Dataset Information

Whole-Body MRI for the Detection of Recurrence in Melanoma Patients at High Risk of Relapse.

ABSTRACT: Introduction: No standard protocol for surveillance for melanoma patients is established. Whole-body magnetic resonance imaging (whole-body MRI) is a safe and sensitive technique that avoids exposure to X-rays and contrast agents. This prospective study explores the use of whole-body MRI for the early detection of recurrences. Material and Methods: Patients with American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7) stages IIIb/c or -IV melanoma who were disease-free following resection of macrometastases (cohort A), or obtained a durable complete response (CR) or partial response (PR) following systemic therapy (cohort B), were included. All patients underwent whole-body MRI, including T1, Short Tau Inversion Recovery, and diffusion-weighted imaging, every 4 months the first 3 years of follow-up and every 6 months in the following 2 years. A total body skin examination was performed every 6 months. Results: From November 2014 to November 2019, 111 patients were included (four screen failures, cohort A: 68 patients; cohort B: 39 patients). The median follow-up was 32 months. Twenty-six patients were diagnosed with suspected lesions. Of these, 15 patients were diagnosed with a recurrence on MRI. Eleven suspected lesions were considered to be of non-neoplastic origin. In addition, nine patients detected a solitary subcutaneous metastasis during self-examination, and two patients presented in between MRIs with recurrences. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were, respectively, 58%, 98%, 58%, 98%, and 98%. Sensitivity and specificity for the detection of distant metastases was respectively 88% and 98%. No patient experienced a clinically meaningful (>grade 1) adverse event. Conclusions: Whole-body MRI for the surveillance of melanoma patients is a safe and sensitive technique sparing patients' cumulative exposure to X-rays and contrast media.

SUBMITTER: Jansen YJL

PROVIDER: S-EPMC7865287 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Whole-Body MRI for the Detection of Recurrence in Melanoma Patients at High Risk of Relapse.

Jansen Yanina J L YJL Willekens Inneke I Seremet Teofila T Awada Gil G Schwarze Julia Katharina JK De Mey Johan J Brussaard Carola C Neyns Bart B

Cancers 20210125 3

<i>Introduction:</i> No standard protocol for surveillance for melanoma patients is established. Whole-body magnetic resonance imaging (whole-body MRI) is a safe and sensitive technique that avoids exposure to X-rays and contrast agents. This prospective study explores the use of whole-body MRI for the early detection of recurrences. <i>Material and Methods:</i> Patients with American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7) stages IIIb/c or -IV melanoma who were diseas ...[more]

PMID: 33503861

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Project description:BackgroundAGI-101H is an allogeneic gene modified whole cell therapeutic melanoma vaccine, evaluated in over 400 melanoma patients in the adjuvant and therapeutic settings. We present updated long-term survival results from two single-arm, phase II adjuvant trials (Trial 3 and Trial 5) with the focus on treatment beyond recurrence of the disease.MethodsPatients with resected high-risk melanoma (stage IIIB-IV) were enrolled to Trial 3 (n = 99) and Trial 5 (n = 97). The primary endpoint was disease-free survival (DFS), and the secondary was overall survival (OS). In the induction phase, the vaccine was administered every 2 weeks (eight times), followed by the maintenance phase every month until progression. At progression, maintenance was continued or re-induction was applied with or without surgery.ResultsIn Trial 3, the 10-year DFS was equal to 33.0% overall and to 52.4, 25.0, and 8.7% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 5, the overall 10-year DFS was equal to 24.2%, and to 37.5, 18.0, and 17.6% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 3, the 10-year OS was equal to 42.3% overall, and to 59.5, 37.5, and 17.4% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 5, the 10-year OS was equal to 34.3% overall and to 46.9, 28.0, and 29.4% for stage IIIB, IIIC, and stage IV patients, respectively. Among the 65 patients of Trial 3 who developed progression, 43 received re-induction with (n = 22) or without (n = 21) surgery. Two patients received surgery without re-induction. All the 22 progressing patients, who did not receive re-induction, died. Among the 75 patients of Trial 5 who experienced progression, 39 received re-induction with (n = 21) or without (n = 18) surgery. Among the 36 progressing patients who did not receive the re-induction, 35 died. Surgery and re-induction reduced (independently) the increase of mortality after progression in both trials, with the effect of re-induction reaching statistical significance in Trial 5.ConclusionsVaccination beyond recurrence of the disease with additional re-induction combined with surgery or alone increased long term survival of melanoma patients. However, further studies on larger patient cohorts are required.Trial registrationCentral Evidence of Clinical Trials (EudraCT Number 2008-003373-40 ).

Project description:The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model.

Dataset Information

Whole-Body MRI for the Detection of Recurrence in Melanoma Patients at High Risk of Relapse.

Publications

Whole-Body MRI for the Detection of Recurrence in Melanoma Patients at High Risk of Relapse.

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