Intraoperative Chemotherapy for Leptomeningeal Metastases After Ommaya Placement

2021 ◽  
Author(s):  
Oluwaseun Adeola Omofoye ◽  
John S Yu ◽  
Ray M Chu
Keyword(s):  
Wound Healing ◽  
Central Nervous System Lymphoma ◽  
Leptomeningeal Metastasis ◽  
Therapeutic Benefit ◽  
Leptomeningeal Metastases ◽  
Ommaya Reservoir ◽  
Intraventricular Chemotherapy ◽  
Common Diagnosis ◽  
Catheter Malfunction ◽  
Intraventricular Infusion

Abstract IntroductionThere is a wide variety in the timing of the first intraventricular chemotherapy dose after Ommaya reservoir placement. Given the rapid nature of leptomeningeal metastasis, it is important to avoid any delays in treatment in order to have the optimal therapeutic benefit. We present the first series of immediate intraoperative intraventricular infusion of chemotherapy after Ommaya placement.MethodsA single-institution, retrospective review of twenty patients who underwent surgical placement of an Ommaya reservoir from 2012 to 2020 and had intraoperative infusion of chemotherapy was conducted. Inclusion criteria consisted of patients 18 years and older with a diagnosis of leptomeningeal metastases, central nervous system lymphoma or leukemia. Outcomes such as leukoencephalopathy, wound healing, intracranial hemorrhage, catheter malfunction, Ommaya days, mortality, and other complications were reviewed.ResultsThe mean patient age was 55.1 years and the most common diagnosis was breast cancer (40%). All catheters were placed into the ventricular system, and there were no wound healing complications, infections or symptomatic leukoencephalopathy. Intraventricular chemotherapy was administered for a total of 201 cycles and a mean of 10 times per patient. The number of Ommaya days ranged from 7 to 2177, with a mean of 326.5 days, and 30-day mortality was 10%.Conclusions Ommaya reservoirs are effective intraventricular delivery mechanism for chemotherapy in patients with leptomeningeal metastases. Endoscopy-assisted placement of Ommaya catheters provides a real-time, visual confirmation of adequate placement. Immediate intraoperative intraventricular infusion of chemotherapy after Ommaya placement is safe, effective, and may increase efficiency in time to treatment for patients.

Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases

1997 ◽  
Vol 87 (5) ◽  
pp. 694-699 ◽  
Author(s):  
Marc C. Chamberlain ◽  
Patty A. Kormanik ◽  
David Barba
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Leptomeningeal Metastases ◽  
Ommaya Reservoir ◽  
Hodgkin's Lymphoma ◽  
Content Type ◽  
Non Hodgkin’S Lymphoma ◽  
Intraventricular Chemotherapy ◽  
Non Hodgkin's Lymphoma ◽  
Catheter Infections ◽  
Fine Print

✓ The authors studied complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases (LM). One hundred twenty consecutive patients with LM (71 females and 49 males) ranging in age from 10 to 72 years (median 42 years) were treated with involved-field radiotherapy and intraventricular chemotherapy using an Ommaya reservoir and intraventricular catheter system. The diagnosis of LM was determined by a combination of clinical presentation (114 patients); cerebrospinal fluid cytological studies (100); or neuroradiographic studies (42). Systemic tumor histological findings included breast (34 patients); non-Hodgkin's lymphoma (22); melanoma (16); primitive neuroectodermal tumors including medulloblastoma (10); glial neoplasms, leukemia, small cell lung, nonsmall cell lung, and colon (six each); prostate and kidney (three each); and gastric cancers (two). Sixteen patients, all with non-Hodgkin's lymphoma, also had acquired immune deficiency syndrome. Patients received one to four (median two) chemotherapeutic drugs and underwent a total of 1110 cycles of intraventricular chemotherapy (median 10). Intraventricular chemotherapy administration and diagnostic Ommaya reservoir punctures totaled 4400, with a median of 46 per patient. Complications included aseptic/chemical meningitis (52 patients); myelosuppression due to intraventricular chemotherapy (21); catheter-related infections (nine); unidirectional catheter obstruction (six); intraventricular catheter malpositioning (two); Ommaya reservoir exposure (two); leukoencephalopathy (two); and chemotherapy-related myelopathy (one). There were no treatment-related deaths; however, seven patients (6%) required additional surgery for either catheter repositioning (two) or reservoir removal (five). Seven patients with catheter-related infections were treated successfully with intraventricular and systemic antibiotic drugs, thereby preserving the Ommaya system. The authors conclude that Ommaya reservoirs are convenient and pharmacologically rational systems for administering intraventricular chemotherapy. Overall, serious complications requiring surgery are infrequent (6%) and most often secondary to catheter infections, Ommaya reservoir exposure, or initial catheter malpositioning. In the majority of instances, catheter infections may be managed medically, as may the most common complications of intraventricular chemotherapy including aseptic meningitis (43% of patients) and myelosuppression (18%).

scholarly journals Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis

Science ◽  
2020 ◽  
Vol 369 (6501) ◽  
pp. 276-282
Author(s):  
Yudan Chi ◽  
Jan Remsik ◽  
Vaidotas Kiseliovas ◽  
Camille Derderian ◽  
Ugur Sener ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Leptomeningeal Metastasis ◽  
Leptomeningeal Metastases ◽  
Lipocalin 2 ◽  
Cancer Cell Growth ◽  
Iron Binding Protein

The tumor microenvironment plays a critical regulatory role in cancer progression, especially in central nervous system metastases. Cancer cells within the cerebrospinal fluid (CSF)–filled leptomeninges face substantial microenvironmental challenges, including inflammation and sparse micronutrients. To investigate the mechanism by which cancer cells in these leptomeningeal metastases (LM) overcome these constraints, we subjected CSF from five patients with LM to single-cell RNA sequencing. We found that cancer cells, but not macrophages, within the CSF express the iron-binding protein lipocalin-2 (LCN2) and its receptor SCL22A17. These macrophages generate inflammatory cytokines that induce cancer cell LCN2 expression but do not generate LCN2 themselves. In mouse models of LM, cancer cell growth is supported by the LCN2/SLC22A17 system and is inhibited by iron chelation therapy. Thus, cancer cells appear to survive in the CSF by outcompeting macrophages for iron.

Treatment of Primary Central Nervous System Lymphoma with a Combination of Intraventricular Administration of Rituximab and Systemic Chemotherapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4695-4695
Author(s):  
Shujie Wang ◽  
Wei Zhang ◽  
Wei Lian ◽  
Yongji Wu ◽  
Nong Zou ◽  
...  
Keyword(s):  
Survival Time ◽  
Systemic Chemotherapy ◽  
Brain Mri ◽  
Combined Treatment ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Ommaya Reservoir ◽  
Intraventricular Injection ◽  
Cns Lymphoma ◽  
Intraventricular Administration

Abstract Primary CNS lymphoma (PCNSL) is an uncommon and progressive form of non-Hodgkin’s lymphoma. Since the majority of PCNSL cases are B-cell neoplasms expressing the CD20 surface antigen, treatment with Rituximab, the anti-CD20 antibody, might be a new therapeutic option. Since 2000, we have been performing a study on PCNSL patients with combined treatment of intraventricular immunochemotherapy and systemic chemotherapy. Ommaya reservoirs were placed in all these patients. The regimen of Intraventricular therapy is as follows: Methotrexate (MTX) 10mg plus Dexamethasone (Dex) 5mg followed by Cytosine arabinoside 25mg plus Dex 5mg via Ommaya reservoir in the first week, and Rituximab30mg plus Dex 2mg were given via Ommaya reservoir every other day for three times in the second week. Above treatments were finished 2 weeks a cycle until complete response (CR) was achieved and then the interval prolonged. Systemic chemotherapy includes regimen A and B. Regimen A: MTX 3~5g/m2 (D1), Vincristine 2mg (D1), Ifosfomide (IFO) 800mg/m2 (D2~4), and Dex. 10mg/m2 (D2~4). Serum MTX levels were monitored and Leucovin rescue began 24 hours after completion of MTX. Mesna rescue for IFO were also given conventionally; Regimen B: Carmustine 125 mg (D1), Teniposide 50mg (D1~3), Vindesine 4mg (D1), and Dex. 20mg (D1~4). Regimen A and B were given alternatively three weeks a cycle until CR was achieved, and then the interval prolonged. Brain MRI or PET was done every 2 or 3 months after treatment for evaluation of the response. Seven patients have been evaluated. The patients are 5 males and 2 females with the mean age of 51 years old (range: 32–82). One of the cases was a relapsed PCNSL who had achieved CR1 after whole-brain radiotherapy, systemic chemotherapy and autologous peripheral blood stem cell transplantation. He relapsed 33 months after CR1 and was enrolled in this study. After therapy he achieved CR2. But the second relapse occurred 18 months after CR2, and CR3 was achieved again after treatment with the same regimens, and total survival time has been 83 months. The other six cases were newly diagnosed PCNSL and all achieved CR after 2 to 3 months’ treatment. Among them only one patient experienced relapse after 26 months of remission, regimen A and intraventricular Rituximab were given but showed no remarkable response and died with survival time of 29 months. Other five patients are in continuing CR for 2, 12, 23, 25, and 40 months respectively. Two patients had nausea or vomiting after each intraventricular injection of Rituximab, but could relieve soon after. Ommaya reservoir infections occured in two patients, and cultures of the cerebrospinal fluid showed MRSCoN and MSSCoN, respectively. They were treated with vancomycin intravenously and via the reservoir. The infections were controlled quickly and their Ommaya reservoirs were kept. One 82 years old patient developed mild ulceration of the month and anus after treatment with regimen A. Hematological toxicities were mild, and could recover quickly with no need of transfusion or the use of G-CSF. In summary, the treatment of Intraventricular Rituximab via Ommaya reservoir combined with systemic chemotherapy for patients with PCNSL was safe and effective. This remedy is likely to improve the prognosis of such patients, but more cases need to be studied for the long-term result.

The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study

2004 ◽  
Vol 40 (18) ◽  
pp. 2726-2733 ◽  
Author(s):  
W. Boogerd ◽  
M.J. van den Bent ◽  
P.J. Koehler ◽  
J.J. Heimans ◽  
J.J. van der Sande ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Leptomeningeal Metastasis ◽  
Randomised Study ◽  
Intraventricular Chemotherapy

Ommaya Reservoir Insertion Guided by Computed Tomography

Neurosurgery ◽  
1981 ◽  
Vol 9 (5) ◽  
pp. 559-561 ◽  
Author(s):  
Walter J. Levy ◽  
Joseph F. Hahn
Keyword(s):  
Computed Tomography ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Ommaya Reservoir ◽  
Ventricular Catheter ◽  
Ct Scanner ◽  
Catheter Malfunction ◽  
Acute Myelogenous ◽  
Entire Procedure

Abstract The placement of a ventricular catheter in patients with small ventricles carries the risks of catheter malfunction and bleeding. We report the use of computed tomography (CT) to place an Ommaya reservoir in two patients with acute myelogenous leukemia and one patient with lymphoma who had normal to small ventricles. The entire procedure was carried out in the scanner and demonstrates the feasibility of operations performed in the CT scanner.

Primary Central Nervous System Lymphoma: Results of a Pilot and Phase II Study of Systemic and Intraventricular Chemotherapy With Deferred Radiotherapy

2003 ◽  
Vol 21 (24) ◽  
pp. 4489-4495 ◽  
Author(s):  
Hendrik Pels ◽  
Ingo G.H. Schmidt-Wolf ◽  
Axel Glasmacher ◽  
Holger Schulz ◽  
Andreas Engert ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Response Duration ◽  
Cns Lymphoma ◽  
High Dose ◽  
Intraventricular Chemotherapy

Purpose: To evaluate response rate, response duration, overall survival (OS), and toxicity in primary CNS lymphoma (PCNSL) after systemic and intraventricular chemotherapy with deferred radiotherapy. Patients and Methods: From September 1995 to July 2001, 65 consecutive patients with PCNSL (median age, 62 years) were enrolled onto a pilot and phase II study evaluating chemotherapy without radiotherapy. A high-dose methotrexate (MTX; cycles 1, 2, 4, and 5) and cytarabine (ARA-C; cycles 3 and 6)–based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ARA-C. Results: Sixty-one of 65 patients were assessable for response. Of these, 37 patients (61%) achieved complete response, six (10%) achieved partial response, and 12 (19%) progressed under therapy. Six (9%) of 65 patients died because of treatment-related complications. Follow-up is 0 to 87 months (median, 26 months). The Kaplan-Meier estimates for median time to treatment failure (TTF) and median OS were 21 months and 50 months, respectively. For patients older than 60 years, median survival was 34 months, and the median TTF was 15 months. In patients younger than 61 years, median survival and median TTF have not been reached yet; the 5-year survival fraction is 75%. Systemic toxicity was mainly hematologic. Ommaya reservoir infection occurred in 12 patients (19%), and permanent cognitive dysfunction possibly as a result of treatment occurred in only two patients (3%). Conclusion: Primary chemotherapy based on high-dose MTX and ARA-C is highly efficient in PCNSL. Response rate and response duration in this series are comparable to the response rates and durations reported after combined radiotherapy and chemotherapy. Neurotoxicity was infrequent.

Image-guided Ommaya reservoir insertion for intraventricular chemotherapy: a retrospective series

2018 ◽  
Vol 160 (3) ◽  
pp. 539-544 ◽  
Author(s):  
Jonathan C. Lau ◽  
Suzanne E. Kosteniuk ◽  
David R. Macdonald ◽  
Joseph F. Megyesi
Keyword(s):  
Ommaya Reservoir ◽  
Image Guided ◽  
Intraventricular Chemotherapy

NIMG-01. INTEROBSERVER VARIABILITY OF THE REVISED IMAGING SCORECARD FOR LEPTOMENINGEAL METASTASIS: A JOINT EORTC BRAIN TUMOR GROUP AND RANO EFFORT

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi126-vi127
Author(s):  
Emilie Le Rhun ◽  
Patrick Devos ◽  
Sebastian Winklhofer ◽  
Hafida Lmalem ◽  
Dieta Brandsma ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Stable Disease ◽  
Leptomeningeal Metastasis ◽  
Leptomeningeal Metastases ◽  
University Hospital ◽  
Overall Response ◽  
Tumor Group ◽  
Medical Oncologists ◽  
The University

Abstract BACKGROUND Validation of the 2016 LANO MRI scorecard for leptomeningeal metastasis failed for multiple reasons. The objective of this joint EORTC Brain Tumor Group and RANO effort was to validate the feasibility of the revised MRI scorecard for assessing response in leptomeningeal metastasis. METHODS Coded paired cerebrospinal MRI of 20 patients with leptomeningeal metastases from solid cancers at baseline and follow-up after treatment and instructions for assessment were provided via the EORTC imaging platform. The kappa coefficient (K) was used to evaluate inter-observer pairwise agreement. Statistical analyses were performed using SAS V9.4 software (Cary, NC). The sponsor of the study was the University Hospital Zurich (2018-00192). RESULTS Thirty-five raters participated, including 9 neuroradiologists, 17 neurologists, 4 radiation oncologists, 3 neurosurgeons and 2 medical oncologists. Among leptomeningeal metastases-related items at baseline, the best median concordance was noted for hydrocephalus (K=0.63), and the worst median for spinal linear enhancing disease (K=0.46). The median concordance for overall response was moderate (K=0.44). Notably, the interobserver agreement for the presence of parenchymal brain metastases at baseline was minimal (K=0.29). Significant differences were observed when considering the specialty of the raters. Only 394 of 700 ratings (56%) were fully completed. Among 394 fully completed ratings, perfect concordance was noted in 293 ratings (74%) when comparing the overall response according to the guidelines provided in the scorecard and the overall response provided by the raters. The main discordances were noted for partial response according to the rater versus stable disease according to the guidelines (n=44), followed by progression according to the raters versus stable disease according to the guidelines (n=23). CONCLUSION Electronic case report forms with "blocking solutions" are probably required to enforce completeness and quality of scoring. These results confirm the necessity of central review and the need for training of MRI assessment in clinical trials.

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