tbuckley/cabot-search huggingface dataset:
High-risk soft tissue sarcoma of extremity and trunk wall: A retrospective comparison of local control in patients treated with or without radiation therapy at a single reference center.
Authors: Marco Fiore, Claudia Sangalli, Elena Palassini, Stefano Radaelli, Chiara Colombo, Carlo Morosi, Dario Callegaro, Andrea Pierluigi Fontana, Paolo Giovanni Casali, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2015)

10543 Background: Wide resection plus RT has been considered in the past 3 decades standard treatment for high-risk STS of extremity and trunk wall. The potential for avoiding RT has been explored in limited groups of patients (pts), e.g. small STS. We retrospectively explored the role of RT in high-risk STS treated at a reference institution over a more recent time spam. Methods: Consecutive pts affected by primary, localized, extremity and trunk wall STS surgically treated between 2000 and 2012 were reviewed. All tumors were ≥ 5 cm, deep, and G2-G3 according to FNCLCC grade. Ewing/pPNET and pediatric STS were excluded. Two groups were identified: Group A, pts who received adjuvant/neoadjuvant RT; Group B, pts who did not. Local recurrence-free survival (LRFS) was analyzed. Results: Study population included 404 pts. Median follow up was 53 months for alive pts (IQR, 30-85). Median size was 10 cm. In Group A, 319 pts received RT (106 preoperative, 211 postoperative, 2 pre- and post). In Group B, 85 pts did not receive RT for individualized reasons. No significant differences were found between groups according to tumor size, age, sex, histotypes. Margins in Group A were R0/R1 in 252 (78.9%), and 67 (21%) cases, respectively; in Group B, 63 (74.1%) and 22 (25.9%), respectively (P value = .380). Group A and Group B were different for: G3 tumors (80.6% and 68.2%, respectively; P value = .0184); trunk tumors (7.5% and 20%, respectively; P value = .0013); (neo-)adjuvant chemotherapy (57.7% and 38.8%, respectively; P value = .002). Five-years LRFS was 83.91% in Group A, and 81.11% in Group B (P value = .1302). No differences in LRFS were found neither between R0 pts treated in Group A and B (P = .1417), nor between R1 pts treated in Group A and B (P = .6971). Conclusions: Local outcome of high-risk STS in pts individually treated without radiation therapy was not significantly different compared to those treated by surgery plus RT. Further studies are needed to investigate which subgroups of high-risk STS may benefit from surgery alone, possibly distinguishing between extremity and trunk sites, as well as between G2 and G3 tumors.
Is there an interaction between epidermal growth factor receptor (EGFR) inhibition and p16-status in patients (pts) with oropharyngeal squamous cell cancer: A retrospective analysis.
Authors: Tobenna Igewonu Nwizu, Lisa A. Rybicki, Deborah Chute, Cristina P. Rodriguez, Shlomo A. Koyfman, John Greskovich, Jerrold P. Saxton, Joseph Scharpf, Robert Lorenz, Brian Burkey, Benjamin J. Wood, Mumtaz Khan, Samer Al-khudari, Aaron P. Hoschar, Denise I. Ives, Joanna Bodmann, David J. Adelstein
Journal: Journal of Clinical Oncology (2013)

6061 Background: Conflicting data exists about whether EGFR inhibition is more or less effective in pts with p16 positive or negative oropharynx cancer (OPC). We update results from two institutional clinical trials in pts with locoregionally advanced head and neck squamous cell carcinoma (LRA HNSCC) given chemoradiotherapy either with or without the oral EGFR inhibitor gefitinib (G), with specific attention to the subset of pts with p16-defined OPC. Methods: Between 1996-2000, 44 pts with LRA HNSCC were treated on a Cleveland Clinic IRB-approved protocol using concurrent cisplatin, fluorouracil and radiation without G (G- cohort). Between 2003-2007, 60 similar pts were treated using the same chemoradiotherapy regimen with the addition of G 250 mg daily for 2 years beginning on day 1 of radiation (G+ cohort). Available biopsy material from 64 OPC pts (23 G-, 41 G+) was retrieved and tested by immunohistochemistry for p16 (as a surrogate for human papillomavirus) positivity. Kaplan-Meier outcome projections were compared using the log-rank test. Results: With a median follow-up in excess of 7 years for all pts, survival and patterns of failure did not differ between the two trials. The 5-year overall survivals (OS) were 68% vs. 64% (p=0.73) and relapse-free survivals (RFS) 65% vs. 63% (p=0.85) in the G+ and G- cohorts respectively. OPC was more frequent in the more recently treated G+ cohort (68% vs. 53%). Excluding 14 pts for whom tumor was unavailable, OPC p16-positivity was also more frequent in the G+ cohort (74% vs. 63%). As expected, outcomes in the p16+ OPC pts were significantly better than in the p16- OPC pts including OS (66% vs. 58%, p=0.049) and RFS (69% vs. 56% p=0.027). However, in comparing the G+ and G- cohorts, the use of G did not significantly alter any survival outcome or pattern of failure in either the p16+ or p16- OPC pts. Conclusions: Although the retrospective nature of this analysis limits the strength of our conclusions, in the definitive management of LRA HNSCC, we could identify no effect of oral EGFR inhibition on any outcome. In subset analysis there was also no differential impact found in either the p16+ or p16- OPC pts. Clinical trial information: NCT00352105.
Ewa Roos #MorningRun #InspirationalLeadership
Authors: Johann Windt
Journal: British Journal of Sports Medicine (2017)

Improving the lives of people with joint injury and osteoarthritis. I am idealistic and want to make a difference. Considering the organisational, financial and political barriers to change in healthcare, I realise that my obligation as a researcher is to work strategically and take every opportunity to promote evidence-based medicine.

For the past 15 years I have started every day with a 2 km run. I have played sport all my life, but trained like most people do—larger amounts at fewer times a week, as we were taught in physiology class. In 2000 I did a postdoc in Boston and prioritised family and work life, leaving me no time to run. Unfortunately, my family did not appreciate the irritated and impossible person they had to deal with. One day our 22-year-old nanny stood in front of me and said: “I will get up earlier in the …
Long-term symptom burden and orodental health of oropharyngeal cancer (OPC) survivors following treatment with chemoradiotherapy (CRT) or sequential therapy (ST).
Authors: Sewanti Atul Limaye, Robert I. Haddad, Ann Partridge, Anne M. O'Neill, Andrea Radossi, Aditya V. Shreenivas, David Lorente, Glenn J. Hanna, Stephen T. Sonis, Lawrence N. Shulman, Marshall R. Posner, Jochen H. Lorch
Journal: Journal of Clinical Oncology (2013)

9530 Background: OPC treatment is associated with significant long-term toxicity. Very little is known about the long-term symptom burden and orodental health in OPC survivors &gt;2 yrs from treatment. Methods: Survivors treated for OPC with CRT/ST (involving definitive RT) at Dana Farber Cancer Institute between 2002-2011 and &gt;2 yrs from treatment completion, were identified by chart review and asked to complete the Vanderbilt Head and Neck Symptom Survey version 2 (VHNSS v2), National Health And Nutrition Examination Survey for Oral Health Questionnaire, health care availability survey. Results: 200 survivors were contacted, 127 responded (RR: 64%). Median age at diagnosis was 54 yrs; 85% males; 85% stage IVA/B, 13% stage III; 56% CRT, 43% ST. HPV status: 47% (+), 10% (-), 43% unknown. Median time from treatment completion: 50 mths (24-135 mths). Residual moderate to severe toxicities reported in VHNSS v2: 71% dry mouth; 59% difficulty chewing/swallowing food; 53% feeling of food becoming stuck in the throat; 53% prolonged time to eat; 31% thick mucus, 6% had difficulty sleeping secondary to this; 16% trouble speaking, 27% trouble hearing;30% limitation of neck/shoulder movement; altered taste/smell - 45%/23%; sensitivity to spicy food and dryness-57%/62%; 30% decreased desire to eat, 11% had moderate weight loss. Orodental health assessment: 13% thermal sensitivity, 21% teeth cracking and chipping, 20% loose teeth, 33% had treatment for gum disease, 42% had lost bone around teeth. 98% survivors had health insurance; only 66% had dental insurance. No statistically significant difference was noted with respect to symptoms between CRT or ST. ST did not affect long-term toxicity compared to CRT alone. Conclusions: OPC is known to correlate with HPV positivity, early age at diagnosis and high rates of long-term survival after appropriate therapy. Our study documents that the OPC survivors have substantial residual long-term head and neck and orodental symptoms directly related to the treatment that significantly impacts their quality of life. A substantial number of patients lack dental health coverage, which likely further impacts symptom burden and QOL.
Association of Hemoglobin S and C Traits with Kidney Disease in African Americans in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Rakhi P. Naik, Marguerite R. Irvin, Suzanne Judd, Orlando Gutierrez, Neil A Zakai, Vimal K. Derebail, Carmen Peralta, Michael Lewis, Degui Zhi, Donna Arnett, William McClellan, James G. Wilson, Alexander Reiner, Jeffrey Kopp, Cheryl Winkler, Mary Cushman
Journal: Blood (2015)
An integrated analysis of comprehensive geriatric assessment (CGA) in elderly patients with non-small cell lung cancer (NSCLC) (JCOG1115-A).
Authors: Hiroshi Katayama, Koji Takeda, Haruhiko Fukuda, Shinichiro Nakamura, Kenichi Nakamura, Junki Mizusawa, Nagahiro Saijo, Akira Yokoyama, Yuichiro Ohe, Tetsu Shinkai, Kazuhiko Nakagawa, Tetsuya Abe, Shigeki Mitsuoka, Yukito Ichinose, Hiroaki Okamoto, Nobuyuki Yamamoto, Hiroshige Yoshioka, Masahiko Ando, Tomohide Tamura
Journal: Journal of Clinical Oncology (2012)

6112 Background: The number of elderly NSCLC patients is increasing all over the world. Actual age and ECOG PS is not always efficient to select "fit-elderly" for chemotherapy. We integrated the data from two phase III trial (JCOG0207, JCOG0803/WJOG4307L) and evaluated 4 CGA items as well as age and PS to determine whether they would predict survival, response and toxicities. Methods: Eligibility criteria of both trials included histologically or cytologically proven NSCLC; stage III/IV; age 70 or more; ECOG PS of 0-1; unfit for bolus cisplatin; no prior treatment; adequate organ function. Patients were randomized to receive either weekly docetaxel (D) or D plus cisplatin (DP) in J0207, and either 3-weekly D or DP in J0803/W4307L. This study included all eligible pts for whom all of 4 CGA items (Activity of Daily Living [ADL], Instrumental Activity of Daily Living [IADL], Mini-Mental State Examination [MMSE], Geriatric Depression Scale [GDS-15]) were assessed before treatment. Primary endpoint was overall survival (OS). Survival curves are estimated by Kaplan-Meier method and multivariate analysis for OS adjusting baseline factors were performed by using stratified Cox regression model. Results: This analysis included 331 pts (J0207/J0803-W4307L: 105/226) in total. The result of multivariate analysis for OS was shown in the table. After adjusting baseline factors, MMSE as well as sex and PS was significantly associated with OS. None of the CGA items were associated with response and toxicities. Conclusions: It is not actual age but MMSE and PS that is useful for predicting prognosis of elderly pts. MMSE should be taken into consideration to determine the indication of chemotherapy for elderly pts. [Table: see text]
Prognostic molecular factors in patients with gastric cancer stage UICC I without lymph-node involvement.
Authors: Christoph Treese, Pedro Sanchez, Ioannis Anagnostopoulos, Michael Kruschewski, Oliver Haase, Ulrich Keilholz, Hendrik Blaeker, Michael Hummel, Severin Daum
Journal: Journal of Clinical Oncology (2014)

e15071 Background: 5-year survival rate in patients with adenocarcinoma of the gastro-esophageal junction or stomach (AGE/S) in UICC stage I is reported to be 60-80% only (Hölscher et al, 2009; Siewert et al. 1998). One option to improve survival might be to intensify therapy in high-risk tumors. Aim of this study was to identify prognostic markers for UICC I patients without lymph-node involvement as this is a known independent prognostic marker. Methods: Tissue specimens and clinical data from patients with AGE/S (UICC stage I without lymph-node involvement treated only by surgery including D1- and D2-lymphnode dissection) treated in the years 1993 to 2010 at the Charité, Berlin were collected retrospectively. Expression of BAX, CDX2, Cyclin E, E-catherin, KI67, MACC1, p53, PTEN, S100, SHH, SURVIVIN and TROP2 was analyzed by using tissue micro arrays. Expression was correlated with known prognostic markers like tumor size, lymphatic vessel or vein invasion, grading or common classification systems (WHO, Lauren, Ming). Marker expressions were compared by using one-sample T-test or performing the one-way analysis of variance. Results: 129 patients (f = 48, mean age 63 years) with a follow-up time from 6 to 224 months were identified. The 5-year survival was 94.57%. For immunohistological examination samples from 75 patients were available. Significant differences were detected between T1a and T1b tumor size, with a higher expression of SURVIVIN (p 0.008) in T1a. Furthermore the expression of p53 (p <0.001), SHH (p <0.001) and Trop2 (p < 0.001) was higher in the V1-positive cohort while the expression of BAX (p 0.001) was lower in the V1- in comparison to the V0 cohort. p53 expression also correlated with L1positivity (p=0.048). Conclusions: In our study patients with gastric cancer in stage UICC I have an excellent prognosis (95%). Overexpression of p53, SHH und Trop2point to a potential mechanism of these molecules in metastasis in early stage gastric cancer. Our molecular approach might also be interesting in other UICC stages. This study was supported by the Berliner Krebsgesellschaft, grant DAFF201101.
A Phase II Study of High Dose Lenalidomide as Initial Therapy for Acute Myeloid Leukemia in Patients &gt; 60 Years Old.
Authors: Ravi Vij, Alissa Nelson, Geoffrey L. Uy, Camille Abboud, Peter Westervelt, Amanda F Cashen, Stockerl-Goldstein Keith, Kathryn M Trinkhaus, John F. DiPersio, Todd A Fehniger
Journal: Blood (2009)
Prognostic role of at-diagnosis positron emission tomography (PET) scan in follicular lymphoma grade 3 (FL3).
Authors: Vijaya Raj Bhatt, Julie Vose, Lynette Smith, Matthew Alexander Lunning, Martin Bast, Hina Naushad, Gregory Bociek, Philip Jay Bierman, James O. Armitage
Journal: Journal of Clinical Oncology (2015)

e19507 Background: FL3 is a heterogeneous disease with mixed behavior and outcome. Pathologic differentiation into FL3A, FL3B and follicular large cleaved cell type (FLC) is challenging and highlights a need for better prognostic tools. Methods: In this retrospective study of 53 FL3 patients treated by the Nebraska Lymphoma Study Groupbetween 2000-2012, we utilized the survival tree method to determine an optimal cutoff of maximum standardized uptake value (SUVmax) in PET to predict overall survival (OS) and event-free survival (EFS). The Kaplan-Meier method was used to estimate OS and EFS. Results: The study population included 55% males; median age was 60 years (range 34-81). Other characteristics included hemoglobin < 12 g/dl in 18%, stage III/IV disease in 70%, elevated lactate dehydrogenase in 14%, involvement of nodal sites > 4 in 42%, involvement of extranodal sites ≥ 2 in 25%, Karnofsky performance score of ≤ 70 in 2% and B-symptoms in 17%. FLIPI was low (score of 0-1) in 39%, intermediate (2) in 31% and high (3-5) in 29%. 70% had FL3A, 10% FL3B and 17% FLC. The mean SUVmax in PET at diagnosis was 9.4 ±6.1. Initial therapy included rituximab-based immunochemotherapy (82%), wait and watch (9%) and other therapies such as alkylator-based regimens (CVP, CHOP), radiotherapy or single-agent rituximab. Maintenance rituximab was utilized in 24%, predominantly after RCHOP. Following the initial therapy, responses included complete response in 72% and partial response in 8%; 11% could not be evaluated. A SUVmax of ≥ 5.8 vs. < 5.8 at diagnosis predicted worse 5-year EFS (53% vs. 86%, p = 0.04) and trend towards worse 5-year relapse/progression rate (47% vs. 14%, p = 0.08). High vs. intermediate vs. low-risk by FLIPI (43% vs. 55% vs. 81%, p = 0.057) and FL3B vs. FL3A vs. FLC (60% vs. 49% vs. 100%, p = 0.09) demonstrated a trend towards worse 5-year EFS. The small number of patients precluded a multivariable analysis. Conclusions: Within the limitation of this study, PET scan at diagnosis (SUVmax cut-off of 5.8) may identify FL3 patients more likely to have worse EFS and appears to be at the least as good as FLIPI and pathologic classification in predicting EFS. PET scan may add to the current prognostic system.
Phase II multicenter study to analyze the predictive value of fusion gene TMPRSS2-ETS assessed both in tumor and blood sample, as a marker of response to enzalutamide in patients with metastatic castration resistant prostate cancer (CRPC) pre-chemotherapy: PREMIERE-SOGUG Trial.
Authors: Enrique Grande, Enrique Gonzalez-Billalabeitia, Ignacio Duran, Carmen Santander, Enrique Gallardo Diaz, Aranzazu Gonzalez del Alba, Javier Puente, Angel Rodriguez Sanchez, Albert Font, Miguel Angel Climent, Luis Leon Mateos, M Isabel Sáez, Begona Mellado, María José Méndez-Vidal, Sergio Vazquez-Estevez, Ovidio Fernandez Calvo, Maria Piedad Fernandez Perez, Teresa Alonso, Daniel E. Castellano
Journal: Journal of Clinical Oncology (2015)

TPS5073 Background: Enzalutamide (E) is a newly authorized drug for metastatic CRPC. E inhibits binding of androgens to androgen receptors, nuclear translocation of activated receptors and DNA transcription. E decreases the growth of prostate cancer cells and can induce cancer cell death and tumour regression. The presence of TMPRSS2-ETS fusion gene rearrangement correlates with the effectiveness of abiraterone (Danila DC, et al 2011). This molecular alteration may also influence E clinical outcome. The aim of this study is to determine whether the efficacy and safety of E when administered to mCRPC before chemotherapy, is influenced by the presence or not of TMPRSS2-ETS fusion gene rearrangement both in primary tumor and circulating blood. Methods: This is a phase II open-label study conducted in chemotherapy naïve mCRPC patients older than 18 years, ECOG 0-1, testosterone < 50 ng/dL and adequate, hematologic, hepatic, and renal function, that progressed to previous castration treatment documented by PSA (PCWG2), radiographic progression (modified RECIST 1.1) or bone scan progression. Patients will receive E treatment (160 mg/d) until clinical and/or radiographic disease progression. Primary objective is to assess the predictive value of the expression of TMPRSS2-ETS gene fusion in primary tumor tissue and circulating tumor cells correlated with progression free survival. Secondary objectives include assessing relationship between the presence of TMPRSS2-ETS fusion gene rearrangements with time to PSA response, overall soft tissue response rate, time to beginning of cytotoxic chemotherapy, safety of E treatment and circulating tumor cells (CTC) conversion rate. In this study is planned to include 98 patients. Sample size has been calculated using a Cox proportional hazards regression model with alpha 0.05, power 80% and 20% drop out rate. Patients will be included in 17 sites in Spain and it is expected to start in February 2015. Clinical trial information: NCT02288936.
Diagnostic and therapeutic role of endoscopic retrograde pancreatography in the management of traumatic pancreatic duct injury patients: Single center experience for 34 years
Authors: Seongyup Kim, Jae Woo Kim, Pil Young Jung, Hye Youn Kwon, Hongjin Shim, Ji Young Jang, Keum Seok Bae
Journal: International Journal of Surgery (2017)
Microarray-based tumor molecular profiling to direct choice of cisplatin plus S-1 or oxaliplatin plus S-1 for advanced gastric cancer: A multicentre, prospective, proof-of-concept phase 2 trial.
Authors: Wei-Peng Yong, Sun Young Rha, Iain B. Tan, Su-Pin Choo, Nicholas Syn, Vivien Koh, Shi Hui Tan, Jimmy So, Asim Shabbir, Chee Seng Tan, Matthew Chau-Hsien Ng, David Wai-Meng Tai, Ming Hui Lee, Jeanie Wu, Khay Guan Yeoh, Patrick Boon Ooi Tan, Hyo Song Kim
Journal: Journal of Clinical Oncology (2017)

48 Background: Theoxaliplatin/S-1 (SOX) and cisplatin/S-1 (SP) regimens are interchangeably used in the management of advanced gastric cancer (AGC). We previously developed a classification tool using gene expression signatures which successfully stratified gastric cancer cell lines and primary tumour samples according to their sensitivity to SOX or SP ( Tan et al, Gastroenterology 2011). We now report the first prospective study to evaluate the feasibility and efficacy of using a genomic classifier to tailor treatment in this setting. Methods: Pts with histologically-confirmed locally-advanced, metastatic and recurrent GC were recruited from 3 centres in Singapore and South Korea. Tumours were analysed using the Affymetrix HG-U133 Plus 2.0 array and results were used to classify pts as G1 (oxaliplatin-sensitive), G2 (cisplatin-sensitive) and G3 (status unclear or gene expression not available). G1 and G2 pts were matched to SOX and SP regimens respectively, while G3 pts were assigned SOX. The primary endpoint was best overall response; secondary endpoints were turnaround time and biomarker analyses. Results: Between July 2, 2010, and Apr 2, 2015, we screened 85 AGC pts. 74 pts received at least 1 cycle of treatment and were evaluable for analysis. Median turnaround time was 7 working days (IQR, 5–9). The misclassification rate was 6%. After an initial 30 pts in the G1 subgroup were treated with SOX, subsequent pts ( N = 13) classified as G1 received the SP regimen. The ORR were 44.8%, 8.3%, 26.7% and 55.6% for G1 SOX, G1 SP, G2 SP ( N = 19), G3 SOX ( N = 12) respectively; and was higher in G1 pts treated with SOX compared with SP ( P = 0.033). Post hoc genomic reclassification based on Lei et al (Gastroenterology 2013) confirmed the utility of the metabolic subtype as a predictive marker of benefit from chemotherapy (log rank P value for PFS = 0.004). Conclusions: This bench-to-bedside effort establishes that molecular profiling to direct choice of conventional chemotherapy for AGC is possible within a reasonable timeframe. The clinical utility of our genomic classifiers in question are promising but warrant further investigation. Clinical trial information: NCT01100801.
Time to sputum culture conversion and treatment outcome of patients with multidrug-resistant tuberculosis: a prospective cohort study from urban China
Authors: Peng Lu, Qiao Liu, Leonardo Martinez, Haitao Yang, Wei Lu, Xiaoyan Ding, Limei Zhu
Journal: European Respiratory Journal (2017)

Sputum culture plays an important role in monitoring treatment response in patients with multidrug-resistant tuberculosis (MDR-TB), and sputum culture conversion is a clinical tool used to predict therapeutic efficacy [1]. Monthly culture monitoring is essential for earlier detection of treatment failure in patients with MDR-TB. More sensitive signals of nonresponse would further avoid adverse outcomes [2]. The timing of testing for culture conversion has potential as a marker of MDR-TB treatment success <http://ow.ly/borO308pPXg> Author contributions: P. Lu and Q. Liu conceived the study, analysed the data and drafted the manuscript; L. Zhu, H. Yang, W. Lu and X. Ding participated in the study design and implemented the field investigation; and L. Martinez participated in the study design and helped draft the manuscript. All authors contributed to the study and have read and approved the final manuscript.