Surgical Management of Wilms Tumors with Intravenous Extension: A Multicenter Analysis of Clinical Management with Technical Insights.

BACKGROUND: About 5% of Wilms tumors present with vascular extension, which sometimes extends to the right atrium. Vascular extension does not affect the prognosis, but impacts the surgical strategy, which is complex and not fully standardized. Our goal is to identify elements of successful surgical management of Wilms tumors with vascular extensions. PATIENTS AND METHODS: A retrospective study of pediatric Wilms tumors treated at three sites (January 1999-June 2019) was conducted. The inclusion criterion was the presence of a renal vein and vena cava thrombus at diagnosis. Tumor stage, pre and postoperative treatment, preoperative imaging, operative report, pathology, operative complications, and follow-up data were reviewed. RESULTS: Of the 696 pediatric patients with Wilms tumors, 69 (9.9%) met the inclusion criterion. In total, 24 patients (37.5%) had a right atrial extension and two presented with Budd-Chiari syndrome at diagnosis. Two died at diagnosis owing to pulmonary embolism. All patients received neoadjuvant chemotherapy and thrombus regressed in 35.6% of cases. Overall, 14 patients had persistent intra-atrial thrombus extension (58%) and underwent cardiopulmonary bypass. Most thrombi (72%) were removed intact with nephrectomy. Massive intraoperative bleeding occurred during three procedures. Postoperative renal insufficiency was identified as a risk factor for patient survival (p = 0.01). With a median follow-up of 9 years (range: 0.5-20 years), overall survival was 89% and event-free survival was 78%. CONCLUSIONS: Neoadjuvant chemotherapy with proper surgical strategy resulted in a survival rate comparable to that of children with Wilms tumors without intravascular extension. Clinicians should be aware that postoperative renal insufficiency is associated with worse survival outcomes.

Outcome and late effects of patients treated for childhood vaginal malignant germ cell tumors.

PURPOSE: Vaginal malignant germ cell tumors (MGCT) are rare, occurring in children less than 2 years old and raise the question of the optimal local treatment. METHODS: We included children treated for vaginal MGCT according to the French TGM-95/2013 regimen. Patients were classified as standard risk (SR: localized disease and alpha-fetoprotein (AFP) < 10,000 ng/mL) or high risk (HiR: metastatic and/or AFP > 10,000 ng/mL) and were treated, respectively, with three to five VBP (vinblastine-bleomycin-cisplatin) or four to six VIP (etoposide-ifosfamide-cisplatin), followed by conservative surgery and/or brachytherapy in case of post-chemotherapy residuum. RESULTS: Fourteen patients were included (median age = 12 months), of which six (43%) were classified as HiR. AFP levels were normalized after first-line chemotherapy in all cases but one. A vaginal post-chemotherapy residuum (median size = 8 mm, range: 1-24 mm) was observed in 13/14 patients, treated by complete resection in seven of 13 (viable cells in three of seven), incomplete resection in four of 13 (viable cells in two of four), with adjuvant brachytherapy in two of 13, and exclusive brachytherapy in two of 13 (viable cells in one of six). Among the six patients with viable disease, four patients received adjuvant chemotherapy. One patient (SR) experienced immediate postoperative relapse despite presenting no viable residual cells and was treated with four VIP cycles and brachytherapy. At last follow-up (median = 4.6 years, range: 0.5-16), all patients were alive in complete remission. Five patients suffered from vaginal sequelae with synechiae and/or stenosis (of whom four had undergone brachytherapy). CONCLUSION: Childhood vaginal MGCTs show a highly favorable prognosis with risk-adapted chemotherapy and local treatment of post-chemotherapy residuum (preferably by conservative surgery with partial vaginectomy). Brachytherapy could be an alternative when conservative surgery is not deemed possible or in cases of incomplete resection with residual viable cells.

ESTRO/ESGO/SIOPe Guidelines for the management of patients with vaginal cancer.

Primary vaginal malignancies are rare, comprising only 2% of all female genital tract malignancies in adults and 4.5% in children. As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) jointly with the European Society for Radiotherapy & Oncology (ESTRO) and the European Society of Pediatric Oncology (SIOPe) developed evidence-based guidelines in order to improve the management of patients with vaginal cancer within a multidisciplinary setting.ESTRO/ESGO/SIOPe nominated practicing clinicians who are involved in the management of vaginal cancer patients and have demonstrated leadership through their expertise in clinical care and research, their national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (13 experts across Europe comprising the international development group). To ensure that the statements were evidence based, the current literature was reviewed and critically appraised.In the case of absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 112 independent international practitionners in cancer care delivery and patient representatives and their comments and input were incorporated and addressed accordingly.These guidelines cover comprehensively the diagnostic pathways as well as the surgical, radiotherapeutical and systemic management and follow-up of adult patients (including those with rare histological subtypes) and pediatric patients (vaginal rhabdomyosarcoma and germ cell tumours) with vaginal tumours.

ESTRO/ESGO/SIOPe guidelines for the management of patients with vaginal cancer.

Primary vaginal malignancies are rare, comprising only 2% of all female genital tract malignancies in adults and 4.5% in children. As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) jointly with the European Society for Radiotherapy & Oncology (ESTRO) and the European Society of Pediatric Oncology (SIOPe) developed evidence-based guidelines in order to improve the management of patients with vaginal cancer within a multidisciplinary setting. ESTRO/ESGO/SIOPe nominated practicing clinicians who are involved in the management of vaginal cancer patients and have demonstrated leadership through their expertise in clinical care and research, their national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (13 experts across Europe comprising the international development group). To ensure that the statements were evidence based, the current literature was reviewed and critically appraised. In the case of absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 112 independent international practitionners in cancer care delivery and patient representatives and their comments and input were incorporated and addressed accordingly. These guidelines cover comprehensively the diagnostic pathways as well as the surgical, radiotherapeutical and systemic management and follow-up of adult patients (including those with rare histological subtypes) and pediatric patients (vaginal rhabdomyosarcoma and germ cell tumours) with vaginal tumours.

Outcome of patients with undifferentiated embryonal sarcoma of the liver treated according to European soft tissue sarcoma protocols.

BACKGROUND: To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy. METHODS: This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy. RESULTS: Out of 65 patients with a median age at diagnosis of 8.7 years (0.6-20.8), 15 had T2 tumors, and one had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, nine IRS II, 38 IRS III, and four IRS IV. Twenty-eight upfront surgeries resulted in five operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (p = .0119) and three infiltrated margins (p = .0238). All patients received chemotherapy, including anthracyclines in 47. RT was administered in 15 patients. With a median follow-up of 78.6 months, 5-year overall and event-free survivals (EFS) were 90.1% (95% confidence interval [CI]: 79.2-95.5) and 89.1% (95% CI: 78.4-94.6), respectively. Two out four local relapses had previous infiltrated margins and two out of three patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (p = .1607), T2 stage (p = .3870), use of RT (p = .8731), and anthracycline-based chemotherapy (p = .1181) were not correlated with EFS. CONCLUSIONS: Multimodal therapy improved the outcome of UESL. Neoadjuvant chemotherapy for pediatric patients increases the probability of complete surgical resection. The role of anthracyclines and RT for localized disease remains unclear.

The Use of Cavitron Ultrasonic Surgical Aspirator for High-Risk Neuroblastoma with Image-Defined Risk Factors in Children.

Aim of the study: The cavitron ultrasonic surgical aspirator (CUSA) has gained popularity in adult surgical oncology, but its application in children is limited to liver surgery and neurosurgical procedures. The complete resection of neuroblastoma with image-defined risk factors (IDRFs) is still considered one of the most difficult procedures to achieve in pediatric surgical oncology, with a high morbidity rate and potential risk of intraoperative mortality. The aim of our study is to describe the application of ultrasonic dissection in neuroblastoma with IDRFs. Methods: A retrospective study was performed, analyzing patients operated on from 2000 to 2018. Patient characteristics, resection completeness, and postoperative surgical and oncology outcomes were analyzed. Main results: Twenty-six patients with high-risk neuroblastoma and IDRFs were operated on in the study period with a CUSA. A complete macroscopic resection was performed in 50% of patients, while the other half was operated on with minimal residual (<5 mL). Six post-operative complications occurred without the need for surgery (Clavien−Dindo < 3). The overall survival was 50%, with a median follow-up of 69.6 months (5.6−140.4). Conclusions: The application of the CUSA in neuroblastoma with IDRFs can be considered an effective and safe alternative technique to achieve a radical resection.

Local treatment of rhabdomyosarcoma of the female genital tract: Expert consensus from the Children's Oncology Group, the European Soft-Tissue Sarcoma Group, and the Cooperative Weichteilsarkom Studiengruppe.

The International Soft-Tissue Sarcoma Consortium (INSTRuCT) was founded as an international collaboration between different pediatric soft-tissue sarcoma cooperative groups (Children's Oncology Group, European Pediatric Soft-Tissue Sarcoma Group, and Cooperative Weichteilsarkom Studiengruppe). Besides other tasks, a major goal of INSTRuCT is to develop consensus expert opinions for best clinical treatment. This consensus paper for patients with rhabdomyosarcoma of the female genital tract (FGU-RMS) provides treatment recommendations for local treatment, long-term follow-up, and fertility preservation. Therefore, a review of the current literature was combined with recommendations of the treatment protocols of the appropriate clinical trials. Additionally, opinions of international FGU-RMS experts were incorporated into recommendations. Results were that the prognosis of FGU-RMS is favorable with an excellent response to chemotherapy. Initial complete surgical resection is not indicated, but diagnosis should be established properly. In patients with tumors localized at the vagina or cervix demonstrating incomplete response after induction chemotherapy, local radiotherapy (brachytherapy) should be carried out. In patients with persistent tumors at the corpus uteri, hysterectomy should be performed. Fertility preservation should be considered in all patients. In conclusion, for the first time, an international consensus for the treatment of FGU-RMS patients could be achieved, which will help to harmonize the treatment of these patients in different study groups.

Implementation of Image-Guided Brachytherapy for Pediatric Vaginal Cancers: Feasibility and Early Clinical Results.

Background: Brachytherapy (BT) has a major role in pediatric cancers of the lower genital tract, as part of a multimodal organ conservative strategy. Scarce data are available on the location of image-guided BT. Methods: Medical records of all consecutive girls treated in our center between 2005 and 2020 for a vaginal tumor with exclusive image-guided PDR-BT were retrospectively examined, with a focus on treatment parameters, patient compliance, and clinical outcome, including analysis of local control, survival and late toxicity rates. Results: Twenty-six patients were identified, with a median age of 25 months. Histological types were rhabdomyosarcoma, malignant germ cell tumor (MGCT) and clear cell adenocarcinoma in 18 (69%), 7 (27%) and 1 (4%) patients, respectively. Ten (33%) patients had prior surgery and 25 (96%) received chemotherapy prior to BT. The median prescribed dose was 60 Gy through pulses of 0.42 Gy. Global compliance was satisfactory, but three (12%) patients required replanning because of applicator displacement. After a median follow-up of 47.5 months, one patient with MGCT referred for salvage treatment of a local recurrence had a local and metastatic relapse. The local control rate probability was 96% at the last follow-up. Late toxicity rates ≥ grade 2 and ≥ grade 3 were reported in 23% and 11%, respectively, with gynecological toxicities being the most frequent side effect. Two patients required dilatation for vaginal stenosis. Conclusions: PDR-BT allowed similar local control compared to the historical low-dose rate technique. An indirect comparison suggests fewer treatment-related toxicities by integrating image guidance and optimization capabilities, but longer follow-up is necessary. Due to the rarity of the disease and the technical aspects of BT in these very young patients, referral to specialized high-volume centers is recommended.

Long-term urological complications after conservative local treatment (surgery and brachytherapy) in children with bladder-prostate rhabdomyosarcoma: A single-team experience.

BACKGROUND: Outcome of children with bladder-prostate rhabdomyosarcoma (RMS) has improved with multimodal therapies, including surgery and/or radiotherapy for local treatment. Our aim was to report long-term urological complications after a conservative approach combining conservative surgery and brachytherapy. PATIENTS AND METHODS: Eighty-six patients, free of disease, were retrospectively reviewed. Symptoms related to urinary tract obstruction, incontinence, infection, and lithiasis were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Only symptomatic patients underwent urodynamic studies. Risk factors for complications were analyzed. RESULTS: There were 76 males and 10 females. The median follow-up was 6.3 years (18 months to 24 years). Complications occurred after a median follow-up of 5 years (0-21). Twenty-two patients (26%) had long-term urological complications. Urinary tract obstruction was found in 15 patients (17%) and urinary incontinence in 14 patients (16%). Recurrent urinary tract infection occurred in four patients and urinary lithiasis in four (5%). The underlying physiopathology included bladder dysfunction in 15 patients (17%), urethral stenosis in six (7%), and ureterovesical junction stenosis in five (6%). On univariate analysis, posterior bladder wall dissection (p = .001), bladder neck trigone dissection (p = .010), and partial prostatectomy (p = .023) were significantly associated with an increased risk of bladder dysfunction; on multivariate analysis, only age ≤2 years (p = .028) at operation and posterior bladder wall dissection (p = .006) were found to be significant. CONCLUSION: The conservative surgical approach combined with brachytherapy for bladder-prostate RMS leads to long-term urological complications in 26% of survivors. Optimizing brachytherapy doses for young children and establishing a clear and long-term follow-up protocol could help to reduce these complications.

Perianal/perineal rhabdomyosarcoma: Results of the SIOP MMT 95, Italian RMS 96, and EpSSG RMS 2005 studies.

BACKGROUND/OBJECTIVES: Rhabdomyosarcoma of the perianal/perineal region (PRMS) is rare, with poor survival and limited understanding of the functional consequences of treatment. DESIGN/METHODS: International Society of Pediatric Oncology (SIOP) malignant mesenchymal tumor (MMT) 95, Italian RMS 96, and European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 studies were interrogated to identify factors that impact survival; in RMS 2005, functional outcomes were analyzed. RESULTS: Fifty patients (nonmetastatic) were identified, median age 6.4 years (range: 0.1-19.6): 29 male, 21 female. Tumors were >5 cm in 33 patients. Histopathological subtype was alveolar in 35. Lymph nodes were involved in 23 patients. In RMS 2005, 16/21 (76%) tested alveolar tumors had positive FOXO1 fusion status. Diagnostic biopsy was performed in 37. Primary resection (13) was complete (R0) in one. Delayed primary excision (16) was complete in three. Radiotherapy (RT) in 34/50 patients included external beam (28), brachytherapy (3), and both (3). Nodal RT was given in 16/23 N1 patients (70%). Median follow-up of alive patients (29) was 84.1 months (range: 3.6-221.1). Relapse or progression occurred in 24 patients (48%), 87% were fatal and most events (63%) were locoregional. Five-year event-free survival (EFS) was 47.8 (95% CI: 32.8-61.3), and 5-year overall survival (OS) was 52.6 (95% CI: 36.7-66.2), with age ≥10 years and tumor size >5 cm impacting 5-year EFS and OS (p < .05). Functional outcome data showed bowel, genito-urinary, and psychological issues; fecal incontinence in four of 21 survivors, and urinary symptoms in two of 21. CONCLUSIONS: About 60% of patients with nonmetastatic PRMS survive; older patients and those with large tumors have the worst outcomes. Biopsy should be the initial procedure, and definitive local therapy individualized. Quality-of-life and functional studies are needed to better understand the consequences of treatment.

Brachytherapy for Pediatric Patients at Gustave Roussy Cancer Campus: A Model of International Cooperation for Highly Specialized Treatments.

PURPOSE: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers. METHODS AND MATERIALS: We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy. RESULTS: We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy. CONCLUSIONS: This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability.

The Impact of Radiation Therapy in Children and Adolescents With Metastatic Rhabdomyosarcoma.

PURPOSE: There is limited evidence to define the role of radiation therapy in children with metastatic rhabdomyosarcoma (mRMS). In the international BERNIE study, children with mRMS or non-RMS soft tissue sarcoma were randomized to receive standard chemotherapy with or without bevacizumab, with radiation therapy to all disease sites recommended after chemotherapy cycle 6. We retrospectively evaluated the impact of radiation therapy on survival in the mRMS cohort. METHODS AND MATERIALS: Patients were grouped according to the radiation therapy they received: radical, partial, or none. Radical irradiation was defined as radiation therapy delivered to all disease sites, unless a site was completely surgically resected. Partial irradiation was defined as radiation therapy to ≥1, but not all, disease sites. Landmark analysis excluded patients with an event before day 221. Overall survival (OS) and event-free survival (EFS) were modeled using Cox proportional hazards models. RESULTS: Of 102 patients with mRMS, 97 were included in the analysis for OS and 85 for EFS. Overall, 27 patients received radical irradiation, 46 partial irradiation, and 24 no irradiation. EFS was not significantly different among patient groups after adjustment for prognostic factors (hazard ratio [HR] = 0.520; P = .054 for any vs no irradiation). Radiation therapy was associated with improved OS compared with no radiation therapy (adjusted HR = 0.249; P = .00025), with OS being greater for radical versus partial irradiation (HR = 0.245; P = .039). The 3-year OS rate was 84%, 54%, and 23% for patients receiving radical, partial, and no irradiation, respectively. Radical treatment (surgery, irradiation, or both) of the primary site improved EFS and OS compared with no treatment. CONCLUSIONS: These findings demonstrate variability in the application of radiation therapy for mRMS and support the routine use of radical treatment to the primary site. Radical irradiation to metastatic sites may further improve OS. The burden of such treatment should be balanced against prognosis; further studies are needed.

Surgical management of paratesticular rhabdomyosarcoma: A consensus opinion from the Children's Oncology Group, European paediatric Soft tissue sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe.

The treatment of paratesticular rhabdomyosarcoma (PT-RMS) has varied over time and by cooperative group. The International Soft Tissue Sarcoma Database Consortium (INSTRuCT) is a collaboration of the Children's Oncology Group (COG) Soft Tissue Sarcoma Committee, European pediatric Soft tissue sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS). The INSTRuCT surgical committee has been given charge of the development of internationally applicable consensus guidelines for the surgical treatment of rhabdomyosarcoma. This clinical consensus opinion document addresses accepted principles and areas of controversy, such as scrotal violation and retroperitoneal nodal evaluation, providing an evidence-based guideline for the surgical treatment for PT-RMS.

Analysis of Radiation Dose/Volume Effect Relationship for Anorectal Morbidity in Children Treated for Pelvic Malignancies.

PURPOSE: To examine dose-volume effect relationships for anorectal morbidity in children treated with image-guided brachytherapy for pelvic tumors. METHODS AND MATERIALS: Medical records of all consecutive children with pelvic tumors treated in our center and receiving image-guided pulsed-dose-rate brachytherapy with or without external beam radiation therapy (EBRT) between 2005 and 2019 were reviewed. The effect of the minimal doses to the most exposed 0.5 cm3, 1 cm3, and 2 cm3 of the anorectum (respectively: D0.5cm3, D1cm3, and D2cm3), total reference air kerma (TRAK), and volume of 100% isodose was examined for anorectal toxicities. RESULTS: Seventy-eight consecutive children were included. Median age was 2.9 years (range, 0.8-14.9 years). Most of the tumors were bladder or prostate (67%) or vaginal (22%) rhabdomyosarcoma. Six patients received EBRT in addition to brachytherapy. Median follow-up was 21.3 months. At last follow-up, 30 children (38%) had experienced Common Terminology Criteria for Adverse Events version 5 grade ≥1 acute or late anorectal events: 24% had grade 1 events, 7.7% had grade 2 events, and 6.4% had grade 3 events. No toxicity greater than grade 3 was observed (eg, fistula or stricture). In univariate analysis, the D0.5cm3 and D1cm3 were significant for probability of grade 1 to 3 (P = .009 and P = .017, respectively) and grade 2 to 3 anorectal morbidity (P = .007 and P = .049, respectively). There was no significant correlation for D2cm3 (P = .057 for grade 1-3; P = .407 for grade 2-3). A 10% probability (95% confidence interval, 4%-20%) for anorectal toxicity of grade 2 or greater was reached for a D0.5cm3 = 52 Gy. The age, EBRT use, TRAK, and treated volume values were not significant. CONCLUSIONS: To our knowledge, this study is the first to show a significant dose-volume effect relationships for anorectal morbidity in children undergoing treatment with brachytherapy. Integrating these data into brachytherapy treatment planning could help to optimize the therapeutic index in these young patients.

Local staging and treatment in extremity rhabdomyosarcoma. A report from the EpSSG-RMS2005 study.

Rhabdomyosarcoma of the extremities present with two main challenges: correct evaluation of initial regional nodal involvement and define adequate local treatment. METHODS: Pediatric patients with localized rhabdomyosarcoma of the extremity included in the EpSSG-RMS2005 study between 2005 and 2014 were evaluated for staging, treatment, and survival. The outcome was compared to the preceding European SIOP-MMT studies. RESULTS: Of the 162 patients included, histology was unfavorable in 113 (70%), 124 (77%) were younger than 10 years, 128 (79%) were IRS III, and 47 (29%) were node-positive. A regional node biopsy was performed in 97 patients (60%) and modified the lymph node stage in 15/97 (16%). Primary and delayed surgery was performed in 155 (96%) and radiotherapy delivered in 118 (73%) patients. Relapse occurred in 61 cases (38%), local in 14 (23%), regional in 13 (21%), distant in 22 (36%), and combined relapse in 12 (20%) with five progressive diseases (8%) and four secondary tumors (7%). Five-year event free (EFS) and overall survival (OS) were 58.4% (95%CI, 50.3-65.7) and 71.7% (63.6-78.4), respectively. In the previous studies MMT89 and MMT95, tumor surgery was performed in 32/53 (60%) and 74/82(90%), respectively, and radiotherapy delivered in 13/53 (25%) and 26/82 (30%), respectively. Five-year EFS and OS were 35.6%, and 50.3% in MMT89 and 54.3% and 68.2% in the MMT95 study. CONCLUSIONS: Even if the lymph node staging was not always complete according to the RMS2005 protocol, node sampling changed lymph node status in a significant number of patients. Despite the higher rate of patients treated with locoregional radiotherapy, survival in RMS2005 did not improve compared to the previous European SIOP-MMT95 study.

Paratesticular rhabdomyosarcoma-Impact of locoregional approach on patient outcome: A report from the European paediatric Soft tissue sarcoma Study Group (EpSSG).

BACKGROUND: Paratesticular rhabdomyosarcoma (PT RMS) is rare compared to benign scrotal pathology. Inappropriate first surgery (InFS) required supplementary treatment to maintain excellent outcomes. Initial staging of regional lymph nodes is important. The aim of this study was to determine to what extent the quality of locoregional approach impacted on patient morbidity and survival. DESIGN/METHODS: Analysis was performed on all nonmetastatic PT RMS patients enrolled in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 protocol. Aspects assessed were adherence to surgical guidelines and impact of protocol violations, relapse analysis, and survival outcomes. RESULTS: Analysis was performed on 237 patients, with median follow up of 67.1 months. Median age was 9.0 years. InFS occurred in 75 of 237 (32%) patients. InFS required intensified chemotherapy (10) and local therapy. After InFS, 61 required primary reexcision and five delayed surgery. Of 26 recurrences, the risk of relapse was higher in patients ≥10 years (21/26) and was mainly locoregional in 16 of 26 recurrences (± metastatic). Sixteen of 26 died with 14 of 16 patients ≥10 years. Nodal relapse neither occurred when N1 nodes were identified at diagnosis, nor after surgical staging. Five-year overall survival (OS) at age <10 years versus ≥10 years was 98.1 and 86.7%, respectively (P = .0013). Event-free survival (EFS) at age <10 years versus ≥10 years was 95.8 and 79.6%, respectively (P = .0004). OS and EFS did not highlight a significant difference in patients undergoing appropriate versus InFS (P = .8479, P = .2780, respectively). CONCLUSIONS: InFS required intensified therapy to maintain excellent OS and EFS, so better anticipation of malignancy is required. Surgical staging of the retroperitoneal lymph nodes should be performed in patients ≥10 years old.

[Retroperitoneal lymph node assessment in pediatric paratesticular rhabdomyosarcoma]. / La place du curage rétropéritonéal dans les Rhabdomyosarcomes para-testiculaires du jeune.

Paratesticular Rhabdomyosarcoma accounts for 7 to 11% of pediatric rhabdomyosarcomas. Children older than 10 years have a worse event-free survival (69 to 80% vs. 87 to 92%) than children younger than 10 years. In this location, the relapses are essentially in the retroperitoneal lymph nodes and are often fatal. In European protocols, the assessment of the retroperitoneal lymph nodes at diagnosis is made by imaging whereas it is performed by retroperitoneal lymph node dissection in the American protocols. This method has been proved to improve event-free survival in the group of patient older than 10 years with a tumour bigger than 5cm. In the next European protocol, when nodes will be enlarged a surgical biopsy will be performed, this will be irrespective of age or size, and when no nodes will be enlarged in patients older than 10 years, retroperitoneal lymph node assessment will be performed. Other techniques of lymph nodes assessment will be tested like sentinel node biopsies or PET-scan.

Outcomes of metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated within the BERNIE study: a randomised, phase II study evaluating the addition of bevacizumab to chemotherapy.

PURPOSE: We analysed the cohort of paediatric patients with metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated in the BERNIE protocol, i.e. open-label, multicentre, randomised phase II study evaluating the role of bevacizumab (BO20924/ITCC-006; ClinicalTrials.gov: NCT00643565). METHODS: Eligible patients were randomised 1:1 to add or not add bevacizumab to nine courses of intensive multi-drug chemotherapy, followed by 12-month maintenance chemotherapy (plus surgery and radiotherapy). The primary end-point was event-free survival (EFS); secondary objectives were objective response rate (ORR) and overall survival (OS). RESULTS: From 2008 and 2013, 49 NRSTS patients (out of 154 cases) were treated, 26 in the standard arm and 23 in the bevacizumab arm. ORR was seen in 10 out of 36 evaluable cases (27.7%), i.e. 4/18 standard arm cases and 6/18 bevacizumab arm cases. Two-year EFS was 27.3% (95% confidence interval [CI] 13.9-42.5) for all NRSTS patients, i.e. 34.9% (95% CI 14.6-56.2) for bevacizumab arm and 22.9% (95% CI 7.1-43.9) for standard arm (p-value = 0.19). Three-year OS (median follow-up 48.6 months) was 35.2%, with no differences in the two arms. Time to event and time to death were 16.3 and 17.2 months for bevacizumab arm and 2.1 and 7.6 months for standard arm, respectively. Patients not receiving any local treatment on primary disease had a worse outcome as compared to others. Treatment results were better for patients receiving surgical resection and worse for those who did not receive any specific treatment. CONCLUSION: The addition of the anti-angiogenic agent to the standard chemotherapy did not show statistically significant improvement in survival in metastatic NRSTS.

African School of Pediatric Oncology Initiative: Implementation of a Pediatric Oncology Diploma Program to Address Critical Workforce Shortages in French-Speaking Africa.

PURPOSE: In 2012, the French African Pediatric Oncology Group established the African School of Pediatric Oncology (EAOP), a training program supported by the Sanofi Espoir Foundation's My Child Matters program. As part of the EAOP, the pediatric oncology training diploma is a 1-year intensive training program. We present this training and certification program as a model for subspecialty training for low- and middle-income countries. METHODS: A 14-member committee of multidisciplinary experts finalized a curriculum patterned on the French model Diplôme Inter-Universitaire d'Oncologie Pédiatrique. The program trained per year 15 to 25 physician participants committed to returning to their home country to work at their parent institutions. Training included didactic lectures, both in person and online; an onsite practicum; and a research project. Evaluation included participant evaluation and feedback on the effectiveness and quality of training. RESULTS: The first cohort began in October 2014, and by January 2019, 72 participants from three cohorts had been trained. Of the first 72 trainees from 19 French-speaking African countries, 55 (76%) graduated and returned to their countries of origin. Four new pediatric oncology units have been established in Niger, Benin, Central African Republic, and Gabon by the graduates. Sixty-six participants registered on the e-learning platform and continue their education through the EAOP Web site. CONCLUSION: This training model rapidly increased the pool of qualified pediatric oncology professionals in French-speaking countries of Africa. It is feasible and scalable but requires sustained funding and ongoing mentoring of graduates to maximize its impact.