Leptomeningeal Carcinomatosis from Brain Metastases of Breast Cancer | JM Jung, et al. Surgery WBRT LMC, and 30 patients (7.5%) had LMC only. The number of breast cancer patients diagnosed with histologic confirmation during the same period was 10172 in that study, and based on this, we inferred the incidence of LMC in patients with PBM as 52/370 (14%), which was much higher than that in patients without PBM (30/9, 802, 0.3%). Lee et al.18) reported that the in- cidence of LMC among CNS metastases of breast cancer was 25% (68 of 272 patients), which was apparently higher than the known incidence proportion of LMC in breast cancer patients which is about to 1-5%5). However, this simple comparison should be understood with caution because many clinical fac- tors including systemic disease status may affect the incidence. The hematogenous pathway can be a route for both PBM and LMC as tumor cells overcome blood-brain and blood-CSF barri- er28). Although it is not clear whether systemic chemotherapy can prevent either PBM or LMC, several studies indicated that sys- temic chemotherapy could prolong patients’ survival with PBM from breast cancer and intra-CSF chemotherapy is currently considered the best treatment option for LMC14,17,26,28,36). It is noteworthy that systemic disease status and chemotherapy were significant factors affecting the incidence of LMC in our study. 1.0 C0.8 M L t u to0.6 h i w n ito0.4 r o p o r P0.2 0.0 0 10 20 30 40 Time from index procedure (months) 50 Fig. 2. Kaplan-Meier curves for time to development of LMC after treat- ment of the parenchymal brain metastases according to index proce- dure. Y-axis represents the proportion of patients without LMC at each follow-up time at the X-axis. Patients in the surgical resection (n=27) conferred greater risk for developing LMC compared to those in the WBRT (n=156) (HR estimated by the Cox proportional hazard mod- el=2.95, 95% confidence interval, 1.33-6.54, p=0.008). LMC : lepto- meningeal carcinomatosis, WBRT : whole brain radiation therapy, HR : hazard ratio. Diagnosis of LMC In view of the poor prognosis of pa- tients with LMC, early diagnosis of LMC with prompt initiation of treat- ment is important to prolong survival, especially in patients with good perfor- mance status and neurological func- tion8). Physicians should be alerted to a differential risk of the condition de- pending on certain characteristics, and the method of treatment; early appro- priate actions to prevent or treat LMC in higher-risk patients should be taken. Recent trends in diagnosing LMC with MRI are highly sensitive although it is not definitive13). A strong adherence of malignant cells to the leptomeninges or the presence of a focal rather than wide- spread leptomeningeal tumor, can con- tribute to false-negative cytological re- sults15,37). Although the neuroimaging- based diagnosis of LMC without CSF cytology is not generally accepted as a definitive diagnosis, a consensus is reached to allow for the treatment of LMC diagnosed by radiographic evi- dence only in known cancer patients. In our study, 10 patients were diag- nosed with LMC based only on an MRI. Four of them revealed a negative CSF finding and in the remaining 6 pa- Table 3. Multivariable analysis of factors potentially affecting the cumulative incidence of leptomen- ingeal carcinomatosis after surgical resection or wholebrain radiation therapy Variables* Hazard ratio Cumulative incidence 95% CI p value Index procedure Surgical Resection 4.03 1.51-10.73 0.005 WBRT 1.0 Age <40 2.89 1.16-7.19 0.022 ≥40 1.0 No. of lesions Single 1.0 0.33-2.00 0.657 Multiple 0.82 Adjuvant chemotherapy No 1.0 0.19-0.99 0.048 Yes 0.43 Systemic disease status NED & stable 1.0 1.35-9.23 0.010 Progressing 3.53 *Factors with marginal significance (p-value <0.2) from the univariable analysis were included in the model. NED : no evidence of disease, WBRT : wholebrain radiation therapy, CI : confidence interval Table 4. Differential effects of the index procedure on the incidence of LMC according to the age group Index procedure Age Surgical resection (%) WBRT (%) p value <40 No LMC 3 (50) 13 (72) 0.362 LMC 3 (50) 5 (28) ≥40 No LMC 14 (67) 126 (91) 0.005 LMC 7 (33) 12 (9) Fisher’s exact test. Numbers in parenthesis represents column percentage. LMC : leptomeningeal carcinomato- sis, WBRT : whole brain radiation therapy 197