In Regard to Wong et al Scarpelli, Daphne B; Murphy, Blair; Chang, Bill H ...
International journal of radiation oncology, biology, physics,
12/2020, Letnik:
108, Številka:
5
Journal Article
Lung cancer remains the leading cause of cancer deaths in the United States and the rest of the world. The advent of molecularly directed therapies holds promise for improvement in therapeutic ...efficacy. Cytosolic phospholipase A2 (cPLA2) is associated with tumor progression and radioresistance in mouse tumor models. Utilizing the cPLA2 specific inhibitor PLA-695, we determined if cPLA2 inhibition radiosensitizes non small cell lung cancer (NSCLC) cells and tumors. Treatment with PLA-695 attenuated radiation induced increases of phospho-ERK and phospho-Akt in endothelial cells. NSCLC cells (LLC and A549) co-cultured with endothelial cells (bEND3 and HUVEC) and pre-treated with PLA-695 showed radiosensitization. PLA-695 in combination with irradiation (IR) significantly reduced migration and proliferation in endothelial cells (HUVEC & bEND3) and induced cell death and attenuated invasion by tumor cells (LLC &A549). In a heterotopic tumor model, the combination of PLA-695 and radiation delayed growth in both LLC and A549 tumors. LLC and A549 tumors treated with a combination of PLA-695 and radiation displayed reduced tumor vasculature. In a dorsal skin fold model of LLC tumors, inhibition of cPLA2 in combination with radiation led to enhanced destruction of tumor blood vessels. The anti-angiogenic effects of PLA-695 and its enhancement of the efficacy of radiotherapy in mouse models of NSCLC suggest that clinical trials for its capacity to improve radiotherapy outcomes are warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Radiation therapy for central nervous system disease commonly involves collaboration between Radiation Oncology and Neurosurgery. We describe our early experience with a multidisciplinary clinic ...model.
In 2016, the novel RADIANS (RADIation oncology And NeuroSurgery) clinic model was initiated at a community hospital. Disease and treatment demographics were collected and analyzed. Patient satisfaction was assessed via a blinded survey questionnaire.
Forty-two patients have been seen since the inception of RADIANS. The median age was 65; and the median patient distance from RADIANS was 42.7 miles (mean = 62.6; range = 0.7–285). Half of the patients traveled >50 miles to receive care, and >80% were seen for central nervous system metastases. Of the patients receiving radiation, 75% received stereotactic radiosurgery/stereotactic body radiation therapy. The mean overall satisfaction from 0 (not satisfied) to 5 (very satisfied) was 4.8.
The RADIANS clinic model has proved viable and well-liked by patients in a community setting, with the majority of radiation therapy administered being stereotactic radiosurgery/stereotactic body radiation therapy rather than conventional fractionation.
Introduction
Single-fraction stereotactic radiosurgery (SRS) is delivered predominantly via two modalities: Gamma Knife, and linear accelerator (LINAC). Implementation of the American Tax Payer ...Relief Act (ATRA) in 2013 represented the first time limitations specifically targeting SRS reimbursement were introduced into federal law. The subsequent impact of the ATRA on SRS utilization in the United States (US) has yet to be examined.
Methods
The National Cancer Database from 2010–2016 identified brain metastases patients from non-small cell lung cancer throughout the US having undergone SRS. Utilization between GKRS and LINAC was assessed before (2010–2012), during (2013–2014) and after (2015–2016) ATRA implementation.
Results
In 2013, there was a substantial decrease of LINAC SRS in favor of GKRS in non-academic centers. Over the 3-year span immediately preceding ATRA implementation, 39% of all eligible SRS cases received LINAC. There was a modest decrease in LINAC utilization over the 2 years immediately following ATRA implementation (35%), followed by an increase over the next two years (40%). SRS modality showed differences over the three time periods (unadjusted, p = 0.043), primarily in non-academic centers (unadjusted, p = 0.003).
Conclusions
ATRA implementation in 2013 caused an initial spike in Gamma Knife SRS utilization, followed by a decline to rates similar to the years before implementation. These findings indicate that the ATRA provision mandating Medicare reduction of outpatient payment rates for Gamma Knife to be equivalent with those of LINAC SRS had a significant short-term impact on the radiosurgical treatment of metastatic brain disease throughout the US, serving as a reminder of the importance/impact of public policy on treatment modality utilization by physicians and hospitals.
•Spinal SBRT has rapidly increased in popularity for treatment of spinal metastases.•The most common primary metastasis source was the lung.•74% of patients treated had no medical ...comorbidities.•Nearly 90% of patients had private insurance or Medicare.•The most common administration was a single-fraction of radiation.
Nationwide utilization of spinal stereotactic body radiotherapy (SBRT) is not known; to address this void, the National Cancer Data Base (NCDB) from 2004 to 2013 was used for analysis. Spinal SBRT was defined as 1–5 fractions (14–32Gy) delivered to the cervical, thoracic, lumbar or sacral spine. From 2004 to 2013, 1044 patients received spinal SBRT, most commonly in single-fraction (38%), three-fraction (26%) and five-fractions (25%). Metastatic spinal disease most commonly originated from the lung (34%), kidney (14%), and blood (9%). The most common insurance status receiving spinal SBRT was private (44%) followed by Medicare (43%), with Medicaid (8%) a distant third. Fifty-six percent of patients were male, and 55% of patients were younger than age 65. 80% of patients were Caucasian, with 13% being African-American. The vast majority (74%) of patients had no Charlson/Deyo comorbidities. The incidence of spinal SBRT gradually increased over time, rising from 2% to 20% of cases from 2004 to 2013. Comprising only 1.4% of spinal metastases radiation in 2004, SBRT rose to a 5.8% share in 2013. In conclusion, SBRT for spine metastases in the United States has more than quadrupled in utilization over a recent ten-year span. Although the majority of spinal SBRT is multi-fraction, the most popular fractionation scheme was single-fraction. It has been most commonly used for Caucasian men under age 65 with private/Medicare insurance and no comorbidities. By far the most common origin of spinal metastases treated by SBRT was the lung, followed by renal cancer. These results provide a baseline for further prospective investigation.
Highlights • Stereotactic radiosurgery and resection of spinal hemangioblastomas are reviewed. • SRS achieves stable or reduced tumor size with little adverse clinical outcome. • Surgical resection ...achieves tumor removal and improved long-term clinical effect. • Authors propose use of a national registry to allow for more accurate future analysis.
Abstract Introduction African Americans experience the highest burden of cancer incidence and mortality in the United States and have been persistently less likely to receive interventional care, ...even when such care has been proven superior to conservative management by randomized controlled trials. The presence of disparities in access to radiation therapy (RT) for African American cancer patients has rarely been examined in an expansive fashion. Methods and materials An extensive literature search was performed using the PubMed database to examine studies investigating disparities in RT access for African Americans. Results A total of 55 studies were found, spanning 11 organ systems. Disparities in access to RT for African Americans were most prominently study in cancers of the breast (23 studies), prostate (7 studies), gynecologic system (5 studies), and hematologic system (5 studies). Disparities in RT access for African Americans were prevalent regardless of organ system studied and often occurred independently of socioeconomic status. Fifty of 55 studies (91%) involved analysis of a population-based database such as Surveillance, Epidemiology and End Result (SEER; 26 studies), SEER-Medicare (5 studies), National Cancer Database (3 studies), or a state tumor registry (13 studies). Conclusions African Americans in the United States have diminished access to RT compared with Caucasian patients, independent of but often in concert with low socioeconomic status. These findings underscore the importance of finding systemic and systematic solutions to address these inequalities to reduce the barriers that patient race provides in receipt of optimal cancer care.
A number of cell death pathways have been recognized. Though apoptosis and autophagy have been well characterized, programmed
necrosis has recently received attention and may provide clinical ...alternatives to suppress resistant tumors. Necrosis is primarily
characterized by large-scale permeabilization, swelling, and rupture of cell membranes and the release of pro-inflammatory
cytokines. Traditionally, necrosis in cancer cells has been indicative of poor prognoses, as chronic inflammation was found
to encourage tumor growth. Yet, many antitumor effects associated with necrosis have been discovered in certain settings,
such as the formation of an effective antitumor immune response. In this way, finding ways to attenuate the pro-tumor effects
of necrosis while engaging the antitumor pathways via drugs, radiation, and sensitization may prove valuable as a clinical
focus for the future. We hypothesize that the use of Bcl-2 inhibitors may enhance necrotic death characterized by inflammation
and antitumor immunity. In this article, we briefly review apoptosis and autophagy and reason how necrosis may be a suitable
alternative therapeutic endpoint. We then highlight novel inhibitors of Bcl-2 that may provide clinical application of our
hypothesis in the future. Mol Cancer Ther 2009;8(6):1421–9
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