editorial original articles review articles clinical case

82 Pages·2017·3.62 MB·English

Volume 16, Núm. 1, JaNuary-February 2017 ISSN: 1665-9201
INDEXADA EN SCOPUS • ARTEMISA • LILACS • IMBIOMED • PERIODICA-UNAM
EDITORIAL
The Mexican Gazette of Oncology (GAMO) Evolves in its Publication
Genetics as a Tool in Oncology Daily Practice
ORIGINAL ARTICLES
Use of Ipilimumab in Patients Diagnosed with Metastatic Melanoma: Three-Year Experience
in a Private Hospital in Mexico City
Latissimus Dorsi Myocutaneous Extended Flap in the Reconstruction of Large Chest Wall Defects
after Extensive Resections in Breast Pathology
Prognostic Factors in Patients Diagnosed with High Grade Glioma Managed with Radiotherapy:
Experience at the Federico Gómez Children’s Hospital of Mexico
Cost-Benefit Study of Febrile Neutropenia Prophylactic Treatment with Pegfilgrastim vs. Filgrastim
in Pediatric Patients with Solid Tumors
Clinical Genetics: Basic Concepts for Oncology Practice
REVIEW ARTICLES
Radiotracers Used in Nuclear Medicine for Prostate Cancer Diagnosis and Follow-Up
Can Omega 3 Supplements Prevent Cancer Therapy Neurocognitive Toxicity?
Health Economic Assessment: Applications, Rationale, Methodology and Common Mistakes
CLINICAL CASE
Paratesticular Desmoplastic Tumor: Case Report and Review of Literature
Medullary Thyroid Cancer Metastatic to the Oral Cavity: Clinical Case
Treatment with Radium 223 in a Patient with Castration-Resistant Metastatic Prostate Cancer:
A Case Report
Incidentally-Diagnosed Multiple Endocrine Neoplasia IIA (Sipple Syndrome) with Bilateral
Pheochromocytoma and Medullary Thyroid Carcinoma
www.smeo.org.mx
www.elsevier.es/gamo
Gaceta Mexicana de Oncologia. 2017;16(1):1-3
www.gamo-smeo.com PERMANYER
EDITORIAL
The Mexican Gazette of Oncology (GAMO) Evolves in its Publication
Samuel Rivera-Rivera1 and Francisco Javier Ochoa-Carrillo2,*
1Chairman, Sociedad Mexicana de Oncología (SMeO), 2Editor in Chief, Gaceta Mexicana de Oncología (GAMO), Mexico City, Mexico
As the official scientific dissemination journal of the Mexi- scientific communication, physicians will mainly cite two:
can Society of Oncology (SMeO – Sociedad Mexicana de On- the influence of English on current medical language and
cología), the Mexican Gazette of Oncology (GAMO – Gaceta the simplification of international communication. Never-
Mexicana de Oncología) has achieved 14 years of existence, theless, the fact that the influence of the English language
hitherto being able to maintain both bimonthly periodicity is more widespread and intense, and that it affects all levels
and continuity in Spanish, meeting the international stand- of language in orthographic, lexical, and syntactic aspects,
ards of professional scientific publications, with a selection seems to be often forgotten.
of peer-reviewed articles, and enriched by contributions The appearance of Medline, which brought literature
coming from Latin America, the USA, and Europe. In addi- search automation, has allowed for it to be amazingly sim-
tion, our journal has maintained an impeccable editorial plified, but has also led scientists to restrict their searches
presentation with color images, high-definition printing, to the last 35 years (Medline only covers the period from
and high-quality paper, with significant indexing, open for 1966 to the present day) and to automatically eliminate ar-
free access on the internet, but especially being increasing- ticles published in other languages, thanks to the possibility
ly consulted in different parts of the world through different to conduct automatic searches with the “English only” re-
international bibliographic databases and with the support striction criterion1.
of a renowned publishing house such as Elsevier. Furthermore, since large bibliographic databases pref-
Development always brings about changes, which is noth- erably incorporate journals in English, articles published in
ing but the result of an evolutionary process that generates large Anglo-North American medical journals barely contain
new phenomena, such as the transition from the printed to references to publications in other languages.
the electronic format, or as once occurred with the transi- Another fact that drives this eagerness of researchers to
tion from handwritten to printed texts. This elicits a change publish in English and, if possible, in journals with interna-
in production, dissemination and information authentication tional circulation, is that the editorial boards of these jour-
processes, and all stakeholders involved with these process- nals, as well as the scientific committees of the main inter-
es (authors, editors, information professionals, etc., all in national congresses, are mainly comprised by Anglo-North
their roles as information providers) have therefore been American scientists.
compelled to open spaces to these new electronic versions, The famous English saying “publish or perish” has thus be-
with this being the case of the GAMO. come, in Spanish-speaking countries, the bilingual disjunc-
On the other hand, one of the most notorious character- tive “publica o muere”; i.e., for Spanish language scientists,
istics of medical writing in the last third of the 20th century, the fact comes down now to a situation of whether “to be or
and so far in the 21st, is the predominance of English as the not to be” in the international medical community2.
only international language of medicine. The SMeO, within its growth and evolution, aware of this
Among the repercussions the boom of English language reality, and in an effort to make the presence of researchers
has had on medicine over the past few decades, which have who collaborate with the GAMO more visible, in addition to
driven to its current situation of absolute predominance in continuing to publish the journal in Spanish, is now simulta-
*E-mail for correspondence: [email protected] (F.J. Ochoa-Carrillo)
http://dx.doi.org/10.24875/j.gamo.17000014
1665-9201 / © 2017 Sociedad Mexicana de Oncología. Publicado por Permanyer México. Este es un artículo Open Access bajo la licencia
CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).
EDITORIAL 2
neously releasing, from this issue onwards, the full-English In addition to the above points, we can add further char-
version. This unprecedented effort, after several years of acteristics that new technologies contribute within elec-
fruitless attempts, is now a reality, and we inform that the tronic devices, such as smartphones or PDAs, where the
printed paper version will disappear, with the journal be- complete collection of one or several titles can be stored.
ing electronically available in both languages (Spanish and The nature of e-publishing eliminates many of the steps
English). related to print publishing in the relationship between pub-
Currently, new scientific and technological advances re- lishers/providers and the libraries: printing, binding, pack-
quire rapid dissemination to the benefit of specific necessi- aging, distribution, transportation, postal fees and storage
ties. Electronic publishing has turned out to be an efficient costs.
vehicle for the dissemination of contents, since it is one of As well as the observed advantages, there are also some
the scientific communities’ main means of communication, disadvantages:
which facilitates exchange between peers from different − Considerable initial investment, although e-journals
geographic locations. are more economical in the long-term.
Electronic publishing requires increasingly more efficient − On-screen visualization inconvenience, although the
means of communication, and demands better skills for PDF file format is an advance in this sense.
consultation as well. The Internet favored the evolution of − High costs of publication subscriptions.
electronic publishing as telecommunication networks were − A language barrier in our countries since the resources
developing; sometimes, other technologies allowed for cov- are mainly in English language.
erage to be broadened, as in the case of CD-ROMs, which − Internet connection is required, with additional costs
came to be a means of electronic distribution par excellence with regard to telecommunication infrastructure.
In light of the attitude of commercial publishers in the
prior to the advent of the internet.
market of information, other initiatives have started to
As it was consolidating, electronic publishing saw the
emerge, including the “Open Access” initiative. Given its
emergence of a variety of information resources (e-journals,
impact, considering a series of definitions on the subject
e-books, e-bulletins, among others), and academic commu-
is suggested: The Open Access (OA) initiative represents
nities began to be assiduous users of such resources.
a new academic publishing model, developed for free in-
vestigators and libraries; it emerged as a reaction to limi-
ADVANTAGES AND DISADVANTAGES tations imposed by excessive increases in subscriptions to
peer-reviewed journals, especially in the fields of science
OF THE E-JOURNAL3
and medicine. By breaking the publishers’ monopoly on
scientific research distribution, Open Access enables more
The conformation of the e-journal is strongly associated
equitable access to information, with the additional ad-
with the publication’s information architecture, and hence
vantage that it allows for authors to keep the copyright
interaction with the document is more or less possible. Nev-
of their works.
ertheless, as such, the electronic publication has the follow-
Open Access Journal: This is a periodical scholarly pub-
ing advantages:
lication that offers full-text articles that are freely and
− It preserves rare and fragile documents, without re-
universally published on the Internet, by immediately and
stricting access to those who wish to consult them.
with no restriction whatsoever depositing them in a wide-
− It facilitates transmission by means of telematic net-
ly recognized, open access repository, as in the case of
works.
GAMO.
− It enables simultaneous access to many users.
The impact factor of a journal is the mean number of
− It offers a solution to the problem of physical space
times an article published in a particular journal is cited.
for storage. It is an instrument to compare journals and to assess the
− It reduces publishing and distribution costs by using relative importance of a journal within a specific scientific
electronic means for the transmission of information. field. Thomson ISI is in charge of analyzing journals for this
− It enables full-text searches. purpose, and this project is therefore intended to consoli-
− It facilitates instantaneous access without the need to date this aspect.
go elsewhere. As of this issue, we have also made some changes in the
− It provides links to other related resources, such as editorial board, enriching it with prominent national and in-
filmed and animation materials, which facilitates the ternational opinion leaders that, with their editorial expe-
expression of ideas that are difficult to capture in a rience, will surely contribute to improving article selection
printed format. since, fortunately, we receive high-quality manuscripts and
− It establishes a close relationship between authors and in a considerable number, which provides the opportunity
readers through e-mail, which favors scientific com- to select.
munication. And so it was that, at this new stage, the SMeO has es-
− It allows immediate publishing, based on a system of tablished an agreement with Permanyer, which is a medical
continuous production. publishing house founded in Barcelona in 1973.
− It enables incorporating corrections or comments Currently, it has offices in Spain, Switzerland, Mexico,
made by readers. Brazil, and Portugal and commercial presence in more than
− It reduces paper consumption costs since printed cop- 25 countries.
ies are made only for articles that are really of inter- Permanyer is specialized in periodical peer-reviewed
est, thus favoring ecology. medical publications, and has systems and channels of its
3 EDITORIAL
own for publishing in English and Spanish, among other lan- In 2000, Permanyer obtained the ISO 9001 quality accred-
guages, as well as for subsequent electronic dissemination itation for scientific publication, and has renewed it every
and content indexing in the main global indexing systems, year by means of detailed audits as a sign of commitment
such as, for example, PubMed, Medline, and Thomson Reu- to the final quality of its publications. This company has had
ters, among others. a presence in Mexico since 2005 and, currently, it publishes
Manuscript handling is carried out by means of an elec- reference journals that meet international quality standards
tronic process with personalized software offered by the for medical/scientific publications.
publishing house, where authors submit their manuscripts Dear reader, the SMeO and GAMO are working to evolve
for review and the system connects Editors and Reviewers and to offer an attractive option for researchers and poten-
for articles to be followed-up until publication approval, tial users and to be consulted in Spanish and/or English, and
thus enabling several reviews and updates of the same man- in this way provide a better service to the oncologic commu-
uscript until its acceptance. Once approved by the editors, nity of Mexico and all over the world.
the publishing house carries out a review of the text under
high-quality standards following the International Commit-
REFERENCES
tee of Medical Journal Editors recommendations and pub-
lishes the articles for indexing, both in the printed and elec-
tronic forms, in the journal’s website, which is provided by 1. Jennings AG. Research or re-search? Why we should read old and
foreign literature. Ann R Coll Surg Eng. 1994;76(5 Suppl):236-7.
the publishing house.
2. Ren S, Liang P, Zu G. The challenge for Chinese scientific journals.
It possesses the electronic infrastructure required to pro- Science. 1999;286(5445):1683.
vide and maintain website functioning of scientific journals 3. Travieso Aguiar M. Las publicaciones electrónicas: una revolución en el
and has wide experience in scientific journal indexing in dif- siglo XXI. Acimed. Marzo-abril de 2003. Vol. 11, n.o 2. [Internet] Dis-
ponible en: http://www.bvs.sld.cu/revistas/aci/vol11_2_03/aci010203.
ferent international information recovery and bibliometric
4. Reitz JM. ODLIS: Online Dictionary for Library and Information Science.
systems such as, for example, Thomson-Reuters, Medline/
Wesport, Washington: Libraries Unlimited. Disponible en: http://www.
PubMed, etc. abc-clio.com/ODLIS/odlis_A.aspx.
Gaceta Mexicana de Oncologia. 2017;16(1):4-6
www.gamo-smeo.com PERMANYER
EDITORIAL
Genetics as a Tool in Oncology Daily Practice
Herber García-Castillo1,* and Francisco Javier Ochoa-Carrillo2
1Life in Genomics, 2Department of Surgical Oncology, Instituto Nacional de Cancerología and Hospital Ángeles del Pedregal;
Mexico City, Mexico
Received for publication: 11 December 2016; accepted for publication: 25 February 2017
Available online: 10 July 2017
The oncology consultation is enriched by genetics. This new terminology and some of it can be foreign to the oncolo-
science is revolutionizing oncological clinical practice. It gist. This article gives an introduction to this world in simple
contributes with elements to understand the pathophysiol- language and with educational examples for better under-
ogy of cancer, and enables comprehensive diagnosis and pa- standing.
tient management from the knowledge of new therapeutic In future issues we will further address subjects such as:
targets, passing through hereditary cancer and new clinical genetic counseling, genetic alterations in cancer, biomark-
diagnoses integration, and up to the prognosis and treat- ers in oncology, international recommendations for the use
ment of sporadic cancers. of genetic tests in oncology practice, hereditary cancer syn-
Currently, there are a wide variety of genetic studies dromes, genes vs. panels, pharmacogenetics, gene expres-
and tools available: tests for hereditary cancer, expression sion tests, assessment and risk management in hereditary
studies for the prediction of metastasis, pharmacogenetics, breast and colon cancer, prophylactic surgery and surgical
microarrays, comparative genomic hybridization, etc. But, approaches based on molecular studies, cost-effectiveness
what do these studies consist in? When should they be or- in the management of hereditary cancer, the patient’s point
dered? Which patients are candidates? Is it better to request of view, and the hereditary cancer management approach
individual studies or gene panels? What requirements should by interdisciplinary teams.
the laboratories that perform these tests meet? In what There are several examples of the usefulness of genetics
cases should consultation with the genetics department be in oncological practice, since over the last years, medica-
requested? The oncologist asks him/herself these and other tions used in oncology have changed, based on the knowl-
questions when faced with the decision to prescribe a ge- edge of molecular pathways and biomarkers (specific mole-
netic study. cules that are over-expressed in cancer)1, which are of great
However, these questions are not that easy to answer value in the prediction of response to therapy and have ac-
since many of them require knowledge on the basic con- quired relevance in oncological daily practice, such as the
cepts of clinical genetics and on the specific areas where the use of HER2 or EGFR, to the benefit of a large subgroup of
knowledge is applied. patients over the past few years (Table 1).
In view of the above, in this issue we will start with a se- Currently, there are more than 50 oncologic drugs with
ries of bimonthly articles intended to update oncologists on FDA-approved genetic biomarker information included in the
the application of genetics to oncological clinical practice. summaries of product characteristics or patient information
We will start with an article appearing in this issue entitled leaflets. This list includes some drugs that are specially pre-
“Clinical genetics: Basic concepts for oncology practice”. scribed when there is some genetic alteration, as in the case
As with any other specialty, clinical genetics uses its own of the treatment of non-small cell lung cancer with afatinib,
*E-mail for correspondence: [email protected] (H. García-Castillo)
http://dx.doi.org/10.24875/j.gamo.17000001
1665-9201 / © 2017 Sociedad Mexicana de Oncología. Publicado por Permanyer México. Este es un artículo Open Access bajo la licencia
CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).
EDITORIAL 5
Table 1. Commonly used biomarkers in oncology
FDA Approval Cancer Benefited patients Drug Biomarker
Nov, 2004 Lung CA 15% Erlotinib EGFR
April, 2003 Chronic myeloid 95% Imatinib BCR-ABL
leukemia
Sept, 1998 Breast CA 15-20% Trastuzumab HER2
CA: cancer; FDA: Food and Drug Administration.
Table 2. US Food and Drug Administration-approved drugs indication or contraindication according to the presence
of mutations
Drug Type of cancer Gene Mutation Implication
Afatinib Metastatic non-small EGFR Exon 19 and 21 Indication
Erlotinib cell lung cancer deletion (L858R)
Gefitinib T790M
Osimertinib
Cobimetinib Metastatic melanoma BRAF V600E/K Indication
Dabrafenib
Pembrolizumab
Trametinib
Vemurafenib
Olaparib Advanced ovarian BRCA1/2 Germline mutations Indication
cancer (inherited)
Cetuximab Metastatic colorectal KRAS Exons 2, 3, 4 deletion Contraindication
Panitumumab cancer (codons 12,13, 59,
61, 117, 147)
erlotinib, gefitinib, osimertinib; chemotherapy in metastat- er than 26 are given chemotherapy and endocrine therapy,
ic melanoma with cobimetinib, dabrafenib, pembrolizumab, and patients with 11 to 25 points remain in an unspecified
trametinib, and vemurafenib; and advanced ovarian cancer group (since benefit of chemotherapy has not been defined
with olaparib. Conversely, some mutations are a contraindi- for them). This expression profile is considered to be pre-
cation for the prescription of certain drugs such as cetuxi- dictive of tamoxifen and adjuvant chemotherapy efficacy.
mab and panitumumab2 (Table 2). The TAILORx prospective trial, carried out in over 10,000
The use of gene expression panels such as MammaPrint® patients, showed that 15.9% of patients belong to the 0-10
and OncotypeDx® is increasingly common in patients with recurrence risk group, which received endocrine therapy
breast cancer at early stages with the purpose to discern alone and have a five-year invasive disease-free survival
which patients can benefit from adjuvant chemotherapy and rate of 93.8% (95% CI: 92.4-94.9)4.
which patients do not require it. In addition to genetic studies as a tool in the prescription
MammaPrint® is a 70-gene assay that uses microarray of chemotherapy, a very interesting field is the use of genet-
technology, requires frozen tissue, and is used in patients ic testing in patients with hereditary cancer; between 5-10%
with stage I and II breast cancer with negative lymph nodes of cancers are estimated to be hereditary, and their clinical
or 1-3 positive lymph nodes to identify those patients who management is different to that of sporadic cancer.
may benefit from adjuvant chemotherapy based on high or For example, in the breast and ovary cancer hereditary
low genomic risk for cancer distant recurrence and at five syndrome positive to BRCA mutation, where the risk for
and 10 years. The MINDACT prospective trial, which is fol- having breast cancer and/or ovarian cancer is as high as
lowing a cohort of more than 6,000 patients, has found that 41-90%, there is also an increased recurrence of contralat-
patients with post-surgery clinical high risk and genomic low eral breast cancer as high as 32% at 10 years and 44% at
risk without chemotherapy have a five-year survival without 70 years of age and, therefore, bilateral mastectomy is
distant metastasis of 94.7% (95% CI: 92.5-96.2)3. recommended in newly-diagnosed patients, and owing to
On the other hand, OncotypeDx® is a 21-gene expression a risk for ovarian cancer of up to 44% at 70 years of age,
assay that includes ER, PR, HER2 and Ki67 in breast can- the risk-reduction salpingo-oophorectomy option is recom-
cer for ER-positive, HER2-negative and lymph node-nega- mended after 35 years of age with satisfied parity. These
tive women. The technology used is reverse transcription procedures help to reduce the risk of breast and ovarian
polymerase chain reaction (RT-PCR), which requires paraf- cancer by 95 and 90%, respectively5. It should be noted that
fin-embedded tissue. Patients are classified according to a some patients do not prefer the risk-reducing surgery option
recurrence score to distinguish those who may benefit from and, consequently, close surveillance with imaging studies
adjuvant chemotherapy: patients with a 0-10 score are as- and serum marker determination every six months is the
signed to receive endocrine therapy, those with a score high- option. The drug olaparib is currently available for patients
6 EDITORIAL
with advanced ovarian cancer positive to inherited muta- genetics in oncological daily practice, and in future issues
tion in the BRCA genes, and 3 poly(ADP-ribose) polymerase we will complement the provided information. We will start
(PARP)-inhibitor drugs are in phase III studies for BRCA-posi- in this issue with the bases of clinical genetics in the arti-
tive breast cancer. cle entitled “Clinical genetics: Basic concepts for oncology
Clinical criteria in hereditary cancer are increasingly less practice”; we hope it will be of interest and serve as a con-
rigorous as a primary screening method in order to include tribution to a current clinical practice update.
the largest number of patient candidates to genetic stud-
ies. In hereditary breast and ovarian cancer syndrome, the
National Comprehensive Cancer Network (NCCN) criteria in-
REFERENCES
clude, among others, patients with breast cancer younger
than 45 years, ovarian cancer at any age, triple-negative
1. Ferté C, André F, Soria JC. Molecular circuits of solid tumors: prognostic
breast cancer prior to 60 years of age, and two cancers of
and predictive tools for bedside use. Nat Rev Clin Oncol. 2010;7:367-80.
the spectrum ovarian, fallopian tube, prostate, pancreas or
2. US Food and Drug Administration. Table of Pharmacogenomic Biomark-
peritoneum in the family5. ers in Drug Labels. Available at: http://www.fda.gov/Drugs/ScienceRe-
There are studies available on high-penetrance genes search/ResearchAreas/Pharmacogenetics/ucm083378.htm (Accessed
Jan 15, 2017).
such as BRCA; however, there are also panels of several
3. Cardoso F, van’t Veer LJ, Bogaerts J, et al. 70-Gene signature as an
genes containing up to 30 genes related to hereditary can-
aid to treatment decisions in early-stage breast cancer. N Engl J Med.
cer, and the clinician should know the degree of penetrance 2016;375:717-29.
of different genes in hereditary cancer, as well as the dif- 4. Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a
ferential diagnoses to know if prescribing a genetic panel is 21-gene expression assay in breast cancer. N Engl J Med. 2015;373:2005-14.
5. National Comprehensive Cancer Network. NCCN Clinical Practice
convenient, since not all results are clinically applicable.
Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast
Genetics is a fascinating science and it is very promis-
and Ovarian, 2017. Available at: https://www.nccn.org/professionals/
ing for oncology. We illustrate some relevant applications of physician_gls/f_guidelines.asp (Accessed Jan 15, 2017).
Gaceta Mexicana de Oncologia. 2017;16(1):7-17
www.gamo-smeo.com PERMANYER
ORIGINAL ARTICLE
Use of Ipilimumab in Patients Diagnosed with Metastatic Melanoma:
Three-Year Experience in a Private Hospital in Mexico City
Christian Patricio Camacho-Limas1,*, Guillermo Olivares-Beltrán1, Raquel Gerson-Cwilich2,
Alberto Villalobos-Prieto1, María del Ángel Góngora-Jurado3 and Alain Sánchez-Rodríguez4
1Department of Medical Oncology, 2Cancer Center, 3Clinical Pathology, and 4Internal Medicine; Centro Médico ABC, Mexico City,
Mexico
Received for publication: 31 August 2016; accepted for publication: 25 February 2017
Available online: 10 July 2017
KEYWORDS Abstract Objective: Ipilimumab is an antibody for the treatment of metastatic melanoma
Melanoma; that currently is scarcely accessible for most cancer centers in Mexico, and this is why a de-
Ipilimumab; scriptive analysis was carried out in the ABC Hospital, with this being one of the few centers
that use this drug in the entire country. Material and methods: A three-year observational
Immunotherapy
study was carried out with the general purpose to describe the clinical course of ipilimumab-
treated patients and with the specific purpose to perform an overall survival analysis. De-
mographic, diagnostic, therapeutic, and clinical variables were analyzed. The response was
assessed according to Wolchok’s immune response criteria. Results: Thirteen patients were
included, out of which 53% (7/13) were females and 46% (6/13) males, with a median age of
54 years at diagnosis. Median total follow-up of the population was 18 months, and all patients
were treated with ipilimumab 3 mg/kg every three weeks for four sessions. Overall survival
and progression-free survival had a median of 18 (IQR: 8-24) and 5 (IQR: 4-24) months, respec-
tively. Conclusions: In this cross-sectional cohort analysis, observations on metastatic or re-
current melanoma treatment with ipilimumab published up to now were corroborated. With a
response rate of 23%, an essential outcome is a response duration of more than 28 months until
current follow-up of the patients who show an objective response with the use of ipilimumab.
(creativecommons.org/licenses/by-nc-nd/4.0/).
*E-mail for correspondence: [email protected] (C.P. Camacho-Limas)
http://dx.doi.org/10.24875/j.gamo.17000002
1665-9201 / © 2017 Sociedad Mexicana de Oncología. Publicado por Permanyer México. Este es un artículo Open Access bajo la licencia
CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Ipilimumab in metastatic melanoma 8
INTRODUCTION EPIDEMIOLOGICAL AND RISK FACTORS
ASSOCIATED WITH MELANOMA
Melanoma accounts for 4% of all malignancies of the skin,
although it is responsible for 80% of deaths associated with Age
this type of neoplasm. Most melanomas are located in the
skin (95%), and less frequently (5%) in mucous membranes
Melanoma can occur at any age, although these lesions
(oral, gastrointestinal tract, genital), the retina, or me-
are increasingly being diagnosed in young people, with the
ninges. Approximately 3% of patients develop occult mel-
highest frequency concentrating at middle age. Forty-one
anomas (metastatic disease with no evidence of a primary
percent of melanomas are diagnosed prior to 55 years of
tumor)1.
age. After 70 years of age, the nodular and acral lentiginous
types are more common (58%), whereas in younger people,
superficial spreading is predominant (74%). There also seems
to be a correlation between age and thickness: elderly pa-
EPIDEMIOLOGY
tients have a higher Breslow index than younger ones.
Worldwide, nearly 160,000 new cases of melanoma are di-
Gender
agnosed every year. According to the report of the World
Health Organization, nearly 57,000 deaths related to this
Melanoma is slightly more common in females, where it pre-
type of cancer occur every year, with an exponential growth
dominates on the lower limbs and zones with higher sun ex-
in melanoma cases over the past few years.
posure and, generally, the prognosis is better than in males.
This increased incidence affects all ages and is only sur-
passed by liver and thyroid cancer. This elevated incidence
Racial factor
has generated social and medical alarm, which calls for
a multidisciplinary approach, essentially focused on pre-
vention. There is a higher incidence of melanoma in blond, red-
haired, and clear-eyed people. Type I and II skin.
The phototype is the skin’s ability to adapt to sun ex-
posure that each individual has since birth, i.e. the set of
MELANOMA IN MEXICO characteristics that determine if the skin becomes tanned or
not, and how and to what extent it does.
Since this is a condition that manifests itself more commonly Fitzpatrick created a six-phototype classification. Pho-
in fair-skinned individuals, in Mexico there are no accurate totype I individuals have milky white skin, blue eyes, red-
reports available on the disease. dish hair, and freckles on the skin. Those with phototype II
The Melanoma Clinic of the National Institute of Cancer are individuals with white skin, blue eyes, blond hair, and
(INCAN – Instituto Nacional de Canceología) reports that the freckles. Phototype III individuals belong to European Cau-
increase of this neoplasm is evident in Mexico, with an evo- casian races that usually are not exposed to the sun. Those
lution of nearly 500% in the past few years. This trend is with Phototype IV have light brown skin with dark hair and
expected to continue through 2020, which will make this eyes (Mediterranean, Mongolian and Oriental people). Pho-
type of cancer increasingly common. totype V individuals have brown skin (Native Americans,
In our country, people with skin tumors, especially pa- Hindustanis, Arabs and Hispanics). Phototype VI individuals
tients who suffer from melanoma, usually attend the hospi- are black-skinned persons.
tal at very advanced stages, which results in a large propor- Black race patients have a 10-fold lower incidence than
tion of cases not being candidates for treatment anymore White race individuals, and in these subjects, the most com-
owing to an important deterioration in performance status. mon locations are the palms, the soles, mucous membranes,
Melanoma is a heterogeneous oncologic entity, and it is and the eyes, which indicates the importance of pigmenta-
characterized by four histopathological types: acral lentig- tion as a protection against melanoma.
inous, nodular, superficial spreading, and lentigo malignant
melanoma. In Mexico, the most commonly occurring type Presence of nevi
is acral lentiginous melanoma, and its clinical presentation
and ethnic distribution usually differentiate it from superfi- The existence of an elevated number of nevi is correlated
cial spreading melanoma (the most common type of melano- with a higher probability for developing melanoma, espe-
ma in Caucasian countries). cially if there are atypical nevi present.
Acral lentiginous melanoma is the most commonly oc- Congenital giant nevi also present higher risk, especially
curring melanoma in dark-skinned populations, which cor- if located on paravertebral regions. However, melanomas
respond to the III and IV skin phenotypes and which are the develop de novo in 75% of cases, with 25% developing on a
most prevalent phenotypes in the Mexican population. preexisting nevus.
Acral lentiginous melanoma can occur on the skin of the Previous existence of a melanoma increases the risk for
nail beds, palms, and soles, which are zones with little ex- the development of a new melanoma 70-fold. People with
posure to sunlight and are protected from ultraviolet (UV) more than 50 common melanocytic nevi have a risk factor
radiation by a thick layer of stratum corneum. Therefore, it threefold higher than the normal population, and people
is highly unlikely for UV radiation to play an important role with more than 100 nevi have a 7.6-fold higher risk for de-
in the pathogenesis of acral lentiginous melanoma2. veloping melanoma.
9 C.P. Camacho-Limas, et al.
Congenital melanocytic giant nevi have a risk for ma- of melanoma. Most initial changes include the presence of
lignant transformation of 6-8%, and generally develop into coloration changes, itching, size enlargement, and satellite
melanoma before the patient is 10 years of age. development. In more evolved lesions, the appearance of
Congenital melanocytic nevi do not appear to confer an hemorrhage and/or ulceration can be observed5,6.
increased risk. In addition to clinical examination, the performance of
Atypical melanocytic nevi are a risk marker for the devel- dermatoscopy either by means of magnifying devices or
opment of melanoma. In these cases, the risk for melanoma by computerized digital analysis of pigmented lesions, has
ranges from twofold to 28-fold, depending on the number increased the sensitivity in the diagnosis of melanoma-sus-
of nevi. pected lesions7,8. (Clinical Stage, Table 1)9.
Genetic factors
MOLECULAR FACTORS AND SERUM MARKER
When there is a family history of melanoma, there is always
an up to 12-fold higher risk. Currently, two susceptibility Clinicopathological factors are currently the basis of clinical
genes for melanoma are known: the CDKN2A gene (p16), lo- care. In spite of the numerous previously described factors
cated at chromosome 9, and CDK4, located at chromosome for identification, there is still broad survival heterogeneity
14. Twenty percent of the families with melanoma have mu- within clinical stages.
tations in CDKN2A. The development of familial melanoma Several gene mutations have been associated with prog-
associated with these mutations probably represents less nosis, including ERBB3, AKT, MITF, PTEN, BCL2, and NCOA3;
than 1% of melanoma cases3. however, their prognostic value has not been clarified.
Sunlight and demographic situation
Table 1 Melanoma staging system
There is a direct relationship between sun exposure and the Clinical staging T N M
incidence of melanoma and this is why it is more common
0 Tis N0 M0
in zones near the equator. However, to consider the sun-
light-melanoma relationship, the patient must have expe- IA T1a N0 M0
rienced three or more sunburns, with blistering, before 20 IB T1b N0 M0
years of age. T2a N0 M0
There is also no doubt that UV radiation is a risk factor IIA T2b N0 M0
for nevi and melanoma. All wavelengths involve danger, but T3a N0 M0
especially those between 290-320 nm. IIB T3b N0 M0
Indoor tanning-users receive double the irradiation than
T4a N0 M0
those who expose themselves to sunlight on the beach at
CII T4b N0 M0
noon and in summer. There is also higher prevalence among
III Any T N > N0 M0
those people with intermittent and intense sun exposure.
IV Any T Any N M1
Immunosuppression Pathologic classification
0 Tis N0 M0
There is higher risk for the development melanoma in pa- IA T1a N0 M0
tients with leukemia, lymphomas, organ transplantation,
IB T1b N0 M0
HIV infection, or any other pathological or drug-induced im-
T2a N0 M0
munosuppression condition4.
IIA T2b N0 M0
T3a N0 M0
IIB T3b N0 M0
DIAGNOSIS
T4a N0 M0
IIC T4b N0 M0
A melanoma clinical diagnosis is based on the recognition of
IIIA T1-4a N1a M0
the melanoma forms’ clinical features, i.e. recognizing and
identifying the transformation of a preexisting nevus by its T1-4a N2a M0
asymmetric growth, imprecise borders, and variegated col- IIIB T1-4b N1a M0
oration with black areas and less pigmented and bluish areas T1-4b N2a M0
representing areas of regression. T1-4a N1b M0
The following features are considered signs for suspicion T1-4a N2b M0
in a pigmented lesion; (i) asymmetry; (ii) imprecise borders; T1-4a N2c M0
(iii) changing color; (iv) diameter larger than 6 mm; (v) pap- IIIC T1-4b N1b M0
ular elevations on the nevus surface; (vi) family history; (vii)
T1-4b N2b M0
different thickness on different zones of the nevus; (viii)
T1-4b N2c M0
presence of hemorrhage.
Any T N3 M0
When there are previously existing nevi, the detec-
IV Any T Any N M1
tion of changes in them should also alert to the presence