tbuckley/cabot-search huggingface dataset:
Treatment-related toxicities in patients with squamous cell carcinoma of the head and neck (SCCHN)
Authors: M. Ulcickas Yood, P. Feng Wang, S. Hensley Alford, S. Oliveria, K. Wells, S. Phillips, H. Ali, C. D. O’Malley
Journal: Journal of Clinical Oncology (2009)

e17041 Background: Although treatment effects and toxicities have been reported from randomized clinical trials of patients with squamous cell carcinoma of the head and neck (SCCHN), little information is available from real-world clinical practice where heterogeneous treatment patterns and patient populations may lead to different estimates than those observed in clinical trials. Methods: Using a population-based tumor registry at a large, Midwestern integrated health system, we identified all cases of stage III or IV SCCHN diagnosed 2000–2006. The incidence/severity of acute and late toxicities associated with SCCHN treatment was obtained from detailed medical record review of health system encounters, including physician notes. Grading of toxicities (using CTCAE3 criteria), distinction between acute and late toxicity, and analyses by treatment are ongoing. The incidence and severity of toxicities will be presented by treatment regimen, tumor location and tumor stage. We presented here an interim analysis. Results: Among the target population of 194 patients that will ultimately be included in this study, 137 medical record reviews have been completed to date. The percentages of patients with toxicities, including 95% confidence intervals are presented in the table , below. Conclusions: Toxicity in patients with advanced SCCHN is common. Data from clinical practice quantifying the incidence are lacking, these data from an observational real-world study provide important baseline information on the incidence of toxicities in patients with advanced SCCHN and also call for safer effective treatment for SCCHN. [Table: see text] [Table: see text]
Assessing 12 or more lymph nodes increases the proportion of stage III disease in colorectal cancer (CRC): Evidence from the Surveillance, Epidemiology and End Results (SEER) cancer registry
Authors: Q. Cai, P. A. Sullivan, Y. Yeh, M. Russell
Journal: Journal of Clinical Oncology (2007)

4016 Background: NCCN guidelines (2001) recommend assessment of ≥12 lymph nodes (LN) to improve accuracy of CRC staging. The impact of aggressive LN sampling on CRC staging has not been explored rigorously to date. This study examines variations in CRC staging by number of LN assessed. Methods: 299,242 patients from SEER aged ≥18 years diagnosed with CRC during 1990–2003 were included. Multivariate logistic regression was used to assess the association between sampling ≥12 LN (vs. &lt;12) and staging, adjusting for age, sex, race, region, tumor size and grade, and year of SEER entry. Results: Patients who had ≥12 LN sampled were 1.3 times more likely to be diagnosed with stage III than stage II CRC [95% CI 1.28–1.34, p&lt; .01]. The odds of being staged as III versus II increased over time [OR=1.01, 95% CI 1.01–1.02, p&lt; .01]. However, the introduction of the NCCN guidelines was not associated with nodal sampling. Conclusion: The proportion of CRC patients who received appropriate sampling with most recent data available is unacceptably low. The significant increase in stage III patients who had ≥12 LN sampled may increase the proportion of patients considered for aggressive treatments. Because accuracy of staging is improved with nodal sampling, clinicians will be better positioned to treat patients if LN sampling recommendations are followed. [Table: see text] [Table: see text]
Breast cancer and hormonal supplements in postmenopausal women
Authors: D. A Viniker
Journal: BMJ (1995)

emergency department a short time after a relatively trivial injury.Even at this stage many of the signs described in the article are present.These include evidence of neuropathic pain, allodynia, and hyperalgesia to all stimuli.These children often undergo extensive radiology as the pain is out of all proportion to the appearance on clinical and x ray examination.Many of the children are overtreated with plaster of Paris casts or other immobilisation splints, often by inexperienced junior staff.This syndrome has been well recognised in accident and emergency care and has been named the "10-15 syndrome."2I believe that, when these children present, the last thing that one should do is immobilise them in any form of splint, including tubular support bandages.These children must be encouraged to move their limbs and ideally should be referred for physiotherapy as soon as possible.Unfortunately, physiotherapy services-and particularly physiotherapists with paediatric skill-are lacking in many accident and emergency departments.Reflex sympathetic dystrophy in children is preventable.A greater awareness of the management of soft tissue injuries in children is needed.
A phase II study of patupilone in patients with metastatic hormone refractory prostate cancer (HRPC) who have progressed after docetaxel
Authors: K. N. Chi, E. K. Beardsley, P. M. Venner, B. J. Eigl, S. J. Hotte, Y. Ko, F. Saad, E. Winquist
Journal: Journal of Clinical Oncology (2008)

5166 Background: Reliably effective chemotherapy for patients (pts) with HRPC who have progressed after docetaxel remains to be identified. Patupilone is an epothilone with broad spectrum pre-clinical activity including in taxane resistant models. Methods: Multi-center, 2-stage design. Pts with metastatic HRPC with progressive disease documented within 6 months of or while receiving docetaxel were eligible. Patupilone was initially given 10 mg/m2 IV every 3 weeks. PSA response (≥50% decline from baseline) was the primary endpoint. Forty-three pts were to be accrued to stage 1 (H0: response rate <15%, H1: PSA response rate > 25%) and continue to stage 2 if > 6 responses seen. Secondary measures of outcome included progression free and overall survival, measurable disease response, and serial pain and analgesics scores. Results: To date, 33 pts have been enrolled with data available on 19 receiving a median of 4 cycles (range 1–7). Baseline characteristics (range): median age 66 (53–78), PSA 248 (17–1170), hemoglobin 114 (94–149), median time from last docetaxel 4.8 months (1.4–15.0), number of prior chemotherapy regimens 1:2:3+ in 5:10:4 pts, ECOG PS 0:1:2 in 3:12:4 pts, disease in bone, lymph nodes and viscera in 18, 13 and 4 pts respectively. Four first cycle gastrointestinal serious adverse events occurred in the first 6 pts (diarrhea and vomiting) and the dose of patupilone was lowered to 8 mg/m2 for subsequent patients with better tolerance. Grade 3/4 related adverse events at the 8 mg/m2 dose (13 pts): fatigue (1 pt), diarrhea (2 pts) and abdominal pain (1 pt). There have been no grade 3/4 hematologic adverse events. Thus far, PSA declines of ≥30% and ≥50% have occurred in 12/19 (63%) and 8/19 (42%) pts with a confirmed PSA response occurring in 5 pts (26%). Three pts (16%) have had PSA progression as best response. Of 8 pts with evaluable measurable disease, 7 (88%) have had stable disease and 1 pt has had progression as best response. Conclusions: In this population, patupilone 8 mg/m2 every 3 weeks is well tolerated. Initial results show encouraging PSA responses in pts with docetaxel resistant/refractory disease and accrual continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
11C-Methionine PET to predict survival of glioma patients treated by radiotherapy
Authors: H. Zhang, M. Tian, C. Zhao, X. Ye, H. Zhan
Journal: Journal of Clinical Oncology (2006)

1523 Background: The early prediction of glioma prognosis is very important. Amino acid metabolism of glioma is associated with numerous catabolic processes favoring tumor growth. As an essential amino acid, L-methionine plays a central role in the altered metabolism of cancer cells. The aim of this study was to evaluate the prognostic value of PET imaging using 11C-methionine (MET) in patients with gliomas treated by radiotherapy. Methods: MET PET was prospectively performed in 36 patients with gliomas before and within one month after radiotherapy. Tumor MET uptake was measured with the semiquantitative tumor-to-nontumor ratio (T/N ratio). The MET uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analysis. Results: All tumors were identified in the baseline MET PET study. Patients with a baseline T/N ratio of &lt; 4.0 had a significant better survival than patients with a baseline T/N ratio &gt; 4.0 (2-year survival rate: 50.8% versus 0%, P=0.026). Patients with a post radiotherapy ratio of &lt;4.0 had a better survival than that with a post radiotherapy ratio &gt; 4.0 (2-year survival rate: 50.4% versus 0%, P=0.0012). The univariate analysis showed that both baseline and postradiotherapy T/N ratio were statistically significant predictors of patient survival, and postradiotherapy T/N ratio was a significant independent survival predictor in multivariate analysis. Tumors with larger T/N ratio had a significantly poorer prognosis. Conclusions: Baseline MET uptake was a potential survival indicator and postradiotherapy MET uptake was a significant independent predicator in glioma patients treated by radiotherapy. MET PET is a valuable tool in the predication of survival in patients with gliomas treated by radiotherapy. No significant financial relationships to disclose.
Phase II study of concurrent temozolomide and whole brain radiation therapy in patients with brain metastasis
Authors: S. Dawood, J. Ragaz, S. Navaratnam, C. Mihalcioiu
Journal: Journal of Clinical Oncology (2006)

1540 Background: 30% of patients (pts) with lung cancer develop brain metastases, with XRT representing the conventional treatment of multiple BM. Methods: Pts with lung cancer, Brain metastases (BM) and performance status of 0–2 were enrolled. TMZ (75mg/m 2 day 1–14) given on cycle 1 with XRT (3000cGy in 10 fractions) followed by cycles 2–4 TMZ (200mg/m 2 day 1–5, q 4 weeks). Pts with active systemic disease received also chemotherapy (cisplatin or docetaxel or paclitaxel) during TMZ cycles 2–4. Primary end points: 1. Radiological response of BM assessed after 4–6 weeks from the end of XRT, 2. Treatment related toxicity, 3.Functional Scale score(FSS)(1 best, 3 worst, based on interaction of WHO performance status, score 0–4, with the neurological status score 1–3). FSS was assessed at baseline, and during the follow up visits. Secondary end points: time to progression and overall survival. Results: 22 patients enrolled, 8 pts received TMZ alone and 14 pts had additional chemotherapy. CR was documented in 2 pts, PR in 6 pts, SD in 5 pts, 4 pts progressed on treatment; 5 pts were not evaluable (death from other causes within 2 months from diagnoses). FSS at baseline was available on 19/22 patients. Of those, thirteen, four and two pts had a FSS of 1, 2 and 3, respectively. Fifteen of the 19 pts maintained their FSS at the end of Tx, with 3 pts exhibiting deterioration, and one patient improved. Post treatment FSS remained stable in 16 patients up to one month prior to death. The median survival (22 pts) from the time of diagnosis of BM was 9 months with average TTP of 3.5 months. Except for moderate nausea and vomiting there was no significant toxicity by combining TMZ with XRT. The addition of single agent chemotherapy to TMZ was well tolerated but two patients who required GCSF support. Conclusion: Adding TMZ to XRT for the treatment of BM from in lung cancer patients showed a response in 13 out of 17 assessable patients with a median survival of 9 months which is above the mean 3 to 6 months survival reported in the literature with XRT alone. More importantly, the majority of patients maintained a stable FSS up to one month prior to death suggesting a quality of life benefit during most of their life span. TMZ can be safely administered concomitantly with either XRT or with other single agent chemotherapy. No significant financial relationships to disclose.
Expression of CD74 by AML blasts and cell lines, and enhanced in vitro cytotoxicity of anti-CD74 antibody after interferon-gamma (IFN-γ) treatment.
Authors: J. D. Burton, R. Stein, A. Chandra, S. Chen, N. Mishra, T. Shah, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2010)

6576 Background: CD74 (DR-associated invariant chain) is expressed alone or with DR in a wide range of hematologic cancers and solid tumors. Humanized anti-CD74 mAb, milatuzumab (Immunomedics, Morris Plains, NJ), exhibits direct cytotoxicity for NHL, CLL and MM cell lines, and is in clinical evaluation for therapy of NHL, MM and CLL. Also, CD74 is induced by interferons in multiple cancer cell lines. Here we report an evaluation of CD74 expression and function in AML, and the effect of CD74 upregulation by treatment with IFN-γ on the cytotoxicity of milatuzumab for AML cell lines. Methods: CD74 expression in bone marrow biopsy (BMB) specimens from non-M3 AML patients was evaluated by immunohistochemistry and, for the 3 human AML cell lines, by flow cytometry, with/without permeabilization and with/without IFN-γ (40 and 200 U/mL). These cell lines were also tested in proliferation assays for responses to milatuzumab, with/without IFN-γ. Results: In 13/14 BMB specimens, there was moderate to strong CD74 expression by leukemic blasts, which was mostly intracellular, usually with a perinuclear distribution. Three AML cell lines also showed moderate to strong expression of CD74, which was mostly intracellular. WithoutIFN-g, surface expression of CD74 was present, but IFN-γ treatment of these 3 lines resulted in upregulation of surface CD74 by 69-117%. Much higher levels of intracellular CD74 were observed in all 3 lines, with and without IFN-γ. IFN- γ induced intracellular CD74 in all 3 lines (from 85%-868%). In 2/3 lines, IFN-γ increased milatuzumab-mediated growth inhibition (23.7 to 44.8% and -3.9 to 30.9%, respectively). Conclusions: CD74 is expressed in AML patient specimens and in AML cell lines, with the majority of CD74 expression found intracellularly. Cell surface and cytoplasmic expression of CD74 were upregulated in AML lines after IFN-γ exposure. This increased expression resulted in increased cytotoxicity of the anti-CD74 mAb, milatuzumab, in 2/3 AML lines. Thus, AML is another cancer type where combined IFN-γ and milatuzumab treatment may be useful. Supported in part by NIH grant PO1- CA103985. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immunomedics, Inc. Immunomedics, Inc.
Experience with endometrial carcinoma (EC): A population-based study in Tarragona Province (Spain)
Authors: M. Arenas Prat, A. Rovirosa, S. Sabater, A. Ameijide, I. Henríquez, S. Servitja, I. Cabezas, E. Mur, J. Gumà
Journal: Journal of Clinical Oncology (2009)

e16550 Background: To evaluate outcome, failure patterns, prognostic factors and radiotherapy (RT) toxicity after postoperative RT for EC in Tarragona Province (Spain). Methods: A retrospective population-based review on 232 patients (pts) between 1997 and 2000 from different gynaecological Dpt. and in a single oncologist institution with RT Units. Multivariate analysis of disease-free survival (DFS), overall survival (OS), adjuvant RT, RT toxicity (RTOG), prognostic factors for survival, and the distance in Km to the RT Units. Results: Mean age: 64 years (35–88). Distance to RT Units &gt;70 Km in 15% pts. Median follow-up: 70 months (2–132). FIGO Stage (S): 8.2% IA; 36.2% IB; 19% IC; 7.8% IIA; 6.5% IIB; 7.3% IIIA; 1.3% IIIB; 3.4% IIIC; 2.6% IVA; 2.2 IVB. Pathology: endometrioid 74.5%, papillary 3.9%, serous 3.4%, clear-cell 2.2%, squamous cell 3%, adenosquamous 1.3%, mixed 3.9%. Grade (G): 35.7% G1, 45.3% G2, 19% G3; miometrial invasion: 44.1% &gt;50%, 46% &lt;50%, 9.9% not invasion. Treatment: 1) Surgery in 93.5%, 49.6% lymph nodes dissection. 2) RT in 73.5%: 47% external beam radiotherapy (EBI) and brachytherapy (BT), 9.4% BT alone, 17.1% EBI alone. 3) Chemotherapy in 11.1% and hormonal treatment in 6.9%. 3). Grade 3 and 4 toxicity: 12 (9%) pts, 6 early and 6 late. Relapses: 26/232 (11.6%), S-I: 11/26 (42%), S-II: 1/26 (3.8%), S-III: 5/26 (19.2%), S-IV: 3/26 (11.5%). Metastasis: 28/232 (12.5%). Survivals at 5 years: 1) OS in all stages was 78.8% and 83%, 89.6%, and 76% for SI, SII, and SIII, respectively. 2) DFS was 76.5% for all pts and 82.3%, 86.22%, and 68.24% for SI, SII, and SIII, respectively. Multivariate analysis: significant prognostic factors for poor outcome were age (p &lt; 0.01), lymph nodes dissection (p &lt; 0.001), pathologic subtype (p &lt; 0.001), grade of differentiation (p &lt; 0.001), and deep myometrial invasion (p &lt; 0.005). Conclusions: Survivals, RT toxicity and relapse sites were similar to the other reported series. Predictors of poor outcome were age, lymph nodes dissection, pathology subtype, grade of differentiation, and deep myometrial invasion. Patients of Tarragona Province are in need of a better accessibility to the radiation units. No significant financial relationships to disclose.
Low-dose sequential multi-drug regimens for advanced pancreatic cancer
Authors: H. Bruckner, K. Simon, V. Hrehorovich
Journal: Journal of Clinical Oncology (2008)

15568 Background: GFLIP is based on ex vivo sensitivity tests performed on a series of de novo human pancreas ca.The assays found many drug interactions occuring optimally at low drug concentrations.This regimen provides conditions for 4–8 drug interactions to be applied simultaneously.These interactions can reverse the individual tumors heterogeneous resistance to single drugs and combinations. Methods: Unresectable, metastatic and recurrent pancreas ca pts were treated with a low dose q2wk version of GFLIP using Cisplatin (P) 40 mg/m2, adding Docetaxel (D) 25–35 mg/m2 on failure of GFLIP. Pts with PS 4, atypical ca, cystic apocrine endocrine,Ro status were excluded from analyses.Prior treatment with test drugs was allowed.Cohorts of consecutively accrued pts provided 185 prospectively registered pts for intent to treat analyses of overall survival from first diagnoses of unresectable or metastatic ca,age, stage,prior therapy and sex as prognostic factors.Another analysis omitted all pts surviving 2 yrs or more. Results: Pt distribution was Stage IV 66%, Stage II-III 34%, prior therapy 30 %, age 106 over age 65, 44 over age 75,14 over age 80 and 94 male pts. Median survival was 16.4 mos (14.7- 18.1 mos). 1 yr survival 62%, 2 yr 36% and 3 yr 28%. Age >65, >75 and >80 were not adverse prognostic factors p0.69-.082. Prior treatment was not an adverse prognostic factor; Median survival was 20 mo 2 yr survival 46% and 3 yr 26%. For unresectable locally advanced pts median survival was 21 mo 2 yr 36% and 3 yr 28% Analyses found no significant differences in the distribution of pts characteristics within the subsets of pts. Analyses excluding pts surviving 2 yrs or more found a median survival of 12.5 (9.6–15.5) mos. There were no treatment related deaths nor unanticipated toxicities. Hospitalization for treatment related adverse events followed less than 1% of cycles. The limiting toxicity for GFLIP was<10% late mild-moderate neuro-toxicity and on adding D brief moderate/severe cytopenias and fatigue. Conclusions: Low dose GFLIP followed by GFLIP/D is safe and offers survival benefit for the majority of pts. These findings identified numerous novel research opportunities and challenge the assumption that 'all' pts with unresectable, metastatic and recurrent pancreatic ca have a dismal prognoses. No significant financial relationships to disclose.
Tumor Dormancy and Cell Signaling. V. Regrowth of the BCL1 Tumor After Dormancy Is Established
Authors: Ellen S. Vitetta, Thomas F. Tucker, Emilian Racila, Yi-Wu Huang, Radu Marches, Nancy Lane, Richard H. Scheuermann, Nancy E. Street, Takeshi Watanabe, Jonathan W. Uhr
Journal: Blood (1997)
Randomized double-blind phase II trial comparing gemcitabine (GEM) plus LY293111 vs. GEM plus placebo in advanced adenocarcinoma of the pancreas
Authors: D. A. Richards, H. Oettle, W. L. Vervenne, M. W. Saif, J. P. Thomas, G. Spitzer, C. Visseren-Grul, N. Enas, A. Weitzman
Journal: Journal of Clinical Oncology (2005)

4092
Reduced pressure-volume response to exercise may reflect subclinical myocardial disease in type 2 diabetes
Authors: Christine L. Jellis, Tony Stanton, Carly Jenkins, Thomas H. Marwick
Journal: Circulation (2009)

Background: The predictive value of negative exercise stressechocardiography in subjects with type 2 diabetes (T2DM) isless than in those without T2DM. A reduced end-systolic pressure-volume(SP/ESV) response may identify at risk pts, but the pathophysiologyof this finding has not been determined. We sought to identifyif the abnormal SP/ESV response reflected subclinical diabeticheart disease. Methods: Myocardial dysfunction was sought with resting andexercise echo in 168 apparently healthy T2DM (97 men, 55 ±10 y). Ischemia was excluded by ExE. Conventional data, tissuevelocity, strain and strain rate were acquired at baseline andpeak stress from 6 basal segts in conventional apical views.{Delta}SP/ESV was calculated as [(peak stress systolic blood pressure/peakstress end systolic volume index) -(rest systolic blood pressure/restend systolic volume index)]. Results: Post exercise, 83 subjects showed a {Delta}SP/ESV ≤12 mmHg/ml/m2.These patients were noted to have significantly lower restingdiastolic tissue velocity, lower peak heart rates on exerciseand poorer exercise capacity than those with {Delta}SP/ESV > 12mmHg/ml/m2 [Table]. There were no significant differences betweenthe groups in terms of age, BMI, fasting glucose and systolicstrain or strain rate. In a logistic regression model incorporatingdiastolic tissue velocity, peak heart rate and exercise capacity,all were significant univariate correlates of {Delta}SP/ESV, althoughexercise capacity was the strongest (OR= 0.88, p= 0.02). Conclusions:{Delta}SP/ESV index correlates with resting diastolictissue velocity, peak heart rate and exercise capacity, allof which have known prognostic implications in T2DM. The systolicresponse to stress may provide information analogous to thatprovided by diastolic dysfunction as a marker of subclinicaldisease. © 2009 American Heart Association, Inc.