New directions for medical artificial intelligence

AbstractThe past decade has seen significant advances in medical artificial intelligence (MAI), but its role in medicine and medical education remains limited. The goal for the next decade must be directed towards maximizing the utility of MAI in the clinic and classroom. Fundamental to achieving this is increasing the involvement of clinicians in MAI development. MAI developers must move from “pet projects” toward generalizable tasks meeting recognized clinical needs. Clinical researchers must be made aware of knowledge engineering, so clinical data bases can be prospectively designed to contribute directly into MAI “knowledge bases”. Closer involvement of MAI scientists with clinicians is also essential to further understanding of cognitive processes in medical decision-making. Technological advances in user interfaces—including voice recognition, natural language processing, enhanced graphics and videodiscs— must be rapidly introduced into MAI to increase physician acceptance. Development of expert systems in non-clinical areas must expand, particularly resource management, e.g. operating room or hospital admission scheduling. The establishment of MAI laboratories at major medical centers around the country, involving both clinicians and computer scientists, represents an ideal mechanism for bringing MAI into the mainstream of medical computing

The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases – A multicenter cohort study

Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4e12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.Carl-Jacob Holmberg ... Brendon Coventry ... Hidde Kroon ... et al

Chemotherapy for metastatic melanoma: Time for a change?

Melanoma is a neoplasm with a rising incidence. Early-stage melanoma is curable, but advanced, metastatic melanoma almost uniformly is fatal, and patients with such advanced disease have a short median survival. Systemic therapy remains unsatisfactory, inducing complete durable responses in a small minority of patients. For the current review, the authors focused on the current role of cytotoxic chemotherapy in the treatment of metastatic melanoma and the future prospects for improvements for multiagent chemotherapy and chemotherapy combined with immunomodulatory and/or molecularly targeted agents. They discuss roles of single-agent chemotherapy, combination chemotherapy, combinations of chemotherapy with immunomodulatory or hormone agents, biochemotherapy, and combination chemotherapy with targeted therapies. © 2007 American Cancer Society

New challenges in endpoints for drug development in advanced melanoma

During the past 3 decades, the field of clinical research for the treatment of advanced melanoma lacked significant advances. Available drugs had low antitumor activity and no proven benefit in overall survival. Recently, new drugs developed based on an in-depth understanding of the biology of this disease have shown significant benefit, with ipilimumab and vemurafenib having recently shown a positive impact in overall survival in patients with metastatic melanoma leading to approval in this indication by the U.S. Food and Drug Administration. This rapid introduction of new active agents is likely to challenge current notions on how to develop future agents for the treatment of melanoma. The strong evidence of benefit for initial agents that modulate immune regulatory checkpoints or target driver oncogenes has spurred great interest in developing other similarly acting agents. However, this will pose problems in the choice of endpoints for the future definitive clinical trials, and the hurdles for achieving these endpoints will be higher given the similar activity for comparator agents or the availability of competing agents for salvage therapy. This new reality will likely require tailoring registrational clinical trial endpoints to the patient benefits shown in early clinical testing. In this perspective article, we illustrate the challenges in the choice of endpoints for registrational trials in metastatic melanoma and that, with an improved understanding of the agent being developed, the design of the registrational programs can be informed by earlier mechanistic studies to define the assumptions for definitive clinical testing. ©2011 AACR

Correlation of molecular human leukocyte antigen typing and outcome in high-risk melanoma patients receiving adjuvant interferon

BACKGROUND: Interferon is approved for adjuvant treatment of patients with stage IIB/III melanoma. The identification of predictive markers that would permit selection of patients would be beneficial. Specific human leukocyte antigen (HLA) class I and II antigens have previously shown an association with response to therapy or overall survival of patients with metastatic melanoma. METHODS: A total of 284 high-risk melanoma patients participating in a randomized trial and 246 healthy controls were molecularly typed for HLA class I and II. Specific allele frequencies were compared between the healthy and patient populations, as well as presence or absence of these in relation to recurrence. Alleles related to autoimmune disease were also investigated. RESULTS: No significant differences were found between the distribution of HLA genotype in the melanoma population compared with healthy controls. Correlations between nonrecurrence and the presence of HLA-Cw*06 allele were noted present in 19.3% of melanoma patients. The median relapse-free survival of the Cw*06-positive cohort was 100.2 months versus 37.3 months in the Cw*06-negative cohort (P =.013).The median overall survival for the Cw*06-positive cohort has not yet been reached, versus 78.9 months in the Cw*06-negative cohort (P = .025). HLA-Cw*06 was present in 29.79% of patients in the autoimmunity group and 15.38% of patients in the nonautoimmunity group (P =.049). CONCLUSIONS: No allele was associated with absence of recurrence in patients receiving adjuvant interferon with the exception of HLA-Cw*06, an allele correlated with psoriasis. HLA-Cw*06-positive patients have better relapse-free and overall survival. © 2010 American Cancer Society