Due to the dismal prognosis of LC, treatment indications and modality are frequently discussed; median overall survival is reported to be in the vicinity of 10–15 weeks.6,12–14 There have, however, been reports identifying patient subgroups with a favorable outcome and even long-term survival in selected cases.6,12–14 Among the most decisive factors reported in the literature to influence survival are initial clinical performance, the availability of efficacious systemic treatment options and an aggressive treatment of LC.6,13–16 The benefit of intrathecal chemotherapy (ITC) has been established in several studies with different regimens based on methotrexate or liposomal cytarabine, among others.17–19 An emerging role can be observed for newer small-molecule and targeted drugs such as epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), potentially guided by molecularly informed decisions.20
Radiotherapy (RT) is frequently employed in the form of whole-brain irradiation (WBRT) with a potential survival benefit, especially if additional brain metastases have been diagnosed.14,15 To achieve symptom palliation and preserve neurologic function, this is often combined with focal RT of symptomatic spinal lesions.14
Craniospinal irradiation (CSI) as a more aggressive and extensive form of RT implies a total or subtotal irradiation of all CNS compartments, including the whole brain and typically complete spine.21It is frequently performed as part of multimodal and curatively intended treatment approaches for pediatric tumors, such as medulloblastomas, or primary CNS tumors with cerebrospinal spread, such as ependymomas.22,23 For the palliative treatment of metastatic LC, there exists very sparse data supporting CSI, and clinical experience is limited.24 Critical consideration has to be given to several clinical as well as technical aspects that make CSI a challenging approach. On the clinical side, dose-limiting toxicity, primarily myelosuppression, can jeopardize the potential benefit and deplete the hematologic reserves needed for subsequent systemic therapy.25 On the technical side, field junctions have been necessary to achieve the required vertical radiation field extension, posing dosimetric challenges. However, the use of modern irradiation techniques, such as intensity-modulated radiotherapy (IMRT), helical treatment delivery and proton therapy, has helped overcome some of the obstacles.21,26–29
In the sparse body of literature available, it has been reported that in rare cases amounting to 10%–15% of the patients, comparably long-term survival after LC diagnosis could be achieved with the help of decisive treatment.24 This report aims to present our institution’s experience with the CSI of 25 metastatic patients with LC over a period of 10 years, evaluating the outcome, toxicity and predictive clinical factors to facilitate patient selection.
PATIENTS AND METHODS
We identified 25 patients who received CSI for the treatment of LC at our institution between 2008 and 2018. Patient data were extracted from an oncologic research database maintained at our institution, as well as from the patients’ detailed medical records. All reviews were performed following institutional guidelines and the Declaration of Helsinki of 1975 in its most recent version.
Median patient age at LC diagnosis was 53 years (IQR: 45–59; min.–max.: 17–74), and median interval from primary diagnosis was 25 months (IQR: 15–85; min.–max.: 0–279). Detailed patient characteristics are illustrated in Table 1. Primary histology varied: breast cancer was the most frequent (n=15, 60%), followed by lung cancer (n=6, 24%).
(To view a larger version of Table 1, click here.)
For LC diagnosis, all patients received an MRI of the neuroaxis, identifying radiographic evidence of contrast enhancement of the spinal or cerebral meninges.3 Histologic confirmation by means of lumbar puncture revealed floating tumor cells in the CSF in 20 cases (80%). The spinal meninges were affected in all presented cases, whereas only eleven patients (44%) showed additional involvement of the intracranial meninges. Additional parenchymal brain metastases were identified in 18 cases (72%). The presence of nodular/bulky disease and CSF flow obstruction were assessed radiologically, as no CSF flow studies were performed.
Symptoms and overall clinical performance (Karnofsky performance scale index [KPI]) at the beginning of RT and during follow-up were extracted from the patients’ medical records and quantified regarding symptom control, improvement or worsening after therapy. Neurologic function was assessed by an experienced radiation oncologist based on the documented symptoms, and a neurologic function scale (NFS) was used to assess the palliative effect achieved by RT.30 Neurologic function was classified as follows: asymptomatic (0), minor neurologic symptoms (1), moderate neurologic symptoms (2), neurologically seriously limited, requiring hospitalization (3) and requiring hospitalization and constant nursing care (4). The outcome of NFS was assessed as either stable, improved or worsened, according to documented symptoms. Symptom control was defined as a constant value of the NFS at therapy completion or first follow-up if available, whereas improvement was defined as a reduction of the NFS by at least 1 point from baseline. Date of death was obtained from medical and official records. Treatment-related toxicity was rated according to the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0.31 Detailed patient characteristics are illustrated in Table 1.