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J Neurooncol (2009) 93:205–212 DOI 10.1007/s11060-008-9758-3

CLINICAL STUDY - PATIENT STUDY

CLINICAL STUDY - PATIENT STUDY

Prognostic factors and clinical outcomes in patients with leptomeningeal metastasis from solid tumors

Fusako Waki Æ Masashi Ando Æ Atsuo Takashima Æ Kan Yonemori Æ Hiroshi Nokihara Æ Mototaka Miyake Æ Ukihide Tateishi Æ Koji Tsuta Æ Yasuhiro Shimada Æ Yasuhiro Fujiwara Æ Tomohide Tamura

Received: 15 April 2008 / Accepted: 17 November 2008 / Published online: 29 November 2008 Springer Science+Business Media, LLC. 2008

Abstract Background Leptomeningeal metastasis (LM) occurs in 4–15% of patients with solid tumors. Although the clinical outcomes in cancer patients have been improving recently, no standard treatment for LM has been established as yet. The purpose of this study was to identify the prognostic factors in patients with solid tumors with cytologically proven LM. Methods We retrospectively analyzed a series of 85 consecutive patients with cytolog- ically proven LM who were treated between 1997 and 2005. Results The primary diseases were as follows; lung cancer (n = 36), breast cancer (n = 33), gastric cancer (n = 8), and others (n = 8). Forty-nine patients had brain metastasis at the time of diagnosis of the LM, and in 51 patients, MRI revealed meningeal dissemination in the

F. Waki (& ) M. Ando K. Yonemori Y. Fujiwara

Breast and Medical Oncology Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan e-mail: fohara@med.kagawa-u.ac.jp

F. Waki

Faculty of Medicine, Division of Hematology, Department of Internal Medicine, Kagawa University, Takamatsu, Japan

A. Takashima H. Nokihara T. Tamura

Thoracic Oncology Division, National Cancer Center Hospital, Tokyo, Japan

M. Miyake U. Tateishi Diagnostic Radiology Division, National Cancer Center Hospital, Tokyo, Japan

K. Tsuta

Clinical Laboratory Division, National Cancer Center Hospital,

Tokyo, Japan

Y. Shimada

Gastrointestinal Division, National Cancer Center Hospital, Tokyo, Japan

brain or spine. The performance status (PS) was 0–1 in 26 patients and 2–4 in 59 patients. Thirty-one patients, including 19 with breast cancer, four with lung cancer, five with gastric cancer and three with other cancers, were treated by intrathecal (IT) chemotherapy. The response rate to the IT was 52% (95% confidence interval (CI):

41.4–62.6%). The median survival was 51 days (range, 3–759 days). A univariate analysis identified breast cancer, good PS (0–1), time to development of the LM ([1 year), and treatment by IT chemotherapy as being associated with a good prognosis, and multivariate analysis identified poor PS (HR: 1.72 (95% CI, 1.04–2.86) P = 0.04) and MRI- proven LM (HR: 1.82 (95% CI, 1.11–2.98) P = 0.02) as being associated with a poor prognosis. Conclusion In patients with poor prognostic factors, such as poor PS or MRI-proven LM, palliative therapy might be the most suitable treatment strategy.

Keywords

Prognostic factor Intrathecal chemotherapy MRI

Cancer

Leptomeningeal metastasis

Introduction

Leptomeningeal metastasis (LM) is a severe complication that occurs in 4–15% of all patients with solid tumors. The most common primary cancers, excluding hematological malignancies, are breast cancer, lung cancer, and mela- noma [1]. Better systemic control of a cancer may delay the appearance of LM, however, once LM is established, the prognosis of the patients is poor and the median survival is around 8 weeks (range, 4–11 weeks) [2, 3]. LM is diagnosed based on the clinical features and the findings on cerebrospinal fluid (CSF) examination and

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neuroimaging studies, such as brain and spinal gadolinium- enhanced magnetic resonance imaging (Gd-MRI). Cyto- logic identification of malignant cells in the CSF is the gold standard for the diagnosis of LM. The specificity of the test is excellent and false-positive results are rare, nonetheless, less than adequate sensitivity, that is, a high frequency of false- negative results, remains a problem for clinicians [4, 5]. MRI plays an important role in supporting the diagnosis and demonstrating the involved site, even in cytology-negative cases [68]. The relationship between the MRI findings and prognosis has, however, not yet been reported. The indications of treatment for LM from a solid tumor are still controversial, as few prospective randomized trials of potential therapeutic strategies have been conducted. The results of previous studies are limited by the small sizes of the study samples and the focus on only one type of tumor [915]. Jayson reported that in breast cancer with LM, patients with a poor performance status (PS) should be treated symptomatically, while those with a good PS should receive more aggressive treatment [12]. On the other hand, Orland reported that intrathecal (IT) chemo- therapy failed to yield any objective response or relief of the clinical symptoms [15]. Some studies have reported the PS, age, protein and/or lactate dehydrogenase (LDH) level in the CSF, and the sites of the metastasis as prognostic factors [9, 1214]. At our center, we diagnose LM based on the signs and symptoms of the patients and the findings on CSF exam- ination and/or imaging studies of the brain or spine. There is a tendency towards administering IT chemotherapy with or without radiation therapy (RT) to LM patients with a good PS, no major neurological deficits and a chemosen- sitive primary disease, such as breast cancer. On the other hand, patients with a poor PS and bulky CNS disease causing serious neurological deficits are considered for supportive care with or without RT to symptomatic sites. Otherwise, the modalities for the diagnosis and treatment interventions depend on the attending physicians, and no consensus or guideline exists yet for the diagnosis/treat- ment of LM. In the present study, we conducted a retrospective evaluation of our experience with 85 patients with cyto- logically proven LM to analyze the prognostic factors and most suitable potential treatment strategies for LM.

Patients and methods

Patients

Between June 1997 and July 2005, 85 patients with solid tumors were diagnosed as having LM at the National Cancer Center Hospital, Tokyo. Information on these

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patients was extracted from electronic and paper medical records, and the imaging findings were reviewed. An experienced cytopathologist (K.T.) diagnosed LM by the identification of malignant cells in the CSF.

Imaging studies

The images reviewed included CT scans (in three patients, all with contrast enhancement) and MR images (in 77 patients, all with contrast enhancement). The CT had been performed with one of two models of the equipment in all patients (Aquilion multislice CT scanner or X-Vigor, Toshiba Med- ical Systems, Tokyo, Japan) after injection of contrast (a total of 100 ml) at the rate of 1.0 ml/s. The scanning parameters were: axial single, 4- or 16-slice mode, section thickness 4.0 or 5.0 mm, 1.0 s/rotation, 120 kVp, 300 mA. The images were reconstructed using a standard algorithm without edge enhancement. MR imaging of the brain and spine had been performed using one of two models of 1.5-T systems (General Electric Medical Systems, Milwaukee, WI, or Toshiba Medical Systems, Tokyo, Japan). Using the spin-echo or fast spin- echo technique, T1-weighted images (460–600/12–27 ms (TR/TE)) were obtained in the transverse plane, and T2-weighted images (3,500–9,800/80–112 ms (TR/TE eff ); 8–12 echo train) were then obtained in the transverse and sagittal planes using the head or body coil. The images were obtained under the following imaging conditions:

field of view, 32–40 cm; image matrix, 128 9 128–256; slice thickness, 6–10 mm; intersection gap, 1.2–2.5 mm. Gadopentetate dimeglumine was then administered intra- venously and T1-weighted images were obtained in the transverse and sagittal planes with fat suppression. Con- trast-enhanced images were also obtained under the same imaging conditions as above.

Image interpretation

Two board-certified radiologists (M.M. and U.T.) reviewed the CT and MR images, and the findings were reported based on consensus. The radiologic features assessed included the lesion location, tumor size, the lesion contours and margins, presence/absence of superficial linear sul- cal, cisternal or dural enhancement, presence/absence of hydrocephalus, the signal characteristics on the T1- and T2-weighted images, and the lesion homogeneity (homogeneous or heterogeneous). Tumor location was determined mainly in terms of whether the lesions were leptomeningeal or subpial metastases. The signal charac- teristics were described as isointense or hyperintense relative to the signal intensity of the normal spinal cord. Neurological examinations were performed at the time of the diagnosis.

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Treatment

Treatment comprised intrathecal (IT) chemotherapy once weekly, mainly with methotrexate 10–15 mg/body plus prednisolone, 20 mg, plus, in rare cases, AraC. Whole- brain radiotherapy (WBRT), at a total radiation dose of 30 Gy administered in 10 fractions, was administered for patients with severe symptoms arising from cranial nerve involvement caused by bulky disease. Patients with symptoms of intracranial hypertension were treated with steroids, glycerol and antiepileptic drugs, as palliative care. In addition, implantation of an intraventricular Ommaya reservoir was undertaken in some patients.

Evaluation and statistical analysis

Response criteria were defined as reported previously, with minor alterations [16]. Complete response (CR) was defined as clinical improvement, negative CSF cytology, and normalization of the CSF biochemis- try. Partial response (PR) was defined as improved or stable clinical status, substantial ([50%) improvement in the CSF biochemistry and reduction of malignant cell counts (CSF cytology was not considered). Stable disease (SD) was defined as a stable clinical status and stable or marginally improved CSF biochemistry (CSF cytology was not considered). Progressive disease (PD) was diag- nosed when none of the above criteria for response were met. Survival was calculated from the time of diagnosis of the LM until death or the last follow-up. Survival curves were estimated using the Kaplan-Meier method. Differences in survivals were tested using the logrank test. Cox proportional hazard models were used for the multivariate analysis to identify the variables influencing the overall survival after the diagnosis of LM. The clinical variables were chosen by considering possible factors based on previous studies and our own experience [1113, 16, 17]. In the analyses for prognostic factors at the time of diagnosis, we performed univariate and multivariate analyses for these factors as follows: age at the time of diagnosis of the LM (\60 years vs. C60 years), gender (male versus female), primary disease (breast cancer versus other), first relapse site (LM versus non-LM), interval from diagnosis of the primary to diagnosis of the LM (B1 year vs.[1 year), past history of WBRT (yes versus no), PS (0–1 vs. 2–4), meningeal enhancement on MRI or CT (yes versus no), brain metastasis on MRI or CT (yes versus no), cell count in the CSF (B100/3 vs.[100/3), and protein level in the CSF (B50 mg/dl vs.\50 mg/dl). We performed univariate analysis (logrank test) for factors of clinical interest related to the treatment of LM or brain metastasis: IT chemotherapy (yes versus no), response to IT

chemotherapy (yes versus no), WBRT (yes versus no), and implantation of an Ommaya reservoir (yes versus no). Data analysis was performed using the SPSS 12.0 J software (SPSS Inc., Chicago, IL), and two-sided P values of \0.05 were considered to denote significance.

Results

Patient characteristics

Data from a total of 85 patients were included for the analysis. The patient characteristics at the time of diagnosis of the LM are shown in Table 1. There were 36 patients with lung cancer (42%), including five with small cell lung cancer, 33 patients with breast cancer (39%), eight patients with gastric cancer (9%), and eight with other cancers (9%). The median age at the time of diagnosis of the LM was 59 years (range, 22–83 years). Brain metastases had been detected in 14 patients (16%) before the diagnosis of LM. At the time of diagnosis of LM, 70 patients (82%) had metastatic disease at sites other than the CNS, including the lung, liver, skin, bones, lymph nodes, and other sites. Twelve patients (14%) had only brain metastasis and three patients developed LM without evidence of metastatic disease in other organs. Forty-four patients (52%) had undergone an operation for the primary tumor, and 65 patients (76%) had received chemotherapy for advanced disease or relapse, with the median number of chemo- therapeutic regimens received of 1 (range, 0–5). Twelve patients (14%) had previously received WBRT for brain metastasis. Of these, one patient had undergone metasta- tectomy and another had undergone metastatectomy and radiosurgery in addition to WBRT. The median time from the diagnosis of the primary tumor to the diagnosis of LM was 446 days (range, 0–5,152 days). Thirty-seven patients were diagnosed to have LM within a year of the diagnosis of the primary tumor, and four patients were diagnosed with LM at the same time as the diagnosis of the primary tumor. Concerning the PS at the time of diagnosis of the LM, it was 0–1 in 26 patients (31%) and 2–4 in 59 patients

(69%).

Symptoms at the time of diagnosis of the LM

The cerebral symptoms included headache (46 patients, 54%), nausea and vomiting (41, 48%), abnormal mental state (confusion) (29, 34%), and seizures (5, 6%). Symp- toms of cranial nerve involvement included dizziness (22, 26%) and diplopia (14, 16%), and those of spinal cord involvement included leg weakness (24, 28%) and back pain/paralysis (15, 18%).

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Table 1 Patient characteristics

 

N (%)

Total patients

85

Gender

Male

36 (42)

Female

49 (58)

Age at diagnosis of LM (years)

Median 59 years (range, 22–83)

Primary site

Lung

36 (42)

Breast

33 (39)

Gastric

8 (9)

Esophagus

2 (2)

Melanoma

2 (2)

Ovarian

2 (2)

Renal

1 (1)

Primary unknown

1 (1)

Metastasis site

LM only

3 (4)

Brain metastasis

49 (58)

Past history

14 (16)

Same time as LM

45 (53)

Metastasis other than in CNS

70 (82)

Past treatment of the primary disease

Operation

44 (58)

Chemotherapy

65 (76)

Radiation therapy

38 (45)

WBRT

12 (14)

Number of chemotherapy regimens received in the past

Median 1

(range, 0–5)

Interval from diagnosis of primary to diagnosis of LM

446 days

(range, 0–5,152)

LM within a year of diagnosis of the primary

37 (44)

Performance status

0–1

26 (31)

2–4

59 (69)

LM leptomeningeal metastasis, CNS central nervous system, WBRT whole-brain radiotherapy

Establishing the diagnosis of LM

All the patients had undergone a lumbar puncture with or without neuroradiography and had a positive CSF cytol- ogy. Increase in the CSF cell counts was observed in 71 patients (84%) ([10/3) and increase of the CSF protein level ([40 mg/dl) was observed in 70 patients (82%). Seventy-seven patients (91%) had undergone MRI and three had undergone CT. Fifty-one patients (64%) showed characteristic MRI or CT findings of LM and 45 patients (53%) showed brain metastasis. We included the five

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patients who had not undergone MRI or CT as patients not showing meningeal enhancement.

Treatment of LM

Thirty-one (36%) patients had received IT chemotherapy, including six who had also received WBRT; these patients comprised 19 of the 33 patients with breast cancer patients (58%), five of the eight patients with gastric cancer (63%), 4 of the 36 patients with lung cancer (11%), two of the two patients with ovarian cancer (100%), and one patient with renal cancer (100%). The median number of IT chemo- therapy sessions was 5 (range, 1–30) and the median duration of the therapy was 26 days (range, 1–694 days). Nine patients (11%) received WBRT alone after the diag- nosis of LM, including five with breast cancer and four with lung cancer. Implantation of an intraventricular Ommaya reservoir was undertaken in 17 patients (20%), including 15 with breast cancer, and two with a ventriculo- peritoneal shunt placed for hydrocephalus. None of the patients had received systemic chemotherapy. Forty-five patients had received no treatment at all.

Response rate to and toxicity of intrathecal chemotherapy

The total response rate to IT chemotherapy, i.e., CR plus PR, was 52% (n = 16/31, CR: 6, PR 10, (95% CI: 41.4–62.6%)). When classified according to the site of the primary, it was 68% (13/19) in breast cancer patients, 50% (2/4) in lung cancer patients, and 20% (1/5) in gastric cancer patients. The neurologic toxicities and complications of IT chemotherapy included nausea/vomiting (n = 9), headache (n = 4), sei- zures (n = 1), confusion (n = 1), and delayed leukoen- cephalopathy (n = 2). One patient who had undergone implantation of an Ommaya reservoir experienced particu- larly severe recurrent vomiting. The two patients in whom leukoencephalopathy occurred (on day 694 and day 175, respectively) had received 30 and 14 sessions of IT chemo- therapy, respectively, and the total doses of MTX in these patients were 220 and 210 mg, respectively. These two patients had not received WBRT either before or after the onset of LM.

Survival

The overall median survival after the diagnosis of LM was 51 days (range, 3–759 days). The median survival for each tumor type was as follows: lung cancer, 43 days (range, 3–375 days), breast cancer, 79 days (range, 13–759 days) and other cancers, 30 days (range, 4–523 days). Patients with breast cancer showed better survival times than patients with lung cancer (P = 0.04), however, there was no significant

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difference in the survival times between patients with breast cancer and those with other cancers (P = 0.1), or those with lung cancer and other cancers (P = 0.7). Figure 1 shows the Kaplan-Meier survival curves after the diagnosis of LM in patients with PS 0–1 as compared with those in patients with PS 2–4, with the median survival times in the two groups being 120 and 41 days, respectively (P \ 0.01). The survival period among patients who were diagnosed with LM within one year of the diagnosis of the primary was poor (median, 39 days; range, 4–391), while the median survival among those who developed LM more than 1 year after the diagnosis of the primary was 69 days (range, 3–759 days) (P = 0.01). The presence of brain metastasis at the time of diagnosis of the LM, and the tumor cell counts and protein levels in the CSF did not affect the survival. The following factors were identified by univariate analysis as good prognostic factors; female gender, LM as the first relapse site, a long interval of more than 1 year between the onset of the primary tumor and the diagnosis of LM, and a good PS (0–1) (Table 2). Furthermore, patients who had received IT chemother- apy showed better survival times than those who had not, with a median survival time of 144 days vs. 39 days in the two groups, respectively (P B 0.01). Univariate analysis revealed that response to IT chemotherapy and implanta- tion of an Ommaya reservoir were significantly associated with better survival (Table 3). In the multivariate analysis, Cox proportional hazard regression identified significant interaction of the survival with a poor PS (HR: 1.72 (95% CI, 1.04–2.86) P = 0.04) and association of the MRI or CT findings of meningeal dis- semination (HR: 1.82 (95% CI, 1.11–2.98) P = 0.02) with a poor survival (Table 4). Figure 2 shows the Kaplan-Meier survival curves for the patients who showed meningeal

survival curves for the patients who showed meningeal Fig. 1 Kaplan-Meier analysis of survival. The solid

Fig. 1 Kaplan-Meier analysis of survival. The solid line indicates patients with a performance status of 0–1, and the dotted line indicates patients with PS of 2–4. The vertical bars indicate censored cases

Table 2 Univariate analysis

Risk factor

N

Median survival (days)

P value

All

85

51

Age

\60 years

48

56

0.6

C60 years

37

47

Sex

Male

36

36

0.001

Female

49

79

Primary site

Lung cancer

36

43

*

Breast cancer

33

79

Other cancers

16

30

First relapse site

LM

5

312

0.02

Non-LM

80

45

Interval from diagnosis of primary to the diagnosis of LM

B1 year

37

39

0.01

[1 year

48

69

Past history of WBRT

Yes

14

85

0.3

No

71

41

Performance status

0–1

26

120

0.005

2–4

59

41

Meningeal enhancement on MRI or CT

 

Yes

51

45

0.09

No

34

67

Brain metastasis on MRI or CT

 

Yes

45

59

0.3

No

40

42

Cell count in CSF

B100/3

59

67

0.06

[100/3

26

42

Protein level in CSF

B50 mg/dl

27

75

0.4

[50 mg/dl

58

45

LM leptomeningeal metastasis, WBRT whole-brain radiotherapy, MRI magnetic resonance imaging, CT computed tomography, CSF cere- brospinal fluid

* The P values were as follows: lung cancer versus breast cancer

(P = 0.04), breast cancer and other cancers except lung cancer (P =

0.1) and lung cancer versus other cancers except breast cancer

(P = 0.7)

enhancement on MRI or CT as compared with those for patients who did not show meningeal enhancement.

Discussion

LM is one of the most serious complications occurring in solid cancer patients. In general, several malignancies are

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Table 3 Influence (logrank test)

of

treatment-related

factors

on

the

survival

Risk factor

N

Median survival (days)

 

P value

All

85

51

IT

Yes

31

144

0.0001

No

54

39

Response to IT chemotherapy

Yes

16

191

0.0004

No

69

41

WBRT

Yes

14

97

0.3

No

71

42

Implantation of Ommaya reservoir

 

Yes

17

206

0.00001

No

68

41

IT intrathecal, WBRT whole-brain radiotherapy

 

Table 4 Multivariate analysis

 

Risk factor

Hazard ratio (95% CI)

 

P value

Performance status (0–1 vs. 2–4)

1.72

(1.04–2.86)

0.036

Meningeal enhancement on MRI or CT

1.82

(1.11–2.98)

0.018

CI confidence interval, MRI magnetic resonance imaging, CT computed tomography

MRI magnetic resonance imaging, CT computed tomography Fig. 2 Kaplan-Meier analysis of survival. The solid line

Fig. 2 Kaplan-Meier analysis of survival. The solid line indicates patients with no meningeal enhancement on MRI or CT, and the dotted line indicates patients with positive findings. The vertical bars indicate censored cases

known to be associated with a high risk of development of LM. In the present study, consistent with previous reports, LM was noted at a high frequency in lung cancer and breast

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cancer patients [1]. LM from solid tumors is often associ- ated with an advanced stage of systemic disease and often occurs with concomitant parenchymal brain metastasis. Surgical resection of brain metastasis, especially piecemeal resection of metastatic posterior fossa lesions, was associ- ated with a risk of development of LM [18]. The present study included 12 patients (14%) with brain metastasis, two of whom had undergone surgery for brain metastasis before the diagnosis of LM. The optimal management strategy of LM in patients with solid tumors is controversial because of lack of evidence from randomized trials comparing specific treatments with best supportive care. In this ret- rospective study, we identified several prognostic factors in patients with LM. Previous studies have reported that PS is one of the most important prognostic factors in cancer patients with LM [12, 14, 15, 19]. Jayson et al. reported that IT chemother- apy was beneficial in LM patients with a good PS [12]. The results of retrospective studies demonstrate a tendency towards the use of IT chemotherapy for LM patients with a good PS. In fact, in this retrospective study, we found that 58% of the patients with PS 0–1 and 27% of patients with PS 2–4 had received IT chemotherapy. This may influence the results of statistical analysis of the prognostic factors. Although this study was a retrospective study and there could have been a selection bias, we consider from our results that it might be better to select patients for IT chemotherapy according to their PS. Although no study until date had examined the radio- logical factors in cases with LM for analysis of the prognostic factors, the present study showed that MRI-proven LM was a poor prognostic factor. MRI of the brain and spine with a T1-weighted gadolinium-enhanced sequence is a standard and sensitive method for the diagnosis of LM. In this study, 77 patients (91%) had undergone MRI at the time of diag- nosis of LM, and 51 patients (66%) showed positive signs of LM on MRI, such as superficial linear sulcal, cisternal or dural enhancement, and hydrocephalus. The sensitivity of Gd-MRI for the diagnosis of LM has been reported to be 66–71% [6, 7]. In addition, 31% of the patients with LM were diagnosed on the basis of the clinical features and abnormal neurological imaging findings alone, despite negative CSF cytology [20]. Rodesch et al. reported that Gd-MRI is important for demonstrating the presence and extent of lep- tomeningeal seeding [8]. In addition to poor PS, the presence of MRI-proven evidence of LM may be useful to identify patients who may not benefit from IT chemotherapy. Unfortunately, we did not perform imaging studies after therapy, because the usefulness of MRI for evaluation of the effects of treatment of LM has not yet been demonstrated. The type of the primary cancer has also been recognized as a major prognostic factor. Wasserstorm reported that 61% of breast cancer patients who received focal irradiation and

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intraventricular methotrexate showed neurological improve- ment or stabilization, and 15% were still alive at 1 year. In contrast, only 39% and 18%, respectively, of lung carcinoma and melanoma patients improved or remained stable, with a median survival of 3–4 months and 1-year survival rate of 0% [5]. Other studies have reported similar results [11, 21]. Our results are comparable to these reports; the response rates to IT chemotherapy was 68% in breast cancer patients, 50% in lung cancer patients and 20% in gastric cancer patients. Furthermore, the 1-year survival rate was 0% in non-breast cancer patients, except for one patient with ovarian cancer. As the survival outcomes have not improved over the past 25 years, it is essential to develop effective therapy for the management of LM. Although a definitive diagnosis of LM is made by cytopathologic examination of the CSF, CSF biochemistry is frequently useful for the assessment of LM. Some pre- vious reports have suggested that the cell counts and protein level in the CSF may be prognostic factors for survival [5, 16]. However, our present study results did not support this suggestion. Several factors influence the CSF biochemistry, including the site of sampling and obstruc- tion of the CSF flow by tumor deposits [22]. Although prolongation of the survival times in cancer patients has been obtained with the development of various anticancer agents, no effective therapy for LM has been established as yet. The aim of treatment of LM is to palliate the symptoms and improve the quality of life. Some previous studies have shown that IT chemotherapy for LM in breast cancer patients did not yield either a neurological response or survival benefit [15, 23]. Other previous studies, although retrospective in nature, have shown that patients with a good PS may be suitable candidates for more aggressive treatment [11, 12]. Not all patients are necessarily suitable candidates for aggressive CNS-directed therapy; in addition, few guidelines exist to guide appropriate choice of therapy. The guidelines of the National Comprehensive Cancer Network Practice recommend that patients should be stratified into ‘‘poor risk’’ and ‘‘good risk’’ groups. The poor-risk group includes patients with a low Karnofsky PS, multiple, serious, fixed neurologic deficits, extensive systemic disease with few treatment options, bulky CNS disease, and neoplastic meningitis related to encephalopathy [24]. Our results revealed that an additional consideration may be the extent of disease in the CNS, especially definitive radiological find- ings of LM on MRI. The findings of the present study suggest that MRI imaging, performed in addition to lumbar puncture for the diagnosis of LM, may also be useful for prediction of the prognosis. Early diagnosis and stratification of patients with LM are important to improve the survival and quality of life of these patients. IT chemotherapy may be beneficial for patients with a good PS and negative MRI findings,

while palliative therapy alone may be a better treatment approach for the other patients.

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