The UMBRELLA SIOP–RTSG 2016 Wilms tumour pathology and molecular biology protocol

Abstract

Paediatric renal tumours account for ~6% of all paediatric malignant tumours, of which ~90% are Wilms tumours (nephroblastoma) 1. Other renal non-Wilms tumours are rare entities and include mesoblastic nephroma, clear cell sarcoma of the kidney, rhabdoid tumour of the kidney, renal cell carcinoma and few other, even rarer tumour types 1. The Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP-RTSG) has developed a new study for all renal tumours of childhood, the UMBRELLA SIOP-RTSG 2016 protocol (the UMBRELLA protocol) 2,3 , on the basis of the experiences from SIOP-2001 and the UK Improving Population Outcomes for Renal Tumours of Childhood (IMPORT) 2013 studies 2-4. The aim of the UMBRELLA protocol is to collect all clinical, biological and outcomes data from children with primary renal tumours in a comprehensive data registry, with central review of diagnostics (radiology, patho logy and surgery), standardized biobanking and precise treatment recommendations for the most common paediatric renal tumours. Molecular biology research within the protocol is primarily focused on the validation of the prognostic value of 1q gain, which might lead to a more personalized treatment approach (Box 1). Consequently, short-term and long-term outcomes might be improved for all children with renal tumours by increasing survival, but also by reducing treatment in specific subgroups, resulting in diminished direct and late adverse effects. Timely genetic analysis and step-wise extension to additional targets such as TP53 (refs 5-7) or several of the newly identified driver candidates for stratification and inclusion of liquid biopsies might help to reach this goal 8-10. The UMBRELLA protocol includes updated guidelines for pathologists for the handling and processing of tissue as well as criteria that are important for postoperative histological classification, staging and treatment stratification. These recommendations were established by a consensus of pathology experts within the SIOP-RTSG (chaired by G. M. Vujanić and I. Leuschner).

Minimally invasive surgery for unilateral Wilms tumors: Multicenter retrospective analysis of 50 transperitoneal laparoscopic total nephrectomies

“…The role and risks of biopsy prior to initiating neoadjuvant chemotherapy in WT remained controversial for a long time 10 . Although SIOP does not advocate it, a fine‐needle retroperitoneal percutaneous biopsy is not considered as a tumor rupture and therefore does not upstage the tumor 8 . It remains unclear currently whether genetic factors are independent risks factors of poorer prognosis or if they are associated with high‐risk histological features post chemotherapy 11 .…”

“…Pathology was reported as per protocol 8 as either local stage I, II, or III and histological subtype low, intermediate, or high risk. This staging was used to inform appropriate adjuvant (chemotherapy and/or radiotherapy) tretament 6,8 …”

“…does not upstage the tumor. 8 It remains unclear currently whether genetic factors are independent risks factors of poorer prognosis or if they are associated with high-risk histological features post chemotherapy. 11 In this setting, it has been the preference of center 1 to perform a percutaneous fine-needle biopsy in all patients except those aged less than six months prior to initiating treatment.…”

Pharmacotherapeutic Management of Wilms Tumor: An Update

“…Due to differences in upfront treatment approaches, slight differences in staging and histology also exist (11). Treatment type and intensity are influenced by several clinical and biological prognostic factors for both groups (table 1) (12,13).…”

“…In the forthcoming UMBRELLA trial they will use tumour volume >500ml found at histology after pre-operative chemotherapy and nephrectomy to stratify patients with stage II and III tumours with non-stromal and non-epithelial histology to re-introduce doxorubicin in post-operative chemotherapy (46). This trial will also evaluate gain of 1q and blastemal volume prospectively as possible markers for poor prognosis (12,47,48). The COG consortium will continue to use LOH at 1p and 16q but will also explore gain of chromosome 1q as a risk factor for stratification.…”