Prognostische Faktoren und Outcome bei Patienten mit Meningeosis carcinomatosa nach Radiotherapie

Hofmann, Doreen (2025): Prognostische Faktoren und Outcome bei Patienten mit Meningeosis carcinomatosa nach Radiotherapie. Dissertation, LMU München: Medizinische Fakultät

Abstract

Background Leptomeningeal metastases (LM) occur especially in progressive stages or in the terminal course of cancer and are associated with a high mortality. The most frequent solid tumor primaries are breast cancer, lung cancer and malignant melanoma. The clinical presentation of LM is varied and non-specific. The diagnosis is based on clinical evaluation, the finding of malignant cells in the cerebrospinal fluid or by neuroimaging procedures. The prognosis is extremely poor, and the treatment is mostly palliative. This retrospective study investigated outcome and prognostic factors of 40 patients with LM from breast and lung cancer (NSCLC (adenocarcinoma)), who were treated with whole brain radiotherapy (WBRT). Patients and methods Patients Patients with LM from breast cancer and NSCLC (adenocarcinoma) who received WBRT extended to the caudal margin of the second vertebral body (C2-WBRT) at the radiotherapy department of Ludwig-Maximilians-University Munich between 2001 and 2014 were included in the study. The impact of primary tumor characteristics, diagnostic procedures, treatment options, and prognostic factors on overall survival (OS) were evaluated. Statistical analysis Overall survival was the primary endpoint of this retrospective study. The Mann-Whitney-U-test examined both groups (breast cancer and lung cancer) on significant differences. Survival was analyzed according to the Kaplan-Meier-method. The log-rank-test was applied to test differences between groups. For univariate and multivariate variables, the Cox proportional hazards model was performed. p<0.05 was considered significant. Results From 2001 to 2014, 40 patients (7 male and 33 female) with LM from breast cancer (25 patients) and NSCLC (adenocarcinoma, 15 patients) with a median age of 63 years were treated with C2-WBRT at our department. The median interval from first diagnosis of the primary disease to LM diagnosis was 27.5 months (range 0-174 months). The majority of patients (n=29, 72.5%) had concomitant brain metastases (lung cancer patients: n=15 (100%) vs. breast cancer patients: n=14 (56.0%)). 34 patients (85.0%) had nodal metastases (N+), 38 patients (95.0%) had distant metastases (M+), 27 patients (67.5%) spine metastases (breast cancer patients (n=20, 80.0%) vs. lung cancer patients (n=7, 46.7%)). All patients underwent WBRT extended to the caudal margin of the second vertebral body (C2-WBRT). The interval between diagnosis of LM and the start of radiotherapy was median 13.5 days (range 1-163 days). The patients received radiotherapy with a median dose per fraction of 2.5 Gy (range 1.8-3.0 Gy) to a median total dose of 35.0 Gy (range 6.0-46.0 Gy). A dose escalation >30.0 Gy did not have a significant influence on overall survival (p=0.366). The interval between start and end of radiotherapy was in median 19 days (range 6-42 days). Five patients (12.5%) underwent additional boost to brain metastases and irradiation to other spine metastases. One patient received craniospinal irradiation. Corticosteroids during radiotherapy were given in 34 patients and 11 patients (27.5%) got sequentially intrathecal methotrexate. Radiotherapy was terminated prematurely in 6 patients (15.0%). Median overall survival time for the entire group was 4.0 months (95%-confidence interval: 1.3-6.7 months). Median OS for patients with LM from breast cancer was 3.0 months (1.0-4.9 months) and for patients with LM from lung cancer (NSCLC (adenocarcinoma)) 5.0 months (0-10.0 months). One- and two-year survival rates were 20% and 10%, respectively. At last follow-up, the majority of patients were deceased (n=39, 97.5%) The median interval between LM detection and death or last follow-up observation was 5.5 months (range 1-76 months). A better patient´s performance status (Eastern Cooperative Oncology Group (ECOG)) significantly correlated with an improved overall survival rate (p=0.008) (univariate analysis, log-rank-test). The median OS rate after 1 year with ECOG-score of 0-1 (n=17, 42.5%) was 29.4%, with ECOG-score of 2 (n=13, 32.5%) was 15.4% and with ECOG-score of 3 (n=10, 25.0%) was 10.0% (Univariate analysis). ECOG remained significant in multivariate analysis. We observed a significantly inferior OS in uni- and multivariate analyses if the intracranial pressure (ICP) was increased (IICP) (One-year survival rates of 24.1% vs. 9.1% without and with IICP (p=0.034)). The OS of patients without supratentorial symptoms before start of radiotherapy was significantly longer (p=0.002). The histology of the primary cancer was not a significant prognostic factor for OS (p=0.946). WBRT was mostly tolerated well. If patients underwent combined therapy (MTX + C2-WBRT), there wasn´t a higher frequency of therapy-related toxicity (p=0.216). Alopecia (Common Toxicity Criteria (CTC)° 1 in 3 patients and CTC° 2 in 9 patients) and headaches (CTC° 1 in 3 patients, CTC° 2 in 1 patient and CTC° 3 in 2 patients) were the most common acute toxicities. 9 patients reported improvement or stabilization of neurological deficits after WBRT, one patient did not benefit. In 30 patients, no information referring to this was available. Data collection of late toxicities could not be done, because there was too little information. Conclusion This retrospective study demonstrates that the prognosis and the OS of patients with LM from breast and lung cancer (NSCLC (adenocarcinoma)), which underwent C2-WBRT, is very poor. A better ECOG-score and the absence of IICP at baseline significantly correlated with improved OS and represent significant prognostic factors. It is important to recognize these symptoms early and start therapy at best physical condition. Radiotherapy, especially WBRT, represents an important part of therapy of LM. It was tolerated well and was able to stabilize or even improve present neurological symptoms. More research and retrospective studies on the therapy of LM are desirable to detect factors who improve overall survival and quality of life. The effect of new systemic therapies is also not elucidated, yet. Individually, the optimal and best-tolerated therapy could be found. An individual still standardized diagnostic and therapeutic approach remains a challenge.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Meningeosis carcinomatosa, Radiotherapie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Deutsch
• Datum der mündlichen Prüfung: 2. Oktober 2025
• 1. Bericht­erstatter:in: Belka, Claus