tbuckley/cabot-search huggingface dataset:
Changing epidemiology of gastric sarcomas in the United States.
Authors: Albert Y. Lin, Peter Ravdin
Journal: Journal of Clinical Oncology (2015)

47 Background: The introduction of imatinib as targeted therapy for the treatment of gastrointestinal stromal tumors (GIST) has supplied a strong impetus for the reclassification of gastric sarcomas (GS). We examined the changes in the incidence and mortality over the last 20 years for GS subtypes using the Surveillance, Epidemiology, and End Results (SEER) database over the last 20 years. Methods: Based on information from SEER, GS cases were identified by primary cancer site and ICD-O-3 codes. SEER*stat was used to make estimates of incidence and cause specific survival. Joinpoint software was used to test for trends. Results: The overall incidence of GS increased of from 1991 and to 2011 from 2.9 (standard error [SE] 0.4) to 6.6 (SE 0.6) cases per million per year. The histologic subtypes of changed over this time interval with the leiomyosarcoma being initially the leading GS subtype with an incidence from 2.3 (SE 0.4) decreasing to 0.1 (SE 0.1). The incidence of gastric GIST increased from 0.1 (SE 0.1) to 6.3 (SE 0.6) representing 95% of all GS cases in 2011. For GS test for trend with Joinpoint model did not detect a discontinuity in the trend (occurring at a rate of 4.7% [p &lt; 0.001]) relative increase per year. Much of the total GS increase in incidence was for localized disease with the incidence rates which increased from 1.2 to 4.5 cases per 10^6/year a relative increase of 6.8% (p &lt; 0.01) per year. During this period the 3-year cause specific mortality improved for localized GS from 9.4% to 0.9%. Improvements were also seen for mortality outcomes for regional and distant disease. Conclusions: Between 1991 and 2011, more than a doubling of incidence of GS was observed with a concurrent rapid change in GIST - most in localized disease and a dramatic improvement in its outcome. It seems unlikely that this is due to changes in the underlying biology of the disease, or to imatinib alone, but may be, in part, due to changes in diagnostic techniques or pathologic evaluation
Hormone replacement therapy improves quality of life in cancer cervix survivors
Authors: M. B. Desai, B. B. Desai
Journal: Journal of Clinical Oncology (2005)

5100 Background: 70% of cervical cancer patients in India are approximately 35 years old and present with stage IIIB disease. Current treatment modalities of concurrent chemo radiotherapy is improving survival in these patients but is also leading to permanent ovarian failure.Aim is to determine if Hormone Replacement Therapy (HRT) can relieve the symptoms and improve quality of life. Methods: A prospective controlled study was initiated from September 1997. 456 histologically proven squamous cell carcinoma cervix III B patients with age 35 years or less where included in the study. A detailed history of patient symptomatology was taken at the initiation of the therapy and after 6 weeks of completion of treatment. Since many symptoms of cancer and menopause are similar it was difficult to attribute it to a particular reason. Becks depression Inventory was used to access depression. All patients underwent counseling for HRT by the counsultant. 278 patients opted to take HRT. 0.625 mg of conjugated estrogen with 2.5mg medroxyprogesterone acetate continuously. Patients were evaluated at 6 weeks, 3 months and 1 year of HRT and results were compared to 178 patients who did not start HRT. Results: After 6 weeks of completion of concurrent chemo radiotherapy treatment, 38.6% patients experienced hot flushes 33.8% suffered from night sweats and 30.4% had palpitations which were all increase from initial 8.3%,7.45% and 10.9% respectively. 62.6% patients had severe depression at the initiation of therapy which reduced to 54.9% on completion of therapy. At the end of one year the HRT group showed marked reduction in depression with only 4.67% patients being depressed compared to 30.3% patients in the non HRT users.This is statistically significant. (chi square) On follow up it was found that there was marked improvement in all symptoms in the HRT group as against the non HRT group. Conclusions: Hot flushes, night sweats, palpitations and depression are common after treatment for cancer cervix in younger patients.HRT plays a significant role in improving the quality of their life. No significant financial relationships to disclose.
A custom cDNA microarray confirms differential transcription factor regulation between neoplastic and non-neoplastic prostatic epithelial cells
Authors: M. S. Benjamin, Y. Li, K. Otto, C. Chen, C.-K. Choo, D. Waddell, L. W. K. Chung, J. Simons, J.-T. Dong
Journal: Journal of Clinical Oncology (2004)

9656 Background: Oligonucleotide and cDNA microarrays are commonly used to profile gene expression in biological samples. These arrays are frequently expensive to design and print, limiting useful application. We hypothesized that since transcription factor (TF) expression changes underly many biological phenomena, small cDNA microarrays could be used to effectively study patterns of TF expression in neoplastic and non-neoplastic prostate cells. Methods: Using online functional annotation databases, we built and used such a microarray to compare gene expression between normal and immortalized prostate cell lines, and androgen-dependent (AD) and -independent (AI) prostate cancer cell lines. Supervised permuted t-tests were used to determine which genes were significantly regulated in the different cell lines, and the identified genes were validated with computerized classification algorithms. Calculations were performed using open source Bioconductor packages in the R programming environment. Results: Microarray experiments identified differential expression in 54 unique ESTs (expressed sequence tags) in 80 sample comparison pairs; expression changes were confirmed by reverse-transcriptase PCR (RT-PCR) normalized to GAPDH expression in 20 comparison pairs and 14 unique ESTs. Confirmation of additional uncertain gene expression differences is ongoing with quantitative real-time PCR. Significant, confirmed TF expression differences were found in all comparisons of prostate cell types, including AD versus AI cancer cell lines. Conclusions: Custom cDNA microarrays are cheap to construct and use, and can identify gene expression changes that correspond to different biological conditions. No significant financial relationships to disclose.
A comparative study of gemcitabine/doxorubicin and cyclophosphamide/doxorubicin combinations in first-line metastatic breast cancer
Authors: Y. Beldjilali, M. Yamouni, K. A. Benhadji, H. Khellafi, A. Abdelaoui, L. Djellali
Journal: Journal of Clinical Oncology (2008)

1050 Background: Doxorubicin is a major drug for the treatment of breast cancer. D combination with cyclophosphamide (C) is commonly used in the treatment of breast cancer. Previous studies reported promising activity of the combination of gemcitabine (G) and D. This study was conducted to assess the efficacy and safety of GD and CD combination regimens in previously untreated patients with metastatic breast cancer (MBC). Methods: Previously untreated patients (pts) with MBC received either GD (G 1,200 mg/m2 and D 25 mg/m2 both on days 1 and 8) or CD (C 600 mg/m2 and D 60 mg/m2 on day 1). Cycles were repeated every 21 days. Treatments were continued until disease progression or unacceptable toxicity. Primary endpoint was overall response rate (ORR). Secondary endpoints were time to progression (TTP), overall survival (OS) and toxicity assessment. Results: 109 pts were enrolled in this trial, 55 in GD arm and 54 in CD arm. Median age was 41 years (GD) and 45 years (CD). Most patients were anthracyclines naives (65.5% vs. 67%). Visceral metastases were present in 94.5 % and 93% of pts, respectively. A median number of 6.6 and 5.6 cycles were delivered in GD and CD arms respectively. GD resulted in a significatively higher ORR (55% vs. 34%) and TTP (13.3 vs. 8.13 months). Detailed efficacy results are reported in the table. G3/4 hematologic toxicities were neutropenia (7.5% vs. 10%), thrombopenia (2% vs. 5%) and anemia (5.5% vs. 6%). The following G3/4 adverse events were significantly lower in GD arm: nausea (10% vs. 20%), vomiting (8% vs. 25%) and alopecia (60% vs. 80%). Conclusions: GD is superior to CD as first line treatment for metastatic breast cancer in terms of ORR and TTP with a better safety profile. GD CD ORR (95% CI) 55% (51–58) 34% (31–36) p=0.032 Complete response 15% 5.6% Partial response 40% 28.3% Stable disease 24.5% 26.4% TTP, months (95% CI) 13.3 (10.18–18.03) 8.13 (7.33–10.79) p=0.001 OS, months (95% CI) 17.15 (12.50–19.59) 12.15 (8.97–13.92) N.S. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly
Phase I trial of combination therapy with <sup>90</sup>Y ibritumomab tiuxetan and gemcitabine in patients with non-Hodgkin’s lymphoma
Authors: H. Borghaei, M. Smith, M. Millenson, K. Krieger, A. Rogatko, R. Schilder
Journal: Journal of Clinical Oncology (2006)

17514 Background: Zevalin (Z) is an effective therapy in patients with relapsed or refractory low grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma (NHL). Gemcitabine (gem) also is active against NHL and is a potent radiation sensitizer. We are conducting a phase I trial to assess the safety of concomitant administration of Z and gem in patients with NHL. Methods: The starting gem dose is 250 mg/m 2 on days 1 and 8. Nine patients in three cohorts will be treated with 250 mg/m 2 of gem with 0.2, 0.3 or 0.4 mCi/kg of Z. The next cohort can accrue after all patients in the prior cohort have hematologic toxicity has recovered to grade 2 or after 60 days from the date of the last treated patient in the previous cohort. Once it is confirmed that a Z dose of 0.4 mg/kg can be safely administered with gem 250 mg/m 2 , gem will be escalated according to a Bayesian based system. Response evaluation is based on the International Workshop on Standardized Response Criteria for Non-Hodgkin’s lymphomas. Eligibility criteria include: any histology of recurrent NHL (not candidates for high dose therapy), platelets ≥ 150,000/ul; &lt; 25% bone marrow involvement by lymphoma; prior radiation to &lt; 25% radiation of bone marrow and no prior bone marrow or stem cell transplant. Results: Five patients have been treated thus far, two with follicular NHL (FL) and three with diffuse large B cell (DLBCL). Median age is 75 (range 55–82). The median number of prior treatments is 2 (range 1–6). One patient with DLBCL is not evaluable. The first three patients received 0.2 mCi/kg and next two patients 0.3 mCi/kg of Zevalin. Toxicity consists of grades 2 &amp; 3 myelosuppression in the first 3 weeks in 3 pts. due to gem and then of grade 2 in 1 pt. at 6 to 8 weeks as is usually seen with Z. One grade 3 leukopenia and one grade 2 thrombocytopenia have been observed resolving within one week. One grade 3 infection occurred, unrelated to the protocol or the study drugs. No grade 3 or 4 non-hematologic toxicity has been seen. In follow up, two patients with FL and one with DLBCL achieved CRu. One patient with DLBCL has progressed and one is not yet evaluable. Conclusions: Our preliminary findings suggest that Z can be safely combined with gem 250 mg/m 2 in the treatment of patients with NHL. Dose escalation to full dose Zevalin and then of gemcitabine is continuing. [Table: see text]
Abstract P222: Sex Differences in the Association of Visceral Adiposity with Lipoprotein Subclass Analysis in Obese Adolescents
Authors: Jacquelyn A Hatch-Stein, Andrea Kelly, Samuel S Gidding, Babette S Zemel, Sheela N Magge
Journal: Circulation (2015)

Background: Visceral adiposity contributes to metabolic syndrome in adults and children. Compared to the standard lipid panel, lipoprotein subclass particle analysis can provide additional information regarding cardiometabolic risk (CMR). The sex-specific relationships of visceral adiposity to lipoprotein subclasses have not been examined in adolescents.

Objectives: To examine the sex-specific relationships between visceral fat area and lipoprotein subclass particles and other CMR factors in obese adolescents.

Methods: This cross sectional study included obese adolescents (BMI ≥ 95th percentile for age), ages 12-18 years. Measurements included visceral fat area, as measured by dual energy x-ray absorptiometry (DXA) scan, standard lipid panel, lipoprotein subclass analysis, and homeostatic model assessment of insulin resistance (HOMA-IR). Linear regression models, adjusted for age, race, Tanner stage, and BMI were developed to evaluate associations of visceral fat area with known CMR factors. Analyses were stratified by sex to further explore the independent associations of the outcomes with visceral fat area.

Results: A total of 141 adolescents (age = 14.5 +/- 1.5 years; n = 77 (54.6%) female (F); n = 123 (87.2%) African-American) with mean BMI = 35.2 +/- 6.4 kg/m2 were included. Visceral fat was negatively associated with LDL particle (-P) size (p=0.0002), large LDL-P concentration (p=0.03), HDL-P size (p<0.0001) and large HDL-P concentration (p<0.0001) while being positively associated with small LDL-P concentration (p=0.0006), small HDL-P concentration (p=0.021), and a marginal positive association with total LDL-P (p=0.075). Visceral fat was also negatively associated with HDL cholesterol (-C) (p=0.0003) and positively associated with triglycerides (TG) (p=0.0021), TG/HDL-C ratio (p=0.0001), and HOMA-IR (p=0.0008). There was no association found with LDL-C (p=0.57). When stratified by sex (female=F, male=M), the associations of visceral fat with LDL-P size (F: p=0.0002, M: p=0.38), small LDL-P concentration (F: p=0.0001, M: p=0.56), and large LDL-P concentration (F: p=0.08, M: p=0.75) persisted only for females. In contrast, the association between visceral fat and small HDL-P concentration was significant only in males (M: p=0.012, F: p=0.50).

Conclusion: In a cohort of largely African American obese adolescents, visceral adiposity is associated with increased cardiometabolic risk and a more atherogenic lipoprotein subclass profile even after adjusting for BMI. The relationships between visceral fat area and certain lipoprotein subclasses are significantly different in males versus females. These findings suggest visceral adiposity provides additional sex-specific information beyond BMI alone.
Chemotherapy and radiation therapy in UPSC
Authors: A. Viswanathan, N. Horick, C. Tanaka, S. Campos, U. Matulonis, R. Berkowitz
Journal: Journal of Clinical Oncology (2007)

5535 Purpose: To analyze the impact of chemotherapy (Ch) and radiation therapy (RT) on relapse rates in patients with uterine papillary serous carcinoma (UPSC). Materials and Methods: The outcomes of 160 women with UPSC seen between 1980–2005 at the BW/DFCC were analyzed. Exclusion criteria included stage IVB disease, no hysterectomy, unknown stage, or unknown type of RT. Results: The median age was 67 years (range 31–90). FIGO Stage was IA (21), IB (28), IC (13), IIA (7), IIB (10), IIIA (42), IIIB (2), IIIC (21), and IVA (16). Treatment included none (40), Ch alone (20), Ch and whole abdominal radiation (WA) (11), Ch and pelvic radiation (P) (30), Ch and vaginal brachytherapy (VB) (2), WA alone (24), P alone (19), and VB alone (14). The median dose of RT was WA 30 Gy and P 45 Gy. Ch was given to 63 patients; the median number of cycles of Carboplatin, Adriamycin and Paclitaxel was 3. Overall survival (OS) and disease-free survival (DFS) for the entire group were 67% and 57% at 2 years, 62% and 51% at 3 years and 51% and 38% at 5 years. A total of 58 patients relapsed. Among those who received no RT or Ch, 48% (19/40) relapsed; among those treated with Ch only, 50% (10/20) relapsed; in the group treated with RT only, 26% (15/57) relapsed; and, in those treated with Ch and RT, 33% (14/43) relapsed. A significant difference in recurrence rate was seen in patients treated with RT compared to those who received no treatment (OR 0.40, p=0.03). This difference persisted after controlling for Stage, which did significantly affect the relationship between RT treatment and recurrence. Local recurrence (in an RT field) was a component of failure for 14% (14/100) treated with RT, versus 42% (25/59) that received no RT (OR 0.22, p=0.0001). Distant metastases were a component of first failure in 15% (9/61) that received Ch versus 11% (11/97) that did not; there was no significant difference in distant recurrence rate for patients treated with Ch (OR 1.35, p=0.53). Conclusion: This single-institution study represents the largest series of UPSC to date. The use of RT significantly decreases the overall recurrence rate of UPSC in this series and should be considered in patients with stages I-IVA UPSC. Future studies looking at the optimal type, dose and duration of chemotherapy, as well as the use of novel agents, are needed to improve outcomes in this population. No significant financial relationships to disclose.
The efficacy and tolerability of transarterial chemo-embolization (TACE) compared with transarterial embolization (TAE) for patients with unresectable hepatocellular carcinoma (HCC)
Authors: B. A. Hanks, P. V. Suhocki, D. M. DeLong, P. L. Doan, E. Liu, A. L. Tsai, C. T. Burke, S. A. Bernard, B. H. O’Neil, M. A. Morse
Journal: Journal of Clinical Oncology (2008)

4595 Background: Radiologic procedures that involve embolizing branches of the hepatic artery lengthen survival for patients with unresectable HCC, but the benefit of administering intrahepatic arterial chemotherapy during the embolization procedure is uncertain. Methods: A retrospective review of all patients with HCC and undergoing an embolization in the last 10 years and with 2 years of follow-up data was undertaken at two institutions to compare the survival and TTP of patients receiving TACE compared with TAE. Prognostic factors analyzed included age, gender, race, largest tumor size, number of tumors, macrovascular invasion, AFP, Child’s class, and CLIP score. Results: 122 pts with the following characteristics were included in the analysis: 71% Caucasian, 22% African American, 52% HCV+, 13% HBV+, 66% with cirrhosis, Child’s A/B/C 70/25/5%, CLIP Score 0,1/2/>3 52/26/21%, 72% had either 1 or 2 tumors, 14% macrovascular invasion, 16% portal vein branch thrombosis, 20% extrahepatic disease. The procedure (TACE (51%, the majority receiving doxorubicin plus mitomycin C) and TAE (49%).was completed in one session in 87%. A subsequent embolization was performed in 37% for progression or new disease. The embolizing material was ethiodised oil in 39%, polyacrylamide/gelatin in 43%, and polyvinyl alcohol in 41%. The procedures were equally well tolerated. Although 37% of patients experienced an adverse event, readmission to the hospital was required in only 10%. One patient experienced fulminant hepatic failure. The median survival for TAE was 19.6 mo (95% CI 10.6–28.4) compared with 12.9mo (95% CI 7.0–19.5) for TACE (p=0.066). The TTP for TAE was 3.2mo (95% CI 2.1–6.0) compared with 4.1 mo (95% CI 2.1–5.6 for TACE (p=0.79). On multivariate analysis, the trend towards a difference in survival for TAE was eliminated and only CLIP score, AFP, and largest tumor remained as prognostic factors. Conclusions: This retropsective review suggests that adding chemotherapy to embolization does not improve survival compared with bland embolization in pts with HCC. Future efforts should focus on adjunctive therapies following the embolization to prevent progression or new primary tumors. No significant financial relationships to disclose.
Phase II trial of capecitabine and oxaliplatin in patients with advanced or metastatic pancreatic adenocarcinoma
Authors: L. C. Garrot, A. Berkenblit, M. Goldstein, E. Florendo, J. Underhill, P. Forino, K. Stuart
Journal: Journal of Clinical Oncology (2006)

14103 Background: Advanced pancreatic adenocarcinoma (PCa) portends a poor prognosis. Both capecitabine (CAP) and oxaliplatin (OX) have demonstrated activity in pancreas cancer, may be synergistic, and are well tolerated. We report the outcomes and toxicities of patients (pts) with PCa treated with CAP and OX in combination. Methods: Entry criteria: ECOG PS ≥ 2, adequate renal, hepatic and bone marrow function and at least one measurable lesion. Pts were allowed to have received one prior chemotherapy for advanced disease, or adjuvant therapy if completed more than 12 months prior. Pts received CAP 2000 mg/m 2 po taken in two divided doses for 14 days starting on day one and OX 130 mg/m 2 IV on day 1 of each 21 day cycle. Response was recorded per RECIST criteria. Results: Sixteen pts have been enrolled, 14 have been treated (2 pts suffered rapid decline prior to start) thus far. The average number of cycles was 2.7, and 3 pts received 4 or more cycles. Of 10 evaluable pts, 6 had stable disease, 1 had a partial response and 3 had progressive disease. Of the 5 pts who had received prior chemotherapy with progression, 3 had stable disease, and one had a partial response, and 1 had progressive disease. Of the 5 pts who had not recieved prior chemotherapy, 3 had stable disease and 2 had progressive disease. Median time to progression was 7 weeks. Four pts are still undergoing treatment. Toxicity was acceptable in the12 pts evaluated. Three grade 4 events occurred and were unrelated to therapy (venous thromboembolism, stroke, hyperbilirubinemia). Grade 3 toxicity was noted in 5 pts (fatigue, nausea, vomiting and diarrhea). Grade 1/2 toxicity was minimal, predominated by neurosensory deficits in 7 pts, hand foot syndrome (HFS) in four pts, and nausea in 4 pts. Two pts stopped therapy due to toxicity, one for HFS (grade 2) after 1 cycle, and one for diarrhea (grade 3) after two cycles. Four pts required dose reduction. Conclusion: The combination of CAP and OX is reasonable and tolerable treatment of pancreas cancer with activity even in pts receiving second line chemotherapy. Accrual is ongoing. No significant financial relationships to disclose.
Overexpression of the Histone Methyltransferase ΕΖΗ2 in Chronic Lymphocytic Leukemia Confers Protection from Apoptosis and Is Linked to Clinical Aggressiveness
Authors: Nikos Papakonstantinou, Stavroula Ntoufa, Elisavet Chartomatsidou, Andreas Agathangelidis, Tzeni Karamanli, Achilles Anagnostopoulos, Paolo Ghia, Richard Rosenquist, Chrysoula Belessi, Kostas Stamatopoulos
Journal: Blood (2014)