NCCTG N0574 (Alliance): A phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases.

Brown, Paul D.; Asher, Anthony L.; Ballman, Karla V.; Farace, Elana; Cerhan, Jane H.; Anderson, S. Keith; Carrero, Xiomara W.; Barker, Frederick G.; Deming, Richard L.; Burri, Stuart H.; Ménard, Cynthia; Chung, Caroline; Stieber, Volker W.; Pollock, Bruce E.; Galanis, Evanthia; Buckner, Jan C.; Jaeckle, Kurt A.

doi:10.1200/jco.2015.33.18_suppl.lba4

Cited by 99 publications

(66 citation statements)

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“…Preliminary findings from a federally funded study have provided new insights into the impact of adjuvant WBRTon cognition (this study was funded by a grant from the NIH). 80 Patients with one to three small brain metastases who received WBRT after SRS were more likely to experience cognitive decline within the first 3 months than those who received SRS alone. Specifically, those who received WBRT had a greater decline in memory and verbal communication.…”

Section: American Society Of Clinical Oncology Continues To Call Formentioning

confidence: 99%

Clinical Cancer Advances 2017: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology

Burstein

Krilov

Aragon‐Ching

et al. 2017

JCO

357

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A MESSAGE FROM ASCO’S PRESIDENT I am pleased to present Clinical Cancer Advances 2017, which highlights the most promising advances in patient-oriented cancer research over the past year. The report gives us an opportunity to reflect on what an exciting time it is for cancer research and how swiftly our understanding of cancer has improved. One year ago, the White House announced the national Cancer Moonshot program to accelerate progress against cancer. This shared vision of progress has reinvigorated the research community, identified new areas of scientific collaboration, and raised our ambitions regarding what may be possible beyond the progress we have already made. When I entered the field 35 years ago, I could not have imagined where we would be today. We can now detect cancer earlier, target treatments more effectively, and manage adverse effects more effectively to enable patients to live better, more fulfilling lives. Today, two of three people with cancer live at least 5 years after diagnosis, up from roughly one of two in the 1970s. This progress has resulted from decades of incremental advances that have collectively expanded our understanding of the molecular underpinnings of cancer. There is no better current example of this than ASCO’s 2017 Advance of the Year: Immunotherapy 2.0. Over the last year, there has been a wave of new successes with immunotherapy. Research has proven this approach can be effective against a wide range of hard-to-treat advanced cancers previously considered intractable. Researchers are now working to identify biologic markers that can help increase the effectiveness of treatment and determine who is most likely to benefit from immunotherapy. This knowledge will enable oncologists to make evidence-based decisions so as many patients as possible might benefit from this new type of treatment. Each successive advance builds on the previous hard work of generations of basic, translational, and clinical cancer researchers. Importantly, the advances described in this report would not have been possible without the individuals who volunteered to participate in clinical trials as part of their treatment. To turn the promising vision of a cancer moonshot into meaningful advances, we need sustained, robust federal funding for continued research and innovation. Approximately 30% of the research highlighted in this report was funded, at least in part, through federal dollars appropriated to the National Institutes of Health or the National Cancer Institute. Without this federal investment—unique internationally in scale, duration, and impact for decades—I fear we may lose the forward momentum needed to further the progress we see highlighted in this report. Federal lawmakers can further fuel progress by advancing initiatives that facilitate the use of big data to achieve the common good of high-quality care for all patients. Such programs, like ASCO’s CancerLinQ, will rapidly increase the pace of progress and dramatically expand the reach of treatment advances to the millions of patients who are living with cancer today or who will do so in the future. This investment will yield medical, scientific, economic, and societal benefits for years to come. Much work still lies ahead. Many questions remain about how cancer develops and spreads and how best to treat it. As you read through Clinical Cancer Advances 2017, I hope you are as inspired as I am by the gains the clinical cancer research community has made over the past year and by the promise of a new era of advances just over the horizon. Daniel F Hayes, MD, FASCO, FACP ASCO President, 2016 to 2017

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Section: American Society Of Clinical Oncology Continues To Call Formentioning

confidence: 99%

Clinical Cancer Advances 2017: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology

Burstein

Krilov

Aragon‐Ching

et al. 2017

JCO

357

View full text Add to dashboard Cite

show abstract

“…Given the minimally invasive nature of SRS, and its ability to treat new additional new lesions over time, SRS, in combination with close follow-up, may increasingly enable avoidance of up-front WBRT in patients with brain metastases. 7 The higher focal doses of radiation employed with SRS, however, are not entirely without consequence. In a recent consecutive series of 271 brain metastases treated with stereotactic radiosurgery, follow-up examination, at a median of 17.2 months, revealed radionecrosis in 25.8% of patients, two-thirds of whom were symptomatic.…”

Section: Multiple Paths To Radiation-induced Brain Injurymentioning

confidence: 99%

“…71 Increasing recognition of the cognitive toll incurred by adults following WBRT is now prompting critical reevaluation of the role of WBRT in adults with brain metastases. 7 At the other extreme, stereotactic radiosurgery (SRS) minimizes off-target radiation exposure, serving as an adjunct to or alternative for discrete resections. Given the minimally invasive nature of SRS, and its ability to treat new additional new lesions over time, SRS, in combination with close follow-up, may increasingly enable avoidance of up-front WBRT in patients with brain metastases.…”

Section: Multiple Paths To Radiation-induced Brain Injurymentioning

confidence: 99%

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

Burns

Awad

et al. 2016

FOC

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Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells. These changes, in combination with a state of chronic neuroinflammation, underlie impairments in memory, attention, executive function, and acquisition of motor and language skills. Animal models of radiation-induced brain injury have demonstrated a robust capacity of both neural stem cells and oligodendrocyte progenitor cells to restore cognitive function after brain irradiation, likely through a combination of cell replacement and trophic effects. Oligodendrocyte progenitor cells exhibit a remarkable capacity to migrate, integrate, and functionally remyelinate damaged white matter tracts in a variety of preclinical models. The authors here critically address the opportunities and challenges in translating regenerative cell therapies from rodents to humans. Although valiant attempts to translate neuroprotective therapies in recent decades have almost uniformly failed, the authors make the case that harnessing human radiation-induced brain injury as a scientific tool represents a unique opportunity to both successfully translate a neuroregenerative therapy and to acquire tools to facilitate future restorative therapies for human traumatic and degenerative diseases of the central nervous system.

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“…These patients either have multiple metastatic lesions or diagnostically challenging asymptomatic lesions, making surgery an inadequate therapeutic option by itself. In addition, the blood-brain barrier (BBB) limits central nervous system (CNS) penetration of systemic therapies, and the negative side effects of radiotherapy (8) pose challenges for the success of existing therapies, contributing to the failure to improve overall patient survival. As such, there is an urgent need for new therapies for melanoma brain metastasis.…”

mentioning

confidence: 99%

Stem cell-released oncolytic herpes simplex virus has therapeutic efficacy in brain metastatic melanomas

Seah

Bougazzoul

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

102

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The recent Food and Drug Administration approval of immunogenic oncolytic virus (OV) has opened a new era in the treatment of advanced melanoma; however, approximately 50% of patients with melanoma develop brain metastasis, and currently there are no beneficial treatment options for such patients. To model the progression of metastases seen in patients and to overcome the hurdles of systemic delivery of OV, we developed melanoma brain metastasis models in immunocompromised and immunocompetent mice, and tested the fate and efficacy of oncolytic herpes simplex virus (oHSV)-armed mesenchymal stem cells (MSCs). Using brain-seeking patient-derived melanoma cells and real-time in vivo imaging, we show a widespread distribution of micrometastases and macrometastases in the brain, recapitulating the progression of multifoci metastases seen in patients. We armed MSCs with different oHSV variants (MSC-oHSV) and found that intracarotid administration of MSC-oHSV, but not of purified oHSV alone, effectively tracks metastatic tumor lesions and significantly prolongs the survival of brain tumor-bearing mice. In a syngeneic model of melanoma brain metastasis, a combination of MSC-oHSV and PD-L1 blockade increases IFNγ-producing CD8 + tumor-infiltrating T lymphocytes and results in a profound extension of the median survival of treated animals. This study thus demonstrates the utility of MSCs as OV carriers to disseminated brain lesions, and provides a clinically applicable therapeutic platform to target melanoma brain metastasis.stem cells | oncolytic virus | tumors | metastasis | imaging M elanoma, the most aggressive type of skin cancer, accounts for a large proportion of skin cancer-related deaths (1). Among all cancer types, melanoma has a particularly high propensity to metastasize to the brain, occurring in >50% of all patients with advanced disease. More than 90% of melanoma brain metastases lead to death, and the median survival is 17-22 wk after detection (2-4).Current therapeutic options of chemotherapy, surgery, and radiation have very limited efficacy for patients with melanoma brain metastasis (5-7). These patients either have multiple metastatic lesions or diagnostically challenging asymptomatic lesions, making surgery an inadequate therapeutic option by itself. In addition, the blood-brain barrier (BBB) limits central nervous system (CNS) penetration of systemic therapies, and the negative side effects of radiotherapy (8) pose challenges for the success of existing therapies, contributing to the failure to improve overall patient survival. As such, there is an urgent need for new therapies for melanoma brain metastasis.The development and characterization of preclinical tumor models that authentically recapitulate the clinical disease settings are critical for developing and testing new therapies. Most previous studies have used either subcutaneous (s.c.) injection or intracranial injection of established melanoma lines in mice (9-11), which do not mimic the actual clinical settings of melanoma brain metastasis,...

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NCCTG N0574 (Alliance): A phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases.

Cited by 99 publications

References 0 publications

Clinical Cancer Advances 2017: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology

Clinical Cancer Advances 2017: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

Stem cell-released oncolytic herpes simplex virus has therapeutic efficacy in brain metastatic melanomas

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