Background
Prior literature has suggested synergy between immune checkpoint therapy (ICT) and radiotherapy (RT) for the treatment of brain metastases (BrM), but to the authors' knowledge the optimal ...timing of therapy to maximize this synergy is unclear.
Methods
A total of 199 patients with melanoma and non–small cell lung cancer with BrM received ICT and RT between 2007 and 2016 at the study institution. To reduce selection biases, individual metastases were included only if they were treated with RT within 90 days of ICT. Concurrent treatment was defined as RT delivered on the same day as or in between doses of an ICT course; all other treatment was considered to be nonconcurrent. Multivariable Cox proportional hazards models were used to assess time to response and local disease recurrence on a per‐metastasis basis, using a sandwich estimator to account for intrapatient correlation.
Results
The final cohort included 110 patients with 340 BrM, with 102 BrM treated concurrently and 238 BrM treated nonconcurrently. Response rates were higher with the use of concurrent treatment (70% vs 47%; P < .001), with correspondingly lower rates of progressive disease (5% vs 26%; P < .001). On multivariable analysis, concurrent treatment was found to be associated with improved time to response (hazard ratio, 1.76; 95% CI, 1.18‐2.63 P = .006) and decreased local recurrence (hazard ratio, 0.42; 95% CI, 0.23‐0.78 P = .006). This effect appeared to be greater for melanoma than for non–small cell lung cancer, although interaction tests were not statistically significant. Only 1 of 103 metastases which had a complete response later developed disease progression.
Conclusions
Concurrent RT and ICT may improve response rates and decrease local recurrence of brain metastases compared with treatment that was nonconcurrent but delivered within 90 days. Further study of this combination in prospective, randomized trials is warranted.
There is significant interest in potential synergy between radiotherapy and immune checkpoint therapy, but the optimal timing of each therapy remains unclear. The current study examines a cohort of patients with melanoma and non–small cell lung cancer with brain metastases who were managed with immune checkpoint therapy and brain‐directed radiotherapy within a 90‐day period. Compared with nonconcurrent therapy, concurrent therapy is associated with an improved brain metastasis response rate and decreased local recurrence.
Background
Up to one‐third of patients with localized Ewing sarcoma (ES) develop recurrent disease, but current biomarkers do not accurately identify this high‐risk group. Therefore, the objective of ...this study was to determine the utility of mutational burden in predicting outcomes in patients with localized ES.
Methods
Clinical and genomic data from 99 patients with ES, of whom 63 had localized disease at diagnosis, were obtained from the cBioPortal for Cancer Genomics. Genomic data included the type and number of somatic mutations using cBioPortal mutation calling. Primary endpoints were overall survival (OS) and the time to progression (TTP).
Results
Patients had a median number of 11 somatic mutations. Patients were stratified according to whether they had a lower or higher mutational burden if they had ≤11 or >11 mutations, respectively. Higher mutational burden was significantly associated with inferior OS and TTP, a finding that was confirmed by univariate and multivariable analyses. In patients who had localized disease at diagnosis, higher mutational burden was the only variable significantly associated with inferior OS and TTP. The presence of a mutation in either stromal antigen 2 (STAG2) or tumor protein 53 (TP53), both of which were correlated previously with shorter OS in patients with ES, were significantly associated with higher mutational burden. Upon stratifying patients who had localized disease based on a standard panel of cancer genes, higher risk stratification was correlated significantly with inferior TTP and trended toward significance with inferior OS.
Conclusions
Patients who have localized ES and a higher mutational burden have inferior OS and TTP compared with those who have lower mutation burden. The current findings suggest that the somatic mutation burden can be used to better risk stratify these patients and to guide clinical decision making.
Higher somatic mutation counts in patients with localized Ewing sarcoma are correlated with worse overall survival and time to progression and likely are independent from global genomic instability. The somatic mutation count may be used to more optimally risk stratify patients who have localized Ewing sarcoma and to guide clinical decision making.
•Pediatric low-grade glioma (pLGG) is a MAPK pathway-altered disease with novel therapeutic options.•Clinical trials are vital in translation of targeted agents to influence patient care.•Targeted ...agents have unknown long-term toxicities and unclear impact on pLGG natural history.•Challenges include rapid clinical trial translation, tumor heterogeneity and need to harmonize molecular profiling techniques.
pLGGs are a group of tumors for which the era of molecular diagnostics has truly shifted treatment paradigms and patient care. The discovery that this group of tumors is driven by single-gene alterations/fusions in the MAPK pathway has resulted in relatively rapid translation into targeted therapy options for patients with this often chronic disease. This translation has been facilitated through efforts of multiple collaboratives and consortia and has led to the development of clinical trials testing the role of targeted therapies in pLGG. Although these developments represent promise, many questions remain regarding these therapies including their long-term toxicities and their potential effects on the natural history of pLGG.
Little is known about the prevalence of pediatric radiation oncologists treating patients off study according to Children's Oncology Group (COG) trials before data are available regarding toxicity ...and efficacy of novel radiotherapy regimens. We conducted a 12‐question survey of 358 pediatric radiation oncologists to characterize practice patterns regarding ongoing and completed COG protocols off study. With 130 responses (40.3%), the prevalence of providing treatment per protocol, but off study, before data are available in or peer‐reviewed form varied from 9.1% (for ACNS1422) to 88.1% (for AHOD1331). Future studies are needed to understand the effects of these practice patterns on outcomes.
WEE1 Kinase As a Target for Cancer Therapy Mueller, Sabine; Haas-Kogan, Daphne A
Journal of clinical oncology,
2015-Oct-20, 2015-10-20, 20151020, Letnik:
33, Številka:
30
Journal Article
Artificial intelligence (AI) has the potential to fundamentally alter the way medicine is practised. AI platforms excel in recognizing complex patterns in medical data and provide a quantitative, ...rather than purely qualitative, assessment of clinical conditions. Accordingly, AI could have particularly transformative applications in radiation oncology given the multifaceted and highly technical nature of this field of medicine with a heavy reliance on digital data processing and computer software. Indeed, AI has the potential to improve the accuracy, precision, efficiency and overall quality of radiation therapy for patients with cancer. In this Perspective, we first provide a general description of AI methods, followed by a high-level overview of the radiation therapy workflow with discussion of the implications that AI is likely to have on each step of this process. Finally, we describe the challenges associated with the clinical development and implementation of AI platforms in radiation oncology and provide our perspective on how these platforms might change the roles of radiotherapy medical professionals.
Central nervous system (CNS) metastases are rare, but devastating complications of pediatric solid tumors. Radiotherapy alone or postresection serves as an important treatment; however, data on the ...use of whole‐brain radiotherapy (WBRT) versus focal radiotherapy, including stereotactic radiosurgery or stereotactic radiotherapy, for these indications are limited. We report a single institution experience of 26 pediatric patients treated with radiotherapy for solid tumor CNS metastases without leptomeningeal disease. Focal radiotherapy (n = 10) was well tolerated and survival outcomes did not differ between patients treated with WBRT (n = 16) versus focal radiation, suggesting that focal radiotherapy may be considered for patients with limited CNS metastases.
High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among ...chromatin regulation, developmental signaling, and tumorigenesis. As we begin to unravel the unique developmental origins and distinct biological drivers of this heterogeneous group of tumors, clinical trials need to keep pace. It is important to avoid therapeutic strategies developed purely using data obtained from studies on adult glioblastoma. This approach has resulted in repetitive trials and ineffective treatments being applied to these children, with limited improvement in clinical outcome. The authors of this perspective, comprising biology and clinical expertise in the disease, recently convened to discuss the most effective ways to translate the emerging molecular insights into patient benefit. This article reviews our current understanding of pediatric high-grade glioma and suggests approaches for innovative clinical management.
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