tbuckley/cabot-search huggingface dataset:
Predictors of radiation field failure after definitive chemoradiation in patients with locally advanced cervical cancer.
Authors: Hyo Sook Bae, Yeon-Joo Kim, Myong Cheol Lim, Sang-Soo Seo, Sang-Yoon Park, Sokbom Kang, Sun Ho Kim, Joo-Young Kim
Journal: Journal of Clinical Oncology (2015)

e16518 Background: Concurrent chemoradiotherapy became the standard treatment for locally advanced cervical cancer. However, there is lack of study exploring the predictive factors for the locoregional failure after definitive chemoradiation in patients with locally advanced cervical cancer. Methods: 397 patients with locally advanced cervical cancer (stage IB2-IVA) were treated by definitive chemoradiation between June 2001 and February 2010. Platinum-based concurrent chemotherapy was given to all patients with median dose of external beam radiotherapy 5,040 cGy in 28 fractions and intracavitary radiotherapy 3,000 cGy in 6 fractions. Competing risk regression analysis was used to reveal the predictive factors for the locoregional failure. Results: During the median follow-up of 7.2 years, locoregional failure occurred in fifty one patients (12.9%). The estimated 3-year rates of locoregional control and overall survival were 89% and 82 %. After univariate and multivariate analysis, large tumor size ( > 5cm), young age ( ≤ 40 years), non-squamous histology, positive lymph node on MRI and advanced stage (III-IV) were identified as risk factors for locoregional failure (P= 0.003, P= 0.075, P= 0.005, P= 0.055 and P< 0.001, respectively). After risk grouping using thecoefficients from the multivariate model, we identified a high risk group for locoregional failure after definitive chemoradiation as follows: 1) tumor size > 5cm, and at least one other risk factor or 2) tumor size ≤ 5cm, and at least three other risk factors. The cumulated estimated 3-year rates of locoregional failure of the high risk group was 26%, which was significantly higher than the low risk group (7%, P< 0.001). The 3-year overall survival rates of the two group were also significantly different (57% vs. 86%, P< 0.001). Conclusions: Large tumor size ( > 5cm), young age ( ≤ 40 years), non-squamous histology, positive lymph node on MRI and advanced stage are the risk factors for locoregional failure after definitive platinum-based chemoradiation in patients with locally advanced cervical cancer. In the high risk group, further clinical trials to improve locoregional control rate are warranted.
Impact of EGFR tyrosine kinase inhibitors in the management of brain metastases from EGFR-mutated and wild-type (WT) non-small cell lung cancer (NSCLC): A survival analysis.
Authors: Antonio Picone, Tindara Franchina, Alessandro Russo, Claudia Proto, Fabio Raiti, Carmelo Buda, Giuseppe Chiofalo, Giuseppa Ferraro, Maria Picciotto, Antonino Scimone, Giuseppe Toscano, Mariangela Zanghì, Vincenzo Adamo
Journal: Journal of Clinical Oncology (2014)

e19164 Background: Most clinical trials in stage IV NSCLC have excluded patients with brain metastases (BM), therefore the outcome of this population remains undefined. EGFR mutations in primary NSCLC lesions have been associated with sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Few data are available on the real efficacy of these agents in this setting. The aim of the study is to evaluate the outcome of patients (pts) with brain metastases to better define the role of TKIs according to mutational status. Methods: Thirty consecutive patients were retrospectively evaluated into the analysis. Patients and disease characteristics, treatment and outcome data were recorded. A multivariate analysis was conducted. P-values <0.05 were considered statistically significant. Results: Pts (18M, 12F) had a median age of 64.3 years (range 44-81). ECOG PS 1 (22 pts); PS 2 (8 pts). Histology was squamous carcinoma 8/30, adenocarcinoma 15/30, undifferentiated 7/30. 20% of patients were EGFR mutated. 40% of patients had brain metastases at first presentation. All pts were treated with platinum-based regimens. 19 pts underwent radiotherapy and 21% received concurrent TKIs. TKIs were administered mainly as second line of therapy. Median survival time was longer in pts treated with TKIs (13 pts) than in the group receiving chemotherapy (16.6 versus 6.1 months). This data is not significant, but there is an interesting trend towards significance (p=0.1). However, the most relevant data is represented by the presence in this group of EGFR WT pts (70%). Conclusions: The results of this analysis underline the important role of TKIs in the management of BM from NSCLC not only in patients harboring EGFR mutations but also in wild type EGFR pts. However, it is important to recognize that NSCLC patients are no longer divided into EGFR mutant or WT groups. In fact, tumors that do not harbor EGFR mutations may harbor other genomic alterations that could secondary influence therapeutic results. Hence, it is far more critical to extend molecular genotyping to go beyond EGFR mutation testing, to find the most effective therapy for patients based on their tumor’s genomic profile.
Evidence-based exercise prescription is facilitated by the Consensus on Exercise Reporting Template (CERT)
Authors: Peter Kent, Peter B O’Sullivan, Jennifer Keating, Susan C Slade
Journal: British Journal of Sports Medicine (2017)

Exercise is effective for the prevention and management of acute and chronic health conditions. Exercise prescription is sensible when supported by high-quality evidence of effectiveness, and it is likely that the design of an exercise programme (eg, how long a person exercises each day, the duration of a programme, the level of intensity of the exercise) influences programme effectiveness. A meta-epidemiological review of 73 systematic reviews (1216 trials) of exercises reported that only 30% of trial reports provided information required to replicate the investigated exercise programme.1 

This means that researchers would, in most cases, be unable to replicate and validate trial outcomes for exercise programmes that have been reported to be effective. In addition, clinicians would be unable to accurately implement treatment based on the reported intervention.1 Furthermore, when trials of exercise are pooled in a meta-analysis, pooling of studies of unknown design may lead to incorrect conclusions regarding specific exercise effects.

A logical solution …
Variations in serum vitamin D status during cancer chemotherapy.
Authors: Bogda Koczwara, Richard John Woodman, Laisa Vicki Teleni, Michael Kimlin, Euan Thomas Walpole, Kunal Jain, Christos Stelios Karapetis, Emma-Louise Smith, Wendy Louise Davidson, Maree Ferguson, Shawgi Sukumaran, Ganessan Kichenadasse, Elizabeth Isenring
Journal: Journal of Clinical Oncology (2012)

e19550 Background: Low serum vitamin D in cancer patients has been associated with inferior cancer outcomes and bone loss. The impact of chemotherapy on vitamin D levels is not known. We examined serum vitamin D levels during chemotherapy to identify magnitude and predictors of change. Methods: A prospective study of chemotherapy naïve patients commencing chemotherapy in two different sun exposure areas. Vitamin D (25(OH)D) deficiency was defined as ≤25 nmol/L and insufficiency 26-50 nmol/L. Demographic data, nutrition, sun exposure, season and biochemical parameters were collected at baseline 6 weeks (6W) and 12 weeks (12W) since commencement of treatment. The effects were assessed using a multivariate multilevel linear regression model that also included age, gender and BMI. Results: 82 Caucasian and 3 indigenous patients were enrolled. Median age was 57 (21-85) years. Forty-nine (58%) were female; 54 (65%) were treated with curative intent. Tumours included 29 (34%) breast,12 (14%) colorectal, 9 (11%) lymphomas, 7 (8%) leukemias, 7 (8%) lung, 5 (6%) ovarian, 3 (4%) testis, 3 (4%) unknown primary and 10 (11%) others. Median weight was 75 kg (50-151) and median BMI was 26.9 kg/m 2 (17.7- 44.5). Seventy-six (89%) and 55 (65%) patients were receiving chemotherapy treatment at 6W and 12W respectively. Mean (±SD) serum 25(OH)D at baseline was 49.2±22.3 nmol/L. Ten (12%) patients were vitamin D deficient at baseline and a further 33 (41%) had insufficient levels. Mean serum 25(OH)D status was higher in higher sun exposure locations (61.9±22.1 nmol/L vs 42.2±19.2 nmol/L, p&lt;0.001), varied according to season (spring=46.9±20.3 nmol/L, summer=50.8±18.2 nmol/L, fall=76.4±25.2 nmol/L, winter=36.5±15.7 nmol/L, p&lt;0.001) and changed with treatment period (baseline=49.2±22.3 nmol/L, 6W=40.9±19.0 nmol/L, 12W=45.9±19.7 nmol/L, p=0.002). There was no association between 25(OH)D status and age, gender, BMI or nutritional status. Conclusions: Chemotherapy is associated with a fall in serum 25(OH)D. Further research is needed to determine the underlying mechanism, the impact of low serum 25(OH)D on patient outcomes and the potential role for screening and vitamin D supplementation in this group.
Triggering receptor expressed on myeloid cells-2 (TREM-2) elicited by lung cancer cells to facilitate tumor immune evasion.
Authors: Yinan Yao, Hequan Li, Yuehong Wang, Jianying Zhou
Journal: Journal of Clinical Oncology (2013)

e22054 Background: More recent evidences have argued that negative regulatory mechanism that serve to impede ongoing immune responses, which gain in interest as a complementary strategy for cancer therapy. Triggering receptor expressed on myeloid cells-2 (TREM-2) restrains phagocytosis of both dendritic cells (DCs) and macrophages(MΦs), and reduces release of inflammatory cytokines through DAP12-mediated inhibitory signal, prompting us to investigate the role of TREM-2 involved in immune dysfunction among tumor-bearing host. Methods: In lung cancer patients, monocytes of peripheral blood were analyzed by flow cytometry and MΦs around tumour cells in lung tissue were detected by immunehistochemistry. Then we prepared conditional medium containing supernatant of 3LL cells mimicing tumor microenvironment for DC and MΦ derivation, and established an orthotopic lung cancer-bearing mice model to explore the further mechanism. Results: It was showed that TREM-2 expression on monocytes was up-regulated in lung cancer patients compared with that of healthy controls, and that TREM-2 levels of macrophages had a positive correlation with TNM stage. Moreover, reduction of tumor burden, by operation or chemotherapy, led to obvious decline of TREM-2 expression. The percentage of TREM-2 + DC in the murine lung signiﬁcantly increased after tumor-bearing, and such DCs preformed lower MHCII-Ia, CD86 expression, and IL-12 production, but higher IL-10 secretion. In vitro, more TREM-2 + DCs and TREM-2 + MΦs were harvested from ‘conditional’ medium instead of ‘normal’ medium. Also, TREM-2 + DCs rather than TREM-2 - DCs markedly inhibited proliferation of T cells, which could be partially abolished by anti-TREM-2 mAb. Conclusions: TREM-2 acts as a negative immune regulator in promoting lung cancer progress. Our study provides new mechanism for tumor immune escape and inhibitory checkpoint for immunotherapy.
Cetuximab and chemotherapy in the treatment of patients with initially “nonresectable” colorectal (CRC) liver metastases: Long-term follow-up of the CELIM trial.
Authors: Gunnar Folprecht, Thomas Gruenberger, Wolf Bechstein, Hans-Rudolf Raab, Juergen Weitz, Florian Lordick, Joerg Thomas Hartmann, Hauke Lang, Tanja Trarbach, Jan Stoehlmacher-Williams, Torsten Liersch, Detlev Ockert, Dirk Jaeger, Ulrich Steger, Thomas Suedhoff, Claus-Henning Kohne
Journal: Journal of Clinical Oncology (2013)

3538 Background: CRC liver metastases can be resected after downsizing with intensive chemotherapy schedules, with a strong correlation between the response and resection rates. Cetuximab plus chemotherapy has been shown to increase the rates of tumor response and resection of liver metastases. (Van Cutsem et al, JCO 2011). Methods: Patients (pts) with technically non-resectable and/or with &gt; 4 liver metastases were randomized to treatment with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated regarding resectability every 2 months. Resection was offered to all patients who became resectable during the study. K-ras and b-raf status were retrospectively evaluated. Data on tumor response and resection were reported earlier (Folprecht et al, Lancet Oncol 2010). Overall and progression free survival were analyzed in December 2012. Results: Between Dec 2004 and March 2008, 56 pts were randomized to arm A, 55 to arm B. For the current analysis, 109 pts were evaluable for overall survival (OS), and 106 patients for PFS. The median OS was 35.7 [95% CI: 27.2-44.2] months (arm A: 35.8 [28.1-43.6], arm B: 29.0 [16.0-41.9], HR 1.03 [0.66-1.61], p=0.9). The median PFS was 10.8 [9.3-12.2] months (Arm A: 11.2 [7.2-15.3], Arm B: 10.5 [8.9-12.2], HR 1.18 [0.79-1.74], p=0.4). Patients with R0 resection had a better OS (median: 53.9 [35.9-71.9] mo) than patients without R0 resection (27.3 [21.1-33.4] mo, p=0.002) and a better PFS (median 15.4 [11.4-19.5] and 8.9 [6.7-11.1] mo in R0 resected and not R0 resected pts, p&lt;0.001). The 5 year survival in R0 resected patients is 46.2% [29.5-62.9%]. Conclusions: This study confirmed a favourable long term survival of patients with initially “nonresectable” CRC liver metastases treated in a multidisciplinary approach of neoadjuvant chemotherapy with cetuximab and subsequent metastasectomy in pts who became resectable. Clinical trial information: NCT00153998. [Table: see text]
Referred by Google: mining Google Trends data to identify patterns in and correlates to searches for dermatological concerns and providers
Authors: J.D. Ransohoff, K.Y. Sarin
Journal: British Journal of Dermatology (2017)

Google Trends is a powerful tool that provides population-level insight into search volumes by time and geography. Since 2004, Google Trends has been profiled across studies of public interest, disease surveillance, prevention, and compliance.1,2 Dermatologists have used Trends data to identify seasonal peaks in skin cancer and tanning searches3,4 Other Google tools, including Health Cards5 and Reverse Image Searching6, have been explored by dermatologists for generating differential diagnoses.

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Analysis of prognostic factors in childhood advanced stage Hodgkin lymphoma: A retrospective study.
Authors: Amol Shankar Dongre, Brijesh Arora, Shripad Dinanath Banavali, Seema Gulia, Siddarth Laskar, Tanuja Shet, Seema Kembhavi
Journal: Journal of Clinical Oncology (2014)

e21000 Background: HL is one of the most curable malignancies of childhood. There is limited published data on outcome from India on local biology and prognostic factors. Methods: 152 advanced stage Hodgkins lymphoma (Stage IIBX, III & IV) ≤ 15 years from January 2005 to December 2010 were analyzed.All patients had received ABVD based chemotherapy followed by IFRT to the bulky/residual sites. Medical records and lymphoma clinic charts were reviewed for presenting symptoms, examination findings and treatment. The response and toxicity to each line of treatment were recorded according to CTC version 3.0. Results: The median age was 9.7 years and M:F ratio was 5.9:1.The major histologic subtype was mixed cellularity. Majority (73%) of patients had stage III disease with 80/152 (53%) of patients having ‘B’ symptoms and 69/152(45%) having bulky disease at presentation. 79% patients had complete-remission (CR) at the end of therapy while 32(21%) patients progressed or relapsed. Median follow up was 37 months. At 3 years, OS and EFS rates were 83.6% and 78%, respectively. Survival rates were lesser as compared with the studies from west. Local prognostic factors evaluated for both Overall survival (OS) and Event free survival (EFS) were histology, bulk of disease, stage of disease B symptoms, ESR, LDH, β2 microglobulin, hemoglobin, interim response to therapy (RER vs SER) and serum albumin. Factor significant for OS on multivariate analysis was interim response whereas for EFS both interim response and hemoglobin level were found to be significant. Interim response evaluation by PET-CT scan in our study showed a better EFS and OS for patients who achieved CR versus non-CR(90% & 92% versus 72% & 62% respectively.) Conclusions: Ours is the first study that has shown PET-CT based early response as an accurate and independent predictor of EFS and OS in HL. This audit also highlights the need for large scale national multicentric trials to understand local biology of HL, define local risk factors, and test regionally relevant treatment strategies.
A multi-site, fixed dose, parallel arm, double-blind, placebo controlled, block randomised trial of the addition of infusional octreotide or placebo to regular ranitidine and dexamethasone for the evaluation of vomiting associated with bowel obstruction at the end of life.
Authors: David C Currow, Katherine Clark, John Cartmill, Selvin Pather, John Plummer, Simon Eckermann, Amy Pickar Abernethy, Meera Agar, Stephen Quinn
Journal: Journal of Clinical Oncology (2012)

TPS9153 Background: Bowel obstruction due to advanced cancer that is surgically inoperable is a major management problem. Studies to date have either been underpowered or have used comparators that may not draw on the best available evidence. Methods: This double-blind, block randomised, placebo controlled, set dose, parallel arm study was conducted across 12 sites in Australia. Eligibility included inoperable bowel obstruction secondary to cancer or its treatments. The intervention was the addition of infusional octreotide or placebo in addition to 200mg ranitidine per 24 hours parenterally and 4mg per 24 hours parenterally of dexamethasone. The primary outcome measure was the numbers of days free of vomiting up to 72 hours after all medications were administered the first time. Participants were also administered between 10-20mls per hour of subcutaneous isotonic fluid over the 72 hour period. Results: This study will close to recruitment in March 2012. To date 89 of 92 required participants have been randomised. Conclusions: This adequately powered study will define the additional net clinical benefit derived from octreotide over placebo in people who have an anti-secretary agent (ranitidine) and glucocorticoids (dexamethasone).
Clinical outcomes following inpatient penicillin allergy testing: A systematic review and meta‐analysis
Authors: K. A. Sacco, A. Bates, T. J. Brigham, J. S. Imam, M. C. Burton
Journal: Allergy (2017)

A documented penicillin allergy is associated with increased morbidity including length of hospital stay and an increased incidence of resistant infections attributed to use of broader-spectrum antibiotics. The aim of the systematic review was to identify whether inpatient penicillin allergy testing affected clinical outcomes during hospitalization.We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library over the past 20 years. Inpatients having a documented penicillin allergy that underwent penicillin allergy testing were included.Twenty-four studies met eligibility criteria. Study sample size was between 24 and 252 patients in exclusively inpatient cohorts. Penicillin skin testing (PST) with or without oral amoxicillin challenge was the main intervention described (18 studies). The population-weighted mean for a negative PST was 95.1% [CI 93.8-96.1]. Inpatient penicillin allergy testing led to a change in antibiotic selection that was greater in the intensive care unit (77.97% [CI 72.0-83.1] vs 54.73% [CI 51.2-58.2], P<.01). An increased prescription of penicillin (range 9.9%-49%) and cephalosporin (range 10.7%-48%) antibiotics was reported. Vancomycin and fluoroquinolone use was decreased. Inpatient penicillin allergy testing was associated with decreased healthcare cost in four studies.Inpatient penicillin allergy testing is safe and effective in ruling out penicillin allergy. The rate of negative tests is comparable to outpatient and perioperative data. Patients with a documented penicillin allergy who require penicillin should be tested during hospitalization given its benefit for individual patient outcomes and antibiotic stewardship.
A metastatic biology gene expression assay to predict the risk of distant metastases in patients with localized prostate cancer treated with primary radical treatment.
Authors: Suneil Jain, Ciara Lyons, Steven M. Walker, Stephen McQuaid, Sean Hynes, Darren M. Mitchell, Brendan Pang, Gemma E Logan, Andrena McCavigan, Declan O'Rourke, Catherine Joan Davidson, Laura A Knight, Viktor Berge, David Neal, Hardev S. Pandha, Paul D Harkin, Jacqueline James, Richard D. Kennedy, Joe M. O'Sullivan, David J. Waugh
Journal: Journal of Clinical Oncology (2017)

11 Background: Approximately 20% of patients with organ confined prostate cancer (PCa) will develop disease recurrence following radical treatment (surgery or external beam radiotherapy (EBRT)). We hypothesized that a molecular subgroup of early PCa may have metastatic potential at presentation, resulting in disease recurrence. Methods: Using unsupervised hierarchical clustering of gene expression from a PCa dataset we identified a novel molecular subgroup with a transcriptional profile similar to metastatic disease. We developed a 70 gene expression assay to prospectively identify patients within the subgroup from formalin fixed and paraffin embedded tissue (FFPE). Initial assessment found the assay to be prognostic in three independent publicly available prostatectomy datasets. We therefore assessed the prognostic value of the assay in FFPE clinical samples collected from multiple international sites. FFPE tumor resections and tumor biopsy specimens were obtained from 322 surgical patients and 248 patients treated with EBRT. Regions of highest Gleason grade were identified for macrodissection, RNA extraction and gene expression analysis. Samples were dichotomized as metastatic biology assay positive or negative using a pre-specified cut-off. The association of assay results with biochemical failure (BF) and distant metastases (DM) was tested on multivariate (MVA). Results: The assay was significantly associated with BF on MVA (HR 1.67 [1.16-2.38]; p = 0.0059), (HR 2.26 [1.26-4.04]; p = 0.0062) and DM on MVA (HR 3.39 [1.88-6.12]; p = 0.0001), (HR 3.26 [1.27-8.30]; p = 0.0137) for surgery and EBRT cohorts respectively. Importantly, in a combined model, the assay demonstrated additional information to the commonly used CAPRA clinical tool for prediction of DM, HR 2.72 [2.10-3.51]; p &lt; 0.0001, and HR 2.72 [1.42-5.20]; p = 0.0026 (Prostate Metastatic Assay combined with CAPRA-S and CAPRA respectively). Conclusions: The metastatic biology assay predicts BF and DM in PCa patients treated with surgery or EBRT. The assay may help to select patients at risk of metastatic disease for additional treatment aimed at preventing disease recurrence.