Management of Soft Tissue Sarcoma

398 Pages·2016·22.442 MB·English

by  Murray F. Brennan, Cristina R. Antonescu, Kaled M. Alektiar, Robert G. Maki (auth.)

Management of
Soft Tissue Sarcoma
Murray F. Brennan
Cristina R. Antonescu
Kaled M. Alektiar
Robert G. Maki
Second Edition
123
Management of Soft Tissue Sarcoma
Murray F. Brennan • Cristina R. Antonescu
Kaled M. Alektiar • Robert G. Maki
Management of Soft
Tissue Sarcoma
Second Edition
Murray F. Brennan, MD Cristina R. Antonescu, MD
International Center Department of Pathology
Department of Surgery Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering Cancer Center New York, NY, USA
New York, NY, USA
Robert G. Maki, MD, PhD
Kaled M. Alektiar, MD Monter Cancer Center
Department of Radiation Oncology Hofstra Northwell School of Medicine
Memorial Sloan Kettering Cancer Center and Cold Spring Harbor Laboratory
New York, NY, USA Lake Success, NY, USA
ISBN 978-3-319-41904-6 ISBN 978-3-319-41906-0 (eBook)
DOI 10.1007/978-3-319-41906-0
Library of Congress Control Number: 2016947364
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Preface
The authors were approached some time ago to write a text regarding the manage-
ment of soft tissue sarcomas. There are several existing texts in the literature, and
before embarking on such a project, it was necessary to identify what could be
added that was unique to the existing literature.
We note that although there have been several texts that discuss management of
sarcomas, there are few that discuss subtypes individually, given the rare nature of
any one of these diagnoses. The prospectively accrued soft tissue sarcoma database
initiated by Dr. Brennan in 1982 represents the largest single collection of individ-
ual soft tissue sarcoma patient data, allowing characterization of subtype by preva-
lence, age, and site. This is a unique resource for patient care and management and
for outlining the clinical outcomes and management for each sarcoma subtype and
has inspired other groups to collect information on an institutional, local, or national
level in the intervening decades.
There are also relatively comprehensive resources regarding systemic therapy for
different sarcoma diagnoses. For example, there have been a large number of phase
II studies and retrospective analyses of outcomes with specific agents; there has not
been a consistent place to refer for subtype-specific data. Despite issues regarding
recall bias and other well-recognized weaknesses of retrospective analyses, we
endeavored to collect at least some of those data herein. Until better data are accu-
mulated, we have resorted to anecdote and case reports regarding treatments for
rarer subtypes.
Since the publication of the first edition of our book, the most dramatic develop-
ments in cancer have been in molecular genomics and in immunotherapy. The
molecular genomics of cancer have undergone a seismic shift in the past 5 years.
While gene mutation panels have not led to revelatory changes in the treatment of
sarcoma subtypes, such testing helps secure the diagnosis with certainty, when
applied correctly. As of 2016, engineered T cells are being used to treat synovial
sarcoma and myxoid-round cell liposarcoma, and we are learning in what context
immune checkpoint inhibitors may be useful.
v
vi Preface
Other advances in sarcoma management involve the greater reporting of clinical
experience over time. The recognition of second cancers even 30–40 years after
initial therapy also makes one take pause as to treating patients with new diagnoses
today. There are agents approved in the past 5 years that impact treatment as well.
Investigators are accumulating data on chemotherapy responses on a sarcoma
subtype- specific basis, which continues to affect the choice of treatments.
While a book becomes out of date the day it is published, it is clear that the prin-
ciples of treatment of sarcoma remain consistent. It is in that light that we provide
the readers with our contribution. We hope this book will help clinicians to better
identify, characterize, treat, and perhaps even someday prevent these unusual and
varied forms of cancer.
New York, NY Murray F. Brennan
New York, NY Cristina R. Antonescu
New York, NY Kaled M. Alektiar
Lake Success, NY Robert G. Maki
Acknowledgments
Limited author texts such as this are a great challenge. They cannot be completed
without the help of many people. Over the 30 years of the MSKCC database, we
have been fortunate to have outstanding support, particularly from our colleagues in
Pathology, Medicine, Surgery, and Radiation Therapy. The accumulation and main-
tenance of such a prospective database, reviewed and updated on a weekly basis,
has been the province of many committed data managers.
As we review a database of more than 10,000 treated patients, it is hard to accept
that each one is an individual patient with individual defining characteristics. We
thank those individuals for the ability to use the data generated during their course
of illness to create information valuable for the treatment of those yet undiagnosed
patients.
The synthesis of the text would not have happened but for the efforts of Ms. Victoria
Frohnhoefer. Her tireless commitment to the project and meticulous oversight of the
authors are what brought this project to fruition. We cannot thank her enough.
vii
Contents
Part I Introduction
1 General Description ................................................................................ 3
1.1 Introduction ...................................................................................... 3
1.2 Incidence and Prevalence ................................................................. 5
1.3 Predisposing and Genetic Factors .................................................... 8
References ................................................................................................. 16
2 Natural History: Importance of Size, Site, Histopathology ................ 19
2.1 Natural History ................................................................................. 19
2.2 Influence of Site ............................................................................... 19
2.3 Staging ............................................................................................. 19
2.4 Staging of Retroperitoneal and Visceral Sarcoma ........................... 27
2.5 Prognostic Factors for Extremity and Superficial
Soft Tissue Sarcoma ......................................................................... 30
2.6 Disease-Specific Survival................................................................. 31
2.7 Prognostic Factors for Survival Following Local Recurrence
of Extremity Sarcoma ...................................................................... 32
2.8 AJCC Staging................................................................................... 33
2.9 Prognostic Factors—Nomograms .................................................... 38
References ................................................................................................. 39
3 General Statement as to Efficacy of Surgery, Chemotherapy,
Radiation Therapy, and Immunotherapy ............................................. 41
3.1 Extent of Primary Surgery ............................................................... 41
3.2 Surgical Treatment of Local Recurrence ......................................... 43
3.3 Diagnostic Imaging .......................................................................... 43
3.4 Surgery for Metastatic Disease ........................................................ 45
3.4.1 Pulmonary Metastasis .......................................................... 45
3.4.2 Surgery and Management of Sarcoma Liver Metastasis ...... 50
ix
x Contents
3.5 Radiation Therapy ............................................................................ 51
3.5.1 Adjuvant Radiation Therapy ................................................ 53
3.5.2 Types of Radiation Therapy ................................................. 54
3.5.3 Dose/Volume of Radiation Therapy ..................................... 56
3.5.4 Morbidity of Adjuvant Radiation Therapy ........................... 57
3.5.5 Definitive Radiation Therapy ............................................... 59
3.6 Adjuvant and Neoadjuvant Chemotherapy
for Soft Tissue Sarcomas ................................................................. 59
3.6.1 Sarcomas More Common in Adults ..................................... 59
3.6.2 Larger Randomized Studies ................................................. 60
3.6.3 Selected Meta-analyses of Randomized
Trials of Adjuvant Chemotherapy ........................................ 62
3.6.4 Adjuvant Therapy for GIST ................................................. 63
3.6.5 Sarcomas More Common in the Pediatric Setting ............... 64
3.7 Brief Comments Regarding Chemotherapy
for Metastatic Soft Tissue Sarcoma ................................................. 65
3.8 Special Techniques for Primary and Locally
Recurrent Disease ............................................................................ 66
3.8.1 Intra-arterial Chemotherapy ................................................. 66
3.8.2 Limb Perfusion and Hyperthermia ....................................... 67
3.9 Immunotherapy for Sarcomas .......................................................... 68
References ................................................................................................. 69
Part II Management by Histopathology
4 Gastrointestinal Stromal Tumors .......................................................... 77
4.1 Imaging .......................................................................................... 77
4.2 Familial GIST ................................................................................ 79
4.3 Natural History ............................................................................... 81
4.4 Diagnosis, Molecular Pathology .................................................... 83
4.5 Treatment ....................................................................................... 84
4.6 Adjuvant Imatinib for Primary GIST ............................................. 84
4.7 Neoadjuvant Therapy for Primary Disease Not Amenable
to Surgery ....................................................................................... 88
4.8 Treatment of Recurrence ................................................................ 89
4.9 First Line Imatinib: For Metastatic GIST ...................................... 89
4.10 Dose Intensity Over Time .............................................................. 94
4.11 Imatinib Pharmacokinetics ............................................................. 95
4.12 Second Line Sunitinib for Imatinib-Resistant Metastatic GIST .... 96
4.13 Regorafenib in Third Line for Metastatic GIST ............................ 97
4.14 Other Tyrosine Kinase Inhibitors for Metastatic
GIST Failing Imatinib and Sunitinib ............................................. 97
4.15 Newer Agents for GIST ................................................................. 98
Contents xi
References ................................................................................................. 100
5 Liposarcoma ............................................................................................ 105
5.1 Imaging .......................................................................................... 109
5.2 Diagnosis ........................................................................................ 111
5.3 Treatment ....................................................................................... 111
5.4 Radiation Therapy for Liposarcoma .............................................. 115
5.5 Systemic Therapy: General Considerations ................................... 117
5.6 Adjuvant Therapy .......................................................................... 117
5.7 Treatment of Metastatic Disease .................................................... 118
5.8 Outcomes ....................................................................................... 121
5.9 Outcome Following Metastasis ...................................................... 122
References ................................................................................................. 123
6 Leiomyosarcoma ..................................................................................... 125
6.1 Imaging .......................................................................................... 125
6.2 Diagnosis, Molecular Pathology .................................................... 128
6.3 Primary Treatment ......................................................................... 131
6.4 Radiation Therapy .......................................................................... 131
6.5 Systemic Therapy ........................................................................... 132
6.5.1 Adjuvant Chemotherapy for Leiomyosarcoma .................. 132
6.6 Outcomes After Primary Therapy .................................................. 132
6.7 Patterns of Recurrence ................................................................... 133
6.7.1 Treatment of Recurrence ................................................... 136
6.8 Metastatic Disease ......................................................................... 136
References ................................................................................................. 139
7 Undifferentiated Pleomorphic Sarcoma (UPS)
(Malignant Fibrous Histiocytoma (MFH) and Myxofibrosarcoma) .. 143
7.1 Imaging .......................................................................................... 143
7.2 Diagnosis, Molecular Pathology .................................................... 145
7.3 Natural History ............................................................................... 145
7.4 Treatment ....................................................................................... 146
7.5 Radiation Therapy .......................................................................... 146
7.6 Metastatic Disease ......................................................................... 146
7.7 Adjuvant Chemotherapy ................................................................ 148
7.8 Outcome ......................................................................................... 148
References ................................................................................................. 150
8 Synovial Sarcoma .................................................................................... 153
8.1 Imaging .......................................................................................... 153
8.2 Diagnosis, Molecular Pathology .................................................... 153
8.3 Treatment ....................................................................................... 156
8.4 Radiation Therapy .......................................................................... 156
8.5 Chemotherapy ................................................................................ 157
8.6 Treatment of Recurrence ................................................................ 158