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.***

Now Available: Watch the Philadelphia Regional Mesothelioma Conference Online

Philadelphia ConferenceThe content from the Meso Foundation’s regional conference, presented as a collaboration between the Mesothelioma Applied Research Foundation and Penn’s Abramson Cancer Center, held in Philadelphia on September 26, 2014, is now available for viewing online on the Abramson Cancer Center website.

The conference featured area experts in the field of mesothelioma.

All sessions are now available online at OncoLink.org/Conference/Mesothelioma.

The conference was co-chaired by Mary Hesdorffer, CRNP, of the Meso Foundation, and Joseph Friedberg, MD, and Daniel Sterman, MD, of the Penn’s Mesothelioma and Pleural Program.

Among topics of discussion were clinical trial participation, latest advances in peritoneal and pleural mesothelioma, palliative care, early detection, genetics, coping with mesothelioma, and survivorship.

Speakers included:
Mary Hesdorffer, CRNP, Mesothelioma Applied Research Foundation
Joseph Friedberg, MD, Penn’s Abramson Cancer Center
Chi Dang, MD, PhD, Penn’s Abramson Cancer Center
Richard Alexander, MD, University of Maryland
Lee Krug, MD, Memorial Sloan Kettering Cancer Center
Andreas Rimner, MD, Memorial Sloan Kettering Cancer Center
Daniel Sterman, MD, Penn’s Abramson Cancer Center
Suzanne Walker, CRNP, MSN, AOCN, BC, Penn’s Abramson Cancer Center
Anil Vachani, MD, Penn’s Abramson Cancer Center
Joseph Testa, PhD, Fox Chase Cancer Center
Eleanor Anderson, MD, Penn’s Abramson Cancer Center

The Meso Foundation is hosting a second regional mesothelioma conference with The University of Chicago Medicine on October 10 in Chicago. To learn more about this conference, visit curemeso.org/chicago.

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.

Meet the Mesothelioma Experts: Stephen Isaacs Discusses New Clinical Trial Using Listeria Bacteria

Stephen IsaacsOn September 10, the Meso Foundation will interview Stephen Isaacs, the chairperson, president, and CEO of Adura BioTech, during a new installment of the Foundation’s Meet the Mesothelioma Experts live broadcast. The interview will be led by the Meso Foundation’s executive director and mesothelioma expert nurse practitioner, Mary Hesdorffer, APRN.

The focus of the interview will be Audo BioTech’s experimental therapy for malignant pleural mesothelioma, known as CRS-207. CRS-207 is a weakened form of Listeria bacteria modified to reduce its ability to cause infections, but still able to stimulate the immune system.

The interview will be available live on September 10, at 1PM EST, by calling into a conference-call number. The interview is free of charge, but listeners must RSVP ahead of time by visiting curemeso.org/experts in order to receive a call-in number.

In his position at Aduro BioTech, Mr. Isaacs initiated the company’s current immunotherapy program based on attenuated strains of Listeria monocytogenes. He was responsible for recruiting key members of the current vaccine team with deep expertise in the biology of Listeria. Mr. Isaacs has published over 20 peer-reviewed scientific articles and is an inventor on over 40 issued patents.

To RSVP for the upcoming session with Stephen Isaacs or to listen to past Meet the Mesothelioma Experts sessions, visit curemeso.org/exerpts.

More Promising Mesothelioma Clinical Trials than Ever Before

Research continues to search for a cure as more mesothelioma clinical trials than ever before are underway.During the July 2014 board meeting of the Mesothelioma Applied Research Foundation, mesothelioma expert and executive director of the Meso Foundation, Mary Hesdorffer, APRN, stated that mesothelioma patients today have more promising clinical trials to choose from than ever before.

In her talk, she mentioned several trials that have been reporting increased survival and response rates. Some include novel radiation treatments, while the focus of others is within the field of immunotherapy. One trial, in particular, is looking very promising with a 69% durable response in a small group of patients. Ms. Hesdorffer stated that a new, larger trial currently underway is looking to confirm these results.

“A clinical trial is a unique opportunity for a patient to try something new and innovative that could have a very positive impact on the patient’s disease,” said Ms. Hesdorffer. “Having options is an important step forward in a disease that merely a decade ago was seen as hopeless,” she added.

Ms. Hesdorffer provides free consultations about clinical trials, as well as other issues pertaining to mesothelioma, as part of the Mesothelioma Applied Research Foundation’s patient services.

“While healthcare providers aren’t able to review all clinical trial options with their patients due to time constrains, at the Meso Foundation it is our job to spend the necessary time to go through all viable options while taking into consideration insurance coverage, stage of disease, histology and readiness to participate in a clinical trial,” added Ms. Hesdorffer.

Mary Hesdorffer, MS, APRN-BC, is a nurse practitioner with over 16 years of experience in mesothelioma treatment. She is an expert in mesothelioma clinical trials and her work has been published in a variety of scientific journals.

The Mesothelioma Applied Research Foundation has recently released a downloadable brochure about mesothelioma clinical trials, which can also be requested by mail, and lists all mesothelioma clinical trials on its website.