tbuckley/cabot-search huggingface dataset:
Cancer of the Cervix Stage I
Authors: Philip Rubin
Journal: JAMA (1965)

In 1953, when the eighth volume of the annual report of the World Health Organization on carcinoma of the cervix was issued, there seemed to be more general agreement on the management of cervical cancer than for virtually any other malignancy. The majority of contributors from cancer centers, both in this country and abroad, were employing radiotherapy and the survival figures continued to show improvement. However, in the past decade, the results accomplished by radical surgical procedures have challenged the favored position held by irradiation. With the demonstration by Meigs<sup>1</sup>that no postoperative mortality occurred in his first hundred cases, the spectre of Wertheim's 25% surgical mortality rate was banished. It is appropriate to reassess current results achieved by improved surgical techniques and by the availability of refinements in radiation treatment. Although different views are available, clinical series have been designed in an attempt to answer the question of
Impact of subspecialty, clinical volume, and years of practice in selection of treatment sequencing in the management of localized extremity soft tissue sarcoma.
Authors: R. J. Canter, N. Wasif, R. M. Tamurian, S. Christensen, L. Do, S. R. Martinez, S. Chen, M. F. Brennan
Journal: Journal of Clinical Oncology (2010)

10085 Background: Although the treatment of localized extremity soft tissue sarcoma (STS) is multimodality in nature, considerable variation exists in the use and timing of radiation (RT) and chemotherapy in relation to surgical resection. Our objective was to identify factors responsible for this variation. Methods: A questionnaire was emailed to active members of ASCO who specialize in the management of STS. Questions pertained to the multimodality management of STS. Survey responses were scored on a five-point Likert scale. Means were compared using independent samples ANOVA with post-hoc Bonferroni correction as indicated. Results: The questionnaire was viewed by 490 potential respondents and completed by 320 (65%). Respondents self-identified by specialty: Medical Oncology (18%), Radiation Oncology (8%), Surgeons (67%), and Other (7%). Sarcoma volume in relation to overall clinical practice comprised: >75% (12%), 25-75% (39%), and <25% (49%). Respondents were evenly distributed on the use of preoperative versus postoperative radiation (mean 3.03 ± 0.06), a decision not influenced by specialty. However, physicians with a >75% STS practice preferred preoperative RT compared to those with <25% (2.58 ± 0.17 vs. 3.19 ± 0.08, p 0.003). Similarly, physicians in practice <5 years preferred preoperative RT compared to those in practice >15 years (2.79 ± 0.12 vs. 3.21 ± 0.09, p 0.025). Factors identified as being important in receipt of RT included tumor size >10cm, high grade, positive margins and proximity to neurovascular bundle. Overall, respondents preferred preoperative chemotherapy (mean 2.89 ± 0.06). No significant difference existed by specialty or years in practice. Physicians with >75% STS practice preferred preoperative chemotherapy compared to those with <25% (2.51 ± 0.16 vs. 3.22 ± 0.07, p <0.001). Factors important for chemotherapy were tumor size >10cm, high grade, age <50, and synovial sarcoma histology. Conclusions: Treatment sequencing in the management of STS is influenced by clinical volume and years in practice but not by physician specialty. This may reflect the recent trend towards regionalization of multimodality STS care. No significant financial relationships to disclose.
Outcomes of supportive/palliative care (SPC) for advanced cancer patients (AdCa) in a general public hospital and a comprehensive cancer center.
Authors: Marvin Omar Delgado-Guay, Jeanette Ferrer, Jewel Ochoa, Hilda Cantu, Janet L. Williams, Minjeong Park, Rechelle L. Asirot, Nneamaka Enwemnwa, Renee Flores, Rodrigo C. Guanlao, Faheem M Haq, Suchrita R. Kamineni, Eduardo Bruera
Journal: Journal of Clinical Oncology (2014)

208 Background: AdCa experience severe physical, psychosocial and existential distress. Their needs might not be met only by standard care. We compared outcomes of AdCa receiving SPC at a General Public Hospital (GPH) and at a Comprehensive Cancer Center (CCC). Methods: We reviewed 364 consecutive AdCa(182 at GPH and 182 at CCC). AdCa were managed by SPC-specialists with common clinical-pathways. We assessed symptoms(Edmonton Symptom Assessment System:ESAS) and outcomes at consult and first follow-up. Results: Race was White, African-American, and Hispanic in 42(23%), 70(39%), 63(35%) at GPH vs. 112(64%, p&lt;0.0001), 30(17%, p&lt;0.0001), 20(11%, p&lt;0.0001) at CCC, respectively. Age, gender and cancer diagnoses were similar at both sites. 98(54%) at GPH vs. 181(99%) at CCC reported to have some health-insurance(p&lt;0.0001). Symptoms at consult-time at GPH and CCC: Pain 133(85%) vs. 151(91%,p=0.0586); Fatigue 127(80%) vs. 153(94%,p&lt;0.0001); Nausea 69(44%) vs. 89(55%,p=0.0438); Depression 79(51%) vs. 109(68%,p=0.0015); Anxiety 72(46%) vs. 121(75%,p&lt;0.0001); Drowsiness 78(50%) vs. 119(76%, p&lt;0.0001); Appetite 89(56%) vs. 146(91%, p&lt;0.0001); Dyspnea 72(46%) vs. 107(65%,p=0.0004); Sleep 90(59%) vs. 142(88%,p&lt;0.0001); and Well-Being 95(63%) vs. 132(93%,p&lt;0.0001). Both SPC provided multiple not different interventions: opioid-management, medication review for polypharmacy, bowel-regimen, antiemetics, and interdisciplinary counseling. At follow-up ESAS-improvement(decrease ≥2 points) was: pain 21/80(26%) at GPH vs. 43/107(40%) at CCC(p=0.0469), anxiety 18/75(24%) vs. 40/98(41%,p=0.0202); appetite 15/74(20%) vs. 37/90(41%,p=0.0043); sleep 20/74(27%) vs. 42/95(44%,p=0.0215); nausea 23/77(30%) vs. 35/97(36%,p=0.3879); depression 18/74(24%) vs. 30/94(32%,p=0.2796). Median Time(range) from consult-to-follow-up at GPH 21 days(0-427) vs. 14 days(1-275,p=0.032), and from consult-to-death at GPH 53 days(1-699) vs. 51 days(1-898,p=0.8473). Conclusions: AdCa at GPH and CCC had frequent and severe-symptoms. Response-rate was lower and follow-up less-frequent at GPH. SPC needs to be more frequent and more resources are needed at GPH.
Updated efficacy findings from the X-ACT phase III trial of capecitabine (X) vs. bolus 5-FU/LV as adjuvant therapy for patients (pts) with Dukes’ C colon cancer
Authors: C. Twelves, A. Wong, M. Nowacki, J. McKendrick, G. van Hazel, J.-Y. Douillard, E. Díaz-Rubio, J. Cassidy, J. Maroun
Journal: Journal of Clinical Oncology (2005)

3521 Background: X is an oral fluoropyrimidine with superior activity and improved safety compared with bolus 5-FU/LV in first-line metastatic colorectal cancer. Based on X’s efficacy in advanced disease and the strong pt preference for oral chemotherapy, the X-ACT trial evaluated X vs. 5-FU/LV as adjuvant treatment for colon cancer. Methods: Pts with resected Dukes’ C colon carcinoma were randomized to receive either oral X (1250mg/m2 bid on days 1–14, every 3 weeks) or i.v. 5-FU/LV (Mayo Clinic regimen: LV20 mg/m2 + 5-FU 425mg/m2 days 1–5, every 4 weeks) for 24 weeks. At least equivalence in disease-free survival (DFS) was the primary endpoint. Results: 1987 pts (1004 to X; 983 to 5-FU/LV) from 164 centers were randomized between Nov 1998 and Nov 2001. Baseline characteristics (median age, ECOG score, sex, nodal status, tumor differentiation, and preoperative CEA values) were well balanced in each arm (p=NS). Here we present data with a median follow-up time of 4.3 years (51 months). Intent to treat (ITT) analysis showed at least equivalence in terms of DFS between the treatment arms with a strong trend towards superior DFS for X vs. 5-FU/LV (HR=0.87 [95% CI, 0.75–1.00], p=0.0525). Relapse-free survival (RFS) was significantly superior for X vs. 5-FU/LV (ITT: HR=0.86 [95% CI, 0.74–0.996], p=0.044). These findings were confirmed in a multivariate analysis of DFS. X caused significantly (p<0.001) less all-grade diarrhea, nausea/vomiting, stomatitis, alopecia, and neutropenia, and less grade 3/4 neutropenia, stomatitis and neutropenic fever/sepsis than 5-FU/LV. Non-life-threatening hand-foot syndrome and hyperbilirubinemia were the only events reported more commonly with X than 5-FU/LV (p<0.001). Conclusion: These updated findings with longer follow-up confirm the previously reported findings that X is at least equivalent to 5-FU/LV in terms of DFS. The superior efficacy of X over 5-FU/LV in metastatic disease (response rate) has translated into superior efficacy in the adjuvant setting (RFS). These findings provide a very clear rationale for replacing 5-FU/LV with X in the adjuvant treatment of colon cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, sanofi-aventis Bristol-Myers, Roche Roche Roche
Tumour initiating cells and IGF/FGF signalling contribute to sorafenib resistance in hepatocellular carcinoma
Authors: Victoria Tovar, Helena Cornella, Agrin Moeini, Samuel Vidal, Yujin Hoshida, Daniela Sia, Judit Peix, Laia Cabellos, Clara Alsinet, Sara Torrecilla, Iris Martinez-Quetglas, Juan José Lozano, Christèle Desbois-Mouthon, Manel Solé, Josep Domingo-Domenech, Augusto Villanueva, Josep M Llovet
Journal: Gut (2015)

Objective Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterise the role of tumour-initiating cells (T-ICs) and signalling pathways involved in sorafenib resistance. Design HCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: (1) role of T-ICs by in vitro sphere formation and in vivo tumourigenesis assays using NOD/SCID mice, (2) activation of alternative signalling pathways and (3) efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, quantitative real-time PCR (qRT-PCR)) and protein analyses (immunohistochemistry, western blot) were conducted. A novel gene signature of sorafenib resistance was generated and tested in two independent cohorts. Results Sorafenib-acquired resistant tumours showed significant enrichment of T-ICs (164 cells needed to create a tumour) versus sorafenib-sensitive tumours (13 400 cells) and non-treated tumours (1292 cells), p&lt;0.001. Tumours with sorafenib-acquired resistance were enriched with insulin-like growth factor (IGF) and fibroblast growth factor (FGF) signalling cascades (false discovery rate (FDR)&lt;0.05). In vitro, cells derived from sorafenib-acquired resistant tumours and two sorafenib-resistant HCC cell lines were responsive to IGF or FGF inhibition. In vivo, FGF blockade delayed tumour growth and improved survival in sorafenib-resistant tumours. A sorafenib-resistance 175 gene signature was characterised by enrichment of progenitor cell features, aggressive tumorous traits and predicted poor survival in two cohorts (n=442 patients with HCC). Conclusions Acquired resistance to sorafenib is driven by T-ICs with enrichment of progenitor markers and activation of IGF and FGF signalling. Inhibition of these pathways would benefit a subset of patients after sorafenib progression.
Letter by Al-Kindi and Oliveira Regarding Article “Cardiac Sarcoidosis: Epidemiology, Characteristics, and Outcome Over 25 Years in a Nationwide Study”
Authors: Sadeer G. Al-Kindi, Guilherme H. Oliveira
Journal: Circulation (2015)

We read with interest the article by Kandolin and colleagues 1 published in Circulation.In a nationwide study in Finland, they report that the annual detection rate of cardiac sarcoidosis (CS) has increased >20-fold over a 25-year period.Interestingly, these findings are in alignment with our own data regarding the increased incidence of heart transplantation (HT) for CS in the United States.Using the United Network for Organ Sharing registry, we identified 150 adult patients with CS listed for HT over a 21-year period .During this period, the percentage of patients who had heart failure with CS requiring HT increased 5-fold from 0.1% (1994)(1995)(1996)(1997) to 0.5% (2010-2014), P<0.001.Similarly, the contribution of CS as a cause of restrictive cardiomyopathy increased from 5.0% (1994)(1995)(1996)(1997) to 15.22% (2010-2014), P<0.001.Among patients in the United States with CS requiring HT, the median age at listing is 54 years, and 92 (61.3%) were male, and 90 (60.0%) were whites, 56 (37.3%) were blacks, and 4 (2.8%) were others.The use of an implantable cardioverter defibrillator is currently at 92.6% and waitlist mortality has decreased by an average of 11% per year (hazard ratio, 0.890; 95% confidence interval, 0.810-0.977;P=0.014) after adjusting for listing status, with 1-year and 3-year waitlist mortality at 89% and 77%, respectively.Correspondingly, posttransplant survival of CS patients is 86% at 1 year, 84% at 5 years, and 58% at 10 years, comparable with other HT recipients (P=0.296).Our findings suggest that the trends described in Finland by Kandolin et al 1 are also occurring in the United States and that CS patients are being increasingly considered for HT with good outcomes.Whether the higher prevalence of CS is a reflection of improved diagnostic modalities or increased incidence of the disease itself needs further investigation.
A Time-Lapse Cinematographic Study &lt;italic&gt;In Vitro&lt;/italic&gt; of Mitosis in Normal Human Cervical Epithelium, Dysplasia, and Carcinoma &lt;italic&gt;In Situ&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Ralph M. Richart, Virginia Lerch, Bruce A. Barron
Journal: JNCI Journal of the National Cancer Institute (1967)

Mitosis in tissue-cultured cells derived from normal human cervical epithelium, dysplasia, and carcinoma in situ was studied by phasecontrast time-lapse cinematography. The morphological conduct of mitosis was strikingly aberrant in the neoplastic cells when compared to the normal cells. When the times spent in the individual mitotic phases were analyzed statistically, it was Found that the normal cells spent significantly less time in prometaphase and telophase than did the neoplastic cells, and the time in metaphase was significantly greater. In addition, there was greater variability in the duration of prometaphase and telophase in the neoplastic cells than in the normal cells. An examination of the correlation coefficients between stages and diagnostic groups suggests a gradual breakdown in the coordination of mitosis during the transition From a normal cell to carcinoma in situ.
The neglected refugee crisis
Authors: Adrianna Murphy, Michael Woodman, Bayard Roberts, Martin McKee
Journal: BMJ (2016)

Frontline states need more international aid

As attention remains focused on the growing numbers of refugees from Syria seeking asylum in the European Union, it is important to acknowledge that the challenges facing the frontline states of Egypt, Iraq, Jordan, Lebanon, and Turkey dwarf those facing Europe. 

In these states, underfunded humanitarian agencies are under enormous pressure, and the situation for most refugees is bleak. Turkey has received over 2.1 million refugees from Syria, more than any other country.1 Lebanon hosts about 1.1 million registered Syrian refugees, a quarter of the country’s previous population, and Jordan almost 650 000, about 10% of its population. These are in addition to large refugee populations from previous conflicts: Lebanon remains home to an estimated 450 000 Palestinian refugees, about half of whom are in camps. The rest of the world has offered resettlement to only 2.6% of the total number of Syrian refugees that are currently living in Egypt, Lebanon, Iraq, Jordan, and …
Structural and Functional Basis for JAK3-Deficient Severe Combined Immunodeficiency
Authors: Fabio Candotti, Scott A. Oakes, James A. Johnston, Silvia Giliani, Richard F. Schumacher, Patrizia Mella, Maurilia Fiorini, Alberto G. Ugazio, Raffaele Badolato, Luigi D. Notarangelo, Fabio Bozzi, Paolo Macchi, Dario Strina, Paolo Vezzoni, R. Michael Blaese, John J. O'Shea, Anna Villa
Journal: Blood (1997)
Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma.
Authors: R P Castleberry, L E Kun, J J Shuster, G Altshuler, I E Smith, R Nitschke, M Wharam, N McWilliams, V Joshi, F A Hayes
Journal: Journal of Clinical Oncology (1991)

Children older than 1 year of age who have neuroblastoma with complete or partial removal of the primary tumor and positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) are a small but higher-risk subset of patients. To further evaluate the importance of identifying patients with POG stage C neuroblastoma and to assess the efficacy and toxicity of adding concurrent radiation therapy (RT) to chemotherapy (CT) in these children, a randomized study was conducted. Eligible patients received cyclophosphamide 150 mg/m2 orally days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR) every 3 weeks for five courses with or without RT to primary tumor and regional lymph nodes (24 to 30 Gy/16 to 20 fractions). Second-look surgery was advised to evaluate response and to remove residual disease. Continuation therapy alternated CYC/ADR every 3 weeks with cisplatin 90 mg/m2 day 1 followed by teniposide 100 mg/m2 day 3 (CDP/VM) for two courses each. Secondary CT with CDP/VM alone was available for patients not achieving complete response (CR) following induction treatment and second-look surgery. Of 29 eligible patients randomized to CT alone, 13 achieved CR, and nine are disease-free (NED) 1 to 52 months (median, 35 months) off therapy. Twenty-two of 33 eligible cases treated with CT/RT attained CR, and 19 are NED 1 to 77 months (median, 23 months) off therapy. Local and metastatic relapses occurred in both arms. Differences in CR, event-free survival, and survival rates were significant, P = .013, .009, and .008, respectively. Surgical compliance was excellent and complications uncommon. Therapy was tolerable in both groups but hematopoietic toxicity was more common in the CT/RT arm. We conclude that POG stage C neuroblastoma in children older than 1 year of age is a higher-risk group that should be identified, that CT/RT provides superior initial and long-term disease control compared with CT alone in this patient subset, and that the occurrence of metastatic failures in both treatment groups suggests a need for more aggressive chemotherapy.
Increased Dose-Intensity in Small-Cell Lung Cancer: A Failed Strategy?
Authors: David H. Johnson, David P. Carbone
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.8.2297 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10561290 Increased Dose-Intensity in Small-Cell Lung Cancer: A Failed Strategy? David H. JohnsonxDavid H. JohnsonSearch for articles by this author , David P. CarbonexDavid P. CarboneSearch for articles by this author Show More Division of Hematology and Oncology, Department of Medicine, Vanderbilt University School of Medicine, The Vanderbilt-Ingram Cancer Center, Nashville, TN https://doi.org/10.1200/JCO.1999.17.8.2297 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Response to comment on “Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2”
Authors: Lawrence Steinman, S. Sohail Ahmed
Journal: Science Translational Medicine (2015)

Vassalli et al.'s study does not involve or provide additional data regarding influenza virus, influenza vaccines, human samples, animal models of narcolepsy, or experiments related to mimicry and cross-reactivity. They present data on the distribution of hypocretin (HCRT) (also known as orexin) receptors in the brain of an engineered mouse developed by them.
해설논문 : B형간염바이러스의 유전자 다양성과 변이
Authors: 임형준 ( Hyung Joon Yim )
Journal: Clinical and Molecular Hepatology (2008)

Hepatitis B virus (HBV) is a partially double stranded DNA virus with genetic diversity represented by eight genotypes (A to H). Natural course and response to treatment could be affected by HBV genotypes. HBV shows high rates of turn over in the absence of proof-reading ability. As a result, large amounts of quasi-species are produced naturally or antiviral-associated. HBV consists of four open reading frames, namely preS/S gene, precore/core gene, polymerase gene, and X gene. Mutations on preS gene can result in undetectable HBsAg even in case that HBV is replicating. Surface gene mutation leads to decreased binding affinity to anti-HBs, which is associated with a vaccine escape mutant. Precore mutation abolishes HBeAg whereas mutations on basal core promoter gene down-regulate the HBeAg production. Mutations on basal core promoter are associated with increased HBV replication and high incidence of progressive liver diseases such as liver cirrhosis and hepatocellular carcinoma. Mutations on polymerase genes are often induced by antiviral therapy. Emergence of antiviral-resistant mutation is the major cause of treatment failure. Furthermore, existence of prior antiviral-resistant mutations limits the options of subsequent antiviral agents. Therefore, judicious use of antivirals and selection of the most potent drug with the lowest resistance rate are of the utmost importance for the prevention of antiviral-associated mutants. Detailed knowledge and understanding of HBV genetic diversity and mutant would be critical to establish strategies for the diagnosis and management of HBV infection. (Korean J Hepatol 2008;14:446-464)
The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: Long-term outcomes in first-line patients (pts)
Authors: C. W. Ryan, R. M. Bukowski, R. A. Figlin, J. J. Knox, T. E. Hutson, J. P. Dutcher, J. George, J. Kirshner, J. Humphrey, W. M. Stadler
Journal: Journal of Clinical Oncology (2007)

5096 Background: Sorafenib (SOR) doubled median progression-free survival (PFS) versus placebo in a phase III study (TARGETs) for previously treated pts with clear cell renal cell carcinoma (RCC). We report on pts who had not received any prior systemic anti- cancer therapy (1 st line) for advanced RCC from the ARCCS program in the US and Canada, which enrolled a broad range of pts. Methods: Pts received SOR 400 mg bid in the ARCCS open-label, nonrandomized treatment protocol if they were =15 years old with advanced (unresectable, recurrent or metastatic) RCC and had ECOG PS 0–2. In the US, ARCCS enrollment ended with SOR approval in 12/05, and pts were transitioned to commercial drug with 1st line pts being eligible for an additional 6-mo follow-up in an extension protocol (EP); Canadian enrollment completed in 8/06. Response evaluation (baseline and =1 post-baseline radiologic assessment) was conducted every 4 wks in the main study and every 8 wks during the EP. Pts without a confirmatory scan were classified as unconfirmed PR. The primary efficacy analysis on PFS was pre-specified to be performed only on the EP-enrolled pts. Results: Of the 2,488 pts valid for safety in ARCCS, nearly 50% were 1st line (n=1239) of which 69% were male with median age 65 yrs; 77% had prior nephrectomy and 29% had prior radiotherapy. Time from diagnoses to treatment was &lt;1 yr for 52% and =1 yr 36% in these 1st line pts. Grade 3 and 4 adverse events with &gt;2% incidence included hand-foot skin reaction 7.7%, fatigue 4.7%, hypertension 3.8%, rash/desquamation 5.2%, dehydration 2.9, diarrhea and dyspnea 2.6%. Confirmed responses are reported in the table ; 15% had unconfirmed PRs. For the 224 1st line pts enrolled in the EP, median PFS was 35.1 wks (95% CI; 32.7, 41.9). Conclusions: SOR toxicity in 1st line pts appeared similar to that in both overall and 2 nd line populations previously reported in the phase III study. The PFS among patients enrolled in the EP is encouraging, but may be biased by low enrollment and selection for non-progressors. [Table: see text] [Table: see text]