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Objectives The change in tumor fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) scan after one cycle of platinum-based chemotherapy has been shown to predict progression-free and overall survival (PFS and OS) among advanced non-small cell lung cancer (NSCLC) patients. Using early FDG-PET response to determine subsequent chemotherapy, we aim to evaluate the role that adaptive chemotherapy regimens have on later CT response, PFS, and OS in patients with advanced NSCLC. Materials and Methods Chemotherapy-naive patients with metastatic NSCLC received carboplatin and paclitaxel (CP) on day one and repeated FDG-PET on day 18. PET-responding patients continued CP chemotherapy for a total of four cycles. PET non-responders were switched to alternate docetaxel and gemcitabine (DG) for three additional cycles. The primary outcome was the CT Response Evaluation Criteria in Solid Tumors (RECIST 1.0) response. Secondary endpoints included PFS and OS. Results Forty-six patients initiated treatment with chemotherapy on trial and were evaluable by PET/CT. Of these, 19 (41%) met the FDG-PET criteria for the response after a single cycle of CP. Only one non-responding patient had a CT response. Despite the lack of CT response in the DG arm, no trend for worse PFS or OS was seen between the two arms. Conclusions This work demonstrates that changing chemotherapy in the event of non-response by PET did not lead to improved CT RECIST response. However, non-responding patients who switched chemotherapy had similar PFS and OS to those who responded by PET and continued the same regimen.

PurposeThis study evaluated the ability of18F-Fluorodeoxyglucose (FDG) and18F-Fluorothymidine (FLT) imaging with positron emission tomography (PET) to measure early response to endocrine therapy from baseline to just prior to surgical resection in estrogen receptor positive (ER+) breast tumors.MethodsIn two separate studies, women with early stage ER+ breast cancer underwent either paired FDG-PET (n = 22) or FLT-PET (n = 27) scans prior to endocrine therapy and again in the pre-operative setting. Tissue samples for Ki-67 were taken for all patients both prior to treatment and at the time of surgery.ResultsFDG maximum standardized uptake value (SUVmax) declined in 19 of 22 lesions (mean 17% (range −45 to 28%)). FLT SUVmax declined in 24 of 27 lesions (mean 26% (range −77 to 7%)). The Ki-67 index declined in both studies, from pre-therapy (mean 23% (range 1 to 73%)) to surgery [mean 8% (range ConclusionsA window-of-opportunity approach using PET imaging to assess early response of breast cancer therapy is feasible. FDG and FLT-PET imaging following a short course of neoadjuvant endocrine therapy demonstrated measurable changes in SUVmax in early stage ER+ positive breast cancers. The percentage change in FDG and FLT-PET uptake did not correlate with changes in Ki-67; post-therapy SUVmax for both tracers was significantly associated with post-therapy Ki-67, an established predictor of endocrine therapy response.

Undulatory swimming in flowing media like water is well-studied, but little is known about loco-motion in environments that are permanently deformed by body–substrate interactions like snakes in sand, eels in mud, and nematode worms in rotting fruit. We study the desert-specialist snakeChion-actis occipitalistraversing granular matter and find body inertia is negligible despite rapid transit and speed dependent granular reaction forces. New surface resistive force theory (RFT) calculation reveals how this snakes wave shape minimizes memory effects and optimizes escape performance given physiological limitations (power). RFT explains the morphology and waveform dependent performance of a diversity of non-sand-specialist, but overpredicts the capability of snakes with high slip. Robophysical experiments recapitulate aspects of these failure-prone snakes and elucidate how reencountering previously remodeled material hinders performance. This study reveals how memory effects stymied the locomotion of a diversity of snakes in our previous studies [Marvi et al, Science, 2014] and suggests the existence of a predictive model for history-dependent granular physics.

e18052 Background: Timely administration of postoperative radiation therapy (PORT) impacts oncologic outcomes in resected squamous cell carcinomas of the head and neck. Salivary gland cancers (SGCs) are uncommon, and timing of PORT has not been extensively explored. We aimed to determine if the interval between surgery and PORT impacts outcomes in SGCs. Methods: We retrospectively identified patients with SGCs who underwent curative intent surgical resection followed by adjuvant PORT at our tertiary referral center. Demographic, tumor, and treatment data were collected. Patients with non-oncologic resections and/or delay of > 6 months to radiation start were excluded. Locoregional control (LRC), relapse free survival (RFS), and overall survival (OS) were estimated using the Kaplan Meier method. A multivariate analysis explored the association between demographics, tumor characteristics, and PORT timing with oncologic outcomes using a stepwise Cox proportional hazards model. Results: Between 1/1/1997 and 12/31/2017 180 eligible patients were identified. Patient characteristics are described in Table. The median time to PORT start was 61 (range 8-121) days, 169 (93.9%) of patients received neutron beam PORT. With a median follow up of 8.2 years in surviving patients, the 5-year OS and LRC estimates were 73% and 67%, respectively. In a multivariate analysis, only nodal involvement, histologic grade, and age at diagnosis were associated with OS, while nodal involvement, tumor size, and age at time of diagnosis were associated with LCR and RFS. Time to PORT start or completion was not statistically associated with survival outcomes on multivariate analysis. Conclusions: SGC patients who underwent surgery in our tertiary institution received PORT within a median of 61 days after surgery. With long term follow up, PORT timing in this retrospective series was not associated with worse oncologic outcomes, and support timely administration of PORT with 3 months of surgical resection. Further work is necessary to assess generalizability of these results.[Table: see text]

Background Neoadjuvant chemotherapy is effective in improving survival of resectable NSCLC. Based on findings in the adjuvant and metastatic setting, FDG positron emission tomography (PET) scans may offer early prognostic or predictive value after one cycle of induction chemotherapy. Methods In this phase II non-randomized trial, patients with AJCC version 6 stage IB to IIIB operable NSCLC were treated with 3 cycles of cisplatin and pemetrexed neoadjuvant chemotherapy. Patients underwent FDG-PET scanning prior to and 18 to 21 days after the first cycle of chemotherapy. Investigators caring for patients were blinded to results, unless the scans showed evidence of disease progression. FDG-PET response was defined prospectively as a ≥ 20% decrease in the SUV of the primary lesion. Results Between October 2005 and February 2010, 25 patients enrolled. Fifty two percent were female, 88% white, and median age was 62 years. Histology was divided into adenocarcinoma 66%, not otherwise specified (NOS) 16%, squamous cell 12%, and large cell 4%. Stage distribution was: 16% IB, 4% IIB, and 79% IIIA. Treatment was well tolerated and only one patient had a grade 4 toxicity. The median follow up was 95 months. The 5 year progression free survival (PFS) and overall survival (OS) for the entire population were 54 and 67%, respectively. Eighteen patients had a baseline FDG-PET scan and a repeat scan at day 18–21 available for comparison. Ten patients (56%) were considered metabolic responders on the day 18–21 FDG-PET scan. Responders had a 5 year PFS and OS of 60 and 70%, respectively, while the percentage for non-responders was 63 and 75% (p = 0.96 and 0.85). Conclusions This phase II trial did not demonstrate that a PET scan after one cycle of chemotherapy can predict survival outcomes of patients with NSCLC treated with neoadjuvant chemotherapy. Trial registration NCT00227539 registered September 28th, 2005.

Lung cancer screening has a mortality benefit to high-risk smokers, but implementation remains suboptimal. Providers represent the key entry point to screening, and an understanding of provider perspectives on lung cancer screening is necessary to improve referral and overall implementation.The objective of this study was to understand knowledge, beliefs, attitudes, barriers, and facilitators to screening in a diverse group of referring pulmonologists and primary care providers.We conducted an electronic survey of primary care and pulmonary providers within a tertiary care medical center across different practice sites. The survey covered the following domains: 1) beliefs and assessment of evidence, 2) knowledge of lung cancer screening and guidelines, 3) current screening practices, 4) barriers and facilitators, and 5) demographic and practice characteristics.The 196 participants included 80% primary care clinicians and 19% pulmonologists (1% others). Forty-one percent practiced at university-based or affiliated clinics, 47% at county hospital-based clinics, and 12% at other or unidentified sites. The majority endorsed lung cancer screening effectiveness (74%); however, performance on knowledge-based assessments of screening eligibility, documentation, and nodule management was suboptimal. Key barriers included inadequate time (36%), inadequate staffing (36%), and patients having too many other illnesses to address screening (38%). Decision aids, which are used at the point of referral, were commonly identified both as important lung cancer screening clinical facilitators (51%) and as provider knowledge facilitators (59%). There were several differences by provider specialty, including primary care providers more frequently reporting time constraints and their patients having too many other illnesses to address screening as significant barriers to lung cancer screening.Providers endorsed the benefits of lung cancer screening, but there are limitations in provider knowledge of key screening components. The most frequently reported barriers to screening represent a lack of clinical time or resources to address lung cancer screening in clinical practice. Facilitators for nodule management as well as point-of-care referral materials may be helpful in reducing knowledge gaps and the clinical burden of referral. These are all modifiable factors, which could be addressed to increase screening referral. Differences in attitudes and barriers by specialty should also be considered to optimize screening implementation.

Introduction Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. Methods A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the β-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [ IFNG ], interleukin 10 gene [ IL10 ], interleukin 1 alpha gene [ IL1A ], interleukin 1 beta gene [ IL1B ], interleukin 2 gene [ IL2 ], interleukin 4 receptor gene [ IL4R ], interleukin 4 gene [ IL4 ], interleukin 6 gene [ IL6 ], prostaglandin-endoperoxide synthase 2 gene [ PTGS2 ] (also known as COX2 ), transforming growth factor beta 1 gene [ TGFB1 ], and tumor necrosis factor alpha gene [ TNFA ]) was evaluated. Results Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1β-511 C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58–0.94] and OR = 0.71 [95% CI: 0.50–1.01], respectively, p = 0.03). Similar results were observed for the IL-1β-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59–0.95] and OR = 0.69 [95% CI: 0.46–1.03], respectively, p = 0.03). Survival was not influenced by genotype. Conclusions This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer.

Objective: Fatigue is a common condition contributing to disability among older patients. We studied self-reported task-specific fatigue and its relation with mobility task performance among community-dwelling primary care patients. Method: Cross-sectional analysis of baseline demographic and health data from a prospective cohort study of 430 primary care patients aged 65 years or older. Fatigue was measured using the Avlund Mobility–Tiredness Scale. Performance tasks included rising from a chair, walking 4 m, and climbing two flights of stairs. Results: Among demographic and health factors, pain was the only attribute consistently predictive of fatigue status. Self-reported chair rise fatigue and walking fatigue were associated with specific task performance. Stair climb fatigue was not associated with stair climb time. Discussion: Pain is strongly associated with fatigue while rising from a chair, walking indoors, and climbing stairs. This study supports the validity of self-reported chair rise fatigue and walking fatigue as individual test items.

11572 Background: 18F-Fluoroestradiol (FES) is an estrogen analogue that has been shown to be a promising biomarker in ER imaging of breast cancer. FES uptake correlates to ER expression, provides qualitative and quantitative assessment of multiple tumor sites simultaneously, and can predict response to endocrine therapies. Tumor heterogeneity is a known feature of metastatic breast cancer. Our work and others has shown that patients that have tumors with high FDG-PET SUV and low FES-PET SUV uptake have a poorer prognosis. Biopsies of metastatic disease may be done initially for diagnosis of metastatic disease, but are generally only performed in the setting of target identification for clinical trials. A change in ER or HER2 expression, however, can result in a change in therapy. FES-PET imaging offers a virtual biopsy and can reveal heterogeneity of the entire tumor burden. Methods: We reviewed our prior evaluations of tumor heterogeneity with FES-PET from 3 different studies. 46 breast cancer patients with metastatic disease (de novo or recurrent) who had biopsy proven ER+ primary breast cancer underwent FES-PET and FDG-PET imaging and a biopsy of a metastatic lesion prior to therapy initiation. ER and HER-2 expression was reviewed. Results: Of the 46 patients, 5 (11%) had ER- metastatic biopsies. One (2%) biopsy changed from ER+/HER-2 neg to ER-/HER-2+, and one (2%) biopsy changed from ER+/HER-2+ to ER+/HER-2-. All 5 patients (11%) with changes in ER/HER2 expression underwent a change in therapy due to the unexpected findings by metastatic biopsy. FDG findings helped to guide selection of biopsy sites. FES quantitative measures correlated with biopsy findings. Conclusions: Biopsy resulted in a change in therapy for > 10 % of patients enrolled in trials of FES imaging. Imaging can help identify heterogeneous tumor locations to assist identification of evolving tumor targets in breast cancer. In addition, FES imaging may reveal a change in tumor phenotype that can ultimately affect choice of therapy. Research Support: P01CA42045, R01CA72064

Purpose. To evaluate the effectiveness of a Web-based interactive teaching tool that uses self-assessment exercises with real-time feedback to aid students’ learning in a gross anatomy class. Method. A total of 107 of 124 first-year medical students at one school were enrolled in the study. Students were divided into three groups: Group 1 (n = 63) received introductory material and activated their Web-based accounts; Group 2 (n = 44) received introductory material but did not activate their Web-based accounts; and Group 3 (n = 17) were not enrolled in the study and received no introductory material. Students in Group 1 had access to a graphic showing the locations of anatomic landmarks, a drill exercise, and a self-evaluation exercise. Students’ ability to identify the anatomic landmarks on a 30-question midterm and a 30-question final exam were compared among the groups. Results. The mean scores of students in Group 1 (midterm = 28.5, final = 28.1) were significantly higher than were the mean scores of students in Group 2 (midterm = 26.8, p < .001; final = 26.9, p < .017) and Group 3 (midterm = 24.8, p < .001; final = 26.4, p < .007). Conclusions. The Web-based tool was effective in improving students’ scores on anatomic landmark exams. Future studies will determine whether the tool aids students in identifying structures located in three-dimensional space within regions such as the cranium and the abdominal cavity. Acad. Med. 2002;77:263‐265.

Microorganisms from Antarctica have evolved particular strategies to cope with cold. Moreover, they have been recently reported as producers of antimicrobial compounds, which inhibit the growth of other bacteria. In this work we characterized from different viewpoints the Gillisia sp. CAL575 strain, a psychrotrophic bacterium that produces microbial volatile organic compounds involved in the growth inhibition of Burkholderia cepacia complex members. Sequencing and analysis of the whole genome of Gillisia sp. CAL575 revealed that it includes genes that are involved in secondary metabolite production, adaptation to cold conditions, and different metabolic pathways for the production of energy. All these features make Gillisia sp. CAL575 a possible tool for biotechnology.

Antarctic bacteria represent a reservoir of unexplored biodiversity, which, in turn, might be correlated to the synthesis of still undescribed bioactive molecules, such as antibiotics. In this work we have further characterized a panel of four marine Antarctic bacteria able to inhibit the growth of human opportunistic multiresistant pathogenic bacteria belonging to the Burkholderia cepacia complex (responsible for the 'cepacia' syndrome in Cystic Fibrosis patients) through the production of a set of microbial Volatile Organic Compounds (mVOCs). A list of 30 different mVOCs synthesized under aerobic conditions by Antarctic bacteria was identified by GC-SPME analysis. Cross-streaking experiments suggested that Antarctic bacteria might also synthesize non-volatile molecules able to enhance the anti-. Burkholderia activity. The biosynthesis of such a mixture of mVOCs was very probably influenced by both the presence/absence of oxygen and the composition of media used to grow the Antarctic strains. The antimicrobial activity exhibited by Antarctic strains also appeared to be more related to their taxonomical position rather than to the sampling site. Different Bcc bacteria were differently sensitive to the 'Antarctic' mVOCs and this was apparently related neither to the taxonomical position of the different strains nor to their source. The genome sequence of three new Antarctic strains was determined revealing that only P. atlantica TB41 possesses some genes belonging to the nrps-pks cluster. The comparative genomic analysis performed on the genome of the four strains also revealed the presence of a few genes belonging to the core genome and involved in the secondary metabolites biosynthesis. Data obtained suggest that the antimicrobial activity exhibited by Antarctic bacteria might rely on a (complex) mixture of mVOCs whose relative concentration may vary depending on the growth conditions. Besides, it is also possible that the biosynthesis of these compounds might occur through still unknown metabolic pathways.