Patterns of Care and Barriers to Utilization of Definitive Concurrent Chemoradiation Therapy for Stage III Non-Small Cell Lung Cancer in Russia.

BACKGROUND: Definitive concurrent chemoradiation (cCRT) is offered to only 3% of Russian patients with stage III NSCLC. To determine the patterns of care and barriers to cCRT utilization in Russia, we conducted a survey of practicing radiation oncologists (ROs). METHODS: Electronic IRB-approved survey containing 15 questions was distributed to Russian ROs. Fisher's exact test or Cochran-Armitage test of trend was used to assess the associations between clinical experience, practice type, and patterns of care. RESULTS: We analyzed 58 questionnaires completed by ROs-16 respondents from tertiary referral hospitals, and 42 from community or private centers. A total of 88% of respondents formulate treatment recommendations in multi-disciplinary tumor boards. For unresectable stage III NSCLC, the most common recommendation is sequential CRT (50%), followed by concurrent CRT (40%), with an observed higher utilization of cCRT in tertiary centers (9/16, 56% vs 14/42, 33%). Of the respondents, 31% do not offer cCRT to their pts. Among reasons for avoiding cCRT are (1) poor performance of pts (76%); (2) high toxicity of therapy (55%); (3) lack of consensus among tumor board members (33%); and (4) preference for sequential CRT (31%). Only 3% do not irradiate elective LNs. Eighty-six percent of respondents counsel their NSCLC pts regarding smoking cessation. CONCLUSIONS: Despite level 1 evidence, cCRT is rarely used in Russia for pts with locally advanced NSCLC, and preference for sequential therapy and concerns over high toxicity are the most common barriers. Education of Russian ROs may increase cCRT utilization, leading to improved survival, notably in the era of maintenance immunotherapy.

Thermal Ablation Versus Stereotactic Body Radiotherapy After Transarterial Chemoembolization for Inoperable Hepatocellular Carcinoma: A Propensity Score-Weighted Analysis.

BACKGROUND. Transarterial chemoembolization (TACE) has synergistic properties when combined with ablative therapies for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of our study was to compare outcomes for inoperable HCC between TACE with percutaneous thermal ablation (TACE-TA) and TACE with stereotactic body radiotherapy (TACE-SBRT) using propensity score-weighted cohorts. METHODS. This retrospective study included 190 patients with a single inoperable HCC treated from 2007 to 2018 by either TACE-SBRT (n = 90) or TACE-TA (n = 100). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS) and hepatotoxicity (defined as Child-Pugh score elevation of ≥ 2 within 2-6 months after treatment). Fine-Gray competing risk models with propensity score weighting and transplant as the competing risk factor were used to model OS and PFS. RESULTS. The median follow-up time was 48.2 months. Both OS and PFS were significantly higher for TACE-TA (77% and 76%, respectively, at 2 years) than TACE-SBRT (49% and 50%, respectively, at 2 years) in the propensity score-weighted multivariate model (OS: subdistribution hazard ratio [sHR] = 2.70, p < .001; PFS: sHR = 1.71, p = .02). Treatment-related hepatotoxicity occurred in 9% of patients who underwent TACE-TA versus 27% of those who underwent TACE-SBRT (p = .01). For the subset of patients with Barcelona Clinic Liver Cancer A HCC and Child-Pugh A cirrhosis (TACE-SBRT, n = 36 patients; TACE-TA, n = 55 patients), OS (p = .11) and PFS (p = .19) were not significantly different between the two treatment modalities. CONCLUSION. Compared with TACE-SBRT, TACE-TA showed superior OS and PFS, possibly from its lesser hepatotoxicity. The two strategies did not differ in OS and PFS for patients with the earliest-stage HCC and preserved liver function. CLINICAL IMPACT. Across all patients, TACE-TA may be superior to TACE-SBRT for inoperable HCC.

Management of Muscle Invasive Bladder Cancer with Bladder Preservation in Russia: a Survey-Based Analysis of Current Practice and the Impact of an Educational Workshop on Clinical Expertise.

Trimodality bladder preservation (BP) is an accepted alternative to radical cystectomy for patients with muscle invasive bladder cancer (MIBC). The global utilization of BP is variable, and practice patterns have not been previously studied in Russia. We sought to elucidate the contemporary BP practice patterns in Russia and determine the impact of the BP workshop on attitudes of Russian radiation oncologists (ROs) towards BP. The workshop was focused on patient workup, selection for BP, chemotherapy choices, radiation therapy (RT) contouring and planning, patient counseling. A total of 77 pre- and 32 matched post-workshop IRB-approved surveys, based on the workshop content, were analyzed using descriptive statistics to determine baseline clinical experience and patterns of care. The impact was judged by changes in participants' responses. A total of 56% of respondents had experience with delivering bladder-directed RT, and 60% of those treated both operable and inoperable MIBC patients. Only 10% felt uncomfortable offering an operable patient BP modality. Prior to the workshop, almost half of respondents estimated universal poor bladder (44%) and erectile functions (47%) after BP. The workshop resulted in dramatic change in participants' attitudes towards long-term urinary (Stuart-Maxwell test, p < 0.01) and sexual (exact McNemar test, p < 0.01) side effects. Prior to the workshop, only 47% of respondents routinely discussed smoking cessation (SC) with their patients, whereas after workshop, 88% agreed that SC discussion is mandatory (exact McNemar test, p = 0.04). BP for MIBC is commonly used in Russia. Our workshop resulted in dramatically improved understanding of long-term BP toxicities and inspired Russian ROs to incorporate SC counseling into routine clinical management.

Impact of hospital volume on mortality for brain metastases treated with radiation.

BACKGROUND: The impact of hospital volume on cancer patient survival has been demonstrated in the surgical literature, but sparsely for patients receiving radiation therapy (RT). This analysis addresses the impact of hospital volume on patients receiving RT for the most common central nervous system tumor: brain metastases. MATERIALS AND METHODS: Analysis was conducted using the National Cancer Database (NCDB) from 2010-2015 for patients with metastatic brain disease from lung cancer, breast cancer, and colorectal cancer requiring RT. Hospital volume was stratified as high-volume (≥ 12 brain RT/year), moderate (5-11 RT/year), and low (< 5 RT/year). The effect of hospital volume on overall survival was assessed using a multivariable Cox regression model. RESULTS: A total of 18,841 patients [9479 (50.3%) men, 9362 (49.7%) women; median age 64 years] met the inclusion criteria. 16.7% were treated at high-volume hospitals, 36.5% at moderate-volume, and the remaining 46.8% at low-volume centers. Multivariable analysis revealed that mortality was significantly improved in high-volume centers (HR: 0.95, p = 0.039) compared with low-volume centers after accounting for multiple demographics including age, sex, race, insurance status, income, facility type, Charlson-Deyo score and receipt of palliative care. CONCLUSION: Hospitals performing 12 or more brain RT procedures per year have significantly improved survival in brain metastases patients receiving radiation as compared to lower volume hospitals. This finding, independent of additional demographics, indicates that the increased experience associated with increased volume may improve survival in this patient population.

Radiotherapy for Hepatocellular Carcinoma in Russia: a Survey-Based Analysis of Current Practice and the Impact of an Educational Workshop on Clinical Expertise.

Radiation therapy (RT) is an effective treatment modality for hepatocellular carcinoma (HCC), but globally, it is underutilized. In Russia, practice patterns with regard to liver-directed radiation are unknown. Under the auspices of Russian Society of Clinical Oncology (RUSSCO), our team conducted an IRB-approved contouring workshop for Russian radiation oncologists. Pre- and post-workshop surveys were analyzed to determine baseline clinical experience and patterns of care for liver-directed RT among Russian providers. The effect of the contouring workshop on participants' knowledge was tested using mixed effects model. Forty pre-workshop and 24 post-workshop questionnaires were analyzable with a 100% response rate. Sixty percent of respondents had never evaluated a patient with HCC and only 8% (3 out of 40) reported treating an HCC patient with liver-directed RT. Nonetheless, 73% of respondents were comfortable offering liver-directed RT prior to the workshop. After the workshop, 85% of respondents felt comfortable treating a patient with HCC with liver-directed RT and 50% were comfortable recommending stereotactic body radiation therapy (SBRT). Measures of knowledge pertaining to evaluation of HCC patients and selection for appropriate liver-directed therapies were dramatically improved after the workshop. Liver-directed RT is not commonly used in Russia in the management of patients with HCC, and few centers are equipped for motion management. Our contouring workshop resulted in dramatically improved understanding of the evaluation and management of HCC patients. We recommend starting with a more protracted fractionated RT and building experience through attendance of additional educational activities, participation in multidisciplinary liver tumor boards, and prospective analysis of treatment toxicity and outcomes.

Extent of resection and role of adjuvant treatment in resected localized breast angiosarcoma.

BACKGROUND: Localized breast angiosarcoma (LBA) is a rare condition with no prospective clinical trials guiding the management of afflicted patients. Management of LBA and the resulting outcomes on a nationwide scale has not been previously examined. METHODS: The National Cancer Data Base (NCDB) from 2004 to 2014 identified resected LBA patients. Treatment patterns were compared between three time periods (2004-2007, 2008-2011, and 2012-2014). Demographic and tumor characteristics, as well as treatments received-extent of surgery and adjuvant therapies-were analyzed for association with overall survival after adjustment for covariates. RESULTS: 826 resected localized breast angiosarcoma patients were identified. Mastectomy was the most common surgical approach (86%); over 60% of patients did not receive adjuvant therapies after surgery. On multivariate analysis, tumor grade, tumor size, and surgical margins were associated with worse survival. Extent of surgery (mastectomy versus lumpectomy) and radiation therapy use were not associated with improved survival. Adjuvant chemotherapy was associated with improved survival in patients with primary tumors 5 cm and greater. CONCLUSIONS: The extent of surgery is not associated with improved survival in women with LBA, and patients may consider breast-conservation surgery. Adjuvant therapies are not associated with improved survival, with the exception of possible role of adjuvant chemotherapy in large primary tumors (5 cm or greater). Further clinical studies are needed to determine the impact of these treatments on local control, progression-free survival, and patients' quality of life. Until then, the findings of our analysis will form basis for the multi-disciplinary discussion of management of women with LBA.

Impact of the American Tax Payer Relief Act on stereotactic radiosurgery utilization in the United States.

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.

Dramatic polarization in genitourinary expert opinions regarding the clinical utility of positron emission tomography (PET) imaging in prostate cancer.

OBJECTIVES: To ascertain the opinions of North American genitourinary (GU) experts regarding inclusion of technologies such as prostate - specific membrane antigen (PSMA) and C - 11 choline positron emission tomography (PET) into routine practice. MATERIALS AND METHODS: A survey was distributed to North American GU experts. Questions pertained to the role of PSMA and C - 11 PET in PCa management. Participants were categorized as "supporters" or "opponents" of incorporation of novel imaging techniques. Opinions were correlated with practice patterns. RESULTS: Response rate was 54% and we analyzed 42 radiation oncologist respondents. 17 participants (40%) have been in practice for > 20 years and 38 (90%) practice at an academic center. 24 (57%) were supporters of PSMA and 29 (69%) were supporters of C - 11. Supporters were more likely to treat pelvic nodes (88% vs. 56%, p < 01) and trended to be more likely to treat patients with moderate or extreme hypofractionation (58% vs. 28%, p = 065). Supporters trended to be more likely to offer brachytherapy boost (55% vs. 23%, p = 09), favor initial observation and early salvage over adjuvant radiation (77% vs. 55%, p = 09), and to consider themselves expert brachytherapists (69% vs. 39%, p = 09). CONCLUSIONS: There is a polarization among GU radiation oncology experts regarding novel imaging techniques. A correlation emerged between support of novel imaging and adoption of treatment approaches that are clinically superior or less expensive. Pre - existing biases among GU experts on national treatment - decision panels and leaders of cooperative group studies may affect the design of future studies and influence the adoption of these technologies in clinical practice.

Is moderate hypofractionation accepted as a new standard of care in north america for prostate cancer patients treated with external beam radiotherapy? Survey of genitourinary expert radiation oncologists.

INTRODUCTION: Several recent randomized clinical trials have evaluated hypofractionated regimens against conventionally fractionated EBRT and shown similar effectiveness with conflicting toxicity results. The current view regarding hypofractionation compared to conventional EBRT among North American genitourinary experts for management of prostate cancer has not been investigated. MATERIALS AND METHODS: A survey was distributed to 88 practicing North American GU physicians serving on decision - making committees of cooperative group research organizations. Questions pertained to opinions regarding the default EBRT dose and fractionation for a hypothetical example of a favorable intermediate - risk prostate cancer (Gleason 3 + 4). Treatment recommendations were correlated with practice patterns using Fisher's exact test. RESULTS: Forty - two respondents (48%) completed the survey. We excluded from analysis two respondents who selected radical hypofractionation with 5 - 12 fractions as a preferred treatment modality. Among the 40 analyzed respondents, 23 (57.5%) recommend conventional fractionation and 17 (42.5%) recommended moderate hypofractionation. No demographic factors were found to be associated with preference for a fractionation regimen. Support for brachytherapy as a first choice treatment modality for low - risk prostate cancer was borderline significantly associated with support for moderate hypofractionated EBRT treatment modality (p = 0.089). CONCLUSIONS: There is an almost equal split among North American GU expert radiation oncologists regarding the appropriateness to consider moderately hypofractionated EBRT as a new standard of care in management of patients with prostate cancer. Physicians who embrace brachytherapy may be more inclined to support moderate hypofractionated regimen for EBRT. It is unclear whether reports with longer followups will impact this balance, or whether national care and reimbursement policies will drive the clinical decisions. In the day and age of patient - centered care delivery, patients should receive an objective recommendation based on available clinical evidence. The stark division among GU experts may influence the design of future clinical trials utilizing EBRT for patients with prostate cancer.

Application of tumor treating fields for newly diagnosed glioblastoma: understanding of nationwide practice patterns.

BACKGROUND: Tumor treating fields (TTF) harness magnetic fields to induce apoptosis in targeted regions. A 2015 landmark randomized phase III trial of newly diagnosed glioblastoma (GBM) patients demonstrated TTF + temozolomide to be superior to temozolomide alone. Given these results, we sought to assess practice patterns of providers in TTF utilization for GBM. METHODS: A survey was administered to practices in the United States self-identifying as specializing in radiation oncology, medical oncology, neuro-oncology, neurosurgery, and/or neurology. Responses were collected anonymously; analysis was performed using Fisher's exact test. RESULTS: A total of 106 providers responded; a minority (36%) were in private practice. Regarding case volume, 82% treated at least six high-grade gliomas/year. The provider most commonly certified to offer TTF therapy to GBM patients was the neuro-oncologist (40%), followed by the radiation oncologist (34%); 31% reported no TTF-certified physician in their practice. TTF users were more likely to have high volume, and be aware of TTF inclusion in National Comprehensive Cancer Network (NCCN) guidelines (p < 0.05). CONCLUSIONS: More than 80% of TTF for GBM in the United States is performed by groups who treat at least six high-grade gliomas per year; unfortunately more than 30% were in practices bereft of anyone certified to offer TTF therapy. These results indicate that there remains fertile soil for TTF therapy nationwide to be introduced into practices for GBM treatment. Providers seeking to refer newly diagnosed GBM patients for TTF should seek out practices with TTF user-associated characteristics to ensure optimal access for their patients.

Perceptions of control and unrealistic optimism in early-phase cancer trials.

PURPOSE: Recent research has found unrealistic optimism (UO) among patient-subjects in early-phase oncology trials. Our aim was to investigate the cognitive and motivational factors that evoke this bias in this context. We expected perceptions of control to be a strong correlate of unrealistic optimism. METHODS: A study of patient-subjects enrolled in early-phase oncology trials was conducted at two sites in the USA. Respondents completed questionnaires designed to assess unrealistic optimism and several risk attribute variables that have been found to evoke the bias in other contexts. RESULTS: One hundred and seventy-one patient-subjects agreed to be interviewed for our study. Significant levels of perceived controllability were found with respect to all nine research-related questions. Perceptions of control were found to predict unrealistic optimism. Two other risk attribute variables, awareness of indicators (p=0.024) and mental image (p=0.022), were correlated with unrealistic optimism. However, in multivariate regression analysis, awareness and mental image dropped out of the model and perceived controllability was the only factor independently associated with unrealistic optimism (p<0.0001). CONCLUSION: Patient-subjects reported that they can, at least partially, control the benefits they receive from participating in an early-phase oncology trial. This sense of control may underlie unrealistic optimism about benefiting personally from trial participation. Effective interventions to counteract unrealistic optimism may need to address the psychological factors that give rise to distorted risk/benefit processing.

On thin ice: barriers to adoption of surveillance for patients with stage I testicular seminoma. Survey of US radiation oncologists.

PURPOSE: Most men with stage I testicular seminoma are cured with surgery alone, which is a preferred strategy per national guidelines. The current pattern of practice among US radiation oncologists (ROs) is unknown. MATERIALS AND METHODS: We surveyed practicing US ROs via an online questionnaire. Respondent's characteristics, self-rated knowledge, perceived patient compliance rates with observation were analyzed for association with treatment recommendations. RESULTS: We received 353 responses from ROs, of whom 23% considered themselves experts. A vast majority (84%) recommend observation as a default strategy, however this rate drops to 3% if the patient is believed to be noncompliant. 33% of respondents believe that survival is jeopardized in case of disease recurrence, and among these respondents only 5% support observation. 22% of respondents over-estimate the likelihood of noncompliance with observation to be in the 50-80% range. Responders with a higher perceived noncompliance rate are more likely to recommend adjuvant therapy (Fisher's exact p<0.01). Only 7% of respondents recommend observation for stage IS seminoma and 45% administer adjuvant RT in patients with elevated pre-orchiectomy alpha-fetal protein levels. CONCLUSIONS: Many US ROs over-estimate the likelihood that stage I testicular seminoma patients will be noncompliant with surveillance and incorrectly believe that overall survival is jeopardized if disease recurs on surveillance. Observation is quickly dismissed for patients who are not deemed to be compliant with observation, and is generally not accepted for patients with stage IS disease. There is clearly an opportunity for improved physician education on evidence-based management of stage I testicular seminoma.

Fibroblast growth factor receptor 3 (FGFR3) is a strong heat shock protein 90 (Hsp90) client: implications for therapeutic manipulation.

Fibroblast growth factor receptor 3 (FGFR3) is a key regulator of growth and differentiation, whose aberrant activation causes a number of genetic diseases including achondroplasia and cancer. Hsp90 is a specialized molecular chaperone involved in stabilizing a select set of proteins termed clients. Here, we delineate the relationship of Hsp90 and co-chaperone Cdc37 with FGFR3 and the FGFR family. FGFR3 strongly associates with these chaperone complexes and depends on them for stability and function. Inhibition of Hsp90 function using the geldanamycin analog 17-AAG induces the ubiquitination and degradation of FGFR3 and reduces the signaling capacity of FGFR3. Other FGFRs weakly interact with these chaperones and are differentially influenced by Hsp90 inhibition. The Hsp90-related ubiquitin ligase CHIP is able to interact and destabilize FGFR3. Our results establish FGFR3 as a strong Hsp90 client and suggest that modulating Hsp90 chaperone complexes may beneficially influence the stability and function of FGFR3 in disease.

The A391E mutation enhances FGFR3 activation in the absence of ligand.

The A391E mutation in the transmembrane domain of fibroblast growth factor receptor 3 leads to aberrant development of the cranium. It has been hypothesized that the mutant glutamic acid stabilizes the dimeric receptor due to hydrogen bonding and enhances its ligand-independent activation. We previously tested this hypothesis in lipid bilayers and showed that the mutation stabilizes the isolated transmembrane domain dimer by -1.3°kcal/mol. Here we further test the hypothesis, by investigating the effect of the A391E mutation on the activation of full-length fibroblast growth factor receptor 3 in human embryonic kidney 293T cells in the absence of ligand. We find that the mutation enhances the ligand-independent activation propensity of the receptor by -1.7°kcal/mol. This value is consistent with the observed strength of hydrogen bonds in membranes, and supports the above hypothesis.

Novel type II collagen reporter mice: New tool for assessing collagen 2α1 expression in vivo and in vitro.

We report the generation of a new mouse strain harboring a Col2-pd2EGFP reporter transgene; pd2EGFP has a much shorter half-life than EGFP, making it a near real-time reporter for Col2α1 expression in vivo and in vitro. In the post-natal growth plate, pd2EGFP fluorescence was expressed in almost all proliferative chondrocytes and in some hypertrophic chondrocytes based on localization with type X collagen. In articular cartilage, pd2EGFP fluorescence diminished over time, nicely illustrating the decrease of type II collagen synthesis in articular chondrocytes during growth. Monolayers of FACS-sorted chondrocytes from P1-2 mice showed faster loss of pd2EGFP compared to EGFP, reflecting rapid chondrocyte de-differentiation. High-density culture of FACS-pd2EGFP- growth plate chondrocytes revealed the typical temporal expression pattern in which type II collagen preceded type X collagen matrix deposition. The Col2-pd2EGFP reporter mouse will be a valuable tool for studies of growth plate chondrocyte biology.

Establishment and Validation of Pre-Therapy Cervical Vertebrae Muscle Quantification as a Prognostic Marker of Sarcopenia in Patients With Head and Neck Cancer.

BACKGROUND: Sarcopenia is prognostic for survival in patients with head and neck cancer (HNC). However, identification of this high-risk feature remains challenging without computed tomography (CT) imaging of the abdomen or thorax. Herein, we establish sarcopenia thresholds at the C3 level and determine if C3 sarcopenia is associated with survival in patients with HNC. METHODS: This retrospective cohort study was conducted in consecutive patients with a squamous cell carcinoma of the head and neck with cross-sectional abdominal or neck imaging within 60 days prior to treatment. Measurement of cross-sectional muscle area at L3 and C3 levels was performed from CT imaging. Primary study outcome was overall survival. RESULTS: Skeletal muscle area at C3 was strongly correlated with the L3 level in both men (n = 188; r = 0.77; p < 0.001) and women (n = 65; r = 0.80; p < 0.001), and C3 sarcopenia thresholds of 14.0 cm2/m2 (men) and 11.1 cm2/m2 (women) were best predictive of L3 sarcopenia thresholds. Applying these C3 thresholds to a cohort of patients with neck imaging alone revealed that C3 sarcopenia was independently associated with reduced overall survival in men (HR = 2.63; 95% CI, 1.79, 3.85) but not women (HR = 1.18, 95% CI, 0.76, 1.85). CONCLUSIONS: This study identifies sarcopenia thresholds at the C3 level that best predict L3 sarcopenia in men and women. In HNC, C3-defined sarcopenia is associated with poor survival outcomes in men, but not women, suggesting sarcopenia may differentially affect men and women with HNC.

Pediatric Pleomorphic Xanthoastrocytoma: A National Database Inquiry on Current Treatment Approaches in the United States.

BACKGROUND: Pleomorphic xanthoastrocytomas (PXAs) account for <1% of primary brain tumors, occurring predominantly in children and young adults. Surgical resection serves as the primary treatment for PXAs, while radiotherapy (RT) and chemotherapy protocols remain poorly defined. AIM: This study aims to determine current care patterns utilized for pediatric patients (≤ 18 years) diagnosed with PXAs and their effect on overall survival. METHODS: The United States National Cancer Database (NCDB) was queried between 2004 and 2015 for pediatric patients (≤18 years) diagnosed with PXAs. RESULTS: From the 224 qualifying patients, most patients proceeded with surgery only (78.1%), while 11.6% of patients received both adjuvant RT and chemotherapy. In the 2010-2015 cohort, patients with subtotal resection were associated with poorer prognosis than those with gross-total resection (hazard ratio = 17.44, 95% confidence interval = 2.10-144.90, p < .001). RT and chemotherapy recipients were similarly associated with poorer survival than those treated with surgery only, with p-values of <.001 and respective hazard ratios of 3.82 (95% confidence interval = 1.85-7.90) and 6.68 (95% confidence interval = 3.21-13.89). The key factors impacting the probability of RT delivery involved WHO grade (p < .001) and chemotherapy administration (p < .001). However, WHO grade alone did not significantly impact survival (p-value = .088). CONCLUSION: Maximally safe resection is the current treatment goal for patients with PXAs. RT and chemotherapy are poorly utilized but had a greater role in managing more aggressive cases of PXAs. Additional research focusing on the impact of adjuvant therapies on tumor progression is needed to better guide treatment decisions.

FGFs in endochondral skeletal development.

The mammalian skeleton developments and grows through two complementary pathways: membranous ossification, which gives rise to the calvarial bones and distal clavicle, and endochondral ossification, which is responsible for the bones of the limbs, girdles, vertebrae, face and base of the skull and the medial clavicle. Fibroblast growth factors (FGFs) and their cognate FGF receptors (FGFRs) play important roles in regulating both pathways. However, the details of how FGF signals are initiated, propagated and modulated within the developing skeleton are only slowly emerging. This prospect will focus on the current understanding of these events during endochondral skeletal development with special attention given to concepts that have emerged in the past few years.

Predictors of linear accelerator versus Gamma Knife stereotactic radiosurgery use for brain metastases in the United States.

INTRODUCTION: Stereotactic radiosurgery (SRS) for brain metastases is predominantly delivered via single-fraction Gamma Knife SRS (GKRS) or linear accelerator (LINAC) in up to five fractions. Predictors of SRS modality have been sparsely examined on a nationwide level. METHODS: An observational cohort study was performed on patients receiving SRS for brain metastases from non-small cell lung cancer from 2010 to 2016 at Commission on Cancer-accredited hospitals throughout the United States (US). A multivariable logistic regression model characterized SRS receipt, adjusting for patient age, dose, geographic location of treatment, facility type, and distance from treatment facility. RESULTS: A total of 2,684 patients received GKRS, while 1,643 patients received LINAC SRS. After adjusting for significant covariates, treatment at non-academic facilities was associated with increased LINAC SRS receipt, most prominently in the Midwestern (OR=6.23;p<0.001), Northeastern (OR=4.42;p<0.001), and Southern US (OR=1.96;p<0.001). Compared to patients receiving 12-17 Gy, patients receiving doses of 18-19 Gy (OR=1.42;p=0.025), 20-21 Gy (OR=1.82;p<0.001), and 22-24 Gy (OR=3.11;p<0.001) were more likely to receive LINAC SRS; similarly, patients located within 20 miles of a radiation treatment facility were more likely to receive LINAC SRS (OR=1.27;p=0.007). CONCLUSIONS: Despite Gamma Knife being more prominently used over LINAC for SRS, patients treated at a non-academic facility outside of the Western US or requiring increased radiation dose were substantially more likely to receive LINAC over Gamma Knife. Additionally, patients residing in close proximity to a treatment center were 27% more likely to receive LINAC, likely indicative of the increased geographic accessibility of LINAC compared with GKRS.

Elective Nodal Irradiation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns.

BACKGROUND: Traditionally, elective nodal irradiation (ENI) has been used in clinical trials that have established thoracic radiotherapy as instrumental in improving survival for patients with limited-stage small-cell lung cancer (LS-SCLC). However, several reports have suggested that the omission of ENI might be appropriate. Current US practice patterns are unknown regarding ENI for patients with LS-SCLC. MATERIALS AND METHODS: We surveyed US radiation oncologists via an institutional review board-approved questionnaire. The questions covered demographics, treatment recommendations, and self-assessed knowledge of key clinical trials. χ2 and Cochran-Armitage tests were used to evaluate for statistically significant correlations between responses. RESULTS: We received 309 responses. Of the respondents, 21% recommended ENI for N0 LS-SCLC, 29% for N1, and 30% for N2; 64% did not recommend ENI for any of these clinical scenarios. The respondents who recommended ENI were more likely to have been practicing for > 10 years (P < .001), more likely to be in private practice (P = .04), and less likely to be familiar with the ongoing Cancer and Leukemia Group B 30610 trial (P = .04). Almost all respondents (93%) prescribed the same radiation dose to the primary disease and involved lymph nodes. When delivering ENI, 36% prescribed the same dose to the involved and elective nodes, and 64% prescribed a lower dose to the elective nodes. CONCLUSION: Nearly two thirds of respondents did not recommend ENI, which represents a shift in practice. A recent large clinical trial that omitted ENI reported greater overall survival than previously reported and lower-than-expected radiation toxicities, lending further evidence that omitting ENI should be considered a standard treatment strategy.