Outcomes of patients with Wilms' tumour stage III due to positive resection margins only: An analysis of patients treated on the SIOP-WT-2001 protocol in the UK-CCLG and GPOH studies

Stage III Wilms' tumour (WT) represents a heterogeneous group which includes different criteria, but all stage III patients are treated according to the same study regiment. The aim of the study was to retrospectively analyse outcomes in patients with stage III due to positive resection margins (RM) only, sub-grouped in RM with viable (RM-v) and nonviable (RM-nv) tumour. Patients were treated pre- and postoperatively according to the SIOP-WT-2001 protocol in the UK-CCLG and GPOH WT trials and studies (2001-2020). There were 197 patients, including 134 with localised, abdominal stage III and 63 with overall stage IV, but abdominal stage III. Stage III due to RM-v had 126 patients, and due to RM-nv 71 patients. The overall 5-year local-relapse-free survival (RFS), event-free (EFS) and overall survival (OS) estimates for all patients with abdominal stage III RM were 95.7% (±SE1.5%), 85.1 (±SE2.6%) and 90.3% (±SE2.2%), respectively. Patients with stage III RM-nv had significantly better RFS and EFS than patients with RM-v (P = .027 and P = .003, respectively). A multivariate analysis showed that RM-v remained a significant factor for EFS when adjusted for age, presence of metastasis at diagnosis, histological risk group and overall stage in Cox regression analysis (P = .006). Patients with stage III due to RM-nv only exhibited no local recurrence and have a significantly better RFS and EFS than patients with RM-v. The results suggest that exclusion of RM-nv as a stage III criterion in the UMBRELLA staging system and consequent treatment reduction is warranted

Outcomes of patients with Wilms' tumour stage III due to positive resection margins only: An analysis of patients treated on the SIOP-WT-2001 protocol in the UK-CCLG and GPOH studies.

Stage III Wilms' tumour (WT) represents a heterogeneous group which includes different criteria, but all stage III patients are treated according to the same study regiment. The aim of the study was to retrospectively analyse outcomes in patients with stage III due to positive resection margins (RM) only, sub-grouped in RM with viable (RM-v) and nonviable (RM-nv) tumour. Patients were treated pre- and postoperatively according to the SIOP-WT-2001 protocol in the UK-CCLG and GPOH WT trials and studies (2001-2020). There were 197 patients, including 134 with localised, abdominal stage III and 63 with overall stage IV, but abdominal stage III. Stage III due to RM-v had 126 patients, and due to RM-nv 71 patients. The overall 5-year local-relapse-free survival (RFS), event-free (EFS) and overall survival (OS) estimates for all patients with abdominal stage III RM were 95.7% (±SE1.5%), 85.1 (±SE2.6%) and 90.3% (±SE2.2%), respectively. Patients with stage III RM-nv had significantly better RFS and EFS than patients with RM-v (P = .027 and P = .003, respectively). A multivariate analysis showed that RM-v remained a significant factor for EFS when adjusted for age, presence of metastasis at diagnosis, histological risk group and overall stage in Cox regression analysis (P = .006). Patients with stage III due to RM-nv only exhibited no local recurrence and have a significantly better RFS and EFS than patients with RM-v. The results suggest that exclusion of RM-nv as a stage III criterion in the UMBRELLA staging system and consequent treatment reduction is warranted

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

On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP–RTSG) has developed a new study protocol for paediatric renal tumours: the UMBRELLA SIOP–RTSG 2016 protocol (the UMBRELLA protocol). Currently, the overall outcomes of patients with Wilms tumour are excellent, but subgroups with poor prognosis and increased relapse rates still exist. The identification of these subgroups is of utmost importance to improve treatment stratification, which might lead to reduction of the direct and late effects of chemotherapy. The UMBRELLA protocol aims to validate new prognostic factors, such as blastemal tumour volume and molecular markers, to further improve outcome. To achieve this aim, large, international, high-quality databases are needed, which dictate optimization and international harmonization of specimen handling and comprehensive sampling of biological material, refine definitions and improve logistics for expert review. To promote broad implementation of the UMBRELLA protocol, the updated SIOP–RTSG pathology and molecular biology protocol for Wilms tumours has been outlined, which is a consensus from the SIOP–RTSG pathology panel

Omission of adjuvant chemotherapy in patients with completely necrotic Wilms tumor stage I and radiotherapy in stage III: The 30-year SIOP-RTSG experience.

BACKGROUND Completely necrotic Wilms tumor (CN-WT) following preoperative chemotherapy has been regarded as low-risk WT since the International Society of Paediatric Oncology (SIOP) 93-01 study, and patients have been treated with reduced postoperative therapy. The aim of the study was to evaluate whether the omission of adjuvant chemotherapy in patients with localized CN-WT stage I and radiotherapy in stage III was safe. PATIENTS AND METHODS The retrospective observational study of outcomes of patients diagnosed with localized CN-WT on central pathology review and treated according to the SIOP 93-01 and SIOP-WT-2001 protocols (1993-2022). RESULTS There were 125 patients with localized CN-WT: 90 with stage I, 10 with stage II, and 25 with stage III. Sixty-two of 125 (49.6%) patients had a discrepant diagnosis and/or staging between the institutional pathologist and central pathology review. In the group of 90 patients with stage I, postoperative chemotherapy was not given to 41 (46%) patients, whereas 49 patients received postoperative chemotherapy-in the latter group, two patients relapsed, and one of them died. One stage I and one stage II patient developed chemotherapy-induced toxicity and died. Nineteen of 25 patients with stage III received no flank radiotherapy. No stage III patient relapsed or died. The overall 5-year event-free survival (EFS) estimate for the entire cohort (stages I-III) was 96.8% [95% confidence interval, CI: 93.6%-99.6%] and the overall survival (OS) was 97.6% [95% CI: 95.0-100%]. The EFS and OS were 97% and 98%, respectively, for stage I, and 100% for stage III. CONCLUSION Omission of postoperative chemotherapy for patients with CN-WT stage I, and radiotherapy for stage III is safe. Rapid central pathology review is required to assign appropriate treatment and avoid treatment-related side effects

Stage I epithelial or stromal type Wilms tumors are low risk tumors: An analysis of patients treated on the SIOP-WT-2001 protocol in the UK-CCLG and GPOH studies (2001-2020)

BACKGROUND: Patients treated with preoperative chemotherapy with stage I intermediate-risk Wilms tumor (IR-WT) represent the largest group of patients with Wilms tumor (WT), and they have excellent outcomes. METHODS: The authors performed a retrospective analysis of patients with stage I epithelial (ET-WT) or stromal type WT (ST-WT) treated pre- and postoperatively according to the International Society of Paediatric Oncology-WT-2001 protocol in the UK Children's Cancer and Leukaemia Group and Gesellschaft für Pädiatrische Onkologie und Hämatologie groups' participation in the relevant WT trials and studies (2001-2020). RESULTS: There were 880 patients with stage I IR-WT, including 124 with ET-WT, 156 with ST-WT, and 600 with other IR-WT (oIR-WT). Patients with stage I ET-WT or ST-WT were significantly younger than patients with oIR-WT, represented a large proportion of stage I WTs in their groups, and tumors showed poor histologic response to preoperative chemotherapy. The 5-year event-free survival (EFS) estimates for patients with stage I ET-WT (96.8% ± 1.8 SE) or ST-WT (96.8% ± 1.6 SE) were significantly better than for patients with oIR-WT (90.3% ± 1.3 SE) (p = .014 and p = .009, respectively). A multivariate analysis showed that histologic type (ET-WT or ST-WT) remained a significant factor for EFS when adjusted for age and gender (p = .032 and p = .022, respectively). In both groups, relapses occurred in 3.2% of patients, and the overall survival was 99.2%. CONCLUSIONS: The results suggest that stage I ET-WT or ST-WT could be regarded as low-risk WT, for which omission of postoperative chemotherapy should be considered. PLAIN LANGUAGE SUMMARY: Patients with pretreated intermediate-risk Wilms tumor (WT) represent the largest group of patients with WT. This study reports the outcomes of patients with stage I epithelial type (ET-WT) or stromal type WT (ST-WT). These patients were significantly younger and had a larger proportion of stage I cases than patients with other intermediate-risk WT (oIR-WT). The event-free survival for patients with stage I ET-WT and ST-WT was significantly better than for patients with oIR-WT. Rare relapses were curable resulting in 99.2% overall survival

Stage I epithelial or stromal type Wilms tumors are low risk tumors: An analysis of patients treated on the SIOP-WT-2001 protocol in the UK-CCLG and GPOH studies (2001-2020).

BACKGROUND Patients treated with preoperative chemotherapy with stage I intermediate-risk Wilms tumor (IR-WT) represent the largest group of patients with Wilms tumor (WT), and they have excellent outcomes. METHODS The authors performed a retrospective analysis of patients with stage I epithelial (ET-WT) or stromal type WT (ST-WT) treated pre- and postoperatively according to the International Society of Paediatric Oncology-WT-2001 protocol in the UK Children's Cancer and Leukaemia Group and Gesellschaft für Pädiatrische Onkologie und Hämatologie groups' participation in the relevant WT trials and studies (2001-2020). RESULTS There were 880 patients with stage I IR-WT, including 124 with ET-WT, 156 with ST-WT, and 600 with other IR-WT (oIR-WT). Patients with stage I ET-WT or ST-WT were significantly younger than patients with oIR-WT, represented a large proportion of stage I WTs in their groups, and tumors showed poor histologic response to preoperative chemotherapy. The 5-year event-free survival (EFS) estimates for patients with stage I ET-WT (96.8% ± 1.8 SE) or ST-WT (96.8% ± 1.6 SE) were significantly better than for patients with oIR-WT (90.3% ± 1.3 SE) (p = .014 and p = .009, respectively). A multivariate analysis showed that histologic type (ET-WT or ST-WT) remained a significant factor for EFS when adjusted for age and gender (p = .032 and p = .022, respectively). In both groups, relapses occurred in 3.2% of patients, and the overall survival was 99.2%. CONCLUSIONS The results suggest that stage I ET-WT or ST-WT could be regarded as low-risk WT, for which omission of postoperative chemotherapy should be considered. PLAIN LANGUAGE SUMMARY Patients with pretreated intermediate-risk Wilms tumor (WT) represent the largest group of patients with WT. This study reports the outcomes of patients with stage I epithelial type (ET-WT) or stromal type WT (ST-WT). These patients were significantly younger and had a larger proportion of stage I cases than patients with other intermediate-risk WT (oIR-WT). The event-free survival for patients with stage I ET-WT and ST-WT was significantly better than for patients with oIR-WT. Rare relapses were curable resulting in 99.2% overall survival

The 'Pleasure&Pregnancy' web-based interactive educational programme versus expectant management in the treatment of unexplained subfertility: protocol for a randomised controlled trial

INTRODUCTION: Many subfertile couples are diagnosed with (relatively) unexplained subfertility and a good prognosis. National professional guidelines (eg, the Netherlands and UK) advise 'expectant management (EM)' for 6-12 months, in which no interaction with healthcare staff is offered. Underpowered studies indicate that face-to-face sex-counselling increases the ongoing pregnancy rates of these couples. In patients with other conditions, web-based interactive educational programmes have the same effect on sexual functioning as face-to-face sex counselling. The 'Pleasure&Pregnancy randomised controlled trial (RCT)' will examine in couples with unexplained subfertility and a good prognosis whether a new web-based interactive educational programme results in a higher chance of naturally conceiving an ongoing pregnancy within 6 months as compared with EM. METHODS AND ANALYSIS: A multicentre RCT with cost-effectiveness analysis will include heterosexual couples diagnosed with (relatively) unexplained subfertility and a good prognosis in Dutch and Belgian secondary or tertiary fertility clinics. Couples will be randomised between 6 months of EM and 6 months of the Pleasure&Pregnancy-programme. This new web-based interactive educational programme includes eight progressive modules of information (on the biology of conception and pleasurable sex) and sensate focus, couple communication and mindfulness exercises. Couples are offered interaction with their coaches via email and can take part in three moderated chat sessions with peers. The primary outcome of this RCT is the probability of naturally conceiving an ongoing pregnancy within 6 months after randomisation. Secondary outcomes include time-to-pregnancy, live birth rate, costs, sexual functioning and personal and relational well-being. Analysis will be according to intention to treat. ETHICS AND DISSEMINATION: This study has been approved by the Medical Ethical Committees of the Academic Medical Centre (the Netherlands) and the Leuven University Hospital (Belgium). The findings of this RCT will be disseminated through presentations at international scientific meetings and peer-reviewed publications. TRAIL REGISTRATION NUMBER: NTR5709; Pre-results.status: publishe

The 'Pleasure&Pregnancy' web-based interactive educational programme versus expectant management in the treatment of unexplained subfertility: Protocol for a randomised controlled trial

Introduction Many subfertile couples are diagnosed with (relatively) unexplained subfertility and a good prognosis. National professional guidelines (eg, the Netherlands and UK) advise 'expectant management (EM)' for 6-12 months, in which no interaction with healthcare staff is offered. Underpowered studies indicate that face-to-face sex-counselling increases the ongoing pregnancy rates of these couples. In patients with other conditions, web-based interactive educational programmes have the same effect on sexual functioning as face-to-face sex counselling. The 'Pleasure&Pregnancy randomised controlled trial (RCT)' will examine in couples with unexplained subfertility and a good prognosis whether a new web-based interactive educational programme results in a higher chance of naturally conceiving an ongoing pregnancy within 6 months as compared with EM. Methods and analysis: A multicentre RCT with cost-effectiveness analysis will include heterosexual couples diagnosed with (relatively) unexplained subfertility and a good prognosis in Dutch and Belgian secondary or tertiary fertility clinics. Couples will be randomised between 6 months of EM and 6 months of the Pleasure&Pregnancy-programme. This new web-based interactive educational programme includes eight progressive modules of information (on the biology of conception and pleasurable sex) and sensate focus, couple communication and mindfulness exercises. Couples are offered interaction with their coaches via email and can take part in three moderated chat sessions with peers. The primary outcome of this RCT is the probability of naturally conceiving an ongoing pregnancy within 6 months after randomisation. Secondary outcomes include time-to-pregnancy, live birth rate, costs, sexual functioning and personal and relational well-being. Analysis will be according to intention to treat. Ethics and dissemination: This study has been approved by the Medical Ethical Committees of the Academic Medical Centre (the Netherlands) and the Leuven University Hospital (Belgium). The findings of this RCT will be disseminated through presentations at international scientific meetings and peer-reviewed publications

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

On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP–RTSG) has developed a new study protocol for paediatric renal tumours: the UMBRELLA SIOP–RTSG 2016 protocol (the UMBRELLA protocol). Currently, the overall outcomes of patients with Wilms tumour are excellent, but subgroups with poor prognosis and increased relapse rates still exist. The identification of these subgroups is of utmost importance to improve treatment stratification, which might lead to reduction of the direct and late effects of chemotherapy. The UMBRELLA protocol aims to validate new prognostic factors, such as blastemal tumour volume and molecular markers, to further improve outcome. To achieve this aim, large, international, high-quality databases are needed, which dictate optimization and international harmonization of specimen handling and comprehensive sampling of biological material, refine definitions and improve logistics for expert review. To promote broad implementation of the UMBRELLA protocol, the updated SIOP–RTSG pathology and molecular biology protocol for Wilms tumours has been outlined, which is a consensus from the SIOP–RTSG pathology panel