Clinical Course after Carmustine Wafer Implantation for Newly Diagnosed Adult-type Diffuse Gliomas; A controlled propensity matched analysis of a single center cohort.

PURPOSE: It remains unclear whether combining carmustine wafer (CW) implantation with the standard treatment for adult-type diffuse gliomas is safe and has a prognostic impact. This study aimed to investigate the prognostic value and safety of CW implantation. METHODS: Adult patients with IDH-wild-type and -mutant gliomas, grades 3-4 treated with surgical resection, radiotherapy, and temozolomide chemotherapy between 2013 and 2023 were surveyed. CWs were implanted except in cases of intraoperative wide ventricle opening or marked preoperative brain swelling. For survival analyses, a case-matched dataset based on propensity score matching (PSM), including multiple factors (patient background, diagnosis, and extent of resection) was generated. Progression-free survival (PFS), overall survival (OS), and frequency of complications of CW implantation (brain edema, infection, and cerebrospinal fluid leakage) were compared between the CW and non-use groups. RESULTS: In total, 127 patients (75 in the CW use group and 52 in the non-use group) were enrolled. Regardless of stratification, no significant differences in PFS and OS were observed between the CW use and non-use groups. The frequency of postoperative brain edema was significantly higher in the CW use group than in the non-use group. An adjusted dataset containing 41 patients in the CW use and nonuse groups was generated. Even after PSM, CW implantation had no prognostic effect. CONCLUSIONS: CW implantation with standard treatment demonstrated little beneficial effect for the present strategy of CW use.

Mizoribine Promotes Molecular Chaperone HSP60/HSP10 Complex Formation.

It has been reported that Mizoribine is an immunosuppressant used to suppress rejection in renal transplantation, nephrotic syndrome, lupus nephritis, and rheumatoid arthritis. The molecular chaperone HSP60 alone induces inflammatory cytokine IL-6 and the co-chaperone HSP10 alone inhibits IL-6 induction. HSP60 and HSP10 form a complex in the presence of ATP. We analyzed the effects of Mizoribine, which is structurally similar to ATP, on the structure and physiological functions of HSP60-HSP10 using Native/PAGE and transmission electron microscopy. At low concentrations of Mizoribine, no complex formation of HSP60-HSP10 was observed, nor was the expression of IL-6 affected. On the other hand, high concentrations of Mizoribine promoted HSP60-HSP10 complex formation and consequently suppressed IL-6 expression. Here, we propose a novel mechanism of immunosuppressive action of Mizoribine.

Relationship between critical care nutrition and post-intensive care syndrome in surviving ventilated patients with COVID-19: a multicenter prospective observational study.

The impact of nutrition therapy in the acute phase on post-intensive care syndrome (PICS) remains unclear. We conducted a multicenter prospective study on adult patients with COVID-19 who required mechanical ventilation for more than three days. The questionnaire was mailed after discharge. Physical PICS, defined as less than 90 points on the Barthel index (BI), was assigned as the primary outcome. We examined the types of nutrition therapy in the first week that affected PICS components. 269 eligible patients were evaluated 10 months after discharge. Supplemental parenteral nutrition (SPN) >400 kcal/day correlated with a lower occurrence of physical PICS (10% vs 21.92%, p = 0.042), whereas the amounts of energy and protein provided, early enteral nutrition, and a gradual increase in nutrition delivery did not, and none correlated with cognitive or mental PICS. A multivariable regression analysis revealed that SPN had an independent impact on physical PICS (odds ratio 0.33, 95% CI 0.12-0.92, p = 0.034), even after adjustments for age, sex, body mass index and severity. Protein provision ≥1.2 g/kg/day was associated with a lower occurrence of physical PICS (odds ratio 0.42, 95% CI 0.16-1.08, p = 0.071). In conclusion, SPN in the acute phase had a positive impact on physical PICS for ventilated patients with COVID-19.

[FLT3-ITD mutation-positive acute myeloid leukemia undergoing clonal transition with PTPN11 mutation at relapse].

A 28-year-old man was diagnosed with acute myelomonocytic leukemia. He achieved complete remission (CR) after two cycles of induction therapy. However, after consolidation therapy, bone marrow aspiration performed to prepare for allogeneic hematopoietic stem cell transplantation revealed disease relapse. Companion diagnostics confirmed the presence of the FLT3-ITD mutation. The patient received gilteritinib monotherapy and achieved CR. Subsequently, he underwent unrelated allogeneic bone marrow transplantation. One year after transplantation, the patient relapsed, and gilteritinib was resumed. However, the leukemia progressed, and panel sequencing using a next-generation sequencer showed that the FLT3-ITD mutation disappeared. A mutation in PTPN11, which regulates the RAS/MAPK signaling pathway, was also detected. Gilteritinib was discontinued, and the patient achieved CR with salvage chemotherapy. He underwent related haploidentical peripheral blood stem cell transplantation but died of relapse. This was a case in which genetic analysis revealed clonal transition and acquisition of resistance to treatment.

[Ruptured mycotic cerebral aneurysm in an adult T-cell leukemia/lymphoma patient undergoing allogeneic stem cell transplantation].

A 63-year-old man with adult T-cell leukemia-lymphoma underwent allogeneic bone marrow transplantation from an HLA-matched unrelated donor. On day 17 after transplantation, chest computed tomography (CT) showed nodules in the lower lobes of both lungs, and invasive pulmonary aspergillosis (IPA) was suspected. Treatment with liposomal amphotericin B was started, and improvement of infectious lesions was confirmed with CT on day 28. The antifungal agent was changed to voriconazole on day 52 because of progressive renal dysfunction. Disorders of consciousness and paralysis of the left upper and lower extremities developed on day 61. Brain CT showed subcortical hemorrhage in the right parietal and occipital lobes, and the patient died on day 62. An autopsy revealed filamentous fungi, suspected to be Aspergillus, in the pulmonary nodules and a ruptured cerebral aneurysm. Although IPA occurs in 10% of transplant recipients, vigilant monitoring for mycotic cerebral aneurysms is required to prevent hematogenous dissemination of Aspergillus, which is associated with a high mortality rate.

[Kidney transplantation for end-stage renal disease after third allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia].

An 18-year-old man underwent allogenic bone marrow transplantation (BMT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Ph+ALL relapsed 3 months after the first BMT, and the patient underwent a second BMT. However, Ph+ALL relapsed 4 months after the second BMT, and he received a haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) from his father. Molecular complete remission was confirmed 29 days after haplo-PBSCT. However, the patient needed dialysis for end-stage renal disease due to thrombotic microangiopathy 3 years and 2 months after haplo-PBSCT. He received a kidney transplantation from his father 7 years and 10 months after haplo-PBSCT, and got off dialysis after the kidney transplantation. Immunosuppressive therapy with methylprednisolone, tacrolimus, and mycophenolate mofetil was started for kidney transplantation, but the dose of immunosuppressive agents was reduced successfully without rejection soon after kidney transplantation. The patient has maintained long-term remission since the haplo-PBSCT, and his kidney function was restored by the kidney transplantation from his father.

[Results of Watch and Wait after Chemoradiotherapy for Locally Advanced Rectal Cancer].

BACKGROUND: Watch and wait(W & W)for rectal cancer after chemoradiotherapy(CRT)is attracting attention. PURPOSE: To examine regimens and indications from the results of follow-up of cases undergoing W & W in our department. MATERIALS AND METHODS: CRT(SOX therapy 2-5 cycles, 45 Gy)was performed on patients with lower rectal cancer over a period of 2016 to 2020, and 7 patients with clinical complete response(cCR)were followed up. RESULTS: With a median follow-up of 33 months(10-74), 4 of 7 patients(57.1%)remained in cCR. Two patients had local relapse more than a year after the start of treatment, were able to undergo salvage surgery, and are alive after surgery. Patients with lateral lymph node metastasis before CRT had para-aortic lymph node metastasis at 8 months. CONCLUSIONS: Patients with maintained cCR were those with localized, node-negative disease. On the other hand, in patients with lymph node metastasis, including lateral metastasis, it was not possible to perform salvage surgery due to distant metastasis. Careful case selection and follow-up are necessary in the future.

[A Case of the Huge GIST in the Transverse Colon Mesentery with Intra-Tumoral Hemorrhage and Jejunal Infiltration].

A 38-year-old woman was admitted to our hospital due to severe anemia. CT showed a 13×12 cm tumor with moderately enhanced wall thickening in the right upper abdomen. The huge tumor located adjacent to the jejunum and compressed the right transverse colon. Hemorrhagic necrosis and air were observed within the tumor, suspecting tumor penetration into the jejunum. The patient was diagnosed with abdominal GIST with jejunal infiltration. Laparotomy revealed a 13× 11 cm solid mass with intra-tumoral hemorrhage and invasion into the jejunum, located in the transverse mesocolon. Tumor resection combined with partial jejunectomy and transverse colectomy were performed. Immunohistochemical findings of the resected specimen was positive for c-kit and DOG-1, and the MIB-1 positive rate was 10%. Three weeks after the operation, re-anastomosis was performed due to transverse colon anastomotic stricture. She was discharged 45 days after first operation. Currently, 9 months after the operation, patient has been prescribed imatinib and is alive without recurrence.

Attenuated humoral response against SARS-CoV-2 mRNA vaccination in allogeneic stem cell transplantation recipients.

Antibody persistence several months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in allogeneic stem cell transplantation recipients remains largely unknown. We sequentially evaluated the humoral response to two doses of mRNA vaccines in 128 adult recipients and identified the risk factors involved in a poor response. The median interval between stem cell transplantation and vaccination was 2.7 years. The SARS-CoV-2 S1 Ab became positive after the second vaccination dose in 87.6% of the recipients, and the median titer was 1235.4 arbitrary units (AU)/ml. In patients on corticosteroid treatment, the corticosteroid dose inversely correlated with Ab titer. Multivariate analysis identified risk factors for poor peak response such as an interval from stem cell transplantation ≤1 year, history of clinically significant CMV infection, and use of >5 mg/day prednisolone at vaccination. Six months after vaccination, the median titer decreased to 185.15 AU/ml, and use of >5 mg/day prednisolone at vaccination was significantly associated with a poor response. These results indicate that early vaccination after stem cell transplantation (<12 months) and CMV infection are risk factors for poor peak response, while steroid use is important for a peak as well as a persistent response. In conclusion, although humoral response is observed in many stem cell transplantation recipients after two doses of vaccination, Ab titers diminish with time, and factors associated with persistence and a peak immunity should be considered separately.

Phase I trial of myeloablative conditioning with 3-day total marrow and lymphoid irradiation for leukemia.

This prospective phase I trial aimed to determine the recommended dose of 3-day total marrow and lymphoid irradiation (TMLI) for a myeloablative conditioning regimen by increasing the dose per fraction. The primary end-point of this single-institution dose escalation study was the recommended TMLI dose based on the frequency of dose-limiting toxicity (DLT) ≤100 days posthematopoietic stem cell transplantation (HSCT); a 3 + 3 design was used to evaluate the safety of TMLI. Three dose levels of TMLI (14/16/18 Gy in six fractions over 3 days) were set. The treatment protocol began at 14 Gy. Dose-limiting toxicities were defined as grade 3 or 4 nonhematological toxicities. Nine patients, with a median age of 42 years (range, 35-48), eight with acute lymphoblastic leukemia and one with chronic myeloblastic leukemia, received TMLI followed by unrelated bone marrow transplant. The median follow-up period after HSCT was 575 days (range, 253-1037). Three patients were enrolled for each dose level. No patient showed DLT within 100 days of HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. All patients achieved neutrophil engraftment at a median of 19 days (range, 14-25). One-year overall and disease-free survival rates were 83.3% and 57.1%, respectively. Three patients experienced relapse, and no nonrelapse mortality was documented during the observation period. One patient died due to disease relapse 306 days post-HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. The efficacy evaluation of this regimen is currently being planned in a phase II study.

Prognostic implications of histologic growth patterns and tumor-infiltrating macrophages in colorectal liver metastases.

PURPOSE: Histopathologic patterns at the invasion fronts of tumors predict metastatic potential and prognosis in several cancers. We examined whether such patterns at the interface between colorectal liver metastases and hepatic parenchyma have similar prognostic value. METHODS: Microscopic growth patterns at edges of metastases including desmoplasia, pushing borders, and replacement of hepatocytes were retrospectively analyzed with respect to surgical outcomes in 142 patients who underwent hepatectomy for colorectal metastases. RESULTS: Patterns included desmoplasia in 58 patients (41%), hepatocyte replacement in 41 (29%), and pushing borders in 43 (30%). Maximum metastasis diameter and serum carcinoembryonic antigen concentration in patients showing desmoplastic tumor growth were lower than those in others (P < 0.05 and P < 0.01). Disease-free survival and overall survival were better in patients showing desmoplastic growth, while a non-desmoplastic tumor growth pattern showed a negative influence. More cluster of differentiation (CD) 68-positive M1 macrophages and fewer CD206-positive M2 macrophages were demonstrated at interfaces of tumors with hepatic parenchyma when desmoplasia was present, although markers for proliferative activity (MIB1 index) and metastatic potential (E-cadherin expression) appeared uninfluenced by desmoplasia. CONCLUSION: Better long-term results were associated with metastatic tumors showing desmoplastic growth patterns at invasion fronts, which may reflect local immune state in a prognostically useful manner.

Clinical significance of late CMV disease in adult patients who underwent allogeneic stem cell transplant.

INTRODUCTION: Late cytomegalovirus (CMV) disease, which was defined as CMV disease occurring >100 days post-transplant, remains an important complication among allogeneic stem cell transplant recipients, even now that the prophylactic strategy using ganciclovir preemptive therapy has been established. Due to the recent expansion of donor sources and conditioning regimens, it is therefore appropriate to reevaluate the incidence, risk factors, and clinical impacts of late CMV disease. METHODS: This study included the 1295 adult patients, who underwent transplant for the first time from 2008 to 2015, without underlying disease relapse or CMV disease within 100 days post-transplant. There were no restrictions on underlying diseases or transplant procedures. RESULTS: During the median follow-up period of 48.4 months, 21 patients developed late CMV disease and the 5-year cumulative incidence of late CMV disease was 1.6%. By multivariate analysis, haploidentical related donor, adult T-cell leukemia lymphoma, and preemptive therapy before 100 days post-transplant were extracted as independent risk factors. Late CMV disease negatively affected transplant outcomes, and was identified as an independent risk factor for the non-relapse mortality rate (hazard ratio 3.83, p < 0.001) and overall survival rate (hazard ratio 4.01, p < 0.001). Although 17 of 21 patients with late CMV disease died, the main causes of death were not related to CMV, except in three patients with CMV pneumonia. CONCLUSIONS: Although the incidence of late CMV disease is low in transplant recipients, this complication negatively affects clinical courses. Therefore, transplant recipients with these risk factors should be more carefully managed.

[Polatuzumab vedotin, bendamustine, and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma, including the outcome as a bridging treatment to CAR-T cell therapy or allogeneic hematopoietic stem cell transplant].

Pola-BR (polatuzumab vedotin, bendamustine, and rituximab) therapy received approval for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in Japan in March 2021. There have been few reports on the efficacy and safety of Pola-BR therapy in Japanese clinical practice. A retrospective analysis was performed on twenty-nine patients with R/R DLBCL who received Pola-BR therapy at our institution (intent to cellular immunotherapy cohort: 20 patients, stand-alone treatment cohort: nine patients). The overall response rate was 69.0% (complete response 27.6%). The median progression-free survival was 5.1 months, with a 9.5-month median overall survival. In the intent to cellular immunotherapy cohort, 11 of 19 patients received chimeric antigen receptor T-cell (CAR-T) infusions, and one patient received allogeneic stem cell transplantation. Four patients received Pola-BR therapy, including bendamustine before leukapheresis, and all produced CAR-T products successfully. 3 of the 28 patients experienced grade3 or higher adverse events, and two required treatment discontinuation. Our single institution, a real-world cohort of R/R DLBCL patients showed high efficacy outcomes and a tolerable toxicity profile for Pola-BR therapy, which is comparable to previous studies. More cases are needed to determine its impact on CAR-T therapy and stem cell transplantation.

[A Case of Pancreatic Tail Cancer Causing Gastrointestinal Hemorrhage Due to Transverse Colon Invasion].

An 81-year-old woman was admitted to our hospital due to frequent bleeding and hemorrhagic shock. Blood tests revealed anemia and contrast-enhanced abdominal CT revealed a pancreatic tail tumor with a diameter of 60 mm. The boundary between pancreatic tumor and the transverse colon, stomach and spleen was unclear, and invasion of the transverse colon as well as the stomach and spleen was suspected. Hemorrhage due to colon invasion of the pancreatic tail cancer and intra-tumoral hemorrhage were suspected. Due to persistent bleeding, the patient had emergency surgery to control bleeding. The pancreatic tail tumor invaded not only the colon but also stomach and spleen, distal pancreatectomy, partial gastrectomy and splenectomy was performed in combination with resection of the transverse colon, and transverse colon colostomy. We report a case of gastrointestinal bleeding caused by transverse colon invasion of pancreatic tail cancer, which resulted in emergency surgery.

[A Case of Perihilar Cholangiocarcinoma with Postoperative Hepatic Encephalopathy Due to Portosystemic Shunt Treated by Percutaneous Embolization].

An 83-year-old woman developed jaundice, and was diagnosed as perihilar cholangiocarcinoma. Abdominal contrast- enhanced CT revealed coexisting portosystemic shunt between portal vein and inferior vena cava, however, her blood ammonia level was normal. She underwent right hemihepatectomy and caudate lobectomy combined with extrahepatic bile duct resection and portal vein resection. Postoperatively, hyperammonemia refractory to conservative treatment was observed. The blood ammonia level increased to 180µg/dL and she was suffered from grade Ⅲ hepatic encephalopathy on the 20th postoperative day. CT showed an increase in the diameter of the portosystemic shunt, while there was only a slight increase in the remnant left lobe of the liver. These findings indicated that hepatic encephalopathy was caused by increased portosystemic shunt blood flow and decreased portal venous flow. Hepatic encephalopathy was rapidly improved by percutaneous transhepatic portosystemic shunt obliteration.

Oligosarcomas, IDH-mutant are distinct and aggressive.

Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile.

Clinical, histopathological, and molecular features of IDH-wildtype indolent diffuse glioma: comparison with typical glioblastoma.

PURPOSE: IDH-wildtype (IDHwt) diffuse gliomas are treated as glioblastoma, however, some of these may show less aggressive clinical courses. The authors investigated the clinical, histopathological, and molecular characteristics of such IDHwt indolent diffuse gliomas (iDGwt), which have not been well documented in the literature. METHODS: Adult patients with IDHwt gliomas admitted between 2011 and 2020 were surveyed. In this particular study, the clinical indolence was defined mainly as having a small enhancing lesion and a stable period for more than 1 month before surgery. The current WHO diagnostic criteria were adapted for the diagnoses. Gene mutations and copy number changes in 43 representative glioma-associated genes, MGMT promoter methylation status, and survival data were compared with those of The Cancer Genome Atlas reference cohort. RESULTS: Nine out of 180 surveyed cases (5.0%) fulfilled the present criteria of the iDGwt. Considering the representative regulatory pathways, 8 (88.9%), 4 (44.4%), and 1 (11.1%) case had genetic alterations in the PI3K/MAPK, TP53, and RB pathways, respectively. The frequency of the RB pathway alteration was significantly lower than that in the reference cohort (281 of 362 cases: 77.6%). Two cases (22.2%) showing EGFR amplification met the diagnostic criteria for glioblastoma, and the frequency was significantly lower than that in the reference cohort (412 of 426 cases: 96.7%). The overall survival (median: 37.5 months) in the present series was significantly longer than that in the reference cohort (n = 426, median: 13.9 months). CONCLUSIONS: iDGwt lacked the molecular features of glioblastoma except for the PI3K/MAPK pathway alteration.

Photoinduced rearrangement of α-(2-nitrophenyl)ketones.

Photoirradiation of α-(2-nitrophenyl)ketones produced cyclic hydroxamates. The reaction proceeded via photoinduced oxygen transfer from the nitro group to the benzylic position, forming an α-hydroxyketone having a nitroso group. Subsequent addition of the nitroso group to the ketone moiety and the concomitant cleavage of the C-C σ bond between the carbonyl group and the benzyl position produced hydroxamic acid, which underwent formation of a hemiacetal to give cyclic hydroxamate.

Central nervous system mucormycosis in a patient with hematological malignancy: A case report and review of the literature.

Invasive mucormycosis is a refractory fungal infection. Central nervous system (CNS) mucormycosis is a rare complication caused by infiltration from the paranasal sinuses or hematogenous dissemination. Here, we present a case of a brain abscess, due to mucormycosis, diagnosed using burr craniotomy. A 25-year-old Japanese woman with relapsed-refractory acute lymphoblastic leukemia underwent cord blood transplantation (CBT). The patient experienced prolonged and profound neutropenia, and oral voriconazole was administered as primary antifungal prophylaxis. The patient received a conditioning regimen on day -11 and complained of aphasia and right hemiparesis on day -6. Magnetic resonance imaging (MRI) revealed a T2-weighted high-intensity area in the left frontal cortex. A brain abscess was suspected, and liposomal amphotericin B (L-AMB) administration was started. The patient underwent CBT as scheduled and underwent neutrophil engraftment on day 14. Although the patient achieved complete remission on day 28, her consciousness level gradually deteriorated. MRI revealed an enlarged brain lesion with a midline shift sign, suggesting brain herniation. Craniotomy was performed to relieve intracranial pressure and drain the abscess on day 38, and a diagnosis of cerebral mucormycosis was confirmed. The L-AMB dose was increased to 10 mg/kg on day 43. Although the patient's consciousness level improved, she died of hemorrhagic cystitis and aspiration pneumonia. Cerebral mucormycosis should be suspected if neurological symptoms are observed in stem cell transplant recipients. Prompt commencement of antifungal therapy and debridement are crucial because mucormycosis has a poor prognosis.

The Real-World status and risk factors for a poor prognosis in elderly patients with primary central nervous system malignant lymphomas: a multicenter, retrospective cohort study of the Tohoku Brain Tumor Study Group.

BACKGROUND: Elderly patients with primary central nervous system malignant lymphoma (EL-PCNSL) may not be given sufficient treatment due to their poor pre-treatment Karnofsky Performance Status (KPS) and comorbidities. Therefore, a retrospective, cohort study was performed to evaluate risk factors associated with a poor prognosis of EL-PCNSL in the Tohoku Brain Tumor Study Group. METHODS: Patients aged ≥ 71 years with PCNSL were enrolled from eight centers. Univariate analysis was performed with the log-rank test. A Cox proportional hazards model was used for multivariate analysis. RESULTS: Three of the total 142 cases received best supportive care (BSC). Treatment was given to 30 cases without a pathological diagnosis, 3 cases with cerebrospinal fluid (CSF) cytology, and 100 cases with a pathological diagnosis. After confirmation of no differences in progression-free survival (PFS) and overall survival (OS) between the group treated without pathology and the groups diagnosed by pathology or CSF cytology and between median age ≥ 76 years and < 76 years, a total of 133 patients were studied. The median pre-treatment KPS was 50%. Median PFS and median OS were 16 and 24 months, respectively. Risk factors associated with poor prognosis on Cox proportional hazards model analysis were pre-treatment cardiovascular disease and central nervous system disease comorbidities, post-treatment pneumonia and other infections, and the absence of radiotherapy or chemotherapy. CONCLUSIONS: Pre-treatment comorbidities and post-treatment complications would affect the prognosis. Radiation and chemotherapy were found to be effective, but no conclusions could be drawn regarding the appropriate content of chemotherapy and whether additional radiotherapy should be used.