Melanoma: Grob JJ

Saiag P, Bosquet L, Guillot B, Verola O, Avril MF, Bailly C, Cupissol D, Dalac S, Danino A, Dréno B, Grob JJ, Leccia MT, Renaud-Vilmer C, Négrier S, Anonymous00110. · Hôpital Ambroise Paré, 92104 Boulogne, Université Versailles-Saint Quentin, France. · Eur J Dermatol. · Pubmed #17540641 links to  free full text

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Négrier S, Saiag P, Guillot B, Verola O, Avril MF, Bailly C, Cupissol D, Dalac S, Danino A, Dreno B, Grob JJ, Leccia MT, Renaud-Vilmer C, Bosquet L, Anonymous00209, Anonymous00210, Anonymous00211, Anonymous00212, Anonymous00213, Anonymous00214, Anonymous00215, Anonymous00216. · Centre Léon-Bérard, Lyon. · Bull Cancer. · Pubmed #16714227 links to  free full text

Abstract: CONTEXT: The National French federation of comprehensive cancer centres (FNCLCC) and the French society of dermatology (SFD) initiated together the update of clinical practice guideline for the management of patients with cutaneous melanoma in collaboration with the French national cancer institute and with specialists from French public universities, general hospitals and private clinics. This work is based on the methodology developed in the "Standards, Options and Recommendations" (SOR) project. OBJECTIVES: To update SOR guidelines for the management of patients with cutaneous melanoma previously validated in 1998 and French melanoma consensus conference published by SFD and ANAES in 1995. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers. RESULTS: This article is a summary version of the updated clinical practice guidelines with algorithms. The main questions addressed by the expert group in this update concerned (1) The new AJCC-UICC classification (2) Excision margins (3) Sentinel node biopsy (4) Adjuvant treatments (5) Initial staging and follow up of operated patients.

Négrier S, Saiag P, Guillot B, Verola O, Avril MF, Bailly C, Cupissol D, Dalac S, Danino A, Dreno B, Grob JJ, Leccia MT, Renaud-Vilmer C, Bosquet L, Anonymous00273, Anonymous00274. · Centre Léon-Bérard, Lyon. · Ann Dermatol Venereol. · Pubmed #16521904 No free full text.

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Grob JJ. · No affiliation provided · Ann Dermatol Venereol. · Pubmed #19084689 No free full text.

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Grob JJ. · No affiliation provided · Ann Dermatol Venereol. · Pubmed #10495857 No free full text.

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Grob JJ. · No affiliation provided · Arch Dermatol. · Pubmed #10086455 No free full text.

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Lavie A, Desouches C, Casanova D, Bardot J, Grob JJ, Legré R, Magalon G. · Service de chirurgie plastique et réparatrice, hôpital de La Conception, 147, boulevard baille, 13385 Marseille cedex 05, France. · Ann Chir Plast Esthet. · Pubmed #17030081 No free full text.

Abstract: Nowadays managing a cutaneous malignant melanoma can concern different kind of physicians: dermatologists, general or plastic surgeons The primary surgical procedure is a major step of the treatment. Biopsy must be total to properly determine the thickness of the tumor in case of malignancy. Wide local excision of the scar is often necessary to decrease the local and general recurrence rates. Wide local excision must be performed conforming to its own surgical rules. Managing tumor located on the face or limb extremities is a matter of plastic surgery. Sentinel node biopsy has succeeded to elective lymph node dissection. This procedure allows research of lymphatic spreading of the disease. Practice of sentinel node biopsy must be achieved in a protocolar way. Topography of the lesion can modified achievement and results of this procedure. Prognosis benefit of sentinel biopsy is now clear. Elective lymph node dissection is only performed in case of invaded sentinel node or clinically invaded lymph nodes. Local or locoregional recurrences mainly respond to surgical treatment using wide excision. However, alternative solutions are being evaluated (isolated limb perfusion).

Grob JJ, Richard MA. · Hôpital Sainte-Marguerite, service de dermato-vénérologie, 13274 Marseille 09. · Rev Prat. · Pubmed #15496024 No free full text.

Abstract: Melanoma incidence and mortality are still increasing, but new leveling-off and even decreasing trends are detected in young women generations in a few countries, where intensive prevention and screening campaigns have been conducted. Sun avoidance remains the basis of prevention, but is facing hard societal resistances. Sunscreens have a more and more theoretical protective profile, but in the real life, their ability to prevent skin cancers is quite uncertain. Some pieces of the melanoma genetic puzzle have been identified, but are not yet useful for the practical identification of patients at high risk for melanoma. Early detection is still the key for improving melanoma mortality. The most useful signs for melanoma detection are the impression of overall irregularity as compared to common nevi, the "ugly duckling sign" and a recent change. However, a subgroup of biologically aggressive melanoma will probably remain out of reach of early detection, due to their very rapid growth. In order to promote self-detection in the general population, a cognitive strategy using photographs is probably more efficacious than teaching the classical "ABCD" algorithm.

Lafuma A, Grob JJ. · CEMKA EVAL, 43, Boulevard du Maréchal Joffre, 92340 Bourg la Reine, France. · Expert Opin Pharmacother. · Pubmed #12614186 No free full text.

Abstract: An extensive literature review on clinical trials and economic studies published on the use of IFN-alpha as adjuvant therapy in stage II - III (AJCC 1992) malignant melanoma was performed. Large clinical trials with sufficient follow-up were selected to assess the efficacy. Medico-economic studies, based on the results of several of these trials, were analysed to estimate the cost-effectiveness ratios of IFN in this disease. IFN-alpha demonstrated efficacy as adjuvant therapy in malignant melanoma with high-dose regimens in patients with overt regional nodal disease (so-called high-risk patients) and with low-dose regimens in stage IIA and -B patients without clinically detectable nodes (so-called intermediate risk patients). This efficacy was associated with high rates of severe side effects using a high-dose regimen. Based on these assumptions, economic analyses performed in different settings and using several methods to extrapolate clinical results are producing similar results of extra costs for IFN associated with a medical benefit. Incremental cost-effectiveness ratios provided are (< US dollars 50,000 per life year gained) in the range of current and widely used medical strategies in different diseases and settings. This should allow the recommendation of the use of IFN-alpha therapy in malignant melanoma, using high doses in high-risk patients and low doses in intermediate-risk patients. In the final decision of whether or not to treat, however, the patient has to be informed that IFN will probably only delay events, with the possibility of any curative effect being uncertain. This limited effect has to be balanced with the severe impact on quality of life of high-dose regimen and with the fact that many patients in whom low doses are indicated would not recur in the absence of treatment. It is also clear that patients with only a positive sentinel node are to be considered with the intermediate risk group in which they were evaluated.

Grob JJ, Richard MA. · Service de dermatologie Hôpital Sainte-Marguerite, Marseille. · Rev Prat. · Pubmed #10337196 No free full text.

Abstract: Skin cancer should be the ideal cancer for prevention. The environmental risk factors subject to modification by primary prevention are known for melanoma and cutaneous carcinoma. Some precursors have been identified, opening the possibility of secondary prevention. In addition, skin cancers are easily visualised, facilitating diagnosis.

Dummer R, Hauschild A, Becker JC, Grob JJ, Schadendorf D, Tebbs V, Skalsky J, Kaehler KC, Moosbauer S, Clark R, Meng TC, Urosevic M. · Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. · Clin Cancer Res. · Pubmed #18245549 links to  free full text

Abstract: PURPOSE: A topical Toll-like receptor 7 (TLR7) agonist induces regression of cutaneous melanocytic neoplasms. We explored antitumor activity of a systemically administered TLR7 agonist, 852A, in patients with metastatic melanoma. EXPERIMENTAL DESIGN: We undertook a phase II, multicenter, open-label study in patients with chemotherapy-refractory metastatic melanoma. Patients received i.v. 852A, starting at 0.6 mg/m(2) and increasing to 0.9 mg/m(2) based on tolerance, thrice per week for 12 weeks. Clinical response was determined by Response Evaluation Criteria in Solid Tumors. Immune effects of 852A were monitored by measuring serum type I IFN and IP-10 together with assessment of immune cell markers in peripheral blood. RESULTS: Twenty-one patients were enrolled. Thirteen patients completed the initial 12-week treatment cycle, with two discontinuing for adverse events considered to be possibly related to study drug. Four (19%) patients had disease stabilization for >100 days. One patient had a partial remission after two treatment cycles, but progressed during the third. Dose-limiting toxicity was observed in two patients. Serum type I IFN and IP-10 increased in most patients on 852A administration. Serum type I IFN increases were greater after dosing with 852A 0.9 mg/m(2) than after 0.6 mg/m(2) (P = 0.009). The maximal increase in IP-10 compared with baseline correlated with the maximal increase in type I IFN (P = 0.003). In the eight patients with immune cell marker data, CD86 expression on monocytes increased significantly post-first dose (P = 0.007). CONCLUSION: Intravenous 852A was well tolerated and induced systemic immune activation that eventually resulted in prolonged disease stabilization in some patients with stage IV metastatic melanoma who had failed chemotherapy.

Bercovici N, Haicheur N, Massicard S, Vernel-Pauillac F, Adotevi O, Landais D, Gorin I, Robert C, Prince HM, Grob JJ, Leccia MT, Lesimple T, Wijdenes J, Bartholeyns J, Fridman WH, Salcedo M, Ferries E, Tartour E. · IDM, Hopital Européen Georges Pompidou, Unité d'Immunologie Biologique, EA 4054 Université Paris, France. · J Immunother. · Pubmed #18157017 No free full text.

Abstract: The primary goal of cancer vaccines is to induce CD8+ T cells specific for tumor-associated antigens (TAA) but the characterization of these cells has been difficult because of the low sensitivity of ex vivo assays. Here, we focused on TAA-specific CD8+ T-cell responses in melanoma patients after vaccination with autologous dendritic cells loaded with lysates derived from allogeneic tumor-cell lines (Lysate-DC). Out of 40 patients treated, 16 patients developed immune response to tumor-cell lysate and/or CD8+ T cells specific for differentiation and cancer-testis antigens. TAA-specific CD8+ T-cell responses were detected by interferon (IFN)-gamma enzyme-linked immunospot after in vitro sensitization and were, either transient during the treatment period or delayed, that is, observed after completion of all vaccinations. We could not correlate these immune responses to clinical data as none of the patients achieved an overall objective response according to Response Evaluation Criteria in Solid Tumors criteria. Three patients were reported as stable disease and 10 patients presented evidence of antitumor activity. We found that TAA-specific T cells characterized in 4 patients produced perforin ex vivo, but no IFN-gamma in enzyme-linked immunospot. Differential expression of IFN-gamma and perforin was also observed for viral-specific T cells. Altogether, our results show that Lysate-DC therapy elicited tumor-specific CD8+ T cells nonlimited to human leukocyte antigen-A2+ patients, with some T cells secreting perforin ex vivo and IFN-gamma only after restimulation. The differential expression of perforin and IFN-gamma by antitumor and antiviral CD8+ T cells supports that the sole use of IFN-gamma production to monitor T cells overlooks functional T-cell subpopulations triggered by vaccines.

Avril MF, Aamdal S, Grob JJ, Hauschild A, Mohr P, Bonerandi JJ, Weichenthal M, Neuber K, Bieber T, Gilde K, Guillem Porta V, Fra J, Bonneterre J, Saïag P, Kamanabrou D, Pehamberger H, Sufliarsky J, Gonzalez Larriba JL, Scherrer A, Menu Y. · Institut Gustave Roussy, 39, rue Camille Desmoulins, 94805 Villejiuf Cedex, France. · J Clin Oncol. · Pubmed #15020614 No free full text.

Abstract: PURPOSE: To compare fotemustine and dacarbazine (DTIC) in terms of overall response rate (ORR) as primary end-point and overall survival, duration of responses, time to progression, time to occurrence of brain metastases (BM), and to assess safety and quality of life in patients with disseminated cutaneous melanoma. PATIENTS AND METHODS: Patients received either intravenous fotemustine 100 mg/m2 weekly for 3 weeks or DTIC 250 mg/m2/d for 5 consecutive days every 4 weeks (two cycles). Nonprogressive patients received a maintenance treatment every 4 weeks (fotemustine 100 mg/m2 or DTIC 250 mg/m2 for 5 days). RESULTS: Two hundred twenty-nine patients were randomly assigned to fotemustine or DTIC arms. The best ORR was higher in the fotemustine arm than in the DTIC arm in the intent-to-treat population (n=229; 15.2% v 6.8%; P=.043) and in full analysis set (n=221) (15.5% v 7.2%; P=.053). Similar median durations of responses (5.8 months with fotemustine v 6.9 months with DTIC) and time to progression (1.8 v 1.9 months, respectively) were observed. In patients without BM at inclusion, the median time to BM was 22.7 months with fotemustine versus 7.2 months with DTIC (P=.059). Median survival was 7.3 months with fotemustine versus 5.6 months with DTIC (P=.067). The main toxicity was grade 3 to 4 neutropenia (51% with fotemustine v 5% with DTIC) and thrombocytopenia (43% v 6%, respectively). No significant difference was noted for quality of life between arms. CONCLUSION: ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced.

Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A, Dreno B, Henz M, Schadendorf D, Kapp A, Weiss J, Fraass U, Statkevich P, Muller M, Thatcher N. · Christie Hospital, Manchester, United Kingdom. · J Clin Oncol. · Pubmed #10623706 No free full text.

Abstract: PURPOSE: To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m(2)/d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m(2)/d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P =.012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.

Richard MA, Martin S, Gouvernet J, Folchetti G, Bonerandi JJ, Grob JJ. · Service de Dermatologie, Hôpital Sainte Marguerite, 270 Bd de Sainte Marguerite,13009 Marseille, France. · Br J Dermatol. · Pubmed #10354031 No free full text.

Abstract: Effectiveness of melanoma prevention depends on how it is accepted by the population. Humour and alarmism are often used in campaigns, but no information is available about how much they may improve or limit the impact of a campaign. Three different leaflets containing the same information about sun exposure and skin cancers were developed using three different tones of presentation: humoristic (H-leaflet), alarmist (A-leaflet) or neutral information (N-leaflet). In this randomized controlled study, each type of leaflet was mailed to a sample of 300 subjects representative of the sociodemographic population of the South of France. A fourth sample to whom no leaflet was sent was used as a control. Fifteen days after the mailing, the 1200 individuals were interviewed by phone. Four hundred and forty-four of the 900 who received the mail read the leaflet. The percentage of individuals with a good awareness of melanoma was higher in leaflet groups than in controls. The percentage of individuals who read a leaflet was lower in the A-leaflet group and the percentage of individuals knowing what a melanoma is tended to be lower in the H-leaflet group. There was no significant difference between groups with regard to ability for self-assessment of skin sun sensitivity, risk factors and sun exposure. The tone of presentation seems to have a limited impact on the effect of a campaign, but alarmism tends to reduce the number of people reached by the message whereas humour tends to decrease the impact of the message.

Gaudy-Marqueste C, Madjlessi N, Guillot B, Avril MF, Grob JJ. · Department of Dermatology, Hôpital Sainte Marguerite, 270 Blvd de Sainte Marguerite, Marseille 13009, France. · Arch Dermatol. · Pubmed #19380663 No free full text.

Abstract: OBJECTIVE: To assess lentigo maligna (LM) as an epidemiological entity separate from other melanomas (OMs) in elderly people. DESIGN: Double age- and sex-matched case-control study to compare the risk factors for LMs and OMs. SETTING: General community. Patients A total of 76 patients with LM were paired by age and sex with 76 patients with OMs and 152 controls. MAIN OUTCOME MEASURES: The association of melanoma risk with the following potential risk factors: sun exposure history by 10-year periods, frequency of sunburns, phenotypic traits, density of freckles and sun sensitivity at age 20 years, counts of nevi larger than 2 mm in diameter on the face and forearm, skin aging features (as assessed using a photographic scale), and history of basal and/or squamous cell carcinomas. RESULTS: Risk of LMs and OMs were similarly associated with history of sunburns, light skin type, and freckling. Cumulative chronic outdoor and occupational sun exposures were not risk factors in any of the 2 groups of melanomas. Lentigo maligna differed from OMs by the absence of a detectable association with the number of nevi and a greater association with nonmelanoma skin cancers. CONCLUSIONS: Although chronically sun-exposed skin is a prerequisite for LM, risk of LM does not increase with the cumulative dose of sun exposure, but LM is associated with sunburn history, like all other types of melanomas. The main epidemiological characteristic of LM is the absence of an apparent relation with the genetic propensity to develop nevi. This epidemiological profile is in accordance with recent molecular findings and may also account for the histoclinical and evolutive characteristics of LM.

Nicol I, Chuto G, Gaudy-Marqueste C, Brenot-Rossi I, Grob JJ, Richard MA. · Service de dermatologie, hôpital Sainte-Marguerite, Marseille, France. · Bull Cancer. · Pubmed #19036682 No free full text.

Abstract: PURPOSE: The indications of FDG PET-CT are well established for some neoplasms, such as lung cancer and lymphoma. The role of FDG PET-CT for the management of cutaneous melanoma is less clear. METHODS: We successively describe the substances and machines used with PET-CT, and review the French recommendations and the latest scientific articles to determine which patients could benefit from this examination. RESULTS: PET-CT is not indicated for the diagnosis of the malignancy of a suspicious cutaneous lesion, or for initial regional node staging. PET-CT is not indicated for the initial staging of melanoma without node involvement. PET-CT could be proposed for the staging of thick melanoma with macroscopic involvement of the sentinel node. PET-CT is useful for distant staging. The sole curative treatment of melanoma being surgery, the most useful indications of PET-CT are preoperative staging of one (or more) nodal or distant metastases, whether histologically confirmed or not. Preoperative PET-CT can spare a patient with unknown metastases a useless surgery. PET-CT is not indicated for the staging of a patient with known inoperable metastatic disease. PET-CT is not indicated for assessing response to chemotherapy, except in clinical trials.

Mahieu-Renard L, Cammilleri S, Giorgi R, Gaudy-Marqueste C, Mundler O, Richard MA, Grob JJ. · Department of Dermatology, Sainte-Marguerite Hospital, 270 boulevard de Sainte-Marguerite, 13009, Marseille, France. · Ann Surg Oncol. · Pubmed #18696157 No free full text.

Abstract: AIMS: To confirm an association between a slow kinetics in the lymphoscintigraphic mapping of the sentinel node (SN), and SN negativity (SN-) in melanoma (MM) patients, and to test whether a long scintigraphic appearance time (SAT) could be a noninvasive surrogate marker of SN-. METHODS: A retrospective cohort of 194 successive MMs with Breslow >/=1.5 mm with follow-up >18 months after SN procedure were retrospectively randomized into two groups: a test sample (T) (two-thirds) to assess the relationship between SN status and lymphoscintigraphy dynamics, and to identify a potential scintigraphic marker of SN-, which was confirmed in the validation sample (V) (one-third). A prospective cohort of 150 consecutive new patients was then used to test the negative predictive value (NPV) of this marker. RESULTS: In sample T, SAT was significantly lower in SN+ than SN- patients (p = 0.04). In a multivariate model, SAT was predictive of SN status, before tumor thickness. SAT was also predictive of disease of disease-free survival (DFS) and overall survival (OS). None of the patients with SAT >30 min (24.8%) were SN+. SAT >30 min was validated as a potential marker for SN- in sample V with NPV = 100% (confidence interval [CI] 84.6-100). In the prospective cohort, the NPV of this marker was however only 84.6% (CI 65.1-95.6). CONCLUSION: Slow SAT is associated with SN- and better survival, which opens interesting hypotheses as to the process of the first nodal metastasis. However, the best possible lymphoscintigraphic marker was not consistent enough to recognize patients in whom the invasive phase of SN biopsy could be avoided.

Grob JJ, Gaudy C. · Service de Dermato-Vénérologie, CHU-Hôpitaux Sud, Marseille. · Rev Prat. · Pubmed #18018536 No free full text.

Abstract: Mortality by melanoma has not decreased, despite intensive medical screening, multiple campaigns based on ABCD, and a more efficacious surveillance of people at risk by dermatologists. We thus have to modify our strategy and to target the general population. Indeed, most melanomas do not develop in people identified as at risk, 2/3 of melanomas are self-detected by individuals, and melanoma responsible for mortality are often fast-growing ones, which give few opportunities to be detected early enough by chance by a doctor, although they can be by any aware individuals. Public campaigns can make everybody able to self-detection of melanoma, on condition that images of nevi and melanoma are used as educational support, and not artificial algorithms such as ABCD which lead to an overload medical system with irrelevant consultations. Self-surveillance and detection of nevus changes must be promoted by providing all at risk people with photographic references. By training general population and involving its responsibility, anybody who will feel that he has a suspicious lesion should have a direct access to the "diagnostic test", which is the dermatologist opinion, ie the "mammography" of the skin cancer. GPs and occupational doctors by the multiple opportunities to see people skin should go on their major role to detect lesions, which would not be self-detected.

Gaudy C, Richard MA, Folchetti G, Bonerandi JJ, Grob JJ. · Dermatology Department, Hôpital Sainte Marguerite, Marseille, France. · J Cutan Med Surg. · Pubmed #17241586 No free full text.

Abstract: BACKGROUND: Electrochemotherapy (ECT) combines intralesional injections of bleomycin with electroporation (EP), which permeabilizes tumor cells and thus increases the bleomycin efficacy at the tumor site. OBJECTIVE: To assess whether EP therapy improves the local control of skin metastases of melanoma by intralesional bleomycin. The secondary objective was to evaluate tolerance of the treatments. PATIENTS: Patients with at least two measurable skin metastases of melanoma that were previously untreated, either in stage III with in-transit melanoma skin metastases or stage IV with no efficacy of systemic chemotherapy on these metastases. DESIGN: A prospective internally controlled study with randomization of melanoma skin metastases in each individual to intralesional injections of bleomycin alone or to intralesional injections of bleomycin with EP. The primary end point was the rate of complete local response per treated melanoma skin metastasis at week 12, and the secondary end point was tolerance. RESULTS: Fifty-four melanoma skin metastases were treated in 12 patients (8 stage IV patients under chemotherapy and 4 stage III patients free of other treatment). A local complete response was obtained in 36% (11 of 30) of melanoma skin metastases treated with bleomycin + EP and only in 8% (2 of 24) of melanoma skin metastases treated with bleomycin alone (p = .016). In the per protocol population, complete response was obtained in 74% (17 of 23) and 13% (2 of 15) of the lesions treated, respectively (p = .017). All patients (12 of 12) reported discomfort during the EP procedure, including local pain for 9 patients (75%) at the treatment site and muscle spasm with myoclonia in 3 cases (25%). No clinical or biologic systemic toxicity was noticed. CONCLUSIONS: EP increases the effect of intralesional bleomycin and improves the rate of local control in melanoma skin metastases without inducing a more systemic effect. This local treatment could be useful in a palliative strategy in patients with melanoma skin metastases.

Derancourt C, Bourdon-Lanoy E, Grob JJ, Guillaume JC, Bernard P, Bastuji-Garin S. · Department of Dermatology, Hôpital Robert-Debré, Université de Reims, Reims, France. · Dermatology. · Pubmed #17191044 No free full text.

Abstract: BACKGROUND: Multiple solar lentigos commonly seen on the upper back and shoulders of adults are classically considered as a sign of photodamage, although epidemiological studies are scarce. AIM: To assess whether these lesions are clinical markers of past severe sunburn. METHODS: A case-control study in two outpatient dermatology clinics in French university hospitals. Past episodes of moderate and severe sunburn were compared between 145 adult patients with multiple solar lentigos on the upper back and 145 matched controls. Results: In multivariate analysis adjusted for potential confounders, recalled episodes of sunburn during childhood, adolescence and adulthood were independently associated with the presence of multiple solar lentigos (adjusted odds ratios, 95% confidence intervals: 2.3 (1.1-5.2) and 28.1 (10.4-75.6) for moderate and severe sunburn, respectively). CONCLUSION: Multiple solar lentigos on the upper back and shoulders of adults are potential clinical markers of past severe sunburn which may thus be used to identify a population at higher risk of developing cutaneous malignant melanoma.

Gaudy-Marqueste C, Regis JM, Muracciole X, Laurans R, Richard MA, Bonerandi JJ, Grob JJ. · Dermatology Department, Hôpital Sainte Marguerite, Marseille, France. · Int J Radiat Oncol Biol Phys. · Pubmed #16682138 No free full text.

Abstract: PURPOSE: To assess retrospectively a strategy that uses Gamma-Knife radiosurgery (GKR) in the management of patients with brain metastases (BMs) of malignant melanoma (MM). METHODS: GKR without whole-brain radiotherapy (WBRT) was performed for patients with Karnofsky Performance Status (KPS) of 60 or above who harbored 1 to 4 BMs of 30 mm or less and was repeated as often as needed. Survival was assessed in the whole population, whereas local-control rates were assessed for patients with follow-up longer than 3 months. RESULTS: A total of 221 BMs were treated in 106 patients; 61.3% had a single BM. Median survival from the time of GKR was 5.09 months. Control rate of treated BMs was 83.7%, with 14% of complete response (14 BMs), 42% of partial response (41 BMs), and 43% of stabilization (43 BMs). In multivariate analysis, survival prognosis factors retained were KPS greater than 80, cortical or subcortical location, and Score Index for Radiosurgery (SIR) greater than 6. On the basis of KPS, BM location, and age, a score called MM-GKR, predictive of survival in our population, was defined. CONCLUSION: Gamma-Knife radiosurgery provides a surgery-like ability to obtain control of a solitary BM and could be consider as an alternative treatment to the combination of GKR+WBRT as a palliative strategy. MM-GKR classification is more adapted to MM patients than are SIR, RPA and Brain Score for Brain Metastasis.

Girardi S, Gaudy C, Gouvernet J, Teston J, Richard MA, Grob JJ. · Department of Dermatology Hôpital Ste Marguerite, Assistance Publique des hôpitaux de Marseille andResearch unit LIMP EA 3291 Université de la méditerranée, Marseille, France. · Int J Cancer. · Pubmed #16331608 No free full text.

Abstract: Most education campaigns for melanoma (MM) detection in the general population have used the "ABCD" algorithm, although recognition of objects in the real life is based on a holistic image recognition rather than on analytic criteria. The objective was to compare analytic (ABCD) and cognitive (photographs) strategies for teaching self-recognition of MM. A prospective 4-arm stratified randomized trial in 255 individuals compared 3 realistic educative interventions by leaflets: 1) ABCD algorithm ("ABCD"), 2) a set of photographs chosen to stimulate recognition of MM among benign pigmented lesions ("Cog"), 3) photographs + explanations ("Cog-Ex" arm) and 4) no intervention ("NI"). A 40-slides test was performed before intervention (T0), 1 week after (T1) and after induction of anxiety (T2). In the "ABCD" arm, sensitivity slightly improved (80 to 83.8%, p = 0.04), but specificity dropped from 65.1 to 56.3% (p < 0.001), with no benefit in accuracy as compared to "NI". In "Cog" arm, there was no change in sensitivity, but a strong increase in specificity (65.9 to 81.1%, p < 0.001) and accuracy (42.1 to 53.1%, p < 0.001). "Cog-ex" resulted in similar although lower benefit. Under stress (T2), there was a dramatic loss of specificity and accuracy in "ABCD" arm (65.1 to 44.1%, p < 0.001 and 40.8% to 35.8%, p < or = 0.001) without higher gain in sensitivity, while sensitivity and accuracy increased (p < 0.005) after "Cog" leaflet, without decreasing specificity. Finally, the "ABCD" message alone does not seem efficacious and is even worse in the context of anxiety, whereas a quick look at a few photographs is sufficient to improve the ability of the laymen to recognize a MM just by optimizing their spontaneous image recognition capacities. Education by photographs is a realistic strategy which should replace or complete "ABCD" message in the campaigns for self-detection of MM.

Gachon J, Beaulieu P, Sei JF, Gouvernet J, Claudel JP, Lemaitre M, Richard MA, Grob JJ. · Service de Dermatologie Hôpital Ste Marguerite and Laboratoire d'Investigation des Maladies de la Peau, Faculté de Médecine, Université de la Méditerranée, Marseille, France. · Arch Dermatol. · Pubmed #15837860 links to  free full text

Abstract: BACKGROUND: Early detection is crucial to improve melanoma prognosis. Different diagnostic guides such as the ABCD rule (asymmetry [A], irregularity of borders [B], unevenness of distribution of color [C], and diameter [D]) have been proposed to identify melanoma, but their efficacy in real life is questionable. We investigated the recognition process of melanoma by dermatologists to use as a model to improve self-detection in the general population and to train students and general practitioners. OBJECTIVES: To understand the major principles of the recognition process of nevi and melanoma unconsciously used by dermatologists. DESIGN: Prospective survey recording the immediate perceptions of dermatologists of the morphologic features of the lesion and intuitive diagnostic opinion about 4036 consecutive resected nevi and melanoma. SETTING: One hundred thirty-five volunteer dermatologists in their daily practices. MAIN OUTCOME MEASURES: Perceptions of the image best explaining the diagnostic opinion and best predicting the final diagnosis by univariate and multivariate analysis. RESULTS: The immediate diagnostic opinion of the dermatologist is mainly explained by an unconscious reference to the overall pattern compared with the common nevi, but also compared with the other nevi of the individual (the "ugly duckling sign"). The dermatologist's ability to discriminate between nevi and melanoma relies on the assessment of the overall pattern, the ugly duckling sign, and the knowledge of a recent change. A separate or combined analysis of individual morphologic criteria such as ABCD does not seem to play a major role in this recognition process. CONCLUSIONS: Persons most skilled at the clinical detection of melanoma seem to unconsciously rely on cognitive (overall pattern) and comparative (ugly duckling sign) processes rather than an algorithm of morphologic criteria (ABCD). These concepts could be tested in the medical training of general practitioners and education of the general population, where they might be more efficient than algorithms such as the ABCD criteria.

Barge J, Decréau R, Julliard M, Hubaud JC, Sabatier AS, Grob JJ, Verrando P. · Laboratoire Activation, Mécanismes, Modélisation Moléculaire, ESA CNRS 6009, Faculté des Sciences de Saint Jérôme, Marseille, France. · Exp Dermatol. · Pubmed #15009114 No free full text.

Abstract: Photodynamic therapy (PDT) is a promising therapeutic modality that utilizes a combination of a photosensitizer and visible light for the destruction of diseased tissues. Using human-pigmented melanoma cells, we examined the photokilling efficacy of new silicon-phthalocyanines (SiPc) that bore bulky axial substituents. The bis(cholesteryloxy) derivate (Chol-O-SiPc) displayed the best in vitro photokilling efficacy (LD(50) = 6-8 x 10(-9) M) and was seven to nine times more potent than chloro-aluminium Pc (ClAlPc), a known photosensitizer used as a reference. Although Chol-O-SiPc was half as potent as ClAlPc for promoting photo-oxidative membrane damage in a cell-free assay, early events of mitochondrion-mediated apoptosis upon PDT were triggered much faster, as demonstrated by kinetics studies examining cells with permeabilized mitochondrial membranes, cytochrome c release and caspase-9 activation. Inhibition of caspase-9 activity by a substrate analogue argued for its central role in the proapoptotic events leading to cell death by Chol-O-SiPc PDT. In addition, immunoblots showed that Bcl-2 antiapoptotic oncoprotein was not a primary target of Chol-O-SiPc in M3Dau cells treated with PDT. Conclusively, Chol-O-SiPc is a useful new photosensitizer with the property of triggering cell apoptosis mediated by mitochondria.