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Thoracic Cancer Feb 2020We investigated the risk factors for leptomeningeal carcinomatosis (LMC) and compared clinical efficacies of various treatment modalities including intrathecal (IT)...
Impact of clinicopathologic features on leptomeningeal metastasis from lung adenocarcinoma and treatment efficacy with epidermal growth factor receptor tyrosine kinase inhibitor.
BACKGROUND
We investigated the risk factors for leptomeningeal carcinomatosis (LMC) and compared clinical efficacies of various treatment modalities including intrathecal (IT) chemotherapy in patients with lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.
METHODS
Using clinical research data from the Asan Medical Center, we retrospectively analyzed data of patients diagnosed with LMC, confirmed via cerebrospinal fluid (CSF) analysis from January 2008 to December 2017.
RESULTS
We identified 1189 patients with lung adenocarcinoma harboring EGFR mutations. Among these, 9.8% had a median duration of 13.5 (interquartile range [IQR] 6.8-23.6) months from the initial lung cancer diagnosis to LMC occurrence. Younger age (hazard ratio [HR] 1.043, P < 0.001), initial metastatic disease (HR 3.768, P < 0.001), and metastasis to the brain (HR 8.682, P < 0.001) or lung (HR 2.317, P = 0.004) were risk factors associated with LMC. Median survival duration from LMC diagnosis was 3.8 (IQR 1.5-8.6) months. Eastern Cooperative Oncology Group performance status score ≤ 2 (HR 0.505, P = 0.007) and insertion of Ommaya reservoir (HR 0.445, P = 0.005) were associated with longer survival. EGFR-tyrosine kinase inhibitor (TKI) conferred survival benefits compared to cytotoxic chemotherapy or best supportive care (HR 2.222, P = 0.018; HR 5.638, P < 0.001, respectively). Although IT chemotherapy showed no survival benefit, it was associated with improved neurologic symptoms and signs and CSF negative conversion.
CONCLUSIONS
Younger age, initial diagnosis of metastatic disease, and metastasis to the brain or different lobes were associated with LMC in patients with EGFR-mutant lung adenocarcinoma. Therapeutic interventions including EGFR-TKIs, cytotoxic chemotherapy, or Ommaya reservoir, and good performance status were related to favorable survival outcomes.
KEY POINTS
Age and disease status were associated with LMC in patients with EGFR-mutant adenocarcinoma, and EGFR-TKI, Ommaya reservoir, and good performance status were related to survival benefit.
Topics: Adenocarcinoma of Lung; Aged; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Meningeal Carcinomatosis; Middle Aged; Mutation; Neoplasm Metastasis; Protein Kinase Inhibitors; Retrospective Studies; Survival Rate; Treatment Outcome
PubMed: 31910497
DOI: 10.1111/1759-7714.13296 -
Arquivos de Neuro-psiquiatria Feb 2011To assess whether the cystic craniopharyngiomas can be controlled with the use of intratumoral applications of interferon alpha.
OBJECTIVE
To assess whether the cystic craniopharyngiomas can be controlled with the use of intratumoral applications of interferon alpha.
METHOD
Nineteen patients with the diagnosis of cystic craniopharyngioma were treated with intratumoral chemotherapy with interferon alpha from January 2002 to April 2006. All patients underwent placement of an intracystic catheter connected to an Ommaya reservoir. Through this reservoir were made applications during chemotherapy cycles. Each cycle corresponded to application of 3,000,000 units of interferon alpha three times per week on alternate days totalizing 36,000,000 units. Response to treatment was evaluated by calculating the tumor volume on MRI control after one, three and six months after the end of each cycle. Patients who developed worsening of symptoms or who had insignificant reduction in tumor volume during follow-up underwent repeat cycle chemotherapy.
RESULTS
Four patients received four cycles of chemotherapy, three patients received three cycles, six patients received two cycles and six patients received one. The lower percentage of reduction in tumor volume was 60% and the bigger reduction was 98.37%. Eleven patients had a reduction greater than 90%. Five patients had a tumor reduction between 75 and 90% and in three patients the tumors were reduced by less than 75%. No deaths occurred during treatment and side effects of interferon alpha were well tolerated. No treatment was discontinued. Follow-up after the last application ranged from one year and five months to three years and nine months.
CONCLUSION
The intratumoral chemotherapy with interferon alpha decreases the volume of cystic craniopharyngiomas and so far can be considered a new therapeutic alternative.
Topics: Adolescent; Antineoplastic Agents; Catheterization; Child; Child, Preschool; Craniopharyngioma; Cysts; Drug Administration Schedule; Female; Humans; Infant; Injections, Intralesional; Interferon-alpha; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Statistics, Nonparametric; Tumor Burden; Young Adult
PubMed: 21359423
DOI: 10.1590/s0004-282x2011000100011 -
AJP Reports Jul 2020Cerebellar hemorrhage is rare in term newborns and is most often seen after traumatic birth. Lifelong sequelae include motor and cognitive impairment. We report the...
Cerebellar hemorrhage is rare in term newborns and is most often seen after traumatic birth. Lifelong sequelae include motor and cognitive impairment. We report the uncommon case of a late preterm infant born by spontaneous delivery who showed right peripheral facial palsy at 24 hours of life. Cranial ultrasound showed lateral ventricles dilatation and a diffuse hyperechoic round lesion in the right cerebellar hemisphere. The computed tomography scan confirmed a hemorrhagic lesion in the right cerebellar hemisphere and in the vermis with midline shift and intraventricular bleeding. Ommaya reservoir was inserted and used for a few days. The facial palsy gradually recovered to a complete remission after 6 weeks. Follow-up examinations at 12 and 18 months evidenced infant's delayed motor function, hyperreflexia, tremors, and speech delay.
PubMed: 33094015
DOI: 10.1055/s-0040-1715162 -
Journal of Neurology Feb 2021To evaluate the effect of intrathecally (IT) delivered rituximab as a therapeutic intervention for progressive multiple sclerosis (PMS) during a 3-year follow-up period. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To evaluate the effect of intrathecally (IT) delivered rituximab as a therapeutic intervention for progressive multiple sclerosis (PMS) during a 3-year follow-up period.
METHODS
Participants of a 1-year open-label phase 1b study of IT delivered rituximab to patients with PMS were offered extended treatment with follow-up for an additional 2 years. During the extension phase, treatment with 25 mg rituximab was administered every 6 months via a subcutaneous Ommaya reservoir connected to the right frontal horn with a ventricular catheter.
RESULTS
Mild to moderate vertigo and nausea occurred in 4 out of 14 participants as temporary adverse events associated with IT rituximab infusion. During the entire 3-year period, two cases of low-virulent bacterial meningitis occurred, which were successfully treated. Walking speed deteriorated significantly during the study.
CONCLUSIONS
IT administration of rituximab via a ventricular catheter was well tolerated. Considering the meningitis cases, the risk of infection was not negligible. The continued loss of walking speed indicates that IT rituximab was not able to stop disease progression.
CLASSIFICATION OF EVIDENCE
This study provides class IV evidence that intraventricularly administered rituximab in progressive MS is associated with a risk for bacterial meningitis and does not halt disease progression.
EU CLINICAL TRIAL REGISTER
EudraCT; 2008-002626-11 and 2012-000721-53.
Topics: Disease Progression; Humans; Immunologic Factors; Multiple Sclerosis, Chronic Progressive; Rituximab
PubMed: 32901316
DOI: 10.1007/s00415-020-10210-0 -
Annals of Palliative Medicine Jul 2020Leptomeningeal metastasis (LM) is one of the most severe complications of non-small cell lung cancer (NSCLC), and it lacks standard treatment guidelines and is always...
Treatment response to intrathecal chemotherapy with pemetrexed via an Ommaya reservoir in EGFR-mutated leptomeningeal metastases from non-small cell lung cancer: a case report.
Leptomeningeal metastasis (LM) is one of the most severe complications of non-small cell lung cancer (NSCLC), and it lacks standard treatment guidelines and is always accompanied by poor prognosis. We report a patient who was definitively diagnosed as LM from NSCLC with a targeted mutation of epidermal growth factor receptor (EGFR) via magnetic resonance imaging (MRI) and positive cerebrospinal fluid (CSF) cytology. Tyrosine kinase inhibitors (TKIs) were implemented but ineffective. Then the patient received the installation of an intraventricular Ommaya reservoir. Thirty mg of pemetrexed and other adjuvant treatments were implemented on days 1 and 8 every 3 weeks via the Ommaya reservoir. This treatment regimen resulted in the alleviation of the neurological symptoms, the clearing of CSF cytology and a reduced lesion of LM without notable side effects. At recent follow-ups, MRI examinations revealed the sustained stable LM lesion. We report the first successful example of administering intrathecal chemotherapy with pemetrexed via an Ommaya reservoir, providing a new therapeutic approach against LM from NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Meningeal Carcinomatosis; Pemetrexed
PubMed: 32648459
DOI: 10.21037/apm-19-521 -
ESMO Open 2018Metastatic melanoma patients with leptomeningeal disease (LMD) have an extremely poor prognosis, with a median survival measured in weeks, and few treatment options....
OBJECTIVES
Metastatic melanoma patients with leptomeningeal disease (LMD) have an extremely poor prognosis, with a median survival measured in weeks, and few treatment options. Outcomes of a retrospective cohort of patients with LMD that were treated with intrathecal interleukin-2 (IT IL-2) were reviewed to assess the long-term efficacy of this therapy.
METHODS
The records of metastatic melanoma patients with LMD who were treated with IT IL-2 from 2006 to 2014 in a Compassionate Investigational New Drug study were reviewed. IL-2 (1.2 mIU) was administered intrathecally via Ommaya reservoir up to five times per week in the inpatient setting for 4 weeks; patients with good tolerance and clinical benefit received maintenance IT IL-2 every 1-3 months thereafter.
RESULTS
The cohort included 43 patients. The median age of the patients was 47 years (range 18-71), and 32 (74%) were male. 23 patients (53%) had positive cerebrospinal fluid (CSF) cytology and radiographic evidence of LMD, 8 (19%) had positive CSF cytology only, 9 (21%) had radiographic evidence only and 3 (7%) were diagnosed based on pathology review after craniotomy. The median overall survival (OS) from initiation of IT IL-2 was 7.8 months (range, 0.4-90.8 months), with 1-year, 2-year and 5-year OS rates of 36%, 26% and 13%. The presence of neurological symptoms (HR 2.1, P=0.03), positive baseline CSF cytology (HR 4.1, P=0.001) and concomitant use of targeted therapy (HR 3.0, P=0.02) was associated with shorter OS on univariate analysis. All patients developed symptoms due to increased intracranial pressure which was managed with supportive medications and/or CSF removal, and there were no treatment-related deaths.
CONCLUSION
These results demonstrate that despite their historically dismal prognosis a subset of metastatic melanoma patients with LMD treated with IT IL-2 can achieve long-term survival, but these data need to be verified in a prospective trial setting.
PubMed: 29387478
DOI: 10.1136/esmoopen-2017-000283 -
Journal of Pediatric Neurosciences 2020GeneXpert MTB/RIF is a test for early, rapid diagnosis of tubercular meningitis (TBM).
BACKGROUND
GeneXpert MTB/RIF is a test for early, rapid diagnosis of tubercular meningitis (TBM).
AIM
The aim of this article was to study the clinical profile, radiological features, yield of GeneXpert, neurosurgical interventions, and outcome of TBM in children.
SETTINGS AND DESIGN
This was a retrospective and prospective observational study.
MATERIALS AND METHODS
Diagnosis was based on the uniform research definition criteria and was staged according to the British Medical Research Council. Mantoux test, analysis of cerebrospinal fluid (CSF), CSF GeneXpert, and radiological investigations were performed.
RESULTS
Of 36 patients, 50% were aged 1-5 years. Fever (100%), headache (82%), altered sensorium (80%), and vomiting (66%) were common features. Twelve (33%) had contact with active case of tuberculosis; 32 received Bacille Calmette Guarin vaccination. Neurological features included severe deterioration in sensorium (Glasgow Coma Scale < 8) (38%), mild and moderate deficit in sensorium (31%), hemiparesis (41%), and involvement of sixth (25%) and seventh (22%) cranial nerves. Cerebral vision impairment (25%), papilledema (25%), and dystonia (22%) were other findings. CSF GeneXpert was positive in 37% (12/33) patients. Hydrocephalus and basal exudates (75%) were noted on neuro-imaging. Surgical intervention was performed in children with hydrocephalus (13/27). Omayya reservoir was placed in seven children, of which five needed conversion to ventriculoperitoneal (VP) shunt; direct VP shunt was carried out in six (6/13). Good outcome was noted in 78% at discharge. Stage III TBM ( = 0.0001), cerebral infarcts ( = 0.0006), and motor deficits ( = 0.03) were associated with poor outcome. Sequelae included learning difficulties with poor scholastic performance (31.5%).
CONCLUSION
GeneXpert has high diagnostic specificity, but negative results do not rule out TBM. CSF GeneXpert provided quick results. Placement of Ommaya reservoir in TBM stage II and III with hydrocephalus was not successful. Hydrocephalus was managed conservatively with success (53%).
PubMed: 33531936
DOI: 10.4103/jpn.JPN_92_19 -
Surgical Neurology International 2015Subcutaneous reservoirs are used to provide therapy by establishing access to cerebrospinal fluid. However, it is associated with complications such as hemorrhage,...
BACKGROUND
Subcutaneous reservoirs are used to provide therapy by establishing access to cerebrospinal fluid. However, it is associated with complications such as hemorrhage, infection, malfunction, and malpositioning. In an irradiated field with thin skin, use of reservoir can result in wound dehiscence, wound infection, and device extrusion.
CASE DESCRIPTION
We introduced a "countersinking" technique for the reservoir placement which involves the creation of bony recess in the skull to effectively accommodate the reservoir and decrease the protrusion. "Countersinking" of the reservoir can result in tension-free closure of the scalp and allow durable coverage of the reservoir. In the representative case, the incisional wound healed completely without any concern for wound dehiscence and the countersink technique may have contributed to effective healing of the radiated scalp.
CONCLUSION
Countersinking of the reservoir can be a strategy to prevent complications such as wound dehiscence, and device extrusion in any patient, but in irradiated patients with very thin skin it also enables tension-free closure of the wound.
PubMed: 26236553
DOI: 10.4103/2152-7806.161409 -
Oman Medical Journal Mar 2017We report a case of meningitis in a 26-year-old Nepalese man who was admitted to Hamad General Hospital with epidermoid cyst for drainage. Ommaya reservoir was placed...
We report a case of meningitis in a 26-year-old Nepalese man who was admitted to Hamad General Hospital with epidermoid cyst for drainage. Ommaya reservoir was placed into the cyst for drainage and externalventricular drainage (EVD) was performed. After four days, the patient was transferred to the ward in stable condition. His weakness resolved partially and headache severity decreased. After three days, the patient developed fever and headache severity increased with deterioration of consciousness level. Cerebrospinal fluid (CSF) through EVD showed 2 200 leucocytes/µL, protein level of 295 mg/dL, and glucose level of < 1.8 mg/dL. Meropenem was started on the patient. Aspirate from Ommaya reservoir and CSF showed gram-negative rods and cultures yielded sensitive to cefepime, gentamycin, ciprofloxacin, and amikacin, but resistant to meropenem and piperacillin-tazobactam. EVD was replaced and the patient received cefepime and ciprofloxacin for 21 days after which he improved and was discharged with right sided residual weakness.
PubMed: 28439390
DOI: 10.5001/omj.2017.30 -
Medicine Sep 2023Reconstruction of wound complications in patients with advanced cancer with distant metastases is challenging for plastic surgeons. This may be due to the cancer...
RATIONALE
Reconstruction of wound complications in patients with advanced cancer with distant metastases is challenging for plastic surgeons. This may be due to the cancer patients' hypercoagulability and potential intolerance to general anesthesia. This article aimed to discuss the risk of free-flap reconstruction in such cases.
PATIENT CONCERNS
The patient was a 58-year-old female with advanced non-small cell lung cancer and brain metastasis. The patient underwent brain radiotherapy and chemotherapy through the Ommaya Reservoir.
DIAGNOSES
A year ago, she underwent several local flap closures for recurrent wound healing failure due to wound complications, including infection, wound dehiscence, and subsequent device removal.
INTERVENTIONS
A radial forearm free flap was created under general anesthesia. The patient was discharged in the third postoperative week since the flap remained stable.
OUTCOMES
At follow-up a month thereafter, the patient exhibited signs of recovery without any complications even while continuing her chemotherapeutic regimen.
LESSONS
Free flap placement is not an absolute contraindication in cancer patients with distant metastases. Nevertheless, it is associated with clinical challenges and operator hesitancy. This is a case of a successful free flap in a cancer patient with hypercoagulability and suspected floating tumor cells. Postoperative management, in this case, is appropriate.
Topics: Humans; Female; Middle Aged; Lung Neoplasms; Scalp; Carcinoma, Non-Small-Cell Lung; Free Tissue Flaps; Brain Neoplasms
PubMed: 37682134
DOI: 10.1097/MD.0000000000035097