Three-year follow-up analysis of phase 1/2 study on tirabrutinib in patients with relapsed or refractory primary central nervous system lymphoma.

Background: The ONO-4059-02 phase 1/2 study showed favorable efficacy and acceptable safety profile of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, for relapsed/refractory primary central nervous system lymphoma (PCNSL). Here, we report the long-term efficacy and safety after a 3-year follow-up. Methods: Eligible patients were aged ≥ 20 years with histologically diagnosed PCNSL and KPS of ≥ 70. Patients received oral tirabrutinib once daily at 320 or 480 mg, or 480 mg under fasted conditions. Results: Between October 19, 2017, and June 13, 2019, 44 patients were enrolled: 33 and 9 had relapsed and refractory, respectively. The 320, 480, and 480 mg fasted groups included 20, 7, and 17 patients, respectively. The median follow-up was 37.1 months. The overall response rate was 63.6% (95% CI: 47.8-77.6) with complete response (CR), unconfirmed CR, and partial response in 9, 7, and 12 patients, respectively. The median duration of response (DOR) was 9.2 months, with a DOR rate of 19.8%; the median progression-free survival (PFS) and median overall survival (OS) were 2.9 months and not reached, respectively, with PFS and OS rates of 13.9% and 56.7%, respectively. Adverse events occurred in 38 patients (86.4%): grade ≥ 3 in 23 (52.3%) including 1 patient with grade 5 events. KPS and quality of life (QoL) scores were well maintained among patients receiving long-term treatment. Conclusions: The results demonstrated the long-term clinical benefit of tirabrutinib, with deep and durable response in a subset of patients and acceptable safety profile, while KPS and QoL scores were maintained.

Karnofsky Performance Status and quality of life in patients with relapsed or refractory primary CNS lymphoma from a phase I/II study of tirabrutinib.

Background: Tirabrutinib, a second-generation inhibitor of Bruton's tyrosine kinase, was approved in March 2020 for the treatment of relapsed or refractory primary central nervous system lymphoma (r/r PCNSL) based on phase I/II studies in Japan. We previously reported the overall response rate and safety profile. We describe Karnofsky Performance Status (KPS) and the quality of life (QoL) in patients with r/r PCNSL receiving tirabrutinib based on more than 1-year follow-up data. Methods: Patients with r/r PCNSL, age ≥20 years, and KPS ≥70 were treated with tirabrutinib once daily at a dose of 320, 480, or 480 mg under fasted conditions. QoL was assessed using questionnaires issued by the European Organization for Research and Treatment of Cancer (EORTC), namely EORTC QLQ-C30, EORTC QLQ-BN20, and EuroQol 5 dimensions 3-level (EQ-5D-3L) along with KPS. Results: Forty-four patients (mean age, 60 years [range 29-86]) were enrolled. The median follow-up period was 14.9 months (range, 1.4-27.7). The median KPS of the patients at baseline was 80.0 (range, 70-100), and this remained constant during the treatment. The global health status/QoL in the QLQ-C30 showed significant improvements from baseline through cycles 3-17 and remained relatively constant thereafter until cycle 23. Improvements were also seen in emotional functioning and constipation in the QLQ-C30 segments. Other items of QLQ-C30 and QLQ-BN20, EQ-5D visual analog scales, and EQ-5D index were maintained during the treatment. Conclusions: Tirabrutinib generally maintains KPS and QoL scores with some improvements in specific QoL items in patients with r/r PCNSL.

Distinct patterns of copy number alterations may predict poor outcome in central nervous system germ cell tumors.

We have previously reported that 12p gain may predict the presence of malignant components and poor prognosis for CNS germ cell tumor (GCT). Recently, 3p25.3 gain was identified as an independent predictor of poor prognosis for testicular GCT. Eighty-one CNS GCTs were analyzed. Copy number was calculated using methylation arrays. Five cases (6.2%) showed 3p25.3 gain, but only among the 40 non-germinomatous GCTs (NGGCTs) (5/40, 12.5%; p = 0.03). Among NGGCTs, those with a yolk sac tumor component showed a significantly higher frequency of 3p25.3 gain (18.2%) than those without (1.5%; p = 0.048). NGGCTs with gain showed significantly shorter progression-free survival (PFS) than those without (p = 0.047). The 3p25.3 gain and 12p gain were independent from each other. The combination of 3p25.3 gain and/or 12p gain was more frequent among NGGCTs with malignant components (69%) than among those without (29%; p = 0.02). Germinomas containing a higher number of copy number alterations showed shorter PFS than those with fewer (p = 0.03). Taken together, a finding of 3p25.3 gain may be a copy number alteration specific to NGGCTs and in combination with 12p gain could serve as a marker of negative prognosis or treatment resistance. Germinoma with frequent chromosomal instability may constitute an unfavorable subgroup.

Multidrug chemotherapy, whole-brain radiation and cytarabine therapy for primary central nervous system lymphoma in elderly patients with dose modification based on geriatric assessment: study protocol for a phase II, multicentre, non-randomised study.

INTRODUCTION: Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL. METHODS AND ANALYSIS: Forty-five elderly patients will be included. If R-MPV does not achieve complete response, the patients will undergo reduced-dose, whole-brain radiotherapy comprising 23.4 Gy/13 fractions, followed by local boost radiotherapy comprising 21.6 Gy/12 fractions. After achieving complete response using R-MPV with or without radiotherapy, the patients will undergo two courses of HD-AraC. All patients will undergo baseline geriatric 8 (G8) assessment before HD-AraC and after three, five and seven R-MPV courses. Patients with screening scores of ≥14 points that decrease to <14 points during subsequent treatment, or those with screening scores <14 points that decrease from the baseline during subsequent treatment are considered unfit for R-MPV/HD-AraC. The primary endpoint is overall survival, and the secondary endpoints are progression-free survival, treatment failure-free survival and frequency of adverse events. The results will guide a later phase III trial and provide information about the utility of a geriatric assessment for defining chemotherapy ineligibility. ETHICS AND DISSEMINATION: This study complies with the latest Declaration of Helsinki. Written informed consent will be obtained. All participants can quit the study without penalty or impact on treatment. The protocol for the study, statistical analysis plan and informed consent form have been approved by the Certified Review Board at Hiroshima University (CRB6180006) (approval number: CRB2018-0011). The study is ongoing within nine tertiary and two secondary hospitals in Japan. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION: jRCTs061180093.

Concurrent Mutations in STK11 and KEAP1 Cause Treatment Resistance in KRAS Wild-type Non-small-cell Lung Cancer.

We herein report a patient with KRAS wild-type non-small-cell lung cancer (NSCLC) with concurrent STK11 and KEAP1 mutations. A 53-year-old man visited a local doctor with a complaint of left shoulder swelling and pain. He was diagnosed with NSCLC cT4N0M1c stage IVB. A comprehensive genome profile test revealed mutations in STK11 and KEAP1 but no KRAS mutations. The patient was refractory to radiotherapy, immunotherapy, and chemotherapy. Thus, STK11 and KEAP1 mutations can be considered resistance mutations that confer resistance to various anticancer therapies in KRAS wild-type NSCLC.

The first-in-human phase I study of a brain-penetrant mutant IDH1 inhibitor DS-1001 in patients with recurrent or progressive IDH1-mutant gliomas.

BACKGROUND: Approximately 70% of lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) mutations, resulting in the accumulation of oncometabolite D-2-hydroxyglutarate (D-2-HG); this leads to epigenetic dysregulation, oncogenesis, and subsequent clonal expansion. DS-1001 is an oral brain-penetrant mutant IDH1 selective inhibitor. This first-in-human study investigated the safety, pharmacokinetics, pharmacodynamics, and efficacy of DS-1001. METHODS: This was a multicenter, open-label, dose-escalation, phase I study of DS-1001 for recurrent/progressive IDH1-mutant (R132) glioma (N = 47) (NCT03030066). DS-1001 was administered orally at 125-1400 mg twice daily. Dose-escalation used a modified continual reassessment method. RESULTS: The maximum tolerated dose was not reached. Eight patients were continuing treatment at the data cutoff. Most adverse events (AEs) were grade 1-2. Twenty patients (42.6%) experienced at least 1 grade 3 AE. No grade 4 or 5 AEs or serious drug-related AEs were reported. Common AEs (>20%) were skin hyperpigmentation, diarrhea, pruritus, alopecia, arthralgia, nausea, headache, rash, and dry skin. The objective response rates were 17.1% for enhancing tumors and 33.3% for non-enhancing tumors. Median progression-free survival was 10.4 months (95% confidence interval [CI], 6.1 to 17.7 months) and not reached (95% CI, 24.1 to not reached) for the enhancing and non-enhancing glioma cohorts, respectively. Seven on-treatment brain tumor samples showed a significantly lower amount of D-2-HG compared with pre-study archived samples. CONCLUSIONS: DS-1001 was well tolerated with a favorable brain distribution. Recurrent/progressive IDH1-mutant glioma patients responded to treatment. A study of DS-1001 in patients with chemotherapy- and radiotherapy-naïve IDH1-mutated WHO grade 2 glioma is ongoing (NCT04458272).

Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors.

BACKGROUND: While immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs, the prevalence of irAEs and potential risk factors have not been clarified. We identified irAE predictive factors and examined the relationship between the effect of ICIs and irAEs for patients with malignancies. METHODS: A total of 533 cases treated with ICIs, including programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), for various malignancies were included retrospectively. We recorded irAEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 5. Prevalence and predictive factors associated with immune-related liver injury and the relationship between irAE and treatment response were analyzed. RESULTS: During a median of 10 (1-103) cycles with a median follow-up after several ICI initiations of 384 (21-1715) days, irAEs with all grades and with grade ≥ 3 developed in 144 (27.0%) and 57 (10.7%) cases. Cumulative irAE development rates were 21.9, 33.5, and 43.0% in all grades and 8.8, 14.9, and 20.7% in grade ≥ 3 at 5, 10, and 20 cycles, respectively. Patients who received anti-CTLA4 therapy were more likely to develop irAEs compared to those who received anti-PD-1 or anti-PD-L1 monotherapy. Liver injury was the most common irAE. Multivariate analysis identified the combination of PD-1 and anti-CTL-4 antibodies (hazard ratio [HR], 17.04; P < 0.0001) and baseline eosinophil count ≥130/µL (HR, 3.01 for < 130; P = 0.012) as independent risk factors for the incidence of immune-related liver injury with grade ≥ 2. Patients who developed irAEs had a higher disease control rate (P < 0.0001) and an increased overall survival rate compared to those without irAEs (P < 0.0001). CONCLUSION: Combination therapy with anti-PD-1 and anti-CTL-4 antibodies resulted in higher a frequency of irAEs. Baseline absolute eosinophil count was found to be a predictive factor for immune-related liver injury. Occurrence of irAEs may be associated with higher efficacy of ICI treatment and longer survival among patients who receive ICI therapy.

Molecular and clinical characterization of H3 K27M-mutant "non-midline" glioblastoma: A case report and literature review.

The WHO classification of tumors of the CNS in 2016 defined "diffuse midline glioma, H3 K27M-mutant" as a new tumor entity locating in the CNS midline. However, the H3 K27M-mutation in "non-midline" glioblastoma are rare and their characteristics have been rarely reported. A 16-year-old girl presented a hyper-intense lesion at her left temporal stem on T2WI, FLAIR and DWI. Biopsy was performed and molecular pathological diagnosis was glioblastoma with H3 K27M-mutant. Accordingly, the possibility of H3 K27M-mutant should be examined not only for diffuse glioma without IDH mutation that develops at a midline location, but also in non-midline locations.

Influence of growth hormone therapy on germinoma survivors.

PURPOSE: Due to the effectiveness of growth hormone therapy (GHT), the number of cancer survivors receiving GHT has increased. Previous studies had indicated that GHT was not associated with the increasing risks of tumor recurrence and development with second neoplasm (SN) in cancer survivors. However, to date, research on those risks in germinoma survivors is still limited. The aim of this study is to evaluate the impact of GHT in relation to tumor recurrence and development with SN in pure germinoma survivors. METHODS: This retrospective cohort study was approved by the Ethical Committee for Epidemiology of our institution. Seventy-three consecutive patients who underwent a biopsy of the lesion and were diagnosed with pure germinoma were retrospectively studied. They (median age, 15.0 years) were followed up more than 1 year after biopsy (median follow-up period, 14.3 years). The following data was obtained from the medical records of the patients: age, sex, preoperative magnetic resonance imaging findings, hormonal replacement, and events including tumor recurrence and/or SN. RESULTS: In our patient series, 16 patients (21.9%) who were more likely to have neurohypophysial lesion and receive multiple hormonal therapies had received GHT. No significant differences in the rates of tumor recurrence and development with SN were observed between the patients who had and had not received GHT. Moreover, the recurrence-free survival and overall survival rates were not different between the patients who had and had not received GHT. CONCLUSIONS: GHT did not increase the risks of tumor recurrence and development with SN in pure germinoma survivors.

Characteristics and therapeutic strategies of radiation-induced glioma: case series and comprehensive literature review.

INTRODUCTION: The so-called radiation-induced glioma (RIG, a secondary glioma after cranial irradiation), is a serious late effect after cranial radiation therapy. The clinical characteristics of and ideal treatment for these tumors are unclear. We analyzed our case series and conducted a comprehensive literature review to reveal the precise characteristics of RIGs. METHODS: We analyzed the cases of six patients with RIGs treated at our institution and 354 patients with RIGs from the literature. The latency period from irradiation to the development of each RIG and the median overall survival of the patients were subjected to Kaplan-Meier analyses. Spearman's correlation test was used to determine the relationship between age at irradiation and the latency period. RESULTS: The mean age of the 360 patients at the development of RIG was 27.42 ± 17.87 years. The mean latency period was 11.35 ± 8.58 years. Multiple gliomas were observed in 28.4%. WHO grade 3 and 4 RIGs accounted for 93.3%. The latency periods were significant shorter in the higher WHO grade group (p = 0.0366) and the concomitant systemic chemotherapy group (p < 0.0001). Age at irradiation was negatively associated with the latency period (r =- 0.2287, p = 0.0219). The patients treated with radiotherapy achieved significantly longer survival compared to those treated without radiotherapy (p = 0.0011). CONCLUSIONS: Development in younger age, multiplicity, and high incidence of grade 3 and 4 are the clinical characteristics of RIGs. Cranial irradiation at older ages and concomitant chemotherapy were associated with shorter latency for the development of RIG. Radiation therapy may be the feasible treatment option despite radiation-induced gliomas.

[Astroblastoma with Rapid Cyst Expansion and Hemorrhage in an Adult: A Case Report].

Astroblastoma is an extremely rare primary brain tumor accounting for 0.45 to 2.8% of all neuroglial tumors and usually occurs in pediatrics and young adults. The natural history of astroblastoma still remains unknown. In the World Health Organization (WHO) classification of tumors of the central nervous system, astroblastoma is classified as other neuroepithelial tumors and standard treatment other than surgery has not been established. As molecular and genetic diagnosis becomes more important in the latest WHO classification of brain tumors, the development of therapeutic options based on the information of molecular genetics are expected. Here we report a case of astroblastoma in a 49-year-old male. Small tumor was discovered by coincidence during his check-up following traffic accident, but three months later, tumor bleeding with cystic enlargement resulted in disturbance of consciousness. Initial diagnosis of low grade astroblastoma with BRAFV600E mutation was made. After 1 year, local tumor recurrence was observed. The histological diagnosis at recurrence was high grade astroblastoma. We here, discuss about diagnosis, treatment and the possibility of usefulness of molecular genetic analysis for astroblastoma with some literature review. (Received 10 August, 2021; Accepted 15 December, 2021; Published 1 April, 2022).

The possible effects of the Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 on the practice of fertility preservation in female cancer patients in Japan.

Purpose: In 2017, the first guidelines for fertility preservation in cancer patients were published in Japan. However, the impact of the guidelines remains unknown. Therefore, the authors conducted a nationwide survey on cryopreservation procedures in the period from shortly before to after publication of the guidelines (2016-2019) and compared the results with our previous survey (2011-2015). The authors also surveyed reproductive specialists' awareness of the guidelines and implementation problems. Methods: The authors sent a questionnaire to 618 assisted reproductive technology facilities certified by the Japanese Society of Obstetrics and Gynecology. Results: The authors received responses from 395 institutions (63.8%). Among them, 144 institutions conducted cryopreservation for cancer patients (vs. 126 in 2011-2015) and performed 2537 embryo or oocyte and 178 ovarian tissue cryopreservation procedures (vs. 1085 and 122, respectively). Compared with the previous period, indications were more varied and protocols for controlled ovarian stimulation were more standardized. Reproductive specialists' interest in oncofertility was high, but many reported three main difficulties: selecting a treatment method, storing samples in the long term, and securing the necessary human resources. Conclusions: The practice of fertility preservation in cancer patients in Japan has been considerably affected by the first Japanese guidelines.

Transcriptome and methylome analysis of CNS germ cell tumor finds its cell-of-origin in embryogenesis and reveals shared similarities with testicular counterparts.

BACKGROUND: CNS germ cell tumors (GCTs) predominantly develop in pediatric and young adult patients with variable responses to surgery, radiation, and chemotherapy. This study aimed to examine the complex and largely unknown pathogenesis of CNS GCTs. METHODS: We used a combined transcriptomic and methylomic approach in 84 cases and conducted an integrative analysis of the normal cells undergoing embryogenesis and testicular GCTs. RESULTS: Genome-wide transcriptome analysis in CNS GCTs indicated that germinoma had a transcriptomic profile representative of primitive cells during early embryogenesis with high meiosis/mitosis potentials, while nongerminomatous GCTs (NGGCTs) had differentiated phenotypes oriented toward tissue formation and organogenesis. Co-analysis with the transcriptome of human embryonic cells revealed that germinomas had expression profiles similar to those of primordial germ cells, while the expression profiles of NGGCTs were similar to those of embryonic stem cells. Some germinoma cases were characterized by extensive immune-cell infiltration and high expression of cancer-testis antigens. NGGCTs had significantly higher immune-cell infiltration, characterized by immune-suppression phenotype. CNS and testicular GCTs (TGCTs) had similar mutational profiles; TGCTs showed enhanced copy number alterations. Methylation analysis clustered germinoma/seminoma and nongerminoma/nonseminoma separately. Germinoma and seminoma were co-categorized based on the degree of the tumor microenvironment balance. CONCLUSIONS: These results suggested that the pathophysiology of GCTs was less dependent on their site of origin and more dependent on the state of differentiation as well as on the tumor microenvironment balance. This study revealed distinct biological properties of GCTs, which will hopefully lead to future treatment development.

Diffusion-weighted imaging-gadolinium enhancement mismatch sign in diffuse midline glioma.

BACKGROUND: Diffuse midline glioma (DMG), H3 K27M-mutant including diffuse intrinsic pontine glioma (DIPG) is a disease with dismal prognosis. We focused on diffusion-weighted imaging (DWI) and gadolinium enhanced T1WI (Gd), especially high intensity on DWI at non-enhanced lesion, i.e. DWI-Gd mismatch sign, to establish as an imaging biomarker of DMG patients. MATERIALS AND METHODS: Our institutional review board approved this retrospective study. Twenty-one patients diagnosed as DMG including DIPG at our institution between 2007 and 2020 were enrolled in this study. All patients underwent local radiotherapy of 54 Gy/30 fractions. We studied the relationship between imaging features including DWI-Gd mismatch sign and prognosis. RESULTS: DWI-Gd mismatch sign was found in 9 out of 21 DMG patients. Among different imaging characteristics, existence of high intensity on DWI (P = 0.0014), gadolinium enhancement (P = 0.00071) were the significant poor prognostic markers in DMG, which were consistent with the previous reports about DIPG. In our results, positive DWI-Gd mismatch sign was statistically strongest poor prognostic imaging biomarker, and patients with positive DWI-Gd mismatch sign had shorter OS compared to those with negative mismatch sign (9.9 months vs 18.6 months, P = 0.00062). DWI/Gd mismatch sign and intratumoral bleeding were more common in DMG at thalamus compared to DMG at pons/DIPG (P = 0.046 and P = 0.0017, respectively). CONCLUSIONS: DWI-Gd mismatch sign may be an imaging biomarker for poor prognosis in DMG. (E-1601).

Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 1.

In 2017, the Japan Society of Clinical Oncology (JSCO) published the JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients. These were the first Japanese guidelines to address issues of oncofertility. In this field of medicine, sustained close cooperation between oncologists and reproductive specialists is essential from the diagnosis of cancer until many years after completion of cancer treatment. These JSCO guidelines were intended to guide multidisciplinary medical staff in considering the availability of fertility preservation options and to help them decide whether to provide fertility preservation to childhood, adolescent, and young adult cancer patients before treatment starts, with the ultimate goal of improving patient survivorship. The guidelines are presented as Parts 1 and 2. This article (Part 1) summarizes the goals of the guidelines and the methods used to develop them and provides an overview of fertility preservation across all oncology areas. It includes general remarks on the basic concepts surrounding fertility preservation and explanations of the impacts of cancer treatment on gonadal function by sex and treatment modality and of the options for protecting/preserving gonadal function and makes recommendations based on 4 clinical questions. Part 2 of these guidelines provides specific recommendations on fertility preservation in 8 types of cancer (gynecologic, breast, urologic, pediatric, hematologic, bone and soft tissue, brain, and digestive).

Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 2.

The Japan Society of Clinical Oncology (JSCO) published the "JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients" in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.

The Japan Society for Neuro-Oncology guideline on the diagnosis and treatment of central nervous system germ cell tumors.

Primary CNS germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. In line with the hypothesis that the primordial germ cell is the cell-of-origin, histopathological examinations for this pathology involve a diverse range of components mirroring the embryogenic developmental dimensions. Chemotherapy and radiotherapy are the mainstays of treatment, with surgery having a limited role for diagnosis and debulking of residual tissue after treatment. While better management has been achieved over recent decades by modifying radiation coverage and selecting appropriate chemotherapy, standardization of treatment remains challenging, partly due to the low volume of cases encountered in each institution. As the incidence is higher in East Asia, including Japan, the Japan Society for Neuro-Oncology established a multidisciplinary task force to create an evidence-based guideline for CNS GCTs. This guideline provides recommendations for multiple dimensions of clinical management for CNS GCTs, with particular focus on diagnostic measures including serum markers, treatment algorithms including surgery, radiotherapy, and chemotherapy, and under-investigated but important areas such as treatment for recurrent cases, long-term follow-up protocols, and long-term sequelae. This guideline serves the purpose of helping healthcare professionals keep up to date with current knowledge and standards of management for patients with this rare disease in daily clinical practice, as well as driving future translational and clinical research by recognizing unmet needs concerning this tumor.

Intratumoral Hemorrhage After Endoscopic Third Ventriculostomy for Obstructive Hydrocephalus Caused by Brain Tumors.

BACKGROUND: Endoscopic third ventriculostomy (ETV) for obstructive hydrocephalus and endoscopic biopsy (EB) for intraventricular and paraventricular tumors are standard therapies because they are minimally invasive procedures. Although EB-associated hemorrhagic risk has been well documented, there have been only a few reports on hemorrhagic risk associated with ETV. We conducted a single-institution retrospective study on the incidence of hemorrhage secondary to EB and/or ETV. METHODS: We retrospectively reviewed patient characteristics, procedure, pathological findings, and complications including hemorrhage of 100 patients with intraventricular and paraventricular tumors who underwent EB and/or ETV at our institution from 2000 to 2020. RESULTS: EB/ETV combined surgery (combined group), EB-alone surgery (EB-alone group), and ETV-alone surgery (ETV-alone group) were performed in 44 (44%), 24 (24%), and 32 (32%) patients, respectively, and all procedures were successful. The rates of definitive and suggestive diagnoses in EB were 76.5% and 23.5%, respectively. Adverse events were observed in 6 patients. In the combined group, acute obstruction of the ETV stoma was observed in 1 patient and transient double vision was observed in 1 patient. Transient aqueductal stenosis/obstruction was observed in 2 patients in the EB-alone group. In the ETV-alone group, hemorrhage was observed in 2 patients; these patients developed intratumoral hemorrhage despite ETV-alone surgery. Subsequently, these 2 patients underwent tumor removal, and the histopathological diagnosis was atypical teratoid/rhabdoid tumor in both. CONCLUSIONS: For obstructive hydrocephalus with atypical teratoid/rhabdoid tumor, physicians must be aware of the risk of postoperative intratumoral hemorrhage after performing ETV.