Global Retinoblastoma Study Group IMPORTANCE Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.OBJECTIVES To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. DESIGN, SETTING, AND PARTICIPANTSA total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. MAIN OUTCOMES AND MEASURESAge at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. RESULTSThe cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI,, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI,). CONCLUSIONS AND RELEVANCEThis study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

No abstract

SummaryBackground Palonosetron has demonstrated efficacy in the prevention of chemotherapy-

Background WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare contiguous gene deletion syndrome with a 45% to 60% risk of developing Wilms tumor (WT). Currently, surveillance and treatment recommendations are based on limited evidence. Methods Clinical characteristics, treatments, and outcomes were analyzed for patients with WAGR and WT/nephroblastomatosis who were identified through International Society of Pediatric Oncology Renal Tumor Study Group (SIOP‐RTSG) registries and the SIOP‐RTSG network (1989‐2019). Events were defined as relapse, metachronous tumors, or death. Results Forty‐three patients were identified. The median age at WT/nephroblastomatosis diagnosis was 22 months (range, 6‐44 months). The overall stage was available for 40 patients, including 15 (37.5%) with bilateral disease and none with metastatic disease. Histology was available for 42 patients; 6 nephroblastomatosis without further WT and 36 WT, including 19 stromal WT (52.8%), 12 mixed WT (33.3%), 1 regressive WT (2.8%) and 2 other/indeterminable WT (5.6%). Blastemal type WT occurred in 2 patients (5.6%) after prolonged treatment for nephroblastomatosis; anaplasia was not reported. Nephrogenic rests were present in 78.9%. Among patients with WT, the 5‐year event‐free survival rate was 84.3% (95% confidence interval, 72.4%‐98.1%), and the overall survival rate was 91.2% (95% confidence interval, 82.1%‐100%). Events (n = 6) did not include relapse, but contralateral tumor development (n = 3) occurred up to 7 years after the initial diagnosis, and 3 deaths were related to hepatotoxicity (n = 2) and obstructive ileus (n = 1). Conclusions Patients with WAGR have a high rate of bilateral disease and no metastatic or anaplastic tumors. Although they can be treated according to existing WT protocols, intensive monitoring of toxicity and surveillance of the remaining kidney(s) are advised. Lay Summary WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare genetic condition with an increased risk of developing Wilms tumor. In this study, 43 patients with WAGR and Wilms tumor (or Wilms tumor precursor lesions/nephroblastomatosis) were identified through the international registry of the International Society of Pediatric Oncology Renal Tumor Study Group (SIOP‐RTSG) and the SIOP‐RTSG network. In many patients (37.5%), both kidneys were affected. Disease spread to other organs (metastases) did not occur. Overall, this study demonstrates that patients with WAGR syndrome and Wilms tumor can be treated according to existing protocols. However, intensive monitoring of treatment complications and surveillance of the remaining kidney(s) are advised.

Adrenocorticotropic hormone (ACTH)-secreting pancreatic neuroendocrine tumors (PanNETs), although rare, are responsible for about 15% of ectopic Cushing syndrome (CS). They represent a challenging entity because their preoperatory diagnosis is frequently difficult, and clear-cut morphologic criteria useful to differentiate them from other types of PanNETs have not been defined. Ectopic ACTH secretion associated with CS can also be rarely due to pancreatic acinar cell carcinoma (ACC) and pancreatoblastoma, rare tumor types with morphologic features sometimes overlapping those of PanNETs and, for this reason, representing a diagnostic challenge for pathologists. We herein describe the clinicopathologic and immunohistochemical features of 10 PanNETs and 1 ACC secreting ACTH and associated with CS together with an extensive review of the literature to give the reader a comprehensive overview on ACTH-producing pancreatic neoplasms. ACTH-secreting PanNETs are aggressive neoplasms with an immunohistochemical profile that partially overlaps that of pituitary corticotroph adenomas. They are generally large and well-differentiated neoplasms without distinctive histologic features but with signs of aggressiveness including vascular and perineural invasion. They are more frequent in female individuals with a mean age of 42 years. At 5 and 10 years after diagnosis, 35% and 16.2% of patients, respectively, were alive. ACTH-secreting ACCs and pancreatoblastomas are very aggressive pediatric tumors with a poor prognosis. Using an appropriate immunohistochemical panel including ACTH, β-endorphin, trypsin, and BCL10 it is possible to recognize ACTH-secreting PanNETs and to distinguish them from the very aggressive ACTH-secreting ACCs.

Thirty-five consecutive, previously untreated patients with intra-abdominal non-Hodgkin's lymphoma (IANHL), seen between January 1971 and June 1978, were entered on the LSA2-L2 protocol. Six patients had Stage II disease, 23 Stage III and six Stage IV. The prevalent histologic types were diffuse lymphocytic poorly differentiated (13 patients) and diffuse undifferentiated (13 patients) followed by diffuse histiocytic (5 patients) and diffuse lymphoblastic (2 patients). All patients received LSA2-L2 protocol chemotherapy. Three of 4 patients with gross residual disease following initial surgery, who were seen prior to 1974, received radiation therapy during induction chemotherapy; there were no survivors among these 3 patients. Our treatment plan was revised in 1974 to include a "second-look" laparotomy during the third week of induction chemotherapy for all patients with gross residual intra-abdominal disease following their initial surgery. The disease-free actuarial survival for the total group of 35 patients is 72%. Fifteen of the 26 surviving patients are off therapy and have shown no evidence of recurrence or metastases (median observation time 26 + months). Fifteen of 26 patients seen after 1973 underwent the second laparotomy and only two were found to have residual disease. The LSA2-L2 protocol has significantly improved the disease-free survival rate of children with IANHL, even with widespread intra-abdominal and extra-abdominal disease at diagnosis. Further, the "second-look" laparotomy in patients with large unresectable disease at presentation has proved a useful method of unequivocal evaluation of response, thus eliminating unnecessary extensive abdominal irradiation in many of these children.

aim:To investigate across multiple cycles the efficacy and safety of palonosetron in the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients receiving highly or moderately emetogenic chemotherapy (HEC/MEC). Patients & methods: Patients were randomly assigned to 10, 20 μg/kg palonosetron or 3 × 150 μg/kg ondansetron for up to four cycles of HEC/MEC. Results: In all on-study chemotherapy cycles, complete response rates were higher in patients in the 20 μg/kg palonosetron group than the ondansetron group. Treatment-emergent adverse events were comparable between the palonosetron 20 μg/kg and ondansetron groups. conclusion: Over four cycles of HEC/ MEC, 20 μg/kg palonosetron was an efficacious and safe treatment for the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients. Chemotherapy-induced nausea and vomiting (CINV) are common and distressing side effects in cancer patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) regimens [1,2]. CINV negatively impacts on patient quality of life [3], and can lead to medical complications and to noncompliance or premature discontinuation of anticancer therapy [4]. It is recognized that children receiving chemotherapy are more prone to vomiting than adults, and it is estimated that 70% of pediatric cancer patients receiving chemotherapy will develop CINV [2].Prevention of CINV in adult cancer patients receiving HEC or MEC regimens can be achieved through the use of antiemetic agents, a combination of a 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonist, a corticosteroid and a neurokinin-1 (NK 1 ) receptor antagonist is recommended [5][6][7]. While fewer studies of these agents have been performed in pediatric cancer patients than in adults, at the time of the study design, the combination of a 5-HT 3 receptor antagonist with a corticosteroid was recommended for pediatric patients receiving HEC or MEC chemotherapy regimens [2,5,6]. In later guidance from the Pediatric Oncology Group of Ontario (POGO), children scheduled to receive HEC are recommended to receive antiemetic prophylactic therapy of ondansetron or granisetron plus dexamethasone and aprepitant (≥12 years of age and receiving antineoplastic drugs not known to interact with aprepitant) or ondansetron or granisetron plus dexamethasone (<12 years of For reprint orders, please contact: reprints@futuremedicine.com

No abstract