A Natural History Study of Nitrous Oxide versus Propofol-Assisted Intrathecal Therapy in the Treatment of Acute Lymphoblastic Leukemia

Background: Childhood acute lymphoblastic leukemia (ALL) treatment requires numerous lumbar punctures (LPs) with intrathecal (IT) chemotherapy to prevent and treat central nervous system disease. Historically, LPs in this setting are performed using propofol sedation. At our institution, LPs are often alternatively performed under nitrous oxide (N2O). To date, there have been no large scale assessments comparing these sedation methods for this purpose. Procedures: Retrospective cohort study of patients aged 0-31 years with ALL treated between 1/1/2013-12/31/2018 at the Children’s Minnesota Cancer and Blood Disorders Center, including all therapeutic LPs performed in the clinic setting under either propofol or N2O. Results: Among 215 patients and 2677 therapeutic LPs, 56.6% (n = 1515) occurred under N2O with 43.3% (n = 93) of patients using exclusively N2O with all LPs. The incidence of traumatic LPs (RBC ≥ 10 cells/µL) were similar between both treatments (27.3% vs 30.2). Successful IT chemotherapy delivery (99.7% N2O vs 99.8% propofol) did not differ between sedation types. Experiencing a traumatic LP under N2O was associated with a sedation switch for the subsequent LP (aOR 2.40, p=0.002) while older age (aOR 1.08, p<0.0001) and higher BMI percentile (aOR 1.01, p=0.009) were associated with increased likelihood for undergoing a traumatic LP. Conclusion: N2O is an effective sedation option for therapeutic LPs in children with ALL with noninferiority to propofol in terms of IT chemotherapy administration and traumatic LP incidence. For many patients, N2O can effectively replace propofol during LP procedures, which has important safety and quality-of-life implications.

Recommendations for Neuromodulation in Diabetic Neuropathic Pain

Over 50% of the 34 million people who suffer from diabetes mellitus (DM) are affected by diabetic neuropathy. Painful diabetic neuropathy (PDN) impacts 40–50% of that group (8.5 million patients) and is associated with a significant source of disability and economic burden. Though new neuromodulation options have been successful in recent clinical trials (NCT03228420), still there are many barriers that restrict patients from access to these therapies. We seek to examine our tertiary care center (Albany Medical Center, NY, USA) experience with PDN management by leveraging our clinical database to assess patient referral patterns and utilization of neuromodulation. We identified all patients with a diagnosis of diabetes type 1 (CODE: E10.xx) or diabetes type 2 (CODE: E11.xx) AND neuralgia/neuropathic pain (CODE: M79.2) or neuropathy (CODE: G90.09) or chronic pain (CODE: G89.4) or limb pain (CODE: M79.6) OR diabetic neuropathy (CODE: E11.4) who saw endocrinology, neurology, and/or neurosurgery from January 1, 2019, to December 31, 2019. We then determined which patients had received pain medications and/or neuromodulation to divide the cohort into three groups: no treatment, conservative treatment, and neuromodulation treatment. The cohorts were compared with chi-square or one-way ANOVA with multiple comparisons to analyze the differences. A total of 2,635 PDN patients were identified, of which 700 received no treatment for PDN, 1,906 received medication(s), and 29 received neuromodulation (intrathecal therapy, spinal cord stimulation, or dorsal root ganglion stimulation). The patients who received pain medications for PDN visited neurology more often than the pain specialists. Of the patients that received neuromodulation, 24 had seen neurology, 6 neurology pain, and 3 anesthesia pain. They averaged 2.78 pain medications prior to implant. Approximately 41% of the patients in the conservative management group were prescribed three or more medications. Of the 1,935 treated patients, only 1.5% of the patients received neuromodulation. The patients on three or more pain medications without symptomatic relief may be potential candidates for neuromodulation. An opportunity, therefore, exists to educate providers on the benefits of neuromodulation procedures.

LMD-18. Detection and serial monitoring of CSF ctDNA in breast cancer leptomeningeal disease (BCLM)

Background CSF cytology is the gold standard diagnostic test for BCLM, but is hampered by a low sensitivity, often necessitating repeated lumbar puncture to confirm or refute the diagnosis. Furthermore, during the treatment of BCLM, there is no robust quantitative response tool to guide treatment decisions. Material and Methods cfDNA was obtained from CSF and plasma in patients with breast cancer undergoing investigation for BCLM (n = 28) and during subsequent intrathecal treatment (n = 13). Ultra low pass whole genome sequencing (ulpWGS) and estimation of the ctDNA fraction was performed. Results were validated by mutation-specific digital droplet PCR (ddPCR). Results 22/28 cases had confirmed BCLM by positive MRI and/or CSF cytology. The remaining 6/28 had suspected but non-confirmed BCLM, and at median 20 months follow up, these patients were BCLM-free. CSF ctDNA fraction was significantly elevated (median 57.5, IQR 38.3 - 84.9%) in confirmed BCLM compared to 6 non-confirmed BCLM (median 5.0, IQR 0.0 - 6.7%) (p &lt;0.0001). ctDNA fraction was detected in BCLM confirmed cases regardless of negative cytology or MRI. Plasma ctDNA fraction was only detected in extra-cranial disease progression. ctDNA fraction was concordant with mutant allele fraction measured by ddPCR (n = 118 samples). Serial CSF ctDNA fraction during intrathecal treatment showed dynamic changes, while CSF cytology and MRI were often unchanged or equivocal. Early reduction in CSF ctDNA fraction was associated with longer responses to intrathecal therapy. Further, rising ctDNA fraction during intrathecal chemotherapy could be detected up to 6 weeks before relapse in neurological symptoms, cytology or MRI. Conclusion Measuring CSF ctDNA fraction is a sensitive diagnostic test for BCLM and could lead to more timely and accurate diagnosis. During intrathecal chemotherapy, CSF ctDNA also provides a quantitative response biomarker to help guide clinical management in this difficult treatment scenario.

LMD-09. Outcomes and symptom benefit from palliative radiotherapy for leptomeningeal disease in breast cancer patients

Objective The benefit of radiotherapy (RT) in patients with leptomeningeal disease (LMD) is poorly characterized. This study assessed the overall survival (OS) and clinical improvement of a largely symptomatic cohort of breast cancer patients with LMD, to identify patient subsets most likely to benefit from palliative RT. Methods Patients with breast cancer-related classic radiographic LMD (36% cytology-confirmed) were treated with palliative whole brain and/or partial spine RT between 2000–2020 at a single academic institution in this retrospective analysis. OS was calculated from date of LMD diagnosis using the Kaplan-Meier method. A multivariate logistic regression model incorporating ER/PR status, HER2 status, ECOG and steroid use was developed to identify factors associated with symptom benefit, which was ascertained retrospectively by chart review. Results Among 64 patients, the radiographic distribution of LMD was in the brain (58%), spine (22%), or both (20%). A total of 63% had brain metastases, and 57% of patients had ER+ and/or PR+, 22% HER2+, and 38% triple-negative disease. Of the symptomatic patients (94%), primary symptom domains included cranial nerve deficits (34%), sensory/motor deficits from intracranial disease (25%) or spinal disease (27%), and headaches/nausea (14%), with 42% of patients reporting &gt;1 symptom domain. Two-thirds of patients were on steroids prior to RT, and 13% of patients received intrathecal therapy. OS was 3.75 months. Following a median dose of 30Gy in 10 fractions, 59% of symptomatic patients experienced symptom improvement, with similar improvement rate across domains (12%, 15%, 19%, 14%, respectively); 21% of patients had improvement in &gt;1 symptom domain. Hormone receptor positivity was independently associated with symptom improvement following RT (OR 3.5, 95% CI 1.2–11, p=0.029). Conclusions In this poor-prognosis cohort of breast cancer patients with LMD, palliative RT yielded symptomatic improvement, and may be particularly beneficial among better-prognosis patients with hormone receptor-positive disease.

Cerebrospinal Fluid Sterilization with Intrathecal Polymyxin in Addition to Parenteral Polymyxin in Nosocomial Acinetobacter Meningitis

Background: For the last few decades there has been a substantial concern regarding the increasing prevalence of multidrug resistant (MDR) Acinetobacter species in hospitals. Aim: To determine the outcomes with intrathecal polymyxins therapy in patients with multidrug resistant Acinetobacter species nosocomial meningitis. Place and duration of study: This Retrospective study was conducted in the Department of Infectious Diseases, Aga Khan University Hospital, Karachi Pakistan between 2010 and 2014. Methodology: Twenty six patients who developed post neurosurgical MDR Acinetobacter nosocomial meningitis age above 18 were included, while those with polymicrobial meningitis, and those patients who only received intravenous polymyxins were excluded. The primary outcome is ability and time to sterilize the cerebrospinal fluid Results: The mean age was 42.9±11.5 years. Cerebrospinal fluid sterilization was observed in 24 patients in a median of 4 days. One patient made complete recovery, 16 patients recovered with neurological deficits and five patients expired. A trend of early cerebrospinal fluid sterilization was observed in patients with continuous intrathecal therapy. The time to cerebrospinal fluid sterilization is similar with intrathecal colistin or polymyxin. Conclusion: Intrathecal polymyxins are safe and efficacious in the treatment of multidrug resistant nosocomial Acinetobacter species meningitis. Keywords: Intrathecal, Polymyxins, Multidrug resistant, Acinetobacter species, Nosocomial, Meningitis