with cancers other than mesothelioma.

Effusion fibulin-3 levels were significantly higher in patients with pleural mesothelioma than in patients with effusions not due to mesothelioma.  The fibulin-3 levels were able to distinguish patients with mesothelioma from those with benign effusions due to other cancer types or non-diagnosed persons who had been exposed to asbestos with a sensitivity of 100% and a specificity of 94.1%.

In 18 patients, fibulin-3 levels fell after surgery, the biomarker could prove to be an efficient tool for not only earlier diagnosis, but also monitoring mesothelioma patient’s response to therapy or disease progression. Click here to read the abstract of this study.

Pacific Meso Center’s 5k Walk & BBQ—A Rousing Success!

This past Sunday, the Pacific Mesothelioma Center hosted the Inaugural 5k Walk & BBQ at Paramount Ranch in Agoura Hills to raise awareness about mesothelioma and to pay tribute to those who have fought the disease or are still fighting. PMC’s sole aim is to discover new treatments for malignant pleural mesothelioma and to improve mesothelioma victims’ lives and longevity.

More than 200 family members, friends, and colleagues gathered in the Old West Town, formerly the site of numerous westerns filmed during Hollywood’s Golden Age, and set off for the hills for the scenic 5K walk/hike/run. The sun was high and the way steep, but our determination won out over the 90 degree weather and our efforts were well rewarded with some of the best BBQ in the West and the musical stylings of Karen Tobin and her country band.

PMC’s original fundraising goal was $25,000. At last count, this event has raised a whopping $66,900 and the donations are still coming in! The top fundraising team was no other than the McCarthy clan with their team Irish Stampede, in loving memory of Gerald McCarthy.

Team Evens in honor of Randy Evens

Also supporting the cause was Team Evens which was made up of family and friends of Randy Evens. Team Evens included Randy's wife Ginny and daughters Laura and Diana.  Team Evens was proud to boast that no matter the distance, they would keep on walking to get the word out and to chase down a cure. There were other great friends and gracious clients of ours also in attendance, including: the Ganoe family and friends, the Belvedere family and friends, the Jarvis family and friends and Kay Simmons-Gilpatrick.

It was admirable to see these families band together to honor their loved ones and give something back to help future victims. I tip my hat to thee. And my sore feet.

Dr. Cameron Proposes IMIG Consensus Statement on the Role of Surgery in Mesothelioma Treatment

Recently several hundred doctors and scientist from all over the world with an interesting in mesothelioma met in Boston to discuss, among other things, the role of surgery in treating meso patients (the "IMIG" group).

Earlier, a paper had been published out of the UK that questioned the merits of extrapleural pneumonectomy (EPP)  as compared to chemotherapy alone (the trial didn't offer pleurectomy/decortication).  The IMIG group pointed out various flaws in the design and operation of the trial.  In particular, the clinical trial, the first of its kind anywhere, had terrible trouble over a period of three years recruiting the 50 patients it needed for a pilot trial. The MARS group's plan was to follow up the pilot study with a full blown and statistical meaningful mega-trial of 670 patients. They never got there. 

Of the 50 meso patients they did recruit, many of those did not complete the arm of the study they started (ie. surgery only or chemo only), or they crossed over (from surgery to chemo, or vice versa) during the trial. 

The MARS authors to their credit did acknowledge this deal-breaker problem. They went so far as to question whether a clincial trial of this kind was ever feasible at all in the real world, where patients simply don't want to be "guniea pigs" even in the greater interests of medical advancement. A clinical trial of this scope has never even been attempted in the US.

In the US, patients have many choices, and it remains "muddy" what the best option is across the board for the "average" meso patient.  Dr. Cameron and Dr. Sugarbaker have publically disagreed over which surgery is "better" - ie. EPP vs Pleurectomy/Decortication. However, both agree today that the role of surgery is to remove as much tumor as you can see (what Dr. Sugarbaker has coined "complete macroscopic resection" (MCR)).  Dr. Cameron has been a long time advocate of pulling up his sleeves and pulling out a much tumor as he can see, without watching the clock, noting that "negative margins" was and always will be a pipedream for a meso surgeon.

I encourage you to read the draft proposal submitted by Dr. Cameron, which is based on an earlier draft proposed by Dr. Sugarbaker.  Although there are stylistic differences, both agree that surgery should be performed along with adjuvant care to attack the unseen tumor cells that remain in the body after surgery.

As Dr. Cameron tactfully writes: "The exact surgical procedure should be based on disease distribution, surgeon preference and experience, and institutional experience and should be performed with a morbidity and mortality consistent with published literature." 

As a patient, before making your decision (e.g., chemo only? What chemo? Surgery? What operation? By whom and where?),  the IMIG Group has also recommended that you follow these important guidelines:

• Pathological diagnosis including histologic subtype should be established by tissue biopsy.
  
• Clinical staging be performed prior to initiation of therapy and should include PET with lymph node sampling and/or MRI as indicated.
• The type of surgery (EPP, P/D, etc) should be based on clinical factors as well as individual surgical judgment and expertise.
• Complete surgical stating should include hilar and mediastinal lymph node removal.

To review a complete text of Dr. Cameron's proposed IMIG consensus statement, please click here.  The IMIG board will review all comments and submit the final approved version for publication in a suitable journal with collective authorship.  Doctors as well as patients need and deserve this kind of up-to-date education. We applaud Dr. Cameron and Dr. Sugarbaker, as well as all the other doctors, who have participated in this project.

RGW

10/16/12