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  • 1
    Online Resource
    Online Resource
    The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases – A multicenter cohort study
    Elsevier BV ; 2022
    In:  European Journal of Cancer Vol. 169 ( 2022-07), p. 210-222
    Details
    In: European Journal of Cancer, Elsevier BV, Vol. 169 ( 2022-07), p. 210-222
    Type of Medium: Online Resource
    ISSN: 0959-8049
    URL: Article
    DOI: 10.1016/j.ejca.2022.03.041
    RVK:
    XA 42017.A
    RVK:
    XA 42017
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1120460-6
    detail.hit.zdb_id: 1468190-0
    detail.hit.zdb_id: 82061-1
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  • 2
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    Pathology Review of Thin Melanoma and Melanoma in Situ in a Multidisciplinary Melanoma Clinic: Impact on Treatment Decisions
    American Society of Clinical Oncology (ASCO) ; 2010
    In:  Journal of Clinical Oncology Vol. 28, No. 3 ( 2010-01-20), p. 481-486
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 28, No. 3 ( 2010-01-20), p. 481-486
    Abstract: Patients with thin melanoma (≤ 1.0 mm) and melanoma in situ (MIS) represent the majority of newly diagnosed melanoma. We estimated the impact of expert review of outside pathology material on the staging and thus treatment decisions affecting patients referred to a multidisciplinary clinic with early-stage melanoma. Patients and Methods We studied patients with a diagnosis of thin melanoma or MIS referred to H. Lee Moffitt Cancer Center from 2006 to 2009. After comparing the referring laboratory and in-house dermatopathologic interpretations, we calculated any differences in diagnosis and tumor staging and the potential impact of differences in diagnosis and staging on prognosis and surgical treatment using the National Comprehensive Cancer Network clinical guidelines. Results The overall pathologic discordance rate in diagnosis was 4% (15 of 420 patients; 95% CI, 2% to 6%). The overall change in tumor staging rate was 24% (97 of 405 patients; 95% CI, 20% to 28%). Pathology review led to changes in surgical excision margins in 12% of patients (52 of 420 patients; 95% CI, 9% to 16%) and in the decision about whether to perform a sentinel lymph node biopsy in 16% of patients (67 of 420 patients; 95% CI, 13% to 20%). Key pathologic factors, particularly mitotic rate, were frequently missing from outside pathology reports. Conclusion Our data suggest that review of thin melanoma or MIS by an expert dermatopathologist results in frequent, clinically meaningful alterations in diagnosis, staging, prognosis, and surgical treatment. Referral of these patients to a multidisciplinary melanoma clinic is appropriate, and management of such patients should include review of the biopsy whenever feasible.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2009.24.7734
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2010
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma
    Elsevier BV ; 2017
    In:  European Journal of Cancer Vol. 75 ( 2017-04), p. 47-55
    Details
    In: European Journal of Cancer, Elsevier BV, Vol. 75 ( 2017-04), p. 47-55
    Type of Medium: Online Resource
    ISSN: 0959-8049
    URL: Article
    DOI: 10.1016/j.ejca.2017.01.009
    RVK:
    XA 42017.A
    RVK:
    XA 42017
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 1120460-6
    detail.hit.zdb_id: 1468190-0
    detail.hit.zdb_id: 82061-1
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  • 4
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    Single-cell Characterization of the Cellular Landscape of Acral Melanoma Identifies Novel Targets for Immunotherapy
    American Association for Cancer Research (AACR) ; 2022
    In:  Clinical Cancer Research Vol. 28, No. 10 ( 2022-05-13), p. 2131-2146
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 28, No. 10 ( 2022-05-13), p. 2131-2146
    Abstract: Acral melanoma is a rare subtype of melanoma that arises on the non–hair-bearing skin of the palms, soles, and nail beds. In this study, we used single-cell RNA sequencing (scRNA-seq) to map the transcriptional landscape of acral melanoma and identify novel immunotherapeutic targets. Experimental Design: We performed scRNA-seq on nine clinical specimens (five primary, four metastases) of acral melanoma. Detailed cell type curation was performed, the immune landscapes were mapped, and key results were validated by analysis of The Cancer Genome Atlas (TCGA) and single-cell datasets. Cell–cell interactions were inferred and compared with those in nonacral cutaneous melanoma. Results: Multiple phenotypic subsets of T cells, natural killer (NK) cells, B cells, macrophages, and dendritic cells with varying levels of activation/exhaustion were identified. A comparison between primary and metastatic acral melanoma identified gene signatures associated with changes in immune responses and metabolism. Acral melanoma was characterized by a lower overall immune infiltrate, fewer effector CD8 T cells and NK cells, and a near-complete absence of γδ T cells compared with nonacral cutaneous melanomas. Immune cells associated with acral melanoma exhibited expression of multiple checkpoints including PD-1, LAG-3, CTLA-4, V-domain immunoglobin suppressor of T cell activation (VISTA), TIGIT, and the Adenosine A2A receptor (ADORA2). VISTA was expressed in 58.3% of myeloid cells and TIGIT was expressed in 22.3% of T/NK cells. Conclusions: Acral melanoma has a suppressed immune environment compared with that of cutaneous melanoma from nonacral skin. Expression of multiple, therapeutically tractable immune checkpoints were observed, offering new options for clinical translation.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-21-3145
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 5
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    Differential gene expression in liposarcoma: Insight into pathways for dedifferentiation?
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 10048-10048
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 10048-10048
    Abstract: 10048 Background: Liposarcoma (LPS) dedifferentiation signifies conversion to a clinically aggressive phenotype, but the biologic processes required for this change have not been determined. We describe differential gene expression patterns between well-differentiated (WD) and dedifferentiated (DD) tumors to determine pathways involved in LPS dedifferentiation. Methods: From 1999 to 2006, 121 fatty tumors were resected at a single institution. Twenty tumors, consisting of atypical lipomatous tumors (ALT), WD LPS or DD LPS, were randomly selected and clinicopathologic characteristics were retrospectively reviewed. Gene expression profiling was performed on extracted RNA using the Affymetrix GeneChip platform. Differentially expressed genes were obtained and gene network analysis was done using GeneGO by MetaCore. Results: Median age was 59 years and 70% of cases were male. WD tumors, consisting of 3 ALT and 6 WD LPS, were compared with 11 DD LPS. After a median follow-up of 64 months, 7 patients had died of whom 6 had DD LPS. DD histology was associated with lower overall survival (p 〈 0.05). Significance Analysis of Microarrays for WD tumors vs. DD LPS using a 0% false discovery rate showed differential expression of 188 genes. Network analysis of genes from WD tumors vs. DD LPS showed significant (p 〈 0.001) differential regulation of glucose-activated transcription factor ChREBP (carbohydrate response element binding protein), a key element involved in lipogenesis, gluconeogenesis and glycolysis. There was also significant differential regulation of insulin signaling, PI3K-dependent and PKA signal transduction pathways and of amino acid, fatty acid and glucose metabolism pathways (p 〈 0.05). These pathways, based on Gene Ontology cellular processes, mapped to gene networks primarily involved in lipid metabolism (p 〈 0.05). Conclusions: Differential expression of genes involved in lipid metabolism networks is seen in DD LPS and changes in lipid metabolism may be associated with dedifferentiation. These differential gene expression patterns may help identify fatty tumors potentially at risk for progressing to a malignant or DD state and provide prognostic factors and therapeutic targets for patients with LPS.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.10048
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 6
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    International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Annals of Surgery Vol. 277, No. 5 ( 2023-05), p. e1106-e1115
    Details
    In: Annals of Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 277, No. 5 ( 2023-05), p. e1106-e1115
    Abstract: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. Summary Background Data: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. Methods: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. Results: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. Conclusions: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.
    Type of Medium: Online Resource
    ISSN: 0003-4932
    URL: Article
    DOI: 10.1097/SLA.0000000000005370
    RVK:
    XA 23900
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2002200-1
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  • 7
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    Final report of a pilot trial combining ipilimumab and adoptive cell therapy.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 7_suppl ( 2017-03-01), p. 147-147
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 7_suppl ( 2017-03-01), p. 147-147
    Abstract: 147 Background: We previously confirmed the feasibility of adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) for patients with advanced melanoma. Patients successfully treated had a 38% response rate, but patient attrition due to progression before ACT (21%) resulted in a response rate of only 26% based on intent to treat (IIT) analysis. We hypothesized that combination immunotherapy would decrease attrition due to progression. Here we present the final report of a pilot trial combining ipilimumab (IPI) and ACT. Methods: Thirteen patients with metastatic melanoma were accrued to an IRB-approved trial. All had 〉 1 cm 3 of soft tissue/nodal metastases amenable to resection leaving residual disease. Patients received 3 mg/kg of IPI two weeks prior to tumor resection for TIL generation. One week following resection, a second dose of IPI was administered. ACT included pre-conditioning chemotherapy and TIL infusion followed by IL-2. Two additional doses of IPI were given 2 and 5 weeks after ACT. Feasibility was a primary endpoint and considered achieved if ≥ 2 doses of IPI and TIL were infused to at least 60% of all patients. The clinical responses were assessed by RECIST 1.1 criteria at 12 weeks following TIL transfer. Results: All patients received at least 2 doses of IPI, and 12 of the 13 patients (92%) received TIL. One patient (7%) dropped out due to progression before TIL infusion. TIL were expanded from 47.2% of tumor fragments and 58.7% of these fragments generated TIL reactive to autologous tumor. Median number of infused TIL was 6.5e10 (2.29e10-1.04e11) and median 85% were CD8+ (27-99). At 12 weeks following infusion, of the 13 patients enrolled, there were 6 responders (46%). Median progression-free survival was 7.4 months (1.4-42.2). Grade ≥3 immune-related adverse events included colitis (1), uveitis (1), and hypothyroidism (1). Conclusions: IPI combined with ACT with TILs for patients with advanced melanoma is feasible with decreased attrition due to progression and is associated with promising clinical results based upon ITT analysis. This combination approach of TIL cell therapy and co-inhibitory blockade serves as a model for future efforts to improve the efficacy of immunotherapy for patients with cancer. Clinical trial information: NCT01701674.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.7_suppl.147
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    Clinicopathologic Predictors of Sentinel Lymph Node Metastasis in Thin Melanoma
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 35 ( 2013-12-10), p. 4387-4393
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 35 ( 2013-12-10), p. 4387-4393
    Abstract: Indications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of sentinel lymph node (SLN) metastasis in thin melanoma. Patients and Methods Retrospective review of the Sentinel Lymph Node Working Group database from 1994 to 2012 identified 1,250 patients who had an SLNB and thin melanomas (≤ 1 mm). Clinicopathologic characteristics were correlated with SLN status and outcome. Results SLN metastases were detected in 65 (5.2%) of 1,250 patients. On univariable analysis, rates of Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, ulceration, and absence of regression differed significantly between positive and negative SLN groups (all P 〈 .05). These four variables and mitotic rate were used in multivariable analysis, which demonstrated that Breslow thickness ≥ 0.75 mm (P = .03), Clark level ≥ IV (P = .05), and ulceration (P = .01) significantly predicted SLN metastasis with 6.3%, 7.0%, and 11.6% of the patients with these respective characteristics having SLN disease. Melanomas 〈 0.75 mm had positive SLN rates of 〈 5% regardless of Clark level and ulceration status. Median follow-up was 2.6 years. Melanoma-specific survival was significantly worse for patients with positive versus negative SLNs (P = .001). Conclusion Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, and ulceration significantly predict SLN disease in thin melanoma. Most SLN metastases (86.2%) occur in melanomas ≥ 0.75 mm, with 6.3% of these patients having SLN disease, whereas in melanomas 〈 0.75 mm, SLN metastasis rates are 〈 5%. By using a 5% metastasis risk threshold, SLNB is indicated for melanomas ≥ 0.75 mm, but further study is needed to define indications for SLNB in melanomas 〈 0.75 mm.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2013.50.1114
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Patterns of histologic response to neoadjuvant targeted therapy in patients with BRAF mutant melanoma.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 9584-9584
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 9584-9584
    Abstract: 9584 Background: While BRAF and MEK inhibitors are approved for patients with BRAF V600 + unresectable/metastatic melanoma, their role in the neoadjuvant setting is less well defined. Results from small trials have noted robust response rates, but less is known about histological patterns of response in resected tumor specimens and relation to outcome in these patients (pts). Methods: In a retrospective study, we analyzed the clinical and pathologic patterns of response to neoadjuvant BRAF ± MEK inhibitor therapy in pts with locally advanced melanoma subsequently rendered disease free with surgery. Results: Twenty pts were identified, nine with stage IIIC and 11 with stage IV melanoma. Seven patients received neoadjuvant vemurafenib (VEM), 12 received dabrafenib + trametinib (D+T), and one encorafenib + binimetinib. The median duration of treatment was 7.8 months. Seven patients (35%) had a pathologic complete response (pCR); six of them had received combination therapy, 5 with D+T, 1 VEM with an HSP90 inhibitor. Four distinct histologic patterns were observed in the resected tumor specimens: necrotic, fibrotic/melanotic (tumoral melanosis), hyalinized, or mixed. With median follow-up of 25 months (range 1-60), six pts (30%) had experienced recurrence; three developed CNS metastases. Four of the six patients had received neoadjuvant D+T; three were restarted on their prior targeted therapy at recurrence and all responded. All 6 pts with recurrence had residual disease in the surgical specimen; three had no necrosis identified. In contrast to the 13 pts with persistent tumor, none of the 7 pCR pts has relapsed (p = 0.05). There was a trend towards improved relapse-free-survival (RFS) with a pCR, with a 1 yr of RFS-rate of 50.4% vs 100% in pCR.(p = 0.08) Of the 14 patients without subsequent recurrence, 9 had either a pure necrotic histology, or a mixed histological pattern that included necrosis. Conclusions: In locally advanced or M1a BRAF mutant melanoma, attaining a pCR to neoadjuvant targeted therapy may correlate with improved patient outcomes and be more likely achieved with combination therapy. Presence of necrosis in the surgical specimen appears be a favorable prognostic factor.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.9584
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Online Resource
    Routine Omission of Sentinel Lymph Node Biopsy for Merkel Cell Carcinoma ≤ 1 cm Is Not Justified
    American Society of Clinical Oncology (ASCO) ; 2010
    In:  Journal of Clinical Oncology Vol. 28, No. 1 ( 2010-01-01), p. e7-e7
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 28, No. 1 ( 2010-01-01), p. e7-e7
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2009.25.9937
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2010
    detail.hit.zdb_id: 2005181-5
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