Management of Uveal Melanoma: Updated Cancer Care Alberta Clinical Practice Guideline.

OBJECTIVE: The purpose of this guideline update is to reassess and update recommendations in the prior guideline from 2016 on the appropriate management of patients with uveal melanoma. METHODS: In 2021, a multidisciplinary working group from the Provincial Cutaneous Tumour Team, Cancer Care Alberta, Alberta Health Services was convened to update the guideline. A comprehensive review of new research evidence in PubMed as well as new clinical practice guidelines from prominent oncology groups informed the update. An enhancement in methodology included adding levels of evidence and strength of recommendations. The updated guideline was circulated to all members of the Provincial Cutaneous Tumour Team for review and endorsement. RESULTS: New and modified recommendations address provider training requirements, diagnostic imaging for the detection of metastases, neo-adjuvant pre-enucleation radiotherapy, intravitreal anti-vascular endothelial growth factor agents for radiation retinopathy, genetic prognostic testing, surveillance following definitive local therapy, and systemic therapy for patients with metastatic uveal melanoma. DISCUSSION: The recommendations represent evidence-based standards of care agreed to by a large multidisciplinary group of healthcare professionals.

Evaluation of Intra-Lesional Interleukin 2 for the Treatment of In-Transit Melanoma Disease: L'évaluation de l'interleukine-2 intralésionnelle pour traiter les mélanomes en transit.

BACKGROUND: Intra-lesional interleukin 2 (IL-2) therapy trials for the treatment of in-transit melanoma using different treatment protocols have been published reporting varied results. This study assesses the results of IL-2 therapy in our institution and to evaluate the reproducibility of our response rates when using the same treatment protocol as another Canadian centre. METHODS: A retrospective review was undertaken of patients with in-transit melanoma who were treated with intralesional IL-2 in a single institution from 2010 to 2016. Responses were evaluated using RECIST criteria. Demographic data, tumour characteristics, follow-up data, in-transit-free interval, and survival data were collected and analysed. RESULTS: Forty-nine patients were identified. Overall tumour response rate was 72%, including complete response in 23 patients (47%) and partial response in 12 patients (24%). Stable disease was observed in 4% of patients and progressive disease in 25%. The main side effects were minor discomfort with injections and auto-limited flu-like symptoms. The presence of tumour-infiltrating lymphocytes may be a predictor of better response. CONCLUSION: This study confirms prior experience with intra-lesional IL-2, demonstrating it to be an effective, safe, and well-tolerated therapy for in-transit melanoma. Tumour-infiltrating lymphocytes as a predictor of better response warrant further study.

HISTORIQUE: Les publications sur l'utilisation d'interleukine-2 (IL-2) intralésionnelle pour traiter les mélanomes en transit faisant appel à divers protocoles thérapeutiques ont rendu compte de résultats variables. Dans la présente étude, les chercheurs évaluent les résultats du traitement à l'IL-2 au sein de leur établissement et la reproductibilité de leur taux de réponse lorsqu'ils utilisent le même protocole thérapeutique qu'un autre centre canadien. MÉTHODOLOGIE: Les chercheurs ont effectué une analyse rétrospective des patients atteints d'un mélanome en transit qui ont reçu de l'IL-2 intralésionnelle dans un même établissement entre 2010 et 2016. Ils ont évalué les réponses selon les critères d'évaluation RECIST et ont colligé et analysé les données démographiques, les caractéristiques des tumeurs, les données de suivi, l'intervalle libre en transit et les données de survie. RÉSULTATS: Les chercheurs ont dénombré 49 patients. Le taux de réponse global des tumeurs s'élevait à 72 %, y compris une réponse complète chez 23 patients (47 %) et une réponse partielle chez 12 patients (24 %). Ils ont observé une maladie stable chez 4 % des patients et une maladie évolutive chez 25 % d'entre eux. Les principaux effets secondaires étaient des malaises mineurs à l'injection et des symptômes pseudogrippaux autolimités. L'infiltration lymphocytaire des tumeurs pourrait être un élément prédicteur d'une meilleure réponse. CONCLUSION: La présente étude confirme l'expérience antérieure de l'IL-2 intralésionnelle et démontre qu'il s'agit d'un traitement efficace, sécuritaire et bien toléré contre le mélanome en transit. D'autres études devront être réalisées pour établir si l'infiltration lymphocytaire des tumeurs est un bon élément prédicteur.

Validation of a scoring system to predict non-sentinel lymph node metastasis in melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has been widely accepted as the lymph node sampling procedure of choice for melanoma patients. Current standards of practice suggest completion lymph node dissection (CLND) for patients with a positive SLNB result. The rationale for SLNB+/-CLND is for staging and prognosis as well as local control and possibly survival improvement. CLND, however, entails significant morbidity. In addition, most patients (approximately 80%) will have no further melanoma metastases in non-sentinel nodes and these patients may not benefit from the additional dissection. We had previously developed a score (based on patient age and the total size of metastasis within the SLN) that predicted which SLN-positive patients would have a positive CLND. Utilization of this scoring system would spare a significant number of melanoma patients the risks associated with CLND. The purpose of this study was to validate this score using different melanoma populations. METHODS: A retrospective chart review of all patients that had undergone SLNB for melanoma at four different Canadian centers was undertaken. Data from the Calgary Foothills Medical Center, the Winnipeg Health Sciences Center, and the Toronto Sunnybrook Health Sciences Center from January 1999 to present was collected. In addition, we identified all patients from April 2007 to present at the Misericordia Hospital in Edmonton for this study. This patient information had not been utilized when we were developing this score. The collected variables included patient age, Breslow thickness, result of SLNB, total size of SLN metastasis, largest size of SLN metastasis, and results of CLND. Logistic regression was used to test the significance of a score system's correlation (based on cutoff age of 55 years and cutoff total SLN metastasis of 5 mm) with the CLND results. We also used logistic regression to test the correlation of cutoff values of total SLN metastasis with non-sentinel lymph node (NSLN) metastasis. RESULTS: Data were collected on 599 patients across the four centers. Breslow thickness significantly correlated with SLN metastasis. The risk score system (based on patient age and total SLN metastasis) was significantly predictive of the CLND result in SLNB-positive patients. However, the age became non-significant on multivariate analysis. Total SLN metastasis emerged as the variable that is most predictive of NSLN metastasis. Patients with total SLN metastasis less than 2 mm had a 3.6% risk of NSLN metastasis, those with SLN metastasis from 2-5 mm had a 12.5% risk of NSLN metastasis, whereas those with total SLN metastasis of 5 mm or greater had a 30% risk of NSLN metastasis. CONCLUSION: Using cutoff values of 2 and 5 mm for total SLN metastasis, prediction of NSLN metastasis can be made in melanoma patients. Patients with less than 2 mm of total SLN metastasis are unlikely (<3.67% likelihood) to harbor NSLN metastasis; these patients may not benefit from additional nodal dissection beyond SLNB.