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H. Hoffman
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MS12 - Loco-Regional Management of MPM (ID 29)
- Event: WCLC 2013
- Type: Mini Symposia
- Track: Mesothelioma
- Presentations: 5
- Moderators:H. Hoffman, T. Nakano
- Coordinates: 10/29/2013, 14:00 - 15:30, Bayside 103, Level 1
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MS12.0 - Chair Intro (ID 510)
14:00 - 14:04 | Author(s): T. Nakano
- Abstract
- Presentation
Abstract not provided
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MS12.1 - How Has the 'MARS' Trial Affected the Surgical Approach to MPM? (ID 511)
14:04 - 14:27 | Author(s): J. Edwards
- Abstract
- Presentation
Abstract not provided
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MS12.2 - Pleurectomy Decortication Vs. Extrapleural Pneumonectomy (ID 512)
14:27 - 14:50 | Author(s): J. Donington
- Abstract
- Presentation
Abstract
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MS12.3 - Peri-Operative Radiotherapy: Current Data and State of the Art (ID 513)
14:50 - 15:10 | Author(s): A. Price
- Abstract
- Presentation
Abstract
Formal prospective evidence of benefit from cancer treatments for patients with mesothelioma exists only for the small survival increment obtained from combinations of cisplatin and anti-folate agents in those with inoperable disease. Despite this absence of evidence of benefit, and some evidence of detriment, trimodality therapy including neoadjuvant chemotherapy, surgery and adjuvant radiotherapy continues to be regarded as a widespread standard of care in early disease. Only one very small randomised trial has addressed this question[1], and the evidence from that trial suggesting a substantial increase in mortality has been disputed by many believers in trimodality therapy. The surgical literature has recently been extensively reviewed, revealing the paucity of high level evidence for these treatments[2-3]. One Swiss trial investigated the role of radiotherapy in this combination, but closed last year because of poor accrual due to changes in surgical fashion (NCT00334594)[ 4]. The two major surgical approaches to early mesothelioma have been extrapleural pneumonectomy (EPP), first described over 30 years ago, and presented in 16 published reports of which 5 were prospective and only 1 randomised[2]. None of these studies directly compare radiation doses or techniques, and no firm conclusions are possible regarding dose response, or the superiority of techniques as variable as a simple opposed pair with or without electrons to intensity modulated radiotherapy (IMRT) or protons. It seems extremely unlikely that such data will ever exist, and what radiotherapy is used will continue to depend mainly on the expertise, technology and time available locally. There have been publications[5,6], reporting an unexpectedly high morbidity and mortality following IMRT and there may be an argument that simplest is best given the general lack of fatal outcomes with conventional radiotherapy, although dose coverage of certain areas is poor. One report suggested lower local failure with IMRT[7], but this may have related to the higher dose given (50.4 Gy vs 30 Gy) and it was unclear why the slightly higher dose (54 Gy)[ 8] normally used postoperatively was not possible. If IMRT is to be used then treatment times may be shorter with volumetric modulated arc therapy[9]. Whether as a result of the MARS trial, or the disappointing outcomes from prospective trials conducted by the EORTC and in the US[8, 10], surgical fashion has moved in the last few years from EPP to various extents of pleurectomy, where the underlying lung is preserved. This is not a conventional cancer operation involving en bloc resection of tumour with a defined margin, and adjuvant radiotherapy is rendered more difficult, if not impossible, by the residual lung. Attempts to spare the lung at least partially must of necessity involve sparing the pleura overlying the fissures, and significant rates of pneumonitis have been reported, albeit less than in the early reports of IMRT[11]. The doses achievable by these techniques remain relatively low by cancerocidal standards in the context of a disease believed to relatively radioresistant. Cao has also reviewed the 34 publications on pleurectomy, none of which are randomised and very few prospective[3]. Radiotherapy in most series, when it is described at all, seems to be at relatively low dose to the port sites, of questionable benefit since 2 randomised trials have shown no effect from this intervention at the time of diagnosis[12, 13]. The MARS group also plan to look at the benefits of pleurectomy, but radiotherapy is not currently included in the trial outline. Currently this is an area in which virtually no data exist to support decision making. Radiotherapy is likely to remain part of the trimodality recipe for those who continue to believe in EPP, at least until the postulated trial of 670 participants is completed[14], and single centre reports on small numbers of patients with more complex treatment techniques likely to continue. If the next generation of larger trials of radiotherapy looking at port site prophylaxis confirm the lack of utility of this intervention, it is difficult to see that there will be a role for radiotherapy after pleurectomy. Rather than assume such a role, it is to be hoped, but not expected, that randomised trials of the benefits of radiotherapy be instituted. 1. Treasure T et al, Lancet Oncol. 2011 Aug;12(8):763-72. 2. Cao CQ et al, J Thorac Oncol. 2010 Oct;5(10):1692-703. 3. Cao CQ et al, Lung Cancer. 2013 Jun 12. doi:pii: S0169-5002(13)00212-2. 4. http://clinicaltrials.gov/show/NCT00334594 5. Allen AM et al., Int J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):640-5. 6. Patel PR et al., Int J Radiat Oncol Biol Phys. 2012 May 1;83(1):362-8. 7. Buduhan G et al., Ann Thorac Surg. 2009 Sep;88(3):870-5. 8. Van Schil PE et al., Eur Respir J. 2010 Dec;36(6):1362-9. 9. Scorsetti M et al., Int J Radiat Oncol Biol Phys. 2010 Jul 1;77(3):942-9. 10. Krug, LM et al., J Clin Oncol. 2009 Jun 20;27(18):3007-13. 11. Rosenzweig KE et al., Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):1278-83. 12. Bydder S et al., Br J Cancer. 2004 Jul 5;91(1):9-10. 13. O’Rourke N et al., Radiother Oncol. 2007 Jul;84(1):18-22. 14. Weder W et al, Lancet Oncol. 2011 Nov;12(12):1093-4.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MS12.4 - Adjuvant Intracavitary Treatments in Mesothelioma (ID 514)
15:10 - 15:30 | Author(s): J. Friedberg
- Abstract
- Presentation
Abstract
Mesothelioma remains an incurable disease. Although there is compelling evidence that some patients can benefit from radical surgery, this modality remains surrounded by controversy and true Level I evidence in the form of a randomized prospective trial has yet to establish surgery as the standard of care. The driving principles behind utilizing surgery-based treatments for this cancer are that: these tumors are not curable with other modalities, they can reach enormous volumes where surgery is the only current modality that has expectation of achieving a significant response, as a general rule these cancers tend to progress locally to the point of patient demise without extrahemithoracic disease being present or of clinical significance. Because it is not possible to achieve completely negative margins in the overwhelming majority of pleural cancers, the realistic goal of any radical surgical procedure is to achieve a macroscopic complete resection. It is logical, therefore, to employ intraoperative adjuvant therapies in an effort to control the microscopic disease that remains after surgery. To date there are several different intraoperative adjuvants that have been employed with any regularity in the treatment of pleural mesothelioma: intraoperative radiation, heated perfusion with either chemotherapy or povidone iodine and photodynamic therapy. Each has its own advantages and disadvantages, from both oncologic and technical perspectives. Intraoperative radiation does not appear to be in active use at this time. The advantages of radiation are the established track record in treating mesothelioma and the penetrating nature of the modality with the disadvantages being damage to normal tissue, from the same penetrating nature. Employment of intraoperative radiation is likely the most expensive and logistically complicated of the intraoperative adjuvants. The technique that has been employed with heated povidone iodine has the advantages of logistical simplicity, with the treatment being delivered as sequential dwells, and low expense. In addition, there is the advantage of povidone iodine being an easy and safe material with which to work, with a high safety profile for both the patient and health care staff delivering the treatment. The disadvantages of this technique include the unclear benefit of povidone iodine as a therapeutic agent against this cancer and the certainty that unifom hyperthermia is not maintained during a dwell, working under the assumption that hyperthermia is an effective modality in and of itself. There is recent evidence, however, that mesothelioma may be resistant to hyperthermia. The common technique utilized for heated chemotherapy perfusion, typically platin-based, is significantly more involved than the dwell technique. In this situation a perfusion pump is employed. Disadvantages include increased expense and logistical complexity and utilization of an agent with a significant toxicity profile for both the patient and health care staff delivering the treatment. Advantages include assurance that hyperthermia is maintained, along with control of the temperature, and application of a perfusion agent that has an established track record in treating malignant pleural mesothelioma. With inflow and outflow catheters, this technique has the ability to simultaneously perfuse both the chest cavity and the abdomen, theoretically of benefit to treating occult peritoneal metastases or cells that are disseminated during surgery. Both perfusion techniques have the additional limitation that they are likely purely surface treatments, without any depth of penetration for the treating agent. Photodynamic therapy is a unique treatment modality and, as such, has unique advantages and limitations. Although it is simple to perform, it is likely the most logistically complex of the currently employed modalities. It requires delivery of visible laser light, pretreatment with a photosensitizing drug and employment of special “light precautions” for some period of time before, during and after surgery. Although the cost and availability of lasers has dropped dramatically, it is still a treatment that currently comes with a significant cost. The advantages are that the treatment works by a unique set of mechanisms, delivers treatment at and below the surface for short distance and is known to incite a significant immune response against treated cancers. Whether or not that tumor-directed immune response occurs with pleural mesothelioma is under investigation. Currently it is not possible to rigorously determine which, if any of these treatments is superior. Factors contributing to this dilemma are among the same that limit comparison of any surgery-based treatments. These include: small numbers of patients, colossal variability in patients not only between series but within series, lack of a highly effective staging system to allow rigorous analyses and comparisons, enormous variability in surgical techniques, lack of prospective randomized trials and the fact that essentially all patients suffer recurrence and overall survival may be greatly affected by subsequent treatments. This presentation will review the different intraoperative modalities, present current results and speculate about future directions.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
