The role of whole-brain radiation therapy after stereotactic radiation surgery for brain metastases

The benefit of whole-brain radiation therapy (WBRT) following stereotactic radiation surgery (SRS) for brain metastases is controversial. We conducted a systematic analysis of published literature to explore the outcome of brain metastases treated with SRS and WBRT versus SRS alone using PubMed and MEDLINE. Outcomes including survival, control, salvage therapy, and other quality of life measures were reported. Three randomized controlled trials involving 389 patients with 1 to 4 brain metastases were selected. In 2 of these trials (n = 190), the mean 1-year survival was 33.2% for SRS + WBRT and 38.7% for SRS alone (P = .5233); 1-year local control was 89% for SRS + WBRT and 71% for SRS alone (P < .001). Mean crude distant recurrence rate for SRS + WBRT was 36.6% and 54% for SRS alone (P < .001). Patients without WBRT were over 3 times more likely to require salvage therapy (P < .001). The addition of WBRT was associated with a decreased health-related quality of life assessment, mini mental status exam, and Hopkins Verbal Learning Test (P < .05). Five retrospective studies (n = 1122) were also included in a separate analysis and yielded findings that supported results from the randomized trials. Our systematic analysis demonstrates that adjuvant WBRT following SRS for the treatment of oligometastases in the brain is more effective at controlling local and distant recurrence than SRS alone, but there is no apparent benefit for survival or symptomology. The proven cognitive decline and neurotoxicity present with WBRT should be weighed against the benefit of local control. Prognosis of brain metastasis is poor regardless of current treatment and further exploration for alternative adjuvant treatment for SRS is warranted.     

The influence of surgery and radiation therapy on patients with brain metastases

The place for operation and for radiation therapy in the management of brain metastases is reviewed from the experience of 1895 patients treated in two studies of the Radiation Therapy Oncology Group. Operative removal may be of benefit to patients with solitary peripheral lesions in non-critical brain locations. Operation is also appropriate when the diagnosis is in doubt. Radiation therapy with appropriate steroid management is of benefit to patients with multiple metastases or where operative intervention is not reasonable. Short course low-dose treatment has been as beneficial as more aggressive prolonged radiation therapy.     

Survival with brain metastases following radiation therapy

The onset of intracranial metastases is a common development during the course of malignancy. The treatment of these patients represents a significant workload in any radiation oncology department. Much debate has occurred regarding the most appropriate fractionation schedules employed given the perception of limited life expectancy and symptomatic relief following cranial radiation. The aim of this study was to identify the spectrum of primary sites in patients developing intracranial metastases and to assess survival postradiation for the group overall and for selected subgroups. The records of 378 patients undergoing palliative cranial radiation in the years 1993?1998 at Sydney's Mater and Royal North Shore hospitals were analysed retrospectively. Major primary sites were lung (42%), breast (18%), colorectal (9%), melanoma (7%), and unknown primary (7%). Overall median survival post‐treatment was 3 months. Lung cancer patients showed a median survival of 6 months, breast 5 months, colorectal 4 months and melanoma 3 months. Long‐term survivors were noted with up to 15% of certain groups alive beyond 12 months and 2% alive at 24 months. Multivariate analysis revealed improved survival in patients undergoing resection, and those receiving higher dose radiation justifying a more aggressive approach in selected patients.     

Vemurafenib and radiation therapy in melanoma brain metastases

Brain metastases in malignant melanoma carries a poor prognosis with minimal response to any therapy. The purpose of this pilot analysis was to find the effectiveness of vemurafenib, an oral BRAF inhibitor, and radiation therapy in V600 mutated melanoma with brain metastases. BRAF mutation status of the melanoma patients was determined by real-time PCR assay. Retrospective analysis was performed on twelve patients who had the mutation and were treated with either stereotactic radiosurgery or whole brain radiation therapy prior to or along with vemurafenib at a dose of 960 mg orally twice a day. Clinical and radiological responses, development of new brain metastases, overall survival and toxicity were assessed. Improvement in neurological symptoms was seen in 7/11 (64 %) following therapy. Radiographic responses were noted in 36/48 (75 %) of index lesions with 23 (48 %) complete responses and 13 (27 %) partial responses. Six month local control, freedom from new brain metastases and overall survival were 75, 57 and 92 %. Four patients had intra-tumoral bleed prior to therapy and two patients developed steroid dependence. One patient experienced radiation necrosis. This retrospective study suggests that melanoma patients with brain metastases harboring BRAF mutation appear to be a distinct sub-group with a favorable response to vemurafenib and radiation therapy and acceptable morbidity.     

Role of radiation therapy in brain metastases management

The challenge of the management of brain metastases has not finished yet. Although new diagnosis-specific prognostic assessment classifications and guidelines for patients with brain metastases help to guide treatment more appropriately, and even if the development of modern technologies in imaging and radiation treatment, as well as improved new systemic therapies, allow to reduce cognitive side effects and make retreatment or multiple and combined treatment possible, several questions remain unanswered. However, tailoring the treatment to the patient and his expectations is still essential; in other words, patients with a poor prognosis should not be over-treated, and those with a favorable prognosis may not be subtracted to the best treatment option. Some ongoing trials with appropriate endpoints could better inform our choices. Finally, a case-by-case inter-disciplinary discussion remains essential.     

Local control after fractionated stereotactic radiation therapy for brain metastases

Stereotactic radiosurgery (SRS) is frequently used in the management of brain metastases, but concerns over potential toxicity limit applications for larger lesions or those in eloquent areas. Fractionated stereotactic radiation therapy (SRT) is often substituted for SRS in these cases. We retrospectively analyzed the efficacy and toxicity outcomes of patients who received SRT at our institution. Seventy patients with brain metastases treated with SRT from 2006–2012 were analyzed. The rates of local and distant intracranial progression, overall survival, acute toxicity, and radionecrosis were determined. The SRT regimen was 25 Gy in 5 fractions among 87 % of patients. The most common tumor histologies were non-small cell lung cancer (37 %), breast cancer (20 %) and melanoma (20 %), and the median tumor diameter was 1.7 cm (range 0.4–6.4 cm). Median survival after SRT was 10.7 months. Median time to local progression was 17 months, with a local control rate of 68 % at 6 months and 56 % at 1 year. Acute toxicity was seen in 11 patients (16 %), mostly grade 1 or 2 with the most common symptom being mild headache. Symptomatic radiation-induced treatment change was seen on follow-up MRIs in three patients (4.3 %). SRT appears to be a safe and reasonably effective technique to treat brain metastases deemed less suitable for SRS, though dose intensification strategies may further improve local control.     

Strategy of radiation therapy for bone metastases and MSCC in breast cancer patients

Bone metastasis is a common event in advanced cancers such as prostate, breast, lung, and renal cancers. Radiation therapy has been widely used for bone metastasis. However, it remains a challenging therapy because no radiation therapeutic guidelines, including radiation dose, radiation field, and fractionation, for patients with bone metastasis have been established. Many randomized controlled trials for bone metastasis have been carried out. They showed no significant difference in pain relief with a short course of radiation therapy such as 8 Gy/1 Fr and 20 Gy/5 Fr or with a long course of radiation therapy such as 30 Gy/10 Fr, 37.5 Gy/15 Fr, and 40 Gy/20 Fr. Toxicity rates with short and long courses were also the same. Recurrence rate at 2 years, however, was significantly higher in patients irradiated with a short course than in patients irradiated with a long course. Those trials also showed that response rate is affected by patient’s age, performance state, tumor type, pathological state, number of metastatic tumors, and span from diagnosis of cancer to development of metastatic tumor. Breast cancer has a better prognosis than most other cancers. Recently, there have been significant advances in cancer therapy techniques and improvement in clinical results. Bone metastasis can cause extreme pain and motor deficits. Quality of life for patients with bone metastasis is drastically worsened. Patients with bad prognosis should be treated with radiation therapy when analgesia is the main aim of treatment. Survival of patients with oligometastasis or predominantly bone metastasis is expected to be better than that of patients with visceral metastasis. For patients with vertebral or weight-bearing long bone metastasis, long-course therapy is recommended. Many patients who are expected to have a good prognosis should be treated with a long course of radiation.     

Focal radiation therapy of brain metastases after complete surgical resection

Brain metastases are a frequent occurrence in cancer patients and result in significant morbidity and mortality. The three main treatments for brain metastases include surgery, radiation, and/or chemotherapy, alone or in combination. After resection alone, local recurrence rates are high. Whole brain radiation therapy can decrease the probability of recurrence; however, this has some disadvantages. Focal radiation therapy (FRT) may provide many of the same benefits without some of these disadvantages. In this study, we retrospectively analyzed patients with single brain metastases treated with FRT after surgery. Doses ranged from 14 Gy as single dose stereotactic radiosurgery (SRS) to 54 Gy in 27 2-Gy fractions as conformal fractionated radiotherapy. Four of the seven patients had a same-site recurrence, with an average time to recurrence of 115.5 d. Median dose in the patients that had same-site recurrence was 42 Gy. One of these patients is currently living. Two patients did not have recurrence, and one patient had a recurrence at a different site within the brain. The low rate of out-of-field recurrences during the patients life indicates focal radiation may be a reasonable therapeutic alternative. Given the number of patients with same-site recurrences, wide field margins around the tumor volume or higher radiation doses than those typically used in palliative regimens may be useful in post-excisional FRT. Additionally, we found that a longer delay in the initiation of FRT after initial diagnosis may result in a decreased time to same-site recurrence. However, further studies are warranted given the small number of patients in this study.     

Integration of stereotactic radiosurgery or whole brain radiation therapy with immunotherapy for treatment of brain metastases

The prognosis of brain metastases(BM) is traditionally poor. BM are mainly treated by local radiotherapy,including stereotactic radiosurgery(SRS) or whole brain radiation therapy(WBRT). Recently, immunotherapy(i.e., immune checkpoint inhibitors, ICI) has demonstrated a survival advantage in multiple malignancies commonly associated with BM. Individually, radiotherapy and ICI both treat BM efficiently; hence, their combination seems logical. In this review, we summarize the existing preclinical a...     

Adjuvant whole-brain radiation therapy after surgical resection of single brain metastases

Adjuvant whole-brain radiation therapy (WBRT) after resection of single brain metastases remains controversial. Despite a phase III trial to the contrary, clinicians often withhold WBRT after resection of single brain metastases based on the argument that available evidence does not inform regarding treatment of all patients, such as those with radioresistant tumors. However, there is limited information about whether subpopulations benefit equally from WBRT after resection. Therefore, we undertook a retrospective study to determine the clinical, radiographic, and histologic features that influenced the effectiveness of adjuvant WBRT. We reviewed 358 patients with newly diagnosed, single brain metastases, who underwent resection, of which 142 (40%) received adjuvant WBRT and 216 (60%) did not. Median follow-up was 60.1 months. There were multiple tumor histologies, including 197 (55%) "radiosensitive" and 161 (45%) "radioresistant" tumors. Compared with observation, WBRT significantly reduced recurrence both locally (HR = 0.58; 95% CI 0.35–0.98, P = .04) and at distant brain sites (HR = 0.43, 95% CI 0.30–0.61, P < .001). Multivariate analyses demonstrated that withholding WBRT was an independent predictor of local and distant recurrence. For local recurrence, tumors with a maximum diameter of ≥3 cm that did not receive adjuvant WBRT had an increased risk of recurring locally (HR = 3.14, 95% CI 1.02–9.69, P = .05). For distant recurrence, patients whose primary disease was progressing and who did not receive WBRT had an increased risk of distant recurrence (HR = 2.16, 95% CI 1.01–4.66, P = .05). There was no effect of WBRT based on tumor type. Adjuvant WBRT significantly reduces local and distant recurrences in subsets of patients, particularly those with metastases >3 cm or with active systemic disease.     

全脑放疗联合靶向治疗与同步放化疗治疗非小细胞肺癌脑转移的疗效及不良反应的Meta分析

目的:采用循证医学的方法评价全脑放疗联合靶向治疗与同步放化疗治疗非小细胞肺癌脑转移的疗效及不良反应。方法:电子检索Pubmed、万方、维普、知网数据库，纳入全脑放疗联合靶向治疗与同步放化疗治疗非小细胞肺癌脑转移的文献，检索时间为建库至2018年6月，采用Revman 5.1 软件对数据进行Meta分析。结果:共纳入16项研究，共990例患者。结果显示，全脑放疗联合靶向治疗的总体有效率、疾病控制率及1年生存率均高于与同步放化疗组，差异具有统计学意义（P＜0.05）；联合组的消化道反应及肝脏损伤均小于同步组，差异有统计学意义（P＜0.05）。结论:Meta分析表明，全脑放疗联合靶向治疗非小细胞肺癌脑转移的疗效优于同步放化疗组，且不良反应更少。     

Results of whole brain radiation therapy in patients with brain metastases from colorectal carcinoma

AIMS AND BACKGROUND: Carcinoma of the colon-rectum is an infrequent cause of brain metastases, constituting 1.5% of all metastatic lesions to the brain. We reviewed our experience in the treatment of brain metastases from colorectal cancer to define the efficacy of whole brain radiation therapy as a palliative measure in this setting of patients. METHODS: Twenty-three consecutive cases of brain metastasis from colorectal cancer treated between 1999 and 2004 were identified in the files of the Division of Radiotherapy of the A Businco Regional Oncological Hospital, Cagliari. Their records were reviewed for patient and tumor characteristics and categorized according to the RTOG RPA classes. RESULTS: Fifteen patients (65%) had multiple metastases. Twenty-one patients (91%) showed extracranial metastases. Fourteen patients were classified as RTOG RPA class II and 9 class III. The median radiation dose delivered was 2000 cGy in 5 fractions in one week (range, 20-36 Gy). In 14 of 20 assessable patients (70%), symptomatic improvement was observed. The median follow-up and survival time for all the patients, 12 females and 11 males, was 3 months. In 3 patients only the cause of death was the brain metastasis. CONCLUSIONS: Despite the disappointing survival time, external radiation therapy to the whole brain proved to be an efficacious palliative treatment for patients with multiple or inoperable brain metastasis from colorectal cancer.     

Palliative radiation therapy for brain metastases from endometrial carcinoma: report of two cases

Although endometrial carcinoma is a common invasive neoplasm of the female genital tract, brain metastases are extremely rare and few reports exist of their treatment with radiation therapy. We report two patients with manifest clinical signs of brain metastases from endometrial carcinoma on computed tomography (CT) or magnetic resonance imaging (MRI). These two patients had multiple brain metastases, with widespread dissemination late in the course of the disease and received palliative whole-brain radiation therapy to a total dose of 50 Gy in 25 fractions (case 1) and 30 Gy in 10 fractions (case 2). After radiation therapy, improvement of neurological function (NF) was observed in both patients. The duration of improvement of NF was 9 weeks in case 1 and 12 weeks in case 2. The patients died 5 months and 3 months after the diagnosis of brain metastases, respectively. In these two cases, palliative radiation therapy was effective in improving the quality of the remaining lifetime and appears to be the best treatment for brain metastases from endometrial carcinoma as well as those frequently seen from other primaries.     

The rationale for adjuvant whole brain radiation therapy with radiosurgery in the treatment of single brain metastases

Randomized trials have established the efficacy of focal treatment (either stereotactic radiosurgery or conventional surgery) for single brain metastases. In the past, adjuvant whole brain radiation therapy (WBRT) was routinely given with focal therapy. Recently, the utility of adjuvant WBRT has been called into question. This paper examines the scientific evidence and the arguments, pro and con, concerning the use of adjuvant WBRT in association with stereotactic radiosurgery or conventional surgery.     

Stereotactic body radiation therapy for lung metastases

Introduction

Stereotactic body radiation therapy (SBRT) has an emerging role in patients affected with pulmonary metastases. Purpose of this study was to evaluate efficacy and tolerability of SBRT in a cohort of patients treated between 2003 and 2009 at our institution.

Methods

A total of 61 patients with oligometastatic lung tumors (single pulmonary nodules in 73.7%) were included in the study. SBRT was performed with a stereotactic body frame and a 3D-conformal technique. Fifty-one patients received 26 Gy in 1 fraction, 22 a dose of 45 Gy in 3 fractions and 3 a dose of 36 Gy in 4 fractions. Primary tumor was lung cancer in 45.7% of patients, colorectal cancer in 21.3% and a variety of other origins in 33%. The primary endpoint was local control, secondary endpoints were survival and toxicity.

Results

After a median follow-up interval of 20.4 months, local control rates at 2 and 3 years were 89% and 83.5%, overall survival 66.5% and 52.5%, cancer-specific survival 75.4% and 67%, progression-free survival 32.4% and 22.3%. Tumor volume was significantly associated to survival, with highest rates in patients with single small tumors. Median survival time was 42.8 months, while median progression-free survival time was 11.9 months. Toxicity profiles were good, with just one case of grade III toxicity (pneumonitis).

Conclusion

This study shows that SBRT is an effective and safe local treatment option for patients with lung metastases. Definitive results are strictly correlated to clinical selection of patients.     

Stereotactic body radiation therapy for spinal metastases

The goal of this paper is to expose the clinical results and review of the literature of the treatment of spinal metastases with Stereotactic Body Radiation Therapy (SBRT) presenting one case. A spinal metastases from rectal cancer treated with a single dose of 18Gy is presented. The following physics aspects are exposed: Treatment volume, tumor volume marginal doses and maximum doses in organs at risk. Clinical and radiographic follow up is presented. Local control and pain relief after one year of follow up was excellent. In properly selected patients, the treatment of limited metastatic disease with SBRT appears to be feasible and safe.     

Stereotactic body radiation therapy for liver metastases

Over the years, early diagnosis of metastatic disease has improved and the prevalence of oligometastatic patients is increasing. Liver is a most common site of progression from gastrointestinal, lung and breast cancer and in the setting of oligometastatic patients, surgical resection is associated with increased survival. Approximately 70-90% of liver metastases, however, are unresectable and an effective and safe alternative therapeutic option is necessary for these patients. The role of stereotactic body radiation therapy (SBRT) was investigated in the treatment of oligometastatic patients with promising results, thanks to the ability of this procedure to deliver a conformal high dose of radiation to the target lesion and a minimal dose to surrounding critical tissues. This paper was performed to review the current literature and to provide the practice guidelines on the use of stereotactic body radiotherapy in the treatment of liver metastases. We performed a literature search using Medical Subject Heading terms “SBRT” and “liver metastases”, considering a period of ten years.