Diagnosing and Treating Blastic Plasmacytoid Dendritic Cell Neoplasm in a Resource-Limited Setting.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with limited treatment options and poor prognosis. This case report presents the clinical course and management of a 62-year-old man with BPDCN in a resource-limited setting. The patient presented with constitutional symptoms and abnormal complete blood count findings. Initial treatment was performed with an acute lymphoblastic leukemia-based chemotherapy regimen, and the patient achieved complete remission, but the disease recurred 7 months after the initial diagnosis was confirmed in April 2022. The subsequent therapy was not effective, and the patient died during treatment. This case highlights the challenges in managing BPDCN and the need for further research to improve outcomes.

Trends in pediatric CNS tumors in Armenia: a multicenter retrospective study.

PURPOSE: Central nervous system (CNS) tumors are the most common solid malignancies in children worldwide, including in Armenia. The current study aims to analyze epidemiological data, treatment, and outcomes of children and young adults (≤25 years) with CNS tumors in Armenia during the last 26 years. METHODS: We collected data from pediatric and young adult patients treated in selected sites in Armenia from 1st January 1995 to 31st December 2020. Incidence by sex, age at diagnosis, time from first complaints to diagnosis, histopathology results, treatment strategies, complications, and overall survival (OS) rates were calculated. RESULTS: The multicenter data analysis revealed 149 patients with diagnosed primary CNS tumors over 26 years. Among them, 84 (56.4%) were male. The median age at diagnosis was 7 years (range, 3 months to 25 years), and the median time from the first complaints to diagnosis was 2 months (range, 1 week to 70 months). Medulloblastomas and other embryonal tumors (47), low-grade gliomas (32), and high-grade gliomas (22) were the most commonly diagnosed malignancies. Ependymomas, craniopharyngiomas, germ cell tumors, and other malignancies were observed in 22 patients. For 26 patients, no histopathological or radiological diagnosis was available. Follow-up information was available for 98 (65.8%) patients. The 5-year OS rate for the whole study group was 67.7%. CONCLUSION: Consistent with international data, embryonal tumors, and gliomas were the most commonly diagnosed CNS malignancies in Armenia. Multimodal treatment was often not available in Armenia during the study period, especially for early cases.

Opsoclonus-Myoclonus-Associated Neuroblastoma With Bone Marrow Metastases: What Would Be the Best Treatment Option?

A 1.9-year-old girl was presented to the hospital with dancing eye movements, ataxia, and behavioral disorders. The MRI showed a retroperitoneal tumor (transversal size: 3.9 x 2.5 cm, craniocaudal size: 4.6 cm) extending from T12 to L3 vertebral bodies (Figure), which was suspicious for neuroblastoma. Afterwards, biopsy of the lesion and bone marrow was performed. The initial pathological evaluation (CD56+, PHOX2B+, NKX2-, Ki67 50%-55%, NSE+, CD99-) of the tumor and bone marrow confirmed the diagnosis of poorly differentiated, high-risk neuroblastoma.

Pediatric Locally Advanced Synovial Sarcoma: What Would Be the Best Treatment Option?

KEY POINTS • Synovial sarcomas are often mistreated with unplanned tumor resection. • Attention from specialists early in the course of SS can minimize the risk of recurrence, metastases, and the necessity for resurgery, all of which are increased with unplanned tumor resection. • Chemotherapy alone does not provide sufficient local control of the tumor. • Resurgery, in conjunction with radiotherapy and chemotherapy, is the best choice of management for this patient.

The clinical impact of time to response in de novo accelerated-phase chronic myeloid leukemia.

We aimed to describe the impact of time to response on the outcomes of 75 patients with accelerated-phase chronic myeloid leukemia (CML-AP) at diagnosis. Patients had at least 1 feature of AP: blasts ≥15% (n = 2), basophils ≥20% (n = 19), platelets <100 × 109 /L (n = 7), cytogenetic clonal evolution (n = 34), or more than one factor (n = 13). Thirty-three patients received imatinib; 42 received a second-generation tyrosine kinase inhibitor (2GTKI) (19 dasatinib and 23 nilotinib). We used chi-square and Kaplan-Meier analyses to determine the impact of various degrees of molecular and cytogenetic response at early time points (3 and 6 months) on rates of overall cytogenetic and molecular response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS). After a median follow-up of 96 months (range: 18-224 months), the overall rate of complete cytogenetic response was 79%, of major molecular response, 71%, and of molecular reponse (MR)4.5, 59%. Patients who achieved a major cytogenetic response (MCyR) (n = 49) at 3 months had significantly better 3-year OS (94% vs 75%; P = .002), TFS (98% vs 73%; P < .001), EFS (93% vs 42%; P < .001), and FFS (83% vs 25%; P < .001) rates than patients who did not have MCyR at 3 months. Most (67%) who eventually achieved sustained MR4.5 had achieved MCyR at 3 months. In de novo CML-AP, early response at 3 and 6 months is a strong determinant of long-term outcome.

Identifying barriers to treatment of childhood rhabdomyosarcoma in resource-limited settings: A literature review.

We performed a literature review to examine barriers for rhabdomyosarcoma treatment in low-resource settings, and identified 29 articles from 14 middle-income countries, with none from low-income countries. Notable findings included inconsistent use of local control modalities, lack of diagnostics in some settings, and high rate of abandonment specifically in low middle-income countries. Reported limitations included lack of surgical expertise and/or radiation therapy, advanced stage of disease, and absence of health insurance. Although very poor outcomes were prevalent in several settings, good outcomes were achievable in others when multidisciplinary therapy and financial coverage of medical care were made available.

Novel insights and therapeutic interventions for pediatric osteosarcoma.

High-grade osteosarcomas are the most common primary malignant tumors of bone. With complete surgical resection and multi-agent chemotherapy up to 70% of patients with high-grade osteosarcomas and localized extremity tumors can become long-term survivors. The prognosis, however, is poor for patients with nonresectable, primary metastatic or relapsed disease. Outcome is essentially unchanged for three decades. Herein, we describe selected novel insights into the genomics, biology and immunology of the disease and discuss selected strategies, which hold promise to overcome the current stagnation in the therapeutic success in childhood osteosarcoma.

Malignancy-associated hemophagocytic lymphohistiocytosis in adults: Relation to hemophagocytosis, characteristics, and outcomes.

BACKGROUND: Malignancy-associated hemophagocytic lymphohistiocytosis (HLH) in adults is a highly lethal disorder. Knowledge gaps have resulted in under diagnosis or delayed diagnosis. METHODS: The University of Texas MD Anderson Cancer Center pathology database (1991-2014) was retrospectively interrogated for the keywords "hemophagocytosis" and/or "lymphohistiocytosis." Seventy-seven adult patients were identified. All had an underlying malignancy. Sixteen patients who had insufficient documentation were excluded. RESULTS: The majority of patients who had pathologic evidence of hemophagocytosis/lymphohistiocytosis had an incomplete workup to confirm or refute HLH using the 2004 HLH criteria (HLH-2004; n = 8 variables), which is a common problem in adult HLH. Only 13 of 61 patients (21%) met the HLH-2004 diagnostic criteria based on available retrospective data. To identify potentially missed cases of HLH, the published literature was reviewed, and selected additional variables known to be associated with adult HLH were selected, resulting in extended diagnostic criteria of 18 variables. Thirty-five patients met the extended criteria, and 33 had follow-up data available. The median overall survival of the 13 patients who met both the extended criteria and the HLH-2004 criteria was similar to that of the 20 patients who met the extended criteria but NOT the HLH-2004 criteria (1.43 vs 1.76 months, respectively; P = .34) indicating a similar underlying, aggressive, systemic process. Twenty-six patients did not meet either criteria, and 17 had follow-up data available. The median overall survival of the 17 patients who had pathologic hemophagocytosis or lymphohistiocytosis but met neither criteria was significantly superior to the survival of those who met both the extended criteria and the HLH-2004 criteria and those who met the extended criteria but not the HLH-2004 criteria (17.27 vs 1.43 vs 1.76, respectively; P = .002). CONCLUSIONS: The addition of diagnostic laboratory variables that are more easily and rapidly available in smaller institutions and primary care settings than the HLH-2004 variables may be a good surrogate to raise early suspicion of malignancy-associated HLH. Prospective validation is warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2857-2866. © 2016 American Cancer Society.

Validating the Sensitivity of High-Resolution Melting Analysis for JAK2 V617F Mutation in the Clinical Setting.

BACKGROUND: Janus kinase 2 (JAK2) plays an important role in normal hematopoietic growth factor signaling. The detection of the JAK2 V617F mutation (c.1849GNT, GTC → TTC) is crucial for the diagnosis of myeloproliferative neoplasm (MPN) and has become the essential criteria for diagnosis of MPN by the WHO. High-resolution melt (HRM) curve analysis is a nongel-based, closed-tube method, in which PCR amplification and subsequent analysis are sequentially performed in the well, making it more convenient than other scanning methodologies. METHODS: We evaluated JAK2 V617F mutation by HRM. Twenty-nine patients diagnosed with MPN were examined. We studied the analytical sensitivity of the HRM analysis using real-time polymerase chain reaction (PCR) for identifying the JAK2 V617F mutation. Additionally, the sensitivity of HRM analysis and allele-specific PCR (AS-PCR) assay was compared. RESULTS: The JAK2 V617F mutation was successfully discriminated at an abundance of 6% or above in HRM analysis. Both HRM analysis and AS-PCR showed 100% accuracy with detection limits of 6% and 2.5%, respectively. CONCLUSION: HRM analysis is a fast, simple, reliable, and nonexpensive method for the detection of the JAK2 V617F mutation. However, more validation of the detection limits of HRM analysis should be performed before declaration of the analytic sensitivity of the method.

Multiple relapses in high-grade osteosarcoma: when to stop aggressive therapy?

The prognosis after relapse of high-grade osteosarcoma is poor and complete resection of all tumors is essential for survival. A 6-year old was diagnosed with high-grade osteosarcoma and treated according to the COSS-96 protocol. Within 5 years from initial diagnosis, five osteosarcoma relapses occurred and every time it was possible to achieve complete surgical remission. Additional treatments included chemotherapy and dendritic cell-based cancer immune therapy. Since the end of therapy of the 5th relapse, he is alive for 11½ years. Our experience further supports that aggressive surgery can help to achieve long-term survival even in patients with multiple osteosarcoma relapses.

Barriers to access to cancer care for patients from the conflict-affected region of the Nagorno-Karabakh Republic: A qualitative study.

Access to essential health services is a basic human right, yet many cancer patients living in conflict-affected regions face multiple obstacles to service use. The (former) Nagorno-Karabakh Republic was a conflict-affected region in the South Caucasus populated predominantly by ethnic Armenians. Multiple acute armed conflicts, the recent military occupation of the region, and the prolonged military blockade of the Lachin Corridor (a humanitarian corridor connecting Nagorno-Karabakh to Armenia) exacerbated existing social, health, economic, and political fragilities in this region. As a result, cancer services were disrupted, with limited clarity on how the ongoing military blockade of a humanitarian corridor affected cancer patients' experiences of accessing cancer care locally and in bordering Armenia. Our study aimed to describe the experiences of patients from Nagorno-Karabakh in accessing the cancer care services they needed. We conducted remote semi-structured interviews with adult (aged ≥18 years) cancer patients receiving cancer care from three university hospitals in Armenia and face-to-face interviews with cancer care professionals from these hospitals. Interviews were conducted during the blockade of the Lachin Corridor between March and May 2023. Data were analysed thematically using a deductive approach. Twelve adult cancer patients (9 women) and 12 cancer care professionals participated. A key barrier to accessing cancer services was attributed to the Azerbaijani military occupation of the region and the blockade of a major roadway connecting Nagorno-Karabakh to Armenia. Patients talked in length about the challenges of finding transport and travelling long distances to reach essential cancer services in Armenia. Policies of free anti-cancer medication provision and decentralised medication supply were paused because of the military occupation, affecting patients' timely access to anti-cancer medication. Out-of-pocket expenses for treatment, anti-cancer medication, travel, and temporary accommodation in Armenia placed a significant financial burden on cancer patients, exacerbated by the humanitarian crisis. Conflict-affected regions blockaded by military forces lack the capacity and targeted support to sustain their essential health services and provide care to those in need of life-saving treatments. Coordinated action from national and international organisations and governments is urgently needed to enhance humanitarian assistance and healthcare support to patients, their families and wider communities affected by military blockades and armed conflicts.

First Global Summit on War and Cancer: The Hidden Impact of War on Cancer-Urging Global Action for Change.

The 1st Global Summit on War and Cancer (GSWC) united leaders, medical professionals, policymakers, and advocates to address cancer issues in conflict zones featuring speakers from around 50 countries.

Evaluating implementation of a hospital-based cancer registry to improve childhood cancer care in low- and middle-income countries.

PURPOSE: Cancer is a leading cause of global childhood mortality, affecting 400,000 children annually. While treatable with modern therapies, children living in low- and middle-income countries (LMICs) have limited access to care and lower survival rates. Hospital-based cancer registries (HBCRs) collect detailed patient information to critically evaluate and evolve care. The St. Jude Global Childhood Cancer Analytics Resource and Epidemiological Surveillance System (SJCARES) is a cloud-based HBCR network facilitating quality data collection of pediatric cancer. Wide variation in the success of implementation has warranted further research into the implementation approach, to create a sustainable and adaptable HBCR in LMICs. METHODS: Seven of 89 sites using the SJCARES registry were selected, stratified by global region and stage of implementation. Semi-structured interviews were conducted with key groups (clinicians, administrators, data clerks) using an interview guide developed from the Consolidation Framework for Implementation Research (CFIR). Interviews were conducted via a video-telephone software program and transcribed by a transcription service. Transcripts were thematically coded using rapid qualitative analysis. RESULTS: A total of 18 participants (11 clinicians, 4 administrators, 3 data clerks) were interviewed. Several barrier themes were identified, including: difficulty integrating the registry into existing workflow; lack of resources; lack of government or administrative support; and damaged, misplaced, or illegible medical records. Facilitator themes were identified, including: internal support for the registry; clear and extensive training; and dedicated support staff. CONCLUSION: Interviewed participants identified key barriers and facilitators to the implementation of the SJCARES registry across multiple phases. We plan to use these results to develop targeted implementation strategies including a readiness assessment tool to help guide more successful implementation of the SJCARES registry and other HBCRs in LMICs.

A Survival Analysis of Patients with Recurrent Epithelial Ovarian Cancer Based on Relapse Type: A Multi-Institutional Retrospective Study in Armenia.

BACKGROUND: Annually, approximately 200 new ovarian cancer cases are diagnosed in Armenia, which is considered an upper-middle-income country. This study aimed to summarize the survival outcomes of patients with relapsed ovarian cancer in Armenia based on the type of recurrence, risk factors, and choice of systemic treatment. METHODS: This retrospective case-control study included 228 patients with relapsed ovarian cancer from three different institutions. RESULTS: The median age of the patients was 55. The median follow-up times from relapse and primary diagnosis were 21 and 48 months, respectively. The incidence of platinum-sensitive relapse was 81.6% (186), while platinum-resistant relapse was observed in only 18.4% (42) of patients. The median post-progression survival of the platinum-sensitive group compared to the platinum-resistant group was 54 vs. 25 months (p < 0.001), respectively, while the median survival after relapse was 25 vs. 13 months, respectively; three- and five-year post-progression survival rates in these groups were 31.2% vs. 23.8%, and 15.1% vs. 9.5%, respectively (p = 0.113). CONCLUSIONS: Overall, despite new therapeutic approaches, ovarian cancer continues to be one of the deadly malignant diseases affecting women, especially in developing countries with a lack of resources, where chemotherapy remains the primary available systemic treatment for the majority of patients. Low survival rates demonstrate the urgent need for more research focused on this group of patients with poor outcomes.

Racial and Ethnic Variation in COVID-19 Vaccination Uptake Among Medicare Beneficiaries with Cancer History.

BACKGROUND: The purpose of this study was to estimate COVID-19 vaccination rate among Medicare beneficiaries with cancer history and determine whether COVID-19 vaccine uptake is higher among non-Hispanic White beneficiaries compared with racially and ethnically minoritized beneficiaries. METHODS: We used US representative, cross-sectional data from the Medicare Current Beneficiary Survey COVID-19 Winter 2021 Rapid Response Community Supplement Survey. A total of 1,863 respondents with self-reported cancer history (other than skin cancer) were included. The outcome was self-reported receipt of at least one coronavirus vaccine dose since vaccines became available. The key independent variable of interest was self-reported race and ethnicity. We applied sample weights to account for the survey design and provide population estimates to 9.6 million beneficiaries with cancer history. Weighted descriptive statistics and multivariable logistic regression analyses were conducted. RESULTS: During the first 4 months of vaccine availability, 69.6% of beneficiaries received at least one vaccine dose of which 65.4% had two vaccine doses. A larger proportion of non-Hispanic White beneficiaries (71.9%) had at least one vaccine dose compared with non-Hispanic Black (60.4%) and Hispanic (57.4%) beneficiaries. An estimated 30.4% of beneficiaries were still unvaccinated, that represents approximately 2.9 million unvaccinated beneficiaries with cancer history. Hispanic beneficiaries were 42% (OR: 0.58; 95% CI: 0.33-0.99; p = .048) less likely to be vaccinated compared with non-Hispanic White beneficiaries. CONCLUSIONS: Results indicate racial and ethnic differences in vaccine uptake among Medicare beneficiaries with cancer history. Effective strategies are needed to help increase vaccine confidence and uptake among adults with cancer history.

Investigating residual leukemic cells in acute lymphoblastic leukemia: a practical approach using a streamlined interphase fluorescence in situ hybridization method on cerebrospinal fluid.

INTRODUCTION: A precise diagnosis of central nervous system involvement in acute lymphoblastic leukemia (ALL) requires comprehensive knowledge of morphological analysis, with a focus on the quantity and quality of cells being examined. Some research has utilized techniques such as immunocytochemistry, flow cytometry, polymerase chain reaction (PCR), and interphase fluorescence in situ hybridization (iFISH) on cerebrospinal fluid (CSF) cytospin samples to detect any remaining leukemic cells in the CSF. To obtain reliable results using immunocytochemistry and flow cytometry, it is essential to use freshly collected specimens within a limited timeframe. At the same time, PCR requires a sufficient number of cells for DNA extraction. On the other hand, the iFISH procedure on CSF cytospin samples can be challenging and requires practice. Therefore, there is a need for a fast, easy method that will be affordable and marketable in laboratories where the above methods are not available, or the sample is insufficient to use those methods. METHODS: The samples were prepared by centrifugation of 1 mL aliquots of CSF collected into EDTA tubes. The CSF sample was centrifuged at 3000 rpm for 3 min, the supernatant was removed, and the pellet was placed in KCl hypotonic solution for 5 min at 37 °C. Other steps (fixation, hybridization, wash steps, and analysis) were the same as in the standard protocol for blood samples. The BCR-ABL1 rearrangements were performed and evaluated in 200 interphase cells. RESULTS: 90% of Ph(+) cells were found in CSF. CONCLUSION: We propose a significantly streamlined iFISH method for detecting blast/residual leukemic cells in acute lymphoblastic leukemia using CSF as a complementary test option.