Addition Of Whole-brain Radiotherapy Research Articles

Survival Impact of Postoperative Whole-brain Radiotherapy and Systemic Chemotherapy After Surgical Resection of Brain Metastases.

Resection of brain metastases is a well-established treatment modality that can prolong the survival of patients for whom surgery is indicated. Whole-brain radiotherapy (WBRT) has been the standard postoperative therapy. In recent years, however, clinicians have increasingly avoided WBRT due to its associated adverse events. This study investigated the impact of postoperative WBRT and systemic chemotherapy as prognostic factors on the survival of patients who had undergone resection of brain metastases. The study subjects were 172 patients who underwent surgical resection for brain metastases. Comparative analyses of survival after WBRT and systemic chemotherapy were performed. Postoperative WBRT had no survival-prolonging effect, whereas postoperative systemic chemotherapy prolonged survival. A comparison based on the number of systemic chemotherapy regimens administered prior to surgery showed that fewer regimens correlated with a better prognosis. The addition of WBRT after surgical resection of brain metastases is no longer a standard treatment strategy and systemic chemotherapy after surgery is a positive prognostic factor.

Stereotactic radiosurgery for patients with small-cell lung cancer brain metastases

Despite the continuous implementation of stereotactic radiosurgery (SRS) for patients with limited (≤4) brain metastases from various solid tumours1 and despite the increasing evidence of neurocognitive toxicity from whole brain radiotherapy (WBRT),2 patients with brain metastases from small-cell lung cancer (SCLC) are still considered typical candidates for WBRT. International guidelines and surveys on care patterns still regard WBRT as a standard of care for this setting in clinical practice. Several studies in various cancers have shown that postoperative SRS instead of additional WBRT can be associated with high control and survival rates and could preserve neurocognitive functioning;3,4 therefore, SRS has replaced WBRT as the standard of care for patients with limited brain metastases from most solid tumours, and its safety and efficacy is suggested for as many as ten targetable lesions.

Confirmatory Analysis of QUARTZ Study Results: Survival Prolongation After Whole-brain Radiotherapy.

The aim of this study was to analyze the survival of patients with brain metastases treated with best supportive care or additional whole-brain radiotherapy (WBRT), in order to confirm results from the prospective randomized QUARTZ study, which suggested prolonged survival after WBRT (5 fractions of 4 Gy) if favorable prognostic factors were present (age younger than 60 years, graded prognostic assessment score 2.5-3 points). We performed a retrospective single institution analysis of 76 patients with favorable prognosis. In contrast to the QUARTZ trial, inclusion was not limited to patients with non-small cell lung cancer (NSCLC). Furthermore, a cohort treated with higher total doses of WBRT was included (10 fractions of 3 Gy). All patients were younger than 60 years or had a graded prognostic assessment score of 2.5-3. The median survival was significantly shorter after best supportive care (1.2 months; 3.2 months after WBRT with 5 fractions of 4 Gy and 3.9 months after 10 fractions of 3 Gy). Also, in multivariate analyses, survival was significantly better after WBRT. Further favorable prognostic factors included better performance status, no or limited extracranial metastases and primary tumor other than gastrointestinal. In line with the QUARTZ trial results, WBRT prolonged survival in patients with favorable prognostic features.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Whole Brain Radiation Therapy in Adults With Newly Diagnosed Metastatic Brain Tumors.

Adult patients (older than 18 yr of age) with newly diagnosed brain metastases. If whole brain radiation therapy (WBRT) is used, is there an optimal dose/fractionation schedule? Level 1: A standard WBRT dose/fractionation schedule (ie, 30 Gy in 10 fractions or a biological equivalent dose [BED] of 39 Gy10) is recommended as altered dose/fractionation schedules do not result in significant differences in median survival or local control. Level 3: Due to concerns regarding neurocognitive effects, higher dose per fraction schedules (such as 20 Gy in 5 fractions) are recommended only for patients with poor performance status or short predicted survival. Level 3: WBRT can be recommended to improve progression-free survival for patients with more than 4 brain metastases. What impact does tumor histopathology or molecular status have on the decision to use WBRT, the dose fractionation scheme to be utilized, and its outcomes? There is insufficient evidence to support the choice of any particular dose/fractionation regimen based on histopathology. Molecular status may have an impact on the decision to delay WBRT in subgroups of patients, but there is not sufficient data to make a more definitive recommendation. Separate from survival outcomes, what are the neurocognitive consequences of WBRT, and what steps can be taken to minimize them? Level 2: Due to neurocognitive toxicity, local therapy (surgery or SRS) without WBRT is recommended for patients with≤4 brain metastases amenable to local therapy in terms of size and location. Level 2: Given the association of neurocognitive toxicity with increasing total dose and dose per fraction of WBRT, WBRT doses exceeding 30 Gy given in 10 fractions, or similar biologically equivalent doses, are not recommended, except in patients with poor performance status or short predicted survival. Level 2: If prophylactic cranial irradiation (PCI) is given to prevent brain metastases for small cell lung cancer, the recommended WBRT dose/fractionation regimen is 25 Gy in 10 fractions, and because this can be associated with neurocognitive decline, patients should be told of this risk at the same time they are counseled about the possible survival benefits. Level 3: Patients having WBRT (given for either existing brain metastases or as PCI) should be offered 6 mo of memantine to potentially delay, lessen, or prevent the associated neurocognitive toxicity. Does the addition of WBRT after surgical resection or radiosurgery improve progression-free or overall survival outcomes when compared to surgical resection or radiosurgery alone? Level 2: WBRT is not recommended in WHO performance status 0 to 2 patients with up to 4 brain metastases because, compared to surgical resection or radiosurgery alone, the addition of WBRT improves intracranial progression-free survival but not overall survival. Level 2: In WHO performance status 0 to 2 patients with up to 4 brain metastases where the goal is minimizing neurocognitive toxicity, as opposed to maximizing progression-free survival and overall survival, local therapy (surgery or radiosurgery) without WBRT is recommended. Level 3: Compared to surgical resection or radiosurgery alone, the addition of WBRT is not recommended for patients with more than 4 brain metastases unless the metastases' volume exceeds 7 cc, or there are more than 15 metastases, or the size or location of the metastases are not amenable to surgical resection or radiosurgery.The full guideline can be found at: https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_3.

Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma.

Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma.

Cognitive functioning and health-related quality of life in patients with newly diagnosed primary CNS lymphoma: a systematic review.

Incidence of primary CNS lymphoma (PCNSL) is increasing, while prognosis is improving as treatments advance. However, declined cognitive functioning remains a major challenge in the treatment of PCNSL. This cognitive decline, in conjunction with other symptoms caused by the disease or its treatment, or both, can compromise health-related quality of life (HRQOL). The aim of this Review was to give a comprehensive overview on cognitive functioning and HRQOL for patients with PCNSL, including an evaluation of patient-related and treatment-related factors that can influence cognitive functioning and HRQOL. We reviewed the literature for studies on cognitive functioning and HRQOL in newly diagnosed adult patients with PCNSL using MEDLINE/PubMed, Embase, Web of Science, Scopus, Cochrane, PsycINFO, CINAHL EBSCO, and Google Scholar, up to Jan 4, 2018. Articles were selected using predetermined inclusion and exclusion criteria; 42 articles were eligible for inclusion. Findings show that the tumour itself has a great effect on cognitive functioning and HRQOL. Initially, induction chemotherapy results in improvement of cognition and HRQOL in most patients. In the long-term, the addition of whole-brain radiotherapy has a negative effect on cognitive functioning, but the magnitude of this effect is not always clinically relevant. HRQOL scores were worse compared with controls, and worse after combined chemotherapy and radiotherapy when compared with chemotherapy only, particularly in the long term. Therefore, combined chemotherapy and radiotherapy seems to have a negative effect on HRQOL and cognition in patients with PCNSL. Although prolonged progression-free survival is achieved with combined treatment, information on its effect on cognition and HRQOL should be included in clinical decision-making.

A Score to Identify Patients with Brain Metastases from Colorectal Cancer Who May Benefit from Whole-brain Radiotherapy in Addition to Stereotactic Radiosurgery/Radiotherapy.

To design a tool to predict the probability of new cerebral lesions after stereotactic radiosurgery/radiotherapy for patients with 1-3 brain metastases from colorectal cancer. In 21 patients, nine factors were evaluated for freedom from new brain metastases, namely age, gender, Karnofsky performance score (KPS), tumor type, number, maximum total diameter of all lesions and sites of cerebral lesions, extra-cranial metastases, and time from cancer diagnosis to irradiation. Freedom from new lesions was positively associated with KPS of 90-100 (p=0.013); maximum total diameter ≤15 mm showed a trend for positive association (p=0.09). Points were assigned as: KPS 70-80=1 point, KPS 90-100=2 points, maximum diameter ≤15 mm=2 points and maximum diameter >15 mm=1 point. Six-month rates of freedom from new lesions were 29%, 45% and 100% for those with total scores of 2, 3 and 4 points, respectively, with corresponding 12-month rates of 0%, 45% and 100% (p=0.027). This study identified three risk groups regarding new brain metastases after stereotactic irradiation. Patients with 2 points could benefit from additional whole-brain radiotherapy.

Brain volume reduction after whole-brain radiotherapy: quantification and prognostic relevance.

Recent studies have questioned the value of adding whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis treatment. Neurotoxicity, including radiation-induced brain volume reduction, could be one reason why not all patients benefit from the addition of WBRT. In this study, we quantified brain volume reduction after WBRT and assessed its prognostic significance. Brain volumes of 91 patients with cerebral metastases were measured during a 150-day period after commencing WBRT and were compared with their pretreatment volumes. The average daily relative change in brain volume of each patient, referred to as the "brain volume reduction rate," was calculated. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the brain volume reduction rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way analysis of variance was used to compare the brain volume reduction rate across recursive partitioning analysis (RPA) classes. On multivariate Cox regression analysis, the brain volume reduction rate was a significant predictor of overall survival after WBRT (P < 0.001), as well as the number of brain metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable prognosis (RPA classes 1 and 2) experienced significantly less brain volume decrease after WBRT than patients with a poor prognosis (RPA class 3) (P = 0.001). There was no significant correlation between delivered radiation dose and brain volume reduction rate (P = 0.147). In this retrospective study, a smaller decrease in brain volume after WBRT was an independent predictor of longer overall survival.

Early whole brain radiotherapy in primary CNS lymphoma: negative impact on quality of life in the randomized G-PCNSL-SG1 trial.

In the randomized G-PCNSL-SG-1 trial, the addition of whole brain radiotherapy (45Gy) to high-dose methotrexate (HD-MTX)-based chemotherapy (early WBRT arm) did not prolong overall survival (OS) as compared to HD-MTX-based chemotherapy alone (no early WBRT arm) in primary CNS lymphoma (PCNSL) patients. To determine whether WBRT might lead to quality of life (QoL)-relevant late neurotoxicity, this trial prospectively monitored QoL. QoL measurements were performed using the EORTC-QLQ-C30 and BN20 questionnaires and combined with repeated Mini Mental State Examinations (MMSE). Exploratory data analysis included the 318 patients in the per-protocol population. In year 2 after randomization, cognitive functioning and global health status were reduced in the early WBRT arm as compared to the no early WBRT arm (p=0.004 and p=0.022, respectively). Also, fatigue (p=0.037), appetite loss (p=0.006) and hair loss (p=0.002) were more intense in the early WBRT arm. MMSE testing revealed lower values (p=0.002) in the early WBRT arm. A mixed model analysis of longitudinal data additionally showed differences favoring the no early WBRT arm in 15 of 26 dimensions of QoL. The analysis of subjective QoL questionnaires and objective MMSE testing revealed that QoL and cognition were conserved in the arm without early WBRT. Thus, even though it was an exploratory analysis, the results of G-PCNSL-SG1 challenge the place of WBRT in the primary therapy of PCNSL.

Case-based review: primary central nervous system lymphoma.

Primary CNS lymphoma (PCNSL) is a rare diffuse large B-cell lymphoma originating within the central nervous system. The overall incidence of PCNSL is rising, particularly in the elderly population. Immunosuppression is a strong risk factor, but most patients with this tumor are apparently immunocompetent. Diagnosis of PCNSL can be challenging. Non-invasive or minimally invasive tests such as ophthalmological evaluation and spinal fluid analysis may be useful, but the majority of patients require tumor biopsy for definitive diagnosis. Our knowledge concerning optimum treatment of PCNSL is fragmentary due to paucity of adequately sized trials. Most patients are now initially treated with high-dose-methotrexate-based chemotherapy alone, as the addition of whole-brain radiotherapy at standard doses has not been shown to increase survival and does increase the risk of neurological toxicity. Ongoing trials are addressing issues such as the roles of reduced-dose radiotherapy, the addition of the CD20 antibody rituximab to chemotherapy, high-dose chemotherapy followed by autologous stem cell transplantation, and maintenance therapy in the primary management of PCNSL.

Discovery of additional brain metastases on the day of stereotactic radiosurgery: risk factors and outcomes.

OBJECTIVE High-resolution double-dose gadolinium-enhanced Gamma Knife (GK) radiosurgery-planning MRI (GK MRI) on the day of GK treatment can detect additional brain metastases undiagnosed on the prior diagnostic MRI scan (dMRI), revealing increased intracranial disease burden on the day of radiosurgery, and potentially necessitating a reevaluation of appropriate management. The authors identified factors associated with detecting additional metastases on GK MRI and investigated the relationship between detection of additional metastases and postradiosurgery patient outcomes. METHODS The authors identified 326 patients who received GK radiosurgery at their institution from 2010 through 2013 and had a prior dMRI available for comparison of numbers of brain metastases. Factors predictive of additional brain metastases on GK MRI were investigated using logistic regression analysis. Overall survival was estimated by Kaplan-Meier method, and postradiosurgery distant intracranial failure was estimated by cumulative incidence measures. Multivariable Cox proportional hazards model and Fine-Gray regression modeling assessed potential risk factors of overall survival and distant intracranial failure, respectively. RESULTS The mean numbers of brain metastases (SD) on dMRI and GK MRI were 3.4 (4.2) and 5.8 (7.7), respectively, and additional brain metastases were found on GK MRI in 48.9% of patients. Frequencies of detecting additional metastases for patients with 1, 2, 3-4, and more than 4 brain metastases on dMRI were 29.5%, 47.9%, 55.9%, and 79.4%, respectively (p < 0.001). An index brain metastasis with a diameter greater than 1 cm on dMRI was inversely associated with detecting additional brain metastases, with an adjusted odds ratio of 0.57 (95% CI 0.4-0.9, p = 0.02). The median time between dMRI and GK MRI was 22 days (range 1-88 days), and time between scans was not associated with detecting additional metastases. Patients with additional brain metastases did not have larger total radiosurgery target volumes, and they rarely had an immediate change in management (abortion of radiosurgery or addition of whole-brain radiation therapy) due to detection of additional metastases. Patients with additional metastases had a higher incidence of distant intracranial failure than those without additional metastases (p = 0.004), with an adjusted subdistribution hazard ratio of 1.4 (95% CI 1.0-2.0, p = 0.04). Significantly worse overall survival was not detected for patients with additional brain metastases on GK MRI (log-rank p = 0.07), with the relative adjusted hazard ratio of 1.07, (95% CI 0.81-1.41, p = 0.65). CONCLUSIONS Detecting additional brain metastases on GK MRI is strongly associated with the number of brain metastases on dMRI and inversely associated with the size of the index brain metastasis. The discovery of additional brain metastases at time of GK radiosurgery is very unlikely to lead to aborting radiosurgery but is associated with a higher incidence of distant intracranial failure. However, there is not a significant difference in survival. ▪ CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort trial; evidence: Class IV.

Pretreatment clinical prognostic factors for brain metastases from breast cancer treated with Gamma Knife radiosurgery.

Background:Brain metastases significantly affect morbidity and mortality rates for patients with metastatic breast cancer. Treatment for brain metastases lengthens survival, and options such as stereotactic radiosurgery (SRS) can increase survival to 12 months or longer. This study retrospectively analyzes the prognostic factors for overall survival (OS) for patients with one or multiple brain metastases from breast cancer treated with SRS.Methods:Between December 2001 and May 2015, 111 patients with brain metastases from breast cancer were grouped by potential prognostic factors including age at diagnosis, Karnofsky Performance Status (KPS) score, number of brain metastases, and whether or not they received adjuvant treatments such as whole brain radiotherapy (WBRT) or surgical resection. Survival rates were determined for all groups, and hazard ratios were calculated using univariate and multivariate analyses to compare differences in OS.Results:Median OS was 16.8 ± 4.22 months. Univariate analysis of patients with a KPS ≤60 and multivariate analysis of KPS 70–80 showed significantly shorter survival than those with KPS 90–100 (5.9 ± 1.22 months, 21.3 ± 11.69 months, and 22.00 ± 12.56 months, P = 0.024 and < 0.001). Other results such as age ≥65 years and higher number of brain metastases trended toward shorter survival but were not statistically significant. No difference in survival was found for patients who had received WBRT in addition to SRS (P = 0.779).Conclusion:SRS has been shown to be safe and effective in treating brain metastases from breast cancer. We found our median survival to be 16.8 ± 4.22 months, an increase from other clinical reports. In addition, 38.4% of our population was alive at 2 years and 15.6% survived 5 years. Significant prognostic factors can help inform clinical treatment decisions. This study found that KPS was a significant prognostic indicator of OS in these patients.

Controversies in neuro-oncology: role of whole-brain radiation therapy in the treatment of newly diagnosed brain metastases.

As therapies for systemic cancers improve and patients survive longer, the incidence of brain metastases is increasing. Current therapies include varying combinations of surgery, stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT), and in a small subset of patients, systemic therapy. The use of SRS to treat brain metastases has been one of the major successes in neuro-oncology, providing effective local control of even radioresistant brain metastases. Several studies have compared the outcomes of patients with a limited number of brain metastases treated with surgery or radiosurgery alone, with the addition of WBRT. – 4 These studies, which usually included heterogeneous tumor histologies and varying extent of systemic disease, have generally shown improved intracranial control with the addition of WBRT, but no significant improvement in overall survival, and an increased risk of neurocognitive impairment. Most recently, at the 2015 American Society of Clinical Oncology annual meeting, Brown et al presented the results of the North Central Cancer Treatment Group (NCCTG) (Alliance) N0574 study, a phase III trial comparing SRS+WBRT to SRS alone in patients with 1–3 brain metastases. This study for the first time used decline in cognitive function at 3 months as the primary endpoint. Cognitive deterioration at 3 months was significantly more frequent in the WBRT+SRS group than the SRS alone group, involving especially immediate recall, memory, and verbal fluency. As with prior studies, intracranial disease control was improved with WBRT but there was no improvement in overall survival. This study adds to the growing body of literature addressing this issue. Nonetheless, there is currently no consensus on the value of WBRT and the optimal management of patients with brain metastases remains a dilemma that confronts clinicians looking after these patients. In this issue of Neuro-Oncology, Dr Arjun Sahgal from the University of Toronto discusses the data in favor of omitting WBRT from patients with newly-diagnosed brain metastases, while Dr. Minesh Mehta from the University of Maryland provides the counter-argument of including WBRT for these patients.

Do patients with very few brain metastases from breast cancer benefit from whole-brain radiotherapy in addition to radiosurgery?

BackgroundAn important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients.MethodsFifty-eight patients with 1–3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy.ResultsThe treatment regimen had no significant impact on local control in the univariate analysis (p = 0.59). Age ≤59 years showed a trend towards improved local control on univariate (p = 0.066) and multivariate analysis (p = 0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p = 0.040) and ECOG 0–1 (p = 0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p = 0.039) and performance status (p = 0.028) maintained significance on multivariate analysis. ECOG 0–1 was positively correlated with survival on univariate analysis (p < 0.001); age ≤59 years showed a strong trend (p = 0.054). On multivariate analysis, performance status (p < 0.001) and age (p = 0.041) were significant.ConclusionsIn breast cancer patients with few brain metastases, radiosurgery plus whole-brain radiotherapy resulted in significantly better freedom from new brain metastases than radiosurgery alone. However, this advantage did not lead to significantly better survival.

The role of additional radiotherapy for primary central nervous system lymphoma.

Prior to the introduction of the chemotherapeutic agent methotrexate, radiotherapy was the sole, first-line option for the treatment of individuals with primary central nervous system lymphoma (PCNSL), Now that methotrexate is available, the role of radiotherapy in the treatment of PCNSL has been called into question. Although various studies suggest promising results with regard to overall and progression-free survival with the use of chemotherapeutic regimens alone as well as in combination with radiotherapy, no evidence-based standard regimen has yet been defined. The objective of this review was to assess and summarise the evidence available regarding the efficacy and tolerability of radiotherapy in addition to chemotherapy in the treatment of immunocompetent individuals with PCNSL. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 01.2014), MEDLINE from January 1950 to February 2014 and conference proceedings from 2005 to 2013. We included randomised controlled trials (RCTs) comparing chemotherapy plus radiotherapy with chemotherapy alone in individuals with PCNSL. Outcomes defined in this review were overall survival, progression-free survival, response to treatment, adverse events, treatment related mortality and quality of life. We excluded trials in which the chemotherapy regimen differed between treatment arms, trials in which fewer than 80% of participants had PCNSL or those recruiting immunocompromised individuals with PCNSL. Two review authors independently screened the results of the search strategies for eligibility for this review. Both assessed risk of bias. Where relevant data was unavailable, we contacted the investigator by email. Of the 556 potentially relevant studies only two met the inclusion criteria. One of those was excluded as the trial was abandoned prematurely and reported only preliminary results. The only analysed trial enrolled 551 participants receiving first-line chemotherapy (methotrexate) followed by whole brain radiotherapy (WBR) or receiving chemotherapy only (methotrexate followed by cytarabine in case of incomplete response). In this non-inferiority trial, the intention-to-treat (ITT) population consisted of 411 participants and the per-protocol (PP) population of 318 participants. We judged the potential for risk of bias in this open-label study as moderate.The estimated effect of chemotherapy plus WBR on survival was similar to that with chemotherapy alone but due to a wide CI we could not rule out the superiority of either therapy. This applied to both the ITT population (HR 1.01, 95% CI 0.79 to 1.30; P = 0.94) and the PP population (HR 1.06, 95% CI 0.80 to 1.40; P = 0.71) (moderate-quality evidence). Due to the low number of participants and a risk of detection bias we found low-quality evidence for an improvement in progression-free survival in participants in the ITT population receiving WBR in addition to chemotherapy (HR 0.79, 95% CI 0.63 to 0.99; P = 0.041). An improvement in PFS was also observed with WBR plus chemotherapy in participants in the PP population, but the CI was slightly wider and the result not significant (HR 0.82,95% CI 0.64 to 1.07; P = 0.14). Treatment-related mortality and health-related quality of life were not evaluated. Treatment-related neurotoxicity was assessed clinically in 79 participants, revealing signs of neurotoxicity in 49% of those receiving chemotherapy plus radiotherapy and in 26% of those receiving chemotherapy only (RR 1.85, 95% CI 0.98 to 3.48; P = 0.054) (very-low-quality evidence). In summary, the currently available evidence (one RCT) is not sufficient to conclude that WBR plus chemotherapy and chemotherapy alone have similar effects on overall survival in people with PCNSL. The findings suggest that the addition of radiotherapy (WBR) to chemotherapy may increase progression-free survival, but may also increase the incidence of neurotoxicity compared to chemotherapy only (methotrexate monotherapy). As the role of chemoradiotherapy in the treatment of PCNSL remains unclear, further prospective, randomised trials are needed before definitive conclusions can be drawn.

Abstract ES09-3: Symptom management and quality of life in metastatic breast cancer

Abstract Approximately 40,000 women in the US die each year of metastatic breast cancer. Because the disease is incurable at this stage, effective symptom management and preservation of quality of life are paramount for these patients. For those with brain metastases, consideration of cognition, quality of life, and overall survival are extremely important because some subsets of patients with breast cancer metastases to the brain may now enjoy prolonged survival of almost 2 years. For solitary brain metastasis, surgical resection followed by whole brain radiotherapy is known to prolong survival, though the addition of whole brain radiotherapy is associated with significant cognitive impairment and decreased quality of life without clear improvement in overall survival. Stereotactic radiosurgery (SRS) shows promise as a therapeutic option for patients with asymptomatic, smaller brain lesions. SRS, as compared to open surgery, results in improved quality of life. Bone metastasis is another common management dilemma for breast cancer patients. Commonly used bone agents, such as bisphosphonates and RANK ligand inhibitors, are known to decrease bone pain and increase quality of life, as well as reduce skeletal-related events. However, safe and optimal duration of bisphosphonates or RANK ligand inhibitors remains unclear in the metastatic breast cancer population. Finally, we will discuss quality measures for delivering end of life care, trends in the country, and methods for improving end of life care with goals of earlier hospice referrals and less treatments at end of life which lead to hospitalizations or ICU stays. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES09-3.

Radiothérapie cérébrale postopératoire : indication de l’irradiation en conditions stéréotaxiques

The addition of whole-brain radiotherapy is a standard of care for patients with single, resectable intracranial metastasis. Stereotactic irradiation of the postoperative resection cavity seems to offer excellent local control rates and avoid the neurocognitive risks of whole-brain radiation therapy. The risk of remote intracranial recurrence imposes a strict surveillance imaging in order to proceed to a possible irradiation before a symptomatic stage. It must be validated in future randomized trials.

Brain metastases as the first symptom of lung cancer: a clinical study from an Asian medical center

Brain metastasis as the first symptom of lung cancer is a unique clinical entity. We conducted a retrospective study to investigate the clinical characteristics and survival of patients with lung cancer whose first symptom was brain metastases in an Asian population. A retrospective study of 186 such patients who had been admitted to one institution in China between January 1, 2003 and December 30, 2008 was performed. The following data were collected and analyzed: manifesting signs and symptoms, imaging studies, extracerebral metastases, initial diagnosis, treatment, and patient survival. This sample population exhibited high rates of misdiagnosis upon initial presentation (46.8 %). Fifty-seven (30.6 %) patients presented with silent extracerebral metastases. Pathologies among this cohort varied, and adenocarcinomas were most commonly observed. Most patients received surgical resection, and some patients had additional whole-brain radiotherapy or stereotactic radiosurgery. The median survival time for the entire cohort was 15 months (95 % confidence interval, 12.9-17.1 months). Survival rates for 1, 2, and 5 years were 58.2, 34.2, and 6.5 %, respectively. The median survival time was 15, 14, 19, and 7 months for the gross total resection, incomplete resection, surgery + whole-brain radiotherapy, and surgery + stereotactic radiosurgery groups, respectively. Brain metastasis as the first symptom of lung cancer is a distinct clinical entity. Although overall survival was poor, combined treatments based on surgery for selected patients were reasonable with the exception of a minority who experienced long-term survival.

Leptomeningeal seeding in patients with brain metastases treated by gamma knife radiosurgery

To characterize the development of leptomeningeal seeding (LMS) in patients with brain metastases after gamma knife radiosurgery (GKRS). Eight hundred and twenty-seven patients that underwent GKRS as a part of an initial treatment plan for brain metastases between January 2002 and December 2010 were included in the study. Six hundred and fifty patients were treated with GKRS alone and 177 patients received GKRS combined with upfront whole brain radiation therapy (WBRT). Actuarial curves for overall survival (OS) and the development of LMS were plotted using the Kaplan-Meier method. Median overall survival for all patients was 55 weeks (95 % CI, 47.8-62.2), and the overall incidence of LMS was 5.3 %. The actuarial rates for LMS at 6 and 12 months were 3.1 and 5.8, respectively. Uni- and multivariate analysis suggested that breast cancer and a large number of metastases (n ≥ 4) are significant risk factors of LMS (P < 0.05). Regarding treatment modalities, the addition of WBRT was found to have a significant impact on lowering the risk of LMS by multivariate analysis (P = 0.045). LMS is an important pattern of CNS failure. The risk of LMS following GKRS may be associated with multiple lesions, breast cancer, and the omission of WBRT. Additional data from large-scale, randomized controlled trials are required to identify risk factors associated with the LMS more accurately.

Do patients with a limited number of brain metastases need whole-brain radiotherapy in addition to radiosurgery?

About 40% of patients with brain metastases have a very limited number of lesions and may be candidates for radiosurgery. Radiosurgery alone is superior to whole-brain radiotherapy (WBRT) alone for control of treated and new brain metastases. In patients with a good performance status, radiosurgery also resulted in better survival. However, the question is whether the results of radiosurgery alone can be further improved with additional WBRT. Information for this review was compiled by searching the PubMed and MEDLINE databases. Very important published meeting abstracts were also considered. Based on both retrospective and prospective studies, the addition of WBRT to radiosurgery improved control of treated and new brain metastases but not survival. However, because a recurrence within the brain has a negative impact on neurocognitive function, it is important to achieve long-term control of brain metastases. The addition of WBRT provides significant benefits. Further randomized studies including adequate assessment of neurocognitive function and a follow-up period of at least 2years are needed to help customize the treatment for individual patients.