bluuebunny/crossref_metadata_2025 huggingface dataset:
Thyroglossal Duct Cyst Carcinoma: A Systematic Review of Clinical Features and Outcomes
Authors: Rayess Hani M. , Monk Ian , Svider Peter F. , Gupta Amar , Raza S. Naweed , Lin Ho‐Sheng
Published: March 2017

Objective

Although thyroglossal duct cysts (TGDCs) are relatively common, malignancies within these lesions are infrequent. As a result, there are no large‐scale series describing clinical characteristics. Our objectives were to perform a systematic review of the literature evaluating patient demographics, pathology, management, and prognosis of these patients.

Data Sources

PubMed, Embase, Cochrane reviews, and Google Scholar were searched for relevant articles. Articles meeting inclusion criteria were reviewed for data detailing epidemiology, treatment, and outcomes.

Review Methods

Inclusion criteria included English‐language articles with original reports on human subjects. Two investigators independently reviewed all articles for the data collected, including epidemiology, treatment, and outcomes.

Results

Ninety‐eight articles comprising 164 patients were included in the final analysis. The mean age at presentation was 39.5 years (9‐83 years); 68.3% of patients were female. In total, 73.3% of cases were found on final pathologic analysis. The most common pathology was papillary cancer (92.1%). Of the patients, 98.9% underwent a Sistrunk procedure and 61.0% underwent total thyroidectomy. There was a 4.3% recurrence rate with a mean time to recurrence of 42.1 months from initial treatment. One patient died of TGDC carcinoma, while all other patients were disease free at the time of last follow‐up (mean follow‐up was 46.1 months).

Conclusion

TGDC carcinoma is typically diagnosed on final pathology. While management encompasses a Sistrunk procedure, further consideration should be given to thyroidectomy among patients ≥45 years of age and individuals with aggressive disease. TGDC carcinoma harbors an exceedingly low rate of mortality.
Factors Associated with Recurrence and Regional Adenopathy for Head and Neck Cutaneous Squamous Cell Carcinoma
Authors: Harris Brianna N. , Bayoumi Ahmed , Rao Shyam , Moore Michael G. , Farwell D. Gregory , Bewley Arnaud F.
Published: March 2017

Objective

Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignancies worldwide. With advanced CSCC of the head and neck, there is conflicting evidence on what constitutes high‐risk disease. Our objective is to evaluate which factors are predictive of recurrence and nodal spread and survival.

Study Design

Case series with chart review.

Setting

Tertiary academic institution.

Subjects and Methods

Patients with advanced head and neck CSCC treated with primary resection identified by chart review.

Results

A total of 212 patients met inclusion criteria, with a mean age of 70.4 years; 87.3% were men. Mean tumor diameter was 3.65 cm, with an average depth of invasion of 1.38 cm. The mean follow‐up time was 35 months (median, 21.5), and over that period 67 recurrences were recorded, 49 of which were local. The 5‐year Kaplan‐Meier estimate of disease‐free survival for the cohort was 53.2%. On Cox multivariate analysis, recurrent disease, perineural invasion (PNI), and poorly differentiated histology were independent predictors of recurrence. On multinomial logistic regression, patients with primary tumors on the ear, cheek, temple, or lip, as well as those with PNI, were more likely to present with nodal metastasis.

Conclusion

For advanced CSCCs of the head and neck, patients with recurrent disease, PNI, and poorly differentiated tumors are at highest risk for local recurrence. Patients with tumors or the ear, cheek, temple, or lip, as well as those with PNI, are at increased risk of harboring nodal disease.
“Making the Ordinary More Extraordinary”: Exploring Creativity as a Health Promotion Practice Among Older Adults in a Community-Based Professionally Taught Arts Program
Authors: Cantu Adelita G. , Fleuriet K. Jill
Published: March 2017

Purpose: Document psychosocial and mental well-being outcomes across artistic mediums and classes of a community-based, professionally taught arts program for older adults. Method: One hundred and thirty-eight students completed pre and post class surveys about expectations/experiences when creating art in four mediums (painting, drawing, mixed media, creative writing). In addition, 162 students composed one-paragraph biographical narratives describing their relationships to art and creative engagement. Text was coded for a priori and emergent themes to identify and explain well-being outcomes. Findings: Results of this new study supported and expanded our earlier model of improved psychosocial and mental well-being due to creative engagement: impact of class-cognitive focus and outcome of class-cognitive focus, happiness as component of mental and social well-being due to creative engagement, and robust sense of calmness during the creative process. Conclusion: Results suggest that professionally taught arts programming can contribute to well-being and may contribute to brain health through promoting an enhanced ability to focus. Holistic nursing treats creativity as healing, and results suggest that creative engagement should be a priority in therapeutic programming, and individual counseling for older adults to begin engaging in some form of art making suited to their abilities should be incorporated into nursing practice.
Decisions at the Boundary
Authors: Luvison Dave , Cummings Jeffrey L.
Published: March 2017

Individuals in a firm tend to operate within a unifying set of organizational role expectations, but this is rarely the case in strategic alliances where different organizations’ interests and expectations are involved. In this conceptual article, we consider how alliance managers (AMs), the boundary spanners responsible for alliance success, navigate receiving firm-sent role expectations while also receiving legitimate partner-sent expectations. Role theory is incomplete regarding how AMs cope with this increasingly common, mixed-motive context and how the pull of the focal firm on AMs is affected. We address this theory gap by conceptualizing how the limiting nature of firm-sent expectations is affected by AMs’ receipt of legitimate partner-sent roles, and is moderated by AMs’ entrepreneurism and the structure of the interfirm collaborative environment.
Bioavailability of micronutrients obtained from supplements and food
Authors: Pressman Peter , Clemens Roger A , Hayes A Wallace
Published: March 2017

Nutritional status is an important determinant of quality of life, morbidity, and mortality. This review is a survey of one of the least appreciated and understood factors that contributes significantly to nutritional health: that of bioavailability. As the economic importance of nutritional supplements and foods carrying claims of health promotion continues to grow, physicians are increasingly accountable for critically evaluating the therapeutic and toxicologic impact of any recommended nutritional supplements and foods, and to do so, an understanding of bioavailability is essential. As we learn more about nutrition, and as it becomes increasingly clear that our fund of knowledge about nutrition is not what it should be, physicians, allied health practitioners, patients, and public health policy makers are obliged to better understand the basis for efficacy and of safety of nutritional supplements and foods. The concept of bioavailability is central to advancing our clinical acumen, particularly for the older adult population (>55 years of age), which according to the Centers for Disease Control and Prevention, typically take 16 scripted medications daily. In addition, over half of all adults consume one or more dietary supplements ( http://www.cdc.gov/nchs/data/databriefs/db61.pdf ). The World Health Organization data demonstrate that older adults form the single largest demographic group at disproportionate risk of inadequate diet and malnutrition ( http://www.who.int/ageing/publications/global_health.pdf ) followed by the pediatric population ( http://data.unicef.org/nutrition/malnutrition.html ). The challenge and the importance of understanding the determinants of bioavailability and the fundamentals of toxicology are demonstrated through the consideration of this construct in polyphenols. In support of this review, we scanned the literature using PubMed and Google Scholar. We selected peer-reviewed studies and review papers using the following search terms: bioavailability, nutritional supplements, food matrix, polyphenols, flavonoids, toxicology, microbiome, dietary intake, and metabolism.
Palm oil and threats to a critically important food source
Authors: Clemens Roger , Hayes A Wallace , Sundram Kalyana , Pressman Peter
Published: March 2017

The oil palm, an ancient tropical tree species that originated in West Africa, has a history of centuries-long use both as a food and a medicine. Based on its higher saturated fatty acid composition, primarily palmitic acid, concerns have been flagged about its nutritional attributes. Elevation of low-density lipoprotein cholesterol effects of the associated palmitic acid is far less profound than animal sources of this fatty acid and is linked with multiple health benefits. Recently, the European Food Safety Authority raised issues about potential health risks of the chloropropanols, heat- or acid-induced food contaminants created during the refining of all edible oils, and some hydrolyzed proteins. Despite the fact that the levels of 3-monochloropropane1,2 diol and its glycidyl esters are generally <800 ppb and without demonstrated toxicological effects in humans, the chloropropanols in palm oil appear to be a lightning rod for global criticism. The toxicological data are reviewed and evaluated, and an approach for mitigation of the emerging challenge is suggested.
Plasmin and plasminogen induce macrophage reprogramming and regulate key steps of inflammation resolution via annexin A1
Authors: Sugimoto Michelle A. , Ribeiro Ana Luíza C. , Costa Bruno R. C. , Vago Juliana P. , Lima Kátia M. , Carneiro Fernanda S. , Ortiz Mylena Maira O. , Lima Graziele Letícia N. , Carmo Aline A. F. , Rocha Renata M. , Perez Denise A. , Reis Alessandra C. , Pinho Vanessa , Miles Lindsey A. , Garcia Cristiana C. , Teixeira Mauro M. , Sousa Lirlândia P.
Published: March 2017

Key Points

Plg and Pla induce macrophage reprogramming and promote resolution of acute inflammation. Plg and Pla enhance the efferocytic capacity of macrophages and override the prosurvival effect of LPS on neutrophils via annexin A1.
Length of hospitalization is associated with selected biomarkers (albumin and lymphocytes) and with co-morbidities: study on 4000 patients
Authors: Pontiroli Antonio E. , Loreggian Lara , Rovati Marco P. L. , De Patto Elena , Folini Laura , Raveglia Federico , De Simone Matilde , Baisi Alessandro , Cioffi Ugo
Published: March 2017

Background

Low albumin levels and low lymphocyte counts are intra hospital conditions that exert a negative influence on prognosis, healing and length of hospitalization. The study aimed to analyze the correlation between low blood levels of albumin, low lymphocytes, and length of stay. The secondary aim was to identify other co-morbidities associated with prolonged hospital stay.

Methods

Retrospective pilot study was conducted by analyzing anamnestic and biochemical data, related to 4038 patients admitted to ten wards of Hospital San Paolo (Milan), collected from July 1st 2012 to December 31st 2012. A statistical analysis was carried out using the Correlation method, Multivariate Analysis and Regression. Lymphocyte count and co-morbidities were evaluated in the whole cohort, albumin levels in 1437 patients.

Results

In the whole sample, low albumin levels and low lymphocyte counts were directly correlated to longer hospitalizations. The stratification of the results by department and diagnosis suggests that there is a higher correlation in certain subpopulations, and albumin shows a greater correlation with length of stay than lymphocytes. Also advanced age, high platelets, type of diagnosis, male gender and emergency admission led to longer hospitalizations.

Conclusions

A routine check of albumin, lymphocytes and a spectrum of significant variables can provide precious information which can eventually lead to a shorter hospital stay. Knowledge of the general health status of a patient and the possibility to estimate his/her length of hospital stay are essential information for Clinical Governance, and for the improvement of internal services of hospitals on a large scale.
Thyroid incidentalomas on 18FDG-PET/CT: A metabolico-pathological correlation
Authors: Hagenimana N. , Dallaire J. , Vallée É. , Belzile M.
Published: March 2017

Background

Thyroid incidentaloma is defined as an unsuspected thyroid lesion found on imaging study or while performing a surgery non-related to the thyroid gland. Most recent scientific literature tends to demonstrate a detection rate of 0.1–4.3% for incidental findings of thyroid focal uptake identified by 18F-fluorodeoxyglugose Positron Emission Tomography with computed tomography (18FDG-PET/CT) initially prescribed for nonthyroid disease. From 10.3 to 80.0% of patients who underwent further evaluation are diagnosed with malignant lesions. Our first objective is to determine the risk of malignancy confined in thyroid incidentalomas(IT) detected on 18FDG-PET/CT in patients treated in a tertiary care center (Centre Hospitalier Universitaire de Sherbrooke). Second, we want to identify a cut-off value for SUVmax in order to distinguish benign from malignant IT. Third, we look for predictive criterion that can be outlined to help in their management.

Methods

We retrospectively reviewed 40 914 charts of patients who had a 18FDG-PET/CT done in a tertiary center from 2004 to 2014. For each patient where a thyroid incidentaloma has been identified, Maximum Standardized Uptake Value (SUVmax), ultrasound report, cytology and histopathological results as well as oncologic outcomes were compiled and analyzed.

Results

In this study, the incidence for thyroid incidentaloma detected with 18FDG-PET/CT is 0.74%. The rate of malignancy present in IT is 8.2% based on histopathological results. Of the patients who underwent surgery, thyroid malignancy was identified in 54.3% of them. Cytoponction showed a strong correlation with final histopathological results ( p = 0.009).

Conclusion

Thyroid incidentalomas detected with 18FDG-PET/CT are relatively infrequent, but the potential risk of malignancy remains elevated. Fine needle aspiration biopsy is the investigation of choice to rule out a malignant incidentaloma when there is no other element in the clinical portrait to preclude such additional work up.
Dynamic X-ray diffraction imaging of the ferroelectric response in bismuth ferrite
Authors: Laanait Nouamane , Saenrang Wittawat , Zhou Hua , Eom Chang-Beom , Zhang Zhan
Published: March 2017

X-ray diffraction imaging is rapidly emerging as a powerful technique by which one can capture the local structure of crystalline materials at the nano- and meso-scale. Here, we present investigations of the dynamic structure of epitaxial monodomain BiFeO3 thin-films using a novel full-field Bragg diffraction imaging modality. By taking advantage of the depth penetration of hard X-rays and their exquisite sensitivity to the atomic structure, we imaged in situ and in operando, the electric field-driven structural responses of buried BiFeO3 epitaxial thin-films in micro-capacitor devices, with sub-100 nm lateral resolution. These imaging investigations were carried out at acquisition frame rates that reached up to 20 Hz and data transfer rates of 40 MB/s, while accessing diffraction contrast that is sensitive to the entire three-dimensional unit cell configuration. We mined these large datasets for material responses by employing matrix decomposition techniques, such as independent component analysis. We found that this statistical approach allows the extraction of the salient physical properties of the ferroelectric response of the material, such as coercive fields and transient spatiotemporal modulations in their piezoelectric response, and also facilitates their decoupling from extrinsic sources that are instrument specific.
Nudge management: applying behavioural science to increase knowledge worker productivity
Authors: Ebert Philip , Freibichler Wolfgang
Published: March 2017

Knowledge worker productivity is essential for competitive strength in the digital century. Small interventions based on insights from behavioural science makes it possible for knowledge workers to be more productive. In this point of view article, we outline and discuss a new management style which we label nudge management.
Inversion gradients for acoustic VTI wavefield tomography
Authors: Li Vladimir , Wang Hui , Tsvankin Ilya , Díaz Esteban , Alkhalifah Tariq
Published: March 2017

Wavefield tomography can handle complex subsurface geology better than ray-based techniques and, ultimately, provide a higher resolution. Here, we implement forward and adjoint wavefield extrapolation for VTI (transversely isotropic with a vertical symmetry axis) media using a generalized pseudospectral operator based on a separable approximation for the P-wave dispersion relation. This operator is employed to derive the gradients of the differential semblance optimization (DSO) and modified image-power objective functions. We also obtain the gradient expressions for a data-domain objective function that can more easily incorporate borehole information necessary for stable VTI velocity analysis. These gradients are similar to the ones obtained with a space-time finite-difference (FD) scheme for a system of coupled wave equations but the pseudospectral method is not hampered by the imprint of the shear-wave artifact. Numerical examples also show the potential advantages of the modified image-power objective function in estimating the anellipticity parameter [Formula: see text].
Initial results of CALGB 80803 (Alliance): A randomized phase II trial of PET scan-directed combined modality therapy for esophageal cancer.
Authors: Goodman Karyn A. , Niedzwiecki Donna , Hall Nathan , Bekaii-Saab Tanios S. , Ye Xing , Meyers Michael O. , Mitchell-Richards Kisha , Boffa Daniel J , Frankel Wendy L , Venook Alan P. , Hochster Howard S. , Crane Christopher H. , O'Reilly Eileen Mary , Ilson David H.
Published: March 2017

1

Background: To determine whether changing chemotherapy (CT) during pre-op chemoradiation (CRT) based on response to induction CT by 18F-fluoro-deoxyglucose PET imaging can lead to improved pathologic complete response (pCR) in patients (pts) with resectable esophageal and gastroesophageal junction (GEJ) adenocarcinomas. Methods: 257 eligible pts were enrolled, underwent baseline PET scan, and were randomized to one of 2 induction CT arms: Modified FOLFOX-6 (oxaliplatin, leucovorin, 5-FU), days 1, 15, 29 or Carboplatin/Paclitaxel (CP), days 1, 8, 22, 29. Repeat PET was performed days 36-42; change in max standardized uptake value (SUV) from baseline was assessed. PET non-responders (≤35% decrease in SUV – PET-NR) crossed over to alternative CT regimen during CRT (50.4Gy/28 fractions). PET responders (>35% decrease in SUV – PET-R) continued on same CT during CRT. Pts underwent surgery 6 wks post-CRT. Pts evaluable if had surgery, disease progression (PD), death due to disease, were unresectable or had adverse event (AE). Primary endpoint was pCR in PET-NR who crossed over to alternative CT (expected 5% under H0 to 20% under Ha). Results: Pre-audit PET response data after induction CT and pCR rates after CRT and surgery are shown in the table. For PET-NR who crossed over to alternative CT during CRT, pCR was 15.6%; 95% CI (0.08, 0.26). Conclusions: Efficacy criteria were met for an improvement in pCR rates among pts who were PET-NR after induction CT and received alternative CT during CRT for esophageal and GEJ adenoca. Pts receiving induction and concurrent CP had an unexpectedly low pCR. Support: U10CA180821, U10CA180882 Clinical trial information: NCT01333033. [Table: see text]
Updated results of a phase 1 study combining the matrix metalloproteinase 9 inhibitor GS-5745 and mFOLFOX6 in patients with advanced gastric/gastroesophageal junction cancer.
Authors: Shah Manish A. , Starodub Alexander , Berlin Jordan , Brachmann Carrie Baker , Huang Xi , Smith Victoria , Maltzman Julia D. , Wainberg Zev A. , Bendell Johanna C.
Published: March 2017

108

Background: GS-5745 is a monoclonal antibody inhibitor of matrix metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. We present updated data from a phase I study of patients (pts) with advanced gastric/gastroesophageal adenocarcinoma (GC) treated with GS-5745 and mFOLFOX6 (NCT01803282). Methods: Following a monotherapy dose finding stage, pts with Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced or metastatic GC received mFOLFOX6 and GS-5745 (800 mg IV) every 2 weeks. Treatment continued until disease progression, unacceptable toxicity or withdrawal of consent. Response was assessed every 8 weeks per RECIST version 1.1 criteria. Results: As of April 2016, 40 pts were enrolled in the expanded cohort (12 continue to receive GS-5745). The most frequently observed adverse events (AEs) of any grade include nausea (62.5%), fatigue (60%), diarrhea (45%), peripheral neuropathy (45%) and neutropenia (37.5%). Grade ≥ 3 AEs observed in ≥ 10% of pts include neutropenia (20%) and nausea and neutrophil count decreased (10% each). Among 29 treatment naïve pts, median progression free survival (PFS) is 12 (90% confidence interval (CI) 5.5-18) months (mos), median duration of response (DOR) 10.6 mos and objective response rate (ORR) of 55.2%. For all pts (n=40), PFS is 7.8 (90% CI 5-13.9) mos, median DOR 10.1 mos and ORR of 50%. Median baseline circulating MMP9 was 44.7 (range 16.8-1395.3) ng/mL and all 34 patients with post-baseline samples had undetectable MMP9 levels within 8 weeks. Conclusions: The combination of GS-5745 with mFOLFOX6 is well tolerated and demonstrates activity, particularly in treatment naïve pts. Reduction in circulating MMP9 level after treatment with GS-5745 suggests specific target engagement. A phase III registration study of mFOLFOX6 +/- GS-5745 in treatment naïve metastatic GC pts is underway. Clinical trial information: NCT01803282.
Potentially preventable readmissions after complex cancer surgery: Analysis of the national readmissions dataset.
Authors: Zafar Syed Nabeel , Shah Adil A , Raoof Mustafa , Wilson Lori L , Wasif Nabil
Published: March 2017

109

Background: Hospital readmissions following surgery are a focus of quality improvement efforts nationwide. Although some reflect appropriate care, others are potentially preventable readmissions (PPRs). We aim to describe the burden, timing, and factors associated with PPRs after complex cancer surgery. Methods: The National Readmissions Dataset (2013) was used to select patients undergoing a complex oncologic resection (defined as esophagectomy/gastrectomy, hepatectomy, pancreatectomy, colorectal resection, lung resection, and cystectomy). All Readmissions occurring within 30 days from discharge were analyzed. Causes for readmissions were categorized in eleven diagnostic groups and tabulated. ICD-9 primary diagnosis codes were reviewed to identify PPRs. Logistic regression analyses were used to identify demographic, clinical and hospital factors associated with PPRs. Results: We analyzed 60,970 patients with 92,260 admissions. A 30 day readmission occurred in 14% of patients, and was highest following cystectomy (25%) and lowest for lung resections (9%). Of all readmissions 82% were deemed to be PPRs. Half of PPRs occurred within the first 10 days of discharge. Infections, gastrointestinal complications and respiratory conditions accounted for 59% of PPRs. Other common causes included dehydration/electrolyte deficiencies (11%), exacerbation of comorbidity (9.2%), bleeding (5%), thromboembolism (3.5%), and wound complications (3.2%). Factors associated with an increased likelihood of PPRs include Medicaid compared with private insurance (OR 1.24, 95%CI 0.8-1.7), higher comorbid conditions (OR 1.44, 95%CI 1.32, 1.59), and discharge to a facility (OR 1.9, 95%CI 1.7-2.1). Patients with a prolonged hospital stay or a major complication during the index admission had a 34% (OR 1.34, 95%CI 1.3-1.4), and 64% (OR 1.64, 95%CI 1.5-1.7) higher likelihood of a PPR respectively. Conclusions: Most 30 day readmissions after complex cancer surgery are potentially preventable and occur within 10 days of discharge. We identify common causes of readmission and high risk populations to help physicians, administrators and policy makers develop strategies to decrease PPRs.
Influence of tumor response and treatment schedule on the distribution of tumor recurrence in esophageal cancer patients treated with neoadjuvant chemoradiotherapy.
Authors: Jipping Kristien M. , Hulshoff Jan-Binne , van Amerongen Evita A. , Bright Tim I. , Watson David I. , Plukker John Theodorus
Published: March 2017

113

Background: Knowledge of pathologic complete tumor response (pCR) and the used neoadjuvant chemoradiotherapy (nCRT) schedule on the distribution of recurrent disease is important in the treatment of esophageal cancer (EC) patients. We assessed the effect of both pCR and different nCRT schedules on the pattern of first tumor recurrences in EC. Methods: The study was performed in two different centers in patients with T1N+/T2-4aN0-3/M0 EC. Patients were treated with nCRT according to the CROSS (carboplatin/paclitaxel/41.4Gy : n=134) and Cis/5FU schedule (Cisplatin/5-fluorouracil/45-50.4Gy : n=88) followed by surgery. First we determined the effect of pCR on tumor recurrence distribution (local, distant or combined) and site-specific recurrences in the CROSS group. After propensity matching on clinical T-stage, clinical N-stage and histology (n=63), we determined the effect of both nCRT schedules on the distribution of tumor recurrence and site specific recurrences. Results: The median follow-up after pCR (n=24) was significant longer ( P=0.001) than in non-complete responders (pNCR); 45.5 (IQR 20.3-69.5) and 20.0 months (12.0-42.3), respectively. The pattern of recurrence also differed significantly ( P=0.001), with 0 (0.0%) and 7 (6.4%) locoregional, 5 (20.8%) and 36 (32.7%) distant, and 0 (0.0%) and 21 (19.1%) local and distant recurrence between the pCR and pNCR group, respectively. Patients with a pCR had significant less local and distant recurrences. With equal median time to recurrence, the distribution of metastases in the matched groups differed only in the numbers of lung metastases ( P=0.029), with 15 (23.8%) and 6 (9.5%), respectively. Conclusions: Patients with a pCR have less local and distant recurrences. With equal time to first recurrence, the nCRT schedule itself had only a minor influence on the distribution of recurrences.
Predictors of survival after trimodality therapy for esophageal adenocarcinoma: Analysis from the National Cancer Database.
Authors: Eng Oliver , Nelson Rebecca A. , Chao Joseph , Erhunmwunsee Loretta , Raz Dan , Kim Jae Y.
Published: March 2017

116

Background: Trimodality therapy with neoadjuvant chemoradiation followed by surgery has been shown to improve survival compared to surgery alone for the treatment of locally advanced esophageal cancer, but there is considerable variation in survival in this population. We sought to analyze factors associated with survival after trimodality therapy in esophageal adenocarcinoma. Methods: We identified 4,679 patients from the National Cancer Database (NCDB) who received chemotherapy and radiation prior to surgery for esophageal adenocarcinoma from 2006-2013. Patients with stage IV disease and unknown pathological nodal status were excluded. We performed a multivariate analysis using a Cox proportional hazards model to identify independent predictors of overall survival. Results: On multivariate analysis, pathologic characteristics associated with decreased overall survival included stage, lymphovascular invasion, and positive surgical margins. Insurance status, age, and comorbidity index were also associated with decreased survival. We found that patients treated at academic programs (HR 0.85, CI 0.78-0.92, p=0.0001) and those who received additional adjuvant chemotherapy had improved survival (HR 0.86, CI 0.75-1.00, p=0.0452), but the vast majority of patients receiving trimodality therapy (4,306; 92.0%) did not receive adjuvant chemotherapy. Patients who received adjuvant chemotherapy were more likely to have private insurance (69 vs. 53%, p<0.0001). Compared to private insurance, Medicaid (HR 1.43, CI 1.20-1.70, p<0.0001), Medicare (HR 1.21, CI 1.07-1.36, p=0.0026), or having no insurance (HR 1.49, CI 1.16-1.90, p=0.0015) were all negative predictors of overall survival. Conclusions: There is wide variation in survival following trimodality therapy for esophageal adenocarcinoma. Both tumor characteristics and patient characteristics play a role. Adjuvant chemotherapy appears to be associated with improved survival, but only a minority of patients receive adjuvant chemotherapy in this setting. Insurance status and treatment setting are independent predictors of overall survival after trimodality therapy and may indicate treatment disparities.
Serial monitoring of imatinib pharmacokinetics (PK) in perioperative imatinib treatment in patients (pts) with gastrointestinal stromal tumors (GISTs): Results from the multinational phase II trial.
Authors: Yoo Changhoon , Ryu Min-Hee , Kurokawa Yukinori , Yang Han-Kwang , Nishida Toshirou , Kong Seong-Ho , Tsujinaka Toshimasa , Lee Kyung Hee , Yabusaki Hiroshi , Song Hong-Suk , Akabane Hiromitsu , Im Seock-Ah , Tanabe Kazuaki , Kang Hye Jin , Nomura Takashi , Kang Byung Wook , Nakamura Tetsu , Okubo Masaaki , Taniguchi Hirokazu , Kang Yoon-Koo
Published: March 2017

118

Background: Imatinib plasma levels may be affected by the duration of exposure to imatinib and resection of the stomach. Therefore, we performed PK study to monitor imatinib plasma levels serially in the multinational phase II trial of perioperative imatinib for pts with large ( ≥ 10 cm) gastric GISTs without distant metastasis. Methods: In this trial conducted in Japan and Korea, 53 pts received neoadjuvant imatinib 400 mg daily and 40 pts received adjuvant imatinib after surgery. Blood samples for imatinib trough levels (Cmin) were collected after 1, 3, 6 months of each neoadjuvant and adjuvant imatinib and measured by using liquid chromatography-tandem mass spectrometry. For the comparison of imatinib Cmin between different time points, values were dose-adjusted and log-transformed. Results: During the neoadjuvant treatment, imatinib Cmin (mean ± standard deviation) was 2253.0 ± 1148.0 ng/mL (n = 49), 1623.3 ± 832.4 ng/mL (n = 47), and 1852.0 ± 1572.4 ng/mL (n = 45) after 1, 3, and 6 months of imatinib, respectively. During the postoperative treatment, imatinib Cmin was 1436.1 ± 852.8 ng/mL (n = 31), 1357.8 ± 646.4 ng/mL (n = 33), and 1084.2 ± 360.8 ng/mL (n = 31) after 1, 3, and 6 months of imatinib, respectively. In the neoadjuvant setting, imatinib Cmin was significantly reduced after 3 months (p = 0.0001) and 6 months (p = 0.004) compared to the value at 1 month. In 36 patients that imatinib Cmin was measured at both preoperative and postoperative setting, imatinib Cmin was significantly reduced after surgery (1732.4 ± 997.9 ng/mL vs 1282.8 ± 557.3 ng/mL; p = 0.04). The magnitude of changes in imatinib Cmin after surgery was greatest in patients who underwent total gastrectomy (10.6%, n = 2) followed by proximal gastrectomy (8.4%, n = 3), and wedge resection (3.3%, n = 30). There were no significant relationships between imatinib Cmin and toxicity or objective response. Conclusions: Imatinib exposure was reduced until approximately 3 months after imatinib treatment. It was also significantly reduced after surgery and the magnitude of changes might be affected by the extent of surgical resection of stomach.
Postoperative mortality after esophageal and gastric cancer surgery: Does age still matter? Results from a nationwide study.
Authors: Mariette Christophe , Pasquer Arnaud , Renaud Florence , Hec Flora , Gandon Anne , Vanderbeken Marguerite , Degisors Sebastien , Caranhac Gilbert , Piessen Guillaume ,   FREGAT Working Group
Published: March 2017

122

Background: More than age, patient comorbidity is increasingly considered as the prominent predictor of postoperative mortality (POM) in esophageal and gastric cancer surgery, leading a growing number of elderly to be operated on. However, the respective impact of age and comorbidity on POM remains to be elucidated. The study objective was to investigate the impact of age on POM according to patient comorbidity. Methods: All consecutive patients who underwent esophageal or gastric cancer surgery between 2010 and 2012 in France were included (n = 11,196). The 30-day POM was compared by age groups (20-39, 40-59, 60-79, ≥ 80) and stratified according to the Charlson score (0, 1-2, ≥ 3). The consistency across esophageal (n = 3286) and gastric (n = 7910) subgroups and variations between 30-day and 90-day POM were analyzed. Results: Patients ≥ 60 years represented 73.8% of cases. A linear increase in 30-day and 90-day POM was observed with increasing age, with rates of 0.9% and 2.1%, 2.4% and 5.4%, 4.8% and 8.8%, and 9.3% and 15.9% in 20-39, 40-59, 60-79, ≥ 80 years age groups, respectively ( P< 0.001). Comparing 20-39 and ≥ 80 years age groups, 30-day POM was 1.0% vs. 7.0% for Charlson 0 ( P< 0.001), 3.1% vs. 11.1% for Charlson1-2 ( P< 0.001) and 0% vs. 19.5% for Charlson ≥ 3 ( P= 0.020) patients. A similar linear increase of POM by growing age groups was observed for 90-day POM and in esophagus and stomach subgroups. By multivariable analysis age groups (OR 1.03 95%CI 1.02-1.04, p < 0.001) and Charlson score (OR 1.56 95%CI 1.43-1.70, p < 0.001) were independent predictors of POM. Conclusions: Age and patient comorbidity have a similar and cumulative impact on POM after esophageal and gastric cancer surgery.
Retrospective review of subsequent treatments (tx) for esophagogastric adenocarcinomas (EGA) refractory to FOLFOX.
Authors: Kelly Ciara Marie , Janjigian Yelena Yuriy , Kelsen David Paul , Capanu Marinela , Chou Joanne F. , Ilson David H. , Ku Geoffrey Yuyat
Published: March 2017

123

Background: FOLFOX is a preferred 1st-line tx for advanced EGA. We sought to characterize outcomes on subsequent tx and to see if MSK-IMPACT, a 410-gene next generation sequencing (NGS) platform, increases tx options. Methods: We retrospectively identified patients (pts) with advanced, Her2-negative EGA treated with 1st-line FOLFOX between Jan 2012 to Dec 2014. Clinicopathologic, tx and outcome data were analyzed. Overall survival (OS) was calculated from start of FOLFOX using Kaplan-Meier methods. Landmark analysis was used to compare OS and response status. Results: 185 pts were identified. The majority were Caucasian (82%), male (76%), ECOG PS 1 (67%), with poorly differentiated histology (72%) and de novo metastatic disease (84%). Median age was 64 years. The disease-control rate (DCR, partial response + stable disease) of FOLFOX was 80% [95%CI: 74%-85%]; 19% were FOLFOX primary refractory (FR). Median time-to-progression (TTP) on FOLFOX was 7 and 2 months (mo) for FOLFOX sensitive (FS) and FR pts, respectively. There was a higher proportion of females (26% vs. 14%, P = 0.18), gastric (43% vs. 23%, P = 0.051) and moderately differentiated tumors (26% vs. 12%, p = 0.113) in the FS vs. FR group. Six mo survival from the landmark time of 2 mo after initiation of FOLFOX was 83% [95%CI: 76%-89%], and 38% [95%CI: 20%-56%] for FS and FR pts, respectively (p < 0.01). A similar proportion of FS and FR pts received 2nd-line tx (65% vs. 69%). The DCR was similar in both groups (31% vs 29%). 2nd-line tx included: irinotecan- (51%) and taxane-based regimens (32%) or a clinical trial (CT) (13%). The median TTP on 2nd-line tx was similar in FS and FR groups (2.5 vs 2 mo). Ramucirumab was given in 14% of 2nd line regimens. 3rd-line chemo use was similar in both groups (37% vs 31%) but the DCR was lower in FR patients (18% vs. 9%). 51 pts had IMPACT; 1 pt (2%) enrolled onto a genotyped-matched CT. 14 pts received immunotherapy; 1 FS Pt has ongoing complete response 1+ year. Conclusions: Surprisingly, FS and FR pts derive similar, marginal benefit from 2nd-line tx, emphasizing the appropriateness of CT options in this setting. NGS rarely expanded tx options. Updated and in-depth NGS data will be presented.
Comparison of chemoradiotherapy (CRT) with carboplatin/paclitaxel (CP) versus cisplatin/5-FU (CF) for esophageal or junctional cancer: Experience from the Princess Margaret Cancer Centre.
Authors: Sim Hao-Wen , Chan Bryan , Natori Akina , Lim Charles Henry , Jiang Di Maria , Chen Eric Xueyu , Liu Geoffrey , Darling Gail Elizabeth , Swallow Carol Jane , Brar Savtaj Singh , Brierley James D. , Ringash Jolie , Wong Rebecca , Kim John , Rogalla Patrik , Hafezi-Bakhtiari Sara , Conner James , Knox Jennifer J. , Jang Raymond Woo-Jun , Elimova Elena
Published: March 2017

126

Background: The optimal CRT regimen for neoadjuvant or definitive treatment of locoregional esophageal or gastroesophageal junctional (GEJ) cancer is uncertain. There has been no direct comparison between concurrent Cisplatin/5-FU (CF) as per the CALGB 9781 trial (50.4 Gy) or Carboplatin/Paclitaxel (CP) as per the CROSS trial (41.4 Gy). Methods: A retrospective analysis comparing CF and CP was performed in all patients (pts) with locoregional esophageal or GEJ cancer treated in 2012-2014. Overall survival (OS) and disease-free survival (DFS) were assessed via uni- and multivariable Cox proportional hazards regression, adjusting for age, performance status and Charlson comorbidity index. Pathological complete response (pCR) rates were compared using Fisher’s exact test. Results: 64/86 (74%) pts were male. Median age was 64 years (range: 34-84). Primary sites were esophageal (56%, with 60% squamous histology) and GEJ (44%, with 11% squamous). 22 pts received CRT in 2012 (100% CF), 33 pts in 2013 (58% CF, 42% CP) and 31 pts in 2014 (16% CF, 84% CP). Surgery was undertaken in 19 (41%) CF and 27 (68%) CP pts. Median follow-up was 38 months. We found no significant OS difference between CF and CP overall (HR 0.82, 95% CI: 0.43-1.56, p = 0.55) or in the subgroup having surgery (n = 46; HR 2.01, 95% CI: 0.62-6.55, p = 0.25). However, in the subgroup without surgery (n = 40), CF (n = 27) was superior to CP (n = 13)(HR 0.11, 95% CI: 0.03-0.38, p < 0.001). OS was similar by histology (adenocarcinoma/squamous) in all-comers (p = 0.96), and in CF (p = 0.66) and CP subgroups (p = 0.66). DFS results were similar to OS. There was a non-significant numerical difference in pCR rates between CF (31%) and CP (18%) (p = 0.45). Conclusions: Survival is similar for CF and CP CRT regimens in patients undergoing trimodality therapy. pCR rates were comparable but lower than previously reported. In contrast, in the absence of surgical resection, CP given for CRT results in significantly inferior outcomes. Clinicians may prefer CP for surgical candidates given its toxicity profile. However, when treating with definitive CRT, CF may be preferable to CP as a standard regimen.
Gastrectomy after chemotherapy: A new paradigm for the treatment of stage IV gastric cancer.
Authors: Seo Ho Seok , Park Cho Hyun , Song Kyo Young , Jung Yoon Ju
Published: March 2017

127

Background: Although there are several traditional treatment modalities for stage IV gastric cancer including chemotherapy, radiation therapy, palliative surgery, or best supportive care, survival result is unsatisfactory. Recently, gastrectomy after chemotherapy which is called conversion surgery or adjuvant surgery was introduced. Methods: In total, 419 patients who were diagnosed stage IV gastric cancer from 2010 to 2015 in eight Catholic Medical Center affiliated hospitals were divided into four groups; 212 for chemotherapy only group (G1), 124 for chemotherapy after primary gastrectomy group (G2), 23 for gastrectomy after chemotherapy group (G3), and 60 for best supportive care group (G4). To compensate chemotherapy effects, cases of complete remission, partial response, and stable disease were selectively analyzed. To identify the factors that affected survival rate, the result of surgery and the intent of surgery of the G3 were analyzed. Results: Three-year survival rate of the G3 was significantly higher than that of the G1 (42.8% vs 12.0%, p = 0.001). In case of the patients with a response to chemotherapy, three-year survival rate showed similar result (G3 vs G1, 46.1% vs 18.4%, p = 0.011). In the G3, R0 resection and curative intent of resection showed better three-year survival rate (R0 vs R1 or R2, 61.1% vs 16.2%, p = 0.003, curative vs palliative, 62.3% vs 23.8%, p = 0.031). Conclusions: The present study showed that gastrectomy after chemotherapy might improve the survival rate for the patients with stage IV gastric cancer, especially who could undergo R0 resection.
Phase II study of S-1 plus docetaxel as first-line treatment for elderly patients with advanced gastric cancer (OGSG0902).
Authors: Matsuyama Jin , Imamura Hiroshi , Kawabata Ryohei , Kawase Tomono , Okada Kazuyuki , Nishikawa Kazuhiro , Kurokawa Yukinori , Fujitani Kazumasa , Shimokawa Toshio , Satoh Taroh
Published: March 2017

129

Background: There is not enough evidence for the treatment of elderly patients with advanced gastric cancer. S-1 plus CDDP is one of the standard treatment for advanced gastric cancer in japan, but the efficacy remains insufficient due to the drug toxicity such as renal function disorders. The efficacy and safety of S-1 plus docetaxel as first-line treatment for elderly patients with unresectable advanced or recurrent gastric cancer were investigated. Methods: 75 years or older patients with unresectable advanced or recurrent gastric cancer were enrolled. Docetaxel was administered i.v. (40mg/m2) on day 1, while S-1 was administered orally (80mg/m2/day, b.i.d.) for 14 days followed by a 7-day rest. This schedule was repeated every 3 weeks. The primary endpoint was response rate (RR) of S-1 plus docetaxel; secondary endpoints were safety, progression free survival (PFS), time to treatment failure (TTF) and overall survival (OS). Sample size was set to be 30, which was determined to reject the response rate of 20% under the expectation of 40% with the power of 90% and two-sided alpha of 5%. Results: 31 patients were enrolled and assessable for efficacy. The response rate was 45.2% (95%CI 27.3-64.0, p = 0.001), and disease control rate was 77.4%. The median progression-free survival time was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1months. In 31 patients assessed for safety, the major grade 3/4 toxic effects were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). Conclusions: These findings indicate that S-1 plus docetaxel as first-line treatment for elderly patients is feasible and shows promising efficacy against advanced gastric cancer. Clinical trial information: UMIN000002785.
Volumetric changes of the primary esophageal tumor during radiation therapy.
Authors: Laughlin Brady , Famoso Justin , Gloss John , Frankl Joseph , Elquza Emad , Howell Krisha
Published: March 2017

134

Background: Management of esophageal cancer with radiotherapy requires weeks of daily treatments. The objective of this study is to identify edematous/obstructive changes in the esophageal tumor occurring during therapy and quantifying its change relative to the original tumor volume. Methods: A total of 66 patients were reviewed on a retrospective IRB-approved protocol between July 2012 – July 2016. The gross tumor volume (GTV) targeted with radiation (GTVsim) was constructed on a CT-simulation image. Cone beam CT images (CBCTs) were taken daily during treatment. GTVs (GTVCT#) were contoured on the CBCT on treatment days 1, 6, 11, 16, 21, and 25. Volumes for the GTVsim and each GTVCT# per patient were calculated. A conformality index (CI) was determined by visual confirmation of overlap and calculation of GTVCT#/GTVsim. The standard deviation (SD) was calculated. A theoretical max volume (GTVCTMAX) was determined per patient based on the upper range of 2SD from the average GTVCT# value. A theoretical PTV created from a 1cm (PTV1) and 0.5cm (PTV0.5) expansions were also calculated with associated CIs for PTVCTMAX/PTV1 and PTVCTMAX/PTV0.5. Results: Twenty-one patients had a total of 94 CBCT volumes. The median age was 67 years (53-83), sixteen patients were male, 5 female. T-stage was 1/2 in 5 patients and 3/4 in 15 patients. Chemotherapy was administered concurrently in 17 patients. Median duration of radiotherapy was 35 days (2-50). Results were analyzed by absolute volume comparison and CI calculations as noted in table 1.The median CI for PTVCTMAX/PTV1 was 0.40 (0.15-0.84) and PTVCTMAX/PTV0.5was 0.65 (0.34-0.89). Conclusions: Review of the weekly CBCTs demonstrated a larger tumor volume in the first day of therapy relative to the subsequent weeks, and even relative to the volume at the time of simulation. However, in projecting potential changes in maximum size of the individual tumors, 100% remained within standard PTV volumes constructed with a 1cm and 0.5cm expansions. [Table: see text]
The impact of proton beam therapy on blood cell count nadir during neoadjuvant chemoradiation therapy for esophageal cancer.
Authors: Shiraishi Yutaka , Xu Cai , Song Juhee , Komaki Ritsuko , Hobbs Brian P , Lin Steven H.
Published: March 2017

137

Background: To analyze the blood cell count nadir, particularly grade 4 hematologic toxicities, in patients with esophageal cancer who were treated with neoadjuvant chemoradiation (nCRT) with either Proton Beam Therapy (PBT) or Intensity Modulated Radiation Therapy (IMRT) in a propensity-matched pair analysis. Methods: Esophageal cancer patients (n = 480) treated from 2005-2016 with nCRT with (n = 167) or without (n = 313) induction chemotherapy (ICT) were analyzed. White blood cell, neutrophil, lymphocyte and platelet counts nadir during ICT and CRT were obtained, and graded according to the CTCAE v.4.0. Univariate and multivariable logistic regression models to identify factors associated with increased risk of grade 4 lymphopenia were fitted. By propensity score matching, 136 PBT cases and 136 propensity score matched IMRT controls were selected for comparison. Results: In the entire study cohort during CRT (n = 480), 2 (0.4%), 1 (0.2%), 159 (33%), and 2 (0.4%) patients experienced grade 4 leukopenia, neutropenia, lymphopenia and thrombocytopenia, respectively. This is not seen in patients who received ICT (n = 167), as only 0 (0%), 2 (1.2%), 1 (0.6%) and 0 (0%) patients experienced grade 4 leukopenia, neutropenia, lymphopenia and thrombocytopenia during the ICT phase. Multivariable analyses identified older age (p = 0.0139), larger planning tumor volume (PTV) (p = 0.0213), distal vs upper/mid tumor location (borderline significance, p = 0.0779) and IMRT vs PBT (p < 0.0001) as factors associated with increased risk of grade 4 lymphopenia during CRT. Among the 272 propensity-matched patients treated with either PBT or IMRT, 24 (17.6 %) and 55 (40.4 %) patients experienced grade 4 lymphopenia, respectively (p < 0.001). Grade 4 lymphopenia correlates with poorer survival (p = 0.0587), lower progression free survival (p = 0.0384) and distant metastatic recurrence (p = 0.0185). Conclusions: The use of PBT may be an important modifying factor in altering the incidence of grade 4 lymphopenia during CRT in esophageal cancer. The dosimetric factors that can modulate this risk is a subject of continued investigation.