Whole brain radiation survival rate quiz,american gangster movie online megavideo,what is my national geographic account number - Good Point

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Purpose: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT) in patients with brain metastases treated with stereotactic radiosurgery (SRS) as their initial radiotherapy approach. Materials and methods: Patients with brain metastases treated with SRS from 2001 to 2013 at our institution were identified.
Conclusion: A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. The appropriate upfront radiotherapy approach for newly diagnosed brain metastases is currently controversial with options that include whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), or both (5–9).
In compliance with institutional review board approval, the records of patients with brain metastases treated with SRS at our institution between 2001 and 2013 were reviewed. Patients were seen in follow-up approximately 1 month after their SRS procedure and every 3 months following their initial post-procedure visit. Actuarial local and distant CNS failures and overall survival were calculated using the Kaplan–Meier method. Three hundred and eight patients were treated with SRS alone and fit inclusion criteria for analysis. The variables significantly associated with favorable WBRT-free survival identified by the univariate analyses were further evaluated with a multivariate binary logistic regression analysis (Table 2). Stereotactic radiosurgery alone has been adopted by many to treat patients with limited brain metastases and expected survival ≥3 months. Several nomograms have been developed to predict survival in patients with brain metastases.
Our study aimed to identify patient, disease, and treatment variables that might predict for patients who are likely to not only have prolonged survival, but also are unlikely to require salvage WBRT. In this study, predictors of ≥1 year WBRT-free survival on univariate analyses included younger age, RPA class I, breast primary, new or controlled primary, asymptomatic presentation, surgical resection of a brain metastasis, fewer brain metastases, absence of extracranial metastases, and oligometastatic disease.
The concept of oligometastatic disease was initially described by Hellman and Weichselbaum in 1995 (17). Another interesting, but not surprising, finding from our analysis is the relationship between primary tumor type and WBRT-free survival. The interpretation of our results is limited by the retrospective nature and non-randomized study design, which introduces multiple well-described biases in data collection and analysis (30).
Our results identify several variables related to intracranial and systemic disease burden that can help select patients that are likely to achieve prolonged survival and less likely to require salvage WBRT.
Aim: To report the survival outcomes of patients with multiple brain metastases treated with whole-brain radiotherapy.
The Treatment of Metastatic Non-small Cell Lung Cancer (NSCLC) in New Era of Personalised Medicine. Brain metastases (BM) are a common and lethal complication of non-small cell lung cancer (NSCLC), which portend a poor prognosis. Despite these grim realities, there is room for optimism among identifiable subsets of these patients. Several variables have been established of prognostic importance in determining potential outcomes for patients harboring BM.
Since then, several other scoring classifications have been described (4, 8–11) as shown in Table 1.
Early integration of palliative care in the management of metastatic NSLCC has been demonstrated to improve both quality of life and mood, and is associated with improved survival despite less aggressive end of life treatment (15).
Up to few decades ago, surgical resection was mainly used to establish a diagnosis or to alleviate mass-effect symptoms. In two of these trials (17, 18), a survival benefit was reported for patients undergoing the combined approach. It should be mentioned that all of these randomized studies had small patient numbers and did not include relatively radiosensitive tumors such as small cell lung cancer, lymphoma, myeloma, and germ cell tumors.
Despite these limitations, the current level 1 evidence supports the use of WBRT post-surgical resection in patients with a single, resectable lesion, good performance, and limited extracranial disease. A follow-up trial by Patchell and colleagues (24) addressed the real need of WBRT post-resection of a single brain metastasis. One major concern with the use of WBRT is the risk of neurocognitive deficits, particularly short-term memory. Recent approaches to reduce the potentially negative effects of WBRT on cognitive function include the concomitant use of memantine (20) and hippocampal sparing during WBRT (21). Stereotactic radiosurgery (SRS) delivers a single high dose of irradiation to the target volume while avoiding the surrounding normal tissues.
Despite differences in patient selection and treatment design, all trials consistently show no significant difference in survival, but have shown a significant reduction in intracranial failures and death from brain causes. Whether SRS can replace WBRT in newly diagnosed BM remains to be determined and treatment decisions should be individualized taking into consideration the patients’ wishes, age, intra and extracranial disease extent, and prognosis.
Due to the failure of most drugs to cross the intact blood–brain barrier (BBB), the role of chemotherapy in the treatment of BM has been viewed critically (2). More recently, two phase II trials have examined the use of cisplatin and pemetrexed for the treatment of NSCLC with BM. The use of drugs targeting the proteins of mutated EGFR and anaplastic lymphoma kinase (ALK) genes has become standard of care in the systemic treatment of metastatic NSCLC (42).
The ALK-inhibitor crizotinib has also demonstrated strong anti-tumor activity systemically.
The mutation status of tumors is usually derived from biopsies obtained at extracranial sites, and thus, does not necessarily guarantee a mutation in the sub-clones within the brain.
Just as targeted therapy with EGFR and ALK inhibitors is highly active systemically among molecularly selected NSCLC patients, there is mounting evidence that this is also true for activity intra-cranially. The management of patients with BM has evolved over the years from an under-studied area to a field of exciting active research.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Successful heart surgery at We Care India partner hospital allows Robert Clarke to live a normal life despite a rare genetic disorder We Care india helped Robert find best super specialised surgeon for his rare condition. Metastatic brain tumors occur more frequently than primary brain tumors and occur in approximately 25% of patients who die of cancer each year.
Two prospective randomized trials have shown a significant survival benefit for patients undergoing surgical resection of single tumors in combination with WBRT compared to patients receiving WBRT alone. Although there have been no prospective randomized studies comparing SRS and WBRT to WBRT alone, there have been numerous large retrospective series reporting a significant survival benefit from SRS.
Metastatic brain disease is a focal disease and focal control of the tumor is paramount to patient survival. Metastatic liver cancer most commonly originates in the lungs, breasts, large intestine, pancreas, or stomach.
Headache is caused by stretching of sensitive structures such as blood vessels or nerves due to edema, spinal fluid obstruction or tumor growth, or by injury to the brain caused by the tumor.
This information is not designed to replace a physician's independent judgment about the appropriateness or risks of a procedure for a given patient. We Care Health Services - India - Mumbai (Bombay), Chennai (Madras), Hyderabad, Kokatta, Delhi, Bangalore.
This means that you will not need to remember your user name and password in the future and you will be able to login with the account you choose to sync, with the click of a button. This page doesn't support Internet Explorer 6, 7 and 8.Please upgrade your browser or activate Google Chrome Frame to improve your experience. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone.
With recent improvements in life-prolonging systemic therapies, the incidence of brain metastases is increasing (2). Given the potential late neurocognitive effects associated with WBRT, it would be particularly attractive to avoid it in patients with longer life expectancies (10–13). Several tools have been developed to estimate survival; however, there are no available methods that predict which patients are likely to achieve long-term survival without the need for salvage WBRT (3, 4, 14, 15). Occasionally, patients were found to have additional occult metastases at the time of SRS and >4 lesions were treated with SRS alone. Age distribution, number of brain metastases, and size of brain metastases were evaluated by two-tailed t-tests with Welch’s correction.
When controlling for covariates, independent predictors of favorable WBRT-free survival were asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden. We intentionally selected two groups of patients with the contrasting outcomes after SRS alone. On multivariate analysis, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained significantly associated with prolonged WBRT-free survival.
It is defined as a state between local-regional disease and wide-spread metastatic disease where metastases are few in number.
Multiple prior reports have demonstrated that compared to other histologies, overall survival outcomes are relatively better in patients with breast cancer (4, 27). In order to post comments, please make sure JavaScript and Cookies are enabled, and reload the page.


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In addition, their management implies several challenges including preservation of neurological and neurocognitive function during surgery or radiation-therapy, minimizing iatrogenic complications of supportive medications, and optimizing drug delivery across the blood–brain barrier.
A recent published series of NSCLC patients with synchronous BM receiving surgery or radiosurgery to the brain and aggressive management of their extracranial disease reported a median overall survival (OS) of 12.1 months (5).
In 1997, the Radiation Therapy Oncology Group (RTOG) performed a recursive partitioning analysis (RPA) from a historical database of 1200 patients treated with whole-brain radiation therapy (WBRT) from three RTOG BM trials and published a prognostic scoring system (7). All these classifications have limitations, but are able to consistently prognosticate outcomes based on the defined scoring.
In addition, microarray-derived gene signatures provide the potential for even greater prognostic ability (14). In addition to general palliative measures, patients with BM often necessitate additional supportive medications such as steroids and anti-seizure medications. More recently, its definitive role in improving disease control for patients with single, resectable metastasis has been shown to be significant.
Also, these trials were not specific for NSCLC patients, although this histology was the predominant one in all trials. For patients with multiple metastatic lesions, poor performance scores, and extensive systemic disease an evidence-based recommendation for the combined approach cannot be made. The rationale for treating the whole brain is based on the presumption that micro-metastatic deposits of tumor cells are present elsewhere in the brain.
Unfortunately, the real rate and magnitude of neurocognitive deficits post-WBRT has not been properly studied.
Memantine, a potential neuroprotector, was used during EBRT in a recent RTOG randomized trial (20). A randomized trial conducted by the RTOG (22) showed that the addition of SRS to WBRT was superior to WBRT alone in patients with a newly diagnosed single brain lesion. First, there is evidence that the BBB of BM is disrupted, as evidenced by the presence of peritumoral edema and the accumulation of contrast media during computed tomography or magnetic resonance assessments (38, 39). In one trial, 43 chemo-naive NSCLC patients (93% non-squamous histology) with BM received up to six cycles of cisplatin and pemetrexed at standard doses (40). In first-line clinical trials of the EGFR-targeted drugs gefitinib, erlotinib, and afatinib, objective response rates (ORRs) of 55–83% were observed, mostly clustering above 70% (43). In a phase III second-line NSCLC trial of patients with ALK-rearranged tumors randomized to receive crizotinib vs. However, a Chinese study of 136 NSCLC patients with resected BM, in which an EGFR mutation was identified in 57% of the BM, found a concordance rate of 93.3% in the EGFR mutation status between the primary tumor and BM (50). A recent review has examined the use of the EGFR inhibitors gefitinib and erlotinib in BM among NSCLC patients (6). The main treatment goals for patients with brain metastases are the relief of neurological symptoms and long-term control of the tumors. The approach in the past has been to treat metastatic brain disease as a whole brain disease, with whole brain radiation (WBR). Leukemia (a cancer of white blood cells) and lymphoma (a cancer of the lymph system), especially Hodgkin's disease, may involve the liver. Within this context, it is not surprising that local therapy is not routinely recommended for patients presenting with stage IV disease and intact primary tumors. Initially, the headache comes and goes, and is usually more common in the morning, just after awakening. Although the estimated median survival for all patients with brain metastases is only 4–6 months, there is substantial variability in prognosis and a subset of patients enjoy survival times well beyond 1 year (3, 4). It is this group of patients that would have the greatest benefit from an initial approach of SRS alone. Patients who underwent surgical resection followed by SRS to the resection bed were included. Local failure was defined as an enlarging, contrast-enhancing lesion on follow-up MRI at the site of SRS treatment. Disease variables included presence of neurological symptoms, number and location of brain metastases, size of the largest brain metastasis, and the presence and status of extracranial metastatic disease. Chi-square or Fisher’s Exact Tests were used to compare groups based on gender, race, smoking status, neurological symptoms, RPA class, prior surgical resection, location of brain metastases, primary histology, primary disease status, and extracranial disease status. Patients who lived beyond 1 year without WBRT had a median survival of almost 3 years, and only 21% eventually required salvage WBRT. In recent years, the oligometastatic disease state has gained much interest, as these patients have a more favorable prognosis compared to other stage IV patients (18, 19). Furthermore, recent data suggest that molecular subtypes of breast cancer are important in predicting survival, as well as CNS control after SRS alone (28, 29). Despite these challenges, advancements in combined modality approaches can deliver hope of improved overall survival and quality of life for a subset of NSCLC patients with BM. Improved surgical techniques and radiation therapy (RT) technology, as well as more effective systemic treatments and multimodality approaches have led to these superior outcomes.
Three scoring classes were identified based on patients’ Karnofsky performance score (KPS), age, status of primary tumor, and extent of extracranial disease (Table 1).
Irrespective of the scoring classification used, age, performance status, number of brain lesions, and the presence of extracranial metastases are the variables that better define prognosis.
However, many of these biomarkers require further validation, and are not yet ready for entry into routine clinical practice. Corticosteroids can be vital drugs in the control of intracranial edema from BM and the relief of related symptoms.
Three randomized studies (17–19) have addressed the potential therapeutic value of surgical resection by comparing surgery followed by WBRT vs. WBRT is the most frequently used treatment for the management of BM and its use is associated with improvement in neurologic symptoms and decreased neurologic death (25). It has been shown that over 90% of patients with BM had impairment in one or more neurocognitive tests at baseline and prior to WBRT (32). A survival benefit was not seen for patients with two or three metastatic lesions, although local brain control was significantly improved with the addition of SRS.
Second, there is evidence of intracranial tumor response, even to drugs that in healthy systems have little central nervous system penetration. This suggests that primary tumor EGFR status is a very good surrogate for EGFR mutation status of the BM.
Additional areas of active research include techniques to preserve neurocognitive functions with radiotherapy (20, 52), improving the detection and clinical utility of circulating tumor cells (53), and novel systemic approaches including immunotherapy alone (54, 55) or in combination with radiotherapy (56), anti-metabolic agents (57), anti-angiogenesis drugs (58), and novel targeted therapies for a growing list of oncogenic mutations (59). Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of epidermal growth factor receptor-mutant non-small cell lung cancer metastatic to the brain. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials.
Radiosurgery for treatment of brain metastases: estimation of patient eligibility using three stratification systems. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database.
A new scoring system to predicting the survival of patients treated with whole-brain radiotherapy for brain metastases. Glucocorticoids and external beam whole brain radiation therapy (WBRT) comprise the current standard of care and increase median survival from one month to three to six months. Despite the lack of rigorous data, there are proponents for each of these treatment modalities. Because of poor local control of tumor growth when treated solely by WBR, brain metastases in the past were rapidly lethal. Cancers spread to the liver because the liver filters most of the blood from the rest of the body, and when cancer cells break away from a primary cancer, they often enter and travel through the bloodstream. Surgery is reserved for patients who develop complications such as bleeding, ulceration, and infection at the primary tumor site, a type of surgery that historically has been described as "toilette" mastectomy. After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival. The aim of this study is to identify patient, disease, and treatment variables that are associated with prolonged survival free from salvage WBRT. The rates of local failure, distant CNS failure, salvage treatments, and overall survival were evaluated. Target lesions were identified using high-resolution magnetic resonance imaging (MRI) with intravenous gadolinium contrast.
Controlled systemic disease was defined as stable or responding disease on most recent imaging prior to SRS. Based on the independent variables that were significantly associated with 1-year WBRT-free survival on univariate analysis, a multivariate binary logistic regression analysis was performed.
One hundred and four patients (34%) survived beyond 1 year without the need for salvage WBRT, while 56 patients (18%) either died or required WBRT within 3 months.
For the group of patients with potential for long-term survival, late treatment-related neurocognitive morbidity of WBRT must be considered (10–13).


It is important to note that the rate of salvage WBRT is dependent on the criteria used to offer salvage WBRT as compared with other salvage options such as repeat SRS.
In our study, oligometastatic disease was strongly associated with longer WBRT-free survival in both univariate and multivariate analyses. Similarly, patients with widespread disease might be more optimally managed with the upfront incorporation of WBRT.
Moreover, new drugs harnessing our greater understanding of tumor biology promise to build on this hope.
Moreover, many will suffer considerable loss of autonomy due to neurocognitive and functional deficits, as well as morbidity associated with medications such as steroids and anti-epileptic drugs. Moreover, renewed hope has emerged from the use of small-molecule drugs targeting oncogenic mutations, which have shown promising activity both extra-cranially and intra-cranially (6). Given the high heterogeneity of the BM patient population, one should not rely exclusively on these indices when assessing the management for such patients. However, in light of their considerable short- and long-term side effects, steroids should be used judiciously.
The group receiving post-operative WBRT experienced a significantly lower rate of brain recurrence (18 vs.
Proponents of WBRT argue that it is the disease progression in the brain not treated by WBRT that, in fact, compromises the patient’s neurocognitive function.
Given its focal delivery of irradiation, there have been concerns that its isolated use could lead to an increased rate of failure elsewhere in the brain. In a recent review (37), the response rates (RRs) of BM to platinum-based regimens in seven clinical trials of treatment-naïve NSCLC patients were similar to those achieved extra-cranially, ranging from 30 to 50%.
The hematologic toxicities were generally mild or moderate and there were no grade 4 or higher non-hematologic toxicities. In this same cohort of patients, the median OS was 24.5 months in the EGFR mutation group, compared to 15 months in the wild-type group. Similarly, intracranial RRs were 56 and 82% for erlotinib in clinically and molecularly selected patients, respectively. Ultimately, the optimal management strategy will employ a multi-disciplinary approach accounting for individual characteristics of both patient and tumor.
Patients with three or less tumors (greater than 70% of patients) also commonly undergo surgery or stereotactic radiosurgery (SRS) with the goal of lengthening survival. Those in favor of surgery cite the ability to achieve a complete resection in most cases, the almost immediate relief of symptoms, and the low rate of local recurrence.
Therefore patients with brain metastases did not benefit from many advances in cancer therapy (immuno therapy, chemo therapy, conformal radiotherapy etc.) because these therapies do no effectively reach brain metastases and individuals died quickly from neurological progression. Sometimes the discovery of metastatic liver cancer is the first indication that a person has cancer.
In this issue of the Journal of Clinical Oncology, Rapiti et al1 present the results of a retrospective, population-based study of the impact of surgical therapy of the primary tumor on survival outcomes in 300 women with metastatic disease at the time of the initial diagnosis of breast cancer.
Among eligible patients (N = 308), two groups with the most divergent outcomes were selected for comparison.
Distant CNS failure was defined as a new contrast-enhancing lesion outside of the SRS treatment volume. Patients who were treated at initial cancer diagnosis were considered to have stable disease as they have not had an opportunity for systemic therapy. Figure 1 shows the survival curve for the entire group of 308 patients treated with SRS alone and the survival curve for the 104 patients that form the subgroup with ≥1 year WBRT-free survival.
Three randomized phase III trials have evaluated SRS alone compared with WBRT and SRS (5–7). A more recent analysis seeking to better stratify patients is the disease-specific graded prognostic assessment (DS-GPA) (4). In our cohort, repeat SRS was offered only for patients with limited (≤4) new metastases and life-expectancy of at least 3 months, the same criteria as primary treatment. They showed that patients with prolonged survival were significantly more likely to have fewer brain lesions, higher initial performance status, and less extracranial disease.
In the favorable group, over three quarters of the patients had oligometastatic disease compared to only one-third in the poor prognosis group. Although a larger, prospective cohort of patients needs to be studied to confirm these findings, the identified predictive variables can be used to compliment and improve multi-disciplinary decision-making. Generalized R2 statistic (ranged from 0 to 1) was calculated to determine the association with the outcome. In this mini-review, we revised the management of BM in NSCLC including advancements in neurosurgery, radiation therapy, as well as systemic and supportive therapy. A comparative review of five of these prognostic indexes using an artificial neural network in patients with BM and receiving WBRT (12) suggests that the graded prognostic assessment index (10) was the most powerful in predicting survival. Of interest, 11% of patients were excluded because no metastatic disease was seen on the biopsy specimens. However, some patients develop cognitive problems that cannot be simply explained by disease progression elsewhere in the brain. However, concerns with cognitive deficits from WBRT led investigators to use SRS alone in selected patients, reserving WBRT for a later date if necessary.
On the other hand, in the Japanese trial (34), there was a significant decline in mini-mental score when SRS was given alone making the authors conclude that BM control was the most important factor for preserving neurocognitive function. This finding is consistent with other studies identifying EGFR mutation status as a positive prognostic factor among patients with BM (51).
Taken together, these results highlight both robust intracranial activity and the importance of EGFR mutation status as a predictor of intracranial response.
The authors observed that women having surgery of the primary tumor had a 50% reduction in breast cancer mortality compared with women who did not undergo surgery, the survival benefit was limited to women with tumor-free margins of resection, and a significant survival benefit for axillary surgery was not observed. The first group was defined as patients who survived and did not require salvage WBRT for at least 1 year following SRS (N = 104). Dose was prescribed based on tumor size according to Radiation Oncology Therapy Group (RTOG) study 90–05 (16).
The comparison groups had similar SRS doses prescribed for the patients’ largest metastases. The RPA and DS-GPA scoring systems were developed based on patients who were primarily treated with WBRT and not with SRS alone. The authors reported a statistically significant improvement in survival (median survival: 40 vs.
Approximately 60% of patients will experience a complete or partial response with a similar rate for symptoms improvement, though usually transient. Late effects from WBRT are usually seen after 6 months post-treatment and are secondary to white matter damage. Although this was a single arm trial, the declines in cognitive function are less than what was observed from historical controls. In the same review, three trials using temozolomide achieved a RR of only 0–10%, suggesting that the selection of chemotherapy drugs should be based mainly on their established anti-tumor activity to extracranial sites, and not on considerations of BBB penetrance. The second group consisted of patients with poor outcomes, which was defined as patients who either died or required salvage WBRT within 3 months of SRS (N = 56).
The median dose to the tumor margin was 20 Gy (range 14–22) generally prescribed to the 50% isodose line.
RTOG recursive partitioning analysis (RPA) classification was also determined for each patient (3). Two other groups have developed predictive models using large databases of patients treated solely with SRS (14, 15). Considering that many patients will not survive beyond 6 months, it is plausible to consider that cognitive deficits would be seen in larger proportion of patients should they survive longer. Additionally, given the potential acute and late side effects of adding WBRT, it would be ideal to identify a patient cohort that is likely to achieve prolonged survival and yet unlikely to gain benefit from WBRT. Although the aforementioned prognostic systems were based on large numbers of patients and have been validated to estimate overall survival, they do not predict the likelihood of regional failure or the need for salvage WBRT.
A median time to distant CNS failure of only 3 months was seen in our experience treating patients with >10 lesions (23).
We, therefore, have not offered routine salvage SRS for patients with >4 metastases. Although OS was not different between groups, importantly, post-operative WBRT significantly prevented death from neurologic causes (14 vs. Histology (melanoma and HER2 negative breast cancer), progressive systemic disease, number of metastases (4–13 vs. 1–3), and occult metastases at time of SRS were found to be predictive of early time to distant CNS failure.
Our data are consistent with these studies, showing that active disease burden, both in the brain and systemically, is the most influential predictor of WBRT-free survival.



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