Cutaneous Melanoma, Fifth Edition: 5th Edition (Paperback) book cover

Cutaneous Melanoma, Fifth Edition

5th Edition

Edited by Charles M. Balch, Alan N. Houghton, Arthur J. Sober, Seng-jaw Soong, Michael B. Atkins, John F. Thompson

CRC Press

921 pages | 650 Color Illus.

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Paperback: 9781576262764
pub: 2009-07-01
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The Classic Text—Expanded, Updated…More Authoritative than Ever!

Cutaneous Melanoma is the definitive and most authoritative textbook on melanoma used worldwide. This 5th edition provides the most up-to-date and comprehensive information needed for the clinical management and scientific study of melanoma. Written by the leading melanoma experts from the United States, Australia, and Europe, this new edition collectively incorporates the clinical outcomes of more than 60,000 patients treated at major melanoma centers throughout the world.

Comprehensive Coverage—from Prevention to Advanced Treatment

This new edition provides in-depth coverage, ranging from precursors of melanoma to advanced stages of metastatic disease; from melanoma genes to population-based epidemiology; and from prevention of melanoma to all forms of multidisciplinary treatments. Basic principles of diagnosis and pathologic examination are combined with treatment approaches for the many clinical presentations. Clinical management is supported by statistical data about natural history, prognosis, and treatment results. The latest information on staging and prognosis, as well as randomized prospective clinical trials involving surgical treatment and systemic treatments, is included. This volume presents a balanced perspective of the risks and benefits involved in each treatment modality. The book also contains: 1) a comprehensive color atlas of melanoma and its precursors, 2) illustrated surgical and perfusion techniques for every stage and anatomic location of melanoma, and 3) complex genetic and molecular pathways involving melanoma biology. Every drug and biologic agent in use today is described with indications and efficacy.

Entirely Revised and Updated

Seven new chapters discuss the emerging clinical data on the use of biomarkers, adjuvant therapies, targeted therapies, and immune modulation as well as significant clinical research advances in the clinical management of melanoma. The remaining 37 chapters have been extensively updated and revised to include the latest clinical, radiological, and pathological data and clinical trial advances.

Cutaneous Melanoma, 5th Edition, retains the logical organization and clarity of expression responsible for its enduring popularity over the last 23 years. This volume will become an invaluable part of your library and a trusted resource that you will refer to again and again.

The most comprehensive reference on melanoma available today!

New Chapters Include:

  • Clinical Genetics and Risk Assessment
  • Sentinel Lymph Node and Regional Micrometastases
  • Multidisciplinary Management of CNS Metastases
  • Adjuvant Therapy for Cutaneous Melanoma
  • Immune Modulation Therapy Using Anti-CTLA-4 Monoclonal Antibodies
  • Melanoma-Specific Targeted Therapies
  • Biomarkers for Cutaneous Melanoma


"This is the fourth edition of the book that is no doubt the premier text on cutaneous melanoma. The book is oriented to all health care workers and researchers involved in the care of patients with melanomas. This includes, but is not limited to, the dermatologist, medical oncologist, surgical oncologist, radiation oncologist, and cosmetic surgeons, as well as nurses and other practitioners who diagnose or treat patients with melanoma. The 73 distinguished contributors have combined to put together 39 chapters in 7 parts or sections. …The photos are outstanding and the information invaluable. The book belongs in every physician’s library, whatever his or her specialty, to raise awareness of the deadly disease."

The American Journal of Cosmetic Surgery

"Overall, the text is easy to use and well indexed. I find that it is my reference text of choice for any melanoma-related questions that arise during the day. The authors should be commended for their fine and highly accessible work."

American Society for Dermatologic Surgery

"…should serve as an invaluable source of information to all clinicians involved in the care of patients with malignant melanoma and to basic scientists who want to become more familiar with various clinical aspects of the disease. I intend to keep it on my desk and refer to it in my practice."

Journal of the American Medical Association

Table of Contents


A History of Melanoma: From Hunter to Milton;Arthur J. Sober, Helen M. Shaw, John F. Thompson

John Hunter (1728-1793)

René Laennec (1781-1826)

William Norris (1792-1877)

Oliver Pemberton (1825-1897)

James Paget (1814-1899)

Sir Jonathan Hutchinson (1828-1913)

William Sampson Handley (1872-1962)

Alexander Breslow (1928-1980)

Vincent J. McGovern (1915-1983)

Sophie Spitz (1910-1956)

Arthur Allen (1910-1994)

Wallace H. Clark, Jr. (1924-1997)

Thomas B. Fitzpatrick, Jr. (1919-2003)

Gerald W. Milton (1924-2007)

Epidemiology, Prognosis, and Staging

Epidemiology of Melanoma; Bruce K. Armstrong, Alisa M. Goldstein

Worldwide incidence and mortality patterns

Correlates of melanoma risk

Demographic correlates

Constitutional correlates

Environmental and behavioral correlates

Present and future trends in melanoma incidence and mortality

Prognostic Factors and Natural History of Melanoma; Jeffrey E. Gershenwald, Charles M. Balch, Seng-jaw Soong, John F. Thompson

AJCC melanoma staging system analyses—overview of the AJCC international melanoma database and 2002 melanoma staging system


Overview of the 2002 (sixth edition) AJCC melanoma database and melanoma staging system

Validation of the AJCC melanoma staging system

Prognostic factors in primary melanoma (stages I and II)

Prognostic factors in regionally metastatic melanoma: lymph node metastases, satellite lesions, and in-transit metastases

AJCC melanoma database: multivariate analysis for stage III patients

Prognostic factor analyses in patients with distant metastatic melanoma (stage IV)

AJCC melanoma database analysis: stage IV

Melanoma Staging and Classification; Charles M. Balch, Jeffrey E. Gershenwald, Seng-jaw Soong, Arthur J. Sober, John M. Kirkwood


Primary sites

Regional lymph nodes

Metastatic sites

Rules for classification

Clinical staging

Pathologic staging

Clinical versus pathologic staging

TNM classification

Primary tumor (T)

Regional lymph nodes (N)

Distant metastatic melanoma (M)

Staging recommendations for metastases from unknown primary site

Stage groupings

Data-recording criteria

Models for Predicting Melanoma Outcome; Seng-jaw Soong, Shouluan Ding, Daniel G. Coit, Charles M. Balch

Description of the statistical model

Hazard function

Survival function

Predicting outcome from initial diagnosis for patients with localized melanoma

Hazard function estimation and parametric modeling for localized melanoma

Predicting outcome from initial diagnosis for patients with regional melanoma

Predicting outcome after a disease-free interval in patients with localized melanoma

Clinical applications

Clinical scoring system

Disease management decisions

Patient risk classification

Planning clinical trials

Analysis of clinical studies

Other applications

Screening: Clinical Assessment and Pathology

Melanoma Prevention and Screening; J. Mark Elwood, Jennifer Kay Makin, Craig A. Sinclair, Robert Burton

Prevention of melanoma

Reducing personal exposure: shade, clothing, and sunscreens

Intervention trials of the prevention of skin cancers and related lesions

Behavioral change programs for reducing personal exposure

Vitamin D

Controlling exposure to sunbeds

Prevention of melanoma: recommendations

Screening for melanoma

Uncertainties and conflicts in melanoma screening

Evidence relating to the effectiveness of screening

Programs of screening

Challenges in the detection of progressive melanoma

Clinical Genetics and Risk Assessment of Melanoma; Graham J. Mann, Hensin Tsao

Clinical risk assessment

Baseline risks attributable to age and sex

Previous melanoma or other skin cancer

Multiple melanocytic nevi

Skin and hair color, skin phototype, and freckling

Sun exposure and its surrogates

Family history of melanoma

Genetic risk of melanoma

Mutations in CDKN2A and CDK4 in familial melanoma

Pancreatic cancer and other phenotypes

CDKN2A mutations in sporadic and multiple primary melanoma

Melanoma risk to CDKN2A mutation carriers

Low-penetrance melanoma susceptibility genes

Genetic testing for melanoma risk?

Management of high-risk individuals

The future

Acquired Precursor Lesions and Phenotypic Markers of Increased Risk for Cutaneous Melanoma; Scott W. Menzies, Hensin Tsao, Arthur J. Sober

Pigment phenotype

Constitutive pigmentation (racial)

Hair and eye color

Oculocutaneous albinism

Ephelis (freckle)


Benign (common) acquired moles (nevi)

Atypical moles

Lentigo maligna

Clinical Characteristics of Melanoma; Allan C. Halpern, Ashfaq A. Marghoob, Arthur J. Sober

Personal history of skin cancer

Clinical presentation

Signs and symptoms

Clinical features

Growth patterns

Clinical assessment


Physical examinations

Diagnostic accuracy and aids to diagnosis

New technologies for diagnosis

Image analysis for diagnosis

Multispectral imaging and automated diagnosis

Confocal scanning laser microscopy

Other techniques: ultrasound imaging, magnetic resonance imaging, and optical coherence tomography

Evolving paradigms in the analysis of dermoscopic images

How we analyze images

Biopsy of Suspected Melanomas; Nanette J. Liégeois,Timothy M. Johnson, Arthur J. Sober

Prebiopsy lesion assessment

Biopsy techniques

Excisional biopsy

Incisional biopsy

Fine-needle aspiration

Frozen sections

Biopsy of the nail unit

Biopsy of the mucosa

Pathology of Melanoma; Richard Anthony Scolyer, Martin C. Mihm, Jr., Alistair J. Cochran, Klaus J. Busam, Stanley William McCarthy

Pathologic assessment of melanocytic tumors: goals and expectations

Biopsy techniques for clinically suspicious melanocytic tumors: the hazards of incomplete biopsies

Pathologic examination of the primary melanoma site

Clinical correlation for enhancement of pathologic accuracy

Specimen orientation

Melanoma tumor progression: the concept of radial and vertical growth phases

Clinicopathologic classification of melanoma

Superficial spreading melanoma

Lentigo maligna melanoma

Acrolentiginous melanoma

Nodular melanoma

Histologic features of vertical growth phase melanoma

Predominantly epithelioid cell vertical growth phase

Predominantly spindle cell vertical growth phase


Mixed spindle cell and epithelioid cell vertical growth phase

Nevoid vertical growth phase (nevoid melanoma)


The melanoma pathology report including a synoptic format

Uncommon melanoma variants

Metastatic melanoma

Fine-needle biopsy in melanoma patients

Clear cell sarcoma (melanoma of soft parts)

Molecular pathology of melanoma

The concept of the cancer stem cell

The metastatic niche concept

Management of Localized Melanoma

Excision of Primary Melanoma; Merrick I. Ross

Excision of primary melanoma: fundamental concepts

Historical perspective and the emergence of a contemporary paradigm

Thin melanoma (T1 and T2; less than 2 mm) excision trials

The Intergroup Melanoma Surgical Trial (T2 and T3 melanomas; 1 to 4 mm)

Thicker melanoma (T3 and T4; greater than 2 mm) excision trials

Current recommendations

Excisions for histologic variants

Techniques for routine wound closure

Excisions for melanomas in unusual or restrictive locations

Complex Closures of Melanoma Excisions; Maurice Y. Nahabedian, Jonathan R. Stretch, Anthony P.Tufaro

Principles of reconstructive surgery

Assessment of the acquired defect

Reconstructive options for complex wounds


Undermining with primary closure

Skin grafts

Composite grafts

Local flaps

Regional flaps

Free tissue transfer

Tissue expansion

Complex closures: regional considerations and clinical application

Head and neck



Surgical salvage for extensive and recurrent melanoma

Local Recurrences of Melanoma and Their Management; Kenneth K.Tanabe, Douglas S. Reintgen, Charles M. Balch



Risk factors for local recurrence

Surgical margins and local recurrence

Sentinel node biopsy and local recurrence

Timing of local recurrences

Local recurrence and survival


Mucosal Melanoma; Merrick I. Ross, Michael A. Henderson


Pathologic features and diagnosis

Staging and prognosis

Mucosal melanomas in the head and neck


Clinical presentation

Differential diagnosis

Prognosis and natural history


Mucosal melanomas in the female genital tract

Vulvar melanoma

Vaginal melanoma


Anorectal mucosal melanomas

Clinical and pathologic features


Mucosal melanomas at other sites

Urinary tract


Role of radiotherapy

Melanoma in Children and Teenagers; Julie R. Lange, Ira J. Dunkel, Helen M. Shaw, Arthur J. Sober


Congenital melanoma

Precursors and risk factors

Giant congenital nevi

Small and medium congenital nevi

Xeroderma pigmentosum

Constitutional risk factors

Ultraviolet exposure

Clinical presentation

Diagnosis and surgical management

Medical management


Vaccine trials



Follow-up and surveillance

Pregnancy and the Use of Hormones in Melanoma Patients; Rona M. MacKie

Nevi and pregnancy

Pregnancy before melanoma

Melanoma before pregnancy

Melanoma during pregnancy

Effect of pregnancy on disease outcome

Transplacental metastases

Treatment of melanoma during pregnancy


Adjuvant nonsurgical therapy for pregnant women


Oral contraception and melanoma

Use of oral contraception and subsequent risk of melanoma

Use of oral contraceptives after treatment for melanoma

Hormone replacement therapy and melanoma

Appropriate advice on planning pregnancy after treatment for melanoma

In vitro fertilization and melanoma

Management of Regional Metastases

The Sentinel Lymph Node and Regional Melanoma Micrometastases; Donald L. Morton, Alistair J. Cochran, John F. Thompson, Vernon K. Sondak

The history and conceptual basis of sentinel node biopsy

Anatomic versus functional definitions of the sentinel lymph node

Incubator versus marker theory

Immunology of the sentinel node

Pathobiology of tumor-induced immunosuppression of the sentinel node

Sentinel node biopsy for staging clinically localized melanoma

Interim results of the first Multicenter Selective Lymphadenectomy Trial


Should lymphatic mapping and sentinel node biopsy be the standard of care for cutaneous melanoma?

LM/SNB increases the chance of remaining disease free

LM/SNB is a superior staging technique for identifying appropriate candidates for adjuvant therapy

No noninvasive staging alternative is available

Early treatment of patients with a positive sentinel node may improve survival

"False-positivity" does not apply to the sentinel node

LM/SNB for melanomas that are not intermediate in thickness

Unresolved issues and ongoing research

The second Multicenter Selective Lymphadenectomy Trial

Carbon particle mapping

Lymphoscintigraphy in Patients with Melanoma; Roger F. Uren, John F. Thompson, Brendon J. Coventry, Barry E. Chatterton

Definition of a sentinel node

Lymphatic mapping of the skin: early studies


The first radiocolloid and early experience with lymphoscintigraphy


99mTc-labeled colloids

99mTc–antimony sulfide colloid

99mTc–rhenium sulfide colloid and 99mTc-albumin nanocolloid

99mTc-sulfur colloid

99mTc–human serum albumin

What is the ideal radiocolloid?

Lymphoscintigraphy for sentinel lymph node biopsy procedures

Lymphoscintigraphy technique

Injecting the tracer

Immediate dynamic imaging

Delayed static imaging

Unexpected lymphatic drainage pathways

Marking the surface location of the sentinel node

Radiation dosimetry: risks to the patient

Radiation dosimetry: risks to the pregnant patient

Radiation dosimetry: risks to attending staff

Patterns of lymphatic drainage from the skin


Head and neck

The limbs

Interval nodes

Drainage to multiple node fields

Complex lymphatic drainage patterns

Lymphoscintigraphy in clinically involved node fields

The future

New tracers for lymphatic mapping

Gamma probes for intraoperative detection of radioactivity

Gamma cameras for intraoperative imaging

Alternate methods of lymphatic mapping

Intraoperative Mapping and Sentinel Node Technology in Patients with Melanoma; Jeffrey E. Gershenwald, John F. Thompson, Nicola Mozzillo, Charles M. Balch

Approach to clinically negative regional lymph node basins in patients with early-stage primary cutaneous melanoma

Rationale for lymphatic mapping and sentinel lymph node biopsy

Technique for lymphatic mapping and sentinel lymph node biopsy

Role of sentinel lymph node biopsy in pathologic regional lymph node staging: prognostic value of sentinel lymph node pathologic status

Early results

Prognostic significance

Patterns of failure after negative sentinel lymph node biopsy

Clinical relevance of submicroscopic disease

Ongoing clinical trials of lymphatic mapping and sentinel lymph node biopsy

Technical planning: overall approach

Patient selection

Special situations

Approach to patients after previous wide local excision

Approach to patients with irregular lymphatic drainage patterns

Desmoplastic histology

Complications and morbidity after lymphatic mapping and sentinel lymph node biopsy

Technical considerations: lymphatic mapping and sentinel lymph node biopsy

General operating room positioning strategies

Axillary and Epitrochlear Lymph Node Dissection for Melanoma; Kelly M. McMasters, Sandra L.Wong, Douglas S.Tyler, Charles M. Balch, John F. Thompson

Axillary dissection


Surgical technique

Operative approaches to the upper axilla for recurrent or bulky axillary metastases

Postoperative management


Epitrochlear dissection



Surgical technique

Inguinofemoral, Iliac/Obturator, and Popliteal Lymphadenectomy in Patients with Melanoma; Lisa K. Jacobs, Charles M. Balch, Daniel G. Coit

Inguinofemoral dissection



Modifications of the classic technique of inguinofemoral lymphadenectomy

Iliac/obturator (deep pelvic) lymph node dissection



Operative technique

Postoperative complications: incidence and risk factors

Complications of lymph node dissection

Management of postoperative complications

Popliteal dissection


Operative technique

Neck Dissection and Parotidectomy for Melanoma; Anthony P. Tufaro, Suhail K. Mithani, Joseph A. Califano III, Ashok Shaha



Patterns of metastatic spread and extent of dissection

Neck dissection

Comprehensive neck dissection

Selective neck dissection



Preoperative evaluation

Anesthesia and positioning



Clinical outcome

Adjuvant radiotherapy

Recurrent Regional Metastases of Melanoma; Daniel G. Coit, Cristina R. Ferrone

In-transit metastases



Adjuvant therapy


Recurrent nodal metastases after lymph node dissection




Adjuvant therapy

Radiotherapy for Primary and Regional Melanoma; Graham Stevens, Bryan Burmeister

Role of radiotherapy in the management of primary melanoma

Adjuvant radiotherapy after surgical excision

Results of curative radiotherapy alone

Radiotherapy for lentigo maligna and lentigo maligna melanoma

Treatment recommendations for the use of radiotherapy in primary melanoma and lentigo maligna

Illustrative cases

Role of radiotherapy in the management of in-transit metastasis

Treatment recommendations for the use of radiotherapy for in-transit melanoma

Illustrative cases

Role of radiotherapy in the management of regional lymph node metastasis

Adjuvant postoperative radiotherapy after regional lymph node dissection

Results of adjuvant radiotherapy after complete lymph node dissection

Adjuvant radiotherapy after limited lymph node dissection

Preoperative radiotherapy for bulky nodal disease

Palliative radiotherapy for unresectable regional nodal disease

Treatment recommendations for the use of radiotherapy in regional nodal metastasis

Adjuvant radiotherapy after complete lymph node dissection

Adjuvant radiotherapy after limited lymph node dissection or no dissection

Therapeutic (palliative) radiotherapy

Illustrative cases

Hyperthermic Regional Perfusion for Melanoma of the Limbs; H. Richard Alexander, Jr., Douglas L. Fraker, Alexander M.M. Eggermont

Epidemiology and natural history

Historical perspective and early clinical series

Technical aspects of isolated limb perfusion


Pharmacokinetics of melphalan in isolated limb perfusion

Other chemotherapeutic agents


Tumor necrosis factor

Toxicity of isolated limb perfusion

Adjuvant isolated limb perfusion

Therapeutic limb perfusion

Melphalan alone

Melphalan and tumor necrosis factor

Isolated Limb Infusion for Melanoma; Georgia M. Beasley, Hidde M. Kroon, Merrick I. Ross, Peter C. A. Kam, John F. Thompson, Douglas S. Tyler

Similarities and differences between isolated limb infusion and conventional hyperthermic isolated limb perfusion

Patient selection for isolated limb infusion

Technical details of the isolated limb infusion procedure

Preoperative assessment and management

Insertion and positioning of arterial and venous catheters

Procedure in the operating room

Postoperative care

Pharmacokinetics of melphalan

Use of microdialysis to monitor drug concentrations in limb tissues and tumor deposits during isolated limb infusion

Limb and systemic toxicity after isolated limb infusion

Factors predicting toxicity after isolated limb infusion

Clinical results of isolated limb infusion

Factors predicting outcome after isolated limb infusion

Limb temperatures during isolated limb infusion

Tourniquet times

Interpretation of prognostic factors data

Repeat isolated limb infusion for disease progression after initial isolated limb infusion

Comparison with hyperthermic isolated limb perfusion

Laboratory studies of isolated limb infusion

Potential use of the isolated limb infusion technique to evaluate other drugs and biologic agents

Diagnosis and Local Treatment of Distant Metastases

Metastatic Surveillance and Follow-up of Melanoma Patients; Julie R. Lange, Axel Hauschild, Anne Brecht Francken

Goals of surveillance

Patterns of melanoma recurrence

Risk of local and regional recurrence

Time to recurrence

Strategies for active follow-up of melanoma patients

Detection of recurrences

Role of physical examination

Patient education

Patient well-being and follow-up

Follow-up schedules

Radiologic studies and laboratory tests

Screening for risk of new primary melanomas

Screening for other primary cancers

Current recommendations for surveillance

Diagnosis of Stage IV Melanoma; Michael B. Atkins, Axel Hauschild, Richard L.Wahl, Charles M. Balch

Timing of distant metastasis

Pattern of metastasis

Prognosis and prognostic factors

Sites of distant metastases

Number of metastatic sites

Elevated serum lactate dehydrogenase

Duration of remission

Performance status

Other prognostic factors

Clinical evaluation of metastasis

History and physical examination

Laboratory tests/biomarkers

Radiologic tests

Pathologic tests

Sites of distant metastases

Skin, subcutaneous tissues, and distant lymph nodes

Lung, pleura, and mediastinum

Brain and spinal cord

Gastrointestinal tract

Liver, biliary tract, and spleen


Kidneys and urinary tract

Heart and pericardium


Peritoneum and mesentery

Endocrine organs


Ovaries, uterus, and placenta

Testes and penis

Oral cavity, pharynx, and larynx

Eye and orbit

Cutaneous melanosis

Metastatic melanoma from an unknown primary site

Surveillance in patients who have localized melanoma

Surgical Excision of Distant Melanoma Metastases; John F. Thompson, Donald L. Morton, Charles M. Balch, Merrick I. Ross

Current status of surgery for stage IV melanoma

Relationships between tumor burden, immune function, and surgical treatment

Selection of patients and prognostic factors

Outcomes after surgical resection of melanoma metastases at specific sites

Skin, subcutaneous tissue, and lymph nodes

Lung, trachea, and bronchi

Brain and spinal cord

Gastrointestinal tract

Liver, biliary tract, and spleen


Kidney and urinary tract

Heart and pericardium

Endocrine organs


Ovaries, uterus, and vagina

Testes and penis

Oral cavity and pharynx

Eye and orbit

Radiotherapy for Distant Metastases and Clinical Radiobiology of Melanoma; Graham Stevens, Angela Hong, Michael J. McKay

Radiotherapy for distant metastases

Skin and subcutaneous metastases

Lymph node metastases

Brain metastases

Malignant spinal cord compression

Bone metastases

Sites irradiated less commonly

Developing sites for focused radiation treatment

Illustrative cases

Clinical radiobiology of melanoma

Biologic factors affecting the ionizing radiation response of melanoma

Intrinsic cellular radiosensitivity

Tumor oxygenation and microenvironmental


Tumor cell proliferation kinetics

Number of clonogenic tumor cells

Influence of melanization on radiosensitivity

Host factors in melanoma response and outcome

Future possibilities

Methods to improve the response of melanoma cells

Methods to improve the delivery of radiation to melanoma metastases

Multidisciplinary Management of CNS Melanoma Metastases; Kim A. Margolin, George M. Cannon, Minesh P. Mehta, Michael Y. Chen

Risk factors and prognosis

Clinical features

Neurosurgical management of brain metastasis

Radiotherapeutic and radiosurgical management of melanoma metastatic to the brain or spine

Whole-brain radiotherapy

Whole-brain radiotherapy alone

Surgery followed by whole-brain radiotherapy

Stereotactic radiosurgery

Systemic therapy for melanoma metastatic to the central nervous system

Systemic therapy considerations after adequate control of the central nervous system

Palliative approach

Aggressive approach

Investigational approach

Systemic Treatment of Metastatic Disease

Adjuvant Systemic Therapy for High-Risk Melanoma Patients; John M. Kirkwood, Vernon K. Sondak, Peter Hersey, Helen Gogas

Who should be considered for adjuvant therapy?

Chemotherapy alone or in multiagent combinations as adjuvant therapy for melanoma

Microbial immunostimulants

Bacillus Calmette-Guérin

Corynebacterium parvum


Hormonal therapy

Melanoma vaccines tested in phase III adjuvant trials

Adjuvant interferons as postoperative adjuvant therapy for melanoma

Adjuvant applications of interferon-alpha-2

Adjuvant applications of interferon-gamma

Emerging new modalities of adjuvant therapy

Biomarkers of prognosis and response

Chemotherapy-Based Treatment of Metastatic Melanoma; Michael B. Atkins, Mark R. Middleton, Paul B. Chapman

Single-agent chemotherapy

Dacarbazine and temozolomide



Microtubule toxins

Combination cytotoxic chemotherapy

Nitrosourea combinations

Taxane-based combination therapy

Cisplatin-based combination therapy

Chemohormonal therapy


Interferon alpha–based biochemotherapy regimens

Interleukin-2–based regimens

Interleukin-2 and DTIC/temozolomide combinations

Cisplatin and interleukin-2–based biochemotherapy regimens

Inpatient concurrent biochemotherapy regimens

Phase III biochemotherapy trials

Other biochemotherapy investigations

Non–interleukin-2 or interferon-based biochemotherapy combinations

Chemotherapy and antiangiogenic or targeted therapy

Antiangiogenic agents

Antiapoptosis-inducing agents

Selection of future phase III trials

Interferon Therapy for Melanoma; Ernest C. Borden, Stergios J. Moschos, John M. Kirkwood

Endogenous interferons as part of the host response to cancer

The family of interferon proteins and signaling activation

Mechanisms of antitumor action in melanoma

Signaling by interferons

Cellular mechanisms of action of interferons

Interferon-alpha-2 in the treatment of melanoma

The future of interferons in melanoma biology and therapy

Interleukins and Cellular Therapies for Melanoma; Douglas J. Schwartzentruber

Pharmacology of interleukin-2

Immunologic activity of interleukin-2

Systemic effects of interleukin-2

Clinical efficacy of high-dose interleukin-2 alone

Clinical efficacy of alternate doses, routes, and schedules of interleukin-2 alone

Clinical efficacy of interleukin-2 combined with interferon-alpha

Clinical efficacy of interleukin-2 combined with other cytokines, immune modulators, antibodies, or vaccines

Agents to reduce the toxicity of interleukin-2

Predictors of clinical response

Other cytokines for treatment of metastatic melanoma

Clinical efficacy of interleukin-2 combined with cellular therapy

Melanoma Vaccines; Jedd D.Wolchok, Jeffrey S.Weber

Tumor immunology

Antigen discovery


Vaccine approaches

Cell vaccines

Transduced cell vaccines

HLA-restricted melanoma-associated antigenic peptides

Ganglioside vaccines

Antiidiotypic monoclonal antibodies mimicking ganglioside antigens

Protein antigens

Heat-shock protein–based vaccines

DNA vaccination

Dendritic cell vaccines

Recombinant viral vaccines

Combination strategies and the future of melanoma vaccines

Immune Modulators in the Treatment of Patients with Melanoma; James P. Allison, F. Stephen Hodi, Yvonne M. Saenger, Jedd D. Wolchok

Biology of CTLA-4–mediated immune inhibition

Preclinical development of anti-CTLA-4 as an anticancer agent

Anti-CTLA-4: clinical experience in melanoma

Efficacy of CTLA-4 blockade: summary of clinical trials to date

CTLA-4 blockade and immune-related adverse events

Kinetics of response

Patient selection and predictors of toxicity and antitumor response

Dose and schedule of anti-CTLA-4 administration

Correlative immunologic studies

Vaccination strategies in combination with CTLA-4 blockade

Combination of CTLA-4 blockade and GM-CSF vaccination in murine models

Clinical investigation of combination CTLA-4 blockade and autologous GM-CSF–secreting tumor vaccination

CTLA-4 blockade with peptide vaccines

Other CTLA-4 antibody and immunotherapy combinations

Melanoma-Specific Targeted Therapies; Paul B. Chapman, David B. Solit, Keith T. Flaherty

Targeting cell surface molecules

Targeting receptor tyrosine kinases expressed in melanoma

Monoclonal antibodies

Targeting intracellular molecules

The mitogen-activated protein kinase pathway in melanoma

Drugs that inhibit BRAF

Hsp90 inhibitors

Drugs that inhibit MEK

Targeting PI3/AKT pathway

Angiogenesis inhibition in melanoma

Biology of Melanoma

Genetics and Molecular Pathology of Melanoma; Boris C. Bastian, Daniel Pinkel, Amaya Viros

Distinct patterns of epidemiologic, clinical, and histopathologic features in melanoma

Emerging melanoma subtypes based on genotypephenotype correlations

Melanomas on sun-exposed sites

Melanomas on relatively or absolutely UV-protected sites

Melanocytic tumors arising without associations to epithelial structures

Biology of Melanocytes and Primary Melanoma; Glenn Merlino, Vincent J. Hearing

Development of melanoblasts

Regulation of specification

Regulation of migration

Regulation of survival and proliferation

Differentiation of melanocytes

Regulation of differentiation

Regulation of survival


From melanocyte to melanoma: a multistep process

Molecular genetics: early lessons from familial and sporadic melanoma

Melanoma: a consequence of homeostatic disruption

Melanoma: cell of origin

Melanoma and the environment

Sun exposure and epidemiology

Photobiology and melanoma

Biology of Melanoma Metastasis; Menashe Bar-Eli, Isaiah J. Fidler

The pathogenesis of melanoma metastasis

Transcriptional regulation of melanoma progression

Role of AP-2-α in melanoma progression

Role of CREB/ATF-1 in melanoma progression

Involvement of ATF-2 in melanoma progression

SNAIL: its regulatory pathway in melanoma

MITF: its role in melanoma progression

Regulation of melanoma metastasis by the tumor microenvironment

Role of platelet-activating factor receptor

Potential therapeutic approaches to inhibiting melanoma metastasis

Using fully humanized antibodies to MCAM/MUC18 to inhibit tumor growth and metastasis of human melanoma

Using fully humanized neutralizing antibodies to interleukin-8 (ABX-IL-8) to inhibit angiogenesis, tumor growth, and metastasis of human melanoma

Immunology of Melanoma; Suzanne L.Topalian, Lieping Chen, Janis M.Taube, Paul F. Robbins, Jedd D.Wolchok, Alan N. Houghton

Innate immunity

Adaptive immunity

Melanoma antigens

General principles for identification of tumor antigens recognized by T cells and antibodies

Nonmutated self-antigens

Mutant melanoma antigens

Altered peptide ligands: enhancing the immunogenicity of low-affinity melanoma epitopes

Experimental models

Immune regulation and tolerance

Costimulatory/coinhibitory receptors

Regulatory T cells


Implications for immunotherapy

Biomarkers for Melanoma; Elizabeth A. Grimm, Dave S.B. Hoon, Lyn McDivitt Duncan

Potential clinical impact of melanoma biomarkers

Melanoma heterogeneity

Melanoma biomarker discovery and validation process

Biomarkers in early-stage melanoma

Molecular markers in primary cutaneous melanoma

Biomarkers for later-stage melanoma

Molecular markers in sentinel lymph nodes

Molecular markers in blood

Molecular markers in metastatic tumors

Additional Credits


Subject Categories

BISAC Subject Codes/Headings:
MEDICAL / Dermatology
MEDICAL / Oncology
MEDICAL / Surgery / Plastic & Cosmetic