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Article ; Online: Toxicity and feasibility of vincristine, etoposide, and carboplatin alternating with vincristine, doxorubicin, and cyclophosphamide in children with advanced retinoblastoma in Guatemala.

Graff, Zachary / Giron, Veronica / Miller, Kristen / Pixtun, Dyna / Alejos, Amanda / Luna-Fineman, Sandra

2023 Volume 70, Issue 7, Page(s) e30392

Abstract: Retinoblastoma is highly curable, with event-free survival (EFS) of greater than 95% in high-income countries. However, in lower middle-income countries, outcomes of EFS are 30%-60% due to delayed diagnosis and lack of resources resulting in extra-ocular ...

Abstract	Retinoblastoma is highly curable, with event-free survival (EFS) of greater than 95% in high-income countries. However, in lower middle-income countries, outcomes of EFS are 30%-60% due to delayed diagnosis and lack of resources resulting in extra-ocular disease. We report the toxicity profile and outcomes of intensified therapy for advanced retinoblastoma: vincristine, etoposide, carboplatin (VEC) alternating with vincristine, doxorubicin, and cyclophosphamide (VDoCx) in Guatemala. Compared to VEC alone, similar rates of neutropenia, anemia, and thrombocytopenia were seen, with no toxic deaths. Although survival was not a primary objective, a modest survival benefit supports further investigation of VEC+VDoCx for advanced retinoblastoma.
MeSH term(s)	Child ; Humans ; Retinoblastoma/therapy ; Etoposide/therapeutic use ; Vincristine/therapeutic use ; Carboplatin/therapeutic use ; Guatemala ; Feasibility Studies ; Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Retinal Neoplasms/drug therapy
Chemical Substances	Etoposide (6PLQ3CP4P3) ; Vincristine (5J49Q6B70F) ; Carboplatin (BG3F62OND5) ; Cyclophosphamide (8N3DW7272P) ; Doxorubicin (80168379AG)
Language	English
Publishing date	2023-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.30392
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Article ; Online: Childhood cancer control during the COVID-19 pandemic.

Luna-Fineman, Sandra / Ortiz, Roberta / Ilbawi, Andre

The Lancet. Oncology

2021 Volume 22, Issue 10, Page(s) 1348–1350

MeSH term(s)	COVID-19 ; Child ; Delivery of Health Care ; Humans ; Neoplasms/epidemiology ; Neoplasms/therapy ; Pandemics/prevention & control ; SARS-CoV-2
Language	English
Publishing date	2021-10-11
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(21)00491-5
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Zs.A 5696: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Global Initiative for Childhood Cancer: progress and challenges in Panama.

Quintero, Karina / Berrio, Iveth / Arenas, Elsa / Fuentes-Alabí, Soad / Vásquez, Liliana / Luna-Fineman, Sandra / Victoria, Jorge / Houghton, Modesta

Revista panamericana de salud publica = Pan American journal of public health

2023 Volume 47, Page(s) e154

Abstract: Despite being classified as a high-income country, Panama still faces challenges in providing care for children and adolescents with cancer. Annually, 170 new cases of childhood cancer are diagnosed in Panama, and the survival rate is around 60%. To ... ...

Abstract	Despite being classified as a high-income country, Panama still faces challenges in providing care for children and adolescents with cancer. Annually, 170 new cases of childhood cancer are diagnosed in Panama, and the survival rate is around 60%. To improve this, the establishment of a Pediatric Cancer Commission comprised of healthcare professionals and nonprofit organizations has been a critical step toward the objectives outlined in the Cure
Language	English
Publishing date	2023-10-15
Publishing country	United States
Document type	Case Reports
ZDB-ID	1376934-0
ISSN	1680-5348 ; 1020-4989
ISSN (online)	1680-5348
ISSN	1020-4989
DOI	10.26633/RPSP.2023.154
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Zs.A 4694: Show issues

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Article: Single cell RNA-sequencing of Ewing sarcoma tumors demonstrates transcriptional heterogeneity and clonal evolution.

Goodspeed, Andrew / Bodlak, Avery / Nelson-Taylor, Sarah / Oike, Naoki / Porfilio, Timothy / Shirai, Ryota / Walker, Deandra / Treece, Amy / Black, Jennifer / Donaldson, Nathan / Cost, Carrye / Garrington, Tim / Greffe, Brian / Luna-Fineman, Sandra / Demedis, Jenna / Lake, Jessica / Danis, Etienne / Verneris, Michael / Hayashi, Masanori

bioRxiv : the preprint server for biology

2024

Abstract: Ewing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those ...

Abstract	Ewing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single cell RNA-sequencing to characterize the transcriptional landscape of primary Ewing sarcoma tumors and surrounding tumor microenvironment (TME). Copy-number analysis identified subclonal evolution within patients even prior to treatment. Primary tumor samples demonstrate a heterogenous transcriptional landscape with several conserved gene expression programs, including those composed of genes related to proliferation and EWS targets. We also were able to identify the composition of the TME and molecularly dissect the transcriptional profile of circulating tumor cells in peripheral blood at the time of diagnosis.
Language	English
Publishing date	2024-01-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.18.576251
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Article ; Online: Treatment of high-risk Hodgkin lymphoma with a modified Stanford V regimen in the AHOPCA: Substituting chemotherapy agents and hampered outcomes.

Luna-Fineman, Sandra / Castellanos, Mauricio / Metzger, Monika L / Baez, L Fulgencio / Peña Hernandez, Armando / Bonilla, Miguel / Fuentes-Alabi, Soad / Nieves, Rosa / Blanco, Jessica / Rossi, Emanuela / Devidas, Meenakshi / Chen, Yichen / Arreola, Magda / de Alarcon, Pedro A

Pediatric blood & cancer

2023 Volume 71, Issue 2, Page(s) e30792

Abstract: Background/objectives: High-risk Hodgkin lymphoma (HRHL) in children is curable with combined modality therapy. The Association of Pediatric Hematology-Oncology of Central America (AHOPCA) is a consortium of cancer centers from Central America. In 2004, ...

Abstract	Background/objectives: High-risk Hodgkin lymphoma (HRHL) in children is curable with combined modality therapy. The Association of Pediatric Hematology-Oncology of Central America (AHOPCA) is a consortium of cancer centers from Central America. In 2004, AHOPCA implemented a guideline with a short course of chemotherapy (mStanfordV), strict diagnostics, and radiation guidelines, aimed at reducing abandonment and improving outcomes. Methods: Newly diagnosed children less than 18 years of age with high-risk HL (Ann Arbor stages: IIB, IIIB, IV) from AHOPCA centers were staged with chest radiography and ultrasound or computed tomography. Therapy was a modified Stanford V (mStanfordV), substituting cyclophosphamide for mechlorethamine and involved field radiation. Results: Of 219 patients with HRHL, 181 patients were eligible and evaluable; 146 (81%) were boys, 22% being less than 6 years; 43 were stage IIB, 84 IIIB, and 54 IV. Thirty-one (17%) abandoned therapy, 28 (15%) progressed, 30 (17%) relapsed, and eight (4%) died of toxicity. Radiation guidelines were not followed. Five-year abandonment-sensitive event-free survival and overall survival (AS-EFS, AS-OS ± SE) for the cohort were 46% ± 4% and 56% ± 4%; 5-year AS-OS for stages IIB, IIIB, and IV was 76% ± 7%, 59% ± 7%, and 35% ± 7% (p = .0006). Conclusion: Despite instituting a short treatment guideline, it did not improve the abandonment rate (17%) and did not achieve the reported outcomes of Stanford V. The cyclophosphamide dose used to replace merchlorethamine was inadequate. Despite strict guidelines, the radiation therapy application was inaccurate. Weekly chemotherapy may have adversely affected abandonment of therapy by increasing the burden of travel time. Based on these results, AHOPCA established a new abandonment strategy and a new guideline.
MeSH term(s)	Male ; Child ; Humans ; Female ; Hodgkin Disease/drug therapy ; Hodgkin Disease/pathology ; Vincristine ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antineoplastic Agents/therapeutic use ; Cyclophosphamide ; Treatment Outcome ; Doxorubicin
Chemical Substances	Vincristine (5J49Q6B70F) ; Antineoplastic Agents ; Cyclophosphamide (8N3DW7272P) ; Doxorubicin (80168379AG)
Language	English
Publishing date	2023-12-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.30792
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Zs.A 1131: Show issues

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Article ; Online: Effects of malnutrition on treatment-related morbidity and survival of children with cancer in Nicaragua.

Pribnow, Allison K / Ortiz, Roberta / Báez, Luis Fulgencio / Mendieta, Luvy / Luna-Fineman, Sandra

Pediatric blood & cancer

2017 Volume 64, Issue 11

Abstract: Background: Most children with cancer live in resource-limited countries where malnutrition is often prevalent. We identified the relationship between malnutrition and treatment-related morbidity (TRM), abandonment of therapy, and survival of children ... ...

Abstract	Background: Most children with cancer live in resource-limited countries where malnutrition is often prevalent. We identified the relationship between malnutrition and treatment-related morbidity (TRM), abandonment of therapy, and survival of children with cancer in Nicaragua to better inform targeted nutritional interventions. Procedure: We conducted a retrospective review of patients aged 6 months to 18 years with newly diagnosed acute lymphoblastic leukemia, acute myeloid leukemia (AML), Wilms tumor, Hodgkin lymphoma, or Burkitt lymphoma (BL) who were treated between January 1, 2004, and December 31, 2007 at Children's Hospital Manuel de Jesus Rivera in Managua, Nicaragua. Statistical analysis examined the relations among nutritional status and cancer type, risk category, TRM, and event-free survival (EFS). Results: Sixty-seven percent of patients (189/282) were malnourished at diagnosis. Malnutrition was highest among patients with Wilms tumor (85.7%), BL (75%), and AML (74.3%). A total of 92.2% of patients (225/244) experienced morbidity during the first 90 days. Malnutrition was associated with severe infection (P = 0.033). Severely malnourished patients had ≥grade 3 TRM on more days (P = 0.023) and were more likely to experience severe TRM on >50% of days (P = 0.032; OR, 3.27 [95% CI, 1.05-10.16]). Malnourished patients had inferior median EFS (2.25 vs. 5.58 years; P = 0.049), and abandoned therapy more frequently (P = 0.015). Conclusions: In Nicaragua, pediatric oncology patients with malnutrition at diagnosis experienced increased TRM, abandoned therapy more frequently, and had inferior EFS. Standardized nutritional evaluation of patients with newly diagnosed cancer and targeted provision of nutritional support are essential to decrease TRM and improve outcomes.
MeSH term(s)	Adolescent ; Burkitt Lymphoma/etiology ; Burkitt Lymphoma/mortality ; Burkitt Lymphoma/therapy ; Child ; Child, Preschool ; Developing Countries ; Female ; Follow-Up Studies ; Hodgkin Disease/etiology ; Hodgkin Disease/mortality ; Hodgkin Disease/therapy ; Humans ; Infant ; Kidney Neoplasms/etiology ; Kidney Neoplasms/mortality ; Kidney Neoplasms/therapy ; Leukemia, Myeloid, Acute/etiology ; Leukemia, Myeloid, Acute/mortality ; Leukemia, Myeloid, Acute/therapy ; Male ; Malnutrition/complications ; Malnutrition/physiopathology ; Morbidity ; Neoplasm Staging ; Nicaragua ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Prognosis ; Retrospective Studies ; Survival Rate ; Wilms Tumor/etiology ; Wilms Tumor/mortality ; Wilms Tumor/therapy
Language	English
Publishing date	2017-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.26590
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Article ; Online: Wilms tumour.

Spreafico, Filippo / Fernandez, Conrad V / Brok, Jesper / Nakata, Kayo / Vujanic, Gordan / Geller, James I / Gessler, Manfred / Maschietto, Mariana / Behjati, Sam / Polanco, Angela / Paintsil, Vivian / Luna-Fineman, Sandra / Pritchard-Jones, Kathy

Nature reviews. Disease primers

2021 Volume 7, Issue 1, Page(s) 75

Abstract: Wilms tumour (WT) is a childhood embryonal tumour that is paradigmatic of the intersection between disrupted organogenesis and tumorigenesis. Many WT genes play a critical (non-redundant) role in early nephrogenesis. Improving patient outcomes requires ... ...

Abstract	Wilms tumour (WT) is a childhood embryonal tumour that is paradigmatic of the intersection between disrupted organogenesis and tumorigenesis. Many WT genes play a critical (non-redundant) role in early nephrogenesis. Improving patient outcomes requires advances in understanding and targeting of the multiple genes and cellular control pathways now identified as active in WT development. Decades of clinical and basic research have helped to gradually optimize clinical care. Curative therapy is achievable in 90% of affected children, even those with disseminated disease, yet survival disparities within and between countries exist and deserve commitment to change. Updated epidemiological studies have also provided novel insights into global incidence variations. Introduction of biology-driven approaches to risk stratification and new drug development has been slower in WT than in other childhood tumours. Current prognostic classification for children with WT is grounded in clinical and pathological findings and in dedicated protocols on molecular alterations. Treatment includes conventional cytotoxic chemotherapy and surgery, and radiation therapy in some cases. Advanced imaging to capture tumour composition, optimizing irradiation techniques to reduce target volumes, and evaluation of newer surgical procedures are key areas for future research.
MeSH term(s)	Child ; Humans ; Kidney Neoplasms/diagnosis ; Kidney Neoplasms/epidemiology ; Kidney Neoplasms/therapy ; Prognosis ; Wilms Tumor/diagnosis ; Wilms Tumor/epidemiology ; Wilms Tumor/therapy
Language	English
Publishing date	2021-10-14
Publishing country	England
Document type	Journal Article ; Review
ISSN	2056-676X
ISSN (online)	2056-676X
DOI	10.1038/s41572-021-00308-8
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Article ; Online: Circulating Plasma Tumor DNA Is Superior to Plasma Tumor RNA Detection in Ewing Sarcoma Patients: ptDNA and ptRNA in Ewing Sarcoma.

Bodlak, Avery / Chang, Kyle / Channel, Jessica / Treece, Amy L / Donaldson, Nathan / Cost, Carrye R / Garrington, Timothy P / Greffe, Brian / Luna-Fineman, Sandra / Sopfe, Jenna / Loeb, David M / Hayashi, Masanori

The Journal of molecular diagnostics : JMD

2021 Volume 23, Issue 7, Page(s) 872–881

Abstract: The detection of tumor-specific nucleic acids from blood increasingly is being used as a method of liquid biopsy and minimal residual disease detection. However, achieving high sensitivity and high specificity remains a challenge. Here, we perform a ... ...

Abstract	The detection of tumor-specific nucleic acids from blood increasingly is being used as a method of liquid biopsy and minimal residual disease detection. However, achieving high sensitivity and high specificity remains a challenge. Here, we perform a direct comparison of two droplet digital PCR (ddPCR)-based detection methods, circulating plasma tumor RNA and circulating plasma tumor DNA (ptDNA), in blood samples from newly diagnosed Ewing sarcoma patients. First, we developed three specific ddPCR-based assays to detect EWS-FLI1 or EWS-ERG fusion transcripts, which naturally showed superior sensitivity to DNA detection on in vitro control samples. Next, we identified the patient-specific EWS-FLI1 or EWS-ERG breakpoint from five patient tumor samples and designed ddPCR-based, patient-specific ptDNA assays for each patient. These patient-specific assays show that although plasma tumor RNA can be detected in select newly diagnosed patients, positive results are low and statistically unreliable compared with ptDNA assays, which reproducibly detect robust positive results across most patients. Furthermore, the unique disease biology of Ewing sarcoma enabled us to show that most cell-free RNA is not tumor-derived, although cell-free-DNA burden is affected strongly by tumor-derived DNA burden. Here, we conclude that, even with optimized highly sensitive and specific assays, tumor DNA detection is superior to RNA detection in Ewing sarcoma patients.
MeSH term(s)	Adolescent ; Biomarkers, Tumor/blood ; Biomarkers, Tumor/genetics ; Child ; Circulating Tumor DNA/blood ; Circulating Tumor DNA/genetics ; Circulating Tumor DNA/isolation & purification ; Female ; Humans ; Male ; Oncogene Proteins, Fusion/blood ; Oncogene Proteins, Fusion/genetics ; Polymerase Chain Reaction/methods ; Proto-Oncogene Protein c-fli-1/blood ; Proto-Oncogene Protein c-fli-1/genetics ; RNA, Neoplasm/blood ; RNA, Neoplasm/genetics ; RNA, Neoplasm/isolation & purification ; RNA-Binding Protein EWS/blood ; RNA-Binding Protein EWS/genetics ; Reproducibility of Results ; Sarcoma, Ewing/blood ; Sarcoma, Ewing/genetics ; Transcription Factors/blood ; Transcription Factors/genetics ; Translocation, Genetic
Chemical Substances	Biomarkers, Tumor ; Circulating Tumor DNA ; EWS-ERG fusion protein, human ; EWS-FLI fusion protein ; Oncogene Proteins, Fusion ; Proto-Oncogene Protein c-fli-1 ; RNA, Neoplasm ; RNA-Binding Protein EWS ; Transcription Factors
Language	English
Publishing date	2021-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2000060-1
ISSN	1943-7811 ; 1525-1578
ISSN (online)	1943-7811
ISSN	1525-1578
DOI	10.1016/j.jmoldx.2021.04.003
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Zs.A 5146: Show issues

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Article ; Online: Classic Hodgkin lymphoma in Guatemalan children of age less than six years: analysis of immune regulatory pathways and the tumor microenvironment.

Silva, Oscar / Charu, Vivek / Ewalt, Mark D / Metcalf, Ryan A / Zhao, Shuchun / Castellanos, E Mauricio / Orellana, Elizabeth / Natkunam, Yasodha / Luna-Fineman, Sandra

Leukemia & lymphoma

2021 Volume 62, Issue 7, Page(s) 1609–1618

Abstract: Classic Hodgkin lymphoma (cHL) in young children (ages 0-6) is rare in high income countries (HICs) but is more prevalent in low- and middle-income countries (LMICs) like Guatemala. Given that the majority of cHL studies have evaluated adolescent/adults, ...

Abstract	Classic Hodgkin lymphoma (cHL) in young children (ages 0-6) is rare in high income countries (HICs) but is more prevalent in low- and middle-income countries (LMICs) like Guatemala. Given that the majority of cHL studies have evaluated adolescent/adults, and the immune system changes with age, we sought to characterize Epstein-Barr virus (EBV) expression, immune regulatory pathway markers and the tumor microenvironment in 42 children ages 0-6 with cHL from Guatemala. We found a very high frequency of EBV expression (97.5%). Hodgkin cells showed increased expression of PD1 ligands and CD137, indicative of shared immune regulatory mechanisms with adult cHL. Pediatric cHL also showed an increase in CD8+ tumor infiltrating lymphocytes and tumor associated macrophages within the tumor microenvironment. Despite 25 having high risk disease, only 4 patients died from progressive disease, relapse or infection.
MeSH term(s)	Adolescent ; Adult ; Child ; Child, Preschool ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/epidemiology ; Herpesvirus 4, Human ; Hodgkin Disease/epidemiology ; Humans ; Infant ; Infant, Newborn ; Neoplasm Recurrence, Local ; Tumor Microenvironment
Language	English
Publishing date	2021-02-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2021.1885666
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Zs.A 2997: Show issues

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Article ; Online: Hodgkin lymphoma following adalimumab for the treatment of Crohn's disease in an adolescent.

Rodriguez, Alexis A / Kerner, John / Luna-Fineman, Sandra / Berry, Gerald J

Digestive diseases and sciences

2014 Volume 59, Issue 10, Page(s) 2403–2405

MeSH term(s)	Adalimumab ; Anti-Inflammatory Agents/adverse effects ; Anti-Inflammatory Agents/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Agents/therapeutic use ; Child ; Crohn Disease/drug therapy ; Female ; Hodgkin Disease/diagnosis ; Hodgkin Disease/drug therapy ; Hodgkin Disease/etiology ; Humans
Chemical Substances	Anti-Inflammatory Agents ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Adalimumab (FYS6T7F842)
Language	English
Publishing date	2014-05-10
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	304250-9
ISSN	1573-2568 ; 0163-2116
ISSN (online)	1573-2568
ISSN	0163-2116
DOI	10.1007/s10620-014-3191-6
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