Surveillance of Sentinel Node-Positive Melanoma Patients with Reasons for Exclusion from MSLT-II:Multi-Institutional Propensity Score Matched Analysis

BACKGROUND: In sentinel lymph node (SLN)-positive melanoma, two randomized trials demonstrated equivalent melanoma-specific survival with nodal surveillance vs completion lymph node dissection (CLND). Patients with microsatellites, extranodal extension (ENE) in the SLN, or >3 positive SLNs constitute a high-risk group largely excluded from the randomized trials, for whom appropriate management remains unknown. STUDY DESIGN: SLN-positive patients with any of the three high-risk features were identified from an international cohort. CLND patients were matched 1:1 with surveillance patients using propensity scores. Risk of any-site recurrence, SLN-basin-only recurrence, and melanoma-specific mortality were compared. RESULTS: Among 1,154 SLN-positive patients, 166 had ENE, microsatellites, and/or >3 positive SLN. At 18.5 months median follow-up, 49% had recurrence (vs 26% in patients without high-risk features, p 3 positive SLN constitute a high-risk group with a 2-fold greater recurrence risk. For those managed with nodal surveillance, SLN-basin recurrences were more frequent, but all-site recurrence and melanoma-specific mortality were comparable to patients treated with CLND. Most recurrences were outside the SLN-basin, supporting use of nodal surveillance for SLN-positive patients with microsatellites, ENE, and/ or >3 positive SLN

Active surveillance of patients who have sentinel node positive melanoma:An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy trial II (MSLT-2)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168248/1/cncr33483.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168248/2/cncr33483_am.pd

Therapy for metastatic melanoma: the past, present, and future

Metastatic melanoma is the most aggressive form of skin cancer with a median overall survival of less than one year. Advancements in our understanding of how melanoma evades the immune system as well as the recognition that melanoma is a molecularly heterogeneous disease have led to major improvements in the treatment of patients with metastatic melanoma. In 2011, the US Food and Drug Administration (FDA) approved two novel therapies for advanced melanoma: a BRAF inhibitor, vemurafenib, and an immune stimulatory agent, ipilimumab. The success of these agents has injected excitement and hope into patients and clinicians and, while these therapies have their limitations, they will likely provide excellent building blocks for the next generation of therapies. In this review we will discuss the advantages and limitations of the two new approved agents, current clinical trials designed to overcome these limitations, and future clinical trials that we feel hold the most promise

Influence of dosing times on cisplatin-induced peripheral neuropathy in rats

Background: Although cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats. Methods: CDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague-Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed. Results: In order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia. Conclusions: It was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy

Role of radiotherapy in extracranial metastatic malignant melanoma in the modern era

Background: To assess the role of radiotherapy in metastatic malignant melanoma (MM) patients in modern era. Materials and methods: This is a retrospective study of MM patients treated with radiotherapy at Mayo Clinic from 1999 to 2014. Patients with pre- and post-treatment imaging studies (CT, MRI, and/or PET/CT) were assessed for metastasis failure (MF), regional/distant failure, and overall survival (OS). Results: In 75 MM patients, 56 and 68 lesions were treated with conventional/hypofractionated radiotherapy (CHRT) and stereotactic body radiotherapy (SBRT), respectively. The median doses for CHRT and SBRT were 30 Gy and 50 Gy, respectively. 1-year MF was 17% (SBRT 6% vs CHRT 31%, p < 0.01). 1-year regional (5% vs 29%, p < 0.01) and distant progression (75% vs 89%, p < 0.01) were improved with SBRT. Median OS was 15.6 months (CHRT 7.0 vs SBRT 22.9, p < 0.01). Prognostic factors for OS included age ≤55 years (RR 0.25), oligometastatic disease (RR 0.34), SBRT (RR 0.38) and treating all lesions (RR 0.28, all p < 0.01). Conclusions: SBRT for extracranial MM exhibited improved MF compared with CHRT, consistent with intracranial radiosurgery data. Though these data are retrospective and subject to selection bias, our findings support the prudent use of SBRT in a select group of favorable, oligometastatic MM patients, and should be discussed as an alternative to surgery and ablation

Role of radiotherapy in extracranial metastatic malignant melanoma in the modern era

Background: To assess the role of radiotherapy in metastatic malignant melanoma (MM) patients in modern era. Materials and methods: This is a retrospective study of MM patients treated with radiotherapy at Mayo Clinic from 1999 to 2014. Patients with pre- and post-treatment imaging studies (CT, MRI, and/or PET/CT) were assessed for metastasis failure (MF), regional/distant failure, and overall survival (OS). Results: In 75 MM patients, 56 and 68 lesions were treated with conventional/hypofractionated radiotherapy (CHRT) and stereotactic body radiotherapy (SBRT), respectively. The median doses for CHRT and SBRT were 30 Gy and 50 Gy, respectively. 1-year MF was 17% (SBRT 6% vs CHRT 31%, p < 0.01). 1-year regional (5% vs 29%, p < 0.01) and distant progression (75% vs 89%, p < 0.01) were improved with SBRT. Median OS was 15.6 months (CHRT 7.0 vs SBRT 22.9, p < 0.01). Prognostic factors for OS included age ≤55 years (RR 0.25), oligometastatic disease (RR 0.34), SBRT (RR 0.38) and treating all lesions (RR 0.28, all p < 0.01). Conclusions: SBRT for extracranial MM exhibited improved MF compared with CHRT, consistent with intracranial radiosurgery data. Though these data are retrospective and subject to selection bias, our findings support the prudent use of SBRT in a select group of favorable, oligometastatic MM patients, and should be discussed as an alternative to surgery and ablation