Out-of-Sequence Signal 3 Paralyzes Primary CD4(+) T-Cell-Dependent Immunity.

Primary T cell activation involves the integration of three distinct signals delivered in sequence: (1) antigen recognition, (2) costimulation, and (3) cytokine-mediated differentiation and expansion. Strong immunostimulatory events such as immunotherapy or infection induce profound cytokine release causing "bystander" T cell activation, thereby increasing the potential for autoreactivity and need for control. We show that during strong stimulation, a profound suppression of primary CD4(+) T-cell-mediated immune responses ensued and was observed across preclinical models and patients undergoing high-dose interleukin-2 (IL-2) therapy. This suppression targeted naive CD4(+) but not CD8(+) T cells and was mediated through transient suppressor of cytokine signaling-3 (SOCS3) inhibition of the STAT5b transcription factor signaling pathway. These events resulted in complete paralysis of primary CD4(+) T cell activation, affecting memory generation and induction of autoimmunity as well as impaired viral clearance. These data highlight the critical regulation of naive CD4(+) T cells during inflammatory conditions.

POU2AF3-rearranged sarcomas: A novel tumor defined by fusions of EWSR1 or FUS to a gene formerly designated COLCA2.

Gene fusions involving EWSR1 or FUS as the 5' partner have been reported in a diverse array of sarcomas. Here, we characterize the histopathology and genomics of six tumors harboring a gene fusion between EWSR1 or FUS and POU2AF3, an understudied, putative colorectal cancer predisposition gene. Striking morphologic features reminiscent of synovial sarcoma were observed including a biphasic appearance with variable fusiform to epithelioid cytomorphology and staghorn-type vasculature. RNA sequencing demonstrated variable breakpoints in EWSR1/FUS along with similar breakpoints in POU2AF3 that encompassed a 3' portion of this gene. For cases in which additional information was available, the behavior of these neoplasms was aggressive with local spread and/or distant metastases. Although further studies are needed to confirm the functional significance of our findings, POU2AF3 fusions to EWSR1 or FUS may define a novel type of POU2AF3-rearranged sarcomas with aggressive, malignant behavior.

Effectiveness of the nutrition referral system in a multidisciplinary pancreatic cancer clinic.

PURPOSE: Proactive nutrition screening and intervention is associated with improved outcomes for patients with pancreatic adenocarcinoma (PDAC). To better optimize nutrition amongst our PDAC population, we implemented systematic malnutrition screening in the Johns Hopkins pancreas multidisciplinary clinic (PMDC) and assessed the effectiveness of our nutrition referral system. METHODS: This was a single institution prospective study of patients seen in the PMDC, screened for malnutrition using the Malnutrition Screening Tool (MST) (score range=0 to 5, score > 2 indicates risk of malnutrition), and offered referrals to the oncology dietitian. Patients that requested a referral but did not attend a nutrition appointment were contacted by phone to assess barriers to seeing the dietitian. Univariate (UVA) and multivariable (MVA) analyses were carried out to identify predictors of referral status and appointment completion status. RESULTS: A total of 97 patients were included in the study, of which 72 (74.2%) requested a referral and 25 (25.8%) declined. Of the 72 patients who requested a referral, 31 (43.1%) attended an appointment with the oncology dietitian. Data on information session attendance was available for 35 patients, of which 8 (22.9%) attended a pre-clinic information session in which the importance of optimal nutrition was highlighted. On MVA, information session attendance was significantly associated with requesting a referral (OR: 11.1, 95% CI 1.12-1.0E3, p=0.037) and successfully meeting with the oncology dietitian (OR: 5.88, 95% CI 1.00-33.3, p=0.049). CONCLUSION: PMDC teams should institute educational initiatives on the importance of optimal nutrition in order to increase patient engagement with nutrition services.

Former Inpatient Psychiatric Patients' Past Experiences With Traditional Frontline Staff and Their Thoughts on the Benefits of Peers as Part of Frontline Staff.

Little is known about how integrating peers into frontline staff might improve the quality of inpatient psychiatric care. In the current study, we interviewed 18 former adult patients of inpatient psychiatric facilities using semi-structured interviews. We first asked about positive and negative past experiences with traditional staff. We then asked participants to share their opinions on the potential benefits of peers as part of frontline staff. We identified themes through a joint inductive and deductive approach. Participants reported past positive experiences with traditional staff as being (a) personable and caring, (b) validating feelings and experiences, (c) de-escalating, and (d) providing agency. Past negative experiences included (a) not sharing information, (b) being inattentive, (c) not providing agency, (d) being dehumanizing/disrespectful, (e) incompetency, (f) escalating situations, and (g) being apathetic. Participants believed that peers as part of frontline staff could champion emotional needs in humanizing and nonjudgmental ways, help navigate the system, and disrupt power imbalances between staff and patients. Further research is needed to understand financial, organizational, and cultural barriers to integrating peers into frontline staff. [Journal of Psychosocial Nursing and Mental Health Services, 60(3), 15-22.].

Comfort Level of US Radiation Oncology Graduates: Assessment of Transition to Independent Clinical Practice.

Radiation training programs are designed to prepare graduates for independent practice, with metrics in place to assess appropriateness of clinical decision-making. Here, we investigated the self-assessed preparedness of US graduates during the transition to independent practice.An anonymous, Internet-based survey was distributed to recent graduates of radiation oncology residencies (2016-2017). A Likert scale was used to assess comfort with various aspects of practice, as well as "time" to development of comfort in independent practice.Responses were obtained from 70/210 (33%), the majority reported training in programs with 5-8 residents (n = 35). Most (77%) reported designing between 500 and 900 treatment plans during training (n = 54). Only 41% of respondents reported the opportunity to review treatment plans and make decisions about safety/adequacy without attending input > 50% of the time (n = 29). Thirty percent of residents reported being responsible for seeing/managing on-treatment visits (OTVs) ≤ 75% of the time. Aspects with which practitioners reported the least comfort were understanding of billing/application to practice (2.43, IQR 2-3), orthovoltage (superficial radiation) setup and field design (2.57, IQR 1-4), and planning/delivery of prostate implants (2.82, IQR 2-4). Increased mean comfort levels were reported by those designing > 700 treatment plans in training as well as those reporting an opportunity to evaluate plans and make clinical decisions prior to attending input > 50% of the time during residency. Comfort with the delivery of stereotactic body radiation (SBRT) correlated with caseload for liver, spine, prostate, and CNS disease sites but not lung.Variations in training experiences exist across institutions. Here, a lower than expected number of residents reported seeing/managing OTVs as well as reviewing treatment plans prior to attending input during training. Overall comfort was correlated with case volume and opportunities to independently review treatment plans prior to attending input. These data highlight areas of opportunity for improving resident education with implications for ease of transition to independent clinical practice.

Stereotactic Body Radiation Therapy in Oligometastatic Uterine Cancer: Clinical Outcomes and Toxicity.

We report on clinical outcomes in patients with oligometastatic uterine cancer treated with stereotactic body radiation therapy (SBRT). Twenty-seven patients with 61 lesions were treated with SBRT. Median follow-up was 16.9 months. Local control was achieved in 49/61 (80.3%) lesions. One-year local-progression-free survival and overall survival were 75.9% and 65.4%. Lesions with favorable response were smaller than lesions with unfavorable response (p = .007). Liver lesions were less likely to achieve favorable response (p = .0128). There were no grade 3 or 4 events. Treatment with SBRT can provide excellent local control in oligometastatic uterine cancer with minimal toxicity.

Long term control and preservation of renal function after multiple courses of stereotactic body radiation therapy for renal cell carcinoma.

Renal cell carcinoma (RCC) is usually treated with surgery, with or without systemic therapy. For select patients, stereotactic body radiation therapy (SBRT) may be a suitable alternative. Although many reports exist on the successful use of SBRT, very few have described long term outcomes with regard to disease progression and renal function. We report a rare case of a single patient with primary, metastatic, and locally recurrent renal cell carcinoma who was successfully treated with SBRT. The patient has been disease-free for 8 years since treatment, with stable renal function even after two courses of SBRT to her solitary functioning kidney.

Determining the role of adjuvant radiotherapy in the management of meningioma: a Surveillance, Epidemiology, and End Results analysis.

OBJECTIVEThe aim of this study was to illustrate the demographic characteristics of meningioma patients and observe the effect of adjuvant radiation therapy on survival by using the Surveillance, Epidemiology, and End Results (SEER) database. More specifically, the authors aimed to answer the question of whether adjuvant radiotherapy following resection of atypical meningioma confers a cause-specific survival benefit. Additionally, they attempted to add to previous characterizations of the epidemiology of primary meningiomas and assess the effectiveness of the standard of care for benign and anaplastic meningiomas. They also sought to characterize the efficacy of various treatment options in atypical and anaplastic meningiomas separately since nearly all other analyses have grouped these two together despite varying treatment regimens for these behavior categories.METHODSSEER data from 1973 to 2015 were queried using appropriate ICD-O-3 codes for benign, atypical, and anaplastic meningiomas. Patient demographics, tumor characteristics, and treatment choices were analyzed. The effects of treatment were examined using a multivariate Cox proportional hazards model and Kaplan-Meier survival analysis.RESULTSA total of 57,998 patients were included in the analysis of demographic, meningioma, and treatment characteristics. Among this population, cases of unspecified WHO tumor grade were excluded in the multivariate analysis, leaving a total of 12,931 patients to examine outcomes among treatment paradigms. In benign meningiomas, gross-total resection (HR 0.289, p = 0.013) imparted a significant cause-specific survival benefit over no treatment. In anaplastic meningioma cases, adjuvant radiotherapy imparted a significant survival benefit following both subtotal (HR 0.089, p = 0.018) and gross-total (HR 0.162, p = 0.002) resection as compared to gross-total resection alone. In atypical tumors, gross-total resection plus radiotherapy did not significantly change the hazard risk (HR 1.353, p = 0.628) compared to gross-total resection alone. Similarly, it was found that adjuvant radiation did not significantly benefit survival after a subtotal resection (HR 1.440, p = 0.644).CONCLUSIONSThe results of this study demonstrate that the role of adjuvant radiotherapy, especially after the resection of atypical meningioma, remains somewhat unclear. Thus, given these results, prospective randomized clinical studies are warranted to provide clear information on the effects of adjuvant radiation in meningioma treatment.

Antineutrophil Cytoplasmic Antibodies Associated Vasculitis Presenting As Neuropathy.

Antineutrophil cytoplasmic antibody-related vasculitis (AAV), is a group of diseases marked by systemic symptoms and severe small vessel inflammation. The three subtypes of AAV are eosinophilic GPA (EGPA), Microscopic Polyangiitis (MPA), and Granulomatosis with Polyangiitis (GPA). The organs that get involved in the disease process are the kidneys and the upper and lower respiratory tracts, with a spectrum of neurological manifestations. Here, we present a case report of a 68-year-old man who came with complaints of tingling and numbness over bilateral lower limbs for two months accompanied by difficulty in walking and bilateral foot drop without any respiratory complaints or involvement of sensory or autonomic system who was diagnosed with AAV (c-ANCA +) on further workup. A sural Nerve biopsy was done for confirmation which was suggestive of chronic, asymmetrical axonal neuropathy with perivascular inflammation, suggestive of vasculitic neuropathy. The patient had no other organ involvement. The patient was started on glucocorticoids and cyclophosphamide therapy for 6 cycles after which his symptoms and quality of life improved drastically.

Upregulated expression of PTTG1 is associated with progression of pancreatic cancer.

Background: Pancreatic cancer (PC) is an aggressive disease with a very poor prognosis. The insidious onset, rapid progression, and resistance to conventional therapies mark the imperious need for novel biomarkers and therapeutic targets. The pituitary tumor transforming gene 1 (PTTG1), implicated in tumorigenesis and cellular transformation, has been studied in various cancers, however, its role and mechanisms in PC remain to be elucidated for better understanding the disease pathology and in enhancing patient management strategies. Methods: The present study examined the PTTG1 messenger RNA (mRNA) expression levels and clinical significance through meta-analysis based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was used to measure PTTG1 protein levels in PC and adjacent non-cancerous tissues. A correlation was observed between PTTG1 expression and some clinical characteristics based on the TCGA and IHC data. Univariate and multivariate Cox regressions were used to identify independent prognostic factors. Kaplan-Meier (KM) survival analysis was performed. The co-expressed genes of PTTG1 were determined by integrating online tools, and the enrichment analyses were performed to determine PTTG1-related pathways and hub co-expressed genes. Results: PTTG1 was highly expressed in PC tissues based on the TCGA, GEO, and IHC data. The combined standard mean difference (SMD) values of PTTG1 expression based on TCGA and GEO databases was 1.02 [95% confidence interval (CI): 0.74-1.30]. The area under the curve (AUC) based on the summary receiver operating characteristic (sROC) curve was 0.93 (95% CI: 0.90-0.95). PTTG1 overexpression was remarkably correlated with an inferior overall survival (OS). A total of 367 genes were identified as co-expressed genes of PTTG1 in PC and were mainly involved in the cell cycle pathway. The four identified core genes were CDK1, CCNA2, CDC20, and MAD2L1. Conclusions: The upregulated expression of PTTG1 plays an essential role in PC's progression as a biomarker.

Solute carrier family 16 member 1 as a potential prognostic factor for pancreatic ductal adenocarcinoma and its influence on tumor immunity.

Background: Solute carrier family 16 member 1 (SLC16A1) serves as a biomarker in numerous types of cancer. Tumor immune infiltration has drawn increasing attention in cancer progression and treatment. The objective of our study was to explore the association between SLC16A1 and the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). Methods: Data were obtained from The Cancer Genome Atlas. The xCell web tool was used to calculate the proportion of immune cells according to SLC16A1 expression. To further explore the mechanism of SLC16A1, immunity-related genes were screened from differentially expressed genes through weighted gene coexpression network analysis, examined via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and filtrated using univariate Cox regression and least absolute shrinkage and selection operator regression model combined correlation analysis (P<0.05). Next, CIBERSORT was used to analyze the correlation between immune cells and five important genes. SLC16A1 expression and its clinical role in pancreatic cancer was clarified via immunohistochemical staining experiments. Finally, the effects of SLC16A1 on the results of cancer immunity were evaluated by in vitro experiments. Results: SLC16A1 was overexpressed in PDAC tissues and could be an independent prognostic factor. SLC16A1 was significantly negatively correlated with overall survival and suppressed the tumor immunity of PDAC. In clinic, SLC16A1 expression was significantly positively correlated with tumor progression and poor prognosis. We also found that SLC16A1 could suppress the antitumor ability of CD8+ T cells. Conclusions: SLC16A1 is a biomarker for the prognosis of PDAC and can influence the immune environment of PDAC. These findings provide new insights into the treatment of PDAC.

Surgical and local control outcomes after sequential short-course radiation therapy and chemotherapy for rectal cancer.

Background: Total neoadjuvant therapy (TNT) is an accepted approach for the management of locally advanced rectal cancer (LARC) and is associated with a decreased risk of development of metastatic disease compared to standard neoadjuvant therapy. However, questions remain regarding surgical outcomes and local control in patients who proceed to surgery, particularly when radiation is given first in the neoadjuvant sequence. We report on our institution's experience with patients who underwent short-course radiation therapy, consolidation chemotherapy, and surgery. Methods: We retrospectively reviewed surgical specimen outcomes, postoperative complications, and local/pelvic control in a large cohort of patients with LARC who underwent neoadjuvant therapy incorporating upfront short-course radiation therapy followed by consolidation chemotherapy. Results: In our cohort of 83 patients who proceeded to surgery, a complete/near-complete mesorectal specimen was achieved in 90 % of patients. This outcome was not associated with the time interval from completion of radiation to surgery. Postoperative complications were acceptably low. Local control at two years was 93.4 % for all patients- 97.6 % for those with low-risk disease and 90.4 % for high-risk disease. Conclusion: Upfront short-course radiation therapy and consolidation chemotherapy is an effective treatment course. Extended interval from completion of short-course radiation therapy did not impact surgical specimen quality.

The Timing of Surgery Following Stereotactic Body Radiation Therapy Impacts Local Control for Borderline Resectable or Locally Advanced Pancreatic Cancer.

We aimed to evaluate the impact of time from stereotactic body radiation therapy (SBRT) to surgery on treatment outcomes and post-operative complications in patients with borderline resectable or locally advanced pancreatic cancer (BRPC/LAPC). We conducted a single-institutional retrospective analysis of patients with BRPC/LAPC treated from 2016 to 2021 with neoadjuvant chemotherapy followed by SBRT and surgical resection. Covariates were stratified by time from SBRT to surgery. A Cox regression model was used to identify variables associated with survival outcomes. In 171 patients with BRPC/LAPC, the median time from SBRT to surgery was 6.4 (range: 2.7-25.3) weeks. Hence, patients were stratified by the timing of surgery: ≥6 and <6 weeks after SBRT. In univariable Cox regression, surgery ≥6 weeks was associated with improved local control (LC, HR 0.55, 95% CI 0.30-0.98; p = 0.042), pathologic node positivity, elevated baseline CA19-9, and inferior LC if of the male sex. In multivariable analysis, surgery ≥6 weeks (p = 0.013; HR 0.46, 95%CI 0.25-0.85), node positivity (p = 0.019; HR 2.09, 95% CI 1.13-3.88), and baseline elevated CA19-9 (p = 0.002; HR 2.73, 95% CI 1.44-5.18) remained independently associated with LC. Clavien-Dindo Grade ≥3B complications occurred in 4/63 (6.3%) vs. 5/99 (5.5%) patients undergoing surgery <6 weeks and ≥6 weeks after SBRT (p = 0.7). In summary, the timing of surgery ≥6 weeks after SBRT was associated with improved local control and low post-operative complication rates, irrespective of the surgical timing. Further investigation of the influence of surgical timing following radiotherapy is warranted.

Exploration of hub genes, lipid metabolism, and the immune microenvironment in stomach carcinoma and cholangiocarcinoma.

Background: Gastric cancer (GC) is the 5th most common cause of cancer in the world and the 3rd largest cause of cancer-related death. It is usually associated with a variety of cancers, of which cholangiocarcinoma (CCA) combined with GC accounts for about 1.6%. This study sought to examine the hub genes and role of lipid metabolism in the development and diagnosis of GC and CCA. Methods: To screen potential hub genes, The Cancer Genome Atlas (TCGA) data sets, including the GC (STAD, dataset of GC) and CCA (CHOL, dataset of CCA) data sets, were used to conduct a differentially expressed gene (DEG) analysis and an enrichment analysis of the DEGs. A weighted-gene co-expression network analysis (WGCNA) was conducted to identify the significant gene module and then find the hub genes in the module. To verify the 4 hub genes, we conducted a differentiation analysis of the 4 genes in GC and CCA and found that there were differences. A survival analysis of the hub genes was performed and mutations were mapped. Additionally, tumor immune microenvironment (TIME) and immune analyses were performed to evaluate how lipid metabolism affects the development of GC with CCA. Results: The principal component analysis showed that both GC and CCA had distinct up-regulated and down-regulated genes, which are involved in a variety of metabolic processes. Upon WGCNA, the turquoise and blue modules were meaningful, and the hub genes were identified from these 2 modules. Four hub genes were identified: amyloid beta precursor protein binding family B member 1 (APBB1), Homo sapiens armadillo repeat containing X-linked 1 (ARMCX1), DAZ interacting zinc finger protein 1 (DZIP1), and methionine sulfoxide reductase B3 (MSRB3). In survival analysis, increased expression of the 4 hub genes was associated with inferior survival outcomes, with variations in all 4 genes. Additionally, we demonstrated that genes related to lipid metabolism had an effect on immune function. Conclusions: APBB1, ARMCX1, DZIP1, and MSRB3 affect the development of GC and CCA and can be used as biomarkers. The expression of lipid metabolism genes is related to the TIME of patients with GC and CCA.

Disparities in Rates of Fusions in Lumbar Disc Pathologies.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To identify disparities in surgical decision making for lumbar disc pathologies based on patient demographics, hospital characteristics, and temporal characteristics of admission. METHODS: A retrospective analysis of patients admitted for surgical intervention of disc herniation or degeneration was performed to observe the effect of demographic, hospital, and admission-related factors on the decision to perform an isolated decompression or decompression with single level fusion using the National Inpatient Sample. RESULTS: Of 84 953 patients with lumbar disc pathologies, 69 975 patients were treated electively, and 14 978 patients were treated nonelectively. Hispanic and Asian/Pacific Islander patients were less likely to receive a fusion for elective cases compared with White patients (odds ratio [OR] 0.88, P = .004; OR 0.70, P < .001, respectively). In elective cases, privately insured and self-paying patients were less likely to receive a fusion compared with Medicare patients (OR 0.83, P < .001; OR 0.66, P < .001, respectively), while this effect was limited to self-pay patients in nonelective cases (OR 0.44, P < .001). Urban teaching and nonteaching hospitals were less likely to perform fusions compared with rural hospitals in nonelective cases (OR 0.47, P < .001; OR 0.58, P < .001, respectively). Private for-profit hospitals were associated with higher rates of fusion in both elective and nonelective cases (OR 1.16, P = .003; OR 1.94, P < .001). CONCLUSION: This study illustrates disparities in the modality of surgical intervention for lumbar disc pathologies in terms of demographics, hospital characteristics, and temporal characteristics of admission. The development of more evidence-based guidelines is warranted to reduce variability seen in treatment regimens for these conditions.

A safety study of intraoperative radiation therapy following stereotactic body radiation therapy and multi-agent chemotherapy in the treatment of localized pancreatic adenocarcinoma: study protocol of a phase I trial.

BACKGROUND: Localized pancreatic adenocarcinoma carries a poor prognosis even after aggressive therapy. Up to 40% of patients may develop locoregional disease as the first site of failure. As such, there may be a role for intensification of local therapy such as radiation therapy. Radiation dose escalation for pancreatic cancer is limited by proximity of the tumor to the duodenum. However, the duodenum is removed during Whipple procedure, allowing the opportunity to dose escalate with intraoperative radiation therapy (IORT). Although prior studies have shown potential benefit of IORT in pancreatic cancer, these studies did not utilize ablative doses (biologically effective dose [BED10] > 100 Gy). Furthermore, the optimal radiation target volume in this setting is unclear. There has been increased interest in a "Triangle Volume" (TV), bordered by the celiac axis, superior mesenteric artery, common hepatic artery, portal vein, and superior mesenteric vein. Dissection of this area, has been advocated for by surgeons from Heidelberg as it contains extra-pancreatic perineural and lymphatic tracts, which may harbor microscopic disease at risk of mediating local failure. Interestingly, a recent analysis from our institution indicated that nearly all local failures occur in the TV. Therefore, the purpose of this protocol is to evaluate the safety of delivering an ablative radiation dose to the TV with IORT following neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT). METHODS: Patients with non-metastatic pancreatic adenocarcinoma centered in the head or neck of the pancreas will be enrolled. Following treatment with multi-agent neoadjuvant chemotherapy, patients will undergo SBRT (40 Gy/5 fractions) followed by IORT (15 Gy/1 fraction) to the TV during the Whipple procedure. The primary objective is acute (< 90 days) toxicity after IORT measured by Clavien-Dindo classification. Secondary objectives include late (> 90 days) toxicity after IORT measured by Clavien-Dindo classification, overall survival, local progression-free survival, distant metastasis-free survival, and progression-free survival. DISCUSSION: If the results show that delivering an ablative radiation dose to the TV with IORT after neoadjuvant chemotherapy and SBRT is safe and feasible, it warrants further investigation in a phase II trial to evaluate efficacy of this approach. Trial Registration This study was registered at ClinicalTrials.gov on 12/2/2021 (NCT05141513). https://clinicaltrials.gov/ct2/show/NCT05141513.

Anterior Cervical Discectomy and Fusion Versus Cervical Disc Arthroplasty: A Comparison of National Trends and Outcomes.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) has been considered the standard treatment for degenerative cervical disc disease; however, recent trials have shown comparable outcomes with cervical disc arthroplasty (CDA). This study aimed to observe disparities in treatment paradigms of single-level cervical disc diseases and compare inpatient outcomes between procedures. METHODS: A retrospective cohort of patients treated for single-level cervical disc herniation or degeneration without myelopathy was queried from the Nationwide Inpatient Sample spanning 2012-2015. Multivariate logistic regression was performed to assess the effects of demographics, temporality of admission, and hospital characteristics on odds of receiving CDA versus ACDF. Propensity-score matching was performed to compare cost, length of stay (LOS), non-home discharge, and inpatient complications. RESULTS: In total, 1028 CDAs and 44,374 ACDFs were performed for single-level cervical disc disease during 2012-2015. Matched comparison showed that while non-home discharges were not different between CDA and ACDF (P = 0.248), patients who received CDA had a 0.19-day shorter LOS (P < 0.001) and $4694 greater total cost (P < 0.001). There were no statistically significant differences in inpatient complication rates. Multivariate analysis showed that patients in the 26th-50th percentile, 51st-75th percentile, and 76th-100th percentile of median household income had greater odds of CDA compared with patients in the 0-25th percentile (odds ratio [OR] 1.35, P = 0.003; OR 1.31, P = 0.013; OR 1.34, P = 0.011, respectively). Patients with private insurance had greater odds of receiving CDA compared with patients on Medicare (OR 1.91, P < 0.001). CONCLUSIONS: CDA was associated with shorter LOS but greater costs compared with ACDF. Patients with greater median income and private insurance were more likely to receive CDA.

Stereotactic body radiation therapy for the treatment of locally recurrent pancreatic cancer after surgical resection.

Background: To report on a cohort of radiation-naïve patients with pancreatic cancer who developed isolated local recurrence following surgical resection and were subsequently treated with stereotactic body radiation therapy (SBRT). Methods: Patients with pancreatic cancer who were treated with SBRT for isolated local recurrence after surgical resection were retrospectively reviewed. Clinical outcomes were calculated from completion of SBRT and included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). Univariate (UVA) analysis was performed to identify variables associated with clinical outcomes. Kaplan-Meier method was used for survival outcomes. Toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. Results: From September 2012 to November 2018, a total of 19 patients with localized pancreatic cancer were treated with SBRT for isolated local recurrence after initial surgical resection. No patients had prior radiation. The median biologically effective dose (BED10) was 54.8 Gy (range, 37.5-54.8 Gy). Median OS was 17.1 months, with 6-month and 1-year OS rates of 94.4% and 69.6%, respectively. Nine patients (47.4%) developed local failure after SBRT. Pattern of first failure after SBRT was distant in 7 patients (46.7%), local in 5 patients (33.3%), and synchronous distant and local in 3 patients (20.0%). One patient developed local failure after developing distant disease first. Of the 9 local failures, 3 (33.3%) were out-of-field. Median LPFS was 22.2 months, with 6-month and 1-year LPFS rates of 86.9% and 63.2%, respectively. A BED10 <54.8 Gy was associated with inferior LPFS (1-year, 25.0% vs. 80.2%, P<0.009). Median DMFS and PFS were 15.6 months. There was 1 case (5.3 %) of grade 3 gastric perforation. There were no cases of grade 4-5 toxicity events. Conclusions: SBRT for locally recurrent pancreatic cancer after initial curative resection is safe and feasible. A BED10 <54.8 Gy was significantly associated with inferior local control. Further studies investigating dose escalation and optimal treatment volumes in the locally recurrent setting are warranted.

High neutrophil-to-lymphocyte ratio following stereotactic body radiation therapy is associated with poor clinical outcomes in patients with borderline resectable and locally advanced pancreatic cancer.

Background: The purpose of this study is to report on the prognostic role of pre- and post-stereotactic body radiation therapy (SBRT) neutrophil-to-lymphocyte ratio (NLR) in a cohort of patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) who was treated with multi-agent induction chemotherapy followed by five-fraction SBRT. Methods: Patients treated with multi-agent induction chemotherapy followed by SBRT from August 2016 to January 2019 and who had laboratory values available for review were included in the study. Univariate (UVA) and multivariate analyses (MVA) were performed to determine associations between pre-/post-SBRT NLR and overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). Results: A total of 156 patients were treated with multi-agent induction chemotherapy followed by SBRT and had laboratory values available for review. On UVA, chemotherapy duration ≥4 months, poorly differentiated disease, inability to undergo resection, pre-SBRT ANC ≥3.7 No./µL, pre-SBRT NLR ≥2.3, and post-SBRT NLR ≥2.6 were associated with worse OS. Patients with post-SBRT NLR ≥2.6 had a median OS of 16.7 months versus median OS not yet reached in patients with post-SBRT <2.6 (P=0.009). On MVA, poorly differentiated disease [hazard ratio (HR) =1.82, 95% CI: 1.04-3.18, P=0.035], inability to undergo resection (HR =2.17, 95% CI: 1.25-3.70, P=0.006), and post-SBRT NLR ≥2.6 (HR =2.55, 95% CI: 1.20-5.45, P=0.015) were associated with inferior OS. On UVA, baseline CA 19-9 ≥219 U/mL, pre-SBRT platelet count ≥157×1,000/µL, and post-SBRT NLR ≥2.6 were associated with inferior LPFS. Patients with post-SBRT NLR ≥2.6 had a median LPFS of 18.3 months versus median LPFS not yet reached in patients with post-SBRT <2.6 (P=0.028). On MVA, only post-SBRT NLR ≥2.6 was associated with worse LPFS (HR =3.22, 95% CI: 1.04-9.98, P=0.043). Conclusions: Post-SBRT NLR ≥2.6 predicted for inferior OS and LPFS in BRPC/LAPC patients treated with multi-agent chemotherapy and SBRT. These findings highlight the importance of further elucidating the immunologic effects of radiation therapy in this setting, which may have significant implications on both radiation design as well as combination strategies.