Background: To describe the clinical features and course of a series of survivors of retinoblastoma who developed a non-pineoblastoma second primary malignant neoplasm (SPMN). Methods: A retrospective review of patients treated for retinoblastoma who developed a SPMN was performed. The demographics, clinical features and treatments for retinoblastoma, pathologic types of SPMN, the intervals between the retinoblastoma diagnosis and treatment and diagnosis of non-pineoblastoma SPMN, treatment provided for the SPMN, and the survival outcomes of the patients were evaluated. Results: Of 550 patients treated initially for retinoblastoma, this series used the 15 (2.7%) that developed a non-pineoblastoma SPMN, 14 of which (93.3%) had been treated for bilateral retinoblastoma. All patients in this series had germline retinoblastoma. The median time from retinoblastoma diagnosis to SPMN diagnosis was 19.0 years (extremes 3.4 and 39.4 years). Six of the fifteen patients died during the follow-up of their SPMN. Nine patients were still alive without active residual SPMN at the last follow-up. The median interval between initial retinoblastoma diagnosis and death in the 6 patients who died of their SPMN was 18.8 years (extremes 6.2 and 34.6 years) and between diagnosis of the SPMN and death was 1.2 years (extremes 0.25 and 4 years). Conclusion: A SPMN occurred in this series in 2.7% of retinoblastoma survivors, and all occurred in patients with germline retinoblastoma. All patients with SPMN who had been treated by EBRT developed the SPMN in the field of prior radiation.

IntroductionSince the initial attempts to treat children with renal cancer over 50 years ago, outcome for children with renal cancer has generally become promising. While the first endeavors mainly included surgical treatment, in the early 60s radiotherapy and chemotherapy were introduced, leading to cure of patients, including some with metastatic disease. (1) Since then, overall survival rates for the most common type of renal tumors in childhood (nephroblastoma or Wilms tumor) have improved to more than 90 percent. These excellent treatment outcomes are similar in the 2 largest clinical trial groups (the Children’s Oncology Group Renal Tumor Committee (COG-RTC; former National Wilms Tumor Study Group (NTWSG)), and the International Society of Pediatric Oncology Renal Tumor Study Group (SIOP-RTSG). Despite the difference in upfront treatment choice (primary surgery when feasible (COG-RTC) or preoperative chemotherapy (SIOP-RTSG)) both groups have optimized the stratification of patients in their trials by modifying the intensity of treatment according to individual risk factors, in order to improve outcome for high-risk renal tumor types, but also to reduce early and late toxicity in lower and intermediate risk tumors as much as possible. (2-4)This improvement in risk stratification has resulted in better outcomes and less cancer related toxicity. However, for remaining small subgroups of pediatric renal tumor patients, with very poor outcomes, further understanding of the underlying biology, in correlation with clinic-pathological characteristics, is an unmet need. Further, standard multidisciplinary treatment (surgery, radiotherapy, chemotherapy) can be challenging to access and/or deliver in some low and middle income countries (LMIC). The power inherent in international collaboration to address these challenges was a driving principle that supported the creation of the HARMONICA (HARMONIzation and COllaboration) initiative in 2015, when we established an organized collaborative structure for transatlantic experts from COG-RTC and SIOP-RTSG. The mandate of HARMONICA is to identify specific challenges for pediatric renal tumor subsets in order to meet the aims of our global approach to cure every child with a renal tumor with limited toxicity.The HARMONICA group meets at least once a month by videoconferences, and as much as possible also face to face, at least once or twice a year, during existing pediatric cancer conferences. In addition, several transatlantic HARMONICA expert subgroups are collaborating on specific topics. All work is currently done by a tremendous engagement of many enthusiastic members of both study groups. Despite the fact of obvious advantages, HARMONICA is still lacking funding and needs to optimize their structure as a legal entity. Notwithstanding such limitations, in this special issue of PBC, we present the achievements, the challenges, and the future perspectives, identified by these expert groups.

Retinoblastoma is the most common ocular tumor of childhood with cure rates exceeding 95%. Patients with high-risk features typically relapse within 3 years of diagnosis. We report a patient with low-risk bilateral retinoblastoma who suffered systemic relapse after eight years. His disease at first relapse was chemosensitive without PET avidity or bone marrow disease following therapy. Six months later, he experienced an isolated CNS relapse and succumbed to refractory disease. “Oncoseq” exome sequencing confirmed the presence of germline RB mutation among all tissues as well as somatic changes which may provide insights into the biology of relapse and tumor.