Anti-programmed cell death protein 1 tolerance and efficacy after ipilimumab immunotherapy: observational study of 39 patients.

In patients with ipilimumab (IPI)-refractory melanoma, the anti-programmed cell death proteins 1 (PD1s) nivolumab (NIV) and pembrolizumab (PEM) are considered to be a new standard of treatment. Few data are available on anti-PD1 safety in patients who develop IPI-related severe adverse events (AEs) (grade≥3). The aim of this study was to compare the anti-PD1 safety and efficacy in patients with previous severe toxicity to IPI versus in those showing moderate and no previous IPI-related AEs. This single institution-based observational study included all patients treated with anti-PD1 (PEM or NIV) and previously treated with IPI for unresectable stage III or IV melanoma. The patients enrolled were classified according to the occurrence of IPI-related AEs: group A: no previous IPI-related AEs; group B: mild to moderate IPI-related AEs; and group C: severe to life-threatening IPI-related AEs. The main outcome measure was safety of the anti-PD1 among the three groups. The secondary endpoints included response parameters. Groups A, B, and C included, respectively, 16, 13, and 10 patients. The incidence of severe anti-PD1-related AEs (grades 3-4) was 12, 23, and 10% in groups A, B, and C, respectively. One-year estimates of survival were 52.2, 73.4, and 66.7% among the patients in groups A, B, and C, respectively. The number of patients was too small to enable a meaningful statistical comparison. We did not observe any difference in anti-PD1 toxicity onset incidence according to the occurrence of previous IPI AEs. These reassuring real-life data should be confirmed in a wider analysis.

Squamous Cell Carcinoma Following Photodynamic Therapy for Cutaneous Bowen's Disease in a Series of 105 Patients.

Photodynamic therapy (PDT) is an alternative to surgery for Bowen's disease. This monocentric retrospective study included 105 patients with Bowen's disease, treated with PDT between 2007 and 2013, who received a total of 151 different PDT fields. Comparison of immunocompromised and non-immunocompromised patients revealed that the former often had a previous history of squamous cell carcinoma (SCC; p = 0.004) and received more PDT fields (p = 0.007) than the latter. At least one SCC occurred post-PDT in 16 out of 105 patients in a PDT field. However, many of the patients were at risk of SCC and the possibility that the lesion did not have a mixed histology at baseline, but might simply be a transformation of non-PDT-responsive Bowen's disease, cannot be excluded. Although it is rare, patients should be closely monitored for SCC post-PDT.

BRAF inhibitor rechallenge in patients with advanced BRAF V600-mutant melanoma.

In around 50% of melanomas, the BRAF V600 mutation, resulting in an activation of the MAP kinase pathway, is detected. BRAF inhibitors have shown remarkable activity on the disease. However, efficacy is short-lived in most cases, with a median disease-free survival of 6 months. This short duration of response could be explained by the acquisition of resistance mechanisms. Some cancers show sensitivity to the reintroduction of previously active drugs after disease progression. We carried out a retrospective monocentric study on patients with BRAF V600-mutated melanoma who were rechallenged with BRAF inhibitors that were previously beneficial, but in whom the disease had progressed. Nine patients were included. Five patients showed a subsequent partial response, two showed a dissociated response leading to clinical improvement, and two showed no radiological nor clinical response. Eight patients who received rechallenge BRAF inhibitor had received an intercurrent treatment with ipilimumab. These cases suggest that intermittent treatment with BRAF inhibitors could provide clinical benefit and that sequential therapies should be further evaluated in clinical trials.

Ultrasound-guided core needle biopsy of superficial lymph nodes: an alternative to fine-needle aspiration cytology for the diagnosis of lymph node metastasis in cutaneous melanoma.

To investigate the diagnostic value of ultrasound-guided core needle biopsy (US-CNB) in suspected cases of lymph node metastasis from cutaneous melanoma. All patients with cutaneous melanoma followed in Saint-Louis Hospital between 2006 and 2010 who underwent US-CNB for suspicion of melanoma lymph node metastasis were reviewed retrospectively. Histopathological results of US-CNB samples were classified as melanoma, other malignancy, suspicious, inadequate, or benign. The diagnostic accuracy of US-CNB was assessed by comparison with two reference standards: histopathological examination of the radical lymph node dissection or, when this was not available, clinical and radiological follow-up. The data from 72 US-CNB were analyzed. Forty-four melanomas, 22 benign, three other malignancies, three inadequate samples, and no inconclusive specimens were diagnosed. Seventy-one US-CNB results were confirmed (98.6%). US-CNB achieved high sensitivity, specificity, and positive predictive value (respectively, 97.9, 100, and 100%). No adverse events were reported after the procedure. US-CNB provided a mean tissue volume of 16.7 mm per lymphadenopathy. US-CNB has diagnostic value similar to that of fine-needle aspiration cytology. It represents a reliable alternative method in melanoma lymph node metastasis to avoid surgery in patients who will not benefit from it. US-CNB provides relatively large samples of tissue suitable for comprehensive genomic analyses currently needed for research and personalized care of melanoma patients.

The "spaghetti technique": an alternative to Mohs surgery or staged surgery for problematic lentiginous melanoma (lentigo maligna and acral lentiginous melanoma).

BACKGROUND: Lentigo maligna (LM) and acral lentiginous melanoma (ALM) are often large and clinically ill defined. The surgical challenge is to spare tissue while still achieving clear margins. OBJECTIVE: We sought to provide a retrospective assessment of a two-phase surgical technique for lentiginous melanomas (MM) not suitable for en bloc resection. METHODS: In the first phase, a narrow band of skin, "the spaghetti", is resected just beyond the clinical outline of the MM, immediately sutured, and sent for pathological examination without removing the MM. The same procedure is repeated beyond the segments which are shown to be not tumor free and so forth until the minimal tumor-free perimeter is outlined. No operative wound is left between operative sessions. In the second phase, the MM resection and reconstruction are performed at the same time. RESULTS: In 21 patients with LM (n = 16) or ALM (n = 5), the mean operative defect size was 27.5 cm(2) (range, 1.97-108.4 cm(2)). The mean number of steps in the procedure was 1.55 (1-4). Grafts were used for reconstruction in all cases. The relevance of the "spaghetti"-defined outline was confirmed in 19 of 21 patients. After a median follow-up period of 25.36 months (range, 0-72 months), the local control rate was 95.24% with one case (4.76%) of in-transit invasive recurrence after 48 months. LIMITATIONS: This study was performed at a single center and included a limited number of patients. The follow-up time was relatively brief. CONCLUSION: The "spaghetti technique" is simple and reliable for LM and ALM. Unlike Mohs surgery, it does not require specific training of surgeons or pathologists. Unlike staged surgery, it does not leave patients with an open wound on the face or soles before final reconstruction.

Risk factors in elderly people for lentigo maligna compared with other melanomas: a double case-control study.

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.