Cancer Institute Gustave Roussy

Le Touquet – Paris-Plage, France

Cancer Institute Gustave Roussy

Le Touquet – Paris-Plage, France

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Balch C.M.,University of Texas Southwestern Medical Center | Soong S.-J.,University of Alabama at Birmingham | Gershenwald J.E.,The Surgical Center | Thompson J.F.,Melanoma Institute Australia | And 14 more authors.
Annals of Surgical Oncology | Year: 2013

Background: We postulated that the worse prognosis of melanoma with advancing age reflected more aggressive tumor biology and that in younger patients the prognosis would be more favorable. Materials and Methods: The expanded AJCC melanoma staging database contained 11,088 patients with complete data for analysis, including mitotic rate. Results: With increasing age by decade, primary melanomas were thicker, exhibited higher mitotic rates, and were more likely to be ulcerated. In a multivariate analysis of patients with localized melanoma, thickness and ulceration were highly significant predictors of outcome at all decades of life (except for patients younger than 20 years). Mitotic rate was significantly predictive in all age groups except patients <20 and >80 years. For patients with stage III melanoma, there were four independent variables associated with patient survival: number of nodal metastases, patient age, ulceration, and mitotic rate. Patients younger than 20 years of age had primary tumors with slightly more aggressive features, a higher incidence of sentinel lymph node metastasis, but, paradoxically, more favorable survival than all other age groups. In contrast, patients >70 years old had primary melanomas with the most aggressive prognostic features, were more likely to be head and neck primaries, and were associated with a higher mortality rate than the other age groups. Surprisingly, however, these patients had a lower rate of sentinel lymph node metastasis per T stage. Among patients between the two age extremes, clinicopathologic features and survival tended to be more homogeneous. Conclusions: Melanomas in patients at the extremes of age have a distinct natural history. © 2013 Society of Surgical Oncology.


PubMed | Netherlands Cancer Institute, Italian National Cancer Institute, St George's, University of London, University of Groningen and 4 more.
Type: Journal Article | Journal: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology | Year: 2016

Worldwide, sentinel node biopsy (SNB) is the recommended staging procedure for stage I/II melanoma. Most melanoma guidelines recommend re-excision plus SNB as soon as possible after primary excision. To date, there is no evidence to support this timeframe.To determine melanoma specific survival (MSS) for time intervals between excisional biopsy and SNB in SNB positive patients.Between 1993 and 2008, 1080 patients were diagnosed with a positive SNB in nine Melanoma Group centers. We selected 1015 patients (94%) with known excisional biopsy date. Time interval was calculated from primary excision until SNB. Kaplan-Meier estimated MSS was calculated for different cutoff values. Multivariable analysis was performed to correct for known prognostic factors.Median age was 51 years (Inter Quartile Range (IQR) 40-62 years), 535 (53%) were men, 603 (59%) primary tumors were located on extremities. Median Breslow thickness was 3.00mm (IQR 1.90-4.80mm), 442 (44%) were ulcerated. Median follow-up was 36 months (IQR 20-62 months). Median time interval was 47 days (IQR 32-63 days). Median Breslow thickness was equal for both <47 days and 47 days interval: 3.00mm (1.90-5.00mm) vs 3.00mm (1.90-4.43mm) (p=0.402). Sentinel node tumor burden was significantly higher in patients operated 47 days (p=0.005). Univariate survival was not significantly different for median time interval. Multivariable analysis confirmed that time interval was no independent prognostic factor for MSS.Time interval from primary melanoma excision until SNB was no prognostic factor for MSS in this SNB positive cohort. This information can be used to counsel patients.


Daud A.,University of California at San Francisco | Soon C.,University of California at San Francisco | Dummer R.,University of Zürich | Eggermont A.M.,Cancer Institute Gustave Roussy | And 4 more authors.
Expert Opinion on Biological Therapy | Year: 2012

Introduction: Both native IFNα2b and pegylated IFNα2b (PegIFNα2b) are approved for the adjuvant treatment of high-risk melanoma. Areas covered: This review compares the toxicity profiles of high-dose IFNα2b (HDI) and PegIFNα2b, and provides recommendations on the management of common PegIFNα2b-related toxicities, based on available clinical data and published literature. Expert opinion: The toxicity profile of PegIFNα2b at the approved dose (6 μg/kg/week for 8 weeks then 3 μg/kg/week for up to 5 years) is qualitatively similar to HDI in melanoma. The most common adverse events (AEs) are fatigue, anorexia, hepatotoxicity, flu-like symptoms, injection site reactions and depression. However, fatigue and flu-like symptoms appear less severe with PegIFNα2b, and toxicity seems to occur earlier, whereas with HDI toxicity may increase with time. Most AEs can be managed effectively by dose modification and aggressive symptom control. Dosing to tolerance using a three-step dose reduction schedule to maintain an ECOG performance status of 0 - 1 may enable patients experiencing toxicity to remain on treatment; this can be applied readily in clinical practice. PegIFNα2b is therefore a valuable alternative option for adjuvant treatment in melanoma, with a toxicity profile similar to that of HDI overall but a more convenient administration schedule. © 2012 Informa UK, Ltd.


Lacouture M.E.,Sloan Kettering Cancer Center | Duvic M.,University of Texas M. D. Anderson Cancer Center | Hauschild A.,University of Kiel | Prieto V.G.,University of Texas M. D. Anderson Cancer Center | And 15 more authors.
Oncologist | Year: 2013

Background. Vemurafenib has been approved for the treatment of patients with advanced BRAFV600E-mutant melanoma. This report by the Vemurafenib Dermatology Working Group presents the characteristics of dermatologic adverse events (AEs) that occur in vemurafenib-treated patients, including cutaneous squamous cell carcinoma (cuSCC). Methods. Dermatologic AEs were assessed from three ongoing trials of BRAFV600E mutation-positive advanced melanoma. Histologic central review and genetic characterization were completed for a subset of cuSCC lesions. Results. A total of 520 patients received vemurafenib. The most commonly reported AEs were dermatologic AEs, occurring in 92%-95% of patients. Rash was the most common AE (64%-75% of patients), and the most common types were rash not otherwise specified, erythema, maculopapular rash, and folliculitis. Rash development did not appear to correlate with tumor response. Photosensitivity occurred in 35%-63% of patients, and palmar-plantar erythrodysesthesia (PPE) occurred in 8%-10% of patients. The severity of rash, photosensitivity, and PPE were mainly grade 1 or 2. In all, 19%-26% of patients developed cuSCC, mostly keratoacanthomas (KAs). The majority of patients with cuSCC continued therapy with outdoser eduction after resection.Genetic analysisof 29 cuSCC/ KA samples demonstrated HRAS mutations in 41%. Conclusions. Dermatologic AEs associated with vemurafenib treatment in patients with melanoma were generally manageable with supportive care measures. Dose interruptions and/or reductions were required in <10% of patients. © AlphaMed Press 2013.


Testori A.,Italian National Cancer Institute | Verhoef C.,Erasmus University Rotterdam | Kroon H.M.,Rijnland Hospital | Pennacchioli E.,Italian National Cancer Institute | And 4 more authors.
Journal of Surgical Oncology | Year: 2011

In-transit melanoma metastases are often confined to a limb. In this circumstance, treatment by isolated limb perfusion or isolated limb infusion can be a remarkably effective regional treatment option. Copyright © 2011 Wiley-Liss, Inc.


Voit C.A.,Charité - Medical University of Berlin | Van Akkooi A.C.J.,Erasmus Medical Center | Eggermont A.M.M.,Cancer Institute Gustave Roussy | Schafer-Hesterberg G.,Charité - Medical University of Berlin | And 5 more authors.
Journal of the National Cancer Institute | Year: 2011

Background Fine needle aspiration cytology (FNAC) is usually used to evaluate palpable nodes in patients with melanoma. The goal of our study is to review the sensitivity and specificity of this technique when applied to palpable but also to nonpalpable nodes. Methods FNAC was performed during 1984-2007 in 1279 patients with suspicious lesions and/or lymph nodes. Indications for biopsy included increased size and/or palpability of nodes or abnormal ultrasound findings such as increased perfusion or focal lesions within the lymph nodes. The sensitivity, specificity, and positive and negative predictive values of FNACs guided by palpation or ultrasound were calculated for all patients and for subgroups of patients with palpable nodes or nonpalpable but sonomorphologically suspicious nodes. Results A total of 2446 FNACs were performed in 1279 melanoma patients, of which 2011 (82.2%) FNACs had clinically or histologically confirmed results. Increased size and/or palpability of nodes was observed in 376 (29.4%) of 1279 patients, and abnormal ultrasound findings occurred for 903 (70.6%), indicating that a biopsy was needed. FNACs guided by palpation had sensitivity, specificity, and positive and negative predictive values similar to that of FNACs guided by ultrasound (sensitivity = 98.4% vs 97.2%, specificity = 100% vs 99.8%, positive predictive value = 100% vs 99.9%, and negative predictive value = 95.2% vs 96.4%, for palpation-guided FNACs vs ultrasound-guided FNACs, respectively). Results did not differ between patients with the palpable nodes and patients with nonpalpable but sonomorphologically suspicious nodes. Conclusions Ultrasound-guided FNAC of suspicious lymph nodes and lesions in melanoma patients has a high sensitivity and specificity, and FNAC should not be limited to palpable nodes. FNAC of normal-sized nodes and/or lymph nodes with abnormal ultrasound findings can be used to identify early metastatic disease. © 2011 The Author.


Balch C.M.,University of Texas Southwestern Medical Center | Thompson J.F.,Melanoma Institute Australia | Gershenwald J.E.,The Surgical Center | Soong S.-J.,University of Alabama at Birmingham | And 16 more authors.
Annals of Surgical Oncology | Year: 2014

Purpose. We have previously reported that older patients with clinical stage I and II primary cutaneous. Melanoma had lower survival rates compared to younger patients. We postulated that the incidence of nodal metastasis would therefore be higher among older melanoma patients. Methods. The expanded American Joint Committee on Cancer melanoma staging database contains a cohort of 7,756 melanoma patients who presented without clinical evidence of regional lymph node or distant metastasis and who underwent a sentinel node biopsy procedure as a component of their staging assessment. Results. Although older patients had primary melanoma features associated with more aggressive biology, we paradoxically observed a significant decrease in the incidence of sentinel node metastasis as patient age increased. Overall, the highest incidence of sentinel node metastasis was 25.8 % in patients under 20 years of age, compared to 15.5 % in patients 80 years and older (p < 0.001). In contrast, 5-year mortality rates for clinical stage II patients ranged from a low of 20 % for those 20-40 years of age up to 38 % for those over 70 years of age. Patient age was an independent predictor of sentinel node metastasis in a multifactorial analysis (p < 0.001). Conclusions. Patients with clinical stage I and II melanoma under 20 years of age had a higher incidence of sentinel lymph node metastasis but, paradoxically, a more favorable survival outcome compared to all other age groups. In contrast, patients >70 years had the most aggressive primary melanoma features and a higher mortality rate compared to all other age groups but a lower incidence of sentinel lymph node metastasis. © 2014 Society of Surgical Oncology.


Autier P.,International Prevention Research Institute IPRI | Dore J.-F.,French Institute of Health and Medical Research | Eggermont A.M.M.,Cancer Institute Gustave Roussy | Coebergh J.W.,Erasmus University Rotterdam | Coebergh J.W.,Comprehensive Cancer Center South
Current Opinion in Oncology | Year: 2011

Purpose of review: Epidemiological data have contributed to the classification in 2009 of the full ultraviolet (UV) radiation spectrum as carcinogenic to humans. We reviewed the epidemiological evidence that UVA could be involved in the genesis of cutaneous melanoma. Recent findings: Use of artificial UV tanning devices (sunbeds) consists mainly of repeated exposure to high UVA doses. Epidemiological studies published over the last years confirmed the association between sunbed use and melanoma. Sunbed use is the most probable cause of an epidemic of melanoma that took place in Iceland from 1990 to 2006. The four-fold increase in melanoma incidence was not followed by an increase in melanoma mortality. Sunscreens were primarily devised for the prevention of sunburn, and UVB is the wavelength causing most sunburns. All observational studies and randomized trials show that sunscreen use may extend sun exposure intended for getting a tan, while it does not necessarily decrease sunburn occurrence. Sunscreen use for tan acquisition would thus lead to similar exposure to UVB and greater exposure to UVA, which could explain the slightly higher melanoma risk often found among sunscreen users. Summary: UVA could be involved in the occurrence of nonlife-threatening melanoma. The increasing use of sunbeds and of sunscreens may partly explain why melanoma incidence increases in most light-skinned populations without concomitant increase in mortality. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Zdzienicki M.,Center of Oncology of Poland | Rutkowski P.,Center of Oncology of Poland | Nowecki Z.I.,Center of Oncology of Poland | Van Akkooi A.C.J.,Erasmus Medical Center | And 7 more authors.
European Journal of Surgical Oncology | Year: 2013

Background: We assessed clinical-pathological features and outcomes of cutaneous melanoma patients after ilio-inguinal lymph node dissection (LND) in relation to the presence of metastases in iliac-obturator nodes. Methods: We analyzed 390 consecutive patients who underwent ilio-inguinal therapeutic LND [TLND] (237) due to clinical/cytologically detected metastases or after completion LND [CLND] (153) due to positive SLN biopsy (in one cancer centre 1994-2009). Median follow-up time was 60 months. Results: The 5-year overall survival (OS) rate was 49% and median OS-52 months in the entire group of patients. According to univariate analysis following factors had significant negative influence on OS: presence of metastases to iliac-obturator nodes (5-year OS for positive versus negative: 54.5% and 32%, respectively), macrometastases, higher Breslow thickness, ulceration, higher Clark level, male gender, number of metastatic lymph nodes, extracapsular extension, and, additionally in the CLND group-micrometastases size ≥0.1 mm according to the Rotterdam criteria and non-subcapsular location of micrometastases. Iliac-obturator involvement was also negative factor for OS in multivariate analysis. The presence of iliac-obturator nodal metastases correlated with the following factors: type of LND-CLND versus TLND (15% versus 27.5%) of iliac-obturator involvement, respectively), higher Breslow thickness, extracapsular extension of nodal metastases, male gender. We have not identified any metastases in iliac-obturator nodes in group of patients with micrometastases size ≤1.0 mm and primary tumour Breslow thickness <4.0 mm or no ulcerated primary tumours. Conclusions: Metastases to iliac-obturator nodes have additional negative prognostic value for melanoma patients with inguinal basin involvement. We are able to identify the subgroup of patients after positive SLN biopsy without metastases to iliac-obturator nodes, probably requiring only inguinal LND. © 2012 Published by Elsevier Ltd.


Eggermont A.M.M.,Cancer Institute Gustave Roussy
Annals of Oncology | Year: 2012

Increased understanding of cellular and molecular tumour immunology over the past two decades has enabled the identification of new and innovative ways to manipulate the immune response to cancer, with recent phase III trials in patients with metastatic melanoma and hormone-resistant prostate cancer providing proof-of-principle that immunotherapies can improve survival. Based on these successes, many new immunotherapies are being developed, including vaccines and other agents that prime or boost the immune system, T-cell modulatory agents, agents that enhance innate immunity and agents designed to inhibit immunosuppression within the tumour microenvironment. Current experience suggests that immunotherapies are a promising foundation to build treatment regimens for a variety of tumour types. Because many approaches target the immune system and not the cancer, immunotherapies are being evaluated in almost every tumour type, including those that were not previously considered likely to respond to immune manipulation. Immunotherapies also have potential for durable and adaptable cancer control at different stages of disease, including those with early-stage disease and low tumour burdens. To maximise benefits, however, it is likely that combination regimens with conventional cancer treatments or other immunotherapies will be necessary. In addition, the identification of biomarkers will allow further optimisation from a mechanistic and a patient selection perspective. Further advances in research will necessitate multidisciplinary collaboration among physicians, basic and translational researchers and the pharmaceutical industry to ensure that immuno-oncology becomes a cornerstone element in the development of cancer therapy. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

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