[Melanoma : the patient's care pathway. From diagnosis to therapy]. / Le mélanome : le trajet de soins du patient. Le mélanome : le trajet de soins du patient Du diagnostic au traitement Du diagnostic au traitement.

The management of melanoma is a typical example of a pluridisciplinary approach, in order to provide the patient with a rapid and adequate treatment plan after the initial diagnosis. Both in the domains of dermatology, pathology and oncology, enormous progress has been made. Recent advances permit a rapid access to diagnostic techniques using teledermoscopy, an improved diagnostic accuracy using dermoscopy, pre-interventional high-frequency ultrasound and optical coherence tomography, a determination of risk factors using immunohistochemistry and genetic analyses on the pathology samples. Furthermore, the development of immunotherapies, in particular the anti-PD1 antibodies, and the directed therapies, therapies permitting an increased number of patients to experience an increased survival with an acceptable tolerance profile in the event of metastatic lesions. This article describes the patient's care pathway, from the initial diagnosis, staging, to an eventual treatment and follow-up.

Le traitement du mélanome est un exemple type de collaboration multidisciplinaire, afin de pouvoir garantir au patient une prise en charge rapide dès le moment de la détection de la lésion. Tant au niveau dermatologique, anatomopathologique et oncologique, d'énormes progrès ont eu lieu ces dernières années. Ils permettent un accès au diagnostic de plus en rapide par la télédermoscopie, une précision diagnostique accrue par la dermoscopie, l'ultrason à haute fréquence et la tomographie par cohérence optique, une détermination des facteurs de risque immunohistochimiques et génétiques sur les analyses anatomo-pathologiques ainsi que le recours à des immunothérapies, notamment les anti-PD1, et à des traitements ciblés. Ces nouveaux traitements permettent souvent une plus longue survie du patient, avec un profil de tolérance acceptable en cas de lésions métastatiques. Cet article reprend le trajet de soins du patient, du diagnostic initial et du staging au traitement éventuel avec son suivi.

[Erdheim-Chester disease : a case report]. / Cas clinique. Maladie d'Erdheim-Chester.

We report the case of a 47-year-old woman with unexplained inflammatory syndrome and asthenia. Imaging findings show bilateral abnormalities of femurs and tibias, suggesting an Erdheim-Chester disease, which is confirmed by a bone marrow biopsy of the left femur. The BRAF V600E mutation is detected, allowing the administration of targeted therapies such as BRAF and MEK inhibitors that lead to the improvement of symptoms.

Nous rapportons le cas d'une patiente de 47 ans explorée pour un syndrome inflammatoire inexpliqué et une asthénie chronique. Les examens en imagerie démontrent la présence d'importants remaniements osseux au niveau du périoste des deux fémurs et tibias, évoquant une maladie d'Erdheim-Chester. Celle-ci est confirmée par l'analyse d'une biopsie ostéomédullaire réalisée au niveau du fémur gauche. La détection de la mutation V600E du gène BRAF permet à la patiente de bénéficier d'un traitement ciblé anti-BRAF et anti-MEK, améliorant sa symptomatologie.

[Locally advanced and metastatic cutaneous squamous cell carcinoma treated with cemiplimab]. / Carcinome spinocellulaire cutané localement avancé et métastatique traité par cémiplimab.

The treatment of locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) essentially relies on surgery and eventually radiotherapy of the treated site and afferent lymph nodes. Unfortunately, some cases are no candidates for surgery or radiotherapy and a systemic treatment may be indicated. Chemotherapies are only partially efficacious and associated with potential toxicities. A recent study evaluating the efficacy and tolerance of cemiplimab, a PD1 antagonist for locally advanced and metastatic cSCC demonstrated an objective response rate of 49 % and 47 % for locally advanced and metastatic cSCC, while maintaining a response of at least 6 months of 63 % and 60 %, respectively. We present a clinical case of a patient with a locally advanced cSCC of the forehead with bone resorption and cervical lymphadenopathies. After failure of multiple surgical interventions and radiotherapies, he responded partially to cemiplimab immunotherapy with a good safety profile.

Le traitement du carcinome spinocellulaire cutané (cSCC) localement avancé et/ou métastatique repose essentiellement sur la chirurgie et, éventuellement, sur une radiothérapie de la zone chirurgicale et de l'aire ganglionnaire afférente. Malheureusement, certains cas ne sont plus opérables ou accessibles à la radiothérapie et un traitement systémique est alors indiqué. Les chimiothérapies sont peu efficaces et potentiellement toxiques. Une étude récente évaluant l'efficacité et la tolérance du cémiplimab, un antagoniste PD1, dans les cSCC localement avancés et métastatiques, démontre une réponse objective confirmée de 49 % et de 47 %, respectivement, avec un maintien de la réponse d'au moins 6 mois de 63 % et de 60 %, respectivement. Nous présentons le cas d'un patient avec un cSCC localement avancé au niveau du front, avec effraction osseuse et adénopathies cervicales, ayant eu de multiples chirurgies et radiothérapies. Il a présenté une réponse partielle au cémiplimab avec un profil de tolérance satisfaisant.

[Could we consider that radiotherapy is effective outside the irradiation area ? The abscopal effect]. / Peut-on considérer que la radiothérapie agit en dehors du site irradié ? L'effet abscopal.

Radiotherapy is known for its action on local tumoral control. However, it is also able to induce immunomodulatory effects at a systemic level. The abscopal effect (from latin ab scopus which means «away from the target¼) is an illustration of this phenomenon. It is defined as a tumor regression observed outside and at a distance of the irradiation fields. The potential application of this effect of treatment in disseminated cancers is a fast-growing field of research. The optimal therapeutic strategy to achieve this effect remains unknown.

La radiothérapie, connue pour son action sur le contrôle tumoral local, est également capable d'induire des effets immuno-modulateurs systémiques. L'effet abscopal (du latin ab scopus qui signifie «à distance de la cible¼) décrit la régression tumorale observée à distance de la zone d'irradiation. L'exploitation thérapeutique de celui-ci comme traitement des cancers disséminés est un domaine de recherche en plein essor. Actuellement, les modalités thérapeutiques optimales visant à obtenir cet effet demeurent inconnues.

[BREAST CANCER: FROM TARGETED THERAPY TO PRECISION MEDICINE]. / CANCER DU SEIN : DE LA THÉRAPIE CIBLÉE À LA MÉDECINE PERSONNALISÉE.

The authors review the principles of systemic therapy in breast cancer. They analyze the degree of treatment individualization in our current approach. New technologies allow the detection of genomic alterations in cancer cells. Unfortunately, we do not know yet how to best use this knowledge for routine patient care. Most genomic alterations are rare events complicating further drug development. Temporal and spatial heterogeneity in tumors also has to be taken into account. An intense international collaboration is ongoing to try and demonstrate that precision medicine will really improve treatment outcome.

[Biopsy of suspicious lesions in patients with breast cancer]. / BIOPSIE DES LÉSIONS SUSPECTES CHEZ LES PATIENTS AYANT PRÉSENTÉ UN CANCER DU SEIN.

Discordances between hormone receptors and HER2 status in primary and metastatic breast cancer have been reported by several studies. In this context, systematic biopsies could be clinically relevant in breast cancer to confirm the biological characteristics of a suspicious lesion. In this article, illustrated by 2 case reports and based on a recent review on this topic, we discuss the clinical significance of receptor discordances and possible diagnosis of a secondary primary tumor. The role of these biopsies for the identification of new therapeutic targets is also envisaged as well as underlying mechanisms for receptors' modification like tumoral heterogeneity, clonal selection and technical artifacts.

[The drug of the month: everolimus (Afinitor) for the treatment of metastatic breast cancer]. / Le médicament du mois: Evérolimus (Afinitor) dans le traitement du cancer du sein métastatique.

Sequential endocrine treatments are recommended for estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER 2) negative metastatic breast cancers except in the case of symptomatic visceral disease. However, patients who suffer from disease progression while receiving a non-steroidal aromatase inhibitor (NSAI) have a very poor prognosis with standard endocrine therapy alone. Recently, based onthe results of the BOLERO 2 trial, the mammalian target of rapamycin (mTOR) inhibitor everolimus, combined with exemestane, a steroidal aromatase inhibitor, has been approved in Europe and the US for patients suffering from ER positive HER2 negative advanced breast cancer previously treated by a NSAI. The median progression-free survival (PFS) increased from 3.2 to 7.8 months in patients receiving everolimus and exemestane compared to placebo and exemestane. The magnitude of benefit was consistent in all pre-specified subgroups. Side effects were manageable and the quality of life was at least maintained. Everolimus has also beenrecently studied in HER2 positive locally advanced or metastatic disease in heavily pretreated patients (BOLERO 3 trial). This trial met its primary endpoint. The median PFS was increased in patients receiving trastuzumab, vinorelbine and everolimus compared to patients receiving trastuzumab, vinorelbine and placebo. We review pharmacological data and side effects of the drug. We also review the most important clinical trials leading to reimbursement of everolimus in metastatic breast cancer.

Ipilimumab induces simultaneous regression of melanocytic naevi and melanoma metastases.

Ipilimumab blocks cytotoxic T-lymphocyte-associated antigen (CTLA)-4, potentiating the antimelanoma T-cell host response. Ipilimumab has been shown to improve overall survival in patients with previously treated metastatic melanoma. CTLA-4 antibodies generate immune responses to the melanoma-associated antigens Melan-A, NY-ESO-1 and glycoprotein (gp)100 in metastatic melanoma. Digital epiluminescence microscopy (DELM) is a noninvasive method permitting the monitoring of the morphology of melanocytic lesions over time. A 50-year-old man with metastatic melanoma received four ipilimumab injections after failure of dacarbazine chemotherapy. Positron emission tomography revealed regression of pulmonary metastases, and simultaneously, DELM showed regression of several melanocytic naevi. On histological examination of the regressing naevi, prominent CD8+, CD4+ and CD45R0 lichenoid lymphohistiocytic infiltrates were seen, whereas nonregressing naevi were almost free of inflammatory infiltrate. Expression of melanoma-associated antigens in benign melanocytic naevi may explain the induction of naevus regression by ipilimumab. DELM could represent a valuable noninvasive method to monitor ipilimumab efficacy.

[Heterogeneity of bone metastases in a patient with breast cancer: case report illustrating the potential of combining various imaging techniques]. / Hétérogénéité des métastases osseuses du cancer du sein: cas clinique illustrant l'intérêt de combiner différentes techniques d'imagerie.

Morphological appearance of bone metastases in breast cancer can be classified into three groups: osteolytic, sclerotic and mixed types. 18F-NaF PET/CT is considered to be superior to bone scintigraphy (BS) for the detection of bone metastases. 18F-NaF PET shows a higher uptake in both lytic and sclerotic bone metastases with a higher contrast and spatial resolution than BS. 18F-FDG PET is generally considered to be superior to BS for detection of lytic bone metastases. However, BS and 18F-NaF PET/CT are more sensitive for sclerotic lesions, as a decreased 18F-FDG uptake in this subtype of lesion has been reported. In conclusion, as various types of bone metastases may coexist in a single patient, the combination of both 18F-FDG and 18F-fluoride PET/CT studies is likely to provide the most comprehensive assessment of metastatic spread to the skeleton.

[Breast cancer and brain metastases]. / Cancer du sein et métastases cérébrales.

The cerebral metastases are frequent in the evolution of breast cancer and convey a poor prognosis. The frequency depends on the histology of the cancer and on the expression of oestrogen and progesterone receptors as well as of HER2 antigen. The treatment is currently based on surgery and the different modalities of radiotherapy used alone or in association. Indeed, chemotherapy agents available for the treatment of breast cancer do not cross the hematoencephalic barrier and are thus ineffective. However, some encouraging results have been recently reported with the therapies targeting HER2.

[Radiotherapy in breast cancer: current standards of treatment, prediction of local recurrence and open questions]. / Radiothérapie et cancer du sein: "standards" de traitement, prédiction de rechute locale et questions ouvertes.

Adjuvant radiotherapy after surgery is a ("well-established standard" in routine clinical practice for breast cancer. Nevertheless, a variety of questions still remain unanswered. We intend to illustrate the overall importance of radiotherapy in breast cancer and highlight some unresolved questions by quoting presentations recently made at ASTRO-2010. More and more emphasis is put on the idea of an individual approach. Predicting the individual local recurrence risk is the search for the "Holy Grail". Methods such as nomograms and genomic profiling are currently tested but need to be validated before their widespread clinical application.

[Systemic chemotherapy and breast cancer]. / Chimiothérapie et cancer du sein.

Breast cancer mortality is decreasing, partly due to better adjuvant treatments with new drugs and new schedules. In Belgium, the overall survival is 76%. Chemotherapy is still an important treatment option. We need to better select patients who really will benefit from treatment in order to decrease toxicity and improve long term outcome.Targeting the specific population is now a priority. Prognostic and predictive factors will enable us to better define the sub-population of patients most benefiting from treatment. We will also discuss the knowledge of systemic treatment. When we have to decide wether chemotherapy is indicated, we need to well balance the treatment risks and benefits because gain in survival is important but reducing short and long term toxicity is also a challenge.

[Targeted therapies in breast cancer]. / Traitements ciblés dans le cancer du sein.

The better understanding of the biology of breast cancer has allowed the identification of new targets for anticancer therapy. Trastuzumab, a monoclonal antibody binding the HER2 receptor, is used since several years in the treatment of HER2 overexpressing breast cancer, including in the adjuvant setting. Lapatinib, a tyrosine kinase inhibitor, was introduced more recently into the clinic. New treatment options under evaluation in HER2 overexpressing breast cancer include combinations of anti-HER2 treatments, drugs targeting the downstream signaling pathway and new anti-HER2 agents such as pertuzumab and T-DM1. This article also reviews other targeted treatments of interest in the field of breast cancer including antiangiogenic agents and drugs targeting the PI3K-AKT-mTOR pathway.

[Breast cancer in young women]. / Le cancer du sein chez la femme jeune.

The outcome of very young patients with early breast cancer is worser compared to older patients with a similar clinical presentation. The triple negative, luminal B, HER2+ subtypes are more frequent in this population. Adequate local treatment (breast-conserving surgery or total mastectomy) must be discussed with the patient. The role of radiotherapy is very important in these patients with high risk of local recurrence. The progress in adjuvant treatment of very young patients requires studies of tailored treatments.

[Hormone therapy for breast cancer]. / Hormonothérapie du cancer du sein.

Following Beatson's publications in 1896, various modalities of endocrine therapy applied to breast cancer have been developed. Endocrine treatment has greatly contributed to the improvement of the disease's prognosis. Tamoxifen has established itself as a first choice adjuvant therapy for patients with tumors expressing hormone receptors. Over the last decade, third generation aromatase inhibitors have demonstrated their efficacy amongst menopausal patients, alone or in combination with tamoxifen. Efficacy of these medications is dependent on patient's compliance. This article proposes a synthesis of the main knowledges available in the field of breast cancer endocrine therapy.

[Breast cancer in the elderly patient]. / Le cancer du sein de la femme âgée.

There is no standard of care for breast cancer treatment in the elderly patient. Given the heterogeneity of this population, the treatment of both localized and metastatic disease, requires to take into account not only the characteristics of this cancer but also factors related to the patient such as co-morbidities, life expectancy and the social environment.

[Adherence to long-term medication: the particular case of the adjuvant endocrine therapy for breast cancer]. / L'observance au traitement de longue durée: le cas particulier de l'hormonothérapie adjuvante du cancer du sein.

The aim of adjuvant hormone therapy for breast cancer is to reach, in daily practice, an efficacy similar to that obtained in clinical trials. In spite of the demonstrated efficacy of hormone therapy, compliance represents a major challenge and a multidimensional problem. A better understanding of the reasons underlying non-compliance would help identify the patients at higher risk and would permit the implementation of strategies to improve compliance to adjuvant hormone therapy. With this in mind, we undertook a review of the recent literature on the topic (Pub Med 2003-2009).

["Triple negative" breast cancer]. / Le cancer du sein "triple négatif".

In western countries, every woman out of eight will develop breast cancer. Over the last two decades, the incidence has considerably increased, but mortality has remained stable and begins to decrease in Europe and the United-States, probably because of new therapy, changes in the use of hormone replacement therapy in postmenopausal women and early diagnosis. Breast cancer is still the first cause of death by cancer in woman under 65. "Triple negative" a breast cancer, a subtype representing 10% of all breast cancers, is characterised by the absence of receptors to oestrogen, progesterone and no histochemical expression of HER-2 growth factor. This subtype carries a poor prognosis and a high incidence of early metastatic recurrence. Furthermore, no target therapy can be defined up to now in this subtype. Thus, identification of new target therapy and prediction of tumoral response to various treatments could help in the global understanding of patients affected by this particularly aggressive type of breast cancer.

[Hypofractionated postoperative radiotherapy for breast cancer]. / Pourquoi les traitements de radiothérapie adjuvante pour cancer du sein ne comptent-ils plus autant de séances?

Postoperative adjuvant radiotherapy for breast cancer is usually applied in twenty five fractions of 2 Gy on the whole breast followed by a boost dose on the initial tumour site. Facing a continuous rise of the workload in radiotherapy departments, investigators have tried to reduce the burden of such a treatment approach both for the patients and the departments as available resources are not unlimited. These hypo-fractionated treatment schedules have been tested and validated in randomized controlled trials. Based on this evidence a new treatment algorithm has been built up as it has been shown that those schedules do provide similar levels of local control with comparable or an even lower risk of toxicity.

[Therapeutic monoclonal antibodies in hemato-oncology]. / Anticorps monoclonaux à usage thérapeutique en hémato-oncologie. Généralités.

For many years, chemotherapy, hormonotherapy and immunotherapy were the mainstay of cancer treatment. Recent advances in our knowledge of cell biology and particularly of cancer cell transformation, growth and metastasis have led to the identification of specific pathways playing a role in the pathophysiology of cancer. New drugs specifically developed to control these targets are collectively named "targeted therapies". Two types of targeted therapies are available: kinase (mainly tyrosine kinase) inhibitors (suffix -nib) are small molecules binding directly to the intracellular kinase domain and acting as competitive inhibitor of ATP binding and monoclonal antibodies (suffix -mab) directed towards specific cell surface receptors or their ligands to prevent receptor activation. This paper will only review monoclonal antibodies (mabs). Thirty years after their discovery mAbs have become efficient therapeutic tools. Progress in molecular engineering as well as improved knowledge of cell signalling pathways together with a better selection of the targets turned them into valuable treatments. Several mAbs are currently licensed for the treatment of hematological or solid malignancies and many others are expected in the near future.