tbuckley/cabot-search huggingface dataset:
Does alopecia predict response to chemotherapy and prognosis in patients with advanced ovarian cancer? A meta-analysis of prospective randomized phase III trials with 5,114 patients of the AGO meta data base.
Authors: Jalid Sehouli, Edibe Erol, Rolf Richter, Alexander Reuss, Christina Fotopoulou, Sven Mahner, Jacobus Pfisterer, Andreas Du Bois
Journal: Journal of Clinical Oncology (2013)

5553 Background: Alopecia is a relevant side effect of chemotherapy. Our aim was to validate and unconfirmed broad patient´s opinion that a low rate of alopecia may predict poor response to chemotherapy and poor overall survival (OS). Methods: Individual patient data analysis of 5114 patients from four prospective randomised phase III trials conducted between 1995 and 2004 to investigate platinum-taxane based chemotherapy regimens in advanced ovarian cancer. Uni- and multivariate analyses were performed adjusted for age, number of cycles, individual trial, residual mass, tumor stage and histology. Results: 5,114 patients with ovarian cancer (OC) were analyzed. Most patients presented with advanced stage FIGO III/IV (87.8%). A median of 6 cycles were applied (range 0-11). Worst alopecia grade was 0 in 2.2%, 1 in 2.7% and 2 in 87.1%. In 8% patients no data about alopecia were documented. Patients with complete alopecia were more likely to achieve remission (OR 2.83, 95% CI 1.68-4.78 for grade 2 compared to grade 0/1) and had favourable progression-free survival of 19.0 months, (95%CI 18,2-19.7) compared to patients with grade 0/1 (13.8, 95%CI 12.2-15.3 and 14.3, 95%CI 10.8-17.8). Median OS was also significantly longer after grade 2 alopecia 48.8 months (95%CI 47.0-50.5), compared to 28.1 months (95%CI 22.3-33.9) and 33.9 months (95%CI24.3-43.6) for grade 0 and 1, respectively. This prognostic impact was not reteined in multivariate analysis. However, onset of alopecia was an independent prognostic factor for OS: patients with complete alopecia after cycle 3 had a favourable outcome compared to patient who experienced alopecia later during therapy (HR 1.22, 95%CI 1.02-1.46) or no alopecia (HR 1.29, 95%CI 0.98-1.70). Conclusions: We could show for the very first time that there is no evidence that the rate of alopecia is associated with the effect of chemotherapy is of any prognostic relevance. The observation that early onset of alopecia is associated with OS should be confirmed.
Erlotinib as frontline treatment for elderly patients (p) with advanced nonsquamous non-small cell lung cancer (nsNSCLC): GGCP044/09 study.
Authors: Jose Luis Firvida Perez, Sergio Vazquez Estevez, Joaquin Casal Rubio, Miguel Alonso Bermejo, Silvia Varela Ferreiro, Maria Jose Villanueva Silva, Francisco J. Afonso Afonso, Martin Lazaro Quintela, Carmen Areses Manrique, Begona Campos Balea, Gerardo Huidobro Vence, Ovidio Fernandez Calvo, Elena Alvarez Gomez, Carlos Grande Ventura, Ana Fernandez Montes, Enrique Castro Gomez, Jose Manuel Mel Lorenzo
Journal: Journal of Clinical Oncology (2012)

e18040 Background: NSCLC is primarily a disease of older people with a median age of approximately 70 years (y) at diagnosis. Platinum combination chemotherapy (CT) has shown to be more effective than single agents but it is associated with more toxicity. Erlotinib is an EGFR TK inhibitor with a favourable toxicity profile and its oral administration makes it suitable to treat elderly p. No much is known about its efficacy and toxicities in this subpopulation, often under-represented in clinical trials. This Galician study aims to evaluate the efficacy and safety of erlotinib as 1st-line treatment (Tx) for elderly p with advanced nsNSCLC. Methods: Elderly p (≥70 years old) with stage IIIB/IV nsNSCLC were included in this prospective observational study. Erlotinib was orally administered at a dose of 150 mg daily until disease progression or intolerable toxicity. PFS (primary objective) and OS were measured from time of diagnosis. Results:A total of 31 p were enrolled. Baseline characteristics: Mean age 78 y (range 70-85); female 67.7%; adenocarcinoma (including BAC) 90.3%; never/current/former smokers (%): 54.8/16.1/22.6 (6.5% unknown), stage IV 84%; ECOG PS 0/1/2 (%): 6.4/45.2/48.4. The median PFS was 6.4 and the median OS was 9.9 months. Out of 26 evaluable p, 8 had PR and 8 SD, for an ORR of 30.8% and a DCR of 61.6%. The most common adverse event was skin rash, 38.7% (9.6% grade 3-4), diarrhoea, 25.8% (3.2% gr. 3-4) and asthenia, 19.3% (no gr 3-4 were reported). 5 p (16.1%) needed dose reduction and 3 p withdrew the Tx due to grade 3 diarrhoea, eye perforation and esofaghitis, respectively. EGFR mutational status was available for 10 p (32.2%); 4 p harboured activating mutations: 3 p achieved PR and 1 p SD. SLP of 31 (ongoing), 22.4 (ongoing), 13.6 and 9.8 months. Conclusions: These results in real-life settings confirm that erlotinib is an active and well tolerated agent as frontline Tx in elderly p (≥70) in nsNSCLC. Response rate is similar to that achieved with CT in younger people; benefit in PFS is modest, but median OS is acceptable, taking into account that half of the p had a PS of 2 EGFR mutation testing should be strongly encouraged among elderly p.
David Oliver: Why shouldn’t nurses be graduates?
Authors: David Oliver
Journal: BMJ (2017)

The Daily Telegraph columnist Allison Pearson has set out her and her readers’ suggestions for saving the NHS.12 Alongside a range of reactionary ideas, she trotted out a recurring and predictable trope, beloved of some commentators in sections of the press: “Too many nurses with degrees who say, ‘I don’t do sick.’”2

This bizarre animus against graduate nurses has given rise to a stereotype that such nurses are “too posh to wash.”34 This is often accompanied by wistful yearnings for a golden age of authoritarian matrons who could spot dust bionically. …
Economic benefits of adequate molecular monitoring in patients with chronic myelogenous leukemia (CML).
Authors: Lei Chen, Annie Guérin, Eric Q. Wu, Katherine Dea, Stuart L. Goldberg
Journal: Journal of Clinical Oncology (2013)

7093 Background: Molecular monitoring every 3 months using quantitative polymerase chain reaction (qPCR) of BCR-ABL mRNA transcripts on International Scale is recommended by the National Comprehensive Cancer Network and the European LeukemiaNet for patients (pts) in chronic phase of CML. A previous study has shown an underutilization of qPCR in the community setting. This study assessed the impact of the frequency of molecular monitoring on hospitalization and medical costs among CML pts receiving 1 st -line tyrosine kinase inhibitor (TKI) therapies. Methods: Two U.S. administrative claims databases were combined (01/2000-06/2012) to identify adult CML pts initiated on TKIs (imatinib, dasatinib, nilotinib). Pts were followed for 12 months from their first TKI prescription and categorized into 3 cohorts based on frequency of qPCR tests (i.e., 0, 1-2, and 3-4). Number of inpatient admissions and medical service costs (measured from a US payer perspective; adjusted to 2012 U.S. dollars) were compared between cohorts. Multivariate regression models adjusted for confounding factors (e.g., age, gender, CML complexity, TKI). Results: The study included 1,205 CML pts. Over the 12-month study period, 41.0% of the pts had no qPCR test, 31.9% had 1-2 tests, and 27.1 % had 3-4 tests. Compared to pts with no qPCR monitoring, those with 3-4 tests incurred 37% fewer CML-related (i.e., a primary CML diagnosis) inpatient admissions (p=.017) during the study period, leading to a $4,000 (p=.009) reduction in CML-related inpatient costs and $5,663 (p=.005) reduction in all-cause inpatient costs, accounting for the majority of the $5,997 reduction in total medical service costs (p=.049). Pts with 1-2 tests a year showed smaller and statistically insignificant reductions from those with no test in the frequency of hospitalization and medical costs. Conclusions: Among CML pts who initiated 1 st -line TKIs, pts with 3-4 qPCR tests a year incurred fewer inpatient admissions and lower medical service costs compared to pts with no test. These findings suggest that pts would benefit from regular qPCR testing and underscore the value of molecular monitoring in the delivery of quality care for Ph+ CML-CP pts on TKI therapies.
Association of time to diagnosis of ESFT with tumor origin and location, metastasis, and survival: A single institutional study of 374 cases.
Authors: Bivas Biswas, Shishir Rastogi, Shah Alam Khan, Sandeep Agarwala, Sreenivas Vishnubhatla, Sameer Bakhshi
Journal: Journal of Clinical Oncology (2014)

e21502 Background: Ewing’s sarcoma family of tumors (ESFT) is a rare aggressive bone tumor of childhood with poor outcome. In developing countries most of ESFT patients have delayed presentation. We studied determinants of duration between first symptoms and diagnosis (time to diagnosis: TtD) of ESFT and its impact on disease extension at diagnosis and outcome. Methods: This is a single institutional study of ESFT patients treated between June 2003 and November 2011. Relations between TtD and baseline demographics and treatment were evaluated. Further, the median time duration was used for categorization to evaluate its impact on survival. Results: The median TtD of the 374 cases was 5.28 months (interquartile range 3.4 months - 8.47 months). The factors associated with a longer TtD were older age (mean 7.8 months for children >15 years vs 6 for those less than 15 years, p=0.009), tumor localization (7.8 months for axial primary vs 6.2 months for appendicular location, p=0.003) and tumor origin (mean 7.1 months for skeletal primary vs 5.4 months for soft tissue origin, p=0.02), but not with tumor volume. We did not find any significant association between TtD and year of diagnosis, sex, tumor diameter, systemic symptom, presence of local pain or swelling, presence or type of metastasis, therapy-related toxicity, amenability for surgical resection or survival [5-years overall survival and EFS of 45.6±4.9% and 31.2±4.1% for patients with TtD shorter than the median (5 months) vs 33.1±5.1% (p=0.37) and 20.7±3.6% (p=0.32), respectively]. Conclusions: TtD of ESFT were unusually long in our cohort. They were associated with older age group, tumor origin and tumor location pain but not with metastasis or survival. These findings should be used to inform care givers at diagnosis and educate primary care physicians to decrease the TtD.
Critical Evaluation of the Quality and Recommendations of Clinical Practice Guidelines for Nasopharyngeal Carcinoma
Authors: Yu-Pei Chen, Ya-Qin Wang, Wen-Fei Li, Lei Chen, Cheng Xu, Tai-Xiang Lu, Ai-Hua Lin, Ji-Jin Yao, Yang-Chan Li, Ying Sun, Yan-Ping Mao, Jun Ma
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: Given the distinct biological characteristics and regional distribution of nasopharyngeal carcinoma (NPC) compared with other head and neck cancers, and uncertainties regarding therapeutic strategies, physicians require high-quality clinical practice guidelines (CPGs) to provide transparent recommendations for NPC treatment. This study aimed to critically appraise the quality of NPC CPGs and assess the consistency of their recommendations. Methods: We identified CPGs that provided recommendations on the diagnosis and management of NPC published up to December 2015. Four investigators independently appraised CPG quality using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Key recommendations by CPGs were also evaluated. Results: A total of 7 CPGs were eligible for this study: 5 produced by professional organizations or governmental agencies and 2 were developed based on expert consensus. Of the 6 AGREE II domains, the applicability domain scored consistently low across CPGs (range, 13.5%–30.2%); no CPG achieved a score of >50% in all 6 domains. The scope and purpose domain (≥73.6% for 4 CPGs) and editorial independence domain (≥75.0% for 6 CPGs) scored highest. Of the 23 AGREE II items, 9 scored less than half of the points available in all 7 CPGs. The recommendations by CPGs were consistent in general; heterogeneity mainly existed among recommended therapeutic strategies. Conclusions: Variation exists in NPC CPG development processes and recommendations. Increased efforts are required to make comprehensive resources available to guide healthcare providers and enhance delivery of high-quality, evidence-based care for NPC. International collaboration is necessary to enable the development of high-quality and regionally relevant CPGs for NPC.
Outcomes of oxaliplatin-based adjuvant chemotherapy in pathologically lymph node positive (ypN+) rectal cancer.
Authors: Ahmad Al Zahrani, James D. Brierley, Erin Diane Kennedy, Monika Krzyzanowska
Journal: Journal of Clinical Oncology (2013)

e14664 Background: Standard therapy for locally advanced rectal cancer( LARC) with pre-operative chemoradiation(CRT) followed by curative surgery and adjuvant 5-flourouracil (5-FU) has resulted in a 5-year local relapse (LR) rate of less than 10% and incidence of distant metastases of about 36%. Accumulating data suggests that pathological lymph node status post CRT (ypN) is a major prognostic factor for long term outcomes in LARC .The role of adjuvant oxaliplatin-based therapy has not yet been well defined in ypN+ patients and is the focus of this study. Methods: Patients with ypN+ rectal cancer who underwent fluoropyrimidine-based preoperative CRT followed by curative surgery and received adjuvant oxaliplatin- (group 1) or fluoropyrimidine-based (group 2) chemotherapy at Princess Margaret Hospital were retrospectively reviewed.The study end point was comparison of three year disease free survival(DFS) and freedom from distant metastasis (FDM) in group 1 vs 2 using log-rank test. Results: Between 2003 and 2010, 25 pts in group 1 (adjuvant FOLFOX, n=23 and FOLFOX/bevacizumab, n=2) and 38 pts in group 2 ( adjuvant 5-FU/LV, n =37; capecitabine, n=1) were reviewed. Baseline characteristics were similar in both groups except more pts in group 2 had &lt; 12 lymph nodes (LNs) retrieved (p=0.02), whereas more pts in group 1 were female (p=0.03)and had ypN2 vs ypN1 (p=0.01). Median follow-up was 33 months in group 1 and 38 months in group 2 (range: 3-86). Median age: 58 years. Male: 51, 80%. Five pts (8%) in the entire cohort experienced LR and 20 pts (31.7%) had distant metastasis. A trend toward better three-year DFS was observed in favour of oxaliplatin-based therapy (76% in group 1 vs. 51% in group 2; HR=0.4, 95%CI = 0.1-1.0; P=0.05). Corresponding three-year FDM rates were 83% and 58%, respectively (HR=0.23; 95% CI = 0.6-0.8; p= 0.01). In multivariate analysis, number of LNs retrieved of ≥12 and adjuvant oxaliplatin-based therapy were independent prognostic factors for improved DFS and FDM, respectively. Conclusions: Our analysis suggests that in ypN+ rectal cancer, addition of oxaliplatin to adjuvant therapy is associated with better outcomes. A prospective confirmatory randomized trial would be informative.
A blood-based epigenetic test for early detection of hepatocellular carcinoma (HCC).
Authors: Elaine H. Lim, Soe Aung, Win Naing, Hlaing Myat Thu, Yi Yi Kyaw, Moh Moh HTun, Maung Maung Khaing, Khin Pyone Kyi, Hwee Yong Yap-Whang, Khin Khin Win, Yew-Oo Tan, Karmen Wong, Emily Corfield, Matthew Salter, Megan Field, Philip Jordan, Alexandre Akoulitchev, Wen Son Hsieh
Journal: Journal of Clinical Oncology (2014)

e15142 Background: HCC is a highly prevalent disease in East Asia, largely due to the prevalence of chronic active hepatitis B and C infection. Despite screening efforts, the majority of HCC patients are diagnosed with advanced disease, leading to high mortality rates. Genetic and epigenetic alterations involved in the pathogenesis of HCC are known. The higher order chromosomal structures reflecting aberrant transcriptional states of these genes can be measured via techniques such as chromosome conformation capture. Detection of these changes in peripheral blood may provide an accurate test for the early cancer detection. Methods: Blood samples were collected from 105 patients with HCC and 100 age and gender matched controls. Patient and control samples were also matched for hepatitis B and C infection status. Samples from 24 HCC patients and 24 controls have been analysed. Fifteen genes known to be dysregulated in HCC were investigated. Potential higher order juxtaposition sites in the candidate genes were predicted using pattern recognition software. PCR primer sets were designed around the chosen sites to screen potential markers. Thirty-two markers showing predictability between HCC and control samples were analysed for optimal reproducibility using alternative primer sets. The optimal sets of markers were then tested amongst the complete set of samples. Classification was performed using the Multilayer Perceptron (MLP) classification method with 10-fold cross-validation. Results: Four markers from four candidate genes were found to be optimal in differentiating between HCC and control samples in the first 48 samples. Using the MLP classification method, the following results were obtained: Sensitivity 91.7% (95% CI–74.2% to 97.7%); Specificity 70.8% (95% CI–50.8% to 85.1%); PPV 75.9% (95% CI–57.9% to 87.8%); NPV 89.5% (95% CI–68.6% to 97.1%). Conclusions: Using a PCR-based method to detect alterations in the cancer epigenome, the feasibility of developing a blood test of potential utility in early diagnosis of HCC was demonstrated. Analysis of larger numbers of patient samples and optimization of markers are ongoing. The performance characteristics of the test in the total population of 205 samples will be presented.
JAK2V617F Mutation and Thrombosis History Are Determinants of Mean Platelet Volume (MPV) in Essential Thrombocythemia Patients
Authors: Marina Marchetti, Cristina Verzeroli, Cinzia Giaccherini, Sara Gamba, Alfonso Vignoli, Laura Russo, Guido Finazzi, Alessandro Rambaldi, Anna Falanga
Journal: Blood (2016)
Never-smoking history predicts long-term survival in patients with non-small cell lung cancer with postoperative recurrence
Authors: Y. Fujiwara, K. Kiura, S. Toyooka, K. Hotta, M. Tabata, N. Takigawa, T. Kozuki, K. Ohashi, K. Matsuo, M. Tanimoto
Journal: Journal of Clinical Oncology (2006)

20047 Background: Factors affecting long-term survival after postoperative recurrence in non-small cell lung cancer (NSCLC) patients have not been fully understood. Furthermore, molecular features of them also have remained undetermined. The aim of this study was to identify these possible factors and to investigate their association with epidermal growth factor receptor (EGFR) mutation. Methods: Fifty-eight patients with postoperative recurrent NSCLC treated at Okayama University Hospital between January 1999 and December 2003 were retrospectively analyzed. We defined those surviving for 2 years or longer after postoperative recurrence as long-term survivors. Tumor samples for EGFR mutation analysis were available in 32 (55%) patients and were examined in exons 18 to 21 of EGFR using direct sequence method. Results: Demographics of 58 patients were as follows: median age 65 years (range, 33–85 years), male/female, 69%/31%; adenocarcinoma/others, 69%/31%; ever/never-smokers, 66%/34% and local/local and distant/distant recurrence; 29%/10%/61%. Median survival time and 1-year survival rate for 58 patients were 22.7 months and 79%, respectively, with a minimum follow-up time of 2 years. Half of 28 long-term survivors did not have any smoking history, whereas only 6 never-smokers were included in the remaining 30 patients who died within 2 years, indicating that never-smoking history is significantly associated with long-term survival (p=0.016). In multivariate analysis, never-smoking history was a significant predictive factor for long-term survival (Odds ratio 4.90, 95% confidence interval: 1.26–19.00, p=0.022). Among 32 patients analyzed for EGFR mutation, patients harboring EGFR mutation in ever-smokers and in never-smokers were 10% and 82%, respectively. Seven (47%) of 15 long-term survivors analyzed had EGFR mutation; however, only 4 (24%) of 17 patients who died within 2 years did (p = 0.169). Conclusions: Our data suggest that never-smoking history might have a favorable effect on long-term survival in postoperative recurrent NSCLC patients, and long-term survivors tend to have EGFR mutation. No significant financial relationships to disclose.
A nomogram to predict pathologic lymph node positivity in clinical stage I-II pancreatic adenocarcinoma.
Authors: Douglas S. Swords, Chong Zhang, Angela P. Presson, Matthew A. Firpo, Sean J. Mulvihill, Courtney L. Scaife
Journal: Journal of Clinical Oncology (2017)

382 Background: Clinical nodal staging in PDAC is inaccurate. Most pts are cN0, but &gt; 70% are pN+. We hypothesize that preoperative variables are associated with pN+ and could be used to create a predictive nomogram. Methods: The NCDB was reviewed from 2010-13 for pts with clinical stage I-II PDAC. Exclusions were neoadjuvant therapy, &lt; 12 nodes examined, and missing data for clinical/pathologic stage, size, and number of nodes examined/positive. Logistic regression assessed factors associated with pN+ and an interaction was included for extrapancreatic extension and cN stage. A logistic regression based nomogram was constructed and 10-fold cross validation evaluated model discrimination. Results: Of 7,475 pts, 28% were cN+ but 74% were pN+ (P &lt; 0.001). Associations of preoperative factors with pN+ are shown. Size was pathology based. We recommend multiplying imaging based size estimates by 1.33 for use in the nomogram based on studies showing that imaging underestimates size by 25%. Interestingly, extrapancreatic extension was protective for cN0 pts but associated with increased odds of pN+ for cN1 relative to cN0 ps. A nomogram was created to predict pN+ using these variables. The 10-fold cross validated AUC was 0.77. Conclusions: Our nomogram has good discrimination to preoperatively predict lymph node positivity for patients with resectable PDAC. It could potentially be useful in identifying biologically aggressive resectable PDAC pts at higher risk of pN+ in order to select pts for neoadjuvant therapy. [Table: see text]
Celiac Disease and Nonceliac Gluten or Wheat Sensitivity
Authors: Nicholas J. Talley, Marjorie M. Walker
Journal: JAMA Internal Medicine (2017)

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