Tumor Study Group Research Articles

Abstract A026: A novel ddPCR detects hypermethylated RASSF1A in plasma of patients with pediatric Wilms tumor

Abstract Background: Wilms tumor is the most common pediatric renal cancer. Within the SIOP-Renal Tumor Study Group (SIOP-RTSG), diagnosis is based on imaging and patients receive neo- adjuvant treatment. Final diagnosis is established via histopathological analysis at the timepoint of surgery, which also determines the intensity of adjuvant treatment. Overall, patients with Wilms tumor have a 90% survival rate, but one in five patients will suffer from a relapse, which requires intensive treatment and induces long-term toxicity. It is challenging to identify patients at risk of suffering from relapse at initial diagnosis. Hence the need for additional biomarkers that will optimize risk stratification and minimal residual disease monitoring. RASSF1A is a tumor suppressor gene that is silenced via hypermethylation of its promotor region in multiple adult and pediatric tumors and is reported to represent an aggressive phenotype. We have previously reported on thirteen patients with Wilms tumor where increased hypermethylation of RASSF1A (RASSF1A-M) was observed in plasma cell-free DNA (cfDNA). The aim of this study was to further investigate the levels of RASSF1A-M in a larger cohort. Methods: The presence of RASSF1A-M in plasma cfDNA of patients with Wilms tumor was quantified using a multiplexed droplet digital PCR comprising methylation-specific restriction enzymes. Diagnosis and pre- surgery samples were included to evaluate RASSF1A-M levels during treatment. Results: A total of 49 patients were evaluated. At diagnosis, 37/46 (80.4%) samples were positive for RASSF1A-M. Negative samples were from patients with localized disease (N=6), regressive type regionally advanced Wilms (N=1) or mixed type metastatic Wilms (N=2). RASSF1A-M levels were significantly elevated in regionally advanced and metastatic disease compared to localized disease. Of the 37 positive diagnosis samples, 23 pre-surgical follow-up samples were available. In 7/23, RASSF1A-M was still detectable. These belong to patients with stromal-, regressive- or diffuse anaplastic predominant tumors. Interestingly, an increasing methylation level was seen in one patient with a regressive tumor. Conclusion: RASSF1A-M is a potential biomarker for patients with Wilms tumor, since it was detected in the majority of patients. Furthermore, significantly increased levels were observed in regionally advanced and metastatic disease. In the small number of patients with persisting levels of RASSF1A-M, we did not observe an association with risk groups. In collaboration with SIOP-RTSG, additional follow-up samples will be analyzed to explore the potential of RASSF1A-M as biomarker for relapse detection. Citation Format: Julia Sprokkerieft, Nathalie S.M. Lak, Zeinab van Gestel-Fadaie, Marry M. van den Heuvel-Eibrink, Godelieve A.M. Tytgat. A novel ddPCR detects hypermethylated RASSF1A in plasma of patients with pediatric Wilms tumor [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A026.

Real-world Referral Pattern of Unplanned Excision in Patients With Soft-tissue Sarcoma: A Multicenter Study Conducted by the Bone and Soft-tissue Tumor Study Group of the Japan Clinical Oncology Group.

Despite the well-publicized clinical outcomes after unplanned excision (UE) and re-excision (re-excision) in patients with soft-tissue sarcoma (STS), there is little information about the real-life referral patterns for UE, such as patient profile, details of procedures, and subsequent management after UE. We aimed to investigate the characteristics of patients with UE who were referred to sarcoma-specific centers. Between May 2022 and June 2023, we registered 97 patients who underwent UE and were referred to sarcoma-specific centers in Japan. We excluded those with well-differentiated liposarcomas and dermatofibrosarcoma protuberances. We investigated the details of UE and additional treatment after UE. There were 49 men and 48 women, with a mean age of 62 years. A broad range of surgeons performed UE; 36 plastic surgeons, 22 orthopedic surgeons, 17 general surgeons, 17 dermatologists, and 5 others. The mean tumor size was 4.1 cm. Local anesthesia was administered to 58 patients. Forty-five patients underwent UE without prior magnetic resonance imaging. Inappropriate transverse skin incisions were performed in 42 patients. Of the 97 patients, 82 underwent re-excision after UE. The mean time between UE and date of initial presentation at the referral hospital was 46 days. The mean interval between UE and re-excision was 96 days. Of the 82 patients, 59 underwent soft-tissue reconstruction after re-excision. A broad range of surgeons performed UE. Continuous education about STS should be considered for all surgeons. UE should be avoided because residual tumors are common, and reconstructive surgery may be necessary.

Incidence and Prognostic Implications of Lymphovascular Invasion in Node-Negative Pancreatic Neuroendocrine Tumors: Results From the US Neuroendocrine Study Group.

Despite the well-known prognostic role of lymph node metastasis (LNM) in pNETs, less is known about the importance of lymphovascular invasion (LVI) among patients with these tumors. Patients undergoing pancreatectomy for pNET between 2002 and 2020 were identified in the US Neuroendocrine Tumor Study Group database. Cox regression analysis was utilized to identify the impact of LVI on recurrence-free survival (RFS) among patients with node-negative pNET. Among 853 patients who underwent resection for pNET, 214 patients (25.1%) had LNM, while 116 (13.6%) and 523 individuals (61.3%) were LVI + N0 and LVI - N0, respectively. The overall incidence of LVI among patients with N0 pNET was 18.1%; the incidence of LVI increased with increasing tumor size and Ki-67 levels (size < 2 cm and Ki-67 < 3%: 5.5%; size < 2 cm and Ki-67 ≥ 3%: 17.2%; size ≥ 2 cm and Ki-67 < 3%: 22.2%; size ≥ 2 cm and Ki-67 ≥ 3%: 43.1%, p < 0.001). Five-year RFS was highest among patients with LVI - N0 disease followed by individuals with LVI + N0 and N+ pNETs (92.8% vs. 61.6% vs. 58.3%, p < 0.001). On multivariable analysis, the presence of LVI on pathology remained independently associated with almost 2.5 times higher hazards of recurrence (HR 2.47, 05% CI 1.44-4.24) among individuals with N0 pNETs. The incidence of LVI varied according to tumor size and Ki-67. LVI was associated with a higher likelihood of recurrence among individuals who underwent formal pancreatic resection for N0 pNETs. LVI is an important prognostic indicator among patients with node-negative pNETs.

Preoperative Glycosylated Hemoglobin A1C Impacts Long-Term Outcomes Following Curative-Intent Resection of Nonfunctional Gastroenteropancreatic Neuroendocrine Tumors.

To investigate the impact of preoperative glycosylated hemoglobin A1C (HbA1c) among patients following curative-intent resection of nonfunctional gastroentropancreatic neuroendocrine tumors (GEP-NETs). Patients who underwent curative-intent resection for GEP-NETs from 2000 to 2020 were identified from the US Neuroendocrine Tumor Study Group (US-NETSG). Preoperative blood HbA1c levels were defined as high HbA1c (≥ 6.5%) versus low HbA1c group (< 6.5%). Impact of HbA1c level on postoperative short-term and long-term overall (OS) were investigated. A total of 130 patients with HbA1c < 6.5% and 60 patients with HbA1c ≥ 6.5% were included. Patients with HbA1c ≥ 6.5% had higher proportion of comorbidities, such as hypertension, obesity, anemia, and lower preoperative albumin levels versus patients with HbA1c < 6.5% (all p < 0.05). In addition, high level of preoperative HbA1c was associated with increased incidence of wound and infectious complications, as well as decreased long-term OS (median OS: high Hb1Ac 89.8 months vs. low Hb1Ac not reached, HR 3.487, p = 0.004) among patients with nonfunctional GEP-NETs, as well as among the subset of pancreatic NET patients (median OS: high Hb1Ac 74.3 months vs. low Hb1Ac not reached, p = 0.004), and patients with normal fasting blood glucose (< 140 mg/dL) (median OS: high Hb1Ac 75.4 months vs. low Hb1Ac not reached, p = 0.001). Hb1Ac might have value as a screening tool to identify high-risk patients following surgical resection of nonfunctional GEP-NETs for consideration of more strict postoperative surveillance and treatment of elevated Hb1Ac level.

Survival after Lung Metastasectomy from Urothelial Carcinoma: A Multi-Institutional Database Study.

The efficacy of lung metastasectomy in patients with urothelial carcinoma remains inconclusive, as there is only limited evidence from small studies. In this study, we aimed to assess the prognostic outcomes of excising pulmonary metastases from urothelial carcinoma. In this study, we utilized data from the Metastatic Lung Tumor Study Group of Japan database, a multi-institutional prospective database of pulmonary metastasectomies. We examined the data of patients who had undergone pulmonary metastasectomy for urothelial carcinoma between 1985 and 2021. Exclusion criteria included insufficient clinical information and follow-up of <3 months. The study cohort comprised 100 patients (63 bladder cancer, 37 renal pelvic and ureteral cancer), with a median follow-up of 34 months. There were 70 male and 30 female patients of average age 66.5 ± 10.4 years at lung metastasectomy. The median interval from treatment of the primary lesion to metastasectomy was 19 months and the maximum tumor diameter was 21 ± 15 mm. Three- and five-year overall survival rates were 69% and 59%, respectively. Three- and five-year disease-free survival rates were 56% and 46%, respectively. Multivariate analysis identified larger tumor diameter (hazard ratio: 1.62, 95% confidence interval: 1.21-2.17) and distant metastases at the time of treatment of the primary cancer (hazard ratio: 4.23; 95% confidence interval: 1.54-11.6) as significant adverse prognostic factors for overall survival. To our knowledge, this is the largest published case series of pulmonary resection for metastatic urothelial carcinoma, providing benchmark data for the assessment of long-term outcomes of this rare entity.

Cost of medical care for malignant brain tumors at hospitals in the Japan Clinical Oncology Group brain-tumor study group.

This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved. We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL. The most used regimen (46.8%) for GBM in patients aged ≤74years was 'Surgery + radiotherapy concomitant with temozolomide'. This regimen's total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, 'Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy' was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month). Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors.

Incorporation of whole-body metabolic tumor burden into current prognostic models for non-small cell lung cancer patients with spine metastasis

BACKGROUND CONTEXTNumerous prognostic models are utilized for surgical decision and prognostication in metastatic spine tumors. However, these models often fail to consider the whole-body tumor burden into account, which may be crucial for the prognosis of metastatic cancers. A potential surrogate marker for tumor burden, whole-body metabolic tumor burden (wMTB), can be calculated from total lesion glycolysis (TLG) obtained from 18F-Fludeoxyglucose positive emission tomography (18F-FDG PET) images. PURPOSEWe aimed to improve prognostic power of current models by incorporating wMTB for non-small cell lung cancer (NSCLC) patients with spine metastases. DESIGNRetrospective analysis using a review of electrical medical records and survival data. PATIENT SAMPLEIn this study, we included 74 NSCLC patients with image proven spine metastases. OUTCOME MEASURESIncrease in Integrated Discrimination Improvement (IDI) index after incorporation of wMTB into prognostic scores. METHODSEnrolled patients’ baseline data, cancer characteristics and survival status were retrospectively collected. Five widely used prognostic scores (Tomita, Katagiri, Tokuhashi, Global Spine Tumor Study Group [GSTSG], New England Spine Metastasis Score [NESMS]), and TLG indexes were calculated for all patients. The relationships among survival time, prognostic models and TLG values were analyzed. Improvement of prognostic power was validated by incorporating significant TLG index into significant current models. RESULTSAmong current prognostic models, Tomita (EGFR wild-type), Katagiri, GSTSG and Tokuhashi were significantly related to patient survival. Among TLG indexes, LogTLG3 was significantly related to survival. Incorporation of LogTLG3 into significant prognostic models resulted in positive IDI index until 3 years in all models. ConclusionThis study showed that incorporation of wMTB improved prognostic power of current prognostic models of metastatic spine tumors.

Pursuit of the optimal therapeutic approach and intensity for children with bilateral Wilms tumour.

Investigators from the International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) report on outcomes of children with bilateral Wilms tumour treated on the SIOP 2001 study. They demonstrate that vincristine and actinomycin-D induction chemotherapy is sufficient in a subset of children, but most required additional agents during their treatment.

Direct correlation of MR-DWI and histopathology of Wilms' tumours through a patient-specific 3D-printed cutting guide.

The International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) discourages invasive procedures to determine the histology of paediatric renal neoplasms at diagnosis. Therefore, the histological subtype of Wilms' tumours (WT) is unknown at the start of neoadjuvant chemotherapy. MR-DWI shows potential value as a non-invasive biomarker through apparent diffusion coefficients (ADCs). This study aimed to describe MR characteristics and ADC values of paediatric renal tumours to differentiate subtypes. Children with a renal tumour undergoing surgery within the SIOP-RTSG 2016-UMBRELLA protocol were prospectively included between May 2021 and 2023. In the case of a total nephrectomy, a patient-specific cutting guide based on the neoadjuvant MR was 3D-printed, allowing a correlation between imaging and histopathology. Whole-tumour volumes and ADC values were statistically compared with the Mann-Whitney U-test. Direct correlation on the microscopic slide level was analysed through mixed model analysis. Fifty-nine lesions of 54 patients (58% male, median age 3.0 years (range 0-17.7 years)) were included. Forty-four lesions involved a WT. Stromal type WT showed the lowest median decrease in volume after neoadjuvant chemotherapy (48.1 cm3, range 561.5-(+)332.7 cm3, p = 0.035). On a microscopic slide level (n = 240 slides) after direct correlation through the cutting guide, stromal areas showed a significantly higher median ADC value compared to epithelial and blastemal foci (p < 0.001). With a cut-off value of 1.195 * 10-3 mm2/s, sensitivity, and specificity were 95.2% (95% confidence interval 87.6-98.4%) and 90.5% (95% confidence interval 68.2-98.3%), respectively. Correlation between histopathology and MR-DWI through a patient-specific 3D-printed cutting guide resulted in significant discrimination of stromal type WT from epithelial and blastemal subtypes. Stromal Wilms' tumours could be discriminated from epithelial- and blastemal lesions based on high apparent diffusion coefficient values and limited decrease in volume after neoadjuvant chemotherapy. This may aid in future decision-making, especially concerning discrimination between low- and high-risk neoplasms. MR-DWI shows potential value as a non-invasive biomarker in paediatric renal tumours. The patient-specific cutting guide leads to a correlation between apparent diffusion coefficient values and Wilms' tumour subtype. Stromal areas could be discriminated from epithelial and blastemal foci in Wilms' tumours based on apparent diffusion coefficient values.

Assessment of survival prediction after surgery in spinal metastases patients using the Global Spine Study Tumor Group (GSTSG) risk calculator; an external validation from a tertiary cancer hospital.

We aim to validate the Global Spine Tumor Study Group (GSTSG) score compared to previous prognostic scoring systems in spinal metastasis. We conducted a retrospective study from January 2013 to December 2022. The survival prediction was compared between the GSTSG, Tomita Score, Revised Tokuhashi Score, and Skeletal Oncology Research Group (SORG) Nomogram. Single-variable factors associated with survival rate were analyzed using univariate Cox regression and multivariable Cox proportional hazard model. Receiver operating characteristic was used for external validity analysis at 3, 6, 12, and 24months. The overall survival rate was reported using the Kaplan-Meier survival curve. 248 spinal metastasis patients were included. The mean age was 59.23 ± 12.55years. The mean duration of follow-up time was 470.29 ± 441.98days. The external validity of GSTSG was the highest at all follow-up times (sufficiently accurate AUC > 0.7), which was about the same as SORG at 3months (both AUC of GSTSG and SORG = 0.76) and higher than modified Tokuhashi and Tomita score at 12months (AUC of GSTSG = 0.78, SORG = 0.71, Tomita = 0.64, and modified Tokuhashi = 0.61, respectively). From our study, the Multivariate Cox regression analysis indicates that the significant factors related to survival rate are regular analgesic use of weak opioids, lung metastasis, and previous chemotherapy. Compared to other traditional spinal metastases prognostic scoring systems, GSTSG shows the highest AUC for external validity in all follow-up times up to 24months.

Free-flap reconstruction methods in head-and-neck oncologic surgery: A CROSS practice survey of members of the French GETTEC Head-and-Neck Tumor Study Group

ObjectiveTo survey practices concerning the use of anticoagulants and antiplatelets in microvascular free-flap reconstruction following oncological surgery of the head and neck. MethodsA survey of practices was carried out between September 2022 and March 2023. An online questionnaire was sent to members of the French GETTEC Head-and-Neck Tumor Study Group in all French centers practicing head-and-neck cancer surgery with reconstruction using microvascular free-flaps. The questionnaire asked surgeons about their practices regarding the use of intra- and postoperative anticoagulants and antiplatelets, preoperative management of comorbidities, and prevention of postoperative complications. ResultsSixty-one percent of the 38 respondents (23/38) used intraoperative intravenous heparin injection, associated to flap irrigation with heparin for 76% of surgeons (29/38) and/or a heparin solution bath for 37% (14/38). Postoperative anticoagulation was used by 95% of surgeons (36/38), and antiplatelets by 40% (15/38). Postoperatively, 40% (15/38) carried out monitoring using an implantable micro-Doppler probe, associated to analysis of clinical characteristics of the flap. ConclusionReconstructive surgery using microvascular free-flaps involves numerous factors that can influence success. Prospective studies, particularly concerning the management of anticoagulants, could enable a national consensus on methods for free-flap reconstruction.

Diagnostic magnetic resonance imaging characteristics of congenital mesoblastic nephroma: a retrospective multi-center International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) radiology panel study

BackgroundCongenital mesoblastic nephroma is the most common solid renal tumor in neonates. Therefore, patients <3 months of age are advised to undergo upfront nephrectomy, whereas invasive procedures at diagnosis in patients ≥3 months of age are discouraged by the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG). Nevertheless, discriminating congenital mesoblastic nephroma, especially from the more common Wilms tumor, solely based on imaging remains difficult. Recently, magnetic resonance imaging (MRI) has become the preferred modality. Studies focusing on MRI characteristics of congenital mesoblastic nephroma are limited.ObjectiveThis study aims to identify diagnostic MRI characteristics of congenital mesoblastic nephroma in the largest series of patients to date.Materials and methodsIn this retrospective multicenter study, five SIOP-RTSG national review radiologists identified 52 diagnostic MRIs of histologically proven congenital mesoblastic nephromas. MRI was performed following SIOP-RTSG protocols, while radiologists assessed their national cases using a validated case report form.ResultsPatients (24/52 classic, 11/52 cellular, and 15/52 mixed type congenital mesoblastic nephroma, 2/52 unknown) had a median age of 1 month (range 1 day–3 months). Classic type congenital mesoblastic nephroma appeared homogeneous with a lack of hemorrhage, necrosis and/or cysts, showing a concentric ring sign in 14 (58.3%) patients. Cellular and mixed type congenital mesoblastic nephroma appeared more heterogeneous and were larger (311.6 and 174.2 cm3, respectively, versus 41.0 cm3 for the classic type (P<0.001)). All cases were predominantly T2-weighted isointense and T1-weighted hypointense, and mean overall apparent diffusion coefficient values ranged from 1.05–1.10×10−3 mm2/s.ConclusionThis retrospective international collaborative study showed classic type congenital mesoblastic nephroma predominantly presented as a homogeneous T2-weighted isointense mass with a typical concentric ring sign, whereas the cellular type appeared more heterogeneous. Future studies may use identified MRI characteristic of congenital mesoblastic nephroma for validation and for exploring the discriminative non-invasive value of MRI, especially from Wilms tumor.Graphical

Anaplasia in Wilms tumor: A critical review.

Anaplasia in Wilms tumor is recognized as the most important prognostically unfavorable histological feature. It is subtyped as focal anaplastic Wilms tumor (FAWT) and diffuse anaplastic Wilms tumor (DAWT). Outcomes of patients with DAWT remain poor in patients with stage III and IV tumors. Important issues relevant to anaplasia in Wilms tumor, including prevalence, treatment, outcomes, biomarkers, anaplasia, and chemotherapy, and the concept of tumor aggressiveness, are reviewed and discussed here. We also consider the differences in clinical approaches to anaplasia in Wilms tumor between the two major renal tumor clinical research groups: the International Society of Paediatric Oncology (SIOP) Renal Tumour Study Group and the Children's Oncology Group (COG) Renal Tumor Group. We emphasize the importance and implications of recognizing FAWT and DAWT as separate clinico-pathological entities.

Survival disparities in rural versus urban patients with pancreatic neuroendocrine tumor: A multi-institutional study from the US neuroendocrine tumor study group

BackgroundPancreatic Neuroendocrine Tumors (PNETs) are indolent malignancies that often have a prolonged clinical course. This study assesses disparities in outcomes between PNET patients who live in urban (UA) and rural areas (RA). MethodsA retrospective cohort study was performed using the US Neuroendocrine Tumor Study Group database. PNET patients with a home zip code recorded were included and categorized as RA or UA according to the Federal Office of Rural Health Policy. Overall survival (OS) was analyzed by Kaplan-Meier method, log-rank test, and logistical regression. ResultsOf the 1176 PNET patients in the database, 1126 (96%) had zip code recorded. While 837 (74%) lived in UA, 289 (26%) lived in RA. RA patients had significantly shorter median OS following primary PNET resection (122 vs 149 months, p ​= ​0.01). After controlling for income, local healthcare access, distance from treatment center, ASA class, BMI, and T/N/M stage, living in a RA remained significantly associated with worse OS (HR 1.60, 95%CI 1.08–2.39, p ​= ​0.02). ConclusionRural patients have significantly shorter OS following PNET resection compared to their urban counterparts.

Treatment Outcomes of Olfactory Neuroblastoma: A Multicenter Study by the Korean Sinonasal Tumor and Skull Base Surgery Study Group.

Due to the rarity of olfactory neuroblastoma (ONB), there is ongoing debate about optimal treatment strategies, especially for early-stage or locally advanced cases. Therefore, our study aimed to explore experiences from multiple centers to identify factors that influence the oncological outcomes of ONB. We retrospectively analyzed 195 ONB patients treated at nine tertiary hospitals in South Korea between December 1992 and December 2019. Kaplan-Meier survival analysis was used to evaluate oncological outcomes, and a Cox proportional hazards regression model was employed to analyze prognostic factors for survival outcomes. Furthermore, we conducted 1:1 nearest-neighbor matching to investigate differences in clinical outcomes according to the use of neoadjuvant chemotherapy. In our cohort, the 5-year overall survival (OS) rate was 78.6%, and the 5-year disease-free survival (DFS) rate was 62.4%. The Cox proportional hazards model revealed that the modified Kadish (mKadish) stage and Dulguerov T status were significantly associated with DFS, while the mKadish stage and Hyams grade were identified as prognostic factors for OS. The subgroup analyses indicated a trend toward improved 5-year DFS with dural resection in mKadish A and B cases, even though the result was statistically insignificant. Induction chemotherapy did not provide a survival benefit in this study after matching for the mKadish stage and nodal status. Clinical staging and pathologic grading are important prognostic factors in ONB. Dural resection in mKadish A and B did not show a significant survival benefit. Similarly, induction chemotherapy also did not show a survival benefit, even after stage matching.

Targeted therapies in children with renal cell carcinoma (RCC): An International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG)-related retrospective descriptive study.

Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC. This retrospective study describes the effects of tyrosine kinase inhibitors (TKI), anti-programmed cell death 1 (PD-(L)1) monoclonal antibodies, and immunotherapeutic regimens in advanced-stage and relapsed pediatric RCC. Of the 31 identified patients (0-18 years) with histologically proven RCC, 3/31 presented with TNM stage I/II, 8/31 with TNM stage III, and 20/31 with TNM stage IV at diagnosis. The majority were diagnosed with translocation type RCC (MiT-RCC) (21/31) and the remaining patients mainly presented with papillary or clear-cell RCC. Treatment in a neoadjuvant or adjuvant setting, or upon relapse or progression, included mono- or combination therapy with a large variety of drugs, illustrating center specific choices in most patients. Sunitinib was often administered as first choice and predominantly resulted in stable disease (53%). Other frequently used drugs included axitinib, cabozantinib, sorafenib, and nivolumab; however, no treatment seemed more promising than sunitinib. Overall, 15/31 patients died of disease, 12/31 are alive with active disease, and only four patients had a complete response. The sample size and heterogeneity of this cohort only allowed descriptive statistical analysis. This study provides an overview of a unique series of clinical and treatment characteristics of pediatric patients with RCC treated with targeted therapies.

Redo nephron-sparing surgery in stage V pediatric renal tumors – A report from the SIOP/GPOH study group for renal tumors

PurposeNephron-sparing Surgery (NSS) is the surgical treatment of choice in children with bilateral renal tumors or in syndromatic patients. With an increasing role of this surgical approach, there is also an increased number of tumor relapses after NSS. Aim of this study was to evaluate a second (“Redo-“) NSS in children with relapsed renal tumors. Materials and methodsWe retrospectively analysed patients undergoing Redo-NSS for relapsed kidney tumors between 2009 and 2021 at our institution, which represents a national reference center of the SIOP/GPOH renal tumor study group. ResultsNine patients (5 girls, 4 boys) underwent Redo-NSS with resection of 15 lesions. Mean age at surgery was 58 months (12-137), mean operative time for Redo-NSS was 195 min (137-260). R0 resection status was achieved in all children. Two patients had second relapses, one of them was resected via NSS, the other child underwent tumor nephrectomy. Two patients with anaplastic relapses died from combined second relapses. Thus, 7/9 patients are alive without evidence of disease, an impaired renal function was observed in one child. Mean follow-up after Redo-NSS was 35 months (6-49). ConclusionsIn renal tumor relapses, Redo-NSS can be performed with satisfactory oncological and functional results. Occurrence of diffuse anaplasia should possibly refrain from this approach. Further evaluation in international multicenter analyses are necessary for a definitive determination of Redo-NSS.

Salivary gland carcinomas in children and adolescents: A retrospective analysis of the European Cooperative Study Group for Pediatric Rare Tumours (EXPeRT)

BackgroundSalivary gland carcinomas (SGCs) are exceedingly rare in children, with a reported annual incidence of 0.8–1.4/1000,000 under 20 years of age. Evidence regarding optimal treatment of pediatric SGCs is limited, and for a long time, no guidelines have been available. Here, we report on an international retrospective series of SGCs in children and adolescents collected by several national rare tumor study groups cooperating in the European Cooperative Study Group of Pediatric Rare Tumors (EXPeRT) Patients and methodsPatients diagnosed between 2000 and 2014 were included. Data were reviewed by the respective national rare tumor working groups and reported on a harmonized data sheet to EXPeRT for central analysis. ResultsOverall, 121 patients were identified, including 103 patients with parotid tumors, 12 with submandibular tumors and six tumors in minor glands. In 11 patients, SGCs were secondary cancers. Mucoepidermoid carcinoma was the most frequent diagnosis (n = 65), followed by acinic cell carcinoma (n = 39), adenocystic carcinoma (n = 7), sialoblastoma (n = 3) and other carcinomas (n = 7). All patients underwent tumor resection (R0: 66%, R1: 34%). Neck dissection was performed in 47 patients, revealing nodal metastases in 13. Twenty-four patients underwent irradiation, and 11 patients received adjuvant chemotherapy. During a median follow-up of 25 (6–140 months), 14 relapses were observed (7 local, 5 with nodal and 2 with distant metastases). Five patients died of disease. Higher histological tumor grade was associated with advanced local tumor stage and risk of recurrence. ConclusionsSGCs in children and adolescents mostly present as localized tumors with low malignant potential. In approximately 10% of patients, regional lymph node metastases present at diagnosis. After complete resection, prognosis is favorable. Surgery is the mainstay of treatment; adjuvant local or cervical irradiation should be reserved to those rare patients with nodal metastases or less favorable biology such as adenocystic carcinoma.

Diagnostic MRI characteristics of pediatric clear cell sarcoma of the kidney and rhabdoid tumor of the kidney: A retrospective multi-center SIOP-RTSG Radiology panel study

IntroductionClear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RTK) are rare malignant pediatric renal tumors, both accounting for 1–5% of diagnoses. Within the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) protocols diagnostic invasive procedures to determine histology are discouraged. MRI has become the preferred imaging modality, however, non-invasive discrimination of CCSK and RTK remains challenging. Therefore, this study aims to identify diagnostic MRI-characteristics of CCSK and RTK, in the largest series of patients to date. Material and methodsFive SIOP-RTSG national review radiologists identified national diagnostic MRIs of histologically proven CCSKs and RTKs. Scan-protocols were based on MRI-guidelines following SIOP-RTSG protocols. Radiologists assessed their national cases using a validated case report form (CRF). ResultsRetrospectively, 59 patients were identified (n = 38 CCSK, n = 21 RTK). CCSKs showed a high median volume (576 cm3, range 54–4414), which was lower for RTKs (290 cm3, range 20–761) (p = 0.006 *10-3). Fifty-two percent (11/21) of RTK-patients showed disease at other locations, predominantly the lungs and brain, compared to 8% of CCSK-patients (3/38). RTKs showed ill-defined margins (12/21, 57%) and infiltrative growth pattern (13/21, 62%). CCSKs appeared hyper-intense on T2-weighted imaging (27/38, 71%) with a characteristics band-like enhancement (13/38, 34%), whereas RTK cases often showed T2-weighted hypo-intensity (11/21, 52%). The overall mean ADC-value for CCSK was 1.11 * 10-3 mm2/s (range 0.57–2.07 *10-3 mm2/s), and 0.72 * 10-3 mm2/s (range 0.53–0.90 *10-3 mm2/s) for RTK. ConclusionsThis retrospective study suggests a small size, T2-weighted hypo-intensity and an aggressive growth pattern may be characteristic for RTK. CCSK often showed a typical band-like enhancement pattern with relatively high ADC-values. Identified MRI-characteristics may be used in future studies focusing on validation and discrimination from especially WT, aiming for an early non-invasive diagnosis.

Update on Wilms tumor

Background: Wilms' tumor is the most common childhood renal neoplasm. Among the worst prognosis forms are the bilateral form. The symptom complex is non-specific for malignancy; the first symptoms may include hypertension. Hematuria occurs in 30% of patients. The incidence of distant metastases at the time of diagnosis in children with Wilms' tumor is estimated to be about 20%.The purpose of this article is to present a review of the literature on the standardization of diagnosis, the latest treatment standards and to assess the prognosis of Wilms' Tumor.&#x0D; Matherial and methods: Using PubMed, SCOPUS and Web of Science databases, the authors reviewed the peer-reviewed international literature from 1980-2023 using the keywords: "Wilms tumor," "renal tumor," "nephroblastoma." &#x0D; Discussion: Bilateral tumors have the worst prognosis - according to the National Wilms Tumor Study Group, long-term survival is achieved in only 12% to 56% of patients. The prognosis of Wilms' tumor is also dependent on the occurrence of recurrences - local as well as localized outside the renal tissue. A factor directly affecting long-term survival is recurrence, mainly observed within 24 months after the end of therapy. The limitations of conventional therapies, including surgery, chemotherapy and radiotherapy, in preventing recurrence in WT patients and their potential to cause long-term side effects.&#x0D; Conclusions:&#x0D; Bilateral Wilms tumor is associated with more aggressive therapy than unilateral disease.In single kidney disease, therapeutic management is aimed at radical removal of all tumor foci, whereas in bilateral tumor, the goal of any management should additionally be to try to preserve the best possible renal function.&#x0D; Screening in children is important in cancer. General physicians should refer patients for additional imaging studies when there are any diagnostic doubts, as cancer is characterized by a long, asymptomatic development.