tbuckley/cabot-search huggingface dataset:
Idiotype vaccine therapy of follicular lymphoma in first remission: Association of t(14;18) and disease free survival in a phase II cohort
Authors: B. L. Gause, S. S. Neelapu, C. M. Cohen, L. M. Katz, T. Watson, A. M. Stergiou, L. W. Kwak
Journal: Journal of Clinical Oncology (2006)

7582 Background: A single-arm Phase 2 study (Nature Med 5:1171–7,1999), evaluated the ability of tumor-specific idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) administered with granulocyte-monocyte colony-stimulating factor - GM-CSF (BiovaxID vaccine) to induce complete remission (CR) and molecular remission (MR) in follicular NHL patients in first CR after chemotherapy. We reported (ASH 2005, Abstr 2441) that at 9.2 years follow-up, disease free survival (DFS) and overall survival (OS) were 45% and 95%, respectively; median DFS was 8.0 years. Previous studies indicated that the t(14;18) chromosomal translocation is associated with follicular NHL. We tested the hypothesis that absence of t(14;18) in peripheral blood (PB) of patients after Id vaccination is predictive of DFS. Methods: A 20-patient cohort in first CR treated with the vaccine was evaluated. t(14;18)- (MR) is defined as &lt;1 t(14;18)+ cell in 10 5 cells using PCR of the MBR breakpoint cluster on DNA from tumor biopsies or PB. Of the 20 patients, 11 had t(14;18)+ tumors and PB before chemotherapy. Following chemotherapy all 11 patients continued to have t(14;18)+ PB despite being in CR. However, at 1 month following final vaccine treatment, 8 of these patients had converted to t(14;18)- . In this ad hoc analysis, the proportion of patients remaining in DFS was stratified by t(14;18) status; Kaplan-Meier analysis compared median DFS of patients across t(14;18) status following vaccination. Results: At median follow-up of 9.2 years, 55% of patients had clinically relapsed. Although not statistically significant, of the 17 patients t(14;18)- post-vaccine, only 47.1% had clinically relapsed while 100% of the 3 t(14;18)+ patients had relapsed [Chi-square test; P=0.089]. Median DFS in t(14;18)+ patients was 60 months (5.0 years) and had not yet been reached in t(14;18)- patients at 91 months (7.6 years) [Log-rank test; P=0.069]. Conclusions: These data show a possible association between t(14;18) negativity following vaccine and prolonged DFS. Additional follow-up on these patients is needed, as well as similar analyses in other cohorts, to further explore this association. [Table: see text]
Moving quality of life measurement into clinical oncology practice
Authors: M. S. Donaldson
Journal: Journal of Clinical Oncology (2004)

8264 Background: How common is quality of life measurement in oncology practice in the US? Factors affecting its use in routine practice are distinct from those in clinical trials. Better understanding is needed of how issues related to the oncology group practice, the larger organization; and the financial, legal, and regulatory environment influence and constrain the clinician-patient encounter. Methods: Systematic review of peer-reviewed and other literature in English after December, 1989 and interviews with oncologists and quality-of-life researchers. Results: Studies report the feasibility of quality-of-life measurement in clinical practice, and clinician surveys indicate acceptance of systematic measurement; but few examples in routine oncology practice were identified. Conclusions: The challenge to quality-of-life measurement may lie not in opposition to measurement than the obstacles to integrating measurement into health care processes. In addition to well-recognized instrument-related issues, challenges include clinician, patient, and health system issues. For clinicians, the effect on clinic work flow, resource constraints for data collection and management, and reimbursement for monitoring quality of life are noteworthy. For patients, acceptability, response burden, data confidentiality and use may be important. Patients providing information will expect it to affect their care. Health care organizations will have to deploy resources for data management, timely review of data, and to respond to patient needs identified through quality-of-life measurement. Even with well-accepted measures, implementation is not likely to occur without using principles of active dissemination and new forms of organizing clinical practice. The way forward does not lie in exhorting clinicians to add the use quality of life information to other tasks of everyday practice. Incorporation of quality of life information into clinical practice will require new attitudes about the function of medical records and patient encounters, new ways of organizing patient-clinician interactions and collecting data, and redesigned systems of care that respond to patients' needs. No significant financial relationships to disclose.
Incidence of local recurrence in patients after breast-conserving surgery and postoperative radiotherapy with or without a supplementary radiation.
Authors: Danijela D. Scepanovic, Andrea Hurakova, Martina Lukacovicova, Zuzana Dolinska, Andrea Masarykova, Pavol Lukacko, Margita Pobijakova
Journal: Journal of Clinical Oncology (2012)

159 Background: We evaluated the incidence of local recurrence (LR) among patients (pts) who received radiotherapy with/without a supplementary dose of radiation (boost) to the tumor bed after breast-conserving surgery (BCS) for early breast cancer (BC). Methods: In our retrospective analysis (from 2000-2004) 449 pts with stage I/II BC received 50Gy of radiation to the whole breast in 2Gy fractions over a five-week period after BCS. There were 328 pts (73%) with microscopically complete excision (&gt;5mm margins) and 121 pts (27%) with a microscopically incomplete excision (≤5mm margins). Patients with a microscopically complete or incomplete excision were randomly assigned to receive either no further local treatment (190) or an additional localized dose (309) of 10-16Gy, usually given in 5-8 fractions (fr) by electrons/15Gy in 3 fr by HDR interstitial brachytherapy. Results: During a median follow-up period of 79 months (min 20, max 120), the cumulative incidence of LR was 3% for all group of pts (449). The LR was observed in 1 of 190 pts in group without boost and 13 of 309 pts in group with boost. There was statistically significant difference between two groups of pts regarding local recurrence rate (LRR) (p= 0.0218).The 5 year actuarial rates of LR were 1% in group of pts with negative surgical margins versus 8% in group of pts with positive margins [95% CI, 6% (1%-26%)] (p&lt;0.001). Multivariate analysis showed that pts with negative surgical margins had strongly statistically significant influence (p&lt;0.001) and pts with negative lymph/angioinvasion had statistically significant influence on low risk of LR (p = 0.007). The 5 year DFS was 90% and OS was 98% in all group of pts (449). There was no statistical significant difference between two groups of pts regarding DFS and OS. Conclusions: In our analysis, the incidence of LR is low. However, there was better result in no boost group of pts regarding LRR. The cause was in more frequent selection among worse group of pts with positive surgical margins for application of boost (73% vs 52%, p&lt;0.0001). The strong criteria for identifying low risk group of pts for LR were: negative surgical margins and absence of lymph/angioinvasion.
33 NOTCH SIGNALLING WITHIN THE TUMOUR-STROMAL MICROENVIRONMENT DRIVES PROGRESSION OF CHOLANGIOCARCINOMA WHILST PATHWAY INHIBITION ENHANCES CHEMOSENSITIVITY
Authors: A. Robson, R.V. Guest, L. Boulter, A. Pellicoro, O. Sansom, S. Forbes
Journal: Journal of Hepatology (2012)
Diffuse alveolar hemorrhage dominant in right lung is due to cardiac comorbidity
Authors: Koji Tamai, Takehiro Otoshi, Daichi Fujimoto, Takahisa Kawamura, Takeshi Matsumoto, Kazuma Nagata, Kyoko Otsuka, Atsushi Nakagawa, Kojiro Otsuka, Keisuke Tomii
Journal: European Respiratory Journal (2013)

Background: Diffuse alveolar hemorrhage (DAH) with lateral dominance, especially on the right side, is often observed in clinical practice.  Aims: To describe clinical aspects of right side dominant DAH.  Methods: We retrospectively reviewed data from 394 bronchoalveolar lavage fluid (BALF) specimens between January 2009 and December 2012 and patients who presented with progressively bloodier BALF were evaluated. Unilateral dominance on chest X-ray (CXR) was determined as follows: Infiltration area of the dominant side was more than twice the infiltration area of the other side.  Results: A total of 43 patients were evaluated. The etiology of DAH was as follows; heart failure (n=12), clotting disorder (n=10), pneumonia (n=4), acute myeloid leukemia (n=3), vasculitis (n=2), systemic lupus erythematosus (n=2), acute exacerbation of interstitial pneumonia (n=2), drug-induced lung injury (n=1), undefined (n=7). Fifteen patients (34.9%) were right lung dominant, 3 patients (7.0%) were left lung dominant and 25 patients (58.1%) showed bilateral infiltration on CXR. Multivariate logistic regression analysis revealed that co-morbidities of cardiovascular diseases (CVD) (OR 31.9, 95% CI 1.6-2598.1), and atrial fibrillation (Af) (OR 38.4, 95% CI 2.9-2036.2) were significant factors in right lung dominant DAH. In addition, need for mechanical ventilation was a simple factor used to denote in-hospital mortality using multivariate logistic regression analysis.  Conclusions: DAH dominance in right lung was significantly related to co-morbidities of CVD and Af, but not related to in-hospital mortality.
Invasive breast cancer clinical outcome is predicted by a novel bright-field assay for the simultaneous detection of HER2 gene amplification and protein expression (SILVERFISH)
Authors: D. Hicks, M. Skacel, E. Downs-Kelly, M. Cheang, J. Pettay, T. Nielsen, D. Huntsman, R. Powell, J. Hainfeld, T. Grogan
Journal: Journal of Clinical Oncology (2004)

667 Background: A bright-field assay, SILVERFISH, simultaneously detects HER2 gene copy and protein expression, We analyzed the accuracy of SILVERFISH in predicting clinical outcome and assessed its concordance with FISH and IHC. Methods: Tissue microarrays from 444 invasive breast carcinomas were evaluated with SILVERFISH which includes enzyme metallography (EnzMetTM, Nanoprobes) for HER2 gene amplification (Am J Pathol. 160:1589–1595;2002), and IHC with CB11 for IHC detection of HER2 protein. Gene amplification was scored qualitatively (amplified vs.non-amplified) and CB11 staining was scored on a 0 to 3+ scale, and correlated with clinical outcomes by Kaplan-Meier survival analysis (log-rank). Results were correlated with FISH (Vysis) and IHC (DAKO) using kappa statistics. Results: SILVERFISH detected HER2 gene amplification in 108 of 444 (24%) tumors. Simultaneous protein overexpression (2+/3+) was identified in 71 (65%) cases, and 37 (34%) of the HER2-amplified cases were IHC negative. 6 of 336 (1%) HER2 non-amplified cases were IHC 2+/3+; 330 were 0 or 1+. SILVERFISH HER2 gene copy and protein status correlated with amplification by FISH (Kappa=.79) and IHC (Kappa=.71). HER2 status defined by either components of SILVERFISH predict survival and correlate with clinical outcome (p=0.02 for gene amplification, p=0.002 for protein overexpression). Conclusion: HER2 status as determined by SILVERFISH has good concordance with FISH and IHC, and correlates with clinical outcome. The simultaneous visualization of HER2 gene signal and protein allows for a practical and complete assessment of HER2 status. Supported in part by NIH SBIR CA83618. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Nanoprobes; Ventana Medical Systems Ventana Ventana Ventana Medical Systems International Ventana Medical Systems International
Association between the use of thiazolidinediones and the risk of cancer in diabetic patients
Authors: R. Govindarajan, L. Ratnasinghe, M. Midathada, P. Kim, M. Darbe, S. Barnhart, E. Siegel, D. Simmons, L. Kim, N. Lang
Journal: Journal of Clinical Oncology (2005)

1005 Background: PPARγ, a member of the super family of nuclear receptors peroxisome proliferator activated receptors (PPAR) is a member of a potential tumor suppressor pathway in colon, breast, pancreas, prostate, and lung cancers. The anti diabetic agents glitazones or thiazolidinediones (TZDs) which are PPARγ ligands have antineoplastic activity in vitro but have no proven clinical benefit. The effect of TZDs on intestinal polyposis in animal models is conflicting. A retrospective study of type 2 diabetes mellitus patients was conducted to determine whether therapy with TZDs might modify the risk of colorectal, prostate and lung cancer. Methods: The data on 127,658 male patients with diabetes mellitus treated at ten veterans affairs (VA) hospitals between 1997 and 2002 was obtained from VISN-16 database. The incidence of colorectal, lung and prostate cancers during this period was determined by using ICD-9 codes. The pharmacy data regarding the use of TZDs, insulin and other treatments, as well as dietary history was also obtained from VISN-16 database. Multi-variate logistic regression was used to assess the association between the use of TZD and the risk of colorectal, lung and prostate cancers. Results: 31509 (25%) patients were treated with TZDs. 16953(13.2%) had colorectal, prostate or lung cancer. Diabetics on TZDs were at 15% reduced risk of lung cancer and 8% increased risk of prostate cancer after adjusting for age, race, diet, insulin use and body mass index compared to those who did not use TZDs. Conclusion: TZDs appear to reduce the risk of lung cancer and appears to increase the risk of prostate cancer in our cohort of male type 2 diabetes patients. The primary limitation of our findings is the lack of smoking data. The differential effect of TZDs on different cancers needs to be further evaluated. No significant financial relationships to disclose.
Abstract 20437: Gene Expression Profiling Identifies Differentially Expressed Genes in Cardiac Allograft Vasculopathy
Authors: Monica Colvin-Adams, Nonyelum Harcourt, Ying Zhang, Adam Mitchell, Kenneth Liao, Kenneth Beckman
Journal: Circulation (2014)

BACKGROUND: Coronary angiography is the current gold standard for screening and diagnosis of cardiac allograft vasculopathy (CAV). Given the invasiveness and marginal sensitivity associated with angiography, minimally invasive sensitive biomarkers are needed to identify CAV early. The goal of our study is to determine differentially expressed genes in CAV that may serve as targets for biomarker development. Methods: Gene expression profiling and transcriptome analysis using Illumina HiSeq 2000, was performed on 23 cardiac transplant recipients (12 severe CAV ISHLT grade 3 and 11 without CAV) who were matched by age, gender, and duration of transplant. Fastqc, Tophat, Samtools, and CuffDiff were utilized for quality control of raw reads, mapping short reads to reference genomes and testing differential expression between healthy subjects and transplant subject, respectively. Pathway analysis to identify molecular pathways that show expression change in transplant recipients was done using ingenuity pathway...
Neurological Complications of Mumps
Authors: R. R. Russell, J. C. Donald
Journal: BMJ (1958)

BaRMSH 27 precaution to avoid provoking a possible reaction at a time when resistance is likely to be relatively low.Summary A case is reported of an 8-months-old normal child who, within 24 hours of a combined diphtheria-pertussis inoculation, became pyrexial, drowsy, and hypotonic.Convulsions and evidence of mental deterioration followed rapidly.At 3 years of age convulsions still persisted and mental retardation was gross (I.Q.=23).Review is made of 107 cases of neurological com- plications of pertussis inoculation reported in the litera- ture.Males predominated; reactions occurred in all age groups in which immunizations were done, irrespec- tive of the dosage used, and followed first or subse- quent inoculations.A wide variety of vaccines, single and combined, were implicated.Past personal and family histories indicated relatively few instances of neurological or allergic abnormalities.The early onset of neurological symptoms was characteristic, with changes of consciousness and convulsions as the most striking features.Pareses or paralyses were not infrequent, and eight children died within 48 hours of inoculation.Follow-up revealed a recovery rate of about 50%, a persisting morbidity rate (physical and/or mental) of about 30%, and a mortality rate of about 15%.The question of aetiology is considered and contra- indications are discussed.The value of pertussis immu- nization is emphasized, as is the grave danger of further inoculations when a previous one has produced any sug- gestion of a neurological reaction.
Prognostic factors for PFS in patients with advanced gastric cancer: Using the data from JCOG9912 study.
Authors: Daisuke Takahari, Narikazu Boku, Junki Mizusawa, Kenichi Nakamura, Yasuhide Yamada, Takayuki Yoshino, Kentaro Yamazaki, Wasaburo Koizumi, Kazutoshi Fukase, Kensei Yamaguchi, Masahiro Goto, Tomohiro Nishina, Takao Tamura, Akihito Tsuji, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2015)

180 Background: In advanced gastric cancer (AGC), there are many reports about prognostic factors for overall survival (OS), and we have proposed a prognostic index using four prognostic factors (PS, number of metastatic sites, prior gastrectomy and ALP; Oncologist 2014) based on a phase III trial JCOG 9912 for the first-line treatment (Lancet Oncol. 2009). However, there is no report about prognostic factors for progression free survival (PFS). In this ancillary study, we explored whether prognostic factors are similar or not between OS and PFS. Methods: The subjects of this study were selected from the JCOG9912 which intended to confirm the superiority of irinotecan plus cisplatin (IP) and the non-inferiority of S-1 to5-FU for patients with AGC. Of all enrolled patients in JCOG9912, those who had target lesions and whose complete data were available were analyzed with multivariate analysis using Cox proportional hazard model. Results: 492 out of the 703 pts of JCOG9912 were analyzed, who received either 5-FU (n=163), IP (n=164) or S-1(n=165). The median PFS was 3.7 months for all the subjects, and 2.2 months for 5-FU, 4.9 months for IP and 3.8 months for S-1. Multivariate analysis in all 492 analyzed patients demonstrated seven independent prognostic factors for PFS (Table). Prognostic factors in each treatment were; sex (HR 1.66, 95%CI 1.11-2.49), PS (1.51, 1.04-2.18), Ca (0.39, 0.17-0.86), GPT (2.46, 1.30-4.66) and LDH (1.67, 1.16-2.48) in 5-FU, sex (1.77, 1.10-2.86) in IP, and Na (2.00, 1.01-3.99) and creatinine clearance (0.37, 0.15-0.93) in S-1. Conclusions: There were no common prognostic factors among the three treatment regimens. Prognostic factors for PFS may be different by treatment regimen, although further investigations with larger sample size are needed. [Table: see text]
Frequency of non-polypotic familiar colon cancer in Uruguayan patients with colorectal cancer
Authors: A. Della Valle, C. Sarroca, R. Fresco
Journal: Journal of Clinical Oncology (2004)

3730 Background: Non-polypotic familiar colon cancer (HNPCC) is an autosomical dominant transmitted syndrome with high aggregation of colorectal cancer (CRC), frequently associated with other solid tumors. Few studies have investigated the frequency of HNPCC in patients (pts.) having undergone surgery for CRC. These have shown a marked geographic variation, ranging from 0.5% to 13%. The aim of this study is to estimate the frequency of HNPCC in the Uruguayan population. Methods: We performed a retrospective analysis of a cohort of non-selected pts. operated for CRC in the Hospital Central de las Fuerzas Armadas (Montevideo, Uruguay) between January 1987 and December 2002. Cases were classified in 3 groups according to personal and family history: 1) those fulfilling Amsterdam criteria, classified as HNPCC; 2) those not fulfilling Amsterdam criteria but considered as a population of increased risk for cancer (PIR); and 3) those classified as sporadic CRC. Genetic analysis to detect mutations in hMLH1 and hMSH2 genes were performed in pts. included in group 1 (in vitro transcription and translation of RNA followed by sequencing of genomic DNA in cases showing aberrant products). Results: 461 pts. were included (251 males, 210 females, median age 66 years). HNPCC group represented 2.6% of pts., PIR 5.6%, and sporadic cases 91.8%. Grouping together HNPCC and PIR, 8.2% of pts. showed an increased family risk for CRC. Mutations in hMLH1 and hMSH2 were found in 3/12 pts. (25%) classified as HNPCC (2 in hMLH1, 1 in hMSH2). Additionally, 5-year survival rates were 91.7% for HNPCC, 65.4% for PIR and 59.6% for sporadic cases (p<0.05, log-rank test). Conclusions: The proportion of all surgical pts. with CRC in our study that fulfilled Amsterdam criteria agrees with the one observed by other authors. However, the percentage of HNPCC cases with identified mutations is lower that the reported in other studies (25% vs. 70%). This may reflect a different genetic profile in the Uruguayan population. The favorable outcome observed in HNPCC pts. demands that we properly identify these group, since our management strategy may vary. No significant financial relationships to disclose.
N997D: Pilot trial of CPT11 during RT followed by CPT11 and BCNU in newly diagnosed glioblastoma (GBM) patients: A North Central Cancer Group (NCCTG) study
Authors: K. A. Jaeckle, K. V. Ballman, P. Schomberg, J. Uhm, B. Schiethauer, C. Giannini, S. Felton, P. Brown, B. C. Jan
Journal: Journal of Clinical Oncology (2005)

1514 Background: Prior studies in gliomas have shown additive therapeutic effects of CPT11 and BCNU, and radiosensitizing effect of CPT11. We evaluated the toxicity of RT and concurrent CPT11, followed post-RT by BCNU plus CPT11 in patients (pts) with newly diagnosed GBM. Methods: All pts had GBM (WHO Grade 4) by central review. Those not receiving anticonvulsants (non-EIAC, Arm A) received RT with concomitant CPT11 (125mg/M2/wk X 4, cycle 1), followed post-RT by BCNU (100mg/M2 q 6 wk) + CPT11 (125 mg/M2/wk X 4, q 6 wks, cycles 2–5). Pts on EIAC (Arm B) received CPT11 (400mg/M2/wk X 4, cycle 1) during RT, then post-RT BCNU (100mg/M2 q 6 wk) + CPT11 (400mg/M2/wk q 6 wks, cycles 2–5). Dose de-escalations (but no escalations) were allowed. Toxicity was graded by CTCAE v 3.0. Results: All pts received treatment, and ≥ 3 cycles were administered in 7/16 non-EIAC and 6/12 EIAC pts. In Arm A (non-EIAC, 48 total cycles), the most frequent treatment-related grade ≥ 3 toxicities included neutropenia (25%), leukopenia (17%), and diarrhea (13%). Although cycle 1 during RT in Arm A was tolerated, unacceptable toxicity (hematologic) during cycles 2–5 required amending the protocol to reduce the CPT11 dose to 75 mg/M2/wk X 4 (cycles 2–5). In Arm A, there were a total of 40 grade 3, five grade 4, and one grade 5 (perforated ulcer) toxicities; 4 patients went off study due to toxicity. In Arm B (EIAC, 45 cycles), the most common treatment-related grade ≥ 3 toxicities included diarrhea (4%) and neutropenia (4%), with nine total grade 3 events, but no grade 4 or 5 events. Dose reductions were required in 10/12 EIAC pts, but no pt went off study due to toxicity. Three of 16 non-EIAC, and 4/12 EIAC pts completed study per protocol. Conclusions: Protocol-specific acceptable toxicity parameters were met for non-EIAC pts, using CPT11 (125mg/M2/wk X 4, cycle 1) during RT, followed post-RT by BCNU (100mg/M2 q 6 wk) + CPT11 (75 mg/M2/wk X 4, q 6 wks, cycles 2–5); and, for EIAC pts, using CPT11 400 mg/M2/wk X 4 during RT, followed post-RT by BCNU 100mg/M2 q 6 wk + CPT11 400 mg/M2/wk X 4 (cycles 2–5) q 6 wks. An expanded NCCTG Phase II efficacy study is in progress, utilizing these dose schedules. No significant financial relationships to disclose.