Abstract
Background
Because of the increased risk in cancer patients of developing complications caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), physicians have to balance the ...competing risks of the negative impact of the pandemic and the primary tumor disease. In this consensus statement, an international group of experts present mitigation strategies and treatment guidance for patients suffering from high grade gliomas (HGGs) during the coronavirus disease 2019 (COVID-19) pandemic.
Methods Sixteen
international experts in the treatment of HGG contributed to this consensus-based practice recommendation, including neuro-oncologists, neurosurgeons, radiation oncologists, and a medical physicist. Generally, treatment of neuro-oncological patients cannot be significantly delayed and initiating therapy should not be outweighed by COVID-19. We present detailed interdisciplinary treatment strategies for molecular subgroups in 2 pandemic scenarios, a scale-up phase and a crisis phase.
Conclusion
This practice recommendation presents a pragmatic framework and consensus-based mitigation strategies for the treatment of HGG patients during the SARS-CoV-2 pandemic.
Brain metastases are associated with significant morbidity and mortality. Population-level data describing the incidence and prognosis of patients with brain metastases are lacking. The aim of this ...study was to characterize the incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy using recently released data from the Surveillance, Epidemiology, and End Results (SEER) program.
We identified 1302166 patients with diagnoses of nonhematologic malignancies originating outside of the CNS between 2010 and 2013 and described the incidence proportion and survival of patients with brain metastases.
We identified 26430 patients with brain metastases at diagnosis of cancer. Patients with small cell and non-small cell lung cancer displayed the highest rates of identified brain metastases at diagnosis; among patients presenting with metastatic disease, patients with melanoma (28.2%), lung adenocarcinoma (26.8%), non-small cell lung cancer not otherwise specified/other lung cancer (25.6%), small cell lung cancer (23.5%), squamous cell carcinoma of the lung (15.9%), bronchioloalveolar carcinoma (15.5%), and renal cancer (10.8%) had an incidence proportion of identified brain metastases of >10%. Patients with brain metastases secondary to prostate cancer, bronchioloalveolar carcinoma, and breast cancer displayed the longest median survival (12.0, 10.0, and 10.0 months, respectively).
In this study we provide generalizable estimates of the incidence and prognosis for patients with brain metastases at diagnosis of a systemic malignancy. These data may allow for appropriate utilization of brain-directed imaging as screening for subpopulations with cancer and have implications for clinical trial design and counseling of patients regarding prognosis.
Purpose
Application of linear‐quadratic (LQ) model to large fractional dose treatments is inconsistent with observed cell survival curves having a straight portion at high doses. We have proposed a ...unified multi‐activation (UMA) model to fit cell survival curves over the entire dose range that allows us to calculate EQD2 for hypofractionated SBRT, SRT, SRS, and HDRB.
Methods
A unified formula of cell survival S=n/eDDo+n‐1 using only the extrapolation number of n and the dose slope of Do was derived. Coefficient of determination, R2, relative residuals, r, and relative experimental errors, e, normalized to survival fraction at each dose point, were calculated to quantify the goodness in modeling of a survival curve. Analytical solutions for α and β, the coefficients respectively describe the linear and quadratic parts of the survival curve, as well as the α/β ratio for the LQ model and EQD2 at any fractional doses were derived for tumor cells undertaking any fractionated radiation therapy.
Results
Our proposed model fits survival curves of in‐vivo and in‐vitro tumor cells with R2 > 0.97 and r < e. The predicted α, β, and α/β ratio are significantly different from their values in the LQ model. Average EQD2 of 20‐Gy SRS of glioblastomas and melanomas metastatic to the brain, 10‐Gy × 5 SBRT of the lung cancer, and 7‐Gy × 5 HDRB of endometrial and cervical carcinomas are 36.7 (24.3–48.5), 114.1 (86.6–173.1),, and 45.5 (35–52.6) Gy, different from the LQ model estimates of 50.0, 90.0, and 49.6 Gy, respectively.
Conclusion
Our UMA model validated through many tumor cell lines can fit cell survival curves over the entire dose range within their experimental errors. The unified formula theoretically indicates a common mechanism of cell inactivation and can estimate EQD2 at all dose levels.
Whole-brain radiation therapy (WBRT) is the standard of care after resection of a brain metastasis. However, concern regarding possible neurocognitive effects and the lack of survival benefit with ...this approach has led to the use of stereotactic radiosurgery (SRS) to the resection cavity in place of WBRT. We report our initial experience using an image-guided linear accelerator-based frameless stereotactic system and review the technical issues in applying this technique.
We retrospectively reviewed the setup accuracy, treatment outcome, and patterns of failure of the first 18 consecutive cases treated at Brigham and Women's Hospital. The target volume was the resection cavity without a margin excluding the surgical track.
The median number of brain metastases per patient was 1 (range, 1-3). The median planning target volume was 3.49 mL. The median prescribed dose was 18 Gy (range, 15-18 Gy) with normalization ranging from 68% to 85%. In all cases, 99% of the planning target volume was covered by the prescribed dose. The median conformity index was 1.6 (range, 1.41-1.92). The SRS was delivered with submillimeter accuracy. At a median follow-up of 12.7 months, local control was achieved in 16/18 cavities treated. True local recurrence occurred in 2 patients. No marginal failures occurred. Distant recurrence occurred in 6/17 patients. Median time to any failure was 7.4 months. No Grade 3 or higher toxicity was recorded. A long interval between initial cancer diagnosis and the development of brain metastasis was the only factor that trended toward a significant association with the absence of recurrence (local or distant) (log-rank p = 0.097).
Frameless stereotactic irradiation of the resection cavity after surgery for a brain metastasis is a safe and accurate technique that offers durable local control and defers the use of WBRT in select patients. This technique should be tested in larger prospective studies.
Management paradigms now allow for systemic targeted drugs before central nervous system (CNS)-directed radiation therapy (RT) in selected asymptomatic patients with non-small cell lung cancer ...(NSCLC) and brain metastases (BM). We aimed to quantify how novel targeted agents with improved CNS activity, such as second-generation anaplastic lymphoma kinase (ALK) inhibitors (eg, alectinib), might affect the role of CNS-directed RT.
This retrospective, observational, real-world, patterns-of-care study used a nationwide, electronic, health record-derived, de-identified, longitudinal database. A random sample of patients with ALK+ advanced NSCLC and BM on first-line ALK-inhibitor monotherapy between January 1, 2014 and August 31, 2019 were included. Using an index date of the first instance of BM, the outcome was brain-directed local treatment within 4 months. Trends over time were reported and tested using multivariable modified Poisson regression with robust error variance, including an indicator during or after 2017 (when alectinib was approved).
Of the 352 included patients, 146 had BM. In addition, 104 patients received CNS-directed local therapy, and 42 did not. The majority of patients (89.4%) were treated with RT alone. Of those receiving RT, stereotactic radiosurgery monotherapy was the most common (53%), followed by whole brain RT alone (39%). On multivariable analysis, patients who had their first BM during or after 2017 had a decreased rate of receiving local BM treatment versus those before 2017 with an adjusted incidence rate ratio of 0.63 (95% confidence interval CI, 0.41-0.95; P = .026). We found no change in the proportion of BM treated with whole brain RT during or after 2017 versus before (adjusted incidence rate ratio: 0.70; 95% CI: 0.24-2.06; P = .517).
We found decreasing use of CNS-directed RT in patients with NSCLC with new BM on first-line ALK inhibitors. Clinical outcomes for these patients require continued investigation, because physicians may become increasingly comfortable deferring upfront local therapy for BM in lieu of novel targeted agents with improved CNS activity.
First-line treatment for nonalcoholic fatty liver disease (NAFLD) focuses on weight loss through lifestyle modifications.1,2 Weight loss ≥5% results in reduction of steatosis and weight loss ≥10% has ...been associated with improvement in hepatic inflammation and fibrosis.3 The incidence and sustainability of weight loss among patients with NAFLD were estimated and associating factors identified.
To study the ability of dual phase FDG-PET/CT imaging to accurately distinguish tumor versus necrosis in patients treated for brain metastases. 32 (22 female, 10 male) consecutive patients with ...treated brain metastases, lesion size greater than 0.5 cm
3
and suspected recurrence on MRI underwent dual-phase FDG-PET/CT. Clinical outcome was assessed by biopsy or by MRI. SUVmax and SUVmean values of the lesion (L) and gray matter (GM) at the level of the thalamus were measured on early (1) and delayed (2) imaging. L1/GM1 and L2/GM2 and the change of L/GM ratios as a function of time were calculated (L2/GM2 − L1/GM1)/(L1/GM1). Cut-off values were obtained by ROC analysis.
P
< 0.05 defined statistical significance. Seven patients were excluded due to indeterminate outcomes. 25 patients (16 female, 9 male; 27 lesions; 28 scan sessions) had clear outcomes, proven by either biopsy (
n
= 16 patients) or serial follow-up MRI (
n
= 9 patients). Primary subtypes included breast (
n
= 9), lung (
n
= 7), melanoma (
n
= 3), squamous cell cancer of the head and neck (
n
= 2) and other (
n
= 4). Twenty-two patients underwent prior radiation (2–113 months) and three received only prior chemotherapy (5 months to 3 years). A change >0.19 of L/GM ratios as a function of time was 95% sensitive, 100% specific, and 96.4% accurate (
P
= 0.0001; AUC = 0.97) for distinguishing tumor versus radiation necrosis. The ratio of the change of the lesion to WM ratios over time was the second best indicator of outcome when compared to all indices used (ROC cut-off = 0.25, sensitivity 89.5% and specificity 90.9%, and accuracy 89.2%;
P
= 0.0001; AUC = 0.95), Early or late SUVs of the lesion alone did not differentiate between tumor and necrosis. Regardless of histological type, differentiation of necrosis from metastatic brain lesions was improved by using the change of lesion to gray matter SUVmax ratios as a function of time.
Purpose of Review
To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC).
Recent Findings
Local treatment has evolved from whole-brain ...radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1–4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for
ALK
rearranged NSCLC have demonstrated improved CNS penetration and activity. Current brain metastasis trials are focused on reducing cognitive toxicity: hippocampal sparing WBRT, SRS for 5–15 metastases, pre-operative SRS, and use of systemic targeted agents or immunotherapy.
Summary
The role for radiotherapy in the management of brain metastases is becoming better defined with local treatment shifting from WBRT to SRS alone for limited brain metastases and post-operative SRS for resected metastases. Further trials are warranted to define the optimal integration of newer systemic agents with local therapies.
In regard to Fokas et al Weiss, Stephanie E
International journal of radiation oncology, biology, physics,
12/2014, Letnik:
90, Številka:
5
Journal Article
The American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for image-guided radiation therapy (IGRT). IGRT ...is radiation therapy that employs imaging to maximize accuracy and precision throughout the entire process of treatment delivery with the goal of optimizing accuracy and reliability of radiation therapy to the target, while minimizing dose to normal tissues.
The ACR-ASTRO Practice Parameter for IGRT was revised according to the process described on the ACR website ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parametersand-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the ASTRO. Both societies then reviewed and approved the document.
This practice parameter is developed to serve as a tool in the appropriate application of IGRT in the care of patients with conditions where radiation therapy is indicated. It addresses clinical implementation of IGRT including personnel qualifications, quality assurance standards, indications, and suggested documentation.
This practice parameter is a tool to guide clinical use of IGRT and does not make recommendations on site-specific IGRT directives. It focuses on the best practices and principles to consider when using IGRT effectively, especially with the significant increase in imaging data that is now available with IGRT. The clinical benefit and medical necessity of the imaging modality and frequency of IGRT should be assessed for each patient.
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