Surveillance evaluations in patients with stage I, II, III, or resectable IV melanoma who were treated with curative intent: A systematic review.

PURPOSE: Appropriate surveillance of patients with melanoma treated with curative intent is vital to improve patient outcomes. A systematic review was conducted to capture locoregional recurrence and metastatic disease, and to evaluate the effectiveness of various surveillance strategies. METHODS: MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews, and National Cancer Institute Clinical Trials Database were searched. Randomized controlled trials (RCTs) and comparative studies reporting at least one patient-related outcome were included. Exclusion criteria included: published in non-English or recruited >20 % or an uncertain percentage of non-target patients without conducting a subgroup analysis for the target patients. This review was registered at PROSPERO (CRD42021246482). RESULTS: Among 17,978 publications from the literature search, one RCT and five non-randomized comparative studies were included and comprised 4016 patients. The aggregate evidence certainty was low for the RCT and very low for the comparative studies, as assessed by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. For patients with stage IA-IIC melanoma, a reduced follow-up schedule with clinical follow-up strategies alone may be safe and cost-effective. For stage IIC-IIIC patients, at least two serial PET/CT or whole-body CT and brain MRI imaging within a median follow-up of 31.2 months may detect 50 % of recurrences that lead to additional management, such as surgery. PET/CT may have a higher positive predictive value and lower false positive rate compared with CT alone in detecting recurrence in stage I-III patients. CONCLUSION: Surveillance protocols should be based on individual risk of recurrence and established best practices when formulating follow-up strategies, as suggested by the studies reviewed. Future high-quality studies are needed to clarify the frequency of imaging follow-up strategies, especially in patients with high-risk stage II melanoma.

A population-based validation study of the 8th edition UICC/AJCC TNM staging system for cutaneous melanoma.

BACKGROUND: The 8th edition UICC/AJCC TNM8 (Tumour, Nodes, Metastasis) melanoma staging system introduced several modifications from the 7th edition (TNM7), resulting in changes in survival and subgroup composition. We set out to address the limited validation of TNM8 (stages I-IV) in large population-based datasets. METHODS: This retrospective cohort-study included 6,414 patients from the population-based Ontario Cancer Registry diagnosed with cutaneous melanoma between January 1, 2007 and December 31, 2012. Kaplan-Meier curves estimated the melanoma-specific survival (MSS) and overall survival (OS). Cox proportional hazard models were used to estimate adjusted hazard ratios for MSS and OS across stage groups. The Schemper-Henderson measure was used to assess the variance explained in the Cox regression. RESULTS: In our sample, 21.3% of patients were reclassified with TNM8 from TNM7; reclassifications in stage II were uncommon, and 44.1% of patients in stage III were reclassified to a higher subgroup. Minimal changes in MSS curves were observed between editions, but the stage IIB curve decreased and the stage IIIC curve increased. For TNM8, Stage I (n = 4,556), II (n = 1,206), III (n = 598), and IV (n = 54) had an estimated 5-year MSS of 98.4%, 82.5%, 66.4%, and 14.4%, respectively. Within stage III, IIIA 5-year MSS was 91.7% while stage IIID was 23.5%. HRs indicated that TNM8 more evenly separates subgroups once adjusted for patient- and disease-characteristics. The variance in MSS explained by TNM7 and TNM8 is 18.9% and 19.7%, respectively. CONCLUSION: TNM8 performed well in our sample, with more even separation of stage subgroups and a modest improvement in predictive ability compared to TNM7.

Impact of the development of immune related adverse events in metastatic melanoma treated with PD -1 inhibitors.

Some clinical trials have described improved outcomes in patients who develop immune-related adverse events (irAEs) while receiving immune checkpoint inhibitors for advanced melanoma. It is unknown if this effect would be seen in a real-world population. This is a single-center retrospective analysis of all patients receiving single-agent PD-1 inhibitor for unresectable stage III or stage IV melanoma between 2012 and 2018. The majority of patients had cutaneous melanoma and were elderly (put in median and range). Totally 33.3% were BRAF mutated and 66.7% had PD-1 inhibitor as first-line treatment for metastatic disease. Also, 22% of patients had brain metastases at presentation. Of the 87 patients included in this analysis, 48 (55%) developed at least one irAE. Dermatologic toxicities were the most common irAE. The median time to develop any irAE was 12 weeks. Only one patient died of immune-related toxicity. Overall survival in the population of patients that had an irAE was significantly greater than those that did not have any toxicity (21.1 vs. 7.5 months; P < 0.001). The development of endocrine toxicity had the strongest correlation with survival as did patient with grade 1 (NCI V.5) toxicity. The development of multiple toxicities did not correlate with survival. In patients with multiple toxicities, the type of irAE that presented initially did not impact the outcome. These findings add to the growing body of literature suggesting an association between irAEs and immune-checkpoint inhibitor efficacy while suggesting that this benefit may depend on the type of toxicity and severity.

Systemic adjuvant therapy for adult patients at high risk for recurrent melanoma: A systematic review.

Cutaneous melanoma is typically treated with wide local excision and, when appropriate, a sentinel node biopsy. Many patients are cured with this approach but for patients who have cancers with high risk features there is a significant risk of local and distant relapse and death. Interferon-based adjuvant therapy was recommended in the past but had modest results with significant toxicity. Recently, new therapies (immune checkpoint inhibitors and targeted therapies) have been found to be effective in the treatment of patients with metastatic melanoma and many of these therapies have been evaluated and found to be effective in the adjuvant treatment of high risk patients with melanoma. This systematic review of adjuvant therapies for cutaneous and mucosal melanoma was conducted for Ontario Health (Cancer Care Ontario) as the basis of a clinical practice guideline to address the question of whether patients with completely resected melanoma should be considered for adjuvant systemic therapy and which adjuvant therapy should be used.

Discordance between conclusions stated in the abstract and conclusions in the article: analysis of published randomized controlled trials of systemic therapy in lung cancer.

PURPOSE: Clinicians may read only the abstract of an article to keep abreast of newly published randomized controlled trials (RCTs). However, discordances have been noticed in summary conclusions in the abstracts and the main body of some articles. This article evaluated such discordances in detail. METHODS: RCTs of systemic therapy for lung cancer published between 2004 and 2009 were considered. Conclusions in the body of the articles and those in the abstracts were graded by using a 7-point Likert scale; 1 for strong endorsement of the control arm, 4 for a neutral statement, and 7 for strong endorsement of the experimental arm. Conclusions were classified as discordant if the difference in scores was ≥ 2. χ(2) tests and logistic regression were used to identify factors associated with discordance. RESULTS: From among 114 eligible RCTs identified (90 for non-small-cell and 24 for small-cell lung cancer), 11 (10%) articles presented discordant conclusions in the abstract and in the body of the articles. Discordance was most common when the experimental arm was strongly supported in the abstract but not in the body of the article (nine of 11; 82%); however, the converse was much less common (two of 11; 18%; P < .001). Intraclass correlations for the two reviewers were ≥ 0.9. The discordances were found to be independent of trial-related factors. CONCLUSION: Conclusive statements in the abstract can differ from those in the full text. Clinicians should use caution when they consider making changes in their practice on the basis of reading only the abstract of a published RCT.