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NCI CANCERLIT® Search: Therapy of Melanoma - May 2002
National Cancer Institute®
Last Modified: May 1, 2002
Table of Contents
1
UI - 11926952
AU - Lens MB; Dawes M; Goodacre T; Newton-Bishop JA
TI -
Elective lymph node dissection in patients with melanoma: systematic
review and meta-analysis of randomized controlled trials.
SO - Arch Surg 2002 Apr;137(4):458-61
AD - Centre for Evidence-Based Medicine, University of Oxford Nuffield
Department of Clinical Medicine, the Oxford Radcliffe National Health
Service Trust, Oxford OX3 9DU, England. markolens@aol.com
HYPOTHESIS: Elective lymph node dissection does not improve survival in
patients with melanoma without clinically detectable lymph node
metastases. OBJECTIVE: To determine whether elective lymph node
dissection in patients with melanoma without clinically detectable
regional metastases decreases overall mortality. DESIGN: Systematic
review and meta-analysis of randomized controlled trials comparing
elective lymph node dissection with delayed lymphadenectomy at the time
of clinical recurrence. SETTING: Randomized controlled trials available
participants. INTERVENTION: Elective lymph node dissection compared with
delayed lymphadenectomy or no lymphadenectomy in patients with melanoma
without clinically detectable regional metastases. MAIN OUTCOME MEASURE:
Overall mortality in treatment groups as compared with control groups at
the end of a 5-year follow-up period. RESULTS: Three randomized
controlled trials met the inclusion criteria. The pooled odds ratio for
overall mortality for the 3 trials was 0.86 (95% confidence interval,
0.68-1.09). Results are statistically nonsignificant, but they have
potential clinical significance. CONCLUSIONS: This systematic review of
randomized controlled trials comparing elective lymph node dissection
with surgery delayed until the time of clinical recurrence shows no
significant overall survival benefit for patients undergoing elective
lymph node dissection. Trials included in this review, however, contain
significant bias. The question is not answered for all patients, and the
results do not exclude the possibility that some subgroups may benefit
from elective lymph node dissection. Further research is required.
2
UI - 11927189
AU - Capuron L; Gumnick JF; Musselman DL; Lawson DH; Reemsnyder A; Nemeroff
TI -
CB; Miller AH
Neurobehavioral effects of interferon-alpha in cancer patients:
phenomenology and paroxetine responsiveness of symptom dimensions.
SO - Neuropsychopharmacology 2002 May;26(5):643-52
AD - Department of Psychiatry and Behavioral Sciences, Emory University
School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
We have previously shown that the risk of major depression in patients
with malignant melanoma undergoing interferon-alpha (IFN-alpha) therapy
can be reduced by pretreatment with the antidepressant, paroxetine.
Using dimensional analyses, the present study assessed the expression
and treatment responsiveness of specific clusters of neuropsychiatric
symptoms over the first three months of IFN-alpha therapy. Forty
patients with malignant melanoma eligible for IFN-alpha treatment were
randomly assigned to receive either paroxetine or placebo in a
double-blind design. Neuropsychiatric assessments were conducted at
regular intervals during the first twelve weeks of IFN-alpha therapy and
included the 21-item Hamilton Depression Rating Scale, the 14-item
Hamilton Anxiety Rating Scale and the Neurotoxicity Rating Scale.
Neurovegetative and somatic symptoms including anorexia, fatigue and
pain appeared within two weeks of IFN-alpha therapy in a large
proportion of patients. In contrast, symptoms of depressed mood, anxiety
and cognitive dysfunction appeared later during IFN-alpha treatment and
more specifically in patients who met DSM-IV criteria for major
depression. Symptoms of depression, anxiety, cognitive dysfunction and
pain were more responsive, whereas symptoms of fatigue and anorexia were
less responsive, to paroxetine treatment. These data demonstrate
distinct phenomenology and treatment responsiveness of symptom
dimensions induced by IFN-alpha, and suggest that different mechanisms
mediate the various behavioral manifestations of cytokine-induced
"sickness behavior."
3
UI - 11858976
AU - Eggermont AM; Keilholz U; Autier P; Ruiter DJ; Lehmann F; Lienard D;
TI -
EORTC Melanoma Group
The EORTC Melanoma Group: a comprehensive melanoma research programme by
clinicians and scientists. European Organisation for Research and
Treatment of Cancer.
SO - Eur J Cancer 2002 Mar;38 Suppl 4():S114-9
AD - Department of Surgical Oncology, Erasmus University Medical Center-Den
Hoed Cancer Center, Rotterdam, The Netherlands. eggermont@chih.azr.nl
The EORTC Melanoma Group (MG) was founded in 1969 by both clinicians and
scientists from various disciplines and fields of research with a common
interest in malignant melanoma. This collaborative approach has always
been the foundation of the groups strength. With an interest in tumour
biology and especially the immunological aspects of the disease, the
group has always pursued a scientific approach to treatment development
in malignant melanoma. Over the years, the group has performed many
clinical trials, epidemiological studies, histopathological studies
defining standards and guidelines, translational research regarding
prognostic factors and various metastatic and immunological aspects of
melanoma, and developed quality assurance programmes for immunological
and molecular biological assays in laboratory networks. At present, the
EORTC MG runs the worldwide largest clinical trial programme in stages
II, III and IV melanoma involving some 140 cancer centres in and outside
Europe. Each trial is associated with the appropriate translational
research programmes.
4
UI - 11955740
AU - Yu C; Chen JC; Apuzzo ML; O'Day S; Giannotta SL; Weber JS; Petrovich Z
TI -
Metastatic melanoma to the brain: prognostic factors after gamma knife
radiosurgery.
SO - Int J Radiat Oncol Biol Phys 2002 Apr 1;52(5):1277-87
AD - Department of Radiation Oncology, University of Southern California Keck
School of Medicine, Los Angeles, CA 90033, USA. chengyu@hsc.usc.edu
PURPOSE: To identify important prognostic factors predictive of survival
and tumor control in patients with metastatic melanoma to the brain who
underwent gamma knife radiosurgery. METHODS AND MATERIALS: A total of
122 consecutive patients with 332 intracranial melanoma metastases
underwent gamma knife radiosurgery over a 5-year period. Of these, 39
(32%) also received whole-brain irradiation (WBI). The median tumor
volume was 0.8 cm(3) (range: 0.02-30.20 cm(3)), and the median
prescribed dose was 20 Gy (range: 14-24 Gy). Median follow-up was 6.8
months. Univariate and multivariate analyses of survival and freedom
from progression were performed using the following parameters: status
of systemic disease, intracranial tumor volume, number of lesions, tumor
location, Karnofsky performance status, gender, age, and WBI. RESULTS:
Overall median survival was 7.0 months from time of radiosurgery and 9.1
months from the onset of brain metastasis. In multivariate analysis,
improved survival was noted in patients with total intracranial tumor
volume <3 cm(3) (p = 0.003) and inactive systemic disease (p = 0.0065),
whereas other parameters studied were of lesser importance (tumor
location, p = 0.056, and Karnofsky performance status, p = 0.086), or of
no significance (number of lesions, WBI, age, and gender). Freedom from
subsequent brain metastasis depended on intracranial tumor volume (p =
0.0018) and status of systemic disease (p = 0.034). CONCLUSIONS:
Stereotactic radiosurgery is an effective treatment modality for
patients with intracranial metastatic melanoma. Tumor volume and status
of systemic disease are good independent predictors of survival and
freedom from tumor progression.
5
UI - 11902552
AU - Fife K; Thompson J F
TI -
Lymph-node metastases in patients with melanoma: what is the optimum
management?
SO - Lancet Oncol 2001 Oct;2(10):614-21
AD - Addenbrooke's Hospital, Cambridge, UK.
Lymph-node metastasis is an indicator of poor prognosis for patients
with melanoma. The management of regional nodes is controversial, with
continuing debate about whether surgery or radiotherapy of positive
lymph nodes improves long-term survival or whether nodal involvement is
merely a marker of aggressive disease. However, there is general
agreement that systemic chemotherapy is rarely an effective form of
management. This review therefore considers surgical and
radiotherapeutic aspects of lymph-node management in patients with
melanoma. We discuss regional control and survival after lymph-node
surgery in retrospective series, randomised trials of elective
lymph-node dissection, the role of 'sentinel' lymph-node biopsy,
radiobiology and radiotherapy fractionation issues in melanoma
treatment, retrospective studies of adjuvant nodal radiotherapy, and
finally, randomised trials of adjuvant radiotherapy after lymph-node
dissection.
6
UI - 11310650
AU - Goldstein BG; Goldstein AO
TI -
Diagnosis and management of malignant melanoma.
SO - Am Fam Physician 2001 Apr 1;63(7):1359-68, 1374
AD - University of North Carolina at Chapel Hill School of Medicine, USA.
The incidence of malignant melanoma has increased in recent years more
than that of any other cancer in the United States. About one in 70
people will develop melanoma during their lifetime. Family physicians
should be aware that a patient with a changing mole, an atypical mole or
multiple nevi is at considerable risk for developing melanoma. Any mole
that is suggestive of melanoma requires an excisional biopsy, primarily
because prognosis and treatment are based on tumor thickness. Staging is
based on tumor thickness (Breslow's measurement) and histologic level of
invasion (Clark level). The current recommendations for excisional
removal of confirmed melanomas include 1-cm margins for lesions
measuring 1.0 mm or less in thickness and 2-cm margins for lesions from
1.0 mm to 4.0 mm in thickness or Clark's level IV of any thickness. No
evidence currently shows that wider margins improve survival in patients
with lesions more than 4.0 mm thick. Clinically positive nodes are
typically managed by completely removing lymph nodes in the area.
Elective lymph node dissection is recommended only for patients who are
younger than 60 years with lesions between 1.5 mm and 4.0 mm in
thickness. In the Eastern Cooperative Oncology Group Trial, interferon
alfa-2b was shown to improve disease-free and overall survival, but in
many other trials it has not been shown to be effective at prolonging
overall survival. Vaccine therapy is currently being used to stimulate
the immune system of melanoma patients with metastatic disease.
7
UI - 11486853
AU - Innet LM; Haripershad V; Van Den Berg J; Cooper L
TI -
Circuit and protocol for hypoxic hyperthermic isolated limb perfusion to
treat malignant melanoma.
SO - Perfusion 2001 Jul;16(4):325-30
AD - Department of Cardiothoracic Surgery-Perfusion, Waikato Hospital,
Hamilton, New Zealand. innetl@hwl.co.nz
In the treatment of cancer, isolated limb perfusion (ILP) allows what
would be a lethal systemic dose of cytotoxic drugs to be administered
directly to a tumour site of an extremity. Unfortunately, ILP is a
complex, expensive, time-consuming treatment that requires general
anaesthesia, vascular surgery and expertise with extracorporeal circuits
that may not be available outside a cardiac centre. By streamlining the
traditional ILP protocols and eliminating the oxygenator from the
circuit, an equally safe and effective technique of hypoxic hyperthermic
isolated limb perfusion has been developed.
8
UI - 11801787
AU - LeBoit PE
TI -
Nevus, redux.
SO - Am J Dermatopathol 2001 Oct;23(5):491-3
AD - Department of Pathology, University of California, San Francisco,
California 94115, USA. philipl@itsa.ucsf.edu
9
UI - 11928800
AU - Spanknebel K; Temple L; Hiotis S; Yeh A; Coit DG
TI -
Randomized clinical trials in melanoma.
SO - Surg Oncol Clin N Am 2002 Jan;11(1):23-52, viii
AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York,
New York 10021, USA. spanknek@mskcc.org
Efforts to improve the survival of patients with metastatic melanoma
have led to 67 prospective randomized clinical trials investigating the
use of agents comprising three main areas of therapy: systemic
chemotherapy-based regimens, immunotherapy, and vaccine therapy
10
UI - 11968423
AU - Sullivan A
TI -
Malignant melanoma: the surgical approach.
SO - Nurs Times 2000 Aug 10-16;96(32):38-9
AD - Wordsley Hospital, Stourbridge, West Midlands.
11
UI - 11959101
AU - Raisova M; Goltz G; Bektas M; Bielawska A; Riebeling C; Hossini AM;
TI -
Eberle J; Hannun YA; Orfanos CE; Geilen CC
Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors
in malignant melanoma and HaCaT keratinocytes.
SO - FEBS Lett 2002 Apr 10;516(1-3):47-52
AD - Department of Dermatology, University Medical Center Benjamin Franklin,
The Free University of Berlin, 14195, Berlin, Germany.
We examined the biological effects of the ceramide analogues
(1S,2R)-2-N-myristoylamino-1-phenyl-1-propanol (D-e-MAPP) and
(1R,2R)-2-N-myristoylamino-1-(4-nitrophenyl)-1,3-propandiol (D-NMAPPD)
on human HaCaT keratinocytes and human melanoma cells. We could
demonstrate that D-e-MAPP and D-NMAPPD are able to suppress acid
ceramidase activity. The elevation of the endogenous level of ceramide
is followed by induction of apoptosis and suppression of proliferation
in HaCaT keratinocytes. Moreover, we recently identified a group of
human melanoma cell populations which are heterogeneously susceptible to
C2-ceramide-mediated apoptosis. Studies with these melanoma cells
revealed correlation between ceramide-mediated apoptosis and
D-NMAPPD-induced apoptosis, confirming the effect of this inhibitor on
ceramide signaling in human melanoma cells. These findings suggest
ceramidase inhibitors as a potential new therapeutical class of
antiproliferative and cytostatic drugs.
12
UI - 11977016
AU - Lewis CW Jr; Harpole D
TI -
Pulmonary metastasectomy for metastatic malignant melanoma.
SO - Semin Thorac Cardiovasc Surg 2002 Jan;14(1):45-8
AD - Duke University Medical Center, Durham, NC 27710, USA.
Melanoma is the most deadly of skin cancers, and metastatic disease most
commonly first appears in the lungs. Because most patients with early
metastatic pulmonary disease are asymptomatic, routine screening with
chest radiographs is the most cost-effective method of discovery. The
therapy for pulmonary metastatic melanoma has drastically changed over
the years. Even today there is no curative immunotherapy or chemotherapy
available. The long-term overall survival for these patients is still
very poor, but early detection and surgery offers the only hope for
control in a small number of patients. Copyright 2002, Elsevier Science
(USA). All rights reserved.
13
UI - 11920589
AU - Jager E; Hohn H; Necker A; Forster R; Karbach J; Freitag K; Neukirch C;
TI -
Castelli C; Salter RD; Knuth A; Maeurer MJ
Peptide-specific CD8+ T-cell evolution in vivo: response to peptide
vaccination with Melan-A/MART-1.
SO - Int J Cancer 2002 Mar 20;98(3):376-88
AD - Medizinische Klinik II, Hamatologie-Onkologie, Krankenhaus Nordwest,
Frankfurt, Germany.
Monitoring of CD8+ T-cell responses in cancer patients during peptide
vaccination is essential to provide useful surrogate markers and to
demonstrate vaccine efficacy. We have longitudinally followed CD8+
T-cell responses in 3 melanoma patients who were immunized with peptides
derived from Melan-A/MART-1. Recombinant HLA-A2 tetramers loaded with
the naturally presented Melan-A/MART-1 nonamer peptide (AAGIGILTV) and
the Melan-A/MART-1 analog (ELAGIGILTV) were used in combination with
phenotypical analysis for different T-cell subsets including naive T
cells, effector T cells, "true memory" T cells and "memory effector" T
cells, based on CD45RA/RO and CCR7-expression. At least in a single
patient, T cells binding to the AAGIGILTV epitope were detected in
naive, precursor (CD45RA+/CCR7+) CD8+ T cells, and CD8+ T cells binding
to the analog ELAGIGILTV peptide were identified in the terminally
differentiated (CD45RA+/CCR7-) T-cell subset. Molecular and functional
analysis of tetramer-binding T cells revealed that the T-cell receptor
(TCR) repertoire was oligo/polyclonal in AAGIGILTV-reactive T cells, but
different and restricted to a few TCR clonotypes in ELAGIGILTV-reactive
T cells prior to vaccination. The TCR repertoire reactive with
Melan-A/MART-1 peptide epitopes was broadened during vaccination and
exhibited a different profile of cytokine release after specific
stimulation: tetramer-binding T cells from 2/3 patients secreted
granulocyte/macrophage colony-stimulating factor (GM-CSF) and
interferon-gamma but not interleukin-2 (IL-2) in response to
Melan-A/MART-1 peptides. In the third patient, tetramer-binding T cells
secreted IL-2 exclusively. Our results show that T-cell responses to
peptide vaccination consist of different T-cell subsets associated with
different effector functions. Complementary analysis for TCR CDR3 and
cytokine profiles may be useful to define the most effective CD8+ T-cell
population induced by peptide vaccination. Copyright 2002 Wiley-Liss,
Inc.
14
UI - 11928697
AU - Schadendorf D
TI -
Is there a standard for the palliative treatment of melanoma?
SO - Onkologie 2002 Feb;25(1):74-6
AD - Skin Cancer Unit of the German Cancer Research Center at the Department
of Dermatology, University Hospital Mannheim. d.schadendorf@dkfz.de
15
UI - 11896440
AU - Carsana M; Tragni G; Nicolini G; Bersani I; Parmiani G; Anichini A; Sun
TI -
YS; Moller P; Schadendorf D; Sensi ML
Comparative assessment of TCRBV diversity in T lymphocytes present in
blood, metastatic lesions, and DTH sites of two melanoma patients
vaccinated with an IL-7 gene-modified autologous tumor cell vaccine.
SO - Cancer Gene Ther 2002 Mar;9(3):243-53
AD - Human Tumor Immunobiology Unit, Department of Experimental Oncology,
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
A phase I clinical trial using autologous, IL-7 gene-modified tumor
cells in patients with disseminated melanoma has been recently
completed. Although no major clinical responses were observed, increased
antitumor cytotoxicity was measured in postvaccine peripheral blood
lymphocytes in a subset of treated patients. To analyze the in situ
immune response, the T cell receptor beta-chain variable region (BV)
repertoire of T cells infiltrating postvaccine lesions was studied in
two patients, and compared with that of T cells present in prevaccine
ones, in peripheral blood lymphocytes, and, in one patient, in delayed
type hypersensitivity (DTH) sites of autologous melanoma inoculum. A
relative expansion of T cells expressing few BVs was observed in all
postvaccine metastases, and their intratumoral presence was confirmed by
immunohistochemistry. Length pattern analysis of the complementarity
determining region 3 (CDR3) indicated that the repertoire of T cells
expressing some of these BVs was heterogeneous. At difference, CDR3,
beta-chain joining region usage, and sequence analysis enabled us to
demonstrate, within a T-cell subpopulation commonly expanded at DTH
sites and at the postvaccine lesion of patient 1, that both DTH sites
contained identical dominant T-cell clonotypes. One of them was also
expressed at increased relative frequency in the postvaccine lesion
compared to prevaccine specimens. These results provide evidence for
immunological changes, including in situ clonally expanded T cells, in
metastases of patients vaccinated with IL-7 gene-transduced cells.
16
UI - 11935312
AU - Margolin K; Atkins B; Thompson A; Ernstoff S; Weber J; Flaherty L; Clark
TI -
I; Weiss G; Sosman J; II Smith W; Dutcher P; Gollob J; Longmate J;
Johnson D
Temozolomide and whole brain irradiation in melanoma metastatic to the
brain: a phase II trial of the Cytokine Working Group.
SO - J Cancer Res Clin Oncol 2002 Apr;128(4):214-8
AD - Department of Medical Oncology and Therapeutics Research, City of Hope
National Medical Center, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
kmargolin@coh.org
PURPOSE: To evaluate the antitumor effects and toxicities of whole brain
irradiation (WBI) with temozolomide (TMZ) administered by prolonged oral
dosing in patients with melanoma metastatic to the brain. BACKGROUND:
Patients with melanoma metastatic to the central nervous system (CNS)
have an extremely poor prognosis and appear to benefit little from WBI.
TMZ is an alkylating agent chemically similar to dacarbazine (DTIC) with
good oral bioavailability and CNS penetration. TMZ has broad preclinical
antitumor activity which in melanoma is comparable to that of DTIC. The
combination of TMZ and WBI may provide enhanced antitumor activity
against CNS metastasis from melanoma. PATIENTS AND METHODS: Patients
with measurable CNS metastases with or without systemic disease were
treated with WBI, 30 Gray over ten fractions (days 1-5 and 8-12). TMZ,
75 mg small middle dotm(2 small middle dot)day, was started on day 1,
continued daily for 6 weeks and repeated every 10 weeks. RESULTS:
Thirty-one patients were treated. There was one CNS complete response of
4.5 months and two CNS partial responses of 2 months and 7 months
duration; the latter patient also had a 4-month complete remission of
systemic metastases. Toxicities were limited to a single episode of
grade 3 transaminase elevation and two episodes of grade 3 neutropenia,
one complicated by fatal sepsis. The median progression-free interval
for both CNS and extracranial sites was 2 months (range 1 week-11
months), and median survival 6 months (range 2-12 months). CONCLUSIONS:
WBI has lower than expected activity in CNS metastasis of malignant
melanoma. Although TMZ can be safely administered with WBI, the
combination has limited anti-tumor activity.
17
UI - 11905765
AU - Wolchok J D; Livingston P O
TI -
Vaccines for melanoma: translating basic immunology into new therapies.
SO - Lancet Oncol 2001 Apr;2(4):205-11
AD - Clinical Immunology Service, Hematologic Department of Medicine,
Memorial Sloan-Kettering Cancer Center, NY 10021, USA.
Advances in molecular biology and immunology in the past 10-15 years
have allowed for a greater understanding of the molecules present on
melanoma cells that are recognised by the immune system. The rising
incidence of melanoma, combined with lack of efficacy of cytotoxic
therapies, means there is a significant need for the development of
effective immunotherapies. We discuss three types of vaccine for
melanoma, which are currently in phase III clinical trials: allogeneic
and autologous cellular vaccines, and carbohydrate vaccines. We also
discuss several new areas of vaccine development, including DNA
vaccines, dendritic-cell-based vaccines, peptide vaccines, and
heat-shock protein vaccines. Although initial clinical trials have shown
the safety and immunological efficacy of vaccines for melanoma, the true
clinical benefit of these strategies will only be revealed in large
randomised trials.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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