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Clinical Lung Cancer Mar 2023Leptomeningeal metastasis (LM) is a highly fatal and debilitating complication of lung adenocarcinoma (LUAD) with limited therapeutic options. This study aimed to...
Safety, Pharmacokinetic and Clinical Activity of Intrathecal Chemotherapy With Pemetrexed via the Ommaya Reservoir for Leptomeningeal Metastases From Lung Adenocarcinoma: A Prospective Phase I Study.
INTRODUCTION
Leptomeningeal metastasis (LM) is a highly fatal and debilitating complication of lung adenocarcinoma (LUAD) with limited therapeutic options. This study aimed to evaluate the efficacy and toxicities of intrathecal chemotherapy (IC) with pemetrexed via Ommaya reservoir in LUAD with refractory LM.
METHODS
In this prospective, single-arm, phase I trial (ChiCTR2000028936), LUAD-LM patients who had progressed after at least two prior treatments were recruited. Pemetrexed from 30 mg to 50 mg was administered on Days 1 and 8 every 3 weeks via Ommaya reservoir. Serial samples of cerebrospinal fluid (CSF) and plasma were obtained for pharmacokinetic studies. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and therapeutic toxicities.
RESULTS
Twenty-three patients were enrolled and analyzed, revealing an ORR of 43.5% (95% CI, 23.2%-63.8%) and DCR of 82.6% (95% CI, 61.2%-95.0%). The median PFS and OS were 6.3 and 9.5 months, respectively. Dose-limiting toxicity was only observed in 2 patients (2/23, 8.7%), and 30 mg pemetrexed was considered as the recommended dose for IC. Pharmacokinetic analysis showed that using Ommaya reservoirs, higher pemetrexed concentrations and prolonged half-lives were achieved in the CSF compared with lumbar puncture (LP).
CONCLUSIONS
Intrathecal pemetrexed at a dose of 30 mg via Ommaya reservoirs on Days 1 and 8 every 21 days achieved promising disease control and satisfactory survival with moderate toxicities in resistant LUAD-LM, providing a feasible and effective option, especially for the patients who cannot tolerate LP.
Topics: Humans; Pemetrexed; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Prospective Studies; Adenocarcinoma of Lung; Meningeal Carcinomatosis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36588048
DOI: 10.1016/j.cllc.2022.11.011 -
Brain Tumor Research and Treatment Oct 2022Intra-cerebrospinal fluid (CSF) chemotherapy for leptomeningeal metastasis (LM) can be delivered intraventricularly via an Ommaya reservoir. However, hydrocephalus...
BACKGROUND
Intra-cerebrospinal fluid (CSF) chemotherapy for leptomeningeal metastasis (LM) can be delivered intraventricularly via an Ommaya reservoir. However, hydrocephalus associated with LM can interfere with chemotherapeutic drug distribution, and ventriculoperitoneal shunts can prevent drug distribution to the extra-ventricular CSF space. This study examined the feasibility of combining a lumboperitoneal (LP) shunt with an Ommaya reservoir to both control intracranial pressure and allow for intraventricular chemotherapy.
METHODS
We identified 16 patients with LM who received both an Ommaya reservoir and an LP shunt, either concurrently or sequentially, and subsequently received intraventricular chemotherapy. The feasibility of this combination for intraventricular chemotherapy was evaluated by assessing 1) the distribution of intraventricularly injected drugs in CSF samples collected 0, 6, and 12 h post-injection and 2) adverse events associated with the procedure and drug administration.
RESULTS
Patients received a median of seven rounds (range 1-37) of intraventricular chemotherapy during a median follow-up period of 5.2 months after LP shunt insertion. Pharmacokinetic data were obtained from six patients. Baseline methotrexate (MTX) levels from Ommaya reservoirs varied from 339.9 µM to 1,523.5 µM. CSF sampled from LP shunt reservoirs revealed an elimination half-life (t) of 2.63 h, and the mean ratio of MTX concentration at 12 h to that at baseline was 0.05±0.05, ensuring drug distribution from the ventricle to the spinal canal. Nine patients (56%) underwent revision surgery due to catheter migration, malfunction, or infection. Among these patients, CSF infections attributable to intraventricular chemotherapy (n=3) occurred, but no infections occurred in later cases after we began to employ a complete aseptic technique.
CONCLUSION
LP shunt combined with Ommaya reservoir insertion is a feasible option for achieving both intracranial pressure control and the continuation of intraventricular chemotherapy in patients with LM.
PubMed: 36347638
DOI: 10.14791/btrt.2022.0022 -
Frontiers in Neurology 2022Glioma is the most common primary brain tumor in adults with poor prognosis. The glioma patients benefit from STUPP strategy, including maximum and safe resection and...
BACKGROUND
Glioma is the most common primary brain tumor in adults with poor prognosis. The glioma patients benefit from STUPP strategy, including maximum and safe resection and adjuvant radiotherapy and chemotherapy. Arsenic trioxide could inhibit various tumors. However, it is a challenge to evaluate the efficiency and safety of srsenic trioxide in glioma patients.
OBJECTIVE
The arsenic trioxide has the potent therapeutic effect on glioma. However, the safety and efficacy of local interstitial chemotherapy with arsenic trioxide in newly diagnosed glioma patients is unclear.
METHODS
All patients received partial or complete tumor resection and intraoperative implantation of Ommaya reservoirs followed by standard radiotherapy. Arsenic trioxide with the starting dose 0.3 mg was administered an Ommaya reservoir catheter inserted into the tumor cavity for 5 consecutive days every 3 months for a total of eight cycles unless tumor progression or excessive toxicity was observed.
RESULTS
No hematological or grade 4 non-hematological toxicity was observed in any patient during arsenic trioxide treatment. The maximum tolerated dose of 1.5 mg of arsenic trioxide was safe and well tolerated. The median overall survival for WHO grade 3 glioma was 33.6 months, and for glioblastoma was 13.9 months. The median progression-free survival for WHO grade 2 glioma was 40.3 months, for grade 3 glioma was 21.5 months, and for glioblastoma was 9.5 months.
CONCLUSION
These results suggest that arsenic trioxide is safe and well tolerated with local delivery into the tumor cavity of the brain, and the dose recommended for a phase II trial is 1.5 mg.
PubMed: 36212657
DOI: 10.3389/fneur.2022.1001829 -
Journal of Neurosurgery. Case Lessons Mar 2022Treatment of pilocytic astrocytomas (PAs) in children can be challenging when they arise in deep midline structures because complete surgical resection may result in...
BACKGROUND
Treatment of pilocytic astrocytomas (PAs) in children can be challenging when they arise in deep midline structures because complete surgical resection may result in significant neurological injury. Laser interstitial thermal therapy (LITT) has provided an alternative treatment modality for lesions that may not be amenable to resection. However, many patients with PAs may be symptomatic from a compressive cyst associated with the PA, and LITT does not obviate the need for cystic decompression in these patients.
OBSERVATIONS
A 12-year-old male presented with left-sided weakness. Magnetic resonance imaging (MRI) revealed an enhancing mass with a large cyst involving the right thalamus and basal ganglia. The patient underwent a reservoir placement for cyst drainage and biopsy of the mass, revealing a pilocytic astrocytoma. He then underwent LITT followed by adjuvant chemotherapy. Sixteen months after LITT, follow-up MRI of the brain revealed no tumor growth.
LESSONS
This is the first case to describe reservoir placement to treat the cystic portion of a pilocytic astrocytoma followed by LITT and targeted chemotherapy. Reservoir placement reduced the cyst's mass effect and resolved the patient's symptoms, allowing for treatment options beyond resection.
PubMed: 36209402
DOI: 10.3171/CASE21363 -
Cureus Aug 2022A 50-year-old male with a history of a dull headache and neck pain for a few weeks presented to the ER with complaints of progressive weakness and difficulty walking....
A 50-year-old male with a history of a dull headache and neck pain for a few weeks presented to the ER with complaints of progressive weakness and difficulty walking. Physical examination revealed a lethargic, confused patient with abnormal tremors at rest. Initial lab work was significant for elevated hemoglobin, hematocrit, and hyponatremia. Additionally, CT imaging was significant for prominent ventricles. Several serologies and polymerase chain reaction (PCR) tests were ordered to determine the etiology of the patient's meningitis. On day 10 of admission, serology results returned positive for antibodies. The patient was started on an IV fluconazole treatment and underwent a ventriculoperitoneal shunt and Ommaya reservoir placement procedure. Cases of coccidioidal meningitis are rarely noted in recent literature. We present this clinical case of coccidioidomycosis dissemination into the central nervous system (CNS) to highlight the rare localization of the fungal infection in a baseline immunocompetent patient.
PubMed: 36120197
DOI: 10.7759/cureus.28643 -
World Journal of Clinical Cases Jun 2022Glioblastoma (GBM) is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis. Leptomeningeal dissemination (LMD)...
BACKGROUND
Glioblastoma (GBM) is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis. Leptomeningeal dissemination (LMD) is a serious complication of GBM that often results in dire outcomes. There is currently no effective treatment.
AIM
To estimate the clinical outcomes of combination therapy in GBM patients with LMD.
METHODS
A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution. All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate (MTX) and systemic chemotherapy. Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.
RESULTS
Twenty-six patients were enrolled in this study. The median time from GBM diagnosis to LMD development was 9.3 mo (range: 2-59 mo). The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo (range: 2-59 mo). In the Cox univariate analysis, gross resection of tumor ( = 0.022), Karnofsky performance status (KPS) > 60 ( = 0.002), and Ommaya reservoir implant ( < 0.001) were correlated with survival. Multivariate analysis showed that KPS > 60 ( = 0.037) and Ommaya reservoir implant ( = 0.014) were positive factors correlated with survival. Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy. According to Common Terminology Criteria of Adverse Events 4.03, most of the patients presented with toxicity less than grade 3.
CONCLUSION
Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD, with mild treatment-related side effects.
PubMed: 35979103
DOI: 10.12998/wjcc.v10.i17.5595 -
Brain Sciences Jun 2022Leptomeningeal carcinomatosis (LMC) is a rare but devastating complication of advanced cancer. Breast cancer, lung cancer, and melanoma are the three most common causes...
Leptomeningeal carcinomatosis (LMC) is a rare but devastating complication of advanced cancer. Breast cancer, lung cancer, and melanoma are the three most common causes of LMC, whereas it is rare in ovarian cancer. Here, we report the case of a 59-year-old woman who was diagnosed with LMC from ovarian cancer and was successfully treated with intrathecal chemotherapy via Ommaya reservoir and radiation therapy. The patient had an amelioration of symptoms and prolonged survival. Though LMC from ovarian cancer is thought to be rare, it is not going to remain a rare entity because the incidence of LMC in general is thought to be increasing, which is also the case with ovarian cancer. According to 31 cases whose treatment course is reported in literature, despite the absence of an established treatment for LMC, intrathecal (IT) chemotherapy whose survival benefit has been suggested in past studies might also prolong survival in patients with LMC from ovarian cancer. IT chemotherapy via Ommaya reservoir may be preferred to the lumbar puncture route. The presentation of non-specific symptoms of LMC in patients may hinder its diagnosis; however, early diagnosis and treatment induction is the key for patients' prolonged survival and restored useful life.
PubMed: 35741633
DOI: 10.3390/brainsci12060748 -
Frontiers in Surgery 2022Therapy for large or deep cystic brain metastases is a troublesome procedure in clinical departments. Stereotactic cyst aspiration, combined with Gamma Knife...
BACKGROUND
Therapy for large or deep cystic brain metastases is a troublesome procedure in clinical departments. Stereotactic cyst aspiration, combined with Gamma Knife radiosurgery, can be an effective treatment for cystic brain metastases. However, there is still a possibility that a reaccumulation of cystic fluid may lead to poor efficacy or even reoperation.
CASE PRESENTATION
We present a case of a 67-year-old man who was diagnosed with lung cancer brain metastasis. The intracranial lesion seen on imaging appeared to be cystic and located deep inside the brain with associated limb dysfunction. The patient did not respond well to chemotherapy and underwent cyst aspiration with Ommaya reservoir implantation under neuronavigation. Repeated cystic fluid reaccumulation and exacerbation of symptoms occurred during treatment. We performed repeated aspiration via the Ommaya reservoir to control the symptoms and combined it with radiotherapy. During the follow-up period of 14 months, the intracranial tumor was effectively and satisfactorily controlled.
CONCLUSIONS
We highlight that Ommaya reservoir implantation during stereotactic cyst aspiration is necessary to prevent fluid reaccumulation, thereby avoiding the need for a second surgical procedure.
PubMed: 35651693
DOI: 10.3389/fsurg.2022.901674 -
International Medical Case Reports... 2022, a common component of the skin and mucosal microbiota of both immunocompetent and immunocompromised individuals, has become an emerging pathogen, colonizing indwelling...
, a common component of the skin and mucosal microbiota of both immunocompetent and immunocompromised individuals, has become an emerging pathogen, colonizing indwelling medical devices and causing infections at multiple sites. A 3-year-old boy with an Ommaya reservoir in the right ventricle and a medical history of grade 3 intraventricular hemorrhage, Hirschsprung disease, catheter-related methicillin-resistant bacteremia, and congenital central hypoventilation syndrome was hospitalized for Ommaya reservoir infection with . He was treated with ampicillin, to which the initial isolate was susceptible. may have acquired multiple-drug resistance during the antibiotic treatment due to biofilm production. The Ommaya reservoir was replaced by external ventricular drainage. Cultures of the removed Ommaya reservoir, and cerebrospinal fluid samples grew , which was susceptible to meropenem and vancomycin and resistant to other antibiotics. The antibiotic was switched to vancomycin to treat this new multidrug-resistant strain. After 8 days of vancomycin treatment, the cerebrospinal fluid culture obtained by a lumbar puncture was negative for . In cases of device-associated infections caused by biofilm-producing bacteria, it is desirable to remove the device as soon as possible.
PubMed: 35535175
DOI: 10.2147/IMCRJ.S361505 -
Surgical Neurology International 2022Glioependymal cysts (GECs) are rare, benign congenital intracranial cysts that account for 1% of all intracranial cysts. Surgical interventions are required for patients...
BACKGROUND
Glioependymal cysts (GECs) are rare, benign congenital intracranial cysts that account for 1% of all intracranial cysts. Surgical interventions are required for patients with symptomatic GECs. However, the optimal treatment remains controversial, especially in infants. Here, we report a male infant case of GECs that successfully underwent minimally invasive combined neuroendoscopic cyst wall fenestration and cyst-peritoneal (CP) shunt.
CASE DESCRIPTION
The boy was delivered transvaginally at 38 weeks and 6 days of gestation with no neurological deficits. Magnetic resonance imaging (MRI) at birth revealed multiple cysts with smooth and rounded borders and a non-enhancing wall in the right parieto-occipital region. The size of the cyst had increased rapidly compared to that of the prenatal MRI, which was performed at 37 weeks and 2 days. On the day of birth, Ommaya cerebrospinal fluid (CSF) reservoir was placed into the largest outer cyst. The patient underwent intermittent CSF drainage; however, he experienced occasional vomiting. At 2 months, he underwent combined neuroendoscopic cyst wall fenestration and CP shunt through a small hole. The patient's postoperative course was uneventful and there was no recurrence of the cyst. The pathological diagnosis was GEC.
CONCLUSION
Combined neuroendoscopic cyst wall fenestration and CP shunt are a minimally invasive and effective treatment for infants with GECs.
PubMed: 35399892
DOI: 10.25259/SNI_133_2022