Perspectives of non-physician partners on barriers and facilitators to AYA cancer care in Latin America.

BACKGROUND: Cancer is the fourth leading cause of death in adolescents and young adults (AYA) worldwide. Although successful treatment of cancer in AYA has increased in recent years in most of the world, this is not true for many low- and middle-income countries (LMIC) where over 80% of all AYA live. This study investigated the needs of AYA with cancer in parts of Latin America (LATAM) through the perspectives of non-physician health care providers and partners. METHODS: Semi-structured interviews (in Spanish) were conducted with non-physician partners from Mexico, Peru, Central America, and the Caribbean over Zoom. Participants were recruited through previously identified local physicians and international non-physician professionals working in these countries. Transcripts were coded and key themes identified until thematic saturation was reached (Atlas.ti). FINDINGS: Thirty participants representing eight countries were interviewed, providing 1202 min of transcript data. Data were organized into barriers, facilitators, and strategies to improve the delivery of health care for AYA with cancer in LATAM at the patient- (e.g., financial barriers, continued schooling), parent- (e.g., limited medical literacy, advocacy), and hospital-level (e.g., structural barriers, increasing funding). INTERPRETATION: There are many similarities in the barriers and facilitators to AYA care between LATAM and high-income countries (HIC); however, some characteristics are more unique to LATAM, for example, strict age restrictions for pediatric care and abandonment of therapy. As LATAM countries continue to build cancer control programs, there is an opportunity to consider our identified barriers, facilitators, and strategies to address the unique needs of AYA with cancer.

International Society of Paediatric Oncology (SIOP) Global Mapping Program: Analysis of healthcare centers in countries of the Latin American Society of Pediatric Oncology (SLAOP).

BACKGROUND: The International Society of Paediatric Oncology Society Global Mapping Program aims to describe the local pediatric oncology capacities. Here, we report the data from Latin America. METHODS: A 10-question survey was distributed among chairs of pediatric oncology services. Centers were classified according to patient volume into high- (HVC; 100 or more new cases per year), medium- (MVC; 31-99 cases), and low-volume centers (LVC; 30 cases or less), respectively. National referral centers (NRC) were identified. RESULTS: Total 307 centers in 20 countries were identified (271 responded), and 264 responses were evaluable, accounting for 78% of the expected cases (21,359 cases per year). Seventy-seven percent of patients are treated in public centers, including additional support by civil society organizations. We found that 66% of the patients are treated in 70 centers of excellence, including 21 NRC. There was a median of one pediatric oncologist every 21 newly diagnosed patients (44 for NRC), and in 84% of the centers, nurses rotated to other services. A palliative care team was lacking in 25% of the centers. LVC with public funding have significantly lower probability of having a palliative care team or trained pediatric oncology surgeons. Psychosocial, pharmacy, and nutrition services were available in more than 93% of the centers. No radiotherapy facility was available on campus in nine of 21 NRC. CONCLUSIONS: Most children with cancer in Latin America are treated in public HVC. There is a scarcity of pediatric oncologists, specialized nurses and surgeons, and palliative care teams, especially in centers with public funding.

International Society of Paediatric Oncology (SIOP) Global Mapping Programme: Latin American Society of Pediatric Oncology (SLAOP) country-level report.

BACKGROUND: Latin American countries are improving childhood cancer care, showing strong commitment to implement the Global Initiative for Childhood Cancer, but there are scant publications of the situation at a continental level. METHODS: As part of the International Society of Paediatric Oncology Global Mapping project, delegates of each country participating in the Latin American Society of Pediatric Oncology (SLAOP) and chairs of national pediatric oncology societies and cooperative groups were invited to provide information regarding availability of national pediatric cancer control programs (NPCCP), pediatric oncology laws, pediatric oncology tumor registries, and training programs and support to diagnosis and treatment. RESULTS: Nineteen of the 20 countries participating in SLAOP responded. National delegates reported nine countries with NPCCP and four of them were launched in the past 5 years. National pediatric tumor registries are available in eight countries, and three provided published survival results. Fellowship programs for training pediatric oncologists are available in 12 countries. National delegates reported that eight countries provide support to most essential diagnosis and treatments and 11 provide partial or minimal support that is supplemented by civil society organizations. Seven countries have a pediatric oncology law. There are three international cooperative groups and four national societies for pediatric oncology. CONCLUSION: Despite many challenges, there were dramatic advances in survivorship, access to treatment, and availability of NPCCP in Latin America. Countries with highest social development scores in general provide more complete support and are more likely to have NPCCP, training programs, and reported survival results.

The Effect of COVID-19 on Oncology Care for Adolescents and Young Adults in Latin America.

Children with cancer in low- and middle-income countries were disproportionately impacted by the COVID-19 pandemic, but little is known about how adolescents and young adults (AYAs) with cancer were affected. Sixty-seven physicians and nonphysician providers were interviewed about their experiences caring for AYAs with cancer in Latin America. Quotes related to the COVID-19 pandemic were identified and grouped into themes. Barriers from the COVID-19 pandemic included limited space, restrictions on travel, reduced funding, limited staff, limited services, and changes to treatment. However, improvements to care that arose from the COVID-19 pandemic included better access to distance learning and telemedicine.

Improving the Quality of the Delivery of Nutritional Care Among Children Undergoing Treatment for Cancer in a Low- and Middle-Income Country.

PURPOSE: International twinning programs have been well-established between institutions in childhood cancer and have led to pediatric cancer units in low- and middle-income countries (LMICs) adopting multidisciplinary forms of care. To advance nutritional care in LMICs, the International Initiative for Pediatrics and Nutrition (IIPAN) provided the structural framework and personnel for the delivery of nutritional care. We describe the impact of a newly established nutrition program on the delivery of nutritional care and nutrition-related clinical outcomes in children and adolescents undergoing treatment for cancer in Nicaragua and Honduras. METHODS: A prospective cohort (N = 126) collected clinical data over a 2-year period. Collection of IIPAN's nutritional services received during treatment and clinical data were abstracted from medical charts and registered in Research Electronic Data Capture (REDCap) database. Chi-square, ANOVA, and generalized linear mixed models were used; P < .05 was considered statistically significant. RESULTS: Nutritional assessments led to a higher number of patients receiving recommended standard of care. Children classified as underweight during treatment presented higher number of infections and toxicities, length of hospital stay, and days of treatment delays during treatment. Overall, from the start to end of treatment, 32.5% of patients improved nutritional status, 35.7% maintained it, and 17.5% worsened. On the basis of metrics, the cost per consultation was less than 4.80 US dollars (USD; Honduras) and 1.60 USD (Nicaragua). CONCLUSION: Integration and equitable access of the nutritional care process for all patients needs to be recognized as a component of the basic management in pediatric oncology care. IIPAN's nutritional program demonstrates that nutritional care is economical and feasible in a limited resource setting.

Interdisciplinary care of pediatric oncology patients: A survey of clinicians in Central America and the Caribbean.

BACKGROUND: Quality cancer care depends on interdisciplinary communication. This study explored the communication practices of interdisciplinary clinicians, the types of healthcare services for which they engage in interdisciplinary collaboration, and the association between interdisciplinary care and perceived quality of care, as well as job satisfaction. METHODS: We conducted a survey of interdisciplinary clinicians from cancer centers in Guatemala, Honduras, Panama, El Salvador, and Haiti. The survey included 68 items including previously validated tools and novel questions. RESULTS: Total 174 interdisciplinary clinicians completed the survey: nurses (n = 60), medical subspecialists (n = 35), oncologists (n = 22), psychosocial providers (n = 20), surgeons (n = 12), pathologists (n = 9), radiologists (n = 9), and radiation oncologists (n = 5). Oncologists reported daily communication with nurses (95%) and other oncologists (91%). While 90% of nurses reported daily communication with other nurses, only 66% reported daily communication with oncologists, and more than 50% of nurses reported never talking to pathologists, radiologists, radiation oncologists, or surgeons. Most clinicians described interdisciplinary establishment of cancer treatment goals and prognosis (84%), patient preferences (81%), and determination of first treatment modality (80%). Clinicians who described more interdisciplinary collaboration had higher job satisfaction (p = .04) and perceived a higher level of overall quality of care (p = .004). CONCLUSIONS: Clinicians in these limited resource settings describe strong interdisciplinary collaboration contributing to higher job satisfaction and perceived quality of care. However, nurses in these settings reported more limited interdisciplinary communication and care. Additional studies are necessary to further define clinical roles on interdisciplinary care teams and their associations with patient outcomes.

How should childhood acute lymphoblastic leukemia relapses in low-income and middle-income countries be managed: The AHOPCA-ALL study group experience.

BACKGROUND: Children with relapsed acute lymphoblastic leukemia (ALL) in low-income and middle-income countries rarely survive. The Pediatric Hematology-Oncology Association of Central America (AHOPCA) developed the AHOPCA-ALL REC 2014 protocol to improve outcomes in resource-constrained settings without access to stem cell transplantation. METHODS: The AHOPCA-ALL REC 2014 protocol was based on a modified frontline induction phase 1A, a consolidation therapy with six modified R-blocks derived from the ALL-Berlin-Frankfurt-Munster REZ 2002 protocol and intermittent maintenance therapy. Children with B-lineage ALL were eligible after a late medullary relapse, an early or late combined relapse, or any extramedullary relapses. Those with T-lineage ALL were eligible after early and late extramedullary relapses, as were those with both B-lineage and T-lineage relapses occurring at least 3 months after therapy abandonment. RESULTS: The study population included 190 patients with T-lineage (n = 3) and B-lineage (n = 187) ALL. Of those with B-lineage ALL, 25 patients had a very early extramedullary relapse, 40 had an early relapse (32 extramedullary and 8 combined), and 125 had a late relapse (34 extramedullary, 19 combined, and 72 medullary). The main cause of treatment failure was second relapse (52.1%). The 3-year event-free survival rate (± standard error) was 25.9% ± 3.5%, and the 3-year overall survival rate was 36.7% ± 3.8%. The 3-year event-free survival rate was 47.2% ± 4.7% for late relapses. The most frequently reported toxicity was grade 3 or 4 infection. Mortality during treatment occurred in 17 patients (8.9%), in most cases because of infectious complications. CONCLUSIONS: Selected children with relapsed ALL in Central America can be cured with second-line regimens even without access to consolidation with stem cell transplantation. Children in low-income and middle-income countries who have lower risk relapses of ALL should be treated with curative intent.

Impact of COVID-19 in pediatric oncology care in Latin America during the first year of the pandemic.

BACKGROUND: The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year. METHOD: Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners. RESULTS: Four hundred fifty-three pediatric onco-hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio [OR]: 1.84, 95% CI: 1.19-2.8), surgeries (OR: 3, 95% CI: 1.9-4.6) and radiotherapy (OR: 6, 95% CI: 3.5-10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR: 3, 95% CI: 1.4-6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6-7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability. CONCLUSION: Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.

Interdisciplinary care of pediatric oncology patients in Central America and the Caribbean.

BACKGROUND: Interdisciplinary teamwork supports high-quality cancer care and effective utilization of limited resources. This study purposed to examine the value, structure, process, and effectiveness of interdisciplinary care (IDC) among pediatric oncology providers in low-income and middle-income countries in Central America and the Caribbean. METHODS: A cross-sectional survey was disseminated to pediatric oncology providers at 5 centers participating in the Pediatric Hematology-Oncology Association of Central America. The survey included previously validated items and novel questions assessing the value (importance), structure (multidisciplinary meeting attendance), process (team climate), and effectiveness (job satisfaction, quality of care and communication) of IDC. RESULTS: The survey was completed by 174 providers, including 22 oncologists, 9 pathologists, 9 radiologists, 5 radiation oncologists, 12 surgeons, 35 subspecialists, 60 nurses, 20 psychosocial providers, and 2 other staff. Participants agreed that IDC benefits team members (95%) and patients (96%). IDC structure and processes varied across the region. Multidisciplinary meeting attendance differed by center (P = .005) and discipline (P < .0001). Participants who frequently attended multidisciplinary meetings reported a more positive team climate (P = .0003). Team climate was positively associated with job satisfaction (P < .001). In multivariable analyses, team climate was predictive of an improved perception of communication between professionals (P < .0001), with families (P < .0001), and with patients (P = .0005), as well as with quality of the care environment (P = .006) and overall care quality (P < .0001). CONCLUSIONS: Nearly all surveyed participants valued IDC, and the structure and processes supporting IDC varied by center. Associations between a collaborative professional climate, job satisfaction, and the perception of quality care encourage continued investigation and prioritization of IDC in these settings.

Delayed Enucleation With Neoadjuvant Chemotherapy in Advanced Intraocular Unilateral Retinoblastoma: AHOPCA II, a Prospective, Multi-Institutional Protocol in Central America.

PURPOSE: Treatment abandonment because of enucleation refusal is a limitation of improving outcomes for children with retinoblastoma in countries with limited resources. Furthermore, many children present with buphthalmos and a high risk of globe rupture during enucleation. To address these unique circumstances, the AHOPCA II protocol introduced neoadjuvant chemotherapy with delayed enucleation. PATIENTS AND METHODS: Patients with advanced unilateral intraocular disease (International Retinoblastoma Staging System [IRSS] stage I) were considered for upfront enucleation. Those with diffuse invasion of the choroid, postlaminar optic nerve, and/or anterior chamber invasion received six cycles of adjuvant chemotherapy (vincristine, carboplatin, and etoposide). Patients with buphthalmos and those with a perceived risk for enucleation refusal and/or abandonment were given two to three cycles of chemotherapy before scheduled enucleation followed by adjuvant chemotherapy to complete six cycles, regardless of pathology. RESULTS: A total of 161 patients had unilateral IRSS stage I disease; 102 underwent upfront enucleation, and 59 had delayed enucleation. The estimated 5-year abandonment-sensitive event-free and overall survival rates for the group were 0.81 ± 0.03 and 0.86 ± 0.03, respectively. The 5-year estimated abandonment-sensitive event-free survival rates for patients undergoing upfront and delayed enucleation were 0.89 ± 0.03 and 0.68 ± 0.06, respectively (P = .001). Compared with AHOPCA I, abandonment for patients with IRSS stage I retinoblastoma decreased from 16% to 4%. CONCLUSION: AHOPCA describes the results of advanced intraocular retinoblastoma treated with neoadjuvant chemotherapy. In eyes with buphthalmos and patients with risk of abandonment, neoadjuvant chemotherapy can be effective when followed by enucleation and adjuvant chemotherapy. Our study suggests that this approach can save patients with buphthalmos from ocular rupture and might reduce refusal of enucleation and abandonment.

Therapeutic targeting of the RB1 pathway in retinoblastoma with the oncolytic adenovirus VCN-01.

Retinoblastoma is a pediatric solid tumor of the retina activated upon homozygous inactivation of the tumor suppressor RB1 VCN-01 is an oncolytic adenovirus designed to replicate selectively in tumor cells with high abundance of free E2F-1, a consequence of a dysfunctional RB1 pathway. Thus, we reasoned that VCN-01 could provide targeted therapeutic activity against even chemoresistant retinoblastoma. In vitro, VCN-01 effectively killed patient-derived retinoblastoma models. In mice, intravitreous administration of VCN-01 in retinoblastoma xenografts induced tumor necrosis, improved ocular survival compared with standard-of-care chemotherapy, and prevented micrometastatic dissemination into the brain. In juvenile immunocompetent rabbits, VCN-01 did not replicate in retinas, induced minor local side effects, and only leaked slightly and for a short time into the blood. Initial phase 1 data in patients showed the feasibility of the administration of intravitreous VCN-01 and resulted in antitumor activity in retinoblastoma vitreous seeds and evidence of viral replication markers in tumor cells. The treatment caused local vitreous inflammation but no systemic complications. Thus, oncolytic adenoviruses targeting RB1 might provide a tumor-selective and chemotherapy-independent treatment option for retinoblastoma.

The My Child Matters programme: effect of public-private partnerships on paediatric cancer care in low-income and middle-income countries.

In low-income and middle-income countries, an excess in treatment failure for children with cancer usually results from misdiagnosis, inadequate access to treatment, death from toxicity, treatment abandonment, and relapse. The My Child Matters programme of the Sanofi Espoir Foundation has funded 55 paediatric cancer projects in low-income and middle-income countries over 10 years. We assessed the impact of the projects in these regions by using baseline assessments that were done in 2006. Based on these data, estimated 5-year survival in 2016 increased by a median of 5·1%, ranging from -1·5% in Venezuela to 17·5% in Ukraine. Of the 26 861 children per year who develop cancer in the ten index countries with My Child Matters projects that were evaluated in 2006, an estimated additional 1343 children can now expect an increase in survival outcome. For example, in Paraguay, a network of paediatric oncology satellite clinics was established and scaled up to a national level and has managed 884 patients since initiation in 2006. Additionally, the African Retinoblastoma Network was scaled up from a demonstration project in Mali to a network of retinoblastoma referral centres in five sub-Saharan African countries, and the African School of Paediatric Oncology has trained 42 physicians and 100 nurses from 16 countries. The My Child Matters programme has catalysed improvements in cancer care and has complemented the efforts of government, civil society, and the private sector to sustain and scale improvements in health care to a national level. Key elements of successful interventions include strong and sustained local leadership, community engagement, international engagement, and capacity building and support from government.

Improving our understanding of the use of traditional complementary/alternative medicine in children with cancer.

BACKGROUND: Children with cancer in high-income and low-income countries often use traditional complementary/alternative medicine (TCAM). With efforts by the World Health Organization and international twinning programs improving access to conventional care for patients with childhood cancer, understanding the global use of TCAM is important because reliance on TCAM may affect time to presentation, adherence, and abandonment of care. In the current study, the authors describe the process and validation of an international survey documenting the use of TCAM among children with cancer. METHODS: The survey was designed to collect information on TCAM use and associated factors through both open-ended and close-ended questions. During the period between June 2012 and December 2013, the survey was administered to 300 children and adolescents (or their parents) who were undergoing treatment for cancer at a collaborating institution located in Mexico, Uruguay, and Nicaragua. RESULTS: For the majority of constructs, the survey demonstrated strong test-retest reliability as evidenced by an intraclass correlation of at least ≥0.79 in each of the participating countries. The survey demonstrated good internal consistency and reliability across countries (α range from. 77 to. 85 for the belief scale; and an α range from. 60 to. 86 for the cause scale) and convergent validity between TCAM beliefs and behavior constructs (adjusted correlation range, 0.35-0.60). CONCLUSIONS: The results of the current study demonstrate the successful development of a cross-cultural survey that produced results that were reliable and valid. These findings will aid investigators in providing guidelines concerning TCAM, support the development of education and research priorities, and identify variables associated with TCAM that are region-specific.

Mucormycosis Rhinosinusitis at Diagnosis of Acute Lymphoblastic Leukemia: Diagnostics and Management Challenges in a Low-Middle-income Country.

We present the case of an adolescent with mucor rhinosinusitis diagnosed concomitantly with acute lymphoblastic leukemia at a hospital in Tegucigalpa, Honduras. We also discuss the challenges faced in the dual management of hematologic malignancies and invasive fungal disease in a low-middle-income country, such as access to diagnostics, immunosuppressants, imaging, and antifungals. Despite these shortcomings, the patient was successfully treated for both the diseases. Low-middle-income country hospitals can effectively treat invasive fungal diseases by providing adequate diagnostic and support services, which can improve the outcomes of pediatric cancer patients.

Outcome of children treated for relapsed acute myeloid leukemia in Central America.

BACKGROUND: Relapsed childhood acute myeloid leukemia (AML) outcomes have not been documented in resource-limited settings. We examined survival after relapse for children with AML (non-APML) and acute promyelocytic leukemia (APML) in Central America. PROCEDURE: We retrospectively evaluated outcomes of children with first relapse of AML (non-APML) and APML in Guatemala, Honduras, or El Salvador diagnosed between 1997 and 2011. Predictors of subsequent event-free survival (EFS) and overall survival (OS) were examined. RESULTS: We identified 140 children with relapsed AML (non-APML), and 24 with relapsed APML. Two-year subsequent EFS and OS (±SE) were 7.0 ± 2.5% and 9.1 ± 2.8%, respectively. Worse outcomes were associated with Hispanic or Indigenous heritage, white blood cell count at diagnosis ≥50 × 10(9) /L, and time to relapse <18 months. For those with relapsed APML, subsequent 2-year EFS and OS were 36.7 ± 10.8% and 43.4 ± 12.1%, although few patients survived beyond 3 years. 15.2% of all patients were managed solely with palliative intent following first relapse. CONCLUSIONS: Children with relapsed AML in Central America rarely survive, so palliative strategies should be considered following relapse in this population. However, children with late relapse or with APML may have a prolonged period of remission with second treatment, and consideration of re-treatment may be appropriate.

Outcome of children treated for relapsed acute lymphoblastic leukemia in Central America.

BACKGROUND: Outcomes for relapsed childhood acute lymphoblastic leukemia (ALL) have not been documented in resource-limited settings. This study examined survival after relapse for children with ALL in Central America. METHODS: A retrospective cohort study was performed and included children with first relapse of ALL in Guatemala, Honduras, or El Salvador between 1990 and 2011. Predictors of subsequent event-free survival (EFS) and overall survival (OS) were examined. RESULTS: There were 755 children identified with relapsed disease. The median time from diagnosis to relapse was 1.7 years (interquartile range, 0.8-3.1 years). Most relapses occurred during (53.9%) or following (24.9%) maintenance chemotherapy, and the majority occurred in the bone marrow (63.1%). Following the initial relapse, subsequent 3-year EFS (± standard error) and OS were 22.0% ± 1.7%, and 28.2% ± 1.9%, respectively. In multivariable analysis, worse postrelapse survival was associated with age ≥ 10 years, white blood cell count ≥ 50 × 10(9) /L, and positive central nervous system status at the original ALL diagnosis, relapse that was not isolated central nervous system or testicular, and relapse < 36 months following diagnosis. Site and time to relapse were used to identify a favorable risk group whose 3-year EFS and OS were 50.0% ± 8.9% and 68.0% ± 8.1%, respectively. CONCLUSIONS: Prognosis after relapsed ALL in Central America is poor, but a substantial number of those with favorable risk features have prolonged survival, despite lack of access to stem cell transplantation. Stratification by risk factors can guide therapeutic decision-making. Cancer 2013. © 2012 American Cancer Society.

Treatment-related mortality in children with acute myeloid leukaemia in Central America: incidence, timing and predictors.

BACKGROUND: Cure rates in paediatric acute myeloid leukaemia in low-income countries lag behind those in high-income countries, in part secondary to higher rates of treatment-related mortality. Patterns of treatment-related mortality are likely to differ between low and high-income centres. Understanding low-income setting patterns is necessary before effective interventions aimed at decreasing treatment-related mortality can be designed. Our aim was to describe the incidence, timing and predictors of treatment-related mortality among Central American children with acute myeloid leukaemia. PATIENTS AND METHODS: We evaluated patients younger than 21 years diagnosed with acute myeloid leukaemia from 2000 to 2008 in El Salvador, Honduras or Guatemala. Biologic, socioeconomic and nutritional variables collected prospectively were examined as potential predictors of treatment-related mortality. RESULTS: Among 279 patients, treatment-related mortality occurred in 65 (23%). Of 65 deaths, 51 (78.5%) occurred before or during induction, resulting in an early death rate of 18.3%. The most common causes of treatment-related mortality were infection (29/65; 45%) and haemorrhage (13/65; 20%). Infection accounted for 33% of treatment-related mortality before remission induction therapy versus 40% during induction and 77% after induction (P = 0.03). Rates of treatment-related mortality did not vary between time periods 1 and 2 (24.8% versus 21.4%; P = 0.32). Only lower initial platelet count predicted early death (odds ratio per 10 × 10(9)/L = 0.88, 95% Confidence Interval (CI) 0.79-0.97; P < 0.001). CONCLUSIONS: Treatment-related mortality remains a significant cause of treatment failure. Supportive care interventions are needed. Children presenting with low initial platelet counts were at highest risk of induction death, suggesting that transfusion practices should be evaluated.

Retinoblastoma in Central America: report from the Central American Association of Pediatric Hematology Oncology (AHOPCA).

BACKGROUND: Retinoblastoma is highly curable in high income countries. Low income countries have poor results due to advanced disease and lack of resources. Central American Association of Pediatric Hematology Oncology (AHOPCA) aimed to standardize the approach and to improve outcomes of patients with retinoblastoma. PROCEDURE: One hundred seventy-one patients, age <18 years newly diagnosed with retinoblastoma were treated according to laterality and stage. Therapeutic modalities were: surgery (enucleation), local control (laser therapy, cryotherapy), chemotherapy, and radiation therapy. Chemotherapy consisted of vincristine, etoposide, and carboplatin (6 cycles). Outcomes were measured by overall survival. Events were abandonment of therapy and death. RESULTS: One hundred seventy-one patients (129 unilateral, 42 bilateral) were treated. Median age was 2 years 4 months; 112 (66%) were diagnosed before 3 years of age. 119 (92%) eyes in patients with unilateral disease were Reese-Ellsworth IV or V versus 52 (62%) eyes in patients with bilateral disease. Extraocular disease was more prevalent in unilateral disease (65% vs. 50%). Older age at diagnosis correlated with higher stage. Estimated overall survival at 60 months was 0.48 ± 0.04. Outcome of patients with bilateral disease was significantly better than unilateral (62% ± 0.09 vs. 42% ± 0.05, P = 0.0006). Thirty-eight patients (22%) refused or abandoned therapy. CONCLUSIONS: Protocol-directed therapy for retinoblastoma in Central America is possible. Patients present with advanced disease and outcome is significantly worse than in middle and high-income countries. Refusal and abandonment of therapy are societal events that affect outcome. Initiatives aimed at improving early diagnosis, while dedicated treatment centers are developed, are critical.

Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.

It is widely believed that the molecular and cellular features of a tumor reflect its cell of origin and can thus provide clues about treatment targets. The retinoblastoma cell of origin has been debated for over a century. Here, we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell type-specific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Furthermore, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro.