| 1. |
- Bethlehem, Martijn S., et al.
(författare)
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Meta-Analysis of Isolated Hepatic Perfusion and Percutaneous Hepatic Perfusion as a Treatment for Uveal Melanoma Liver Metastases
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:18
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Isolated hepatic perfusion is one of the available treatment options for patients with liver metastases from uveal melanoma. This is an open surgical procedure where the liver is isolated from the circulation and perfused with a chemotherapeutic agent. A modern development is the minimally invasive percutaneous hepatic perfusion, where the liver is endovascularly isolated and then perfused with a chemotherapeutic agent through a catheter in the arterial system. Within this systematic review and meta-analysis, we aim to compare these modalities in terms of overall survival, progression-free survival, complications and response. Background: Uveal melanoma is the most commonly occurring primary intraocular malignancy in adults, and patients have a high risk of developing metastatic disease, mostly in the liver. Isolated hepatic perfusion (IHP) with melphalan is a liver-directed therapy for patients with liver metastases. Percutaneous hepatic perfusion (PHP), a minimally invasive technique, is available as well. PHP benefits from the fact that the procedure can be repeated and therefore possibly offers better survival. We conducted a systematic review and meta-analysis comparing both techniques. Methods: A systematic literature search was performed using the electronic databases of Scopus, MEDLINE, Web of Science, PubMed and Cochrane CENTRAL. A total of nine articles reporting on eight studies were included in the analysis. Individual survival data were extracted from each study. Results: The median overall survival (OS) was 17.1 months for IHP and 17.3 months for PHP. The median progression-free survival (PFS) was 7.2 months for IHP and 9.6 months for PHP. The median hepatic progression-free survival was 10 months for IHP and 9.5 months for PHP. The complication rate and 30-day mortality rate were 39.1% and 5.5% for IHP and 23.8% and 1.8% for PHP. Conclusion: There was no difference in OS or PFS between IHP and PHP for patients with uveal melanoma liver metastases, but patients have significantly less of a risk for complications and mortality following PHP.
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| 2. |
- Broman, K. K., et al.
(författare)
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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)
- 2021
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 127:13, s. 2251-2261
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Tidskriftsartikel (refereegranskat)abstract
- Background For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. Methods In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. Results Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. Conclusions Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. Lay Summary For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.
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| 3. |
- Broman, K. K., et al.
(författare)
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Surveillance of Sentinel Node-Positive Melanoma Patients with Reasons for Exclusion from MSLT-II: Multi-Institutional Propensity Score Matched Analysis
- 2021
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Ingår i: Journal of the American College of Surgeons. - : Ovid Technologies (Wolters Kluwer Health). - 1072-7515. ; 232:4, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- 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 < 0.01). Among high-risk patients, 52 (31%) underwent CLND and 114 (69%) received surveillance. Fifty-one CLND patients were matched to 51 surveillance patients. The matched cohort was balanced on tumor, nodal, and adjuvant treatment factors. There were no significant differences in any-site recurrence (CLND 49%, surveillance 45%, p = 0.99), SLN-basin-only recurrence (CLND 6%, surveillance 14%, p = 0.20), or melanoma-specific mortality (CLND 14%, surveillance 12%, p = 0.86). CONCLUSIONS: SLN-positive patients with microsatellites, ENE, or >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. Crown Copyright (C) 2020 Published by Elsevier Inc. on behalf of the American College of Surgeons. All rights reserved.
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| 4. |
- Eriksson, H., et al.
(författare)
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The Proportion Cured of Patients with Resected Stage II-III Cutaneous Melanoma in Sweden
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Simple summary Patients diagnosed with stage II-III cutaneous melanoma (CM) are at high risk of recurrences, but the CM-specific survival ranges from approximately 40-70%. Here, the cure proportions and survival among uncured stage II-III CM patients were estimated. The 1- and 5-year relative survival ratios, cure proportions and the median survival times of uncured stage II-III CM patients in Sweden (n = 6466) were calculated based on data from the nationwide population-based Swedish Melanoma Register 2005-2013 with a follow-up through 2018. Proportions cured by surgery are low for sub-groups of stage II-III cutaneous melanoma showing that cure analyses can serve as a complement to established survival analyses. Background: Cure proportion represents the proportion of patients who experience the same mortality rate as the general population and can be estimated together with the survival of the proportion experiencing excess mortality (the uncured). The aim was to estimate the cure proportions and survival among uncured stage II-III cutaneous melanoma (CM) patients. Methods: 1- and 5-year relative survival ratios, cure proportions and the median survival times of uncured stage II-III CM patients in Sweden (n = 6466) were calculated based on data from the nationwide population-based Swedish Melanoma Register 2005-2013 with a follow-up through 2018. Results: Stages IIB and IIC showed significant differences in standardized cure proportions vs. stage IIA CM (0.80 (95% CI 0.77-0.83) stage IIA; 0.62 (95% CI 0.59-0.66) stage IIB; 0.42 (95% CI 0.37-0.46) for stage IIC). Significant differences in standardized cure proportions were found for stages IIIB and IIIC-D CM vs. stage IIIA (0.76 (95% CI 0.68-0.84) stage IIIA; 0.52 (95% CI 0.45-0.59) stage IIIB; 0.35 (95% CI 0.30-0.39) for stage IIIC-D). Conclusions: The results are emphasizing the poor prognosis with low proportions cured by surgery only for sub-groups of stage II-III CM, specifically within stages IIB-C CM.
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| 5. |
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| 6. |
- Hersi, Abdi-Fatah, et al.
(författare)
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Optimizing Dose and Timing in Magnetic Tracer Techniques for Sentinel Lymph Node Detection in Early Breast Cancers: The Prospective Multicenter SentiDose Trial
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Superparamagnetic iron oxide (SPIO) nanoparticles have comparable performance to the combination of radioisotope and blue dye (RI + BD) for sentinel lymph node (SLN) biopsy in breast cancer. In this multicenter prospective study, lower SPIO doses (undiluted 1.5 vs. 1.0 mL) in different timeframes (perioperative vs. 1-7 days preoperative) and injection sites (subareolar vs. peritumoral) were compared to the previous standard (diluted 2.0 mL perioperatively) from the earlier Nordic trial. RI + BD were co-administered as background. In total, 534 patients were analyzed. SPIO SLN detection rates were similar (97.5% vs. 100% vs. 97.6%, p = 0.11) and respectively non-inferior to the dual technique. Significantly more SLNs were retrieved in the preoperative 1.0 mL cohort compared with 1.5 mL and the Nordic cohorts (2.18 vs. 1.85 vs. 1.83, p = 0.003). Thus, SPIO at 1.5 and 1.0 mL was non-inferior to both Sienna+(R) and the dual technique for SLN detection. Superparamagnetic iron oxide nanoparticles (SPIO) are non-inferior to radioisotope and blue dye (RI + BD) for sentinel lymph node (SLN) detection. Previously, 2 mL SPIO (Sienna+(R)) in 3 mL NaCl was used. In this dose-optimizing study, lower doses of a new refined SPIO solution (Magtrace(R)) (1.5 vs. 1.0 mL) were tested in different timeframes (0-24 h perioperative vs. 1-7 days preoperative) and injections sites (subareolar vs. peritumoral). Two consecutive breast cancer cohorts (n = 328) scheduled for SLN-biopsy were included from 2017 to 2019. All patients received isotope +/- blue dye as back-up. SLNs were identified primarily with the SentiMag(R) probe and thereafter a gamma-probe. The primary endpoint was SLN detection rate with SPIO. Analyses were performed as a one-step individual patient-level meta-analysis using patient-level data from the previously published Nordic Trial (n = 206) as a third, reference cohort. In 534 patients, the SPIO SLN detection rates were similar (97.5% vs. 100% vs. 97.6%, p = 0.11) and non-inferior to the dual technique. Significantly more SLNs were retrieved in the preoperative 1.0 mL cohort compared with 1.5 and the 2.0 mL cohorts (2.18 vs. 1.85 vs. 1.83, p = 0.003). Lower SPIO volumes injected up to 7 days before the operation have comparable efficacy to standard SPIO dose and RI + BD for SLN detection.
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| 9. |
- Kiffin, Roberta, et al.
(författare)
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Anti-PD-1 checkpoint blockade improves the efficacy of a melphalan-based therapy in experimental melanoma
- 2021
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Ingår i: Ejso. - : Elsevier BV. - 0748-7983. ; 47:9, s. 2460-2464
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The induction of adaptive cellular immunity in patients with in-transit melanoma metastasis treated with hyperthermic isolated limb perfusion (ILP) with melphalan has been shown to contribute to the effectiveness of the therapy. Activated CD8(+) T cells appear to be of particular importance for the efficacy of melphalan-based ILP therapy, as observed in both patients and animal models. In this study, we explored the possible synergistic effects of combining melphalan-based therapy with the checkpoint inhibitor anti-PD-1 on tumours in a mouse melanoma model. Methods: A murine vaccination model that utilized melphalan-exposed melanoma cells was used to mimic certain immunological features of melphalan-based ILP. The effects of the vaccine on tumour growth and PD-1 expression on CD8(+) tumour-infiltrating T cells were analyzed. The melphalan-based vaccine was then combined with an anti-PD-1 antibody and tumour growth was assessed. Results: Treatment with melphalan-based therapy significantly induced the expression of PD-1 on CD8(+) tumour-infiltrating lymphocytes. Combination therapy using melphalan-based therapy followed by treatment with PD-1 antibodies significantly reduced early-stage tumour growth relative to mono-therapies and no treatment. Conclusions: This study thus suggests that the addition of PD-1 blockade to melphalan-based therapies, such as ILP, may be therapeutically beneficial. (C) 2021 Published by Elsevier Ltd.
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| 10. |
- Ny, Lars, 1967, et al.
(författare)
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The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The authors report the results of the phase II PEMDAC clinical study testing the combination of the HDAC inhibitor entinostat with the anti- PD-1 antibody pembrolizumab in uveal melanoma. Low tumor burden, a wildtype BAP1 gene in the tumor or iris melanoma correlates with response and longer survival. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.
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