Value and difficulties of a common European strategy for recurrent Wilms’ tumor

Spreafico, Filippo; Pritchard‐Jones, Kathy; Bergeron, Christophe; Kraker, Jan de; Dallorso, Sandro; Graf, Norbert

doi:10.1586/era.09.45

Cited by 10 publications

(7 citation statements)

References 21 publications

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“…Advances in rescue protocols mainly consisting of intensified chemotherapy regimens have lead to salvage rates of 50% to 70% overall, depending on the tumor biology, disease stage, and other characteristics such as the length of remission. 10,13,14 The salvage rate in our study for stage 4 disease independent of tumor histology was 42.9% and therefore somewhat lower.…”

Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

“…10 It is reported to occur in approximately 10% to 20% of cases and fundamentally depends on tumor stage and biology at initial diagnosis. [10][11][12][13] The recurrence rate in our patient collective was 22.6%. Advances in rescue protocols mainly consisting of intensified chemotherapy regimens have lead to salvage rates of 50% to 70% overall, depending on the tumor biology, disease stage, and other characteristics such as the length of remission.…”

Section: Discussionmentioning

confidence: 99%

“…It is a key future objective to further reduce treatment intensities without compromising the patient's prognosis. 10,[15][16][17][18][19] None of the children who received radiation to the lung developed pulmonary fibrosis. One child in this group, however, developed thoracolumbar scoliosis, potentially due to a combination of thoracotomy and radiation.…”

Section: Discussionmentioning

confidence: 99%

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The Relationship Between the Site of Metastases and Outcome in Children With Stage IV Wilms Tumor

Berger

Fernández-Pineda

Cabello

et al. 2013

Journal of Pediatric Hematology/Oncology

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Summary:The aim of this study was to analyze in detail the site of metastasis of stage 4 Wilms tumor (WT) and its correlation with outcome. The databases from 3 major European pediatric cancer institutions were screened for children with WT between 1994 and 2011. Of 208 children identified, 31 (14.9%) had metastases at diagnosis. The lung was affected in 29 children (93.5%) and the liver in 6 children (19.4%). Twenty-seven children (87.1%) had metastases isolated to 1 organ, with the lung being the most common site (80.7%). Five-year overall survival was significantly better in those children with distant disease in either lung or liver (95.8%) compared with those affected in both lung and liver (57.1%, P = 0.028). Further, prognostic markers were the response of metastases to preoperative chemotherapy (P = 0.0138), high-risk histology (P = 0.024), and local stage (P = 0.026). Five-year overall survival was 82.1% and 5-year event-free survival was 67.9%. The overall follow-up time was 74.1 and 87.2 (2 to 151) months among survivors, and the treatment-related complication rate was 16.7%. In conclusion, in our series of stage 4 WT, prognosis was excellent if histology was favorable, metastatic disease was isolated to either lungs or liver, and if metastases responded to preoperative chemotherapy.Key Words: metastases, pediatric cancer, risk stratification, survival, Wilms tumor (J Pediatr Hematol Oncol 2013;35:518-524) W ilms tumor (WT) is the most common renal malignancy in childhood and the second most frequent intraabdominal pediatric cancer after neuroblastoma. 1 Many recent advances in clinical care and the biology of this tumor have pushed the overall survival (OS) to 90%. Naturally, for children with distant metastases the OS is lower. 1 Little is known on metastatic disease in stage 4 WT and its implication on therapy and outcome. 2,3 The lungs have long been recognized as a common site of distant tumor spread in stage 4 WT and several recent studies focus on this entity. 1,2 To our knowledge, no complete description of the metastatic profile of stage 4 WT at diagnosis exists at present. Therefore, in this study we reviewed children treated at 3 European pediatric cancer institutions for WT regarding their metastatic profile at diagnosis and its implication on long-term outcome. METHODS AND PATIENTS PatientsA retrospective analysis of the WT databases at the following 3 institutions was carried out: Hannover Medical School, Hannover (Germany); Dr. von Hauner Children's Hospital, Munich (Germany); and Virgen del Rocı´o Children's Hospital, Seville (Spain). Inclusion criteria were metastatic disease at diagnosis. Consequently, children with lower stage tumors who relapsed with metastatic disease were excluded. Additional exclusion criteria were other renal tumor entities like clear cell sarcoma, rhabdoid tumor, or renal cell carcinoma. TreatmentStaging criteria for WT was based on an upfront chemotherapy-based system developed by the International Society of Pediatric Oncology (SIOP). Treatment was accord...

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Relationship Between the Site of Metastases and Outcome in Children With Stage IV Wilms Tumor

Berger

Fernández-Pineda

Cabello

et al. 2013

Journal of Pediatric Hematology/Oncology

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“…With improved multimodality therapy, WT survival rates have risen over the last 40 years to 85-90%; however, for those whose disease relapses or metastasizes, even intensive salvage regimens result in subsequent survival closer to 50% (Geenen et al, 2007;Spreafico et al, 2009). Moreover, survivors are at increased risk for a broad spectrum of adverse outcomes caused by chemotherapy and radiation therapy, such as late mortality and secondary cancers (Robison, 2005;Geenen et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Resistance or sensitivity of Wilms’ tumor to anti-FZD7 antibody highlights the Wnt pathway as a possible therapeutic target

et al. 2011

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Wilms' tumor (WT), the most frequent renal solid tumor in children, has been linked to aberrant Wnt signaling. Herein, we demonstrate that different WTs can be grouped according to either sensitivity or resistance to an antibody (Ab) specific to frizzled7 (FZD7), a Wnt receptor. In the FZD7-sensitive WT phenotype, the Ab induced cell death of the FZD7 þ fraction, which in turn depleted primary WT cultures of their clonogenic and sphere-forming cells and decreased in vivo proliferation and survival on xenografting to the chick chorio-allantoic-membrane. In contrast, FZD7-resistant WT in which no cell death was induced showed a different intracellular route of the Ab-FZD7 complex compared with sensitive tumors and accumulation of b-catenin. This coincided with a low sFRP1 and DKK1 (Wnt inhibitors) expression pattern, restored epigenetically with de-methylating agents, and lack of b-catenin or WTX mutations. The addition of exogenous DKK1 and sFRP1 to the tumor cells enabled the sensitization of FZD7-resistant WT to the FZD7 Ab. Finally, although extremely difficult to achieve because of dynamic cellular localization of FZD7, sorting of FZD7 þ cells from resistant WT, showed them to be highly clonogenic/proliferative, overexpressing WT 'stemness' genes, emphasizing the importance of targeting this fraction. FZD7 Ab therapy alone or in combination with Wnt pathway antagonists may have a significant role in the treatment of WT via targeting of a tumor progenitor population.

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