tbuckley/cabot-search huggingface dataset:
Absence of chlamydial infection in Japanese patients with orbital adnexal MALT lymphoma
Authors: Y. Yakushijin, T. Kodama, K. Tanimoto, J. Yamanouchi, T. Azuma, H. Narumi, T. Hato, H. Hasegawa, M. Yasukawa
Journal: Journal of Clinical Oncology (2007)

18523 Background: The extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct B-cell lymphoma that develops in extranodal sites and usually has an indolent clinical course as a localized disease. Recent clinicopathological studies suggest a strong relation between MALT lymphoma and inflammatory diseases of the epithelium such as autoimmune diseases and infections (Sjogren’s syndrome, Hashimoto’s thyroiditis, Helicobacter pylori infection, and etc.), because chronic antigen stimulation has been causally linked to the development of B-cells lymphoproliferative diseases. MALT lymphoma grows in extranodal lymphoid tissue and exists in epithelium tissues, and it is often difficult to distinguish malignant lymphoid tissue from benign inflammation. This is one cause since recent positive or negative correlations between ocular adnexal MALT lymphomas and chlamydial infections have been reported from different researchers, indicate several possible explanations. Methods: Twenty-three cases of ocular adnexal MALT lymphoma in southern regions of Japan, whose monoclonality was confirmed by immunoglobulin heavy chain gene rearrangement and/or cell surface antigens, were analyzed for evidence of several causative factors using ELISA analysis to detect antibodies and Southern blot analysis followed by specific PCR gene amplification. Results: Our series of patients did not show any serological relations to Epstein-Barr virus, Hepatitis C virus, and Chlamydophila psittaci. Two cases had positive serum antibodies for autoimmunity, and another two cases had positive antibodies against Chlamydia trachomatis. None of our cases showed the presence of chlamydial 16S rRNA and 16S-23S spacer rRNA genes (C. psittac, C trachomatis, C. pneumoniae, and C. felis) after Southern blot analysis followed by PCR amplification. Conclusions: Inflammatory agents are still unknown in our series of orbital adnexal MALT lymphomas, and some types of chlamydial infections are not associated with orbital adnexal MALT lymphoma in southern regions of Japan. No significant financial relationships to disclose.
A two-arm prospective trial evaluating the ability of EBV PCR to diagnose and monitor posttransplant lymphoproliferative disorder
Authors: D. E. Tsai, L. Douglas, C. Andreadis, S. Arnoldi, R. Blood, K. Olthoff, S. Brozena, E. A. Stadtmauer, R. Kotloff, V. Ahya
Journal: Journal of Clinical Oncology (2007)

8057 Background: EBV PCR is known to be useful in the management of patients with PTLD. However, the optimal DNA target, relative importance of peripheral blood intracellular versus free plasma EBV, and baseline profile of these EBV PCR variations in a transplant population remains unclear. This study explored these issues as well as assessed the utility of a 6 assay EBV PCR panel in the management of patients with suspected PTLD. Methods: A prospective 2-arm study was performed. Arm A consisted of 31 patients who underwent lung transplantation. Arm B consisted of 35 patients evaluated for possible PTLD. All patients underwent an initial evaluation with EBV PCR and EBV VCA antibody titer. Arm B patients were evaluated for PTLD with CT scans and biopsies of lesions. All patients in Arm A and those in Arm B with documented PTLD were then followed. For the EBV PCR panel, peripheral blood was separated into plasma and whole blood cells and then DNA was purified. Real time EBV PCR was then performed on both samples using primer sets against LMP, EBER and EBNA. Results: No patients on control Arm A developed PTLD. Seventeen (49%) patients on Arm B were found to have PTLD. Thirteen of 17 (76%) had EBV(+) PTLD. Eighteen Arm B patients were given non-PTLD diagnoses. Of 62 patients evaluable for EBV antibody titers, 60 (97%) had IgG for EBV VCA. In Arm A, only 1/31 (3%) patients developed a transient positive low level plasma EBV load. Fourteen of 31 (42%) had detectable low-level intracellular EBV. In patients with EBV(+) PTLD, 11/13 had EBV in plasma and intracellular samples, 1 had intracellular EBV only and 1 patient with isolated CNS PTLD had a negative EBV panel. The EBV PCR panel had high sensitivity (92%) and specificity (67%) for diagnosing EBV(+) PTLD. Comparing the individual PCR assays, whole blood EBER had the best sensitivity (92%) and plasma EBNA &amp; EBER had the best specificity (100%). The EBV PCR panel tracked patient's clinical course well (p=0.06) as they proceeded through treatment. EBV plasma (p=&lt;0.01) and whole blood (p=0.04) copy numbers by EBNA PCR inversely correlated with EBV VCA IgG titers. Conclusion: Peripheral blood EBV PCR is useful in the diagnosis and monitoring of patients with EBV(+) PTLD. No significant financial relationships to disclose.
Pemetrexed and carboplatin plus bevacizumab as first-line therapy for advanced non-squamous non-small cell lung cancer: preliminary safety results of a phase II trial
Authors: J. D. Patel, T. A. Hensing, P. O’Keeffe, K. Frantonius, E. Hart, P. Bonomi
Journal: Journal of Clinical Oncology (2006)

17111 Background: Bevacizumab is a novel antiangiogenic agent that has been shown to improve response rates and survival of patients with advanced non-squamous NSCLC when added to paclitaxel and carboplatin. Pemetrexed is a multitargeted antimetabolite that has shown activity in NSCLC as a single agent and when combined with carboplatin. Because the combination of pemetrexed and carboplatin has activity comparable to that of other standard platinum doublets and promising toxicity profile (Zinner, 2005), the addition of bevacizumab to this regimen is investigated. Methods: This single cohort, phase 2 study evaluates the safety and efficacy of the combination of pemetrexed and carboplatin plus bevacizumab in patients with untreated non-squamous NSCLC. Eligibility requires ECOG performance status 0–1, Stage IIIB (malignant effusion) or Stage IV non- squamous NSCLC, no evidence of CNS metastases, no anticoagulation. Treatment consists of pemetrexed 500 mg/m 2 over 10 minutes, carboplatin AUC 6 over 30 minutes, and bevacizumab 15 mg/kg over 30–90 minutes. Treatment is repeated every 21 days for 6 cycles. For patients who have either stable disease or partial response, pemetrexed 500 mg/m 2 and bevacizumab 15 mg/kg are continued every 21 days until progression of disease or toxicity. All patients receive folic acid, vitamin B 12 and steroid prophylaxis. Tumor response is assessed using RECIST every 2 cycles during treatment with carboplatin and then every 3 cycles during treatment with pemetrexed and bevacizumab alone. Results: From 8/2005 to 12/2005, 10 (of planned 50) patients with Stage IIIB and IV non-squamous NSCLC have been enrolled and treated. Patient characteristics are: median age: 65 (48–71), 20% female, 80% male, 30% stage IIIB, 70% stage IV. Median number of cycles delivered is 5 (range 1–9). No patient has discontinued therapy secondary to progressive disease or toxicity to date. 6 patients are evaluable for response: 1 PR, 1 minor response (24% reduction), 4 SD. No grade 3/4 toxicities have been experienced. Conclusions: This is a highly tolerable and active regimen with little toxicity to date. Updated response and toxicity data will be forthcoming. Supported by Genentech Inc and Lilly Pharmaceuticals. [Table: see text]
Developmentally restricted differentiation antigens in human ovarian cancer
Authors: K. Odunsi, N. E. Tchabo, A. F. Beck, A. J. Miliotto, O. Cabellero, E. Sato, P. Mhawech-Fauceglia, C. Andrews, S. Lele
Journal: Journal of Clinical Oncology (2008)

16523 Background: Cancer cells recapitulate many behaviors of pluripotent stem cells. Cancer embryo antigens or developmentally restricted differentiation antigens (DRDAG) such as PLAC1, a human X-linked gene with placenta-specific expression and Developmental Pluripotency-Associated-2 (DPPA2) are expressed in pluripotent embryonic cells. These antigens may prove to be markers of ‘repopulating’ cells with stem-cell like characteristics that could be critical targets for immunotherapy in epithelial ovarian cancer (EOC). Our objective was to define the frequency of PLAC1 and DPPA2 expression in these patients and correlate expression with clinical outcome. Methods: A RNA master panel of 20 human tissues was used to evaluate expression of PLAC1 and DPPA2 using standard PCR. RNA was isolated from 101 patient specimens with ovarian, primary peritoneal or fallopian tube cancers. Expression for PLAC1 and DPPA2 was performed using standard PCR. Immunohistochemistry (IHC) with anti-human CD4, CD8, and CD25/FOXP3 was performed on a subset of these tumor specimens. The Wilcoxon Mann Whitney test was used to determine the relationship between tumor infiltrating lymphocytes (TILs) and DRDAG expression. Recurrence free (RFS) and overall survival (OS) estimates were calculated using the Kaplan Meier method. Results: PLAC1 was expressed in placenta, bone marrow, fetal liver, lung, prostate, thymus, thyroid, and trachea. DPPA2 expression was restricted to placenta and testis. Of the 101 patient specimens, 21 expressed PLAC 1, 31 expressed DPPA2, 6 expressed both, and 40 expressed either PLAC1 or DPPA2. DPPA2 positivity is associated with older age at diagnosis (p=0.0024) and larger residual tumor burden at initial surgery (p=0.03). DPPA2 positivity also showed a trend toward higher stromal infiltrating CD8+ T-cells (p=0.056). The presence of PLAC1 and DPPA2 did not have a statistically significant effect on RFS or OS. Conclusions: The data shows aberrant expression of PLAC1 and DPPA2 by PCR in a significant proportion of EOC patients. The tissue restricted expression of the DRDAGs, potential to represent markers of stem cells, and possible existence of DRDAG-specific T cells indicate that PLAC1 and DPPA2 are attractive targets for antigen-specific immunotherapy in EOC. No significant financial relationships to disclose.
Neoadjuvant versus upfront surgical strategies in patients with resectable pancreatic adenocarcinoma: A decision analysis.
Authors: J. F. Tseng, D. B. Evans, J. K. Smith, G. R. Varadhachary, C. H. Crane, R. A. Wolff, M. C. Weinstein
Journal: Journal of Clinical Oncology (2010)

e14514 Background: Postop chemotherapy ± radiation therapy (CRT) is standard for US patients (pts) with resected pancreatic cancer (PC). Neoadjuvant advantages include timely systemic treatment and optimal pt selection for surgery by excluding pts with rapidly progressive disease. Using a decision analysis model, benefits and risks of a neoadjuvant PC strategy were evaluated. Methods: We developed a Markov model to compare life expectancy (LE) in a simulated cohort of 10,000 resectable PC pts who were randomized to strategies of 1) attempted pancreatic resection, recovery and postop CRT; or 2) neoadjuvant CRT, restaging and surgery in the absence of progression. Probabilities were calculated using published data including median survival, assuming exponential survival decreases. Additional analyses used quality-adjusted life expectancy (QALE). Results: Neoadjuvant strategy offered a survival benefit over up-front surgical strategy (LE 20.1 vs. 18.9 mos). Sensitivity analyses were used to assess the importance of progression during preop CRT; when progression > 39.5%, upfront surgery became favored (in order to minimize Type I error, this analysis did not adjust for the fact that pts who progress on preop CRT would likely be early recurrences if randomized to upfront surgery). In an adapted model compensating for quality of life including surgery impact, neoadjuvant CRT proved increasingly superior to upfront surgery (QALE 19.8 vs. 16.4 mos). In a sensitivity analysis to test the potential effect of neoadjuvant regimens with different efficacy, neoadjuvant was favored provided that median survival > 21.5 mo after diagnosis among pts who received neoadjuvant + resection; the advantage of neoadjuvant improved as this median survival increased. Conclusions: Decision analysis modeling suggests that a neoadjuvant CRT strategy offers improved survival compared to a postoperative CRT strategy for resectable PC. Adjusting for quality of life increases the potential neoadjuvant advantage. Importantly, as survival duration increases, the neoadjuvant strategy is increasingly favored – suggesting an added value to neoadjuvant treatment as improved systemic therapies are developed. No significant financial relationships to disclose.
High-Dose Therapy With Autologous Bone Marrow Support as Consolidation of Remission in Follicular Lymphoma: Long-Term Clinical and Molecular Follow-Up
Authors: John Apostolidis, Rajnish K. Gupta, Demetrios Grenzelias, Peter W. M. Johnson, Vassiliki I. Pappa, Karin E. Summers, Ashiq Salam, Keith Adams, Andrew J. Norton, John A. L. Amess, Janet Matthews, Mike Bradburn, T. Andrew Lister, Ama Z. S. Rohatiner
Journal: Journal of Clinical Oncology (2000)

To evaluate the long-term results of high-dose therapy (HDT) in follicular lymphoma, with specific emphasis on the prognostic significance of polymerase chain reaction (PCR)-detectable Bcl-2/IgH rearrangements.Between June 1985 and October 1995, 99 patients with follicular lymphoma received HDT as consolidation of second or subsequent remission. Bone marrow was treated in vitro with anti-B-cell antibodies and complement.Sixty-five patients remained alive, 49 treatment-failure free, with a median follow-up of 5.5 years (range, 1.5 to 12.5 years). Four "early" and 10 "late" deaths occurred from treatment-related causes; seven of the latter were due to secondary myelodysplasia (s-MDS) or secondary acute myeloblastic leukemia. Overall, 12 (12%) of the 99 patients developed s-MDS or acute myeloblastic leukemia. Kaplan-Meier estimates of freedom from recurrence (FFR) and survival rates at 5 years were 63% (95% confidence interval [CI], 52% to 72%) and 69% (95% CI, 58% to 78%), respectively. For all 99 patients, in multivariate analysis, absence of the Bcl-2/IgH rearrangement at the time of diagnosis (hazards ratio [HR], 0.39; P =.04) and three or fewer treatment episodes before HDT (HR, 0.03; P =.001) were significant prognostic factors for improved survival. For patients bearing Bcl-2/IgH rearrangements, in univariate and multivariate analyses, absence of a PCR-detectable Bcl-2/IgH rearrangement during follow-up was associated with a significantly lower risk of recurrence (adjusted HR, 0.13; P <.001) and death (HR, 0.25; P =.02), whereas the PCR status of the reinfused bone marrow did not correlate with outcome.Prolonged FFR can be achieved in patients with follicular lymphoma after HDT, but as yet there is no survival advantage compared with conventional treatment. These results confirm that elimination of cells bearing the Bcl-2/IgH rearrangement is highly desirable and should be attempted. The incidence of s-MDS is of increasing concern in this setting.
Gemcitabine plus docetaxel versus docetaxel in patients (pts) with HER2-negative locally advanced or metastatic breast cancer (MBC): A randomized phase III study
Authors: D. L. Nielsen, S. T. Langkjer, K. Bjerre, S. Cold, L. Stenbygaard, P. G. Soerensen, C. Kamby
Journal: Journal of Clinical Oncology (2009)

1015 Background: Gemcitabine (G), either as a single agent or in combination with taxanes, has demonstrated efficacy in MBC in phase II and III studies. We conducted a phase III study to compare time to progression (TTP) of G plus docetaxel (T) versus (vs.) T alone. The secondary endpoints included overall survival (OS), overall response rate (ORR), and toxicity. Methods: Females with HER-2-negative locally advanced or MBC and a WHO performance status ≤ 2 were randomized to GT (G 1,000mg/m 2 day 1 + 8; T 75mg/m 2 day 1) or T (100mg/m 2 day 1) every 21 days. Pts were previously untreated, had prior anthracycline-based (neo)adjuvant chemotherapy or had received a single prior anthracycline-bsed chemotherapy regimen for MBC. Time-to-event endpoints were estimated using the Kaplan-Meier method, and the log-rank test was applied for comparisons between regimens. The planned sample size was 254 evaluable pts with α I and β of 0.05 and 0.90, respectively. Results: A total of 336 pts were randomized (170 GT; 166 T), data from one centre are yet missing and the present evaluation is based on data from 306 pts (155 GT; 151 T). The pts had a median age of 58 years in both regimens; range 36–73 years and 30–74 years, respectively. The median TTP was 7.5 months for the GT regimen vs. 6.5 months for the T regimen. The GT arm demonstrated an ORR of 44% vs. 38% in the T arm with 4 and 3 % complete responses, respectively. The OS was 13.4 vs. 13.2 months in the GT and T arm, respectively. Hematologic toxicity was common, especially grade 3–4 neutropenia (GT = 69%; T = 61%); infection was reported in 22 and 20% of the pts, respectively (none of the pts received G-CSF). The most commonly reported non-hematologic toxicities of grade 3–4 included mucositis (GT = 2%; T = 5%), diarrhea (GT = 4%; T = 7 %), fatigue (GT = 6%; T = 11%), oedema (GT = 10%; T = 3%), and peripheral neuropathy (GT = 9%; T = 28%). Conclusions: Preliminary data of GT as first- or second-line chemotherapy demonstrates a TTP advantage among HER-2-negative pts with advanced breast cancer. Updated results and proper statistical analyses will be presented. No significant financial relationships to disclose.
Rhoキナーゼ長期阻害は内皮性NO合成とは無関係に低酸素誘発肺高血圧を改善する(Long-term Inhibition of Rho-kinase Ameliorates Hypoxia-Induced Pulmonary Hypertension in Mice Independent of Endothelial NO Synthase)
Authors: Abe Kohtaro, Uwatoku Toyokazu, Oi Keiji, Hizume Takatoshi, Shimokawa Hiroaki
Journal: Circulation (2004)
Nilotinib in accelerated phase chronic myelogenous leukemia (CML-AP) patients with imatinib-resistance or -intolerance: Update of a phase II study
Authors: P. le Coutre, F. J. Giles, J. Apperley, O. G. Ottmann, R. A. Larson, A. Haque, N. Gallagher, G. Rosti, J. E. Cortes, H. M. Kantarjian
Journal: Journal of Clinical Oncology (2008)

7050 Background: The potent and highly selective BCR-ABL inhibitor nilotinib has been approved in both the US and Europe for the treatment of patients (pts) with Philadelphia chromosome-positive (Ph+) chronic phase chronic myelogenous leukemia (CML- CP) and CML-AP who are resistant or intolerant to prior therapy, including imatinib. Methods: This phase 2, open-label study evaluated the efficacy and safety of nilotinib in pts with Ph+ CML-AP with imatinib resistance or intolerance. Primary and key secondary endpoints were rate of confirmed hematologic response (HR) and MCyR, respectively. Nilotinib was started at 400 mg twice daily (BID) and escalated to 600 mg BID for inadequate responses. Results: Included in the analysis were 136 pts who received at least 1 dose of nilotinib. Median age was 58 (22–82) yrs; median dose intensity was 781 mg/day; median treatment duration was 210 days. Confirmed HR occurred in 69/129 pts (54%); 34 (26%) had complete HR. Of imatinib-resistant pts, 55/104 pts (53%) had a confirmed HR, and 14/25 imatinib- intolerant pts (56%) had a confirmed HR. A majority of responding pts (82%) maintained HR for at least 12 months. MCyR occurred in 40/129 pts (31%); 24/129 pts (19%) had complete CyR. Of imatinib-resistant pts, 30/104 pts (29%) had a MCyR, and 10/25 imatinib-intolerant pts (40%) had a MCyR. Time to first HR and MCyR was 1 and 2.8 months, respectively. At 12 months, it is estimated that 57% of pts were without progression and the estimated overall survival rate was 81%. At data cutoff, treatment was ongoing for 57/136 pts (42%). The most common grade 3/4 laboratory abnormalities were thrombocytopenia (41%), neutropenia (39%), anemia (25%), and elevated serum lipase (16%). Grade 3/4 non-hematologic AEs were rare and included nausea, fatigue, headache, and diarrhea. Conclusions: The results of this study confirm that nilotinib induces significant and durable responses in CML-AP pts with imatinib resistance or intolerance. There was minimal nilotinib cross- intolerance in patients intolerant to prior imatinib treatment. Nilotinib is well tolerated, with minimal occurrence of grade 3/4 AEs, and is an effective treatment option for this pt population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Bristol-Myers Squibb, Innovive, Novartis Bristol-Myers Squibb, Novartis Bristol-Myers Squibb, Novartis, Wyeth
Induction chemotherapy with gemcitabine and cisplatin in paranasal sinus tumours
Authors: R. Hussain, A. Jamshed, M. Bilal, K. Shehzad, R. Azhar, M. A. Shah, S. Hameed, M. Arif, Z. Faruqui
Journal: Journal of Clinical Oncology (2006)

15542 Background: There is no standard treatment for locally advanced carcinoma of paranasal sinuses. Induction chemotherapy is frequently used to down stage the disease. Surgery, radiotherapy and chemoradiation are all in use to treat the primary following neoadjuvant chemotherapy treatment. Cisplatin and gemcitabine are active agents in head and neck cancers. We evaluated the response of induction chemotherapy with cisplatin and gemcitabine in carcinoma of the paranasal sinuses. Methods: Between August 2005–November 2005, 5 patients with locally advanced carcinoma paranasal sinuses received induction chemotherapy at Shaukat Khanum Cancer Hospital and Research Centre. There were three males and two females, 19 to 65 (median 45) years of age. Three patients had maxillary and 2 patients had ethmoid sinus tumors. Four patients had Stage IVa and 1 patient had Stage IVb disease. All patients had biopsy proven carcinoma. Histologically the tumour was adenocarcinoma in 1 patient and squamous cell carcinoma in 4 patients. Four patients received 2 cycles and 1 patient received 1 cycle of cisplatin 75 mg/m 2 day 1 and gemcitabine 1000 mg/m 2 day 1 and 8 (repeat day 22) before radical treatment. Response was assessed in all patients with pre and post induction chemotherapy with CT or MRI scan. Results: Overall response rate was 60%. Complete response was seen in one patient and over 50% tumor regression in 2 patients. Disease remained unchanged (no response) in 1 patient. One patient progressed following one cycle and did not receive the second cycle of chemotherapy treatment. The treatment was well tolerated and no grade III or IV toxicity was seen. Conclusions: The combination of gemcitabine and cisplatin in this schedule has low toxicity and significant activity in patients with locally advanced paranasal sinus tumors and is worthy of further study. No significant financial relationships to disclose.