tbuckley/cabot-search huggingface dataset:
Egfr Del19/L858R Activating Mutation (M+) Subgroup in Radiant: Baseline Characteristics, Prognostic Role, and Disease-Free Survival (Dfs) By Stage
Authors: N.K. Altorki, K. Kelly, M.E.R. O'Brien, W.E.E. Eberhardt, J. Wang, J.D. Horan, M.A. Foley, F.A. Shepherd
Journal: Annals of Oncology (2014)
Phase II double-blind, randomized study of selumetinib (SEL) plus dacarbazine (DTIC) versus placebo (PBO) plus DTIC as first-line treatment for advanced <i>BRAF</i>-mutant cutaneous or unknown primary melanoma.
Authors: Mark R. Middleton, Reinhard Dummer, Ralf Gutzmer, Paul Lorigan, Kevin Kim, Marta Nyakas, Ana Maria Arance, Gabriella Liszkay, Dirk Schadendorf, Mireille Veronique Cantarini, Stuart Spencer, Caroline Robert
Journal: Journal of Clinical Oncology (2013)

9004 Background: BRAF mutations play an oncogenic role in melanomas. Selumetinib (AZD6244, ARRY-142886) inhibits MEK1/2 downstream of B-Raf and may have an additive effect to chemotherapy. We prospectively evaluated SEL + DTIC vs PBO + DTIC in patients with stage III-IV BRAF mutation-positive advanced cutaneous or unknown primary melanoma (NCT00936221). Methods: Eligible patients (pts) received iv DTIC 1000 mg/m 2 , and po SEL 75 mg or matched PBO bd as first-line treatment. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety and tolerability. Results: A total of 385 pts were screened across 44 centers; 91 patients were randomized (SEL + DTIC, 45; PBO + DTIC, 46). One pt from each group did not receive the randomized treatment. Baseline characteristics were balanced between the two groups, with the exception of histology, gender and previous medications. At data cut-off, 66 deaths had occurred (73% maturity) and median follow-up was 12.3 mo. OS was longer for SEL + DTIC vs PBO + DTIC (median 13.9 vs 10.5 mo), but this did not meet statistical significance (HR 0.93; 80% CI 0.67, 1.28; 1-sided p=0.3873). PFS was significantly improved for SEL + DTIC vs PBO + DTIC, median 5.6 vs 3.0 mo (HR 0.63; 80% CI 0.47, 0.84; 1-sided p=0.021). ORR was 40% with SEL + DTIC vs 26% with PBO + DTIC. Most frequent adverse events (AEs) observed with SEL + DTIC were: nausea (64%), dermatitis acneiform (52%), diarrhea (48%), vomiting (48%), and peripheral edema (43%). AEs that led to hospitalization were higher for SEL + DTIC vs PBO + DTIC (36 vs 13%), and were mostly infections and gastrointestinal disorders. The incidence of grade ≥3 AEs (68 vs 42%), serious AEs (50 vs 18%) and discontinuation of the randomized treatment due to AEs were higher for SEL + DTIC vs PBO + DTIC (16 vs 4%). Conclusions: Clinical activity was observed in patients with BRAF mutation-positive melanoma treated with SEL + DTIC, reflected by a nonsignificant improvement in OS and a significant benefit in PFS. Tolerability of this combination was generally consistent with the monotherapy safety profiles. Clinical trial information: NCT00936221.
Management of ankle injuries
Authors: Matthew Welck, Michael Rafferty, Stephanie Eltz, Shafic Said Al-Nammari, Kelechi Chika Eseonu
Journal: BMJ (2015)

A 26 year old woman presented to the emergency department after injuring her left ankle. While walking on an uneven pavement in the rain she lost her footing and described a sudden “buckling” of her ankle (plantar flexion and inversion injury). She could not bear weight so an ambulance was called.

She was previously fit and well and was on no regular drugs. Six months earlier she had twisted the same ankle while playing hockey. Radiographs taken at the emergency department had been normal, and she was discharged with crutches and a compression bandage. She returned to work after two weeks but had not returned to sport because she did not trust her ankle.

Clinical examination identified tenderness, swelling, and ecchymosis over the anterior talofibular and calcaneofibular ligaments, with some bony tenderness on the posterior edge of the lateral malleolus. She had no medial tenderness. Ankle ligament stress testing was not performed owing to pain.



### 1. What is the most likely diagnosis?

#### Short answer

Lateral ankle ligamentous injury.

#### Discussion

The most common injury sustained during an ankle plantar flexion and inversion injury is a lateral ankle ligamentous injury. The bony architecture of the ankle joint is most stable in dorsiflexion. Ankle sprains are therefore more likely to occur with the ankle in plantar flexion because ligamentous support is more important.

A 2014 meta-analysis found a higher incidence of ankle sprain in females than in males, in children than in adolescents, and in adolescents than in adults. Indoor and court …
Prognostic role of body composition parameters in renal cell carcinoma (RCC).
Authors: Emilie Lanoy, Sami Antoun, Roberto Iacovelli, Laurence Albiges, Yohann Loriot, Mansouriah Merad, Karim Fizazi, Mario Di Palma, Vickie E. Baracos, Bernard J. Escudier
Journal: Journal of Clinical Oncology (2012)

4621 Background: Previous studies have shown that body component i.e. muscle tissue (MT) and adipose tissue (AT) are linked to overall survival (OS) and progression free survival (PFS). The aim of our study is to analyze whether MT and AT have a prognostic role in metastatic RCC treated with targeted therapy. Methods: We investigated body mass index (BMI), MT and AT in RCC pts. Analysis of CT image was used to evaluate cross-sectional areas (cm 2 ) of total AT (TAT), MT, and the grey level image (GLI) of MT, reflecting physical properties of the scanned tissue and used as a proxy to describe the quality of muscle. The 3 rd lumbar vertebra (L3) was chosen as a landmark since L3 and whole-body measurements are linearly related. Images were analyzed using Slice-O-Matic software V4.3 (Tomovision). Indexed on height MT (cm 2 /m 2 ), indexed on height TAT (cm 2 /m 2 ) and mean GLI of MT were computed and described stratified on sex. For each measurement, population was divided in two groups: patients with values &lt; or &gt;= median observed in patient of the same gender and OS and PFS were estimated using Kaplan-Meier method and compared with the log-rank test. Multivariable Cox proportional hazards model were adjusted for modified MSKCC risk group and treatment (active versus placebo). Results: There were 113 men aged of 60 (interquartile range=52-56) years with BMI of 26 (24-29) kg 2 /m 2 and 36 women aged of 58 (54-65) years with BMI of 23 (20-26) kg 2 /m 2 . After adjustment for MSKCC (OS and PFS) and active treatment (PFS), GLI of MT over the median was associated with longer OS (HR=1.85, 95%CI=[1.22;2.82], p=.004) and PFS (HR=1.81, 95%CI=[1.22;2.65], p=.002) Conclusions: Quality of muscular tissue is independently associated with better outcome in RCC. Surprisingly, adipose tissue as well as BMI is not associated with survival in this study. [Table: see text]
Abstract 15313: The association between diet quality and mortality in incident type 2 diabetic women
Authors: Hyun Joon Shin, Ja Young Kim, Eunyoung Cho, Seungyoun Jung, Eric Rimm, Bernard Rosner, JoAnn E. Manson, Frank B. Hu
Journal: Circulation (2013)

Hyun Joon Shin, 2013 Finalist and Presenting Author
Rates and predictors of adjuvant chemotherapy use in older breast cancer patients with hormone receptor-negative disease
Authors: E. B. Elkin, K. S. Panageas, A. Hurria
Journal: Journal of Clinical Oncology (2005)

6020 Background: For women with hormone receptor-negative (HR-) breast cancer, chemotherapy (CTX) is the only adjuvant systemic treatment option, since hormonal therapies are largely ineffective in this patient subgroup. Older women are less likely than younger women to receive adjuvant CTX, although age alone is not a contraindication to treatment. Our objective was to identify predictors of adjuvant CTX use in older US women with HR-negative breast cancer, using population-based cancer registry data linked with Medicare claims. Methods: We identified all first primary breast cancers reported to the SEER cancer registries from 1992 through 1999. We included women age 66 and older with non-metastatic, HR- breast cancer. Chemotherapy use within 6 months of diagnosis was identified in Medicare claims. Results: Of 45,701 women diagnosed with Stage I-Stage III breast cancer, 5,081 (11%) had HR- disease. Overall, 31% of the HR- cohort received chemotherapy within 6 months of diagnosis. Adjuvant CTX use increased over time, and was negatively associated with age at diagnosis. In multivariate analysis, age remained a strong predictor of adjuvant CTX use. Women under 75 were at least 4 times more likely to receive CTX than those age 75 and older. Large tumor size, poorly differentiated tumor cells, and lymph node involvement increased the odds of receiving CTX, while greater comorbidity and lower socioeconomic status decreased these odds. Controlling for other factors, the association between year of diagnosis and adjuvant CTX was not significant. Conclusions: Among older women with HR- breast cancer, receipt of adjuvant CTX is strongly correlated with age and prognosis. Although use of adjuvant CTX increased during the 1990s, this trend was attenuated after adjusting for other factors. Further analyses will examine trends in the use specific adjuvant CTX agents, as well as CTX toxicities, in this patient population. No significant financial relationships to disclose.
The role of maintenance bevacizumab in patients with metastatic breast cancer treated with chemotherapy and bevacizumab upon achieving complete response or maximal radiologic response with stable disease
Authors: S. E. Waintraub, V. Tuchman
Journal: Journal of Clinical Oncology (2008)

12022 Background: One of the drawbacks of the E-2100 trial that compared paclitaxel (P)/bevacizumab (B) to P in previously untreated patients (pts) with metastatic breast cancer (mbc) is that pts were treated until disease progression (DP), and no maintenance (M) arm was permitted with single agent B in pts with a complete response (CR) or maximal radiologic benefit with stable disease (MRB). Newer trials in mbc will look at the benefit of M therapy with single agent B in such pts. Methods: We have administered single agent maintenance B (MB) at 15mg/kg iv q 3 weeks in 5 pts with mbc, 3 of whom received initial B+chemotherapy (C) regimens first line and achieved a CR or MRB, and 2 who received B+C regimens upon progression from other chemotherapy regimens who achieved a MRB. Results: We have observed that all 3 pts who received B+C regimens as their first line therapy for mbc who achieved a CR or MRB have been maintained on B alone for 13 months (m), 7m, and 4m, respectively, with restaging done q 3m to assess for DP. The 2 pts with mbc who had previous C before getting a C+B based regimen that achieved MRB all progressed after 3m of MB, but then responded again when C+B was resumed. Conclusions: This suggests that there is a group of pts that may be able to be treated with MB without C after a CR or a MRB from C+B has been achieved, without DP, similar to what is commonly done with trastuzumab in HER2neu + mbc patients. This group of pts may be the group that is previously untreated for mbc, like those in E-2100. It is encouraging to note that the pts previously treated with C who then got C+B upon progression and then responded to that combination did not do well with MB, but they did however again respond to C+B upon progression from MB therapy. New C+B trials for mbc should have maintenance arms with B alone when patients achieve a CR or MRB with stable disease to the C+B regimen. This observation may be explained by 2 different mechanisms of action of B, initially acting as a chemotherapy delivery enhancer to the tumor, and then in maintenance acting as an anti-angiogenic agent to prevent tumor regrowth. The use of MB after MRB or CR to C+B could clearly have a positive benefit to the quality of life of these patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Genentech
Folfoxiri plus Bevacizumab as first-line treatment of BRAF mutant metastatic colorectal cancer patients.
Authors: L Salvatore, F Loupakis, Chiara Cremolini, M Schirripa, G Masi, C Antoniotti, L Fornaro, E Sensi, C Lupi, F Bergamo, S Lonardi, Zagonel, Gabriella Fontanini, Alfredo Falcone
Journal: Annals of Oncology (2012)
The multimodality therapy for patients with advanced non-small cell lung cancer (Stage IIIB and IV)
Authors: H. Guo, Z. Li, H. Cheng, J. Sun
Journal: Journal of Clinical Oncology (2005)

7350 Background: To investigate the effectiveness of multimodality therapy for patients with advanced non-small cell lung cancer in stage IIIB(T4 or N3) and IV(M1),to evaluate the role of surgical treatment,elemene emulsion (Chinese drug) and bioimmunotherapy. Methods: Between 1995 and 2003 in PUMC Hospital 51 patients with advanced non-small cell lung cancer in stage IIIB(T4 or N3) and IV(M1) underwent surgery followed by postoperative chemotherapy,some of them received postoperative radiotherapy and bioimmunotherapy.Kaplan-Meier analysis was used to evaluate the median survival time(MST) and the 1-year and 3-year survival rate.The quality of life pre-operation and post-operation were compared. Results: 1.The median survival time was 37 months.The overall 1-year and 3-year survival rate were about 86% and 53% respectively.2. The overall KPS is 71.8± 9.7 before surgery and 74.8±8.6 1-month after surgery,the difference is significant.3.In the controlled studies,patients with elemene emulsion have more advantages than patients without elemene emulsion on the elevation of MST, survival rate and quality of life, also on the alleviation of adverse reaction of chemotherapy, especially on leucopienia. 4. The median survial time, 1-year and 3-year survival rate of 32 patients with bioimmunotherapy were 38 months, 96.55% and 58.4%, 26 months, 63.63% and 26.51% i 19 patients without bioimmunotherapy. Log-rank test showed significant difference between them. Conclusions: For some patients with advanced Non-small lung cancer (Stage IIIB and IV) the individualized optional multimodality therapy can improve the postoperative quality of life and survival time. Surgery, elemene emulsion and bioimmunotherapy are important prognostic factors. No significant financial relationships to disclose.
Long term results of induction carboplatin (CBDCA) and docetaxel (DOC) with concurrent radiation in early-stage non-small cell lung cancer (NSCLC)
Authors: N. Katakami, R. Naya, T. Nishimura, A. Ikeda, M. Hayashi, M. Okazaki, K. Tomii, Y. Takahashi, K. Hirokawa, B. Umeda
Journal: Journal of Clinical Oncology (2005)

7237 Background: Despite surgical resection, patients with clinical T2N0, T1–2N1 and T3N0 NSCLC have poor 5-year survivals (30% to 50%). Since a significant proportion of patients with early-stage NSCLC experience distant as well as loco-regional recurrences, multimodality therapy has recently been encouraged in an attempt to prolong survival. We conducted a phase II study to determine the feasibility and efficacy of induction CBDCA and DOC with concurrent radiation in early-stage NSCLC. Methods: Eligible were patients with previously untreated stage IB, and II histologically proven NSCLC. Clinical nodal stage was assessed by mediastinoscopy, mediastinotomy and CT imaging. A negative biopsy result of all enlarged mediastinal lymph nodes (shortest diameter ≥1.0 cm on CT scan) was required. CBDCA (AUC=5) and DOC (60 mg/m2) were administered once every 3 weeks for 2 cycles concurrent with 40 Gy (2Gy/fx/day) radiation. In patients with no evidence of disease progression thoracotomy was performed 3–5 weeks later. Results: Forty patients were entered into the study between 02/99 and 07/01. Patient characteristics included M/F: 27/13; median age (range): 59 (39–73); clinical stage T2N0/T1N1/T2N1/T3N0: 21/2/13/4; adeno/squamous/large cell: 26/12/2. Despite a high rate of grade 3/4 neutropenia (88%), no serious infectious events were observed. All the patients completed induction chemoradiotherapy and major responses were observed in 29 (73%). Of these, thirty-nine patients underwent thoracotomy and were resected completely. The type of operation was pneumonectomy in 2 and lobectomy in 37. A pathologic response (T or N downstaging) was identified in 30 (77%) and 10 (26%) had no residual disease. One patient had a bronchopleural fistula after left pneumonectomy. Median follow up was 57 months. Actuarial 3-year and estimated 5-year survivals were 82.5% and 69.9%, respectively. Three-year and 5-year disease free survivals were 76.9% and 71.0%, respectively. Conclusions: Induction concurrent chemotherapy (CBDCA + DOC) with thoracic radiotherapy is feasible, tolerable and deserves further evaluation in a randomized phase III study. No significant financial relationships to disclose.
Activation of the MDA-5–IPS-1 Viral Sensing Pathway Induces Cancer Cell Death and Type I IFN-Dependent Antitumor Immunity
Authors: Xiaofei Yu, Hongxia Wang, Xia Li, Chunqing Guo, Fang Yuan, Paul B. Fisher, Xiang-Yang Wang
Journal: Cancer Research (2016)

Abstract Melanoma differentiation–associated gene 5 (MDA-5, IFIH1), a cytosolic innate pattern recognition receptor, functions as a first line of defense against viral infection by sensing double-stranded RNA. Ectopic expression of MDA-5 has been shown to induce cancer cell death, but the mechanism of action by which MDA-5 exerts these cytotoxic effects is unclear. Here, we demonstrate that ectopic expression of MDA-5 via replication-incompetent adenovirus (Ad.Mda-5) initiates multiple signaling cascades, culminating in cytotoxicity and type I IFN production in mouse and human prostate cancer cells. This intrinsic dual activity of MDA-5 required the adaptor protein IFNβ promoter stimulator 1 (IPS-1, MAVS) and could be functionally uncoupled. MDA-5 lacking N-terminal caspase recruitment domains (CARD) engaged an intracellular death program in cancer cells but was unable to efficiently stimulate the expression of IFNβ. In contrast to cancer cells susceptible to MDA-5–mediated cytotoxicity, normal cells were highly resistant and instead developed a robust type I IFN response. Strikingly, intratumoral delivery of Ad.Mda-5 led to regression of preestablished prostate cancers and development of long-lasting antitumor immune memory, which was primarily attributed to the activation of tumor-reactive cytotoxic T lymphocytes and/or natural killer cells. Using the CARD-truncated MDA-5 mutant, silencing of IPS-1, and antibody blockade of the IFNα/β receptor, we further demonstrate that type I IFN signaling was crucial for in situ MDA-5–induced protective antitumor immunity. Therefore, deliberately targeting the evolutionarily conserved MDA-5–IPS-1 antiviral pathway in tumors can provoke parallel tumoricidal and immunostimulatory effects that bridge innate and adaptive immune responses for the therapeutic treatment of cancer. Cancer Res; 76(8); 2166–76. ©2016 AACR.
Abstract P011: White Blood Cell Count in Young Adulthood and Coronary Artery Calcification in Early Middle Age: Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Lifang Hou, Donald Lloyd-Jones, Hongyan Ning, Mark . D Huffman, Myriam Fornage, Ka He, Jacobs R David, David C Goff, Stephen Sidney, Jeffrey J Carr, Kiang Liu
Journal: Circulation (2012)

Background: White blood cell (WBC) count is associated with incident coronary heart disease (CHD). Coronary artery calcification (CAC) is a measure of subclinical atherosclerosis that predicts CHD events. Since data are sparse regarding the association of WBC count with future CAC, we examined the association of WBC count in early adulthood (age 18-30 yrs.) with the presence of CAC 15 or 20 years later (age 33-50 yrs.). Methods: We included CARDIA participants who had baseline data on risk factors and WBC counts, and participated in the Year (Y) 15 or Y20 examinations with CAC score information. We performed age-, sex-, and race-adjusted linear regression analyses to examine the cross-sectional association between baseline (Y0) WBC count (total and subtypes) and known CHD risk factors, including systolic blood pressure (SBP), BMI, smoking (packs/year), total and HDL-cholesterol. We used multiple logistic regressions to assess prospective associations between Y0 WBC count and the presence of CAC at Y15 and Y20. Results: Among 3094 participants, mean (SD) age at baseline was 25± 4 years, 57% were women and 45% were black. In total, 263 and 566 subjects had CAC score&gt;0 at Y15 and Y20 examination, respectively. Y0 SBP, BMI, and smoking (p&lt;0.001), and HDL-cholesterol (p=0.01) were significantly associated with Y0 total WBC counts. Compared to participants without CAC at Y20, those with CAC score&gt;0 had higher Y0 counts (10 9 /L, SD) of total WBC (6.0 ± 1.8 vs. 6.2 ± 1.9, p=0.04), lymphocyte (2.16 ± 0.75 vs. 2.23 ± 0.76 p=0.05), and eosinophil (0.16 ± 0.13 vs. 0.18 ± 0.16, p&lt;0.001). These counts were positively associated with the presence of Y20 CAC after adjusting for potential confounders ( Table 1 ). Similar patterns were observed for Y15 CAC (data not shown). Conclusion: Total WBC and certain subtype counts in young adulthood are significantly associated with presence of CAC 15 or 20 years later in early middle age. These findings suggest the possible involvement of WBC in the initiation and/or early development of atherosclerosis. Table 1. Y0 WBC counts and CAC presence at Y20 (OR (95% CI) per 1 x 10 9 /L WBC counts Model 1 * Model 2 ** Total WBC 1.24 (1.12, 1.37) 1.11 (1.00, 1.24) Monocyte 1.02 (0.93, 1.13) 0.96 (0.87, 1.07) Neutrophils 1.13 (0.99, 1.28) 1.06 (0.93, 1.21) Lymphocyte 1.16 (1.05, 1.28) 1.03 (0.93, 1.14) Eosinophil 1.17 (1.05, 1.29) 1.14 (1.02, 1.27) * Age, sex, race adjusted; ** Model 1 plus Y0 education, SBP, BMI, TC, HDL, smoking and blood pressure lowering medication use.
Endocardial Tumors Induced by Carbamate or Fluorenylacetamide Derivatives in Rats
Authors: C Hoch-Ligeti, P N Harris, H L Stewart
Journal: JNCI Journal of the National Cancer Institute (1983)

Endocardial tumors were induced in 18 rats treated with derivatives of carbamates and in 4 rats treated with derivatives of fluorenylacetamide. The endocardial tumor of 1 rat treated with N,N'-2,7-fluorenylenebisacetamide metastasized to the lung. This is the first report of metastasis of an endocardial tumor. Among the more than 60,000 accessions at the Registry of Experimental Cancers, Division of Cancer Cause and Prevention, National Cancer Institute, there are 4 untreated rats with endocardial tumors. On the basis of the light microscopic morphology, we have classified these endocardial tumors as mesenchymal.
Long-Term Outcome of Chronic Myelomonocytic Leukemia (CMML) Patients Treated with Hypomethylating Agents (HMA): A Single-Institution Experience
Authors: Adolfo Diaz Duque, Monica Cabrero, Farhad Ravandi, Naveen Pemmaraju, Gautam Borthakur, Hagop M. Kantarjian, Jorge E. Cortes, Tapan M. Kadia, Naval G. Daver, Elias Jabbour, Guillermo Garcia Manero, Koji Sasaki
Journal: Blood (2014)
Impact Of Clinical and Biological Factors On Outcome In a Cohort Of Unselected Chronic Lymphocytic Leukemia (CLL) Patients
Authors: Giovanna Piras, Roberta Murru, Angelo D. Palmas, Rosanna Asproni, Antonella Uras, Maria Monne, Marco Murineddu, Giovanna Pira, Anna Calvisi, Emanuele Angelucci, Giancarlo Latte
Journal: Blood (2013)
Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β
Authors: Javed Mohammed, Lalit K Beura, Aleh Bobr, Brian Astry, Brian Chicoine, Sakeen W Kashem, Nathan E Welty, Botond Z Igyártó, Sathi Wijeyesinghe, Emily A Thompson, Catherine Matte, Laurent Bartholin, Alesia Kaplan, Dean Sheppard, Alina G Bridges, Warren D Shlomchik, David Masopust, Daniel H Kaplan
Journal: Nature Immunology (2016)