Leptomeningealmetastasis (LM), also known as leptomeningeal carcinomatosis (LMC), is the dissemination of both solid tumors and hematological malignancies to the CSF and leptomeninges. Approximately 5%–10% of all malignancies metastasize to the leptomeninges,1and 1%–5% of these patients develop leptomeningeal metastasis–associated hydrocephalus (LM-H). The evolving efficacy of therapies for primary malignancies and advancements in neuroimaging have resulted in a surge in LM prevalence encountered in clinical practice.2–4Patients with symptomatic hydrocephalus secondary to LM can be palliated with CSF diversion, including ventriculoperitoneal, ventriculoatrial, and lumboperitoneal shunting. Although these surgical procedures are often regarded as the most direct form of immediate management, there is controversy regarding their effectiveness due to limited understanding of their impact on quality of life (QOL) and survival outcomes. The overall oncological and medical care of this population remains poorly defined and only studied in limited small case series.5
The incidence of LM in patients with extracranial tumors is highly dependent on the primary cancer type. It is most common in patients with lung (10%–26% of all LMC cases), breast (12%–34%), melanoma (17%–25%), and gastrointestinal (GI) tract (e.g., esophageal carcinoma, gastric adenocarcinoma, cholangiocarcinoma) (4%–14%) malignancies.6The most common hematological malignancies that give rise to LMC are acute lymphoblastic leukemia and non-Hodgkin lymphoma.7
Although currently available studies have generated conflicting findings, an estimated 50%–70% of patients diagnosed with leptomeningeal disease have abnormal CSF flow patterns on radionuclide ventriculography,8,9often resulting in communicating hydrocephalus and raised intracranial pressure.1These patients may present with debilitating neurological symptoms, namely altered level of consciousness, headache, nausea, vomiting, and focal neurological deficits including cranial nerve palsies. Subjecting fragile patients to a palliative interventions with risks of infection, bleeding, stroke, CSF leak, device malfunction, and peritoneal seeding10–13requires striking a delicate balance between the risks and potential benefits of symptomatic relief and improvement in survival.5
This systematic review and meta-analysis aimed to provide a current informative landscape regarding the survival benefit of CSF diversion and QOL outcomes in patients with LM-H.
开云体育世界杯赔率
This systematic review was conducted in accordance with the PRISMA-P and the Cochrane Handbook for Systematic Reviews of Interventions.14,15This review was registered with the PROSPERO international prospective register of systematic reviews (registration no. CRD42022371223).
Search Strategy and Information Sources
PubMed/Medline (Classic and Ovid), Embase, Web of Science, and Scopus were searched for articles published between 1980 and 2022. Medical Subject Headings were applied to maximize the search results and facilitate uniformity to the indexing of biomedical literature.
从2022年10月14日,张成的审核期,to January 11, 2022. The article search parameterizations for each database were detailed. After review and scrutinization of the original results identified with the search strategy, additional studies were included through review of the citations.
Exclusion Criteria
We excluded studies that included patients under the age of 18 years, as pediatric treatment and palliative management can differ significantly. Additionally, we excluded studies with primary CNS malignancy patients due to the poor prognosis independent of LM in this population. Furthermore, the following study designs were also excluded: case reports, case series with ≤ 3 patients, literature reviews (systematic reviews), letters to the editor, commentaries, and non–peer reviewed publications or conference abstracts.
Study Records Data Management
The literature search results were imported into Rayyan AI manager16for article screening, selection, and deduplication.
Selection Process
The titles and abstracts of the retrieved articles were independently screened by two authors (J.D. and M.R.P.) on the basis of the aforementioned eligibility and inclusion criteria. Full-text versions of all relevant publications were retrieved and reviewed. Discrepancies of opinion between reviewers were resolved with the opinion of another reviewer (A.C.) and through discussion. The article selection process is summarized in the PRISMA flow diagram (Fig. 1)。
PRISMA flow diagram. *Records identified from each database. **The Rayyan automation tool was used. Data added to the PRISMA template (from Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.BMJ。2021; 372: n71)根据创意有限公司mmons Attribution (CC BY 4.0) License (https://creativecommons.org/licenses/by/4.0/)。
Data Items
Data extracted from the relevant articles were tabulated and recorded, including author, year of publication, study design, time of study, country, number of patients, median age, primary cancer, presentation, Karnofsky Performance Status (KPS), CSF diversion method employed, patients who received alternative treatment, median OS, symptoms, and complications.
Outcomes and Prioritization
The primary outcome was the clinical impact of surgical CSF diversion on OS and QOL in LM-H patients. An assessment of QOL was made using the following surrogate measures: symptomatic relief, KPS, and complications.
Risk of Bias
The risk of bias in the individual studies included was evaluated using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool.17,18Two reviewers (J.D. and M.R.P.) independently assessed the studies and resolved any differences in judgment through discussion or referring this query to 2 other independent reviewers (A.C. and A.M.V.).
Statistical Analysis
Continuous variables were reported as mean ± SD. To meta-analyze median OS, the effect-estimate HR was used in line with Cochrane guidelines.19When studies were considered too methodically heterogenous to enable pooling, the results were summarized quantitatively in tables according to related categories. Categorical data were reported as the percentage or in absolute numbers.
Several data conversions were required to uniformly analyze the KPS scores from the included studies. Preoperative and postoperative KPS were assumed to have normal distributions. For studies that reported median and range, conversion to mean ± SD was performed using the following formulae:20,21mean = (a + 2m + b)/4, and SD = (b − a)/(2ϕ−1[(n − 0.75)/(n + 0.25)]), where a = minimum, b = maximum, m = median, n = sample size, and ϕ = probability density function.
Meta-Analysis
Statistical heterogeneity was evaluated using the I2statistic, and the results were interpreted on the basis of the Cochrane guidelines (0%–40% indicates no heterogeneity; 30%–60% moderate heterogeneity; 50%–90% substantial heterogeneity; and 75%–100% considerable heterogeneity).19Statistical significance was considered at p < 0.05, and all analyses were performed using IBM SPSS Statistics version 29.0 and Review Manager version 5.4 (RevMan). Due to variability in patient demographic characteristics and effect-estimate computations, all meta-analyses employed a random effects model.
Results
The database search retrieved 221 articles. Deduplication, performed with Rayyan,16导致119文章,然后筛选by title and abstract. Two additional articles were included from the citation search. A total of 10 articles met all the inclusion criteria. The article selection process is summarized in the PRISMA flow diagram (Fig. 1)。
Characteristics of the Eligible Studies
The characteristics of the studies are summarized inTable 1。2,22–30All studies were retrospective: 9 were cohort studies, and 1 was a 4-patient case-series.
Descriptive characteristics of included studies
| Authors & Year | Time of Study | Country | No. of Patients (Male/Female) | Age (yrs)* | Primary Cancer | Presentation | KPS† | CSF Diversion | Alternative Treatment‡ | Additional Treatment | OS From LM Diagnosis (mos)† | OS From Surgery (mos)† | Symptomatic Relief (%) | Complication Rate (%) | Reintervention Rate (%) | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Before Diversion | After Diversion | |||||||||||||||
| Su et al., 202222 | 2017–2020 | Taiwan | 50 (18/32) | 59 (41.9–74.8) | Lung (50) | Headache (26), nausea/vomiting (27), focal deficits (15), encephalopathy (14), gait disturbance (39) | Preop 60 (40–80); postop 70 (50–90) | VPS (33);有限合伙人(7) | 10 | SRS (12), WBRT (16), ctx (32), targeted therapy (73) | SRS (1), WBRT (6), ctx (12), targeted therapy (33) | CSF diversion 6.21 (0.8–36.2); no CSF diversion 1.95 (0.4–22.4) | No data | No data | Overall 17.5; infection 2.5; mechanical failure 10; functional failure 5 | Overall 42.9; after infection 100; after mechanical failure 50; after functional failure 0 |
| Yoshioka et al., 202123 | 2010–2019 | Japan | 14 (3/11) | 64.5 (36–76) | Lung (8), breast (6) | Headache (6), focal deficits (11), encephalopathy (5) | Preop 35 (20–50); postop 70 (40–80) | VPS (5); LPS (9) | 0 | No data | WBRT (4), targeted therapy (4), no further treatment (6) | 3.7 (1.8–17) | No data | 100 | Overall 7.1; mechanical failure 7.1 | Overall 100; after mechanical failure 100 |
| Murakami et al., 201824 | 2007–2016 | Japan | 11 (2/9) | 58 (52–68) | Lung (4), breast (4), other organs (3) | Headache (10), nausea/vomiting (6), encephalopathy (6), gait disturbance (4) | Preop 40 (30–40); postop 60 (40–60) | VPS (8); LPS (3) | 0 | WBRT (9), ctx (9) | WBRT (3), ctx (6), no further treatment (5) | Primary malignancy 27.4 (19.6–63.1); brain parenchymal metastasis 7.2 (5.1–14.); LM 3.9 (3.5–6.3) | 3.3 (2.9–5.7) | Headache 87.5; nausea/vomiting 66.6; encephalopathy 66.6; gait disturbance 25 | Overall 9.1; infection 9.1 | Overall 100; after infection 100 |
| Jung et al., 201425 | 2005–2012 | South Korea | 71 (38/33)§ | 60 (37–89) | Lung (45), breast (14), urinary tract (1), GI tract (9), other organs (2) | Headache (58), nausea/vomiting (58), focal deficits (7), spinal cord & roots deficits (6) | Preop RTOG-RPA class II 29, class III 42; postop no data | VPS (7) | 11 | WBRT (25), CSI (6), systemic ctx (18), intrathecal ctx (2), no further treatment (33) | No data | No hydrocephalus 2.3; hydrocephalus 1.9; untreated 1.7; surgically treated 5.7 | No data | No data | No data | No data |
| Gonda et al., 201226 | 2005–2010 | USA | 36 (16/20) | 59 (31–78) | Lung (13), melanoma (10), breast (9), renal (3), colon (1) | Headache (36), nausea/vomiting (18), focal deficits (5), encephalopathy (7) | Preop 69 (57–81); postop 84 (72–96) | VPS (36) | 0 | No data | VPS 5.5 | No data | Headache 75; nausea/vomiting 88.9; focal deficits 20; encephalopathy 100 | Overall 19.4; infection 11.1; mechanical failure 5.6; functional failure 2.8 | Overall 100; after infection 100; after mechanical failure 100; after functional failure 0 | |
| Lee et al., 201127 | 2003–2010 | Korea | 50 (20/30) | 55 (25–77) | 肺癌(32)、乳腺癌(8)、肾细胞癌(2),colorectal (3), other solid organs (5), hematological (1) | Headache (35), encephalopathy (19), gait disturbance (7), urinary incontinence (5) | Preop 37.8; postop 46 | VPS (50) | 0 | Resection (5), SRS (24), WBRT (23), systemic ctx (43), intrathecal ctx (23) | Resection (1), SRS (4), WBRT (6), ctx (11) | Primary malignancy 21.0 (1–113); CNS involvement 7.5 (1–55); LMS 3.5 (0–28) | 3.0 (2 days to 54 mos) | Headache 85.7; encephalopathy 73.7; gait disturbance 71.4; urinary incontinence 40 | Overall 10; functional failure 8; intraparenchymal bleeding 2 | Overall 80; after infection 0; after mechanical failure 0; after functional failure 100 |
| Mitsuya et al., 201928 | 2008–2017 | Japan | 31 (11/20) | 59 (36–76) | Lung (31) | All patients presented w/ symptomatic hydrocephalus (no data on specific symptoms) | Preop ECOG grade 0/2/17/7; postop ECOG 5/14/6/1¶ | VPS (13); LPS (18) | 0 | WBRT (9), ctx (1), targeted therapy (23), no further treatment (2) | WBRT (9), CSI (4), ctx (1), targeted therapy (21), no further treatment (4) | 4.5 | 3.5 | No data | Overall 16.1; infection 6.5; mechanical failure 3.2; functional failure 9.7 | Overall 20; after infection 0; after mechanical failure 100; after functional failure 0 |
| Bander et al., 202129 | 2010–2019 | USA | 190 (61/129) | 56.7 (44.5–68.9) | Lung (80), breast (65), melanoma (15), urinary tract (3), GI tract (5), other organs (22) | Headache (59), nausea/vomiting (25), focal deficits (22), encephalopathy (32), gait disturbance (31), urinary incontinence (3) | Preop ≥60 in 35%, <60 in 12%; not prospectively collected in 53%; postop No data | VPS (188); ventriculopleural (2) | 0 | 切除(38),SRS (43), WBRT (44), systemic ctx (148), intrathecal ctx (4), targeted therapy (113) | WBRT (91), ctx (87), targeted therapy (80) | 4.14 | 2.43 | 83% overall symptomatic improvement | Overall 21.1; infection 4.7; mechanical failure 4.7; functional failure 13.2 | Overall 37.5; after infection 33.3; after mechanical failure 100; after functional failure 12 |
| Omuro et al., 200530 | 1995–2003 | USA | 37 (7/30) | 53 (31–80) | Breast (23), lung (6), melanoma (3), other cancers (5) | Headache (24), nausea/vomiting (18), focal deficits (16), encephalopathy (19), gait disturbance (20) | Preop 30 (20–40); postop no data | VPS (37) | 0 | WBRT (14) | Systemic ctx (19), intrathecal ctx(3) | 4 (3 days to >3.6 yrs) | 2 mos (2 days to >3.6 yrs) | 73% overall symptomatic improvement | Overall 10.8; mechanical failure 8.1; functional failure 2.7 | Overall 100; after mechanical failure 100; after functional failure 100 |
| Yamashiro et al., 20172 | No data | Japan | 4 (1/3) | 61.25 (53–68) | Lung (4) | Headache, nausea, or vomiting | No data | LPS (4) | 0 | No data | No data | Survival time from surgery (mos): 10, 30, 5, 3 | 75% overall symptomatic improvement | No postop complications | No reinterventions | |
CSI = craniospinal irradiation; ctx = chemotherapy; ECOG = Eastern Cooperative Oncology Group; LMS = leptomeningeal seeding; LPS = lumboperitoneal shunting; RTOG-RPA = Radiation Therapy Oncology Group–recursive partitioning analysis; VPS = ventriculoperitoneal shunting.
Data are shown as number of patients unless indicated otherwise.
Median (range) is shown.
Median (range) is shown unless indicated otherwise.
CSF diversion was not administered.
18 patients had hydrocephalus.
Values are shown for ECOG grades 1/2/3/4.
Cumulative Results
A total of 494 patients with LMC from systemic cancers were included across the studies (Table 1)。Of these, 35.8% were male (n = 177) and 64.2% (n = 317) were female. The majority were lung cancer patients (55.3%, n = 273), followed by those with breast cancer (26.1%, n = 129), melanoma (5.7%, n = 28), GI tract malignancies (3.8%, n = 19), and urinary tract malignancies (i.e., renal cell and urothelial carcinoma) (1.8%, n = 9). Only 1 patient with a hematological malignancy was included in the study by Lee et al.27A total of 420 patients (85%) underwent CSF shunting for symptomatic hydrocephalus, with ventriculoperitoneal shunting being the most commonly performed procedure (89.8%, n = 377). A minority of patients were treated with lumboperitoneal shunting (9.8%, n = 41) and only 2 patients with ventriculopleural shunting (0.5%).
Eight of 10 papers published data on treatment undertaken prior to surgery and/or adjuvant treatment performed at the time of or after CSF diversion (Table 2)。Prior to shunting, a total of 43 patients underwent tumor resection, 79 stereotactic radiosurgery (SRS), 140 whole-brain radiotherapy (WBRT), 6 craniospinal irradiation, 251 systemic chemotherapy, 29 intrathecal chemotherapy, and 209 targeted molecular or immunotherapy. After CSF diversion, only 1 patient underwent further surgical management, 5 SRS, 119 WBRT, 4 craniospinal radiotherapy, 136 systemic chemotherapy, 3 intrathecal chemotherapy, and 138 targeted molecular or immunotherapy. Thirty-five patients were deemed unfit for any form of treatment prior to CSF diversion, and after shunting 15 patients received best supportive care.
Preoperative and postoperative management
| Authors & Year | No. of Patients | Preop | Postop | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Surgery | SRS | Radiotherapy | Chemotherapy | Targeted Therapy | No Further Treatment | Surgery | SRS | Radiotherapy | Chemotherapy | Targeted Therapy | No Further Treatment | ||||||
| WBRT | CSI | Sys | IT | WBRT | CSI | Sys | IT | ||||||||||
| Su et al., 202222 | 50 | 0 | 12 | 16 | 0 | 32 | 0 | 73 | 0 | 0 | 1 | 6 | 0 | 12 | 0 | 33 | 0 |
| Yoshioka et al., 202123 | 14 | No data | 0 | 0 | 4 | 0 | 0 | 0 | 4 | 6 | |||||||
| Murakami et al., 201824 | 11 | 0 | 0 | 9 | 0 | 9 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 6 | 0 | 0 | 5 |
| Jung et al., 201425 | 71 | 0 | 0 | 25 | 6 | 18 | 2 | 0 | 33 | No data | |||||||
| Gonda et al., 201226 | 36 | No data | |||||||||||||||
| Lee et al., 201127 | 50 | 5 | 24 | 23 | 0 | 43 | 23 | 0 | 0 | 1 | 4 | 6 | 0 | 11 | 0 | 0 | 0 |
| Mitsuya et al., 201928 | 31 | 0 | 0 | 9 | 0 | 1 | 0 | 23 | 2 | 0 | 0 | 9 | 4 | 1 | 0 | 21 | 4 |
| Bander et al., 202129 | 190 | 38 | 43 | 44 | 0 | 148 | 4 | 113 | 0 | 0 | 0 | 91 | 0 | 87 | 0 | 80 | 0 |
| Omuro et al., 200530 | 37 | 0 | 0 | 14 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 19 | 3 | 0 | 0 |
| Yamashiro et al., 20172 | 4 | No data | |||||||||||||||
| Total | 494 | 43 | 79 | 140 | 6 | 251 | 29 | 209 | 35 | 1 | 5 | 119 | 4 | 136 | 3 | 138 | 15 |
| Percentage | 100.0 | 8.7 | 16.0 | 28.3 | 1.2 | 50.8 | 5.9 | 42.3 | 7.1 | 0.2 | 1.0 | 24.1 | 0.8 | 27.5 | 0.6 | 27.9 | 3.0 |
Sys = systemic; IT = intrathecal.
Values are shown as number unless indicated otherwise.
操作系统分析
All studies measured OS after CSF diversion, but single-arm OS data cannot be meaningfully meta-analyzed (see开云体育世界杯赔率)。两个10研究执行风险成比例analysis (with Cox models) to determine the association of CSF diversion with prognosis and survival probability in 121 patients. These 2 studies were meta-analyzed using multivariate hazard ratios.22,25A proportional hazards assumption was made, and the random effects model was employed to create a forest plot (Fig. 2A)。
Upper:Forest plot of the hazard ratios for the OS of patients who underwent shunting and patients without shunting. Thevertical linerepresents the line of null effect. Thehorizontal linesrepresent the 95% CIs corresponding to each study and thered squaresindicate the hazard ratio. Theblack diamondat the bottom of the forest plot represents the overall HR difference and the associated 95% CI (0–40% indicates no heterogeneity; 30–60% moderate heterogeneity; 50–90% substantial heterogeneity; and 75–100% considerable heterogeneity).Lower:Forest plot of the mean difference in preoperative versus postoperative KPS measures. Thebold vertical linerepresents the null effect. Thehorizontal linesrepresents the 95% CIs corresponding to each study, and thegreen squaresare the estimated mean difference of the study result. Theblack diamondat the bottom of the forest plot represents the overall KPS difference and the associated 95% CI (0–40% indicates no heterogeneity; 30–60% moderate heterogeneity; 50–90% substantial heterogeneity; and 75–100% considerable heterogeneity). IV = inverse variance.
KPS Improvement
Four studies reported preoperative and postoperative KPS measures and evaluated a total of 111 patients preoperatively and 109 patients postoperatively. The random effects model revealed a significant difference between preoperative and postoperative KPS of 17.6 points (CI 10.44–24.68, p < 0.0001). However, substantially high heterogeneity levels were detected among the included studies (Q = 23.58, I2= 87%, p < 0.0001) (Fig. 2B)。The specific recorded times for postoperative KPS assessments were not reported in the included studies.
Effect of Novel Therapies
Three of the studies included patients who received molecular targeted adjuvant treatment alongside shunting. The survival times of this subset of patients appeared to be longer.22,25,28这种效应是represented through the correlation between the chronology of the included studies (2010 onwards) and OS improvement (Fig. 3)。
Effect of novel therapies on OS. The correlation between the chronology of the included studies (2010 onwards) and OS improvement is shown. Values are shown as median (range) in months unless reported otherwise.
Symptomatic Improvement
Six studies addressed specific symptoms before and after shunt surgery in 338 patients. The main symptoms were grouped into the following categories for analysis of symptomatic improvement: headache, nausea and/or vomiting, focal neurological deficits (including cranial nerve palsies, visual deficits, and hemiparesis), encephalopathy (confusion, altered mental state, cognitive disturbance), gait disturbance, and urinary incontinence. The distributions of the percentages of patients who experienced each symptom preoperatively and those who experienced improvement in each symptom postoperatively are displayed inFig. 4Aand4B, respectively.
Box plots showing the distributions of the percentages of patients with each symptom before CSF diversion (upper) and after CSF diversion (lower)。We categorized the main symptoms into the following groups for analysis: headache, nausea and/or vomiting, focal neurological deficits (including cranial nerve palsies, visual deficits, and hemiparesis), encephalopathy (confusion, altered mental state, cognitive disturbance), gait disturbance, and urinary incontinence. Patients with focal symptoms and urinary incontinence were less likely to improve. Median (middle line), interquartile range (box), minimum and maximum (whiskers), and extreme outliers (asterisk) are shown.
The main presenting symptoms were headache, nausea or vomiting, and gait disturbance before CSF diversion. Across all studies, a significant improvement in symptoms, with a rate of 67%–100%, was observed.
Complications
Nine of 10 studies reported on complications, with rates ranging from 0% to 21.1% (Table 1andFig. 5)。最常见的并发症是并联失败者e (13.6%, n = 57), primarily due to mechanical causes such as obstruction, fracture, disconnection, migration, or intestinal perforation in 36 patients (8.6%), and functional causes such as overdrainage, subdural hematoma, hygroma, slit ventricle syndrome, pseudocyst, ascites, and peritoneal metastasis in 21 patients (5%). The infection rate was 3.8% (n = 16). Thirty-six patients diagnosed with a complication (51.4%) required at least an additional surgical procedure, either shut removal, revision/repair, externalization, or subdural hematoma drainage. Across studies, a total of 8 patients (50%) underwent revision surgery for infection, 19 for mechanical failure (90.5%), and 8 for functional failure (22.2%). Only 2 patients (2.9%) received best supportive care after shunt obstruction.22Factors that influenced the decision to reoperate were not reported.
Bar chart showing complication rates (%). Mechanical failure refers to obstruction, fracture, disconnection, migration, or intestinal perforation, and functional failure refers to overdrainage, subdural hematoma, hygroma, slit ventricle syndrome, pseudocyst, ascites, and peritoneal metastasis.
Across all studies, 1 patient’s death was attributed to an intraparenchymal hematoma, most likely secondary to multiple ventricular punctures because of an inadequate initial trajectory.27Three reports of peritoneal metastasis were observed, although 2 of these happened prior to surgery22and 1 was attributed to systemic cancer progression.28
Risk of Bias
Critical bias was assessed across the studies using the ROBINS-I tool, and insufficient individual patient data for the outcomes of the included studies further exacerbated the uncertainty of our findings. Therefore, definitive recommendations for clinical practice cannot currently be made (Fig. 6)。
Risk of bias, as determined according to the Cochrane ROBINS-I tool. Risk of bias in each domain is classified as serious, moderate, low, or no information, as shown in the legend.
Discussion
To our knowledge, this is the first systematic review and meta-analysis to evaluate the impact of shunting on OS and QOL in LM-H patients.
操作系统的结果
Contrary to individual studies, the meta-analysis did not show an increase in OS. The two studies considered in the multivariate analysis22–25(Fig. 2A) revealed an increase in OS but found no significant statistical difference (p = 0.27), and the CI did not include 0, perhaps due to the following confounding factors: adjuvant treatment, histology of the primary tumor type, and baseline functional and nutritional status. Thus, we cannot conclude that CSF shunting improves survival on the basis of our study.
We acknowledge additional causes for variation across studies. Lung and breast cancer were the most prevalent primary cancer types5–7in our review, and 7 of our 10 studies originated from Asia. This correlation perhaps reflects the high incidence of breast and lung cancer worldwide, and the review by Zhang et al. further corroborates this by suggesting that Asian populations with non–small cell lung carcinoma have the highest prevalence of epidermal growth factor receptor (EGFR) mutation (38.8%).31Molecular targeted therapy for EGFR and tyrosine kinase inhibitor has revolutionized the treatment of LM and has consequently increased OS, as emphasized by Mitsuya et al.28and shown inFig. 3。As these therapeutic choices become more available at the time of LM-H diagnosis, we anticipate an increase in demand for shunting in the future.
QOL: KPS and Symptom-Related Outcomes
There is a lack of validated tools for postsurgical QOL assessment of these patients. A limited number of studies have reported QOL measurements and have instead specified "symptomatic relief" and the KPS as surrogate measures. The variation in prognosis of LM is attributed to performance status, systemic disease control, and primary tumor histology.4,32Greater information is required to develop a more personalized approach for managing LM-H that incorporates the patient’s best interests and clinical status.5
An average improvement of 17.6 points in KPS was observed across all studies. Because no minimum clinically relevant difference for KPS has been defined in the literature, it is difficult to determine whether this statistically important difference is clinically significant.
More than 50% of patients across all studies experienced symptomatic relief, particularly for headache and nausea. Most studies, however, failed to demonstrate improvement in focal neurological impairments, particularly cranial nerve palsies, indicating the limitations of shunting and aiding patient selection.
Effect of Intrathecal Chemotherapy
Only 3 studies included patients who underwent intrathecal chemotherapy,25,27,29most frequently prior to CSF shunting and via an Ommaya reservoir. Selection of patients with better performance status and controlled primary disease has apparently led to longer survival times, however no study has specifically addressed the OS and QOL outcomes of patients who receive intrathecal chemotherapy. It is important to note that most surgeons decided against post-CSF shunting intrathecal chemotherapy. Factors influencing surgeons to decide against insertion of an Ommaya reservoir for delivery of the pharmacological agents include a higher rate of infection26and the possibility of further revision surgical procedures due to increased intracranial pressure by the infusion of agent24in patients already at risk due to CSF flow abnormalities. Additionally, there is limited evidence regarding the optimal chemotherapy regimen. Further prospective cohort studies will be needed to address this.
Complications
Our review found an overall shunt failure rate ranging from 0% to 13.2%, which is marginally comparable to the rate of 11%–25% reported for other populations by Paff et al.33It is important to note that the infection rate across all studies (0%–11%) was significantly lower than the rates reported in the literature.34Nevertheless, reintervention rates were high, with considerable heterogeneity, particularly for mechanical failure and infection. Authors did not consistently report on factors that influenced decision-making for additional interventions, reflecting the lack of clear criteria for revision surgical procedures in this population. The risk profile for CSF shunting is thus a crucial consideration in the treatment for LM patients.
Functional failure revision surgery rates were lower, probably due to the wider use of programmable valves. Given the frequency of readjustments required in certain cohorts, programmable valves appear to be highly advantageous due to their valve pressure adjustments that can effectively alleviate the symptoms associated with over-shunting.24,27,30Our results do not propose a superior shunting type, as OS appears unaffected by this variable.2,22–24,28However, Murakami et al.24suggested that lumboperitoneal shunting is exclusively preferable for communicating hydrocephalus, as it can be performed irrespective of ventricular size and can potentially reduce intracranial vascular damage.
Strengths and Limitations
The evidence summarized in this review was based on retrospective studies. Only 2 of the 10 studies provided a full comparison between the effect of surgical intervention and none. Thus, a conclusive interpretation of the results cannot be made due to insufficient data, confounding factors, and critical risk of bias in most studies.
We aimed to reduce bias in our review process by requiring at least two reviewers to complete screening, risk of bias assessments, and data extraction separately. Our comprehensive review exhausted several databases for rigorous analysis.
Future Directions
Considering the futility of more invasive focal treatment in the context of disseminated cancer, our data indicate that CSF diversion is a viable palliative surgery for LMC patients. This necessitates early involvement of the oncology and palliative care teams in diagnosis, shared decision-making, and management. The significance of individualizing care goals and utilizing collaborative decision-making is important to note. Surgeons must consider the risk-benefit ratio of CSF diversion, patient autonomy, and decision-making capacity. Considering that severe hydrocephalus frequently manifests with encephalopathy, an advanced directive (if available) or a surrogate decision-maker should be consulted when patients are unable to provide consent. Furthermore, a comprehensive alternative management plan for symptomatic management and comfort care must be in place for patients who decline shunt operation.
这是初步审查的证据和英蒂rect, and it emphasizes a significant need for greater research into this field. Case-controlled, prospective cohort studies and, if possible, randomized controlled trials are required to fully investigate the clinical impact of CSF diversion for LM-H patients. Our review has provided clinical equipoise for a nested-precision randomized controlled trial35to be undertaken or registry research to identify specific patient population subsets that may benefit from this palliative intervention.
Furthermore, no patient-centered outcome measurement exists to justify this palliative procedure. Future studies should aim to investigate the implementation of a standardized decision-making tool or a minimum clinically important difference for QOL outcomes. Fundamentally, a standardized scale for these measurements would aid in providing clinicians with an algorithm to define patients who may or may not benefit from shunting and hence collectively strive for meaningful palliation.
Conclusions
Our systematic review draws attention to this area after an initial scoping search revealed a paucity of studies on the subject. Based on the current literature, shunting does not improve OS but does relieve symptoms, therefore suggesting that individuals who exhibit certain symptoms should be considered for CSF diversion (Fig. 4A and B)。然而,从我们的研究结果决定性的影响cannot be elucidated owing to the risk of bias and nonstatistical significance found in our analyses. We hope this review encourages academics and clinicians to consider the generation of a standardized decision-making tool, a critical analysis of individual patient risk-benefit ratio, and the use of QOL scales for LM-H patients. Hence, further comprehensive trials/registries are needed to evaluate the efficacy of CSF diversion for these patients.
Disclosures
The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Author Contributions
概念和设计:沙里河,达利瓦,Ruiz-Perez, Hill, Thorne. Acquisition of data: Dhaliwal, Ruiz-Perez. Analysis and interpretation of data: Chari, Dhaliwal, Ruiz-Perez, Vasilica, Hill. Drafting the article: Chari, Dhaliwal, Ruiz-Perez, Vasilica, Thorne. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Chari. Statistical analysis: Chari, Dhaliwal, Ruiz-Perez, Vasilica. Administrative/technical/material support: Dhaliwal, Ruiz-Perez, Thorne. Study supervision: Chari, Dhaliwal, Ruiz-Perez.
Supplemental Information
Previous Presentations
The work was presented as an oral abstract at the Association of Surgeons in Training 47th Annual Conference, Liverpool, UK, March 4–5, 2023. This work was presented as an oral abstract at the Society of British Neurological Surgeons Spring Meeting, Cork, Ireland, March 29–31, 2023.
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