tbuckley/cabot-search huggingface dataset:
The prognostic significance of the number of extranodal sites in the patients with disseminated diffuse large B-cell lymphoma treated with R-CHOP
Authors: C. Yoo, B. Sohn, J. Kim, D. Yoon, J. Huh, S. Kim, D. Lee, S. Kim, J. Lee, C. Suh
Journal: Journal of Clinical Oncology (2009)

8570 Background: The combination of rituximab and CHOP chemotherapy (R-CHOP) has improved survival of patients with diffuse large B-cell lymphoma (DLBCL). Recently, several reports have shown that standard International Prognostic Index (IPI) became less powerful prognostic predictor in patients with DLBCL in the era of R-CHOP. We evaluated the prognostic factors of DLBCL patients treated with R-CHOP. Detailed analysis was planned regarding the number of extranodal sites because of its higher frequency in Korea. Methods: Between January 2002 and May 2008, 126 patients with stage III/IV DLBCL treated with R-CHOP were identified. We performed the retrospective analysis of the clinicopathologic factors and verified the predictive power of standard IPI and revised IPI (R-IPI) which was reported by the study group of British Columbia. Various numbers of extranodal sites were analyzed for further stratification and we set E-IPI as the IPI when the number of extranodal sites is stratified in ≤2 vs &gt;2. Results: In the univariate analysis, the number of extranodal sites (≤2 vs &gt;2) was a significant prognostic factor for complete response (CR) (p=0.04), event-free survival (EFS) (p=0.01) and overall survival (OS) (p&lt;0.001). Age was also significant for EFS (p=0.03). When the number of extranodal site was stratified differently (0 vs &gt;0, or ≤1 vs &gt;1), these were not associated with CR, EFS and OS. On the multivariate analysis, the number of extranodal sites (≤2 vs &gt;2) remained significant for EFS (p&lt;0.01, HR 2.6) and OS (p&lt;0.01, HR 3.5). The standard IPI identified 3 risk groups with 2-year EFS; 68%, 55%, 56% (p=0.17) and 2-year OS; 85%, 68%, 58%, respectively (p=0.04). The R-IPI classified 2 risk groups with 2-year EFS; 65%, 50% (p=0.02) and 2-year OS 76%, 62%, respectively (p=0.04). The E-IPI represented 3 risk groups with 2-year EFS; 79%, 56%, 42% (p=0.01) and 2-year OS; 86%, 70%, 39%, respectively (p=0.001). The patient group with survival of less than 50% was only recognized by E-IPI. Conclusions: The number of extranodal sites (≤2 vs &gt;2) is the most significant prognostic factor of EFS and OS. Although all three indices remain predictive, E-IPI is the best model to identify the prognostic group in this cohort with stage III/IV DLBCL treated with R-CHOP. No significant financial relationships to disclose.
A phase II study of sunitinib on a continuous dosing schedule in patients (pts) with relapsed or refractory urothelial carcinoma (UC)
Authors: D. J. Gallagher, M. I. Milowsky, S. R. Gerst, S. Tickoo, N. Ishill, N. Ishill, A. Regazzi, A. Trout, D. F. Bajorin
Journal: Journal of Clinical Oncology (2009)

5072 Background: Suntinib has demonstrated activity in the second-line setting for pts with advanced UC when administered on a 4 week on/2 week off schedule. This study was designed to evaluate an alternative 37.5 mg/day continuous dosing schedule for sunitinib in the same setting. Methods: The primary objectives of this single institution phase II study of sunitinib in pts with UC who have failed prior chemotherapy were: 1) to determine the response rate (by RECIST); and 2) to evaluate toxicity. Secondary endpoints include: 1) correlation of response and toxicity with HIF and mTOR pathway marker expression; and 2) phamacokinetics. Pts may not have received &gt;4 prior cytotoxic agents. Pts received sunitinib 37.5 mg/day continuous dosing.. Response was assessed after each of the initial 4 cycles and every other cycle thereafter. A minimax 2-stage design was used (maximal 32 pts). Results: 31 pts (21 M, 10 F) with a median age of 68 yrs and median KPS of 90 were enrolled between 10/15/07 and 12/18/08. Primary sites included bladder (28), and renal pelvis (3). Prior therapy included 1 pt with 1 drug, 19 pts with 2, 7 with 3 and 4 with 4. 25 pts had visceral metastases and 6 pts had lymph node only metastases. 25 pts were evaluable for response after completing at least 1 cycle. One pt achieved PR, 12 pts had SD, 12 had PD, 2 are too early to assess for response, and 4 patients did not complete cycle 1 (2 related to toxicity, and 2 related to non-treatment-related deaths). Radiographic regression was seen in liver, lung, soft tissue and lymph nodes. With a median follow up of 4 months, median progression free survival was 2 months (95% CI, 1 - 4 months) and median overall survival was 7 months (95% CI, 4 months - not achieved). Clinically significant toxicity (Grade 3/4) included: abdominal pain (1), anorexia (1), diarrhea (1), fatigue (4), hand and foot syndrome (2), hemorrhage (2), hypertension (2), mucositis (2), thrombosis (2), and emesis (1). Conclusions: Sunitinib has modest activity when administered on a 37.5 mg continuous dosing schedule to patients with relapsed or refractory UC with a similar toxicity profile to the 50 mg in the 4 /2 schedule. Upcoming trials will evaluate sunitinib in combination with standard chemotherapy in pts with UC. [Table: see text]
Objective antitumor activity of acivicin in patients with recurrent CNS malignancies: a Southwest Oncology Group trial.
Authors: S A Taylor, J Crowley, T W Pollock, H J Eyre, C Jaeckle, H E Hynes, R L Stephens
Journal: Journal of Clinical Oncology (1991)

Acivicin (AT-125) is a glutamine antagonist with dose-limiting, schedule-dependent CNS toxicity and predictable CSF penetration after intravenous administration. Because of these properties, a trial in CNS malignancies was initiated. Thirty-two patients with recurrent or residual malignant astrocytomas were treated with AT-125. The majority of patients had glioblastoma multiforme (24) and had received prior nitrosoureas (21). The median age was 50 years, and Southwest Oncology Group (SWOG) performance status was 2. The major determinant of response was based upon radiologic criteria using computed tomographic (CT) scanning and/or magnetic resonance imaging (MRI) scans. The tumor mass was measured in two perpendicular planes, which yielded the largest cross-sectional area. Standard solid tumor criteria for response were used. All responding patients also had a stable or tapered dose of corticosteroids with stable or improved performance status and neurologic examination. There were four objective responses (12%): one complete remission (3 1/2+ years) and three partial remissions (57, 86, and 322 days). Two patients had improvement in disease that did not meet requirements for a partial remission. Toxicity was mild and primarily consisted of nausea, vomiting, and lethargy. Two patients were removed from study due to neurotoxicity (depression and hallucinations). The strict response criteria used in this trial were not those that have been used in testing other active agents such as carmustine (BCNU). We conclude that AT-125 has objective antitumor activity in malignant astrocytomas and warrants further study.
Screening candidate targets by SAGE evaluation of rectal cancer transcriptome after chemoradiotherapy: Association of trefoil factor-family 3 (TFF3) expression with patients prognosis
Authors: E. Casado, P. Cejas, J. Sanchez, M. Blanco, J. Maurel, B. Castelo, J. Feliu, R. Miquel, J. De Castro, M. Sereno, M. Gonzalez Baron
Journal: Journal of Clinical Oncology (2009)

4107 Background: Treatment resistance and the lack of reliable prognostic factors are major obstacles in rectal cancer (RC) management. A blind screening of RC transcriptome changes after chemoradiotherapy (CRT) could pinpoint proteins potentially involved in CRT resistance. Evaluation of their relation with disease outcome could help to identify novel therapeutic and prognostic candidates. Methods and Results: In a first stage we screened dynamic changes of RC transcriptome after CRT using blind and directed strategies. On one side, we selected fresh RC samples, before and after CRT, from three uT3N0 patients with poor response, as assessed by Dworak´s TRG2 and minimal downstaging (ypT2–3N0). Serial Analysis of Gene Expression (microSAGE) was conducted, six libraries were generated, sequencing around 30.000 tags. MonteCarlo analysis of dynamic “intra-patient” changes, and “inter-patient” comparisons revealed a set of 25 genes with shared significant changes. On another side, a collection of 29 genes was selected from the literature, In a second stage we evaluated dynamic changes in the mixed set of 54 genes in a cohort of 125 stage II-III RC patients treated with preopCRT. Samples from 74 patients assured sufficient tumor quality and quantity before and after CRT. mRNA dynamic changes of gene expression were evaluated by TaqMan Low Density Arrays (TLDAs), and statistical analysis done by Wilcoxon test with bootstrap and regulated genes selected for discriminant and Cox proportional-hazards regression analysis. Induction of mRNA TFF3, screened in the blind phase SAGE and exhibiting important tumor promotion and progression functions, was associated with tumor relapse and shorter survival. Also, analysis of TFF3 immunohistochemical expression in surgical samples revealed that an on/off pattern of intraluminal gland expression (PAS independent) strongly predicted tumor relapse. Conclusions: Upregulation of TFF3 after CRT, and an easily determined IHC pattern, predicted RC relapse in preoperatively treated patients. Confirmatory prognostic studies in independent series should be conducted, and its potential therapeutic merits as a candidate target evaluated. No significant financial relationships to disclose.
IDH mutation-induced suppression of type-1 anti-glioma immune response
Authors: Gary Kohanbash, Shruti Shrivastav, Brian Ahn, Yafei Hou, Joseph Costello, Hideho Okada
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Isocitrate dehydrogenase (IDH) mutations are the first mutations that occur during the oncogenic process of lower-grade glioma (LGG) and confers a novel gain-of-function activity by converting α-ketoglutarate (αKG) to 2-hydroxyglutarate (2HG), promoting DNA hyper-methylation.
Plasma Protein Biomarker Signatures As Indicators Of The Effects Of Immuno Gene Tumor Therapy In Patients With Glioblastoma Multiforme
Authors: Leif Salford, Oscar Persson, Anders Carlsson, Bengt Widegren, Peter Siesjö, Gunnar Skagerberg, Johan Ingvarsson, Christer Wingren, Carl Borrebaeck
Journal: Neuro-Oncology (2008)
Comorbidity and survival in advanced non-small cell lung cancer (NSCLC) veteran patients
Authors: V. T. Chang, D. R. Hoover, J. Cogswell, M. Cholankeril, S. Badin, W. Yang, H. Yan, M. L. Gonzalez, J. Einhorn, B. S. Kasimis
Journal: Journal of Clinical Oncology (2009)

e20675 Background: Prognostic value of comorbidity at diagnosis has received increasing attention. We studied whether the Charlson Comorbidity Index (CMI), Cumulative Illness Rating Scale (CIRS), Kaplan Feinstein Index (KFI), and/or VA Comorbidity Scale (VA) independently predicted survival for NSCLC patients Methods: In an IRB approved protocol, the charts of 101 patients with Stage IIIA, IIIB or IV Non small cell lung cancer seen from 2004 through 2006 at a VA medical center were reviewed of whom 94 have already died. Comorbidity scores ECOG performance status (PS), stage, number of treatments, serum LDH, and albumin levels were obtained or coded from medical records. Survival analyses were performed using proportional hazards models. Results: Median (M) patient age was 69 years (range 51–88), the M ECOG PS was 1 (range 0–4); 13 (13%) had stage IIIA, 27 (26%) IIB and 62 (61%) IV. The M number of treatments was 1 (range 0–6). Histologies were adenocarcinoma in 48 (48%) pts, squamous cell in 37 (37%) pts, and other 17 (15%) pts. The M survival was 207 days (range 4–1785 days). The Median (and ranges) were: 4.2 (1.2–12.8) for CMI, 3 (0–6) for CIRS15, 5(0–11) for CIRS16, 1.8 (0–4) for CIRS17, 0(0–1) for CIRS18, 2 (0–3) for KFI, and 4 (0–8) for VA. The M albumin was 3.7 (range 1.9–5.3) and LDH 201 (range 104–1036). In univariate survival analyses, the stage (p&lt;0.001), ECOG PS (p&lt;0.001), albumin (p&lt;0.003), and the CIRS 17 (p &lt;0.052) were predictive of survival; when, however, bisected by median values, the VA scale (p&lt;0.027), ECOG PS (p&lt;0.052) and albumin (p&lt;.0017) were significantly related to survival but age, LDH, CMI, KFI and subscales of the CIRS (CIRS 16, CIRS 17, CIRS18) were not related to survival. In multivariate proportional hazards analyses that included stage and a comorbidity index, the CIRS16 (p&lt;.032) was an independent predictor of survival; the combinations of stage (p&lt;0.008), ECOG PS (p&lt;.004), stage (p&lt;.006) and albumin (p&lt;.002) were independent predictors of survival. Conclusions: In this small sample, current comorbidity indices did not add to determinations of survival of veterans with advanced NSCLC. Further research is needed in a larger sample. Supported in part by the New Jersey Commission for Cancer Research 09–1133-CCR-EO and VA HSRD IIR 02–103. No significant financial relationships to disclose.
Overexpression of <i>EphA2</i> gene in invasive human breast cancer and its association with hormone receptor status
Authors: M. Pan
Journal: Journal of Clinical Oncology (2005)

9583 Background: EphA2 is a receptor tyrosine kinase for ephrin A-1 that has been implicated in a broad spectrum of functions, including angiogenesis, cell migration, and cancer development. Expression of EphA2 is regulated by p53. This study is aimed to determine if expression of EphA2 is associated with development of invasive human breast cancer and breast cancer histologic prognostic characteristics. Methods: Paraffin blocks of 134 invasive human breast cancer cases and fifteen normal human breast tissues were studied with immunohistochemistry staining using two polyclonal antibodies against EphA2 protein. The expression patterns were determined as overexpression (expression in more than 50% of cells) or low expression (expression in less than 10% of cells). Histologic data of these breast cancer cases were retrieved from computerized patient medical records. Results: In normal breast tissues, the expression of EphA2 protein was found to be low and to be predominantly restricted to the cytoplasm of discontinuous satellite myoepithelial cells and scattered epithelial cells. Normal breast ductal epithelial cells showed low EphA2 expression in less than 5% of cells. However, 110 out of 134 (82%) human invasive breast cancer cases showed overexpression of EphA2 protein. Three EphA2 protein expression patterns were identified in these breast cancer cases: predominantly nuclear expression, diffuse nuclear and cytoplasmic expression, and predominantly membrane expression. The expression of EphA2 is at least 10 fold higher in invasive human breast cancer than normal breast tissue. Interestingly, 90% of ER (estrogen receptor)-positive cases were found to overexpress EphA2, while only 60% of ER-negative cases overexpress EphA2 (p<0.001). In another word, 10% of ER-positive cases showed low expression of EphA2, compared to 40% of ER-negative cases. PR status, HER2/NEU overexpression, nodal status, and grade were not associated with pattern or intensity of EphA2 expression. Conclusions: Receptor tyrosine kinase EphA2 is highly overexpressed in more than 80% cases of invasive human breast cancer. Absence of overexpression of EphA2 was associated with negative ER status, and hence, poorer prognosis. No significant financial relationships to disclose.
Factors associated with chemotherapy receipt and intensity for stage IV colorectal cancer (CRC): A multihealth system, population-based study
Authors: Y. Zafar, S. C. Grambow, D. H. Abbott, J. L. Malin, L. L. Zullig, J. T. Kolimaga, D. T. Provenzale
Journal: Journal of Clinical Oncology (2009)

6519 Background: Little is known about chemotherapy practice patterns for patients with stage IV CRC. Methods: Cancer Outcomes Research &amp; Surveillance Consortium (CanCORS) is a prospective cohort study including patients with incident CRC sampled from a set of defined populations and health systems. Eligible patients for this analysis (n = 742) had stage IV CRC and abstracted medical record data, including stage, chemotherapy, comorbidity (measured by the Adult Comorbidity Evaluation 27 index), and sociodemographic data. Logistic regression models were used to evaluate factors associated with chemotherapy receipt and intensity. Results: A majority of patients were male (62%) and white (62%). 27% were ≥75 years old, and 14% had severe comorbidity. 34% had private insurance, 32% had public insurance (including Medicare/Medicaid), 18% were Veterans Affairs patients, 4% had no insurance, and 13% were missing insurance information. Overall, 77% received chemotherapy, and 57% received &gt;1 line of therapy. Patients were less likely to receive chemotherapy if they were older (65–74 vs. &lt;55 years = adjusted odds ratio [OR] 0.14, 95%CI 0.06–0.33, p &lt; 0.001; ≥75 vs. &lt;55 years = OR 0.04, 95%CI 0.02–0.64, p &lt; 0.001), or had severe comorbidity (OR 0.38; 95%CI 0.23–0.64; p &lt; 0.001). When treated, patients ≥75 years were more likely to receive capecitabine vs. 5-fluorouracil (5-FU) (p &lt; 0.001), less likely to receive &gt;1 line of therapy (p &lt; 0.001), and less likely to receive oxaliplatin or irinotecan combination therapy vs. a single-agent fluorouracil (p &lt; 0.001). Although only 4% were uninsured, lack of insurance did not appear to be a factor in receipt of chemotherapy. Patients with public vs. private insurance were more likely to receive chemotherapy (OR 2.58; 95%CI 1.49–4.47; p &lt; 0.001) but were less likely to receive combination therapy versus a single-agent 5-FU (p = 0.02). Conclusions: The elderly are less likely to receive standard therapy. While patients with public insurance are more likely to receive chemotherapy, they are less likely to receive recommended first-line combination regimens. Future research should investigate how insurance coverage and demographics influence physician and patient preferences for advanced CRC treatment. No significant financial relationships to disclose.
A phase I trial of gefitinib (ZD1839) plus rapamycin for patients with recurrent malignant glioma
Authors: J. N. Rich, D. A. Reardon, J. A. Quinn, J. J. Vredenburgh, A. Desjardins, S. Sathornsumetee, S. Gururangan, P. Lyons, D. D. Bigner, H. S. Friedman
Journal: Journal of Clinical Oncology (2005)

1565 Abnormal signaling of the PI3K/Akt pathway is a hallmark of malignant glioma. The primary objective of this phase 1 study is to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of Gefitinib, an inhibitor of the EGFR receptor tyrosine kinase, when combined with rapamycin, a macrolide antibiotic capable of inhibiting mTOR, a critical downstream regulator of PI3K/Akt signaling, among patients with recurrent malignant glioma. Eligibility criteria include: recurrent malignant glioma; no more than 3 prior episodes of recurrence; age greater than 18 years; KPS greater than 60%; adequate hepatic, renal, pulmonary and bone marrow function. Patients with prior with EGFR or mTOR-directed therapies are excluded. A standard “3+3” dose escalation design was employed. Patients are stratified based on concurrent use of enzyme-inducing anticonvulsants (EIAC; phenytoin, carbamazepine and phenobarbitol) and both strata are independently escalated. Gefitinib and rapamycin are administered on a continuous daily dosing regimen. Each treatment cycle is 28 days and evaluation for response is performed after every other cycle. Twenty-three patients have been enrolled to date: 20 with recurrent GBM and 3 with recurrent AA. The median age is 51 (range 33 to 66); 65% are male and 52% are on EIAC. Accrual and dose escalation are ongoing. The MTD has yet to be defined for either stratum. A single DLT has been observed thus far and consisted of an episode of grade 3 mucositis. Approximately half of the patients have undergone pharmacokinetic sampling. Seventeen patients continue on study having received 1–3 cycles of therapy while 6 patients have discontinued therapy due to progressive disease. Two marked radiographic responses has been observed to date. An update of the outcome and toxicity of Gefitinib plus rapamycin for patients with recurrent malignant glioma will be presented based on additional follow up and enrollment. No significant financial relationships to disclose.
Mature results of Radiation Therapy Oncology Group (RTOG) Trial 9615 using intra-arterial cisplatin (IA-P) and concurrent radiation therapy (RT) for stage IV-T4 head/neck (H/N) squamous cell carcinoma (SCCa)
Authors: P. Kumar, K. T. Robbins, J. Harris, T. McCulloch, A. Cmelak, R. Sofferman, P. Levine, K. Fu
Journal: Journal of Clinical Oncology (2005)

5579
Endothelial activation in non-metastatic breast cancer
Authors: P. Tesarova, J. Barkmanova, G. Pazdrova, M. Kalousova, O. Mestek, Z. Dlouha, T. Zima, L. Petruzelka
Journal: Journal of Clinical Oncology (2008)

22075 Background: Endothelial activation and/or dysfunction with increased expression of adhesion molecules (E-selectin, P-selectin, ICAM-1) and increased production of prothrombotic (t-PA, Fbg, D-dimers) and antifibrinolytic (e.g. PAI-1) factors has been demonstrated in patients with advanced cancer and may be the prerequisite for the formation of metastases and neoangiogenesis. Currently it is unclear if the signs of endothelial activation (and endothelial dysfunction) are present already in patients with non-metastatic breast cancer. Methods: We examined soluble P-selectin, E-selectin, ICAM-1, VEGF, von Willebrand factor, coagulation parameters and flow-mediated vasodilation and their relation to TNM classification, size of the tumor, its grade, expression of estrogen and progesteron and Her/neu receptors and the clinical outcome in 87 patients with non-metastatic breast cancer (stage I-III). Results: Plasma levels of sE-selectin, but not sP-selectin, sICAM-1 and VEGF correlated with the size of the tumour (median levels 43.2 vs. 77.4 vs. 95.5 ng/ml in T2, T3 and T4 tumours, respectively, p<0.05). sE-selectin correlated with Fbg (r=0.230, p<0.05) and protein C (r=0.311, p<0.01), sP-selectin correlated with VEGF (r=0.349, p<0.001), PAI-1 (r=0.227, p<0.05) and protein S (r=0.247, p<0.05) and von Willebrand factor correlated with protein C (r=0.250, p<0.05). Fbg tightly correlated with antithrombin III, D-dimers and protein C. Conclusions: Increase of plasma levels of sE-selectin could have been demonstrated not only in patients with metastatic breast cancer, but also in patients with large non-metastatic tumour. Endothelial activation was accompanied by the activated coagulation. Further studies should delineate if the increase of sE-selectin is also accompanied by other signs of endothelial dysfunction, e.g. impaired flow-mediated vasodilation. Supported by the grant of IGA of the Ministry of Health of the Czech Republic No. 9020–3. No significant financial relationships to disclose.