Forty-year prognosis after plaque brachytherapy of uveal melanoma

Stålhammar, Gustav

doi:10.1038/s41598-020-68232-7

Cited by 36 publications

(39 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The maximum estimate is 38 years between tumor initiation and diagnosis, and 15 years from diagnosis to metastatic death for an overall course of 53 years. Later metastases are rare 3 , 22 . Note: The presence of micrometastases does not necessarily imply a worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…It is the most common primary intraocular malignancy in adults, affecting approximately 5 individuals per million per year worldwide 2 . More than one third of patients suffer from metastatic spread, after which the median survival is less than 1 year 3 , 4 . Gene expression profiles are of great value in stratifying patient prognosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Estimation of the timing of BAP1 mutation in uveal melanoma progression

Uner

See

Szalai

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

Uveal melanoma is the most common primary intraocular malignancy. A vast majority of metastasizing tumors have mutations in the BAP1 gene. Here, we investigate the spatiotemporal timing of these mutations. The size of 177 uveal melanomas and 8.3 million individual tumor cells was measured. BAP1 sequencing results and BAP1 IHC were available and for 76 (43%) and 101 (57%) of these, respectively. Tumors with a BAP1 mutation had significantly larger volume (2109 vs. 1552 mm3, p = 0.025). Similarly, tumor cells with loss of BAP1 protein expression had significantly larger volume (2657 vs. 1593 μm3, p = 0.027). Using observations of the time elapsed between mitoses, the BAP1 mutation was calculated to occur when the primary tumor had a size of a few malignant cells to 6 mm3, 0.5 to 4.6 years after tumor initiation and at least 9 years before diagnosis. We conclude that BAP1 mutations occur early in the growth of uveal melanoma, well before the average tumor is diagnosed. Its timing coincides with the seeding of micrometastases.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Estimation of the timing of BAP1 mutation in uveal melanoma progression

Uner

See

Szalai

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…The association between advancing age and mortality in patients diagnosed with ocular cancers is inherently complex and multi-faceted. 14 Progressive age allows additional time for increased propensities of metastatic spread, direct extension into the ciliary body, tumor growth, and all-cause mortality. 14 , 15 In addition, a later age at diagnosis likely indicates delayed therapeutic implementation.…”

Section: Discussionmentioning

confidence: 99%

“… 14 Progressive age allows additional time for increased propensities of metastatic spread, direct extension into the ciliary body, tumor growth, and all-cause mortality. 14 , 15 In addition, a later age at diagnosis likely indicates delayed therapeutic implementation. 4 Chromosomal aberrations contribute to underlying genetic predispositions to malignant behaviors and tend to manifest at later ages when decreased efficacy of cellular repair and genomic stability take greater precedence.…”

Section: Discussionmentioning

confidence: 99%

Impact of Therapy & Age in Choroidal Cancers: A Retrospective Cohort Analysis of 7722 Patients from a US National Database

Hussain¹,

Khan²,

Ali³

2021

OPTH

View full text Add to dashboard Cite

Background Collectively, choroidal cancers represent a vast array of histopathologically diverse constituencies with profound repercussions related to mortality and metastasis. Prognosticated factors provide utility in determining clinical management and outcome propensities. To date, measures to collectively characterize choroidal cancers as a class are not impressive. This study aims to shed light on the affiliation of age and therapeutic modalities to survival in patients diagnosed with choroidal cancers. Methods Cohort analysis using the Surveillance, Epidemiology, and End Results (SEER) program, a freely accessible population-based database, was executed from 1975 to 2016, a 41-year time window. Univariable and multivariable Cox regression assessed survival with age and various therapeutic modalities as primary independent variables. Adjustment for several demographical and clinical variables was performed. Results This cohort consisted of 7722 patients at the time of diagnosis. Multivariable Cox regression demonstrated increased cause-specific hazards of 71.8% for patients aged 75+ years (HR = 1.718, CI 1.155–2.555, p < 0.008) as compared to patients aged 0–24 years. 16.2% and 58.0% increases in cause-specific mortality were showcased in patients diagnosed with 8770/3: mixed epithelioid and spindle cell melanoma (HR = 1.16, p = 0.029) and 8771/3: epithelioid cell melanoma of the choroid (HR = 1.580, p < 0.001) compared to individuals diagnosed with 8720/3: malignant melanoma NOS of the choroid. Chemotherapy significantly influenced survival in patients with choroidal cancers compared to those who did not receive chemotherapy or had an unknown status (HR = 0.377, CI 0.292–0.486, p < 0.001). Conclusion Like most cancers, choroidal cancers showcase poor clinical trajectory with advanced age. Specific ICD-O-3 histological subtypes predispose to increased mortality. Therapeutic modalities such as radioactive implants and chemotherapeutic agents demonstrate decreased cause-specific mortality compared to alternative treatments. Altogether, nuanced influences of age and therapy are revealed when evaluating choroidal cancers as a class, irrespective of subtype.

show abstract

“…Two to four percent of patients have detectable metastases at the time of diagnosis [ 2 ]. At a later stage however, more than one third of patients develop unvaryingly fatal metastatic disease [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression

Stålhammar

Grossniklaus

2021

Cancers

Self Cite

View full text Add to dashboard Cite

Malignant tumors are rarely homogenous on the morphological, genome, transcriptome or proteome level. In this study, we investigate the intratumor heterogeneity of BAP-1 expression in uveal melanoma with digital image analysis of 40 tumors. The proportion of BAP-1 positive cells was measured in full tumor sections, hot spots, cold spots and in scleral margins. The mean difference between hot spots and cold spots was 41 percentage points (pp, SD 29). Tumors with gene expression class 1 (associated with low metastatic risk) and 2 (high metastatic risk) had similar intratumor heterogeneity. Similarly, the level of intratumor heterogeneity was comparable in tumors from patients that later developed metastases as in patients that did not. BAP-1 measured in any tumor region added significant prognostic information to both American Joint Committee on Cancer (AJCC) tumor size category (p ≤ 0.001) and gene expression class (p ≤ 0.04). We conclude that there is substantial intratumor heterogeneity in uveal melanoma BAP-1 expression. However, it is of limited prognostic importance. Regardless of region, analysis of BAP-1 expression adds significant prognostic information beyond tumor size and gene expression class.

show abstract

Forty-year prognosis after plaque brachytherapy of uveal melanoma

Cited by 36 publications

References 21 publications

Estimation of the timing of BAP1 mutation in uveal melanoma progression

Estimation of the timing of BAP1 mutation in uveal melanoma progression

Impact of Therapy & Age in Choroidal Cancers: A Retrospective Cohort Analysis of 7722 Patients from a US National Database

Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression

Contact Info

Product

Resources

About