Single Institution Experience Research Articles

In Vivo Anti-BCMA CAR T-Cell Expansion Kinetics Correlate with Early IMWG Response in RRMM: A Single Institution Study with Comparative Analysis of Idecabtagene Vicleucel and Ciltacabtagene Autoleucel

Introduction: The most recent breakthrough in the treatment of relapsed/refractory MM (RRMM) is chimeric antigen receptor (CAR) T-cell (CAR T) therapy which led to high overall response rates with acceptable toxicity. Here we present our single-institution experience with MM-specific CAR T performing a comparative analysis of clinical data and expansion kinetics after infusion of two commercially available myeloma CAR-T products. Methods: Out of 76 RRMM patients treated with CAR T, 23 patients provided consent, enrolled, apheresed and treated with commercial CAR-T between 6/20/2022 and 4/24/2023. Majority of patients had relapsed and multi-refractory MM. 11 patients received idecabtagene (idecel) and 12 received ciltacabtagene (ciltacel). Manufacturing slot availability was the primary deterministic factor for CAR T-type assignment. Study was IRB approved and informed consent was obtained to collect blood and clinical data. Blood samples were obtained at apheresis, pre-lymphodepleting (LD) chemotherapy, and on days 0, +7, +14, +21, +28 and +3 months post CAR T-cell infusion. PBMCs were generated from whole blood using density gradient centrifugation and were stained using BCMA or control CAR detection reagents and monoclonal antibodies against T-cell surface antigens. Samples were analyzed using MacsQuant-10 flow cytometer, gating on CD3+ and CAR+ cells. Fisher's Exact Test and Pearson Chi-Square tests were used for assessment of categorical variables whereas Independent-Samples Median Test was employed for non-categorical variables. Mann-Whitney U test was used for CAR T cell expansion analyses at individual timepoints. Results: As of July 10, 2023, 23 commercial patients were enrolled. Baseline clinical characteristics were comparable between the idecel and ciltacel cohorts with regard to age (median 66, p=0.827), prior lines of treatment, ASCT history (Table 1). Two patients in each cohort were penta-refractory. Three patients in each cohort had EMD (27.3%). There was balanced distribution of del 17p and t(4;14) across cohorts (p=1.000, p=0.175). Each cohort had 1 RISS-3 patient (p=0.476). Seven patients (30.4%) were previously treated with belantamab. Pre-apheresis and pre-LD absolute lymphocyte count (ALC) were comparable across cohorts. (Table 1). There were no G3 CRS events whereas G1/2 CRS events were not statistically significant between cohorts (p=0.256). Three G3 ICANS were observed, 2 in idecel and 1 in ciltacel cohorts (18.2% and 8.3%). Distribution of all-grade ICANS across cohorts were not statistically significant (p=0.676). Post-CAR T ferritin max correlated with the baseline b2m (p<0.001) and tocilizumab dose number (p=0.009) but none correlated with peak CAR T expansion (p=0.315). Responses were assessed by IMWG criteria at months 1,3,6,9 for efficacy-evaluable patients at that timepoint (n=19,14,8 and 2 in grand cohort (82.6%, 60.9%, 34.8% and 8.7%)). Global cohort ORR was 78.3% (n=18) and 60.9% (n=14) at days 30 and 90 respectively. +1 month IMWG responses were comparable with 72.7% (8/11) in idecel and 83.3% (10/12) in ciltacel cohort (p=0.625). Similarly, there was no statistically significant ORR difference between cohorts at 3, 6, and 9 months. Two-way ANOVA revealed a trend towards an effect of treatment type on CAR-T expansion (p=0.0595) (Figure 1A). Time-to-peak analysis reached statistical significance (p=0.0127) between two products (Figure 1B). Despite its delayed peak, ciltacel had significantly higher magnitude of expansion (p=0.043) (Figure 1C). Peak CAR-T expansion was associated with clinical responses across cohorts at +1 (p=0.034) and +3 months (p=0.050) but not at +6 months (p=0.449). Day +30 responses were indicative of Day +90 and Day +180 responses (p<0.001, p=0.011). Conclusions: In our single-center study of comparative analysis of commercial BCMA targeting CAR T-cell treatments, peak CAR T-cell expansion showed a positive correlation with +1 and +3 month post-CAR-T clinical responses. Despite the delayed peak expansion with ciltacel, the expansion was more robust with a higher level of circulating CAR T-cells. Baseline ALC or fludarabine dose reduction did not have an impact on overall CAR T expansion in combined cohort. Studies are underway at our institution investigating anti-BCMA CAR T cell responses in more detail and larger numbers of patients and functional studies will be further presented.

Glofitamab in Aggressive B Non-Hodgkin Lymphoma (B-NHL): A Real World Experience

Background Glofitamab is a bispecific monoclonal antibody that targets CD20 and CD3, with a unique 2:1 (bivalency for CD20; monovalency for CD3) configuration. In the pivotal trial leading to regulatory approval 1, glofitamab demonstrated remarkable efficacy in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). Objective responses were observed in 80% of patients, with 39% achieving complete response. Additionally, complete response was maintained in 78% of patients at 12 months, suggesting that the response might be durable. Most grade 3 or 4 adverse events were hematologic in nature and generally manageable. Despite its efficacy in clinical trials, the real-world safety and efficacy of glofitamab have not been extensively studied, particularly in patient groups such as those with prior exposure to hepatitis B virus (i.e. occult HBV infection, as evidenced by positive anti-HBV core antigen antibody). Here, we report a single-institution experience of glofitamab in Chinese patients with relapsed or refractory DLBCL, with one-third of them having occult HBV infection. Methods This is a retrospective study to evaluate the safety and efficacy of glofitamab in Chinese patients with relapsed or refractory DLBCL. Patients were enrolled through a compassionate program and were required to have failed at least three prior lines of therapy. Patients with active central nervous system lymphoma or active HBV infection (defined as detectable serum hepatitis B surface antigen) were ineligible for treatment. Glofitamab was administered according to the published protocol, with obinutuzumab given on the first day to mitigate the severity of cytokine release syndrome (CRS). Patients with occult HBV infection were given antiviral prophylaxis with entecavir. Positron emission tomography/computerized tomography (PET-CT) was performed after at least two cycles of treatment for response evaluation. Response assessment was made according to published criteria 2. Survival was analyzed using Kaplan-Meier method. Statistical calculations were performed with SPSS Statistics version 28. Results Nine men and six women at a median age of 60 (range: 41-83 years) were treated. Underlying diseases were DLBCL (N=12;80%); transformed follicular lymphoma (N=1, 7%); transformed marginal zone lymphoma (N=1, 7%); and high-grade B-cell lymphoma (N=1, 7%). Other relevant features included staging (I, N=1, 7%; II, N=1, 7%; IV, N=13, 87%); cell of origin (germinal centre B-cell: N=7, 47%; non-germinal centre B-cell: N=7, 47%; not available: N=1, 7%); double-expressor status (positive: N=9, 60%; negative: N=1, 7%; unknown: N=5, 33%); double-hit status(positive: N=3, 20%; negative: N=3, 20%;, unknown: N=9, 60%), prior lines of therapy (median: 6, range: 3-8); prior chimeric receptor T-cell therapy (N=7, 47%); prior autologous transplant (N=4, 27%); elevated serum lactate dehydrogenase (N=9, 60%), and occult HBV infection (N=5, 33%). Eleven patients had a response assessment, showing complete response N=6, 55%), partial response (N=1, 9%) and no response/progressive disease (N=4, 36%). At a median follow-up of 7 months (range 1-22 months) (Figure 1), the median progression-free survival (PFS) was 12 months and the median overall survival (OS) was 15 months(Figure 2). Adverse events included >= grade 3 haematological (anaemia: N=7, 47%; neutropenia: N=8, 53%; thrombocytopenia: N=5, 33%); CRS (grade 1: N=4, 27%; grade 2: N=3, 20%); and cytomegalovirus retinitis (N=1; 6%). Conclusion Glofitamab showed similar efficacy in real-world patients compared with published results. It was safe in patients with occult HBV infection given antiviral prophylaxis. Reference: 1. Dickinson MJ, Carlo-Stella C, Morshhauser F, et al. N Engl J Med 2022; 387:2220-2231 2. Cheson BD, Fisher LI, Barrington SF, et al. J Clin Oncol 2014; 32: 3059-3067

Outcomes of Extramedullary Acute Myeloid Leukemia with Gemtuzumab Ozogamicin: Real-World Experience

Introduction: Extramedullary AML (EM AML) is characterized by the presence of leukemic cells in organs or tissues outside of the blood or bone marrow and remains a therapeutic challenge with dismal response rates to standard chemotherapy and short overall survival. Gemtuzumab Ozogamicin (GO) is an anti-CD33 antibody drug conjugate currently approved for single-agent therapy or in combination regimens for CD33+ relapsed/refractory (R/R) or newly diagnosed (ND) AML, respectively. Although GO is an active drug in AML, the optimal employment of this agent for treatment of EM AML at initial diagnosis, or at relapse, remains to be defined. Methods: A retrospective chart review on outcomes of GO in adults with EM AML at our institute from 2000 to 2023 was performed. Variables collected included age, sex, type of myeloid malignancy, and European LeukemiaNet (ELN) risk, bone marrow, peripheral blood and radiographic involvement, Response Evaluation Criteria in Solid Tumors (RECIST), prior lines of treatments, including stem cell transplant, next-generation sequencing (NGS), cytogenetics, mutational profile, and overall survival (OS). We screened patients with a diagnosis of EM AML who received GO at any point during their EM AML therapy. Patients with only CNS involvement as the extramedullary site were excluded. The aims of this study were to characterize responses and potential clinical benefit of EM AML to GO based regimens in the upfront and R/R settings. Results: 32 patients(pts) with EM AML received GO: 8 (25%) were ND and received GO-based induction regimen, while 22 (68.75%) received GO for R/R AML, and 2 (6.25%) patients received GO both at initial diagnosis and relapse. The median age of patient with ND EM AML was 66 years (y) (range: 28-84), and 60.5 (43-73) y in R/R EM AML. Twenty-four (75%) were men. One (12.5%) ND EM AML and 5 (10.1%) R/R EM AML had >1 extramedullary sites involved. The most frequent sites of EM-AML were skin (25%), lymph nodes (25%), soft tissues (25%), solid organs (25%), and visceral body cavity fluids (12.5%). Based on ELN 2022 risk group criteria, 17 patients were adverse, 8 with intermediate, and 3 with favorable risk. Next-Generation Sequencing (NGS) available for 21 patients identified mutations in TP53 (14.28%), FLT3 (19.04%), NPM1 (19.04%), KMT2A (19.04%), and ASXL1 (19.04%) as the most common mutations. Normal karyotype was noted in 6 (25%) R/R EM AML, while complex karyotype was present in 1 (12.5%) ND EM AML and 10 (41.67%) of R/R EM AML. While none of the ND pts had prior myeloid malignancy, R/R pts had prior AML (15), MDS (2), MDS-EB (1), CMML (1), therapy-related AML (1), myelofibrosis (1), and myeloid sarcoma (1). Concomitant bone marrow involvement at identification of EM AML was present in most ND cases (7/8, 88%) and R/R settings (16/23, 69.56%) (Table 1). Combination 7+3 plus GO was most frequently administered for ND EM AML (3/8) and R/R EM AML (8/24, 33%). Eleven patients had measurable radiologic findings prior to and following GO. Median OS was 10.91 months (m) (range: 0.2 to 27.1) for ND EM AML and 1.58 m (range: 0.7 to 7.5) for R/R EM-AML (Figure 1). 3 of 8 newly diagnosed EM-AML underwent allogeneic bone marrow transplant (AlloBMT) after GO based induction, followed by relapsed EM AML in 1 patient. Despite 50 percent of R/R EM AML pts undergoing prior AlloBMT, none had a durable disease-free response and received GO after relapse. Based on RECIST criteria, 7 of 11 (63.63%) pts achieved a response including 1 Complete Response (disappearance of all target lesions), 6 Partial Response (at least a 30% decrease in the sum of target lesions), and 2 Stable Disease (neither sufficient shrinkage nor increase). The 30-day mortality for ND and R/R were 12.5% and 8.33%, respectively. The 60-day mortality for ND and R/R were 25% and 50%, respectively. Conclusion: Our real-world single-institute experience in patients with EM AML suggests that GO combined with chemotherapy in the upfront setting results in promising outcomes with high overall response rates (CR 50%, PR 13%) by RECIST criteria, durable remissions, and prolonged overall survival in largely favorable and intermediate risk AML. However, despite high partial response rates (4% CR, 50% PR) following GO-based therapy in R/R EM AML, survival was less than 2 months likely due to the high proportion of patients in this cohort with poor risk disease. Further investigations and larger studies are warranted to establish the optimal use of GO in EM AML.

A Real-World Single-Institution Experience with Vitamin C Supplementation for Hypomethylated Drugs Combined with Venetoclax Versus “7+3” in Elderly AML Patients

Background: Vitamin C deficiency is frequently observed in AML patients compared to the normal population (Huijskens, et al. 2016; Liu, et al. 2016), and in vitro and in vivo studies have demonstrated that Vitamin C improves the response of AML patients to demethylated drug epigenetic therapy by directly regulating the activity of TET enzymes (Liu, et al. 2016; Zhao, et al. 2018). In addition, a number of in vitro and in vivo studies have shown that Vitamin C selectively kills cancer cells by generating ROS and can enhance the activity of chemotherapy drugs (Chen, et al. 2007; Verrax and Calderon 2009; Yun, et al. 2015). Today, optimal treatment for elder AML patients remains challenging, and treatment options include intensive chemotherapy (anthracyclines combined with cytarabine, known as “7+3”), hypomethylated drugs (HMA), and the addition of venetoclax to HMAs (azacytidine or decitabine) significantly improve median OS(DiNardo, et al. 2020; Ossenkoppele and Löwenberg 2015). However, it is unclear whether Vitamin C has a synergistic effect with chemotherapy and demethylated drug therapy in elderly patients with AML. Our objective was to investigate whether adding Vitamin C to “7+3” or VEN/HMA can improve the efficacy and survival of elderly AML patients. Patients and methods: A retrospective cohort study of newly diagnosed elderly AML patients treated with a “7+3” regimen or HMA/Ven from 2010 to 2023 at the First Affiliated Hospital of Anhui Medical University, following approval by an institutional ethics Review committee, was conducted. The analysis included 126 patients. Collect clinical, demographic and genomic data. In SPSS (v.26), bilateral Student's t test or one-way ANOVA were used for inter-group difference analysis, Chi-square test was used to analyze the composite complete remission rate, and Kaplan-Meier method was used for survival analysis. Result: The median age of patients in the “7+3” cohort was 65 years, and the median age of patients in the VEN/HMA cohort was 69 years. Compared with VEN/HMA cohort, patients in the “7+3” cohort had better physical status(p＜0.001)(Table 1). Compared with the patients in the “7+3” cohort, the cCR (CR+CRi) in the VEN/HMA cohort was not statistically significant (Table 1). The cCR (CR+CRi) rates of VEN/HMA + Vitamin C and “VEN/HMA” treatment after 1 cycle were 82% and 68% (p=0.69). Compare OS between queues, the median OS (mOS) was 400 days in the “7+3” + Vitamin C cohort and 276 days in the “7+3” cohort (Figure a, p=0.220). Additionally, VEN/HMA+Vitamin C patients demonstrated a superior, yet not statistically significant, median overall survival (OS) benefit compared to VEN/HMA (median OS not reached, Figure b, p = 0.083). Conclusion: VEN/HMA and “7+3” are effective frontline treatment options with similar response rates in newly diagnosed elderly AML. Additionally, the overall survival in VEN/HMA+Vitamin C appeared to be better, but did not reach statistical significance. Our data demonstrated that in the VEN/HMA cohort, VEN/HMA+Vitamin C the OS was longer and approached statistical significance. Future prospective trial designs or larger cohorts are needed to confirm these findings.

A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for Metastatic or Locally Advanced HR+, HER2− Breast Cancer: A Single-Institution Experience

Introduction: Alpelisib is approved in combination with endocrine therapy (ET) to treat patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) progressive metastatic breast cancer (MBC). The SOLAR-1 trial demonstrated the efficacy of this oral agent and showed that, while alpelisib improves outcomes compared to placebo, it is also associated with clinically relevant adverse events (AEs). There is a pressing need for improved knowledge on the effectiveness and tolerability of this agent in real-world patient populations. Methods: We conducted a retrospective cohort study of patients with HR+, HER2− MBC treated with alpelisib and ET. We assessed the safety, tolerability, and effectiveness of alpelisib in a real-world population. Deidentified patient-, tumor-, and outcome-related data, including AEs, were collected and summarized. Kaplan-Meier methods were applied for survival analyses, and stratified analyses of interest were conducted. A p value <0.05 was considered statistically significant. Results: A total of 76 women treated with alpelisib + ET were included in our cohort. Most had been previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and chemotherapy for MBC. The estimated median progression-free survival was 5.2 months (95% CI, 4.1–8.0). The median overall survival was longer among patients without prior everolimus therapy (hazard ratio, 4.28 [95% CI, 1.64–11.16]; p = 0.0012), and no significant outcome differences were observed between patients treated with different starting doses of alpelisib. Approximately 31.6% of patients permanently discontinued alpelisib due to AEs, and 32.9% had at least one dose reduction. The most common grade 3/4 AEs were hyperglycemia (21%), fatigue (13.2%), and diarrhea (10.5%). Conclusions: For progressive HR+, HER2− MBC, alpelisib + ET showed effectiveness in a real-world patient population that was comparable to published clinical trial data, regardless of starting dose. However, the effectiveness of alpelisib following previous everolimus exposure may be limited and, hence, should be a consideration to decide sequencing of therapy in these patients. Patients treated with alpelisib are at risk for clinically relevant AEs and require close monitoring.

2438. Positive Cerebrospinal Fluid Cultures from Intraventricular Reservoirs for CLN2 Patients: One Institution's Experience

Abstract Background Enzyme replacement therapy (ERT) with cerliponase alfa (Brineura) has been shown to slow progression of milestone deterioration in Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), an inherited neurodegenerative lysosomal storage disorder. Brineura must be administered intraventricularly every 2 weeks, necessitating the placement of ventricular reservoirs and requiring frequent access. Traditionally, positive cerebrospinal fluid (CSF) cultures are managed with device replacement and antibiotic treatment. We sought to establish which circumstances might allow for careful observation without device removal. In this study, we report our single-institution experience with clinical outcomes of positive CSF cultures in 16 CLN2 patients over 6 years. Methods We retrospectively reviewed a cohort of 16 patients with CLN2 disease who had ventricular reservoirs placed for ERT administration. At each ERT infusion, CSF was collected by sterile technique and cultured by both thioglycolate broth and agar plate. Epidemiologic and microbiologic data, symptomatology, total antibiotic days, removal and replacement of ventricular reservoir, hospital length of stay, and mortality were analyzed for each patient. Results In our cohort, 11 of 16 patients (69%) had at least one positive CSF culture (Fig 1). Of the 11 with positive cultures, only 3 had their device removed and replaced for a positive culture with concurrent antibiotic treatment at our center, and 2 patients subsequently have been treated with prophylactic antibiotics at infusions (Fig 2). Out of 1401 total CSF cultures, 64 (4.56%) were positive. The most common organism grown was Cutibacterium acnes, which typically grew in only broth culture (82%), suggesting low bacterial burden (Fig 3). The other 7 patients with positive cultures remained asymptomatic with no intervention required. Conclusion At our institution, we have found that in asymptomatic patients with frequently accessed ventricular reservoirs, positive CSF culture with low virulence skin flora was common, and rarely required intervention. This strategy reduced the risks of invasive surgery, prolonged antibiotic courses, and missed infusions. In the future, routine screening cultures in asymptomatic patients can be avoided. Disclosures Raymond Wang, MD, Biomarin Pharmaceutical: Advisor/Consultant|Biomarin Pharmaceutical: Grant/Research Support|Biomarin Pharmaceutical: equity interest Antonio C. Arrieta, MD, FIDSA, FPIDS, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Grant/Research Support|Astellas Pharma Global Development, Inc.: Honoraria|Cumberland Pharmaceutical: Grant/Research Support|IDbyDNA: Advisor/Consultant|IDbyDNA: Grant/Research Support|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Nabriva: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Pfizer, Inc: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Roche/Genentech: Grant/Research Support|The Medicine Company: Grant/Research Support

Diagnostic impact of RNA-based next-generation sequencing fusion panel for solid tumors: A single-institution experience.

Gene rearrangements frequently act as oncogenic driver mutations and determine the onset and progression of cancer. RNA-based next-generation sequencing (NGS) is being used with increasing frequency for solid tumors. The purpose of our study is to investigate the feasibility and utility of an RNA-based NGS fusion panel for solid tumors. We conducted a retrospective, single-institution review of fusion panels requested between May 2022 and March 2023. Demographic, clinical, pathologic, and molecular findings of the patients were reviewed. The utility of the RNA-based NGS fusion panel for the pathologic diagnosis of solid tumors was assessed. Our study included 345 cases, and a fusion event was identified in 24.3% (78/321) of cases. Among the 110 cases submitted for diagnostic purposes, a fusion event was detected in 42.7% (47/110) of cases. The results led to refinement or clarification of the initial diagnosis in 31.9% (15/47) of cases and agreement or support for the initial diagnosis in 59.6% (28/47) of cases. Furthermore, our study indicated that the overall cellularity (tumor and normal tissue) of the tested specimen influences the success of the testing process. In summary, this study demonstrated the feasibility and utility of an RNA-based NGS fusion panel for a wide variety of solid tumors in the appropriate clinicopathologic context. These findings warrant further validation in larger studies involving multiple institutional patient cohorts.

Pancreatic resection for metastasis from renal cell carcinoma: A single institution experience and meta-analysis of survival outcomes

AimsTo evaluate short-term clinical and long-term survival outcomes of pancreatic resection for pancreatic metastasis from renal cell carcinoma (RCC). MethodsA retrospective evaluation of patients undergoing pancreatic resection for metastasis from RCC over a 12-years period was conducted. Furthermore, a systematic search of electronic data sources and bibliographic reference lists were conducted to identify studies investigating the same clinical question. Short-term clinical and long-term survival outcomes were evaluated. Kaplan-Meier survival plots were constructed for survival outcomes. Cox-proportional regression analysis was performed to determine factors associated with survival. Finally, meta-analysis of survival outcomes was conducted using random-effects modelling. ResultsEighteen patients underwent pancreatic resections for RCC pancreatic metastasis within the study period. The mean age of the included patients was 63.8 ± 8.0 years. There were 10(55.6 %) male and 8(44.4 %) female patients. Pancreatectomy was associated with 4(25.0 %) Clavien–Dindo (C-D) I, 5(31.3 %) C-D II, and 7(43.7 %) C-D III complications, 7(38.8 %) pancreatic fistula, 3(16.7 %) post-pancreatectomy acute pancreatitis, 1(5.6 %) delayed gastric emptying, and 1(5.6 %) chyle leak. The mean length of hospital stay was 18 ± 16.3 days. The median survival was 64 months (95 % CI 60–78). The 3-and 5-year disease-free survival rates were 83.3 % and 55.5 %, respectively. The 3-and 5-year survival rates were 100 % and 55.6 %, respectively. The pooled analyses of 553 patients demonstrated 3-and 5-year survival rates of 77.6 % and 60.7 %, respectively. ConclusionsPancreatectomy for RCC metastasis is associated with acceptable short-term clinical and promising long-term survival outcomes. Considering the rarity of the entity, escalation of level of evidence in this context is challenging.

Neurological outcomes after gamma knife radiosurgery for symptomatic skull base meningiomas based on their locations: Single institution experience

Background and objectiveGross total resection of skull base meningioma is so challenging due to its relevant high morbidity. Gamma knife radiosurgery is concerned by providing a favorable therapeutic option in the management of SBM. This study aims to evaluate the neurological outcome after GKRS as an adjuvant or primary treatment for SBM according to their locations. MethodsThis retrospective cross-sectional study consisted of 108 patients with SBM who underwent GKRS as an adjuvant or primary treatment. We found 40 patients with cavernous sinus meningioma (CSM), 36 patients with petroclival meningioma (PCM), and 22 patients with cerebellopontine angle meningioma (CPM). 81.1% of whom were female (n = 90) with a median age of 52.68 years. The mean tumor volume was 4.5 cm3 and the mean marginal dose was 13 Gy. ResultsTumor control was achieved in 96.4 % of patients at a median follow-up of 38.4 months. Over all 17 of 108 patients (15.6%) report improvement in their neurological symptoms. Patients with CPM demonstrated lower rates of neurological symptoms improvement compared to patients with PCM and CSM. Deterioration of neurological symptoms after GKRS developed in 11 patients (10.1%) which was more reported by patients with CSM than the others. The most improvement in cranial nerve deficit was in CN Ⅵ, Ⅴ, VIII among patients with CSM, PCM, and CPM respectively. ConclusionGKRS is acceptable as a primary or adjuvant treatment for SBM by providing an appreciable rate of improvement in neurological symptoms.

Complement-mediated thrombotic microangiopathy treated with anticomplement protein 5 therapy, a retrospective study.

Complement-mediated thrombotic microangiopathy (CM-TMA), also called atypical hemolytic uremic syndrome (aHUS), is a difficult-to-diagnose rare disease that carries severe morbidity and mortality. Anti-C5 monoclonal antibodies (aC5-mab) are standard treatments, but large studies and long-term data are scarce. Here, we report our single institution experience to augment the knowledge of CM-TMA treated with aC5-mab therapy. We aimed to assess the short and long-term effects of aC5-mab in patients diagnosed with CM-TMA treated outside of a clinical trial. This was a retrospective study. We included all patients diagnosed with CM-TMA and treated with aC5-mab at our institution. There were no exclusion criteria. Endpoints included complete TMA response (CR) defined as normalization of hematological parameters and ≥25% improvement in serum creatinine (Cr) from baseline in patients with renal disease, relapse defined as losing the previously achieved CR, morbidity, adverse events, and survival. We found 28 patients with CM-TMA treated with aC5-mab. The median age was 50 years. Baseline laboratories: platelet counts 93 × 109 /L, hemoglobin 8.6 g/dL, lactate dehydrogenase 1326 U/L, serum Cr 4.7 mg/dL, and estimated glomerular filtration rate 19 mL/min. One individual was on renal replacement therapy (RRT) and 10 initiated RRT within 5 days of the first dose of aC5-mab. Genetic variants associated with CM-TMA included mutations in C3, CFB, CFH, CFHR1/3, CFI, and MCP. The mean duration of hospitalization was 24 days. The median time to initiation of aC5-mab was 10 days. Sixteen subjects received RRT. At the time of hospital discharge, 27 were alive, 14 remained on RRT, and 4 had a CR. At 6 months, 23 patients were alive, 18 continued aC5-mab, 8 remained on RRT, and 9 had a CR. At the last follow-up visit past 6 months, 20 were alive, 14 continued aC5-mab, 5 remained on RRT, 12 had a CR, and 1 was lost to follow-up. Our study provides real-world experience and insight into the long-term outcomes of CM-TMA treated with aC5-mab. Our findings validate that CM-TMA is an aggressive disease with significant morbidity and mortality, and confirm that aC5-mab is a relatively effective therapy for CM-TMA. Our study adds practical, real-world experience to the literature, but future research remains imperative.

The Role of Stereotactic Radiosurgery in Patients With Brain Metastases From Colorectal Cancers.

The role of stereotactic radiosurgery (SRS) in patients with brain metastases (BMs) from colorectal cancers (CRCs) has not been established. The authors present a single-institution experience of patients with CRC who underwent SRS with metastatic brain spread. We retrospectively analyzed 111 patients with metastatic CRC (64 female, 57.7%), with 449 BMs treated with Gamma Knife SRS between 2000 and 2022. The median age during SRS was 63 years (range: 28-86), and the median Karnofsky Performance Scale was 80 (range: 60-100). The primary sites were colon (85 patients, 76.6%) and rectal (26 patients, 23.4%). Three patients underwent hypofractionated SRS (3 sessions) with a median margin dose of 27 Gy (range: 27-30). All other patients underwent single-session SRS with a median margin dose of 18 Gy (range: 13-20). The median patient survival after SRS was 7 months (range: 1-174). Ninety-eight (88.3%) patients expired at last follow-up and 15 patients (15.3%) died related to progressive intracranial disease. A Karnofsky Performance Scale of <80 at SRS presentation ( P = .02, hazard ratio [HR]: 0.6, 95% CI: 0.4-0.9) and no previous surgical resection ( P < .01, HR: 0.4, 95% CI: 0.3-0.7) were associated with inferior overall survival using multivariate analysis. Seventeen patients (15.3%) had documented local tumor progression after SRS, at a median time of 7 months (range: 3-34) between SRS and progression. Twenty-six patients (23.4%) developed new BMs at a median of 5 months (range: 2-26) between SRS and new tumor detection. Less than three BMs at SRS presentation ( P = .02, HR: 2.6, 95% CI: 1.2-5.6) were associated with better distant tumor control on multivariate analysis. The incidence of adverse radiation effects was 5.4%. SRS effectively controls BMs from CRC with low risk of treatment-related toxicity. During follow-up, the development of additional metastases can be safely treated by repeat SRS.

Successful robotic kidney transplantation for surgeons with no experience in minimally invasive surgery: a single institution experience

Successful robotic kidney transplantation for surgeons with no experience in minimally invasive surgery: a single institution experience

Treatment results of Para-Testicular Rhabdomyosarcoma (PT-RMS) using radiation as an alternative to retro-peritoneal nodal dissection: A single Institution experience.

Para-testicular Rhabdomyosarcoma (PT-RMS) has a favorable treatment outcome adopting multidisciplinary management; resection, namely high inguinal orchiectomy ± retro-peritoneal lymph node dissection (RPLND) followed by standard or intensive chemotherapy ± adjuvant radiation therapy. This is a retrospective study including all patients with pathologically proven PT-RMS, presented to the National Cancer Institute, Cairo University, during the period from 2005 to 2020. Endpoints included overall survival, disease free survival and patterns of failure of different treatment modalities. Forty one patients were identified. Median age in our cohort was 15 years (range: 2-54 years). After a median follow up of 26 months (range, 3-75 months) ,two and five years OS were 100% and 91.7% respectively and median survival was not reached. Patients who underwent retro-peritoneal nodal dissection had a 5-year DFS rate of 100% versus 73% for those who received radiation to para-aortic nodes (p = 0.185). Limitations include retrospective nature and deviation from COG protocol. This study shows promising results suggesting that less aggressive local treatment modalities including radiation to para-aortic chain could be an option in PT-RMS, given the excellent results of this subtype. However further validation in a prospective study is warranted.

Survival outcomes of lung metastases from colorectal cancer treated with pulmonary metastasectomy or modern systemic chemotherapy: a single institution experience

BackgroundAlthough pulmonary metastasectomy is an accepted treatment strategy for resectable lung metastases (LM) from colorectal cancer (CRC), its survival benefits are controversial. In contrast, recent advancements in chemotherapy have significantly improved metastatic CRC prognosis. This study aimed to evaluate survival outcome of LM from CRC in the age of newly developed chemotherapy.MethodsWe retrospectively reviewed 50 patients who underwent complete resection and 22 patients who received chemotherapy as definitive treatment for LM from resected CRC at our hospital. The present study was limited to patients who started treatment for isolated LM after molecular targeted drugs became available in Japan.ResultsOverall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS) rates after pulmonary resection were 64.5%, 66.4%, and 32.6% at five years, respectively. OS and CSS rates of chemotherapy patients were 26.8% and 28.3% at five years, with a median progression-free survival time of 10.0 months. When compared the characteristics of surgical and chemotherapy patients, patients with pN factors of CRC (p = 0.013), smaller size (p < 0.001), larger number (p < 0.001), and bilateral (p < 0.001) LM received chemotherapy. Univariate analysis showed that multiple LM and rectal lesions were poor prognostic factors for OS (p = 0.012) and DFS (p = 0.017) in surgical patients, and rectal lesions were a poor prognostic factor for OS (p = 0.013) in chemotherapy patients.ConclusionsPulmonary metastasectomy showed a favorable survival in patients with LM from CRC. Despite the high recurrence rate after metastasectomy and recent advances in chemotherapy, surgical resection could still be considered as a valid option among multidisciplinary treatments.Trial registrationThe research plan was approved by the Institutional Review Board of Shinko Hospital (No. 2142) on February 7, 2022.

Prognostic impact of pre-referral tumor resection in unilateral Wilms tumor: A single-institute experience from a lower middle-income country.

The objectives of this study were to evaluate the prognostic impact of pre-referral surgical resection of Wilms tumor (WT) performed at non-oncology centers, and to strategize an improved care plan for this very curable pediatric tumor. In this study conducted in a large pediatric cancer center in Pakistan, we retrospectively reviewed the electronic medical records (EMR) of 149 patients with unilateral WT from September 2008 to August 2017. Based on treatment approach, patients were categorized into two groups: (i) pre-referral tumor resection (PTR: n=75), and (ii) post-neoadjuvant chemo nephrectomy (PCN: n=74). The proportion of metastatic disease in PTR and PCN groups was 33.3% and 35.1%, respectively. In the PTR subset, median time to admission after PTR was 5weeks (mean 11, SEM 2.8, range: 2-202) weeks, with 53.3% (n=40) presenting more than 4weeks after PTR. Twenty patients had no cross-sectional imaging prior to PTR and underwent surgery after abdominal ultrasound only. On baseline imaging at our center, 58.7% (n=44) of the PTR group had radiologically evaluable disease (four metastases only, 19 local residual tumor only, 21 both localized tumor and visible metastases). Disease staging was uncertain in 23 patients because of no or inadequate histology specimens and/or lymph node sampling in patients with no evaluable disease. Statistically significant differences were recorded for the two subsets regarding tumor volume, extent and nodularity, renal vein and renal sinus involvement, lymph node status, tumor rupture and histopathologic features, and tumor stage, with a 10-year event-free survival (EFS) for PCN and PTR of 74.3% and 50.7%, respectively (p<.001). In the PTR group, EFS for those presenting within 4weeks and later was 91.4% versus 15.0%, respectively (p<.0001). Suboptimal pre-referral surgical intervention results in poor survival outcomes in unilateral WT. Our findings highlight the need for a comprehensive action plan for educating healthcare professionals engaged in WT diagnosis and referral process. PCN in a multidisciplinary team approach can reduce surgical morbidity and seems to be a better strategy to improve the survival rates in low-resource settings.

Use of the Kono-S anastomosis in pediatric Crohn's disease: a single-institution experience.

About 24% of children with Crohn's Disease (CD) require surgery. In 2003, Kono et al. described a novel anastomosis reported to decrease the rate of anastomotic CD recurrence. Subsequent studies have reproduced these outcomes, but none has demonstrated its effect in pediatric patients. This study evaluates short-term outcomes of pediatric patients following ileocolic resection and Kono-S anastomosis. A retrospective review of patients < 18 years old who underwent ileocolic resection followed by Kono-S anastomosis compared with those who underwent a stapled anastomosis. Nine Kono-S patients were matched with nine patients preceding them who received traditional side-to-side and end-to-side anastomoses. All patients underwent minimally invasive surgery. Demographics, pre-operative medication usage, and symptom profiles were not significantly different. Traditional anastomosis (TA) patients had longer lengths of stay (4.6 vs 2.9 days; p = 0.03) but had no statistically significant differences in blood loss, procedure length, and pathologic findings. One Kono-S patient had a superficial surgical site infection, and one TA patient had an anastomotic leak requiring reoperation within 30 days. More TA patients experienced post-operative symptoms at both 30-day and 6-month follow-up (66.7% vs 33.3%; p = 0.16 and 77.8% vs 25%; p = 0.03). The Kono-S anastomosis appears to be safe in pediatric CD when compared to traditional stapled anastomoses.

PATH-43. INFRATENTORIAL IDH-MUTANT ASTROCYTOMAS REQUIRE HIGH INDEX OF SUSPICION FOR ACCURATE DIAGNOSIS

Abstract BACKGROUND Banan et al (PMID 2776277) recently identified infratentorial IDH-mutant astrocytomas (Inf-IDHmt) as a distinct subtype in which 80% have non-canonical mutations, precluding the use of IDH1 R132H immunohistochemistry (IHC) for diagnosis. They note “molecular testing is critical for detection of these tumors”. Only 47% have ATRX loss by IHC and only 56% have MGMT promotor methylation. Thus, it is critical that neurosurgeons take this into account during surgical planning due to the requirement for adequate tissue sample volume necessary for diagnosis. We review these diagnostic challenges in our recent single institution experience with these tumors. METHODS Database text word searches were conducted for the years 2007-2023 to generate cases, coupled with chart review. RESULTS 7 cases were identified: 3 male and 4 female, ages 27-44. All cases were small stereotactic biopsies. The histological diagnosis was made exceptionally challenging by paucity of tumor cells (especially in grade 2), coupled with the fact that 5 of 7 had non-canonical IDH-mutation and 5 of 7 showed ATRX retention by IHC, necessitating a very high index of suspicion on the part of the pathologist to send for next-generation sequencing (NGS). Due to the rare co-expression of IDH and histone mutations in this subtype, 6 of 7 had H3 K27M IHC conducted; all were negative. Due to small tissue volumes, MGMT promotor methylation testing could only be conducted on 3 of 7 cases; testing was uninformative on these 3. CONCLUSION Preoperative high index of suspicion is required to obtain maximal safe biopsy volumes of tissue for molecular and MGMT methylation testing, which should be conducted on virtually all brainstem and cerebellar biopsies.

Surgical repair of post myocardial infarction ventricular septal defect: a retrospective analysis of a single institution experience

IntroductionVentricular septal defect (VSD) is a mechanical complication of acute myocardial infarction (MI) with a very high mortality, despite advances in surgical and circulatory support. The tremendous hemodynamic disturbance and the severely fragile myocardium render surgical repair a great challenge. The optimal time of surgical repair with or without circulatory support is still controversial.ObjectiveThe aim of this study is to review our experience with early surgical repair of post-MI VSD in a single major cardiac institution in China.MethodsFrom January 2013 to October 2020, 9consecutive patients presented to our emergency department with a diagnosis of post-MI VSD. Among them, 8 were male, and the mean age was 58 ± 7years. The mean VSD size was 22.5 ± 5.7 mm. In all patients, an intra-aortic balloon pump (IABP)was inserted immediately after admission to cardiac surgery service. All patients were operated at a mean of 3.3 ± 2.9 days, and 4 within 24 h of the rupture (range 1 to 9 days post-VSD). In 5 cases, the VSD was located superiorly, and 4 cases in the posterior septum.ResultsThe overall 30-day mortality was 11% (1/9). Coronary angiography was performed in all nine patients, four with single vessel disease had coronary stents implanted, and the other five received concomitant coronary artery bypass grafting during VSD repair surgery. There was no death in all 5 patients with anterior septal perforation. One patient with posterior septal perforation died in the operating room due to bleeding from the ventriculotomy site. Three survived patients were diagnosed with a small residual defect and mild left to right shunt post-repair. However, no further intervention was required, and patients remained asymptomatic (Killip II in 1 and III in 2).ConclusionIn our experience, immediate insertion of IABP and hemodynamic stabilization with early surgical intervention of VSD repair and concomitant coronary revascularization provided an 89% survival rate.

Characteristic Changes of Ulcerative Colitis–Associated Neoplasm Patients in the Era of Biologics: a 20-Year Single Institution Experience of Surgical Cases

Characteristic Changes of Ulcerative Colitis–Associated Neoplasm Patients in the Era of Biologics: a 20-Year Single Institution Experience of Surgical Cases

Ruxolitinib add-on therapy in steroid-refractory graft-vs-host disease following hematopoietic cell transplantation: A single institutional experience

Steroid-refractory graft-vs-host disease (SR-GVHD) remains a significant cause of mortality after allogeneic hematopoietic cell transplantation (HCT), and the trajectory of treatment response for that vary. In our case series, we introduced six cases experiencing SR-GVHD who achieved better disease control after applying ruxolitinib (RUX). Of the six cases, five of them achieved symptoms-free while one of them, unfortunately, died of invasive fungal infection. Three alive cases were weaned off the RUX treatment successfully, while the remaining were on a medication tapering program. We demonstrated mixed efficacy in patients with SR-GVHD, suggesting that the RUX add-on may be a useful therapeutic adjunct in combination with other immunosuppressants.