tbuckley/cabot-search huggingface dataset:
Duodenal follicular lymphoma: Clinical and pathologic characteristics, management, and outcomes.
Authors: A. P. Jhaveri, J. Maragulia, A. D. Zelenetz
Journal: Journal of Clinical Oncology (2010)

e18527 Background: Data on the clinical characteristics of duodenal follicular lymphoma (DFL) and outcomes of these patients (pts) are limited. The purpose of this study is to understand clinical and pathologic characteristics of DFL in the context of current treatment (tx) practices. Methods: For the purpose of this analysis, DFL was defined as any case of follicular lymphoma (FL) with involvement of the duodenum at presentation. A retrospective review identified 55 pts with DFL between 9/1993 and 9/2008. Demographics, clinical presentation, pathology, tx, and outcomes were reviewed. Kaplan-Meier (K-M) analysis was performed to evaluate OS and comparisons were made by the log-rank statistic. Results: Clinical features at diagnosis were: median age 57 (33-82); stage I/II, 65%; FLIPI low risk, 55% (22/40); FLIPI intermediate risk, 25% (10/40); incidental presentation, 29%. Of the 39 cases presenting with symptoms, 77% had abdominal pain. Histologic grade of DFL was grade 1 in 80% of cases and grade 2 in 11%. Disease was confined to the duodenum in 20 cases. Other areas of small bowel involvement were observed in 13 pts. Immunohistochemistry studies were consistent with FL: CD20+ 51/51; CD10+ 38/40; BCl2+ 46/48; CD3- 30/35; CD5- 27/29; and cyclin D1- 24/24 cases. Initial tx regimens (n=48) were observation (35.4%), radiation (12.5%), rituximab (12.5%), chemotherapy ± rituximab (22.9%), surgery (10.4%), and antibiotics (6.3%). Complete response was achieved with initial tx in 31.3% cases. After a mean follow-up of 4.8 years (0.5-13.8 years), 18 pts (33%) had no evidence of disease, 32 (58%) were alive with disease, 1 (2%) died of lymphoma, and 4 (7%) died of other causes. Transformation to DLBCL occurred in 6 of the 55 pts at a median of 1.1 years. Of the 17 pts with observation as the initial tx, 5 had progression of disease (POD) (1 transformation to DLBCL) and 0 died of disease. K-M analysis demonstrated that neither initial tx nor stage had an impact on OS. Conclusions: DFL typically presents with localized disease and low or intermediate risk FLIPI. Stage at diagnosis does not affect survival of pts with DFL. Initial tx choice does not affect outcome. Deaths were uncommon and therapy may be deferred until pts have clinical symptoms or POD. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, GlaxoSmithKline, sanofi-aventis Physicians' Education Resource Amgen, Biogen Idec, Genentech, GlaxoSmithKline, Roche
Phase II study of oxaliplatin, capecitabine, and irinotecan (OCI) in patients (pts) with previously untreated advanced colorectal cancer (crc)
Authors: O. A. Pavia, J. Cangiano, R. Crisostomo, W. Caceres, E. Barranco, M. Wright, T. Antonia, S. Antonia, D. Sullivan, C. Garrett
Journal: Journal of Clinical Oncology (2005)

3746 Background: Combination chemotherapy for pts with advanced crc has led to an improved overall survival (os) when compared to monotherapy. Retrospective review of phase III studies demonstrates that pts who are exposed to all three cytotoxic agents (oxaliplatin, 5-fluorouracil and irinotecan) have the longest median os (Grothey A et al: J Clin Oncol. 2004 Apr 1;22(7):1209–14). Current chemotherapy regimens for advanced crc are cumbersome and involve prolonged infusion times. Methods: We propose a phase II study of OCI (oxaliplatin 130mg/m2 day 1 intravenously (iv), irinotecan 180 mg/m2 day 21 iv, and capecitabine 825 mg/m2 by mouth days 1–14, and days 21–35, every 42 days) in pts with advanced, surgically unresectable crc. Results: Eight pts have been enrolled to date: median age 60 years, five females and three males. Three pts have been withdrawn from the study (one for recurrent bowel obstructions due to adhesions, two due to withdrawal of consent due to toxicity). Of four pts evaluable for response, two confirmed partial responses and two unconfirmed partial responses have been observed. Conclusions: This preliminary data show tolerance and encouraging radiographic activity, suggesting that this combination is worthy of further study. Accrual is ongoing, and updated results will be presented at the meeting. No significant financial relationships to disclose.
The Hasford Score Correlates with the Long-Term Molecular Response to Imatinib Treatment for Chronic Myeloid Leukemia Patients and May be Useful for Differentiating Low and Intermediate Risk Patients: A Single Institution Experience
Authors: Jaroslaw Dybko, Ewa Medras, Olga Haus, Bozena Jazwiec, Tomasz Wrobel, Kazimierz Kuliczkowski
Journal: Blood (2014)
Morphometric study of immunohistochemical expression of topoisomerase IIa and p16 correlating with molecular detection of chromosome 17 and 9 instability, in pancreatic adenocarcinoma, using Tissue Microarrays application
Authors: E. Tsiambas, A. Stamatelopoulos, G. Vilaras, E. Thanopoulou, A. Karameris
Journal: Journal of Clinical Oncology (2005)

4100 Background: Aberrations of chromosome 17 and 9 are common genetic events in many cancers including pancreatic adenocarcinoma. Topoisomerase IIa (17q21) is a nucleic enzyme, which affect the topological structure of DNA. Cells die when topoisomerase is inhibited and for this reason is a target for chemotherapy. Also p16 (9q21) is a suppressor gene, a negative regulator of cell cycle, which appear to be inactivated in pancreatic adenocarcinoma. Methods: Using Tissue Microarray Technology (Chemicon TMArrayer ATA100), we created two 50 tumor TMAs. 100 pancreatic adenocarcinomas (26 High, 43 Moderate and 31 Low differentiated) including 7 Pan Ins (I-III) were obtained and embedded into two paraffin blocks (core diameter: 1mm). Immunohistochemical stain for anti-Topoisomerase IIa (Ki S1-DAKO Corp) and anti-p16 (DAKO) combined with CISH for the detection of chromosome 17 and 9 instability (Chr 17 Centromeric probe, Zymed kit) and specific gene status (Topo IIa Amplification probe-Zymed kit) were performed in 2 and 5 μm sections. Finally using a semi-automated Image Analysis System we evaluated the nuclear features of number, optical density and the number of signals of chromosome 17 and 9 centromeres and gene copies per nucleus. Statistical analysis was performed by SPSS version 11.0 software. Results: A significant proportion of pancreatic adenocarcinomas showed overexpression of the TopoIIa (42/100) and a high proportion showed loss of the specific p16 stain (83/100), while CISH application showed TopoIIa amplification (high or low level) or deletion of one allele in 38/42 cases. Also chromosome 17 and 9 instability were observed in 39/42 and 38/83 cases, which were displayed as aneusomy, monosomy or polysomy. Conclusions: The results indicate that topo IIa amplification or deletion is a critical genetic event correlating with biological behavior in pancreatic adenocarcinomas and p16 inactivation happens frequently. But, the most important is the early inactivation of p16 gene, which we observed in PanIns. No significant financial relationships to disclose.
Prediction of response to RAD001 (everolimus) in patients with metastatic renal cell carcinoma.
Authors: C. Seidel, M. Fenner, A. Merseburger, M. Heuser, A. Ganser, V. Gruenwald
Journal: Journal of Clinical Oncology (2010)

e15126 Background: RAD001 inhibits mTOR and is the standard treatment after failure of anti-VEGF-targeted therapies in patients with metastatic renal cell carcinoma (mRCC). We analyzed the course of disease of 42 patients and explored patients characteristics to predict the treatment outcome in patients receiving RAD001. Methods: We retrospectively analyzed 42 patients who received RAD001 within RECORD1 and Expanded access trial since April 2007. Eight patients still receive RAD001. First-line therapy before RAD001 consisted of tyrosine kinase inhibitors (TKI) sunitinib (N=39) or sorafenib (N=3). Fifteen patients received an additional TKI as 2nd line prior to RAD001 exposure. 23 patients received immunotherapy before targeted therapy was available. Tumor burden (TB) was determined by sum of largest diameter according to RECIST. Factors associated with overall survival (OS) since start of RAD001 treatment and progression-free survival (PFS) were analysed by the Kaplan-Meyer estimator and the Log-Rank Test. Results: The median PFS for first line TKI was 7.7 months and the median PFS for second line TKI was 6.4 months. Subsequent treatment with RAD001 achieved a median PFS of 4.4 months (range 0.3-17.8) and the median OS was 8.3 months (range 0.4-26.3). Disease control (stable disease or partial remission) was achieved in 28 of 40 patients (70%). Response to therapy was not evaluated in two patients. Twenty patients received additional systemic therapy after failure of RAD001. Patients with progressing liver lesions during RAD001 treatment showed a trend for inferior PFS (p=0.08). Inferior OS was detected in patients with either TB above the median (155 mm) (p<0.0001) or liver metastases (p=0.017). Patients with a MSKCC-score 0-2 had a superior survival (p=0.05) compared with patients with a MSKCC-score above three. Conclusions: In our retrospective analysis PFS for RAD001 treatment was similar for all patients. However, patients with progressing liver lesions showed a trend for inferior PFS. Furthermore, high TB, high MSKCC-score, and liver metastases were negative predictors for OS in patients treated with RAD001. No significant financial relationships to disclose.
TBCRC 006: A multicenter phase II study of neoadjuvant lapatinib and trastuzumab in patients with HER2-overexpressing breast cancer.
Authors: J. C. N. Chang, I. A. Mayer, A. Forero-Torres, R. Nanda, M. P. Goetz, A. A. Rodriguez, A. C. Pavlick, T. Wang, S. G. Hilsenbeck, C. Gutierrez, R. Schiff, C. K. Osborne, M. F. Rimawi
Journal: Journal of Clinical Oncology (2011)

505 Background: We reported that inhibition of the HER2 pathway with lapatinib (L) and trastuzumab (T) to block all homo- and hetero-dimer signaling leads to rapid eradication of HER2-amplified human xenografts in mice. In this clinical trial, we sought to translate these findings to patients (pts) using the L+T regimen without chemotherapy. Methods: Women with HER2+ breast cancers (>3cm or >2cm with palpable lymph nodes) were eligible. Pts received weekly T (4 mg/kg loading then 2mg/kg) and daily L 1,000 mg for 12 weeks. ER+ pts also received letrozole (plus goserelin if premenopausal), to block ER/HER crosstalk. Biopsies were obtained at baseline and weeks 2, 8, and 12 (surgery). This stratified study (ER+, ER−) was designed to detect an increase in pathologic response rate (pRR; defined as pathologic complete response in the breast (pCR) plus residual disease that is <1 cm (npCR)) from 10% with T alone to 35% in each stratum, using a Simon optimal two stage design, with one-sided alpha=5% and power=85%. Both strata met criteria to continue to full accrual (at least 21 per stratum). Results: We enrolled 66 eligible pts; 64 were evaluable for response (Table). Median tumor size was 6 cm (range 1.5-30 cm). Adverse events (AEs) were overall modest: mainly grade 1-2 (GI: 64%, skin: 45%). Grade 3 metabolic, GI, and liver (18%, 12 pts) and grade 4 liver toxicity (1 pt) were also observed. Two pts had treatment related serious AEs (GI, liver). Efficacy results below are for the first 57 pts who had surgery as of 1/4/2011. Results from all pts will be presented at the meeting. Overall pRR was 53% (ER+: 55%, ER−: 47%). More importantly, the overall pCR rate was 28% (ER+: 21%, ER−: 42%). Conclusions: L+T for 12 weeks led to a high pCR rate in pts with large HER2+ tumors without chemotherapy. Pts with npCR might be converted to pCR with longer therapy, a hypothesis to be tested in a follow up study. Our data strongly suggest that selected pts with HER2+ tumors may not need chemotherapy. N % Menopausal status Pre 32 48 Peri 4 6 Post 30 46 Age ≤50 35 53 >50 31 47 Race White 48 73 Black 14 21 Other 4 6 Ethnicity Hispanic 22 33 Not Hispanic 43 65 Tumor size ≤5 cm 24 39 >5 cm 38 61 Median 6 cm ER + 41 62 - 25 38
Is there increased risk of clostridium difficile infection with hematologic malignancies?
Authors: K. Bishop, S. E. Reinert, J. J. Castillo
Journal: Journal of Clinical Oncology (2011)

e19705 Background: Clostridium difficile (C. difficile) infection has become a significant health care issue. Antibiotic exposure is a known risk factor for this infection. Current febrile neutropenia (F&N) management guidelines recommend the initiation of broad-spectrum antibiotics, even if no infection is identified. This may place cancer patients with F&N at increased risk for C. difficile infection. We aim to compare the characteristics between cancer patients who developed or did not develop a C. difficile infection after an episode of F&N. Methods: Between 2005 and 2009, medical records from our institutions were reviewed to identify patients hospitalized for fever, neutropenia and C. difficile infection. Patients with ANC >500 x 109/L, were not treated for their F&N, or had F&N for reasons other than malignancy or chemotherapy were excluded. The primary outcome was a positive C. difficile test after an F&N episode. Logistic regression tests were used to compare characteristics between C. difficile-positive and negative groups. Results: 139 patients with F&N were identified, 28 of whom were diagnosed with C. difficile infection within 3 months of admission (20%). Logistic regression tests comparing C. difficile-positive and negative patients showed statistically significant differences in duration of hospital stay (24 vs. 9 days; OR 1.06 95% CI 1.03-1.1, p=0.0004), total antibiotic days (23 vs. 11 days, OR 1.04 95% CI 1.01-1.07, p=0.001) and having a primary diagnosis of hematologic vs. solid malignancy (OR 2.6 95% CI 1.1-6.5, p=0.03). There were no significant differences in age, ANC or duration of neutropenia between the C. difficile-positive and negative groups. Conclusions: Patients with hematologic malignancies had a higher OR of developing C. difficile infection after an F&N episode than patients with solid tumors. There were also small but significant increases in duration of hospital stay and total antibiotic days during F&N episodes in cancer patients who later developed C. difficile infection. These findings suggest that further study is needed into C. difficile prevention strategies in specific types of cancer patients.
NGS-based targeted RNA sequencing for expression analysis of patients with triple-negative breast cancer using a modulized, 96-gene biomarker panel.
Authors: Byung-In Lee, Kahuku Oades, Lien Vo, Jerry Lee, Mark Landers, Yipeng Wang, Joseph Monforte
Journal: Journal of Clinical Oncology (2012)

56 Background: Gene expression profiling has been shown to be effective in analyzing postoperative tumor samples in various cancers. However, in analyzing small specimens such as core biopsies, the limited amount of available material makes multi-gene analyses difficult or impossible. Microarray-based analyses also provide limited dynamic range. We describe the development of targeted RNA-sequencing methodology which combines the power of a universal RNA amplification with NGS for an ultra-deep expression analysis of multiple target genes, enabling &lt;100 ng of sample input for multi-gene analysis in a single tube format. Methods: The gene expression patterns of triple-negative breast cancer FFPE samples were analyzed using a 96-gene breast cancer biomarker panel across three different platforms: Affymetrix Human Gene ST 1.0 microarrays, a pre-developed OncoScore qRT-PCR panel, and targeted RNA-seq. For targeted RNA-seq analysis, the 96-gene panel was amplified using a universal, single-tube “XP-PCR” amplification strategy followed by sequence analysis using the Ion-Torrent Personal Genome Machine. Results: Targeted RNA-seq provided the most sensitivity in terms of detection rates with &lt;100 ng FFPE RNA input and provides unlimited dynamic range with increased sequencing depth. Expression ratio compression issues typically associated with a high number of pre-amplification cycles in standard multiplex-primed methods were not observed here. Low expressing genes, undetectable by qRT-PCR analysis from 1,000 ng input FFPE RNA, were detected and eligible for expression analysis with a significant number of sequencing reads. Alternative transcription/splicing analysis is also possible from sequence analysis of the target transcripts using targeted RNA-seq. Conclusions: By combining universally primed pre-amplification and NGS in multi-gene expression analysis, targeted RNA-seq provides the most sensitive gene expression analysis methodology.
Embedded palliative medicine model for inpatient solid tumor oncology patients utilizing corounding and consultation criteria: A quality improvement pilot.
Authors: Susan McInnes, Bassam N. Estfan, Alberto J. Montero
Journal: Journal of Clinical Oncology (2016)

148 Background: Hospitalized patients (pts) on solid tumor oncology (STO) services have palliative needs including pain management. This quality improvement project sought to establish a new STO-specific co-rounding PM consult service, evaluate the use of consult criteria for STO inpatients, assess the impact/interest in an embedded service, improve access to PM for STO pts and improve palliative education to STO teams. Methods: During October 2015 to January 2016, a new PM consult service was established for the 2 STO inpatient services at Cleveland Clinic. The PM attending physician (MD) rounded with each of the STO teams twice a week. On weekdays, the PM MD chart-screened all STO pts for palliative needs such as uncontrolled pain (2 pain scores ≥ 6 out of 10 in 24 hours), unplanned readmission within 30 days or contact with a PM MD as an outpatient. Other PM needs were assessed on rounds. PM consults were offered for pts who screened positive and were performed if approved by the STO team. STO MDs were surveyed anonymously regarding acceptance of the embedded service. Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) data regarding pain management during the pilot period was reviewed. Results: Average daily census for the 2 STO teams was 28 pts. There were 282 positive palliative screens in 4 months, 119 of whom were seen in consultation (42%.) The embedded service saw 42-45 new consults per month. The PM team followed 22-35% of all STO inpatients. 14-18 pts/month new to PM were referred to the outpatient PM clinic after discharge. STO MDs indicated strong acceptance of the embedded PM team for pain management, STO team education and coordination of care. All STO MDs wanted the service to continue. HCAHPS pain scores for the entire STO floor improved from a baseline 39 th percentile to 98 th percentile. Conclusions: PM was integrated successfully into daily hospital care of STO pts at our institution using a co-rounding model and consult criteria. The service was busy and well received by STO MDs. Continuity with outpatient PM was provided. HCAHPS pain scores improved for the entire STO floor, including pts not directly seen by PM.
Thalidomide plus tegafur/uracil for the treatment of advanced/metastatic hepatocellular carcinoma (HCC): A phase II single-arm study
Authors: C. Hsu, D. Chang, Z. Lin, K. Lee, C. Hsiao, Y. Shen, A. Cheng, C. Hsu
Journal: Journal of Clinical Oncology (2008)

15598 Background: Thalidomide (T), an agent with potential anti-angiogenic activity, has shown modest activity in advanced/metastatic HCC. Tegafur/uracil (UFT), an oral prodrug of 5-fluorouracil, is active in various gastrointestinal tract cancers. Metronomic administration of UFT has shown anti-angiogenic effect in preclinical models. This study tested the efficacy and safety of the combination of T with low-dose UFT in advanced HCC. Methods: Patient (Pts) with untreated, advanced HCC received T 100mg bid and UFT 125mg/m2 (based on tegafur) bid continuously. HCC should be diagnosed by either histology examination or by fulfillment of all 3 clinical criteria [(1) chronic HBV or HCV carrier, (2) hepatic tumors with image findings compatible with HCC, (3)α-fetoprotein ≥ 400ng/ml]. Treatment was continued in the absence of disease progression or unacceptable toxicity. Primary endpoint was response rate (RR) by RECIST; secondary endpoints were disease control rate (CR+PR+SD), progression-free survival (PFS), overall survival (OS), and safety. Simon's two-stage phase II optimal design (P0 = .05, P1 = .20, and α = .05, β= .10) was used. Twenty-one evaluable pts were planned to be enrolled in the first stage, a total of 41 pts will be recruited if ≥ 2 responders were observed in the first stage. Results: Between Jul. 2006 to May 2007, 23 intent-to-treat pts (M/F 22/1, median age 56) were enrolled for the first stage. There were 13 (57%) patients with AJCC stage IV, 14 (61%) with portal vein thrombosis, 13 (57%) with extrahepatic metastasis, and 9 (39%) with CLIP score = 4. The virology profiles of HBV/HCV/non-B non-C were 16/3/4. Among 21 pts evaluable for tumor response, there were 2 PR (9.5%) and 4 SD (19%), with a disease control rate of 28.5%. Median OS was 5.4 (range, 1.5–14.5) months and median PFS was 1.8 (range, 0.6–9.0) months. The most common treatment-related grade 3 toxicity was somnolence (n=3) and there was no grade 4 toxicities. Conclusions: The combination of T+UFT is a safe and potential effective regimen for advanced HCC. The second stage of patient enrollment is currently ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration TTY Biopharm