Best of iMig 2014: Day 1

CocktailReception***The Best of iMig 2014 updates were created by iMig and distributed to conference attendees during iMig 2014. The following is a verbatim re-post of those updates.***

In the opening plenary session of iMig 2014, Dr. Jim te Water Naudé and Dr. Steven Mutsaers welcomed close to 300 healthcare professionals to Cape Town, South Africa.

It’s an impressive number of attendees for this somewhat remote but beautiful venue and given iMig’s membership of around 500 members. The assembled group comprises the finest minds in mesothelioma related research, treatment, and advocacy from around the world. It’s quickly evinced as a heavily scientific affair with a fun spirit as Dr. te Water Naudé jokingly threatens to use a vuvuzela horn on speakers who defy their time restrictions.

The initial plenary session focused on several areas of interest to the broad range of delegates traveling to iMig. The opening plenary speakers’ presentations are outlined below as are several key presentations chosen by iMig peers as the “Best of iMig 2014”.

Dr. Constantine Alifrangis Speaks on Next Generation Sequencing in Mesothelioma 
Click here to watch Dr. Alifrangis’s Presentation
Dr. Constantine Alifrangis focused on the study of cancer genomes and how it might be used to identify new treatments and individualize care for patients with mesothelioma. These approaches have identified specific genomic alterations in mesothelioma associated with unexpected drug sensitivities in mesothelioma. As for other cancers, study of cancer genomes in mesothelioma has the potential to guide development of novel therapies for this disease. Click here to hear and see more about this work.

Dr. Ravi Salgia presents “From Chaos to Mitochondrial Functionality” 
Click here to watch Dr. Salgia’s Presentation
Dr. Salgia summarized efforts from his group to bring mathematical modeling to the study of malignant mesothelioma and how the rules of this theory can be applied to consideration of mutations associated with mesothelioma, suggesting that DNA acts much likes fractals. He emphasized that the fractal dimensionality of mesothelioma cells is dramatically different from that of normal cells and that mitochondrial networks in mesothelioma can also be modeled with fractal analysis. Click here to learn more about this new approach to understanding mesothelioma and the biology of other cancer cells.

Dr. Robert Weinberg speaks on Cancer Stem Cell Targeting Therapies 
Click here to watch Dr. Weinberg’s Presentation
Dr. Weinberg focused on the importance of cancer stem cells in mesothelioma. The concept of a stem cell origin of cancer was first described over fifty years ago as a small subset of cells capable of re-initiating a clonal tumor, and there is evidence for both a stem cell origin of mesothelioma, and a stem cell population in the mesothelioma tumor microenvironment. These cells play an essential role in the invasion-metastasis cascade, they are risk to conventional chemotherapy,and are believed to underlie resistance and relapse in mesothelioma. Click here for a summary of the latest information on cancer stem cells in mesothelioma.

Laurie Kazan-Allen Presents on The Global Asbestos Landscape 
Click here to hear Ms. Kazan-Allen’s Presentation
Ms. Kazan-Allen emphasized that the battle with mesothelioma is being fought on two fronts: countries where asbestos has been banned and those in which consumption remains legal. In 2014 the asbestos dialogue has become a mainstream discourse encompassing fundamental matters such as human rights, public health, social justice and economic sustainability. Decisions about asbestos use must now be driven by political, social and environmental considerations, not just economics. Click here for a detailed discussion of these critical issues and the “asbestos war”.

Improving outcomes in mesothelioma: an international approach to meeting nurses’ educational needs
Click here for Liz’s Commentary
Effective management of patients with mesothelioma requires large cadres of well-trained nurses in parts of the world in which the incidence of disease is high. The United Kingdom has >2,500 cases of mesothelioma diagnosed each year and nursing education is critical for optimizing care for these individuals. The Royal Marsden School of Cancer Nursing and Rehabilitation in cooperation with Mesothelioma UK has developed an accredited interactive on-line accredited mesothelioma course to help meet this need. The course can be taken by undergraduates and graduate students.

The content of this course is tailored to meet the needs of international students and the curriculum includes two introductory, nine didactic, and three practically focused weeks of training. Content delivered by expert faculty includes global asbestos consumption, signs and symptoms of mesothelioma, diagnosis, treatment, symptom management, and medico legal issues. Patient and carers perspectives and end-of-life issues are also addressed in detail. The course content is focused on the diagnosis/treatment journey of the patient with mesothelioma.

To date, the course has been delivered 5 times to a total of 56 healthcare professionals have completed the course including several international students from Australia, South Africa, Japan, Ireland, and the United States. The course received a Quality in Health Care award in 2012. Two former course participants have gone on to develop similar educational programs in their own countries.

Courses similar to that described in this summary have been established in Australia and Japan.

Nursing collaborations, such as this online educational program, can help fill important gaps in meeting the health care needs of those affected by asbestos- related disease.

Clinicopathological features of patients with malignant mesothelioma in a multicenter, retrospective study – Dr. Manlio Mancoboni 
Dr. Mencoboni and his colleagues have focused on understanding factors that predict outcomes for patients with mesothelioma. They carried out a retrospective analysis of 235 patients with mesothelioma who were treated at 4 centers in Italy. These patients were typical of the larger population with mesothelioma: 76.6% were males and they were generally elderly with a median age of 69.6 years. Tumor histology was epitheliod in 82.6% and sarcomatoid in 4% of the cohort.

The treatment histories for these patients were also typical of those for patients with mesothelioma. Surgery was carried out in 20.4% of patients and radiotherapy was performed in 39.6%. In addition, 9.3% of patients underwent trimodal treatment. First-line chemotherapy was administered to 98.3% of the patients in the study cohort and 78% receive pemetrexed-based chemotherapy was administered to 78%. Overall, 68% of patients received second-line chemotherapy and 27% received third-line treatment.

The overall median survival for the patients study was 22.0 months and 19% survived for >36 months. Prognostic factors for survival were identified with univariate and multivariate analyses. Factors significantly associated with survival in univariate analysis were younger age, better performance scores, receipt of radiotherapy or surgery, epithelioid histology, and best response to first-line chemotherapy.

Multivariate analysis confirmed significant independent influences for younger age, surgery, sarcomatoid morphology (shorter survival), and first-line chemotherapeutic treatment (shorter survival vs best supportive care, but only for patients with a poor response to this treatment). 

Neoadjuvant Therapy and Surgery- Dr. Raphael Bueno 
Standard therapy for malignant pleural mesothelioma (MPM) has not advanced significantly in the past 10 years and new approaches to treatment are needed. Results from genomic studies indicate that mesothelioma is not a “disease of mutations” and those associated with disease are well known. These studies have shown that MPM is associated with changes in copy number, most often recurrent loss. Biological agents are being developed that can have significant activity in specific cancers based on mutation or other aberrant patterns and several have demonstrated significant activity in animal models and early phase clinical studies. There is an urgent need to rapidly evaluate these agents and identify biomarkers predictive of clinical responses. An attractive cohort for studies of this type is pre-operative with lower disease burden, availability of tumor for biomarker analysis, and the potential for standardization of prognostic markers. This approach is currently being taken with defactinib, a potent inhibitor of focal adhesion kinase in a biomarker-driven study with safety and pharmacokinetics with as secondary end points. Patients enrolled in this study have histologically confirmed MPM that is not metastatic or unresectable and are eligible to undergo excisional surgery such as extrapleural pneumonectomy or pleurectomy/decortication or any other mesothelioma surgery. Additional agents that might be evaluated in this should have:

  • Rational targets predictive of efficacy in MPM based on preclinical studies
  • Demonstrated activity in phase 1 trials
  • No toxicities that may complicate surgery (e.g., pneumonitis)
  • No requirement for significant delay in surgery
  • Comprehensive biomarker analysis
  • No significant impact on local hospital approach to patient management

Carrying out multicenter studies of this type will permit rapid evaluation of novel therapies and advance improvement of clinical outcomes for patients with MPM.

Tremelimumab at an optimized dosing schedule in second-line mesothelioma patients: a phase 2 single-arm study – Dr. Luana Calabro 
Dr. Calabro reported results from the MESOT-TREM-2012 study, a second-line, single arm, phase 2 clinical study with tremelimumab, a fully human anti-CTLA-4 monoclonal antibody, as monotherapy in patients with unresectable malignant mesothelioma.

In this trial, 29 patients with malignant mesothelioma patients progressing on a first-line platinum-based regimen received tremelimumab at 10 mg/kg on day 1, every 4 weeks for 6 cycles, then every 12 weeks until progressive disease or severe toxicity. Primary endpoint was objective response rate (ORR); and secondary endpoints included disease control rate (DCR), overall survival (OS), and safety. Tumor assessment per immune-related RECIST was done at screening and every 12 weeks.

Patients enrolled had a median age of 65 years; 11 had stage III and 18 had stage IV disease. Eastern Cooperative Oncology Group performance status was 0-1 or 2 in 23 and 6 patients, respectively. Twenty-one patients had epithelioid histotype, 6 biphasic, 1 sarcomatoid, and 1 undefined. Patients received a median 6 doses of tremelimumab (range 1-11) and were followed for a median of 16.5 months.

Study results indicated 4 partial responses and 11 patients had stable disease resulting in a DCR of 51.7%. Study results also indicated a delayed response to tremelimumab treatment in some patients. The median OS was 11.5 months. Grade 1-2 and 3-4 treatment-related adverse events occurred in 89.6% and 6.8% of patients, respectively. The most common treatment-related adverse events were gastrointestinal, dermatologic and fever. Adverse events generally resolved with steroid treatment.

To learn more about the conference, read Best of iMig 2014: Day 2 and Best of iMig 2014: Day 3.

“Best of iMig 2014” has been supported by the unrestricted sponsorship of Versastem, Inc.

***The Best of iMig 2014 updates were created by iMig and distributed to conference attendees during iMig 2014. The following is a verbatim re-post of those updates.***

Wednesday Update from iMig Conference

Mary Hesdorffer, NP, the executive director of the Meso Foundation is in attendance at the International Mesothelioma Interest Group (iMig) conference in Cape Town, South Africa. Mary has sent the following photo updates from Wednesday at the conference.

Cocktail Reception

The entertainment at the cocktail reception.

Dario Barbone, PhD

Dario Barbone, PhD, shared that he will be submitting a grant for consideration to the NCI next week. He credits the Meso Foundation’s grant for providing the funding that permitted him to carry out experiments from which the resulting data can be used in applying for larger grants. We will continue to update you on the careers of these young scientists who are the future of mesothelioma research.

Joe Friedberg and Melissa Culligan

Joe Friedberg, MD, and Melissa Culligan, BSN, RN, are in attendance.

Melissa Culligan

Melissa Culligan, BSN, RN, was the only nurse invited to present in the surgical session. Congratulations for a thoughtful presentation.

David Schrump, MD

David Schrump, MD, head of the Thoracic and Gastrointestinal Oncology Branch at the National Cancer Institute, seen during the poster discussion session.

Mary Hesdorffer to Present at iMig Conference This Week

Mary Speaking at 2013 SymposiumMary Hesdorffer, MS, APRN-BC, the executive director of the Meso Foundation, will be presenting at the 12th International Mesothelioma Interest Group (iMig) Conference in Cape Town, South Africa this week. iMig is an international group of scientists and clinicians working to understand, cure, and prevent mesothelioma. iMig presents an important conference that brings together mesothelioma professionals from around the world to discuss the current state of research and advancements in the field.

Mary is chairing a nursing panel and she will give two presentations at the conference. The first presentation, titled “The Voice of the Meso Community in the United States,” will discuss how the Meso Foundation, with the help of community members, advocated for $9.3 million in federal research funding directed to mesothelioma research since 2008. Mary’s second presentation is title “Promoting Entry into Clinical Trials and Improving Access to Specialist Treatment and Care.”

Mary is a nurse practitioner with over 16 years of experience in mesothelioma treatment. She is an expert in clinical trials for mesothelioma and her work has been published in a variety of scientific journals. Mary serves as the executive director of the Mesothelioma Applied Research Foundation.

Common Asian Spice Shows Promise in Slowing Progression of Mesothelioma

SpicesIt has recently been discovered that the use of curcumin appears promising in slowing the progression of mesothelioma. As Medical Xpress reports, “Scientists from Case Western Reserve University and the Georg-Speyer-Haus in Frankfurt, Germany, demonstrate that application of curcumin, a derivative of the spice turmeric, and cancer-inhibiting peptides increase levels of a protein inhibitor known to combat the progression of this cancer. Their findings appeared in the Aug. 14 online edition Clinical Cancer Research.”

Medical Xpress goes on to explain, “The culprit in sparking many cancers, particularly mesothelioma, is the intracellular protein and transcription factor STAT3 (signal transducer and activator of transcription 3). A signal transducer and activator is a pathway for instructing the growth and survival of cells, and a transcription factor is a protein that controls genetic information directing cells how to perform. STAT3 is notorious for sending signals to trigger the onset of human cancers and to fuel their continued growth. The great neutralizer of STAT3 is PIAS3 (protein inhibitor of activated STAT3). PIAS3 possesses the strength to inhibit and block STAT3′s ability to cause cancer.”

As the article continues, the logistics of the study are explained in further detail. “Investigators assessed PIAS3 expression in tissue samples of mesothelioma solid tumors and the protein inhibitor’s subsequent effects on STAT3 activity. Tissue samples came from three different locations in the country, and information logged for each specimen detailed how long the patient lived and the types of mesothelioma they had. Investigators then linked the levels of PIAS3 with STAT3 activity in each sample. Additionally, investigators examined the effects of curcumin and peptides extracted from PIAS3 segments on malignant mesothelioma cells in vitro.”

Medical Xpress spoke with Afshin Dowlati, MD, a professor of medicine at Case Western Reserve University School of Medicine and the director of the Center for Cancer Drug Development at University Hospitals Seidman Cancer Center. Dowlati stated, “In those mesothelioma patients where PIAS3 is low, indeed STAT3 is activated. Mesothelioma patients who have low PIAS3 and high STAT3 have a greater chance of dying early. On the flip side, those patients with a high PIAS3 levels have a 44 percent decreased chance of dying in one year, which is substantial.”

In explaining the findings of the study, Medical Xpress continues, “Investigators also found that curcumin and PIAS3 peptides raised PIAS3 levels, which brought down STAT3 activity and caused mesothelioma cells to die. Their study served as proof of principle about the effectiveness of these two compounds in treating malignant mesothelioma, a first step in moving a treatment toward clinical trials. Additionally, their findings demonstrated that PIAS3 could serve as a predictive marker for managing mesothelioma because the disease’s tumors do not always progress in a consistent, predictable manner, even when tumor stages, grades and clinical presentations appear similar.”

Dowlati further explained the results, stating, “Our findings suggest that PIAS3 expression positively affects survival in mesothelioma patients and that PIAS3 activation could become a therapeutic strategy. Our interest for the future is that we want to find better, more simple ways to increase intracellular levels of PIAS3 for malignant mesothelioma through the use of synthetic PIAS3 peptide or curcumin analogs. We must develop a curcumin analog that is absorbable by the human body. Currently, curcumin ingested as the spice turmeric has practically no absorption within the gut.”

Visit Medical Xpress to read the full article.

Bill Ziegler on his Experience as a Survivor Advocate

Bill ZieglerIn June, mesothelioma warrior Bill Ziegler represented the mesothelioma community as a Survivor Advocate at the 7th Biennial Cancer Survivorship Research Conference: Advancing Survivorship Care through Multilevel Collaboration after being nominated by the Meso Foundation.  He was one of twenty survivors accepted out of 100 applications. Survivor Advocates attended the conference to participate in the conversation about the latest advances in survivorship care and how to improve the quality of life for cancer survivors. He wanted to share what he learned with the meso community:

Greetings Meso Community!

A little over a month ago I attended a survivorship conference in Atlanta.  It has taken me a while to formulate my thoughts on the overall experience and information I received during the conference.  There were over 500 people in attendance at the conference—20 of whom were survivor advocates.  The advocates represented different cancer support organizations across the US.  On the first day, there were sessions that placed survivor advocates at the tables of researchers.  Every 20 minutes you would switch tables and meet and learn something new.  Every researcher and advocate brought something uniquely different to the table.

I did attend a few breakout sessions.  The sessions I attended ranged from Adolescent and Young Adult (AYA) cancer survivorship to financial impact of a cancer diagnosis.  These were great sessions that provided a lot of relevant information on how much more money cancer patients will spend on healthcare over time to social stigma of a cancer diagnosis within a social group.  Without a doubt, there was a lot of information presented.  But the core reason I wanted to attend the conference was because of the specific nature of the challenges that a diagnosis of mesothelioma presents to patients.

I wanted to understand how, as patients, we can get the best treatment possible, and then continue to be followed over time from cancer care and then transition to primary care.  It was clear that this gap in care was the biggest elephant in the room—and identified repeatedly by a multitude of researchers.  For a lot of mesothelioma patients, as well as myself, this diagnosis of mesothelioma means that you will have to travel to a specific treatment center and have a plan tailored to your own personal needs.  Whether it is to have surgery, chemo, radiation, or trials, a plan is usually made at one of a handful of treatment centers across the US.  After treatment, which is usually hundreds of miles or hours away, patients are sent back home to recover and be followed once every few months back at the specialists office.  Any non-cancer treatment follow up will usually be done with your primary care physician—and it is rare that they have all of your records from your other healthcare providers unless you specifically provide them to your primary care physician.  It is this disconnect that so many of our community members have expressed concern with, as well as myself.

I often reflect on my own adventure and ask myself how I’ve been successful.  I’ve done well because I try to have a resource for everything.  It has become clear to me that patients who have the right resources win.  Whether it be a mental support resource, a doctor resource, a travel resource, or a cancer “best practice” resource, I can always find what I need.

Patient resource management is critical for their success.  At the conference, there was a clear trend towards “nurse navigators.” Nurse navigators help patients find health resources, and guide patients through treatment options.  Nurse navigators are popping up in health organizations across the country to assist patients and providers becoming more aligned.  It’s a good thing for survivorship, and while it’s something that is growing, not everyone has a navigator and there are still a lot of gaps in total care for cancer patients. I was proud to know that the Meso Foundation has been at the forefront of this trend for nearly a decade, providing medical consultations and support, and helping mesothelioma patients, through Mary Hesdorffer, Nurse Practitioner.

I’ve thought a lot about how each patient can manage resources effectively and be organized in keeping those resources and in the way they receive care.  I told this to another advocate and he showed me a portable handbook that he brought with him.  This handbook was standardized for patients, caregivers, and doctors.  It kept all vital information so resources could be available and easily shared.  I thought it was great, and extremely helpful!  I’m going to get a couple copies of the book because I think it would be beneficial for our patients to have.  It will provide a standard handbook for patient resource management.  So, I’m going to talk with Mary on how we can develop something that can be a “patient resource management tool.”

I am extremely happy that we, as mesothelioma patients, have a great cancer community facilitated by the Meso Foundation that allows us to connect and learn from one another.  It is a GREAT resource and wonderful tool!  By attending the conference, I have also learned that there are many different components of survivorship, and that it means something different to everyone.  I would also like to thank everyone in the community for allowing me to participate and be an advocate for our mesothelioma community—attending the conference was just more proof that we have some of the best people and resources available.

-Bill Ziegler

Read more about Bill on our blog.