A Perplexing Case of a Germ Cell Tumor: A Case Report.

Germ cell tumors (GCTs) are associated with pure gonadal dysgenesis or Swyer syndrome. Swyer syndrome usually presents with primary amenorrhea, streak ovaries, and mixed GCT. However, our patient presented with secondary amenorrhea, normal female external genitalia, and a mixed GCT. Constitutional karyotype was suggestive of 46,XY. Management comprised chemotherapy, followed by surgery. Histopathology was suggestive of dysgerminoma complicating a gonadoblastoma. The purpose of reporting this case is its rarity and the importance of diagnosing an XY karyotype, as the incidence of GCTs is higher in these patients.

Outcomes and prognostic variables of extracranial germ cell tumors in children and adolescents treated over a decade: A developing world perspective.

BACKGROUND: The purpose of this single-center study was to analyze the outcomes of extracranial germ cell tumors (GCTs) in children treated on a multimodality regimen. METHODS: Retrospective study of children (<18 years) with a histopathologically confirmed diagnosis of extracranial GCT over a period of 10 years (January 2009 to December 2018) treated on a uniform institution-based protocol consisting of both cisplatin- and carboplatin-based regimens. All completely excised teratomas and stage I gonadal tumors received no further therapy (low risk [LR]); stage IV ovarian, stage III-IV extragonadal GCTs received six cycles of chemotherapy (high risk [HR]), and the remaining received four cycles of chemotherapy (intermediate risk [IR]). RESULTS: A total of 297 children were treated with a female:male ratio of 1.72:1 and median age of 4 years. Forty-three children had pure teratomas. Gonadal GCTs (N = 180) were more common than extragonadal GCTs (N = 117) with ovary as primary site in 128 children (43%) and sacrococcygeal site being the commonest extragonadal location (N = 41; 14%). LR, IR, and HR disease were noted in 60 (20.2%), 125 (42%), and 112 (37.8%) patients, respectively. Three-fourths of ovarian tumors and half of testicular tumors operated prior to presentation needed upstaging. Forty-one patients relapsed and 43 children expired (disease-related: 33; toxic deaths: 9; unknown: 1). The 5-year event-free survival (EFS)/overall survival (OS) of malignant GCT (n = 254) was 72.50%/82.70%, respectively, with gonadal site (p = .001), LR and IR (p = .001) and nonmetastatic disease (p = .001) being favorable prognostic variables. CONCLUSIONS: The LR and IR GCTs in our cohort had an excellent outcome. A significant proportion of IR gonadal GCTs can be spared of systemic chemotherapy by adhering to strict surgical guidelines. In HR GCTs however, intensifying therapies to improve outcomes must be balanced against the risk of cumulative toxicity, more so in a resource-limited setting.

Safety and efficacy of concurrent carboplatin during full-dose craniospinal irradiation for high-risk/metastatic medulloblastoma in a resource-limited setting.

PURPOSE: To assess the safety and efficacy of concurrent carboplatin during craniospinal irradiation (CSI) in high-risk/metastatic medulloblastoma defined as either residual tumor >1.5 cm2 or leptomeningeal metastases. METHODS: This single-arm combined prospective (2005-2011) and retrospective (2011-2019) study was undertaken at a tertiary care cancer center in India. Following surgery, patients with newly diagnosed high-risk/metastatic medulloblastoma received concurrent carboplatin (35 mg/m2 ) for 15 days (day 1 to day 15) during CSI plus posterior fossa/tumor bed boost, followed by six cycles of standard adjuvant chemotherapy. RESULTS: All 97 patients completed their planned course of radiotherapy without interruptions, except for two (2.1%) patients who had brief gaps due to treatment-related toxicity. Grade 3-4 anemia, neutropenia, thrombocytopenia, and febrile neutropenia were seen in four (4.1%), 41 (42.2%) 21 (21.6%), and 18 (18.6%) patients, necessitating packed cell transfusion, granulocyte colony-stimulating factor, and platelet support in five (5.1%), 41 (42.2%), and five (5.1%) patients, respectively, during the concurrent phase. Following myelorecovery, 92 (94.9%) patients completed the planned six cycles of standard adjuvant systemic chemotherapy. There were no treatment-related deaths during the concurrent chemo-radiotherapy phase, while three (3.1%) toxic deaths were ascribed to adjuvant chemotherapy-related complications. At a median follow-up of 82 months, the 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 60.2% and 62.1%, respectively. On univariate analysis, leptomeningeal metastases (M0/M1 vs. M2/M3) and histological subtype (large cell/anaplastic vs. others) emerged as significant prognostic factors for survival. CONCLUSION: Addition of concurrent carboplatin to RT as radiosensitizing chemotherapy is a simple and effective way of treatment intensification in high-risk/metastatic medulloblastoma.

Childhood cancer survivorship and late effects: The landscape in India in 2020.

Survivorship care is a major area of focus in the holistic management of childhood cancer with current knowledge and information almost exclusively from high-income countries. In this review, we summarize the state of scientific knowledge, service delivery, advocacy initiatives, and research efforts in this field in India. Twenty-one single-center studies published until today (20 in the last decade) confirm some of the well-documented issues in childhood cancer survivors and highlight the high prevalence of hepatitis B and hepatitis C infection in our survivors. Heterogeneity in methodology, outcome metrics, and quality precludes drawing further conclusions, and the ongoing multicenter Indian Pediatric Oncology Group study would address this. Besides the usual model of follow-up clinics in hospital settings, innovative models of service delivery led by not-for-profit organizations are being developed. Advocacy initiatives driven by survivors and support groups are also under way. All of these portend a promising future.

Customized approach for upfront or delayed resection using radiological criteria in unilateral, nonmetastatic pediatric renal tumors: A prospective study.

BACKGROUND: The availability of robust, equivalent data regarding outcomes for upfront or delayed surgery for renal tumors in children leads to a dilemma in selecting the initial treatment. Imaging criteria associated with the probability of rupture or incomplete resection may provide a more objective assessment for customization for the timing of surgery. PROCEDURE: Eighty-three children with unilateral, nonmetastatic renal tumors were enrolled between January 2012 and April 2018. Upfront nephrectomy was performed in the absence or delayed surgery (after a biopsy and chemotherapy) in the presence of one or more imaging-based high-risk features, including perinephric spread or adjacent organ infiltration, tumors crossing the midline, intravascular thrombus, and extensive adenopathy. Post hoc analysis for interobserver concordance for high-risk imaging features was also performed. RESULTS: The upfront surgery group (19) had predominantly stage I or II diseases (89%) and the histological types were Wilms (13), non-Wilms (5) renal tumor, and an inflammatory lesion. The delayed surgery group had 60% with stage I or II diseases and the histological types were Wilms (60) and non-Wilms (4) tumor. In addition, high-risk pathology was identified in nine patients. Overall, 27 patients with Wilms tumors required radiotherapy and anthracycline because of stage III disease, including one in the immediate surgery group. The event-free and overall survival (OS) at a median follow-up of 39 months for Wilms tumor are 88% (95% confidence interval [CI]: 78.5-94.9%) and 89% (95% CI: 81.4-96.6%), 85.1% (95% CI: 73.8-93.4%) and 86.5% (95% CI: 77.4-95.8%) for the delayed, and 100% event-free survival as well as OS (P = .1) in the upfront surgery group. CONCLUSION: A customized approach pivoted on image-based high-risk features facilitates identification of patients with early-stage renal tumor when the timing of surgery is tailored. Moreover, non-Wilms tumor and high-risk pathology are also identified.

Very small embryonic-like stem cells (VSELs) detected in azoospermic testicular biopsies of adult survivors of childhood cancer.

BACKGROUND: Infertility is a known side-effect of oncotherapy in cancer survivors, and often compromises the quality of life. The present study was undertaken to detect very small embryonic-like stem cells (VSELs) in testicular biopsies from young adult survivors of childhood cancer who had azoospermia. VSELs have been earlier reported in human and mouse testes. They resist busulphan treatment in mice and potentially restore spermatogenesis when the somatic niche is restored by transplanting Sertoli or mesenchymal cells. VSELs also have the potential to differentiate into sperm in vitro. METHODS: The study had clearance from Institutional review board (IRB). Seven azoospermic survivors of childhood cancer were included in the study after obtaining their informed consent. Semen analysis was done to confirm azoospermia prior to inclusion in the study. Testicular biopsies were performed at the Uro-oncology Unit of the hospital and then used for various studies to detect VSELs. RESULTS: Hematoxylin and Eosin stained tubular sections confirmed azoospermia and smears revealed the presence of very small, spherical VSELs with high nucleo-cytoplasmic ratio, in addition to the Sertoli cells. Immuno-localization studies on testicular smears showed that the VSELs were CD133+/CD45-/LIN-, expressed nuclear OCT-4, STELLA and cell surface SSEA-4. Pluripotent transcripts Oct-4A, Nanog and Sox-2 were detected in azoospermic samples whereas marked reduction was observed in germ cell markers Oct-4 and Boule. CONCLUSIONS: The present study demonstrates the presence of pluripotent VSELs in the testicular biopsy of azoospermic adult survivors of childhood cancer. It is likely that these persisting VSELs can restore spermatogenesis as demonstrated in mice studies. Therefore, pilot studies need to be undertaken using autologous mesenchymal cells with a hope to restore testicular function and fertility in cancer survivors. The results of this study assume a great significance in the current era, where cryopreservation of testicular tissue in young pre-pubertal boys for restoring spermatogenesis in adulthood is still in experimental stages.

Primary non-metastatic Ewing sarcoma of the jaw in children: results of surgical resection and primary reconstruction.

BACKGROUND AND OBJECTIVE: The rarity of Ewing sarcoma (ES) of the jaw coupled with the technical challenge of resection and associated functional and cosmetic impairment has resulted in deficient data on surgical management of these tumors. The purpose of this study is to describe the results of surgical excision and reconstruction of primary non-metastatic ES of the mandible and maxilla in children. METHODS: Consecutive patients (mandible = 6, maxilla = 5) treated with surgery from August 2005 to January 2013 were selected. All patients received induction chemotherapy and were selected for surgical resection based on the presence of specific criteria for operability. RESULTS: The median age was 11.5 years (range 5-16 years). Free fibular osteocutaneous flap was commonly used for reconstruction. There were no complications related to microvascular anastomosis or flap loss. Five patients had 100% tumor necrosis and did not receive radiotherapy. Teeth alignment, chewing, swallowing, and speech were normal in all and donor site morbidity occurred in one. The 5-year overall, event-free survival, and local control are 87.5%, 72.9%, and 90%, respectively. CONCLUSION: In eligible patients, surgery with contemporary reconstruction results in optimal oncological and functional outcome. Surgery also has the added advantage of identifying patients who may not need radiotherapy.

Outcome and morbidity of surgical resection of primary cervical and cervicothoracic neuroblastoma in children: a comparative analysis.

INTRODUCTION: Primary cervical (CN) and cervicothoracic neuroblastoma (CTN) is generally associated with good outcome; however, surgical resection can be challenging and not without morbidity. The aim of this study is to assess the overall outcome and compare the clinico-radiological features, treatment, and complications of CN and CTN. MATERIALS AND METHODS: Sixteen consecutive patients, (CN = 9, CTN = 7) treated between November 2006 and December 2012 were selected from the prospective database for this analysis. RESULTS: The 2-year overall and event-free survival of entire cohort is 100 and 72 %, respectively. Respiratory symptoms due to compression of airway and intraspinal extension were common in CTN. Gross total resection was feasible in all patients with CN; in contrast, incomplete excision along with significantly longer duration of surgery and more blood loss occurred in CTN. Postoperative morbidity was seen in three patients with CN and only one patient with CTN. The extent of surgery did not affect the overall and event-free survival of CTN (p = NS). CONCLUSION: CN and CTN have characteristic clinico-radiological presentation and surgical specification. However, both have a favorable outcome, even though with a distinct but acceptable morbidity. The favorable outcome in CTN is unrelated to the extent of surgical excision.

Oncofertility and Pregnancy in Adolescent and Young Adult Cancers: Physicians' Knowledge and Preferences in India.

PURPOSE: The treatment outcomes of adolescent and young adult (AYA) cancers have improved with advanced oncology care. Hence, fertility preservation (FP) and post-therapy pregnancies (PTPs) become vital issues. MATERIALS AND METHODS: An online survey link with 17 questions regarding oncofertility and PTPs was circulated among oncologists to assess the knowledge, understand the oncofertility care patterns, and seek suggestions to improve oncofertility services. RESULTS: The median age of 179 respondents, predominantly medical oncologists (68.7%), was 37 years (IQR, 10; range, 29-74), working in academic centers (39%) having a median experience of 4 years (IQR, 4; range, 1-42); 23 (12.8%) had dedicated AYA cancer units. Although a quarter (19%-24%) of respondents discussed fertility issues in >90% of AYA patients with cancer, only a tenth (8%-11%) refer >90% for FP, with significantly higher (P < .05) discussions and referrals in males and by more experienced oncologists (P < .05). Forty-six (25.6%) were not well versed with international guidelines for FP. Most (122, 68.1%) oncologists knew about the referral path for semen cryopreservation; however, only 46% were knowledgeable about additional complex procedures. One hundred and ten (61.5%) oncologists never or rarely altered the systemic treatment for FP. Prominent barriers to FP were ignorance, lack of collaboration, and fear of delaying cancer treatment. Lead thrust areas identified to improve FP practices are education, and enhanced and affordable access to FP facilities. Seventy-four (41.3%) respondents knew about international guidelines for PTPs; however, only half (20%) of them often monitored fertility outcomes in survivors. Oncologists have conflicting opinions and uncertainties regarding pregnancy safety, assisted reproductive techniques, breastfeeding, and pregnancy outcomes among survivors. CONCLUSION: Oncologists are uncertain about the guidelines, FP practices, referral pathways, and PTPs. Multipronged approaches to improve awareness and provision for affordable oncofertility facilities are needed to enhance AYA cancer outcomes in India, which will be applicable to other low- and middle-income countries too.

Can multiparametric MRI and FDG-PET predict outcome in diffuse brainstem glioma? A report from a prospective phase-II study.

PURPOSE: To study the impact of multiparametric MRI and (18)F-FDG-PET on the outcome of children with diffuse intrinsic pontine gliomas (DIPG). MATERIALS AND METHODS: Imaging data from a phase-II prospective therapeutic study in children with newly diagnosed DIPG were considered for evaluation. They included baseline MRI with contrast enhancement before treatment. Functional imaging included MR spectroscopy, MR perfusion and FDG-PET studies. All patients (n = 20) had baseline MRI and 11 patients had FDG-PET. Response was assessed by MRI and PET 4 weeks after therapy. Baseline imaging findings were correlated with survival. Presence or absence of adverse parameters on MRI (heterogeneous contrast enhancement, hyperperfusion or increased choline:NAA ratio) was used to develop a cumulative radiological prognostic index (RPI). Sensitivity and specificity of each imaging modality in tumour grading was estimated. RESULTS: The cumulative RPI was able to classify the patients into different grades and was predictive of overall survival (p = 0.02). MR perfusion also predicted survival (p = 0.039). Sensitivity and specificity of MRI and FDG-PET to detect low-grade gliomas were low to moderate (33-66%), but moderate to high in detecting high-grade gliomas (50-100%). Baseline FDG uptake on PET scan did not correlate with survival (p = 0.7). CONCLUSIONS: Cumulative RPI was able to classify tumours into different grades and predicted clinical outcome. At baseline, MR hyperperfusion indicated a shorter survival for DIPG patients. Sensitivity and specificity of imaging modalities to detect low-grade gliomas were poor.

Extraskeletal Ewing sarcoma in children and adolescents: impact of narrow but negative surgical margin.

PURPOSE: The aim of the study was to determine the impact of negative but close resection margins on local recurrence in children with extraskeletal Ewing sarcoma (EES). METHOD: We reviewed records of 32 patients with EES treated between March 2005 and March 2013. All patients except one underwent surgical excision either upfront or after induction chemotherapy. Patients with viable tumor and negative surgical margins, which were categorized as less than or greater than 1 cm, were selected. Local control and survival analysis were performed for patients in both the groups. RESULTS: The 5-year event-free and overall survival rates of entire cohort is 68 and 77 %, respectively. Surgical margins were negative in 23/26 (90.3 %) patients. There were no local recurrences in any of the patients with margins of less than 1 cm. Only one patient with a margin greater than 1 cm had a local recurrence along with distant metastases. A tumor-free margin of more than 1 cm did not affect overall or event-free survival (p = NS). CONCLUSION: Optimal local control is feasible in children with EES regardless of the quantitative extent of negative margins. Achieving a three-dimensional tumor-free margin should be the goal of surgical resection.

Current Challenges of Asian National Children's Cancer Study Groups on Behalf of Asian Pediatric Hematology and Oncology Group.

In Asia, a few countries have a long and established history of collaborative clinical trials successfully formed national children's cancer study groups, but many still do not have such groups. The process of forming national children's cancer groups is fraught with many hurdles, which varies among the countries. One of the basic requirements for running clinical trials is an affordable health care system in which most of the children with cancer can receive the proposed treatment. The health insurance coverage for children with cancer varies from <20% to as high as 100% among Asian countries, and the operation of clinical trials must also be adjusted accordingly. Shortage of research personnel is common, including medical, nursing, research coordinators, and data managers. The establishment of the Asian Pediatric Hematology and Oncology Group aims to provide a good platform for promotion of international clinical trials in the Asian countries.

Complete remission and long-term survival in a child with relapsed medulloblastoma with extensive osteosclerotic bony metastasis with a novel metronomic chemobiological approach.

Extraneural metastases in medulloblastoma are rare. We report a boy with medulloblastoma who was initially treated with gross total excision of primary tumor followed by radiotherapy. Six years later, he developed disseminated osteosclerotic bony relapse associated with bone marrow involvement. He was successfully salvaged with metronomic low-dose cyclophosphamide, etoposide, and zoledronic acid. In patients with medulloblastoma and bone pain, metastases to bone should be excluded, and medulloblastoma should be considered while investigating osteosclerotic bone lesions. Furthermore, metronomic chemotherapy should be considered in this setting until better therapeutic modalities emerge.

Long-Term Outcomes in Survivors of Childhood Cancer: A 30-Year Experience From India.

PURPOSE: Despite an increasing number of survivors of childhood cancer (CCS) in low- and middle-income countries, survivorship care is in its nascent stages. We describe the spectrum of late effects seen, challenges faced, and lessons learnt over three decades of a late effects program in India. METHODS: We describe the demographics and profile of late effects of all CCS survivors enrolled in our After Completion of Treatment Clinic from February 5, 1991 (inception) to February 4, 2021. We analyzed the trends by the decade of diagnosis. RESULTS: There were 3,067 CCS survivors, the median age was 18 years (range, 3-57 years), and the median follow-up was 11 years (range, 2-46 years). Two thirds (62.4%) had either no or mild late effects, 480 (15.6%), 497 (16.2%), and 162 (5.3%) had grades 2, 3, and 4 late effects, with 67 deaths reported. Notable late effects were chronic viral hepatitis (7.8%), thyroid dysfunction (7.5%), other endocrine issues (13.6%), psychosocial issues (57%), neurocognitive impairment (4.1%), and metabolic syndrome (4%). The cumulative incidence and severity of late effects showed a consistent decline by the decade of diagnosis. Twenty-two percent of survivors are lost to follow-up. CONCLUSION: Survivors of childhood cancer treated on contemporary treatment protocols have a significantly lower side-effect profile. Attrition to long-term follow-up and psychosocial issues are significant concerns. Understanding the unique spectrum of late effects and establishing a holistic support system go a long way in ensuring the long-term physical and mental health and psychosocial concerns of childhood cancer survivors in low- and middle-income countries.

Radiation Therapy Dose Escalation in Unresectable Ewing Sarcoma: Final Results of a Phase 3 Randomized Controlled Trial.

PURPOSE: Our aim was to assess the effect of radiation therapy (RT) dose escalation on outcomes in surgically unresectable Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET). METHODS AND MATERIALS: Patients with nonmetastatic unresectable ES/PNET (excluding intracranial/chest wall) receiving vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide chemotherapy, planned for definitive RT, were accrued in this single-institution, open-label, phase 3 randomized controlled trial. Randomization was between standard dose RT (SDRT; 55.8 Gy/31 fractions/5 days a week) versus escalated dose RT (EDRT; 70.2 Gy/39 fractions/5 days a week) with a primary objective of improving local control (LC) by 17% (65%-82%). Secondary outcomes included disease-free survival (DFS), overall survival (OS), and functional outcomes by Musculoskeletal Tumor Society score. RESULTS: Between April 2005 and December 2015, 95 patients (SDRT 47 and EDRT 48) with a median age of 17 years (interquartile range, 13-23 years) were accrued. The majority of patients were male (59%). Pelvis was the most common site of primary disease (n = 60; 63%). The median largest tumor dimension (9.7 cm) and the median maximum standardized uptake value (8.2) on pretreatment fluorodeoxyglucose positron emission tomography-computed tomography were similar. At a median follow-up of 67 months, the 5-year LC, DFS, and OS for the entire cohort was 62.4%, 41.3%, and 51.9%, respectively. The 5-year LC was significantly better in EDRT compared with SDRT (76.4% vs 49.4%; P = .02). The differences in DFS and OS at 5 years (for EDRT vs SDRT) did not achieve statistical significance (DFS 46.7% vs 31.8%; P = .22 and OS 58.8% vs 45.4%; P = .08). There was a higher incidence of Radiation Therapy Oncology Group grade >2 skin toxic effects (acute) in the EDRT arm (10.4% vs 2.1%; P = .08) with excellent functional outcomes (median Musculoskeletal Tumor Society score = 29) in both arms. CONCLUSIONS: EDRT results in improved LC with good functional outcomes without a significant increase in toxic effects. Radiation dose escalation should be considered for surgically unresectable nonmetastatic ES/PNET.

ISNO Position Statement on Treatment Guidance in Neuro-oncology During Pandemics.

The entire world including India is currently fighting the coronavirus disease 19 (COVID-19) pandemic that threatens to disrupt healthcare systems globally in terms of capacity and resources. This outbreak necessitates an urgent review of existing management guidelines for commonly encountered tumors of the brain and central nervous system (CNS). Such a review should include a reassessment of benefit-risk ratio to align with local, national, and international priorities without compromising on delivery of care in terms of safety, compassion, efficiency, and effectiveness. Towards this end, the Indian Society of Neuro-Oncology (ISNO) constituted an online expert panel with adequate representation from all major treatment modalities (neuro-surgery, radiation oncology, and pediatric/medical oncology) to formulate a "COVID-19 context" position statement to guide the care of neuro-oncology patients during the ongoing crisis. The ISNO position statement suggests graded prioritization (based on clinical presentation, type of tumor, expected prognosis, and relevance of immediate therapy) for efficient utilization of resources and provides a framework through a set of general considerations, treatment modality-based considerations, and disease-specific considerations for the guidance of healthcare professionals involved in the delivery of care and services to patients with CNS tumors. The views expressed herein represent the current consensus of key opinion leaders from within the Indian neuro-oncology community and should not be in any case considered binding medically or legally to individual physicians and/or hospitals who may formulate their guidelines based on local setup and health-environment and update them periodically based on emerging evidence through the COVID-19 pandemic.

A pragmatic clinicopathobiological grouping/staging system for gliomas: proposal of the Indian TNM subcommittee on brain tumors.

BACKGROUND: There is no universally accepted staging system for primary brain tumors wherein prognostication is mainly based on complex composite indices. AIM: To develop a simple, pragmatic, and widely applicable grouping/staging system for gliomas, the most common primary brain tumor. MATERIALS AND METHODS: An expert neurooncology panel with representation from radiation oncology, neurosurgery, pathology, radiology, and medical oncology had several rounds of discussion on issues pertinent to brain tumor staging. The trade off was between the accuracy of prognostic categorization and a pragmatic, widely applicable approach. RESULTS AND RECOMMENDATIONS: The Tumor-Node-Metastasis staging was considered irrelevant for gliomas that seldom metastasize to lymphatics or outside the neuraxis. Instead, a 4-point staging/grouping system is proposed, using histological grade as the main prognostic variable and at least one stage migration based on other unfavorable features such as tumor location (brainstem); age (<5 years for all grades, >50 years for high-grade, and >40 years for low-grade gliomas); poor neurological performance status (NPS 2-4); multicentricity and/or gliomatosis; and adverse biological parameters (proliferative index, angiogenesis markers, apoptotic index, cytogenetic abnormalities, and molecular markers). CONCLUSION: In absence of a grouping/staging system for primary brain tumors, prognostification is mostly based on complex composite indices. The proposed clinicopathobiological grouping/staging system for gliomas is a simple, pragmatic, and user-friendly tool with a potential to fulfill the objectives of staging classification.

RUNX1 aberrations in ETV6/RUNX1-positive and ETV6/RUNX1-negative patients: its hemato-pathological and prognostic significance in a large cohort (619 cases) of ALL.

A large-cohort study (619) of acute lymphoblastic leukemia (ALL) revealed an ETV6/RUNX1 (previously known as TEL/AML1) incidence of 18% in pediatric B-cell precussor ALL, indicating no geographical heterogeinity. Association of CD34-negative phenotype, peak incidence in the 3- to 7-year age group, and a comparatively low frequency of ETV6 homologue loss in ETV6/RUNX1-positive cases were distinct findings in this series. Additional genetic changes, such as ETV6 loss, extra RUNX1, ETV6/RUNX1 duplication, and MLL aberrations in the ETV6/RUNX1-positive group, supported the hypothesis of the ETV6/RUNX1 leukemogenic model that these secondary changes are necessary for leukemogenesis rather than progression of disease. This study disclosed RUNX1 alterations in the ETV6/RUNX1-negative group of BCP-ALL that encourages the investigation of RUNX1 at a large scale with longer follow-up, which will focus on the prognostic importance and the underlying biology of disease.

Models of Care for Survivors of Childhood Cancer From Across the Globe: Advancing Survivorship Care in the Next Decade.

With improvements in cancer treatment and supportive care, a growing population of survivors of childhood cancer at risk for significant and potentially life-threatening late effects has been identified. To provide a current snapshot of the models of care from countries with varying levels of resources and health care systems, stakeholders in childhood cancer survivorship clinical care and research were identified from 18 countries across five continents. Stakeholders responded to a survey and provided a brief narrative regarding the current state of survivorship care. Findings indicate that among pediatric-age survivors of childhood cancer (allowing for differences in age cutoffs across countries), resources are generally available, and a large proportion of survivors are seen by a physician familiar with late effects in most countries. After survivors transition to adulthood, only a minority are seen by a physician familiar with late effects. Despite the need to improve communication between pediatric oncology and primary care, only a few countries have existing national efforts to educate primary care physicians, although many more reported that educational programs are in development. These data highlight common challenges and potential solutions for the lifelong care of survivors of childhood cancer. Combining risk-based and patient-oriented solutions for this population is likely to benefit both providers and patients.