Publications by authors named "Charlotta All-Eriksson"

10 Publications

  • Page 1 of 1

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries.

Br J Ophthalmol 2020 Sep 15. Epub 2020 Sep 15.

Pediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.

Background: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.

Methods: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.

Results: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease.

Conclusions: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316613DOI Listing
September 2020

Molecular profiling of driver events in metastatic uveal melanoma.

Nat Commun 2020 04 20;11(1):1894. Epub 2020 Apr 20.

Sahlgrenska Cancer Center, Departments of Surgery, Oncology or Transplantation Surgery, Institute of Clinical Sciences at University of Gothenburg and Sahlgrenska University Hospital, Box 425, 40530, Gothenburg, Sweden.

Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has a high mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genes associated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease.
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http://dx.doi.org/10.1038/s41467-020-15606-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171146PMC
April 2020

Global Retinoblastoma Presentation and Analysis by National Income Level.

JAMA Oncol 2020 05;6(5):685-695

Imam Hussein Cancer Center, Karbala, Iraq.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.

Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis.

Design, Setting, And Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017.

Main Outcomes And Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis.

Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]).

Conclusions And Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.
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http://dx.doi.org/10.1001/jamaoncol.2019.6716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047856PMC
May 2020

Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): protocol for a multicenter phase II open label study.

BMC Cancer 2019 05 2;19(1):415. Epub 2019 May 2.

Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Blå stråket 2, 413 45, Gothenburg, Sweden.

Background: While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in metastatic uveal melanoma. Thus, metastatic uveal melanoma remains a disease with an urgent unmet medical need. Reports of treatment with immune checkpoint inhibitors have thus far been disappointing. Based on animal experiments, it is reasonable to hypothesize that the effect of immunotherapy may be augmented by epigenetic therapy. Proposed mechanisms include enhanced expression of HLA class I and cancer antigens on cancer cells, as well as suppression of myeloid suppressor cells.

Methods: The PEMDAC study is a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD1 inhibitor pembrolizumab and the class I HDAC inhibitor entinostat in adult patients with metastatic uveal melanoma. Primary endpoint is objective response rate. Eligible patients have histologically confirmed metastatic uveal melanoma, ECOG performance status 0-1, measurable disease as per RECIST 1.1 and may have received any number of prior therapies, with the exception of anticancer immunotherapy. Twenty nine patients will be enrolled. Patients receive pembrolizumab 200 mg intravenously every third week in combination with entinostat 5 mg orally once weekly. Treatment will continue until progression of disease or intolerable toxicity or for a maximum of 24 months.

Discussion: The PEMDAC study is the first trial to assess whether the addition of an HDAC inhibitor to anti-PD1 therapy can yield objective anti-tumoral responses in metastatic UM.

Trial Registration: ClinicalTrials.gov registration number: NCT02697630 . (Registered 3 March 2016). EudraCT registration number: 2016-002114-50.
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http://dx.doi.org/10.1186/s12885-019-5623-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498539PMC
May 2019

Ruthenium-106 versus iodine-125 plaque brachytherapy of 571 choroidal melanomas with a thickness of ≥5.5 mm.

Br J Ophthalmol 2020 01 25;104(1):26-32. Epub 2019 Mar 25.

St. Erik Eye Hospital, Stockholm, Sweden

Background: Episcleral brachytherapy is the most common eye-preserving treatment for medium-sized choroidal melanomas. γ-emitting iodine-125 (I) and β-emitting ruthenium-106 (Ru) are widely used. The latter is however generally reserved for thinner tumours (<6 mm). In this study, we compare ocular and patient survival in thicker tumours treated with the respective radioisotope.

Methods: All patients with ≥5.5 mm thick choroidal melanomas who were treated with plaque brachytherapy at a single institution between 1 November 1979 and 31 December 2015 were included (n=571). Size-controlled Cox regression HRs for postbrachytherapy enucleation, repeated brachytherapy and melanoma-related mortality were calculated, as well as Kaplan-Meier disease-specific survival and relative 10-year survival in matched subgroups.

Results: 317 patients were treated with Ru and 254 with I. The rate of repeated brachytherapy was significantly higher among patients treated with Ru (8%) than with I (1%, p<0.001). Size-controlled Cox regression HRs for postbrachytherapy enucleation (I vs Ru 0.7, p=0.083) and melanoma-related mortality were not significant (I vs Ru 1.1, p=0.63). Similarly, Kaplan-Meier disease-specific and relative 10-year survival was comparable in matched groups of 5.5-7.4 mm (relative survival Ru 59%, I 56%) and ≥7.5 mm thick tumours (relative survival Ru 46%, I 44%).

Conclusions: Rates of repeated brachytherapy were significantly higher among patients treated with Ru versus I for thick choroidal melanomas. There were, however, no significant differences in rates of enucleation or patient survival.
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http://dx.doi.org/10.1136/bjophthalmol-2018-313419DOI Listing
January 2020

Intra-arterial chemotherapy for retinoblastoma in Sweden - evaluation of treatment efficacy and complications.

Acta Ophthalmol 2018 Dec 24;96(8):e1040-e1041. Epub 2018 Apr 24.

Department of Neuroradiology, Karolinska University Hospital Solna, Stockholm, Sweden.

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http://dx.doi.org/10.1111/aos.13796DOI Listing
December 2018

Tumour thickness, diameter, area or volume? The prognostic significance of conventional versus digital image analysis-based size estimation methods in uveal melanoma.

Acta Ophthalmol 2018 Aug 16;96(5):510-518. Epub 2018 Jan 16.

Ophthalmic Pathology and Oncology Service, St. Erik Eye Hospital, Stockholm, Sweden.

Purpose: The aim of this study was to compare conventional and novel size estimation methods' ability to predict survival in uveal melanoma (UM).

Methods: The study was designed as a retrospective consecutive chart review of patients with UM, enucleated between the years 1984 and 1993. Area and volume were estimated based on the largest histopathological cross-section, the second centroid theorem of Pappus and digital image analysis, correlated to overall and relative survival.

Results: Of 168 patients analysed, 20 (12%) of tumours were categorized as T1, 47 (28%) as T2, 67 (40%) as T3 and 19 (11%) as T4 (15 N/a). A total of 91 tumours with complete survival and measurement data were included and recategorized into small, medium and large volume groups. Increased separation of overall survival was seen compared with current American Joint Committee on Cancer T categories. Difference between the large and small volume groups was 8.6 years (p = 0.001), compared to a difference of 5.6 years (p = 0.091) between T1 and T4. Hazard ratio for all-cause mortality in the large versus small volume group was 2.6 compared to 1.9 for T4 versus T1. Relative survival rates for small, medium and large volumes were 62, 44 and 31% at 10 years, versus 50, 45, 56 and 0% for T1, T2, T3 and T4.

Conclusion: This study provides evidence that a novel UM volume estimation method might offer a practical and cost-efficient alternative to improve the prognostic value intrinsic to a tumour's size.
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http://dx.doi.org/10.1111/aos.13668DOI Listing
August 2018

[Melanoma in places other than the skin: eye and mucous membrane melanomas].

Lakartidningen 2017 05 9;114. Epub 2017 May 9.

Karolinska Institutet - institutionen för lärande, informatik, Stockholm, Sweden Karolinska Institutet - institutionen för lärande, informatik, Stockholm, Sweden.

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May 2017

Heterogenic final cell cycle by chicken retinal Lim1 horizontal progenitor cells leads to heteroploid cells with a remaining replicated genome.

PLoS One 2013 19;8(3):e59133. Epub 2013 Mar 19.

Department of Neuroscience, Uppsala University, Uppsala, Sweden.

Retinal progenitor cells undergo apical mitoses during the process of interkinetic nuclear migration and newly generated post-mitotic neurons migrate to their prospective retinal layer. Whereas this is valid for most types of retinal neurons, chicken horizontal cells are generated by delayed non-apical mitoses from dedicated progenitors. The regulation of such final cell cycle is not well understood and we have studied how Lim1 expressing horizontal progenitor cells (HPCs) exit the cell cycle. We have used markers for S- and G2/M-phase in combination with markers for cell cycle regulators Rb1, cyclin B1, cdc25C and p27Kip1 to characterise the final cell cycle of HPCs. The results show that Lim1+ HPCs are heterogenic with regards to when and during what phase they leave the final cell cycle. Not all horizontal cells were generated by a non-apical (basal) mitosis; instead, the HPCs exhibited three different behaviours during the final cell cycle. Thirty-five percent of the Lim1+ horizontal cells was estimated to be generated by non-apical mitoses. The other horizontal cells were either generated by an interkinetic nuclear migration with an apical mitosis or by a cell cycle with an S-phase that was not followed by any mitosis. Such cells remain with replicated DNA and may be regarded as somatic heteroploids. The observed heterogeneity of the final cell cycle was also seen in the expression of Rb1, cyclin B1, cdc25C and p27Kip1. Phosphorylated Rb1-Ser608 was restricted to the Lim1+ cells that entered S-phase while cyclin B1 and cdc25C were exclusively expressed in HPCs having a basal mitosis. Only HPCs that leave the cell cycle after an apical mitosis expressed p27Kip1. We speculate that the cell cycle heterogeneity with formation of heteroploid cells may present a cellular context that contributes to the suggested propensity of these cells to generate cancer when the retinoblastoma gene is mutated.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059133PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602602PMC
September 2013

Nuclear HER3 is associated with favorable overall survival in uveal melanoma.

Int J Cancer 2012 Mar 18;130(5):1120-7. Epub 2011 Jun 18.

Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.

HER3 is a member of the epidermal growth factor receptor (EGFR) family and is expressed in several types of cancer. Both the cytoplasmic and nuclear appearances of the receptor have been reported. Here, we investigate the expression and subcellular distribution of HER3 in uveal melanoma (UM) cells and tissues and its potential impact on clinical outcome of patients. Paraffin-embedded samples from 128 consecutive UM patients, enucleated without alternative treatment on UM diagnosis, were evaluated for HER3 using immunohistochemistry. Immunoreactivity was scored for frequency, intensity of positive cells, and subcellular distribution. The results were correlated with the established clinicopathological parameters using univariate and multivariate statistical analyses. HER3 expression was shown in 70% of the cases (89/128). This contrasts with the other EGFR family receptors (EGFR, HER2 and HER4) that are infrequently expressed in UM. Surprisingly, HER3 was found to be localized solely in the cell nuclei in 56 cases. The remaining 33 HER3 positive cases showed diffuse distribution (cytoplasmic ± nuclear). Nuclear HER3 was independently correlated with a more favorable overall survival (p = 0.043 and hazard ratio = 0.618) compared to cases with diffuse and/or no HER3. Nuclear localization of HER3 was also confirmed in fresh UM material and in UM cell lines. In conclusion, HER3 is frequently localized solely in the cell nuclei in UM and as such it predicts a more favorable overall survival.
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http://dx.doi.org/10.1002/ijc.26118DOI Listing
March 2012
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