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J. de la Garza
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GR 02 - Difficult Mesothelioma Cases (ID 15)
- Event: WCLC 2015
- Type: Grand Rounds
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 4
- Moderators:J. de la Garza, A. Rimner, A. Tsao
- Coordinates: 9/08/2015, 14:15 - 15:45, 102+104+106
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GR02.01 - Case 1: A 70 Year Old with a Biphasic Stage I MPM (ID 1832)
14:20 - 14:40 | Author(s): H.I. Pass
- Abstract
- Presentation
Abstract:
A 70 year old retired insulator presented to the emergency room with progressive shortness of breath limiting his ability to complete his daily 5 mile runs. Physical examination reveals minimal breath sounds and dullness to percussion on the right side. The patient denies chest pain or weight loss. There is no history of cardiac disease and he is a never smoker. Family histroy reveals a brother with cured uveal melanoma. Chest radiography reveals a completely opacified right hemithorax. WBC is 7000, platelet count 245,000, and his HgB is 13.2 gms. A thoracentesis reveals 3.5 liters of serosanguinous fluid, and post thoracentesis radiograph reveals complete expansion. Fluid is sent for culture and cytology, and the patient is discharged to home with a 2 day supply analgesics. The culture report at 5 days reveals no growth and the cytology reveals atypical mesothelial hyperpplasia. Two months after his thoracentesis he returns to see his PCP with similar complaints of shortness of breath with exertion without chest pain. 1. What is the proper further management of this patient? 2. What is unusual about his family history, and what are the possible implications?
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GR02.02 - Case 2: A 65 Year Old with an Uncytoreduceable MPM (ID 1833)
14:40 - 15:00 | Author(s): P. Baas
- Abstract
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Abstract:
Malignant Pleural Mesothelioma: A patient with unresectable disease It is generally accepted that only a minority of patient are candidates for combined modality treatment. Surgery or radiation alone is not able to achieve a complete pathological control of the tumor. Therefore most patients have to be considered for a systemic treatment. Since the nineties of last century only a slow progress has been achieved with the advent of chemotherapy. Single agents were tried but failed to achieve durable responses and did not achieve response rates over 20%. It was until the beginning of the current century that a standard therapy was defined using platin and an anti-folate. The response rate was 30-35% and the median survival increased from 9 to 13 months. Unfortunately 80% of the patients succumbed to the disease in the 2 years after chemotherapy. The new approaches that are currently available can be grossly divided into a maintenance; immunological and signal-pathway approach. For the case presented to our tumor board it is the challenge to decide which treatment is the most successful with acceptable toxicity. The choice of treatment strongly depends on the patients’ characteristics since cure is not very realistic. The standard of treatment consists of the administration of 4-6 courses of (cis)platin with pemetrexed given every 3 weeks. MPM is well known to respond slowly to chemotherapy and ongoing responses can be seen even after 6 courses of therapy. This has lead to the idea of maintenance therapy. In line with the results in NSCLC one can choose to continue with single agent pemetrexed but to date no randomized study has addressed this issue. Switch maintenance is currently under study with different drugs. The most mature phase III study is with bevacizumab (MAPS study), which showed an improvement in survival in the combination arm. This randomized study showed a very high survival in the control arm of 16 months. The addition of bevacizumab increased the OS to 18.8 months with statistical significance. The full data have not yet been presented and selection of the very best patients might account for this success. An ongoing randomized phase II study with defactinib tests the effect in a maintenance setting. The drug inhibits the Focal Adhesion Kinase pathway, rendering cells susceptible for apoptosis and it reduces the stem cells after chemotherapy. The results are expected in 2016. Since the disease recurs within 1 year, often second line therapy is offered. In table 1 a summary of different approaches is presented. Besides different chemotherapy regimens, inhibition of signal transduction pathways or immunotherapy has been tested. Until now no chemotherapeutic agent or oral TKI has been identified as promising agent. Immunotherapy however, is now one of the new and perhaps most promising developments of this decade. In this particular anti-PD-1 monoclonal antibodies and antibody drug conjugates have shown interesting results in phase I setting. There are a few issues to be resolved in the near future: How to select the best drug for each patient. How to compare study results in patients with different pathology/biological characteristics With a relatively small number of patients per year we must not embark blindly in to large phase 3 studies. We must try to personalize the treatment by increasing our TR efforts. Pre- and post-treatment biopsies can help to identify promising drugs at an early stage. Pre-treatment cell cultures can help to improve the selection of patients who might be good responders to certain chemical compounds. And finally we must improve our collaboration between centers to offer optimal service to our patients. Table 1
cis: cisplatin; pem: pemetrexed; vin: vinorelbine; bev: bevacizumab; a-CTL4: anti cytotoxic lymphocyte 4; a-PD1: anti-programmed death; LoE: level of evidence; PFS: progression free survival Selected references 1.Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. J Clin Oncol 2003;21:2636–44 2, Jassem J, Ramlau R, Santoro A, et al. J Clin Oncol 2008;26:1698-1704 3. Zalcman et al. pASCO 2015 4. Hassan R, Miller AC, Sharon E et al. Sci Transl Medicine. 2013;5(208):208ra147. 5. Alley E et al. pAACR 2015Agent group line Recommended Agents LoE Remark Chemotherapy 1 cis/pem I Standard since 2003 (1) 2 pem; vin II pem showed improved PFS (2) Maintenance 1 bev I Reported at ASCO 2015 (3) TKI 2 none - Many tested; no conclusive results Immunotherapy 2 Immunotoxins III Phase I study of pseudomonas toxin (4) a-CTL4; a-PD1 III Trametinib now tested in maintenance setting in phase III; pembrolizumab showed promising results in phase I (5)
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GR02.03 - Case 3: A 65 Year Old with a Clinical Stage II MPM and Chest Pain (ID 1834)
15:00 - 15:20 | Author(s): J. Friedberg
- Abstract
- Presentation
Abstract not provided
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GR02.04 - Addressing the Needs of the Mesothelioma Patient Who Has Exhausted Treatment Options: Palliation and Support for Family and Patient (ID 1835)
15:20 - 15:45 | Author(s): H. Clayson, L. Darlison, M. Hesdorffer
- Abstract
Abstract:
The care of people with end-stage mesothelioma is complex due to the interplay of severe physical symptoms, intense psychological distress, and social factors related to mesothelioma being a fatal occupational disease. In comparison with people suffering from lung cancer, patients with mesothelioma experience more pain and greater negative impact on role and functioning and insomnia (1). Patients and family members should expect effective management of symptoms, support during the continuum of the illness and a rapid response to crisis. The high symptom burden experienced by patients with mesothelioma in the last year of life is shown in the table below (2):
Patients with incurable disease deserve and need to receive clear information and to share in the decision-making about each stage of their cancer journey. Once oncological treatments are exhausted, healthcare professionals hold the responsibility for helping patients and their families shift their expectation from “cure” to palliation of symptoms. A care plan for a good death needs to be sensitively eased into the clinical discussions, taking into account each individual patient’s preferences (3). In rare diseases such as mesothelioma a feeling of isolation tends to overwhelm the patient and their family. Unlike most cancers mesothelioma has an explained occupational and/or environmental cause. In many cases understanding that the fatal illness was caused by asbestos exposure due to neglect of health and safety precautions at work can lead to blame, anger, depression and inability to cope. The complicated processes concerning claims for welfare benefits and civil compensation litigation often exacerbate this psychological distress. Meeting the care needs of patients and their families in this situation requires a compassionate and specialised multi-disciplinary approach. Expert timely supportive and palliative care can address the burdens associated with advanced disease and guide the patient and family in accepting and planning for a good death. Transition to focus care on the family during the grief process completes the cycle in the care of the mesothelioma patient and family. Panel discussion will include the following areas: · Advanced education and the expanded role of a nursing team solely focused on mesothelioma (4). · The roles and availability of on-line, in person and telephone support groups · The need for early referral into palliative, supportive and hospice care References 1. Nowak AK, Stockler MR, Byrne MJ (2004) Assessing quality of life during chemotherapy for pleural mesothelioma: feasibility, validity, and results of using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire and Lung Cancer Module. J Clin Oncol. Aug 1;22 (15):3172-80. 2. Clayson H (2007) Thesis: The Experience of Mesothelioma in Northern England. University of Sheffield. Available online at etheses.whiterose.ac.uk/1775/ 3. Pass HI, Hesdorfer M, Lake SE, Lake SA. (2012) 100 Questions and Answers about Mesothelioma. Third Edition 4. Moore S, Darlison L (2011) Improving the nursing care of patients with mesothelioma. Nurs Stand May 25-31;25(38):35-8Pleural mesothelioma: Symptoms in the last year of life Breathlessness 96% Social 16% Pain 91% Nausea 14% Cough 41% Fatigue 13% Weight loss 41% Dysphagia 11% Anxiety 31% Psychiatric 10% Anorexia (loss of appetite) 25% Constipation 8% Depression 19% Ascites 8% Sweating 18% Vomiting 5% Emotional disturbance 16% Painful metastasis 5%
