tbuckley/cabot-search huggingface dataset:
Bleomycin dose modification in Hodgkin disease (HD) treated with ABVD: Patient characteristics, treatment outcomes, and association with mixed cellularity (MC) histology
Authors: U. Iqbal, N. Radhakrishnan, M. Kaufman, A. Thomas, D. Patel, B. Mehrotra, R. Roy
Journal: Journal of Clinical Oncology (2007)

18525 Background: Bleomycin used in the ABVD regimen is associated with a risk of pulmonary toxicity (10 - 19%). Pts with early signs of suspected bleomycin toxicity are often treated with modifications of the regimen. We conducted a retrospective study of patients with HD at our institution in whom bleomycin dose was modified or discontinued during their course of therapy with ABVD. Their response to modified therapy and possible predisposing factors were analysed. Methods: IRB approval was obtained for this study. Tumor registry data for adult pts diagnosed with HD between 2004 and 2006 were analysed for age, stage, sex, histology, smoking history, reduction in bleomycin dose and outcomes. Results: 38 pts were diagnosed with HD at our institution during this time period. Histology: NS: n=15(39.4%), MC: n=16(42.1%), NLP: n=2(5.2%), LR: n=2(5.2%). Histology NOS: n=4(10.5%). 8 pts with bleomycin dose modifications were identified. Pt. characteristics : Med.age 46 yrs (28- 64 ), M:F3:5; 7 of 8 were newly diagnosed and one pt had recurrent HDs. Stages: Stg I: n = 1; Stg II: n= 3; Stg III: n = 3, Stage IV: n= 1, B symptoms : n = 3. Histology: MC (n = 6), NS (n = 1). Unk n=1. 4 of 8 pts were ex-smokers. One patient never received bleomycin due to initial poor PFTs. 7 pts had bleomycin discontinued due to symptoms and decrease in DLCO during their treatment. One patient was continued on 50% reduced dose bleomycin for 2 cycles prior to discontinuation of bleomycin. The distribution of the number of patients discontinuing bleomycin by cycle of treatment is as follows: C#2: n=1; C#3: n=2; C#4: n=1; C#5: n=2. The complete response rate was 100% in this group despite bleomycin dose modification. There were no relapses after a median follow up of 18 mos (range: 8- 33). One patient treated for recurrent HD had severe pulmonary toxicity and did not receive any further treatments. All other patients completed their intended cycles of treatment. Conclusions: Despite bleomycin modification in this small series of pts treated initially with ABVD, DFS remains excellent with no noted relapses at this early follow up. Majority of pts requiring dose modifications had MC histology. Further trials are needed to evaluate the role of bleomycin in the ABVD regimen. No significant financial relationships to disclose.
Effect of tandem high-dose chemotherapy (HDC) on long-term complete remissions (LTCR) in metastatic breast cancer (MBC), compared to conventional dose (CDC) in patients (pts) who were not selected on the basis of response to prior C: Mature results of the IBDIS-I
Authors: J. P. Crown, S. Leyvraz, M. Verrill, V. Guillem, A. Efremidis, J. Garcia-Conde Bru, R. Welch, A. Montes, R. Leonard, J. Baselga
Journal: Journal of Clinical Oncology (2004)

631 Background: In single arm studies, HDC (usually single-cycle) with autograft support appeared to produce an unusually high percentage of LTCR in MBC, an observation which was not confirmed in prospective randomised trials (PRT). We have previously reported the results of the protocol-mandated interim three-year analysis of IBDIS I-a, prematurely terminated (post-Bezwoda)PRT of HDC versus CDC in MBC (ASCO 2003). Despite relatively small numbers (110pts), the primary protocol endpoint-event-free survival (EFS i.e. alive without relapse)-was statistically significantly superior for HDC pts. We now present updated results. Methods: PRT in pts without prior CDC for MBC. CDC (mg/m2): doxorubicin 50/ docetaxel 75 (AT) x 4 followed by cyclophosphamide / methotrexate/5FU; versus HD: 3xAT followed by tandem autograft-supported HDC (#1-Ifosphamide12,000/carboplatin AUC18/etoposide 1200; #2:-cyclophosphamide 6000/thiotepa 800). The median five year F/U will coincide with ASCO 2004, however, as median EFS will still be statistically significantly superior in 5/2004 even if all remaining HDC CR relapse immediately, it was decided to analyze the data now, at 55 months of F/U. Results: All are intention to treat. The study remains statistically significantly positive at a median follow-up of 55 months (range 76–30) The median EFS were: HDC 416 and CDC 312 days (EFS: p=0.017 log-rank, RR 0.62). Progression–free survivals were: HDC 439, CDC 322 days (RR=0.57; p=.006). There were 5 treatment-related deaths on HDC, and 2 on CDC. Six of 56 HDC pts are still alive and relapse free (74, 62, 56, 56, 55, 54 months), versus 1 CDC patient (49 months). Nineteen HDC pts are alive, versus 10 CDC (median survival: 961v 804 days, RR=0.68; p=0.08) Conclusion: These results do not justify routine HDC, but, given the failure of other treatments to produce a meaningful rate of LTCR in this “incurable cancer”, do mandate further study of this approach. IBDIS II will soon be open for accrual. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
The effect of protocol inclusion on the outcomes of ovarian cancer patients receiving first-line chemotherapy
Authors: A. K. Brown, S. Donfrancesco, C. O. Granai, P. Disilvestro
Journal: Journal of Clinical Oncology (2005)

5070 Background: Clinical trials are the gold standard for evidence based medicine however only 2% of cancer patients enroll in clinical trials. Recent data has shown improved outcomes with protocol treatment in a variety of cancers. We investigated the outcomes of patients receiving first-line chemotherapy for ovarian cancer on or off protocol. Methods: Subjects were identified from a database of protocol subjects and from the tumor registry. Controls must have been eligible for entry into protocol. The primary end-point was progression free survival (PFS) in months. Secondary end-points were cycle delays or hospital admissions during treatment and overall survival (OS). Kaplan-Meier survival analysis was performed. Continuous variables were compared with t-tests, and categorical variables with Chi-square or Fisher’s exact. Results: There was no difference in PFS between the two groups. (21 months for patient treated on protocol compared to 23 for patients treat off protocol) Subset analysis revealed improved PFS and OS in suboptimal patients treated on protocol, however the number of subjects was small. Survival curves for both progression free and overall survival showed no difference between patients on and off protocol. Comparisons between those receiving the experimental arm on protocol and those treated off protocol showed an improvement in overall survival. Median overall survival in the experimental arm was 61 months compared to 40 months for those treated off protocol. 53% of those on protocol had a delay of at least 1 cycle compared to 62% of those off protocol. There was no difference in hospital admissions during treatment. On multivariate analysis, optimal debulking was the only factor significantly associated with either recurrence or survival. Conclusions: Enrollment in a clinical protocol had no adverse impact on the clinical outcomes of patients receiving first line chemotherapy for ovarian cancer. Improved outcomes for suboptimally debulked patients treated on protocol was also suggested, although numbers were small. No significant financial relationships to disclose.
Improved Survival of Patients with Acute Myeloid Leukemia Following Implementation of Swedish National Guidelines: Results from the AML Registry 1997-2013
Authors: Gunnar Juliusson, Vladimir Lazarevic, Sören Lehmann, Åsa Rangert Derolf, Lars Möllgård, Hege Garelius, Lovisa Wennström, Bertil Uggla, Petar Antunovic, Kristina Myhr-Eriksson, Anders Wahlin, Martin Höglund
Journal: Blood (2014)
Small leucine-rich proteoglycan, decorin expression as a biomarker of outcome in soft tissue tumor
Authors: A. Matsumine, K. Kusuzaki, T. Ueda, A. Okamura, A. Uchida
Journal: Journal of Clinical Oncology (2004)

9052 Background: Decorin is a member of the small leucine rich proteoglycan (SLRP) gene family that has recently become focus in various area of cancer research. It has been reported that low levels of decorin expression are associated with worse prognosis in patients with breast, colon, and ovarian cancer. However the expression and role of decorin in human soft tissue tumor has not yet been characterized. To investigate whether decorin gene expression is a biomarker of aggressiveness in soft tissue sarcoma, 51 biopsy samples from 44 patients were studied. Methods: The tumors included benign neurogenic tumor in 8, malignant peripheral nerve sheath tumor(MPNST) in 6, liposarcoma(LPS) in 11, malignant fibrous histiocytoma(MFH) in 9, synovial sarcoma(SS) in 8 and clear cell sarcoma(CCS) in 2. In 7 patients, we analyzed the specimens form both of primary and locally recurrent lesions. For the quantitative analysis, real-time polymerase chain reaction (Real-time PCR) analysis using ABI PRISM 7700 Sequence Detection System was performed. Results: Reduced expression of decorin is significantly more observed in high-grade malignancies (MFH, SS, CCS) than in benign neurogenic tumor and low-grade malignancy (LPS, MPNST) (p<0.05). In all of 7 cases with locally recurrent lesions, the level of decorin expression were lower in locally recurrent lesions than in the primary lesion. Moreover in high grade spindle cell sarcoma patients (MFH in 9, SS in 8), the patients with sarcoma expressing lower levels of decorin have a worse disease-free survival rate (Logrank; p<0.05). Conclusions: These results suggest that reduced expression of the small leucine rich proteoglycan, decorin in soft tissue tumor may be associated with a poor prognosis. No significant financial relationships to disclose.
Targeting bladder tumor cells in vivo and in the urine by a peptide identified using phage display
Authors: T. Kwon, B. Lee, E. Yoo, S. Chung, Y. Park, B. Kim
Journal: Journal of Clinical Oncology (2006)

10071 Background: Bladder cancer is one of the most common tumors of genitourinary tract. Selective delivery of drugs to tumor tissues is important for effective tumor therapy. Here we identified a peptide targeting bladder tumor cells using phage display. Methods: Phage peptide library containing CX 7 C (C-cysteine and X-any amino acid residue) was based on T7 415–1b phage vector (Novagen). Tumor xenografts were prepared by subcutaneously injecting BALB/c Nu/nu female nude mice with HT-1376 bladder tumor cells. For a carcinogen-induced tumor model, Fischer 344 female rats were supplied ad libitum with tap water containing 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) for 8 weeks. Results: A phage library containing CX7C random peptides was screened for selective binding to cells from human bladder tumor xenografts. Selected phage clones were individually evaluated for binding to cultured bladder tumor cells and for binding to cells from human tumor tissues of six patients. The peptide displayed by the most promising clone was synthesized and designated as Bld-1. Fluorescein-conjugated Bld-1 peptide showed selective binding to frozen sections of human bladder tumor tissues of three patients. In vivo tumor targeting was examined in a carcinogen-induced rat tumor model (n=20). When the fluorescent peptide was introduced into the bladder lumen, it selectively bound to tumor epithelium. Next, when the fluorescent peptide was intravenously injected into the tail vein, it homed to the bladder tumor, but was not detectable in normal bladder and control organs such as lung. Moreover, the fluorescent peptide bound to cells from urinary specimens of tumor patients (n=10), whereas little binding was observed in cells from healthy individuals (n=3). Conclusions: The Bld-1 peptide may be useful for targeting bladder tumor cells in vivo and in the urine. No significant financial relationships to disclose.
Evaluation of occurence of cancer of the lung among young people in six regions of the western Ukraine
Authors: N. Kitsera, J. Shparyk
Journal: Journal of Clinical Oncology (2007)

21188 Background: Analysis of the cases of malignant lung tumors of young people (&lt;34 yrs, born in 1963–2004) and diagnosed in 1997–2004 was made using the materials of the database of cancer registers of Volyn (V), Ivano-Frankivsk (IF), Lviv (L), Rivne (R), Ternopil (T) and Chernivtsi (C) regions. The population of young people &lt;34 yrs of this region - 4.2 million/year. Results: Among 7541 cases of cancer in the six regions of the Western Ukraine malignant tumors of the lungs were diagnosed in 102 cases (1.4%). This pathology was registered in males in 57 cases, and in females in 45. The number of males with tumors of the lungs prevailed in V, IF, L, T. The number of young males and females with such pathology during the said period was the same - 11 cases in each gender group - in R. The youngest among the 102 individuals from the above said six regions were a boy aged 6 and a girl aged 16 from R. Combination with other tumors was observed in three females (C49, C53, C58) and one male (C81). In C among 766 cases of malignant tumors in young people &lt;34 years lung cancer were detected in 5 (0.7%). Among 959 cases of cancer such tumors of the lungs were detected in 8 (0.8%) in V. Among the young people &lt;34 years this pathology was detected in 14 (1.2%) in IF out of all 1156 cases of malignant tumors, in T - 947 tumor - 15 cases (1.6%). Among the six above regions in L there have been detected 2465 cases of malignant tumors, of which lung cancer were diagnosed in 38 - 1.5%. The highest frequency of occurrence of this pathology was registered in R (1.8%) - 22 cases in 1248 cases of malignant tumors. Conclusions: Fluctuation of frequency of this pathology in all these regions in various years during the investigated period had a wave-like character. As each of these regions is characterized by different geographic and climatic conditions, physical and chemical factors, exhausts of industrial enterprises, the study of frequency of malignant tumors in young people will permit to evaluated more objectively contribution of hereditary factor in the development of this pathology. The perspectives of further research in this field lie in the study of the role of genetic predisposition to the occurrence and development of malignant tumors in each patient, taking into account ecological zone of residence, occupational hazards and harmful habits. No significant financial relationships to disclose.
A prospective evaluation of the relationship between bone mineral density and breast cancer.
Authors: David Barry Geffen, Victor Novack, Tali Shafat, Margarita Tokar, Irena Lazarev, Leonid Bogomolni, Rita Troitsa, Hila Magidovich, Yair Liel, Michael Koretz, Ethel Siris, Larry Norton, Shraga Shany, Merav Fraenkel
Journal: Journal of Clinical Oncology (2014)

9 Background: Osteoporosis and breast cancer (BC) are each mediated by circulating estrogens. Insulin and insulin growth factors 1-2 have been linked to increased bone mineral density (BMD) and BC cell growth. The relationship between BMD and BC incidence has been analyzed in a number of retrospective studies with conflicting results. We have previously reported on a study of BC risk in 15,268 women who underwent BMD testing. Women in the highest Z-score tertile at the femoral neck had a higher risk of developing BC compared to those in the lowest tertile (OR 2.15, p = 0.004). The current study was undertaken in order to determine whether there is a direct correlation between BMD and BC when evaluated prospectively. Methods: This case-control study is planned to include 400 consecutive patients (pts) with newly diagnosed BC and 800 matched controls without BC. Pts and controls undergo BMD examination using dual photon technology. Serum is obtained for vitamin D, calcium, and a panel of bone turnover markers and cytokines. Pts and controls are interviewed and a questionnaire about BC and osteoporosis risk factors is completed. Results: We present clinical and BMD data from the first 200 BC patients recruited to the study. Median age 60, interquartile range 49.5-66. Body Mass Index: 28.4 ± 5.4 (mean ± SD). Postmenopausal: 148 patients, 74%. T-scores (mean ± SD): femoral neck: -0.68 ±-1.10, total hip: -0.28 ± 1.17, L1-L4: -0.52 ± 1.39. T-score of less than minus 2.5 (cut-off for osteoporosis) at any of the 3 sites, 24 (11.9 %) pts. Estrogen receptor pos: 162 (81%).BC stage: T0-T2, 175 (87.5 %). N0: 108 (54.5%), N1-2-3: 86 (43.4%). % pts node pos (N1-2-3) in each T score range: ≤ -2.5, 20%; -2.5 &lt; T score ≤ -1,36%; -1 &lt; T-score ≤+ 1,50%; +1 &lt; T-score, 60%. % pts low grade in each T score range: ≤ -2.5, 25%;-2.5 &lt; T-score ≤ -1,35%;-1 &lt; T-score ≤ +1,37 % ;+1 &lt; T-score, 20%. Conclusions: Only 11.9% of the first 200 BC patients studied had osteoporosis by BMD at diagnosis.Pts with higher BMD showed a trend for more nodal involvement. Pts with T-score &gt; +1 had fewer cases of low grade histology compared to pts with lower T-scores. These preliminary results hint that higher BMD may be associated with more aggressive BC.
Clinical response to imatinib mesylate in recurrent and metastatic gastrointestinal stromal tumors
Authors: R. Villalobos, G. Hernández, M. Martinez-Prieto, A. Silva
Journal: Journal of Clinical Oncology (2007)

20528 Background: We analyzed the efficacy and safety of imatinib mesylate in GIST (Gastrointestinal Stromal Tumors) in various anatomic sites. Methods: Out of 24 patients with recurrent or metastatic disease receiving treatment, clinical and tomographic evaluation was possible only in 21 pts. RECIST criteria were used to evaluate response and NCI guidelines were used for evaluation of toxicity. The treatment given between March 2003 and December 2006 was imatinib mesylate 200mg twice daily until disease progression or drug intolerance. All included patients had histopathologic confirmation and CD 117 positive inmunohistochemistry. Results: Patient characteristics were as follows: 19 females, 2 males, average age: 37.8 years (range: 36 - 80), Functional status according to ECOG: 0 in 19 pts, 1 in one patient and 3 in one patient. Anatomic sites were: 4 stomach, 7 small intestine, 3 rectum-sigmoid, 4 carcinomatosis from unknown primary, 2 peripancreatic and one esophageal. Nine patients had recurrent disease, 12 unresectable disease and 11 pts had liver metastases and 13 had retroperitoneal metastatic disease. Comorbidities: 3 pts with Type 2 Diabetes Mellitus one patient with Systemic Hypertension, and deep vein thrombosis each, two patients with a previous diagnosis of cancer: Thyroid and Lung Cancer respectively. Responses:2 (9.5%)CR, 6 (28.5%) PR, 12 (57.1%) stable disease, one (4.7%) pt. with progressive disease. Toxicity: one patient had rash, one patient presented bone pain, one patient with face discoloration, one with cephalea and nausea, and two patients with bipalpebral edema. Median duration for response was 5.7 months (range 2–30) at the moment. Conclusions: Efficacy of imatinib mesylate in recurrent and metastatic GIST's is high with overall response rates of 95% and adequate tolerance. Studies as adyuvant and second line therapy are needed in our population. No significant financial relationships to disclose.
Safety and pharmacokinetics of intravenous VEGF Trap plus irinotecan, 5-fluorouracil, and leucovorin (I-LV5FU2) in a combination phase I clinical trial of patients with advanced solid tumors
Authors: O. Rixe, C. Verslype, J. B. Méric, S. Tejpar, J. Bloch, M. Crabbe, D. Khayat, E. S. Furfine, S. Assadourian, E. Van Cutsem
Journal: Journal of Clinical Oncology (2006)

13161 Background: VEGF Trap is a potent angiogenesis inhibitor comprising portions of human VEGF receptor VEGFR1 (Flt-1) and VEGFR2 (Flk-1) extracellular domains fused to the Fc portion of human IgG. VEGF Trap binds VEGF and neutralizes all VEGF-A isoforms plus placental growth factor. I-LV5FU2 is an approved chemotherapy regimen for the first-line treatment of metastatic colorectal cancer. This study was designed to evaluate the safety and pharmacokinetics (PK) of VEGF Trap plus I-LV5FU2 administered intravenously. Methods: Successive cohorts of 3–6 patients (pts) with relapsed or refractory solid tumors received intravenous VEGF Trap plus I-LV5FU2 every 2 weeks. Study endpoints included safety, PK, and immunogenicity. Antitumor activity was assessed by CT scan. Results: Ten pts (3 male/7 female), median age 59 (34–67), ECOG PS 0/1/2: 8/2/0, with a variety of advanced solid tumors, including 5 colorectal and 2 ovarian, have received a total of 50 cycles of VEGF Trap plus I-LV5FU2 across 2 VEGF Trap dose levels (2.0 mg/kg, 4.0 mg/kg) to date. Only 1 dose-limiting toxicity (G3 proteinuria &gt;2 wks with normal plasma creatinine levels) has been encountered so far (4.0 mg/kg, Cycle 2). This pt also had controlled G2 HTN (renal biopsy pending). No other G3/4 VEGF Trap-related AEs have been reported so far. Preliminary free VEGF Trap clearance was 15.4 mL/kg/day. Three pts (synovial sarcoma, ovarian and colon cancers) achieved partial responses. Conclusions: VEGF Trap may be safely combined with I-LV5FU2 at the dose levels studied. Preliminary free VEGF Trap clearance did not differ significantly from that seen with single-agent exposure; chemotherapy PK analysis is pending. The maximum tolerated dose has not yet been reached, and dose escalation continues. Updated safety, pharmacokinetic, and preliminary efficacy results from this ongoing study will be presented. [Table: see text]
Neoadjuvant paclitaxel/radiation for Stage II/III breast cancer with correlative molecular markers
Authors: A. Chakravarthy, P. Chaurand, B. McLaren, M. Kelley, C. Truica, A. Erskine, J. Simpson, D. Billheimer, R. Caprioli, J. A. Pietenpol
Journal: Journal of Clinical Oncology (2004)

9622 Background: Chemotherapy is currently given as adjuvant therapy in patients with high-risk operable breast cancer. Although this results in a significant reduction in breast cancer mortality, it is currently impossible to determine at the outset which patients are likely to benefit from this treatment. We propose that proteomic analysis of serial core biopsies can be used to detect biomarkers of response. Methods: Thirty-nine patients with operable breast cancer were treated with paclitaxel 175-mg/m2 q 3 weeks for 3 cycles. This was followed by concurrent paclitaxel (30 mg/m2 twice weekly) and radiation to a total dose of 4680cGy (breast) and 4500cGy (regional nodes). Core biopsies were obtained before and 24–72 hours after the first cycle of paclitaxel. Following completion of chemoradiation all patients went on to definitive surgery consisting of segmental resection or mastectomy. This was followed by four cycles of Adriamycin/Cytoxan and tamoxifen (if receptor positive). The primary endpoint was pathologic complete response defined as the absence of invasive cancer at surgery. Results: Grade 3 or 4 toxicity was seen in only four patients during the neoadjuvant component of therapy. Three patients progressed during the neoadjuvant component of therapy and did not go on to definitive surgery. Five patients are currently undergoing neoadjuvant treatment. Pathologic complete response was observed in 10 of 29 patients (34%). Direct mass spectrometric analyses of tumor cells obtained by laser capture microdissection from select biopsies have shown differences in proteomic patterns amongst the patient population. We are currently analyzing all the proteomic data and laboratory correlates with pathologic outcome. Conclusions: Neoadjuvant paclitaxel followed by paclitaxel/RT is well tolerated and achieves pathological complete responses, in up to 34% of patients with Stage II/III breast cancer. Thus far we have established the feasibility of obtaining serial core biopsies and using imaging mass spectrometry to identify specific proteins that correspond to histologically defined tumor cells extracted from surrounding normal breast parenchyma. No significant financial relationships to disclose.