tbuckley/cabot-search huggingface dataset:
Safety study of induction chemotherapy and synchronous radiotherapy (RT) and cetuximab in stage III non-small cell lung cancer (NSCLC): SCRATCH (Cohort I)
Authors: S. R. Hughes, J. L. Liong, A. Miah, S. Ahmad, M. Leslie, P. Ross, P. Harper, J. Prendiville, S. Rankin, D. Landau
Journal: Journal of Clinical Oncology (2007)

18032 Background: The addition of cetuximab can increase the efficacy of chemotherapy for advanced NSCLC. Concomitant cetuximab and RT is superior to RT alone for locally advanced squamous cell head &amp; neck carcinoma. The SCRATCH study (cohort I) is a phase I study to assess the safety of synchronous cetuximab and radical RT in patients with Stage III NSCLC. Methods: Cohort I will contain 12 patients with inoperable stage III NSCLC. Inclusion criteria are performance status 0–1, adequate organ function, and disease encompassable within a radical RT volume. Exclusion criteria are previous malignancy, thoracic RT or treatment with EGFR targeted therapy. Patients receive platinum-based induction chemotherapy, followed by weekly intravenous cetuximab (initial dose 400mg/m 2 ; maintenance dose 250mg/m 2 ) and concomitant RT (64Gy/32fractions/45days). The primary end-point is toxicity. NCI Common Toxicity Criteria (CTC) V3.0 assessments are performed weekly during radiotherapy, and at regular follow-up visits. Results: Data from the first 9 patients is available. 2 patients stopped receiving cetuximab early due to toxicity. 1 experienced grade 3 fatigue following the initial dose, and the other declined further treatment after developing grade 2 skin toxicity. 2 patients have died, 1 from disease progression and 1 from thromboembolic disease. Both deaths occurred between months 2 and 4 post RT and were not attributed to the cetuximab therapy. Of the 7 living patients, 2 have survived 1 year (measured from the first day of induction chemotherapy). The maximum NCI CTC V3.0 scores are summarised in the table below. Conclusions: The results suggest that the early and late toxicities of synchronous cetuximab and radical RT are acceptable. Data on all 12 patients will be available by June 2007. SCRATCH Study cohorts II-IV follow on and will recruit sequentially. They will assess the safety of adding concomitant cisplatin (±vinorelbine) to cetuximab and radical RT. [Table: see text] No significant financial relationships to disclose.
Dyspepsia
Authors: P. A. Cooke, G. J. Gormley, A. Gilliland, M. E. Cupples
Journal: BMJ (2011)

A 35 year old woman attends with a three month history of a recurrent burning sensation in her upper abdomen. The symptom is worse at night and has no relation to exercise. The periods of discomfort have increased in frequency and they are no longer relieved by over the counter remedies. This history is typical of dyspepsia. Self management before presenting to a doctor is common. Distinguishing between epigastric pain, heartburn, and acid reflux is unlikely to change management, but atypical or increasingly severe symptoms require consideration of other diagnoses such as angina, biliary colic, or pancreatitis. Consider:
The global burden of melanoma: results from the Global Burden of Disease Study 2015
Authors: C. Karimkhani, A.C. Green, T. Nijsten, M.A. Weinstock, R.P. Dellavalle, M. Naghavi, C. Fitzmaurice
Journal: British Journal of Dermatology (2017)

Despite recent improvements in prevention, diagnosis and treatment, vast differences in melanoma burden still exist between populations. Comparative data can highlight these differences and lead to focused efforts to reduce the burden of melanoma. To assess global, regional and national melanoma incidence, mortality and disability‐adjusted life year (DALY) estimates from the Global Burden of Disease Study 2015. Vital registration system and cancer registry data were used for melanoma mortality modelling. Incidence and prevalence were estimated using separately modelled mortality‐to‐incidence ratios. Total prevalence was divided into four disease phases and multiplied by disability weights to generate years lived with disability (YLDs). Deaths in each age group were multiplied by the reference life expectancy to generate years of life lost (YLLs). YLDs and YLLs were added to estimate DALYs. The five world regions with the greatest melanoma incidence, DALY and mortality rates were Australasia, North America, Eastern Europe, Western Europe and Central Europe. With the exception of regions in sub‐Saharan Africa, DALY and mortality rates were greater in men than in women. DALY rate by age was highest in those aged 75–79 years, 70–74 years and ≥ 80 years. The greatest burden from melanoma falls on Australasian, North American, European, elderly and male populations, which is consistent with previous investigations. These substantial disparities in melanoma burden worldwide highlight the need for aggressive prevention efforts. The Global Burden of Disease Study results can help shape melanoma research and public policy.
Antibodies to Human Factor XII with Antithrombotic Properties
Authors: Anton Matafonov, Adam E. Gailani, Stephanie L. Grach, Philberta Y Leung, Qiufang Cheng, Yipeng Geng, Owen J.T. McCarty, Erik I Tucker, Thomas Renne, James H. Morrissey, Andras Gruber, David Gailani
Journal: Blood (2012)
Tissue-based analytics provide the next generation of prostate cancer risk models.
Authors: Michael Donovan, Richard Scott, Faisal m Khan, Jack Zeineh, Giovanni Koll, Nataliya Gladoun, Elizabeth Charytonowicz, Gerardo Fernandez
Journal: Journal of Clinical Oncology (2017)

236 Background: Quantitative analysis of formalin-fixed paraffin-embedded (FFPE) prostate samples post radical-prostatectomy (RP) can help guide management of post-operative prostate cancer (PCa) patients. We have previously published on the results of our systems (precise) pathology platform which includes integration of clinical data with immunofluorescent (IF) morphology and biomarkers to predict disease progression in post-RP patients. We extended this approach by developing quantitative image features that further refine risk discrimination by directly competing with Gleason through the incorporation of biological attributes. Methods: Tissue microarrays representing a 892 RP population from Roswell Park Cancer Institute and the Henry Ford Hospital, with median 8 years follow-up were stained with a multiplex IF assay incorporating CK18 (epithelial cells), CK5/6 (basal cells), AMACR, the Androgen Receptor (AR), and Ki67. Images were captured with a Nikon i90 microscope / CRI multiplex camera and a Bayesian probabilistic approach was used to derive micro-anatomic quantitative image attributes. We generated a 50:50 balanced training / test cohort and optimized feature construction using clinical variables. Multivariate models were produced on the 324 training set to predict disease progression (i.e. clinical failure) which included a PSA rise post-adjuvant therapy, metastasis or death from PCa. The concordance index (CI), sensitivity and specificity were used to assess performance of the model. Results: A multivariate training model yielded a CI of 0.80, sensitivity 85% and specificity 74% with a hazard ratio of 9.8. By comparison a clinical only model produced a CI of 0.77, sensitivity 80% and specificity 73%, with a hazard ratio of 6. The IF model consisted of 3 features including pathologic stage and two imaging features that combine morphometry integrated with levels of AR and Ki67. Neither the Gleason score nor PSA were selected. Conclusions: Tissue-based models which incorporate objective and biological attributes accurately predict disease progression. Once validated, such approaches may replace the subjective Gleason grading system and provide an additional tool for pathologists when assigning risk.
“Intrinsic Gene Expression” subtypes correlated with grade and morphometric parameters reveal a high proportion of aggressive basal-like tumors among black women of African ancestry
Authors: O. I. Olopade, F. O. Ikpatt, J. J. Dignam, A. Khramtsov, M. Tetriakova, T. Grushko, J. Fackenthal, R. Nanda, R. Ndoma-Egba, C. M. Perou
Journal: Journal of Clinical Oncology (2004)

9509 Background: DNA microarray studies have identified 3 distinct subtypes of breast cancers (BC) based on “Intrinsic Gene Expression” patterns: basal-like tumors (ER-, HER2-), tumors with amplification of HER2/neu (ER-/+, HER2+), and luminal tumors (ER+, HER2-) (Perou et al. Nature 2000). BRCA1-associated BCs are characterized by poor differentiation, hormone receptor negativity, and a distinct basal-like pattern of gene expression. These aggressive features also characterize BC in women of African ancestry. In this study, we examined the proportion of BC within a given “intrinsic gene expression” subtype from a random cohort of Nigerians (N). Methods: H&E stained slides from archival BC, were evaluated for volume corrected mitotic index (smi), mean nuclear area (mna), and fraction of fields with tubular differentiation (ftd). Immunohistochemical staining for ER and HER2 were performed using Anti-ER (clone 6F11; 1:40, Novocastra) and rabbit antihuman HER2 antibody (1: 200; DAKO). Results: Of the 148 cases, 66.9% were premenopausal with a mean age of 43.8±11.2 years; large tumor size (mean 4.2±1.3cm); 77.8% had histological grade 2 or 3. ER expression was present in only 22.3% and HER2 was overexpressed in 18.9%. The proportion of tumors in each subtype was: ER-HER2- 87/148 (58.8%), HER2+ 28/148 (18.9%) and ER+ 33/148 (22.3%). Subtypes showed relatively weak association with clinical stage. However, overall grade and morphomety showed significant differences that persisted after adjustment for other patient and tumor characteristics (age, tumor size, and stage).Conclusions: The majority of BCs from Nigeria are basal-like, which suggest a distinct pathogenesis probably involving genes in the BRCA1 pathway. Future work will evaluate components of this pathway to develop more effective targeted therapies. No significant financial relationships to disclose.
Survival outcomes of patients with unresectable hepatocellular carcinoma in a national population-based study: SEER versus tertiary cancer center.
Authors: Taoreed O. Lawal, Bassel F. El-Rayes, Hyun Sik Kim
Journal: Journal of Clinical Oncology (2012)

e14736 Background: To evaluate long-term survival in patients with unresectable hepatocellular carcinoma (HCC) in large national population-based database and to assess the impact of subspecialized care on similarly matched patients at a tertiary cancer center. Methods: Using the Surveillance, Epidemiology and End Results (SEER) registry, patients diagnosed between 2004 and 2008 with advanced unresectable HCC not amendable to radiation therapy or cancer-directed surgery were extracted. Additionally, similar matched patients receiving drug eluting bead transarterial chemoembolizaton (DEB TACE) for unresectable HCC were included in the study. Demographic, clinical, and procedural data were collected. Patients were stratified based on Contract Health Service Delivery Areas (CHSDA) and the rural- urban continuum. The Kaplan Meier method was used for survival analysis, and survival curves were compared using the log rank test in SPSS. Results: 14,369 patients were studied and demographics were as follows: mean age at time of diagnosis was 63.97 years (SD 12.5); 76.1% were male; 66.7% were Caucasian; 13.3% were African-American; and 19.4% were Asian or American Indian. The overall median observed survival from diagnosis of the 136 patients receiving DEB TACE was significantly higher when compared to the 404 Atlanta patients and the 12,012 SEER patients (median OS = 22 vs 4 vs 4 months respectively, p&lt; 0.05). When compared to CHSDA, the median overall survival for patients receiving DEB TACE was 5 times longer than all other geographical areas (22 months vs 3, 4, 3, 4, and 4 in Alaska, East, Northern Plains, Pacific Coast, and the Southwest, respectively, p&lt;0.05). Metropolitan, urban, and rural areas demonstrated similar survival outcomes and patients receiving DEB TACE had superior survival (22 vs 3-4 months, p&lt;0.05). Conclusions: This study suggests that DEB TACE is viable treatment option that confers significantly beneficial survival results when compared to similar patients nationwide diagnosed with advanced unresectable HCC in the same 5-year time frame regardless of population demographics and health service delivery area.
Association of ongoing systemic inflammatory response (SIR) at diagnosis with lymph node retrieval and node positivity in patients undergoing surgery for colonic cancer.
Authors: Ross Dolan, Stephen Thomas McSorley, Donald C McMillan, Paul G. Horgan
Journal: Journal of Clinical Oncology (2017)

550 Background: Prognosis in colonic cancer is largely based on pathological criteria such as TNM staging. However, there are deficiencies in this approach and the lymph node ratio (LNR) has been promoted as improving prediction of outcomes. In this context retrieval of lymph nodes and their examination is of considerable importance. Kennelly et al (World J Gastrointest Oncol 2016) in a recent study, in 331 patients undergoing surgery for colon cancer, reported an elevated LNR and lower lymph node retrieval in those patients with a SIR. In the present study these relationships were examined in a larger cohort of patients (n = 881). Methods: A prospectively maintained database of all patients undergoing elective curative colonic resection in our institution was examined. The SIR was measured by scores mGPS (C-reactive protein/ albumin), NLR (neutrophils/ lymphocytes), PLR (platelets/ lymphocytes) and LMR (lymphocytes/ monocytes) using standard thresholds mGPS (0,1,2), NLR ( ≥ 5), PLR ( ≥ 150) and LMR ( ≤ 2.4). Statistical analysis was carried out in SPSS using Independent Mann Whitney U and Kruskal-Wallis tests where appropriate. Results: Of the 881 patients included in the study, 467 (53%) were male, 414 (47%) female, the median lymph node count was 16 (0-48) and the median LNR in patients with positive nodal disease was 0.13 (0.02-1). There was a significant relationship between increased lymph node retrieval and laparoscopic surgery (p = 0.01), age &lt; 70 (p = 0.021), lower BMI (p = 0.047), right sided tumours (p &lt; 0.001), lymphatic invasion (p = 0.02) and neoadjuvant treatment (n = 0.001). There was a significant relationship between increased LNR and lower BMI (P = 0.022) and lymphatic invasion (p = 0.029). In contrast, lymph node retrieval was not associated with mGPS (p = 0.366), NLR (p = 0.523), PLR (P = 0.180) or LMR (p = 0.571). Similarly, LNR was not associated with mGPS (p = 0.313), NLR (p = 0.362), PLR (p = 0.592) or LMR (p = 0.263). Conclusions: The SIR as measured by a number of validated prognostic scores was not associated with either lymph node retrieval or positivity in patients undergoing elective surgery for colon cancer.
Near infrared imaging using indocyanine green for sentinel lymph node biopsy in women with early breast cancer: Results of a meta-analysis.
Authors: Tomoharu Sugie, Atsushi Kawaguchi, Takafumi Ikeda, Masakazu Toi
Journal: Journal of Clinical Oncology (2015)

e12044 Background: A number of groups have already reported results of near infrared (NIR) imaging using indocyanine green (ICG) for sentinel lymph node (SLN) biopsy in breast cancer. The aim of this meta- analysis is to evaluate clinical performance of this novel technique for SLN detection and axillary staging in comparison with the radioisotope (RI) method. Methods: We did a systematic review of publications and reports to identify studies published until January 27, 2015. The inclusion criteria was as follows: patients in the study underwent SLN mapping using ICG and RI and procedural detection rate for each modality was reported. Proportion meta- analysis was performed using the fixed effect and/or the random effects model based on the study heterogeneity. The statistical heterogeneity among studies was evaluated using I2 statistics and P values. Results: A total of 8 studies including 1556 women met the inclusion criteria. Reported overall detection rate for SLN using ICG fluorescence and RI ranged from 93% to 100%, from 85% to 99%, respectively. Significant heterogeneity did not exist among studies for SLN detection between ICG and RI (I2= 32.8%, P= 0.1659). ICG fluorescence was better than RI for SLN detection (odds ratio [OR], 1.75; 95% CI, 1.14-2.71) in the fixed effect model but not in the random effects model (OR, 2.00; 95% CI, 0.90-4.46). Of 8 studies, four studies reported detection rate for tumor-positive SLN. Reported detection rate for positive SLN ranged from 92% to 100% for the ICG fluorescence method, from 77% to 93% for the RI method. Heterogeneities of positive SLN detection were very low among studies (I2= 0%, P= 0.44). In the fixed effect model, the ICG fluorescence method was significantly better than the RI method (OR, 2.20; 95% CI, 1.14-4.27) but there was no statistically significant difference between these two methods in the random effects model (OR, 1.95; 95% CI, 0.98-3.89). Conclusions: These meta-analysis results, including 1556 women with early breast cancer, provide evidence that NIR fluorescence imaging using ICG is not superior but would be a good alternative to a standard SLN mapping using RI.
Association of Spontaneous Preterm Delivery and Future Maternal Cardiovascular Disease
Authors: Margo B. Minissian, Sarah Kilpatrick, Jo-Ann Eastwood, Wendie A. Robbins, Eynav E. Accortt, Janet Wei, Chrisandra L. Shufelt, Lynn V. Doering, C. Noel Bairey Merz
Journal: Circulation (2018)

Cardiovascular disease (CVD) risk factors are well established. However, little is known about a woman’s cardiovascular response to pregnancy, which appears to be an early marker of future maternal CVD risk. Spontaneous preterm delivery (sPTD) has been associated with a ≤3-fold increased risk of maternal CVD death later in life compared with having a term delivery. This review focuses on 3 key areas to critically assess the association of sPTD and future maternal CVD risk: (1) CVD risk factors, (2) inflammatory biomarkers of interest, and (3) specific forms of vascular dysfunction, such as endothelial function and arterial stiffness, and mechanisms by which each may be linked to sPTD. The association of sPTD with subsequent future maternal CVD risk suggests that a woman’s abnormal response to pregnancy may serve as her first physiological stress test. These findings suggest that future research is needed to understand why women with sPTD may be at risk for CVD to implement effective interventions earlier in a woman’s life.
Two cycles of carboplatin as adjuvant therapy in stage I seminoma: 8-year experience by the Hellenic Co-operative Oncology Group (HECOG).
Authors: Konstantinos Koutsoukos, Michael Liontos, Maria Lykka, Georgios Rigakos, Anna Andreadou, Eleni Efstathiou, Angelos Koutras, Athanasios Papatsoris, Michael Chrisofos, Kostas Stravodimos, Ioanis Adamakis, Christos Alamanis, Vasilios Karavasilis, Thomas Makatsoris, Eleni P. Galani, George Klouvas, Paris A. Kosmidis, George Fountzilas, Meletios A. Dimopoulos, Aristotelis Bamias
Journal: Journal of Clinical Oncology (2013)

4558 Background: Adjuvant chemotherapy is used in stage I testicular seminoma. We have reported a risk-adapted strategy of 2 cycles of cisplatin/etoposide (EP) in 64 patients with age &lt; 34 and/or tumor diameter &gt; 4cm) (Bamias et al, Urology 2007), resulting in no relapses over a median follow up of 5 years. Following the establishment of adjuvant carboplatin as a standard, we adopted this treatment for all patients with stage I seminoma. We report our 8-year experience and compare these results with our previous EP strategy. Methods: Patients with stage I seminoma, treated with 2 cycles of carboplatin AUC 6 and a minimum follow up of 1 year after chemotherapy were selected. All patients consented for the use of their medical information and the analysis was approved by the centers involved. Survival functions were presented using Kaplan-Meier curves. The log-rank test was used to test for survival differences across different categories. Results: 137 patients (Median age: 34; Age&lt;34: 49%, tumor diameter&gt;4cm: 42%; rete testis invasion: 24%), treated between 11/2003-12/2011 were selected. During a median follow up of 4 years, there were 5 relapses (5-y relapse rate [RR]: 97% [SE: 2%]): retroperitoneal lymph nodes (n=4) and isolated brain (n=1). All patients with relapse had tumor diameter &gt; 4cm and/or age &lt; 34. No relapse was associated with rete testis invasion. Patients with at least 1 of the above risk factors (n=94) had a significantly higher relapse rate compared with a similar population (n=64) treated with 2 cycles of adjuvant EP: 5-y RR was 95% (SE: 2%) vs.100% (SE 0%), (p=0.033). All relapsed patients were treated with BEP chemotherapy and are currently alive with no evidence of relapse. Neutropenia and nausea/vomiting were less frequent with carboplatin than with EP (11% vs. 36% and 15% vs. 65%). Conclusions: Our analysis confirms the association of age and tumor diameter with relapse in stage I seminoma treated with adjuvant carboplatin. Although adjuvant carboplatin in patients with age&lt;34 and/or tumor diameter&gt; 4 cm is associated with higher RR than EP, the prognosis of these patients is excellent with salvage chemotherapy and, therefore, the use of less toxic treatment is justified.
Surgical removal of primary tumor in metastatic breast cancer: Impact on health-related quality of life (HR-QOL) in a randomized controlled trial (RCT).
Authors: Rajendra A. Badwe, Vani Parmar, Rohini W Hawaldar, Nita S. Nair, Rucha Vishal Kaushik, Shabina Siddique, Amol Nawale, Ashwini Budrukkar, Indraneel Mittra, Sudeep Gupta
Journal: Journal of Clinical Oncology (2014)

1124 Background: We have previously reported in a RCT that surgical removal of the primary tumor (versus not) did not significantly improve median overall survival (18.8 Vs 20.5 months) in women with MBC1. This procedure would still be worthwhile if it improved the quality of life in these women. We report here HR-QOL analysis of this RCT. [NCT: 00193778]. Methods: HR-QOL was assessed in these women using the EORTC QLQC30 and BR23 (English or validated local language versions). The questionnaires were completed by these women at baseline (at randomization) and at protocol defined follow-up time points thereafter. Results: Of the 350 women randomized to surgical removal of the primary Vs not, HR-QOL assessment was available at baseline for 178 (surgery=84, no surgery=94), 3-6 months for 139(surgery=74, no surgery=65), 6-9 months for 122 (surgery=65, no surgery=57) and 18-24 months for 94(surgery=45, no surgery=49). The groups were balanced and representative of patients in the main study (N=350) with respect to age, hormone receptor status, site of metastasis, no of metastatic lesions. The mean BR23 arm score was worse in the surgical arm at 3-6 month evaluation (18.9 Vs 10.4, p=0.003) but not at subsequent evaluations whereas mean BR23 breast symptom score was worse in no-surgery arm at 18-24 month evaluation (18.7 Vs 10.0, p=0.009), which corresponds to median OS in these women. There was no significant difference in mean global QOL score between the 2 arms at baseline (64.2 Vs 65.8, p=0.5), 6-9 months (69.9 Vs 67.7, p=0.5), 18-24 months (64.7 Vs 60.0, p=0.3) and all other time points. There was no significant difference between the 2 arms in all other domains of HR-QOL at any time point. Conclusions: Surgical removal of the primary tumor did not significantly improve the HR-QOL in women with MBC. Taken together with survival results our data provides strong evidence that surgery for primary should not be routinely performed in women with metastatic breast cancer. Clinical trial information: 00193778.