tbuckley/cabot-search huggingface dataset:
Obesity and tumor characteristics in nodal-positive early-stage breast cancer: Results of the German ADEBAR study.
Authors: U. Andergassen, B. K. Rack, K. Annecke, H. Forstbauer, F. Ruhland, N. Harbeck, H. L. Sommer, K. Friese, W. Janni, M. Kiechle
Journal: Journal of Clinical Oncology (2010)

591 Background: Overweight and obesity are often associated with an increased risk of dying from breast cancer and poor outcomes of therapy. Tumor characteristics are relevant in prognosis and treatment of breast cancer and potentially strongly associated with the body mass index. Methods: The ADEBAR study is a german multicenter phase III trial (n = 1,502) with the goal to evaluate whether breast cancer (BC) pts with > 3 axillary lymph node metastases benefit from a sequential anthracycline-docetaxel regimen (EC - Doc) compared to dose-intensive anthracycline-containing polychemotherapy (FEC). For our evaluation Adebar-Patients were grouped according the WHO global database on body mass index (BMI). Results: There is a strong correlation between BMI, age and menopausal status at clinical diagnosis of breast cancer. Overweight and obese patients in median are 55 years old (range 27-71 year) and already postmenopausal (70%, n = 540). This analysis shows no connection of tumor localisation (unilateral left or right and bilateral breast cancer) and BMI. The tumor size at clinical diagnosis was strongly associated to the patient's weight (< 0.0001). Breast tumors in overweight and obese patients have shown a size > 3 cm in 61 % (n = 479) and a size > 5 cm in 72% (n = 111). In underweight, normal, overweight as well obese patients there was no sign for a significant difference in the number of positive lymph nodes (p = 0.2890), tumor histology (p = 0.9750) and grading (p = 0.9520). Breast Cancer Positivity for ER and PR hormone receptors (ER p = 0.9708, PR p = 0.7785) and the expression of HER2 at the tumor surface (p = 0.1710) were not significant associated to overweight and obesity in study patients. Conclusions: Our analysis shows a highly significant coherence between BMI and tumor size in patients with early stage node positive breast cancer. This finding is in line with current publications which show that overweight and obese woman's have often been diagnosed at a more advanced stage of disease and the treatment in this patients being less effective as a consequence. Weight reduction might be an additional approach on breast cancer therapy and prevention. No significant financial relationships to disclose.
Bacillus Calmette-Guérin therapy alters the progression of superficial bladder cancer.
Authors: H W Herr, V P Laudone, R A Badalament, H F Oettgen, P C Sogani, B D Freedman, M R Melamed, W F Whitmore
Journal: Journal of Clinical Oncology (1988)

The effectiveness of BCG in preventing disease progression in patients with superficial bladder cancer is evaluated. Long-term follow-up of high-risk patients treated in a previously reported randomized control trial of intravesical plus percutaneous BCG shows that progression occurred in 41/43 (95%) of control and 23/43 (53%) of BCG-treated patients. Muscle invasive and/or metastatic disease occurred with equal frequency in the two groups, but was significantly delayed by BCG treatment (P = .012). Cystectomies were required in 18/43 (42%) control and 11/43 (26%) BCG-treated patients. Median time to cystectomy was 8 months for control v 24 months for BCG-treated patients. Based on initial treatment, survival was improved by BCG therapy (P = .032) (median follow-up 6 years). These results suggest that in high-risk patients intravesical BCG can delay disease progression, prolong the period of bladder preservation, and increase overall survival.
Predicting Radiation Esophagitis Using 18F-FDG PET During Chemoradiotherapy for Locally Advanced Non–Small Cell Lung Cancer
Authors: Qurrat Mehmood, Alexander Sun, Nathan Becker, Jane Higgins, Andrea Marshall, Lisa W. Le, Douglass C. Vines, Paula McCloskey, Victoria Ford, Katy Clarke, Mei Yap, Andrea Bezjak, Jean-Pierre Bissonnette
Journal: Journal of Thoracic Oncology (2015)
First-in-human phase I trial of a novel epothilone, KOS-1584
Authors: M. Villalona-Calero, S. Goel, L. Schaaf, B. McCracken, K. Desai, G. Cropp, Y. Zhou, R. G. Johnson, A. L. Hannah, S. Mani
Journal: Journal of Clinical Oncology (2006)

2003 Background: KOS-1584 (9,10-didehydroepothilone D) was discovered as part of a screening program to develop a new generation of epothilones with higher potency and an improved pharmacologic/pharmacokinetic (PK) profile. Epothilones stabilize microtubule polymerization, inducing rapid G2/M arrest and apoptosis. Antitumor activity of KOS-1584 (Chou et al 2003) is approximately 3–12 fold more potent when compared to the structurally related Epothilone D. KOS-1584 demonstrates enhanced tumor tissue penetration and reduced exposure to selected tissues (including CNS). We report the results of the initial dose-escalation trial in which KOS-1584 was administered to pts with advanced solid malignancies. Methods: Define the MTD, toxicity profile and PK of KOS-1584 when administered via 3-hour infusion every 3 weeks. PK was determined after the 1 st and 2 nd infusion. Pharmacodynamics were assessed by serial sampling of PBMCs for microtubule bundle formation. Results: 27 pts (17 F; median age 60; median ECOG PS 1; median prior regimens 3, range 0–7) enrolled in 8 dose levels (between 0.8 - 11.3 mg/m 2 ). To date, no Cycle 1 DLT has been seen. Toxicities (n=24) did not show obvious dose dependency; common toxicity (Grade 1–2) included gastrointestinal (diarrhea, constipation, nausea), fatigue, and ↑AST. Drug-related Grade 3 toxicity: constipation, fatigue and ↑AST (1 each). Drug-related neurotoxicity was not notable. PK/parent (n=25): t½ 17.7 ± 4.6h, Vz 741±330 L and CL 30.2± 16.5 L/h. At 8.5 mg/m 2 Cmax 78 ± 29 ng/mL; AUCtot 631 ± 337 ng*h/mL. Cmax and AUCtot increased linearly with dose over the range tested. Vz is ∼5-fold and t½ 2-fold higher than that of Epothilone D. Dose dependent increases in microtubule bundle formation were observed (8.5 mg/m 2 : 40–50% at end of infusion, compared to 60–65% for ixabepilone and 50–60% for Epothilone D using the same assay at their phase 2 dose). A sigmoidal Emax model described the relationship between plasma concentration and microtubule bundle formation. Activity consisted of 4 pts with extended stable disease (6 cycles leiomyosarcoma and ovarian cancer; 5 cycles colon cancer; a 2nd patient with ovarian cancer is active at 5 cycles). Of these, 3 had document progressive disease prior to study. Conclusions: Accrual is continuing in order to define the optimal dose on the 3-week regimen. [Table: see text]
A phase II study of ixabepilone (BMS 247550) in metastatic renal cell carcinoma
Authors: E. M. Posadas, S. Undevia, A. D. Colevas, E. Manchen, E. E. Vokes, W. M. Stadler
Journal: Journal of Clinical Oncology (2006)

14646 Introduction Ixabepilone (BMS) is a semi-synthetic analog of Epothilone B that functions as a microtubule stabilizer and has anti-cancer effects in several cancers including renal cell carcinoma (RCC) (Zhuang, ASCO 2004). The initial phase II study in RCC utilized a difficult and unconventional dosing schedule (6 mg/m 2 IV days 1–5 every 21 days). Hence, this phase II study in RCC was designed to verify previous observations and to test the safety, feasibility, and activity of administering BMS once every 3 weeks- a schedule used in other malignancies. Methods Treatment consists of BMS 40 mg/m 2 IV on day 1 every 3 weeks. Eligibility included metastatic RCC with clear or non-clear cell histology, no limits on the number of previous treatments, performance status 0–2, and normal organ function. The primary endpoint is the overall response rate by RECIST criteria on radiologic evaluation conducted every 9 weeks. Accrual to the full planned 41 patients (pts) will proceed provided that 2 or more responses are observed in the first 21 pts. Results Ten pts have enrolled (4 clear cell) with 1 declining participation prior to receiving any treatment. Eight pts have completed at least 3 cycles. Grade 3–4 toxicities include lymphopenia-2, diarrhea-2, alopecia-1, and infection-1. Grade 1–2 toxicities seen in more than 50% of pts include alopecia, neuropathy, nausea, fatigue, anemia, and lymphopenia. We have observed 1 unconfirmed partial response of short duration and 1 pt exhibited stable disease with a minor response but discontinued treatment due to excessive neurotoxicity. Three pts continue on treatment. Conclusions Toxicity at 40 mg/m 2 IV on day 1 every 3 weeks is higher than previously reported with the daily x 5 schedule. While lymphopenia, diarrhea, neuropathy, and fatigue are all expected adverse events, the rates of toxicity across all grades is higher than previous reports. VHL mutation analysis is planned and will be correlated with response to therapy. Accrual and pt follow up continue. No significant financial relationships to disclose.
Gastric adenocarcinoma in young patients: A population-based appraisal
Authors: W. B. Al-Refaie, P. W. Pisters, G. J. Chang
Journal: Journal of Clinical Oncology (2007)

4547 Background: While gastric adenocarcinoma is uncommon in young patients, reports of their outcomes remain inconsistent. We performed a population-based study of survival outcomes for gastric cancer in young adults (&lt;45 years). Methods: Patients with gastric adenocarcinoma who underwent cancer directed surgery were identified from the Surveillance Epidemiology and End Results registry from 1991 to 2002. Patient demographics, tumor grade, AJCC stage and use of radiation were categorized by age to &lt;45 years, 45 to 70 years and &gt;70 years old. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis with log rank comparisons. Cox multiple regression analysis was performed to adjust for confounder effects. Results: A total of 20,830 patients were identified: 1,051 (5%) &lt;45 years old [Grp 1], 8,456 (40.6%) 45–70 years old [Grp 2], and 11,323 (54.4%) &gt;70 years old [Grp 3]. Grp 1 was more likely than Grp 2 to have advanced nodal disease (multinomial odds ratio [OR]=1.5 for N2 vs N0, 95% confidence interval [CI] 1.14–2.0, p=0.004; OR=2.0 for N3 vs N0, CI 1.4–3.0, p=0.0002) and more likely to have metastases at presentation (OR 1.5, p&lt;0.00001). Stage-stratified 3-year cancer- specific survival [CSS] was not associated with age at diagnosis except for stage IV disease ( Table ). On Cox regression, young age did not impact survival (OR 0.95, CI 0.87–1.03, p=0.19). However, female gender, Asian race, earlier disease stage, lower grade, cancer- directed surgery and use of radiotherapy were predictors of better outcome (all p=0.003). Conclusions: Although young patients with gastric cancer in this population-based study present with more advanced disease, their stage-stratified cancer specific survival is similar to that of older patients. Stage-dependent, but not age-dependent, treatment should therefore be performed in young patients with gastric cancer. [Table: see text] No significant financial relationships to disclose.
Expression of CD133+ in the brain of a mouse model with a lacZ reporter knock-in at the CD133 locus
Authors: A. Hormigo, S. V. Shmelkov, A. T. Hooper, J. Butler, D. Lyden, S. Rafii
Journal: Journal of Clinical Oncology (2008)

2000 Background: CD133 is a surface antigen considered a marker of normal and cancer stem cells in many tissues, including the brain. According to the current hypothesis CD133+ cells play a central role in the initiation, maintenance and recurrence of malignant gliomas. All previous studies have been based on the detection of this protein using commercially available monoclonal antibodies, which recognize a glycosylated form of CD133 protein. We generated a mouse model with a lacZ reporter knock-in at the CD133 locus to track CD133 positive cells in the brain and to determine the neurogenesis capacity of these cells. Methods: Fresh frozen brain tissue and neurospheres generated from the subventricular zone (SVZ) were used for detection of β-galactosidase activity and co-staining for antibodies for specific cell types (NeuN, neuron-specific nuclear protein; Tuj1, neuronal-specific class III β-tubulin; Olig1 and Olig2, transcription factors involved in oligodendrocyte differentiation and myelin production; NG2, chondroitin sulfate proteoglycan; GFAP, glial fibrillary acid protein) by using either chromogenic assay or immunofluorescence for confocal microscopy. Results: β-galactosidase activity was detected in ependymal epithelium and subcortical structures, although it was also found in cells of the gray matter, including cerebellar granular layer. β-galactosidase was more often seen within the white matter, including corpus callosum, rostral migratory stream, cerebral and cerebellum peduncles, hippocampal fimbria and commissural tracts. No co-staining was seen with NeuN. Neurospheres formed from cultured SVZ expressed β-galactosidase activity. No co-staining with β-galactosidase activity and Tuj1 antibody was seen in differentiated neurospheres, but there was co-staining with anti-Olig1, Olig2, NG2 and GFAP antibodies. Conclusions: Our neurosphere cultures from the SVZ support that stem cells express CD133 surface antigen. When neurosphere cells are differentiated, CD133 is persistently expressed by both cell types of glial lineage, astrocytes and oligodendrocytes, but not by neurons. The widespread finding of CD133+ cells in the adult lacZ reporter mouse brain suggests that other cells types and not only stem cells express CD133 antigen. No significant financial relationships to disclose.
Benchmarking as an instrument in the quality management in the treatment of breast cancer in Germany from 2003 to 2006
Authors: M. K. Graeser, R. Wuerstlein, G. Bonatz, G. Tuschen, U. Nitz, T. Schwenzer, G. Schrappe, M. Rezai, M. Warm
Journal: Journal of Clinical Oncology (2008)

17526 Background: Breast cancer (bc) remains the most common cancer to affect women, with an incidence of 55,100 per year in Germany. Germany still does not have a register of cancer pts. This has led to the development of national guidelines, certification of breast centers (cts) and the opening of the WBC (West German Breast Center) in 2000 which in turn led to the introduction of benchmarking for the treatment of bc pts. To help improve treatment, the breast cts will need to publish their data. This will enable a comparison of success rates, so that the cts will be able to learn from each other. Here we estimate the effects of benchmarking from 2003 to 2006. Methods: The implementation of the benchmarking system has been voluntary. The first step was to inform about the advantages of benchmarking. The next step was creating electronic infrastructure to gather, store and compare data to be used to evaluate the quality of bc treatment. The cts receive twice a year a benchmarking report and have the opportunity to compare themselves to cts of the same size as well as smaller and larger cts. As early as 2006, over 50% of new cases of bc in Germany were documented in 206 cts and cooperating institutes according to the WBC criteria Results: To compare the quality of treatment in the cts, it is necessary to choose particular indicators which adhere to the national guidelines. We compared the results of pathological and surgical treatment in 2003 and 2006. In 2003 66 breast cts with 5,994 cases of primary bc took part in the scheme, compared to 206 cts with 25,417 primary bc in 2006. The number of bc cases diagnosed preoperatively via biopsy rose from 58% to 84% in 2006. Correct indication of breast-conserving surgery at the T1 tumor stage rose from 64% to 83%. Conclusions: It has been shown that benchmarking results in an improvement in a range of indicators. It will be some years before we can be sure whether better treatment or better data processing, have caused these improvements when we have more data on mortality and morbidity. Benchmarking leads to an improvement in the quality of the already-certified cts and an increase in the certification of previously non-certified institutions. No significant financial relationships to disclose.
Pelvic metastases from pancreatic carcinoma: a pattern observed on bone scan.
Authors: J D Lyons, B Alibazoglu, J E Harris, A Ali, E F Hollinger
Journal: Clinical Nuclear Medicine (2001)

Metastases to the bony pelvis is an unusual pattern of the spread of primary pancreatic tumors. The authors report the presence of metastatic disease in the bony pelvis observed on bone scans in several patients who had been treated recently for pancreatic carcinoma. When bone scans that show metastatic disease in the pelvis are evaluated in patients with unknown primaries, the diagnosis of pancreatic carcinoma should be considered.
Dasatinib in patients with chronic phase chronic myeloid leukemia (CP-CML) who are resistant or intolerant to imatinib: Results of the CA180013 ’START-C’ Study
Authors: A. Hochhaus, H. Kantarjian, M. Baccarani, F. Cervantes, T. Facon, S. Goldberg, P. Erben, A. Countouriotis, R. Ezzedine, B. J. Druker
Journal: Journal of Clinical Oncology (2006)

6508 Background: Dasatinib (BMS-354825) is a novel, oral, multi-targeted kinase inhibitor of BCR-ABL and SRC kinases with proven preclinical and clinical activity against imatinib resistant BCR-ABL mutations. Methods: CA180013 is an open-label Phase II study of dasatinib in imatinib-resistant (IM-R) or -intolerant (IM-I) patients (pts) with CP-CML. Between February-August 2005, 424 pts were recruited from 75 centers worldwide. Dasatinib was given at 70 mg twice daily (BID) with dose escalation to 90 mg BID in pts lacking response, and dose reductions to 50 and 40 mg BID for toxicity. Evaluations were weekly blood counts for the first 12 weeks; bone marrow cytology and cytogenetics every 3 months. The primary endpoint was rate of major cytogenetic response (MCyR; ≤35% Philadelphia pos. metaphases) in IM-R pts. Results: Data are currently available from the first 186 pts (127 IM-R, 59 IM-I) accrued prior to May 12, 2005. Median age was 59 yrs (range 24–79); 46% were male. Median time from diagnosis of CML was 64 months. Of the IM-R pts, 72% received IM &gt;3 yrs, and 72% had &gt;600 mg/day of IM. Overall, 70% had received prior interferon alpha. 62 (33%) pts achieved a prior MCyR to IM. With ≥6 months of follow up, 168 (90%) pts had a complete hematologic response (CHR). MCyR were achieved in 83 (45%) pts including 40 (31%) of IM-R pts, and 43 (73%) of IM-I pts. Mutations in the BCR-ABL domain were found in 65/176 (37%) pts; 57 (88%) achieved CHR, and 24 (37%) MCyR. Molecular response analysis is ongoing. 160 (86%) pts remain on study without progression. Grade 3/4 neutropenia or thrombocytopenia was reported in 83 (45%) pts and 85 (46%) pts with onset after 4–8 weeks of therapy in most pts. Temporary dose interruptions occurred in 146 (78%), and dose reductions in 96 (52%) pts with a median daily of 108 (range 19–169) mg. Non-hematologic toxicity consisted mainly of Grade 1/2 diarrhea, headache, superficial edema, and pleural effusion, with ≤2% Grade 3/4. There was no cross-intolerance between dasatinib and IM. Conclusions: Dasatinib demonstrated substantial hematologic and cytogenetic activity in IM-R and IM-I pts with CP-CML. An updated analysis of 424 pts with ≥6 months of follow up will be presented. [Table: see text]
Nomogram for the prediction of high-grade prostate cancer on ultrasound-guided needle biopsy
Authors: M. Garzotto, L. Collins, R. Priest, S. Spurgeon, Y.-C. Hsieh, T. M. Beer, M. Mori
Journal: Journal of Clinical Oncology (2005)

4621 Background: Prostate cancer is characterized by a wide spectrum of biologic heterogeneity that results in divergent clinical outcomes. Thus, not all patients benefit from aggressive therapy. Tumor grade is the most important of the clinicopathologic factors that predict tumor aggressiveness and therefore drive decisions regarding aggressive local therapy vs. observation. The goal of this study was to develop a nomogram for the prediction of high-grade prostate cancer (defined as Gleason ≥ 7) using pre-biopsy factors. Methods: Data were prospectively collected on 1,699 referred men with a serum PSA of ≤ 10 ng/ml who underwent a prostate biopsy (minimum 6 cores). Variables analyzed included: age, race, family history, digital rectal exam (DRE), prostate-specific antigen (PSA), PSA density (PSAD), prostate volume, PSA doubling time (PSADT), and ultrasound (US) findings. Thirty percent of the data were randomly reserved for study validation. Logistic regression analysis was performed to estimate the relative risk (RR) and 95% confidence intervals (CI). Results: The cohort was characterized as follows (values: median ± SD): age = 66.0 ± 7.5 years, PSA = 5.0 ± 2.5 ng/ml/cc, PSAD = 0.12 ± 0.10 ng/ml/cc, volume = 35.0 ± 23.6 cc. High-grade prostate cancer was detected in 157 subjects (9.2%). The results of the multivariate analysis are shown in the table and a user-friendly nomogram was constructed based on these results. Using the independent validation set the area under the ROC was 0.74 for the model. Conclusions: The presence of high-grade prostate cancer was successfully predicted using a multi-factor logistic regression-based model. Models such as this have the potential to significantly reduce the number of biopsy procedures performed when subsequent therapy is contingent upon the detection of high-grade prostate cancer. No significant financial relationships to disclose.
Hb-level stabilisation with epoetin alfa in patients with advanced NSCLC undergoing concurrent neoadjuvant chemo-radiation therapy (phase III study)
Authors: W. Wagner, A. Granetzny, L. Hilejan, A. Marra, O. M. Koch, M. G. Krukemeyer, G. J. Wiedemann
Journal: Journal of Clinical Oncology (2006)

17110 Background: Patients suffering from advanced stage IIIA/B NSCLC still have a bad prognosis despite the development of new and more effective treatment methods. Improved therapy options include multi-modal treatment approaches with sequential and/or concurrent chemo-radiation therapy and, alternatively, subsequent surgery. The patients have to accept a higher incidence of side effects and longer therapy cycles, which can last up to six months. This means that most patients spend a considerable part of their survival time undergoing therapy, where, in the short or medium term, they are likely to die of a relapse or haematogenous metastatic spread. Therefore we have decided to offer patients with unfavourable prognostic factors (poor general health, high age, comorbidity) a shortened, three-week neoadjuvant and concomitant chemo-radiation therapy plus possible surgery. This form of treatment is expected to produce more positive outcomes than the purely palliative radiation therapy at 40–50 Gy. Preventive dosing with Epoetin alfa as part of an intensive therapy regimen might lead to higher compliance, increased quality of life and possibly even to a better prognosis as a result of stabilising patients’ Hb levels. Methods: 51 stage IIIA/B NSCLC patients received neoadjuvant concurrent chemo-radiation therapy (daily cisplatin (6 mg/m 2 ), 45 Gy hyperfractionated accelerated radiotherapy). 25 patients received additional treatment with Epoetin alfa 3 times a week (10,000 IU sc). Results: While Hb levels dropped significantly (−0.54 g/dL) during therapy in the control group, the Epoetin-alfa group showed a significant rise after only three weeks (+1,35 g/dL). There were no significant differences in remission rates between the goups. Conclusions: In this patient group, preventive treatment with Epoetin alfa stabilises Hb levels at a target level of around 12 g/dL even under intensive therapy. To what extent treatment with erythropoietin affects prognosis should be examined in further studies. No significant financial relationships to disclose.