Whole-brain Radiation Therapy For Treatment Research Articles

The role of whole brain radiation therapy in treatment of primary central nervous system lymphoma: necessary or not

Primary central nervous system lymphoma (PCNSL) is a type of extranodal non-Hodgkin lymphoma. Whole brain radiation therapy (WBRT) combined with high-dose methotrexate is the standard treatment. Although PCNSL patients are sensitive to radiation therapy, the duration of response is relatively short and it is likely to provoke delayed neurotoxicity, especially in the elderly patients. Reduced-dose WBRT and autologous stem cell transplantation (ASCT) can lower the risk of neurotoxicity, whereas the clinical efficacy remains to be validated. For the elderly patients with PCNSL, application of WBRT in the first-line treatment should be cautiously considered. Key words: Lymphoma/radiotherapy; Whole brain radiation therapy; Lymphoma/chemotherapy; Methotrexate; Neurotoxicity

433 - Pemetrexed and Whole-Brain Radiation Therapy for Treatment of Brain Metastases from Non Small-Cell Lung Adenocarcinoma: A Single Instituton Analysis

ABSTRACT Background Folate antimetabolite pemetrexed was approved for treatment of patients with metastatic non small-cell lung carcinoma (NSCLC). Its activity on brain metastases makes it attractive in combination with whole brain radiation therapy (WBRT), but this regimen could also potentially increase toxicity. Patients and treatment We retrospectively assessed the use of pemetrexed concurrently with WBRT in 12 consecutive patients with brain metastases from NSCLC. Patients received pemetrexed 500 mg/m2, either alone (n = 4) or combined with cisplatin 75mg/m2 (n = 6) or carboplatin AUC5 (n = 2). Median total number of pemetrexed-based chemotherapy cycles was 3.5 (range: 1–8). In the course of chemotherapy, patients received WBRT delivering 30 Gy in 10 fractions (n = 8) or 20 Gy in 5 fractions (n = 4). Results Six patients improved neurologically with treatment (five complete and one partial responses). Four patients had their neurological symptoms stable. Best radiological response was complete response lasting until last follow-up in one patient. Five patients experienced partial response. One patient had stable disease. Progressions were identified in four patients, within a median time interval of 17 weeks (range: 6–58 weeks). Three patients were not analyzable for tumor response because of rapid systemic progression leading to death. Two of them had improved neurologically. No high-grade WBRT-toxicity was reported but one patient developed symptoms suggestive of a limbic encephalopathy five weeks after WBRT completion. Conclusion The combination of pemetrexed with WBRT was associated with a substantial improvement of neurological deficits and tumor responses in most patients. However, survival remained disappointing and there were concerns about toxicity in one patient. A clinical trial is required for better analyzing the potential synergistic effects of drug with radiation and evaluating neurological toxicity. Disclosure All authors have declared no conflicts of interest.

Neurosurgical management of metastases in the central nervous system

Metastases in the central nervous system (CNS) are identified in up to 30% of patients at autopsy. Rates of CNS involvement in metastatic cancer are believed to be increasing, possibly owing to better control of systemic disease with novel chemotherapies or improved metastasis detection. The neurosurgical treatment of patients with metastatic cancer is an integral component of multimodality therapy for brain and spinal metastases. Survival benefit has been demonstrated for the addition of open surgery as well as the use of stereotactic radiosurgery (SRS) to whole-brain radiation therapy for treatment of patients with isolated cranial and spinal metastases compared with whole-brain radiation therapy alone. New clinical trials that directly compare open surgical procedures with SRS are underway, as are trials examining the role of neurosurgical procedures, such as vertebroplasty and kyphoplasty, in association with radiotherapy as methods for pain control in cancer patients with metastatic lesions in the spinal column. In this article, I review data from current randomized clinical trials that examine the role of neurosurgical intervention in the treatment of patients with CNS metastases.

Resection for solitary brain metastasis. Role of adjuvant radiation and prognostic variables in 229 patients.

The authors reviewed 229 consecutive patients treated intramurally by resection of solitary cerebral metastasis. Patients were classified into four groups on the basis of whether a gross total resection or subtotal resection was performed and whether systemic disease was present or absent at the time of craniotomy. Group 1 had gross total resection and no systemic disease; Group 2 had subtotal resection and no systemic disease; Group 3 had subtotal resection and systemic disease; and Group 4 had gross total resection and systemic disease. All four groups were further subdivided into Subgroup A (adjuvant whole-brain radiation therapy) or Subgroup B (no adjuvant radiation). Data were collected regarding multiple patient and tumor variables for multivariate analysis. Survival data for the 46 patients in Group 1A (median 1.3 years, 2-year survival rate 41%, 5-year survival rate 21%) were markedly better than those for the 75 in Group 1B (median 0.7 year, 2-year survival rate 19%, 5-year survival rate 4%). The 20 patients in Group 2A also had superior survival data (median 1.1 years, 2-year survival rate 30%, 3-year survival rate 30%) when compared with the eight patients in Group 2B (median 3 months, 1-year survival rate 0%). However, the 16 and 22 patients in Groups 3A and 4A, respectively, had no discernible differences compared to the seven and 35 patients in their Group 3B and 4B counterparts. Multivariate analyses were performed to assess the association of survival with multiple patient, disease, and treatment variables. Poor neurological status and systemic disease were significantly associated with inferior survival, while longer (greater than 36 months) intervals between primary diagnosis and craniotomy were significantly associated with improved survival. After adjusting for the effects of other patient, disease, and treatment characteristics, adjuvant whole-brain radiotherapy was significantly associated with improved survival times. These data support the continued use of craniotomy followed by adjuvant whole-brain radiation therapy for treatment of solitary brain metastasis. However, this aggressive therapy appears relatively contraindicated in the face of either systemic disease or substantial neurological deficit.