CHAPTER 26: SURGERY AND RADIATION FOR MESOTHELIOMA
26.0 SURGERY IN TREATING MESOTHELIOMA
26.01 Overview
In early stage non-small lung cancer patients, the tumor is removed leading in
some cases to a complete cure. That type of surgery is rarely an option in
mesothelioma. “Because the tumor is either broadly extensive on the pleural
surface or multi-focal at the time of detection, it does not lend itself to
localized surgical excision.” Butchart (1). Instead, a more complicated
procedure called pleuropneumonectomy is used.
26.02 Surgery Combined with Chemotherapy and Radiation
Where surgery is recommended, it is generally combined with chemotherapy and
radiation. This three-pronged approach was pioneered by Dr. David Sugarbaker at
Boston‘s Langham and Woman‘s Hospital where they operated on a number of
mesothelioma patients and generated at least four medical articles assessing
longevity patterns. See, Butchert (1). Their conclusions as to when surgery is
recommended have been adopted by many throughout the world, with the combination
of surgery, radiation, and chemotherapy the starting point, though scientists
continue to try to define the optimal mix, and investigate less intrusive gene
therapies. Given the complexity of this surgery, it is generally recommended
only for patients with a certain type of early disease though scientists have
not precisely defined when it should be performed. The originator of this
treatment plan explains, “Cytoreductive surgery (pleuropneumonectomy) followed
by sequential chemotherapy and radiotherapy have demonstrated improved survival,
especially for patients with epithelial histology, negative resection margins,
and no metastases to extrapleural lymph nodes.” Jaklitsch (13).
26.1 PLEUROPNEUMONECTOMY
The primary surgery for mesothelioma is a pleuropneuemonectomy. “All of the
ipsilateral pleura, lung and pericardium are removed, and because diaphragmatic
pleura cannot be separated from the diaphramatic muscle... it is necessary to
remove (that also).” Butchart (1). “The goal of pleuropneumonectomy is radical
resection of the tumor, which often requires combined resection of adjacent
structures.”
26.11 Eligibility for Surgery
26.111 Performance Status
This is major and complicated surgery suitable for fit patients with normal
cardiopulmonary function.” Butchart (1).
“Patients were considered surgical candidates if they had a
Karnofsky performance status of greater than 70%, a creatinine level within
normal limits, liver function test results within the norm. (Exclusive criteria
included lower readings on various pulmonary function tests.)” Sugarbaker (2).
26.12 Mortality Rates
Mortality levels from this surgery are not low, and one Japanese study estimated
6% mortality rate from the surgery. Takagi (6). A Scottish hospital reported 9%
mortality during the course of its study, Aziz (3), while another English
hospital reported 30 day mortality of 7.8% Martin (8). Sugarbaker’s
post-operative mortality of 4% is one of the lowest but is still substantial.
Sugarbaker (3). Given the surgery risk and complexity, choosing a hospital and
physician with substantial experience in the procedure should be a prerequisite.
26.13 Type
Studies have study found that patients with the epithelial type benefited most
from the surgery. Sugarbaker states, “Univariate analysis found epithelial cell
type associated with improved survival in the study, (52% 2 year survival, 21% 5
year survival, 26 month median survival).” Sugarbaker (2). In comparison,
“The patients with non-epithelial cell type (sarcomatoid and mixed cell type)
have a significantly worse survival, with only 16% living for 2 years after the
operation. This suggests that our current trimodality treatment plan is having a
small impact within this group with unfavorable histologic features, and new
strategies for local control are needed.”
Based on Sugarbaker’s data, those within the non-epithelial group should
consider alternatives such as chemotherapy and gene therapy. While his results
are persuasive, Sugarbaker is less successful in explaining why cell type should
be so important and what it is about epithelial type that improves prognosis. Or
conversely, what do the other types do that diminishes one’s chances for
recovery? Another study found that cell type did not impact survival. Aziz (3).
“Survival was, surprisingly, not affected by lymph node involvement (P=0.08) or
pathological type of MPM.” Aziz (3). However, an Italian study also found that
epithelial type improved survival. Serisoli (7).
26.14 Stage
Not surprisingly, patients with limited disease received the most benefit from
this surgery.
“Negative resection margins and lack of extrapleural lymph nodal involvement
were significant prognostic factors associated with prolonged survival... The 66
patients with negative resection margins had a 2 year survival of 44% and a 5
year survival of 25% compared with the 110 patients with positive resection
margins, who had a 2 year survival of 33% and a five year survival of 9%. The
136 patients with negative extrapleural nodal status had a 2 year survival of
42% and a 5 year survival of 17%; the 40 patients with extrapleural nodal status
had a 2 year survival of 23% and none survived 4 years.” Sugarbaker (2).
Similar findings were reported in an Italian study. Serisoli (7). This is
consistent with results with non-small cell lung cancer and even small cell,
with surgery recommended for those with early disease.
26.141 Stage 1 Patients
The impressive results of the tri-modal surgery make it a promising alternative
for stage 1 patients. A later study reported “survival has improved to a mean of
35 months for patients treated by radical surgery followed by systemic
post-operative chemotherapy.... In selected patients with MPM, complete surgical
resection by EPP represents an important initial step in their management.
Systemic chemotherapy improves survival in surgically treated patients.” Aziz
(3). Again, patients would have to be in otherwise good medical condition. As to
stage 1 with epithelial type, Sugarbaker explains that. “thirty one patients
with 3 positive variables had the best survival”, 68% 2 year survival, 46% 5
year survival, median 51 months. Sugarbaker (2).
26.142 Stage 2 Patients
Perhaps the most difficult determinations are to be made in this group. For
patients with early disease, the combined regimen makes sense, for those with
advanced disease, the risks are clearly too great and the benefits too limited.
Where there is or may be limited spread, intelligent minds can disagree. Even
with positive resection margins, the 2 year survival of 33% and 5 year of 9%
reported by Sugarbaker still exceeds most other treatments. If the results in
this group exceed other treatments, it may make sense. Indeed, these results
include epithelial and non-epithelial mesothelioma; if we include only
epithelial type, the two and five year survival figures would be higher in
Sugarbaker’s study. But see Butchart, (“It would appear that patients with
sarcomatous histology or involved intrathoracic nodes will derive little benefit
from the trimodality therapy according to the protocols used by Sugarbaker and
collagues.” Butchart (1).
26.143 Quality of Life Issues
Difficult judgments must be made. Assessing quality of life in a demanding
tri-modal regimen is difficult. Is 12 months of easier treatment better than 20
months enduring complex surgery, chemotherapy, and radiation? How does one
evaluate the increased possibility of five year long term survival when it is
still only in the area of 10%?
Sloan Kettering reported median survival of 33.8 months for stage 1 and II
grouped together. This study used surgery and radiation without chemotherapy.
Rusch (9).
26.15 Nodal Status
Sugarbaker did not report his results based on stage, but on nodes and other
factors. Sugarbaker writes, “the 136 patients with negative extrapleural nodal
status had a 2 year survival of 42% and a 5 year survival of 17%; the 40
patients with positive extrapleural nodal status had a 2 year survival of 23%,
and none survived 5 years.” Sugarbaker (2). Thus, the existence of positive
nodes essentially precluded long-term survival in this tri-modal regimen.
Positive nodes may not always be identified pre-operatively, indeed, it may be
those with identifiable cancerous nodes would not have been eligible for the
Sugarbaker trial surgery. However, one can conclude that positive nodal status
would preclude this regimen.
In the future, more sophisticated techniques may identify positive nodes. Pet
Scans were not extensively used in the mid-90’s when the surgeries in the
Sugarbaker study were conducted. Today, Pet-Scans, and other diagnostic tests
may reveal positive nodal status.
Given the impact of positive nodes and positive resection margins, most
physicians would not recommend the arduous tri-modal plan for patients with
advanced mesothelioma. Sugarbaker found that positive lymph nodes essentially
precluded long-term survival. Instead, less demanding chemotherapy and gene
therapy regimens would be recommended because of the risks of surgery and to
improve quality of life.
26.16 Specialized Facilities
Since mesothelioma is a relatively rare disease and pleuropneumo-nectomy is a
difficult and unusual surgery, it should probably be done at a facility
specializing in mesothelioma by a physician experienced in this surgery. “The
attendant morbidity and potential mortality from extrapleural pneumonectomy
stresses the importance of performing the procedure at specialized
institutions.” Sugarbaker (2). Indeed, with various types of surgery, experience
not unexpectedly tends to reduce mortality rates.
26.2 PLEURECTOMY
A more modest surgery is called pleurectomy. Butchart distinguishes a
pleurectomy as living diaphragmatic pleura in place which he suggest will
usually result in some amount of tumor remaining. While pleurectomy is lesser
surgery, its benefits are not clear.
26.3 RADIATION FOR MESOTHELIOMA
26.41 Its Curative Role
Radiation is used both to relieve symptoms of disease and increase survival. It
is clear radiation is not a complete cure, and not even its proponents suggest
it can eradicate the disease. Whether radiation increases survival alone or in
combination with other treatments continues to be disputed. “External beam
radiation therapy, like chemotherapy, has been ineffective in prolonging
survival in mesothelioma patients, although several studies have demonstrated
some degree of regression of gross disease.”
Another author writes, “The effectiveness of primary radiation therapy remains
controversial. Even very high doses of radiation cannot control tumor growth. It
remains unclear whether radiation therapy may palliate tumor associated
symptoms.” There have been only a limited number of clinical trials testing
radiation making it difficult to pinpoint its efficacy.
26.43 Hyperfractionation
Radiotherapy works by destroying the cancer cells in the treated area. The
treatment is normally divided into several sessions (called fractions). An
increase in the number of fractions is called hyperfractionated radiotherapy.
One study with radiation found a higher than expected 5 year survival rate of
9%. Though the researchers experimented with 6 different fractionation
schedules, “the pattern of progression was similar in each treatment group”.
26.431 Dose Limitations
Higher doses could arguably improve radiation, however, “delivery of optimal
radiation schedules, which may involve large fractions as well as large total
doses, is limited by the presence of nearby dose-limiting structures”. Ho (9).
26.44 Photodynamic Therapy
Photodynamic therapy is also being evaluated with or without surgery:
“Local failure in particular is a large part of the natural history of
mesothelioma, especially after surgery alone. Therefore, one of the major
considerations in the development of new treatments is the inclusion of
aggressive local therapies. Photodynamic therapy (PDT), a local treatment
modality, is being evaluated as an adjuvant therapy to surgical resection.”
REFERENCES
1. Butchart, Contemporary Management of Malignant Pleural Mesothelioma,
Oncologist, Vol 4, No 6, 488-500, December 1999.
2. Sugarbaker, Resection Margins, extra pleural nodal status, and cell type
determine postoperative long term survival in trimodality therapy of Malignant
Pleural Mesothelioma: results in 183 cases. J. Thoracic Cardiovascular Surgery
1999, Jan, 117:1, 54,65.
3. Aziz, The management of malignant pleural mesothelioma; single centre
experience in 10 years, Eur. J. Cardiothorac Surg 2002 Aug;22(2):298-305.
3. Melluni, Treatment of malignant pleural mesothelioma, Minerva Chir 2001
Jun;56(3):243-50.
4. Jaklitchs, Treatment of Malignant Mesothelioma, World J Surg 25:210-217
(2001).
5. Takahashi, Extrapleural pneumonectomy for diffuse malignant pleural
mesothelioma. A treatment option in selected cases? Jpn J Thorac Cardiovasc Surg
2001 Feb;49(2):89-93.
6. Takagi, Surgical approach to pleural diffuse mesothelioma in Japan, Lung
Cancer 2001 Jan;31(1):57-65.
7. Serrisoli, Therapeutic outcome according to histologic subtype in 121
patients with malignant pleural mesothelioma, Lung Cancer 2001 Nov;34(2):279-87.
8. Martin, Palliative surgical debulking in malignant mesothelioma. Predictors
of survival and symptom control, Eur J Cardiothorac Surg 2001 Dec;20(6):1117-21.
9. Rusch, A phase II trial of surgical resection and adjuvant high-dose
hemithoracic radiation for malignant pleural mesothelioma, J Thorac Cardiovasc
Surg 2001 Oct;122(4):788-95.
10. Ho, Malignant pleural Mesothelioma.Cancer Treat Res 2001;105:327-73
11. Neumesister, Prognosis, staging and therapy of malignant pleural
mesothelioma, Med Klin 2002 Aug 15;97(8):459-71.
12. Hahn, Photodynamic therapy for mesothelioma, Treat Curr Treat Options Oncol
2001 Oct;2(5):375-83.
13. Jaklitsch & Sugarbaker,,Treatment of malignant mesothelioma, World
J Surg 2001 Feb;25(2):210-7.
Leading Hospitals and Surgeons for Mesothelioma
Given that mesothelioma is a rare disease and the surgery is complicated, one
would want to select a physician and hospital with considerable experience. I
have listed some of the physicians and institutions which have done work
specifically with mesothelioma and in some cases, journal articles where the
institution is cited.
United States Hospitals
Brigham is probably the leading hospital for mesothelioma and is where the
tri-modal treatment plan was pioneered.
Dr. David Sugarbaker, Department of Surgery, Division of Thoracic Surgery,
Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115,
USA.
Other U.S. Hospitals with specialized experience are:
M.D. Anderson Cancer Center, Houston, Texas
Sloan Kettering Cancer Center, New York, Rusch, A phase II trial of surgical
resection and adjuvant high-dose hemithoracic radiation for malignant pleural
mesothelioma. J Thorac Cardiovasc Surg 2001 Oct;122(4):788-95
Australia
University of New South Wales Department of Surgery, St George Hospital, Kogarah,
New South Wales, Australia.
France
Institut Gustave-Roussy, Departement de Medecine, 39, rue Camille Desmoulins,
F94805 Villejuif.
Italy
Department of Radiochemotherapy, San Raffaele H Scientific Institute, Via
Olgettina 60, 20132 Milan, Italy. ceresoli.giovanni@hsr.it
Japan
Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa,
Japan.
Netherlands
Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam,
the Netherlands.
United Kingdom
Dr. Eric Butchart, University Hospital, Cardiff, CF 4, 4XW, Wales UK.
Department of Thoracic Surgery, Glenfield Hospital, Groby Road, Leicester LE3
9QP, UK.
mesothelioma overview
Home Page
keywords mesothelioma, mesothelioma
mesothelioma surgery , mesothelioma attorney, mesothelioma treatment
mesothelioma cancer, pleural mesothelioma, peritoneal mesothelioma, mesothelioma
symptom, mesothelioma lawsuit
mesothelioma asbestos, malignant mesothelioma, mesothelioma lung cancer,
prognosis in mesothelioma cases
malignant pleural mesothelioma, mesothelioma information, mesothelioma law,
mesoethelioma.com, asbestos lawsuit mesothelioma surgery mesothelioma
Comments are welcomed and may be included in revisions of our book.
howian@aol.com This article is not intended
to provide medical advice and for treatment, please see your doctor.
Lung Cancer and Mesothelioma
is a comprehensive overview of
lung cancer treatment and research comprising 41 chapters and over 480 pages.
The book reviews chemotherapy, gene therapy, radiation, experimental treatments
and other topics, with excerpts available below.
REVIEWS
Quality Books
"This book provides an invaluable resource for anyone who has or who is caring
others with Mesothelioma or other Lung cancers. It provides a wealth of relevant
and useful information on various types of lung cancers, medical trials,
treatments and medications. This well researched and comprehensive book is quite
unique on the subject. This book also contains a detailed discussion on the
emotional burden of Lung Cancer upon the patient and their families and ways to
manage it."
Lorraine Kember. Author of "Lean on Me -
Cancer through a Carer's Eyes", "The very
mention of the word Cancer, strikes fear into all of us.... From personal
experience I know that knowledge is the key to providing a better "quality of
life" for the cancer patient. Better understanding of the stages of the disease
and of methods and medications available to treat the pain and symptoms caused
by it, allow for the patient and those who care for them, to make informed
decisions regarding their care. In this way, they are able to regain some
control over their lives. Rarely does one find all the information they need in
one book, however I believe Howard's well researched and comprehensive book
"Lung Cancer & Mesothelioma", is quite unique. It provides a wealth of relevant
and useful information including; how various types of cancer are formed,
medical trials, available treatments and medications, insight and discussion
regarding the emotional burden of cancer upon the patient and their families and
ways by which to manage grief. I believe this book will provide an invaluable
resource for anyone who has or who is caring for someone with cancer.
keywords continued mesothelioma law firm,
mesothelioma diagnosis, new york mesothelioma mesothelioma surgery ,
abcmesothelioma.com, asbestos cancer mesothelioma surgery mesothelioma, mesothelioma
litigation, mesothelioma research
abcmesothelioma.com asbestos mesothelioma surgery mesothelioma symptom, new jersey
mesothelioma mesothelioma surgery , new york mesothelioma attorney
new jersey mesothelioma attorney, survival stage iii malignant mesothelioma,
attorney mesothelioma peritoneal
well differentiated papillary mesothelioma, nattorney mesothelioma, pericardial
mesothelioma,
mesothelioma prognosis, asbestos disease mesothelioma settlement, mesothelioma
doctor, mesothelioma hospital,
new york city mesothelioma attorney,