Tumor Study Group Research Articles

Outcome of Stage IV Completely Necrotic Wilms Tumour and Local Stage III Treated According to the SIOP 2001 Protocol.

Simple SummaryAround 15–20% of all Wilms tumour (WT) patients present with metastatic disease. Approximately 10% of these patients achieve complete necrosis after preoperative chemotherapy, which is associated with a favourable prognosis. The aim of this observational study is to describe the outcome of metastatic patients with completely necrotic (low-risk histology), local stage III WT treated according to the SIOP 2001 protocol, whether or not postoperative radiotherapy was applied.Objective: Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the SIOP 2001 protocol, the SIOP– Renal Tumour Study Group (SIOP–RTSG) has omitted radiotherapy for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However, for metastatic patients with local stage III, completely necrotic WT, the recommendations led to ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or not. Methods and materials: all metastatic patients with local stage III, completely necrotic WT after 6 weeks of preoperative chemotherapy who were registered in the SIOP 2001 study were included in this analysis. The pattern of recurrence according to the usage of radiation treatment and 5 year event-free survival (EFS) and overall survival (OS) was analysed. Results: seven hundred and three metastatic WT patients were registered in the SIOP 2001 database. Of them, 47 patients had a completely necrotic, local stage III WT: 45 lung metastases (11 combined localisations), 1 liver/peritoneal, and 1 tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial embolism. Abdominal radiotherapy was administered in 29 patients (62%; 29 flank/abdominal irradiation and 9 combined with lung irradiation). Eighteen patients did not receive radiotherapy. Median follow-up was 6.6 years (range 1–151 months). Two of the 47 patients (4%) developed disease recurrence in the lung (one combined with abdominal relapse) and eventually died of the disease. Both patients had received abdominal radiotherapy, one of them combined with lung irradiation. Five-year EFS and OS were 95% and 95%, respectively. Conclusions: the outcome of patients with stage IV, local stage III, completely necrotic Wilms tumours is excellent. Our results suggest that abdominal irradiation in this patient category may not be of added value in first-line treatment, consistent with the current recommendation in the SIOP–RTSG 2016 UMBRELLA protocol.

Characteristics and outcome of pediatric renal cell carcinoma patients registered in the International Society of Pediatric Oncology (SIOP) 93-01, 2001 and UK-IMPORT database: A report of the SIOP-Renal Tumor Study Group.

In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric Oncology‐Renal Tumor Study Group (SIOP‐RTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93‐01, 2001 and UK‐IMPORT databases, were included. Event‐free survival (EFS) and overall survival (OS) were analyzed using the Kaplan‐Meier method. Between 1993 and 2019, 122 pediatric patients with RCC were registered. Available detailed data (n = 111) revealed 56 localized, 30 regionally advanced, 25 metastatic and no bilateral cases. Histological classification according to World Health Organization 2004, including immunohistochemical and molecular testing for transcription factor E3 (TFE3) and/or EB (TFEB) translocation, was available for 65/122 patients. In this group, the most common histological subtypes were translocation type RCC (MiT‐RCC) (36/64, 56.3%), papillary type (19/64, 29.7%) and clear cell type (4/64, 6.3%). One histological subtype was not reported. In the remaining 57 patients, translocation testing could not be performed, or TFE‐cytogenetics and/or immunohistochemistry results were missing. In this group, the most common RCC histological subtypes were papillary type (21/47, 44.7%) and clear cell type (11/47, 23.4%). Ten histological subtypes were not reported. Estimated 5‐year (5y) EFS and 5y OS of the total group was 70.5% (95% CI = 61.7%‐80.6%) and 84.5% (95% CI = 77.5%‐92.2%), respectively. Estimated 5y OS for localized, regionally advanced, and metastatic disease was 96.8%, 92.3%, and 45.6%, respectively. In conclusion, the registered pediatric patients with RCC showed a reasonable outcome. Survival was substantially lower for patients with metastatic disease. This descriptive study stresses the importance of full, prospective registration including TFE‐testing.

Incidence and impact of textbook outcome among patients undergoing resection of pancreatic neuroendocrine tumors: results of the US neuroendocrine tumor study group

Introduction: Textbook outcome (TO) is an increasingly recognized composite measure of quality. We sought to define the incidence and impact of TO on conditional disease-free survival (cDFS) among patients undergoing resection of pancreatic neuroendocrine tumors (PNET). Methods: Patients undergoing resection of PNET between 2000-2018 were identified using an international multi-institutional database. TO was defined as no postoperative >3 grade complication, no 90-day mortality, no prolonged length-of-hospital stay(LOS)(ie. LOS > 75thpercentile), no 90-day readmission after discharge, and R0 resection. 3-year cDFS was calculated and the association of TO with cDFS was examined. Results: Among 821 patients with PNET, median tumor size was 2.1 cm (IQR:1.4-14.6) with a median Ki-67 index of 2.4 (IQR:1.4-5.0). Resection consisted of pancreatoduodenectomy (PD)(n=231, 28.1%), distal pancreatectomy (DP)(n=492, 59.9%) and enucleation (EN)(n=98, 11.9%). Incidence of TO varied by procedure type (PD, 32.5% vs. DP, 56.7% vs. EN, 52.0%; p< 0.001). While certain TO factors such asno 90-day mortality (PD: 99.1% vs. DP: 99.0% vs EN: 99.0%) was comparable among surgery subtypes, other factors such as avoidance ofprolonged LOS (PD: 59.7% vs. DP: 85.4% vs. EN: 73.5%), no complications (PD: 70.1% vs. DP: 78.9% vs. EN: 82.7%), and readmission (PD: 74.0% vs. DP: 81.7% vs EN: 84.7%) were all achieved more often following DP and EN versusPD(all p< 0.05)(Figure).TO was independently associated with improved cDFS (HR:0.54, 95%CI 0.35-0.81; p=0.003). Conclusions: Many patients undergoing resection of PNET did not experience a TO, which varied markedly based on procedure type. Achieving TO was associated, however, with improved cDFS.

The Clinical Characteristics and Survival Profiles of Wilms Tumor in the United Arab Emirates: A Single-center Retrospective Analysis

Background: Wilms Tumor (WT) is the most common pediatric kidney tumor, yet the disease has variable clinical characteristics and prognostic outcomes across different populations. Objectives: This study aims to review the clinical characteristics and survival outcomes of children with WT who have received treatment at Dubai Hospital, UAE. Methods: A retrospective study was conducted involving the medical records of confirmed WT children (aged &lt; 14 years) who had received treatment between 2013 and 2018. Diagnosis should have been established based on the histopathological examination of operable tumors and needle biopsy for inoperable tumors. The Société Internationale d’Oncologie Pédiatrique (SIOP) WT 2001 protocol was used for patient management, and the UMBRELLA SIOP–RTSG 2016 Wilms tumor pathology and molecular biology protocol was used for histopathologic classification and clinical staging. The presenting sign and symptoms, the findings of diagnostic imaging techniques, histological grading, the received treatments, and follow-up outcomes were collected and analyzed. Kaplan-Meier survival analysis was used to carry out the survival analysis. Results: Ten children were diagnosed with WT (median age of 3.40 years, 60% males). All patients presented with abdominal masses without prominent pain. Synchronous bilateral lesions were found at diagnosis in one patient and metastatic lesions in three patients. Four children were discharged against medical advice; five received treatment according to the SIOP WT 2001 regimen, while the remaining patient was managed in the United States according to the National Wilms Tumor Study Group (NWTSG) protocol. The overall 6-year and relapse-free survival rates were 90% and 80%, respectively. Conclusion: The clinical characteristics and managemental outcomes of children presenting with WT are promising, possibly owing to adopting the SIOP protocol. Considering the small sample size, more large-scale, nation-wide studies are warranted.

New approaches to risk stratification for Wilms tumor.

The treatment of Wilms tumor is one of the great achievements in the field of oncology. One of the key success factors has been improved risk stratification, enabling augmentation or reduction of therapy depending on a patient's risk of relapse. This article highlights the evolution of clinical and biological prognostic markers that have been applied in the treatment of Wilms tumor. Historically, tumor stage and histology were the sole determinants of Wilms tumor treatment. Recent clinical trials conducted by the Children's Oncology Group (COG) and the International Society of Pediatric Oncology (SIOP) Renal Tumor Study Group have expanded the menu of prognostic factors to include histologic and volumetric response to therapy and tumor-specific loss of heterozygosity (LOH) at chromosomes 1p and 16q. Augmentation of therapy has been able to overcome the adverse risk factors. An emerging prognostic marker is chromosome 1q gain, will be incorporated into future clinical trials. The application of new clinical and biological prognostic factors has created unprecedented ability to tailor therapy for Wilms tumor, accompanied with improved outcomes. Current and future trials will continue to enhance precision medicine for Wilms tumor.

Unmet needs for relapsed or refractory Wilms tumour: Mapping the molecular features, exploring organoids and designing early phase trials - A collaborative SIOP-RTSG, COGand ITCC session at the first SIOPE meeting.

Wilmstumour(WT) accounts for about 6% of all childhood cancers and overall survival of WT is about 90% in international protocols. However, for WT subgroups with much poorer prognoses, i.e. typically high-risk (unfavorable) histology and/or relapse, there is an unmet need to better understand the biology of WT and to translate biological findings into clinics through early phase clinical trials that evaluate innovative therapies. The main challenges are the small numbers of children suitable for early phase trials, the genetic heterogeneity of WT and the low number of somatic mutations that are currently considered 'druggable'. Accordingly, a joint meeting between clinical and biology experts from the international cooperative groups of the Renal Tumour Study Group of the International Society of Paediatric Oncology, the Renal Tumour Committee of the Children's Oncology Group and the European Innovative Therapies for Children with Cancer consortiumand parents representatives was organised during the first SIOPE meeting in Prague, 2019. We reviewed WT molecular features, ongoing/planned early phase trials and explored available knowledge on organoid technology. The key messages were: (1) relapsed WT should undergo whenever possible thorough molecular characterization and be enrolled in protocols or trials with systematic data collecting and reporting; (2) WT displays few known 'actionable' targets and currently no novel agent has appeared promising; (3) we need to improve the enrolment rate of WT candidates in early phase trials especially for the relatively small subgroup of relapses with an adverse prognostic signature; (4) despite some agnostic early phase trials existing, development of WT-focused trials are warranted; (5) growing organoids with parallel testing of drug panels seems feasible and may direct individual treatment and encourage clinical researchers to incorporate the most promising agents into early phase trials.

Adjuvant and neoadjuvant chemotherapy for soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group.

The standard therapy for all localized soft tissue sarcomas is surgical resection of the tumor. For patients with soft tissue sarcomas who are at high risk for recurrence and/or metastasis, perioperative chemotherapy is a potential treatment option. Adriamycin plus ifosfamide is currently the most promising chemotherapy regimen for localized soft tissue sarcomas. Randomized controlled trials and meta-analyses of adjuvant postoperative chemotherapy for soft tissue sarcomas have suggested that adjuvant chemotherapy may provide an advantage, however small, compared with surgery alone. On the other hand, recent randomized trials have demonstrated the efficacy of neoadjuvant preoperative chemotherapy using full-dose anthracycline plus ifosfamide for high-risk soft tissue sarcomas and showed survival benefits in patients with large, deep-seated and high-grade soft tissue sarcomas of the trunk and extremities. In this review, adjuvant and neoadjuvant chemotherapies for soft tissue sarcomas and future perspectives are discussed.

ML-09 The REAL-WORLD of Elderly PCNSL Therapy in Tohoku and Niigata Area According to Retrospective Analysis: A Collaborative Investigation of the Tohoku Brain Tumor Study Group

Introduction: Recently, the number of cases of primary central nervous system lymphoma in elderly patients(EL-PCNSL) has been increasing. However, the treatment may be insufficient because of poor performance status and pre- and posttreatment complications. Therefore, we analyzed the risk factors for EL-PCNSL in the Tohoku and Niigata areas of Japan and clarified the REAL-WORLD of EL-PCNSL therapy. Materials & Methods: We investigated surgical and nonsurgical cases of patients aged 71 years or older from eight facilities during the last 8 years. We analyzed patient information, radiotherapy/chemotherapy or not, PFS, OS, RRs, second-line therapy, pre- and posttreatment complications, outcomes, and risk factors for poor prognosis. The log-rank test was used for univariate analysis, and Cox regression analysis was used for a multivariate analysis of risk factors. Results: Of the 142 cases registered, five differed from PCNSL pathologically, three receiving BSC were excluded, 31 were treated without biopsy, three were treated based on CSF-findings, and 100 were treated with biopsy. Total 134 cases were followed. The median age was 76 years, pretreatment KPS was 50%, and 118 cases(88%) had 217 pretreatment complications. The treatment contents consisted of various combinations depending on the attending physician. The retrospective overall PFS was 16 months and OS was 24 months. In the early treatment phase, out of 16 cases with dropout, four tumor and four complication deaths occurred. There were 77 deaths(58%), 39 internal tumor deaths(51%), and 33 complication deaths(43%). Poor prognostic risk factors were <60% posttreatment KPS, complications involving pretreatment cardiovascular and central nervous system disease, posttreatment pneumonia or severe infection, and absence of radiation or chemotherapy. Conclusions: Pretreatment KPS did not affect poor outcomes, but posttreatment KPS <60% and pre- and posttreatment complications did. Radiotherapy and chemotherapy are reportedly effective, but additional research to clarify the details of these modalities is needed.

Clinical characteristics and outcomes of children with WAGR syndrome and Wilms tumor and/or nephroblastomatosis: The 30-year SIOP-RTSG experience.

BackgroundWAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare contiguous gene deletion syndrome with a 45% to 60% risk of developing Wilms tumor (WT). Currently, surveillance and treatment recommendations are based on limited evidence.MethodsClinical characteristics, treatments, and outcomes were analyzed for patients with WAGR and WT/nephroblastomatosis who were identified through International Society of Pediatric Oncology Renal Tumor Study Group (SIOP‐RTSG) registries and the SIOP‐RTSG network (1989‐2019). Events were defined as relapse, metachronous tumors, or death.ResultsForty‐three patients were identified. The median age at WT/nephroblastomatosis diagnosis was 22 months (range, 6‐44 months). The overall stage was available for 40 patients, including 15 (37.5%) with bilateral disease and none with metastatic disease. Histology was available for 42 patients; 6 nephroblastomatosis without further WT and 36 WT, including 19 stromal WT (52.8%), 12 mixed WT (33.3%), 1 regressive WT (2.8%) and 2 other/indeterminable WT (5.6%). Blastemal type WT occurred in 2 patients (5.6%) after prolonged treatment for nephroblastomatosis; anaplasia was not reported. Nephrogenic rests were present in 78.9%. Among patients with WT, the 5‐year event‐free survival rate was 84.3% (95% confidence interval, 72.4%‐98.1%), and the overall survival rate was 91.2% (95% confidence interval, 82.1%‐100%). Events (n = 6) did not include relapse, but contralateral tumor development (n = 3) occurred up to 7 years after the initial diagnosis, and 3 deaths were related to hepatotoxicity (n = 2) and obstructive ileus (n = 1).ConclusionsPatients with WAGR have a high rate of bilateral disease and no metastatic or anaplastic tumors. Although they can be treated according to existing WT protocols, intensive monitoring of toxicity and surveillance of the remaining kidney(s) are advised.Lay Summary WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare genetic condition with an increased risk of developing Wilms tumor.In this study, 43 patients with WAGR and Wilms tumor (or Wilms tumor precursor lesions/nephroblastomatosis) were identified through the international registry of the International Society of Pediatric Oncology Renal Tumor Study Group (SIOP‐RTSG) and the SIOP‐RTSG network. In many patients (37.5%), both kidneys were affected. Disease spread to other organs (metastases) did not occur.Overall, this study demonstrates that patients with WAGR syndrome and Wilms tumor can be treated according to existing protocols. However, intensive monitoring of treatment complications and surveillance of the remaining kidney(s) are advised.

Impact of uterus-preserving surgery on Stage I primary mucinous epithelial ovarian carcinoma: A multi-institutional study with propensity score-weighted analysis.

To investigate the clinical characteristics of women with Stage I primary mucinous epithelial ovarian carcinoma (mEOC) and evaluate the impact of uterus-preserving surgery (UPS) in terms of survival prognosis. A regional multi-institutional retrospective study conducted between January 1986 and March 2017 by reviewing records of the Tokai Ovarian Tumor Study Group. Clinical and pathologic data and survival outcomes were assessed for women with Stage I primary mEOC. The baseline imbalance between women with and those without UPS was adjusted by an inverse probability of treatment weighting method using the propensity score (PS) of independent clinical variables. Among 4730 women with malignant ovarian tumors, 185 had Stage I primary mEOC and were included in the study. The mean age was 47.6years (range 12-87years), and 56 (30.3%) women underwent UPS. After PS-based adjustment, women in the UPS group did not have a poorer prognosis regarding overall survival (P=0.776) or recurrence-free survival (P=0.683). Even after age stratification, there was no statistical difference in survival outcomes between the UPS and non-UPS groups. UPS was not associated with decreased survival and may be a treatment option for women with Stage I primary mEOC irrespective of age.

Editorial introductions

Editorial introductions

Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors.

Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear. A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000-2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65years were excluded, as these patients are almost universally covered by Medicare. Kaplan-Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS). The USNETSG database included 2022 patients. Of those, 1425 were aged 18-64years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32-5.48, p = 0.006]. Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.

Incidence and impact of Textbook Outcome among patients undergoing resection of pancreatic neuroendocrine tumors: Results of the US Neuroendocrine Tumor Study Group.

We sought to define the incidence and impact of Textbook Outcome (TO) on disease-freesurvival [DFS] among patients undergoing resection of pancreatic neuroendocrine tumors (PNET). Patients undergoing resection of a PNET between 2000 and 2016 were identified using a multi-institutional database. TO was defined as no postoperative severe complications (Clavien-Dindo grade ≥ III), no 90-day mortality, no prolonged length-of-hospital stay (LOS) (ie, > 75th percentile), no 90-day readmission after discharge, and R0 resection. The 5-year DFS was calculated and the association with TO was examined. Among 821 patients with a PNET, median tumor size was 2.1 cm (IQR 1.4-14.6). Resection consisted of pancreatoduodenectomy (PD) (n = 231, 28.1%), distal pancreatectomy (DP) (n = 492, 59.9%), and enucleation (EN) (n = 98, 11.9%). Overall TO rate was 49.3% (n = 405). The incidence of TO varied by procedure type (PD: 32.5% vs DP: 56.7% vs EN: 52.0%; P < .001). After adjusting for all competing factors, achievement of a TO was independently associated with improved DFS (hazard ratio: 0.54, 95% CI, 0.35-0.81; P = .003). Only one in two patients undergoing resection of a PNET achieved a TO, which varied markedly based on procedure type. Achievement of a TO was associated with improved DFS.

Outcome of patients with stage IV high-risk Wilms tumour treated according to the SIOP2001 protocol: A report of the SIOP Renal Tumour Study Group

IntroductionHigh-risk (HR) metastatic (stage IV) Wilms tumours (WTs) have a particular poor outcome. MethodsHere, we report the results of HR (diffuse anaplastic [DA] or blastemal type [BT]) stage IV WT treated patients according to the HR arm in the SIOP2001 prospective study. ResultsFrom January 2002 to August 2014, 3559 patients with WT were included in the SIOP2001 trial. Among the 525 patients (15%) with metastatic WT, 74 (14%) had stage IV HR-WT. The median age at diagnosis was 5.5 years (range: 1.4–18.3). Thirty-four patients (47%) had BT-WT and 40 (53%) had DA-WT. Five-year event-free survival rates were 44 ± 17% and 28 ± 15% for BT-WT and DA-WT, respectively (p = 0.09). Five-year overall survival rates were 53 ± 17% and 29 ± 16% for BT-WT and DA-WT, respectively (p = 0.03). Metastatic complete response after preoperative treatment was significantly associated with outcome in univariate and multivariate analyses (hazards ratio = 0.3; p = 0.01). Postoperative radiotherapy of metastatic sites might also be beneficial. Forty-three of 74 patients experienced a relapse or progression predominantly in the lungs (80%). The median time to relapse/progression after diagnosis was 7.3 months (range: 1.6–33.3) and 4.9 months (range: 0.7–28.4) for BT-WT and DA-WT, respectively (p = 0.67). This is the first prospective evidence of inferior survival of stage IV BT-WT as compared with historical intermediate-risk WT. Survival of patients with stage IV DA-WT has not improved compared to the previous SIOP93-01 study. ConclusionThese results call for new treatment approaches for patients with HR stage IV WT.

Challenges on participation in a cooperative group of childhood renal tumors in Brasil.

Children with renal tumors included in clinical trials have significantly better outcomes. In Brasil, the enrollment of patients in clinical trials remains challenging. Here we aimed to describe participation accrual in the Brazilian Wilms Tumor Study Group (BWTSG) and to identify barriers to trial registration of children with renal tumors. We determined the numbers of renal tumor diagnoses in 105 hospital-based cancer registries from 2001-2009. We then compared these totals with the numbers of renal tumor cases registered in the BWTSG from the same hospitals during the same time period. We also invited members of the Brazilian Pediatric Oncology Society to complete a 5-point Likert-type scale questionnaire regarding their opinions of the importance of participation in cooperative group trials. The accrual rate of patient participation per hospital varied from 25% to 76%, and was highest in the South region. The accrual rate of hospital participation also varied according to the region (20-31%) and was highest in the Southeast region. For the questionnaire regarding the importance of participation in cooperative groups, the responses showed an agreement of >75% on 10 of the 13 statements. Our results demonstrated low accrual of participation in a cooperative group trial in Brasil. We identified variations in registration rates according to geographic region and hospital, which may help targeted efforts to increase registration rates. The survey responses demonstrated that colleagues understand the importance of trial participation.

Long-Term Outcomes after Spleen-Preserving Distal Pancreatectomy for Pancreatic Neuroendocrine Tumors: Results from the US Neuroendocrine Study Group

Background: The adoption of spleen-preserving distal pancreatectomy (SPDP) for malignant disease such as pancreatic neuroendocrine tumors (pNETs) has been controversial. The objective of the current study was to assess the impact of SPDP on outcomes of patients with pNETs. Methods: Patients undergoing a distal pancreatectomy for pNET between 2002 and 2016 were identified in the US Neuroendocrine Tumor Study Group database. Propensity score matching (PSM) was used to compare short- and long-term outcomes of patients undergoing SPDP versus distal pancreatectomy with splenectomy (DPS). Results: Among 621 patients, 103 patients (16.6%) underwent an SPDP. Patients who underwent SPDP were more likely to have lower BMI (median, 27.5 [IQR 24.0–31.2] vs. 28.7 [IQR 25.7–33.6]; p = 0.005) and have undergone minimally invasive surgery (n = 56, 54.4% vs. n = 185, 35.7%; p < 0.001). After PSM, while the median total number of lymph nodes examined among patients who underwent an SPDP was lower compared with DPS (3 [IQR 1–8] vs. 9 [5–13]; p < 0.001), 5-year overall survival (OS) and recurrence-free survival (RFS) were comparable (OS: 96.8 vs. 92.0%, log-rank p = 0.21, RFS: 91.1 vs. 84.7%, log-rank p = 0.93). In addition, patients undergoing SPDP had less intraoperative blood loss (median, 100 mL [IQR 10–250] vs. 150 mL [IQR 100–400]; p = 0.001), lower incidence of serious complications (n = 13, 12.8% vs. n = 28, 27.5%; p = 0.014), and shorter length of stay (median: 5 days [IQR 4–7] vs. 6 days [IQR 5–13]; p = 0.049) compared with patients undergoing DPS. Conclusion: SPDP for pNET was associated with acceptable perioperative and long-term outcomes that were comparable to DPS. SPDP should be considered for patients with pNET.

Molecular Features and Prognostic Factors of Pleomorphic Xanthoastrocytoma: A Collaborative Investigation of the Tohoku Brain Tumor Study Group.

Pleomorphic xanthoastrocytoma (PXA) is a rare glial tumor, however, its histological differentiation from high-grade gliomas is often difficult. Molecular characteristics may contribute to a better diagnostic discrimination. Prognostic factors of PXA are also important but few relevant reports have been published. This study investigated the molecular features and prognostic factors of PXAs. Seven university hospitals participated in this study by providing retrospective clinical data and tumor samples of PXA cases between 1993 and 2014. Tumor samples were analyzed for immunohistochemical (IHC) neuronal and glial markers along with Ki67. The status of the BRAF and TERT promoter (TERTp) mutation was also evaluated using the same samples, followed by feature extraction of PXA and survival analyses. In all, 19 primary cases (17 PXA and 2 anaplastic PXA) were included. IHC examination revealed the stable staining of nestin and the close association of synaptophysin to NFP. Of the PXA cases, 57% had the BRAF mutation and only 7% had the TERTp mutation. On univariate analysis, age (≥60 years), preoperative Karnofsky performance status (KPS) (≤80%), and marked peritumoral edema were significantly associated with progression-free survival (PFS). No independent factor was indicated by the multivariate analysis. In conclusion, PXA was characterized by positive nestin staining and a few TERTp mutations. The neuronal differential marker and BRAF status may help in diagnosis. Patient age, preoperative KPS, and marked perifocal edema were associated with PFS. The present study is limited because of small number of cases and its retrospective nature. Further clinical study is needed.

COT-11 EFFECT OF PHYSICIAN SUPPORTS ON QUALITY CONTROL AND QUALITY ASSURANCE IN CLINICAL BRAIN TUMOR RESEARCH

BACKGROUNDClinical physicians have difficulties in conducting investigator-initiated-trials because of increasing clinical duties in Japan. Therefore, physician support can be one of the important factors for quality control and quality assurance. In Kyoto University Hospital, clinical research professional’s support for physician had started at November 2012. In this study, we evaluate effect of physician supports on quality control and quality assurance in clinical brain tumor research.METHODSOur department of Neurosurgery has been a member of Brain Tumor Study Group in Japan Clinical Oncology Group (JCOG) since 2007. The number of registered patients, the status of periodic monitoring, the occurrence of inquiries per case, and details of physicians’ support (items, frequency, methods, etc.) in each clinical trial were investigated. The factors affecting the audit results conducted by JCOG Audit Committee on January 2013 and February 2019 are examined.RESULTSThere are seven trials have been ongoing on or started since November 2012. There are fifty patients registered in the clinical studies until July 2019. Periodic monitoring has been carried out in 214 patients of cumulative total number since 2012. Physicians’ support mainly involved the preparation of ethical review documents, CRF documentation, responses to data queries, preparation of SAE reports, study schedule check and monitoring of observation items. The audit results of site visit were acceptable, total evaluation score 68.80 on January 2013 and excellent, total evaluation score 99.9 on February 2019.CONCLUSIONClinical Trials Act has been implemented, and further improvement in the quality of clinical trials has been demanded. As the results of this study, we clarified the necessity for physician support and the contribution to quality improvement.

Is standard radical surgery necessary for elderly patients with early-stage epithelial ovarian carcinoma? ~Propensity score matched analysis~.

The impact of 'standard full-staged radical surgery (SRS)' on overall survival (OS) in elderly patients with early-stage epithelial ovarian cancer (EOC) remains unclear. In the current study, we investigated the impact of SRS on OS in elderly patients with early-stage EOC in a multicentric analysis using a propensity score (PS)-matching technique. Between 1986 and 2017, 3227 patients with EOC were registered and accumulated by the Tokai Ovarian Tumor Study Group, consisting of 14 collaborating institutions, after a central pathological review. Among them, 204 elderly patients aged older than or equal to 65years who had a stage I EOC were analyzed, including 72 patients who had received SRS (Group I) and 132 who had undergone non-SRS limited surgery (Group II). Oncologic outcomes were compared between the two groups using a PS-matching technique to adjust for various clinicopathologic risk factors. The median follow-up duration of all surviving patients was 55.9months. Consequently, 54 patients (26.5%) developed recurrence. In addition, 33 patients (16.2%) died of the disease. In the original cohort, the 5-year OS rates of Groups I and II were 95.8 and 82.3%, respectively. We identified a marginally significant difference between the two groups (Log-rank: P=0.086). In the PS-matched cohort after adjustment for multiple clinicopathologic factors, there was no significant difference in OS between the two groups [OS (Group I vs. II), HR: 0.766 (95% CI: 0.271-2.165), P=0.615]. After adjustment for clinicopathologic factors, non-SRS limited surgery may not worsen the oncologic outcome in elderly women with early-stage EOC. A large-scale clinical study is necessary to validate the findings.

Trends in the Number of Lymph Nodes Evaluated Among Patients with Pancreatic Neuroendocrine Tumors in the United States: A Multi-Institutional and National Database Analysis.

The role of routine lymphadenectomy in the surgical treatment of pancreatic neuroendocrine tumors (pNET) remains poorly defined. The objective of the current study was to investigate trends in the number of lymph nodes (LN) evaluated for pNET treatment at a nationwide level. Patients undergoing surgery for pNET between 2000 and 2016 were identified in the U.S. Neuroendocrine Tumor Study Group (US-NETSG) database as well as the Surveillance, Epidemiology, and End Results (SEER) database. The number of LNs examined was evaluated over time. The median number of evaluated LNs increased roughly fourfold over the study period (US-NETSG, 2000: 3 LNs vs. 2016: 13 LNs; SEER, 2000: 3 LNs vs. 2016: 11 LNs, both p < 0.001). While no difference in 5-year OS and RFS was noted among patients who had 1-3 lymph node metastases (LNM) vs. ≥ 4 LNM between 2000-2007 (OS 73.5% vs. 69.9%, p = 0.12; RFS: 64.9% vs. 40.1%, p = 0.39), patients who underwent resection and LN evaluation during the period 2008-2016 had an incrementally worse survival if the patient had node negative disease, 1-3 LNM and ≥ 4 LNM (OS 86.8% vs. 82.7% vs. 74.9%, p < 0.001; RFS: 86.3% vs. 64.7% vs. 50.4%, p < 0.001). On multivariable analysis, a more recent year of diagnosis, pancreatic head tumor location, and tumor size > 2cm were associated with 12 or more LNs evaluated in both US-NETSG and SEER databases. The number of LNs examined nearly quadrupled over the last decade. The increased number of LNs examined suggested a growing adoption of the AJCC staging manual recommendations regarding LN evaluation in the treatment of pNET.