tbuckley/cabot-search huggingface dataset:
Evaluation of PET scan in small cell lung cancer
Authors: M. D. Craig, J. S. Rogers, N. Gupta
Journal: Journal of Clinical Oncology (2004)

7214 Background: Small cell lung cancer remains a major health concern. Prognosis, survival, and treatment options correlate with stage at diagnosis. We hypothesize PET scanning may have a role in the staging procedure of patients with small cell lung cancer. Methods: A retrospective chart review of all patients between 1998–2003 diagnosed with small cell lung cancer was performed. Those who received a PET scan as part of the initial evaluation were reviewed and comparison was made against CT scanning and MRI imaging. Follow-up imaging and clinical outcome were used to evaluate any areas of disagreement between imaging. Results: A total of 116 new patients with small cell lung cancer were reviewed. 44 patients (44/116) received a PET scan. Sensitivity of PET imaging was 100%. Agreement between PET imaging and standard imaging for limited and extensive stage disease was 80% (35/44). Five patients were diagnosed with limited stage disease instead of extensive disease based on PET results. CT scan suggested adrenal metastasis in 4 patients, and opposite lung lesions in another, but the PET scan was not hypermetabolic. All but one (who was lost to follow-up) were treated as limited stage disease with concurrent radiation and chemotherapy. The four who remain have had survival and response suggestive of limited stage disease (alive at 6 months, 18 months, 32 months, and 3 years). Two patients were increased from limited to extensive stage by PET scan results, one survived 9 months and the other is 5 months into therapy. One patient had a biopsy proven false positive PET finding of lymphoid hyperplasia in the nasopharynx that would have increased the stage to extensive. PET scan missed diffuse liver metastases in one patient (false negative), who was staged with limited disease. PET scan was insensitive to detect brain metastasis (40% sensitive), although this did not change the patients' stage. Conclusions: As in non-small cell lung cancer, changes in the adrenal glands seen on CT scan may be difficult to interpret. These results suggest PET can clarify incidental findings of CT scan imaging. A PET scan may be helpful to insure patients with small cell lung cancer are accurately staged and offered appropriate treatment. No significant financial relationships to disclose.
<i>EGFR</i> mutation and copy number, EGFR protein expression and <i>KRAS</i> mutation as predictors of outcome with erlotinib in bronchioloalveolar cell carcinoma (BAC): Results of a prospective phase II trial
Authors: V. A. Miller, M. Zakowski, G. J. Riely, W. Pao, M. Ladanyi, A. S. Tsao, A. Sandler, R. Herbst, M. G. Kris, D. H. Johnson
Journal: Journal of Clinical Oncology (2006)

7003 Background: Erlotinib produces dramatic responses in a subset of patients with NSCLC. Mutations in the EGFR tyrosine kinase domain, EGFR amplification or polysomy and EGFR overexpression on immunohistochemistry have all been associated with sensitivity and benefit; pts with KRAS mutation are commonly resistant to this agent. These correlative studies were prospectively undertaken to characterize the ability of these markers to predict response rate, time to progression and survival in pts with BAC treated with the EGFR-TKI, erlotinib. Methods: One hundred and two patients received erlotinib as part of a phase II trial in BAC (Kris, Proc ASCO 2005); 84 had one or more correlative studies completed. Analysis of EGFR exons 19 and 21 (n=82) (Pao, et al PNAS 2004), EGFR IHC (n=62) (DAKO) was performed and EGFR copy number was determined by chromogenic in situ hybridization (CISH) (n=74) (Zymed); detection of ≥ 4 signals per cell was considered evidence of amplified copy number. KRAS exon 2 (n=79) testing was performed by direct sequencing. Fisher’s exact test was used to study the association of each feature in pts with partial response or no partial response. Time to progression and survival were analyzed with log-rank test. Results: See table below. Conclusions: 1) EGFR exon 19 or 21 mutation is a powerful predictor of response and TTP but not OS in pts with BAC treated with erlotinib. 2) CISH ≥4 is associated with response and improved TTP but not OS. 3) Patients with both EGFR mutation and amplification fare well supporting the concept of “oncogene addiction”; erlotinib should be considered as initial therapy in this population. 4) EGFR amplification without mutation is uncommon. 5) There is no clear utility of EGFR IHC in clinical decision making. 6) The presence of KRAS mutation predicts resistance to erlotinib. Supported, in part, by Genentech. [Table: see text] [Table: see text]
HDL: A Novel Target or Marker for Cardiovascular Risk
Authors: H. Bryan Brewer
Journal: Circulation (2012)

HDL has become a potential therapeutic target to reduce the residual cardiovascular (CV) risk in statin treated patients. Over the last several years it has been established that HDL is heterogeneous and contains several discrete lipoproteins particles with different lipid compositions and separate anti-atherosclerotic functions. These functions include increasing ABCA1 and ABCG1 mediated cholesterol efflux from cholesterol loaded macrophages, and decreasing inflammation, LDL oxidation, and thrombosis. Epidemiological data, animal models and initial imaging and pilot trials have shown promise, however proof that increasing HDL-C levels will reduce CV clinical events independent of changes in plasma levels of LDL-C and triglycerides has been elusive. HDL cholesterol is now recognized as an ineffective biomarker for accessing HDL mediated changes in CV events since HDL-C is a static measurement with no information on the dynamic flux through the HDL-C pathway, the variability of the cholesterol content in the different HDL particles, and the recognition that &gt;90% of HDL-C is derived from the liver and intestine with &lt;2% coming from the cholesterol loaded peripheral vascular tissue macrophages. The focus of the elucidation of the role of HDL in CV disease has now shifted from the quantitation of HDL-C to a systematic analysis of HDL particle number, HDL proteome, HDL lipidome and functions of the individual HDL particles. Low HDL due to genetic mutations in apoA-I, the structural protein of HDL, is causative in the pathway of increased vascular disease. In contrast HDL can also be a marker of a generalized dyslipoproteinemia as is present in the metabolic syndrome and diabetes Thus; HDL can be both a player in the development of CV disease as well as a marker of CV disease risk. Novel therapeutic agents that may substantiate the potential importance of HDL as a therapeutic target under development include niacin/laropiprant, CETP inhibitors and HDL infusions in acute coronary syndrome patients. The outcome of clinical trials with these new therapeutic modalities will provide definitive data on the future of HDL as an importance approach to decreasing CV events in high risk patients with cardiovascular disease.
Yttrium-90 microsphere treatment for liver dominant hepatic metastases from lung cancer
Authors: R. Murthy, Y. Oh, A. Tam, S. Gupta, D. C. Madoff, B. Glisson
Journal: Journal of Clinical Oncology (2006)

17122 Background: Hepatic metastases are a common manifestation of primary lung malignancies; the primary and other extrahepatic sites are often less responsive to systemic therapy. A new method of regional therapy for hepatic metastases, called SIR-Spheres, a 32μ resin sphere incorporating a pure Beta emitter, Yttrium - 90, has advantages to older forms of regional hepatic therapy, used to treat colorectal liver metastases. The effectiveness and relatively response durability suggests a favorable alternative to chemotherapy for patients with liver-dominant metastatic lung cancers. We report our experience using SIR-Spheres in this setting. Methods: 6 patients (2 well differentiated carcinoid, 2 well &amp; 1 poorly differentiated adenocarcinoma, 1 poorly differentiated small cell carcinoma) with unresectable hepatic metastases were treated with 8 infusions of SIR-Spheres after failing systemic chemotherapy, radiofrequency ablation or arterial embolization were included in the study. SIR-Spheres were administered as 2nd-6th line therapy. Median interval from diagnosis to SIR-Spheres treatment was 20.5 months (6–51 m). Results: Abdominal visceral arteriography demonstrated vasculature conducive for SIR-Spheres delivery in all patients. The median dose of 36.1 mCi (12.9–54 mCi) was delivered. SPECT - CT fusion Bremsstrahlung scans post therapy confirmed preferential deposition of SIR-Spheres within metastases. Responses to therapy included a decrease in the size of the hepatic metastases in one patient and stable disease in two patients. One patient had a mixed response and two patients had progression of disease. One Gr. III and one Gr. IV hepatic toxicity occurred. All patients experienced transient Gr. 1 or 2 fatigue. Time to progression of liver disease ranged from 3 to 9 months. Conclusion: SIR-Spheres is a feasible alternative to systemic therapy for patients with liver dominant metastases from lung cancers. Although serious hepatotoxicity was noted in patients with advanced liver metastases, the treatment was tolerated with only reversible fatigue in the majority of patients. When the treatment was effective, the duration of local disease control after one treatment equaled or exceeded what would be expected with chemotherapy. [Table: see text]
Improving the care of acute lymphocytic leukemia (ALL) at a large county hospital.
Authors: Meghan Sri Karuturi, Jeffrey Thomas Yorio, Annie Titus, Stephenie Jeanette Pharr, Alyssa G. Rieber
Journal: Journal of Clinical Oncology (2013)

213 Background: The treatment of ALL involves complex chemotherapy regimens that are difficult to deliver to underserved populations. Lyndon B. Johnson General Hospital (LBJGH) provides care to uninsured and underinsured patients in Harris County, the third largest county in the United States. Our goal is to achieve 80% adherence to National Comprehensive Cancer Network guidelines in the care of newly diagnosed ALL patients at LBJGH. Methods: The charts of 14 patients with newly diagnosed ALL were reviewed. Demographics, initial work-up (e.g., bone marrow biopsy and aspirate), type of treatment, adherence to scheduled treatment, use of supportive medications, outpatient follow-up, stem cell transplant referral and quality of provider documentation were collected. Areas of potential improvement were then identified using provider focus groups and Ishikowa Diagram. The project was approved by the MD Anderson Quality Improvement Assessment Board. Results: 12/14 patients were evaluable, having received their full course of care at LBJGH. The median age was 35, 9/12 (75%) were female and 9/12 (75%) were Hispanic. 6/11 (55%) cases expressed CD20 (CD20+) and 3/11 (27%) were Philadelphia chromosome positive (Ph+). All 12 patients received induction and consolidation therapy with the HyperCVAD regimen (cyclophosphamide/vincristine/doxorubicin/dexamethasone alternating with high-dose methotrexate/cytarabine). Bone marrow biopsy at time of diagnosis, use of a tyrosine kinase inhibitor for Ph+ ALL, and use of supportive medications occurred &gt;80% of the time. Administration of outpatient chemotherapy, use of rituximab for CD20+ ALL, outpatient lab follow-up, intrathecal chemotherapy and appropriate referral for allogeneic transplant occurred 50-80% of the time. Provider documentation was appropriate &lt;50% of the time. Conclusions: Based on these findings, we established a standard algorithm of care for ALL patients at LBJGH, enhanced provider education through the design and distribution of teaching tools, created a checklist to facilitate handoffs between providers and established expectations for documentation. In the future, we would also like to add a patient navigator to further improve coordination of care.
Open labeled phase II observation study of gemcitabine plus cisplatin plus trastuzumab (GCT) in metastatic breast cancer patients with prior anthracyclines and taxanes exposures: Preliminary results
Authors: M. Demiray, T. Evrensel, O. Kanat, E. Kurt, M. Arslan, S. Gokgoz, S. Tolunay, O. Manavoglu
Journal: Journal of Clinical Oncology (2006)

10720 Background: Trastuzumab provides significant clinical benefit in HER2 positive metastatic breast cancer. Gemcitabine and cisplatin (GC) combination is attractive treatment options for anthracyclines-taxanes-pretreated metastatic breast cancer. These agents demonstrated synergistic activity and minimal overlapping toxicity. On the other hand, additional synergistic activity was observed with trastuzumab and GC. Methods: Histologically confirmed metastatic breast cancer patients with FISH positive tumors (HER2/choromosome 17 ≥2) were eligible if they were at least one measurable disease; ≥18 and ≤70 years; life expectancy &gt;3 month; ECOG 0–2; prior anthracyclines and taxanes treatment but no prior trastuzumab therapy; adequate marrow, renal and hepatic function. Treatment schedule was as follows: Gemcitabine 1000 mg/m 2 and cisplatin 30 mg/m 2 d1, 8 every 3 weeks conjunction with trastuzumab 4 mg/kg d1 and 2 mg/kg for weekly. Chemotherapy was scheduled for up to eight cycles. Treatment was discontinued in case of progression or prohibitive toxicity. After progression additional regimen was administered with trastuzumab. Results: Eleven women were enrolled. All patients were eligible for toxicity and efficacy evaluations. Median age was 48 (range 28–64) years and median ECOG performance status was 0. Ten patients (90.9%) had visceral metastases, most commonly located in the liver (8 pts) and lung (4 pts). Estrogen receptor positivity was 63.6% (7 pts). A total of 80 cycles were delivered with a median of 8 cycles. Objective response rate was 54.5% (6 pts) with 27.2% (3 pts) complete response and 27.2% (3 pts) partial response. Stabile disease was achieved 36.3% (4 pts). Median time to progression and overall survival were 8 (95% CI: 3.97–12.02) and 18 months (95% CI: 15.89–20.10) respectively. Grade 3–4 toxicity was observed in 18.1% (2 pts). Treatment of one patient was discontinued due to grade 4 thrombocytopenia. Dose reductions due to myelotoxicity were performed in 1 (9.0%) patients. Conclusions: Our preliminary data shows that gemcitabine and cisplatin and trastuzumab combination regimen is effective and has manageable toxicity profile. No significant financial relationships to disclose.
Quality of life (QOL) assessment in patients with relapsed/refractory multiple myeloma (MM) treated with thalidomide (T) plus celecoxib (Cxb)
Authors: L. R. Mileshkin, A. Roberts, V. Ganju, C. Underhill, J. Catalano, R. Bell, K. Lillie, A. D. Milner, J. B. Zeldis, H. M. Prince
Journal: Journal of Clinical Oncology (2005)

8233 Background: Thalidomide (T) has established efficacy in the treatment (Rx) of MM. The side-effect profile is known but effects on QOL are not well studied. Pre-clinical data suggests Cox-2 inhibition may be synergistic with T. We examined the addition of celecoxib (Cxb) to T in MM, and explored the effects of Rx on QOL. Methods: Prospective multi-centre Phase-II trial in 66 pts with relapsed/refractory MM using T up to 800 mg/day + Cxb (400mg bid). Objectives were to determine toxicity, response rate (RR), progression-free survival (PFS), overall survival (OS), and perform an exploratory analysis of QOL. EORTC QLQ-C30 QOL questionnaires were administered prior to Rx, q4/52 during, and once after Rx. Baseline scores were compared with the best on-Rx score using Fisher’s exact test. Changes on Rx were also examined as the mean change score for each item. Effect of baseline QOL on survival was examined. Results: Overall RR (CR+PR) was 42% with 48% stable disease. At 20 months (mo) median follow-up, the actuarial median PFS and OS were 6.8 and 21.4 mo. 55 pts (83%) completed ≥ 1 QOL assessment (Ax). 50 completed a pre and ≥ 1 later Ax (median = 7, range: 1–26). Fatigue, insomnia and pain were the worst symptoms at baseline. Median baseline global health status (GHS) was markedly impaired at 58 (range: 8 - 100). GHS declined at some point post Rx in 80%, mainly due to worsening functional scales, particularly physical function. In CR+PR pts, GHS declined from baseline to first QOL Ax post CR/PR in 15 (54%), improved in 8 (29%), and did not change in 4 (14%). Responders (n=28) vs non-responders (n=22) were more likely to show improvement in their best on-Rx GHS score cf baseline (61% vs 27%: p=0.024). On Rx, mean symptom scores for insomnia and diarrhoea significantly improved (p<0.05). Fatigue, dyspnoea and constipation worsened, consistent with Rx toxicities. In responders, trends to improvement were seen in pain, appetite, nausea & vomiting. A trend was seen for lower (< 58) baseline GHS (5.6 vs 12.7 mo: p=0.052) and social score (6.5 vs 13.8 mo: p=0.076) to predict inferior PFS. Conclusions: Changes in QOL with T plus Cxb are consistent with Rx toxicities. Some responding pts showed evidence of improved QOL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chief Medical Officer of Celgene
Chromosome Conditions of Hypodiploid Moloney Virus-Induced Mouse Leukemia, Its Transplantability and Inductivity
Authors: N Ida, Y Ohba, A Fukuhara, M Kohno
Journal: JNCI Journal of the National Cancer Institute (1968)

Moloney virus-induced leukemia of BALB/c mice became transplantable in adult C3H mice after 2 successive transplant generations in suckling mice of the same strain. Cells with 39 chromosomes served as a stemline for the growth of the transplantable leukemias in the C3H mice. Thirty-nine mice were examined from the third through the sixteenth transplant generation, and a high percentage of the cells derived from their thymuses, spleens, and mesenteric lymph nodes, and livers showed predominantly 39 acrocentric chromosomes. Karyotype analyses revealed a depletion of 1 chromosome from the 40-chromosome complement of the control tissues. In 14 isologous whole-cell transplantations in C3H mice, 77% of 203 recipient hosts developed leukemias. Homologous transplantations of these leukemic cells in adult mice of the BALB/c, DBA, Rlll, and Swiss strains were negative. Only newborn Swiss mice developed the disease, and cells from their leukemic tissues showed 39 chromosomes. Evidence was presented that the transplantable leukemic cells contained virus; these cell-free extracts from the leukemic tissues of BALB/c mice of the second transplant generation induced the disease in Swiss mice inoculated at birth. The incidence of tumor growth was 92% (12/13), and the latent period, ranging from 9–30 weeks, averaged 16 weeks. In spleen cells of the cell-free, extract-induced leukemias of Swiss mice, the modal number of chromosomes was 40–41.
A randomized, open-label, multicenter phase II study of bortezomib with fludarabine in comparison to rituximab with fludarabine in follicular lymphoma subjects previously treated with rituximab.
Authors: P. Theocharous, O. Shpilberg, Y. A. Elsayed
Journal: Journal of Clinical Oncology (2010)

TPS303 Background: Rituximab is routinely administered in several consecutive lines of therapy for follicular lymphoma. Although the frequency and significance of emerging rituximab resistance is not being prospectively quantified, a major question remains as to the therapeutic value of continuing rituximab beyond ≥2 lines of therapy. It is clear that the response rate decreases with subsequent treatment with rituximab. This study intends to compare the response rate of continued rituximab in combination with fludarabine (in patients heavily pretreated with rituximab), versus a new regimen of bortezomib (VELCADE) in combination with fludarabine. In vitro, the combination of bortezomib and fludarabine resulted in increased cytotoxicity associated with enhanced apoptosis. A phase I dose-escalation study combining fludarabine and bortezomib was previously reported by Snell et al (2006). The combination was found to be safe and tolerable, and several patients in this heavily pretreated cohort achieved CR/CRu and PRs. Methods: Eligible subjects must have received at least 12 prior doses of rituximab (and be fludarabine naïve), and have documented relapse or progression. One hundred ten subjects are expected to participate and will be randomized in a 1:1 ratio between the 2 treatment arms. It is expected that there will be 17 months of accrual. There are currently 7 countries and 34 sites participating, with the first patient now randomized. Subjects randomized to Arm A will receive bortezomib 1.6 mg/m2 i.v. on Days 1, 8, 15, 22 and fludarabine 40 mg/m2/day orally on Days 1 to 5. Subjects randomized to Arm B will receive fludarabine 40 mg/m2/day on Days 1 to 5 and rituximab 375 mg/m2 on Day 1 of every cycle. Treatment cycles will be repeated every 35 days for a maximum of 8 cycles. The primary efficacy endpoint is complete response rate. Disease response and progression will be evaluated according to modified IWRC criteria by radiographic imaging. The CT scans and other radiographic evaluations will be centrally assessed by an Independent Review Committee (IRC) to confirm disease response for the purpose of the efficacy analyses. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson Johnson & Johnson Johnson & Johnson Johnson & Johnson Johnson & Johnson
Renal response to blood pressure elevation in normal and glomerulonephritic rats.
Authors: F B Gabbai, L De Nicola, O W Peterson, S Obagi, S C Thomson, B J Tucker, J A Keiser, C B Wilson, R C Blantz
Journal: Journal of the American Society of Nephrology (1996)

Concurrent renal disease appears to augment greatly the adverse effects of systemic hypertension on renal function and the development of glomerulosclerosis. This study examined the effects of systemic hypertension and treatment of hypertension in groups of normal non-nephritic rats and rats submitted to 16 wk of glomerulonephritis induced by the administration of anti-glomerular basement membrane antibody. Hypertension was produced by application of a clip to the right renal artery and blood pressure was treated with an angiotensin-converting enzyme (ACE) inhibitor, quinapril. Glomerulosclerosis of two types developed: a diffuse type that is characteristic of anti-glomerular basement membrane glomerulonephritis, and a focal segmental glomerulosclerosis that is characteristic of systemic hypertension. Glomerulonephritis significantly reduced the capacity of ACE inhibitors to decrease systolic blood pressure in awake animals. In addition, glomerulonephritis produced significant effects on plasma angiotensin II concentrations, whereby ACE inhibition no longer lowered plasma angiotensin II levels and in fact produced an increase. Glomerular capillary hydrostatic pressure and hydrostatic pressure gradient correlated with systolic blood pressure and with the incidence of focal glomerulosclerosis in non-nephritic rats. However, in glomerulonephritis, systolic blood pressure no longer correlated with glomerular capillary pressure, and glomerular capillary pressure no longer correlated with the development of glomerulosclerosis, although systolic blood pressure did correlate with the degree of focal segmental glomerulosclerosis. Concurrent glomerulonephritis strongly conditions the effects of superimposed hypertension by altering the relationship between systemic blood pressure and glomerular capillary hydrostatic pressure and by decreasing the response of hypertension to therapy.
The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score: Design and validation.
Authors: M. Extermann, I. Boler, R. Reich, G. H. Lyman, R. H. Brown, J. DeFelice, R. M. Levine, E. T. Lubiner, P. Reyes, F. J. Schreiber
Journal: Journal of Clinical Oncology (2010)

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